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Sample records for monophosphate crystalline complex

  1. Structural Studies of Thiamin Monophosphate Kinase in Complex with Substrates and Products.

    SciTech Connect

    McCulloch, K.M.; Kinsland, C.; Begley, T.P.; Ealick, S E.

    2008-06-03

    Thiamin monophosphate kinase (ThiL) catalyzes the ATP-dependent phosphorylation of thiamin monophosphate (TMP) to form thiamin pyrophosphate (TPP), the active form of vitamin B1. ThiL is a member of a small ATP binding superfamily that also includes the purine biosynthetic enzymes, PurM and PurL, NiFe hydrogenase maturation protein, HypE, and selenophosphate synthase, SelD. The latter four enzymes are believed to utilize phosphorylated intermediates during catalysis. To understand the mechanism of ThiL and its relationship to the other superfamily members, we determined the structure of Aquifex aeolicus ThiL (AaThiL) with nonhydrolyzable AMP-PCP and TMP, and also with the products of the reaction, ADP and TPP. The results suggest that AaThiL utilizes a direct, inline transfer of the {gamma}-phosphate of ATP to TMP rather than a phosphorylated enzyme intermediate. The structure of ThiL is compared to those of PurM, PurL, and HypE, and the ATP binding site is compared to that of PurL, for which nucleotide complexes are available.

  2. Repetitive mechanical strain suppresses macrophage uptake of immunoglobulin G complexes and enhances cyclic adenosine monophosphate synthesis.

    PubMed Central

    Mattana, J.; Sankaran, R. T.; Singhal, P. C.

    1995-01-01

    Uptake of immunoglobulin G (IgG) complexes by macrophages (M phi) may play an important role in disease states characterized by increased levels of circulating immune complexes. In sites such as the glomerular mesangium M phi may be subjected to repetitive mechanical strain, although in vitro studies of M phi endocytosis are typically carried out with cells grown on rigid surfaces. We undertook the present study to determine whether repetitive mechanical strain could modulate M phi endocytosis of IgG complexes. IgG complex uptake was significantly diminished in M phi that were subjected to repetitive mechanical strain using parameters corresponding to peak and minimal intraglomerular pressures compared with control, and uptake varied according to the amount of mechanical strain applied. There was no significant difference in surface binding of IgG between M phi subjected to strain and those not. Mechanical strain did not significantly influence the rate of IgG complex degradation. Inhibition of nitric oxide synthase and guanylate cyclase activity did not alter the effect of mechanical strain, although this effect was potentiated by 3-isobutyl-1-methylxanthine (IBMX). Angiotensin II, which has been shown to reduce adenosine 3',5'-cyclic monophosphate (cAMP) production in M phi, significantly attenuated the suppressive effect of mechanical strain on IgG complex uptake as well as another inhibitor of cAMP generation, indomethacin. Enzyme immunoassay demonstrated significantly enhanced levels of cAMP in M phi that were subjected to mechanical strain compared with control, an effect that was potentiated by IBMX and attenuated by angiotensin II and indomethacin. These results demonstrate that repetitive mechanical strain significantly reduces IgG complex uptake by M phi, most likely by enhancing cAMP synthesis. Such an effect might play a significant role in macromolecule handling by M phi in sites in which they are subjected to repetitive mechanical deformation such as

  3. Osmium (VI) complexes of the 3', 5'-dinucleoside monophosphates, ApU and UpA.

    PubMed

    Daniel, F B; Behrman, E J

    1976-02-10

    The dinucleoside monophosphates, ApU and UpA, react with potassium osmate (VI) and 2,2'-bipyridyl to form the corresponding oxo-osmium (VI) bipyridyl sugar ester in which the osmate group is bonded to the terminal 2',3'-glycol. Osmium (VIII) tetroxide and 2,2'-bipyridyl react with the dinucleosides to form the corresponding oxo-osmium (VI) bipyridyl heterocyclic esters which result from addition of the tetroxide to the 5,6-double bond of the uracil residue. Although capable of transesterification reactions, these heterocyclic esters are exceptionally stable toward exchange reactions in solution. No apparent exchange was observed after 1 month. This reaction thus seems promising for single-site osmium labeling in polynucleotides.

  4. Study of orotidine 5'-monophosphate decarboxylase in complex with the top three OMP, BMP, and PMP ligands by molecular dynamics simulation.

    PubMed

    Jamshidi, Shirin; Jalili, Seifollah; Rafii-Tabar, Hashem

    2015-01-01

    Catalytic mechanism of orotidine 5'-monophosphate decarboxylase (OMPDC), one of the nature most proficient enzymes which provides large rate enhancement, has not been fully understood yet. A series of 30 ns molecular dynamics (MD) simulations were run on X-ray structure of the OMPDC from Saccharomyces cerevisiae in its free form as well as in complex with different ligands, namely 1-(5'-phospho-D-ribofuranosyl) barbituric acid (BMP), orotidine 5'-monophosphate (OMP), and 6-phosphonouridine 5'-monophosphate (PMP). The importance of this biological system is justified both by its high rate enhancement and its potential use as a target in chemotherapy. This work focuses on comparing two physicochemical states of the enzyme (protonated and deprotonated Asp91) and three ligands (substrate OMP, inhibitor, and transition state analog BMP and substrate analog PMP). Detailed analysis of the active site geometry and its interactions is properly put in context by extensive comparison with relevant experimental works. Our overall results show that in terms of hydrogen bond occupancy, electrostatic interactions, dihedral angles, active site configuration, and movement of loops, notable differences among different complexes are observed. Comparison of the results obtained from these simulations provides some detailed structural data for the complexes, the enzyme, and the ligands, as well as useful insights into the inhibition mechanism of the OMPDC enzyme. Furthermore, these simulations are applied to clarify the ambiguous mechanism of the OMPDC enzyme, and imply that the substrate destabilization and transition state stabilization contribute to the mechanism of action of the most proficient enzyme, OMPDC.

  5. Study of orotidine 5'-monophosphate decarboxylase in complex with the top three OMP, BMP, and PMP ligands by molecular dynamics simulation.

    PubMed

    Jamshidi, Shirin; Jalili, Seifollah; Rafii-Tabar, Hashem

    2015-01-01

    Catalytic mechanism of orotidine 5'-monophosphate decarboxylase (OMPDC), one of the nature most proficient enzymes which provides large rate enhancement, has not been fully understood yet. A series of 30 ns molecular dynamics (MD) simulations were run on X-ray structure of the OMPDC from Saccharomyces cerevisiae in its free form as well as in complex with different ligands, namely 1-(5'-phospho-D-ribofuranosyl) barbituric acid (BMP), orotidine 5'-monophosphate (OMP), and 6-phosphonouridine 5'-monophosphate (PMP). The importance of this biological system is justified both by its high rate enhancement and its potential use as a target in chemotherapy. This work focuses on comparing two physicochemical states of the enzyme (protonated and deprotonated Asp91) and three ligands (substrate OMP, inhibitor, and transition state analog BMP and substrate analog PMP). Detailed analysis of the active site geometry and its interactions is properly put in context by extensive comparison with relevant experimental works. Our overall results show that in terms of hydrogen bond occupancy, electrostatic interactions, dihedral angles, active site configuration, and movement of loops, notable differences among different complexes are observed. Comparison of the results obtained from these simulations provides some detailed structural data for the complexes, the enzyme, and the ligands, as well as useful insights into the inhibition mechanism of the OMPDC enzyme. Furthermore, these simulations are applied to clarify the ambiguous mechanism of the OMPDC enzyme, and imply that the substrate destabilization and transition state stabilization contribute to the mechanism of action of the most proficient enzyme, OMPDC. PMID:24559040

  6. Nucleoside monophosphate complex structures of the endonuclease domain from the influenza virus polymerase PA subunit reveal the substrate binding site inside the catalytic center.

    PubMed

    Zhao, Cong; Lou, Zhiyong; Guo, Yu; Ma, Ming; Chen, Yutao; Liang, Shuaiyi; Zhang, Liang; Chen, Shoudeng; Li, Xuemei; Liu, Yingfang; Bartlam, Mark; Rao, Zihe

    2009-09-01

    Highly pathogenic influenza virus strains currently in circulation pose a significant risk of a global pandemic. Following the reported crystal structure of the endonuclease domain from the avian influenza virus polymerase PA subunit, here we report the results of a systematic X-ray crystallographic analysis of its complex with adenosine, uridine, and thymidine nucleoside monophosphates (NMPs). Electron density corresponding to the monophosphate moiety of each nucleotide was apparent in each NMP complex and bound to the catalytic metal. A hydrophobic site was found to contribute to nucleoside binding. The NMP complex structures should represent the conformation of the bound product after nuclease cleavage. Moreover, one solvent molecule was found to occupy an equivalent position to the second reported Mn(2+) ion, where it mediates the interaction between bound NMPs and the N-terminal PA domain in the presence of the Mg(2+) ion. The results presented here indicate a possible cleavage mechanism and identify a distinct nucleotide binding pocket. The identification of this binding pocket opens a new avenue for anti-influenza drug discovery, targeting the cap-dependent endonuclease, in response to the worldwide threat of influenza. PMID:19587036

  7. Adenosine 3',5'-cyclic monophosphate (cAMP)-dependent phosphoregulation of mitochondrial complex I is inhibited by nucleoside reverse transcriptase inhibitors

    SciTech Connect

    Lund, Kaleb C. Wallace, Kendall B.

    2008-01-01

    Nucleoside analog reverse transcriptase inhibitors (NRTIs) are known to directly inhibit mitochondrial complex I activity as well as various mitochondrial kinases. Recent observations that complex I activity and superoxide production are modulated through cAMP-dependent phosphorylation suggests a mechanism through which NRTIs may affect mitochondrial respiration via kinase-dependent protein phosphorylation. In the current study, we examine the potential for NRTIs to inhibit the cAMP-dependent phosphorylation of complex I and the associated NADH:CoQ oxidoreductase activities and rates of superoxide production using HepG2 cells. Phosphoprotein staining of immunocaptured complex I revealed that 3'-azido-3'-deoxythymidine (AZT; 10 and 50 {mu}M), AZT monophosphate (150 {mu}M), and 2',3'-dideoxycytidine (ddC; 1 {mu}M) prevented the phosphorylation of the NDUFB11 subunit of complex I. This was associated with a decrease in complex I activity with AZT and AZT monophosphate only. In the presence of succinate, superoxide production was increased with 2',3'-dideoxyinosine (ddI; 10 {mu}M) and ddC (1 {mu}M). In the presence of succinate + cAMP, AZT showed an inverse dose-dependent effect on superoxide production. None of the NRTIs examined inhibit PKA activity suggesting that the observed effects are due to a direct interaction with complex I. These data demonstrate a direct effect of NRTIs on cAMP-dependent regulation of mitochondrial bioenergetics independent of DNA polymerase-{gamma} activity; in the case of AZT, these observations may provide a mechanism for the observed long-term toxicity with this drug.

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

    PubMed

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

    2013-01-01

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

  9. Positronium formation studies in crystalline molecular complexes: Triphenylphosphine oxide - Acetanilide

    NASA Astrophysics Data System (ADS)

    Oliveira, F. C.; Denadai, A. M. L.; Guerra, L. D. L.; Fulgêncio, F. H.; Windmöller, D.; Santos, G. C.; Fernandes, N. G.; Yoshida, M. I.; Donnici, C. L.; Magalhães, W. F.; Machado, J. C.

    2013-04-01

    Hydrogen bond formation in the triphenylphosphine oxide (TPPO), acetanilide (ACN) supramolecular heterosynton system, named [TPPO0.5·ACN0.5], has been studied by Positron Annihilation Lifetime Spectroscopy (PALS) and supported by several analytical techniques. In toluene solution, Isothermal Titration Calorimetry (ITC) presented a 1:1 stoichiometry and indicated that the complexation process is driven by entropy, with low enthalpy contribution. X-ray structure determination showed the existence of a three-dimensional network of hydrogen bonds, allowing also the confirmation of the existence of a 1:1 crystalline molecular complex in solid state. The results of thermal analysis (TGA, DTA and DSC) and FTIR spectroscopy showed that the interactions in the complex are relatively weaker than those found in pure precursors, leading to a higher positronium formation probability at [TPPO0.5·ACN0.5]. These weak interactions in the complex enhance the possibility of the n- and π-electrons to interact with positrons and consequently, the probability of positronium formation is higher. Through the present work is shown that PALS is a sensible powerful tool to investigate intermolecular interactions in solid heterosynton supramolecular systems.

  10. Crystal structures of Tritrichomonasfoetus inosine monophosphate dehydrogenase in complex with substrate, cofactor and analogs: a structural basis for the random-in ordered-out kinetic mechanism.

    PubMed

    Prosise, Glen L; Luecke, Hartmut

    2003-02-14

    The enzyme inosine monophosphate dehydrogenase (IMPDH) is responsible for the rate-limiting step in guanine nucleotide biosynthesis. Because it is up-regulated in rapidly proliferating cells, human type II IMPDH is actively targeted for immunosuppressive, anticancer, and antiviral chemotherapy. The enzyme employs a random-in ordered-out kinetic mechanism where substrate or cofactor can bind first but product is only released after the cofactor leaves. Due to structural and kinetic differences between mammalian and microbial enzymes, most drugs that are successful in the inhibition of mammalian IMPDH are far less effective against the microbial forms of the enzyme. It is possible that with greater knowledge of the structural mechanism of the microbial enzymes, an effective and selective inhibitor of microbial IMPDH will be developed for use as a drug against multi-drug resistant bacteria and protists. The high-resolution crystal structures of four different complexes of IMPDH from the protozoan parasite Tritrichomonas foetus have been solved: with its substrate IMP, IMP and the inhibitor mycophenolic acid (MPA), the product XMP with MPA, and XMP with the cofactor NAD(+). In addition, a potassium ion has been located at the dimer interface. A structural model for the kinetic mechanism is proposed.

  11. Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action.

    PubMed

    Baca, A M; Sirawaraporn, R; Turley, S; Sirawaraporn, W; Hol, W G

    2000-10-01

    The enzyme 7,8-dihydropteroate synthase (DHPS) catalyzes the condensation of para-aminobenzoic acid (pABA) with 6-hydroxymethyl-7, 8-dihydropterin-pyrophosphate to form 7,8-dihydropteroate and pyrophosphate. DHPS is essential for the de novo synthesis of folate in prokaryotes, lower eukaryotes, and in plants, but is absent in mammals. Inhibition of this enzyme's activity by sulfonamide and sulfone drugs depletes the folate pool, resulting in growth inhibition and cell death. Here, we report the 1.7 A resolution crystal structure of the binary complex of 6-hydroxymethylpterin monophosphate (PtP) with DHPS from Mycobacterium tuberculosis (Mtb), a pathogen responsible for the death of millions of human beings each year. Comparison to other DHPS structures reveals that the M. tuberculosis DHPS structure is in a unique conformation in which loop 1 closes over the active site. The Mtb DHPS structure hints at a mechanism in which both loops 1 and 2 play important roles in catalysis by shielding the active site from bulk solvent and allowing pyrophosphoryl transfer to occur. A binding mode for pABA, sulfonamides and sulfones is suggested based on: (i) the new conformation of the closed loop 1; (ii) the distribution of dapsone and sulfonamide resistance mutations; (iii) the observed direction of the bond between the 6-methyl carbon atom and the bridging oxygen atom to the alpha-phosphate group in the Mtb DHPS:PtP binary complex; and (iv) the conformation of loop 2 in the Escherichia coli DHPS structure. Finally, the Mtb DHPS structure reveals a highly conserved pterin binding pocket that may be exploited for the design of novel antimycobacterial agents.

  12. 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

  13. Simultaneous interaction with base and phosphate moieties modulates the phosphodiester cleavage of dinucleoside 3',5'-monophosphates by dinuclear Zn2+ complexes of di(azacrown) ligands.

    PubMed

    Wang, Qi; Lönnberg, Harri

    2006-08-23

    Five dinucleating ligands (1-5) and one trinucleating ligand (6) incorporating 1,5,9-triazacyclododecan-3-yloxy groups attached to an aromatic scaffold have been synthesized. The ability of the Zn(2+) complexes of these ligands to promote the transesterification of dinucleoside 3',5'-monophosphates to a 2',3'-cyclic phosphate derived from the 3'-linked nucleoside by release of the 5'-linked nucleoside has been studied over a narrow pH range, from pH 5.8 to 7.2, at 90 degrees C. The dinuclear complexes show marked base moiety selectivity. Among the four dinucleotide 3',5'-phosphates studied, viz. adenylyl-3',5'-adenosine (ApA), adenylyl-3',5'-uridine (ApU), uridylyl-3',5'-adenosine (UpA), and uridylyl-3',5'-uridine (UpU), the dimers containing one uracil base (ApU and UpA) are cleaved up to 2 orders of magnitude more readily than those containing either two uracil bases (UpU) or two adenine bases (ApA). The trinuclear complex (6), however, cleaves UpU as readily as ApU and UpA, while the cleavage of ApA remains slow. UV spectrophotometric and (1)H NMR spectroscopic studies with one of the dinucleating ligands (3) verify binding to the bases of UpU and ApU at less than millimolar concentrations, while no interaction with the base moieties of ApA is observed. With ApU and UpA, one of the Zn(2+)-azacrown moieties in all likelihood anchors the cleaving agent to the uracil base of the substrate, while the other azacrown moiety serves as a catalyst for the phosphodiester transesterification. With UpU, two azacrown moieties are engaged in the base moiety binding. The catalytic activity is, hence, lost, but it can be restored by addition of a third azacrown group on the cleaving agent.

  14. Simultaneous interaction with base and phosphate moieties modulates the phosphodiester cleavage of dinucleoside 3',5'-monophosphates by dinuclear Zn2+ complexes of di(azacrown) ligands.

    PubMed

    Wang, Qi; Lönnberg, Harri

    2006-08-23

    Five dinucleating ligands (1-5) and one trinucleating ligand (6) incorporating 1,5,9-triazacyclododecan-3-yloxy groups attached to an aromatic scaffold have been synthesized. The ability of the Zn(2+) complexes of these ligands to promote the transesterification of dinucleoside 3',5'-monophosphates to a 2',3'-cyclic phosphate derived from the 3'-linked nucleoside by release of the 5'-linked nucleoside has been studied over a narrow pH range, from pH 5.8 to 7.2, at 90 degrees C. The dinuclear complexes show marked base moiety selectivity. Among the four dinucleotide 3',5'-phosphates studied, viz. adenylyl-3',5'-adenosine (ApA), adenylyl-3',5'-uridine (ApU), uridylyl-3',5'-adenosine (UpA), and uridylyl-3',5'-uridine (UpU), the dimers containing one uracil base (ApU and UpA) are cleaved up to 2 orders of magnitude more readily than those containing either two uracil bases (UpU) or two adenine bases (ApA). The trinuclear complex (6), however, cleaves UpU as readily as ApU and UpA, while the cleavage of ApA remains slow. UV spectrophotometric and (1)H NMR spectroscopic studies with one of the dinucleating ligands (3) verify binding to the bases of UpU and ApU at less than millimolar concentrations, while no interaction with the base moieties of ApA is observed. With ApU and UpA, one of the Zn(2+)-azacrown moieties in all likelihood anchors the cleaving agent to the uracil base of the substrate, while the other azacrown moiety serves as a catalyst for the phosphodiester transesterification. With UpU, two azacrown moieties are engaged in the base moiety binding. The catalytic activity is, hence, lost, but it can be restored by addition of a third azacrown group on the cleaving agent. PMID:16910666

  15. Studies on structures of lipid A-monophosphate clusters

    NASA Astrophysics Data System (ADS)

    Faunce, Chester A.; Reichelt, Hendrik; Paradies, Henrich H.

    2011-03-01

    Single crystalline clusters of lipid A-monophosphate were grown from organic dispersions containing 5-15% (v/v) water at various volume fractions, ϕ, and temperatures. The morphology of the single lipid A-monophosphate crystals was either rhombohedral or hexagonal. The hexagonal crystals were needlelike or cylindrical in shape, with the long dimension parallel to the c axis of the unit cell. The crystalline clusters were studied using electron microscopy and x-ray powder diffraction. Employing molecular location methods following a Rietveld refinement and whole-pattern refinement revealed two monoclinic crystal structures in the space groups P21 and C2, both converged with RF = 0.179. The two monoclinic crystal structures were packing (hydrocarbon chains) and conformational (sugar) polymorphs. Neither of these two structures had been encountered previously. Only intramolecular hydrogen bonding was observed for the polymorphs, which were located between the amide and the carboxyl groups. Another crystalline structure was found in the volume-fraction range 2.00 × 10-3 ≤ ϕ ≤ 2.50 × 10-3, which displayed hexagonal symmetry. The hexagonal symmetry of the self-assembled lipid A-monophosphate crystalline phase might be reconciled with the monoclinic symmetry found at low-volume-fractions. Therefore, lowering the symmetry from cubic, i.e., Ia overline 3d, to rhombohedral R overline 3 m, and finally to the monoclinic space group C2 was acceptable if the lipid A-monophosphate anion was completely orientationally ordered.

  16. Mechanisms of dielectric polarization in thermotropic liquid-crystalline complexes based on lanthanides

    NASA Astrophysics Data System (ADS)

    Dobrun, L. A.; Kovshik, A. P.; Ryumtsev, E. I.; Knyazev, A. A.; Galyametdinov, Yu. G.

    2016-06-01

    The components of the dielectric constant of a terbium-based liquid-crystalline complex have been measured in the frequency range of 350-5 × 106 Hz. The magnitude and sign of the dielectric anisotropy of the complex have been determined. Dispersion of the dielectric constants in the liquid-crystalline and isotropic phases has been found. The mechanisms responsible for the relaxation phenomena that appear in the studied sample have been determined. The time of dielectric relaxation, the activation energy, and the dipole moment of the complex have been obtained.

  17. Ion-polyether coordination complexes: crystalline ionic conductors for clean energy storage.

    PubMed

    Bruce, Peter G

    2006-03-21

    Ion-polyether complexes are the solid state analogues of crown ether and cryptand complexes. They represent a fascinating class of coordination compounds in their own right, with the ability to support ionic conductivity and the potential to be used as electrolytes in all-solid-state rechargeable lithium batteries. Here the recent discovery of ionic conductivity in crystalline ion-polyether complexes, when for 30 years such materials were considered to be insulators, is described, along with their closely related structural chemistry.

  18. A new crystal form of human histidine triad nucleotide-binding protein 1 (hHINT1) in complex with adenosine 5′-monophosphate at 1.38 Å resolution

    PubMed Central

    Dolot, Rafał; Ozga, Magdalena; Włodarczyk, Artur; Krakowiak, Agnieszka; Nawrot, Barbara

    2012-01-01

    Histidine triad nucleotide-binding protein 1 (HINT1) represents the most ancient and widespread branch of the histidine triad protein superfamily. HINT1 plays an important role in various biological processes and has been found in many species. Here, the structure of the human HINT1–adenosine 5′-monophosphate (AMP) complex at 1.38 Å resolution obtained from a new monoclinic crystal form is reported. The final structure has R cryst = 0.1207 (R free = 0.1615) and the model exhibits good stereochemical quality. Detailed analysis of the high-resolution data allowed the details of the protein structure to be updated in comparison to the previously published data. PMID:22869114

  19. Ion-polyether coordination complexes: crystalline ionic conductors for clean energy storage.

    PubMed

    Bruce, Peter G

    2006-03-21

    Ion-polyether complexes are the solid state analogues of crown ether and cryptand complexes. They represent a fascinating class of coordination compounds in their own right, with the ability to support ionic conductivity and the potential to be used as electrolytes in all-solid-state rechargeable lithium batteries. Here the recent discovery of ionic conductivity in crystalline ion-polyether complexes, when for 30 years such materials were considered to be insulators, is described, along with their closely related structural chemistry. PMID:16518503

  20. Estrogen regulates energy metabolic pathway and upstream adenosine 5'-monophosphate-activated protein kinase and phosphatase enzyme expression in dorsal vagal complex metabolosensory neurons during glucostasis and hypoglycemia.

    PubMed

    Tamrakar, Pratistha; Ibrahim, Baher A; Gujar, Amit D; Briski, Karen P

    2015-02-01

    The ability of estrogen to shield the brain from the bioenergetic insult hypoglycemia is unclear. Estradiol (E) prevents hypoglycemic activation of the energy deficit sensor adenosine 5'-monophosphate-activated protein kinase (AMPK) in hindbrain metabolosensory A2 noradrenergic neurons. This study investigates the hypothesis that estrogen regulates A2 AMPK through control of fuel metabolism and/or upstream protein kinase/phosphatase enzyme expression. A2 cells were harvested by laser microdissection after insulin or vehicle (V) injection of E- or oil (O)-implanted ovariectomized female rats. Cell lysates were evaluated by immunoblot for glycolytic, tricarboxylic acid cycle, respiratory chain, and acetyl-CoA-malonyl-CoA pathway enzymes. A2 phosphofructokinase (PFKL), isocitrate dehydrogenase, pyruvate dehydrogenase, and ATP synthase subunit profiles were elevated in E/V vs. O/V; hypoglycemia augmented PFKL and α-ketoglutarate dehydrogenase expression in E only. Hypoglycemia increased A2 Ca(2+) /calmodulin-dependent protein kinase-β in O and reduced protein phosphatase in both groups. A2 phospho-AMPK levels were equivalent in O/V vs. E/V but elevated during hypoglycemia in O only. These results implicate E in compensatory upregulation of substrate catabolism and corresponding maintenance of energy stability of A2 metabolosensory neurons during hypoglycemia, outcomes that support the potential viability of molecular substrates for hormone action as targets for therapies alleviating hypoglycemic brain injury.

  1. Iridium Complexes and Clusters in Dealuminated Zeolite HY: Distribution between Crystalline and Impurity Amorphous Regions

    SciTech Connect

    Martinez-Macias, Claudia; Xu, Pinghong; Hwang, Son-Jong; Lu, Jing; Chen, Cong-Yan; Browning, Nigel D.; Gates, Bruce C.

    2014-07-08

    Dealuminated zeolite HY was used to support Ir(CO)2 complexes formed from Ir(CO)2(C5H7O2). Infrared and X-ray absorption spectra and atomic-resolution electron microscopy images identify these complexes, and the images and 27Al NMR spectra identify impurity amorphous regions in the zeolite where the iridium is more susceptible to aggregation than in the crystalline regions. The results indicate a significant stability limitation of metal in amorphous impurity regions of zeolites.

  2. Conformational remodeling of femtomolar inhibitor-acetylcholinesterase complexes in the crystalline state

    PubMed Central

    Bourne, Yves; Radic, Zoran; Taylor, Palmer; Marchot, Pascale

    2010-01-01

    The active center of acetylcholinesterase (AChE), a target site for competitive inhibitors, resides centrosymmetric to the subunit at the base of a deep, narrow gorge lined by aromatic residues. At the gorge entry, a peripheral site encompasses overlapping binding loci for non-competitive inhibitors, which alter substrate access to the gorge. The click-chemistry inhibitor TZ2PA6 links the active center ligand, tacrine, to the peripheral site ligand, propidium, through a biorthogonal reaction of an acetylene and an azide that forms either a syn1 or an anti1 triazole. Compared with wild-type mouse AChE, a Tyr337Ala mutant displays full catalytic activity, albeit with two to three orders of magnitude higher affinities for the TZ2PA6 syn1 and anti1 regioisomers, reflected in low femtomolar Kd values, diffusion-limited association and dissociation half-times greater than one month and one week, respectively. Three structures of each of the co-crystallized syn1 and anti1 complexes of the Tyr337Ala mutant were solved at three distinct times of crystal maturation, consistent with or exceeding the half-lives of the complexes in solution, while crystalline complexes obtained from soaked Tyr337Ala crystals led to picturing “freshly formed” complexes. The structures, at 2.55-2.75Å resolution, reveal a range of unprecedented conformations of the bound regioisomers, not observed in the wild-type AChE complexes, associated with concerted positional rearrangements of side chains in the enzyme gorge. Moreover, time-dependent conformational remodeling of the crystalline complexes appears to correlate with the dissociation half-times of the solution complexes. Hence for the tight-binding TZ2PA6 inhibitors, the initial complexes kinetically driven in solution slowly form more stable complexes governed by thermodynamic equilibrium and observable in mature crystals. PMID:21090615

  3. Immune cell activation from multivalent interactions with liquid-crystalline polycation-DNA complexes

    NASA Astrophysics Data System (ADS)

    Schmidt, Nathan; Jin, Fan; Lande, Roberto; Curk, Tine; Xian, Wujing; Frasca, Loredana; Dobnikar, Jure; Frenkel, Daan; Gilliet, Michel; Wong, Gerard

    2014-03-01

    Microbial DNA can trigger type I interferon (IFN) production in plasmacytoid cells (pDCs) by binding to endosomal toll-like receptor 9 (TLR9). TLR9 in pDCs do not normally respond to self-DNA, but in certain autoimmune diseases self-DNA can complex with the polycationic antimicrobial peptide LL37 into condensed structures which allow DNA to access endosomal compartments and stimulate TLR9 in pDCs. We use x-ray studies and cell measurements of IFN secretion by pDCs to show that a broad range of polycation-DNA complexes stimulate pDCs and elucidate the criterion for high IFN production. Furthermore, we show via experiments and computer simulations that the distinguishing factor for why certain complexes activate pDCs while others do not is the self-assembled structure of the liquid-crystalline polycation-DNA complex.

  4. Free Energy Calculations of Crystalline Hard Sphere Complexes Using Density Functional Theory

    SciTech Connect

    Gunawardana, K. G.S.H.; Song, Xueyu

    2014-12-22

    Recently developed fundamental measure density functional theory (FMT) is used to study binary hard sphere (HS) complexes in crystalline phases. By comparing the excess free energy, pressure and phase diagram, we show that the fundamental measure functional yields good agreements to the available simulation results of AB, AB2 and AB13 crystals. Additionally, we use this functional to study the HS models of five binary crystals, Cu5Zr(C15b), Cu51Zr14(β), Cu10Zr7(φ), CuZr(B2) and CuZr2 (C11b), which are observed in the Cu-Zr system. The FMT functional gives well behaved minimum for most of the hard sphere crystal complexes in the two dimensional Gaussian space, namely a crystalline phase. However, the current version of FMT functional (white Bear) fails to give a stable minimum for the structure Cu10Zr7(φ). We argue that the observed solid phases for the HS models of the Cu-Zr system are true thermodynamic stable phases and can be used as a reference system in perturbation calculations.

  5. Free Energy Calculations of Crystalline Hard Sphere Complexes Using Density Functional Theory

    DOE PAGES

    Gunawardana, K. G.S.H.; Song, Xueyu

    2014-12-22

    Recently developed fundamental measure density functional theory (FMT) is used to study binary hard sphere (HS) complexes in crystalline phases. By comparing the excess free energy, pressure and phase diagram, we show that the fundamental measure functional yields good agreements to the available simulation results of AB, AB2 and AB13 crystals. Additionally, we use this functional to study the HS models of five binary crystals, Cu5Zr(C15b), Cu51Zr14(β), Cu10Zr7(φ), CuZr(B2) and CuZr2 (C11b), which are observed in the Cu-Zr system. The FMT functional gives well behaved minimum for most of the hard sphere crystal complexes in the two dimensional Gaussian space,more » namely a crystalline phase. However, the current version of FMT functional (white Bear) fails to give a stable minimum for the structure Cu10Zr7(φ). We argue that the observed solid phases for the HS models of the Cu-Zr system are true thermodynamic stable phases and can be used as a reference system in perturbation calculations.« less

  6. Structure characterization of the non-crystalline complexes of copper salts with native cyclodextrins.

    PubMed

    Velasco, Manuel I; Krapacher, Claudio R; de Rossi, Rita H; Rossi, Laura I

    2016-06-28

    The characterization of non-crystalline complexes is particularly difficult when techniques like X-ray diffraction or NMR cannot be used. We propose a simple procedure to characterize the physicochemical properties of amorphous new coordination compounds between cyclodextrins (CD) and Cu(2+) salts, by means of the integration of the information provided by several techniques including elemental analysis, flame atomic absorption, TGA, UV-Vis diffuse reflectance, colorimetry, FT-IR and EPR. On the basis of these procedures, we suggest geometrical and structural approximations resulting in an octahedral or distorted octahedral geometry with diverse positions for the metallic centre. According to the EPR spectrum, only one of the complexes may have rhombic symmetry. We also analyzed enthalpy-entropy compensation and the isokinetic effect. In addition, general trends in thermal stability, spectroscopic properties and inclusion in the cavity were analysed. This complete characterization methodology becomes essential for their future application as catalysts. PMID:27272478

  7. Structural Studies of Potassium Transport Protein KtrA Regulator of Conductance of K+ (RCK) C Domain in Complex with Cyclic Diadenosine Monophosphate (c-di-AMP).

    PubMed

    Kim, Henna; Youn, Suk-Jun; Kim, Seong Ok; Ko, Junsang; Lee, Jie-Oh; Choi, Byong-Seok

    2015-06-26

    Although it was only recently identified as a second messenger, c-di-AMP was found to have fundamental importance in numerous bacterial functions such as ion transport. The potassium transporter protein, KtrA, was identified as a c-di-AMP receptor. However, the co-crystallization of c-di-AMP with the protein has not been studied. Here, we determined the crystal structure of the KtrA RCK_C domain in complex with c-di-AMP. The c-di-AMP nucleotide, which adopts a U-shaped conformation, is bound at the dimer interface of RCK_C close to helices α3 and α4. c-di-AMP interacts with KtrA RCK_C mainly by forming hydrogen bonds and hydrophobic interactions. c-di-AMP binding induces the contraction of the dimer, bringing the two monomers of KtrA RCK_C into close proximity. The KtrA RCK_C was able to interact with only c-di-AMP, but not with c-di-GMP, 3',3-cGAMP, ATP, and ADP. The structure of the KtrA RCK_C domain and c-di-AMP complex would expand our understanding about the mechanism of inactivation in Ktr transporters governed by c-di-AMP.

  8. Electron tomography of the nucleoid of Gemmata obscuriglobus reveals complex liquid crystalline cholesteric structure

    PubMed Central

    Yee, Benjamin; Sagulenko, Evgeny; Morgan, Garry P.; Webb, Richard I.; Fuerst, John A.

    2012-01-01

    The nucleoid of the planctomycete Gemmata obscuriglobus is unique within the Bacteria in being both highly condensed and enclosed by a double-membrane nuclear envelope, seemingly analogous to the nucleus of eukaryotes. Here we have applied electron tomography to study high-pressure frozen, cryosubstituted cells of G. obscuriglobus and found multiple nested orders of DNA organization within the condensed nucleoid structure. Detailed examination of the nucleoid revealed a series of nested arcs characteristic of liquid crystalline cholesteric DNA structure. The finest fibers were arranged in parallel concentrically in a double-twist organization. At the highest order of nucleoid organization, several of these structures come together to form the core of the G. obscuriglobus nucleoid. The complex structure of DNA within this nucleoid may have implications for understanding the evolutionary significance of compartmentalized planctomycete cells. PMID:22993511

  9. Metamorphic and tectonic evolution of the Greater Himalayan Crystalline Complex in Nyalam region, south Tibet

    NASA Astrophysics Data System (ADS)

    Wang, Jia-Min; Zhang, Jin-Jiang; Rubatto, Daniela

    2016-04-01

    Recent studies evoke dispute whether the Himalayan metamorphic core - Greater Himalayan Crystalline Complex (GHC) - was exhumed as a lateral crustal flow or a critical taper wedge during the India-Asia collision. This contribution investigated the evolution of the GHC in the Nyalam region, south Tibet, with comprehensive studies on structural kinematics, metamorphic petrology and geochronology. The GHC in the Nyalam region can be divided into the lower and upper GHC. Phase equilibria modelling and conventional thermobarometric results show that peak temperature conditions are lower in the lower GHC (~660-700°C) and higher in the upper GHC (~740-780°C), whereas corresponding pressure conditions at peak-T decrease from ~9-13 kbar to ~4 kbar northward. Monazite, zircon and rutile U-Pb dating results reveal two distinct blocks within the GHC of the Nyalam region. The upper GHC underwent higher degree of partial melting (15-25%, via muscovite dehydration melting) that initiated at ~32 Ma, peaked at ~29 Ma to 25 Ma, possibly ended at ~20 Ma. The lower GHC underwent lower degree of melting (0-10%) that lasted from 19 to 16 Ma, which was produced mainly via H2O-saturated melting. At different times, both the upper and lower blocks underwent initial slow cooling (35 ± 8 and 10 ± 5°C/Myr, respectively) and subsequent rapid cooling (120 ± 40°C/Myr). The established timescale of metamorphism suggests that high-temperature metamorphism within the GHC lasted a long duration (~15 Myr), whereas duration of partial melting lasted for ~3 Myr in the lower GHC and lasted for 7-12 Myr in the upper GHC. The documented diachronous metamorphism and discontinuity of peak P-T conditions implies the presence of the Nyalam Thrust in the study area. This thrust is probably connected to the other thrusts in Nepal and Sikkim Himalaya, which extends over ~800 km and is named the "High Himalayan Thrust". Timing of activity along this thrust is at ~25-16 Ma, which is coeval with active

  10. Liquid-crystalline ordering of antimicrobial peptide-DNA complexes controls TLR9 activation

    NASA Astrophysics Data System (ADS)

    Schmidt, Nathan W.; Jin, Fan; Lande, Roberto; Curk, Tine; Xian, Wujing; Lee, Calvin; Frasca, Loredana; Frenkel, Daan; Dobnikar, Jure; Gilliet, Michel; Wong, Gerard C. L.

    2015-07-01

    Double-stranded DNA (dsDNA) can trigger the production of type I interferon (IFN) in plasmacytoid dendritic cells (pDCs) by binding to endosomal Toll-like receptor-9 (TLR9; refs , , , , ). It is also known that the formation of DNA-antimicrobial peptide complexes can lead to autoimmune diseases via amplification of pDC activation. Here, by combining X-ray scattering, computer simulations, microscopy and measurements of pDC IFN production, we demonstrate that a broad range of antimicrobial peptides and other cationic molecules cause similar effects, and elucidate the criteria for amplification. TLR9 activation depends on both the inter-DNA spacing and the multiplicity of parallel DNA ligands in the self-assembled liquid-crystalline complex. Complexes with a grill-like arrangement of DNA at the optimum spacing can interlock with multiple TLR9 like a zipper, leading to multivalent electrostatic interactions that drastically amplify binding and thereby the immune response. Our results suggest that TLR9 activation and thus TLR9-mediated immune responses can be modulated deterministically.

  11. Liquid-crystalline ordering of antimicrobial peptide-DNA complexes controls TLR9 activation.

    PubMed

    Schmidt, Nathan W; Jin, Fan; Lande, Roberto; Curk, Tine; Xian, Wujing; Lee, Calvin; Frasca, Loredana; Frenkel, Daan; Dobnikar, Jure; Gilliet, Michel; Wong, Gerard C L

    2015-07-01

    Double-stranded DNA (dsDNA) can trigger the production of type I interferon (IFN) in plasmacytoid dendritic cells (pDCs) by binding to endosomal Toll-like receptor-9 (TLR9; refs 1-5). It is also known that the formation of DNA-antimicrobial peptide complexes can lead to autoimmune diseases via amplification of pDC activation. Here, by combining X-ray scattering, computer simulations, microscopy and measurements of pDC IFN production, we demonstrate that a broad range of antimicrobial peptides and other cationic molecules cause similar effects, and elucidate the criteria for amplification. TLR9 activation depends on both the inter-DNA spacing and the multiplicity of parallel DNA ligands in the self-assembled liquid-crystalline complex. Complexes with a grill-like arrangement of DNA at the optimum spacing can interlock with multiple TLR9 like a zipper, leading to multivalent electrostatic interactions that drastically amplify binding and thereby the immune response. Our results suggest that TLR9 activation and thus TLR9-mediated immune responses can be modulated deterministically.

  12. Up-regulation of 3'5'-cyclic guanosine monophosphate-specific phosphodiesterase in the porcine cumulus-oocyte complex affects steroidogenesis during in vitro maturation.

    PubMed

    Sasseville, Maxime; Côté, Nancy; Gagnon, Marie-Claude; Richard, François J

    2008-11-01

    The 3'5'-cyclic GMP (cGMP) pathway is known to influence ovarian functions, including steroidogenesis, ovulation, and granulosa cell proliferation. We show here that cGMP-phosphodiesterase (PDE) activity increased in a gonadotropin-dependent manner more than 3-fold in the cumulus-oocyte complex (COC) after 24 h in vitro maturation (IVM) and up to 5-fold after 48 h. Further characterization of this increase demonstrated that the activity was located primarily in cumulus cells, and was sensitive to sildenafil and zaprinast, two inhibitors specific to both type 5 and 6 PDEs. RT-PCR experiments showed that the mRNAs for cGMP-degrading PDEs 5A and 6C are present in the COC before and after 30 h IVM. Western blotting confirmed the presence of PDE 5A in the COC. Western blotting of PDE 6C revealed a significant up-regulation in the COC during IVM. Isolation and analysis of detergent-resistant membranes suggested that PDE 6C protein, along with half of the total sildenafil-sensitive cGMP-degradation activity, is associated with detergent-resistant membrane in the COC after 30 h IVM. Treatment of porcine COC with sildenafil during IVM caused a significant decrease in gonadotropin-stimulated progesterone secretion. Together, these results constitute the first report exploring the contribution of cGMP-PDE activity in mammalian COC, supporting a functional clustering of the enzyme, and providing the first evidence of its role in steroidogenesis.

  13. Structure of the crystalline complex between ribonuclease A and D(pA)4.

    PubMed Central

    McPherson, A; Brayer, G; Morrison, R

    1986-01-01

    Crystals of a complex formed between ribonuclease A and d(pA)4 were grown and their structure determined by a combination of multiple isomorphous replacement (MIR) and molecular replacement techniques. The known structure of ribonuclease A in the correct orientation in the unit cell yielded a conventional crystallographic R factor of 0.32 at 2.8 A resolution when refined as a rigid body. Difference Fourier syntheses permitted determination of the disposition of the DNA in the unit cell. Refinement of both protein and DNA by constrained-restrained least squares procedures resulted in an R factor of 0.22 at 2.5 A resolution. The structure of the crystalline complex is comprised of four ordered oligomers of d(pA)4 associated with each molecule of RNAse. If the sites of interaction between protein and d(pA)4 fragments are mapped on the surface of the protein, they describe an essentially continuous path into and through the active site, across the surface of the enzyme and finally into the basic amino acid cluster on the opposite side of the protein. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 6 PMID:3955171

  14. Radiation effects and annealing kinetics in crystalline silicates, phosphates and complex Nb-Ta-Ti oxides. FInal Report

    SciTech Connect

    Ewing, R.C.

    1987-08-10

    Interaction of heavy particles (alpha-recoil nuclei, fission fragments, implanted ions) with ceramics is complex because they have a wide range of structure types, complex compositions and chemical bonding is variable. Radiation damage can produce diverse results, but most commonly, crystalline periodic materials become either polycrystalline or aperiodic (metamict state). We studied the transition from crystalline to aperiodic state in natural materials that have been damaged by alpha recoil nuclei in the U and Th decay series and in synthetic, analogous structure types which have been amorphized by ion implantation. Transition from crystalline to aperiodic was followed by analysis of XRD, high resolution TEM, and EXAFS/XANE spectroscopy. Use of these techniques with increasing dose provided data on an increasing finer scale as the damage process progressed.

  15. Characterization of the alpha-gamma and alpha-beta complex: evidence for an in vivo functional role of alpha-crystallin as a molecular chaperone

    NASA Technical Reports Server (NTRS)

    Boyle, D.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    Previous studies have demonstrated that in vitro, alpha-crystallin can protect other lens proteins against extensive denaturation and aggregation. The mechanism of this protection involves preferential binding of the partially denatured protein to a central region of the native alpha-crystallin complex. To test whether a similar phenomenon might occur in vivo, a high molecular weight aggregate (HMWA) fraction was isolated from the aged bovine lens. Negative staining of this preparation revealed the presence of particles of 13-14 nm diameter, characteristic of alpha-crystallin. Immunolocalization of the same particles using antiserum specific for gamma- and beta-crystallins demonstrated preferential binding of these crystallins to the central region of the alpha-crystallin complex. Together, these results provide evidence that in the intact lens, the alpha-crystallins are functionally important molecular chaperones.

  16. Genetics Home Reference: adenosine monophosphate deaminase deficiency

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions adenosine monophosphate deaminase deficiency adenosine ...

  17. Tetrakis(dimethoxyphenyl)adamantane (TDA) and its inclusion complexes in the crystalline state: a versatile carrier for small molecules.

    PubMed

    Schwenger, Alexander; Frey, Wolfgang; Richert, Clemens

    2015-06-01

    Molecular storage solutions for incorporating small molecules in crystalline matrices are of interest in the context of structure elucidation, decontamination, and slow release of active ingredients. Here we report the syntheses of 1,3,5,7-tetrakis(2,4-dimethoxyphenyl)adamantane, 1,3,5,7-tetrakis(4-methoxyphenyl)adamantane, 1,3,5,7-tetrakis(4-methoxy-2-methylphenyl)adamantane, and 1,3,5,7-tetrakis(4-methoxy-2-ethylphenyl)adamantane, together with their X-ray crystal structures. All four compounds crystallize readily. Only the octaether shows an unusual level of (pseudo)polymorphism in its crystalline state, combined with the ability to include a number of different small molecules in its crystal lattices. A total of 20 different inclusion complexes with guest molecules as different as ethanol or trifluorobenzene were found. For nitromethane and benzene, schemes for uptake and release are presented. PMID:25925766

  18. Assembling an alkyl rotor to access abrupt and reversible crystalline deformation of a cobalt(II) complex

    PubMed Central

    Su, Sheng-Qun; Kamachi, Takashi; Yao, Zi-Shuo; Huang, You-Gui; Shiota, Yoshihito; Yoshizawa, Kazunari; Azuma, Nobuaki; Miyazaki, Yuji; Nakano, Motohiro; Maruta, Goro; Takeda, Sadamu; Kang, Soonchul; Kanegawa, Shinji; Sato, Osamu

    2015-01-01

    Harnessing molecular motion to reversibly control macroscopic properties, such as shape and size, is a fascinating and challenging subject in materials science. Here we design a crystalline cobalt(II) complex with an n-butyl group on its ligands, which exhibits a reversible crystal deformation at a structural phase transition temperature. In the low-temperature phase, the molecular motion of the n-butyl group freezes. On heating, the n-butyl group rotates ca. 100° around the C–C bond resulting in 6–7% expansion of the crystal size along the molecular packing direction. Importantly, crystal deformation is repeatedly observed without breaking the single-crystal state even though the shape change is considerable. Detailed structural analysis allows us to elucidate the underlying mechanism of this deformation. This work may mark a step towards converting the alkyl rotation to the macroscopic deformation in crystalline solids. PMID:26531811

  19. Assembling an alkyl rotor to access abrupt and reversible crystalline deformation of a cobalt(II) complex.

    PubMed

    Su, Sheng-Qun; Kamachi, Takashi; Yao, Zi-Shuo; Huang, You-Gui; Shiota, Yoshihito; Yoshizawa, Kazunari; Azuma, Nobuaki; Miyazaki, Yuji; Nakano, Motohiro; Maruta, Goro; Takeda, Sadamu; Kang, Soonchul; Kanegawa, Shinji; Sato, Osamu

    2015-01-01

    Harnessing molecular motion to reversibly control macroscopic properties, such as shape and size, is a fascinating and challenging subject in materials science. Here we design a crystalline cobalt(II) complex with an n-butyl group on its ligands, which exhibits a reversible crystal deformation at a structural phase transition temperature. In the low-temperature phase, the molecular motion of the n-butyl group freezes. On heating, the n-butyl group rotates ca. 100° around the C-C bond resulting in 6-7% expansion of the crystal size along the molecular packing direction. Importantly, crystal deformation is repeatedly observed without breaking the single-crystal state even though the shape change is considerable. Detailed structural analysis allows us to elucidate the underlying mechanism of this deformation. This work may mark a step towards converting the alkyl rotation to the macroscopic deformation in crystalline solids.

  20. Partial 13C isotopic enrichment of nucleoside monophosphates: useful reporters for NMR structural studies

    PubMed Central

    Kishore, Anita I.; Mayer, Michael R.; Prestegard, James H.

    2005-01-01

    Analysis of the 13C isotopic labeling patterns of nucleoside monophosphates (NMPs) extracted from Escherichia coli grown in a mixture of C-1 and C-2 glucose is presented. By comparing our results to previous observations on amino acids grown in similar media, we have been able to rationalize the labeling pattern based on the well-known biochemistry of nucleotide biosynthesis. Except for a few notable absences of label (C4 in purines and C3′ in ribose) and one highly enriched site (C1′ in ribose), most carbons are randomly enriched at a low level (an average of 13%). These sparsely labeled NMPs give less complex NMR spectra than their fully isotopically labeled analogs due to the elimination of most 13C–13C scalar couplings. The spectral simplicity is particularly advantageous when working in ordered systems, as illustrated with guanosine diphosphate (GDP) bound to ADP ribosylation factor 1 (ARF1) aligned in a liquid crystalline medium. In this system, the absence of scalar couplings and additional long-range dipolar couplings significantly enhances signal to noise and resolution. PMID:16254075

  1. Structural Analysis of Crystalline R(+)-α-Lipoic Acid-α-cyclodextrin Complex Based on Microscopic and Spectroscopic Studies.

    PubMed

    Ikuta, Naoko; Endo, Takatsugu; Hosomi, Shota; Setou, Keita; Tanaka, Shiori; Ogawa, Noriko; Yamamoto, Hiromitsu; Mizukami, Tomoyuki; Arai, Shoji; Okuno, Masayuki; Takahashi, Kenji; Terao, Keiji; Matsugo, Seiichi

    2015-10-16

    R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability of its complexes with cyclodextrins (CDs). In this study, we have prepared and purified a crystalline RALA-αCD complex and evaluated its properties in the solid state. The results of ¹H NMR and PXRD analyses indicated that the crystalline RALA-αCD complex is a channel type complex with a molar ratio of 2:3 (RALA:α-CD). Attenuated total reflection/Fourier transform infrared analysis of the complex showed the shift of the C=O stretching vibration of RALA due to the formation of the RALA-αCD complex. Raman spectroscopic analysis revealed the significant weakness of the S-S and C-S stretching vibrations of RALA in the RALA-αCD complex implying that the dithiolane ring of RALA is almost enclosed in glucose ring of α-CD. Extent of this effect was dependent on the direction of the excitation laser to the hexagonal morphology of the crystal. Solid-state NMR analysis allowed for the chemical shift of the C=O peak to be precisely determined. These results suggested that RALA was positioned in the α-CD cavity with its 1,2-dithiolane ring orientated perpendicular to the plane of the α-CD ring.

  2. Structural Analysis of Crystalline R(+)-α-Lipoic Acid-α-cyclodextrin Complex Based on Microscopic and Spectroscopic Studies

    PubMed Central

    Ikuta, Naoko; Endo, Takatsugu; Hosomi, Shota; Setou, Keita; Tanaka, Shiori; Ogawa, Noriko; Yamamoto, Hiromitsu; Mizukami, Tomoyuki; Arai, Shoji; Okuno, Masayuki; Takahashi, Kenji; Terao, Keiji; Matsugo, Seiichi

    2015-01-01

    R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability of its complexes with cyclodextrins (CDs). In this study, we have prepared and purified a crystalline RALA-αCD complex and evaluated its properties in the solid state. The results of 1H NMR and PXRD analyses indicated that the crystalline RALA-αCD complex is a channel type complex with a molar ratio of 2:3 (RALA:α-CD). Attenuated total reflection/Fourier transform infrared analysis of the complex showed the shift of the C=O stretching vibration of RALA due to the formation of the RALA-αCD complex. Raman spectroscopic analysis revealed the significant weakness of the S–S and C–S stretching vibrations of RALA in the RALA-αCD complex implying that the dithiolane ring of RALA is almost enclosed in glucose ring of α-CD. Extent of this effect was dependent on the direction of the excitation laser to the hexagonal morphology of the crystal. Solid-state NMR analysis allowed for the chemical shift of the C=O peak to be precisely determined. These results suggested that RALA was positioned in the α-CD cavity with its 1,2-dithiolane ring orientated perpendicular to the plane of the α-CD ring. PMID:26501268

  3. Infrared band extinctions and complex refractive indices of crystalline C2H2 and C4H2

    NASA Technical Reports Server (NTRS)

    Khanna, R. K.; Ospina, Mario J.; Zhao, Guizhi

    1988-01-01

    Thermal IR absorption intensities are obtained for thin films of crystalline C2H2 and C4H2 at 70 K, and their n and k complex refractive indices are ascertained by separating true film absorption from interface reflection on the basis of an analysis of the transmission spectrum ratio for two sample thicknesses. This method significantly simplifies the n and k iteration process. The n and k values determined in the laboratory will in most cases reproduce a given sample thickness' observed transmission to within + or - 5 percent.

  4. Crystalline sulfur dioxide: Crystal field splittings, absolute band intensities and complex refractive indices derived from infrared spectra

    NASA Technical Reports Server (NTRS)

    Khanna, R. K.; Zhao, Guizhi

    1986-01-01

    The infrared absorption spectra of thin crystalline films of sulfur dioxide at 90 K are reported in the 2700 to 450/cm region. The observed multiplicity of the spectral features in the regions of fundamentals is attributed to factor group splittings of the modes in a biaxial crystal lattice and the naturally present minor S-34, S-36, and O-18 isotopic species. Complex refractive indices determined by an iterative Kramers-Kronig analysis of the extinction data, and absolute band strengths derived from them, are also reported in this region.

  5. Review of ''Draft - Area Recommendation Report for the Crystalline Repository Project'', January 1986. [Rolesville pluton and Elk River complex

    SciTech Connect

    Butler, J.R.

    1986-03-13

    The Draft-Area Recommendation Report identifies portions of crystalline rock bodies as proposed potentially acceptable sites for consideration as repositories of high-level radioactive waste. The review is in three parts. Part I is a general summary of the main comments, written in semi-technical language and without detailed documentation or references. It includes summaries of comments on the two preliminary candidate areas for a nuclear-waste repository in North Carolina (Rolesville pluton and Elk River complex) and on the rest of the report. The following two parts are written in the technical language of a geological report and include both documentation and references for each of the points discussed: Part II - Rolesville pluton, Site SE-4; Part III - Elk River complex, Site SE-5.

  6. PRODUCTION OF EXTRACELLULAR GUANOSINE-5'-MONOPHOSPHATE BY BACILLUS SUBTILIS

    PubMed Central

    Demain, A. L.; Miller, I. M.; Hendlin, D.

    1964-01-01

    Demain, A. L. (Merck Sharp & Dohme Research Laboratories, Rahway, N.J.), I. M. Miller, and D. Hendlin. Production of extracellular guanosine-5'-monophosphate by Bacillus subtilis. J. Bacteriol. 88:991–995. 1964.—Wild-type Bacillus subtilis colonies were found to feed purineless mutants. A strain with high feeding capacity was selected for study, with a guanineless mutant of B. subtilis used as the assay organism. The factor was excreted during its growth phase in a complex medium containing starch and soybean meal extract. Nutritional studies led to the development of a defined medium to be used for biochemical studies and to aid in the isolation of the factor. Starch was replaced by maltose and the soybean meal extract by Mn++. Production of the factor was sensitive to the pH of the medium during growth. Practically its entire extracellular accumulation occurred before visible lysis. The factor was identified as guanosine-5'-monophosphate derived by extracellular enzymatic hydrolysis of excreted ribonucleic acid. PMID:14219064

  7. NEXAFS Sensitivity to Bond Lengths in Complex Molecular Materials: A Study of Crystalline Saccharides.

    PubMed

    Gainar, Adrian; Stevens, Joanna S; Jaye, Cherno; Fischer, Daniel A; Schroeder, Sven L M

    2015-11-12

    Detailed analysis of the C K near-edge X-ray absorption fine structure (NEXAFS) spectra of a series of saccharides (fructose, xylose, glucose, galactose, maltose monohydrate, α-lactose monohydrate, anhydrous β-lactose, cellulose) indicates that the precise determination of IPs and σ* shape resonance energies is sensitive enough to distinguish different crystalline saccharides through the variations in their average C-OH bond lengths. Experimental data as well as FEFF8 calculations confirm that bond length variations in the organic solid state of 10(-2) Å can be experimentally detected, opening up the possibility to use NEXAFS for obtaining incisive structural information for molecular materials, including noncrystalline systems without long-range order such as dissolved species in solutions, colloids, melts, and similar amorphous phases. The observed bond length sensitivity is as good as that originally reported for gas-phase and adsorbed molecular species. NEXAFS-derived molecular structure data for the condensed phase may therefore be used to guide molecular modeling as well as to validate computationally derived structure models for such systems. Some results indicate further analytical value in that the σ* shape resonance analysis may distinguish hemiketals from hemiacetals (i.e., derived from ketoses and aldoses) as well as α from β forms of otherwise identical saccharides. PMID:26459024

  8. Nature of the metastable boron-oxygen complex formation in crystalline silicon

    NASA Astrophysics Data System (ADS)

    Crandall, Richard S.

    2010-11-01

    Transient capacitance measurements reveal new physics of metastable defect formation in boron-doped oxygen-containing crystalline silicon solar cells. These measurements demonstrate that holes are deeply trapped during defect formation and removed during thermal annealing with activation energy of 1.3 eV. Previous theoretical models {Du et al., [Phys. Rev. Lett. 97, 256602 (2006)] and Adey et al., [Phys. Rev. Lett. 93, 055504 (2004)]} are supported by present findings that defect formation is a slow two-stage process with activation energies of 0.17 eV and 0.4 eV at high and low temperature, respectively. Repulsive hole capture by a positive oxygen-dimer determines the defect formation rate at low temperature {Du et al., [Phys. Rev. Lett. 97, 256602 (2006)]}. The high temperature process is governed by a structural conversion of the dimer {Du et al., [Phys. Rev. Lett. 97, 256602 (2006)] and Adey et al., [Phys. Rev. Lett. 93, 055504 (2004)]}. An abnormally low rate prefactor allows this low-enthalpy reaction to be observed at the higher temperature. This dimer conversion presents an excellent example of an "entropy barrier" that explains the low conversion rate. Disparate formation and annealing results published here and in other publications are related by the Meyer-Neldel rule with an isokinetic temperature of 410 K.

  9. A review of immune amplification via ligand clustering by self-assembled liquid-crystalline DNA complexes.

    PubMed

    Lee, Ernest Y; Lee, Calvin K; Schmidt, Nathan W; Jin, Fan; Lande, Roberto; Curk, Tine; Frenkel, Daan; Dobnikar, Jure; Gilliet, Michel; Wong, Gerard C L

    2016-06-01

    We examine how the interferon production of plasmacytoid dendritic cells is amplified by the self-assembly of liquid-crystalline antimicrobial peptide/DNA complexes. These specialized dendritic cells are important for host defense because they quickly release large quantities of type I interferons in response to infection. However, their aberrant activation is also correlated with autoimmune diseases such as psoriasis and lupus. In this review, we will describe how polyelectrolyte self-assembly and the statistical mechanics of multivalent interactions contribute to this process. In a more general compass, we provide an interesting conceptual corrective to the common notion in molecular biology of a dichotomy between specific interactions and non-specific interactions, and show examples where one can construct exquisitely specific interactions using non-specific interactions. PMID:26956527

  10. Lattice location and thermal evolution of small B complexes in crystalline Si

    SciTech Connect

    Romano, L.; Piro, A.M.; Mirabella, S.; Grimaldi, M.G.; Rimini, E.

    2005-11-14

    The lattice location of B in Si has been investigated by channelling analyses using nuclear reactions (650 keV proton beam, {sup 11}B(p,{alpha}){sup 8}Be). The formation at room temperature of a specific, small B complex in presence of an excess of point defects has been inferred. In particular, B implanted in Si or B substitutional dissolved in Si and irradiated with proton beam form a unique B complex with B atoms not randomly located. The angular scans along the <100> and <110> axes are compatible with B-B pairs aligned along the <100> axis. The thermal annealing in the 200-950 deg. C range of the B complexes, analyzed by lattice location and carrier concentration measurements, depends on the residual defect density in the lattice. The B complexes dissolve at low temperature if no excess of Si self-interstitials (Is) exists or they evolve into large B clusters and then dissolve at high temperature if Is supersaturation holds.

  11. Complex dendrimer-lyotropic liquid crystalline systems: structural behavior and interactions.

    PubMed

    Bitan-Cherbakovsky, Liron; Libster, Dima; Aserin, Abraham; Garti, Nissim

    2011-10-27

    The incorporation of dendrimer into three lyotropic liquid crystalline (LLCs) mesophases is demonstrated for the first time. A second generation (G2) of poly(propylene imine) dendrimer (PPI) was solubilized into lamellar, diamond reverse cubic, and reverse hexagonal LLCs composed of glycerol monooleate (GMO), and water (and D-α-tocopherol in the H(II) system). The combination of PPI with LLCs may provide an advantageous drug delivery system. Cross-polarized light microscope, small-angle X-ray scattering (SAXS), and attenuated total reflectance Fourier transform infrared (ATR-FTIR) were utilized to study the structural behavior of the mesophases, the localization of PPI within the system, and the interactions between the guest molecule and the system's components. It was revealed that PPI-G2 functioned as a "water pump", competing with the lipid headgroups for water binding. As a result, L(α)→H(II) and Q(224)→H(II) structural shifts were detected (at 10 wt % PPI-G2 content), probably caused by the dehydration of monoolein headgroups and subsequent increase of the lipid's critical packing parameter (CPP). In the case of H(II), as a result of the balance between the dehydration of the monoolein headgroups and the significant presence of PPI within the interfacial region, increasing the quantity of hydrogen bonds, no structural transitions occurred. ATR-FTIR analysis demonstrated a downward shift of the H-O-H (water), as a result of PPI-G2 embedment, suggesting an increase in the mean water-water H-bond angle resulting from binding PPI-G2 to the water network. Additionally, the GMO hydroxyl groups at β- and γ-C-OH positions revealed a partial interaction of hydrogen bonds with N-H functional groups of the protonated PPI-G2. Other GMO interfacial functional groups were shown to interact with the PPI-G2, in parallel with the GMO dehydration phenomenon. In the future, these outcomes can be used to design advanced drug delivery systems, allowing administration of

  12. Complex dendrimer-lyotropic liquid crystalline systems: structural behavior and interactions.

    PubMed

    Bitan-Cherbakovsky, Liron; Libster, Dima; Aserin, Abraham; Garti, Nissim

    2011-10-27

    The incorporation of dendrimer into three lyotropic liquid crystalline (LLCs) mesophases is demonstrated for the first time. A second generation (G2) of poly(propylene imine) dendrimer (PPI) was solubilized into lamellar, diamond reverse cubic, and reverse hexagonal LLCs composed of glycerol monooleate (GMO), and water (and D-α-tocopherol in the H(II) system). The combination of PPI with LLCs may provide an advantageous drug delivery system. Cross-polarized light microscope, small-angle X-ray scattering (SAXS), and attenuated total reflectance Fourier transform infrared (ATR-FTIR) were utilized to study the structural behavior of the mesophases, the localization of PPI within the system, and the interactions between the guest molecule and the system's components. It was revealed that PPI-G2 functioned as a "water pump", competing with the lipid headgroups for water binding. As a result, L(α)→H(II) and Q(224)→H(II) structural shifts were detected (at 10 wt % PPI-G2 content), probably caused by the dehydration of monoolein headgroups and subsequent increase of the lipid's critical packing parameter (CPP). In the case of H(II), as a result of the balance between the dehydration of the monoolein headgroups and the significant presence of PPI within the interfacial region, increasing the quantity of hydrogen bonds, no structural transitions occurred. ATR-FTIR analysis demonstrated a downward shift of the H-O-H (water), as a result of PPI-G2 embedment, suggesting an increase in the mean water-water H-bond angle resulting from binding PPI-G2 to the water network. Additionally, the GMO hydroxyl groups at β- and γ-C-OH positions revealed a partial interaction of hydrogen bonds with N-H functional groups of the protonated PPI-G2. Other GMO interfacial functional groups were shown to interact with the PPI-G2, in parallel with the GMO dehydration phenomenon. In the future, these outcomes can be used to design advanced drug delivery systems, allowing administration of

  13. The standard enthalpies of combustion and formation of crystalline cobalt tetrakis(4-metoxyphenyl)porphin complex

    NASA Astrophysics Data System (ADS)

    Tarasov, R. P.; Volkov, A. V.; Bazanov, M. I.; Semeikin, A. S.

    2009-05-01

    The energy of combustion of cobalt tetrakis(4-metoxyphenyl)porphin was determined in an isothermic-shell liquid calorimeter with a stationary calorimetric bomb. The standard enthalpies of combustion and formation of the complex were calculated, -Δ c H o = 27334.06 ± 50.98 kJ/mol and Δf H o = 3062.90 ± 50.97 kJ/mol.

  14. A charge transfer complex nematic liquid crystalline gel with high electrical conductivity

    SciTech Connect

    Bhargavi, R.; Nair, Geetha G. E-mail: skpras@gmail.com; Krishna Prasad, S. E-mail: skpras@gmail.com; Majumdar, R.; Bag, Braja G.

    2014-10-21

    We describe the rheological, dielectric and elastic properties of a nematic liquid crystal gel created using an anthrylidene derivative of arjunolic acid, a chiral triterpenoid, obtained from the extracts of the wood of Terminalia arjuna. In this novel gel, having the electron-donor and acceptor components as minority constituents, the gelation and strengthening of charge-transfer complex (CTC) formation are seen to be occurring concomitantly. In addition to being mechanically strong with a large storage modulus, the gel with the maximized CTC exhibits Frank bend elastic constant values that approach nanonewton levels. The highlight of the study is the observation of 4–5 orders of magnitude increase in electrical conductivity for this gel, a value that is higher than even in the CT complexes of 2-d ordered columnar structures. A further important advantage of the present system over the columnar complex is that the high conductivity is seen for ac probing also, and owing to the nematic nature can be switched between its anisotropic limits. Some of these features are ascribed to a specific molecular packing architecture, which reduces the trapping of the charge carriers.

  15. Isolation of Elusive HAsAsH in a Crystalline Diuranium(IV) Complex

    PubMed Central

    Gardner, Benedict M.; Balázs, Gábor; Wooles, Ashley J.; Tuna, Floriana; McInnes, Eric J. L.; McMaster, Jonathan; Lewis, William; Blake, Alexander J.

    2015-01-01

    Abstract The HAsAsH molecule has hitherto only been proposed tentatively as a short‐lived species generated in electrochemical or microwave‐plasma experiments. After two centuries of inconclusive or disproven claims of HAsAsH formation in the condensed phase, we report the isolation and structural authentication of HAsAsH in the diuranium(IV) complex [{U(TrenTIPS)}2(μ‐η2:η2‐As2H2)] (3, TrenTIPS=N(CH2CH2NSiPri 3)3; Pri=CH(CH3)2). Complex 3 was prepared by deprotonation and oxidative homocoupling of an arsenide precursor. Characterization and computational data are consistent with back‐bonding‐type interactions from uranium to the HAsAsH π*‐orbital. This experimentally confirms the theoretically predicted excellent π‐acceptor character of HAsAsH, and is tantamount to full reduction to the diarsane‐1,2‐diide form. PMID:27478272

  16. Isolation of Elusive HAsAsH in a Crystalline Diuranium(IV) Complex

    PubMed Central

    Gardner, Benedict M; Balázs, Gábor; Scheer, Manfred; Wooles, Ashley J; Tuna, Floriana; McInnes, Eric J L; McMaster, Jonathan; Lewis, William; Blake, Alexander J; Liddle, Stephen T

    2015-01-01

    The HAsAsH molecule has hitherto only been proposed tentatively as a short-lived species generated in electrochemical or microwave-plasma experiments. After two centuries of inconclusive or disproven claims of HAsAsH formation in the condensed phase, we report the isolation and structural authentication of HAsAsH in the diuranium(IV) complex [{U(TrenTIPS)}2(μ-η2:η2-As2H2)] (3, TrenTIPS=N(CH2CH2NSiPri3)3; Pri=CH(CH3)2). Complex 3 was prepared by deprotonation and oxidative homocoupling of an arsenide precursor. Characterization and computational data are consistent with back-bonding-type interactions from uranium to the HAsAsH π*-orbital. This experimentally confirms the theoretically predicted excellent π-acceptor character of HAsAsH, and is tantamount to full reduction to the diarsane-1,2-diide form. PMID:26510123

  17. Crystalline structure of the poly(ethylene oxide)--p-nitrophenol complex; 2: Fourier transform infrared spectroscopy

    SciTech Connect

    Damman, P.; Point, J.J. . Service de Chimie-Physique et Thermodynamique)

    1994-07-04

    The authors have previously reported the existence of a crystalline compound made of poly(ethylene oxide) (PEO) and p-nitrophenol (pnp). From x-ray fiber patterns on stretched and spherulitic samples of this complex, a triclinic unit cell (a = 1.172 nm, b = 0.555 nm, c = 1.557 nm, [alpha] = 90.7[degree], [beta] = 87.1[degree], and [gamma] = 104.0[degree]) was deduced; the unit cell contains 6 PEO monomeric units and 4 pnp molecules, in agreement with the stoichiometry deduced from the phase diagram. The aim of this paper is to elucidate the conformation of the PEO chains and the mutual arrangement of the PEO and pnp molecules in the unit cell. To carry out this, the authors studied the dichroism of the IR bands of pnp in two differently oriented samples, namely, in stretched samples and in spherulites. The benzene rings are found to be perpendicular to the c crystallographic parameter (chain axis), and the 1--4 axis of pnp is found to be parallel to the a* reciprocal parameter. These observations completely determine the orientation of the pnp molecules in the unit cell. The conformation of the polymeric chains in the complex is not helical as in pure PEO. From the C[sub 2h] factor group of the PEO molecules, deduced from the FTIR observations, and the normal mode analysis of hydrogenated and deuterated PEO, they propose the (t[sub 2]gt[sub 2]gt[sub 3]t[sub 2]g[prime]t[sub 2]g[prime]t[sub 3]) glide type conformation. In conclusion, it appears that in the PEO--pnp complex a stack of pnp molecules stabilizes the surrounding PEO molecules in this new conformation.

  18. Thermal history and extensional exhumation of a high-temperature crystalline complex (Hırkadağ Massif, Central Anatolia)

    NASA Astrophysics Data System (ADS)

    Lefebvre, Côme; Kalijn Peters, M.; Wehrens, Philip C.; Brouwer, Fraukje M.; van Roermund, Herman L. M.

    2015-12-01

    The Central Anatolian Crystalline Complex (CACC) is a large continental domain exposed in central Turkey that was affected by high temperature metamorphism during the Late Cretaceous. As a result of this event, Paleozoic sediments became metamorphosed, initially under Barrovian conditions, then overprinted locally by high temperature-low pressure metamorphism, and intruded by widespread batholiths. In this study we focus on the crystalline Hırkadağ Massif located in the central part of the CACC, where we applied an integrated approach involving metamorphic, structural and geochronological analysis in order to elucidate its tectonic history from burial to exhumation. Our metamorphic study reveals that conditions of metamorphism reached ~ 7-8 kbar/700 °C and were relatively homogeneous at the scale of the Hırkadağ Massif. Coeval with the regional metamorphism, the rocks were intensely deformed as reflected by isoclinal folding, the development of a pervasive foliation and top-to-the-SE shearing. This was followed by decompression to pressures of ~ 3-4 kbar at 800 °C, which may be linked to the emplacement of local granodioritic intrusions at ~ 77 Ma. Subsequent cooling of the Hırkadağ high-grade metamorphic and intrusive rocks is indicated by 40Ar/39Ar cooling ages of 68.8 ± 0.9 Ma (biotite) and 67.0 ± 1.2 Ma (potassium feldspar). Evidence for tectonic exhumation has been identified within the marbles at the NE margin of the Hırkadağ Massif, in the form of discrete protomylonitic and mylonitic shear bands showing a consistent N40-60 top-to-NE sense of shear. Further east, the contact between brecciated mylonitic marbles and non-metamorphic conglomerates preserves the typical structural features of an upper-crustal detachment fault. Restoration of the Hırkadağ Massif and the CACC to their late Cretaceous configuration suggests that the LP-HT metamorphism, magmatism and extensional structures evolved as a result of the development and exhumation of a ~ N

  19. Photo protection of RNA building blocks: Adenosine 5‧-monophosphate, cytidine 5‧-monophosphate and cytosine

    NASA Astrophysics Data System (ADS)

    Nielsen, Jakob Brun; Thøgersen, Jan; Jensen, Svend Knak; Keiding, Søren Rud

    2013-04-01

    Photoprotection of the RNA nucleotides adenosine 5'-monophosphate and cytidine 5'-monophosphate, and the nucleobase cytosine was studied using UV pump, IR probe femtosecond transient absorption spectroscopy. The excitation energy is contained in the aromatic ring system, protecting the RNA backbone. All three molecules dissipate the excitation energy by internal conversion and subsequent vibrational relaxation to the electronic ground state in less than 10 ps. In addition, a second deactivation channel is found in cytidine 5'-monophosphate, illustrated by a signal at 1563 cm-1 with a lifetime of 33 ps assigned to an nπ∗ state in agreement with observations in the UV region.

  20. Complex Refractive Index, Specific Heat Capacity, and Thermal Conductivity for Crystalline Sb-Te Alloys and ZnS-SiO2 with Various Compositions at High Temperatures

    NASA Astrophysics Data System (ADS)

    Kuwahara, Masashi; Suzuki, Osamu; Yagi, Takashi; Taketoshi, Naoyuki

    2013-12-01

    We have measured the temperature dependence of the complex refractive index, specific heat capacity, and thermal conductivity of crystalline Sb-Te alloys and ZnS-SiO2 with various compositions by using a spectroscopic ellipsometer, differential scanning calorimeter, and nanosecond pulsed light heating thermoreflectance system. The temperature range was set from room temperature to several hundred degrees Celsius. The values of these properties are useful for calculating realistic temperatures in memory devices and for designing device structures.

  1. Substrate distortion contributes to the catalysis of orotidine 5'-monophosphate decarboxylase

    PubMed Central

    Fujihashi, Masahiro; Ishida, Toyokazu; Kuroda, Shingo; Kotra, Lakshmi P.; Pai, Emil F.; Miki, Kunio

    2014-01-01

    Orotidine 5'-monophosphate decarboxylase (ODCase) accelerates the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP) by 17 orders of magnitude. Eight new crystal structures with ligand analogues combined with computational analyses of the enzyme’s short-lived intermediates and the intrinsic electronic energies to distort the substrate and other ligands improve our understanding of the still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion of its methyl substituent bond, 6-amino-UMP shows the competition between the K72 and C6 substituents for a position close to D70, and the methyl- and ethyl-ester of OMP both induce rotation of the carboxylate group substituent out of the plane of the pyrimidine ring. MD and QM/MM computations of the enzyme-substrate (ES) complex also show the bond between the carboxylate group and the pyrimidine ring to be distorted with the distortion contributing a 10–15% decrease of the ΔΔG‡ value. These results are consistent with ODCase using both substrate distortion as well as transition state stabilization, primarily exerted by K72, in its catalysis of the OMP decarboxylation reaction. PMID:24151964

  2. Crystal versus solution structure of enzymes: NMR spectroscopy of a peptide boronic acid-serine protease complex in the crystalline state.

    PubMed Central

    Farr-Jones, S; Smith, S O; Kettner, C A; Griffin, R G; Bachovchin, W W

    1989-01-01

    The effectiveness of boronic acids as inhibitors of serine proteases has been widely ascribed to the ability of the boronyl group to form a tetrahedral adduct with the active-site serine that closely mimics the putative tetrahedral intermediate or transition state formed with substrates. However, recent 15N NMR studies of alpha-lytic protease (EC 3.4.21.12) in solution have shown that some boronic acids and peptide boronic acids form adducts with the active-site histidine instead of with the serine. Such histidine-boron adducts have not thus far been reported in x-ray diffraction studies of boronic acid-serine protease complexes. Here, we report an 15N NMR study of the MeOSuc-Ala-Ala-Pro-boroPhe complex of alpha-lytic protease in the crystalline state using magic-angle spinning. Previous 15N NMR studies have shown this complex involves the formation of a histidine-boron bond in solution. The 15N NMR spectra of the crystalline complex are essentially identical to those of the complex in solution, thereby showing that the structure of this complex is the same in solution and in the crystal and that both involve formation of a histidine-boron adduct. PMID:2780549

  3. Absorption intensities and complex refractive indices of crystalline HCN, HC3N, and C4N2 in the infrared region

    NASA Technical Reports Server (NTRS)

    Masterson, C. M.; Khanna, R. K.

    1990-01-01

    IR absorption intensities are presented for thin crystalline films of HCN, HC3N, and C4N2, together with n and k complex refractive indices determined on the basis of an iterative program for the Kramers-Konig integral via a least-squares, point-by-point fitting of the experimental transmission data. It is established that the transmission spectra generated by means of these n and k values can reproduce the experimental transmission observation values to within + or - 2 percent.

  4. Analysis of rapidly synthesized guest-filled porous complexes with synchrotron radiation: practical guidelines for the crystalline sponge method.

    PubMed

    Ramadhar, Timothy R; Zheng, Shao Liang; Chen, Yu Sheng; Clardy, Jon

    2015-01-01

    A detailed set of synthetic and crystallographic guidelines for the crystalline sponge method based upon the analysis of expediently synthesized crystal sponges using third-generation synchrotron radiation are reported. The procedure for the synthesis of the zinc-based metal-organic framework used in initial crystal sponge reports has been modified to yield competent crystals in 3 days instead of 2 weeks. These crystal sponges were tested on some small molecules, with two being unexpectedly difficult cases for analysis with in-house diffractometers in regard to data quality and proper space-group determination. These issues were easily resolved by the use of synchrotron radiation using data-collection times of less than an hour. One of these guests induced a single-crystal-to-single-crystal transformation to create a larger unit cell with over 500 non-H atoms in the asymmetric unit. This led to a non-trivial refinement scenario that afforded the best Flack x absolute stereochemical determination parameter to date for these systems. The structures did not require the use of PLATON/SQUEEZE or other solvent-masking programs, and are the highest-quality crystalline sponge systems reported to date where the results are strongly supported by the data. A set of guidelines for the entire crystallographic process were developed through these studies. In particular, the refinement guidelines include strategies to refine the host framework, locate guests and determine occupancies, discussion of the proper use of geometric and anisotropic displacement parameter restraints and constraints, and whether to perform solvent squeezing/masking. The single-crystal-to-single-crystal transformation process for the crystal sponges is also discussed. The presented general guidelines will be invaluable for researchers interested in using the crystalline sponge method at in-house diffraction or synchrotron facilities, will facilitate the collection and analysis of reliable high-quality data

  5. Analysis of rapidly synthesized guest-filled porous complexes with synchrotron radiation: practical guidelines for the crystalline sponge method

    SciTech Connect

    Ramadhar, Timothy R.; Zheng, Shao-Liang; Chen, Yu-Sheng

    2015-01-01

    This report describes complete practical guidelines and insights for the crystalline sponge method, which have been derived through the first use of synchrotron radiation on these systems, and includes a procedure for faster synthesis of the sponges. These guidelines will be applicable to crystal sponge data collected at synchrotrons or in-house facilities, and will allow researchers to obtain reliable high-quality data and construct chemically and physically sensible models for guest structural determination. A detailed set of synthetic and crystallographic guidelines for the crystalline sponge method based upon the analysis of expediently synthesized crystal sponges using third-generation synchrotron radiation are reported. The procedure for the synthesis of the zinc-based metal–organic framework used in initial crystal sponge reports has been modified to yield competent crystals in 3 days instead of 2 weeks. These crystal sponges were tested on some small molecules, with two being unexpectedly difficult cases for analysis with in-house diffractometers in regard to data quality and proper space-group determination. These issues were easily resolved by the use of synchrotron radiation using data-collection times of less than an hour. One of these guests induced a single-crystal-to-single-crystal transformation to create a larger unit cell with over 500 non-H atoms in the asymmetric unit. This led to a non-trivial refinement scenario that afforded the best Flack x absolute stereochemical determination parameter to date for these systems. The structures did not require the use of PLATON/SQUEEZE or other solvent-masking programs, and are the highest-quality crystalline sponge systems reported to date where the results are strongly supported by the data. A set of guidelines for the entire crystallographic process were developed through these studies. In particular, the refinement guidelines include strategies to refine the host framework, locate guests and determine

  6. Novel liquid-crystalline polymeric materials via noncovalent grafting: Hydrogen-bonded complexes with poly(4-vinyl pyridine)

    SciTech Connect

    Brandys, F.A.; Bazuin, C.G.

    1993-12-31

    A new type of liquid crystalline polymeric material can be formed by mixing a classical small molecule liquid crystal, which has been functionalized by a strongly polar, ionic or ionisable group, with a polymer possessing complementary groups. Noncovalent {open_quotes}grafting{close_quotes} of the small molecule mesogen to the polymer can then take place through hydrogen-bonding or electrostatic interactions. The authors have end-functionalized a 4,4`-n-alkoxy-biphenyl mesogen with a carboxylic acid group, and mixed it with poly(4-vinyl pyridine). FTIR spectroscopy clearly shows that hydrogen-bonding takes place between the two species. Differential scanning calorimetry, polarizing optical microscopy and X-ray scattering studies show that the disordered smectic phase which exists in the functionalized liquid crystal alone is thermally stabilized when mixed with the polymer, and an ordered mesophase present in the liquid crystal disappears in the mixtures, at molar ratios of liquid crystal to polymer repeat unit of less than 1. Dynamic mechanical analysis, possible for mixtures with molar rations of 0.1 or less, show that the glass transition temperature of the polymer decreases by 80{degrees}C up to a molar ratio of 0.02, confirming the effectiveness of the interactions between the two species. No further decrease occurs at higher molar ratios, due to formation of the solid phase of the liquid crystalline material.

  7. The interaction of propidium diiodide with self-complementary dinucleoside monophosphates.

    PubMed

    Davidson, M W; Griggs, B G; Lopp, I G; Wilson, W D

    1977-12-14

    The interactions of a quinacrine derivative, methylated at both the aromatic and aliphatic nitrogens, and propidium diiodide with the dinucleoside monophosphates CpG, GpC, UpA and ApU have been investigated using 13C-NMR (for the quinacrine derivative prepared with [13C]methyl substituents and 1H-NMR and ultraviolet-visible spectroscopy. The quinacrine derivative displayed negligible interaction with the dinucleosides at concentrations up to 5 - 10(-4) M. Propidium did form complexes with dinucleosides even at concentrations as low as 10(-4) M. Propidium displayed a pyrimidine-purine binding preference and gave especially large changes in ultraviolet-visible and 1H-NMR spectra in the presence of CpG. This suggests that propidium forms an intercalated complex with a Watson-Crick hydrogen-bonded CpG dimer. At higher concentrations UpA and GpC gave similar spectral changes indicating that they could also form significant amounts of an intercalated complex with propidium under appropriate conditions. The changes caused by ApU were small under all conditions and were more similar to the effects caused by mononucleotides. These results indicate that, at least for phenanthridines, cationic side chains do not greatly inhibit complex formation with dinucleoside monophosphates, and suggest that the weak interaction of the quinacrine derivative with dinucleosides is due to weaker interactions of the acridine ring system with nucleoside bases relative to the phenanthridine ring system.

  8. The effect of p,p'-dichlorodiphenyltrichloroethane on levels of guanosine 3',5'-cyclic monophosphate and adenosine 3',5'-cyclic monophosphate in two species of insects.

    PubMed

    Bodnaryk, R P

    1976-11-01

    Within 1 h after topical application of a convulsive dose (4 mug per fly, 47 mg/kg) of p,p'-dichlorodiphenyltrichloroethane (DDT) to the adult male of Sarcophaga bullata Parker, guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels rose by 71.5% (P less than 0.05) in the head, 159.5% (P less than 0.01) in the thorax, and 23.4% (P greater than 0.05) in the abdomen compared to controls. Adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels were not significantly affected by the DDT treatment. A convulsive dose (100 mug per larva, 250 mg/kg) of DDT applied to larvae of Mamestra configurata Wlk. caused the whole body level of cyclic GMP to rise by 81.6% (P less than 0.01) after 1 h, and by 95.9% (P less than 0.01) after 3 h. Levels of cyclic AMP were not affected. A hypothesis is advanced suggesting that an abnormally high rate of discharge of acetylcholine (and in the later stages of poisoning, its actual accumulation) at central cholinergic synapses causes cyclic GMP levels to rise, perhaps in post-synaptic cells. The elevated cyclic GMP-cyclic AMP ratio found in DDT-poisoned insects may be of fundamental importance in the complex sequence of events leading to tremor, hyperexcitability, paralysis, and death.

  9. Analysis of rapidly synthesized guest-filled porous complexes with synchrotron radiation: Practical guidelines for the crystalline sponge method

    DOE PAGES

    Ramadhar, Timothy R.; Zheng, Shao -Liang; Chen, Yu -Sheng; Clardy, Jon

    2015-01-01

    A detailed set of synthetic and crystallographic guidelines for the crystalline sponge method based upon the analysis of expediently synthesized crystal sponges using third-generation synchrotron radiation are reported. The procedure for the synthesis of the zinc-based metal–organic framework used in initial crystal sponge reports has been modified to yield competent crystals in 3 days instead of 2 weeks. These crystal sponges were tested on some small molecules, with two being unexpectedly difficult cases for analysis with in-house diffractometers in regard to data quality and proper space-group determination. These issues were easily resolved by the use of synchrotron radiation using data-collectionmore » times of less than an hour. One of these guests induced a single-crystal-to-single-crystal transformation to create a larger unit cell with over 500 non-H atoms in the asymmetric unit. This led to a non-trivial refinement scenario that afforded the best Flack x absolute stereochemical determination parameter to date for these systems. The structures did not require the use of PLATON/SQUEEZE or other solvent-masking programs, and are the highest-quality crystalline sponge systems reported to date where the results are strongly supported by the data. A set of guidelines for the entire crystallographic process were developed through these studies. In particular, the refinement guidelines include strategies to refine the host framework, locate guests and determine occupancies, discussion of the proper use of geometric and anisotropic displacement parameter restraints and constraints, and whether to perform solvent squeezing/masking. The single-crystal-to-single-crystal transformation process for the crystal sponges is also discussed. The presented general guidelines will be invaluable for researchers interested in using the crystalline sponge method at in-house diffraction or synchrotron facilities, will facilitate the collection and analysis of reliable high

  10. Analysis of rapidly synthesized guest-filled porous complexes with synchrotron radiation: Practical guidelines for the crystalline sponge method

    SciTech Connect

    Ramadhar, Timothy R.; Zheng, Shao -Liang; Chen, Yu -Sheng; Clardy, Jon

    2015-01-01

    A detailed set of synthetic and crystallographic guidelines for the crystalline sponge method based upon the analysis of expediently synthesized crystal sponges using third-generation synchrotron radiation are reported. The procedure for the synthesis of the zinc-based metal–organic framework used in initial crystal sponge reports has been modified to yield competent crystals in 3 days instead of 2 weeks. These crystal sponges were tested on some small molecules, with two being unexpectedly difficult cases for analysis with in-house diffractometers in regard to data quality and proper space-group determination. These issues were easily resolved by the use of synchrotron radiation using data-collection times of less than an hour. One of these guests induced a single-crystal-to-single-crystal transformation to create a larger unit cell with over 500 non-H atoms in the asymmetric unit. This led to a non-trivial refinement scenario that afforded the best Flack x absolute stereochemical determination parameter to date for these systems. The structures did not require the use of PLATON/SQUEEZE or other solvent-masking programs, and are the highest-quality crystalline sponge systems reported to date where the results are strongly supported by the data. A set of guidelines for the entire crystallographic process were developed through these studies. In particular, the refinement guidelines include strategies to refine the host framework, locate guests and determine occupancies, discussion of the proper use of geometric and anisotropic displacement parameter restraints and constraints, and whether to perform solvent squeezing/masking. The single-crystal-to-single-crystal transformation process for the crystal sponges is also discussed. The presented general guidelines will be invaluable for researchers interested in using the crystalline sponge method at in-house diffraction or synchrotron facilities, will facilitate the collection and analysis of

  11. Mechanochemical surface functionalisation of superparamagnetic microparticles with in situ formed crystalline metal-complexes: a fast novel core-shell particle formation method.

    PubMed

    Brede, F A; Mandel, K; Schneider, M; Sextl, G; Müller-Buschbaum, K

    2015-05-21

    An innovative mechanochemical method is reported for the in situ formation of crystalline metal-complexes on the surface of superparamagnetic nanocomposite microparticles. The process is demonstrated for coating Fe3O4 multicore-silica matrix particles with the 1,2,4-1H-triazole complex [ZnCl2(TzH)2]. The use of mechanochemistry demonstrates a flexible process to obtain functional shells on magnetic particle cores without the need for complicated surface-functionalisation reactions in solution. Simple mixing of the desired shell-precursors ZnCl2 and 1,2,4-1H-triazole (TzH) with the magnetic particles in a ball mill is sufficient to tailor the particle surfaces with novel functionalities while retaining the superparamagnetic behaviour.

  12. Fluoroquinolones as potential photochemotherapeutic agents: covalent addition to guanosine monophosphate.

    PubMed

    Fasani, Elisa; Manet, Ilse; Capobianco, Massimo L; Monti, Sandra; Pretali, Luca; Albini, Angelo

    2010-08-21

    The triplet aryl cation photochemically generated from fluoroquinolones bearing a fluoro atom at position 8 attacks guanosine monophosphate (k(r) > 10(9) M(-1)s(-1)) and forms covalent adducts. The reaction is a model for the implementation of oxygen-independent photochemotherapy. PMID:20571620

  13. Rate and Equilibrium Constants for an Enzyme Conformational Change during Catalysis by Orotidine 5'-Monophosphate Decarboxylase.

    PubMed

    Goryanova, Bogdana; Goldman, Lawrence M; Ming, Shonoi; Amyes, Tina L; Gerlt, John A; Richard, John P

    2015-07-28

    The caged complex between orotidine 5'-monophosphate decarboxylase (ScOMPDC) and 5-fluoroorotidine 5'-monophosphate (FOMP) undergoes decarboxylation ∼300 times faster than the caged complex between ScOMPDC and the physiological substrate, orotidine 5'-monophosphate (OMP). Consequently, the enzyme conformational changes required to lock FOMP at a protein cage and release product 5-fluorouridine 5'-monophosphate (FUMP) are kinetically significant steps. The caged form of ScOMPDC is stabilized by interactions between the side chains from Gln215, Tyr217, and Arg235 and the substrate phosphodianion. The control of these interactions over the barrier to the binding of FOMP and the release of FUMP was probed by determining the effect of all combinations of single, double, and triple Q215A, Y217F, and R235A mutations on kcat/Km and kcat for turnover of FOMP by wild-type ScOMPDC; its values are limited by the rates of substrate binding and product release, respectively. The Q215A and Y217F mutations each result in an increase in kcat and a decrease in kcat/Km, due to a weakening of the protein-phosphodianion interactions that favor fast product release and slow substrate binding. The Q215A/R235A mutation causes a large decrease in the kinetic parameters for ScOMPDC-catalyzed decarboxylation of OMP, which are limited by the rate of the decarboxylation step, but much smaller decreases in the kinetic parameters for ScOMPDC-catalyzed decarboxylation of FOMP, which are limited by the rate of enzyme conformational changes. By contrast, the Y217A mutation results in large decreases in kcat/Km for ScOMPDC-catalyzed decarboxylation of both OMP and FOMP, because of the comparable effects of this mutation on rate-determining decarboxylation of enzyme-bound OMP and on the rate-determining enzyme conformational change for decarboxylation of FOMP. We propose that kcat = 8.2 s(-1) for decarboxylation of FOMP by the Y217A mutant is equal to the rate constant for cage formation from the

  14. Crystalline Membranes

    NASA Technical Reports Server (NTRS)

    Tsapatsis, Michael (Inventor); Lai, Zhiping (Inventor)

    2008-01-01

    In certain aspects, the invention features methods for forming crystalline membranes (e.g., a membrane of a framework material, such as a zeolite) by inducing secondary growth in a layer of oriented seed crystals. The rate of growth of the seed crystals in the plane of the substrate is controlled to be comparable to the rate of growth out of the plane. As a result, a crystalline membrane can form a substantially continuous layer including grains of uniform crystallographic orientation that extend through the depth of the layer.

  15. Polymerized Complex Sol-Gel Synthesis, Structural and Optical Properties of Monoclinic Eu3+ Doped KGd(WO4)2 Crystalline Red Phosphors

    NASA Astrophysics Data System (ADS)

    Thangaraju, D.; Durairajan, A.; Babu, S. Moorthy; Hayakawa, Y.

    2011-10-01

    1% Eu3+ doped KGd(WO4)2 (KGW) was synthesized through Pechini sol-gel process and crystallized by subsequent annealing at high temperature. Potassium nitrate, gadolinium nitrate and ammonium para tungstate precursors were mixed with citric acid and ethylene glycol to synthesis the polymerizable complex gel. The gel was heated to 250 °C for decomposition of polymer, which after the brownish white powder was used to synthesis the pure form of 1% Eu:KGW. The pre-fired powder was further heated at high temperature/s (550, 600, 650 and 700 °C) for calcination. The properties of heat treated samples were characterized by powder XRD, FT-IR, Raman, FESEM and fluorescence analysis to understand the crystallinity, organic liberation, tungstate ribbon formation, surface morphology and emission nature, respectively. Phase evaluation from the amorphous pre-fired sample to well crystalline KGW powder formation was confirmed with powder XRD analysis. Powders calcined at 600 °C show the appearance of monoclinic phase of KGW. Crystalline peaks without intermediate compound peaks were observed for samples calcined at 700 °C. Gel degradation and formation of double tungstate was clearly seen in the FT-IR spectrum. FT-IR spectrum of synthesized gel also, confirms the citrate formation and etherification. FESEM analysis reveals the size and morphology of the powder. Double tungstate formation from the amorphous powder was analyzed using laser Raman spectral analysis. The emission property of the europium doped KGW was analyzed using fluorescence. Changes in emission intensity was observed for samples calcined at different temperatures.

  16. [Isolation of inosine-5'-monophosphate from fish muscles].

    PubMed

    Tugaĭ, V A; Akulin, V N; Epshteĭn, L M

    1987-01-01

    Conditions for transformation of tissue adenosine-5'-monophosphate (AMP) into inosine-5'-monophosphate (IMP) with the aid of endogenic AMP-aminohydrolase are developed resting on the studied properties of AMP-aminohydrolase (EC 3.5.4.6) from saltwater fish muscles (one of the enzymes participating in the nucleotide metabolism). Sorption of the nucleotide is performed on the activated charcoals A gamma-3 A gamma-5 which eluate IMP from acid solutions. It reduces the process of isolation, permits application of the acid wash solutions to remove salts; the alkaline ethyl alcohol-aid elution at the subsequent stages accelerates the process of nucleotide concentration by means of vacuum evaporation. The suggested approaches allow developing a simple method of IMP production from fish tissues which diminishes the cost of preparation.

  17. RECIPIENT PRETRANSPLANT INOSINE MONOPHOSPHATE DEHYDROGENASE ACTIVITY IN NONMYELOABLATIVE HCT

    PubMed Central

    Bemer, Meagan J.; Risler, Linda J.; Phillips, Brian R.; Wang, Joanne; Storer, Barry E.; Sandmaier, Brenda M.; Duan, Haichuan; Raccor, Brianne S.; Boeckh, Michael J.; McCune, Jeannine S.

    2014-01-01

    Mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), inhibits inosine monophosphate dehydrogenase (IMPDH) activity. IMPDH is the rate-limiting enzyme involved in de novo synthesis of guanosine nucleotides and catalyzes the oxidation of inosine 5’- monophosphate (IMP) to xanthosine 5’-monophosphate (XMP). We developed a highly sensitive liquid chromatography–mass spectrometry method to quantitate XMP concentrations in peripheral blood mononuclear cells (PMNC) isolated from the recipient pretransplant and used this method to determine IMPDH activity in 86 nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) patients. The incubation procedure and analytical method yielded acceptable within-sample and within-individual variability. Considerable between-individual variability was observed (12.2-fold). Low recipient pretransplant IMPDH activity was associated with increased day +28 donor T-cell chimerism, more acute graft-versus-host disease (GVHD), lower neutrophil nadirs, and more cytomegalovirus reactivation, but not with chronic GVHD, relapse, non-relapse mortality, or overall mortality. We conclude that quantitation of the recipient’s pretransplant IMPDH activity in PMNC lysate could provide a useful biomarker to evaluate a recipient’s sensitivity to MMF, but confirmatory studies are needed. Further trials should be conducted to confirm our findings and to optimize postgrafting immunosuppression in nonmyeloablative HCT recipients. PMID:24923537

  18. Structure-based design, synthesis, evaluation, and crystal structures of transition state analogue inhibitors of inosine monophosphate cyclohydrolase.

    PubMed

    Xu, Lan; Chong, Youhoon; Hwang, Inkyu; D'Onofrio, Anthony; Amore, Kristen; Beardsley, G Peter; Li, Chenglong; Olson, Arthur J; Boger, Dale L; Wilson, Ian A

    2007-04-27

    The inosine monophosphate cyclohydrolase (IMPCH) component (residues 1-199) of the bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase (AICAR Tfase, residues 200-593)/IMPCH (ATIC) catalyzes the final step in the de novo purine biosynthesis pathway that produces IMP. As a potential target for antineoplastic intervention, we designed IMPCH inhibitors, 1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one 2,2-dioxide (heterocycle, 1), the corresponding nucleoside (2), and the nucleoside monophosphate (nucleotide) (3), as mimics of the tetrahedral intermediate in the cyclization reaction. All compounds are competitive inhibitors against IMPCH (K(i) values = 0.13-0.23 microm) with the simple heterocycle 1 exhibiting the most potent inhibition (K(i) = 0.13 microm). Crystal structures of bifunctional ATIC in complex with nucleoside 2 and nucleotide 3 revealed IMPCH binding modes similar to that of the IMPCH feedback inhibitor, xanthosine 5'-monophosphate. Surprisingly, the simpler heterocycle 1 had a completely different IMPCH binding mode and was relocated to the phosphate binding pocket that was identified from previous xanthosine 5'-monophosphate structures. The aromatic imidazole ring interacts with a helix dipole, similar to the interaction with the phosphate moiety of 3. The crystal structures not only revealed the mechanism of inhibition of these compounds, but they now serve as a platform for future inhibitor improvements. Importantly, the nucleoside-complexed structure supports the notion that inhibitors lacking a negatively charged phosphate can still inhibit IMPCH activity with comparable potency to phosphate-containing inhibitors. Provocatively, the nucleotide inhibitor 3 also binds to the AICAR Tfase domain of ATIC, which now provides a lead compound for the design of inhibitors that simultaneously target both active sites of this bifunctional enzyme.

  19. Structure-Based Design, Synthesis, Evaluation And Crystal Structures of Transition State Analogue Inhibitors of Inosine Monophosphate Cyclohydrolase

    SciTech Connect

    Xu, L.; Chong, Y.; Hwang, I.; D'Onofrio, A.; Amore, K.; Beardsley, G.P.; Li, C.; Olson, A.J.; Boger, D.L.; Wilson, I.A.; /Skaggs Inst. Chem. Biol. /Scripps Res. Inst. /Yale U.

    2007-07-13

    The inosine monophosphate cyclohydrolase (IMPCH) component (residues 1-199) of the bifunctional enzyme aminoimidazole-4-carboxamide ribonucleotide transformylase (AICAR Tfase, residues 200-593)/IMPCH (ATIC) catalyzes the final step in the de novo purine biosynthesis pathway that produces IMP. As a potential target for antineoplastic intervention, we designed IMPCH inhibitors, 1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one 2,2-dioxide (heterocycle, 1), the corresponding nucleoside (2), and the nucleoside monophosphate (nucleotide) (3), as mimics of the tetrahedral intermediate in the cyclization reaction. All compounds are competitive inhibitors against IMPCH (K(i) values = 0.13-0.23 microm) with the simple heterocycle 1 exhibiting the most potent inhibition (K(i) = 0.13 microm). Crystal structures of bifunctional ATIC in complex with nucleoside 2 and nucleotide 3 revealed IMPCH binding modes similar to that of the IMPCH feedback inhibitor, xanthosine 5'-monophosphate. Surprisingly, the simpler heterocycle 1 had a completely different IMPCH binding mode and was relocated to the phosphate binding pocket that was identified from previous xanthosine 5'-monophosphate structures. The aromatic imidazole ring interacts with a helix dipole, similar to the interaction with the phosphate moiety of 3. The crystal structures not only revealed the mechanism of inhibition of these compounds, but they now serve as a platform for future inhibitor improvements. Importantly, the nucleoside-complexed structure supports the notion that inhibitors lacking a negatively charged phosphate can still inhibit IMPCH activity with comparable potency to phosphate-containing inhibitors. Provocatively, the nucleotide inhibitor 3 also binds to the AICAR Tfase domain of ATIC, which now provides a lead compound for the design of inhibitors that simultaneously target both active sites of this bifunctional enzyme.

  20. Structural Basis for the Specificity of Human NUDT16 and Its Regulation by Inosine Monophosphate

    PubMed Central

    Trésaugues, Lionel; Lundbäck, Thomas; Welin, Martin; Flodin, Susanne; Nyman, Tomas; Silvander, Camilla; Gräslund, Susanne; Nordlund, Pär

    2015-01-01

    Human NUDT16 is a member of the NUDIX hydrolase superfamily. After having been initially described as an mRNA decapping enzyme, recent studies conferred it a role as an “housecleaning” enzyme specialized in the removal of hazardous (deoxy)inosine diphosphate from the nucleotide pool. Here we present the crystal structure of human NUDT16 both in its apo-form and in complex with its product inosine monophosphate (IMP). NUDT16 appears as a dimer whose formation generates a positively charged trench to accommodate substrate-binding. Complementation of the structural data with detailed enzymatic and biophysical studies revealed the determinants of substrate recognition and particularly the importance of the substituents in position 2 and 6 on the purine ring. The affinity for the IMP product, harboring a carbonyl in position 6 on the base, compared to purine monophosphates lacking a H-bond acceptor in this position, implies a catalytic cycle whose rate is primarily regulated by the product-release step. Finally, we have also characterized a phenomenon of inhibition by the product of the reaction, IMP, which might exclude non-deleterious nucleotides from NUDT16-mediated hydrolysis regardless of their cellular concentration. Taken together, this study details structural and regulatory mechanisms explaining how substrates are selected for hydrolysis by human NUDT16. PMID:26121039

  1. A Novel Non-Lens βγ−Crystallin and Trefoil Factor Complex from Amphibian Skin and Its Functional Implications

    PubMed Central

    Zhang, Yun; Lee, Wen-Hui; Qian, Jin-Qiao; Lai, Ren; Jin, Yang

    2008-01-01

    Background In vertebrates, non-lens βγ-crystallins are widely expressed in various tissues, but their functions are unknown. The molecular mechanisms of trefoil factors, initiators of mucosal healing and being greatly involved in tumorigenesis, have remained elusive. Principal Findings A naturally existing 72-kDa complex of non-lens βγ-crystallin (α-subunit) and trefoil factor (β-subunit), named βγ-CAT, was identified from frog Bombina maxima skin secretions. Its α-subunit and β-subunit (containing three trefoil factor domains), with a non-covalently linked form of αβ2, show significant sequence homology to ep37 proteins, a group of non-lens βγ-crystallins identified in newt Cynops pyrrhogaster and mammalian trefoil factors, respectively. βγ-CAT showed potent hemolytic activity on mammalian erythrocytes. The specific antiserum against each subunit was able to neutralize its hemolytic activity, indicating that the two subunits are functionally associated. βγ-CAT formed membrane pores with a functional diameter about 2.0 nm, leading to K+ efflux and colloid-osmotic hemolysis. High molecular weight SDS-stable oligomers (>240-kDa) were detected by antibodies against the α-subunit with Western blotting. Furthermore, βγ-CAT showed multiple cellular effects on human umbilical vein endothelial cells. Low dosages of βγ-CAT (25–50 pM) were able to stimulate cell migration and wound healing. At high concentrations, it induced cell detachment (EC50 10 nM) and apoptosis. βγ-CAT was rapidly endocytosed via intracellular vacuole formation. Under confocal microscope, some of the vacuoles were translocated to nucleus and partially fused with nuclear membrane. Bafilomycin A1 (a specific inhibitor of the vacuolar-type ATPase) and nocodazole (an agent of microtuble depolymerizing), while inhibited βγ-CAT induced vacuole formation, significantly inhibited βγ-CAT induced cell detachment, suggesting that βγ-CAT endocytosis is important for its activities

  2. Nucleic acid molecules encoding isopentenyl monophosphate kinase, and methods of use

    DOEpatents

    Croteau, Rodney B.; Lange, Bernd M.

    2001-01-01

    A cDNA encoding isopentenyl monophosphate kinase (IPK) from peppermint (Mentha x piperita) has been isolated and sequenced, and the corresponding amino acid sequence has been determined. Accordingly, an isolated DNA sequence (SEQ ID NO:1) is provided which codes for the expression of isopentenyl monophosphate kinase (SEQ ID NO:2), from peppermint (Mentha x piperita). In other aspects, replicable recombinant cloning vehicles are provided which code for isopentenyl monophosphate kinase, or for a base sequence sufficiently complementary to at least a portion of isopentenyl monophosphate kinase DNA or RNA to enable hybridization therewith. In yet other aspects, modified host cells are provided that have been transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence encoding isopentenyl monophosphate kinase. Thus, systems and methods are provided for the recombinant expression of the aforementioned recombinant isopentenyl monophosphate kinase that may be used to facilitate its production, isolation and purification in significant amounts. Recombinant isopentenyl monophosphate kinase may be used to obtain expression or enhanced expression of isopentenyl monophosphate kinase in plants in order to enhance the production of isopentenyl monophosphate kinase, or isoprenoids derived therefrom, or may be otherwise employed for the regulation or expression of isopentenyl monophosphate kinase, or the production of its products.

  3. Enhancing the performance of multi-crystalline silicon photovoltaic module by encapsulating high efficient Eu3+ complex into its pre-existing EVA layer

    NASA Astrophysics Data System (ADS)

    Wang, Tongxin; Yu, Bo; Hu, Zhijia; Wang, Xin; Zou, Gang; Zhang, Qijin

    2013-03-01

    Luminescent down shifting (LDS) technique is one effective way to improve the poor response of multi-crystalline silicon (mc-Si) photovoltaic (PV) modules at short wavelength less than 400 nm. Eu3+ complexes are effective LDS species for PV modules due to their large stokes' shift and high luminescent quantum efficiency (LQE). Although Eu3+ complexes have been utilized in PV modules as LDS species widely, they have not been encapsulated into the pre-existing poly-ethylene vinyl acetate (EVA) layer of modules between glass and solar cell by now. The aim of our work is to enhance the performance of mc-Si PV modules by encapsulating high efficient Eu3+ complexes into their pre-existing EVA layers which would not modify the well-established manufacturing process for PV modules. In this work, two Eu3+ complexes with different absorption spectrum were encapsulated into the commercial EVA layer by soaking method for the first time and used in the encapsulation of mc-Si PV modules. Hereinto, Eu(TTA)3(TPPO)2 (TTA = 2-thenoyltrifluoroacetonate, TPPO = triphenylphosphine oxide) (EuTT) with absorption spectrum less than 400 nm and high LQE (0.73) improves the external quantum efficiency of mc-Si PV module from 0.05 to 0.20, which produces a 0.42% increases in its power conversion efficiency. In addition, it is found that the enhancement brought by Eu(TTA)3(TPPO)2 can reduce cost of power generated by mc-Si devices from US1/Wp to US0.98/Wp according to the calculation. Therefore, Eu(TTA)3(TPPO)2 as LDS species with high LQE and low cost is promising for enhancing the performance of mc-Si PV modules in practical application.

  4. Tunable molecular distortion in a nickel complex coupled to a reversible phase transition in the crystalline state

    SciTech Connect

    Falvello, L.R.; Hitchman, M.A.; Palacio, F.; Pascual, I.; Schultz, A.J.; Stratemeier, H.; Tomas, M.; Urriolabeitia, E.P.; Young, D.M.

    1999-03-31

    The six-coordinate coordination complex trans-[Ni(cyan-{kappa}N){sub 2}(NH{sub 3}){sub 4}] has been characterized in the solid state by X-ray and neutron diffraction at temperatures ranging from 11 to 298 K, by electronic spectroscopy over the temperature range 14--297 K, and by magnetic susceptibility measurements from 1.8 to 300 K. At room temperature the observed space group if Fmmm, although there is reason to believe that at a finer level of distinction it is really Cmcm approximating Fmmm. The nickel center lies on a site of apparent point symmetry mmm. At lower temperatures, the space group is unambiguously Cmcm without appreciable change in the unit cell parameters, and the molecule lies at a site of m2m symmetry. The shape of the molecule changes smoothly with temperature variations from room temperature down to about 140 K, in a behavior characteristic of second-order phase transformations. The molecular shape varies, but by lesser amounts, below 140 K. Possible causes of this phenomenon are discussed. The increase in intensity on cooling of some of the bands observed in the polarized crystal spectrum of the complex is consistent with the change in the molecular structure. Bonding parameters derived from the transition energies indicate that the cyanurate produces a very weak ligand field, which is consistent with the long metal-ligand bond to this ligand. The magnetic properties of the solid display Curie-Weiss behavior through the temperature range of the most pronounced molecular shape changes, but antiferromagnetic interactions become significant below 50 K, with antiferromagnetic ordering at 2.61 K. The propagation pathways for the magnetic interactions are inferred.

  5. Crystal structure of the complex of carboxypeptidase A with a strongly bound phosphonate in a new crystalline form: Comparison with structures of other complexes

    SciTech Connect

    Kim, Hidong; Lipscomb, W.N. )

    1990-06-12

    O-(((1R)-((N-(Phenylmethoxycarbonyl)-L-alanyl)amino)ethyl)hydroxyphosphinyl)-L-3-phenyllacetate (ZZA{sup P}(O)F), an analogue of (benzyloxycarbonyl)-Ala-Ala-Phe or (benzyloxycarbonyl)-Ala-Ala-phenyllactate, binds to carboxypeptidase A with great affinity. Similar phosphonates have been shown to be transition-state analogues of the CPA-catalyzed hydrolysis. In the present study, the structure of the complex of phosphonate with carboxypeptidase A has been determined by X-ray crystallography to a resolution of 2.0 {angstrom}. The structure of the complex was solved by molecular replacement. Refinement of the structure against 20,776 unique reflections between 10.0 and 2.0 {angstrom} yields a crystallographic residual of 0.193, including 140 water molecules. The two phosphinyl oxygens of the inhibitor bind to the active-site zinc at 2.2 {angstrom} on the electrophilic (Arg-127) side and 3.1 {angstrom} on the nucleophilic (Glu-270) side. Various features of the binding mode of this phosphonate inhibitor are consistent with the hypothesis that carboxypeptidase A catalyzed hydrolysis proceeds through a general-base mechanism in which the carbonyl carbon of the substrate is attached by Zn-hydroxyl (or Zn-water). This complex structure is compared with previous structures of carboxypeptidase A, including the complexes with the potato inhibitor, a hydrated keto methylene substrate analogue, and a phosphonamidate inhibitor. Comparisons are also made with the complexes of thermolysin with some phosphonamidate inhibitors.

  6. The anisotropy1 D604N mutation in the Arabidopsis cellulose synthase1 catalytic domain reduces cell wall crystallinity and the velocity of cellulose synthase complexes.

    PubMed

    Fujita, Miki; Himmelspach, Regina; Ward, Juliet; Whittington, Angela; Hasenbein, Nortrud; Liu, Christine; Truong, Thy T; Galway, Moira E; Mansfield, Shawn D; Hocart, Charles H; Wasteneys, Geoffrey O

    2013-05-01

    Multiple cellulose synthase (CesA) subunits assemble into plasma membrane complexes responsible for cellulose production. In the Arabidopsis (Arabidopsis thaliana) model system, we identified a novel D604N missense mutation, designated anisotropy1 (any1), in the essential primary cell wall CesA1. Most previously identified CesA1 mutants show severe constitutive or conditional phenotypes such as embryo lethality or arrest of cellulose production but any1 plants are viable and produce seeds, thus permitting the study of CesA1 function. The dwarf mutants have reduced anisotropic growth of roots, aerial organs, and trichomes. Interestingly, cellulose microfibrils were disordered only in the epidermal cells of the any1 inflorescence stem, whereas they were transverse to the growth axis in other tissues of the stem and in all elongated cell types of roots and dark-grown hypocotyls. Overall cellulose content was not altered but both cell wall crystallinity and the velocity of cellulose synthase complexes were reduced in any1. We crossed any1 with the temperature-sensitive radial swelling1-1 (rsw1-1) CesA1 mutant and observed partial complementation of the any1 phenotype in the transheterozygotes at rsw1-1's permissive temperature (21°C) and full complementation by any1 of the conditional rsw1-1 root swelling phenotype at the restrictive temperature (29°C). In rsw1-1 homozygotes at restrictive temperature, a striking dissociation of cellulose synthase complexes from the plasma membrane was accompanied by greatly diminished motility of intracellular cellulose synthase-containing compartments. Neither phenomenon was observed in the any1 rsw1-1 transheterozygotes, suggesting that the proteins encoded by the any1 allele replace those encoded by rsw1-1 at restrictive temperature. PMID:23532584

  7. Brittle structures and their role in controlling porosity and permeability in a complex Precambrian crystalline-rock aquifer system in the Colorado Rocky Mountain front range

    USGS Publications Warehouse

    Caine, J.S.; Tomusiak, S.R.A.

    2003-01-01

    Expansion of the Denver metropolitan area has resulted in substantial residential development in the foothills of the Rocky Mountain Front Range. This type of sub-urban growth, characteristic of much of the semiarid intermountain west, often relies on groundwater from individual domestic wells and is exemplified in the Turkey Creek watershed. The watershed is underlain by complexly deformed and fractured crystalline bedrock in which groundwater resources are poorly understood, and concerns regarding groundwater mining and degradation have arisen. As part of a pilot project to establish quantitative bounds on the groundwater resource, an outcrop-based geologic characterization and numerical modeling study of the brittle structures and their controls on the flow system was initiated. Existing data suggest that ground-water storage, flow, and contaminant transport are primarily controlled by a heterogeneous array of fracture networks. Inspections of well-permit data and field observations led to a conceptual model in which three dominant lithologic groups underlying sparse surface deposits form the aquifer system-metamorphic rocks, a complex array of granitic intrusive rocks, and major brittle fault zones. Pervasive but variable jointing of each lithologic group forms the "background" permeability structure and is an important component of the bulk storage capacity. This "background" is cut by brittle fault zones of varying structural styles and by pegmatite dikes, both with much higher fracture intensities relative to "background" that likely make them spatially complex conduits. Probabilistic, discrete-fracture-network and finite-element modeling was used to estimate porosity and permeability at the outcrop scale using fracture network data collected in the field. The models were conditioned to limited aquifer test and borehole geophysical data and give insight into the relative hydraulic properties between locations and geologic controls on storage and flow

  8. Simulation analysis of formycin 5'-monophosphate analog substrates in the ricin A-chain active site.

    PubMed

    Olson, M A; Scovill, J P; Hack, D C

    1995-06-01

    Ricin is an RNA N-glycosidase that hydrolyzes a single adenine base from a conserved loop of 28S ribosomal RNA, thus inactivating protein synthesis. Molecular-dynamics simulation methods are used to analyze the structural interactions and thermodynamics that govern the binding of formycin 5'-monophosphate (FMP) and several of its analogs to the active site of ricin A-chain. Simulations are carried out initiated from the X-ray crystal structure of the ricin-FMP complex with the ligand modeled as a dianion, monoanion and zwitterion. Relative changes in binding free energies are estimated for FMP analogs constructed from amino substitutions at the 2- and 2'-positions, and from hydroxyl substitution at the 2'-position.

  9. Study of phase transformation of guanosine 5'-monophosphate in drowning-out crystallization.

    PubMed

    Kang, Jeongki; Tuan, Nguyen Anh; Kim, Jong-Min; Chang, Sang-Mok; Kim, Woo-Sik

    2010-01-01

    The present study used a mechanistic approach to control the phase transformation of guanosine 5'-monophosphate (GMP) via the operating conditions of agitation and feed concentration during drowning-out crystallization. First, Fourier transform infrared and UV/vis spectrophotometry were successfully applied to monitor the mass fraction of GMP polymorphs (amorphous and hydrate crystalline GMPs) and GMP supersaturation, respectively, during the crystallization. The phase transformation of amorphous GMP into hydrate crystals was significantly influenced by the agitation, which promoted the mass transfer of GMP dissolution and growth. Therefore, the phase transformation was quickly finished when increasing the agitation speed. However, a high agitation caused breakage of the hydrate crystals, resulting in a reduced crystal size with a bimodal distribution. The phase transformation was also influenced by the GMP feed concentration, as the crystal growth was promoted and the crystal size increased when increasing the feed concentration up to 61 g/l. However, a further increase in the feed concentration caused secondary nucleation due to the induction of a high supersaturation level during the phase transformation, leading to a small crystal size with a bimodal distribution. In addition, the rectangular-shaped hydrate GMP crystals exhibited a higher growth rate in the b direction rather than the a direction. Therefore, the crystal morphology shifted from a long rectangle to a square when increasing the feed concentration. PMID:19031052

  10. A continuous spectrophotometric assay for monitoring adenosine 5'-monophosphate production.

    PubMed

    First, Eric A

    2015-08-15

    A number of biologically important enzymes release adenosine 5'-monophosphate (AMP) as a product, including aminoacyl-tRNA synthetases, cyclic AMP (cAMP) phosphodiesterases, ubiquitin and ubiquitin-like ligases, DNA ligases, coenzyme A (CoA) ligases, polyA deadenylases, and ribonucleases. In contrast to the abundance of assays available for monitoring the conversion of adenosine 5'-triphosphate (ATP) to ADP, there are relatively few assays for monitoring the conversion of ATP (or cAMP) to AMP. In this article, we describe a homogeneous assay that continuously monitors the production of AMP. Specifically, we have coupled the conversion of AMP to inosine 5'-monophosphate (IMP) (by AMP deaminase) to the oxidation of IMP (by IMP dehydrogenase). This results in the reduction of oxidized nicotine adenine dinucleotide (NAD(+)) to reduced nicotine adenine dinucleotide (NADH), allowing AMP formation to be monitored by the change in the absorbance at 340 nm. Changes in AMP concentrations of 5 μM or more can be reliably detected. The ease of use and relatively low expense make the AMP assay suitable for both high-throughput screening and kinetic analyses. PMID:25957126

  11. Vascular relaxation and cyclic guanosine monophosphate in hypertension

    SciTech Connect

    Otsuka, Y.; DiPiero, A.; Lockette, W.

    1986-03-01

    Isolated aortae from hypertensive rats have a decreased relaxation response to acetylcholine (Ach), A23187, and nitroprusside (SNP). Since cyclic guanosine monophosphate (cGMP) has been shown to increase in response to these vasodilators, the authors measured cGMP in response to these agents in isolated aortae from normotensive rats and DOCA, 1K1C, and coarctation induced hypertension. cGMP was measured by radioimmunoassay in vessels after exposure to phenylephrine followed by either Ach, A23187, or SNP. The aortae from the hypertensive rats had decreased basal levels of cGMP and attenuated increases in cGMP in response to Ach and A23187. Rises in cGMP in response to SNP were also attenuated in aortae from the hypertensive rats, even at concentrations which induced similar relaxation in normotensive and hypertensive blood vessels. The data suggest that changes in cGMP do not necessarily reflect changes in endothelium independent vascular relaxation in hypertension.

  12. Adenosine Monophosphate-Based Detection of Bacterial Spores

    NASA Technical Reports Server (NTRS)

    Kern, Roger G.; Chen, Fei; Venkateswaran, Kasthuri; Hattori, Nori; Suzuki, Shigeya

    2009-01-01

    A method of rapid detection of bacterial spores is based on the discovery that a heat shock consisting of exposure to a temperature of 100 C for 10 minutes causes the complete release of adenosine monophosphate (AMP) from the spores. This method could be an alternative to the method described in the immediately preceding article. Unlike that method and related prior methods, the present method does not involve germination and cultivation; this feature is an important advantage because in cases in which the spores are those of pathogens, delays involved in germination and cultivation could increase risks of infection. Also, in comparison with other prior methods that do not involve germination, the present method affords greater sensitivity. At present, the method is embodied in a laboratory procedure, though it would be desirable to implement the method by means of a miniaturized apparatus in order to make it convenient and economical enough to encourage widespread use.

  13. Paleoposition of the northern margin of Armorica in Late Devonian times: Paleomagnetic and rock magnetic results from the Frankenstein Intrusive Complex (Mid-German Crystalline Rise)

    NASA Astrophysics Data System (ADS)

    Zwing, Alexander; Bachtadse, Valerian

    2000-09-01

    A detailed rockmagnetic and paleomagnetic study of the Frankenstein Intrusive Complex (FIC, 363±7 Ma in age), southwestern Germany, has been carried out in order to test whether the paleomagnetic declinations within the internal parts of the European Variscides follow a common trend controlled by the structural grain of the orogen or whether the distribution of declinations follows a random pattern. In addition, new paleomagnetic data will contribute to further refine the drift history of the Armorican Terrane Assemblage during late Paleozoic times. The unmetamorphosed Frankenstein Igneous Complex forms part of the Mid-German Crystalline Rise within the Armorican Terrane Assemblage, amalgamated to Avalonia and Baltica during the Variscan orogeny, Stepwise thermal and alternating field (AF) demagnetization experiments identify four components (A, B, Cn, and Cr) of magnetization. Component A is a recent viscous overprint that parallels the present-day geomagnetic field. The high unblocking temperatures of A in some samples can be explained by the presence of multidomain magnetite. Component B is carried by hematite and is considered to be a late Carboniferous remagnetization. Components Cr and Cn, found in 110 samples from 20 sites, are antiparallel and pass a class C reversal test. Their primary origin is further supported by a contact test. Cr and Cn have maximum unblocking temperatures of up to 580°C and occasionally above over 600°C, indicating magnetite and hematite to carry the characteristic remanent magnetization. Ore microscopy revealed that primary hematite lamellae in ilmenite carry Cr and Cn and that a secondary generation of hematite is the carrier of B. The overall site mean direction of Cr and Cn (20 sites) based on endpoints and remagnetization circle analysis of 198°/40° (declination/inclination) with a 95% confidence limit (α95) of 4.9° and a precision parameter (k) of 45.0 defines a paleopole at 15°S, 9°W. When comparing to the apparent

  14. Rate and Equilibrium Constants for an Enzyme Conformational Change during Catalysis by Orotidine 5′-Monophosphate Decarboxylase

    PubMed Central

    2016-01-01

    The caged complex between orotidine 5′-monophosphate decarboxylase (ScOMPDC) and 5-fluoroorotidine 5′-monophosphate (FOMP) undergoes decarboxylation ∼300 times faster than the caged complex between ScOMPDC and the physiological substrate, orotidine 5′-monophosphate (OMP). Consequently, the enzyme conformational changes required to lock FOMP at a protein cage and release product 5-fluorouridine 5′-monophosphate (FUMP) are kinetically significant steps. The caged form of ScOMPDC is stabilized by interactions between the side chains from Gln215, Tyr217, and Arg235 and the substrate phosphodianion. The control of these interactions over the barrier to the binding of FOMP and the release of FUMP was probed by determining the effect of all combinations of single, double, and triple Q215A, Y217F, and R235A mutations on kcat/Km and kcat for turnover of FOMP by wild-type ScOMPDC; its values are limited by the rates of substrate binding and product release, respectively. The Q215A and Y217F mutations each result in an increase in kcat and a decrease in kcat/Km, due to a weakening of the protein–phosphodianion interactions that favor fast product release and slow substrate binding. The Q215A/R235A mutation causes a large decrease in the kinetic parameters for ScOMPDC-catalyzed decarboxylation of OMP, which are limited by the rate of the decarboxylation step, but much smaller decreases in the kinetic parameters for ScOMPDC-catalyzed decarboxylation of FOMP, which are limited by the rate of enzyme conformational changes. By contrast, the Y217A mutation results in large decreases in kcat/Km for ScOMPDC-catalyzed decarboxylation of both OMP and FOMP, because of the comparable effects of this mutation on rate-determining decarboxylation of enzyme-bound OMP and on the rate-determining enzyme conformational change for decarboxylation of FOMP. We propose that kcat = 8.2 s–1 for decarboxylation of FOMP by the Y217A mutant is equal to the rate constant for cage formation

  15. Activation of R235A mutant orotidine 5'-monophosphate decarboxylase by the guanidinium cation: effective molarity of the cationic side chain of Arg-235.

    PubMed

    Barnett, Shonoi A; Amyes, Tina L; Wood, B McKay; Gerlt, John A; Richard, John P

    2010-02-01

    The R235A mutation at yeast orotidine 5'-monophosphate decarboxylase (OMPDC) results in a 1300-fold increase in K(m) and a 14-fold decrease in k(cat) for decarboxylation of orotidine 5'-monophosphate, corresponding to a 5.8 kcal/mol destabilization of the transition state. There is strong activation of this mutant enzyme by added guanidinium cation (Gua(+)): 1 M Gua(+) stabilizes the transition state by ca. 3 kcal/mol. This stabilization is due to the binding of Gua(+) to the binary E(mut) x OMP complex, with a K(d) of 50 mM, to form the 9-fold more reactive ternary E(mut) x OMP x Gua(+) complex. The "effective molarity" of the cationic side chain of Arg-235 at the wild-type enzyme is calculated to be 160 M.

  16. A first find of retrogressed eclogites in the Odenwald Crystalline Complex, Mid-German Crystalline Rise, Germany: evidence for a so far unrecognised high-pressure metamorphism in the Central Variscides

    NASA Astrophysics Data System (ADS)

    Will, Thomas M.; Schmädicke, Esther

    2001-11-01

    Metabasic rocks were recently found in the Böllsteiner Odenwald, being part of the Variscan Mid-German Crystalline Rise (MGCR), that give evidence of a so far unrecognised eclogite-facies metamorphic event and testify, for the first time, to high-pressure metamorphism in the MGCR, the assumed suture zone of the European Variscides. Eclogite-facies metamorphism is indicated by both widespread clinopyroxene-plagioclase symplectites—interpreted as breakdown products of omphacite—and the composition of symplectitic clinopyroxene with measured jadeite contents of up to 27 mol%, extending into the omphacite field. Reintegration of numerous clinopyroxene-plagioclase symplectites implies minimum jadeite contents of the former omphacite of at least 38 mol%. For the eclogite stage, the four-phase assemblage omphacite-garnet-quartz-rutile can be reconstructed. A post-eclogitic overprint led to the formation of symplectitic intergrowths of clinopyroxene and plagioclase, amphibole-plagioclase coronas around garnet and domains with recrystallised amphibole and plagioclase. Preliminary P- T estimates for the eclogite-facies metamorphism indicate minimum pressures of some 16-17 kbar and temperatures of approximately 700±50 °C. Geothermobarometry for the subsequent symplectitic breakdown of omphacite yields some 14 kbar and 700 °C. P- T estimates on retrograde amphibolite-facies domains and on prograde mineral assemblages preserved in garnet cores point to a clockwise P- T path experienced by these rocks. The eclogites formed from a tholeiitic protolith, that may have been genetically linked to a continental extension zone or a young oceanic ridge or back-arc environment.

  17. Nitric oxide and cyclic guanosine monophosphate signaling in the eye.

    PubMed

    Murad, Ferid

    2008-06-01

    This brief review describes the components and pathways utilized in nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) signaling. Since the discovery of the effects of NO and cGMP on smooth muscle relaxation about 30 years ago, the field has expanded in many directions such that many, but not all, biochemical and biological effects seem to be regulated by these unique signaling molecules. While many of the effects of NO are due to activation of soluble guanylyl cyclase (sGC) that can be considered the receptor for NO, cGMP, in turn, can activate a cGMP-dependent protein kinase (PKG) to phosphorylate an array of proteins. Some of the effects of cGMP can be independent of PKG and are due to effects on ion channels or cyclic nucleotide phosphodiesterases. Also, some of the effects of NO can be independent of sGC activation. The isoenzymes and macromolecules that participate in these signaling pathways can serve as molecular targets to identify compounds that increase or decrease their activation and thus serve as chemical leads for discovering novel drugs for a variety of diseases. Some examples are given. However, with about 90,000 publications in the field since our first reports in 1977, this brief review can only give the readers a sample of the excitement and opportunities we have found in this cell signaling system.

  18. [Identification of thiamine monophosphate hydrolyzing enzymes in chicken liver].

    PubMed

    Kolos, I K; Makarchikov, A F

    2014-01-01

    In animals, thiamine monophosphate (TMP) is an intermediate on the path of thiamine diphosphate, the coenzyme form of vitamin B1, degradation. The enzymes involved in TMP metabolism in animal tissues are not identified hitherto. The aim of this work was to study TMP hydrolysis in chicken liver. Two phosphatases have been found to contribute to TMP hydrolysis in liver homogenate. The first one, possessing a maximal activity at pH 6.0, is soluble, whereas the second one represents a membrane-bound enzyme with a pH optimum of 9.0. Membrane-bound TMPase activity was enhanced 1.7-fold by 5 mM Mg2+ ions and strongly inhibited by levamisole in uncompetitive manner with K1 of 53 μM, indicating the involvement of alkaline phosphatase. An apparent Km of alkaline phosphatase for TMP was calculated from the Hanes plot to be 0.6 mM. The soluble TMPase has an apparent Km of 0.7 mM; this enzyme is Mg2+ independent and insensitive to levamisole. As estimated by gel filtration on a Toyopearl HW-55 column, the soluble enzyme has a molecular mass of 17.8 kDa, TMPase activity being eluted simultaneously with peaks of flavinmononucleotide and p-nitrophenyl phosphatase activity. Thus, TMP appears to be a physiological substrate for a low-molecular weight acid phosphatase, also known as low-molecular-weight protein phosphotyrosine phosphatase.

  19. Development of Potent Adenosine Monophosphate Activated Protein Kinase (AMPK) Activators.

    PubMed

    Dokla, Eman M E; Fang, Chun-Sheng; Lai, Po-Ting; Kulp, Samuel K; Serya, Rabah A T; Ismail, Nasser S M; Abouzid, Khaled A M; Chen, Ching-Shih

    2015-11-01

    Previously, we reported the identification of a thiazolidinedione-based adenosine monophosphate activated protein kinase (AMPK) activator, compound 1 (N-[4-({3-[(1-methylcyclohexyl)methyl]-2,4-dioxothiazolidin-5-ylidene}methyl)phenyl]-4-nitro-3-(trifluoromethyl)benzenesulfonamide), which provided a proof of concept to delineate the intricate role of AMPK in regulating oncogenic signaling pathways associated with cell proliferation and epithelial-mesenchymal transition (EMT) in cancer cells. In this study, we used 1 as a scaffold to conduct lead optimization, which generated a series of derivatives. Analysis of the antiproliferative and AMPK-activating activities of individual derivatives revealed a distinct structure-activity relationship and identified 59 (N-(3-nitrophenyl)-N'-{4-[(3-{[3,5-bis(trifluoromethyl)phenyl]methyl}-2,4-dioxothiazolidin-5-ylidene)methyl]phenyl}urea) as the optimal agent. Relative to 1, compound 59 exhibits multifold higher potency in upregulating AMPK phosphorylation in various cell lines irrespective of their liver kinase B1 (LKB1) functional status, accompanied by parallel changes in the phosphorylation/expression levels of p70S6K, Akt, Foxo3a, and EMT-associated markers. Consistent with its predicted activity against tumors with activated Akt status, orally administered 59 was efficacious in suppressing the growth of phosphatase and tensin homologue (PTEN)-null PC-3 xenograft tumors in nude mice. Together, these findings suggest that 59 has clinical value in therapeutic strategies for PTEN-negative cancer and warrants continued investigation in this regard.

  20. Phosphatidylinositol 3-monophosphate is involved in toxoplasma apicoplast biogenesis.

    PubMed

    Tawk, Lina; Dubremetz, Jean-François; Montcourrier, Philippe; Chicanne, Gaëtan; Merezegue, Fabrice; Richard, Véronique; Payrastre, Bernard; Meissner, Markus; Vial, Henri J; Roy, Christian; Wengelnik, Kai; Lebrun, Maryse

    2011-02-01

    Apicomplexan parasites cause devastating diseases including malaria and toxoplasmosis. They harbour a plastid-like, non-photosynthetic organelle of algal origin, the apicoplast, which fulfils critical functions for parasite survival. Because of its essential and original metabolic pathways, the apicoplast has become a target for the development of new anti-apicomplexan drugs. Here we show that the lipid phosphatidylinositol 3-monophosphate (PI3P) is involved in apicoplast biogenesis in Toxoplasma gondii. In yeast and mammalian cells, PI3P is concentrated on early endosomes and regulates trafficking of endosomal compartments. Imaging of PI3P in T. gondii showed that the lipid was associated with the apicoplast and apicoplast protein-shuttling vesicles. Interference with regular PI3P function by over-expression of a PI3P specific binding module in the parasite led to the accumulation of vesicles containing apicoplast peripheral membrane proteins around the apicoplast and, ultimately, to the loss of the organelle. Accordingly, inhibition of the PI3P-synthesising kinase interfered with apicoplast biogenesis. These findings point to an unexpected implication for this ubiquitous lipid and open new perspectives on how nuclear encoded proteins traffic to the apicoplast. This study also highlights the possibility of developing specific pharmacological inhibitors of the parasite PI3-kinase as novel anti-apicomplexan drugs. PMID:21379336

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

    PubMed

    Qiao, Yuanbiao; Jian, Fangfang; Bai, Qian

    2008-03-14

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

  2. Excretion of intracorporeal cadmium with S-benzoylthiamin monophosphate

    SciTech Connect

    Yamamoto, J.; Kaneda, Y.

    1995-05-01

    Examination was made of the excretion of intracorporeal methylmercury into body hair by the administration of thiamin tetrahydrofurfuryl disulfide (TTFD) which caused significant increase in mercury content in human mustache. The thiamin derivative, S-benzoylthiamin monophosphate (BTMP) failed to have such effect. The mechanism of mercury excretion is thus based on the side chain structure of TTFD, mercaptan. At the start of the 20th century in Japan, many multiparae were found to have itai-itai disease, the main symptom of which is general pain. The cause of this disease was considered cadmium deposition on the bone from sourced such as soil and river water which contaminated rice and cereals. The previous system for mercury was applied based on cadmium content variation in human mustache. Although TTFD worked well in the mercury excretion system, the usual dosage of TTFD administered orally did not cause significant increase in cadmium in the mustache. BTMP appeared to exert effect by generating thiol-type thiamin. Experiments in vitro should be conducted to demonstrate the chelating effects of thiol-type thiamin. It is quite important to find evidence for cadmium excretion from human body. 3 refs., 2 figs., 2 tabs.

  3. Development of Novel Adenosine Monophosphate-Activated Protein Kinase Activators

    PubMed Central

    Guh, Jih-Hwa; Chang, Wei-Ling; Yang, Jian; Lee, Su-Lin; Wei, Shuo; Wang, Dasheng; Kulp, Samuel K.; Chen, Ching-Shih

    2010-01-01

    In light of the unique ability of thiazolidinediones to mediate peroxisome proliferator-activated receptor (PPAR)γ-independent activation of adenosine monophosphate-activated protein kinase (AMPK) and suppression of interleukin (IL)-6 production, we conducted a screening of an in-house, thiazolidinedione-based focused compound library to identify novel agents with these dual pharmacological activities. Cell-based assays pertinent to the activation status of AMPK and mammalian homolog of target of rapamycin (i.e., phosphorylation of AMPK and p70 ribosomal protein S6 kinase, respectively), and IL-6/IL-6 receptor signaling (i.e., IL-6 production and signal transducer and activator of transcription 3 phosphorylation, respectively) in lipopolysaccharide (LPS)-stimulated THP-1 human macrophages were used to screen this compound library, which led to the identification of compound 53 (N-{4-[3-(1-Methylcyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidene-methyl]-phenyl}-4-nitro-3-trifluoromethyl-benzenesulfonamide) as the lead agent. Evidence indicates that this drug-induced suppression of LPS-stimulated IL-6 production was attributable to AMPK activation. Furthermore, compound 53-mediated AMPK activation was demonstrated in C-26 colon adenocarcinoma cells, indicating that it is not a cell line-specific event. PMID:20170185

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

    PubMed

    Qiao, Yuanbiao; Jian, Fangfang; Bai, Qian

    2008-03-14

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

  5. Ag(+)-mediated assembly of 5'-guanosine monophosphate.

    PubMed

    Loo, Kristine; Degtyareva, Natalya; Park, Jihae; Sengupta, Bidisha; Reddish, Michaeal; Rogers, Christopher C; Bryant, Andrea; Petty, Jeffrey T

    2010-04-01

    Polymorphic forms of nucleic acids provide platforms for new nanomaterials, and transition metal cations give access to alternative arrangements of nucleobases by coordinating with electron-rich functional groups. Interaction of Ag(+) with 5'-guanosine monophosphate (5'-GMP) is considered in this work. Ag(+) promotes nucleotide stacking and aggregation, as indicated by the increased viscosity of 5'-GMP solutions with Ag(+), magnification of the circular dichroism response of guanine by Ag(+), and exothermic reactions between Ag(+) and guanine derivatives. Isothermal titration calorimetry studies show that the reaction is favored starting at 10 microM 5'-GMP. Utilizing the exothermic heat change associated with reaction of Ag(+) with 5'-GMP, local structure within the aggregate was assessed. On the basis of the salt dependence of the reaction and comparison with the corresponding nucleoside, the dianionic phosphate of 5'-GMP is one binding site for Ag(+), although this electrostatic interaction is not a dominant contribution to the overall heat change. Another binding site is the N7 on the nucleobase, as determined via studies with 7-deazaguanosine. Besides this binding site, Ag(+) also associates with the O6, as earlier studies deduced from the shift in the carbonyl stretching frequency associated with adduct formation. With these two binding sites on the nucleobase, the empirical stoichiometry of approximately 1 Ag(+):nucleobase derived from the calorimetry studies indicates that Ag(+) coordinates two nucleobases. The proposed structural model is a Ag(+)-mediated guanine dimer within a base stacked aggregate. PMID:20205377

  6. Crystalline and Crystalline International Disposal Activities

    SciTech Connect

    Viswanathan, Hari S.; Chu, Shaoping; Reimus, Paul William; Makedonska, Nataliia; Hyman, Jeffrey De'Haven; Karra, Satish; Dittrich, Timothy M.

    2015-12-21

    This report presents the results of work conducted between September 2014 and July 2015 at Los Alamos National Laboratory in the crystalline disposal and crystalline international disposal work packages of the Used Fuel Disposition Campaign (UFDC) for DOE-NE’s Fuel Cycle Research and Development program.

  7. UHP-UHT peak conditions and near-adiabatic exhumation path of diamond-bearing garnet-clinopyroxene rocks from the Eger Crystalline Complex, North Bohemian Massif

    NASA Astrophysics Data System (ADS)

    Haifler, Jakub; Kotková, Jana

    2016-04-01

    Intermediate garnet-clinopyroxene rocks from the Eger Crystalline Complex, North Bohemian Massif, contain microdiamonds enclosed in garnet and zircon. The variable mineral assemblage of these rocks allows for an evaluation of the P-T evolution using numerous univariant equilibria and thermodynamic modelling, in addition to the ternary feldspar solvus, Ti-in-garnet, Zr-in-rutile and Ti-in-zircon thermometry. Zircon mantle domains with diamond inclusions contain 111-189 ppm Ti, reflecting temperatures of 1037-1117 °C. The peak pressure consistent with diamond stability corresponds to c. 4.5-5.0 GPa. Ti-in-garnet thermometry using the Ti content of diamond-bearing garnet core yielded temperatures of 993-1039 °C at c. 5.0 GPa. An omphacite inclusion in garnet (reflecting c. 2.3-2.4 GPa at c. 1050 °C) and metastably preserved kyanite represent relics of eclogite-facies conditions. The dominant high-pressure granulite-facies mineral assemblage of low-Ca garnet, diopsidic clinopyroxene, antiperthitic feldspar and quartz equilibrated at 1.8-2.1 GPa and c. 1050 °C, based on the XGrs isopleth of the garnet mantle, garnet-feldspar-kyanite-quartz univariant equilibria and ternary feldspar solvus. Our thermodynamic modelling shows that a steep decrease of XGrs from a maximum core value of 0.32 to 0.17 at the rim as well as a rimward XMg increase (from 0.42 to 0.50) are consistent with significant decompression without heating. The latter is related to omphacite and kyanite breakdown reactions producing garnet and plagioclase. The Ti content in the rim zone of zircon (13-42 ppm), exsolved plagioclase and K-feldspar associated with matrix diopside and garnet rim, and late biotite reflect temperatures of c. 830-900 °C at c. 1.4 GPa. A similar temperature is recorded by matrix rutile grains, containing 2028-4390 ppm Zr and representing a relatively homogeneous population in contrast to rutile enclosed in garnet with variable Zr content. Our results show that the garnet

  8. 5'-C-Malonyl RNA: Small Interfering RNAs Modified with 5'-Monophosphate Bioisostere Demonstrate Gene Silencing Activity.

    PubMed

    Zlatev, Ivan; Foster, Donald J; Liu, Jingxuan; Charisse, Klaus; Brigham, Benjamin; Parmar, Rubina G; Jadhav, Vasant; Maier, Martin A; Rajeev, Kallanthottathil G; Egli, Martin; Manoharan, Muthiah

    2016-04-15

    5'-Phosphorylation is a critical step in the cascade of events that leads to loading of small interfering RNAs (siRNAs) into the RNA-induced silencing complex (RISC) to elicit gene silencing. 5'-Phosphorylation of exogenous siRNAs is generally accomplished by a cytosolic Clp1 kinase, and in most cases, the presence of a 5'-monophosphate on synthetic siRNAs is not a prerequisite for activity. Chemically introduced, metabolically stable 5'-phosphate mimics can lead to higher metabolic stability, increased RISC loading, and higher gene silencing activities of chemically modified siRNAs. In this study, we report the synthesis of 5'-C-malonyl RNA, a 5'-monophosphate bioisostere. A 5'-C-malonyl-modified nucleotide was incorporated at the 5'-terminus of chemically modified RNA oligonucleotides using solid-phase synthesis. In vitro silencing activity, in vitro metabolic stability, and in vitro RISC loading of 5'-C-malonyl siRNA was compared to corresponding 5'-phosphorylated and 5'-nonphosphorylated siRNAs. The 5'-C-malonyl siRNAs showed sustained or improved in vitro gene silencing and high levels of Ago2 loading and conferred dramatically improved metabolic stability to the antisense strand of the siRNA duplexes. In silico modeling studies indicate a favorable fit of the 5'-C-malonyl group within the 5'-phosphate binding pocket of human Ago2MID domain.

  9. Inhibition of initiation of protein synthesis by 7-methylguanosine-5'-monophosphate.

    PubMed Central

    Hickey, E D; Weber, L A; Baglioni, C

    1976-01-01

    Translation of rabbit globin mRNA in a wheat germ protein-synthesizing system is inhibited by the nucleotide 7-methylguanosine-5'-monophosphate (m7G5'p) but not by other guanosine nucleotides without the 7-methyl group or with the phosphate in a different position. Translation of RNA of tobacco mosaic virus and poly(A) + HeLa RNA is also inhibited by m7G5'p. We show that m7G5'p prevents the association of mRNA with ribosomal subunits to form an initiation complex. We propose that m7G5'p interacts with a site on initiation factor(s) or ribosomes which is involved in mRNA recognition, presumably by binding to the 5'-terminal sequence m7G5'ppp. m7G5'p does not inhibit translation of poly(U) and RNA of satellite tobacco necrosis virus, which do not have the 5'-terminal sequence m7G5'ppp. In the case of RNA of satellite tobacco necrosis virus, some stimulation of its translation is consistently observed in the presence of m7G5'p; possible interpretations of this finding are discussed. PMID:1061116

  10. Resonant Infrared Multiple Photon Dissociation Spectroscopy of Anionic Nucleotide Monophosphate Clusters.

    PubMed

    Ligare, Marshall R; Rijs, Anouk M; Berden, Giel; Kabeláč, Martin; Nachtigallova, Dana; Oomens, Jos; de Vries, Mattanjah S

    2015-06-25

    We report mid-infrared spectra and potential energy surfaces of four anionic, 2'-deoxynucleotide-5'-monophosphates (dNMPs) and the ionic DNA pairs [dGMP-dCMP-H](1-), [dAMP-dTMP-H](1-) with a total charge of the complex equal to -1. We recorded IR action spectra by resonant IR multiple-photon dissociation (IRMPD) using the FELIX free electron laser. The potential energy surface study employed an on-the-fly molecular dynamics quenching method (MD/Q), using a semiempirical AM1 method, followed by an optimization of the most stable structures using density functional theory. By employing infrared multiple-photon dissociation (IRMPD) spectroscopy in combination with high-level computational methods, we aim at a better understanding of the hydrogen bonding competition between the phosphate moieties and the nucleobases. We find that, unlike in multimer double stranded DNA structures, the hydrogen bonds in these isolated nucleotide pairs are predominantly formed between the phosphate groups. This intermolecular interaction appears to exceed the stabilization energy resulting from base pairing and directs the overall cluster structure and alignment.

  11. Recognition of Nucleoside Monophosphate Substrates by Haemophilus influenzae Class C Acid Phosphatase

    SciTech Connect

    Singh, Harkewal; Schuermann, Jonathan P.; Reilly, Thomas J.; Calcutt, Michael J.; Tanner, John J.

    2010-12-08

    The e (P4) phosphatase from Haemophilus influenzae functions in a vestigial NAD{sup +} utilization pathway by dephosphorylating nicotinamide mononucleotide to nicotinamide riboside. P4 is also the prototype of class C acid phosphatases (CCAPs), which are nonspecific 5{prime},3{prime}-nucleotidases localized to the bacterial outer membrane. To understand substrate recognition by P4 and other class C phosphatases, we have determined the crystal structures of a substrate-trapping mutant P4 enzyme complexed with nicotinamide mononucleotide, 5{prime}-AMP, 3{prime}-AMP, and 2{prime}-AMP. The structures reveal an anchor-shaped substrate-binding cavity comprising a conserved hydrophobic box that clamps the nucleotide base, a buried phosphoryl binding site, and three solvent-filled pockets that contact the ribose and the hydrogen-bonding edge of the base. The span between the hydrophobic box and the phosphoryl site is optimal for recognizing nucleoside monophosphates, explaining the general preference for this class of substrate. The base makes no hydrogen bonds with the enzyme, consistent with an observed lack of base specificity. Two solvent-filled pockets flanking the ribose are key to the dual recognition of 5{prime}-nucleotides and 3{prime}-nucleotides. These pockets minimize the enzyme's direct interactions with the ribose and provide sufficient space to accommodate 5{prime} substrates in an anti conformation and 3{prime} substrates in a syn conformation. Finally, the structures suggest that class B acid phosphatases and CCAPs share a common strategy for nucleotide recognition.

  12. Recognition of nucleoside monophosphate substrates by Haemophilus influenzae class C acid phosphatase.

    PubMed

    Singh, Harkewal; Schuermann, Jonathan P; Reilly, Thomas J; Calcutt, Michael J; Tanner, John J

    2010-12-10

    The e (P4) phosphatase from Haemophilus influenzae functions in a vestigial NAD(+) utilization pathway by dephosphorylating nicotinamide mononucleotide to nicotinamide riboside. P4 is also the prototype of class C acid phosphatases (CCAPs), which are nonspecific 5',3'-nucleotidases localized to the bacterial outer membrane. To understand substrate recognition by P4 and other class C phosphatases, we have determined the crystal structures of a substrate-trapping mutant P4 enzyme complexed with nicotinamide mononucleotide, 5'-AMP, 3'-AMP, and 2'-AMP. The structures reveal an anchor-shaped substrate-binding cavity comprising a conserved hydrophobic box that clamps the nucleotide base, a buried phosphoryl binding site, and three solvent-filled pockets that contact the ribose and the hydrogen-bonding edge of the base. The span between the hydrophobic box and the phosphoryl site is optimal for recognizing nucleoside monophosphates, explaining the general preference for this class of substrate. The base makes no hydrogen bonds with the enzyme, consistent with an observed lack of base specificity. Two solvent-filled pockets flanking the ribose are key to the dual recognition of 5'-nucleotides and 3'-nucleotides. These pockets minimize the enzyme's direct interactions with the ribose and provide sufficient space to accommodate 5' substrates in an anti conformation and 3' substrates in a syn conformation. Finally, the structures suggest that class B acid phosphatases and CCAPs share a common strategy for nucleotide recognition. PMID:20934434

  13. Adenosine 3', 5'-cyclic monophosphate levels in Thermomonospora curvata during cellulase biosynthesis

    SciTech Connect

    Fennington, G.; Neubauer, D.; Stutzenberger, F.

    1983-01-01

    The enzymatic degradation of cellulose requires the synergistic activity of at least three enzymes: exo-beta-1,4-glucanase (EC3.2.1.91), endo-beta-1,4-glucanase (EC3.2.1.4), and beta-glucosidase (EC3.2.1.21). Despite extensive studies on a variety of cellulolytic bacteria and fungi, the mechanism(s) regulating the biosynthesis of this inducible catabolic enzyme complex remains unknown. The intracellular concentrations of cyclic nucleotides such as adenosine 3',5'-cyclic monophosphate (cAMP) have been shown to play a major role in mediating catabolite repression of enzyme biosynthesis. The cAMP acts through a cAMP receptor protein (termed CRP or CAP) which is a dimer having two identical subunits each capable of binding one molecule of cAMP. The N-terminal domain of the CRP binds the cAMP while the C-terminal domain binds to DNA at the promotor region of a cAMP-dependent operon and stimulates transcription by promoting the formation of a preinitiation complex between RNA polymerase and the DNA. Intracellular cAMP levels in E. coli (the prototype organism for such studies) are influenced by the type and availability of carbon source used for growth. High intracellular cAMP levels should lead to higher concentrations of cAMP-CRP complexes which should increase the transcription rates for cAMP-dependent operons (such as the lac operon of beta-galactosidase) and indeed the differential rate of beta-galactosidase biosynthesis correlates to intracellular cAMP levels. In the case of cellulase, catabolite repression by glucose or other readily metabolizable compounds closely controls production in an apparently similar manner and therefore a correlation may exist between enzyme biosynthesis and intracellular cAMP levels. This communication describes the fluctuation in cAMP levels during cellulase induction and repression in the thermophilic actinomycete, Thermomonospora curvata.

  14. 1,3-Dimethyl-5-(3,4,5-tris(alkoxy)benzoyl) barbituric acid derivatives and their liquid crystalline difluoroboron complexes: Synthesis, characterization and comparative investigations of mesomorphic, thermotropic and thermo-morphologic properties

    NASA Astrophysics Data System (ADS)

    Giziroglu, Emrah; Nesrullajev, Arif; Orhan, Nil

    2014-01-01

    A series of 1,3-dimethyl-5-(3,4,5-tris(alkoxy)benzoyl) barbituric acid derivatives 1a-4a with various chain length were synthesized by our group for the first time through the addition of 1,3-dimethyl barbituric acid to 3,4,5-tris(alkoxy)benzoyl chloride at room temperature in presence of pyridine. For preparation of their difluoroboron complexes, the derivatives 1a-4a reacts with borontrifluoride in the presence of triethylamine affording 1b-4b in moderate yields. All derivatives and complexes have been fully characterized by MS, FT-IR and multinuclear NMR spectroscopy. We also explored their liquid crystal properties by using POM, OM, CTW and DSC techniques. The results show that 3b and 4b with longer alkyl chain are monomorphic mesogens and exhibited enantiotropic thermotropic liquid crystalline mesophases. Investigation of their mesomorphic, thermo-morphologic and thermotropic properties is presented in this work.

  15. Design of inhibitors of orotidine monophosphate decarboxylase using bioisosteric replacement and determination of inhibition kinetics.

    PubMed

    Poduch, Ewa; Bello, Angelica M; Tang, Sishi; Fujihashi, Masahiro; Pai, Emil F; Kotra, Lakshmi P

    2006-08-10

    Inhibitors of orotidine monophosphate decarboxylase (ODCase) have applications in RNA viral, parasitic, and other infectious diseases. ODCase catalyzes the decarboxylation of orotidine monophosphate (OMP), producing uridine monophosphate (UMP). Novel inhibitors 6-amino-UMP and 6-cyano-UMP were designed on the basis of the substructure volumes in the substrate OMP and in an inhibitor of ODCase, barbituric acid monophosphate, BMP. A new enzyme assay method using isothermal titration calorimetry (ITC) was developed to investigate the inhibition kinetics of ODCase. The reaction rates were measured by monitoring the heat generated during the decarboxylation reaction of orotidine monophosphate. Kinetic parameters (k(cat) = 21 s(-1) and KM = 5 microM) and the molar enthalpy (DeltaH(app) = 5 kcal/mol) were determined for the decarboxylation of the substrate by ODCase. Competitive inhibition of the enzyme was observed and the inhibition constants (Ki) were determined to be 12.4 microM and 29 microM for 6-aza-UMP and 6-cyano-UMP, respectively. 6-Amino-UMP was found to be among the potent inhibitors of ODCase, having an inhibition constant of 840 nM. We reveal here the first inhibitors of ODCase designed by the principles of bioisosterism and a novel method of using isothermal calorimetry for enzyme inhibition studies.

  16. Induction of phosphodiesterase by cyclic adenosine 3':5'-monophosphate in differentiating Dictyostelium discoideum amoebae.

    PubMed

    Klein, C

    1975-09-25

    Cyclic adenosine 3':5'-monophosphate added to the starvation media of Dictyostelium discoideum amoebae induces both intracellular and extracellular phosphodiesterase activities of these cells. The induced enzyme activity appears several hours earlier than that in starved cells which have not been induced with cyclic nucleotide. In both cases, the appearance of enzyme is inhibited by cycloheximide, and actinomycin D, and daunomycin. The KmS for the extracellular enzyme(s) of nucleotide-induced and uninduced control cells are identical. The induction of enzyme activity seems specific for cyclic adenosine 3':5'-monophosphate since cyclic guanosine 3':5'-monophosphate, as well as other nucleotides, have no effect. No differences in the activity or excretion of either N-acetylglucosaminidase or the inhibitory of the extracellular phosphodiesterase are observed between cyclic adenosine 3':5'-monophosphate-induced and control cells. A direct activation of phosphodiesterase by cyclic adenosine 3':5'-monophosphate can be excluded, since the addition of this nucleotide to cell lysates has no effect on the enzyme activity. PMID:170256

  17. Identification of cytidine 2',3'-cyclic monophosphate and uridine 2',3'-cyclic monophosphate in Pseudomonas fluorescens pfo-1 culture.

    PubMed

    Bordeleau, Emily; Oberc, Christopher; Ameen, Eve; da Silva, Amanda Mendes; Yan, Hongbin

    2014-09-15

    Cytidine 2',3'-cyclic monophosphate (2',3'-cCMP) and uridine 2',3'-cyclic monophosphate (2',3'-cUMP) were isolated from Pseudomonas fluorescens pfo-1 cell extracts by semi-preparative reverse phase HPLC. The structures of the two compounds were confirmed by NMR and mass spectroscopy against commercially available authentic samples. Concentrations of both intracellular and extracellular 2',3'-cCMP and 2',3'-cUMP were determined. Addition of 2',3'-cCMP and 2',3'-cUMP to P. fluorescens pfo-1 culture did not significantly affect the level of biofilm formation in static liquid cultures. PMID:25139571

  18. Rationally fabricating hollow particles of complex oxides by a templateless hydrothermal route: the case of single-crystalline SrHfO3 hollow cuboidal nanoshells.

    PubMed

    Ye, Tiannan; Dong, Zhenghong; Zhao, Yongnan; Yu, Jianguo; Wang, Fengqin; Zhang, Lingling; Zou, Yongcun

    2011-03-21

    Based on the theory of sol-gel science, perovskite SrHfO(3) hollow cuboidal particles with tunable sizes were rationally synthesized by templateless hydrothermal reactions in KOH solutions. The concentrated KOH solution not only elevated the supersaturation of the reactants to promote the grain growth of SrHfO(3) but also controlled the aggregated particle sizes by compressing the electrical double layers of the primary particulates. The following Ostwald ripening process produced hollow particles with sizes ranging from submicrometer to hundred nanometre. The HRTEM image and SAED pattern revealed the single crystal nature of each hollow cuboidal nanoshell. The KOH concentration and reaction time related experiments confirmed that the formation of SrHfO(3) hollow cuboidal nanoshell was driven by the Ostwald ripening process and followed our assumption. The particles experienced solid, core-shell and hollow morphologies as the reaction proceeded. Also, the formation of SrHfO(3) hollow cuboidal nanoshells favored high reaction temperature which initiated and accelerated the ripening process. The as-prepared hollow cuboidal nanoshells displayed blue light emission under UV laser excitation at room temperature. After calcination, the photoluminescence intensity declined due to the improvement of crystallinity.

  19. The role of Drosophila cytidine monophosphate-sialic acid synthetase in the nervous system.

    PubMed

    Islam, Rafique; Nakamura, Michiko; Scott, Hilary; Repnikova, Elena; Carnahan, Mindy; Pandey, Dheeraj; Caster, Courtney; Khan, Saba; Zimmermann, Tina; Zoran, Mark J; Panin, Vladislav M

    2013-07-24

    While sialylation plays important functions in the nervous system, the complexity of glycosylation pathways and limitations of genetic approaches preclude the efficient analysis of these functions in mammalian organisms. Drosophila has recently emerged as a promising model for studying neural sialylation. Drosophila sialyltransferase, DSiaT, was shown to be involved in the regulation of neural transmission. However, the sialylation pathway was not investigated in Drosophila beyond the DSiaT-mediated step. Here we focused on the function of Drosophila cytidine monophosphate-sialic acid synthetase (CSAS), the enzyme providing a sugar donor for DSiaT. Our results revealed that the expression of CSAS is tightly regulated and restricted to the CNS throughout development and in adult flies. We generated CSAS mutants and analyzed their phenotypes using behavioral and physiological approaches. Our experiments demonstrated that mutant phenotypes of CSAS are similar to those of DSiaT, including decreased longevity, temperature-induced paralysis, locomotor abnormalities, and defects of neural transmission at neuromuscular junctions. Genetic interactions between CSAS, DSiaT, and voltage-gated channel genes paralytic and seizure were consistent with the hypothesis that CSAS and DSiaT function within the same pathway regulating neural excitability. Intriguingly, these interactions also suggested that CSAS and DSiaT have some additional, independent functions. Moreover, unlike its mammalian counterparts that work in the nucleus, Drosophila CSAS was found to be a glycoprotein-bearing N-glycans and predominantly localized in vivo to the Golgi compartment. Our work provides the first systematic analysis of in vivo functions of a eukaryotic CSAS gene and sheds light on evolutionary relationships among metazoan CSAS proteins.

  20. Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5'-monophosphate dehydrogenase.

    PubMed

    Gorla, Suresh Kumar; Kavitha, Mandapati; Zhang, Minjia; Chin, James En Wai; Liu, Xiaoping; Striepen, Boris; Makowska-Grzyska, Magdalena; Kim, Youngchang; Joachimiak, Andrzej; Hedstrom, Lizbeth; Cuny, Gregory D

    2013-05-23

    Cryptosporidium parvum is an enteric protozoan parasite that has emerged as a major cause of diarrhea, malnutrition, and gastroenteritis and poses a potential bioterrorism threat. C. parvum synthesizes guanine nucleotides from host adenosine in a streamlined pathway that relies on inosine 5'-monophosphate dehydrogenase (IMPDH). We have previously identified several parasite-selective C. parvum IMPDH (CpIMPDH) inhibitors by high-throughput screening. In this paper, we report the structure-activity relationship (SAR) for a series of benzoxazole derivatives with many compounds demonstrating CpIMPDH IC50 values in the nanomolar range and >500-fold selectivity over human IMPDH (hIMPDH). Unlike previously reported CpIMPDH inhibitors, these compounds are competitive inhibitors versus NAD(+). The SAR study reveals that pyridine and other small heteroaromatic substituents are required at the 2-position of the benzoxazole for potent inhibitory activity. In addition, several other SAR conclusions are highlighted with regard to the benzoxazole and the amide portion of the inhibitor, including preferred stereochemistry. An X-ray crystal structure of a representative E·IMP·inhibitor complex is also presented. Overall, the secondary amine derivative 15a demonstrated excellent CpIMPDH inhibitory activity (IC50 = 0.5 ± 0.1 nM) and moderate stability (t1/2 = 44 min) in mouse liver microsomes. Compound 73, the racemic version of 15a, also displayed superb antiparasitic activity in a Toxoplasma gondii strain that relies on CpIMPDH (EC50 = 20 ± 20 nM), and selectivity versus a wild-type T. gondii strain (200-fold). No toxicity was observed (LD50 > 50 μM) against a panel of four mammalian cells lines.

  1. Enzyme architecture: deconstruction of the enzyme-activating phosphodianion interactions of orotidine 5'-monophosphate decarboxylase.

    PubMed

    Goldman, Lawrence M; Amyes, Tina L; Goryanova, Bogdana; Gerlt, John A; Richard, John P

    2014-07-16

    The mechanism for activation of orotidine 5'-monophosphate decarboxylase (OMPDC) by interactions of side chains from Gln215 and Try217 at a gripper loop and R235, adjacent to this loop, with the phosphodianion of OMP was probed by determining the kinetic parameters k(cat) and K(m) for all combinations of single, double, and triple Q215A, Y217F, and R235A mutations. The 12 kcal/mol intrinsic binding energy of the phosphodianion is shown to be equal to the sum of the binding energies of the side chains of R235 (6 kcal/mol), Q215 (2 kcal/mol), Y217 (2 kcal/mol), and hydrogen bonds to the G234 and R235 backbone amides (2 kcal/mol). Analysis of a triple mutant cube shows small (ca. 1 kcal/mol) interactions between phosphodianion gripper side chains, which are consistent with steric crowding of the side chains around the phosphodianion at wild-type OMPDC. These mutations result in the same change in the activation barrier to the OMPDC-catalyzed reactions of the whole substrate OMP and the substrate pieces (1-β-D-erythrofuranosyl)orotic acid (EO) and phosphite dianion. This shows that the transition states for these reactions are stabilized by similar interactions with the protein catalyst. The 12 kcal/mol intrinsic phosphodianion binding energy of OMP is divided between the 8 kcal/mol of binding energy, which is utilized to drive a thermodynamically unfavorable conformational change of the free enzyme, resulting in an increase in (k(cat))(obs) for OMPDC-catalyzed decarboxylation of OMP, and the 4 kcal/mol of binding energy, which is utilized to stabilize the Michaelis complex, resulting in a decrease in (K(m))(obs).

  2. RNA initiation with dinucleoside monophosphates during transcription of bacteriophage T4 DNA with RNA polymerase of Escherichia coli.

    PubMed

    Hoffman, D J; Niyogi, S K

    1973-02-01

    The effects of dinucleoside monophosphates on the transcription of phage T4 DNA by E. coli RNA polymerase have been examined at various concentrations of the sigma subunit and extremely low concentration of ribonucleoside triphosphate. The following conclusions were reached: (i) Labeled specific dinucleoside monophosphates are incorporated as chain initiators. (ii) When the ratio of sigma factor to core enzyme is small, there is a general stimulation by most 5'-guanosyl dinucleoside monophosphates. (iii) When the ratio is increased or holoenzyme is present, ApU, CpA, UpA, and GpU are the most effective stimulators. (iv) At high concentrations of sigma factor, only certain adenosine-containing dinucleoside monophosphates (ApU, CpA, UpA, and ApA) stimulate the reaction. (v) Competition hybridization studies indicate that the RNAs stimulated by dinucleoside monophosphates (ApU, CpA, UpA, and GpU) are of the T4 "early" type. (vi) Studies involving both combinations of stimulatory dinucleoside monophosphates and competitive effects of these compounds on chain initiation by ATP and GTP suggest that the stimulatory dinucleoside monophosphates act as chain initiators and may recognize part of a continuous sequence in a promoter region. Studies based on the incorporation of (3)H-labeled stimulatory dinucleoside monophosphates support the above conclusions.

  3. A label-free and self-assembled electrochemical biosensor for highly sensitive detection of cyclic diguanylate monophosphate (c-di-GMP) based on RNA riboswitch.

    PubMed

    Xie, Qingyun; Zhao, Fulin; Liu, Hongrui; Shan, Yanke; Liu, Fei

    2015-07-01

    Cyclic diguanylate monophosphate (c-di-GMP) is an important second messenger that regulates a variety of complex physiological processes involved in motility, virulence, biofilm formation and cell cycle progression in several bacteria. Herein we report a simple label-free and self-assembled RNA riboswitch-based biosensor for sensitive and selective detection of c-di-GMP. The detectable concentration range of c-di-GMP is from 50 nM to 1 μM with a detection limit of 50 nM.

  4. Synthesis, structure, solution and DFT studies of a pyrazine-bridged binuclear Cu(II) complex: On the importance of noncovalent interactions in the formation of crystalline network

    NASA Astrophysics Data System (ADS)

    Mirzaei, Masoud; Eshtiagh-Hosseini, Hossein; Karrabi, Zahra; Notash, Behrouz; Bauzá, Antonio; Frontera, Antonio; Habibi, Morteza; Ardalani, Mehdi; Shamsipur, Mojtaba

    2015-01-01

    A pyrazine-bridged binuclear Cu(II) complexes with formulae of [Cu2(chel)2(pyz)(H2O)4], (1, pyz = pyrazine, H2chel = chelidamic acid), has been synthesized and characterized by elemental analyses, IR spectroscopy and solution studies. The crystal structure of the binuclear Cu(II) complex has been determined by X-ray single-crystal diffraction technique. Both copper(II) metal centers are bridged by pyrazine. The coordination environment around each copper(II) atom can be described as a distorted octahedral geometry. The axial positions of each Cu(II) complex are occupied by two water molecules and equatorial positions are occupied by a tridentate chelidamic acid dianion and a pyrazine molecule that functions as a linear bidentate ligand bridging two Cu(II) complexes to form a dimer. Hydrogen bonding and Csbnd O⋯π interactions link the binuclear Cu(II) complex generating the 3D infinite network. These assemblies are described and analyzed by means of density functional theory (DFT) calculations since they play an important role in the construction of three-dimensional supramolecular frameworks. The protonation constants of pyrazine and chelidamic acid as the building blocks of the proton transfer systems (H2chel-pyz) and their corresponding stability constants were determined by potentiometric studies. The stoichiometry and stability constants of H2chel-pyz complex with Cu2+ was investigated by potentiometric technique in aqueous solution. The results from solution studies were compared with the solid state data, in details.

  5. Topological crystalline insulator nanostructures.

    PubMed

    Shen, Jie; Cha, Judy J

    2014-11-01

    Topological crystalline insulators are topological insulators whose surface states are protected by the crystalline symmetry, instead of the time reversal symmetry. Similar to the first generation of three-dimensional topological insulators such as Bi₂Se₃ and Bi₂Te₃, topological crystalline insulators also possess surface states with exotic electronic properties such as spin-momentum locking and Dirac dispersion. Experimentally verified topological crystalline insulators to date are SnTe, Pb₁-xSnxSe, and Pb₁-xSnxTe. Because topological protection comes from the crystal symmetry, magnetic impurities or in-plane magnetic fields are not expected to open a gap in the surface states in topological crystalline insulators. Additionally, because they have a cubic structure instead of a layered structure, branched structures or strong coupling with other materials for large proximity effects are possible, which are difficult with layered Bi₂Se₃ and Bi₂Te₃. Thus, additional fundamental phenomena inaccessible in three-dimensional topological insulators can be pursued. In this review, topological crystalline insulator SnTe nanostructures will be discussed. For comparison, experimental results based on SnTe thin films will be covered. Surface state properties of topological crystalline insulators will be discussed briefly.

  6. Mechanism of the Orotidine 5′-Monophosphate Decarboxylase-Catalyzed Reaction: Evidence for Substrate Destabilization

    SciTech Connect

    Chan, K.; Wood, M; Fedorov, A; Fedorov, E; Imker, H; Amyes, T; Richard, J; Almo, S; Gerlt, J

    2009-01-01

    The reaction catalyzed by orotidine 5'-monophosphate decarboxylase (OMPDC) involves a stabilized anionic intermediate, although the structural basis for the rate acceleration (kcat/knon, 7.1 x 1016) and proficiency (kcat/KM)/knon, 4.8 x 1022 M-1 is uncertain. That the OMPDCs from Methanothermobacter thermautotrophicus (MtOMPDC) and Saccharomyces cerevisiae (ScOMPDC) catalyze the exchange of H6 of the UMP product with solvent deuterium allows an estimate of a lower limit on the rate acceleration associated with stabilization of the intermediate and its flanking transition states (=1010). The origin of the 'missing' contribution, =107 (1017 total - =1010), is of interest. Based on structures of liganded complexes, unfavorable electrostatic interactions between the substrate carboxylate group and a proximal Asp (Asp 70 in MtOMPDC and Asp 91 in ScOMPDC) have been proposed to contribute to the catalytic efficiency. We investigated that hypothesis by structural and functional characterization of the D70N and D70G mutants of MtOMPDC and the D91N mutant of ScOMPDC. The substitutions for Asp 70 in MtOMPDC significantly decrease the value of kcat for decarboxylation of FOMP (a more reactive substrate analogue) but have little effect on the value of kex for exchange of H6 of FUMP with solvent deuterium; the structures of wild-type MtOMPDC and its mutants are superimposable when complexed with 6-azaUMP. In contrast, the D91N mutant of ScOMPDC does not catalyze exchange of H6 of FUMP; the structures of wild-type ScOMPDC and its D91N mutant are not superimposable when complexed with 6-azaUMP, with differences in both the conformation of the active site loop and the orientation of the ligand vis vis the active site residues. We propose that the differential effects of substitutions for Asp 70 of MtOMPDC on decarboxylation and exchange provide additional evidence for a carbanionic intermediate as well as the involvement of Asp 70 in substrate destabilization.

  7. Mechanism of the orotidine 5'-monophosphate decarboxylase-catalyzed reaction: evidence for substrate destabilization.

    PubMed

    Chan, Kui K; Wood, B McKay; Fedorov, Alexander A; Fedorov, Elena V; Imker, Heidi J; Amyes, Tina L; Richard, John P; Almo, Steven C; Gerlt, John A

    2009-06-23

    The reaction catalyzed by orotidine 5'-monophosphate decarboxylase (OMPDC) involves a stabilized anionic intermediate, although the structural basis for the rate acceleration (k(cat)/k(non), 7.1 x 10(16)) and proficiency [(k(cat)/K(M))/k(non), 4.8 x 10(22) M(-1)] is uncertain. That the OMPDCs from Methanothermobacter thermautotrophicus (MtOMPDC) and Saccharomyces cerevisiae (ScOMPDC) catalyze the exchange of H6 of the UMP product with solvent deuterium allows an estimate of a lower limit on the rate acceleration associated with stabilization of the intermediate and its flanking transition states (>or=10(10)). The origin of the "missing" contribution, or=10(10)), is of interest. Based on structures of liganded complexes, unfavorable electrostatic interactions between the substrate carboxylate group and a proximal Asp (Asp 70 in MtOMPDC and Asp 91 in ScOMPDC) have been proposed to contribute to the catalytic efficiency [Wu, N., Mo, Y., Gao, J., and Pai, E. F. (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 2017-2022]. We investigated that hypothesis by structural and functional characterization of the D70N and D70G mutants of MtOMPDC and the D91N mutant of ScOMPDC. The substitutions for Asp 70 in MtOMPDC significantly decrease the value of k(cat) for decarboxylation of FOMP (a more reactive substrate analogue) but have little effect on the value of k(ex) for exchange of H6 of FUMP with solvent deuterium; the structures of wild-type MtOMPDC and its mutants are superimposable when complexed with 6-azaUMP. In contrast, the D91N mutant of ScOMPDC does not catalyze exchange of H6 of FUMP; the structures of wild-type ScOMPDC and its D91N mutant are not superimposable when complexed with 6-azaUMP, with differences in both the conformation of the active site loop and the orientation of the ligand vis a vis the active site residues. We propose that the differential effects of substitutions for Asp 70 of MtOMPDC on decarboxylation and

  8. Low-dose, sublingual AZT-monophosphate therapy for HIV+ patients?

    PubMed

    Johnson, S

    2001-03-01

    AZT concentrations as low as 0.001 mg/l inhibit viral replication, while concentrations above 0.3 mg/l cause considerable damage to erythroid, myeloid progenitor cells and inhibit blastogenesis in mononuclear cells. Furthermore, AZT must be converted first to monophosphate and then to diphosphate and finally to triphosphate by the same enzyme: thymidine kinase (TK). Therefore, large doses of AZT overwhelm TK, causing massive production of monophosphate and reducing the production of di and triphosphate. Yet the recommended dosage of 100 mg AZT every 4 hours results in a peak concentration of 0.5 mg/l and a trough concentration of 0.1 mg/l (harmful to human cells and resulting in reduced production of triphosphate). On the other hand, sublingual administration of 1 mg AZT monophosphate every 8 hours (since the intracellular half life of AZT triphosphate is 3 hours) would be desirable, resulting in more damage to the virus and less harm to the patient. Finally, the small dose of monophosphate ensures that most of the AZT be converted to triphosphate, greatly increasing the efficiency and reducing the likelihood of the virus developing resistance due to reverse transcriptase binding to the similar but non inhibiting mono and diphosphate. PMID:11359372

  9. Models of the Membrane-Bound Cytochromes: Mössbauer Spectra of Crystalline Low-Spin Ferriheme Complexes Having Axial Ligand Plane Dihedral Angles Ranging from 0° to 90°

    PubMed Central

    Teschner, Thomas; Yatsunyk, Liliya; Schünemann, Volker; Paulsen, Hauke; Winkler, Heiner; Hu, Chuanjiang; Scheidt, W. Robert; Walker, F. Ann; Trautwein, Alfred X.

    2006-01-01

    Crystalline samples of four low-spin Fe(III) octaalkyltetraphenylporphyrinate and two low-spin Fe(III) tetramesitylporphyrinate complexes, all of which are models of the bis-histidine-coordinated cytochromes of mitochondrial complexes II, III and IV, and chloroplast complex b6f, and whose molecular structures and EPR spectra have been reported previously, have been investigated in detail by Mössbauer spectroscopy. The six complexes and the dihedral angles between axial ligand planes of each are [(TMP)Fe(1-MeIm)2]ClO4 (0°, paral-[(OMTPP)Fe(1-MeIm)2]Cl (19.5°, paral-[(TMP)Fe(5-MeHIm)2]ClO4 (26°, 30° for two molecules in the unit cell whose EPR spectra overlap), [(OETPP)Fe(4-Me2NPy)2]Cl (70°, perp-[(OETPP)Fe(1-MeIm)2]Cl (73°, and perp-[(OMTPP)Fe(1-MeIm)2]Cl (90°. Of these, the first three have been shown to exhibit normal rhombic EPR spectra with three clearly-resolved g-values, while the last three have been shown to exhibit “large gmax” EPR spectra at 4.2 K. It is found that the hyperfine coupling constants of the complexes are consistent with those reported previously for low-spin ferriheme systems, with the largest-magnitude hyperfine coupling constant, Azz, being considerably smaller for the “parallel” complexes (400-540 kG) than for the strictly perpendicular complex (902 kG), Axx being negative for all six complexes, and Azz and Axx being of similar magnitude for the “parallel” complexes (for example, for [(TMP)Fe(1-MeIm)2]Cl, Azz = 400 kG, Axx = - 400 kG), and finally, Ayy is small, but difficult to estimate with accuracy for all complexes. With results for six structurally-characterized model systems we find qualitative correlations of gzz, Azz, and △EQ with axial ligand plane dihedral angle △φ. PMID:16433558

  10. Crystalline Silica Primer

    USGS Publications Warehouse

    ,

    1992-01-01

    substance and will present a nontechnical overview of the techniques used to measure crystalline silica. Because this primer is meant to be a starting point for anyone interested in learning more about crystalline silica, a list of selected readings and other resources is included. The detailed glossary, which defines many terms that are beyond the scope of this publication, is designed to help the reader move from this presentation to a more technical one, the inevitable next step.

  11. The crystalline sponge method updated

    PubMed Central

    Hoshino, Manabu; Khutia, Anupam; Xing, Hongzhu; Inokuma, Yasuhide; Fujita, Makoto

    2016-01-01

    Crystalline sponges are porous metal complexes that can absorb and orient common organic molecules in their pores and make them observable by conventional X-ray structure analysis (crystalline sponge method). In this study, all of the steps in the crystalline sponge method, including sponge crystal preparation, pore–solvent exchange, guest soaking, data collection and crystallographic analysis, are carefully examined and thoroughly optimized to provide reliable and meaningful chemical information as chemical crystallography. Major improvements in the method have been made in the guest-soaking and data-collection steps. In the soaking step, obtaining a high site occupancy of the guest is particularly important, and dominant parameters for guest soaking (e.g. temperature, time, concentration, solvents) therefore have to be optimized for every sample compound. When standard conditions do not work, a high-throughput method is useful for efficiently optimizing the soaking conditions. The X-ray experiments are also carefully re-examined. Significant improvement of the guest data quality is achieved by complete data collection at high angle regions. The appropriate disorder treatment of the most flexible ZnI2 portions of the host framework and refinement of the solvents filling the remaining void are also particularly important for obtaining better data quality. A benchmark test for the crystalline sponge method toward an achiral molecule is proposed with a guaiazulene guest, in which the guest structure (with ∼ 100% site occupancy) is refined without applying any restraints or constraints. The obtained data quality with R int = 0.0279 and R 1 = 0.0379 is comparable with that of current conventional crystallographic analysis for small molecules. Another benchmark test for this method toward a chiral molecule is also proposed with a santonin guest. The crystallographic data obtained [R int = 0.0421, R 1 = 0.0312, Flack (Parsons) = −0.0071 (11)] represents the

  12. Molecular aggregation in selected crystalline 1:1 complexes of hydrophobic D- and L-amino acids. IV. The L-phenylalanine series.

    PubMed

    Görbitz, Carl Henrik; Rissanen, Kari; Valkonen, Arto; Husabø, Asmund

    2009-06-01

    The amino acid L-phenylalanine has been cocrystallized with D-2-aminobutyric acid, C(9)H(11)NO(2).C(4)H(9)NO(2), D-norvaline, C(9)H(11)NO(2).C(5)H(11)NO(2), and D-methionine, C(9)H(11)NO(2).C(5)H(11)NO(2)S, with linear side chains, as well as with D-leucine, C(9)H(11)NO(2).C(6)H(13)NO(2), D-isoleucine, C(9)H(11)NO(2).C(6)H(13)NO(2), and D-allo-isoleucine, C(9)H(11)NO(2).C(6)H(13)NO(2), with branched side chains. The structures of these 1:1 complexes fall into two classes based on the observed hydrogen-bonding pattern. From a comparison with other L:D complexes involving hydrophobic amino acids and regular racemates, it is shown that the structure-directing properties of phenylalanine closely parallel those of valine and isoleucine but not those of leucine, which shares side-chain branching at C(gamma) with phenylalanine and is normally considered to be the most closely related non-aromatic amino acid.

  13. Liquid crystalline composites containing phyllosilicates

    DOEpatents

    Chaiko, David J.

    2004-07-13

    The present invention provides phyllosilicate-polymer compositions which are useful as liquid crystalline composites. Phyllosilicate-polymer liquid crystalline compositions of the present invention can contain a high percentage of phyllosilicate while at the same time be transparent. Because of the ordering of the particles liquid crystalline composite, liquid crystalline composites are particularly useful as barriers to gas transport.

  14. The anisotropy1 D604N Mutation in the Arabidopsis Cellulose Synthase1 Catalytic Domain Reduces Cell Wall Crystallinity and the Velocity of Cellulose Synthase Complexes1[W][OA

    PubMed Central

    Fujita, Miki; Himmelspach, Regina; Ward, Juliet; Whittington, Angela; Hasenbein, Nortrud; Liu, Christine; Truong, Thy T.; Galway, Moira E.; Mansfield, Shawn D.; Hocart, Charles H.; Wasteneys, Geoffrey O.

    2013-01-01

    Multiple cellulose synthase (CesA) subunits assemble into plasma membrane complexes responsible for cellulose production. In the Arabidopsis (Arabidopsis thaliana) model system, we identified a novel D604N missense mutation, designated anisotropy1 (any1), in the essential primary cell wall CesA1. Most previously identified CesA1 mutants show severe constitutive or conditional phenotypes such as embryo lethality or arrest of cellulose production but any1 plants are viable and produce seeds, thus permitting the study of CesA1 function. The dwarf mutants have reduced anisotropic growth of roots, aerial organs, and trichomes. Interestingly, cellulose microfibrils were disordered only in the epidermal cells of the any1 inflorescence stem, whereas they were transverse to the growth axis in other tissues of the stem and in all elongated cell types of roots and dark-grown hypocotyls. Overall cellulose content was not altered but both cell wall crystallinity and the velocity of cellulose synthase complexes were reduced in any1. We crossed any1 with the temperature-sensitive radial swelling1-1 (rsw1-1) CesA1 mutant and observed partial complementation of the any1 phenotype in the transheterozygotes at rsw1-1’s permissive temperature (21°C) and full complementation by any1 of the conditional rsw1-1 root swelling phenotype at the restrictive temperature (29°C). In rsw1-1 homozygotes at restrictive temperature, a striking dissociation of cellulose synthase complexes from the plasma membrane was accompanied by greatly diminished motility of intracellular cellulose synthase-containing compartments. Neither phenomenon was observed in the any1 rsw1-1 transheterozygotes, suggesting that the proteins encoded by the any1 allele replace those encoded by rsw1-1 at restrictive temperature. PMID:23532584

  15. Adenosine 3′:5′-cyclic monophosphate- and guanosine 3′:5′-cyclic monophosphate-dependent protein kinases: Possible homologous proteins

    PubMed Central

    Lincoln, Thomas M.; Corbin, Jackie D.

    1977-01-01

    The properties of purified mammalian adenosine 3′:5′-cyclic monophosphate (cAMP)- and guanosine 3′:5′-cyclic monophosphate (cGMP)-dependent protein kinases were compared. Several physical characteristics of the two enzymes were similar, including size, shape, affinity for cyclic nucleotide binding, and Km for ATP. In addition, the amino acid composition of the two proteins indicated a close composition homology (70-90%). Both cyclic nucleotide-dependent protein kinases catalyzed phosphorylation of rat liver pyruvate kinase (EC 2.7.1.40) and fructose 1,6-diphosphatase (EC 3.1.3.11), rabbit skeletal muscle glycogen synthase (EC 2.4.1.11) and phosphorylase b kinase (EC 2.7.1.38), and calf thymus histone H2b. The phosphorylation of several synthetic peptides and of trypsin-sensitive and trypsin-insensitive sites in glycogen synthase suggested similar recognition sites on the protein substrates for the two kinases. The cAMP-dependent protein kinase was the better catalyst with each protein or peptides substrate. The results suggest that the two enzymes evolved from a common ancestral protein. Images PMID:198777

  16. Crystalline molecular flasks.

    PubMed

    Inokuma, Yasuhide; Kawano, Masaki; Fujita, Makoto

    2011-05-01

    A variety of host compounds have been used as molecular-scale reaction vessels, protecting guests from their environment or restricting the space available around them, thus favouring particular reactions. Such molecular 'flasks' can endow guest molecules with reactivities that differ from those in bulk solvents. Here, we extend this concept to crystalline molecular flasks, solid-state crystalline networks with pores within which pseudo-solution-state reactions can take place. As the guest molecules can spontaneously align along the walls and channels of the hosts, structural changes in the substrates can be directly observed by in situ X-ray crystallography during reaction. Recently, this has enabled observation of the molecular structures of transient intermediates and other labile species, in the form of sequential structural snapshots of the chemical transformation. Here, we describe the principles, development and applications of crystalline molecular flasks.

  17. Fluorescence decay studies of modified dinucleoside monophosphates containing 1-N6-ethenoadenosine.

    PubMed

    Kubota, Y; Motoda, Y; Fujisaki, Y; Steiner, R F

    1983-10-01

    Five dinucleoside monophosphates containing 1-N6-ethenoadenosine (epsilon A) have been studied using fluorescence measurements. The fluorescence spectra of these dinucleoside monophosphates are almost the same as the fluorescence spectrum of epsilon AMP. Fluorescence quantum yields of these dimers are greatly reduced compared to that of epsilon AMP. Intramolecular base-base interactions may be responsible for fluorescence quenching. It is found that the fluorescence decay kinetics does not obey a simple decay law but that the decay data can be well described as a sum of three exponentials. This implies that these dimers cannot be characterized as a two-state system, but can be described as systems consisting of three or more conformational states. Sequence effects upon the fluorescence behavior are observed. The fluorescence quenching and decay parameters of Gp epsilon A and Up epsilon A indicate a higher degree of base-base interaction than in their epsilon ApG and epsilon ApU counterparts.

  18. Topological crystalline insulators.

    PubMed

    Fu, Liang

    2011-03-11

    The recent discovery of topological insulators has revived interest in the band topology of insulators. In this Letter, we extend the topological classification of band structures to include certain crystal point group symmetry. We find a class of three-dimensional "topological crystalline insulators" which have metallic surface states with quadratic band degeneracy on high symmetry crystal surfaces. These topological crystalline insulators are the counterpart of topological insulators in materials without spin-orbit coupling. Their band structures are characterized by new topological invariants. We hope this work will enlarge the family of topological phases in band insulators and stimulate the search for them in real materials.

  19. Novel Characteristics of Trypanosoma brucei Guanosine 5'-monophosphate Reductase Distinct from Host Animals.

    PubMed

    Bessho, Tomoaki; Okada, Tetsuya; Kimura, Chihiro; Shinohara, Takahiro; Tomiyama, Ai; Imamura, Akira; Kuwamura, Mitsuru; Nishimura, Kazuhiko; Fujimori, Ko; Shuto, Satoshi; Ishibashi, Osamu; Kubata, Bruno Kilunga; Inui, Takashi

    2016-01-01

    The metabolic pathway of purine nucleotides in parasitic protozoa is a potent drug target for treatment of parasitemia. Guanosine 5'-monophosphate reductase (GMPR), which catalyzes the deamination of guanosine 5'-monophosphate (GMP) to inosine 5'-monophosphate (IMP), plays an important role in the interconversion of purine nucleotides to maintain the intracellular balance of their concentration. However, only a few studies on protozoan GMPR have been reported at present. Herein, we identified the GMPR in Trypanosoma brucei, a causative protozoan parasite of African trypanosomiasis, and found that the GMPR proteins were consistently localized to glycosomes in T. brucei bloodstream forms. We characterized its recombinant protein to investigate the enzymatic differences between GMPRs of T. brucei and its host animals. T. brucei GMPR was distinct in having an insertion of a tandem repeat of the cystathionine β-synthase (CBS) domain, which was absent in mammalian and bacterial GMPRs. The recombinant protein of T. brucei GMPR catalyzed the conversion of GMP to IMP in the presence of NADPH, and showed apparent affinities for both GMP and NADPH different from those of its mammalian counterparts. Interestingly, the addition of monovalent cations such as K+ and NH4+ to the enzymatic reaction increased the GMPR activity of T. brucei, whereas none of the mammalian GMPR's was affected by these cations. The monophosphate form of the purine nucleoside analog ribavirin inhibited T. brucei GMPR activity, though mammalian GMPRs showed no or only a little inhibition by it. These results suggest that the mechanism of the GMPR reaction in T. brucei is distinct from that in the host organisms. Finally, we demonstrated the inhibitory effect of ribavirin on the proliferation of trypanosomes in a dose-dependent manner, suggesting the availability of ribavirin to develop a new therapeutic agent against African trypanosomiasis. PMID:26731263

  20. Novel Characteristics of Trypanosoma brucei Guanosine 5'-monophosphate Reductase Distinct from Host Animals

    PubMed Central

    Kimura, Chihiro; Shinohara, Takahiro; Tomiyama, Ai; Imamura, Akira; Kuwamura, Mitsuru; Nishimura, Kazuhiko; Fujimori, Ko; Shuto, Satoshi; Ishibashi, Osamu; Kubata, Bruno Kilunga; Inui, Takashi

    2016-01-01

    The metabolic pathway of purine nucleotides in parasitic protozoa is a potent drug target for treatment of parasitemia. Guanosine 5’-monophosphate reductase (GMPR), which catalyzes the deamination of guanosine 5’-monophosphate (GMP) to inosine 5’-monophosphate (IMP), plays an important role in the interconversion of purine nucleotides to maintain the intracellular balance of their concentration. However, only a few studies on protozoan GMPR have been reported at present. Herein, we identified the GMPR in Trypanosoma brucei, a causative protozoan parasite of African trypanosomiasis, and found that the GMPR proteins were consistently localized to glycosomes in T. brucei bloodstream forms. We characterized its recombinant protein to investigate the enzymatic differences between GMPRs of T. brucei and its host animals. T. brucei GMPR was distinct in having an insertion of a tandem repeat of the cystathionine β-synthase (CBS) domain, which was absent in mammalian and bacterial GMPRs. The recombinant protein of T. brucei GMPR catalyzed the conversion of GMP to IMP in the presence of NADPH, and showed apparent affinities for both GMP and NADPH different from those of its mammalian counterparts. Interestingly, the addition of monovalent cations such as K+ and NH4+ to the enzymatic reaction increased the GMPR activity of T. brucei, whereas none of the mammalian GMPR’s was affected by these cations. The monophosphate form of the purine nucleoside analog ribavirin inhibited T. brucei GMPR activity, though mammalian GMPRs showed no or only a little inhibition by it. These results suggest that the mechanism of the GMPR reaction in T. brucei is distinct from that in the host organisms. Finally, we demonstrated the inhibitory effect of ribavirin on the proliferation of trypanosomes in a dose-dependent manner, suggesting the availability of ribavirin to develop a new therapeutic agent against African trypanosomiasis. PMID:26731263

  1. X-ray studies of crystalline complexes involving amino acids and peptides. XLIV. Invariant features of supramolecular association and chiral effects in the complexes of arginine and lysine with tartaric acid.

    PubMed

    Selvaraj, M; Thamotharan, S; Roy, Siddhartha; Vijayan, M

    2007-06-01

    The tartaric acid complexes with arginine and lysine exhibit two stoichiometries depending upon the ionization state of the anion. The structures reported here are DL-argininium DL-hydrogen tartrate, bis(L-argininium) L-tartrate, bis(DL-lysinium) DL-tartrate monohydrate, L-lysinium D-hydrogen tartrate and L-lysinium L-hydrogen tartrate. During crystallization, L-lysine preferentially interacts with D-tartaric acid to form a complex when DL-tartaric acid is used in the experiment. The anions and the cations aggregate into separate alternating layers in four of the five complexes. In bis(L-argininium) L-tartrate, the amino acid layers are interconnected by individual tartrate ions which do not interact among themselves. The aggregation of argininium ions in the DL- and the L-arginine complexes is remarkably similar, which is in turn similar to those observed in other dicarboxylic acid complexes of arginine. Thus, argininium ions have a tendency to assume similar patterns of aggregation, which are largely unaffected by a change in the chemistry of partner molecules such as the introduction of hydroxyl groups or a change in chirality or stoichiometry. On the contrary, the lysinium ions exhibit fundamentally different aggregation patterns in the DL-DL complexes on the one hand and L-D and L-L complexes on the other. Interestingly, the pattern in the L-D complex is similar to that in the L-L complex. The lysinium ions in the DL-DL complex exhibit an aggregation pattern similar to those observed in the DL-lysine complexes involving other dicarboxylic acids. Thus, the effect of change in the chirality of a subset of the component complexes could be profound or marginal, in an unpredictable manner. The relevant crystal structures appear to indicate that the preference of L-lysine for D-tartaric acid is perhaps caused by chiral discrimination resulting from the amplification of a small energy difference.

  2. Recipient pretransplant inosine monophosphate dehydrogenase activity in nonmyeloablative hematopoietic cell transplantation.

    PubMed

    Bemer, Meagan J; Risler, Linda J; Phillips, Brian R; Wang, Joanne; Storer, Barry E; Sandmaier, Brenda M; Duan, Haichuan; Raccor, Brianne S; Boeckh, Michael J; McCune, Jeannine S

    2014-10-01

    Mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), inhibits inosine monophosphate dehydrogenase (IMPDH) activity. IMPDH is the rate-limiting enzyme involved in de novo synthesis of guanosine nucleotides and catalyzes the oxidation of inosine 5'-monophosphate to xanthosine 5'-monophosphate (XMP). We developed a highly sensitive liquid chromatography-mass spectrometry method to quantitate XMP concentrations in peripheral blood mononuclear cells (PMNCs) isolated from the recipient pretransplant and used this method to determine IMPDH activity in 86 nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) patients. The incubation procedure and analytical method yielded acceptable within-sample and within-individual variability. Considerable between-individual variability was observed (12.2-fold). Low recipient pretransplant IMPDH activity was associated with increased day +28 donor T cell chimerism, more acute graft-versus-host disease (GVHD), lower neutrophil nadirs, and more cytomegalovirus reactivation but not with chronic GVHD, relapse, nonrelapse mortality, or overall mortality. We conclude that quantitation of the recipient's pretransplant IMPDH activity in PMNC lysate could provide a useful biomarker to evaluate a recipient's sensitivity to MMF. Further trials should be conducted to confirm our findings and to optimize postgrafting immunosuppression in nonmyeloablative HCT recipients.

  3. Recipient pretransplant inosine monophosphate dehydrogenase activity in nonmyeloablative hematopoietic cell transplantation.

    PubMed

    Bemer, Meagan J; Risler, Linda J; Phillips, Brian R; Wang, Joanne; Storer, Barry E; Sandmaier, Brenda M; Duan, Haichuan; Raccor, Brianne S; Boeckh, Michael J; McCune, Jeannine S

    2014-10-01

    Mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), inhibits inosine monophosphate dehydrogenase (IMPDH) activity. IMPDH is the rate-limiting enzyme involved in de novo synthesis of guanosine nucleotides and catalyzes the oxidation of inosine 5'-monophosphate to xanthosine 5'-monophosphate (XMP). We developed a highly sensitive liquid chromatography-mass spectrometry method to quantitate XMP concentrations in peripheral blood mononuclear cells (PMNCs) isolated from the recipient pretransplant and used this method to determine IMPDH activity in 86 nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) patients. The incubation procedure and analytical method yielded acceptable within-sample and within-individual variability. Considerable between-individual variability was observed (12.2-fold). Low recipient pretransplant IMPDH activity was associated with increased day +28 donor T cell chimerism, more acute graft-versus-host disease (GVHD), lower neutrophil nadirs, and more cytomegalovirus reactivation but not with chronic GVHD, relapse, nonrelapse mortality, or overall mortality. We conclude that quantitation of the recipient's pretransplant IMPDH activity in PMNC lysate could provide a useful biomarker to evaluate a recipient's sensitivity to MMF. Further trials should be conducted to confirm our findings and to optimize postgrafting immunosuppression in nonmyeloablative HCT recipients. PMID:24923537

  4. Crystalline, liquid crystalline, and isotropic phases of sodium deoxycholate in water

    SciTech Connect

    Su, Ziyang; Luthra, Suman; Krzyzaniak, Joseph F.; Agra-Kooijman, Dena M.; Kumar, Satyendra; Byrn, Stephen R.; Shalaev, Evgenyi Y.

    2012-09-06

    Sodium deoxycholate (NaDC) is an important example of bile salts, representing systems with complex phase behavior involving both crystalline and mesophase structures. In this study, properties of NaDC-water mixtures were evaluated as a function of composition and temperature via X-ray diffraction with synchrotron (sXRD) and laboratory radiation sources, water sorption, polarized light, hot-stage microscopy, and freezing-point osmometry. Several phases were detected depending on the composition and temperature, including isotropic solution phase, liquid crystalline (LC) phase, crystalline hydrate, and ice. The LC phase was identified as hexagonal structure by sXRD, with up to 14 high-order reflections detected. The crystalline phase was found to be nonstoichiometric hydrate, based on XRD and water sorption data. The phase diagram of NaDC-water system has been refined based on both results of this study and other reports in literature.

  5. Characterization of α-Crystallin-Plasma Membrane Binding*

    PubMed Central

    Cobb, Brian A.; Petrash, J. Mark

    2010-01-01

    α-Crystallin, a large lenticular protein complex made up of two related subunits (αA- and αB-crystallin), is known to associate increasingly with fiber cell plasma membranes with age and/or the onset of cataract. To understand better the binding mechanism, we developed a sensitive membrane binding assay using lens plasma membranes and recombinant human αA- and αB-crystallins conjugated to a small fluorescent tag (Alexa350®). Both αA and αB homopolymer complexes, as well as a reconstituted 3:1 heteromeric complex, bind to lens membranes in a specific, saturable, and partially irreversible manner that is sensitive to both time and temperature. The amount of α-crystallin that binds to the membrane increases under acidic pH conditions and upon removal of exposed intrinsic membrane protein domains but is not affected at high ionic strength, suggesting that α-crystallin binds to the fiber cell plasma membranes mainly through hydrophobic interactions. The binding capacity and affinity for the reconstituted 3:1 heteromeric complex were measured to be 3.45 ± 0.11 ng/μg of membrane and 4.57 ± 0.50 × 10−4 μg−1 of membrane, respectively. The present membrane binding data support the hypothesis that the physical properties of a mixed α-crystallin complex may hold particular relevance for the function of α-crystallin within the lens. PMID:10692476

  6. Liquid Crystalline Materials for Biological Applications

    PubMed Central

    Lowe, Aaron M.; Abbott, Nicholas L.

    2012-01-01

    Liquid crystals have a long history of use as materials that respond to external stimuli (e.g., electrical and optical fields). More recently, a series of investigations have reported the design of liquid crystalline materials that undergo ordering transitions in response to a range of biological interactions, including interactions involving proteins, nucleic acids, viruses, bacteria and mammalian cells. A central challenge underlying the design of liquid crystalline materials for such applications is the tailoring of the interface of the materials so as to couple targeted biological interactions to ordering transitions. This review describes recent progress toward design of interfaces of liquid crystalline materials that are suitable for biological applications. Approaches addressed in this review include the use of lipid assemblies, polymeric membranes containing oligopeptides, cationic surfactant-DNA complexes, peptide-amphiphiles, interfacial protein assemblies and multi-layer polymeric films. PMID:22563142

  7. Crystalline bipyridinium radical complexes and uses thereof

    SciTech Connect

    Fahrenbach, Albert C.; Barnes, Jonathan C.; Li, Hao; Stoddart, J. Fraser; Basuray, Ashish Neil; Sampath, Srinivasan

    2015-09-01

    Described herein are methods of generating 4,4'-bipyridinium radical cations (BIPY.sup..cndot.+), and methods for utilizing the radical-radical interactions between two or more BIPY.sup..cndot.+ radical cations that ensue for the creation of novel materials for applications in nanotechnology. Synthetic methodologies, crystallographic engineering techniques, methods of physical characterization, and end uses are described.

  8. Gas-Phase Conformations and Energetics of Protonated 2^'-DEOXYADENOSINE-5^'-MONOPHOSPHATE and ADENOSINE-5^'-MONOPHOSPHATE: Irmpd Action Spectroscopy and Theoretical Studies

    NASA Astrophysics Data System (ADS)

    Wu, Ranran; Nei, Y.-W.; He, Chenchen; Hamlow, Lucas; Berden, Giel; Oomens, J.; Rodgers, M. T.

    2015-06-01

    Nature uses protonation to alter the structures and reactivities of molecules to facilitate various biological functions and chemical transformations. For example, in nucleobase repair and salvage processes, protonation facilitates nucleobase removal by lowering the activation barrier for glycosidic bond cleavage. Systematic studies of the structures of protonated 2'-deoxyribonucleotides and ribonucleotides may provide insight into the roles protonation plays in altering the nucleobase orientation relative to the glycosidic bond and sugar puckering. In this study, infrared multiple photon dissociation (IRMPD) action spectroscopy experiments in conjunction with electronic structure calculations are performed to probe the effects of protonation on the structures and stabilities of 2^'-deoxyadenosine-5^'-monophosphate (pdAdo) and adenosine-5^'-monophosphate (pAdo). Photodissociation as a function of IR wavelength is measured to generate the IRMPD action spectra. Geometry optimizations and frequency analyses performed at the B3LYP/6-311+G(d,p) level of theory are used to characterize the stable low-energy structures and to generate their linear IR spectra. Single point energy calculations performed at the B3LYP/6-311+G(2d,2p) and MP2(full)/6-311+G(2d,2p) levels of theory provide relative stabilities of the optimized conformations. The structures accessed in the experiments are determined by comparing the calculated linear IR spectra for the stable low-energy conformers computed to the measured IRMPD action spectra. The effects of the 2^'-hydroxyl moiety are elucidated by comparing the structures and IRMPD spectra of [pAdo+H]+ to those of its DNA analogue. Comparisons are also made to the deprotonated forms of these nucleotides and the protonated forms of the analogous nucleosides to elucidate the effects of protonation and the phosphate group on the structures.

  9. Acid-base catalysis in the chemical mechanism of inosine monophosphate dehydrogenase.

    PubMed

    Markham, G D; Bock, C L; Schalk-Hihi, C

    1999-04-01

    Inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the K+-dependent reaction IMP + NAD + H2O --> XMP + NADH + H+ which is the rate-limiting step in guanine nucleotide biosynthesis. The catalytic mechanism of the human type-II IMPDH isozyme has been studied by measurement of the pH dependencies of the normal reaction, of the hydrolysis of 2-chloro-IMP (which yields XMP and Cl- in the absence of NAD), and of inactivation by the affinity label 6-chloro-purine-ribotide (6-Cl-PRT). The pH dependence of the IMPDH reaction shows bell-shaped profiles for kcat and the kcat/Km values for both IMP and NAD, illustrating the involvement of both acidic and basic groups in catalysis. Half-maximal kcat values occur at pH values of 7.2 and 9.8; similar pK values of 6.9 and 9.4 are seen in the kcat/Km profile for NAD. The kcat/Km profile for IMP, which binds first in the predominantly ordered kinetic mechanism, shows pK values of 8.1 and 7.3 for acidic and basic groups, respectively. None of the kinetic pK values correspond to ionizations of the free substrates and thus reflect ionization of the enzyme or enzyme-substrate complexes. The rate of inactivation by 6-Cl-PRT, which modifies the active site sulfhydryl of cysteine-331, increases with pH; the pK of 7.5 reflects the ionization of the sulfhydryl in the E.6-Cl-PRT complex. The pKs of the acids observed in the IMPDH reaction likely also reflect ionization of the cysteine-331 sulfhydryl which adds to C-2 of IMP prior to NAD reduction. The kcat and kcat/Km values for hydrolysis of 2-Cl-IMP show a pK value of 9.9 for a basic group, similar to that seen in the overall reaction, but do not exhibit the ionization of an acidic group. Surprisingly, the rates of 2-Cl-IMP hydrolysis and of inactivation by 6-Cl-PRT are not stimulated by K+, in contrast to the >100-fold K+ activation of the IMPDH reaction. Apparently the enigmatic role of K+ lies in the NAD(H)-dependent segment of the IMPDH reaction. To evaluate the importance of

  10. Liquid crystalline composites containing phyllosilicates

    DOEpatents

    Chaiko; David J.

    2007-05-08

    The present invention provides barrier films having reduced gas permeability for use in packaging and coating applications. The barrier films comprise an anisotropic liquid crystalline composite layer formed from phyllosilicate-polymer compositions. Phyllosilicate-polymer liquid crystalline compositions of the present invention can contain a high percentage of phyllosilicate while remaining transparent. Because of the ordering of the particles in the liquid crystalline composite, barrier films comprising liquid crystalline composites are particularly useful as barriers to gas transport.

  11. Crystalline titanate catalyst supports

    DOEpatents

    Anthony, Rayford G.; Dosch, Robert G.

    1993-01-01

    A series of new crystalline titanates (CT) are shown to have considerable potential as catalyst supports. For Pd supported catalyst, the catalytic activity for pyrene hydrogenation was substantially different depending on the type of CT, and one was substantially more active than Pd on hydrous titanium oxide (HTO). For 1-hexene hydrogenation the activities of the new CTs were approximately the same as for the hydrous metal oxide supports.

  12. Crystalline titanate catalyst supports

    DOEpatents

    Anthony, R.G.; Dosch, R.G.

    1993-01-05

    A series of new crystalline titanates (CT) are shown to have considerable potential as catalyst supports. For Pd supported catalyst, the catalytic activity for pyrene hydrogenation was substantially different depending on the type of CT, and one was substantially more active than Pd on hydrous titanium oxide (HTO). For 1-hexene hydrogenation the activities of the new CTs were approximately the same as for the hydrous metal oxide supports.

  13. Subunit exchange demonstrates a differential chaperone activity of calf alpha-crystallin toward beta LOW- and individual gamma-crystallins.

    PubMed

    Putilina, Tatiana; Skouri-Panet, Fériel; Prat, Karine; Lubsen, Nicolette H; Tardieu, Annette

    2003-04-18

    complexes involved various binding sites. The changes in subunit exchange associated with the chaperone properties of alpha-crystallins toward the other lens crystallins demonstrate the dynamic character of the heat-activated alpha-crystallin structure.

  14. Fluorescent Sensing of Guanine and Guanosine Monophosphate with Conjugated Receptors Incorporating Aniline and Naphthyridine Moieties.

    PubMed

    Lu, Shao-Hung; Phang, Riping; Fang, Jim-Min

    2016-04-15

    Ethyne-linked naphthyridine-aniline conjugated molecules are selective sensors of decylguanine in dichloromethane and guanosine monophosphate in water (Kass = 16,000 M(-1)). The 2-acetamido-1,8-naphthyridine moiety binds with guanine in a DAA-ADD triply hydrogen-bonded motif. The aniline moiety enhances an electron-donating effect, and the substituent is tuned to attain extra hydrogen bonds, π-π stacking, and electrostatic interactions. The proposed binding modes are supported by a Job plot, ESI-MS, (1)H NMR, UV-vis, and fluorescence spectral analyses.

  15. Histone deacetylases 6 increases the cyclic adenosine monophosphate level and promotes renal cyst growth.

    PubMed

    Wu, Ming; Mei, Changlin

    2016-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by abnormal enhanced cell proliferation and fluid secretion, which are triggered by increased levels of cyclic adenosine monophosphate (cAMP). Cebotaru et al. showed that a HDAC6 inhibitor reduced the cAMP level and inhibited cyst formation in Pkd1 knockout mice, which may become a new potential therapeutic agent for ADPKD. This study also raised several intriguing questions that might advance our understanding of the molecular pathogenesis of ADPKD. PMID:27312442

  16. Investigations of structural, dielectric and optical properties on silicon ion irradiated glycine monophosphate single crystals

    NASA Astrophysics Data System (ADS)

    Kanagasekaran, T.; Mythili, P.; Bhagavannarayana, G.; Kanjilal, D.; Gopalakrishnan, R.

    2009-08-01

    The 50 MeV silicon ion irradiation induced modifications on structural, optical and dielectric properties of solution grown glycine monophosphate (GMP) crystals were studied. The high-resolution X-ray diffraction study shows the unaltered value of integrated intensity on irradiation. The dielectric constant as a function of frequency and temperature was studied. UV-visible studies reveal the decrease in bandgap values on irradiation and presence of F-centers. The fluorescence spectrum shows the existence of some energy levels, which remains unaffected after irradiation. The scanning electron micrographs reveal the defects formed on irradiation.

  17. Pre-eruptive rejuvenations of crystalline mush by reservoir heating: the case of trachy-dacitic lavas of Quetrupillán Volcanic Complex, Chile (39º30' lat. S)

    NASA Astrophysics Data System (ADS)

    Brahm, R.; Parada, M. Á.; Morgado, E. E.; Contreras, C.

    2015-12-01

    The Southern Volcanic Zone of the Andes is dominated by mainly basaltic to andesitic products, as is the case of the Villarrica 2015 eruption. An exception is the case of the nearby Quetrupillán Volcanic Complex (QVC). The QVC forms part of the NW-SE Villarrica-Quetrupillán-Lanín active volcanic chain and contains products of mainly trachy-dacitic composition that differs from the basaltic and basaltic-andesite composition of the neighboring stratovolcanoes. The studied Holocene QVC trachy-dacites exhibit similar geochemical, mineralogical features. They are crystal-poor (<12% phenocrysts) with phenocrysts occurring as isolated crystals or forming crystal clots within a glass-rich groundmass. Two groups of plagioclase phenocrysts were found: Group 1 plagioclases are commonly associated with pyroxene in crystal clots and with oscillatory zoning of An40-50, and Group 2 plagioclases occur as isolated crystals of variable composition (An70-85), with rims of similar composition to Group 1. Some Group 2 crystals have cores with compositions similar to the rims with resorption features. Clinopyroxenes within clots have compositions of En40-46Fs11-21Wo39-43 similar to the isolated clinopyroxenes. Orthopyroxene phenocrysts have composition of En36-68Fs15-34Wo03-04. Microphenocrysts of magnetite-ilmenite pairs (Mt14-36-Il90-94) were identified. Pyroxene phenocrysts are in disequilibrium with the whole-rock composition, suggesting that they are antecrysts. Two-pyroxene thermometry gives temperatures of 911-980ºC, while the Mt-Il equilibrium gives higher temperatures of 963-1114ºC, for the later stages of lava crystallization. The presence of a crystalline mush is suggested by the abundance of crystal clots in disequilibrium with the host rock composition whose calculated formation conditions of 0.5-1.5 kbar, 950-990ºC and 2.1-3.1 wt% of H2O, were obtained from a Rhyolite-MELTS simulation. Rejuvenation of a crystal mush by reservoir heating events is suggested due to

  18. Viral keratitis-inhibitory effect of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate.

    PubMed

    Sidwell, R W; Allen, L B; Huffman, J H; Revankar, G R; Robins, R K; Tolman, R L

    1975-10-01

    Topical application of 9-beta-d-arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP) significantly inhibited the development of keratitis induced by types 1 and 2 herpes simplex virus and vaccinia virus in the eyes of rabbits. Parameters for evaluation of efficacy were infectivity (corneal opacity, lesion size, and type), Draize (erythema, conjunctival swelling, and discharge), and reduction in titer of recoverable virus from the eye. When the relative efficacy of the related compounds 9-beta-d-arabinofuranosyladenine (ara-A), ara-A 5'-monophosphate (ara-AMP), and ara-Hx was determined against type 1 herpes simplex virus in a parallel experiment, the more water-soluble compounds (ara-HxMP, ara-AMP) were the most effective. The relative efficacy of ara-A was also determined against type 2 herpes and vaccinia virus-induced keratitis. Mortality in rabbits due to central nervous system involvement caused by types 1 and 2 herpes simplex virus was inhibited. Ara-HxMP was not discernibly toxic to the eye at concentrations of at least 20%; efficacy was still discernible with a 0.1% solution.

  19. THE EFFECT OF CHLORINATION OF NUCLEOTIDE BASES ON THE CONFORMATIONAL PROPERTIES OF THYMIDINE MONOPHOSPHATE.

    PubMed

    Mukhina, T M; Nikolaienko, T Yu

    2015-01-01

    Recent studies on Escherichia coli bacteria cultivation, in which DNA thymine was replaced with 5-chlorouracil have refreshed the problem of understanding the changes to physical properties of DNA monomers resultant from chemical modifications. These studies have shown that the replacement did not affect the normal activities and division of the bacteria, but has significantly reduced its life span. In this paper a comparative analysis was carried out by the methods of computational experiment of a set of 687 possible conformers of natural monomeric DNA unit (2'-deoxyribonucleotide thymidine monophosphate) and 660 conformers of 5-chloro-2'-deoxyuridine monophosphate - a similar molecules in which the natural nitrogenous base thymine is substituted with 5-chlorouracil. Structures of stable conformers of the modified deoxyribonucleotide have been obtained and physical factors, which determine their variation from the conformers of the unmodified molecule have been analyzed. A comparative analysis of the elastic properties of conformers of investigated molecules and non-covalent interactions present in them was conducted. The results can be usedfor planning experiments on synthesis of artficial DNA suitable for incorporation into living organisms. PMID:26255348

  20. THE DIFFUSION COEFFICIENT OF CRYSTALLINE TRYPSIN

    PubMed Central

    Scherp, Henry W.

    1933-01-01

    The diffusion coefficient of crystalline trypsin in 0.5 saturated magnesium sulfate at 5°C. is 0.020 ±0.001 cm.2 per day, corresponding to a molecular radius of 2.6 x 10–7 cm. The rate of diffusion of the proteolytic activity is the same as that of the protein nitrogen, indicating that these two properties are held together in chemical combination and not in the form of an adsorption complex. PMID:19872740

  1. An assay for intermolecular exchange of alpha crystallin

    NASA Technical Reports Server (NTRS)

    Gopalakrishnan, S.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    An affinity column of alpha crystallin linked to cyanogen bromide-activated Sepharose was developed to study the exchange of alpha subunits. Alpha crystallin bound to the Sepharose-alpha complex was dissociated with 8 mol/l urea, followed by quantitation using high-performance reverse-phase liquid chromatography. The time course of binding at 37 degrees C showed a hyperbolic binding pattern reaching equilibrium between 6-18 hr. Under these conditions, binding of beta and gamma crystallins to the same matrix was less than 10% of the alpha values, as was binding of alpha to glycine-coupled Sepharose. This assay was used to demonstrate changes in the subunit exchange of alpha crystallins present in high molecular weight versus lower molecular weight aggregates of the human lens. These results show that this binding procedure was a specific reproducible assay that might be used to study intermolecular interactions of the alpha crystallins.

  2. Cubozoan crystallins: evidence for convergent evolution of pax regulatory sequences.

    PubMed

    Kozmik, Zbynek; Swamynathan, Shivalingappa K; Ruzickova, Jana; Jonasova, Kristyna; Paces, Vaclav; Vlcek, Cestmir; Piatigorsky, Joram

    2008-01-01

    Cnidaria is the earliest-branching metazoan phylum containing a well-developed, lens-containing visual system located on specialized sensory structures called rhopalia. Each rhopalium in a cubozoan jellyfish Tripedalia cystophora has a large and a small complex, camera-type eye with a cellular lens containing distinct families of crystallins. Here, we have characterized J2-crystallin and its gene in T. cystophora. The J2-crystallin gene is composed of a single exon and encodes a 157-amino acid cytoplasmic protein with no apparent homology to known proteins from other species. The non-lens expression of J2-crystallin suggests nonoptical as well as crystallin functions consistent with the gene-sharing strategy that has been used during evolution of lens crystallins in other invertebrates and vertebrates. Although nonfunctional in transfected mammalian lens cells, the J2-crystallin promoter is activated by the jellyfish paired domain transcription factor PaxB in co-transfection tests via binding to three paired domain sites. PaxB paired domain-binding sites were also identified in the PaxB-regulated promoters of the J1A- and J1B-crystallin genes, which are not homologous to the J2-crystallin gene. Taken together with previous studies on the regulation of the diverse crystallin genes, the present report strongly supports the idea that crystallin recruitment of multifunctional proteins was driven by convergent changes involving Pax (as well as other transcription factors) in the promoters of nonhomologous genes within and between species as well as within gene families. PMID:18184357

  3. Liquid Crystalline Microemulsions

    NASA Astrophysics Data System (ADS)

    Huang, Chien-Yueh; Petschek, Rolfe G.

    2000-03-01

    If an isotropic component of an emulsion is replaced by one having liquid crystalline (e.g. nematic) order the equilibrium behavior can change dramatically. There are long range enthalpic effects which can result in either repulsive or attractive interactions between the surfaces of an emulsion and entropic effects which generally result in an attractive interaction between these surfaces. We review briefly the possibility of stable blue-phase like microemulsions in mixtures of chiral nematics, appropriate surfactants and an incompatible isotropic solvent. We discuss the entropic effects in a lamellar phase, including the effects of changes in elastic constants and surface-nematic coupling. The effects of fluctuations on blue phases will be briefly discussed.

  4. Liquid crystalline polymers

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The remarkable mechanical properties and thermal stability of fibers fabricated from liquid crystalline polymers (LCPs) have led to the use of these materials in structural applications where weight savings are critical. Advances in processing of LCPs could permit the incorporation of these polymers into other than uniaxial designs and extend their utility into new areas such as nonlinear optical devices. However, the unique feature of LCPs (intrinsic orientation order) is itself problematic, and current understanding of processing with control of orientation falls short of allowing manipulation of macroscopic orientation (except for the case of uniaxial fibers). The current and desirable characteristics of LCPs are reviewed and specific problems are identified along with issues that must be addressed so that advances in the use of these unique polymers can be expedited.

  5. Multiple Decay Mechanisms and 2D-UV Spectroscopic Fingerprints of Singlet Excited Solvated Adenine-Uracil Monophosphate.

    PubMed

    Li, Quansong; Giussani, Angelo; Segarra-Martí, Javier; Nenov, Artur; Rivalta, Ivan; Voityuk, Alexander A; Mukamel, Shaul; Roca-Sanjuán, Daniel; Garavelli, Marco; Blancafort, Lluís

    2016-05-23

    The decay channels of singlet excited adenine uracil monophosphate (ApU) in water are studied with CASPT2//CASSCF:MM potential energy calculations and simulation of the 2D-UV spectroscopic fingerprints with the aim of elucidating the role of the different electronic states of the stacked conformer in the excited state dynamics. The adenine (1) La state can decay without a barrier to a conical intersection with the ground state. In contrast, the adenine (1) Lb and uracil S(U) states have minima that are separated from the intersections by sizeable barriers. Depending on the backbone conformation, the CT state can undergo inter-base hydrogen transfer and decay to the ground state through a conical intersection, or it can yield a long-lived minimum stabilized by a hydrogen bond between the two ribose rings. This suggests that the (1) Lb , S(U) and CT states of the stacked conformer may all contribute to the experimental lifetimes of 18 and 240 ps. We have also simulated the time evolution of the 2D-UV spectra and provide the specific fingerprint of each species in a recommended probe window between 25 000 and 38 000 cm(-1) in which decongested, clearly distinguishable spectra can be obtained. This is expected to allow the mechanistic scenarios to be discerned in the near future with the help of the corresponding experiments. Our results reveal the complexity of the photophysics of the relatively small ApU system, and the potential of 2D-UV spectroscopy to disentangle the photophysics of multichromophoric systems. PMID:27113273

  6. The pH dependence of the thermodynamics of the interaction of 3'-cytidine monophosphate with ribonuclease A.

    PubMed

    Flogel, M; Biltonen, R L

    1975-06-17

    The apparent free energy (deltaGapp) and enthalpy changes (deltaHB) associated with the interaction of 3'-cytosine monophosphate (3'-CMP) and ribonuclease A (RNase) are reported for the pH range 4--9, T = 25 degrees, mu = 0.05. The pH dependence of deltaGapp and deltaHB has been interpreted in terms of coupled ionization of histidine residues 12, 48, and 119, assuming that only the dianionic form of the inhibitor is bound. The results of this analysis are consistent with the calorimetric and potentiometric titration results for the free enzyme and its 3'-CMP complex reported in the previous paper (M. Flogel and R. L. Biltonen ((1975), Biochemistry, preceding paper in this issue). This analysis allows the calculation of the thermodynamic quantities associated with hypothetical but clearly defined reactions (e.g., the reaction of the dianionic inhibitor with the completely protonated enzyme). It is concluded that the primary thermodynamic driving forces for the reaction are van der Waals interactions between the riboside moiety and the protein fabric and electrostatic interaction between the negatively charged phosphate group of the inhibitor and the positively charged histidine residues at the binding locus. It is also suggested that the binding reaction is weakly coupled (approximately to 0.5 kcal/mol) with a conformational change of the protein associated with protonation of residue 48. These results are consistent with the model originally proposed by G. G. Hammes ((1968), Adv. Protein Chem. 23, 1) and lend additional quantitative detail to the nature of the reaction.

  7. A Novel Function for the NTN Hydrolase Fold Demonstrated by the Structure of an Archeal Inosine Monophosphate Cyclohydrolase†,‡

    PubMed Central

    Kang, You-Na; Tran, Anh; White, Robert H.; Ealick, Steven E.

    2008-01-01

    Inosine 5′-monophosphate (IMP) cyclohydrolase catalyzes the cyclization of 5-formaminoimidazole-4-carboxamide ribonucleotide (FAICAR) to IMP in the final step of de novo purine biosynthesis. Two major types of this enzyme have been discovered to date: PurH in Bacteria and Eukarya, and PurO in Archaea. The structure of the MTH1020 gene product from Methanothermobacter thermoautotrophicus was previously solved without functional annotation but shows high amino acid sequence similarity to other PurOs. We determined the crystal structure of the MTH1020 gene product in complex with either IMP or 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) at 2.0 Å and 2.6 Å resolution, respectively. Based on the sequence analysis, ligand-bound structures, and biochemical data, MTH1020 is confirmed as an archaeal IMP cyclohydrolase, thus designated as MthPurO. MthPurO has a four-layered αββα core structure, showing an N-terminal nucleophile (NTN) hydrolase fold. The active site is located at the deep pocket between two central β-sheets and contains residues strictly conserved within PurOs. Comparisons of the two types of IMP cyclohydrolase, PurO and PurH, revealed that there are no similarities in sequence, structure, or the active site architecture, suggesting that they are evolutionarily not related to each other. The MjR31K mutant of PurO from Methanocaldococcus jannaschii showed 76% decreased activity and MjE102Q mutation completely abolished enzymatic activity, suggesting that these highly conserved residues play critical roles in catalysis. Interestingly, green fluorescent protein (GFP), which has no structural homology to either PurO or PurH but catalyzes a similar intramolecular cyclohydrolase reaction required for chromophore maturation, utilizes Arg96 and Glu222 in a mechanism analogous to that of PurO. PMID:17407260

  8. Multiple Decay Mechanisms and 2D-UV Spectroscopic Fingerprints of Singlet Excited Solvated Adenine-Uracil Monophosphate.

    PubMed

    Li, Quansong; Giussani, Angelo; Segarra-Martí, Javier; Nenov, Artur; Rivalta, Ivan; Voityuk, Alexander A; Mukamel, Shaul; Roca-Sanjuán, Daniel; Garavelli, Marco; Blancafort, Lluís

    2016-05-23

    The decay channels of singlet excited adenine uracil monophosphate (ApU) in water are studied with CASPT2//CASSCF:MM potential energy calculations and simulation of the 2D-UV spectroscopic fingerprints with the aim of elucidating the role of the different electronic states of the stacked conformer in the excited state dynamics. The adenine (1) La state can decay without a barrier to a conical intersection with the ground state. In contrast, the adenine (1) Lb and uracil S(U) states have minima that are separated from the intersections by sizeable barriers. Depending on the backbone conformation, the CT state can undergo inter-base hydrogen transfer and decay to the ground state through a conical intersection, or it can yield a long-lived minimum stabilized by a hydrogen bond between the two ribose rings. This suggests that the (1) Lb , S(U) and CT states of the stacked conformer may all contribute to the experimental lifetimes of 18 and 240 ps. We have also simulated the time evolution of the 2D-UV spectra and provide the specific fingerprint of each species in a recommended probe window between 25 000 and 38 000 cm(-1) in which decongested, clearly distinguishable spectra can be obtained. This is expected to allow the mechanistic scenarios to be discerned in the near future with the help of the corresponding experiments. Our results reveal the complexity of the photophysics of the relatively small ApU system, and the potential of 2D-UV spectroscopy to disentangle the photophysics of multichromophoric systems.

  9. Multiple Decay Mechanisms and 2D‐UV Spectroscopic Fingerprints of Singlet Excited Solvated Adenine‐Uracil Monophosphate

    PubMed Central

    Li, Quansong; Giussani, Angelo; Segarra‐Martí, Javier; Nenov, Artur; Rivalta, Ivan; Voityuk, Alexander A.; Mukamel, Shaul; Roca‐Sanjuán, Daniel

    2016-01-01

    Abstract The decay channels of singlet excited adenine uracil monophosphate (ApU) in water are studied with CASPT2//CASSCF:MM potential energy calculations and simulation of the 2D‐UV spectroscopic fingerprints with the aim of elucidating the role of the different electronic states of the stacked conformer in the excited state dynamics. The adenine 1La state can decay without a barrier to a conical intersection with the ground state. In contrast, the adenine 1Lb and uracil S(U) states have minima that are separated from the intersections by sizeable barriers. Depending on the backbone conformation, the CT state can undergo inter‐base hydrogen transfer and decay to the ground state through a conical intersection, or it can yield a long‐lived minimum stabilized by a hydrogen bond between the two ribose rings. This suggests that the 1Lb, S(U) and CT states of the stacked conformer may all contribute to the experimental lifetimes of 18 and 240 ps. We have also simulated the time evolution of the 2D‐UV spectra and provide the specific fingerprint of each species in a recommended probe window between 25 000 and 38 000 cm−1 in which decongested, clearly distinguishable spectra can be obtained. This is expected to allow the mechanistic scenarios to be discerned in the near future with the help of the corresponding experiments. Our results reveal the complexity of the photophysics of the relatively small ApU system, and the potential of 2D‐UV spectroscopy to disentangle the photophysics of multichromophoric systems. PMID:27113273

  10. [Representation and mathematical analysis of human crystalline lens].

    PubMed

    Tălu, Stefan; Giovanzana, Stefano; Tălu, Mihai

    2011-01-01

    The surface of human crystalline lens can be described and analyzed using mathematical models based on parametric representations, used in biomechanical studies and 3D solid modeling of the lens. The mathematical models used in lens biomechanics allow the study and the behavior of crystalline lens on variables and complex dynamic loads. Also, the lens biomechanics has the potential to improve the results in the development of intraocular lenses and cataract surgery. The paper presents the most representative mathematical models currently used for the modeling of human crystalline lens, both optically and biomechanically.

  11. TAOK3 Phosphorylates the Methylenecyclopropane Nucleoside MBX 2168 to its Monophosphate

    PubMed Central

    Komazin-Meredith, Gloria; Cardinale, Steven C.; Comeau, Katelyn; Magalhaes, Kevin J.; Hartline, Caroll B.; Williams, John D.; Opperman, Timothy J.; Prichard, Mark N.; Bowlin, Terry L.

    2015-01-01

    Monohydroxymethyl methylenecyclopropane nucleosides (MCPNs) with ether or thioether substituents at the 6-position show promise as broad-spectrum herpes virus inhibitors. Their proposed mechanism of action involves sequential phosphorylation to a triphosphate, which can then inhibit viral DNA polymerase. The inhibition of herpes simplex virus (HSV) by these compounds is not dependent on the viral thymidine kinase (TK), which is known to phosphorylate acyclovir (ACV), a standard treatment for HSV infections. Previous studies on the mechanism of action of these compounds against human cytomegalovirus (HCMV) implicated a host kinase in addition to HCMV UL97 kinase in performing the initial phosphorylation. After first eliminating other candidate HSV-1 encoded kinases (UL13 and US3) as well as potential host nucleoside kinases, using activity-based fractionation, we have now identified the host serine-threonine protein kinase TAOK3 as the kinase responsible for transforming the representative monohydroxymethyl MCPN analog MBX 2168 to its monophosphate. PMID:25857706

  12. Structural determinants for the inhibitory ligands of orotidine-5′-monophosphate decarboxylase

    SciTech Connect

    Meza-Avina, Maria Elena; Wei, Lianhu; Liu, Yan; Poduch, Ewa; Bello, Angelica M.; Mishra, Ram K.; Pai, Emil F.; Kotra, Lakshmi P.

    2010-06-14

    In recent years, orotidine-5{prime}-monophosphate decarboxylase (ODCase) has gained renewed attention as a drug target. As a part of continuing efforts to design novel inhibitors of ODCase, we undertook a comprehensive study of potent, structurally diverse ligands of ODCase and analyzed their structural interactions in the active site of ODCase. These ligands comprise of pyrazole or pyrimidine nucleotides including the mononucleotide derivatives of pyrazofurin, barbiturate ribonucleoside, and 5-cyanouridine, as well as, in a computational approach, 1,4-dihydropyridine-based non-nucleoside inhibitors such as nifedipine and nimodipine. All these ligands bind in the active site of ODCase exhibiting distinct interactions paving the way to design novel inhibitors against this interesting enzyme. We propose an empirical model for the ligand structure for rational modifications in new drug design and potentially new lead structures.

  13. Adenosine monophosphate deaminase 3 activation shortens erythrocyte half-life and provides malaria resistance in mice.

    PubMed

    Hortle, Elinor; Nijagal, Brunda; Bauer, Denis C; Jensen, Lora M; Ahn, Seong Beom; Cockburn, Ian A; Lampkin, Shelley; Tull, Dedreia; McConville, Malcolm J; McMorran, Brendan J; Foote, Simon J; Burgio, Gaetan

    2016-09-01

    The factors that determine red blood cell (RBC) lifespan and the rate of RBC aging have not been fully elucidated. In several genetic conditions, including sickle cell disease, thalassemia, and G6PD deficiency, erythrocyte lifespan is significantly shortened. Many of these diseases are also associated with protection from severe malaria, suggesting a role for accelerated RBC senescence and clearance in malaria resistance. Here, we report a novel, N-ethyl-N-nitrosourea-induced mutation that causes a gain of function in adenosine 5'-monophosphate deaminase (AMPD3). Mice carrying the mutation exhibit rapid RBC turnover, with increased erythropoiesis, dramatically shortened RBC lifespan, and signs of increased RBC senescence/eryptosis, suggesting a key role for AMPD3 in determining RBC half-life. Mice were also found to be resistant to infection with the rodent malaria Plasmodium chabaudi. We propose that resistance to P. chabaudi is mediated by increased RBC turnover and higher rates of erythropoiesis during infection. PMID:27465915

  14. Adenosine 3',5'-monophosphate waves in dictyostelium discoideum: a demonstration by isotope dilution-fluorography

    SciTech Connect

    Tomchik, K.J.; Devreotes, P.N.

    1981-04-24

    The distribution of adenosine 3',5'-monophosphate (cyclic AMP) in fields of aggregating amoebae of Dictyostelium discoidenum was examined by a novel isotope dilution-fluorographic technique. Cellular cyclic AMP was visualized by its competition with exogenous /sup 3/H-labeled cyclic AMP for high-affinity binding sites on protein kinase immobilized on a Millipore filter used to blot the monolayer. The cyclic AMP was distributed in spiral or concentric circular wave patterns which centered on the foci of the aggregations. These patterns were correlated with those of cell shape change that propagate through the monolayers. These observations support the hypothesis that the aggregation process in Dictyostelium is mediated by the periodic relay of cyclic AMP signals and suggest a simple scheme for the dynamics of the aggregation process.

  15. Increased riboflavin production by manipulation of inosine 5'-monophosphate dehydrogenase in Ashbya gossypii.

    PubMed

    Buey, Rubén M; Ledesma-Amaro, Rodrigo; Balsera, Mónica; de Pereda, José María; Revuelta, José Luis

    2015-11-01

    Guanine nucleotides are the precursors of essential biomolecules including nucleic acids and vitamins such as riboflavin. The enzyme inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the ratelimiting step in the guanine nucleotide de novo biosynthetic pathway and plays a key role in controlling the cellular nucleotide pools. Thus, IMPDH is an important metabolic bottleneck in the guanine nucleotide synthesis, susceptible of manipulation by means of metabolic engineering approaches. Herein, we report the functional and structural characterization of the IMPDH enzyme from the industrial fungus Ashbya gossypii. Our data show that the overexpression of the IMPDH gene increases the metabolic flux through the guanine pathway and ultimately enhances 40 % riboflavin production with respect to the wild type. Also, IMPDH disruption results in a 100-fold increase of inosine excretion to the culture media. Our results contribute to the developing metabolic engineering toolbox aiming at improving the production of metabolites with biotechnological interest in A. gossypii. PMID:26150243

  16. TAOK3 phosphorylates the methylenecyclopropane nucleoside MBX 2168 to its monophosphate.

    PubMed

    Komazin-Meredith, Gloria; Cardinale, Steven C; Comeau, Katelyn; Magalhaes, Kevin J; Hartline, Caroll B; Williams, John D; Opperman, Timothy J; Prichard, Mark N; Bowlin, Terry L

    2015-07-01

    Monohydroxymethyl methylenecyclopropane nucleosides (MCPNs) with ether or thioether substituents at the 6-position show promise as broad-spectrum herpes virus inhibitors. Their proposed mechanism of action involves sequential phosphorylation to a triphosphate, which can then inhibit viral DNA polymerase. The inhibition of herpes simplex virus (HSV) by these compounds is not dependent on the viral thymidine kinase (TK), which is known to phosphorylate acyclovir (ACV), a standard treatment for HSV infections. Previous studies on the mechanism of action of these compounds against human cytomegalovirus (HCMV) implicated a host kinase in addition to HCMV UL97 kinase in performing the initial phosphorylation. After first eliminating other candidate HSV-1 encoded kinases (UL13 and US3) as well as potential host nucleoside kinases, using activity-based fractionation, we have now identified the host serine-threonine protein kinase TAOK3 as the kinase responsible for transforming the representative monohydroxymethyl MCPN analog MBX 2168 to its monophosphate. PMID:25857706

  17. Repurposing cryptosporidium inosine 5'-monophosphate dehydrogenase inhibitors as potential antibacterial agents.

    PubMed

    Mandapati, Kavitha; Gorla, Suresh Kumar; House, Amanda L; McKenney, Elizabeth S; Zhang, Minjia; Rao, Suraj Nagendra; Gollapalli, Deviprasad R; Mann, Barbara J; Goldberg, Joanna B; Cuny, Gregory D; Glomski, Ian J; Hedstrom, Lizbeth

    2014-08-14

    Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the pivotal step in guanine nucleotide biosynthesis. IMPDH is a target for immunosuppressive, antiviral, and anticancer drugs, but, as of yet, has not been exploited for antimicrobial therapy. We have previously reported potent inhibitors of IMPDH from the protozoan parasite Cryptosporidium parvum (CpIMPDH). Many pathogenic bacteria, including Bacillus anthracis, Staphylococcus aureus, and Listeria monocytogenes, contain IMPDHs that should also be inhibited by these compounds. Herein, we present the structure-activity relationships for the inhibition of B. anthracis IMPDH (BaIMPDH) and antibacterial activity of 140 compounds from five structurally distinct compound series. Many potent inhibitors of BaIMPDH were identified (78% with IC50 ≤ 1 μM). Four compounds had minimum inhibitory concentrations (MIC) of less than 2 μM against B. anthracis Sterne 770. These compounds also displayed antibacterial activity against S. aureus and L. monocytogenes. PMID:25147601

  18. Adsorption of nucleotides on biomimetic apatite: The case of adenosine 5‧ monophosphate (AMP)

    NASA Astrophysics Data System (ADS)

    Hammami, K.; Feki, H. El; Marsan, O.; Drouet, C.

    2015-10-01

    This work investigates the interaction between the nucleotide adenosine 5‧ monophosphate molecule (AMP) and a biomimetic nanocrystalline carbonated apatite as a model for bone mineral. The analogy of the apatite phase used in this work with biological apatite was first pointed out by complementary techniques. AMP adsorption isotherms were then investigated. Obtained data were fitted to a Sips isotherm with an exponent greater than one suggesting positive cooperativity among adsorbed molecules. The data were compared to a previous study relative to the adsorption of another nucleotide, cytidine monophosphate (CMP) onto a similar substrate, evidencing some effect of the chemical nature of the nucleic base. An enhanced adsorption was observed under acidic (pH 6) conditions as opposed to pH 7.4, which parallels the case of DNA adsorption on biomimetic apatite. An estimated standard Gibbs free energy associated to the adsorption process (ΔG°ads ≅ -22 kJ/mol) intermediate between "physisorption" and "chemisorption" was found. The analysis of the solids after adsorption pointed to the preservation of the main characteristics of the apatite substrate but shifts or enhancements of Raman bands attributed to AMP showed the existence of chemical interactions involving both the phosphate and adenine parts of AMP. This contribution adds to the works conducted in view of better understanding the interaction of DNA/RNA and their constitutive nucleotides and the surface of biomimetic apatites. It could prove helpful in disciplines such as bone diagenesis (DNA/apatite interface in aged bones) or nanomedicine (setup of DNA- or RNA-loaded apatite systems). Also, the adsorption of nucleic acids on minerals like apatites could have played a role in the preservation of such biomolecules in the varying conditions known to exist at the origin of life on Earth, underlining the importance of dedicated adsorption studies.

  19. Mutation of archaeal isopentenyl phosphate kinase highlights mechanism and guides phosphorylation of additional isoprenoid monophosphates.

    PubMed

    Dellas, Nikki; Noel, Joseph P

    2010-06-18

    The biosynthesis of isopentenyl diphosphate (IPP) from either the mevalonate (MVA) or the 1-deoxy-d-xylulose 5-phosphate (DXP) pathway provides the key metabolite for primary and secondary isoprenoid biosynthesis. Isoprenoid metabolism plays crucial roles in membrane stability, steroid biosynthesis, vitamin production, protein localization, defense and communication, photoprotection, sugar transport, and glycoprotein biosynthesis. Recently, an alternative branch of the MVA pathway was discovered in the archaeon Methanocaldococcus jannaschii involving a small molecule kinase, isopentenyl phosphate kinase (IPK). IPK belongs to the amino acid kinase (AAK) superfamily. In vitro, IPK phosphorylates isopentenyl monophosphate (IP) in an ATP and Mg(2+)-dependent reaction producing IPP. Here, we describe crystal structures of IPK from M. jannaschii refined to nominal resolutions of 2.0-2.8 A. Notably, an active site histidine residue (His60) forms a hydrogen bond with the terminal phosphate of both substrate and product. This His residue serves as a marker for a subset of the AAK family that catalyzes phosphorylation of phosphate or phosphonate functional groups; the larger family includes carboxyl-directed kinases, which lack this active site residue. Using steady-state kinetic analysis of H60A, H60N, and H60Q mutants, the protonated form of the Nepsilon(2) nitrogen of His60 was shown to be essential for catalysis, most likely through hydrogen bond stabilization of the transition state accompanying transphosphorylation. Moreover, the structures served as the starting point for the engineering of IPK mutants capable of the chemoenzymatic synthesis of longer chain isoprenoid diphosphates from monophosphate precursors. PMID:20392112

  20. In Search of Enzymes with a Role in 3', 5'-Cyclic Guanosine Monophosphate Metabolism in Plants.

    PubMed

    Gross, Inonge; Durner, Jörg

    2016-01-01

    In plants, nitric oxide (NO)-mediated 3', 5'-cyclic guanosine monophosphate (cGMP) synthesis plays an important role during pathogenic stress response, stomata closure upon osmotic stress, the development of adventitious roots and transcript regulation. The NO-cGMP dependent pathway is well characterized in mammals. The binding of NO to soluble guanylate cyclase enzymes (GCs) initiates the synthesis of cGMP from guanosine triphosphate. The produced cGMP alters various cellular responses, such as the function of protein kinase activity, cyclic nucleotide gated ion channels and cGMP-regulated phosphodiesterases. The signal generated by the second messenger is terminated by 3', 5'-cyclic nucleotide phosphodiesterase (PDEs) enzymes that hydrolyze cGMP to a non-cyclic 5'-guanosine monophosphate. To date, no homologues of mammalian cGMP-synthesizing and degrading enzymes have been found in higher plants. In the last decade, six receptor proteins from Arabidopsis thaliana have been reported to have guanylate cyclase activity in vitro. Of the six receptors, one was shown to be a NO dependent guanylate cyclase enzyme (NOGC1). However, the role of these proteins in planta remains to be elucidated. Enzymes involved in the degradation of cGMP remain elusive, albeit, PDE activity has been detected in crude protein extracts from various plants. Additionally, several research groups have partially purified and characterized PDE enzymatic activity from crude protein extracts. In this review, we focus on presenting advances toward the identification of enzymes involved in the cGMP metabolism pathway in higher plants. PMID:27200049

  1. Cyclic adenosine 3',5'-monophosphate and germination of sporangiospores from the fungus Mucor.

    PubMed

    Orlowski, M

    1980-06-01

    Cyclic adenosine 3',5'-monophosphate (cAMP) metabolism was examined in germinating sporangiospores of Mucor genevensis and Mucor mucedo. Exogenous cAMP prevented normal hyphal development from sporangiospores. Internal pools of cAMP fluctuated profoundly during development. Spherical growth of the spores was characterized by large pools of cAMP whereas germ tube emergence and hyphal elongation were characterized by small pools of cAMP. These observations suggest a possible role for cAMP in sporangiospore germination. Adenylate cyclase activities fluctuated significantly during germination with maximum values attained during spherical growth. In contrast, cAMP phosphodiesterase activities remained constant throughout germination. Internal cAMP levels may therefore be regulated by adjustment of adenylate cyclase activities. The binding of cAMP by soluble cell proteins was measured. cAMP-binding activity changed greatly during germination. Dormant and spherically growing spores possessed the highest activities. Developing hyphae contained the lowest activities. Use of the photoaffinity label, 8-azido-[32P]cAMP, in conjunction with sodium dodecyl sulfate-polyacrylamide-gel electrophoresis allowed the identification of a small population of morphogenetic-stage-specific proteins which bind cAMP and may be of regulatory significance to development.

  2. The binding of inosine monophosphate to Escherichia coli carbamoyl phosphate synthetase.

    PubMed

    Thoden, J B; Raushel, F M; Wesenberg, G; Holden, H M

    1999-08-01

    Carbamoyl phosphate synthetase (CPS) from Escherichia coli catalyzes the formation of carbamoyl phosphate, which is subsequently employed in both the pyrimidine and arginine biosynthetic pathways. The reaction mechanism is known to proceed through at least three highly reactive intermediates: ammonia, carboxyphosphate, and carbamate. In keeping with the fact that the product of CPS is utilized in two competing metabolic pathways, the enzyme is highly regulated by a variety of effector molecules including potassium and ornithine, which function as activators, and UMP, which acts as an inhibitor. IMP is also known to bind to CPS but the actual effect of this ligand on the activity of the enzyme is dependent upon both temperature and assay conditions. Here we describe the three-dimensional architecture of CPS with bound IMP determined and refined to 2.1 A resolution. The nucleotide is situated at the C-terminal portion of a five-stranded parallel beta-sheet in the allosteric domain formed by Ser(937) to Lys(1073). Those amino acid side chains responsible for anchoring the nucleotide to the polypeptide chain include Lys(954), Thr(974), Thr(977), Lys(993), Asn(1015), and Thr(1017). A series of hydrogen bonds connect the IMP-binding pocket to the active site of the large subunit known to function in the phosphorylation of the unstable intermediate, carbamate. This structural analysis reveals, for the first time, the detailed manner in which CPS accommodates nucleotide monophosphate effector molecules within the allosteric domain. PMID:10428826

  3. 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

  4. PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSIS OF INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH) ACTIVITY IN MMF-TREATED HCT RECIPIENTS

    PubMed Central

    Li, Hong; Mager, Donald E.; Sandmaier, Brenda M.; Storer, Barry E.; Boeckh, Michael J.; Bemer, Meagan J.; Phillips, Brian R.; Risler, Linda J.; McCune, Jeannine S.

    2014-01-01

    A novel approach to personalizing postgrafting immunosuppression in hematopoietic cell transplant (HCT) recipients is evaluating inosine monophosphate dehydrogenase (IMPDH) activity as a drug-specific biomarker of mycophenolic acid (MPA)-induced immunosuppression. This prospective study evaluated total MPA, unbound MPA, and total MPA glucuronide plasma concentrations and IMPDH activity in peripheral blood mononuclear cells (PMNC) at five time points after the morning dose of oral mycophenolate mofetil (MMF) on day +21 in 56 nonmyeloablative HCT recipients. Substantial interpatient variability in the pharmacokinetics and pharmacodynamics was observed and accurately characterized by the population pharmacokinetic/dynamic model. IMPDH activity decreased with increasing MPA plasma concentration, with maximum inhibition coinciding with maximum MPA concentration in most patients. The overall relationship between MPA concentration and IMPDH activity was described by a direct inhibitory Emax model with an IC50 = 3.23 mg/L total MPA and 57.3 ng/mL unbound MPA. The day +21 IMPDH area under the effect curve (AUEC) was associated with cytomegalovirus reactivation, non-relapse mortality, and overall mortality. In conclusion, a pharmacokinetic/dynamic model was developed that relates plasma MPA concentrations with PMNC IMPDH activity after an MMF dose in HCT recipients. Future studies should validate this model and confirm that day +21 IMPDH AUEC is a predictive biomarker. PMID:24727337

  5. Modification of human placental alkaline phosphatase by periodate-oxidized 1,N6-ethenoadenosine monophosphate.

    PubMed Central

    Chang, G G; Shiao, M S; Lee, K R; Wu, J J

    1990-01-01

    Oxidation of 1,N6-ethenoadenosine monophosphate (epsilon AMP) with periodate cleaved the cis-diol of the ribose ring and resulted in the formation of a dialdehyde derivative (epsilon AMP-dial). At room temperature epsilon AMP-dial was unstable and underwent beta-elimination to give 4',5'-anhydro-1,N6-ethenoadenosine dialdehyde acetal (A epsilon Ado-dial). These nucleotide analogues were found to inactivate human placental alkaline phosphatase in a time- and concentration-dependent manner. epsilon AMP-dial was shown to be an affinity label for the enzyme on the basis of the following criteria. (a) Kinetics of the enzyme activity loss over a wide range of epsilon AMP-dial concentration showed a saturating phenomenon. Removal of the phosphate group made the reagent (A epsilon Ado-dial) become a general chemical modifying reagent. (b) The artificial substrate p-nitrophenyl phosphate gave substantial protection of the enzyme against inactivation. (c) epsilon AMP-dial was a substrate and a partial mixed-type inhibitor for the enzyme. Results of the inhibition and protection studies indicated that the reagent and substrate could combine with the enzyme simultaneously. Besides the phosphate-binding domain, an induced hydrophobic region is proposed for the substrate-binding site for human placental alkaline phosphatase. PMID:2176472

  6. Lymphocyte beta 2-adrenoceptors and adenosine 3':5'-cyclic monophosphate during and after normal pregnancy.

    PubMed Central

    von Mandach, U.; Gubler, H. P.; Engel, G.; Huch, R.; Huch, A.

    1993-01-01

    1. The beta 2-sympathomimetics, used to inhibit preterm labour, bind predominantly to beta 2-adrenoceptors, activating adenylate cyclase to form adenosine 3':5'-cyclic monophosphate (cyclic AMP), a messenger substance which inhibits the enzyme cascade triggering smooth muscle contraction. beta 2-Adrenoceptor density and cyclic AMP formation can be used as markers of beta 2-adrenergic effect. 2. The present study addresses the influence of pregnancy on the beta-adrenoceptor system. beta 2-Adrenoceptor density and cyclic AMP concentrations (basal and evoked by isoprenaline) in circulating lymphocytes were determined at three points in gestation (16, 29 and 37 weeks) and 9 weeks post partum in 22 normal pregnancies. (-)-[125Iodo]-cyanopindolol was used as the ligand to identify a homogeneous population of beta 2-adrenoceptors on lymphocytes. B- and T-cell fractions were estimated from the same samples. 3. beta 2-Adrenoceptor density decreased significantly during gestation until week 37 (P < 0.01), then increased post partum (P < 0.005). Cyclic AMP concentrations (basal and evoked by isoprenaline) were significantly lower after 16 weeks of gestation than post partum (P < 0.05). 4. The results, which cannot be explained in terms of a shift in the lymphocyte (B- and T-cell) ratio, indicate that beta-adrenoceptor density and function are reduced in normal pregnancy and only return to normal post partum. These findings may be of significance in devising future tocolytic therapy with beta 2-adrenoceptor agonists. PMID:8383562

  7. Xylazine Activates Adenosine Monophosphate-Activated Protein Kinase Pathway in the Central Nervous System of Rats.

    PubMed

    Shi, Xing-Xing; Yin, Bai-Shuang; Yang, Peng; Chen, Hao; Li, Xin; Su, Li-Xue; Fan, Hong-Gang; Wang, Hong-Bin

    2016-01-01

    Xylazine is a potent analgesic extensively used in veterinary and animal experimentation. Evidence exists that the analgesic effect can be inhibited using adenosine 5'-monophosphate activated protein kinase (AMPK) inhibitors. Considering this idea, the aim of this study was to investigate whether the AMPK signaling pathway is involved in the central analgesic mechanism of xylazine in the rat. Xylazine was administrated via the intraperitoneal route. Sprague-Dawley rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus and brainstem were collected for determination of liver kinase B1 (LKB1) and AMPKα mRNA expression using quantitative real-time polymerase chain reaction (qPCR), and phosphorylated LKB1 and AMPKα levels using western blot. The results of our study showed that compared with the control group, xylazine induced significant increases in AMPK activity in the cerebral cortex, hippocampus, thalamus and cerebellum after rats received xylazine (P < 0.01). Increased AMPK activities were accompanied with increased phosphorylation levels of LKB1 in corresponding regions of rats. The protein levels of phosphorylated LKB1 and AMPKα in these regions returned or tended to return to control group levels. However, in the brainstem, phosphorylated LKB1 and AMPKα protein levels were decreased by xylazine compared with the control (P < 0.05). In conclusion, our data indicates that xylazine alters the activities of LKB1 and AMPK in the central nervous system of rats, which suggests that xylazine affects the regulatory signaling pathway of the analgesic mechanism in the rat brain. PMID:27049320

  8. A Fluorometric Activity Assay for Light-Regulated Cyclic-Nucleotide-Monophosphate Actuators.

    PubMed

    Schumacher, Charlotte Helene; Körschen, Heinz G; Nicol, Christopher; Gasser, Carlos; Seifert, Reinhard; Schwärzel, Martin; Möglich, Andreas

    2016-01-01

    As a transformative approach in neuroscience and cell biology, optogenetics grants control over manifold cellular events with unprecedented spatiotemporal definition, reversibility, and noninvasiveness. Sensory photoreceptors serve as genetically encoded, light-regulated actuators and hence embody the cornerstone of optogenetics. To expand the scope of optogenetics, ever more naturally occurring photoreceptors are being characterized, and synthetic photoreceptors with customized, light-regulated function are being engineered. Perturbational control over intracellular cyclic-nucleotide-monophosphate (cNMP) levels is achieved via sensory photoreceptors that catalyze the making and breaking of these second messengers in response to light. To facilitate discovery, engineering and quantitative characterization of such light-regulated cNMP actuators, we have developed an efficient fluorometric assay. Both the formation and the hydrolysis of cNMPs are accompanied by proton release which can be quantified with the fluorescent pH indicator 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF). This assay equally applies to nucleotide cyclases, e.g., blue-light-activated bPAC, and to cNMP phosphodiesterases, e.g., red-light-activated LAPD. Key benefits include potential for parallelization and automation, as well as suitability for both purified enzymes and crude cell lysates. The BCECF assay hence stands to accelerate discovery and characterization of light-regulated actuators of cNMP metabolism. PMID:26965118

  9. Novel interactions of fluorinated nucleotide derivatives targeting orotidine-5′-monophosphate decarboxylase

    PubMed Central

    Lewis, Melissa; Avina, Maria Elena Meza; Wei, Lianhu; Crandall, Ian E.; Bello, Angelica Mara; Poduch, Ewa; Liu, Yan; Paige, Christopher J.; Kain, Kevin C.; Pai, Emil F.; Kotra, Lakshmi P.

    2011-01-01

    Fluorinated nucleosides and nucleotides are of considerable interest to medicinal chemists due to their antiviral, anticancer, and other biological activities. However, their direct interactions at target binding sites are not well understood. A new class of 2′-deoxy-2′-fluoro-C6-substituted uridine and UMP derivatives were synthesized and evaluated as inhibitors of orotidine-5′-monophosphate decarboxylase (ODCase). These compounds were synthesized from the key intermediate, fully-protected 2′-deoxy-2′-fluorouridine. Among the synthesized compounds, 2′-deoxy-2′-fluoro-6-iodo-UMP covalently inhibited human ODCase with a second-order rate constant of 0.62 ± 0.02 M−1sec−1. Interestingly, the 6-cyano-2′-fluoro derivative covalently interacted with ODCase defying the conventional thinking, where its ribosyl derivative undergoes transformation into BMP by ODCase. This confirms that the 2′-fluoro moiety influences the chemistry at the C6 position of the nucleotides, thus interactions in the active site of ODCase. Molecular interactions of the 2′-fluorinated nucleotides are compared to those with the 3′-fluorinated nucleotides bound to the corresponding target enzyme, and the carbohydrate moieties were shown to bind in different conformations. PMID:21417464

  10. Adenosine 3′:5′-Cyclic Monophosphate in Chlamydomonas reinhardtii: Isolation and Characterization

    PubMed Central

    Amrhein, Nikolaus; Filner, Philip

    1973-01-01

    Chlamydomonas reinhardtii contains a factor that can replace adenosine 3′:5′-cyclic monophosphate (cAMP) in the stimulation of rabbit-muscle protein kinase. The factor cochromatographs and coelectrophoreses with authentic cAMP, and is inactivated by beef heart cyclic nucleotide phosphodiesterase. When C. reinhardtii is exposed to aminophylline (theophylline2 ethylenediamine), the concentration of the factor in the cells increases within 1 hr, from about 25 pmol of cAMP equivalents per g dry weight to more than 250 pmol. Cyclic nucleotide phosphodiesterase activity is present in crude extract of C. reinhardtii and is inhibited by theophylline. We conclude that cAMP occurs in C. reinhardtii and that the endogenous concentration is governed at least in part by a theophylline-sensitive cyclic nucleotide phosphodiesterase. These findings provide a sound basis for attributing the effects of methylxanthines on flagellar function and regeneration in C. reinhardtii to the resultant elevation of endogenous cAMP. PMID:16592076

  11. 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. PMID:22634191

  12. Control of cyclic adenosine 3',5'-monophosphate levels by depolarizing agents in fungi.

    PubMed

    Trevillyan, J M; Pall, M L

    1979-05-01

    It has been reported that diverse treatments which depolarize the plasma membrane of Neurospora crassa produce rapid increases in cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels. In the current study, membrane active antibiotics, which are known or putative depolarizing agents, were found to produce similar cyclic AMP increases, not only in N. crassa, but also in the distantly related fungi Saccharomyces cerevisiae and Mucor racemosus. Uncouplers of oxidative phosphorylation, which have been found to depolarize Neurospora, also produced cyclic AMP increases in all three fungi. The time course of the cyclic AMP response to these various treatments was similar in all three fungi. The fungal studies and studies on depolarized central nervous tissue suggest that cyclic AMP increases may be produced in response to plasma membrane depolarization in diverse eucaryotic cells. A model is proposed for eucaryotic microorganisms in which membrane depolarization serves as a signal of breakdown of the plasma membrane integrity. The subsequent cyclic AMP increase, in turn, may mediate cellular response to help protect the plasma membrane from chemical and mechanical threats to its integrity.

  13. Target validation of the inosine monophosphate dehydrogenase (IMPDH) gene in Cryptosporidium using Phylomer(®) peptides.

    PubMed

    Jefferies, R; Yang, R; Woh, C K; Weldt, T; Milech, N; Estcourt, A; Armstrong, T; Hopkins, R; Watt, P; Reid, S; Armson, A; Ryan, U M

    2015-01-01

    Cryptosporidiosis, a gastroenteric disease characterised mainly by diarrheal illnesses in humans and mammals is caused by infection with the protozoan parasite Cryptosporidium. Treatment options for cryptosporidiosis are limited, with the current therapeutic nitazoxanide, only partly efficacious in immunocompetent individuals. The parasite lacks de novo purine synthesis, and is exclusively dependant on purine salvage from its host. Inhibition of the inosine 5' monophosphate dehydrogenase (IMPDH), a purine salvage enzyme that is essential for DNA synthesis, thereby offers a potential drug target against this parasite. In the present study, a yeast-two-hybrid system was used to identify Phylomer peptides within a library constructed from the genomes of 25 phylogenetically diverse bacteria that targeted the IMPDH of Cryptosporidium parvum (IMPcp) and Cryptosporidium hominis (IMPch). We identified 38 unique interacting Phylomers, of which, 12 were synthesised and screened against C. parvum in vitro. Two Phylomers exhibited significant growth inhibition (81.2-83.8% inhibition; P < 0.05), one of which consistently exhibited positive interactions with IMPcp and IMPch during primary and recapitulation yeast two-hybrid screening and did not interact with either of the human IMPDH proteins. The present study highlightsthe potential of Phylomer peptides as target validation tools for Cryptosporidium and other organisms and diseases because of their ability to bind with high affinity to target proteins and disrupt function. PMID:25447124

  14. Attempts to detect cyclic adenosine 3':5'-monophosphate in higher plants by three assay methods.

    PubMed

    Bressan, R A; Ross, C W

    1976-01-01

    Endogenous levels of cyclic adenosine-3':5'-monophosphate in coleoptile first leaf segments of oat (Avena sativa L.), potato (Solanum tuberosum L.) tubers, tobacco (Nicotiana tabacum L.) callus, and germinating seeds of lettuce (Lactuca sativa L.) were measured with a modified Gilman binding assay and a protein kinase activation assay. The incorporation of adenosine-8-(14)C into compounds with properties similar to those of cyclic AMP was also measured in studies with germinating lettuce seeds. The binding assay proved reliable for mouse and rat liver analyses, but was nonspecific for plant tissues. It responded to various components from lettuce and potato tissues chromatographically similar to but not identical with cyclic AMP. The protein kinase activation assay was much more specific, but it also exhibited positive responses in the presence of compounds not chromatographically identical to cyclic AMP. The concentrations of cyclic AMP in the plant tissues tested were at the lower limits of detection and characterization obtainable with these assays. The estimates of maximal levels were much lower than reported in many previous studies. PMID:16659419

  15. Conformational Changes in Orotidine 5’-Monophosphate Decarboxylase: A Structure-Based Explanation for How the 5’-Phosphate Group Activates the Enzyme†

    PubMed Central

    Desai, Bijoy J.; Wood, McKay; Fedorov, Alexander A.; Fedorov, Elena V.; Goryanova, Bogdana; Amyes, Tina L.; Richard, John P.; Almo, Steven C.; Gerlt, John A.

    2012-01-01

    The binding of a ligand to orotidine 5’-monophosphate decarboxylase (OMPDC) is accompanied by a conformational change from an open, inactive conformation (Eo) to a closed, active conformation (Ec). As the substrate traverses the reaction coordinate to form the stabilized vinyl carbanion/carbene intermediate, interactions are enforced that destabilize the carboxylate group of the substrate as well as stabilize the intermediate (in the Ec•S‡ complex). Focusing on the OMPDC from Methanothermobacter thermautotrophicus, the “remote” 5’-phosphate group of the substrate activates the enzyme 2.4 × 108-fold; the activation is equivalently described by an intrinsic binding energy (IBE) of 11.4 kcal/mol. We studied residues in the activation that 1) directly contact the 5’-phosphate group; 2) participate in a hydrophobic cluster near the base of the active site loop that sequesters the bound substrate from solvent; and 3) form hydrogen-bonding interactions across the interface between the “mobile” and “fixed” half-barrel domains of the (β/α8-barrel structure. Our data support a model in which the IBE provided by the 5’-phosphate group is used to enable interactions both near the N-terminus of the active site loop and across the domain interface that stabilize both the Ec•S and Ec•S‡ complexes relative to the Eo•S complex. The conclusion that the IBE of the 5’-phosphate group provides stabilization of both the Ec•S and Ec•S‡ complexes, not just the Ec•S‡ complex, is central to understanding the structural origins of enzymatic catalysis as well as the requirements for the de novo design of enzymes that catalyze novel reactions. PMID:23030629

  16. Workshop on hydrology of crystalline basement rocks

    SciTech Connect

    Davis, S.N.

    1981-08-01

    This workshop covered the following subjects: measurements in relatively shallow boreholes; measurement and interpretation of data from deep boreholes; hydrologic properties of crystalline rocks as interpreted by geophysics and field geology; rock mechanics related to hydrology of crystalline rocks; the possible contributions of modeling to the understanding of the hydrology of crystalline rocks; and geochemical interpretations of the hydrology of crystalline rocks. (MHR)

  17. Crystallization and preliminary crystallographic analysis of orotidine 5′-monophosphate decarboxylase from the human malaria parasite Plasmodium falciparum

    SciTech Connect

    Krungkrai, Sudaratana R.; Tokuoka, Keiji; Kusakari, Yukiko; Inoue, Tsuyoshi; Adachi, Hiroaki; Matsumura, Hiroyoshi; Takano, Kazufumi; Murakami, Satoshi; Mori, Yusuke; Kai, Yasushi; Krungkrai, Jerapan; Horii, Toshihiro

    2006-06-01

    Orotidine 5′-monophosphate decarboxylase of human malaria parasite P. falciparum was crystallized by the seeding method in a hanging drop using PEG 3000 as a precipitant. A complete set of diffraction data from a native crystal was collected to 2.7 Å resolution at 100 K using synchrotron radiation. Orotidine 5′-monophosphate (OMP) decarboxylase (OMPDC; EC 4.1.1.23) catalyzes the final step in the de novo synthesis of uridine 5′-monophosphate (UMP) and defects in the enzyme are lethal in the malaria parasite Plasmodium falciparum. Active recombinant P. falciparum OMPDC (PfOMPDC) was crystallized by the seeding method in a hanging drop using PEG 3000 as a precipitant. A complete set of diffraction data from a native crystal was collected to 2.7 Å resolution at 100 K using synchrotron radiation at the Swiss Light Source. The crystal exhibits trigonal symmetry (space group R3), with hexagonal unit-cell parameters a = b = 201.81, c = 44.03 Å. With a dimer in the asymmetric unit, the solvent content is 46% (V{sub M} = 2.3 Å{sup 3} Da{sup −1})

  18. Nanostructures having crystalline and amorphous phases

    DOEpatents

    Mao, Samuel S; Chen, Xiaobo

    2015-04-28

    The present invention includes a nanostructure, a method of making thereof, and a method of photocatalysis. In one embodiment, the nanostructure includes a crystalline phase and an amorphous phase in contact with the crystalline phase. Each of the crystalline and amorphous phases has at least one dimension on a nanometer scale. In another embodiment, the nanostructure includes a nanoparticle comprising a crystalline phase and an amorphous phase. The amorphous phase is in a selected amount. In another embodiment, the nanostructure includes crystalline titanium dioxide and amorphous titanium dioxide in contact with the crystalline titanium dioxide. Each of the crystalline and amorphous titanium dioxide has at least one dimension on a nanometer scale.

  19. Rotationally Molded Liquid Crystalline Polymers

    NASA Technical Reports Server (NTRS)

    Rogers, Martin; Scribben, Eric; Baird, Donald; Hulcher, Bruce

    2002-01-01

    Rotational molding is a unique process for producing hollow plastic parts. Rotational molding offers low cost tooling and can produce very large parts with complicated shapes. Products made by rotational molding include water tanks with capacities up to 20,000 gallons, truck bed liners, playground equipment, air ducts, Nylon fuel tanks, pipes, toys, stretchers, kayaks, pallets, and many others. Thermotropic liquid crystalline polymers are an important class of engineering resins employed in a wide variety of applications. Thermotropic liquid crystalline polymers resins are composed of semirigid, nearly linear polymeric chains resulting in an ordered mesomorphic phase between the crystalline solid and the isotropic liquid. Ordering of the rigid rod-like polymers in the melt phase yields microfibrous, self-reinforcing polymer structures with outstanding mechanical and thermal properties. Rotational molding of liquid crystalline polymer resins results in high strength and high temperature hollow structures useful in a variety of applications. Various fillers and reinforcements can potentially be added to improve properties of the hollow structures. This paper focuses on the process and properties of rotationally molded liquid crystalline polymers. This paper will also highlight the interactions between academia and small businesses in developing new products and processes.

  20. Rotationally Molded Liquid Crystalline Polymers

    NASA Technical Reports Server (NTRS)

    Rogers, Martin; Stevenson, Paige; Scribben, Eric; Baird, Donald; Hulcher, Bruce

    2002-01-01

    Rotational molding is a unique process for producing hollow plastic parts. Rotational molding offers advantages of low cost tooling and can produce very large parts with complicated shapes. Products made by rotational molding include water tanks with capacities up to 20,000 gallons, truck bed liners, playground equipment, air ducts, Nylon fuel tanks, pipes, toys, stretchers, kayaks, pallets, and many others. Thermotropic liquid crystalline polymers are an important class of engineering resins employed in a wide variety of applications. Thermotropic liquid crystalline polymers resins are composed of semi-rigid, nearly linear polymeric chains resulting in an ordered mesomorphic phase between the crystalline solid and the isotropic liquid. Ordering of the rigid rod-like polymers in the melt phase yields microfibrous, self-reinforcing polymer structures with outstanding mechanical and thermal properties. Rotational molding of liquid crystalline polymer resins results in high strength and high temperature hollow structures useful in a variety of applications. Various fillers and reinforcements can potentially be added to improve properties of the hollow structures. This paper focuses on the process and properties of rotationally molded liquid crystalline polymers.

  1. Source of /sup 3/H-labeled inositol bis- and monophosphates in agonist-activated rat parotid acinar cells

    SciTech Connect

    Hughes, A.R.; Putney, J.W. Jr.

    1989-06-05

    The kinetics of (3H)inositol phosphate metabolism in agonist-activated rat parotid acinar cells were characterized in order to determine the sources of (3H)inositol monophosphates and (3H)inositol bisphosphates. The turnover rates of D-myo-inositol 1,4,5-trisphosphate and its metabolites, D-myo-inositol 1,4-bisphosphate and D-myo-inositol 1,3,4-trisphosphate, were examined following the addition of the muscarinic receptor antagonist, atropine, to cholinergically stimulated parotid cells. D-myo-Inositol 1,4,5-trisphosphate declined with a t1/2 of 7.6 +/- 0.7 s, D-myo-inositol 1,3,4-trisphosphate declined with a t1/2 of 8.6 +/- 1.2 min, and D-myo-inositol 1,4-bisphosphate was metabolized with a t1/2 of 6.0 +/- 0.7 min. The sum of the rates of flux through D-myo-inositol 1,4-bisphosphate and D-myo-inositol 1,3,4-trisphosphate (2.54% phosphatidylinositol/min) did not exceed the calculated rate of breakdown of D-myo-inositol 1,4,5-trisphosphate (2.76% phosphatidylinositol/min). Thus, there is no evidence for the direct hydrolysis of phosphatidylinositol 4-phosphate in intact cells since D-myo-inositol 1,4-bisphosphate formation can be attributed to the dephosphorylation of D-myo-inositol 1,4,5-trisphosphate. The source of the (3H)inositol monophosphates also was examined in cholinergically stimulated parotid cells. When parotid cells were stimulated with methacholine, D-myo-inositol 1,4,5-trisphosphate, D-myo-inositol 1,3,4,5-tetrakisphosphate, D-myo-inositol 1,4-bisphosphate, and D-myo-inositol 4-monophosphate levels increased within 2 s, whereas D-myo-inositol 1-monophosphate accumulation was delayed by several seconds. Rates of (3H)inositol monophosphate accumulation also were examined by the addition of LiCl to cells stimulated to steady state levels of (3H)inositol phosphates.

  2. Single crystalline mesoporous silicon nanowires

    SciTech Connect

    Hochbaum, A.I.; Gargas, Daniel; Jeong Hwang, Yun; Yang, Peidong

    2009-08-04

    Herein we demonstrate a novel electroless etching synthesis of monolithic, single-crystalline, mesoporous silicon nanowire arrays with a high surface area and luminescent properties consistent with conventional porous silicon materials. These porous nanowires also retain the crystallographic orientation of the wafer from which they are etched. Electron microscopy and diffraction confirm their single-crystallinity and reveal the silicon surrounding the pores is as thin as several nanometers. Confocal fluorescence microscopy showed that the photoluminescence (PL) of these arrays emanate from the nanowires themselves, and their PL spectrum suggests that these arrays may be useful as photocatalytic substrates or active components of nanoscale optoelectronic devices.

  3. Single crystalline mesoporous silicon nanowires

    SciTech Connect

    Hochbaum, Allon; Dargas, Daniel; Hwang, Yun Jeong; Yang, Peidong

    2009-08-18

    Herein we demonstrate a novel electroless etching synthesis of monolithic, single-crystalline, mesoporous silicon nanowire arrays with a high surface area and luminescent properties consistent with conventional porous silicon materials. The photoluminescence of these nanowires suggest they are composed of crystalline silicon with small enough dimensions such that these arrays may be useful as photocatalytic substrates or active components of nanoscale optoelectronic devices. A better understanding of this electroless route to mesoporous silicon could lead to facile and general syntheses of different narrow bandgap semiconductor nanostructures for various applications.

  4. Catalysis by Orotidine 5′-Monophosphate Decarboxylase: Effect of 5-Fluoro and 4′-Substituents on the Decarboxylation of Two-Part Substrates†

    PubMed Central

    Goryanova, Bogdana; Spong, Krisztina; Amyes, Tina L.; Richard, John P.

    2013-01-01

    The syntheses of two novel truncated analogs of the natural substrate orotidine 5′-monophosphate (OMP) for orotidine 5′-monophosphate decarboxylase (OMPDC) with enhanced reactivity towards decarboxylation are reported: 1-(β-D-erythrofuranosyl)-5-fluoroorotic acid (FEO) and 5′-deoxy-5-fluoroorotidine (5′-dFO). A comparison of the second-order rate constants for the OMPDC-catalyzed decarboxylations of FEO (10 M−1 s−1) and 1-(β-D-erythrofuranosyl)orotic acid (EO, 0.026 M−1 s−1) shows that the vinyl carbanion-like transition state is stabilized by 3.5 kcal/mol by interactions with the 5-F substituent of FEO. The OMPDC-catalyzed decarboxylations of FEO and EO are both activated by exogenous phosphite dianion (HPO32−), but the 5-F substituent results in only a 0.8 kcal stabilization of the transition state for the phosphite-activated reaction of FEO. This provides strong evidence that the phosphite-activated OMPDC-catalyzed reaction of FEO is not limited by the chemical step of decarboxylation of the enzyme-bound substrate. Evidence is presented that there is a change in rate-limiting step from the chemical step of decarboxylation for the phosphite-activated reaction of EO, to closure of the phosphate gripper loop and an enzyme conformational change at the ternary E·FEO·HPO32− complex for the reaction of FEO. The 4′-CH3 and 4′-CH2OH groups of 5′-dFO and orotidine, respectively, result in identical destabilizations of the transition state for the unactivated decarboxylation of 2.9 kcal/mol. By contrast, the 4′-CH3 group of 5′-dFO and the 4′-CH2OH group of orotidine result in very different 4.7 and 8.3 kcal/mol destabilizations of the transition state for the phosphite-activated decarboxylation. Here, the destabilizing effect of the 4′-CH3 substituent at 5′-dFO is masked by the rate-limiting conformational change that depresses the third-order rate constant for the phosphite-activated reaction of the parent substrate FEO. PMID

  5. Catalysis by orotidine 5'-monophosphate decarboxylase: effect of 5-fluoro and 4'-substituents on the decarboxylation of two-part substrates.

    PubMed

    Goryanova, Bogdana; Spong, Krisztina; Amyes, Tina L; Richard, John P

    2013-01-22

    The syntheses of two novel truncated analogs of the natural substrate orotidine 5'-monophosphate (OMP) for orotidine 5'-monophosphate decarboxylase (OMPDC) with enhanced reactivity toward decarboxylation are reported: 1-(β-d-erythrofuranosyl)-5-fluoroorotic acid (FEO) and 5'-deoxy-5-fluoroorotidine (5'-dFO). A comparison of the second-order rate constants for the OMPDC-catalyzed decarboxylations of FEO (10 M⁻¹ s⁻¹) and 1-(β-d-erythrofuranosyl)orotic acid (EO, 0.026 M⁻¹ s⁻¹) shows that the vinyl carbanion-like transition state is stabilized by 3.5 kcal/mol by interactions with the 5-F substituent of FEO. The OMPDC-catalyzed decarboxylations of FEO and EO are both activated by exogenous phosphite dianion (HPO₃²⁻), but the 5-F substituent results in only a 0.8 kcal stabilization of the transition state for the phosphite-activated reaction of FEO. This provides strong evidence that the phosphite-activated OMPDC-catalyzed reaction of FEO is not limited by the chemical step of decarboxylation of the enzyme-bound substrate. Evidence is presented that there is a change in the rate-limiting step from the chemical step of decarboxylation for the phosphite-activated reaction of EO, to closure of the phosphate gripper loop and an enzyme conformational change at the ternary E•FEO•HPO₃²⁻ complex for the reaction of FEO. The 4'-CH₃ and 4'-CH₂OH groups of 5'-dFO and orotidine, respectively, result in identical destabilizations of the transition state for the unactivated decarboxylation of 2.9 kcal/mol. By contrast, the 4'-CH₃ group of 5'-dFO and the 4'-CH₂OH group of orotidine result in very different 4.7 and 8.3 kcal/mol destabilizations of the transition state for the phosphite-activated decarboxylation. Here, the destabilizing effect of the 4'-CH₃ substituent at 5'-dFO is masked by the rate-limiting conformational change that depresses the third-order rate constant for the phosphite-activated reaction of the parent substrate FEO.

  6. Conformational properties of purine-pyrimidine and pyrimidine-purine dinucleoside monophosphates.

    PubMed

    Ezra, F S; Lee, C H; Kondo, N S; Danyluk, S S; Sarma, R H

    1977-05-01

    The detailed conformational features and dynamics of heterodinucleoside monophosphates ApU, ApC, GpU, GpC, UpA, CpA, UpG, and CpG have been studied in aqueous solution by high field nuclear magnetic resonance (NMR) spectroscopy. Analysis of the resultant NMR parameters leads to a number of discernible trends throughout the series. Thus the ribose rings of the dimers exist as equilibrium mixtures of C(2')-endo(2E) in equilibrium C(3')-endo(3E) conformers with a proclivity for the 3E pucker in most cases; the C(4')-C(5') bonds of both nucleotidyl units show significant preference (74-96%) for a gg conformation and the dominant conformer (85-89%) about C(5')-O(5') is g'g'. Orientation about the C(3')-O(3') bond is coupled to the ribose conformational equilibrium and the system exists with a bias for the 3Eg- coupled conformation in which the H(3')-C(3')-O(3')-P dihedral angle occupies the narrow range of 33-35 degrees. Dimerization, on the average, causes about 10% increase in gg and g'g' populations and the g-domain becomes increasingly populated about the C(3')-O(3') bond. The ribose equilibrium 2E in equilibrium 3E shifts in favor of 3E upon dimerization, the effect being very conspicuous for the pu-py series (similar to 40 yields 60%) and less noticeable for the py-pu systems (similar to 47 yields 58%), clearly suggesting a correlation between sequence and ribose conformational equilibrium. The temperature and dimerization data for the heterodinucleoside monophosphates show that the transition 2E yields 3E is directly related to XCN changes induced by dimerization and stacking. Analysis of the ribose coupling data shows that the percentage populations of stacked species vary from dimer to dimer with GpC displaying a maximum of 45% stacked population and UpG about 10%. However, in general, the pu-py dimers show a higher preference (27-45%) for stacked conformations than py-pu dimers (10-25%). It is proposed that the pronounced deshielding of H(5') of the 5

  7. Xylazine Activates Adenosine Monophosphate-Activated Protein Kinase Pathway in the Central Nervous System of Rats

    PubMed Central

    Shi, Xing-Xing; Yin, Bai-Shuang; Yang, Peng; Chen, Hao; Li, Xin; Su, Li-Xue; Fan, Hong-Gang; Wang, Hong-Bin

    2016-01-01

    Xylazine is a potent analgesic extensively used in veterinary and animal experimentation. Evidence exists that the analgesic effect can be inhibited using adenosine 5’-monophosphate activated protein kinase (AMPK) inhibitors. Considering this idea, the aim of this study was to investigate whether the AMPK signaling pathway is involved in the central analgesic mechanism of xylazine in the rat. Xylazine was administrated via the intraperitoneal route. Sprague-Dawley rats were sacrificed and the cerebral cortex, cerebellum, hippocampus, thalamus and brainstem were collected for determination of liver kinase B1 (LKB1) and AMPKα mRNA expression using quantitative real-time polymerase chain reaction (qPCR), and phosphorylated LKB1 and AMPKα levels using western blot. The results of our study showed that compared with the control group, xylazine induced significant increases in AMPK activity in the cerebral cortex, hippocampus, thalamus and cerebellum after rats received xylazine (P < 0.01). Increased AMPK activities were accompanied with increased phosphorylation levels of LKB1 in corresponding regions of rats. The protein levels of phosphorylated LKB1 and AMPKα in these regions returned or tended to return to control group levels. However, in the brainstem, phosphorylated LKB1 and AMPKα protein levels were decreased by xylazine compared with the control (P < 0.05). In conclusion, our data indicates that xylazine alters the activities of LKB1 and AMPK in the central nervous system of rats, which suggests that xylazine affects the regulatory signaling pathway of the analgesic mechanism in the rat brain. PMID:27049320

  8. Novel adenosine 3 prime ,5 prime -cyclic monophosphate dependent protein kinases in a marine diatom

    SciTech Connect

    Lin, P.P.C.; Volcani, B.E. )

    1989-08-08

    Two novel adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) dependent protein kinases have been isolated from the diatom Cylindrotheca fusiformis. The kinases, designated I and II, are eluted from DEAE-Sephacel at 0.10 and 0.15 M NaCl. They have a high affinity for cAMP and are activated by micromolar cAMP. They exhibit maximal activity at 5 mM Mg{sup 2+} and pH 8 with the preferred phosphate donor ATP and phosphate acceptor histone H1. They phosphorylate sea urchin sperm histone H1 on a single serine site in the sequence Arg-Lys-Gly-Ser({sup 32}P)-Ser-Asn-Ala-Arg and have an apparent M{sub r} of 75,000 as determined by gel filtration and sucrose density sedimentation. In the kinase I preparation a single protein band with an apparent M{sub r} of about 78,000 is photolabeled with 8-azido({sup 32}P)cAMP and is also phosphorylated with ({gamma}-{sup 32}P)ATP in a cAMP-dependent manner, after autoradiography following sodium dodecyl sulfate gel electrophoresis. The rate of phosphorylation of the 78,000-dalton band is independent of the enzyme concentration. The results indicate that (i) these diatom cAMP-dependent protein kinases are monomeric proteins, possessing both the cAMP-binding regulatory and catalytic domains on the same polypeptide chain, (ii) the enzymes do not dissociate into smaller species upon activation by binding cAMP, and (iii) self-phosphorylation of the enzymes by an intrapeptide reaction is cAMP dependent. The two diatom cAMP kinases are refractory to the heat-stable protein kinase modulator from rabbit muscle, but they respond differently to proteolytic degradation and to inhibition by arachidonic acid and several microbial alkaloids.

  9. Adsorption of nucleotides on biomimetic apatite: The case of cytidine 5' monophosphate (CMP).

    PubMed

    Choimet, Maëla; Tourrette, Audrey; Drouet, Christophe

    2015-10-15

    The chemical interaction between DNA macromolecules and hard tissues in vertebrate is of foremost importance in paleogenetics, as bones and teeth represent a major substrate for the genetic material after cell death. Recently, the empirical hypothesis of DNA "protection" over time thanks to its adsorption on hard tissues was revisited from a physico-chemical viewpoint. In particular, the existence of a strong interaction between phosphate groups of DNA backbone and the surface of apatite nanocrystals (mimicking bone/dentin mineral) was evidenced on an experimental basis. In the field of nanomedicine, DNA or RNA can be used for gene transport into cells, and apatite nanocarriers then appear promising. In order to shed some more light on interactions between DNA molecules and apatite, the present study focuses on the adsorption of a "model" nucleotide, cytidine 5' monophosphate (CMP), on a carbonated biomimetic apatite sample. The follow-up of CMP kinetics of adsorption pointed out the rapidity of interaction with stabilization reached within few minutes. The adsorption isotherm could be realistically fitted to the Sips model (Langmuir-Freundlich) suggesting the influence of surface heterogeneities and adsorption cooperativity in the adsorption process. The desorption study pointed out the reversible character of CMP adsorption on biomimetic apatite. This contribution is intended to prove helpful in view of better apprehending the molecular interaction of DNA fragments and apatite compounds, independently of the application domain, such as bone diagenesis or nanomedicine. This study may also appear informative for researchers interested in the origins of life on Earth and the occurrence and behavior of primitive biomolecules.

  10. Adsorption of nucleotides on biomimetic apatite: The case of cytidine 5' monophosphate (CMP).

    PubMed

    Choimet, Maëla; Tourrette, Audrey; Drouet, Christophe

    2015-10-15

    The chemical interaction between DNA macromolecules and hard tissues in vertebrate is of foremost importance in paleogenetics, as bones and teeth represent a major substrate for the genetic material after cell death. Recently, the empirical hypothesis of DNA "protection" over time thanks to its adsorption on hard tissues was revisited from a physico-chemical viewpoint. In particular, the existence of a strong interaction between phosphate groups of DNA backbone and the surface of apatite nanocrystals (mimicking bone/dentin mineral) was evidenced on an experimental basis. In the field of nanomedicine, DNA or RNA can be used for gene transport into cells, and apatite nanocarriers then appear promising. In order to shed some more light on interactions between DNA molecules and apatite, the present study focuses on the adsorption of a "model" nucleotide, cytidine 5' monophosphate (CMP), on a carbonated biomimetic apatite sample. The follow-up of CMP kinetics of adsorption pointed out the rapidity of interaction with stabilization reached within few minutes. The adsorption isotherm could be realistically fitted to the Sips model (Langmuir-Freundlich) suggesting the influence of surface heterogeneities and adsorption cooperativity in the adsorption process. The desorption study pointed out the reversible character of CMP adsorption on biomimetic apatite. This contribution is intended to prove helpful in view of better apprehending the molecular interaction of DNA fragments and apatite compounds, independently of the application domain, such as bone diagenesis or nanomedicine. This study may also appear informative for researchers interested in the origins of life on Earth and the occurrence and behavior of primitive biomolecules. PMID:26117294

  11. Turning an antiviral into an anticancer drug: Nanoparticle delivery of acyclovir monophosphate

    PubMed Central

    Yao, Jing; Zhang, Yuan; Ramishetti, Srinivas; Wang, Yuhua; Huang, Leaf

    2013-01-01

    Anti-herpes simplex virus (HSV) drug acyclovir (ACV) is phosphorylated by the viral thymidine kinase (TK), but not the cellular TK. Phosphorylated ACV inhibits cellular DNA synthesis and kills the infected cells. We hypothesize that ACV monophosphate (ACVP), which is an activated metabolite of ACV, should be efficient in killing cells independent of HSV-TK. If so, ACVP should be a cytotoxic agent if properly delivered to the cancer cells. The Lipid/Calcium/Phosphate (LCP) nanoparticles (NPs) with a membrane/core structure were used to encapsulate ACVP to facilitate the targeted delivery of ACVP to the tumor. The LCP NPs showed entrapment efficiency of ~69%, the nano-scaled particle size and positive zeta potential. Moreover, ACVP-loaded LCP NPs (A-LCP NPs) exhibited concentration-dependent cytotoxicity against H460 cells and increased S-phase arrest. More importantly, a significant reduction of the tumor volume over 4 days following administration (p<0.05~0.005) of A-LCP NPs, suggests excellent in vivo efficacy. Whereas, two free drugs (ACV and ACVP) and blank LCP NPs showed little or no therapeutic effect. It was also found that the high efficacy of A-LCP NPs was associated with the ability to induce dramatic apoptosis of the tumor cells, as well as significantly inhibit tumor cell proliferation and cell cycle progression. In conclusion, with the help of LCP NPs, monophosphorylation modification of ACV can successfully modify an HSV-TK-dependent antiviral drug into an anti-tumor drug. PMID:23791977

  12. Protective mechanisms of adenosine 5'-monophosphate in platelet activation and thrombus formation.

    PubMed

    Fuentes, E; Badimon, L; Caballero, J; Padró, T; Vilahur, G; Alarcón, M; Pérez, P; Palomo, I

    2014-03-01

    Platelet activation is relevant to a variety of acute thrombotic events. We sought to examine adenosine 5'-monophosphate (AMP) mechanisms of action in preventing platelet activation, thrombus formation and platelet-related inflammatory response. We assessed the effect of AMP on 1) P-selectin expression and GPIIb/IIIa activation by flow cytometry; 2) Platelet aggregation and ATP secretion induced by ADP, collagen, TRAP-6, convulxin and thrombin; 3) Platelet rolling and firm adhesion, and platelet-leukocyte interactions under flow-controlled conditions; and, 4) Platelet cAMP levels, sP-selectin, sCD40L, IL-1β, TGF-β1 and CCL5 release, PDE3A activity and PKA phosphorylation. The effect of AMP on in vivo thrombus formation was also evaluated in a murine model. The AMP docking with respect to A2 adenosine receptor was determined by homology. AMP concentration-dependently (0.1 to 3 mmol/l) inhibited P-selectin expression and GPIIb/IIIa activation, platelet secretion and aggregation induced by ADP, collagen, TRAP-6 and convulxin, and diminished platelet rolling and firm adhesion. Furthermore, AMP induced a marked increase in the rolling speed of leukocytes retained on the platelet surface. At these concentrations AMP significantly decreased inflammatory mediator from platelet, increased intraplatelet cAMP levels and inhibited PDE3A activity. Interestingly, SQ22536, ZM241385 and SCH58261 attenuated the antiplatelet effect of AMP. Docking experiments revealed that AMP had the same orientation that adenosine inside the A2 adenosine receptor binding pocket. These in vitro antithrombotic properties were further supported in an in vivo model of thrombosis. Considering the successful use of combined antiplatelet therapy, AMP may be further developed as a novel antiplatelet agent. PMID:24306059

  13. Evidence for the Calvin cycle and hexose monophosphate pathway in Thiobacillus ferrooxidans.

    PubMed

    Gale, N L; Beck, J V

    1967-10-01

    The enzymes of the Calvin reductive pentose phosphate cycle and the hexose monophosphate pathway have been demonstrated in cell-free extracts of Thiobacillus ferrooxidans. This, together with analyses of the products of CO(2) fixation in cell-free systems, suggests that these pathways are operative in whole cells of this microorganism. Nevertheless, the amount of CO(2) fixed in these cell-free systems was limited by the type and amount of compound added as substrate. The inability of cell extracts to regenerate pentose phosphates and to perpetuate the cyclic fixation of CO(2) is partially attributable to low activity of triose phosphate dehydrogenase under the experimental conditions found to be optimal for the enzymes involved in the utilization of ribose-5-phosphate or ribulose-1,5-diphosphate as substrate for CO(2) incorporation. With the exception of ribulose-1,5-diphosphate, all substrates required the addition of adenosine triphosphate (ATP) or adenosine diphosphate (ADP) for CO(2) fixation. Under optimal conditions, with ribose-5-phosphate serving as substrate, each micromole of ATP added resulted in the fixation of 1.5 mumoles of CO(2), whereas each micromole of ADP resulted in 0.5 mumole of CO(2) fixed. These values reflect the activity of adenylate kinase in the extract preparations. The K(m) for ATP in the phosphoribulokinase reaction was 0.91 x 10(-3)m. Kinetic studies conducted with carboxydismutase showed K(m) values of 1.15 x 10(-4)m and 5 x 10(-2)m for ribulose-1,5-diphosphate and bicarbonate, respectively.

  14. Deciphering the photochemical mechanisms describing the UV-induced processes occurring in solvated guanine monophosphate

    NASA Astrophysics Data System (ADS)

    Altavilla, Salvatore; Segarra-Martí, Javier; Nenov, Artur; Conti, Irene; Rivalta, Ivan; Garavelli, Marco

    2015-04-01

    The photophysics and photochemistry of water-solvated guanine monophosphate (GMP) are here characterized by means of a multireference quantum-chemical/molecular mechanics theoretical approach (CASPT2//CASSCF/AMBER) in order to elucidate the main photo-processes occurring upon UV-light irradiation. The effect of the solvent and of the phosphate group on the energetics and structural features of this system are evaluated for the first time employing high-level ab initio methods and thoroughly compared to those in vacuo previously reported in the literature and to the experimental evidence to assess to which extent they influence the photoinduced mechanisms. Solvated electronic excitation energies of solvated GMP at the Franck-Condon (FC) region show a red shift for the ππ* La and Lb states, whereas the energy of the oxygen lone-pair nπ* state is blue-shifted. The main photoinduced decay route is promoted through a ring-puckering motion along the bright lowest-lying La state towards a conical intersection (CI) with the ground state, involving a very shallow stationary point along the minimum energy pathway in contrast to the barrierless profile found in gas-phase, the point being placed at the end of the minimum energy path (MEP) thus endorsing its ultrafast deactivation in accordance with time-resolved transient and photoelectron spectroscopy experiments. The role of the nπ* state in the solvated system is severely diminished as the crossings with the initially populated La state and also with the Lb state are placed too high energetically to partake prominently in the deactivation photo-process. The proposed mechanism present in solvated and in vacuo DNA/RNA chromophores validates the intrinsic photostability mechanism through CI-mediated non-radiative processes accompanying the bright excited-state population towards the ground state and subsequent relaxation back to the FC region.

  15. Cyclic Adenosine Monophosphate Accumulation and beta-Adrenergic Binding in Unweighted and Denervated Rat Soleus Muscle

    NASA Technical Reports Server (NTRS)

    Kirby, Christopher R.; Woodman, Christopher R.; Woolridge, Dale; Tischler, Marc E.

    1992-01-01

    Unweighting, but not denervation, of muscle reportedly "spares" insulin receptors, increasing insulin sensitivity. Unweighting also increases beta-adrenergic responses of carbohydrate metabolism. These differential characteristics were studied further by comparing cyclic adenosine monophosphate (cAMP) accumulation and beta-adrenergic binding in normal and 3-day unweighted or denervated soleus muscle. Submaximal amounts of isoproterenol, a p-agonist, increased cAMP accumulation in vitro and in vivo (by intramuscular (IM) injection) to a greater degree (P less than .05) in unweighted muscles. Forskolin or maximal isoproterenol had similar in vitro effects in all muscles, suggesting increased beta-adrenergic sensitivity following unweighting. Increased sensitivity was confirmed by a greater receptor density (B(sub max)) for iodo-125(-)-pindolol in particulate preparations of unweighted (420 x 10(exp -18) mol/mg muscle) than of control or denervated muscles (285 x 10(exp-18) mol/mg muscle). The three dissociation constant (Kd) values were similar (20.3 to 25.8 pmol/L). Total binding capacity (11.4 fmol/muscle) did not change during 3 days of unweighting, but diminished by 30% with denervation. This result illustrates the "sparing" and loss of receptors, respectively, in these two atrophy models. In diabetic animals, IM injection of insulin diminished CAMP accumulation in the presence of theophylline in unweighted muscle (-66% +/- 2%) more than in controls (-42% +'- 6%, P less than .001). These results show that insulin affects CAMP formation in muscle, and support a greater in vivo insulin response following unweighting atrophy. These various data support a role for lysosomal proteolysis in denervation, but not in unweighting, atrophy.

  16. Turning an antiviral into an anticancer drug: nanoparticle delivery of acyclovir monophosphate.

    PubMed

    Yao, Jing; Zhang, Yuan; Ramishetti, Srinivas; Wang, Yuhua; Huang, Leaf

    2013-09-28

    Anti-herpes simplex virus (HSV) drug acyclovir (ACV) is phosphorylated by the viral thymidine kinase (TK), but not the cellular TK. Phosphorylated ACV inhibits cellular DNA synthesis and kills the infected cells. We hypothesize that ACV monophosphate (ACVP), which is an activated metabolite of ACV, should be efficient in killing cells independent of HSV-TK. If so, ACVP should be a cytotoxic agent if properly delivered to the cancer cells. The Lipid/Calcium/Phosphate (LCP) nanoparticles (NPs) with a membrane/core structure were used to encapsulate ACVP to facilitate the targeted delivery of ACVP to the tumor. The LCP NPs showed entrapment efficiency of ~70%, the nano-scaled particle size and positive zeta potential. Moreover, ACVP-loaded LCP NPs (A-LCP NPs) exhibited concentration-dependent cytotoxicity against H460 cells and increased S-phase arrest. More importantly, a significant reduction of the tumor volume over 4 days following administration (p<0.05-0.005) of A-LCP NPs, suggests excellent in vivo efficacy. Whereas, two free drugs (ACV and ACVP) and blank LCP NPs showed little or no therapeutic effect. It was also found that the high efficacy of A-LCP NPs was associated with the ability to induce dramatic apoptosis of the tumor cells, as well as significantly inhibit tumor cell proliferation and cell cycle progression. In conclusion, with the help of LCP NPs, monophosphorylation modification of ACV can successfully modify an HSV-TK-dependent antiviral drug into an anti-tumor drug.

  17. Involvement of Cyclic Guanosine Monophosphate-Dependent Protein Kinase I in Renal Antifibrotic Effects of Serelaxin

    PubMed Central

    Wetzl, Veronika; Schinner, Elisabeth; Kees, Frieder; Hofmann, Franz; Faerber, Lothar; Schlossmann, Jens

    2016-01-01

    Introduction: Kidney fibrosis has shown to be ameliorated through the involvement of cyclic guanosine monophosphate (cGMP) and its dependent protein kinase I (cGKI). Serelaxin, the recombinant form of human relaxin-II, increases cGMP levels and has shown beneficial effects on kidney function in acute heart failure patients. Antifibrotic properties of serelaxin are supposed to be mediated via relaxin family peptide receptor 1 and subsequently enhanced nitric oxide/cGMP to inhibit transforming growth factor-β (TGF-β) signaling. This study examines the involvement of cGKI in the antifibrotic signaling of serelaxin. Methods and Results: Kidney fibrosis was induced by unilateral ureteral obstruction in wildtype (WT) and cGKI knock-out (KO) mice. After 7 days, renal antifibrotic effects of serelaxin were assessed. Serelaxin treatment for 7 days significantly increased cGMP in the kidney of WT and cGKI-KO. In WT, renal fibrosis was reduced through decreased accumulation of collagen1A1, total collagen, and fibronectin. The profibrotic connective tissue growth factor as well as myofibroblast differentiation were reduced and matrix metalloproteinases-2 and -9 were positively modulated after treatment. Moreover, Smad2 as well as extracellular signal-regulated kinase 1 (ERK1) phosphorylation were decreased, whereas phosphodiesterase (PDE) 5a phosphorylation was increased. However, these effects were not observed in cGKI-KO. Conclusion: Antifibrotic renal effects of serelaxin are mediated via cGMP/cGKI to inhibit Smad2- and ERK1-dependent TGF-β signaling and increased PDE5a phosphorylation. PMID:27462268

  18. Arsenic Sorption on TiO2 Nanoparticles: Size And Crystallinity Effects

    EPA Science Inventory

    Single solute As (III) and As (V) sorption on nano-sized amorphous and crystalline TiO2 was investigated to determine: size and crystallinity effects on arsenic sorption capacities, possible As (III) oxidation, and the nature of surface complexes. Amorphous and cryst...

  19. Glycation precedes lens crystallin aggregation

    SciTech Connect

    Swamy, M.S.; Perry, R.E.; Abraham, E.C.

    1987-05-01

    Non-enzymatic glycosylation (glycation) seems to have the potential to alter the structure of crystallins and make them susceptible to thiol oxidation leading to disulfide-linked high molecular weight (HMW) aggregate formation. They used streptozotocin diabetic rats during precataract and cataract stages and long-term cell-free glycation of bovine lens crystallins to study the relationship between glycation and lens crystallin aggregation. HMW aggregates and other protein components of the water-soluble (WS) and urea-soluble (US) fractions were separated by molecular sieve high performance liquid chromatography. Glycation was estimated by both (/sup 3/H)NaBH/sub 4/ reduction and phenylboronate agarose affinity chromatography. Levels of total glycated protein (GP) in the US fractions were about 2-fold higher than in the WS fractions and there was a linear increase in GP in both WS and US fractions. This increase was parallelled by a corresponding increase in HMW aggregates. Total GP extracted by the affinity method from the US fraction showed a predominance of HMW aggregates and vice versa. Cell-free glycation studies with bovine crystallins confirmed the results of the animals studies. Increasing glycation caused a corresponding increase in protein insolubilization and the insoluble fraction thus formed also contained more glycated protein. It appears that lens protein glycation, HMW aggregate formation, and protein insolubilization are interrelated.

  20. Study of the physical properties of crystalline rocks in the southeast Voronezh anteclise

    NASA Technical Reports Server (NTRS)

    Dmitriyevskiy, V. S.; Afanasyev, N. S.; Frolov, S. M.

    1985-01-01

    The physical properties of rocks, in the crystalline mass of the Voronezh anteclise, were studied. The study of the physical properties of rocks is important for the improvement of geophysical methods for mapping crystalline rocks in the foundation and exploration of different geological objects which are associated with the crystalline foundation, covered by the sedimentary mantle. It is found that: (1) rocks in the crystalline foundation are very different in physical properties; (2) the physical properties are closely related to their substance composition and genesis; (3) petrographic properties give clues of rock afficiation to certain complexes; and (4) physical and magnetic properties should be examined by petrography, chemical and X-ray analysis.

  1. Condensed matter effects on the structure of crystalline glucose

    NASA Astrophysics Data System (ADS)

    Molteni, C.; Parrinello, M.

    1997-08-01

    By means of ab initio simulations based on the Car-Parrinello method, we have calculated the crystalline structures of σ-D-glucose, σ-D-glucose monohydrate and β-D-glucose. The good agreement with the available experimental data gives us confidence in the applicability of the method to carbohydrates and opens the path towards the investigation of more complex problems, where a quantum mechanical description is essential. Condensed matter effects are discussed by comparing the structures of the glucose molecule in the crystalline and gas phases.

  2. Generic Crystalline Disposal Reference Case

    SciTech Connect

    Painter, Scott Leroy; Chu, Shaoping; Harp, Dylan Robert; Perry, Frank Vinton; Wang, Yifeng

    2015-02-20

    A generic reference case for disposal of spent nuclear fuel and high-level radioactive waste in crystalline rock is outlined. The generic cases are intended to support development of disposal system modeling capability by establishing relevant baseline conditions and parameters. Establishment of a generic reference case requires that the emplacement concept, waste inventory, waste form, waste package, backfill/buffer properties, EBS failure scenarios, host rock properties, and biosphere be specified. The focus in this report is on those elements that are unique to crystalline disposal, especially the geosphere representation. Three emplacement concepts are suggested for further analyses: a waste packages containing 4 PWR assemblies emplaced in boreholes in the floors of tunnels (KBS-3 concept), a 12-assembly waste package emplaced in tunnels, and a 32-assembly dual purpose canister emplaced in tunnels. In addition, three failure scenarios were suggested for future use: a nominal scenario involving corrosion of the waste package in the tunnel emplacement concepts, a manufacturing defect scenario applicable to the KBS-3 concept, and a disruptive glaciation scenario applicable to both emplacement concepts. The computational approaches required to analyze EBS failure and transport processes in a crystalline rock repository are similar to those of argillite/shale, with the most significant difference being that the EBS in a crystalline rock repository will likely experience highly heterogeneous flow rates, which should be represented in the model. The computational approaches required to analyze radionuclide transport in the natural system are very different because of the highly channelized nature of fracture flow. Computational workflows tailored to crystalline rock based on discrete transport pathways extracted from discrete fracture network models are recommended.

  3. 5'-Adenosine monophosphate and adenosine metabolism, and adenosine responses in mouse, rat and guinea pig heart.

    PubMed

    Headrick, J P; Peart, J; Hack, B; Garnham, B; Matherne, G P

    2001-11-01

    We examined myocardial 5'-adenosine monophosphate (5'-AMP) catabolism, adenosine salvage and adenosine responses in perfused guinea pig, rat and mouse heart. MVO(2) increased from 71+/-8 microl O(2)/min per g in guinea pig to 138+/-17 and 221+/-15 microl O(2)/min per g in rat and mouse. VO(2)/beat was 0.42+/-0.03, 0.50+/-0.03 and 0.55+/-0.04 microl O(2)/g in guinea pig, rat and mouse, respectively. Resting and peak coronary flows were highest in mouse vs. rat and guinea pig, and peak ventricular pressures and Ca(2+) sensitivity declined as heart mass increased. Net myocardial 5'-AMP dephosphorylation increased significantly as mass declined (3.8+/-0.5, 9.0+/-1.4 and 11.0+/-1.6 nmol/min per g in guinea pig, rat and mouse, respectively). Despite increased 5'-AMP catabolism, coronary venous [adenosine] was similar in guinea pig, rat and mouse (45+/-8, 69+/-10 and 57+/-14 nM, respectively). Comparable venous [adenosine] was achieved by increased salvage vs. deamination: 64%, 41% and 39% of adenosine formed was rephosphorylated while 23%, 46%, and 50% was deaminated in mouse, rat and guinea pig, respectively. Moreover, only 35-45% of inosine and its catabolites derive from 5'-AMP (vs. IMP) dephosphorylation in all species. Although post-ischemic purine loss was low in mouse (due to these adaptations), functional tolerance to ischemia decreased with heart mass. Cardiovascular sensitivity to adenosine also differed between species, with A(1) receptor sensitivity being greatest in mouse while A(2) sensitivity was greatest in guinea pig. In summary: (i) cardiac 5'-AMP dephosphorylation, VO(2), contractility and Ca(2+) sensitivity all increase as heart mass falls; (ii) adaptations in adenosine salvage vs. deamination limit purine loss and yield similar adenosine levels across species; (iii) ischemic tolerance declines with heart mass; and (iv) cardiovascular sensitivity to adenosine varies, with increasing A(2) sensitivity relative to A(1) sensitivity in larger hearts.

  4. Regulation of guanosine 3′:5′-cyclic monophosphate in ovine tracheal epithelial cells

    PubMed Central

    Range, Simon P; Holland, Elaine D; Basten, Graham P; Knox, Alan J

    1997-01-01

    Guanosine 3′:5′-cyclic monophosphate (cyclic GMP) is an important second messenger mediating the effects of nitric oxide (NO) and natriuretic peptides. Cyclic GMP pathways regulate several aspects of lung pathophysiology in a number of airway cells. The regulation of this system has not been extensively studied in pulmonary epithelial tissue.We have studied the production of cyclic GMP by suspensions of ovine tracheal epithelial cells in response to activators of soluble guanylyl cyclase (sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP) and particulate guanylyl cyclase (atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and E. coli heat stable enterotoxin (STa)).Both 10−710−3 M and 10−710−3 M SNAP generated a concentration-dependent marked elevation in cyclic GMP production when incubated with 10−3 M 3-isobutyl-1-methylxanthine (IBMX) (both greater than 25×baseline values with highest drug concentration).The increase in production of cyclic GMP in response to 10−6 M SNP and 10−5 M SNAP was markedly inhibited by both 5×10−5 M haemoglobin (102% and 92% inhibition) and 5×10−5 M methylene blue (82% and 84% inhibition).The increase in cyclic GMP in response to 10−3 M SNP was measured following co-incubation with the phosphodiesterase inhibitors 10−710−3 M IBMX, 10−710−4 M milrinone and 10−710−4 M SKF 96231. Only 10−410−3 M IBMX significantly increased cyclic GMP levels.Cyclic GMP production was also significantly elevated from baseline by 10−5 M ANP, 10−5 M BNP, 10−5 M CNP and 200 iu ml−1 of E. coli STa toxin in the presence of 10−3 M IBMX. Increases with these natriuretic peptides and STa toxin were smaller in magnitude (24 fold) than those seen with SNP and SNAP. CNP was the most potent of the natriuretic peptides studied suggesting type B membrane bound guanylate cyclase is the predominant form expressed

  5. Molecular mechanism of the chaperone function of mini-α-crystallin, a 19-residue peptide of human α-crystallin.

    PubMed

    Banerjee, Priya R; Pande, Ajay; Shekhtman, Alexander; Pande, Jayanti

    2015-01-20

    α-Crystallin is the archetypical chaperone of the small heat-shock protein family, all members of which contain the so-called "α-crystallin domain" (ACD). This domain and the N- and C-terminal extensions are considered the main functional units in its chaperone function. Previous studies have shown that a 19-residue fragment of the ACD of human αA-crystallin called mini-αA-crystallin (MAC) shows chaperone properties similar to those of the parent protein. Subsequent studies have confirmed the function of this peptide, but no studies have addressed the mechanistic basis for the chaperone function of MAC. Using human γD-crystallin (HGD), a key substrate protein for parent α-crystallin in the ocular lens, we show here that MAC not only protects HGD from aggregation during thermal and chemical unfolding but also binds weakly and reversibly to HGD (Kd ≈ 200-700 μM) even when HGD is in the native state. However, at temperatures favoring the unfolding of HGD, MAC forms a stable complex with HGD similar to parent α-crystallin. Using nuclear magnetic resonance spectroscopy, we identify the residues in HGD that are involved in these two modes of binding and show that MAC protects HGD from aggregation by binding to Phe 56 and Val 132 at the domain interface of the target protein, and residues Val 164 to Leu 167 in the core of the C-terminal domain. Furthermore, we suggest that the low-affinity, reversible binding of MAC on the surface of HGD in the native state is involved in facilitating its binding to both the domain interface and core regions during the early stages of the unfolding of HGD. This work highlights some structural features of MAC and MAC-like peptides that affect their chaperone activity and can potentially be manipulated for translational studies. PMID:25478825

  6. Designed synthesis of copper(II) and nickel(II) complexes with a tridentate N2O donor Schiff base: Modulation of crystalline architectures through Csbnd H⋯π and anion⋯π interactions

    NASA Astrophysics Data System (ADS)

    Das, Mithun; Chattopadhyay, Shouvik

    2013-11-01

    Two copper(II) complexes, Cu(L1)Cl (1), Cu(L1)NCS (3) and two nickel(II) complexes Ni(L1)Cl (2), Ni(L1)NCS (4), where HL1 = 1-[(2-diethylamino-ethylimino)-methyl]-naphthalen-2-ol act as tridentate N2O donor ligand, have been prepared and characterized by elemental analysis, IR and UV-Vis spectroscopy and single crystal X-ray diffraction studies. The geometry of the central metal ion in each of the four complexes is square planar. The existence of Csbnd H⋯π interactions in 2 gives rise to one dimensional chain structure. Complex 3 shows two Csbnd H⋯π interactions and one anion⋯π interactions which leads to a two dimensional layer structure. Each mononuclear unit of 4 has two Csbnd H⋯π interactions along b axis to form a double strand one dimensional array of the molecules in crystal packing.

  7. Soliton structure in crystalline acetanilide

    NASA Astrophysics Data System (ADS)

    Eilbeck, J. C.; Lomdahl, P. S.; Scott, A. C.

    1984-10-01

    The theory of self-trapping of amide I vibrational energy in crystalline acetanilide is studied in detail. A spectrum of stationary, self-trapped (soliton) solutions is determined and tested for dynamic stability. Only those solutions for which the amide I energy is concentrated near a single molecule were found to be stable. Exciton modes were found to be unstable to decay into solitons.

  8. Soliton structure in crystalline acetanilide

    SciTech Connect

    Eilbeck, J.C.; Lomdahl, P.S.; Scott, A.C.

    1984-10-15

    The theory of self-trapping of amide I vibrational energy in crystalline acetanilide is studied in detail. A spectrum of stationary, self-trapped (soliton) solutions is determined and tested for dynamic stability. Only those solutions for which the amide I energy is concentrated near a single molecule were found to be stable. Exciton modes were found to be unstable to decay into solitons.

  9. EELS from organic crystalline materials

    NASA Astrophysics Data System (ADS)

    Brydson, R.; Eddleston, M. D.; Jones, W.; Seabourne, C. R.; Hondow, N.

    2014-06-01

    We report the use of the electron energy loss spectroscopy (EELS) for providing light element chemical composition information from organic, crystalline pharmaceutical materials including theophylline and paracetamol and discuss how this type of data can complement transmission electron microscopy (TEM) imaging and electron diffraction when investigating polymorphism. We also discuss the potential for the extraction of bonding information using electron loss near-edge structure (ELNES).

  10. Biocompatibility of crystalline opal nanoparticles

    PubMed Central

    2012-01-01

    Background Silica nanoparticles are being developed as a host of biomedical and biotechnological applications. For this reason, there are more studies about biocompatibility of silica with amorphous and crystalline structure. Except hydrated silica (opal), despite is presents directly and indirectly in humans. Two sizes of crystalline opal nanoparticles were investigated in this work under criteria of toxicology. Methods In particular, cytotoxic and genotoxic effects caused by opal nanoparticles (80 and 120 nm) were evaluated in cultured mouse cells via a set of bioassays, methylthiazolyldiphenyl-tetrazolium-bromide (MTT) and 5-bromo-2′-deoxyuridine (BrdU). Results 3T3-NIH cells were incubated for 24 and 72 h in contact with nanocrystalline opal particles, not presented significant statistically difference in the results of cytotoxicity. Genotoxicity tests of crystalline opal nanoparticles were performed by the BrdU assay on the same cultured cells for 24 h incubation. The reduction of BrdU-incorporated cells indicates that nanocrystalline opal exposure did not caused unrepairable damage DNA. Conclusions There is no relationship between that particles size and MTT reduction, as well as BrdU incorporation, such that the opal particles did not induce cytotoxic effect and genotoxicity in cultured mouse cells. PMID:23088559

  11. Inelastic deformation in crystalline rocks

    NASA Astrophysics Data System (ADS)

    Rahmani, H.; Borja, R. I.

    2011-12-01

    The elasto-plastic behavior of crystalline rocks, such as evaporites, igneous rocks, or metamorphic rocks, is highly dependent on the behavior of their individual crystals. Previous studies indicate that crystal plasticity can be one of the dominant micro mechanisms in the plastic deformation of crystal aggregates. Deformation bands and pore collapse are examples of plastic deformation in crystalline rocks. In these cases twinning within the grains illustrate plastic deformation of crystal lattice. Crystal plasticity is governed by the plastic deformation along potential slip systems of crystals. Linear dependency of the crystal slip systems causes singularity in the system of equations solving for the plastic slip of each slip system. As a result, taking the micro-structure properties into account, while studying the overall behavior of crystalline materials, is quite challenging. To model the plastic deformation of single crystals we use the so called `ultimate algorithm' by Borja and Wren (1993) implemented in a 3D finite element framework to solve boundary value problems. The major advantage of this model is that it avoids the singularity problem by solving for the plastic slip explicitly in sub steps over which the stress strain relationship is linear. Comparing the results of the examples to available models such as Von Mises we show the significance of considering the micro-structure of crystals in modeling the overall elasto-plastic deformation of crystal aggregates.

  12. Liquid crystalline order in mucus

    NASA Technical Reports Server (NTRS)

    Viney, C.; Huber, A. E.; Verdugo, P.

    1993-01-01

    Mucus plays an exceptionally wide range of important biological roles. It operates as a protective, exchange, and transport medium in the digestive, respiratory, and reproductive systems of humans and other vertebrates. Mucus is a polymer hydrogel. It is secreted as discrete packages (secretory granules) by specialized secretory cells. Mucus hydrogel is stored in a condensed state inside the secretory granules. Depending upon the architecture of their constituent macromolecules and on the composition of the solvent, polymer gels can form liquid crystalline microstructures, with orientational order being exhibited over optically resolvable distances. Individual mucin molecules consist of alternating rigid segments (heavily glycosylated; hydrophilic) and flexible segments (nonglycosylated; hydrophobic). Polymer molecules consisting of rigid units linked by flexible spacers are frequently associated with liquid crystalline behavior, which again raises the possibility that mucus could form anisotropic fluid phases. Suggestions that mucins may be self-associating in dilute solution have previously been challenged on the basis of sedimentation-equilibrium studies performed on mucus in which potential sites of association were competitively blocked with inhibitors. However, the formation of stable liquid crystalline phases does not depend on the existence of inter- or intramolecular associations; these phases can form on the basis of steric considerations alone.

  13. Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds

    PubMed Central

    Makowska-Grzyska, Magdalena; Kim, Youngchang; Gorla, Suresh Kumar; Wei, Yang; Mandapati, Kavitha; Zhang, Minjia; Maltseva, Natalia; Modi, Gyan; Boshoff, Helena I.; Gu, Minyi; Aldrich, Courtney; Cuny, Gregory D.; Hedstrom, Lizbeth; Joachimiak, Andrzej

    2015-01-01

    Tuberculosis (TB) remains a worldwide problem and the need for new drugs is increasingly more urgent with the emergence of multidrug- and extensively-drug resistant TB. Inosine 5’-monophosphate dehydrogenase 2 (IMPDH2) from Mycobacterium tuberculosis (Mtb) is an attractive drug target. The enzyme catalyzes the conversion of inosine 5’-monophosphate into xanthosine 5’-monophosphate with the concomitant reduction of NAD+ to NADH. This reaction controls flux into the guanine nucleotide pool. We report seventeen selective IMPDH inhibitors with antitubercular activity. The crystal structures of a deletion mutant of MtbIMPDH2 in the apo form and in complex with the product XMP and substrate NAD+ are determined. We also report the structures of complexes with IMP and three structurally distinct inhibitors, including two with antitubercular activity. These structures will greatly facilitate the development of MtbIMPDH2-targeted antibiotics. PMID:26440283

  14. Distinct Requirements for 5'-Monophosphate-assisted RNA Cleavage by Escherichia coli RNase E and RNase G.

    PubMed

    Richards, Jamie; Belasco, Joel G

    2016-03-01

    RNase E and RNase G are homologous endonucleases that play important roles in RNA processing and decay in Escherichia coli and related bacterial species. Rapid mRNA degradation is facilitated by the preference of both enzymes for decay intermediates whose 5' end is monophosphorylated. In this report we identify key characteristics of RNA that influence the rate of 5'-monophosphate-assisted cleavage by these two ribonucleases. In vitro, both require at least two and prefer three or more unpaired 5'-terminal nucleotides for such cleavage; however, RNase G is impeded more than RNase E when fewer than four unpaired nucleotides are present at the 5' end. Each can tolerate any unpaired nucleotide (A, G, C, or U) at either of the first two positions, with only modest biases. The optimal spacing between the 5' end and the scissile phosphate appears to be eight nucleotides for RNase E but only six for RNase G. 5'-Monophosphate-assisted cleavage also occurs, albeit more slowly, when that spacing is greater or at most one nucleotide shorter than the optimum, but there is no simple inverse relationship between increased spacing and the rate of cleavage. These properties are also manifested during 5'-end-dependent mRNA degradation in E. coli.

  15. A study of the hydration of deoxydinucleoside monophosphates containing thymine, uracil and its 5-halogen derivatives: Monte Carlo simulation.

    PubMed

    Alderfer, J L; Danilov, V I; Poltev, V I; Slyusarchuk, O N

    1999-04-01

    An extensive Monte Carlo simulation of hydration of various conformations of the dinucleoside monophosphates (DNP), containing thymine, uracil and its 5-halogen derivatives has been performed. An anti-anti conformation is the most energetically stable one for each of the DNPs. In the majority of cases the energy preference is determined by water-water interaction. For other dimers conformational energy is the most important factor, or both the factors are of nearly equal importance. The introduction of the methyl group into the 5-position of uracil ring most noticeably influences the conformational energy and leads to the decrease of its stabilizing contribution to the total interaction energy. The introduction of halogen atoms increases the relative content of anti-syn and syn-anti conformations of DNPs as compared to the parent ones due to the formation of an energetically more favorable water structure around these conformations. A correlation is observed between the Monte Carlo results for the halogenated DNPs and their experimental photoproduct distribution. The data obtained demonstrates a sequence dependence in the photochemistry of the halogenated dinucleoside monophosphates.

  16. Effects of alkaline or liquid-ammonia treatment on crystalline cellulose: changes in crystalline structure and effects on enzymatic digestibility

    PubMed Central

    2011-01-01

    Background In converting biomass to bioethanol, pretreatment is a key step intended to render cellulose more amenable and accessible to cellulase enzymes and thus increase glucose yields. In this study, four cellulose samples with different degrees of polymerization and crystallinity indexes were subjected to aqueous sodium hydroxide and anhydrous liquid ammonia treatments. The effects of the treatments on cellulose crystalline structure were studied, in addition to the effects on the digestibility of the celluloses by a cellulase complex. Results From X-ray diffractograms and nuclear magnetic resonance spectra, it was revealed that treatment with liquid ammonia produced the cellulose IIII allomorph; however, crystallinity depended on treatment conditions. Treatment at a low temperature (25°C) resulted in a less crystalline product, whereas treatment at elevated temperatures (130°C or 140°C) gave a more crystalline product. Treatment of cellulose I with aqueous sodium hydroxide (16.5 percent by weight) resulted in formation of cellulose II, but also produced a much less crystalline cellulose. The relative digestibilities of the different cellulose allomorphs were tested by exposing the treated and untreated cellulose samples to a commercial enzyme mixture (Genencor-Danisco; GC 220). The digestibility results showed that the starting cellulose I samples were the least digestible (except for corn stover cellulose, which had a high amorphous content). Treatment with sodium hydroxide produced the most digestible cellulose, followed by treatment with liquid ammonia at a low temperature. Factor analysis indicated that initial rates of digestion (up to 24 hours) were most strongly correlated with amorphous content. Correlation of allomorph type with digestibility was weak, but was strongest with cellulose conversion at later times. The cellulose IIII samples produced at higher temperatures had comparable crystallinities to the initial cellulose I samples, but achieved

  17. Simulation of shrinkage and warpage of semi-crystalline thermoplastics

    NASA Astrophysics Data System (ADS)

    Hopmann, Ch.; Borchmann, N.; Spekowius, M.; Weber, M.; Schöngart, M.

    2015-05-01

    Today, the simulation of the injection molding process is state of the art. Besides the simulation of the manufacturing process, commercial simulation tools allow a prediction of the structural properties of the final part. Especially the complex shrinkage and warpage behavior is of interest as it significantly influences the part quality. Although modern simulation tools provide qualitatively correct results for several materials and processing conditions, significant deviations from the real component's behavior can occur for semi-crystalline thermoplastics. One underlying reason is the description on the macro scale used in these simulation tools. However, in semi-crystalline materials significant effects take place on the micro scale, e.g. crystalline superstructures that cannot be neglected. As part of a research project at IKV, investigations are carried out to improve the simulation accuracy of shrinkage and warpage. To point out differences in the accuracy of commercially available simulation tools, a reference part is computed for the materials polypropylene and polyoxymethylene. The results are validated by injection molding experiments. The shrinkage and warpage behavior is characterized by optical measuring technology. In future, models for the description of the pvT behavior of semi-crystalline thermoplastics will be implemented into the software package SphäroSim which was developed at IKV. With this software, crystallization kinetics for semi-crystalline thermoplastics can be calculated on the micro scale. With the newly implemented pvT models the calculation of shrinkage and warpage for semi-crystalline thermoplastics will be enabled on the micro scale.

  18. Activation of 5' adenosine monophosphate-activated protein kinase blocks cumulus cell expansion through inhibition of protein synthesis during in vitro maturation in Swine.

    PubMed

    Santiquet, Nicolas; Sasseville, Maxime; Laforest, Martin; Guillemette, Christine; Gilchrist, Robert B; Richard, François J

    2014-08-01

    The serine/threonine kinase 5' adenosine monophosphate-activated protein kinase (AMPK), a heterotrimeric protein known as a metabolic switch, is involved in oocyte nuclear maturation in mice, cattle, and swine. The present study analyzed AMPK activation in cumulus cell expansion during in vitro maturation (IVM) of porcine cumulus-oocyte complexes (COC). 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) is a well-known activator of AMPK. It inhibited oocyte meiotic resumption in COC. Moreover, cumulus cell expansion did not occur in the presence of AICAR, demonstrating its marked impact on cumulus cells. Activation of AMPK was supported by AICAR-mediated phosphorylation of alpha AMPK subunits. Furthermore, the presence of AICAR increased glucose uptake, a classical response to activation of this metabolic switch in response to depleted cellular energy levels. Neither nuclear maturation nor cumulus expansion was reversed by glucosamine, an alternative substrate in hyaluronic acid synthesis, through the hexosamine biosynthetic pathway, which ruled out possible depletion of substrates. Both increased gap junction communication and phosphodiesterase activity in COC are dependent on protein synthesis during the initial hours of IVM; however, both were inhibited in the presence of AICAR, which supports the finding that activation of AMPK by AICAR mediated inhibition of protein synthesis. Moreover, this protein synthesis inhibition was equivalent to that of the well-known protein synthesis inhibitor cycloheximide, as observed on cumulus expansion and protein concentration. Finally, the phosphorylation level of selected kinases was investigated. The pattern of raptor phosphorylation is supportive of activation of AMPK-mediated inhibition of protein synthesis. In conclusion, AICAR-mediated AMPK activation in porcine COC inhibited cumulus cell expansion and protein synthesis. These results bring new considerations to the importance of this kinase in ovarian

  19. Genetics of Bietti Crystalline Dystrophy.

    PubMed

    Ng, Danny S C; Lai, Timothy Y Y; Ng, Tsz Kin; Pang, Chi Pui

    2016-01-01

    Bietti crystalline dystrophy (BCD) is an inherited retinal degenerative disease characterized by crystalline deposits in the retina, followed by progressive atrophy of the retinal pigment epithelium (RPE), choriocapillaris, and photoreceptors. CYP4V2 has been identified as the causative gene for BCD. The CYP4V2 gene belongs to the cytochrome P450 superfamily and encodes for fatty acid ω-hydroxylase of both saturated and unsaturated fatty acids. The CYP4V2 protein is localized most abundantly within the endoplasmic reticulum in the RPE and is postulated to play a role in the physiological lipid recycling system between the RPE and photoreceptors to maintain visual function. Electroretinographic assessments have revealed progressive dysfunction of rod and cone photoreceptors in patients with BCD. Several genotypes have been associated with more severe phenotypes based on clinical and electrophysiological findings. With the advent of multimodal imaging with spectral domain optical coherence tomography, fundus autofluorescence, and adaptive optics scanning laser ophthalmoscopy, more precise delineation of BCD severity and progression is now possible, allowing for the potential future development of targets for gene therapy. PMID:27228076

  20. Particle motion in crystalline beams

    SciTech Connect

    Haffmans, A.F.; Maletic, D.; Ruggiero, A.G.

    1994-04-20

    Studying the possibility of storing a low emittance (or ``cooled``) beam of charged particles in a storage ring, the authors are faced with the effect of space charge by which particles are repelled and influence each others` motion. The correct evaluation of the space-charge effects is important to determine the attainment and properties of Crystalline Beams, a phase transition which intense beams of ions can undergo when cooling is applied. In this report they derive the equations of motion of a particle moving under the action of external resorting forces generated by the magnets of the storage ring, and of the electromagnetic fields generated by the other particles. The motion in every direction is investigated: in the longitudinal, as well as vertical and horizontal direction. The external forces are assumed to be linear with the particle displacement from the reference orbit. The space-charge forces are comparable in magnitude to the external focusing forces. The equations of motion so derived are then used to determine confinement and stability conditions for the attainment of Crystalline Beams, using transfer matrices.

  1. Ferromagnetic viscoelastic liquid crystalline materials

    NASA Astrophysics Data System (ADS)

    Schlesier, Cristina; Shibaev, Petr; McDonald, Scott

    2012-02-01

    Novel ferromagnetic liquid crystalline materials were designed by mixing ferromagnetic nanoparticles with glass forming oligomers and low molar mass liquid crystals. The matrix in which nanoparticles are embedded is highly viscous that reduces aggregation of nanoparticles and stabilizes the whole composition. Mechanical and optical properties of the composite material are studied in the broad range of nanoparticle concentrations. The mechanical properties of the viscoelastic composite material resemble those of chemically crosslinked elastomers (elasticity and reversibility of deformations). The optical properties of ferromagnetic cholesteric materials are discussed in detail. It is shown that application of magnetic field leads to the shift of the selective reflection band of the cholesteric material and dramatically change its color. Theoretical model is suggested to account for the observed effects; physical properties of the novel materials and liquid crystalline elastomers are compared and discussed. [1] P.V. Shibaev, C. Schlesier, R. Uhrlass, S. Woodward, E. Hanelt, Liquid Crystals, 37, 1601 (2010) [2] P.V. Shibaev, R. Uhrlass, S. Woodward, C. Schlesier, Md R. Ali, E. Hanelt, Liquid Crystals, 37, 587 (2010)

  2. Thermodynamics of rock forming crystalline solutions

    NASA Technical Reports Server (NTRS)

    Saxena, S. K.

    1971-01-01

    Analysis of phase diagrams and cation distributions within crystalline solutions as means of obtaining thermodynamic data on rock forming crystalline solutions is discussed along with some aspects of partitioning of elements in coexisting phases. Crystalline solutions, components in a silicate mineral, and chemical potentials of these components were defined. Examples were given for calculating thermodynamic mixing functions in the CaW04-SrW04, olivine-chloride solution, and orthopyroxene systems.

  3. Association of actin with alpha crystallins

    NASA Technical Reports Server (NTRS)

    Gopalakrishnan, S.; Boyle, D.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

    1993-01-01

    The alpha crystallins are cytosolic proteins that co-localize and co-purify with actin-containing microfilaments. Affinity column chromatography employing both covalently-coupled actin or alpha crystallin was used to demonstrate specific and saturable binding of actin with alpha crystallin. This conclusion was confirmed by direct visualization of alpha aggregates bound to actin polymerized in vitro. The significance of this interaction in relation to the functional properties of these two polypeptides will be discussed.

  4. Photo-cycle dynamics of LOV1-His domain of phototropin from Chlamydomonas reinhardtii with roseoflavin monophosphate cofactor

    NASA Astrophysics Data System (ADS)

    Tyagi, A.; Penzkofer, A.; Mathes, T.; Hegemann, P.

    2010-09-01

    The wild-type phototropin protein phot from the green alga Chlamydomonas reinhardtii consists of two N-terminal LOV domains LOV1 and LOV2 with flavin mononucleotide (FMN) cofactor and a C-terminal serine-threonine kinase domain. It controls multiple steps in the sexual lifecycle of the alga. Here the LOV1-His domain of phot with modified cofactor is studied. FMN is replaced by roseoflavin monophosphate (8-dimethylamino-8-demethyl-FMN, RoFMN). The modified LOV1 domain is called RoLOV1. The photo-dynamics consequences of the cofactor change are studied. The absorption, emission, and photo-cyclic behaviour of LOV1-His and RoLOV1-His are compared. A spectroscopic characterisation of the cofactors FMN and RoFMN (roseoflavin) is given.

  5. Stereoselective aminoacylation of a dinucleoside monophosphate by the imidazolides of DL-alanine and N-(tert-butoxycarbonyl)-DL-alanine

    NASA Technical Reports Server (NTRS)

    Profy, A. T.; Usher, D. A.

    1984-01-01

    The aminoacylation of diinosine monophosphate was studied experimentally. When the acylating agent was the imidazolide of N-(tert-butoxycarbonyl)-DL-alanine, a 40 percent enantiomeric excess of the isomer was incorporated at the 2' site and the positions of equilibrium for the reversible 2'-3' migration reaction differed for the D and L enantiomers. The reactivity of the nucleoside hydroxyl groups was found to decrease on the order 2'(3') less than internal 2' and less than 5', and the extent of the reaction was affected by the concentration of the imidazole buffer. Reaction of IpI with imidazolide of unprotected DL-alanine, by contrast, led to an excess of the D isomer at the internal 2' site. Finally, reaction with the N-carboxy anhydride of DL-alanine occurred without stereoselection. These results are found to be relevant to the study of the evolution of optical chemical activity and the origin of genetically directed protein synthesis.

  6. Investigation on the occurrence and significance of cyclic adenosine 3':5'-monophosphate in phytoplankton and natural aquatic communities

    SciTech Connect

    Francko, D.A.

    1980-01-01

    This study demonstrates, on the basis of several analyanalytical criteria, that the production and extracellular release of cyclic adenosine 3':5'-monophosphate (cAMP) is widespread among phytoplankton species. The production and release of CAMP varied markedly among different species grown under similar environmental conditions, and intraspecifically during the life cycle of a given algal species. This investigation marks the first time cAMP has been investigated in natural aquatic systems. An examination of epilimnetic lakewater samples from Lawrence Lake, a hardwater oligotrophic lake, and Wintergreen Lake, a hardwater hypereutrophic lake, both in southwestern Michigan, demonstrated that cAMP existed in both particulate-associated and dissolved forms in these systems.

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

    PubMed

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

    1996-05-01

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

  8. In Silico Design for Adenosine Monophosphate-Activated Protein Kinase Agonist from Traditional Chinese Medicine for Treatment of Metabolic Syndromes

    PubMed Central

    Tang, Hsin-Chieh

    2014-01-01

    Adenosine monophosphate-activated protein kinase (AMPK) acts as a master mediator of metabolic homeostasis. It is considered as a significant millstone to treat metabolic syndromes including obesity, diabetes, and fatty liver. It can sense cellular energy or nutrient status by switching on the catabolic pathways. Investigation of AMPK has new findings recently. AMPK can inhibit cell growth by the way of autophagy. Thus AMPK has become a hot target for small molecular drug design of tumor inhibition. Activation of AMPK must undergo certain extent change of the structure. Through the methods of structure-based virtual screening and molecular dynamics simulation, we attempted to find out appropriate small compounds from the world's largest TCM Database@Taiwan that had the ability to activate the function of AMPK. Finally, we found that two TCM compounds, eugenyl_beta-D-glucopyranoside and 6-O-cinnamoyl-D-glucopyranose, had the qualification to be AMPK agonist. PMID:24899913

  9. Nuclear magnetic resonance and molecular modeling study on mycophenolic acid: implications for binding to inosine monophosphate dehydrogenase.

    PubMed

    Makara, G M; Keserû, G M; Kajtár-Peredy, M; Anderson, W K

    1996-03-15

    The conformation of the sodium salt of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase (IMPD), derived from 1D DIFNOE and 2D ROESY experiments in water and molecular dynamics (MD) is described. The hexenoic acid side chain conformation consistent with the NMR data was similar to that seen in the X-ray structure of MPA. The solution conformation was applied in a molecular modeling study in order to explore the potential features of enzyme binding. Our results, based on striking similarities in molecular volume and electrostatic isopotential between MPA and cofactor NAD+, lead to the suggestion that MPA is capable of binding to the nicotinamide site of IMPD and mimicking the NAD+ inverse regulation of the enzyme. In addition, our proposed model is in good agreement with the observed high affinity of the dinucleotide analogues thiazole- and selenazole-4-carboxamide adenine dinucleotide to IMPD.

  10. Crystalline imide/arylene ether copolymers

    NASA Technical Reports Server (NTRS)

    Jensen, Brian J. (Inventor); Hergenrother, Paul M. (Inventor); Bass, Robert G. (Inventor)

    1995-01-01

    Crystalline imide/arylene ether block copolymers are prepared by reacting anhydride terminated poly(amic acids) with amine terminated poly)arylene ethers) in polar aprotic solvents and chemically or thermally cyclodehydrating the resulting intermediate poly(amic acids). The block copolymers of the invention have one glass transition temperature or two, depending on the particular structure and/or the compatibility of the block units. Most of these crystalline block copolymers for tough, solvent resistant films with high tensile properties. While all of the copolymers produced by the present invention are crystalline, testing reveals that copolymers with longer imide blocks or higher imide content have increased crystallinity.

  11. Elasticity of crystalline molecular explosives

    SciTech Connect

    Hooks, Daniel E.; Ramos, Kyle J.; Bolme, C. A.; Cawkwell, Marc J.

    2015-04-14

    Crystalline molecular explosives are key components of engineered explosive formulations. In precision applications a high degree of consistency and predictability is desired under a range of conditions to a variety of stimuli. Prediction of behaviors from mechanical response and failure to detonation initiation and detonation performance of the material is linked to accurate knowledge of the material structure and first stage of deformation: elasticity. The elastic response of pentaerythritol tetranitrate (PETN), cyclotrimethylene trinitramine (RDX), and cyclotetramethylene tetranitramine (HMX), including aspects of material and measurement variability, and computational methods are described in detail. Experimental determinations of elastic tensors are compared, and an evaluation of sources of error is presented. Furthermore, computed elastic constants are also compared for these materials and for triaminotrinitrobenzene (TATB), for which there are no measurements.

  12. Elasticity of crystalline molecular explosives

    DOE PAGES

    Hooks, Daniel E.; Ramos, Kyle J.; Bolme, C. A.; Cawkwell, Marc J.

    2015-04-14

    Crystalline molecular explosives are key components of engineered explosive formulations. In precision applications a high degree of consistency and predictability is desired under a range of conditions to a variety of stimuli. Prediction of behaviors from mechanical response and failure to detonation initiation and detonation performance of the material is linked to accurate knowledge of the material structure and first stage of deformation: elasticity. The elastic response of pentaerythritol tetranitrate (PETN), cyclotrimethylene trinitramine (RDX), and cyclotetramethylene tetranitramine (HMX), including aspects of material and measurement variability, and computational methods are described in detail. Experimental determinations of elastic tensors are compared, andmore » an evaluation of sources of error is presented. Furthermore, computed elastic constants are also compared for these materials and for triaminotrinitrobenzene (TATB), for which there are no measurements.« less

  13. In Search of Enzymes with a Role in 3′, 5′-Cyclic Guanosine Monophosphate Metabolism in Plants

    PubMed Central

    Gross, Inonge; Durner, Jörg

    2016-01-01

    In plants, nitric oxide (NO)-mediated 3′, 5′-cyclic guanosine monophosphate (cGMP) synthesis plays an important role during pathogenic stress response, stomata closure upon osmotic stress, the development of adventitious roots and transcript regulation. The NO-cGMP dependent pathway is well characterized in mammals. The binding of NO to soluble guanylate cyclase enzymes (GCs) initiates the synthesis of cGMP from guanosine triphosphate. The produced cGMP alters various cellular responses, such as the function of protein kinase activity, cyclic nucleotide gated ion channels and cGMP-regulated phosphodiesterases. The signal generated by the second messenger is terminated by 3′, 5′-cyclic nucleotide phosphodiesterase (PDEs) enzymes that hydrolyze cGMP to a non-cyclic 5′-guanosine monophosphate. To date, no homologues of mammalian cGMP-synthesizing and degrading enzymes have been found in higher plants. In the last decade, six receptor proteins from Arabidopsis thaliana have been reported to have guanylate cyclase activity in vitro. Of the six receptors, one was shown to be a NO dependent guanylate cyclase enzyme (NOGC1). However, the role of these proteins in planta remains to be elucidated. Enzymes involved in the degradation of cGMP remain elusive, albeit, PDE activity has been detected in crude protein extracts from various plants. Additionally, several research groups have partially purified and characterized PDE enzymatic activity from crude protein extracts. In this review, we focus on presenting advances toward the identification of enzymes involved in the cGMP metabolism pathway in higher plants. PMID:27200049

  14. Folding Properties of Cytosine Monophosphate Kinase from E. coli Indicate Stabilization through an Additional Insert in the NMP Binding Domain

    PubMed Central

    Beitlich, Thorsten; Lorenz, Thorsten; Reinstein, Jochen

    2013-01-01

    The globular 25 kDa protein cytosine monophosphate kinase (CMPK, EC ID: 2.7.4.14) from E. coli belongs to the family of nucleoside monophosphate (NMP) kinases (NMPK). Many proteins of this family share medium to high sequence and high structure similarity including the frequently found α/β topology. A unique feature of CMPK in the family of NMPKs is the positioning of a single cis-proline residue in the CORE-domain (cis-Pro124) in conjunction with a large insert in the NMP binding domain. This insert is not found in other well studied NMPKs such as AMPK or UMP/CMPK. We have analyzed the folding pathway of CMPK using time resolved tryptophan and FRET fluorescence as well as CD. Our results indicate that unfolding at high urea concentrations is governed by a single process, whereas refolding in low urea concentrations follows at least a three step process which we interpret as follows: Pro124 in the CORE-domain is in cis in the native state (Nc) and equilibrates with its trans-isomer in the unfolded state (Uc - Ut). Under refolding conditions, at least the Ut species and possibly also the Uc species undergo a fast initial collapse to form intermediates with significant amount of secondary structure, from which the trans-Pro124 fraction folds to the native state with a 100-fold lower rate constant than the cis-Pro124 species. CMPK thus differs from homologous NMP kinases like UMP/CMP kinase or AMP kinase, where folding intermediates show much lower content of secondary structure. Importantly also unfolding is up to 100-fold faster compared to CMPK. We therefore propose that the stabilizing effect of the long NMP-domain insert in conjunction with a subtle twist in the positioning of a single cis-Pro residue allows for substantial stabilization compared to other NMP kinases with α/β topology. PMID:24205218

  15. Interactions between Small Heat Shock Protein α-Crystallin and Galectin-Related Interfiber Protein (GRIFIN) in the Ocular Lens†

    PubMed Central

    Barton, Kelly A.; Hsu, Cheng-Da; Petrash, J. Mark

    2013-01-01

    As a member of the small heat shock protein superfamily, α-crystallin has a chaperone-like ability to recognize and bind denatured or unfolded proteins and prevent their aggregation. Recent studies suggest that α-crystallin may also interact with a variety of proteins under native conditions in vitro. To identify potential binding partners for α-crystallin in the intact ocular lens, we conducted cross-linking studies in transgenic mouse lenses designed for overexpression of His-tagged human αA-crystallin. Interacting proteins were copurified with the epitope-tagged crystallin complexes and were identified by tandem mass spectrometry. This approach identified GRIFIN (galectin-related interfiber protein) as a novel binding partner. Consistent with results from cross-linking, GRIFIN subunits copurified with α-crystallin complexes during size exclusion chromatography of nontransgenic mouse lens extracts prepared without chemical cross-linking. Equilibrium binding to GRIFIN was studied using native α-crystallin isolated from calf lenses as well as oligomeric complexes reconstituted from recombinant αA- and αB-crystallin subunits. Calf lens α-crystallin binds GRIFIN with relatively high affinity (Kd=6.5 ± 0.8 μM) at a stoichiometry of 0.25 ± 0.01 GRIFIN monomer/α-crystallin subunit. The binding interaction between α-crystallin and GRIFIN is enhanced up to 5-fold in the presence of 3 mM ATP. These binding data support the hypothesis that GRIFIN is a novel binding partner of α-crystallin in the lens. PMID:19296714

  16. Visual Pattern Memory Requires "Foraging" Function in the Central Complex of "Drosophila"

    ERIC Educational Resources Information Center

    Wang, Zhipeng; Pan, Yufeng; Li, Weizhe; Jiang, Huoqing; Chatzimanolis, Lazaros; Chang, Jianhong; Gong, Zhefeng; Liu, Li

    2008-01-01

    The role of the "foraging" ("for)" gene, which encodes a cyclic guanosine-3',5'-monophosphate (cGMP)-dependent protein kinase (PKG), in food-search behavior in "Drosophila" has been intensively studied. However, its functions in other complex behaviors have not been well-characterized. Here, we show experimentally in "Drosophila" that the "for"…

  17. Osmium(VI) complexes as a new class of potential anti-cancer agents.

    PubMed

    Ni, Wen-Xiu; Man, Wai-Lun; Cheung, Myra Ting-Wai; Sun, Raymond Wai-Yin; Shu, Yuan-Lan; Lam, Yun-Wah; Che, Chi-Ming; Lau, Tai-Chu

    2011-02-21

    A nitridoosmium(VI) complex [Os(VI)(N)(sap)(OH(2))Cl] (H(2)sap = N-salicylidene-2-aminophenol) displays prominent in vitro and in vivo anti-cancer properties, induces S- and G2/M-phase arrest and forms a stable adduct with dianionic 5'-guanosine monophosphate.

  18. Hyperbranched Polyether Polyols with Liquid Crystalline Properties.

    PubMed

    Sunder; Quincy; Mülhaupt; Frey

    1999-10-01

    The attachment of mesogens as end groups to hyperbranched polyglycerol (degree of polymerization 22-45; see schematic representation, the rigid mesogens are shown as rods and the flexible alkyl chains as lines) leads to liquid crystalline polymers with narrow polydispersity, whose liquid crystalline behavior is induced by the mesogenic end groups only.

  19. Navigating the Waters of Unconventional Crystalline Hydrates

    PubMed Central

    2015-01-01

    Elucidating the crystal structures, transformations, and thermodynamics of the two zwitterionic hydrates (Hy2 and HyA) of 3-(4-dibenzo[b,f][1,4]oxepin-11-yl-piperazin-1-yl)-2,2-dimethylpropanoic acid (DB7) rationalizes the complex interplay of temperature, water activity, and pH on the solid form stability and transformation pathways to three neutral anhydrate polymorphs (Forms I, II°, and III). HyA contains 1.29 to 1.95 molecules of water per DB7 zwitterion (DB7z). Removal of the essential water stabilizing HyA causes it to collapse to an amorphous phase, frequently concomitantly nucleating the stable anhydrate Forms I and II°. Hy2 is a stoichiometric dihydrate and the only known precursor to Form III, a high energy disordered anhydrate, with the level of disorder depending on the drying conditions. X-ray crystallography, solid state NMR, and H/D exchange experiments on highly crystalline phase pure samples obtained by exquisite control over crystallization, filtration, and drying conditions, along with computational modeling, provided a molecular level understanding of this system. The slow rates of many transformations and sensitivity of equilibria to exact conditions, arising from its varying static and dynamic disorder and water mobility in different phases, meant that characterizing DB7 hydration in terms of simplified hydrate classifications was inappropriate for developing this pharmaceutical. PMID:26075319

  20. Chaperone-like activity and quaternary structure of alpha-crystallin.

    PubMed

    Raman, B; Rao, C M

    1994-11-01

    alpha-Crystallin has been shown to function as a molecular chaperone in preventing thermal aggregation of crystallins and other proteins. The molecular mechanism of this protection is not yet clear. gamma-Crystallin aggregates upon exposure to UV light. We have investigated the effect of the presence of alpha-crystallin in the photoaggregation process and find that alpha-crystallin does not prevent photoaggregation at low temperatures. The protection starts around 30 degrees C and steeply increases with temperature. The plot of protection ability versus temperature is sigmoidal, indicating a structural transition. Perturbation of the quaternary structure of alpha by non-thermal mode, such as 3 M urea, also results in enhanced protection. Pyrene, a hydrophobic fluorophore, is sparingly soluble in water. alpha-Crystallin enhances the solubility of pyrene by severalfold. Temperature dependence of this solubilization shows a transition around 30 degrees C (another at about 50 degrees C). Fluorescence intensity ratio of third and first peaks of pyrene emission (I3/I1,), indicative of hydrophobicity of the reporting area, also shows similar transitions suggesting enhanced hydrophobicity. Gel filtration experiments of irradiated samples indicate the complex formation between gamma- and alpha-crystallins. alpha-Crystallin does not prevent cold precipitation of gamma-crystallin. On the basis of these results, we hypothesize that alpha-crystallin prevents aggregation of non-native structures by providing appropriately placed hydrophobic surfaces. A structural transition above 30 degrees C enhances the protective ability, perhaps by increasing or reorganizing the hydrophobic surfaces. A similar temperature dependence has been reported for GroEL. Whether a structural switch, either activated by temperature, solvent conditions, or small molecule binding, forms a part of the general mechanism of chaperone activity needs to be investigated.

  1. Binding of actin to lens alpha crystallins

    NASA Technical Reports Server (NTRS)

    Gopalakrishnan, S.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    Actin has been coupled to a cyanogen bromide-activated Sepharose 4B column, then tested for binding to alpha, beta, and gamma crystallin preparations from the bovine lens. Alpha, but not beta or gamma, crystallins bound to the actin affinity column in a time dependent and saturable manner. Subfractionation of the alpha crystallin preparation into the alpha-A and alpha-B species, followed by incubation with the affinity column, demonstrated that both species bound approximately the same. Together, these studies demonstrate a specific and saturable binding of lens alpha-A and alpha-B with actin.

  2. Interaction and permeability of water with liquid crystalline thermoset

    NASA Astrophysics Data System (ADS)

    Feng, Jianxun

    The complex transport behavior of water in both liquid crystalline thermoset and non-liquid crystalline thermoset systems were investigated. The liquid crystalline thermoset was 4,4'-diglycidyloxy-alpha-methylstilbene with sulfanilamine (SAA) as the crosslinking agent, the non-liquid crystalline thermoset the diglycidyl ether of bisphenol A. The liquid crystalline thermosets have higher barrier properties than isotropic non-LC epoxy resins. The efficient chain packing of the smectic mesophase of the liquid crystalline thermosets is attributed as the main factor for this difference. Permeation testing results show that the diffusion coefficient, permeability, and solubility coefficient depend on the amine/epoxide functional ratio. FTIR results confirmed that hydrophilic groups in the crosslinked network are one of the major factors that control the sorption and diffusion of water in epoxy resins. Two possible water-epoxy hydrogen bond configurations are identified, namely hydrogen bond formation of water to amine groups and hydrogen bond formation of water molecules to hydroxyl groups. Thus, diffusion of water molecules into epoxy resins depends on two major factors, namely, the availability of appropriate microvoids in the cured network and the interaction between the water molecules and the epoxy resin matrix. Depression of glass transition temperature was revealed by dynamic mechanical thermal analysis. The intrinsic moisture sensitivity of the epoxy resins is traceable directly to the molecular structure of the network. The presence of polar groups provides the chemical basis for moisture sensitivity. The entropy model can satisfactorily describe the nature of the depression of glass transition temperature. The hypothesis of a heterogeneous network was confirmed by phase images of atomic force microscopy for all of the epoxy samples. High crosslinked domains are surrounded by low crosslinked regions. Quantitative analysis of phase images shows that the relative

  3. Characterization of the major cyanogen bromide fragment of alpha-A crystallin

    NASA Technical Reports Server (NTRS)

    Ifeanyi, F.; Takemoto, L.; Spooner, B. S. (Principal Investigator)

    1991-01-01

    Alpha crystallin from the bovine lens has been digested with cyanogen bromide, and the major fragment (CB-1) has been purified using reverse phase HPLC. Characterization of this fragment by Edman degradation and antisera to synthetic peptides indicates that it originates from alpha-A crystallin, but lacks the N-terminal methionine and the last 35 amino acids from the C-terminus of the molecule. The purified CB-1 fragment binds as well as native alpha crystallin to lens membrane, but is unable to self-assemble into the correct size of high molecular weight oligomeric complexes characteristic of the intact alpha-A chain. Together, these results demonstrate that the alpha-A chain is comprised of at least two functional domains, one of which is involved in binding of alpha-A crystallin to lens membrane, and another which is necessary for correct self-assembly of the molecule into high molecular weight oligomers.

  4. The amazing properties of crystalline color superconductors

    NASA Astrophysics Data System (ADS)

    Mannarelli, Massimo

    2014-07-01

    This paper is a brief journey into the amazing realm of crystalline color superconductors. Starting from a qualitative description of superfluids, superconductors and supersolids, we show how inhomogeneous phases may arise when the system is under stress. These basic concepts are then extended to quark matter, in which a richer variety of phases can be realized. The most interesting properties of the crystalline color superconductors are presented. This brief journey ends with a discussion of crystalline color superconductors in compact stars and related astrophysical observables. We aim at providing a pedagogical introduction for nonexpert in the field to a few interesting properties of crystalline color superconductors, without discussing the methods and the technicalities. Thus, the results are presented without a proof. However, we try to give a qualitatively clear description of the main concepts, using standard quantum field theory and analogies with condensed matter systems.

  5. Genetics Home Reference: Bietti crystalline dystrophy

    MedlinePlus

    ... on PubMed Central Mansour AM, Uwaydat SH, Chan CC. Long-term follow-up in Bietti crystalline dystrophy. ... VD, Zhang J, Gesualdo C, Corte MD, Chan CC, Fielding Hejtmancik J, Simonelli F. An atypical form ...

  6. Analysis of nitric oxide-cyclic guanosine monophosphate signaling during metamorphosis of the nudibranch Phestilla sibogae Bergh (Gastropoda: Opisthobranchia).

    PubMed

    Bishop, Cory D; Pires, Anthony; Norby, Shong-Wan; Boudko, Dmitri; Moroz, Leonid L; Hadfield, Michael G

    2008-01-01

    The gas nitric oxide (NO), and in some cases its downstream second messenger, cyclic guanosine monophosphate (cGMP) function in different taxa to regulate the timing of life-history transitions. Increased taxonomic sampling is required to foster conclusions about the evolution and function of NO/cGMP signaling during life-history transitions. We report on the function and localization of NO and cGMP signaling during metamorphosis of the nudibranch Phestilla sibogae. Pharmacological manipulation of NO or cGMP production in larvae modulated responses to a natural settlement cue from the coral Porites compressa in a manner that suggest inhibitory function for NO/cGMP signaling. However, these treatments were not sufficient to induce metamorphosis in the absence of cue, a result unique to this animal. We show that induction of metamorphosis in response to the settlement cue is associated with a reduction in NO production. We documented the expression of putative NO synthase (NOS) and the production of cGMP during larval development and observed no larval cells in which NOS and cGMP were both detected. The production of cGMP in a bilaterally symmetrical group of cells fated to occupy the distal tip of rhinophores is correlated with competence to respond to the coral settlement cue. These results suggest that endogenous NO and cGMP are involved in modulating responses of P. sibogae to a natural settlement cue. We discuss these results with respect to habitat selection and larval ecology. PMID:18460091

  7. An evaluation of short-term corticosteroid response in perennial allergic rhinitis using histamine and adenosine monophosphate nasal challenge

    PubMed Central

    Wilson, Andrew M; Sims, Erika J; Orr, Linda C; Robb, Fiona; Lipworth, Brian J

    2003-01-01

    Aims To evaluate the role of AMP nasal challenge as a measure of short-term treatment response in patients receiving intranasal corticosteroids. Adenosine monophosphate (AMP) challenge has been shown to be a good inflammatory surrogate in the lower airways, but it has not been properly evaluated as a nasal challenge test. Methods Fourteen patients with perennial allergic rhinitis (PAR) were randomized to receive 2 weeks treatment with placebo (PL) or 200 µg intranasal mometasone furoate (MF) once daily in a randomized single-blind crossover study. AMP (25–800 mg ml−1) and histamine (0.25–8 mg ml−1) nasal challenge testing were performed after each treatment period with 30% decrease in minimal cross-sectional area (MCA). Domiciliary symptom data were collected. Results There was a significant (P < 0.05) improvement in PC30 MCA and nasal volume with AMP but not with histamine comparing MF vs PL. This amounted to a 2.8 (95% CI 1.5, 4.0) and 0.7 (95% CI −0.5, 1.9) doubling-dose change for AMP and histamine challenges, respectively. There were significant (P < 0.05) improvements in nasal symptoms and quality of life. Conclusions AMP nasal challenge using acoustic rhinometry may be a useful test to assess short-term treatment response in patient with PAR. PMID:12680883

  8. Characterization of a dual-active enzyme, DcpA, involved in cyclic diguanosine monophosphate turnover in Mycobacterium smegmatis.

    PubMed

    Sharma, Indra Mani; Prakash, Sunita; Dhanaraman, Thillaivillalan; Chatterji, Dipankar

    2014-10-01

    We have reported previously that the long-term survival of Mycobacterium smegmatis is facilitated by a dual-active enzyme MSDGC-1 (renamed DcpA), which controls the cellular turnover of cyclic diguanosine monophosphate (c-di-GMP). Most mycobacterial species possess at least a single copy of a DcpA orthologue that is highly conserved in terms of sequence similarity and domain architecture. Here, we show that DcpA exists in monomeric and dimeric forms. The dimerization of DcpA is due to non-covalent interactions between two protomers that are arranged in a parallel orientation. The dimer shows both synthesis and hydrolysis activities, whereas the monomer shows only hydrolysis activity. In addition, we have shown that DcpA is associated with the cytoplasmic membrane and exhibits heterogeneous cellular localization with a predominance at the cell poles. Finally, we have also shown that DcpA is involved in the change in cell length and colony morphology of M. smegmatis. Taken together, our study provides additional evidence about the role of the bifunctional protein involved in c-di-GMP signalling in M. smegmatis.

  9. Effect of caffeine on erectile function via up-regulating cavernous cyclic guanosine monophosphate in diabetic rats.

    PubMed

    Yang, Rong; Wang, Jiuling; Chen, Yun; Sun, Zeyu; Wang, Run; Dai, Yutian

    2008-01-01

    Erectile dysfunction (ED) is a common complication of diabetes mellitus. Phosphodiesterase-5 (PDE5) inhibitors, which inhibit the breakdown of intracellular cyclic guanosine monophosphate (cGMP), are used to treat diabetic ED. Caffeine, a nonselective PDE inhibitor used in our daily diet, is controversial regarding its effect on erectile function. To investigate the effect of caffeine on erectile function in diabetic rat models and explore the mechanism, male Sprague-Dawley rats were injected with streptozotocin to induce diabetes mellitus. The rats with blood glucose levels above 300 mg/dL were selected for the study. The rats were divided into 4 groups: group A (normal control rats), group B (diabetic rats treated with normal saline), group C (diabetic rats treated with caffeine, 10 mg/kg per day), and group D (diabetic rats treated with caffeine, 20 mg/kg per day). After 8 weeks of treatment, intracavernous pressure (ICP) was measured to assess erectile function. The radioimmunoassay was used to evaluate the level of cGMP in the cavernosum. The ICP and the cavernous cGMP decreased significantly in the diabetic rats compared with normal controls. An 8-week administration of caffeine at the given dosages increased the ICP and cavernous cGMP in diabetic rats. Caffeine consumption improved the erectile function of diabetic rats by up-regulating cavernous cGMP.

  10. Characterization of two 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase isozymes from Saccharomyces cerevisiae.

    PubMed

    Tibbetts, A S; Appling, D R

    2000-07-01

    The Saccharomyces cerevisiae ADE16 and ADE17 genes encode 5-aminoimidazole-4-carboxamide ribonucleotide transformylase isozymes that catalyze the penultimate step of the de novo purine biosynthesis pathway. Disruption of these two chromosomal genes results in adenine auxotrophy, whereas expression of either gene alone is sufficient to support growth without adenine. In this work, we show that an ade16 ade17 double disruption also leads to histidine auxotrophy, similar to the adenine/histidine auxotrophy of ade3 mutant yeast strains. We also report the purification and characterization of the ADE16 and ADE17 gene products (Ade16p and Ade17p). Like their counterparts in other organisms, the yeast isozymes are bifunctional, containing both 5-aminoimidazole-4-carboxamide ribonucleotide transformylase and inosine monophosphate cyclohydrolase activities, and exist as homodimers based on cross-linking studies. Both isozymes are localized to the cytosol, as shown by subcellular fractionation experiments and immunofluorescent staining. Epitope-tagged constructs were used to study expression of the two isozymes. The expression of Ade17p is repressed by the addition of adenine to the media, whereas Ade16p expression is not affected by adenine. Ade16p was observed to be more abundant in cells grown on nonfermentable carbon sources than in glucose-grown cells, suggesting a role for this isozyme in respiration or sporulation.

  11. A Mycobacterium smegmatis mutant with a defective inositol monophosphate phosphatase gene homolog has altered cell envelope permeability.

    PubMed Central

    Parish, T; Liu, J; Nikaido, H; Stoker, N G

    1997-01-01

    A bacteriophage infection mutant (strain LIMP7) of Mycobacterium smegmatis was isolated following transposon mutagenesis. The mutant showed an unusual phenotype, in that all phages tested produced larger plaques on this strain compared to the parent strain. Other phenotypic characteristics of the mutant were slower growth, increased clumping in liquid culture, increased resistance to chloramphenicol and erythromycin, and increased sensitivity to isoniazid and several beta-lactam antibiotics. Permeability studies showed decreases in the accumulation of lipophilic molecules (norfloxacin and chenodeoxycholate) and a small increase with hydrophilic molecules (cephaloridine); taken together, these characteristics indicate an altered cell envelope. The DNA adjacent to the transposon in LIMP7 was cloned and was shown to be highly similar to genes encoding bacterial and mammalian inositol monophosphate phosphatases. Inositol is important in mycobacteria as a component of the major thiol mycothiol and also in the cell wall, with phosphatidylinositol anchoring lipoarabinomannan (LAM) in the cell envelope. In LIMP7, levels of phosphatidylinositol dimannoside, the precursor of LAM, were less than half of those in the wild-type strain, confirming that the mutation had affected the synthesis of inositol-containing molecules. The impA gene is located within the histidine biosynthesis operon in both M. smegmatis and Mycobacterium tuberculosis, lying between the hisA and hisF genes. PMID:9401044

  12. Pharmacokinetic and pharmacodynamic analysis of inosine monophosphate dehydrogenase activity in hematopoietic cell transplantation recipients treated with mycophenolate mofetil.

    PubMed

    Li, Hong; Mager, Donald E; Sandmaier, Brenda M; Storer, Barry E; Boeckh, Michael J; Bemer, Meagan J; Phillips, Brian R; Risler, Linda J; McCune, Jeannine S

    2014-08-01

    A novel approach to personalizing postgrafting immunosuppression in hematopoietic cell transplantation (HCT) recipients is evaluating inosine monophosphate dehydrogenase (IMPDH) activity as a drug-specific biomarker of mycophenolic acid (MPA)-induced immunosuppression. This prospective study evaluated total MPA, unbound MPA, and total MPA glucuronide plasma concentrations and IMPDH activity in peripheral blood mononuclear cells (PMNCs) at 5 time points after the morning dose of oral mycophenolate mofetil (MMF) on day +21 in 56 nonmyeloablative HCT recipients. Substantial interpatient variability in pharmacokinetics and pharmacodynamics was observed and accurately characterized by the population pharmacokinetic-dynamic model. IMPDH activity decreased with increasing MPA plasma concentration, with maximum inhibition coinciding with maximum MPA concentration in most patients. The overall relationship between MPA concentration and IMPDH activity was described by a direct inhibitory maximum effect model with an IC50 of 3.23 mg/L total MPA and 57.3 ng/mL unbound MPA. The day +21 IMPDH area under the effect curve (AUEC) was associated with cytomegalovirus reactivation, nonrelapse mortality, and overall mortality. In conclusion, a pharmacokinetic-dynamic model was developed that relates plasma MPA concentrations with PMNC IMPDH activity after an MMF dose in HCT recipients. Future studies should validate this model and confirm that day +21 IMPDH AUEC is a predictive biomarker.

  13. Directed breeding of an Arthrobacter mutant for high-yield production of cyclic adenosine monophosphate by N + ion implantation

    NASA Astrophysics Data System (ADS)

    Song, He; Chen, Xiaochun; Cao, Jiaming; Fang, Ting; Bai, Jianxin; Xiong, Jian; Ying, Hanjie

    2010-08-01

    To obtain a cyclic adenosine monophosphate (cAMP) high-yield production strain, Arthrobacter NG-1 was mutated by N + ion implantation with an energy level of 10 keV and dose of 7×10 15 ions/cm 2. Combined with directed screening methods, a xanthine-defective and 8-azaguanine (8-AG)-resistant mutant Arthrobacter A302 was selected. The concentration of cAMP produced by this mutant was 41.7% higher than that of the original strain and reached 9.78 g/L. Through ten-generation investigation, the capability of cAMP production of A302 was found to be stable. Compared with the original strain, the special activities of key enzymes in A302, which influenced the cAMP biosynthesis, was analyzed. IMP dehydrogenase activity was defective, whereas PRPP amidotransferase, sAMP synthetase and adenylate cyclase activities were increased by 61.5%, 147% and 21.7%, respecitively, which might explain the mutagenesis mechanism by N + ions implantation under the enzymatic level.

  14. A Mo(V) Monophosphate with an Intersecting Tunnel Structure: K 2Mo 2P 2O 11

    NASA Astrophysics Data System (ADS)

    Gueho, C.; Borel, M. M.; Grandin, A.; Leclaire, A.; Raveau, B.

    1993-06-01

    A new molybdenum (V) monophosphate K 2Mo 2P 2O 11 has been isolated. The single crystal X-ray diffraction study of this phase has shown that it is isotypic with K 2Nb 2As 2O 11. It crystallizes in the P21/ c space group with a = 9.867 (2), b = 10.122 (1), c = 9.903 (2) Å, β = 97.95 (1)°. A new description of the structure is given, based on the existence of Mo 2P 2O 15 units formed of one Mo 2O 11 group sharing four of its corners with two PO 4 tetrahedra and leading to [Mo 2P 2O 13] ∞ chains running along c. The [Mo 2P 2O 11] 1 x framework forms two different intersecting tunnels running along c and <110>, respectively, where the K + cations are located. The existence of one free apex for each MoO 6 octahedron, which characterizes Mo(V), allows a great flexibility of the structure.

  15. Favism: effect of divicine on rat erythrocyte sulfhydryl status, hexose monophosphate shunt activity, morphology, and membrane skeletal proteins.

    PubMed

    McMillan, D C; Bolchoz, L J; Jollow, D J

    2001-08-01

    Favism is an acute anemic crisis that can occur in susceptible individuals who ingest fava beans. The fava bean pyrimidine aglycone divicine has been identified as a hemotoxic constituent; however, its mechanism of toxicity remains unknown. We have shown recently that divicine can induce a favic-like response in rats and that divicine is directly toxic to rat red cells. In the present study, we have examined the effect of hemotoxic concentrations of divicine on rat erythrocyte sulfhydryl status, hexose monophosphate (HMP) shunt activity, morphology, and membrane skeletal proteins. In vitro exposure of rat red cells to divicine markedly stimulated HMP shunt activity and resulted in depletion of reduced glutathione with concomitant formation of glutathione-protein mixed-disulfides. Examination of divicine-treated red cells by scanning electron microscopy revealed transformation of the cells to an extreme echinocytic morphology. SDS-PAGE and immunoblotting analysis of the membrane skeletal proteins indicated that hemotoxicity was associated with the apparent loss of skeletal protein bands 2.1, 3, and 4.2, and the appearance of membrane-bound hemoglobin. Treatment of divicine-damaged red cells with dithiothreitol reversed the protein changes, which indicated that the observed alterations were due primarily to the formation of disulfide-linked hemoglobin-skeletal protein adducts. The data suggest that oxidative modification of hemoglobin and membrane skeletal proteins by divicine may be key events in the mechanism underlying favism. PMID:11452148

  16. Inhaled Nitric Oxide Increases Urinary Nitric Oxide Metabolites and Cyclic Guanosine Monophosphate in Premature Infants: Relationship to Pulmonary Outcome

    PubMed Central

    Ballard, Philip L.; Keller, Roberta L.; Black, Dennis M.; Durand, David J.; Merrill, Jeffrey D.; Eichenwald, Eric C.; Truog, William E.; Mammel, Mark C.; Steinhorn, Robin; Ryan, Rita M.; Courtney, Sherry E.; Horneman, Hart; Ballard, Roberta A.

    2016-01-01

    Objective Inhaled nitric oxide (iNO) has been tested to prevent bronchopulmonary dysplasia (BPD) in premature infants, however, the role of cyclic guanosine monophosphate (cGMP) is not known. We hypothesized that levels of NO metabolites (NOx) and cGMP in urine, as a noninvasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome. Study Design Studies were performed on 125 infants who required mechanical ventilation at 7 to 14 days and received 24 days of iNO at 20–2 ppm. A control group of 19 infants did not receive iNO. Results In NO-treated infants there was a dose-dependent increase of both NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10–20 ppm iNO) compared with off iNO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease during the 1st month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared with other infants at all iNO doses. Conclusion Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and some levels reflect the severity of lung disease. These results support a role of the NO–cGMP pathway in lung development. PMID:24968129

  17. Targeted Lipidomics Studies Reveal that Linolenic Acid Promotes Cotton Fiber Elongation by Activating Phosphatidylinositol and Phosphatidylinositol Monophosphate Biosynthesis.

    PubMed

    Liu, Gao-Jun; Xiao, Guang-Hui; Liu, Ning-Jing; Liu, Dan; Chen, Pei-Shuang; Qin, Yong-Mei; Zhu, Yu-Xian

    2015-06-01

    The membrane lipids from fast-elongating wild-type cotton (Gossypium hirsutum) fibers at 10 days post-anthesis, wild-type ovules with fiber cells removed, and ovules from the fuzzless-lintless mutant harvested at the same age, were extracted, separated, and quantified. Fiber cells contained significantly higher amounts of phosphatidylinositol (PI) than both ovule samples with PI 34:3 being the most predominant species. The genes encoding fatty acid desaturases (Δ(15)GhFAD), PI synthase (PIS) and PI kinase (PIK) were expressed in a fiber-preferential manner. Further analysis of phosphatidylinositol monophosphate (PIP) indicated that elongating fibers contained four- to five-fold higher amounts of PIP 34:3 than the ovules. Exogenously applied linolenic acid (C18:3), soybean L-α-PI, and PIPs containing PIP 34:3 promoted significant fiber growth, whereas a liver PI lacking the C18:3 moiety, linoleic acid, and PIP 36:2 were completely ineffective. The growth inhibitory effects of carbenoxolone, 5-hydroxytryptamine, and wortmannin were reverted by C18:3, PI, or PIP, respectively, suggesting that PIP signaling is essential for fiber cell growth. Furthermore, cotton plants expressing virus-induced gene-silencing constructs that specifically suppressed GhΔ(15)FAD, GhPIS, or GhPIK expression, resulted in significantly short-fibered phenotypes. Our data provide the basis for in-depth studies on the roles of PI and PIP in mediating cotton fiber growth.

  18. Investigation on the occurrence and significance of cyclic adenosine 3':5'-monophosphate in phytoplankton and natural aquatic communities

    SciTech Connect

    Francko, D.A.

    1980-01-01

    This study is an investigation into the occurrence and potential functions of cyclic adenosine 3':5'-monophosphate (cAMP), a potent and ubiquitous metabolic regulatory molecule in heterotrophic organisms, in phytoplankton and in natural aquatic communities. Laboratory-cultured phytoplankton were grown under both optimal and suboptimal nutrient regimes under constant temperature and illumination regimes. Cellular and extracellular cAMP production, characterized by a number of biochemical techniques, was correlated with growth rate dynamics, chlorophyll a synthesis, /sup 14/C-bicarbonate uptake, alkaline phosphatase activity, and heterocyst formation. The blue-green alga Anabaena flos-aquae was used as a model system in the examination of these metabolic variables. Additionally, this alga was used to test the effects of perturbation of cAMP levels on the aforementioned metabolic variables. Investigations on the occurrence and seasonal dynamics of cAMP in aquatic systems were conducted on Lawrence Lake, a hardwater oligotrophic lake, and on Wintergreen Lake, a hardwater hypereutrophic lake, both in southwestern Michigan. Putative cAMP from both systems was characterized by several biochemical techniques. Weekly sampling of particulate and dissolved cAMP in the epilimnia of both lakes was correlated with data on the rates of primary productivity, alkaline phosphatase activity, chlorophyll a synthesis and changes in phytoplankton community structure.

  19. Chronic intermittent hypoxia induces cardiac hypertrophy by impairing autophagy through the adenosine 5'-monophosphate-activated protein kinase pathway.

    PubMed

    Xie, Sheng; Deng, Yan; Pan, Yue-Ying; Ren, Jie; Jin, Meng; Wang, Yu; Wang, Zhi-Hua; Zhu, Die; Guo, Xue-Ling; Yuan, Xiao; Shang, Jin; Liu, Hui-Guo

    2016-09-15

    Autophagy is tightly regulated to maintain cardiac homeostasis. Impaired autophagy is closely associated with pathological cardiac hypertrophy. However, the relationship between autophagy and cardiac hypertrophy induced by chronic intermittent hypoxia (CIH) is not known. In the present study, we measured autophagy-related genes and autophagosomes during 10 weeks of CIH in rats, and 6 days in H9C2 cardiomyocytes, and showed that autophagy was impaired. This conclusion was confirmed by the autophagy flux assay. We detected significant hypertrophic changes in myocardium with impaired autophagy. Rapamycin, an autophagy enhancer, attenuated the cardiac hypertrophy induced by CIH. Moreover, silencing autophagy-related gene 5 (ATG5) exerted the opposite effect. The role of adenosine monophosphate-activated protein kinase (AMPK) in regulating autophagy under CIH was confirmed using AICAR to upregulate this enzyme and restore autophagy flux. Restoring autophagy by AICAR or rapamycin significantly reversed the hypertrophic changes in cardiomyocytes. To investigate the mechanism of autophagy impairment, we compared phospho (p)-AMPK, p-Akt, cathepsin D, and NFAT3 levels, along with calcineurin activity, between sham and CIH groups. CIH activated calcineurin, and inhibited AMPK and AMPK-mediated autophagy in an Akt- and NFAT3-independent manner. Collectively, these data demonstrated that impaired autophagy induced by CIH through the AMPK pathway contributed to cardiac hypertrophy. PMID:27412517

  20. Chronic intermittent hypoxia induces cardiac hypertrophy by impairing autophagy through the adenosine 5'-monophosphate-activated protein kinase pathway.

    PubMed

    Xie, Sheng; Deng, Yan; Pan, Yue-Ying; Ren, Jie; Jin, Meng; Wang, Yu; Wang, Zhi-Hua; Zhu, Die; Guo, Xue-Ling; Yuan, Xiao; Shang, Jin; Liu, Hui-Guo

    2016-09-15

    Autophagy is tightly regulated to maintain cardiac homeostasis. Impaired autophagy is closely associated with pathological cardiac hypertrophy. However, the relationship between autophagy and cardiac hypertrophy induced by chronic intermittent hypoxia (CIH) is not known. In the present study, we measured autophagy-related genes and autophagosomes during 10 weeks of CIH in rats, and 6 days in H9C2 cardiomyocytes, and showed that autophagy was impaired. This conclusion was confirmed by the autophagy flux assay. We detected significant hypertrophic changes in myocardium with impaired autophagy. Rapamycin, an autophagy enhancer, attenuated the cardiac hypertrophy induced by CIH. Moreover, silencing autophagy-related gene 5 (ATG5) exerted the opposite effect. The role of adenosine monophosphate-activated protein kinase (AMPK) in regulating autophagy under CIH was confirmed using AICAR to upregulate this enzyme and restore autophagy flux. Restoring autophagy by AICAR or rapamycin significantly reversed the hypertrophic changes in cardiomyocytes. To investigate the mechanism of autophagy impairment, we compared phospho (p)-AMPK, p-Akt, cathepsin D, and NFAT3 levels, along with calcineurin activity, between sham and CIH groups. CIH activated calcineurin, and inhibited AMPK and AMPK-mediated autophagy in an Akt- and NFAT3-independent manner. Collectively, these data demonstrated that impaired autophagy induced by CIH through the AMPK pathway contributed to cardiac hypertrophy.

  1. DNA sequence polymorphism within the bovine adenosine monophosphate deaminase 1 (AMPD1) is associated with production traits in Chinese cattle.

    PubMed

    Wei, C-B; Wang, J-Q; Chen, F-Y; Niu, H; Li, K

    2015-02-06

    The objectives of the present study were to detect an 18-bp deletion mutation in the bovine adenosine monophosphate deaminase 1 (AMPD1) gene and analyze its effect on growth traits in 2 Chinese cattle breeds using DNA sequencing and agarose electrophoresis. The five 19-bp polymerase chain reaction products of the AMPD1 gene exhibited 3 genotypes and 2 alleles: WW: homozygote genotype (wild-type); DD: homozygote genotype (mutant-type); WD: heterozygote genotype. Frequencies of the W allele varied from 66.15-70.35%. The associations between the 18-bp deletion mutation in the AMPD1 gene with production traits in 226 Jia-Xian red cattle was analyzed. The animals with genotype WW showed significantly higher heart girth and body weight than those with genotypes WD and DD at 24 months (P < 0.01). Our results indicate that the deletion mutation in the AMPD1 gene is associated with production traits, and may be used for marker-assisted selection in beef cattle breeding programs.

  2. Mining the key regulatory genes of chicken inosine 5'-monophosphate metabolism based on time series microarray data.

    PubMed

    Ma, Teng; Xu, Lu; Wang, Hongzhi; Chen, Jing; Liu, Lu; Chang, Guobin; Chen, Guohong

    2015-01-01

    IMP (inosine 5'-monophosphate) is a compound that enhances the flavor of poultry meat. IMP has become a new breeding trait to improve poultry meat quality. We tried to identify several potential regulatory genes, and construct their predicted regulatory relationships. Time series gene expression profiles of thigh muscle tissues of Rugao chicken, a famous indigenous breed in China, were performed for analysis of genes that are co-expressed or correlated with the concentration of IMP. We found 15 crucial co-expression genes, which are Hspa2, Pten, Gabpa, Bpi, Mkl1, Srf, Cd34, Hspa4, Etv6, Bmpr2, Gde1, Igfbp5, Cd28, Pecam1 and Gja1, that may directly or indirectly regulate IMP metabolism. Eventually, we computed the correlation coefficient between 19 IMP Genes and 15 CGs (15 co-expression genes), and we identified and constructed a predicted regulation network. In conclusion, variation of IMP concentration was primarily connected with the muscle development process. During this process, 15 CGs were identified that may have significant influence on IMP metabolism. In particular, Bmpr2, Pten and co-expression genes correlated with Entpd8 might play important roles in regulating IMP de novo synthesis, decomposition and salvage synthesis.

  3. Antifolate-induced misincorporation of deoxyuridine monophosphate into DNA: inhibition of high molecular weight DNA synthesis in human lymphoblastoid cells.

    PubMed Central

    Sedwick, W D; Kutler, M; Brown, O E

    1981-01-01

    In vitro exposure of a human lymphoblastoid cell line (WIL-2) to the antifolate metoprine (DDMP), when followed by the addition of exogenous deoxyuridine, led to intracellular accumulation of deoxyuridine triphosphate (dUTP) and incorporation of deoxyuridine monophosphate (dUMP) into DNA. When newly synthesized DNA was extracted from DDMP-treated cells that had been labeled with deoxyuridine for up to 3 min, most of the DNA synthesized was no larger than 4 S on alkaline sucrose gradients. In contrast, the predominant form of newly synthesized alkali-stable DNA in cells not treated with drug was larger than 4 S. Abnormal progression of DNA synthesis, degradation of newly synthesized DNA, or both occurred as a delayed consequence of DDMP treatment in the absence of exogenous deoxyuridine when thymidine was used to label DNA of DDMP-treated stability of antifolate-induced misincorporation of dUMP into DNA was not elucidated, it was clear that antifolates can directly perturb the quality as well as the quantity of DNA synthesized by drug-treated cells. PMID:6940156

  4. Interrelations between glycolysis and the hexose monophosphate shunt in erythrocytes as studied on the basis of a mathematical model.

    PubMed

    Schuster, R; Holzhütter, H G; Jacobasch, G

    1988-01-01

    A mathematical model is presented which comprises the reactions of glycolysis, the hexose monophosphate shunt (HMS) and the glutathione system in erythrocytes. The model is used to calculate stationary and time-dependent metabolic states of the cell in vitro and in vivo. The model properly accounts for the following metabolic features observed in vitro: (a) stimulation of the oxidative pentose pathway after addition of pyruvate due to a NADP-dependent lactate dehydrogenase as coupling enzyme between glycolysis and the oxidative pentose pathway, (b) relative share of the oxidative pentose pathway in the total consumption of glucose amounting to approximately 10% in the normal case and to approximately 90% under conditions of oxidative stress excreted by methylene blue. From the application of the model to in vivo conditions it is predicted that (c) under normal conditions glycolysis and the HMS are independently regulated by the energetic and oxidative load, respectively, (d) under conditions of enhanced energetic or oxidative load both glycolysis and the HMS are mainly controlled by the hexokinase; in this situation the highest possible values of the energetic and oxidative load which are compatible with cell integrity are strongly coupled and considerably restricted in comparison with the normal case, (e) the stationary states possess bifurcation points at high and low values of the energetic load. PMID:3191218

  5. Estradiol and chlordecone (Kepone) decrease adenosine 3'5'-cyclic monophosphate concentrations in the ovariectomized immature rat uterus.

    PubMed

    Johnson, D C; Banerjee, S; Chatterjee, S

    1995-10-01

    Adenosine 3'5'-cyclic monophosphate (cAMP) has been repeatedly shown to mimic some actions of estrogen in the rat uterus. However, the relationship between estrogens and uterine cAMP remains controversial. The effect of chronic exposure (3 days) to a biologically potent, long-acting estrogen, estradiol benzoate (EB), or the xenoestrogen chlordecone (Kepone), which has a long half-life in the circulation, was examined in ovariectomized immature rats. Both compounds, when administered in doses that provided equal increases in uterine weight, produced equivalent decreases in uterine cAMP content. Although the decrease in cAMP was apparent within 48 hr, it was more pronounced at 72 hr. There was no reduction in cAMP produced in response to direct stimulation of uterine adenylyl cyclase by forskolin, indicating that loss of the enzyme was not a factor in the lowering of cAMP content. The pure anti-estrogen ICI-182,780, in a dose-dependent fashion, prevented the action the estradiol benzoate and chlordecone, suggesting that the lowering of cAMP was dependent on an estrogen receptor. The physiological significance of reduced uterine cAMP with chronic estrogen treatment remains to be determined. PMID:7545817

  6. Lanthanum enhances glutamate-nitric oxide-3',5'-cyclic guanosine monophosphate pathway in the hippocampus of rats.

    PubMed

    Du, Yanqiu; Yang, Jinghua; Yan, Bo; Bai, Yan; Zhang, Lifeng; Zheng, Linlin; Cai, Yuan

    2016-10-01

    Lanthanum (La) appears to impair learning and memory and increase the toxicity of excitatory amino acids in the central nervous system. The mechanism underlying excitotoxicity induced by La is still unclear. The purpose of this study was to investigate the hippocampal impairment of La exposure and possible mechanism involving the glutamate-nitric oxide (NO)-3'-5'-cyclic guanosine monophosphate (cGMP) pathway. In this study, lactating rats were exposed to 0, 0.25, 0.50, and 1.0% lanthanum chloride (LaCl3) in drinking water, respectively. Their offsprings were exposed to LaCl3 by parental lactation and then administrated with 0, 0.25, 0.50, and 1.0% LaCl3 in drinking water for 1 month. The results showed that La exposure impaired the neuronal ultrastructure and significantly increased the glutamate level, intracellular calcium ion concentrations, and NR1 and NR2B expression in the hippocampi. La exposure significantly enhanced messenger RNA expression and activity levels of inducible NO synthase and increased NO and cGMP levels in the hippocampi in a dose-dependent manner. These results indicate that the mechanism underlying excitotoxicity induced by La is possibly due to alterations of the glutamate-NO-cGMP signaling pathway in the hippocampus. The study provides new findings that may help prevent and improve treatments for La-induced neurotoxicity.

  7. The expression of cyclic adenosine monophosphate responsive element modulator in rat sertoli cells following seminal extract administration

    PubMed Central

    Akmal, Muslim; Siregar, Tongku Nizwan; Wahyuni, Sri; Hamny; Nasution, Mustafa Kamal; Indriati, Wiwik; Panjaitan, Budianto; Aliza, Dwinna

    2016-01-01

    Aim: This study aims to determine the effect of seminal vesicle extract on cyclic adenosine monophosphate responsive element modulator (CREM) expression in rat Sertoli cells. Materials and Methods: This study examined the expression of CREM on 20 male rats (Rattus norvegicus) at 4 months of age, weighing 250-300 g. The rats were divided into four groups: K0, KP1, KP2, and KP3. K0 group was injected with 0.2 ml normal saline; KP1 was injected with 25 mg cloprostenol (Prostavet C, Virbac S. A); KP2 and KP3 were injected with 0.2 and 0.4 ml seminal vesicle extract, respectively. The treatments were conducted 5 times within 12-day interval. At the end of the study, the rats were euthanized by cervical dislocation; then, the testicles were necropsied and processed for histology observation using immunohistochemistry staining. Results: CREM expression in rat Sertoli cells was not altered by the administration of either 0.2 or 0.4 ml seminal vesicle extract. Conclusion: The administration of seminal vesicle extract is unable to increase CREM expression in rat Sertoli cells. PMID:27733803

  8. The effect of polystyrene beads on cyclic 3′,5′-adenosine monophosphate concentration in leukocytes

    PubMed Central

    Manganiello, Vincent; Evans, Warren H.; Stossel, Thomas P.; Mason, Robert J.; Vaughan, Martha

    1971-01-01

    After incubation with polystyrene latex beads for 5 min. the cyclic 3′,5′-adenosine monophosphate (cyclic AMP) content of human peripheral blood leukocyte suspensions was increased severalfold. Preparations enriched in mononuclear cells and containing only 0-20% polymorphonuclear leukocytes (PMN) and no visible platelets exhibited a quantitatively similar response. Purified fractions of cells containing 85-90% PMN responded to polystyrene beads with a much smaller increase in cyclic AMP content. Phagocytosis of paraffin oil emulsion in the unfractionated mixed human leukocyte preparation was associated with little or no change in cyclic AMP levels. There was no change in cyclic AMP content of rabbit alveolar macrophages or guinea pig PMN during phagocytosis of polystyrene beads. All of these observations are consistent with the view that particle uptake per se does not increase cyclic AMP levels in phagocytic cells. It seems probable that the increase in cyclic AMP concentration that results when unfractionated human blood leukocytes are incubated with polystyrene beads occurs in cells other than PMN. PMID:4331596

  9. Influence of salt additives on phase transformation of guanosine 5-monophosphate disodium in anti-solvent crystallization

    NASA Astrophysics Data System (ADS)

    Nguyen, Anh-Tuan; Kang, Jeongki; Kim, Woo-Sik

    2013-06-01

    The influence of sodium chloride (NaCl) as an additive on the anti-solvent crystallization of guanosine 5-monophosphate disodium (GMP-2Na) was investigated in continuous Couette-Taylor (CT) and batch mixing tank (MT) crystallizers. The anti-solvent crystallization initially precipitated amorphous solids of GMP-2Na, which then slowly transformed into hydrate crystals in the solution. However, the phase transformation of GMP-2Na was markedly promoted by the sodium chloride additive due to the common ion effect. While the normal phase transformation in the batch MT crystallizer required over 120 min of crystallization time without using the sodium chloride additive, the process was completed within 60 min when a small amount of the salt additive was added. The phase transformation was also significantly accelerated in the continuous CT crystallizer. Without using the sodium chloride additive, 7 min of the mean residence time was required for the production of 100% hydrate GMP crystals. However, when using the sodium chloride additive, a mean residence time of only 2 min was sufficient to completely transform the amorphous solids of GMP-2Na into hydrate crystals due to the common ion effect combined with the effective fluid motion of the Taylor vortex for the mass transfer.

  10. Effect of Sea Buckthorn Leaves on Inosine Monophosphate and Adenylosuccinatelyase Gene Expression in Broilers during Heat Stress

    PubMed Central

    Zhao, Wei; Chen, Xin; Yan, Changjiang; Liu, Hongnan; Zhang, Zhihong; Wang, Pengzu; Su, Jie; Li, Yao

    2012-01-01

    The trial was conducted to evaluate the effects of sea buckthorn leaves (SBL) on meat flavor in broilers during heat stress. A total 360 one-day-old Arbor Acre (AA) broilers (male) were randomly allotted to 4 treatments with 6 replicates pens pretreatment and 15 birds per pen. The control group was fed a basal diet, the experimental group I, II and III were fed the basal diet supplemented with 0.25%, 0.5%, 1% SBL, respectively. During the 4th week, broilers were exposed to heat stress conditions (36±2°C), after which, muscle and liver samples were collected. High performance liquid chromatography (HPLC) was performed to measure the content of inosine monophosphate (IMP); Real-Time PCR was performed to determine the expression of the ADSL gene. The results showed that the content of breast muscle IMP of group I, II and III was significantly increased 68%, 102% and 103% (p<0.01) compared with the control, respectively; the content of thigh muscle IMP of group II and III was significantly increased 56% and 58% (p<0.01), respectively. Additionally, ADSL mRNA expression in group I, II and III was increased significantly 80%, 65% and 49% (p<0.01) compared with the control, respectively. The content of IMP and expression of ADSL mRNA were increased by basal diet supplemented with SBL, therefore, the decrease of meat flavor caused by heat stress was relieved. PMID:25049483

  11. Pharmacokinetic and pharmacodynamic analysis of inosine monophosphate dehydrogenase activity in hematopoietic cell transplantation recipients treated with mycophenolate mofetil.

    PubMed

    Li, Hong; Mager, Donald E; Sandmaier, Brenda M; Storer, Barry E; Boeckh, Michael J; Bemer, Meagan J; Phillips, Brian R; Risler, Linda J; McCune, Jeannine S

    2014-08-01

    A novel approach to personalizing postgrafting immunosuppression in hematopoietic cell transplantation (HCT) recipients is evaluating inosine monophosphate dehydrogenase (IMPDH) activity as a drug-specific biomarker of mycophenolic acid (MPA)-induced immunosuppression. This prospective study evaluated total MPA, unbound MPA, and total MPA glucuronide plasma concentrations and IMPDH activity in peripheral blood mononuclear cells (PMNCs) at 5 time points after the morning dose of oral mycophenolate mofetil (MMF) on day +21 in 56 nonmyeloablative HCT recipients. Substantial interpatient variability in pharmacokinetics and pharmacodynamics was observed and accurately characterized by the population pharmacokinetic-dynamic model. IMPDH activity decreased with increasing MPA plasma concentration, with maximum inhibition coinciding with maximum MPA concentration in most patients. The overall relationship between MPA concentration and IMPDH activity was described by a direct inhibitory maximum effect model with an IC50 of 3.23 mg/L total MPA and 57.3 ng/mL unbound MPA. The day +21 IMPDH area under the effect curve (AUEC) was associated with cytomegalovirus reactivation, nonrelapse mortality, and overall mortality. In conclusion, a pharmacokinetic-dynamic model was developed that relates plasma MPA concentrations with PMNC IMPDH activity after an MMF dose in HCT recipients. Future studies should validate this model and confirm that day +21 IMPDH AUEC is a predictive biomarker. PMID:24727337

  12. Alterations in the Cerebellar (Phospho)Proteome of a Cyclic Guanosine Monophosphate (cGMP)-dependent Protein Kinase Knockout Mouse*

    PubMed Central

    Corradini, Eleonora; Vallur, Raghavan; Raaijmakers, Linsey M.; Feil, Susanne; Feil, Robert; Heck, Albert J. R.; Scholten, Arjen

    2014-01-01

    The cyclic nucleotide cyclic guanosine monophosphate (cGMP) plays an important role in learning and memory, but its signaling mechanisms in the mammalian brain are not fully understood. Using mass-spectrometry-based proteomics, we evaluated how the cerebellum adapts its (phospho)proteome in a knockout mouse model of cGMP-dependent protein kinase type I (cGKI). Our data reveal that a small subset of proteins in the cerebellum (∼3% of the quantified proteins) became substantially differentially expressed in the absence of cGKI. More changes were observed at the phosphoproteome level, with hundreds of sites being differentially phosphorylated between wild-type and knockout cerebellum. Most of these phosphorylated sites do not represent known cGKI substrates. An integrative computational network analysis of the data indicated that the differentially expressed proteins and proteins harboring differentially phosphorylated sites largely belong to a tight network in the Purkinje cells of the cerebellum involving important cGMP/cAMP signaling nodes (e.g. PDE5 and PKARIIβ) and Ca2+ signaling (e.g. SERCA3). In this way, removal of cGKI could be linked to impaired cerebellar long-term depression at Purkinje cell synapses. In addition, we were able to identify a set of novel putative (phospho)proteins to be considered in this network. Overall, our data improve our understanding of cerebellar cGKI signaling and suggest novel players in cGKI-regulated synaptic plasticity. PMID:24925903

  13. Thick crystalline films on foreign substrates

    DOEpatents

    Smith, Henry I.; Atwater, Harry A.; Geis, Michael W.

    1986-01-01

    To achieve a uniform texture, large crystalline grains or, in some cases, a single crystalline orientation in a thick (>1 .mu.m) film on a foreign substrate, the film is formed so as to be thin (<1 .mu.m) in a certain section. Zone-melting recrystallization is initiated in the thin section and then extended into the thick section. The method may employ planar constriction patterns of orientation filter patterns.

  14. Thick crystalline films on foreign substrates

    DOEpatents

    Smith, H.I.; Atwater, H.A.; Geis, M.W.

    1986-03-18

    To achieve a uniform texture, large crystalline grains or, in some cases, a single crystalline orientation in a thick (>1 [mu]m) film on a foreign substrate, the film is formed so as to be thin (<1 [mu]m) in a certain section. Zone-melting recrystallization is initiated in the thin section and then extended into the thick section. The method may employ planar constriction patterns of orientation filter patterns. 2 figs.

  15. Electrochemical synthesis of highly crystalline copper nanowires

    SciTech Connect

    Kaur, Amandeep; Gupta, Tanish; Kumar, Akshay; Kumar, Sanjeev; Singh, Karamjeet; Thakur, Anup

    2015-05-15

    Copper nanowires were fabricated within the pores of anodic alumina template (AAT) by template synthesis method at pH = 2.9. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were used to investigate the structure, morphology and composition of fabricated nanowires. These characterizations revealed that the deposited copper nanowires were highly crystalline in nature, dense and uniform. The crystalline copper nanowires are promising in application of future nanoelectronic devices and circuits.

  16. Hypoxanthine-guanine phosphoribosyltransferase and inosine 5'-monophosphate dehydrogenase activities in three mammalian species: aquatic (Mirounga angustirostris), semi-aquatic (Lontra longicaudis annectens) and terrestrial (Sus scrofa).

    PubMed

    Barjau Pérez-Milicua, Myrna; Zenteno-Savín, Tania; Crocker, Daniel E; Gallo-Reynoso, Juan P

    2015-01-01

    Aquatic and semiaquatic mammals have the capacity of breath hold (apnea) diving. Northern elephant seals (Mirounga angustirostris) have the ability to perform deep and long duration dives; during a routine dive, adults can hold their breath for 25 min. Neotropical river otters (Lontra longicaudis annectens) can hold their breath for about 30 s. Such periods of apnea may result in reduced oxygen concentration (hypoxia) and reduced blood supply (ischemia) to tissues. Production of adenosine 5'-triphosphate (ATP) requires oxygen, and most mammalian species, like the domestic pig (Sus scrofa), are not adapted to tolerate hypoxia and ischemia, conditions that result in ATP degradation. The objective of this study was to explore the differences in purine synthesis and recycling in erythrocytes and plasma of three mammalian species adapted to different environments: aquatic (northern elephant seal) (n = 11), semiaquatic (neotropical river otter) (n = 4), and terrestrial (domestic pig) (n = 11). Enzymatic activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was determined by spectrophotometry, and activity of inosine 5'-monophosphate dehydrogenase (IMPDH) and the concentration of hypoxanthine (HX), inosine 5'-monophosphate (IMP), adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), ATP, guanosine 5'-diphosphate (GDP), guanosine 5'-triphosphate (GTP), and xanthosine 5'-monophosphate (XMP) were determined by high-performance liquid chromatography (HPLC). The activities of HGPRT and IMPDH and the concentration of HX, IMP, AMP, ADP, ATP, GTP, and XMP in erythrocytes of domestic pigs were higher than in erythrocytes of northern elephant seals and river otters. These results suggest that under basal conditions (no diving, sleep apnea or exercise), aquatic, and semiaquatic mammals have less purine mobilization than their terrestrial counterparts.

  17. Hypoxanthine-guanine phosphoribosyltransferase and inosine 5'-monophosphate dehydrogenase activities in three mammalian species: aquatic (Mirounga angustirostris), semi-aquatic (Lontra longicaudis annectens) and terrestrial (Sus scrofa).

    PubMed

    Barjau Pérez-Milicua, Myrna; Zenteno-Savín, Tania; Crocker, Daniel E; Gallo-Reynoso, Juan P

    2015-01-01

    Aquatic and semiaquatic mammals have the capacity of breath hold (apnea) diving. Northern elephant seals (Mirounga angustirostris) have the ability to perform deep and long duration dives; during a routine dive, adults can hold their breath for 25 min. Neotropical river otters (Lontra longicaudis annectens) can hold their breath for about 30 s. Such periods of apnea may result in reduced oxygen concentration (hypoxia) and reduced blood supply (ischemia) to tissues. Production of adenosine 5'-triphosphate (ATP) requires oxygen, and most mammalian species, like the domestic pig (Sus scrofa), are not adapted to tolerate hypoxia and ischemia, conditions that result in ATP degradation. The objective of this study was to explore the differences in purine synthesis and recycling in erythrocytes and plasma of three mammalian species adapted to different environments: aquatic (northern elephant seal) (n = 11), semiaquatic (neotropical river otter) (n = 4), and terrestrial (domestic pig) (n = 11). Enzymatic activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was determined by spectrophotometry, and activity of inosine 5'-monophosphate dehydrogenase (IMPDH) and the concentration of hypoxanthine (HX), inosine 5'-monophosphate (IMP), adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), ATP, guanosine 5'-diphosphate (GDP), guanosine 5'-triphosphate (GTP), and xanthosine 5'-monophosphate (XMP) were determined by high-performance liquid chromatography (HPLC). The activities of HGPRT and IMPDH and the concentration of HX, IMP, AMP, ADP, ATP, GTP, and XMP in erythrocytes of domestic pigs were higher than in erythrocytes of northern elephant seals and river otters. These results suggest that under basal conditions (no diving, sleep apnea or exercise), aquatic, and semiaquatic mammals have less purine mobilization than their terrestrial counterparts. PMID:26283971

  18. Crystalline Silicon Dielectrics for Superconducting Qubit Circuits

    NASA Astrophysics Data System (ADS)

    Hover, David; Peng, Weina; Sendelbach, Steven; Eriksson, Mark; McDermott, Robert

    2009-03-01

    Superconducting qubit energy relaxation times are limited by microwave loss induced by a continuum of two-level state (TLS) defects in the dielectric materials of the circuit. State-of-the-art phase qubit circuits employ a micron-scale Josephson junction shunted by an external capacitor. In this case, the qubit T1 time is directly proportional to the quality factor (Q) of the capacitor dielectric. The amorphous capacitor dielectrics that have been used to date display intrinsic Q of order 10^3 to 10^4. Shunt capacitors with a Q of 10^6 are required to extend qubit T1 times well into the microsecond range. Crystalline dielectric materials are an attractive candidate for qubit capacitor dielectrics, due to the extremely low density of TLS defects. However, the robust integration of crystalline dielectrics with superconducting qubit circuits remains a challenge. Here we describe a novel approach to the realization of high-Q crystalline capacitor dielectrics for superconducting qubit circuits. The capacitor dielectric is a crystalline silicon nanomembrane. We discuss characterization of crystalline silicon capacitors with low-power microwave transport measurements at millikelvin temperatures. In addition, we report progress on integrating the crystalline capacitor process with Josephson qubit fabrication.

  19. Stability and cytotoxicity of crystallin amyloid nanofibrils

    NASA Astrophysics Data System (ADS)

    Kaur, Manmeet; Healy, Jackie; Vasudevamurthy, Madhusudan; Lassé, Moritz; Puskar, Ljiljana; Tobin, Mark J.; Valery, Celine; Gerrard, Juliet A.; Sasso, Luigi

    2014-10-01

    Previous work has identified crystallin proteins extracted from fish eye lenses as a cheap and readily available source for the self-assembly of amyloid nanofibrils. However, before exploring potential applications, the biophysical aspects and safety of this bionanomaterial need to be assessed so as to ensure that it can be effectively and safely used. In this study, crude crystallin amyloid fibrils are shown to be stable across a wide pH range, in a number of industrially relevant solvents, at both low and high temperatures, and in the presence of proteases. Crystallin nanofibrils were compared to well characterised insulin and whey protein fibrils using Thioflavin T assays and TEM imaging. Cell cytotoxicity assays suggest no adverse impact of both mature and fragmented crystallin fibrils on cell viability of Hec-1a endometrial cells. An IR microspectroscopy study supports long-term structural integrity of crystallin nanofibrils.Previous work has identified crystallin proteins extracted from fish eye lenses as a cheap and readily available source for the self-assembly of amyloid nanofibrils. However, before exploring potential applications, the biophysical aspects and safety of this bionanomaterial need to be assessed so as to ensure that it can be effectively and safely used. In this study, crude crystallin amyloid fibrils are shown to be stable across a wide pH range, in a number of industrially relevant solvents, at both low and high temperatures, and in the presence of proteases. Crystallin nanofibrils were compared to well characterised insulin and whey protein fibrils using Thioflavin T assays and TEM imaging. Cell cytotoxicity assays suggest no adverse impact of both mature and fragmented crystallin fibrils on cell viability of Hec-1a endometrial cells. An IR microspectroscopy study supports long-term structural integrity of crystallin nanofibrils. Electronic supplementary information (ESI) available: ThT fluorescence graphs of buffers and solvents used for

  20. Variation of bagasse crystallinity and cellulase activity during the fermentation of cellulomonas bacteria

    SciTech Connect

    Enriquez, A.; Montalvo, R.; Canales, M.

    1981-07-01

    A characteristic behavior of the fermentation process was observed during the growth of Cellulomonas on sugarcane bagasse. At the early stage of the fermentation the crystallinity index of bagasse increased, suggesting that the major metabolized fraction corresponded to the hemicellulose during this stage. Some time later the crystallinity achieved a steady state and then decreased, which indicated that the most complex structure of bagasse was being attacked. The analysis of the cellulolytic activity of extracellular enzyme in the medium showed a sharp increase followed by an abrupt leveling off and decline in activity. These results along with the reduction of crystallinity index and bagasse utilization (70%) justify the assumption that the C1 component was present in the cellulase complex synthesized by the bacteria. (Refs. 12).

  1. Role of K(V)LQT1 in cyclic adenosine monophosphate-mediated Cl(-) secretion in human airway epithelia.

    PubMed

    Mall, M; Wissner, A; Schreiber, R; Kuehr, J; Seydewitz, H H; Brandis, M; Greger, R; Kunzelmann, K

    2000-09-01

    Ion transport defects underlying cystic fibrosis (CF) lung disease are characterized by impaired cyclic adenosine monophosphate (cAMP)-dependent Cl(-) conductance. Activation of Cl(-) secretion in airways depends on simultaneous activation of luminal Cl(-) channels and basolateral K(+) channels. We determined the role of basolateral K(+) conductance in cAMP- dependent Cl(-) secretion in native human airway epithelium obtained from non-CF and CF patients. CF tissues showed typical alterations of short-circuit currents with enhanced amiloride-sensitive Na(+) conductance and defective cAMP-mediated Cl(-) conductance. In non-CF tissues, Cl(-) secretion was significantly inhibited by the chromanol 293B (10 micromol/liter), a specific inhibitor of K(V)LQT1 K(+) channels. Inhibition was increased after cAMP-dependent stimulation. Similar effects were obtained with Ba(2+) (5 mmol/liter). In patch-clamp experiments with a human bronchial epithelial cell line, stimulation with forskolin (10 micromol/liter) simultaneously activated Cl(-) and K(+) conductance. The K(+) conductance was reversibly inhibited by Ba(2+) and 293B. Analysis of reverse-transcribed messenger RNA from non-CF and CF airways showed expression of human K(V)LQT1. We conclude that the K(+) channel K(V)LQT1 is important in maintaining cAMP-dependent Cl(-) secretion in human airways. Activation of K(V)LQT1 in CF airways in parallel with stimulation of residual CF transmembrane conductance regulator Cl(-) channel activity or alternative Cl(-) channels could help to circumvent the secretory defect.

  2. Erythrocyte metabolism in hyperthyroidism: a microcalorimetric study on changes in the Embden-Meyerhof and the hexose monophosphate pathways.

    PubMed

    Monti, M; Hedner, P; Ikomi-Kumm, J; Valdemarsson, S

    1987-05-01

    Erythrocyte metabolism was studied in vitro by microcalorimetry in 10 hyperthyroid subjects before and after treatment. By inhibiting the enzyme enolase in the Embden-Meyerhof pathway with sodium fluoride (NaF) we have recorded the anaerobic and aerobic contributions in erythrocyte thermogenesis. The decrease in heat production rate in samples with NaF corresponds to the anaerobic contribution, whereas the values from samples with NaF reflect aerobic processes. Before treatment, total heat production rate was 120 +/- 2 mW/l erythrocytes which was higher than the post-treatment value of 99 +/- 2 (P less than 0.001) as well as the value for 14 euthyroid subjects, 108 +/- 2 mW/l (P less than 0.001). The NaF inhibitable rate was 73 +/- 2 before and 63 +/- 1 mW/l after therapy (P less than 0.01). These values correspond to 61 +/- 1 and 64 +/- 1% (n.s.) of the total heat production rate, and were similar to that of 61 +/- 2% for the controls. Heat production rates in the presence of NaF were 47 +/- 1 before and 36 +/- 1 mW/l after therapy (P less than 0.001), representing 39 +/- 1 and 36 +/- 1% of total values, respectively. The present results show that overall metabolism is increased in erythrocytes from hyperthyroid subjects before treatment and returns to normal after normalization of the thyroid function. Moreover, by using microcalorimetry we found that the metabolic activity along the Embden-Meyerhof anaerobic pathway as well as along the hexose monophosphate aerobic pathway in erythrocytes is stimulated by thyroid hormones.

  3. Cyclic adenosine monophosphate phosphodiesterase activity in peripheral blood mononuclear leucocytes from patients with atopic dermatitis: correlation with respiratory atopy.

    PubMed

    Sawai, T; Ikai, K; Uehara, M

    1998-05-01

    We determined the cyclic adenosine monophosphate phosphodiesterase (cAMP-PDE) activity in peripheral blood mononuclear leucocytes from 100 patients with atopic dermatitis (AD) aged 13-57 years (mean +/- SD, 29.8 +/- 17.7 years). The correlation between cAMP-PDE activity and clinical parameters such as the severity of eczema and a personal or family predisposition to atopic respiratory diseases (ARD) (asthma or allergic rhinitis) was examined. Although the enzymic activity varied from normal to very high in the AD patients, cAMP-PDE activity was significantly (P < 0.005) elevated in AD patients (42.1 +/- 22.0 units) as compared with the normal controls (12.4 +/- 5.6) and clinical control subjects (13.4 +/- 9.5). In contrast, we found no correlation between cAMP-PDE activity and the severity of eczema when AD patients were classified into four categories (remission, mild, moderate and severe) according to the extent of their skin involvement. Furthermore, we found that systemic corticosteroid therapy in severe AD patients did not alter the cAMP-PDE activity. cAMP-PDE activity was significantly (P < 0.01) higher in those AD patients who had a personal history of ARD (47.2 +/- 11.2) than in AD patients with a family history of ARD (37.2 +/- 17.4) and those without a personal or family history ('pure' AD) (34.4 +/- 19.8). Nevertheless, the cAMP-PDE activity was significantly higher even in 'pure' AD patients than in the controls. These results suggest that an elevation of cAMP-PDE activity is closely related to a predisposition to respiratory atopy, and does not follow inflammation in AD patients. PMID:9666832

  4. Analysis of nitric oxide-cyclic guanosine monophosphate signaling during metamorphosis of the nudibranch Phestilla sibogae Bergh (Gastropoda: Opisthobranchia)

    PubMed Central

    Bishop, Cory D.; Pires, Anthony; Norby, Shong-Wan; Boudko, Dmitri; Moroz, Leonid L.; Hadfield, Michael G.

    2014-01-01

    SUMMARY The gas nitric oxide (NO), and in some cases its downstream second messenger, cyclic guanosine monophosphate (cGMP) function in different taxa to regulate the timing of life-history transitions. Increased taxonomic sampling is required to foster conclusions about the evolution and function of NO/cGMP signaling during life-history transitions. We report on the function and localization of NO and cGMP signaling during metamorphosis of the nudibranch Phestilla sibogae. Pharmacological manipulation of NO or cGMP production in larvae modulated responses to a natural settlement cue from the coral Porites compressa in a manner that suggest inhibitory function for NO/cGMP signaling. However, these treatments were not sufficient to induce metamorphosis in the absence of cue, a result unique to this animal. We show that induction of metamorphosis in response to the settlement cue is associated with a reduction in NO production. We documented the expression of putative NO synthase (NOS) and the production of cGMP during larval development and observed no larval cells in which NOS and cGMP were both detected. The production of cGMP in a bilaterally symmetrical group of cells fated to occupy the distal tip of rhinophores is correlated with competence to respond to the coral settlement cue. These results suggest that endogenous NO and cGMP are involved in modulating responses of P. sibogae to a natural settlement cue. We discuss these results with respect to habitat selection and larval ecology. PMID:18460091

  5. Effects of dietary supplementation of inosine monophosphate on growth performance, innate immunity and disease resistance of olive flounder (Paralichthys olivaceus).

    PubMed

    Song, Jin-Woo; Lim, Se-Jin; Lee, Kyeong-Jun

    2012-10-01

    This study was investigated to examine the effects of dietary inosine monophosphate (IMP) supplementation on growth performance, feed utilization, innate immunity, hematological parameters and disease resistance of juvenile olive flounder. Five experimental diets were formulated to contain IMP at levels of 0, 0.1, 0.2, 0.4 and 1.0%. All diets were maintained isonitrogenous (48% crude protein) and isocaloric (20.7 MJ/kg diet). Triplicate groups of olive flounder (initial body weight, 7.5 ± 0.02 g) were fed one of the experimental diets to apparent satiation (twice a day) for 14 weeks. Final body weight of fish fed 0.1-0.2% IMP were significantly higher than that of fish fed the 1.0% IMP. Groups of fish fed 0.2 or 0.4% IMP diet had significantly higher myeloperoxidase and lysozyme activities than fish fed the control diet. However, nitro-blue-tetrazolium and superoxide dismutase activities were not significantly different among all treatments. In the challenge test against Streptococcus iniae, cumulative mortality of fish fed IMP supplemented diets was significantly lower (15%, 4%, 4% and 9% for 0.1%, 0.2%, 0.4% and 1.0% IMP, respectively) than that of fish fed the control group (87%). The results suggest that IMP supplementation of 0.46-1.84 g into a kg of fish meal based diet (0.1-0.4% IMP product) can enhance innate immunity and disease resistance of olive flounder.

  6. Adenosine monophosphate-activated protein kinase (AMPK) activators for the prevention, treatment and potential reversal of pathological pain

    PubMed Central

    Price, Theodore J.; Das, Vaskar; Dussor, Gregory

    2015-01-01

    Pathological pain is an enormous medical problem that places a significant burden on patients and can result from an injury that has long since healed or be due to an unidentifiable cause. Although treatments exist, they often either lack efficacy or have intolerable side effects. More importantly, they do not reverse the changes in the nervous system mediating pathological pain, and thus symptoms often return when therapies are discontinued. Consequently, novel therapies are urgently needed that have both improved efficacy and disease-modifying properties. Here we highlight an emerging target for novel pain therapies, adenosine monophosphate-activated protein kinase (AMPK). AMPK is capable of regulating a variety of cellular processes including protein translation, activity of other kinases, and mitochondrial metabolism, many of which are thought to contribute to pathological pain. Consistent with these properties, preclinical studies show positive, and in some cases disease-modifying effects of either pharmacological activation or genetic regulation of AMPK in models of nerve injury, chemotherapy-induced peripheral neuropathy (CIPN), postsurgical pain, inflammatory pain, and diabetic neuropathy. Given the AMPK-activating ability of metformin, a widely prescribed and well-tolerated drug, these preclinical studies provide a strong rationale for both retrospective and prospective human pain trials with this drug. They also argue for the development of novel AMPK activators, whether orthosteric, allosteric, or modulators of events upstream of the kinase. Together, this review will present the case for AMPK as a novel therapeutic target for pain and will discuss future challenges in the path toward development of AMPK-based pain therapeutics. PMID:26521775

  7. [Genetic parameter estimation for inosine-5-monophosphate and intramuscular fat contents and other meat quality traits in chicken muscle].

    PubMed

    Chen, Ji-Lan; Wen, Jie; Zhao, Gui-Ping; Zheng, Mai-Qing; Yang, Ning

    2005-11-01

    The genetic parameters for some important flavor traits like inosine-5'-monophosphate (IMP) and intramuscular fat (IMF) contents in breast meat were estimated using a MTDFREML procedure on 1063 male, 90-day-old, purebred Beijing-You meat-type chicks (BJY). The result showed that the heritability of IMP and IMF contents in BJY breast meat was moderate or low (h2=0.23, 0.10), whereas these parameters were higher for abdominal fat weight (AFW), breast meat yield (BMY), ratio of BMY to carcass weight (BMR), leg muscle yield (LMY), body weight (BW), comb weight(CW) and comb weight percentage (CWB) (h2=0.56-0.79). The heritability of abdominal fat percentage (AFP), leg meat yield (LMY), testicle weight (TW) and testicle weight percentage (TWP) were 0.24, 0.32, 0.39 and 0.35, respectively. IMP exhibited low phenotypic correlations with BMY, LMY and SFT and no significant phenotypic correlations with other traits. IMF, to some extent, exhibited positive phenotypic correlation with BW, AFP, SFT and FSW (rP=0.11-0.33). In terms of genetic correlation, IMP was moderately or significantly negatively correlated with BW and CWP (rA=-0.38,-0.62), and a high level of positive correlation was observed with BMY (rA=0.57). Moreover, IMF was highly correlated with BW and AFW (rA=0.75,0.66), and moderately correlated with AFP and CWP (rA=0.32, 0.40). A low level of positive correlation was observed between IMP and IMF (rA =0.27). We propose that IMP and IMF contents in chicken meat could be increased with selection through line-breeding.

  8. Study of the Renal Tubular Interactions of Thyrocalcitonin, Cyclic Adenosine 3′, 5′ -Monophosphate, 25-Hydroxycholecalciferol, and Calcium Ion

    PubMed Central

    Puschett, Jules B.; Beck, William S.; Jelonek, Adam; Fernandez, Pedro C.

    1974-01-01

    Acute clearance studies were performed in thyroparathyroidectomized animals to determine the actions and interactions of thyrocalcitonin (TCT), cyclic adenosine 3′5′-monophosphate (cAMP), 25-hydroxycholecalciferol (25HCC), and calcium ion on the reabsorption of phosphate, calcium, sodium, and potassium by the kidney. The infusion of 25HCC in a dosage of 60 U/h to moderately saline-expanded animals (2.5% body weight) induced a fall in the excretion of all of the ions under study after 90-120 min similar to that observed in previous experiments from this laboratory. Mean decrements in fractional excretion were: phosphate, 42.0% (P < 0.005); calcium, 25.0% (P < 0.005); sodium, 23.4% (P < 0.001); and potassium, 14.7% (P < 0.005). The superimposition of either porcine or salmon TCT (1-100 MRC U/h for 2 h) resulted in no further alterations in electrolyte excretion. However, the infusion of TCT during steady-state saline expansion, before the administration of 25HCC, obviated the renal transport effects of the vitamin D metabolite. Both in the latter studies, as well as those in which similar doses of TCT were given to hydropenic animals, the hormone itself failed to induce any consistent alteration in electrolyte excretion. Cyclic AMP (50 mg/h) caused an increase in the excretion of phosphate, sodium, and potassium and no change in calcium excretion. Like TCT, the nucleotide blocked the action of 25HCC on the kidney. Raising the mean level of serum ultrafilterable calcium to 3.02±0.25 mEq/liter from 1.62±0.17 mEq/liter likewise prevented enhanced ionic reabsorption due to 25HCC. PMID:4359939

  9. Enhanced Molecular Recognition between Nucleobases and Guanine-5'-monophosphate-disodium (GMP) by Surfactant Aggregates in Aqueous Solution.

    PubMed

    Liu, Zhang; Wang, Dong; Cao, Meiwen; Han, Yuchun; Xu, Hai; Wang, Yilin

    2015-07-15

    Only specific base pairs on DNA can bind with each other through hydrogen bonds, which is called the Watson-Crick (W/C) pairing rule. However, without the constraint of DNA chains, the nucleobases in bulk aqueous solution usually do not follow the W/C pairing rule anymore because of the strong competitive effect of water and the multi-interaction edges of nucleobases. The present work applied surfactant aggregates noncovalently functionalized by nucleotide to enhance the recognition between nucleobases without DNA chains in aqueous solution, and it revealed the effects of their self-assembling ability and morphologies on the recognition. The cationic ammonium monomeric, dimeric, and trimeric surfactants DTAB, 12-3-12, and 12-3-12-3-12 were chosen. The surfactants with guanine-5'-monophosphate-disodium (GMP) form micelles, vesicles, and fingerprint-like and plate-like aggregates bearing the hydrogen-bonding sites of GMP, respectively. The binding parameters of these aggregates with adenine (A), uracil (U), guanine (G), and cytosine(C) indicate that the surfactants can promote W/C recognitions in aqueous solution when they form vesicles (GMP/DTAB) or plate-like aggregates (GMP/12-3-12) with proper molecular packing compactness, which not only provide hydrophobic environments but also shield non-W/C recognition edges. However, the GMP/12-3-12 micelles with loose molecular packing, the GMP/12-3-12 fingerprint-like aggregates where the hydrogen bond sites of GMP are occupied by itself, and the GMP/12-3-12-3-12 vesicles with too strong self-assembling ability cannot promote W/C recognition. This work provides insight into how to design self-assemblies with the performance of enhanced molecule recognition.

  10. Estradiol regulation of hypothalamic astrocyte adenosine 5'-monophosphate-activated protein kinase activity: role of hindbrain catecholamine signaling.

    PubMed

    Tamrakar, Pratistha; Briski, Karen P

    2015-01-01

    Recent work challenges the conventional notion that metabolic monitoring in the brain is the exclusive function of neurons. This study investigated the hypothesis that hypothalamic astrocytes express the ultra-sensitive energy gauge adenosine 5'-monophosphate-activated protein kinase (AMPK), and that the ovarian hormone estradiol (E) controls activation of this sensor by insulin-induced hypoglycemia (IIH). E- or oil (O)-implanted ovariectomized (OVX) rats were pretreated by caudal fourth ventricular administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) prior to sc insulin or vehicle injection. Individual astrocytes identified in situ by glial fibrillary acidic protein immunolabeling were laser-microdissected from the ventromedial (VMH), arcuate (ARH), and paraventricular (PVH) nuclei and the lateral hypothalamic area (LHA), and pooled within each site for Western blot analysis of AMPK and phosphoAMPK (pAMPK) protein expression. In the VMH, baseline astrocyte AMPK and pAMPK levels were respectively increased or decreased in OVX+E versus OVX+O; these profiles did not differ between E and O rats in other hypothalamic loci. In E animals, astrocyte AMPK protein was reduced [VMH] or augmented [PVH; LHA] in response to either 6-OHDA or IIH. IIH increased astrocyte pAMPK expression in each structure in vehicle-, but not 6-OHDA-pretreated E rats. Results provide novel evidence for hypothalamic astrocyte AMPK expression and hindbrain catecholamine-dependent activation of this cell-specific sensor by hypoglycemia in the presence of estrogen. Further research is needed to determine the role of astrocyte AMPK in reactivity of these glia to metabolic imbalance and contribution to restoration of neuro-metabolic stability.

  11. Improved Josephson Qubits incorporating Crystalline Silicon Dielectrics

    NASA Astrophysics Data System (ADS)

    Gao, Yuanfeng; Maurer, Leon; Hover, David; Patel, Umeshkumar; McDermott, Robert

    2010-03-01

    Josephson junction phase quibts are a leading candidate for scalable quantum computing in the solid state. Their energy relaxation times are currently limited by microwave loss induced by a high density of two-level state (TLS) defects in the amorphous dielectric films of the circuit. It is expected that the integration of crystalline, defect-free dielectrics into the circuits will yield substantial improvements in qubit energy relaxation times. However, the epitaxial growth of a crystalline dielectric on a metal underlayer is a daunting challenge. Here we describe a novel approach in which the crystalline silicon nanomembrane of a Silicon-on-Insulator (SOI) wafer is used to form the junction shunt capacitor. The SOI wafer is thermocompression bonded to the device wafer. The handle and buried oxide layers of the SOI are then etched away, leaving the crystalline silicon layer for subsequent processing. We discuss device fabrication issues and present microwave transport data on lumped-element superconducting resonators incorporating the crystalline silicon.

  12. Rotating Anisotropic Crystalline Silicon Nanoclusters in Graphene.

    PubMed

    Chen, Qu; Koh, Ai Leen; Robertson, Alex W; He, Kuang; Lee, Sungwoo; Yoon, Euijoon; Lee, Gun-Do; Sinclair, Robert; Warner, Jamie H

    2015-10-27

    The atomic structure and dynamics of silicon nanoclusters covalently bonded to graphene are studied using aberration-corrected transmission electron microscopy. We show that as the cluster size increases to 4-10 atoms, ordered crystalline cubic phases start to emerge. Anisotropic crystals are formed due to higher stability of the Si-C bond under electron beam irradiation compared to the Si-Si bond. Dynamics of the anisotropic crystalline Si nanoclusters reveal that they can rotate perpendicular to the graphene plane, with oscillations between the two geometric configurations driven by local volume constraints. These results provide important insights into the crystalline phases of clusters of inorganic dopants in graphene at the intermediate size range between isolated single atoms and larger bulk 2D forms.

  13. Crystalline silica: Old problem, new problem

    SciTech Connect

    Burst, J.F. )

    1993-03-01

    Known as an industrial health hazard for centuries, crystalline silica has recently gained enhanced recognition as a threat to human health by being classified as a 2A probable carcinogen'' by The International Agency for Research on Cancer. Its maximum allowable concentration as an impurity is established as 0.1%. This has led to consternation in the mining and mineral industries inasmuch as the accuracy of methodology available to measure crystalline silica content at this level in heterogeneous matrices has been severely questioned and unlabeled products distributed with crystalline silica contents in excess of 0.1% are considered in violation of the Hazard Communication Standard. Three problems exist: (1) defining acceptable reference standards; (2) establishing adequate measurement procedures; (3) marketing products in compliance with State and Federal regulations. A review and update of these problems has been developed for the guidance of quarry operators and mineral product manufacturers.

  14. Crystallinity of inorganic films grown by atomic layer deposition: Overview and general trends

    NASA Astrophysics Data System (ADS)

    Miikkulainen, Ville; Leskelä, Markku; Ritala, Mikko; Puurunen, Riikka L.

    2013-01-01

    Atomic layer deposition (ALD) is gaining attention as a thin film deposition method, uniquely suitable for depositing uniform and conformal films on complex three-dimensional topographies. The deposition of a film of a given material by ALD relies on the successive, separated, and self-terminating gas-solid reactions of typically two gaseous reactants. Hundreds of ALD chemistries have been found for depositing a variety of materials during the past decades, mostly for inorganic materials but lately also for organic and inorganic-organic hybrid compounds. One factor that often dictates the properties of ALD films in actual applications is the crystallinity of the grown film: Is the material amorphous or, if it is crystalline, which phase(s) is (are) present. In this thematic review, we first describe the basics of ALD, summarize the two-reactant ALD processes to grow inorganic materials developed to-date, updating the information of an earlier review on ALD [R. L. Puurunen, J. Appl. Phys. 97, 121301 (2005)], and give an overview of the status of processing ternary compounds by ALD. We then proceed to analyze the published experimental data for information on the crystallinity and phase of inorganic materials deposited by ALD from different reactants at different temperatures. The data are collected for films in their as-deposited state and tabulated for easy reference. Case studies are presented to illustrate the effect of different process parameters on crystallinity for representative materials: aluminium oxide, zirconium oxide, zinc oxide, titanium nitride, zinc zulfide, and ruthenium. Finally, we discuss the general trends in the development of film crystallinity as function of ALD process parameters. The authors hope that this review will help newcomers to ALD to familiarize themselves with the complex world of crystalline ALD films and, at the same time, serve for the expert as a handbook-type reference source on ALD processes and film crystallinity.

  15. Tensile Deformation of Polyethylenes: Crystallinity Effects

    NASA Astrophysics Data System (ADS)

    Crist, Buckley; Metaxas, Costas

    2004-03-01

    The crystalline fraction of polyethylene can be reduced by increasing the cooling rate, the molecular weight or the fraction of comonomer. All three methods have been used in this study of tensile deformation which shows that true stress - true strain behavior depends systematically on morphology. The dependence of uniaxial yield stress on crystal thickness is well understood in terms of dislocation nucleation. Post yield flow is dominated by the strain hardening rate that is larger in polyethylenes of lower crystallinity. Noncrystalline polymer evidently reduces the plastic compliance while providing for elastic (reversible) strains. These observations are examined in terms of old and new theories for deformation of semicrystalline polymers.

  16. Monolithic aerogels with nanoporous crystalline phases

    NASA Astrophysics Data System (ADS)

    Daniel, Christophe; Guerra, Gaetano

    2015-05-01

    High porosity monolithic aerogels with nanoporous crystalline phases can be obtained from syndiotactic polystyrene and poly(2,6-dimethyl-1,4-phenylene)oxide thermoreversible gels by removing the solvent with supercritical CO2. The presence of crystalline nanopores in the aerogels based on these polymers allows a high uptake associated with a high selectivity of volatile organic compounds from vapor phase or aqueous solutions even at very low activities. The sorption and the fast kinetics make these materials particularly suitable as sorption medium to remove traces of pollutants from water and moist air.

  17. Liquid crystalline thermosetting polyimides. Final report

    SciTech Connect

    Hoyt, A.E.; Huang, S.J.

    1993-07-01

    Phase separation of rodlike reinforcing polymers and flexible coil matrix polymers is a common problem in formulating molecular composites. One way to reduce phase separation might be to employ liquid crystalline thermosets as the matrix material. In this work, functionally terminated polyimide oligomers which exhibit lyotropic liquid crystalline behavior were successfully prepared. Materials based on 2,2{prime}-bis(trifluoromethyl)-4,4{prime}-diaminobiphenyl and 3,3{prime},4,4{prime}-biphenylenetetra-carboxylic dianhydride have been synthesized and characterized.

  18. A Single-Crystalline Mesoporous Quartz Superlattice.

    PubMed

    Matsuno, Takamichi; Kuroda, Yoshiyuki; Kitahara, Masaki; Shimojima, Atsushi; Wada, Hiroaki; Kuroda, Kazuyuki

    2016-05-10

    There has been significant interest in the crystallization of nanostructured silica into α-quartz because of its physicochemical properties. We demonstrate a single-crystalline mesoporous quartz superlattice, a silica polymorph with unprecedentedly ordered hierarchical structures on both the several tens of nanometers scale and the atomic one. The mesoporous quartz superlattice consists of periodically arranged α-quartz nanospheres whose crystalline axes are mostly oriented in an assembly. The superlattice is prepared by thermal crystallization of amorphous silica nanospheres constituting a colloidal crystal. We found that the deposition of a strong flux of Li(+) only on the surface of silica nanospheres is effective for crystallization.

  19. Chiral selection on inorganic crystalline surfaces

    NASA Technical Reports Server (NTRS)

    Hazen, Robert M.; Sholl, David S.

    2003-01-01

    From synthetic drugs to biodegradable plastics to the origin of life, the chiral selection of molecules presents both daunting challenges and significant opportunities in materials science. Among the most promising, yet little explored, avenues for chiral molecular discrimination is adsorption on chiral crystalline surfaces - periodic environments that can select, concentrate and possibly even organize molecules into polymers and other macromolecular structures. Here we review experimental and theoretical approaches to chiral selection on inorganic crystalline surfaces - research that is poised to open this new frontier in understanding and exploiting surface-molecule interactions.

  20. Electrochemically synthesized amorphous and crystalline nanowires: dissimilar nanomechanical behavior in comparison with homologous flat films

    NASA Astrophysics Data System (ADS)

    Zeeshan, M. A.; Esqué-de Los Ojos, D.; Castro-Hartmann, P.; Guerrero, M.; Nogués, J.; Suriñach, S.; Baró, M. D.; Nelson, B. J.; Pané, S.; Pellicer, E.; Sort, J.

    2016-01-01

    The effects of constrained sample dimensions on the mechanical behavior of crystalline materials have been extensively investigated. However, there is no clear understanding of these effects in nano-sized amorphous samples. Herein, nanoindentation together with finite element simulations are used to compare the properties of crystalline and glassy CoNi(Re)P electrodeposited nanowires (φ ~ 100 nm) with films (3 μm thick) of analogous composition and structure. The results reveal that amorphous nanowires exhibit a larger hardness, lower Young's modulus and higher plasticity index than glassy films. Conversely, the very large hardness and higher Young's modulus of crystalline nanowires are accompanied by a decrease in plasticity with respect to the homologous crystalline films. Remarkably, proper interpretation of the mechanical properties of the nanowires requires taking the curved geometry of the indented surface and sink-in effects into account. These findings are of high relevance for optimizing the performance of new, mechanically-robust, nanoscale materials for increasingly complex miniaturized devices.The effects of constrained sample dimensions on the mechanical behavior of crystalline materials have been extensively investigated. However, there is no clear understanding of these effects in nano-sized amorphous samples. Herein, nanoindentation together with finite element simulations are used to compare the properties of crystalline and glassy CoNi(Re)P electrodeposited nanowires (φ ~ 100 nm) with films (3 μm thick) of analogous composition and structure. The results reveal that amorphous nanowires exhibit a larger hardness, lower Young's modulus and higher plasticity index than glassy films. Conversely, the very large hardness and higher Young's modulus of crystalline nanowires are accompanied by a decrease in plasticity with respect to the homologous crystalline films. Remarkably, proper interpretation of the mechanical properties of the nanowires

  1. Crystallinity determination by curvefit procedure for a semi-crystalline polymer

    NASA Technical Reports Server (NTRS)

    Wakelyn, N. T.

    1985-01-01

    Wide angle X-ray scattering (WAXS) data from poly(etheretherketone) (PEEK) was resolved into a crystalline contribution represented as four reflections and an amorphous contribution represented as a broad, smoothly varying curve. The crystalline scatter is described as a linear combination of Cauchy and Gaussian functions while that of the amorphous halo is expressed as a cubic polynomial. Statistical analysis of the measured scattered intensity from an amorphous specimen with that calculated from the cubic polynomial, as a function of the combination parameter (fraction of Cauchy and Gaussian functions), suggests that the crystalline fraction of the polymer specimen studied is about 0.39.

  2. Urothermal Synthesis of Crystalline Porous Materials

    PubMed Central

    Zhang, Jian; Bu, Julia T.; Chen, Shumei; Wu, Tao; Zheng, Shoutian; Chen, Yigang; Nieto, Ruben A.; Feng, Pingyun

    2015-01-01

    Pores from Urea Urea derivatives are shown here to be a highly verstaile solvent system for the synthesis of crystalline solids. In particular, reversible binding of urea derivatives to framework metal sites has been utilized to create a variety of materials integrating both porosity and open-metal sites. PMID:20954225

  3. Kinetics of chaperoning of dithiothreitol-denatured alpha-lactalbumin by alpha-crystallin.

    PubMed

    Bettelheim, Frederick A

    2002-06-18

    Molecular chaperones prevent the aggregation of partially folded or misfolded forms of protein. alpha-Crystallin performs such a function in the ocular lens. Dynamic light scattering (DLS) measurements were performed to gain insight into the kinetics and mechanism of alpha-crystallin chaperoning. Experiments were conducted as a function of alpha-lactalbumin concentration as well as the alpha-crystallin/alpha-lactalbumin ratio over a 24 h period. In the particle distribution patterns the lactalbumin concentration was partitioned into three compartments: (a) monomeric free lactalbumin; (b) lactalbumin in the chaperoning complex; and (c) lactalbumin aggregates. DLS intensities were converted to molar concentrations by assuming a model of a spherical chaperoning complex. In the model, alpha-crystallin is the central core and alpha-lactalbumin molecules occupy a ring surrounding the core. The kinetics of chaperoning was studied by proposing a simple scheme with four rate constants. The reversible reaction of the formation of the chaperoning complex is characterized by rate constants k(1) and k(2). The rate constants k(3) and k(4) govern the irreversible aggregation of lactalbumin: the former from the free monomeric lactalbumin pool and the latter describing the aggregation of the denatured lactalbumin released from the chaperoning complex. The rate constants, k(3) and k(4) are four magnitudes larger than k(1) and k(2). The equilibrium constant of chaperoning complex formation lies in favor of the reactants. k(4) is somewhat faster than k(3) and it is three times faster than k(s) governing the self-aggregation of lactalbumin in the absence of alpha-crystallin.

  4. Kinetic dissection of individual steps in the poly(C)-directed oligoguanylate synthesis from guanosine 5'-monophosphate 2-methylimidazolide

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Bernasconi, C. F.; Alberas, D. J.; Baird, E. E.

    1993-01-01

    A kinetic study of oligoguanylate synthesis on a polycytidylate template, poly(C), as a function of the concentration of the activated monomer, guanosine 5'-monophosphate 2-methylimidazolide, 2-MeImpG, is reported. Reactions were run with 0.005-0.045 M 2-MeImpG in the presence of 0.05 M poly(C) at 23 degrees C. The kinetic results are consistent with a reaction scheme (eq 1) that consists of a series of consecutive steps, each step representing the addition of one molecule of 2-MeImpG to the growing oligomer. This scheme allows the calculation of second-order rate constants for every step by analyzing the time-dependent growth of each oligomer. Computer simulations of the course of reaction based on the determined rate constants and eq 1 are in excellent agreement with the product distributions seen in the HPLC profiles. In accord with an earlier study (Fakhrai, H.; Inoue, T.; Orgel, L. E. Tetrahedron 1984, 40, 39), rate constants, ki, for the formation of the tetramer and longer oligomers up to the 16-mer were found to be independent of length and somewhat higher than k3 (formation of trimer), which in turn is much higher than k2 (formation of dimer). The ki (i > or = 4), k3, and k2 values are not true second-order rate constants but vary with monomer concentration. Mechanistic models for the dimerization (Scheme I) and elongation reactions (Scheme II) are proposed that are consistent with our results. These models take into account that the monomer associates with the template in a cooperative manner. Our kinetic analysis allowed the determination of rate constants for the elementary processes of covalent bond formation between two monomers (dimerization) and between an oligomer and a monomer (elongation) on the template. A major conclusion from our study is that bond formation between two monomer units or between a primer and a monomer is assisted by the presence of additional next-neighbor monomer units. This is consistent with recent findings with hairpin

  5. Mechanism of the Orotidine 5’-Monophosphate Decarboxylase-Catalyzed Reaction: Importance of Residues in the Orotate Binding Site†

    PubMed Central

    Iiams, Vanessa; Desai, Bijoy J.; Fedorov, Alexander A.; Fedorov, Elena V.; Almo, Steven C.; Gerlt, John A.

    2011-01-01

    The reaction catalyzed by orotidine 5’-monophosphate decarboxylase (OMPDC) is accompanied by exceptional values for the rate enhancement [kcat/knon = 7.1 × 1016] and catalytic proficiency [(kcat/KM)/knon = 4.8 × 1022 M−1]. Although a stabilized vinyl carbanion/carbene intermediate is located on the reaction coordinate, the structural strategies by which the reduction in the activation energy barrier is realized remain incompletely understood. This laboratory recently reported that “substrate destabilization” by Asp 70 in the OMPDC from Methanothermobacter thermoautotrophicus (MtOMPDC) lowers the activation energy barrier by ~5 kcal/mol (contributing ~2.7 × 103 to the rate enhancement) [K. K. Chan, B. M. Wood, A. A. Fedorov, E. V. Fedorov, H. J. Imker, T. L. Amyes, J. P. Richard, S. C. Almo, and J. A. Gerlt (2009) Biochemistry 48, 5518–31]. We now report that substitutions of hydrophobic residues in a pocket proximal to the carboxylate group of the substrate (Ile 96, Leu 123, and Val 155) with neutral hydrophilic residues decrease the value of kcat by as much as 400-fold but have minimal effect on the value of kex for exchange of H6 of the FUMP product analog with solvent deuterium; we hypothesize that this pocket destabilizes the substrate by preventing hydration of the substrate carboxylate group. We also report that substitutions for Ser 127 that is proximal to O4 of the orotate ring decrease the value of kcat/KM, with the S127P substitution that eliminates hydrogen-bonding interactions with O4 producing a 2.5 × 106-fold reduction in the value of kcat/KM; this effect is consistent with delocalization of the negative charge of the carbanionic intermediate on O4 to produce an anionic carbene intermediate and thereby provide a structural strategy for stabilization of the intermediate. These observations provide additional information on the identities of the active site residues that contribute to the rate enhancement and, therefore, insights into the

  6. Role of αA-crystallin-derived αA66-80 peptide in guinea pig lens crystallin aggregation and insolubilization.

    PubMed

    Raju, Murugesan; Mooney, Brian P; Thakkar, Kavi M; Giblin, Frank J; Schey, Kevin L; Sharma, K Krishna

    2015-03-01

    Earlier we reported that low molecular weight (LMW) peptides accumulate in aging human lens tissue and that among the LMW peptides, the chaperone inhibitor peptide αA66-80, derived from α-crystallin protein, is one of the predominant peptides. We showed that in vitro αA66-80 induces protein aggregation. The current study was undertaken to determine whether LMW peptides are also present in guinea pig lens tissue subjected to hyperbaric oxygen (HBO) in vivo. The nuclear opacity induced by HBO in guinea pig lens is the closest animal model for studying age-related cataract formation in humans. A LMW peptide profile by mass spectrometry showed the presence of an increased amount of LMW peptides in HBO-treated guinea pig lenses compared to age-matched controls. Interestingly, the mass spectrometric data also showed that the chaperone inhibitor peptide αA66-80 accumulates in HBO-treated guinea pig lens. Following incubation of synthetic chaperone inhibitor peptide αA66-80 with α-crystallin from guinea pig lens extracts, we observed a decreased ability of α-crystallin to inhibit the amorphous aggregation of the target protein alcohol dehydrogenase and the formation of large light scattering aggregates, similar to those we have observed with human α-crystallin and αA66-80 peptide. Further, time-lapse recordings showed that a preformed complex of α-crystallin and αA66-80 attracted additional crystallin molecules to form even larger aggregates. These results demonstrate that LMW peptide-mediated cataract development in aged human lens and in HBO-induced lens opacity in the guinea pig may have common molecular pathways.

  7. Organization and mobility of water in amorphous and crystalline trehalose

    NASA Astrophysics Data System (ADS)

    Kilburn, Duncan; Townrow, Sam; Meunier, Vincent; Richardson, Robert; Alam, Ashraf; Ubbink, Job

    2006-08-01

    The disaccharide trehalose is accumulated by microorganisms, such as yeasts, and multicellular organisms, such as tardigrades, when conditions of extreme drought occur. In this way these organisms can withstand dehydration through the formation of an intracellular carbohydrate glass, which, with its high viscosity and hydrogen-bonding interactions, stabilizes and protects the integrity of complex biological structures and molecules. This property of trehalose can also be harnessed in the stabilization of liposomes, proteins and in the preservation of red blood cells, but the underlying mechanism of bioprotection is not yet fully understood. Here we use positron annihilation lifetime spectroscopy to probe the free volume of trehalose matrices; specifically, we develop a molecular picture of the organization and mobility of water in both amorphous and crystalline states. Whereas in amorphous matrices, water increases the average intermolecular hole size, in the crystalline dihydrate it is organized as a confined one-dimensional fluid in channels of fixed diameter that allow activated diffusion of water in and out of the crystallites. We present direct real-time evidence of water molecules unloading reversibly from these channels, thereby acting as both a sink and a source of water in low-moisture systems. We postulate that this behaviour may provide the overall stability required to keep organisms viable through dehydration conditions.

  8. Impact of Subunit Composition on the Uptake of α-Crystallin by Lens and Retina.

    PubMed

    Mueller, Niklaus H; Fogueri, Uma; Pedler, Michelle G; Montana, Kameron; Petrash, J Mark; Ammar, David A

    2015-01-01

    Misfolded protein aggregation, including cataract, cause a significant amount of blindness worldwide. α-Crystallin is reported to bind misfolded proteins and prevent their aggregation. We hypothesize that supplementing retina and lens with α-crystallin may help to delay disease onset. The purpose of this study was to determine if αB-crystallin subunits containing a cell penetration peptide (gC-tagged αB-crystallin) facilitate the uptake of wild type αA-crystallin (WT-αA) in lens and retina. Recombinant human αB-crystallin was modified by the addition of a novel cell penetration peptide derived from the gC gene product of herpes simplex virus (gC-αB). Recombinant gC-αB and wild-type αA-crystallin (WT-αA) were purified from E. coli over-expression cultures. After Alexa-labeling of WT-αA, these proteins were mixed at ratios of 1:2, 1:5 and 1:10, respectively, and incubated at 37°C for 4 hours to allow for subunit exchange. Mixed oligomers were subsequently incubated with tissue culture cells or mouse organ cultures. Similarly, crystallin mixtures were injected into the vitreous of rat eyes. At various times after exposure, tissues were harvested and analyzed for protein uptake by confocal microscopy or flow cytometry. Chaperone-like activity assays were performed on α-crystallins ratios showing optimal uptake using chemically-induced or heat induced substrate aggregation assays. As determined by flow cytometry, a ratio of 1:5 for gC-αB to WT-αA was found to be optimal for uptake into retinal pigmented epithelial cells (ARPE-19). Chaperone-like activity assays demonstrated that hetero-oligomeric complex of gC-αB to WT-αA (in 1:5 ratio) retained protein aggregation protection. We observed a significant increase in protein uptake when optimized (gC-αB to WT-αA (1:5 ratio)) hetero-oligomers were used in mouse lens and retinal organ cultures. Increased levels of α-crystallin were found in lens and retina following intravitreal injection of homo- and

  9. Evolution of crystallins for a role in the vertebrate eye lens

    PubMed Central

    Slingsby, Christine; Wistow, Graeme J; Clark, Alice R

    2013-01-01

    The camera eye lens of vertebrates is a classic example of the re-engineering of existing protein components to fashion a new device. The bulk of the lens is formed from proteins belonging to two superfamilies, the α-crystallins and the βγ-crystallins. Tracing their ancestry may throw light on the origin of the optics of the lens. The α-crystallins belong to the ubiquitous small heat shock proteins family that plays a protective role in cellular homeostasis. They form enormous polydisperse oligomers that challenge modern biophysical methods to uncover the molecular basis of their assembly structure and chaperone-like protein binding function. It is argued that a molecular phenotype of a dynamic assembly suits a chaperone function as well as a structural role in the eye lens where the constraint of preventing protein condensation is paramount. The main cellular partners of α-crystallins, the β- and γ-crystallins, have largely been lost from the animal kingdom but the superfamily is hugely expanded in the vertebrate eye lens. Their structures show how a simple Greek key motif can evolve rapidly to form a complex array of monomers and oligomers. Apart from remaining transparent, a major role of the partnership of α-crystallins with β- and γ-crystallins in the lens is to form a refractive index gradient. Here, we show some of the structural and genetic features of these two protein superfamilies that enable the rapid creation of different assembly states, to match the rapidly changing optical needs among the various vertebrates. PMID:23389822

  10. Cellulose crystallinity index: measurement techniques and their impact on interpreting cellulase performance

    PubMed Central

    2010-01-01

    Although measurements of crystallinity index (CI) have a long history, it has been found that CI varies significantly depending on the choice of measurement method. In this study, four different techniques incorporating X-ray diffraction and solid-state 13C nuclear magnetic resonance (NMR) were compared using eight different cellulose preparations. We found that the simplest method, which is also the most widely used, and which involves measurement of just two heights in the X-ray diffractogram, produced significantly higher crystallinity values than did the other methods. Data in the literature for the cellulose preparation used (Avicel PH-101) support this observation. We believe that the alternative X-ray diffraction (XRD) and NMR methods presented here, which consider the contributions from amorphous and crystalline cellulose to the entire XRD and NMR spectra, provide a more accurate measure of the crystallinity of cellulose. Although celluloses having a high amorphous content are usually more easily digested by enzymes, it is unclear, based on studies published in the literature, whether CI actually provides a clear indication of the digestibility of a cellulose sample. Cellulose accessibility should be affected by crystallinity, but is also likely to be affected by several other parameters, such as lignin/hemicellulose contents and distribution, porosity, and particle size. Given the methodological dependency of cellulose CI values and the complex nature of cellulase interactions with amorphous and crystalline celluloses, we caution against trying to correlate relatively small changes in CI with changes in cellulose digestibility. In addition, the prediction of cellulase performance based on low levels of cellulose conversion may not include sufficient digestion of the crystalline component to be meaningful. PMID:20497524

  11. Cobalt-assisted in situ synthesis of crystalline bismuth nanoparticle arrays

    NASA Astrophysics Data System (ADS)

    Lee, Ho Seok; Noh, Jin-Seo; Suh, Kwang S.

    2014-12-01

    Almost monodisperse, crystalline Bi nanoparticle arrays were synthesized using a newly developed method, magnetically assisted growth of Bi nanoparticles (MAGBINs). The MAGBIN utilizes co-sputtering from Bi and Co targets at an elevated temperature. Crystalline Bi nanoparticles with hexagonal morphology were formed in situ on a Si substrate with a thin surface oxide during this process. The size and density of Bi nanoparticles could be controlled by adjusting the relative powers applied to Bi and Co targets, and they showed opposite trends against the relative powers. Several physical processes such as Co agglomeration, element-selective growth, and Ostwald ripening were proposed to be involved in this Bi nanoparticle growth. The MAGBIN is a facile method to synthesize crystalline Bi nanoparticle arrays, which does not need any chemical agents, complex process, or lithography.

  12. Cobalt-assisted in situ synthesis of crystalline bismuth nanoparticle arrays.

    PubMed

    Seok Lee, Ho; Noh, Jin-Seo; Suh, Kwang S

    2014-12-12

    Almost monodisperse, crystalline Bi nanoparticle arrays were synthesized using a newly developed method, magnetically assisted growth of Bi nanoparticles (MAGBINs). The MAGBIN utilizes co-sputtering from Bi and Co targets at an elevated temperature. Crystalline Bi nanoparticles with hexagonal morphology were formed in situ on a Si substrate with a thin surface oxide during this process. The size and density of Bi nanoparticles could be controlled by adjusting the relative powers applied to Bi and Co targets, and they showed opposite trends against the relative powers. Several physical processes such as Co agglomeration, element-selective growth, and Ostwald ripening were proposed to be involved in this Bi nanoparticle growth. The MAGBIN is a facile method to synthesize crystalline Bi nanoparticle arrays, which does not need any chemical agents, complex process, or lithography.

  13. GhLTPG1, a cotton GPI-anchored lipid transfer protein, regulates the transport of phosphatidylinositol monophosphates and cotton fiber elongation

    PubMed Central

    Deng, Ting; Yao, Hongyan; Wang, Jin; Wang, Jun; Xue, Hongwei; Zuo, Kaijing

    2016-01-01

    The cotton fibers are seed trichomes that elongate from the ovule epidermis. Polar lipids are required for the quick enlargement of cell membrane and fiber cell growth, however, how lipids are transported from the ovules into the developing fibers remains less known. Here, we reported the functional characterization of GhLTPG1, a GPI-anchored lipid transport protein, during cotton fiber elongation. GhLTPG1 was abundantly expressed in elongating cotton fibers and outer integument of the ovules, and GhLTPG1 protein was located on cell membrane. Biochemical analysis showed that GhLTPG1 specifically bound to phosphatidylinositol mono-phosphates (PtdIns3P, PtdIns4P and PtdIns5P) in vitro and transported PtdInsPs from the synthesis places to the plasma membranes in vivo. Expression of GhLTPG1 in Arabidopsis caused an increased number of trichomes, and fibers in GhLTPG1-knockdown cotton plants exhibited significantly reduced length, decreased polar lipid content, and repression of fiber elongation-related genes expression. These results suggested that GhLTPG1 protein regulates the cotton fiber elongation through mediating the transport of phosphatidylinositol monophosphates. PMID:27311358

  14. t(3;11) translocation in treatment-related acute myeloid leukemia fuses MLL with the GMPS (GUANOSINE 5' MONOPHOSPHATE SYNTHETASE) gene.

    PubMed

    Pegram, L D; Megonigal, M D; Lange, B J; Nowell, P C; Rowley, J D; Rappaport, E F; Felix, C A

    2000-12-15

    The partner gene of MLL was identified in a patient with treatment-related acute myeloid leukemia in which the karyotype suggested t(3;11)(q25;q23). Prior therapy included the DNA topoisomerase II inhibitors, teniposide and doxorubicin. Southern blot analysis indicated that the MLL gene was involved in the translocation. cDNA panhandle polymerase chain reaction (PCR) was used, which does not require partner gene-specific primers, to identify the chimeric transcript. Reverse-transcription of first-strand cDNAs with oligonucleotides containing known MLL sequence at the 5' ends and random hexamers at the 3' ends generated templates with an intra-strand loop for PCR. In-frame fusions of either MLL exon 7 or exon 8 with the GMPS (GUANOSINE 5'-MONOPHOSPHATE SYNTHETASE) gene from chromosome band 3q24 were detected. The fusion transcript was alternatively spliced. Guanosine monophosphate synthetase is essential for de novo purine synthesis. GMPS is the first partner gene of MLL on chromosome 3q and the first gene of this type in leukemia-associated translocations. (Blood. 2000;96:4360-4362)

  15. Lipid peroxidation and haemoglobin degradation in red blood cells exposed to t-butyl hydroperoxide. Effects of the hexose monophosphate shunt as mediated by glutathione and ascorbate.

    PubMed

    Trotta, R J; Sullivan, S G; Stern, A

    1982-05-15

    Lipid peroxidation and haemoglobin degradation were the two extremes of a spectrum of oxidative damage in red cells exposed to t-butyl hydroperoxide. The exact position in this spectrum depended on the availability of glucose and the ligand state of haemoglobin. In red cells containing oxy- or carbonmono-oxy-haemoglobin, hexose monophosphate-shunt activity was mainly responsible for metabolism of t-butyl hydroperoxide; haem groups were the main scavengers in red cells containing methaemoglobin. Glutathione, via glutathione peroxidase, accounted for nearly all of the hydroperoxide metabolizing activity of the hexose monophosphate shunt. Glucose protection against lipid peroxidation was almost entirely mediated by glutathione, whereas glucose protection of haemoglobin was only partly mediated by glutathione. Physiological concentrations of intracellular or extracellular ascorbate had no effect on consumption of t-butyl hydroperoxide or oxidation of haemoglobin. Ascorbate was mainly involved in scavenging chain-propagating species involved in lipid peroxidation. The protective effect of intracellular ascorbate against lipid peroxidation was about 100% glucose-dependent and about 50% glutathione-dependent. Extracellular ascorbate functioned largely without a requirement for glucose metabolism, although some synergistic effects between extracellular ascorbate and glutathione were observed. Lipid peroxidation was not dependent on the rate or completion of t-butyl hydroperoxide consumption but rather on the route of consumption. Lipid peroxidation appears to depend on the balance between the presence of initiators of lipid peroxidation (oxyhaemoglobin and low concentrations of methaemoglobin) and terminators of lipid peroxidation (glutathione, ascorbate, high concentrations of methaemoglobin).

  16. Interaction of βA3-Crystallin with Deamidated Mutants of αA- and αB-Crystallins.

    PubMed

    Tiwary, Ekta; Hegde, Shylaja; Purushotham, Sangeetha; Deivanayagam, Champion; Srivastava, Om

    2015-01-01

    Interaction among crystallins is required for the maintenance of lens transparency. Deamidation is one of the most common post-translational modifications in crystallins, which results in incorrect interaction and leads to aggregate formation. Various studies have established interaction among the α- and β-crystallins. Here, we investigated the effects of the deamidation of αA- and αB-crystallins on their interaction with βA3-crystallin using surface plasmon resonance (SPR) and fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET) methods. SPR analysis confirmed adherence of WT αA- and WT αB-crystallins and their deamidated mutants with βA3-crystallin. The deamidated mutants of αA-crystallin (αA N101D and αA N123D) displayed lower adherence propensity for βA3-crystallin relative to the binding affinity shown by WT αA-crystallin. Among αB-crystallin mutants, αB N78D displayed higher adherence propensity whereas αB N146D mutant showed slightly lower binding affinity for βA3-crystallin relative to that shown by WT αB-crystallin. Under the in vivo condition (FLIM-FRET), both αA-deamidated mutants (αA N101D and αA N123D) exhibited strong interaction with βA3-crystallin (32±4% and 36±4% FRET efficiencies, respectively) compared to WT αA-crystallin (18±4%). Similarly, the αB N78D and αB N146D mutants showed strong interaction (36±4% and 22±4% FRET efficiencies, respectively) with βA3-crystallin compared to 18±4% FRET efficiency of WT αB-crystallin. Further, FLIM-FRET analysis of the C-terminal domain (CTE), N-terminal domain (NTD), and core domain (CD) of αA- and αB-crystallins with βA3-crystallin suggested that interaction sites most likely reside in the αA CTE and αB NTD regions, respectively, as these domains showed the highest FRET efficiencies. Overall, results suggest that similar to WT αA- and WTαB-crystallins, the deamidated mutants showed strong interactionfor βA3-crystallin. Variable

  17. Interaction of βA3-Crystallin with Deamidated Mutants of αA- and αB-Crystallins

    PubMed Central

    Tiwary, Ekta; Hegde, Shylaja; Purushotham, Sangeetha; Deivanayagam, Champion; Srivastava, Om

    2015-01-01

    Interaction among crystallins is required for the maintenance of lens transparency. Deamidation is one of the most common post-translational modifications in crystallins, which results in incorrect interaction and leads to aggregate formation. Various studies have established interaction among the α- and β-crystallins. Here, we investigated the effects of the deamidation of αA- and αB-crystallins on their interaction with βA3-crystallin using surface plasmon resonance (SPR) and fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET) methods. SPR analysis confirmed adherence of WT αA- and WT αB-crystallins and their deamidated mutants with βA3-crystallin. The deamidated mutants of αA–crystallin (αA N101D and αA N123D) displayed lower adherence propensity for βA3-crystallin relative to the binding affinity shown by WT αA-crystallin. Among αB-crystallin mutants, αB N78D displayed higher adherence propensity whereas αB N146D mutant showed slightly lower binding affinity for βA3-crystallin relative to that shown by WT αB-crystallin. Under the in vivo condition (FLIM-FRET), both αA-deamidated mutants (αA N101D and αA N123D) exhibited strong interaction with βA3-crystallin (32±4% and 36±4% FRET efficiencies, respectively) compared to WT αA-crystallin (18±4%). Similarly, the αB N78D and αB N146D mutants showed strong interaction (36±4% and 22±4% FRET efficiencies, respectively) with βA3-crystallin compared to 18±4% FRET efficiency of WT αB-crystallin. Further, FLIM-FRET analysis of the C-terminal domain (CTE), N-terminal domain (NTD), and core domain (CD) of αA- and αB-crystallins with βA3-crystallin suggested that interaction sites most likely reside in the αA CTE and αB NTD regions, respectively, as these domains showed the highest FRET efficiencies. Overall, results suggest that similar to WT αA- and WTαB-crystallins, the deamidated mutants showed strong interactionfor βA3-crystallin

  18. Interaction of βA3-Crystallin with Deamidated Mutants of αA- and αB-Crystallins.

    PubMed

    Tiwary, Ekta; Hegde, Shylaja; Purushotham, Sangeetha; Deivanayagam, Champion; Srivastava, Om

    2015-01-01

    Interaction among crystallins is required for the maintenance of lens transparency. Deamidation is one of the most common post-translational modifications in crystallins, which results in incorrect interaction and leads to aggregate formation. Various studies have established interaction among the α- and β-crystallins. Here, we investigated the effects of the deamidation of αA- and αB-crystallins on their interaction with βA3-crystallin using surface plasmon resonance (SPR) and fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET) methods. SPR analysis confirmed adherence of WT αA- and WT αB-crystallins and their deamidated mutants with βA3-crystallin. The deamidated mutants of αA-crystallin (αA N101D and αA N123D) displayed lower adherence propensity for βA3-crystallin relative to the binding affinity shown by WT αA-crystallin. Among αB-crystallin mutants, αB N78D displayed higher adherence propensity whereas αB N146D mutant showed slightly lower binding affinity for βA3-crystallin relative to that shown by WT αB-crystallin. Under the in vivo condition (FLIM-FRET), both αA-deamidated mutants (αA N101D and αA N123D) exhibited strong interaction with βA3-crystallin (32±4% and 36±4% FRET efficiencies, respectively) compared to WT αA-crystallin (18±4%). Similarly, the αB N78D and αB N146D mutants showed strong interaction (36±4% and 22±4% FRET efficiencies, respectively) with βA3-crystallin compared to 18±4% FRET efficiency of WT αB-crystallin. Further, FLIM-FRET analysis of the C-terminal domain (CTE), N-terminal domain (NTD), and core domain (CD) of αA- and αB-crystallins with βA3-crystallin suggested that interaction sites most likely reside in the αA CTE and αB NTD regions, respectively, as these domains showed the highest FRET efficiencies. Overall, results suggest that similar to WT αA- and WTαB-crystallins, the deamidated mutants showed strong interactionfor βA3-crystallin. Variable

  19. Liquid Crystalline Phases of Polymer Brushes

    NASA Astrophysics Data System (ADS)

    Amini, Kiana; Abukhdeir, Nasser; Matsen, Mark

    The phase behavior of liquid-crystal polymeric brushes in solvent are investigated using self-consistent field theory. The polymers are modeled as freely-jointed chain consisting of N rigid segments. The isotropic interactions between the polymer and the solvent are treated using the standard Flory-Huggins theory, while the anisotropic liquid-crystalline (LC) interactions between rigid segments are taken into account using the Mayer-Saupe theory. For weak LC interactions, the brush exhibits the conventional parabolic-like profile, while for strong LC interactions, the polymers crystallize into a dense brush with a step-like profile. At intermediate interaction strengths, we find the microphase-segregated phase observed previously for lattice-model calculations. In this phase, the brush exhibits a crystalline layer next to the grafting surface with an external layer similar to the conventional brush. This work was supported by NSERC of Canada.

  20. Topological crystalline metal in orthorhombic perovskite iridates.

    PubMed

    Chen, Yige; Lu, Yuan-Ming; Kee, Hae-Young

    2015-03-16

    Since topological insulators were theoretically predicted and experimentally observed in semiconductors with strong spin-orbit coupling, increasing attention has been drawn to topological materials that host exotic surface states. These surface excitations are stable against perturbations since they are protected by global or spatial/lattice symmetries. Following the success in achieving various topological insulators, a tempting challenge now is to search for metallic materials with novel topological properties. Here we predict that orthorhombic perovskite iridates realize a new class of metals dubbed topological crystalline metals, which support zero-energy surface states protected by certain lattice symmetry. These surface states can be probed by photoemission and tunnelling experiments. Furthermore, we show that by applying magnetic fields, the topological crystalline metal can be driven into other topological metallic phases, with different topological properties and surface states.

  1. Application of thermodynamics to silicate crystalline solutions

    NASA Technical Reports Server (NTRS)

    Saxena, S. K.

    1972-01-01

    A review of thermodynamic relations is presented, describing Guggenheim's regular solution models, the simple mixture, the zeroth approximation, and the quasi-chemical model. The possibilities of retrieving useful thermodynamic quantities from phase equilibrium studies are discussed. Such quantities include the activity-composition relations and the free energy of mixing in crystalline solutions. Theory and results of the study of partitioning of elements in coexisting minerals are briefly reviewed. A thermodynamic study of the intercrystalline and intracrystalline ion exchange relations gives useful information on the thermodynamic behavior of the crystalline solutions involved. Such information is necessary for the solution of most petrogenic problems and for geothermometry. Thermodynamic quantities for tungstates (CaWO4-SrWO4) are calculated.

  2. Basic research challenges in crystalline silicon photovoltaics

    SciTech Connect

    Werner, J.H.

    1995-08-01

    Silicon is abundant, non-toxic and has an ideal band gap for photovoltaic energy conversion. Experimental world record cells of 24 % conversion efficiency with around 300 {mu}m thickness are only 4 % (absolute) efficiency points below the theoretical Auger recombination-limit of around 28 %. Compared with other photovoltaic materials, crystalline silicon has only very few disadvantages. The handicap of weak light absorbance may be mastered by clever optical designs. Single crystalline cells of only 48 {mu}m thickness showed 17.3 % efficiency even without backside reflectors. A technology of solar cells from polycrystalline Si films on foreign substrates arises at the horizon. However, the disadvantageous, strong activity of grain boundaries in Si could be an insurmountable hurdle for a cost-effective, terrestrial photovoltaics based on polycrystalline Si on foreign substrates. This talk discusses some basic research challenges related to a Si based photovoltaics.

  3. Morphological and electrochemical properties of crystalline praseodymium oxide nanorods.

    PubMed

    Shamshi Hassan, M; Shaheer Akhtar, M; Shim, Kyung-Bo; Yang, O-Bong

    2010-02-05

    Highly crystalline Pr6O11 nanorods were prepared by a simple precipitation method of triethylamine complex at 500°C. Synthesized Pr6O11 nanorods were uniformly grown with the diameter of 12-15 nm and the length of 100-150 nm without any impurities of unstable PrO2 phase. The Pr6O11 nanorod electrodes attained a high electrical conductivity of 0.954 Scm-1 with low activation energy of 0.594 eV at 850°C. The electrochemical impedance study showed that the resistance of electrode was significantly decreased at high temperature, which resulted from its high conductivity and low activation energy. The reduced impedance and high electrical conductivity of Pr6O11 nanorod electrodes are attributed to the reduction of grain boundaries and high space charge width.

  4. Variable low-temperature FTIR study of crystalline sugars

    NASA Astrophysics Data System (ADS)

    Lutz, E. T.; van der Maas, John H.; van Duijneveldt, F. B.; Kanters, J. A.; Baran, J.; Ratajczak, H.

    1992-03-01

    The complex chains of hydrogen bonds of (Beta) -L-arabinose (I), methyl (alpha) -D- glucopyranoside (II) and di-(Beta) -D-fructopyranose 1,2':2,1'-dianhydride (III) in the crystalline state have been studied at variable low temperature. In addition to the increase of information showing up in the overall region upon cooling, the effect on intensity, bandshape and bandmaximum has also been studied. Most surprising is the contradictive behavior of the shift of the band maxima of methyl (alpha) -D-glucopyranoside, for which an increase is observed for the 'free' OH group, while H-bonds absorbing at lower wave-numbers are red shifted. Deuterium exchange experiments show the presence of vibrational coupling in the crystal of II whereas this phenomenon is absent in III.

  5. The phase diagram of crystalline surfaces

    SciTech Connect

    Anagnostopoulos, K.N.; Bowick, M.J.; Catterall, S.M.

    1995-09-22

    We report the status of a high-statistics Monte Carlo simulation of non-self-avoiding crystalline surfaces with extrinsic curvature on lattices of size up to 128{sup 2} nodes. We impose free boundary conditions. The free energy is a gaussian spring tethering potential together with a normal-normal bending energy. Particular emphasis is given to the behavior of the model in the cold phase where we measure the decay of the normal-normal correlation function.

  6. Structural Characterization of Crystalline Ice Nanoclusters

    NASA Technical Reports Server (NTRS)

    Blake, David

    2000-01-01

    Water ice nanoclusters are useful analogs for studying a variety of processes that occur within icy grains in the extraterrestrial environment. The surface of ice nanoclusters prepared in the laboratory is similar to the surface of interstellar ice grains. In cold molecular clouds, the silicate cores of interstellar grains are typically approx. 100 nm in diameter and have a coating of impure amorphous water ice. Depositional, thermal and radiolytic processes leave the surface and subsurface molecules in a disordered state. In this state, structural defects become mobile and reactions of trapped gases and small molecules can occur. The large surface area of nanocluster deposits relative to their bulk allows for routine observation of such surface-mediated processes. Furthermore, the disordered surface and subsurface layers in nanocluster deposits mimic the structure of amorphous ice rinds found on interstellar dust grains. Transmission Electron Microscopy (TEM has been used tn characterize the crystallinity, growth mechanism, and size distribution of nanoclusters formed from a mixture of water vapor with an inert carrier gas that has been rapidly cooled to 77K. E M imaging reveals a Gaussian size distribution around a modal diameter that increases from approx. 15 to 30 nm as the percentage of water vapor within the mixture increases from 0.5 to 2.007, respectively . TEM bright and dark field imaging also reveals the crystalline nature of the clusters. h4any of the clusters show a mosaic structure in which crystalline domains originate at the center Other images show mirror planes that are separated by approx. 10 nm. Electron diffraction patterns of these clusters show that the clusters are composed of cubic ice with only a small hexagonal component. Further, the crystalline domain size is approximately the same as the modal diameter suggesting that the clusters are single crystals.

  7. Cystoid Macular Edema in Bietti's Crystalline Retinopathy

    PubMed Central

    2014-01-01

    A 27-year-old man with progressive bilateral visual decline was diagnosed to have Bietti's crystalline dystrophy (BCD). Fluorescein angiography revealed bilateral petaloid type late hyperfluorescence implicating concurrent cystoid macular edema (CME). Optical coherence tomography exhibited cystoid foveal lacunas OU. During the follow-up of six years, intraretinal crystals reduced in amount but CME persisted angiographically and tomographically. CME is among the rare macular features of BCD including subfoveal sensorial detachment, subretinal neovascular membrane, and macular hole. PMID:24949209

  8. University Crystalline Silicon Photovoltaics Research and Development

    SciTech Connect

    Ajeet Rohatgi; Vijay Yelundur; Abasifreke Ebong; Dong Seop Kim

    2008-08-18

    The overall goal of the program is to advance the current state of crystalline silicon solar cell technology to make photovoltaics more competitive with conventional energy sources. This program emphasizes fundamental and applied research that results in low-cost, high-efficiency cells on commercial silicon substrates with strong involvement of the PV industry, and support a very strong photovoltaics education program in the US based on classroom education and hands-on training in the laboratory.

  9. Photorefractivity in liquid crystalline composite materials

    SciTech Connect

    Wiederrecht, G.P.; Wasielewski, M.R.

    1997-09-01

    We report recent improvements in the photorefractive of liquid crystalline thin film composites containing electron donor and acceptor molecules. The improvements primarily result from optimization of the exothermicity of the intermolecular charge transfer reaction and improvement of the diffusion characteristics of the photogenerated ions. Intramolecular charge transfer dopants produce greater photorefractivity and a 10-fold decrease in the concentration of absorbing chromophores. The mechanism for the generation of mobile ions is discussed.

  10. 21 CFR 522.313a - Ceftiofur crystalline free acid.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ceftiofur crystalline free acid. 522.313a Section... § 522.313a Ceftiofur crystalline free acid. (a) Specifications. The product is a suspension of ceftiofur crystalline free acid. (1) Each milliliter (mL) contains 100 milligrams (mg) ceftiofur equivalents. (2) Each...

  11. Effect of polylactic acid crystallinity on its electret properties

    NASA Astrophysics Data System (ADS)

    Guzhova, A. A.; Galikhanov, M. F.; Kuznetsova, N. V.; Petrov, V. A.; Khairullin, R. Z.

    2016-09-01

    Electret properties of the polylactic acid films with different degree of crystallinity due to different cooling and annealing conditions were studied. Samples with the higher degree of crystallinity showed more stable electret characteristics resulting from amorphous-crystalline interface boundary growth and capturing bigger amount of injected charge carriers by volume energy traps.

  12. 21 CFR 522.313a - Ceftiofur crystalline free acid.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ceftiofur crystalline free acid. 522.313a Section... § 522.313a Ceftiofur crystalline free acid. (a) Specifications. The product is a suspension of ceftiofur crystalline free acid. (1) Each milliliter (mL) contains 100 milligrams (mg) ceftiofur equivalents. (2) Each...

  13. 21 CFR 522.313a - Ceftiofur crystalline free acid.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ceftiofur crystalline free acid. 522.313a Section... § 522.313a Ceftiofur crystalline free acid. (a) Specifications. The product is a suspension of ceftiofur crystalline free acid. (1) Each milliliter (mL) contains 100 milligrams (mg) ceftiofur equivalents. (2) Each...

  14. 21 CFR 522.313a - Ceftiofur crystalline free acid.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ceftiofur crystalline free acid. 522.313a Section... § 522.313a Ceftiofur crystalline free acid. (a) Specifications. The product is a suspension of ceftiofur crystalline free acid. (1) Each milliliter (mL) contains 100 milligrams (mg) ceftiofur equivalents. (2) Each...

  15. The segal crystallinity index as it relates to crystallite size

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cotton fibers are composed of crystals of cellulose that yield a diffraction pattern, although fibers from varying sources and histories are said to have different degrees of crystallinity. There are many methods to assess this crystallinity. One of the most popular is the Segal Crystallinity Index ...

  16. Crystalline beams: Theory, experiments, and proposals

    SciTech Connect

    Ruggiero, A.G.

    1995-12-31

    Crystalline Beams are an ordered state of an ensemble of ions, circulating in a storage ring, with very small velocity fluctuations. They can be obtained from ordinary warm ion beams with the application of intense cooling techniques (stochastic, electron, laser). A phase transition occurs when sufficiently small velocity spreads are reached, freezing the particle-to-particle spacing in strings, Zigzags, and helices ... The properties and the feasibility of Crystalline Beams depend on the choice of the lattice of the Storage Ring. There are three issues closely related to the design of the Storage Ring; namely: the determination of Equilibrium Configurations, Confinement Conditions, and Stability Conditions. Of particular concern is the effect of the trajectory curvature and of the beam momentum spread, since they set the requirements on the amount of momentum cooling, on the focussing, and on the distribution of bending in the lattice of the storage ring. The practical demonstration of Crystalline Beams may create the basis for an advanced technology for particle accelerators, where the limitations due to Coulomb intrabeam scattering and space-charge forces would finally be brought under control, so that beams of ions, more dense than normal, can be achieved for a variety of new applications.

  17. Properties of crystalline phase in waste glass

    SciTech Connect

    Usami, T.; Uruga, K.; Tsukada, T.; Miura, Y.; Komamine, S.; Ochi, E.

    2013-07-01

    Depending on the operating conditions of the vitrification process of high-level liquid waste, some crystalline phases can be present. The crystalline phase exists as molten salt at glass melting temperature. In this study, the chemical and physical properties of the crystalline phase were determined. Two samples rich in Mo and a sample rich in Re were examined. One of the samples rich in Mo was obtained from simulated waste solution and glass beads in a middle scale melter, while two other samples were made from mixed reagents. The chemical forms of the constituents were determined by XRD and SEM-EDX. When Mo is dominant, the crystal is mainly composed of molybdates of Na, Li, Ba and Ca, Na{sub 2}SO{sub 4} and CsReO{sub 4}. When Re is dominant, (Na{sub x}Cs{sub 1-x})ReO{sub 4} and NaLiMoO{sub 4} are added. The characteristic temperature and the heat of transition were determined by differential scanning calorimetry. The density of the molten salt at high temperature was measured from buoyancy. The density of the molten salt is larger than that of molten glass, and increases with Re content. (authors)

  18. Molecular Sensing by Nanoporous Crystalline Polymers

    PubMed Central

    Pilla, Pierluigi; Cusano, Andrea; Cutolo, Antonello; Giordano, Michele; Mensitieri, Giuseppe; Rizzo, Paola; Sanguigno, Luigi; Venditto, Vincenzo; Guerra, Gaetano

    2009-01-01

    Chemical sensors are generally based on the integration of suitable sensitive layers and transducing mechanisms. Although inorganic porous materials can be effective, there is significant interest in the use of polymeric materials because of their easy fabrication process, lower costs and mechanical flexibility. However, porous polymeric absorbents are generally amorphous and hence present poor molecular selectivity and undesired changes of mechanical properties as a consequence of large analyte uptake. In this contribution the structure, properties and some possible applications of sensing polymeric films based on nanoporous crystalline phases, which exhibit all identical nanopores, will be reviewed. The main advantages of crystalline nanoporous polymeric materials with respect to their amorphous counterparts are, besides a higher selectivity, the ability to maintain their physical state as well as geometry, even after large guest uptake (up to 10–15 wt%), and the possibility to control guest diffusivity by controlling the orientation of the host polymeric crystalline phase. The final section of the review also describes the ability of suitable polymeric films to act as chirality sensors, i.e., to sense and memorize the presence of non-racemic volatile organic compounds. PMID:22303150

  19. Liquid Crystalline Compositions as Gas Sensors

    NASA Astrophysics Data System (ADS)

    Shibaev, Petr; Murray, John; Tantillo, Anthony; Wenzlick, Madison; Howard-Jennings, Jordan

    2015-03-01

    Droplets and films of nematic and cholesteric liquid crystalline mixtures were studied as promising detectors of volatile organic compounds (VOCs) in the air. Under increasing concentration of VOC in the air the detection may rely on each of the following effects sequentially observed one after the other due to the diffusion of VOC inside liquid crystalline matrix: i. slight changes in orientation and order parameter of liquid crystal, ii. formation of bubbles on the top of the liquid crystalline droplet due to the mass transfer between the areas with different order parameter, iii. complete isotropisation of the liquid crystal. All three stages can be easily monitored by optical microscopy and photo camera. Detection limits corresponding to the first stage are typically lower by a factor of 3-6 than detection limits corresponding to the beginning of mass transfer and isotropisation. The prototype of a compact sensor sensitive to the presence of organic solvents in the air is described in detail. The detection limits of the sensor is significantly lower than VOC exposure standards. The qualitative model is presented to account for the observed changes related to the diffusion, changes of order parameter and isotropisation.

  20. Generation of crystalline silica from sugarcane burning.

    PubMed

    Le Blond, Jennifer S; Horwell, Claire J; Williamson, Ben J; Oppenheimer, Clive

    2010-07-01

    Sugarcane leaves contain amorphous silica, which may crystallise to form crystalline silica polymorphs (cristobalite or quartz), during commercial sugarcane harvesting where sugarcane plants are burned. Respirable airborne particulate containing these phases may present an occupational health hazard. Following from an earlier pilot study (J. S. Le Blond, B. J. Williamson, C. J. Horwell, A. K. Monro, C. A. Kirk and C. Oppenheimer, Atmos. Environ., 2008, 42, 5558-5565) in which experimental burning of sugarcane leaves yielded crystalline silica, here we report on actual conditions during sugarcane burning on commercial estates, investigate the physico-chemical properties of the cultivated leaves and ash products, and quantify the presence of crystalline silica. Commercially grown raw sugarcane leaf was found to contain up to 1.8 wt% silica, mostly in the form of amorphous silica bodies (with trace impurities e.g., Al, Na, Mg), with only a small amount of quartz. Thermal images taken during several pre-harvest burns recorded temperatures up to 1056 degrees C, which is sufficient for metastable cristobalite formation. No crystalline silica was detected in airborne particulate from pre-harvest burning, collected using a cascade impactor. The sugarcane trash ash formed after pre-harvest burning contained between 10 and 25 wt% SiO(2), mostly in an amorphous form, but with up to 3.5 wt% quartz. Both quartz and cristobalite were identified in the sugarcane bagasse ash (5-15 wt% and 1-3 wt%, respectively) formed in the processing factory. Electron microprobe analysis showed trace impurities of Mg, Al and Fe in the silica particles in the ash. The absence of crystalline silica in the airborne emissions and lack of cristobalite in trash ash suggest that high temperatures during pre-harvest burning were not sustained long enough for cristobalite to form, which is supported by the presence of low temperature sylvite and calcite in the residual ash. The occurrence of quartz and

  1. Generation of crystalline silica from sugarcane burning.

    PubMed

    Le Blond, Jennifer S; Horwell, Claire J; Williamson, Ben J; Oppenheimer, Clive

    2010-07-01

    Sugarcane leaves contain amorphous silica, which may crystallise to form crystalline silica polymorphs (cristobalite or quartz), during commercial sugarcane harvesting where sugarcane plants are burned. Respirable airborne particulate containing these phases may present an occupational health hazard. Following from an earlier pilot study (J. S. Le Blond, B. J. Williamson, C. J. Horwell, A. K. Monro, C. A. Kirk and C. Oppenheimer, Atmos. Environ., 2008, 42, 5558-5565) in which experimental burning of sugarcane leaves yielded crystalline silica, here we report on actual conditions during sugarcane burning on commercial estates, investigate the physico-chemical properties of the cultivated leaves and ash products, and quantify the presence of crystalline silica. Commercially grown raw sugarcane leaf was found to contain up to 1.8 wt% silica, mostly in the form of amorphous silica bodies (with trace impurities e.g., Al, Na, Mg), with only a small amount of quartz. Thermal images taken during several pre-harvest burns recorded temperatures up to 1056 degrees C, which is sufficient for metastable cristobalite formation. No crystalline silica was detected in airborne particulate from pre-harvest burning, collected using a cascade impactor. The sugarcane trash ash formed after pre-harvest burning contained between 10 and 25 wt% SiO(2), mostly in an amorphous form, but with up to 3.5 wt% quartz. Both quartz and cristobalite were identified in the sugarcane bagasse ash (5-15 wt% and 1-3 wt%, respectively) formed in the processing factory. Electron microprobe analysis showed trace impurities of Mg, Al and Fe in the silica particles in the ash. The absence of crystalline silica in the airborne emissions and lack of cristobalite in trash ash suggest that high temperatures during pre-harvest burning were not sustained long enough for cristobalite to form, which is supported by the presence of low temperature sylvite and calcite in the residual ash. The occurrence of quartz and

  2. Epoxy + liquid crystalline epoxy coreacted network

    NASA Astrophysics Data System (ADS)

    Punchaipetch, Prakaipetch

    2000-10-01

    Molecular reinforcement through in-situ polymerization of liquid crystalline epoxies (LCEs) and a non-liquid crystalline epoxy has been investigated. Three LCEs: diglycidyl ether of 4,4'-dihydroxybiphenol (DGE-DHBP) and digylcidyl ether of 4-hydroxyphenyl-4″-hydroxybiphenyl-4 '-carboxylate (DGE-HHC), were synthesized and blended with diglycidyl ether of bisphenol F (DGEBP-F) and subsequently cured with anhydride and amine curing agents. Curing kinetics were determined using differential scanning calorimetry (DSC). Parameters for autocatalytic curing kinetics of both pure monomers and blended systems were determined. The extent of cure for both monomers was monitored by using Fourier transform infrared spectroscopy (FT-IR). The glass transitions were evaluated as a function of composition using DSC and dynamic mechanical analysis (DMA). The results show that the LC constituent affects the curing kinetics of the epoxy resin and that the systems are highly miscible. The effects of molecular reinforcement of DGEBP-F by DGE-DHBP and DGE-HHC were investigated. The concentration of the liquid crystalline moiety affects mechanical properties. Tensile, impact and fracture toughness tests results are evaluated. Scanning electron microscopy of the fracture surfaces shows changes in failure mechanisms compared to the pure components. Results indicate that mechanical properties of the blended samples are improved already at low concentration by weight of the LCE added into epoxy resin. The improvement in mechanical properties was found to occur irrespective of the absence of liquid crystallinity in the blended networks. The mechanism of crack study indicates that crack deflection and crack bridging are the mechanisms in case of LC epoxy. In case of LC modified epoxy, the crack deflection is the main mechanism. Moreover, the effect of coreacting an epoxy with a reactive monomer liquid crystalline epoxy as a matrix for glass fiber composites was investigated. Mechanical

  3. Crystallins of the octopus lens. Recruitment from detoxification enzymes.

    PubMed

    Tomarev, S I; Zinovieva, R D; Piatigorsky, J

    1991-12-15

    The eye lens crystallins of the octopus Octopus dofleini were identified by sequencing abundant proteins and cDNAs. As in squid, the octopus crystallins have subunit molecular masses of 25-30 kDa, are related to mammalian glutathione S-transferases (GST), and are encoded in at least six genes. The coding regions and deduced amino acid sequences of four octopus lens cDNAs are 75-80% identical, while their non-coding regions are entirely different. Deduced amino acid sequences show 52-57% similarity with squid GST-like crystallins, but only 20-25% similarity with mammalian GST. These data suggest that the octopus and squid lens GST-like crystallin gene families expanded after divergence of these species. Northern blot hybridization indicated that the four octopus GST-like crystallin genes examined are lens-specific. Lens extracts showed about 40 times less GST activity using 1-chloro-2,4-dinitrobenzene as substrate than liver extracts of the octopus, indicating that the major GST-like crystallins are specialized for a lens structural role. A prominent 59-kDa crystallin polypeptide, previously observed in octopus but not squid and called omega-crystallin (Chiou, S.-H. (1988) FEBS Lett. 241, 261-264), has been identified as an aldehyde dehydrogenase. Since cytoplasmic aldehyde dehydrogenase is a major protein in elephant shrew lenses (eta-crystallin; Wistow, G., and Kim, H. (1991) J. Mol. Evol. 32, 262-269) the octopus aldehyde dehydrogenase crystallin provides the first example of a similar enzyme-crystallin in vertebrates and invertebrates. The use of detoxification stress proteins (GST and aldehyde dehydrogenase) as cephalopod crystallins indicates a common strategy for recruitment of enzyme-crystallins during the convergent evolution of vertebrate and invertebrate lenses. For historical reasons we propose that the octopus GST-like crystallins, like those of the squid, are called S-crystallins. PMID:1721068

  4. Crystalline cataract caused by a heterozygous missense mutation in γD-crystallin (CRYGD)

    PubMed Central

    Andrews, Caroline; Nihalani, Bharti R.; Engle, Elizabeth C.

    2011-01-01

    Purpose To describe phenotypic characteristics of two pedigrees manifesting early onset crystalline cataract with mutations in the γD-crystallin gene (CRYGD). Methods A detailed medical history was obtained from two Caucasian pedigrees manifesting autosomal dominant congenital cataracts. Genomic DNA was extracted from saliva (DNA Genotek). Single Nucleotide Polymorphism (SNP) based genome analysis of the larger pedigree revealed linkage to an 8.2 MB region on chromosome 2q33-q35 which encompassed the crystallin-gamma gene cluster (CRYG). Exons and flanking introns of CRYGA, CRYGB, CRYGC and CRYGD were amplified and sequenced to identify disease-causing mutations. Results A morphologically unique cataract with extensive refractile “crystals” scattered throughout the nucleus and perinuclear cortex was found in the probands from both pedigrees. A heterozygous C→A mutation was identified at position 109 of the coding sequence (R36S of the processed protein) in exon 2 of CRYGD and this missense mutation was found to cosegregate with the disease in the larger family; this mutation was then identified in affected individuals of pedigree 2 as well. Conclusions The heterozygous 109C→A CRYGD missense mutation is associated with a distinct crystalline cataract in two US Caucasian pedigrees. This confirms crystalline cataract formation with this mutation, as previously reported in sporadic childhood case from the Czech Republic and in members of a Chinese family. PMID:22219628

  5. Enzymatic diversity of the Clostridium thermocellum cellulosome is crucial for the degradation of crystalline cellulose and plant biomass

    PubMed Central

    Hirano, Katsuaki; Kurosaki, Masahiro; Nihei, Satoshi; Hasegawa, Hiroki; Shinoda, Suguru; Haruki, Mitsuru; Hirano, Nobutaka

    2016-01-01

    The cellulosome is a supramolecular multienzyme complex comprised of a wide variety of polysaccharide-degrading enzymes and scaffold proteins. The cellulosomal enzymes that bind to the scaffold proteins synergistically degrade crystalline cellulose. Here, we report in vitro reconstitution of the Clostridium thermocellum cellulosome from 40 cellulosomal components and the full-length scaffoldin protein that binds to nine enzyme molecules. These components were each synthesized using a wheat germ cell-free protein synthesis system and purified. Cellulosome complexes were reconstituted from 3, 12, 30, and 40 components based on their contents in the native cellulosome. The activity of the enzyme-saturated complex indicated that greater enzymatic variety generated more synergy for the degradation of crystalline cellulose and delignified rice straw. Surprisingly, a less complete enzyme complex displaying fewer than nine enzyme molecules was more efficient for the degradation of delignified rice straw than the enzyme-saturated complex, despite the fact that the enzyme-saturated complex exhibited maximum synergy for the degradation of crystalline cellulose. These results suggest that greater enzymatic diversity of the cellulosome is crucial for the degradation of crystalline cellulose and plant biomass, and that efficient degradation of different substrates by the cellulosome requires not only a different enzymatic composition, but also different cellulosome structures. PMID:27759119

  6. Structure of a Highly Active Cephalopod S-crystallin Mutant: New Molecular Evidence for Evolution from an Active Enzyme into Lens-Refractive Protein

    PubMed Central

    Tan, Wei-Hung; Cheng, Shu-Chun; Liu, Yu-Tung; Wu, Cheng-Guo; Lin, Min-Han; Chen, Chiao-Che; Lin, Chao-Hsiung; Chou, Chi-Yuan

    2016-01-01

    Crystallins are found widely in animal lenses and have important functions due to their refractive properties. In the coleoid cephalopods, a lens with a graded refractive index provides good vision and is required for survival. Cephalopod S-crystallin is thought to have evolved from glutathione S-transferase (GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We’ve also identified four historical mutations that are able to produce a “GST-like” S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution. PMID:27499004

  7. Structure of a Highly Active Cephalopod S-crystallin Mutant: New Molecular Evidence for Evolution from an Active Enzyme into Lens-Refractive Protein.

    PubMed

    Tan, Wei-Hung; Cheng, Shu-Chun; Liu, Yu-Tung; Wu, Cheng-Guo; Lin, Min-Han; Chen, Chiao-Che; Lin, Chao-Hsiung; Chou, Chi-Yuan

    2016-01-01

    Crystallins are found widely in animal lenses and have important functions due to their refractive properties. In the coleoid cephalopods, a lens with a graded refractive index provides good vision and is required for survival. Cephalopod S-crystallin is thought to have evolved from glutathione S-transferase (GST) with various homologs differentially expressed in the lens. However, there is no direct structural information that helps to delineate the mechanisms by which S-crystallin could have evolved. Here we report the structural and biochemical characterization of novel S-crystallin-glutathione complex. The 2.35-Å crystal structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site architecture that is different from that of GST. S-crystallin has a preference for glutathione binding, although almost lost its GST enzymatic activity. We've also identified four historical mutations that are able to produce a "GST-like" S-crystallin that has regained activity. This protein recapitulates the evolution of S-crystallin from GST. Protein stability studies suggest that S-crystallin is stabilized by glutathione binding to prevent its aggregation; this contrasts with GST-σ, which do not possess this protection. We suggest that a tradeoff between enzyme activity and the stability of the lens protein might have been one of the major driving force behind lens evolution. PMID:27499004

  8. Biomimetic processing of oriented crystalline ceramic layers

    SciTech Connect

    Cesarano, J.; Shelnutt, J.A.

    1997-10-01

    The aim of this project was to develop the capabilities for Sandia to fabricate self assembled Langmuir-Blodgett (LB) films of various materials and to exploit their two-dimensional crystalline structure to promote the growth of oriented thin films of inorganic materials at room temperature. This includes the design and synthesis of Langmuir-active (amphiphilic) organic molecules with end groups offering high nucleation potential for various ceramics. A longer range goal is that of understanding the underlying principles, making it feasible to use the techniques presented in this report to fabricate unique oriented films of various materials for electronic, sensor, and membrane applications. Therefore, whenever possible, work completed in this report was completed with the intention of addressing the fundamental phenomena underlying the growth of crystalline, inorganic films on template layers of highly organized organic molecules. This problem was inspired by biological processes, which often produce exquisitely engineered structures via templated growth on polymeric layers. Seashells, for example, exhibit great toughness owing to their fine brick-and-mortar structure that results from templated growth of calcium carbonate on top of layers of ordered organic proteins. A key goal in this work, therefore, is to demonstrate a positive correlation between the order and orientation of the template layer and that of the crystalline ceramic material grown upon it. The work completed was comprised of several parallel efforts that encompassed the entire spectrum of biomimetic growth from solution. Studies were completed on seashells and the mechanisms of growth for calcium carbonate. Studies were completed on the characterization of LB films and the capability developed for the in-house fabrication of these films. Standard films of fatty acids were studied as well as novel polypeptides and porphyrins that were synthesized.

  9. Hydrogeologic controls on induced seismicity in crystalline basement rocks due to fluid injection into basal reservoirs.

    PubMed

    Zhang, Yipeng; Person, Mark; Rupp, John; Ellett, Kevin; Celia, Michael A; Gable, Carl W; Bowen, Brenda; Evans, James; Bandilla, Karl; Mozley, Peter; Dewers, Thomas; Elliot, Thomas

    2013-01-01

    A series of Mb 3.8-5.5 induced seismic events in the midcontinent region, United States, resulted from injection of fluid either into a basal sedimentary reservoir with no underlying confining unit or directly into the underlying crystalline basement complex. The earthquakes probably occurred along faults that were likely critically stressed within the crystalline basement. These faults were located at a considerable distance (up to 10 km) from the injection wells and head increases at the hypocenters were likely relatively small (∼70-150 m). We present a suite of simulations that use a simple hydrogeologic-geomechanical model to assess what hydrogeologic conditions promote or deter induced seismic events within the crystalline basement across the midcontinent. The presence of a confining unit beneath the injection reservoir horizon had the single largest effect in preventing induced seismicity within the underlying crystalline basement. For a crystalline basement having a permeability of 2 × 10(-17)  m(2) and specific storage coefficient of 10(-7) /m, injection at a rate of 5455 m(3) /d into the basal aquifer with no underlying basal seal over 10 years resulted in probable brittle failure to depths of about 0.6 km below the injection reservoir. Including a permeable (kz  = 10(-13)  m(2) ) Precambrian normal fault, located 20 m from the injection well, increased the depth of the failure region below the reservoir to 3 km. For a large permeability contrast between a Precambrian thrust fault (10(-12)  m(2) ) and the surrounding crystalline basement (10(-18)  m(2) ), the failure region can extend laterally 10 km away from the injection well.

  10. Hydrogeologic controls on induced seismicity in crystalline basement rocks due to fluid injection into basal reservoirs.

    PubMed

    Zhang, Yipeng; Person, Mark; Rupp, John; Ellett, Kevin; Celia, Michael A; Gable, Carl W; Bowen, Brenda; Evans, James; Bandilla, Karl; Mozley, Peter; Dewers, Thomas; Elliot, Thomas

    2013-01-01

    A series of Mb 3.8-5.5 induced seismic events in the midcontinent region, United States, resulted from injection of fluid either into a basal sedimentary reservoir with no underlying confining unit or directly into the underlying crystalline basement complex. The earthquakes probably occurred along faults that were likely critically stressed within the crystalline basement. These faults were located at a considerable distance (up to 10 km) from the injection wells and head increases at the hypocenters were likely relatively small (∼70-150 m). We present a suite of simulations that use a simple hydrogeologic-geomechanical model to assess what hydrogeologic conditions promote or deter induced seismic events within the crystalline basement across the midcontinent. The presence of a confining unit beneath the injection reservoir horizon had the single largest effect in preventing induced seismicity within the underlying crystalline basement. For a crystalline basement having a permeability of 2 × 10(-17)  m(2) and specific storage coefficient of 10(-7) /m, injection at a rate of 5455 m(3) /d into the basal aquifer with no underlying basal seal over 10 years resulted in probable brittle failure to depths of about 0.6 km below the injection reservoir. Including a permeable (kz  = 10(-13)  m(2) ) Precambrian normal fault, located 20 m from the injection well, increased the depth of the failure region below the reservoir to 3 km. For a large permeability contrast between a Precambrian thrust fault (10(-12)  m(2) ) and the surrounding crystalline basement (10(-18)  m(2) ), the failure region can extend laterally 10 km away from the injection well. PMID:23745958

  11. Optical density of the crystalline lens

    SciTech Connect

    Hemenger, R.P.

    1982-01-01

    The optical density for the noncataractous crystalline lens is written as a sum of two terms, each with a specific dependence on wavelength. The first term, proportional to 1/lambda 2, represents all light-scattering processes in the lens. The second term, assumed significant only for lambda less than or equal to 500 nm, accounts for absorption by lens pigments. By analyzing transmittance data on lenses of subjects aged 21 to 63 years, a spectrum for light absorption by lens pigment is derived and it is shown to be essentially the same for all of the lenses.

  12. (Preoxidation cleaning optimization for crystalline silicon)

    SciTech Connect

    Not Available

    1991-01-01

    A series of controlled experiments has been performed in Sandia's Photovoltaic Device Fabrication Laboratory to evaluate the effect of various chemical surface treatments on the recombination lifetime of crystalline silicon wafers subjected to a high-temperature dry oxidation. From this series of experiments we have deduced a relatively simple yet effective cleaning sequence. We have also evaluated the effect of different chemical damage-removal etches for improving the recombination lifetime and surface smoothness of mechanically lapped wafers. This paper presents the methodology used, the experimental results obtained, and our experience with using this process on a continuing basis over a period of many months. 7 refs., 4 figs., 1 tab.

  13. Crystalline silicotitanates for cesium/strontium removal

    SciTech Connect

    Brown, N.; Miller, J.; Sherman, J.

    1996-10-01

    A new class of inorganic ion exchangers called crystalline silicotitanates (CST) has been developed that exhibits very high selectivity for cesium and strontium in the highly alkaline radioactive wastes at the Hanford Site and other DOE sites. Tests have also shown that CSTs have high selectivity for cesium in acidic and neutral solutions. The ESP is supporting an effort at Sandia National Laboratories and Texas A & M University to further develop and characterize the important chemical and physical properties that will determine the applicability of CST to radioactive waste treatment at Hanford and other DOE facilities.

  14. Vibrational dynamics of crystalline L-alanine

    SciTech Connect

    Bordallo, H.N.; Eckert, J.; Barthes, M.

    1997-11-01

    The authors report a new, complete vibrational analysis of L-alanine and L-alanine-d{sub 4} which utilizes IINS intensities in addition to frequency information. The use of both isotopomers resulted in a self-consistent force field for and assignment of the molecular vibrations in L-alanine. Some details of the calculation as well as a comparison of calculated and observed IINS spectra are presented. The study clarifies a number of important issues on the vibrational dynamics of this molecule and presents a self-consistent force field for the molecular vibrations in crystalline L-alanine.

  15. Controlled synthesis of single-crystalline graphene

    SciTech Connect

    Xueshen, Wang Jinjin, Li Qing, Zhong; Yuan, Zhong; Mengke, Zhao; Yonggang, Liu

    2014-03-15

    This paper reports the controlled synthesis of single-crystalline graphene on the back side of copper foil using CH{sub 4} as the precursor. The influence of growth time and the pressure ratio of CH{sub 4}/H{sub 2} on the structure of graphene are examined. An optimized polymer-assisted method is used to transfer the synthesized graphene onto a SiO{sub 2}/Si substrate. Scanning electron microscopy and Raman spectroscopy are used to characterize the graphene.

  16. Heat capacities of crystalline tetraalkylammonium salts

    NASA Astrophysics Data System (ADS)

    Manin, N. G.; Kustov, A. V.; Antonova, O. A.

    2012-05-01

    The behavior of crystalline tetraalkylammonium salts at 290-350 K was studied by differential scanning calorimetry. For tetraethyl- and tetrabutylammonium bromides (Et4NBr and Bu4NBr), the experimental heat capacities agreed well with the literature values. For tetrahexyl-, tetraheptyl-, and tetraoctylam-monium bromides (Hex4NBr, Hep4NBr, and Oct4NBr), phase transitions were found between crystal modifications whose characteristic temperatures depended significantly on the size of the cation. Empirical equations for the temperature dependences of the heat capacities of the salts within the ranges of homogeneous equilibrium phases were derived.

  17. Mycophenolic acid inhibits inosine 5'-monophosphate dehydrogenase and suppresses production of pro-inflammatory cytokines, nitric oxide, and LDH in macrophages.

    PubMed

    Jonsson, Charlotte A; Carlsten, Hans

    2002-01-01

    Mycophenolic acid (MPA) inhibits reversibly inosine 5(')-monophosphate dehydrogenase, an enzyme involved in the de novo synthesis of guanine nucleotides. Previously, mycophenolate mofetil (MMF), the pro-drug of MPA, was shown to exert beneficial effects on the systemic lupus erythematosus (SLE)-like disease in MRLlpr/lpr mice. In this study MPA's immunomodulating effects in vitro on the murine macrophage cell line IC-21 were investigated. The cells were exposed to MPA together with lipopolysaccharide and IFN-gamma. Cytokine, NO(2)(-), and lactate dehydrogenase levels in supernatants and cell lysates were analysed as well as the proliferation of IC-21 cells. MPA exposure reduced the total levels of all molecules investigated and suppressed the proliferation. All MPA-induced effects were reversed by the addition of guanosine to the cultures. Since macrophages play a role in lupus nephritis, our results indicate that modulation of macrophages may be involved in the ameliorating effects of MMF in SLE. PMID:12381354

  18. Dielectric spectra broadening as a signature for dipole-matrix interaction. III. Water in adenosine monophosphate/adenosine-5'-triphosphate solutions.

    PubMed

    Puzenko, Alexander; Levy, Evgeniya; Shendrik, Andrey; Talary, Mark S; Caduff, Andreas; Feldman, Yuri

    2012-11-21

    In this, the third part of our series on the dielectric spectrum symmetrical broadening of water, we consider the nucleotide aqueous solutions. Where in Parts I [E. Levy et al., J. Chem. Phys. 136, 114502 (2012)] and II [E. Levy et al., J. Chem. Phys. 136, 114503 (2012)], the dipole-dipole or ion-dipole interaction had a dominant feature, now the interplay between these two types of dipole-matrix interactions will be considered. We present the results of high frequency dielectric measurements of different concentrations of adenosine monophosphate/adenosine-5'-triphosphate aqueous solutions. We observed the Cole-Cole broadening of the main relaxation peak of the solvent in the solutions. Moreover, depending on the nucleotide concentration, we observed both types of dipole-matrix interaction. The 3D trajectory approach (described in detail in Part I) is applied in order to highlight the differences between the two types of interaction.

  19. Can selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphadiesterase type 5 (PDE 5) offer protection against contrast induced nephropathy?

    PubMed

    Morcos, Sameh K

    2014-08-01

    Parenchymal hypoxia within the renal outer medulla plays an important role in the pathogenesis of contrast induced nephropathy (CIN). Nitric oxide (NO) is crucial for medullary oxygenation by enhancing regional blood flow. Augmenting the effect of NO in the renal medulla by the use of selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphadiesterase type 5 (PDE 5) such as sildenafil (Viagra™), vardenafil (Levitra™) or tadalafil (Cialis™) could reduce the severity of the hypoxic insult induced by the contrast medium and reduce the risk of CIN. Prophylactic administration of one of these drugs particularly the long acting one tadalafil before and after the administration of CM could offer a simple and rational approach to reduce the risk of this complication. This hypothesis deserves serious investigation to determine its clinical efficacy.

  20. Guanosine Quadruplexes in Solution: A Small-Angle X-Ray Scattering Analysis of Temperature Effects on Self-Assembling of Deoxyguanosine Monophosphate

    PubMed Central

    Mariani, P.; Spinozzi, F.; Federiconi, F.; Ortore, M. G.; Amenitsch, H.; Spindler, L.; Drevensek-Olenik, I.

    2010-01-01

    We investigated quadruplex formation in aqueous solutions of 2′-deoxyriboguanosine 5′-monophosphate, d(pG), which takes place in the absence of the covalent axial backbone. A series of in-solution small angle X-ray scattering experiments on d(pG) have been performed as a function of temperature in the absence of excess salt, at a concentration just above the critical one at which self-assembling occurs. A global fit approach has been used to derive composition and size distribution of the scattering particles as a function of temperature. The obtained results give thermodynamical justification for the observed phase-behavior, indicating that octamer formation is essential for quadruplex elongation. Our investigation shows that d(pG) quadruplexes are very suitable to assess the potential of G-quadruplex formation and to study the self-assembling thermodynamics. PMID:20725625

  1. Behavior of the monophosphate tungsten bronzes (PO 2) 4(WO 3) 2 m (m = 4 and 6) in electrochemical lithium insertion

    NASA Astrophysics Data System (ADS)

    Longoria Rodríguez, F. E.; Martínez-de la Cruz, A.; López Cuéllar, E.

    The electrochemical lithium insertion process has been studied in the family of monophosphate tungsten bronzes (PO 2) 4(WO 3) 2 m, where m = 4 and 6. Structural changes in the pristine oxides were followed as lithium insertion proceeded. Through potentiostatic intermittent technique, the different processes which take place in the cathode during the discharge of the cell were analysed. The nature of the bronzes Li x(PO 2) 4(WO 3) 2 m formed was determined by in situ X-ray diffraction experiments. These results have allowed establishment of a correlation with the reversible/irreversible processes detected during the electrochemical lithium insertion. Measurements of resistivity showed that upon lithium insertion, the metallic pristine oxides become insulating.

  2. Muscle A-Kinase Anchoring Protein-α is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival.

    PubMed

    Wang, Yan; Cameron, Evan G; Li, Jinliang; Stiles, Travis L; Kritzer, Michael D; Lodhavia, Rahul; Hertz, Jonathan; Nguyen, Tu; Kapiloff, Michael S; Goldberg, Jeffrey L

    2015-12-01

    Neurotrophic factor and cAMP-dependent signaling promote the survival and neurite outgrowth of retinal ganglion cells (RGCs) after injury. However, the mechanisms conferring neuroprotection and neuroregeneration downstream to these signals are unclear. We now reveal that the scaffold protein muscle A-kinase anchoring protein-α (mAKAPα) is required for the survival and axon growth of cultured primary RGCs. Although genetic deletion of mAKAPα early in prenatal RGC development did not affect RGC survival into adulthood, nor promoted the death of RGCs in the uninjured adult retina, loss of mAKAPα in the adult increased RGC death after optic nerve crush. Importantly, mAKAPα was required for the neuroprotective effects of brain-derived neurotrophic factor and cyclic adenosine-monophosphate (cAMP) after injury. These results identify mAKAPα as a scaffold for signaling in the stressed neuron that is required for RGC neuroprotection after optic nerve injury. PMID:26844267

  3. Can selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphadiesterase type 5 (PDE 5) offer protection against contrast induced nephropathy?

    PubMed

    Morcos, Sameh K

    2014-08-01

    Parenchymal hypoxia within the renal outer medulla plays an important role in the pathogenesis of contrast induced nephropathy (CIN). Nitric oxide (NO) is crucial for medullary oxygenation by enhancing regional blood flow. Augmenting the effect of NO in the renal medulla by the use of selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphadiesterase type 5 (PDE 5) such as sildenafil (Viagra™), vardenafil (Levitra™) or tadalafil (Cialis™) could reduce the severity of the hypoxic insult induced by the contrast medium and reduce the risk of CIN. Prophylactic administration of one of these drugs particularly the long acting one tadalafil before and after the administration of CM could offer a simple and rational approach to reduce the risk of this complication. This hypothesis deserves serious investigation to determine its clinical efficacy. PMID:25202655

  4. Isolation of cyclic adenosine 3':5'-monophosphate (cAMP) from lakes of differing trophic status: Correlation with planktonic metabolic variables

    SciTech Connect

    Francko, D.A.; Wetzel, R.G.

    1982-01-01

    The seasonal dynamics of particulate and dissolved cyclic adenosine 3':5'-monophosphate (cAMP) were examined in the epilimnia and littoral zones of two trophically dissimilar lakes. Each cAMP fraction was found in quantities comparable to those reported for cultured phytoplankton species. Both cAMP fractions varied greatly in concentration during the season and between the oligotrophic and hypereutrophic lakes. Increases in phytoplankton community densities were paralleled by weight-specific changes in particulate cAMP levels, depending on the phytoplankton species present. A linear relationship between cellular cAMP levels and in situ primary productivity rates was found in the oligotrophic lake. In both lakes, certain phytoplanktonic associations had particulate cAMP levels linearly related to chlorophyll a content and specific activity of alkaline phosphatase.

  5. Characterization of Fructose 1,6-Bisphosphatase and Sedoheptulose 1,7-Bisphosphatase from the Facultative Ribulose Monophosphate Cycle Methylotroph Bacillus methanolicus

    PubMed Central

    Stolzenberger, Jessica; Lindner, Steffen N.; Persicke, Marcus; Brautaset, Trygve

    2013-01-01

    The genome of the facultative ribulose monophosphate (RuMP) cycle methylotroph Bacillus methanolicus encodes two bisphosphatases (GlpX), one on the chromosome (GlpXC) and one on plasmid pBM19 (GlpXP), which is required for methylotrophy. Both enzymes were purified from recombinant Escherichia coli and were shown to be active as fructose 1,6-bisphosphatases (FBPases). The FBPase-negative Corynebacterium glutamicum Δfbp mutant could be phenotypically complemented with glpXC and glpXP from B. methanolicus. GlpXP and GlpXC share similar functional properties, as they were found here to be active as homotetramers in vitro, activated by Mn2+ ions and inhibited by Li+, but differed in terms of the kinetic parameters. GlpXC showed a much higher catalytic efficiency and a lower Km for fructose 1,6-bisphosphate (86.3 s−1 mM−1 and 14 ± 0.5 μM, respectively) than GlpXP (8.8 s−1 mM−1 and 440 ± 7.6 μM, respectively), indicating that GlpXC is the major FBPase of B. methanolicus. Both enzymes were tested for activity as sedoheptulose 1,7-bisphosphatase (SBPase), since a SBPase variant of the ribulose monophosphate cycle has been proposed for B. methanolicus. The substrate for the SBPase reaction, sedoheptulose 1,7-bisphosphate, could be synthesized in vitro by using both fructose 1,6-bisphosphate aldolase proteins from B. methanolicus. Evidence for activity as an SBPase could be obtained for GlpXP but not for GlpXC. Based on these in vitro data, GlpXP is a promiscuous SBPase/FBPase and might function in the RuMP cycle of B. methanolicus. PMID:24013630

  6. Highly Crystalline Nanoparticle Suspensions for Low-Temperature Processing of TiO2 Thin Films.

    PubMed

    Watté, Jonathan; Lommens, Petra; Pollefeyt, Glenn; Meire, Mieke; De Buysser, Klaartje; Van Driessche, Isabel

    2016-05-25

    In this work, we present preparation and stabilization methods for highly crystalline TiO2 nanoparticle suspensions for the successful deposition of transparent, photocatalytically active TiO2 thin films toward the degradation of organic pollutants by a low temperature deposition method. A proof-of-concept is provided wherein stable, aqueous TiO2 suspensions are deposited on glass substrates. Even if the processing temperature is lowered to 150-200 °C, the subsequent heat treatment provides transparent and photocatalytically active titania thin layers. Because all precursor solutions are water-based, this method provides an energy-efficient, sustainable, and environmentally friendly synthesis route. The high load in crystalline titania particles obtained after microwave heating opens up the possibility to produce thin coatings by low temperature processing, as a conventional crystallization procedure is in this case superfluous. The impact of the precursor chemistry in Ti(4+)-peroxo solutions, containing imino-diacetic acid as a complexing ligand and different bases to promote complexation was studied as a function of pH, reaction time and temperature. The nanocrystal formation was followed in terms of colloidal stability, crystallinity and particle size. Combined data from Raman and infrared spectroscopy, confirmed that stable titanium precursors could be obtained at pH levels ranging from 2 to 11. A maximum amount of 50.7% crystallinity was achieved, which is one of the highest reported amounts of anatase nanoparticles that are suspendable in stable aqueous titania suspensions. Decoloring of methylene blue solutions by precipitated nanosized powders from the TiO2 suspensions proves their photocatalytic properties toward degradation of organic materials, a key requisite for further processing. This synthesis method proves that the deposition of highly crystalline anatase suspensions is a valid route for the production of photocatalytically active, transparent

  7. Crystalline marble beats limestone for fluegas desulfurization

    SciTech Connect

    1996-05-01

    NovaCon Energy Systems, Inc. (Bedford, NY) has developed an alternative to conventional limestone sorbents. The new process uses a class of marble, selected with a proprietary model. Recent pilot- and full-scale demonstrations in pulverized-coal (PC) and circulating fluidized bed (CFB) boilers suggest that these patented sorbents outperform conventional limestone for the simultaneous control of SOx, NOx, and particulates during the combustion of coal and sulfur-rich fuels, such as oil, mixed municipal waste and used tires. Dubbed thermally active marbles (TAMs), these sorbents are chemically identical to grainy limestone (whose main constituent is calcium carbonate or calcite). However, thanks to the increased pressures and temperatures experienced during their geologic history, these metamorphic minerals have a regular crystalline structure that offers some advantages in the combustion zone. TAMs, on the other hand, enjoy better calcium-utilization rates because upon heating, they cleave along inter- and intra-crystalline faces, continuously exposing fresh surfaces. By minimizing the self-extinguishment suffered by limestone sorbents, TAMs are effective over operating temperatures from 1,200 F to 2,800 F, which is 400 F higher than other calcium-based sorbents. This allows them to be injected closer to the burner or combustion grate to maximize residence time in the unit.

  8. Crystalline surfactant dispersions by radio frequency absorption

    SciTech Connect

    Tedder, S.H.

    1986-03-01

    Recently interest has increased in the use of liquid crystalline surfactant dispersions for enhanced oil recovery. The object of the work described in the report was to develop a method of measuring the electrical properties of colloidal surfactant particles, which control the structure and stability of the surfactant dispersion. A further object was to find how these electrical properties are affected by the method used to mix the components of the dispersion. The results may be useful in solving several practical problems, including the identification of optimally performing liquid crystalline surfactant formulations for oil recovery use. Another possible use is to identify and categorize effects of the method of mixing surfactants on the final product. This information would provide guidelines for field handling of chemical recovery agents. The absorption of radio frequency energy, a process which is mediated by the surface electrical properties of the surfactant particles, was used to measure several electrical parameters of the surfactant mixtures. Two commercial petroleum sulfonate surfactants were tested by the radio frequency absorption method, and a model of their electrical properties was developed and used to fit the data. The strength of the layer of electric charges surrounding the surfactant particles was found to be related to the stability of the solution. 10 refs., 4 figs., 3 tabs.

  9. Topology of nonsymmorphic crystalline insulators and superconductors

    NASA Astrophysics Data System (ADS)

    Shiozaki, Ken; Sato, Masatoshi; Gomi, Kiyonori

    2016-05-01

    Topological classification in our previous paper [K. Shiozaki and M. Sato, Phys. Rev. B 90, 165114 (2014), 10.1103/PhysRevB.90.165114] is extended to nonsymmorphic crystalline insulators and superconductors. Using the twisted equivariant K theory, we complete the classification of topological crystalline insulators and superconductors in the presence of additional order-two nonsymmorphic space-group symmetries. The order-two nonsymmorphic space groups include half-lattice translation with Z2 flip, glide, twofold screw, and their magnetic space groups. We find that the topological periodic table shows modulo-2 periodicity in the number of flipped coordinates under the order-two nonsymmorphic space group. It is pointed out that the nonsymmorphic space groups allow Z2 topological phases even in the absence of time-reversal and/or particle-hole symmetries. Furthermore, the coexistence of the nonsymmorphic space group with time-reversal and/or particle-hole symmetries provides novel Z4 topological phases, which have not been realized in ordinary topological insulators and superconductors. We present model Hamiltonians of these new topological phases and analytic expressions of the Z2 and Z4 topological invariants. The half-lattice translation with Z2 spin flip and glide symmetry are compatible with the existence of boundaries, leading to topological surface gapless modes protected by the order-two nonsymmorphic symmetries. We also discuss unique features of these gapless surface modes.

  10. Diffusion of silicon in crystalline germanium

    SciTech Connect

    Silvestri, H.H.; Bracht, H.; Hansen, J. Lundsgaard; Larsen, A.Nylandsted; Haller, E.E.

    2005-06-06

    We report the determination of the diffusion coefficient of Si in crystalline Ge over the temperature range of 550 to 900 C. A molecular beam epitaxy (MBE) grown buried Si layer in an epitaxial Ge layer on a crystalline Ge substrate was used as the source for the diffusion experiments. For samples annealed at temperatures above 700 C, a 50 nm thick SiO{sub 2} cap layer was deposited to prevent decomposition of the Ge surface. We found the temperature dependence of the diffusion coefficient to be described by a single activation energy (3.32 eV) and pre-factor (38 cm{sup 2}/s) over the entire temperature range studied. The diffusion of the isovalent Si in Ge is slower than Ge self-diffusion over the full temperature range and reveals an activation enthalpy which is higher than that of self-diffusion. This points to a reduced interaction potential between the Si atom and the native defect mediating the diffusion process. For Si, which is smaller in size than the Ge self-atom, a reduced interaction is expected for a Si-vacancy (Si-V{sub Ge}) pair. Therefore we conclude that Si diffuses in Ge via the vacancy mechanism.

  11. Strong liquid-crystalline polymeric compositions

    DOEpatents

    Dowell, Flonnie

    1993-01-01

    Strong liquid-crystalline polymeric (LCP) compositions of matter. LCP backbones are combined with liquid crystalline (LC) side chains in a manner which maximizes molecular ordering through interdigitation of the side chains, thereby yielding materials which are predicted to have superior mechanical properties over existing LCPs. The theoretical design of LCPs having such characteristics includes consideration of the spacing distance between side chains along the backbone, the need for rigid sections in the backbone and in the side chains, the degree of polymerization, the length of the side chains, the regularity of the spacing of the side chains along the backbone, the interdigitation of side chains in sub-molecular strips, the packing of the side chains on one or two sides of the backbone to which they are attached, the symmetry of the side chains, the points of attachment of the side chains to the backbone, the flexibility and size of the chemical group connecting each side chain to the backbone, the effect of semiflexible sections in the backbone and the side chains, and the choice of types of dipolar and/or hydrogen bonding forces in the backbones and the side chains for easy alignment.

  12. Strong liquid-crystalline polymeric compositions

    DOEpatents

    Dowell, F.

    1993-12-07

    Strong liquid-crystalline polymeric (LCP) compositions of matter are described. LCP backbones are combined with liquid crystalline (LC) side chains in a manner which maximizes molecular ordering through interdigitation of the side chains, thereby yielding materials which are predicted to have superior mechanical properties over existing LCPs. The theoretical design of LCPs having such characteristics includes consideration of the spacing distance between side chains along the backbone, the need for rigid sections in the backbone and in the side chains, the degree of polymerization, the length of the side chains, the regularity of the spacing of the side chains along the backbone, the interdigitation of side chains in sub-molecular strips, the packing of the side chains on one or two sides of the backbone to which they are attached, the symmetry of the side chains, the points of attachment of the side chains to the backbone, the flexibility and size of the chemical group connecting each side chain to the backbone, the effect of semiflexible sections in the backbone and the side chains, and the choice of types of dipolar and/or hydrogen bonding forces in the backbones and the side chains for easy alignment. 27 figures.

  13. Interaction-enabled topological crystalline phases

    NASA Astrophysics Data System (ADS)

    Lapa, Matthew F.; Teo, Jeffrey C. Y.; Hughes, Taylor L.

    2016-03-01

    In this article we provide a general mechanism for generating interaction-enabled fermionic topological phases. We illustrate the mechanism with crystalline symmetry-protected topological phases in one, two, and three spatial dimensions. These nontrivial phases require interactions for their existence, and in the cases we consider, the free-fermion classification yields only a trivial phase. For the one- and two-dimensional phases we consider, we provide explicit exactly solvable models which realize the interaction-enabled phases. Similar to the interpretation of the Kitaev Majorana wire as a mean-field p -wave superconductor Hamiltonian arising from an interacting model with quartic interactions, we show that our systems can be interpreted as "mean-field" charge-4 e superconductors arising, e.g., from an interacting model with eight-body interactions or through another physical mechanism. The quartet superconducting nature allows for the teleportation of full Cooper pairs and, in two dimensions, for interesting semiclassical crystalline defects with non-Abelian anyon bound states.

  14. In vivo human crystalline lens topography

    PubMed Central

    Ortiz, Sergio; Pérez-Merino, Pablo; Gambra, Enrique; de Castro, Alberto; Marcos, Susana

    2012-01-01

    Custom high-resolution high-speed anterior segment spectral domain optical coherence tomography (OCT) was used to characterize three-dimensionally (3-D) the human crystalline lens in vivo. The system was provided with custom algorithms for denoising and segmentation of the images, as well as for fan (scanning) and optical (refraction) distortion correction, to provide fully quantitative images of the anterior and posterior crystalline lens surfaces. The method was tested on an artificial eye with known surfaces geometry and on a human lens in vitro, and demonstrated on three human lenses in vivo. Not correcting for distortion overestimated the anterior lens radius by 25% and the posterior lens radius by more than 65%. In vivo lens surfaces were fitted by biconicoids and Zernike polynomials after distortion correction. The anterior lens radii of curvature ranged from 10.27 to 14.14 mm, and the posterior lens radii of curvature ranged from 6.12 to 7.54 mm. Surface asphericities ranged from −0.04 to −1.96. The lens surfaces were well fitted by quadrics (with variation smaller than 2%, for 5-mm pupils), with low amounts of high order terms. Surface lens astigmatism was significant, with the anterior lens typically showing horizontal astigmatism (Z22 ranging from −11 to −1 µm) and the posterior lens showing vertical astigmatism (Z22 ranging from 6 to 10 µm). PMID:23082289

  15. Crystallinity in apatites: how can a truly disordered fraction be distinguished from nanosize crystalline domains?

    PubMed

    Celotti, Giancarlo; Tampieri, Anna; Sprio, Simone; Landi, Elena; Bertinetti, Luca; Martra, Gianmario; Ducati, Caterina

    2006-11-01

    In the last decade synthetic apatites mimicking the human natural one have been widely prepared and characterized from the physico-chemical point of view; however a shading zone is still remaining related to the evaluation and distinction of the less crystalline part, almost amorphous, and the crystallographically well ordered, nano-sized part, inside the apatite itself. Actually natural apatite forming bone tissue can include both types of crystals whose prevalence is dependent from the specific bone evolution stage and the specialized tissue performance. The quantitative description of such a combination usually represents a puzzling problem, but the result can also clarify the definition of "crystallinity in apatite" that appears still controversial. Many different synthetic apatites, including those nucleated on organic templates, were analyzed with different techniques (X-ray diffraction, transmission electron microscopy, and so on) to clarify the true nature of the disordered part. The results, manipulated by the classical methodologies devised for substances with highly perturbed structural order, led to establish that only specifically prepared amorphous calcium phosphate is really a glass, while the distorted portion coexisting with more or less crystalline regions is simply nanocrystalline. Moreover, at the conceptual limit of crystallinity tending to zero, the two models surprisingly cease to be conflicting.

  16. Aqueous hafnium sulfate chemistry: structures of crystalline precipitates.

    PubMed

    Kalaji, Ali; Soderholm, L

    2014-10-20

    Crystalline precipitates resulting from the hydrolysis and subsequent condensation of Hf(IV) aqueous acidic solutions at 60-95 °C are examined and compared. By varying the concentrations of the acid and sulfate source, a variety of complex hafnium-oxo-hydroxo-sulfate clusters are isolated and structures accessed. Four novel compounds were discovered, while the structures of two known compounds, an 18-mer and a planar hexamer, were updated. In total, the compounds described herein each contain one of four cluster architectures: 18-mer, 11-mer, nonamer, and planar hexamer. In addition, one compound contains small amounts of 19-mers together with 18-mers. As well as examining the individual structure of each complex cluster, we relate them to one another, as well as to the dense phases of HfO2, to gain an understanding of their formation and stability. Finally, the solution conditions under which each cluster forms are identified by plotting the crystallization regions of each cluster against acidity and sulfate concentration. Most clusters form under slightly acidic conditions, in decreasing size as the sulfate concentration is raised. The flat hexamer is the single exception; it appears to require more acidic solutions. The degree of hydroxo- versus oxo-bridges with changing solution conditions is assessed within the broader context of the condensates. Of specific interest is the identification of these products as they relate to the use of hydrolysis reactions in designing new materials.

  17. Comparison of non-crystalline silica nanoparticles in IL-1β release from macrophages

    PubMed Central

    2012-01-01

    Background Respirable crystalline silica (silicon dioxide; SiO2, quartz) particles are known to induce chronic inflammation and lung disease upon long-term inhalation, whereas non-crystalline (amorphous) SiO2 particles in the submicrometre range are regarded as less harmful. Several reports have demonstrated that crystalline, but also non-crystalline silica particles induce IL-1β release from macrophages via the NALP3-inflammasome complex (caspase-1, ASC and NALP3) in the presence of lipopolysaccharide (LPS) from bacteria. Our aim was to study the potential of different non-crystalline SiO2 particles from the nano- to submicro-sized range to activate IL-1β responses in LPS-primed RAW264.7 macrophages and primary rat lung macrophages. The role of the NALP3-inflammasome and up-stream mechanisms was further explored in RAW264.7 cells. Results In the present study, we have shown that 6 h exposure to non-crystalline SiO2 particles in nano- (SiNPs, 5–20 nm, 50 nm) and submicro-sizes induced strong IL-1β responses in LPS-primed mouse macrophages (RAW264.7) and primary rat lung macrophages. The primary lung macrophages were more sensitive to Si-exposure than the RAW-macrophages, and responded more strongly. In the lung macrophages, crystalline silica (MinUsil 5) induced IL-1β release more potently than the non-crystalline Si50 and Si500, when adjusted to surface area. This difference was much less pronounced versus fumed SiNPs. The caspase-1 inhibitor zYVAD and RNA silencing of the NALP3 receptor reduced the particle-induced IL-1β release in the RAW264.7 macrophages. Furthermore, inhibitors of phagocytosis, endosomal acidification, and cathepsin B activity reduced the IL-1β responses to the different particles to a similar extent. Conclusions In conclusion, non-crystalline silica particles in the nano- and submicro-size ranges seemed to induce IL-1β release from LPS-primed RAW264.7 macrophages via similar mechanisms as crystalline silica, involving particle

  18. Relaxed crystalline and icosahedral molecular clusters - CO2

    NASA Astrophysics Data System (ADS)

    van de Waal, B. W.

    1987-05-01

    The differences between the icosahedral arrangement and crystalline packing following the addition of more molecule shells are examined. The applicability of the Mackay (1962) procedure for constructing concentric icosahedra is evaluated. The relaxation of molecule crystal fragments by shifting molecular positions following deformation is studied. The relative energy difference between relaxed crystalline and icosahedral structure as a function of cluster size is calculated as ranging from 2.4 to 0.8 percent. The evolution of shells in the relaxed crystalline growth sequence reveals that the inner shells become crystalline when more shells are added; the icosahedral deformation is more prominent in the outer shell, but decreases with increasing cluster size. It is suggested that, when multilayer icosahedral structures are larger than critical size, they do not transform as a whole into a crystalline arrangement but develop a growing crystalline core.

  19. Single Crystalline Film of Hexagonal Boron Nitride Atomic Monolayer by Controlling Nucleation Seeds and Domains

    PubMed Central

    Wu, Qinke; Park, Ji-Hoon; Park, Sangwoo; Jung, Seong Jun; Suh, Hwansoo; Park, Noejung; Wongwiriyapan, Winadda; Lee, Sungjoo; Lee, Young Hee; Song, Young Jae

    2015-01-01

    A monolayer hexagonal boron nitride (h-BN) film with controllable domain morphology and domain size (varying from less than 1 μm to more than 100 μm) with uniform crystalline orientation was successfully synthesized by chemical vapor deposition (CVD). The key for this extremely large single crystalline domain size of a h-BN monolayer is a decrease in the density of nucleation seeds by increasing the hydrogen gas flow during the h-BN growth. Moreover, the well-defined shape of h-BN flakes can be selectively grown by controlling Cu-annealing time under argon atmosphere prior to h-BN growth, which provides the h-BN shape varies in triangular, trapezoidal, hexagonal and complex shapes. The uniform crystalline orientation of h-BN from different nucleation seeds can be easily confirmed by polarized optical microscopy (POM) with a liquid crystal coating. Furthermore, seamlessly merged h-BN flakes without structural domain boundaries were evidence by a selective hydrogen etching after a full coverage of a h-BN film was achieved. This seamless large-area and atomic monolayer of single crystalline h-BN film can offer as an ideal and practical template of graphene-based devices or alternative two-dimensional materials for industrial applications with scalability. PMID:26537788

  20. Two-dimensional short-range disordered crystalline networks from flexible molecular modules.

    PubMed

    Ecija, David; Vijayaraghavan, Saranyan; Auwärter, Willi; Joshi, Sushobhan; Seufert, Knud; Aurisicchio, Claudia; Bonifazi, Davide; Barth, Johannes V

    2012-05-22

    Studies of complex condensed matter systems have led to the discovery of materials of unexpected spatial organization as glasses, glassy crystals, quasicrystals, and protein and virus crystals. Here, we present two-dimensional (2D) short-range disordered molecular crystalline networks, which, regarding spatial organization, can be considered as surface analogues of 3D glassy crystals. In particular, the deposition of a flexible molecular module on Cu(111) gives rise to distinct phases whose characteristics have been examined in real space by scanning tunneling microscopy: a 2D short-range distortional disordered crystalline network and a 2D short-range orientational disordered crystalline network, respectively. Both phases exhibit a random arrangement of nanopores that are stabilized by the simultaneous presence of metal-organic and pyridyl-pyridyl interactions. The 2D short-range distortional disordered crystalline network displayed intriguing flexibility, as probed by the STM tip that modifies the pore shape, a prerequisite for adaptive behavior in host-guest processes.

  1. Crystalline rocks of the Lake Superior region, United States. Part 1

    SciTech Connect

    Harrison, W.; Sood, M.; Flower, M.; Tisue, M.

    1983-10-01

    This report is a compendium of the available information on exposed crystalline rocks in the Lake Superior region (Wisconsin, Minnesota, and the Upper Peninsula of Michigan). The report provides background information to assist in evaluating the suitability of these crystalline rock bodies for isolating high-level radioactive waste. For each crystalline rock body or complex greater than approximately 78 km/sup 2/ (30 mi/sup 2/) in area, information is presented on size, shape, location, relative and absolute age, origin, petrography, rock structure, and geophysics. Precambrian crystalline rocks of the Lake Superior region are predominantly tonalite to granite in composition in the Archean; granodiorite and granite, with subordinate tonalite, in the early Proterozoic; and alkalic syenite, rapakivi granite, and layered gabbro-troctolite-anorthosite in the Middle Proterozoic. Vertical and horizontal movements, regional and thermal metamorphism, deformation, and intrusion are evident in the region. Based on radiometric ages, three major episodes of orogenic/igneous activity are recognized: Algoman (approx. 2650 My), Penokean (approx. 1850 My), and Keweenawan (900 to 1200 My). Anorogenic magmatism approximately 1500 My ago also played an important role, particularly in Wisconsin. References, 66 figures, 10 tables.

  2. Electrochemically synthesized amorphous and crystalline nanowires: dissimilar nanomechanical behavior in comparison with homologous flat films.

    PubMed

    Zeeshan, M A; Esqué-de Los Ojos, D; Castro-Hartmann, P; Guerrero, M; Nogués, J; Suriñach, S; Baró, M D; Nelson, B J; Pané, S; Pellicer, E; Sort, J

    2016-01-21

    The effects of constrained sample dimensions on the mechanical behavior of crystalline materials have been extensively investigated. However, there is no clear understanding of these effects in nano-sized amorphous samples. Herein, nanoindentation together with finite element simulations are used to compare the properties of crystalline and glassy CoNi(Re)P electrodeposited nanowires (ϕ ≈ 100 nm) with films (3 μm thick) of analogous composition and structure. The results reveal that amorphous nanowires exhibit a larger hardness, lower Young's modulus and higher plasticity index than glassy films. Conversely, the very large hardness and higher Young's modulus of crystalline nanowires are accompanied by a decrease in plasticity with respect to the homologous crystalline films. Remarkably, proper interpretation of the mechanical properties of the nanowires requires taking the curved geometry of the indented surface and sink-in effects into account. These findings are of high relevance for optimizing the performance of new, mechanically-robust, nanoscale materials for increasingly complex miniaturized devices. PMID:26399166

  3. Single Crystalline Film of Hexagonal Boron Nitride Atomic Monolayer by Controlling Nucleation Seeds and Domains.

    PubMed

    Wu, Qinke; Park, Ji-Hoon; Park, Sangwoo; Jung, Seong Jun; Suh, Hwansoo; Park, Noejung; Wongwiriyapan, Winadda; Lee, Sungjoo; Lee, Young Hee; Song, Young Jae

    2015-01-01

    A monolayer hexagonal boron nitride (h-BN) film with controllable domain morphology and domain size (varying from less than 1 μm to more than 100 μm) with uniform crystalline orientation was successfully synthesized by chemical vapor deposition (CVD). The key for this extremely large single crystalline domain size of a h-BN monolayer is a decrease in the density of nucleation seeds by increasing the hydrogen gas flow during the h-BN growth. Moreover, the well-defined shape of h-BN flakes can be selectively grown by controlling Cu-annealing time under argon atmosphere prior to h-BN growth, which provides the h-BN shape varies in triangular, trapezoidal, hexagonal and complex shapes. The uniform crystalline orientation of h-BN from different nucleation seeds can be easily confirmed by polarized optical microscopy (POM) with a liquid crystal coating. Furthermore, seamlessly merged h-BN flakes without structural domain boundaries were evidence by a selective hydrogen etching after a full coverage of a h-BN film was achieved. This seamless large-area and atomic monolayer of single crystalline h-BN film can offer as an ideal and practical template of graphene-based devices or alternative two-dimensional materials for industrial applications with scalability. PMID:26537788

  4. Coupled-layer description of topological crystalline insulators

    NASA Astrophysics Data System (ADS)

    Fulga, I. C.; Avraham, N.; Beidenkopf, H.; Stern, A.

    2016-09-01

    We introduce a coupled-layer construction to describe three-dimensional topological crystalline insulators protected by reflection symmetry. Our approach uses stacks of weakly coupled two-dimensional Chern insulators to produce topological crystalline insulators in one higher dimension, with tunable number and location of surface Dirac cones. As an application of our formalism, we turn to a simplified model of topological crystalline insulator SnTe, showing that its protected surface states can be described using the coupled-layer construction.

  5. Interrelation between the crystallinity of polysaccharides and water absorption

    NASA Astrophysics Data System (ADS)

    Prusov, A. N.; Prusova, S. M.; Radugin, M. V.; Zakharov, A. G.

    2014-05-01

    The maximum sorption of water and its vapors is calculated using experimental data from calorimetric and effusion studies of flax, wood, and cotton cellulose. X-day diffraction is used to determine the crystallinity of cellulose samples. The equations relating crystallinity ( X) with maximum sorption and the enthalpy of interaction between cellulose and water are presented. Experimental results and the literature data on water sorption by chitin, chitosan and other polysaccharides show that our equations for calculating crystallinity are correct.

  6. Highly ordered monodomain ionic self-assembled liquid-crystalline materials.

    PubMed

    Zakrevskyy, Y; Smarsly, B; Stumpe, J; Faul, C F J

    2005-02-01

    Liquid-crystalline properties of the ionic self assembled complex benzenehexacarboxylic- (didodecyltrimethylammonium)6 [BHC- (C12D)6] were investigated by polarizing microscopy, differential scanning calorimetry (DSC), x-ray analysis, null ellipsometry, UV and IR spectroscopy. The complex exhibits a bilayer smectic Sm- A2 liquid-crystalline phase and aligns spontaneously. Alignment properties do not depend on the hydrophobic or hydrophilic treatment of the surfaces. The aligned complex possesses a negative (delta n=-0.02) homeotropically oriented optical axis, with layers aligned parallel to the surface. X-ray analysis of the aligned sample revealed a lamellar structure with a d spacing of 3.15 nm, consisting of sublayers of thicknesses d1 = 1.41 and d2 = 1.74 nm . This was confirmed by simple geometrical calculations and detailed temperature-dependent investigations, revealing that the first layer contains the BHC molecules and oppositely charged groups of the surfactants, and the second the alkyl tails of the surfactant. Changes in the order parameters (as calculated from the IR investigations) are correlated with the phase transitions as found by DSC. The properties of the complex are strongly influenced by the ionic interactions within the complex. The presence of these groups slows down the dynamics within the material sufficiently to allow for crystallization of the complex from an aligned LC phase into a single crystal domain, as well as restricting the transition to the isotropic phase.

  7. Crosslinked crystalline polymer and methods for cooling and heating

    DOEpatents

    Salyer, Ival O.; Botham, Ruth A.; Ball, III, George L.

    1980-01-01

    The invention relates to crystalline polyethylene pieces having optimum crosslinking for use in storage and recovery of heat, and it further relates to methods for storage and recovery of heat using crystalline polymer pieces having optimum crosslinking for these uses. Crystalline polymer pieces are described which retain at least 70% of the heat of fusion of the uncrosslinked crystalline polymer and yet are sufficiently crosslinked for the pieces not to stick together upon being cycled above and below the melting point of said polymer, preferably at least 80% of the heat of fusion with no substantial sticking together.

  8. Curing of liquid crystalline epoxy resins with a biguanide

    NASA Astrophysics Data System (ADS)

    Szczepaniak, Barbara; Penczek, Piotr; Frisch, Kurt C.; Rejdych, Jerzy

    1998-01-01

    This work extends the authors' investigation son liquid crystalline epoxy resins prepared from diglycidyl ether of 4,4'-dihydroxybiphenyl and aliphatic dicarboxylic compounds or difunctional aromatic compounds. Syntheses and properties of these liquid crystalline epoxy resins are described elsewhere. In this paper a study on the curing reaction of two from the above mentioned liquid crystalline epoxy resins is presented. Ortho-tolylbiguanide was applied as the curing agent. The curing reactions were investigated by differential scanning calorimetry, microscopic observations and IR spectroscopy. Depending upon the temperature program of curing, it was possible to obtain polymeric networks with liquid crystalline order.

  9. Lattice matched semiconductor growth on crystalline metallic substrates

    SciTech Connect

    Norman, Andrew G; Ptak, Aaron J; McMahon, William E

    2013-11-05

    Methods of fabricating a semiconductor layer or device and said devices are disclosed. The methods include but are not limited to providing a metal or metal alloy substrate having a crystalline surface with a known lattice parameter (a). The methods further include growing a crystalline semiconductor alloy layer on the crystalline substrate surface by coincident site lattice matched epitaxy. The semiconductor layer may be grown without any buffer layer between the alloy and the crystalline surface of the substrate. The semiconductor alloy may be prepared to have a lattice parameter (a') that is related to the lattice parameter (a). The semiconductor alloy may further be prepared to have a selected band gap.

  10. Mechanical Properties of Crystalline Silicon Carbide Nanowires.

    PubMed

    Zhang, Huan; Ding, Weiqiang; Aidun, Daryush K

    2015-02-01

    In this paper, the mechanical properties of crystalline silicon carbide nanowires, synthesized with a catalyst-free chemical vapor deposition method, were characterized with nanoscale tensile testing and mechanical resonance testing methods inside a scanning electron microscope. Tensile testing of individual silicon carbide nanowire was performed to determine the tensile properties of the material including the tensile strength, failure strain and Young's modulus. The silicon carbide nanowires were also excited to mechanical resonance in the scanning electron microscope vacuum chamber using mechanical excitation and electrical excitation methods, and the corresponding resonance frequencies were used to determine the Young's modulus of the material according to the simple beam theory. The Young's modulus values from tensile tests were in good agreement with the ones obtained from the mechanical resonance tests.

  11. Actuators Based on Liquid Crystalline Elastomer Materials

    PubMed Central

    Jiang, Hongrui; Li, Chensha; Huang, Xuezhen

    2013-01-01

    Liquid crystalline elastomers (LCEs) exhibit a number of remarkable physical effects, including the unique, high-stroke reversible mechanical actuation when triggered by external stimuli. This article reviews some recent exciting developments in the field of LCEs materials with an emphasis on their utilization in actuator applications. Such applications include artificial muscles, industrial manufacturing, health and microelectromechanical systems (MEMS). With suitable synthetic and preparation pathways and well-controlled actuation stimuli, such as heat, light, electric and magnetic field, excellent physical properties of LCE materials can be realized. By comparing the actuating properties of different systems, general relationships between the structure and the property of LCEs are discussed. How these materials can be turned into usable devices using interdisciplinary techniques is also described. PMID:23648966

  12. Modeling of Crystalline Silicotitanate Ion Exchange Columns

    SciTech Connect

    Walker, D.D.

    1999-03-09

    Non-elutable ion exchange is being considered as a potential replacement for the In-Tank Precipitation process for removing cesium from Savannah River Site (SRS) radioactive waste. Crystalline silicotitanate (CST) particles are the reference ion exchange medium for the process. A major factor in the construction cost of this process is the size of the ion exchange column required to meet product specifications for decontaminated waste. To validate SRS column sizing calculations, SRS subcontracted two reknowned experts in this field to perform similar calculations: Professor R. G. Anthony, Department of Chemical Engineering, Texas A&038;M University, and Professor S. W. Wang, Department of Chemical Engineering, Purdue University. The appendices of this document contain reports from the two subcontractors. Definition of the design problem came through several meetings and conference calls between the participants and SRS personnel over the past few months. This document summarizes the problem definition and results from the two reports.

  13. Energy transport in crystalline DNA composites

    SciTech Connect

    Xu, Zaoli; Xu, Shen; Tang, Xiaoduan; Wang, Xinwei

    2014-01-15

    This work reports on the synthesis of crystalline DNA-composited films and microfibers, and details the study of thermal energy transport in them. The transient electro-thermal technique is used to characterize the thermal transport in DNA composite microfibers, and the photothermal technique is used to explore the thermal transport in the thickness direction of DNA films. Compared with microfibers, the DNA films are found to have a higher thermal transport capacity, largely due to the carefully controlled crystallization process in film synthesis. In high NaCl concentration solutions, the bond of the Na{sup +} ion and phosphate group aligns the DNA molecules with the NaCl crystal structure during crystallization. This results in significant enhancement of thermal transport in the DNA films with aligned structure.

  14. Actuators based on liquid crystalline elastomer materials

    NASA Astrophysics Data System (ADS)

    Jiang, Hongrui; Li, Chensha; Huang, Xuezhen

    2013-05-01

    Liquid crystalline elastomers (LCEs) exhibit a number of remarkable physical effects, including the unique, high-stroke reversible mechanical actuation when triggered by external stimuli. This article reviews some recent exciting developments in the field of LCE materials with an emphasis on their utilization in actuator applications. Such applications include artificial muscles, industrial manufacturing, health and microelectromechanical systems (MEMS). With suitable synthetic and preparation pathways and well-controlled actuation stimuli, such as heat, light, electric and magnetic fields, excellent physical properties of LCE materials can be realized. By comparing the actuating properties of different systems, general relationships between the structure and the properties of LCEs are discussed. How these materials can be turned into usable devices using interdisciplinary techniques is also described.

  15. Mirrorless lasing in liquid crystalline materials

    NASA Astrophysics Data System (ADS)

    Cao, Wenyi; Finkelmann, Heino; Kim, Seok-Tae; Munoz, Antonio; Palffy-Muhoray, Peter; Taheri, Bahman; Twieg, Robert J.

    2002-06-01

    Cholesteric liquid crystals, because of their birefringence and periodic structure, and 1-d photonic band-gap materials. In the reflection band, classical light propagation is forbidden for one of the two eigenmodes; for this mode, the material acts as a distributed cavity host. This inherent distributed cavity effect modifies the fluorescence spectrum, and, if the material is optically pumped, allows population inversion and mirrorless lasing. We have studied emission from thin samples of liquid crystalline materials optically pumped by pico- and nanosecond laser pulses. We have observed laser emission, without an external cavity, from dye-doped liquid crystals, from pure cholesteric liquid crystals without dyes, and from cholesteric liquid crystal elastomers. We present the results of these experiments, discuss the relation between material properties and the lasing process, and consider promising materials and applications.

  16. Crystalline Motion of Interfaces Between Patterns

    NASA Astrophysics Data System (ADS)

    Braides, Andrea; Cicalese, Marco; Yip, Nung Kwan

    2016-09-01

    We consider the dynamical problem of an antiferromagnetic spin system on a two-dimensional square lattice ɛ {Z}^2 with nearest-neighbour and next-to-nearest neighbour interactions. The key features of the model include the interaction between spatial scale ɛ and time scale τ , and the incorporation of interfacial boundaries separating regions with microstructures. By employing a discrete-time variational scheme, a limit continuous-time evolution is obtained for a crystal in {R}^2 which evolves according to some motion by crystalline curvatures. In the case of anti-phase boundaries between striped patterns, a striking phenomenon is the appearance of some "non-local" curvature dependence velocity law reflecting the creation of some defect structure on the interface at the discrete level.

  17. Semiclassical and quantum polarons in crystalline acetanilide

    NASA Astrophysics Data System (ADS)

    Hamm, P.; Tsironis, G. P.

    2007-08-01

    Crystalline acetanilide is a an organic solid with peptide bond structure similar to that of proteins. Two states appear in the amide I spectral region having drastically different properties: one is strongly temperature dependent and disappears at high temperatures while the other is stable at all temperatures. Experimental and theoretical work over the past twenty five years has assigned the former to a selftrapped state while the latter to an extended free exciton state. In this article we review the experimental and theoretical developments on acetanilide paying particular attention to issues that are still pending. Although the interpretation of the states is experimentally sound, we find that specific theoretical comprehension is still lacking. Among the issues that that appear not well understood is the effective dimensionality of the selftrapped polaron and free exciton states.

  18. Simulation of melting in crystalline polyethylene.

    PubMed

    Zubova, E A; Balabaev, N K; Musienko, A I; Gusarova, E B; Mazo, M A; Manevitch, L I; Berlin, A A

    2012-06-14

    We carry out a molecular dynamics simulation of the first stages of constrained melting in crystalline polyethylene (PE). When heated, the crystal undergoes two structural phase transitions: from the orthorhombic (O) phase to the monoclinic (M) phase, and then to the columnar (C), quasi-hexagonal, phase. The M phase represents the tendency to the parallel packing of planes of PE zigzags, and the C phase proves to be some kind of oriented melt. We follow both the transitions O→M and M→C in real time and establish that, at their beginning, the crystal tries (and fails) to pass into the partially ordered phases similar to the RI and RII phases of linear alkanes, correspondingly. We discuss the molecular mechanisms and driving forces of the observed transitions, as well as the reasons why the M and C phases in PE crystals substitute for the rotator phases in linear alkanes.

  19. Reactive Liftoff of Crystalline Cellulose Particles

    PubMed Central

    Teixeira, Andrew R.; Krumm, Christoph; Vinter, Katherine P.; Paulsen, Alex D.; Zhu, Cheng; Maduskar, Saurabh; Joseph, Kristeen E.; Greco, Katharine; Stelatto, Michael; Davis, Eric; Vincent, Brendon; Hermann, Richard; Suszynski, Wieslaw; Schmidt, Lanny D.; Fan, Wei; Rothstein, Jonathan P.; Dauenhauer, Paul J.

    2015-01-01

    The condition of heat transfer to lignocellulosic biomass particles during thermal processing at high temperature (>400 °C) dramatically alters the yield and quality of renewable energy and fuels. In this work, crystalline cellulose particles were discovered to lift off heated surfaces by high speed photography similar to the Leidenfrost effect in hot, volatile liquids. Order of magnitude variation in heat transfer rates and cellulose particle lifetimes was observed as intermediate liquid cellulose droplets transitioned from low temperature wetting (500–600 °C) to fully de-wetted, skittering droplets on polished surfaces (>700 °C). Introduction of macroporosity to the heated surface was shown to completely inhibit the cellulose Leidenfrost effect, providing a tunable design parameter to control particle heat transfer rates in industrial biomass reactors. PMID:26057818

  20. Crystalline corneal opacities in the Siberian Husky.

    PubMed

    MacMillan, A D; Waring, G O; Spangler, W L; Roth, A M

    1979-10-15

    Bilaterally symmetric opacities were detected in the corneal stroma of 78 (14%) of 560 Siberian Huskies, aged 7 months to 12 years, examined in ophthalmology screening clinics. The opacities were round or horizontally oval and consisted of a diffuse gray homogeneous haze in the anterior stroma or an array of fine polychromatic crystals in the posterior stroma, or both. The corneas were not inflamed. The frequency of occurrence and density of the opacities increased with age. Several affected dogs were closely related, but a specific inheritance pattern could not be established. Light and electron microscopy disclosed clusters of extracellular, thin, needle-shaped, crystalline clefts. Histochemical stains on frozen sections identified neutral fats, phospholipids, and cholesterol as components of the crystals.

  1. Quantum vibrational polarons: Crystalline acetanilide revisited

    NASA Astrophysics Data System (ADS)

    Hamm, Peter; Edler, Julian

    2006-03-01

    We discuss a refined theoretical description of the peculiar spectroscopy of crystalline acetanilide (ACN). Acetanilide is a molecular crystal with quasi-one-dimensional chains of hydrogen-bonded units, which is often regarded as a model system for the vibrational spectroscopy of proteins. In linear spectroscopy, the CO stretching (amide I) band of ACN features a double-peak structure, the lower of which shows a pronounced temperature dependence which has been discussed in the context of polaron theory. In nonlinear spectroscopy, both of these peaks respond distinctly differently. The lower-frequency band exhibits the anharmonicity expected from polaron theory, while the higher-frequency band responds as if it were quasiharmonic. We have recently related the response of the higher-frequency band to that of a free exciton [J. Edler and P. Hamm, J. Chem. Phys. 117, 2415 (2002)]. However, as discussed in the present paper, the free exciton is not an eigenstate of the full quantum version of the Holstein polaron Hamiltonian, which is commonly used to describe these phenomena. In order to resolve this issue, we present a numerically exact solution of the Holstein polaron Hamiltonian in one dimension (1D) and 3D. In 1D, we find that the commonly used displaced oscillator picture remains qualitatively correct, even for relatively large exciton coupling. However, the result is not in agreement with the experiment, as it fails to explain the free-exciton band. In contrast, when taking into account the 3D nature of crystalline acetanilide, certain parameter regimes exist where the displaced oscillator picture breaks down and states appear in the spectrum that indeed exhibit the characteristics of a free exciton. The appearance of these states is a speciality of vibrational polarons, whose source of exciton coupling is transition dipole coupling which is expected to have opposite signs of interchain and intrachain coupling.

  2. Efficient Crystalline Si Solar Cell with Amorphous/Crystalline Silicon Heterojunction as Back Contact: Preprint

    SciTech Connect

    Nemeth, B.; Wang, Q.; Shan, W.

    2012-06-01

    We study an amorphous/crystalline silicon heterojunction (Si HJ) as a back contact in industrial standard p-type five-inch pseudo-square wafer to replace Al back surface field (BSF) contact. The best efficiency in this study is over 17% with open-circuit (Voc) of 0.623 V, which is very similar to the control cell with Al BSF. We found that Voc has not been improved with the heterojunction structure in the back. The typical minority carrier lifetime of these wafers is on the order of 10 us. We also found that the doping levels of p-layer affect the FF due to conductivity and band gap shifting, and an optimized layer is identified. We conclude that an amorphous/crystalline silicon heterojunction can be a very promising structure to replace Al BSF back contact.

  3. Fault Zone Hydrogeology of Crystalline and Sedimentary Aquifers in Arid Regions: The Case Sinai Peninsula, Egypt.

    NASA Astrophysics Data System (ADS)

    Ahmed, M.; Mohamed, L.; Sultan, M.; Farag, A. Z. A.

    2015-12-01

    Structural control on the groundwater flow in arid regions is still poorly understood. Understanding the distribution of structural discontinuities (i.e. faults, joints and shear zones), their cross cutting relationships, and their relation with the regional hydraulic gradient are critical for deciphering the complexity of water resources distribution in the highly fractured crystalline and sedimentary aquifers in Sinai. In order to achieve that, we conducted an integrated approach using remote sensing, geophysical and hydrogeological datasets: (1) identification of the spatial and temporal rainfall events using Tropical Rainfall Measuring Mission (TRMM) data; (2) delineation of major faults and shear zones using Landsat 8 and ASTER image ratioing, geological datasets and field investigation; (3) generation of a normalized difference ratio image using Envisat radar images before and after the rain events to identify preferential water-channeling discontinuities in the crystalline terrain; (4) validation of the water-channeling discontinuities using Very Low Frequency (VLF) method; (5) generation of regional groundwater flow and isotopic (18O and 2H ) distribution maps for the sedimentary aquifer and an approximation flow map for the crystalline aquifer; (6) developing a conceptual model for the groundwater flow in the fractured crystalline and sedimentary aquifers; (7) testing the model accuracy using Vertical Electrical Sounding (VES) method in seven locations. Our findings include: (1) in the crystalline aquifer, discontinuities that are sub-parallel to groundwater flow direction act as preferred pathways for groundwater flow, whereas those that intersect groundwater flow directions at high angles act as barriers causing considerable groundwater accumulations at the upstream side; (2) in the sedimentary aquifer, high angle E-W discontinuities (i.e. Themed shear zone and Sinai Hinge Belt) cause a considerable groundwater elevation, redirection of the groundwater

  4. Direct optical imaging of structural inhomogeneities in crystalline materials.

    PubMed

    Grigorev, A M

    2016-05-10

    A method for optical imaging of structural inhomogeneities in crystalline materials is proposed, based on the differences in the optical properties of the structural inhomogeneity and the homogeneous material near the fundamental absorption edge of the crystalline material. The method can be used to detect defects in both semiconductors and insulators.

  5. Molybdenum enhanced low-temperature deposition of crystalline silicon nitride

    DOEpatents

    Lowden, Richard A.

    1994-01-01

    A process for chemical vapor deposition of crystalline silicon nitride which comprises the steps of: introducing a mixture of a silicon source, a molybdenum source, a nitrogen source, and a hydrogen source into a vessel containing a suitable substrate; and thermally decomposing the mixture to deposit onto the substrate a coating comprising crystalline silicon nitride containing a dispersion of molybdenum silicide.

  6. Single Molecule Study of Cellulase Hydrolysis of Crystalline Cellulose

    SciTech Connect

    Liu, Y.-S.; Luo, Y.; Baker, J. O.; Zeng, Y.; Himmel, M. E.; Smith, S.; Ding, S.-Y.

    2009-12-01

    This report seeks to elucidate the role of cellobiohydrolase-I (CBH I) in the hydrolysis of crystalline cellulose. A single-molecule approach uses various imaging techniques to investigate the surface structure of crystalline cellulose and changes made in the structure by CBH I.

  7. Elevated intracranial dopamine impairs the glutamate-nitric oxide-cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy

    PubMed Central

    DING, SAIDAN; HUANG, WEILONG; YE, YIRU; YANG, JIANJING; HU, JIANGNAN; WANG, XIAOBIN; LIU, LEPING; LU, QIN; LIN, YUANSHAO

    2014-01-01

    In a previous study by our group memory impairment in rats with minimal hepatic encephalopathy (MHE) was associated with the inhibition of the glutamate-nitric oxide-cyclic guanosine monophosphate (Glu-NO-cGMP) pathway due to elevated dopamine (DA). However, the effects of DA on the Glu-NO-cGMP pathway localized in primary cortical astrocytes (PCAs) had not been elucidated in rats with MHE. In the present study, it was identified that when the levels of DA in the cerebral cortex of rats with MHE and high-dose DA (3 mg/kg)-treated rats were increased, the co-localization of N-methyl-d-aspartate receptors subunit 1 (NMDAR1), calmodulin (CaM), nitric oxide synthase (nNOS), soluble guanylyl cyclase (sGC) and cyclic guanine monophosphate (cGMP) with the glial fibrillary acidic protein (GFAP), a marker protein of astrocytes, all significantly decreased, in both the MHE and high-dose DA-treated rats (P<0.01). Furthermore, NMDA-induced augmentation of the expression of NMDAR1, CaM, nNOS, sGC and cGMP localized in PCAs was decreased in MHE and DA-treated rats, as compared with the controls. Chronic exposure of cultured cerebral cortex PCAs to DA treatment induced a dose-dependent decrease in the concentration of intracellular calcium, nitrites and nitrates, the formation of cGMP and the expression of NMDAR1, CaM, nNOS and sGC/cGMP. High doses of DA (50 μM) significantly reduced NMDA-induced augmentation of the formation of cGMP and the contents of NMDAR1, CaM, nNOS, sGC and cGMP (P<0.01). These results suggest that the suppression of DA on the Glu-NO-cGMP pathway localized in PCAs contributes to memory impairment in rats with MHE. PMID:25059564

  8. Optimising reaction coordinates for crystallisation by tuning the crystallinity definition

    NASA Astrophysics Data System (ADS)

    Jungblut, Swetlana; Singraber, Andreas; Dellago, Christoph

    2013-12-01

    We apply maximum likelihood analysis to optimise crystallisation measures based on Steinhardt bond order parameters. Assuming that the size of the largest cluster of crystalline particles serves as a good reaction coordinate for the freezing transition, we write down the likelihood to observe the committor values computed for a large number of configurations. We then maximise the likelihood function by varying the parameters that enter the definition of crystallinity. For the crystallinity definition considered here this parameter set consists of the thresholds for the next-neighbour distance, the strength of the crystalline bonds and the number of crystalline connections. The optimum parameter set found by the likelihood maximisation differs considerably from the parameters that are commonly used, but leads only to a marginal improvement of the quality of the reaction coordinate.

  9. Nanowire Oriented On-Surface Growth of Chiral Cystine Crystalline Nanosheets.

    PubMed

    Zhang, Shenxiang; Zhang, Feng; Qin, Haili; Hu, Liang; Jin, Jian

    2015-08-18

    Exploration of an effective route to achieve the controlled growth of two-dimensional (2D) molecular crystal is of scientific significance yet greatly underdeveloped due to the complexity of weak intermolecular interactions, thus leading to difficulty of inducing anisotropic 2D growth. We report here a facile nanowire oriented on-surface growth strategy for the fabrication of cystine crystalline nanosheets with finely controlled thickness (1.1, 1.9, 2.9, and 4.8 nm which correspond to one layer, two layers, three layers, and five layers of crystal cystine, respectively) and large areas (>100 μm(2)). The cystine crystalline nanosheets display chirality delivered by chiral cysteine monomers, either l-cysteine or d-cysteine. The chiral nanosheets with structural precision and chemical diversity could serve as a novel 2D platform for constructing advanced hybrid materials. PMID:26203777

  10. Double-twist cylinders in liquid crystalline cholesteric blue phases observed by transmission electron microscopy

    PubMed Central

    Tanaka, Shu; Yoshida, Hiroyuki; Kawata, Yuto; Kuwahara, Ryusuke; Nishi, Ryuji; Ozaki, Masanori

    2015-01-01

    Cholesteric blue phases are liquid crystalline phases in which the constituent rod-like molecules spontaneously form three-dimensional, helical structures. Despite theoretical predictions that they are composed of cylindrical substructures within which the liquid crystal molecules are doubly twisted, real space observation of the arrangement of such structures had not been performed. Through transmission electron microscopy of photopolymerized blue phases with controlled lattice plane orientations, we report real space observation and comparison of the lattice structures of blue phases I and II. The two systems show distinctly different contrasts, reflecting the theoretically predicted, body centred and simple cubic arrangement of the double-twist cylinders. Transmission electron microscopy also reveals different tendencies of the two blue phases to align on unidirectionally rubbed surfaces. We thus show that TEM observation of alignment-controlled, photopolymerized liquid crystals can be a powerful tool to investigate complex liquid crystalline order. PMID:26530779

  11. Double-twist cylinders in liquid crystalline cholesteric blue phases observed by transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Tanaka, Shu; Yoshida, Hiroyuki; Kawata, Yuto; Kuwahara, Ryusuke; Nishi, Ryuji; Ozaki, Masanori

    2015-11-01

    Cholesteric blue phases are liquid crystalline phases in which the constituent rod-like molecules spontaneously form three-dimensional, helical structures. Despite theoretical predictions that they are composed of cylindrical substructures within which the liquid crystal molecules are doubly twisted, real space observation of the arrangement of such structures had not been performed. Through transmission electron microscopy of photopolymerized blue phases with controlled lattice plane orientations, we report real space observation and comparison of the lattice structures of blue phases I and II. The two systems show distinctly different contrasts, reflecting the theoretically predicted, body centred and simple cubic arrangement of the double-twist cylinders. Transmission electron microscopy also reveals different tendencies of the two blue phases to align on unidirectionally rubbed surfaces. We thus show that TEM observation of alignment-controlled, photopolymerized liquid crystals can be a powerful tool to investigate complex liquid crystalline order.

  12. Broadband terahertz time-domain spectroscopy : crystalline and glassy drug materials

    NASA Astrophysics Data System (ADS)

    Kojima, Seiji; Shibata, Tomohiko; Igawa, Hikaru; Mori, Tatsuya

    2014-03-01

    Low-energy IR active modes of glassy and crystalline drug materials were studied by the broadband Terahertz Time Domain Spectroscopy (THz-TDS) in the frequency range from 0.5 to 6.5 THz using a Cherenkov type THz generator. In order to determine the real and imaginary parts of complex dielectric constant, all samples were measured by the transmission using a pure pellet without mixing polyethylene. For glassy indomethacine, the broadband THz spectrum of real part of dielectric constant shows step-wise decrease with the increase of frequency, while the imaginary part shows a broad peak at about 3 THz reflecting quenched glassy disordered structure. The observed spectra of crystalline racemic ketoprofen show the noncoincidence of peak frequencies between low-frequency Raman scattering and THz absorbance spectra. It can be attributed to the fact that the mutual exclusion principle between Raman and IR activities holds below 6 THz.

  13. Epitaxial Growth of Zinc Oxide on Single Crystalline Gold Plates

    NASA Astrophysics Data System (ADS)

    Greenberg, Kathryn; Joo, John; Baram, Mor; Clarke, David; Hu, Evelyn

    2012-02-01

    Although metal-oxide interfaces are the critical components of many electronic and optical devices, it is rare to find epitaxial metal-oxide structures. We demonstrate for the first time, a method for the low temperature, epitaxial growth of zinc oxide (ZnO) on single crystalline gold plates. The gold plates, up to 100μm in width, are grown from a gold-surfactant complex. Even with the large lattice mismatch between (111) gold and (0001) ZnO, we are able to form epitaxial zinc oxide at 90^oC on top of the single crystal gold plates. This epitaxial growth is confirmed using transmission electron microscopy, electron diffraction, and electron backscatterer diffraction. Micro-photoluminescence is also performed to investigate the optical properties of the epitaxial zinc oxide. We remove the grown ZnO membranes from the gold plates using a stamping and etching process. These membranes can potentially be used to fabricate high quality microdisks and photonic crystals. The metal-oxide interfaces that we have fabricated may have the ability to be used in a number of technologically important applications, including as better electrical contacts and for improved light extraction from planar LED structures.

  14. External-Field-Driven Nanopatterning on Crystalline Substrate Surfaces

    NASA Astrophysics Data System (ADS)

    Kumar, Ashish; Dasgupta, Dwaipayan; Maroudas, Dimitrios

    Current-driven dynamics of single-layer epitaxial islands on fcc crystalline substrates can lead to surface pattern formation with significant implications for nanofabrication. We have developed and validated a fully nonlinear model of driven island evolution on { 110 } , { 100 } and { 111 } substrate surfaces due to diffusional mass transport along the island edge and accounting for edge diffusional anisotropy. We find that the migration speed of a morphologically stable island is inversely proportional to the island size, R, up to a critical size that marks the onset of island morphological transition; further increase in R triggers edge fingering and/or necking or dynamical transitions. We report formation of complex nanopatterns emerging from individual larger-than-critical islands with two different types of initial configuration: a slender, high-aspect-ratio island shape and an equilibrium, rounded morphology. We have developed a linear stability theory that explains the observed morphological instabilities. We characterize the nanopatterns formed and study the dependence of the nanopattern features on the duration of application of the electric field and the misorientation angle between a fast edge diffusion direction and the electric field direction.

  15. Geophysical siting of boreholes in crystalline basement areas of Africa

    NASA Astrophysics Data System (ADS)

    Olayinka, A. I.

    1992-02-01

    This paper assesses the effectiveness of surface geophysical methods namely electrical resistivity, electromagnetic, seismic refraction, magnetic, gravity and induced polarization for groundwater exploration in crystalline basement complex areas. Most of these geophysical techniques can provide quantitative information on the characteristics of the weathered zone which relate to the occurrence of an economic aquifer. The critical factors in the choice of a particular method include the local geological setting, the initial and maintenance costs of the equipment, the speed of surveying, the manpower required as field crew, the degree of sophistication entailed in data processing to enable a geologically meaningful interpretation, and anomaly resolution. The particular advantages and limitations of each technique are highlighted. Several case histories from Nigeria and the rest of Africa indicate that electrical resistivity (both vertical sounding and horizontal profiling) is the most widely used, followed by electromagnetic traversing. These are often employed in combination to improve upon the percentage of successful boreholes. Due to the high cost of equipment, large scale of the field operations and difficulties in data interpretation, seismic refraction is not widely adopted in commercial-type surveys. Similarly, magnetic, gravity and induced polarization are used only sparingly.

  16. Binding of nickel /II/ to 5-prime-nucleoside monophosphates and related compounds. [role in origin of life

    NASA Technical Reports Server (NTRS)

    Orenberg, J. B.; Kjos, K. M.; Winkler, R.; Link, J.; Lawless, J. G.

    1982-01-01

    The interactions of Ni(II) cation with a representative suite of purine bases and the respective nucleosides and nucleotides have been studied by ultraviolet difference spectroscopy. Apparent association constants were determined for each system at pH 7.0, using computer linear regression coupled with an iteration technique. The specificity of binding of Ni(2+) for the purine nucleotides studied at pH 7.0 was 5-prime-GMP greater than 5-prime-AMP; a similar ordering was also found for the respective nucleosides and bases. In this study binding was not observed for the suite of pyramidines used, although an Ni(2+) -cytidine complex has been observed (Fiskin and Beer, 1965). It was also found that Ni(2+) bound more strongly to the purine 5-prime-nucleotides than to the respective nucleosides and bases. These trends are explained in terms of metal-ligand bonds and available bonding positions on the ligands. A role for metal-ion-nucleotide types of complexes is suggested in the processes that might have given rise to the origin of life.

  17. Patterned Aqueous Growth of Single Crystalline Zinc Oxide for Photonic Applications

    NASA Astrophysics Data System (ADS)

    Pooley, Kathryn Jessica

    Typically a top-down approach is used in the fabrication of functional nanodevices beginning with the bulk material and imposing a two or three-dimensional structure on the material through a combination of lithography and etching. Pre-patterning of a substrate, resulting in the selective growth of a material, has potential for forming three-dimensional device structures in ways that can be more efficient and which can avoid process complexity and process induced damage. In this thesis, the low temperature (90°C) aqueous growth of complex, single crystalline zinc oxide (ZnO) three-dimensional devices through pre-patterned micron and nanometer sized molds is presented. This work focuses on the quality of the single crystalline ZnO material, the constrained growth of ZnO through various sizes and shapes of molds, and the fabrication of several device structures including pillars, rings, and photonic crystals. Due to their single crystalline nature and crystallographically smooth sidewalls, photonic devices created using this growth method have the potential to outperform traditionally fabricated structures in a range of optoelectronic applications. In addition, metal-oxide interfaces are the critical components of many electrical and optical devices, and it is rare to find epitaxial metal-oxide structures. In this work, the first demonstration of low temperature, epitaxial growth of ZnO on single crystalline gold plates is presented. The quality and structure of the ZnO on the gold plates is investigated using scanning electron microscopy, atomic force microscopy, and photoluminescence spectroscopy. The epitaxial growth is confirmed using electron backscatter diffraction and transmission electron microscopy. The metal-oxide interfaces fabricated have the potential to be used in a number of technologically important applications. Possible examples include creating high quality electrical contacts on high bandgap materials and improving light extraction from planar

  18. Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway.

    PubMed

    Mehta, Suresh L; Mendelev, Natalia; Kumari, Santosh; Andy Li, P

    2013-03-01

    Mitochondrial biogenesis is activated by nuclear encoded transcription co-activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is regulated by several upstream factors including protein kinase A and Akt/protein kinase B. We have previously shown that selenoprotein H enhances the levels of nuclear regulators for mitochondrial biogenesis, increases mitochondrial mass and improves mitochondrial respiratory rate, under physiological condition. Furthermore, overexpression of selenoprotein H protects neuronal HT22 cells from ultraviolet B irradiation-induced cell damage by lowering reactive oxygen species production, and inhibiting activation of caspase-3 and -9, as well as p53. The objective of this study is to identify the cell signaling pathways by which selenoprotein H initiates mitochondrial biogenesis. We first confirmed our previous observation that selenoprotein H transfected HT22 cells increased the protein levels of nuclear-encoded mitochondrial biogenesis factors, peroxisome proliferator-activated receptor γ coactivator-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A. We then observed that total and phosphorylation of protein kinase A, Akt/protein kinase B and cyclic adenosine monophosphate response element-binding protein (CREB) were significantly increased in selenoprotein H transfected cells compared to vector transfected HT22 cells. To verify whether the observed stimulating effects on mitochondrial biogenesis pathways are caused by selenoprotein H and mediated through CREB, we knocked down selenoprotein H mRNA level using siRNA and inhibited CREB with napthol AS-E phosphate in selenoprotein H transfected cells and repeated the measurements of the aforementioned biomarkers. Our results revealed that silencing of selenoprotein H not only decreased the protein levels of PGC-1α, nuclear respiratory factor 1 and mitochondrial transcription factor A, but also decreased the total and

  19. Crystalline rare-earth activated oxyorthosilicate phosphor

    DOEpatents

    McClellan, Kenneth J.; Cooke, D. Wayne

    2004-02-10

    Crystalline, transparent, rare-earth activated lutetium oxyorthosilicate phosphor. The phosphor consists essentially of lutetium yttrium oxyorthosilicate activated with a rare-earth metal dopant M and having the general formula Lu(.sub.2-x-z)Y.sub.x M.sub.z SiO.sub.5, wherein 0.00.ltoreq.x.ltoreq.1.95, wherein 0.001.ltoreq.z.ltoreq.0.02, and wherein M is selected from Sm, Tb, Tm, Eu, Yb, and Pr. The phosphor also consists essentially of lutetium gadolinium oxyorthosilicate activated with a rare-earth metal dopant M and having the general formula Lu(.sub.2-x-z)Gd.sub.x M.sub.z SiO.sub.5, wherein 0.00.ltoreq.x.ltoreq.1.95, wherein 0.001.ltoreq.z.ltoreq.0.02, and wherein M is selected from Sm, Tb, Tm, Eu, Yb, and Pr. The phosphor also consists essentially of gadolinium yttrium oxyorthosilicate activated with a rare-earth metal dopant M and having the general formula Gd(.sub.2-x-z)Y.sub.x M.sub.z SiO.sub.5, wherein 0.00.ltoreq.x.ltoreq.1.95, wherein 0.001.ltoreq.z.ltoreq.0.02, and wherein M is selected from Sm, Tb, Tm, Eu, Yb, and Pr. The phosphor may be optically coupled to a photodetector to provide a radiation detector.

  20. Low-Dimensional Topological Crystalline Insulators.

    PubMed

    Wang, Qisheng; Wang, Feng; Li, Jie; Wang, Zhenxing; Zhan, Xueying; He, Jun

    2015-09-01

    Topological crystalline insulators (TCIs) are recently discovered topological phase with robust surface states residing on high-symmetry crystal surfaces. Different from conventional topological insulators (TIs), protection of surface states on TCIs comes from point-group symmetry instead of time-reversal symmetry in TIs. The distinct properties of TCIs make them promising candidates for the use in novel spintronics, low-dissipation quantum computation, tunable pressure sensor, mid-infrared detector, and thermoelectric conversion. However, similar to the situation in TIs, the surface states are always suppressed by bulk carriers, impeding the exploitation of topology-induced quantum phenomenon. One effective way to solve this problem is to grow low-dimensional TCIs which possess large surface-to-volume ratio, and thus profoundly increase the carrier contribution from topological surface states. Indeed, through persistent effort, researchers have obtained unique quantum transport phenomenon, originating from topological surface states, based on controllable growth of low-dimensional TCIs. This article gives a comprehensive review on the recent progress of controllable synthesis and topological surface transport of low-dimensional TCIs. The possible future direction about low-dimensional TCIs is also briefly discussed at the end of this paper.

  1. Open-cell glass crystalline porous material

    DOEpatents

    Anshits, Alexander G.; Sharonova, Olga M.; Vereshchagina, Tatiana A.; Zykova, Irina D.; Revenko, Yurii A.; Tretyakov, Alexander A.; Aloy, Albert S.; Lubtsev, Rem I.; Knecht, Dieter A.; Tranter, Troy J.; Macheret, Yevgeny

    2003-12-23

    An open-cell glass crystalline porous material made from hollow microspheres which are cenospheres obtained from fly ash, having an open-cell porosity of up to 90 vol. % is produced. The cenospheres are separated into fractions based on one or more of grain size, density, magnetic or non-magnetic, and perforated or non-perforated. Selected fractions are molded and agglomerated by sintering with a binder at a temperature below the softening temperature, or without a binder at a temperature about, or above, the softening temperature but below the temperature of liquidity. The porous material produced has an apparent density of 0.3-0.6 g/cm.sup.3, a compressive strength in the range of 1.2-3.5 MPa, and two types of openings: through-flow wall pores in the cenospheres of 0.1-30 micrometers, and interglobular voids between the cenospheres of 20-100 micrometers. The porous material of the invention has properties useful as porous matrices for immobilization of liquid radioactive waste, heat-resistant traps and filters, supports for catalysts, adsorbents and ion-exchangers.

  2. Open-cell glass crystalline porous material

    DOEpatents

    Anshits, Alexander G.; Sharonova, Olga M.; Vereshchagina, Tatiana A.; Zykova, Irina D.; Revenko, Yurii A.; Tretyakov, Alexander A.; Aloy, Albert S.; Lubtsev, Rem I.; Knecht, Dieter A.; Tranter, Troy J.; Macheret, Yevgeny

    2002-01-01

    An open-cell glass crystalline porous material made from hollow microspheres which are cenospheres obtained from fly ash, having an open-cell porosity of up to 90 vol. % is produced. The cenospheres are separated into fractions based on one or more of grain size, density, magnetic or non-magnetic, and perforated or non-perforated. Selected fractions are molded and agglomerated by sintering with a binder at a temperature below the softening temperature, or without a binder at a temperature about, or above, the softening temperature but below the temperature of liquidity. The porous material produced has an apparent density of 0.3-0.6 g/cm.sup.3, a compressive strength in the range of 1.2-3.5 MPa, and two types of openings: through-flow wall pores in the cenospheres of 0.1-30 micrometers, and interglobular voids between the cenospheres of 20-100 micrometers. The porous material of the invention has properties useful as porous matrices for immobilization of liquid radioactive waste, heat-resistant traps and filters, supports for catalysts, adsorbents and ion-exchangers.

  3. Post-shock relaxation in crystalline nitromethane

    NASA Astrophysics Data System (ADS)

    Rivera-Rivera, Luis A.; Sewell, Thomas D.; Thompson, Donald L.

    2013-02-01

    Molecular dynamics simulations of shocked (100)-oriented crystalline nitromethane were carried out to determine the rates of relaxation behind the shock wave. The forces were described by the fully flexible non-reactive Sorescu-Rice-Thompson force field [D. C. Sorescu, B. M. Rice, and D. L. Thompson, J. Phys. Chem. B 104, 8406 (2000)], 10.1021/jp000942q. The time scales for local and overall thermal equilibration in the shocked crystal were determined. The molecular center-of-mass and atomic kinetic energy distributions rapidly reach substantially different local temperatures. Several picoseconds are required for the two distributions to converge, corresponding to establishment of thermal equilibrium in the shocked crystal. The decrease of the molecular center-of-mass temperature and the increase of the atomic temperature behind the shock front exhibit essentially exponential dependence on time. Analysis of covalent bond distance distributions ahead of, immediately behind, and well behind the shock front showed that the effective bond stretching potentials are essentially harmonic. Effective force constants for the C-N, C-H, and N-O bonds immediately behind the shock front are larger by factors of 1.6, 2.5, and 2.0, respectively, than in the unshocked crystal; and by factors of 1.2, 2.2, and 1.7, respectively, compared to material sufficiently far behind the shock front to be essentially at thermal equilibrium.

  4. High efficiency crystalline silicon solar cells

    NASA Technical Reports Server (NTRS)

    Sah, C. Tang

    1986-01-01

    A review of the entire research program since its inception ten years ago is given. The initial effort focused on the effects of impurities on the efficiency of silicon solar cells to provide figures of maximum allowable impurity density for efficiencies up to about 16 to 17%. Highly accurate experimental techniques were extended to characterize the recombination properties of the residual imputities in the silicon solar cell. A numerical simulator of the solar cell was also developed, using the Circuit Technique for Semiconductor Analysis. Recent effort focused on the delineation of the material and device parameters which limited the silicon efficiency to below 20% and on an investigation of cell designs to break the 20% barrier. Designs of the cell device structure and geometry can further reduce recombination losses as well as the sensitivity and criticalness of the fabrication technology required to exceed 20%. Further research is needed on the fundamental characterization of the carrier recombination properties at the chemical impurity and physical defect centers. It is shown that only single crystalline silicon cell technology can be successful in attaining efficiencies greater than 20%.

  5. Deep drilling technology for hot crystalline rock

    SciTech Connect

    Rowley, J.C.

    1984-01-01

    The development of Hot Dry Rock (HDR) geothermal systems at the Fenton Hill, New Mexico site has required the drilling of four deep boreholes into hot, Precambrian granitic and metamorphic rocks. Thermal gradient holes, four observation wells 200 m (600 ft) deep, and an exploration core hole 800 m (2400 ft) deep guided the siting of the four deep boreholes. Results derived from the exploration core hole, GT-1 (Granite Test No. 1), were especially important in providing core from the granitic rock, and establishing the conductive thermal gradient and heat flow for the granitic basement rocks. Essential stratigraphic data and lost drilling-fluid zones were identified for the volcanic and sedimentary rocks above the contact with the crystalline basement. Using this information drilling strategies and well designs were then devised for the planning of the deeper wells. The four deep wells were drilled in pairs, the shallowest were planned and drilled to depths of 3 km in 1975 at a bottom-hole temperature of nearly 200/sup 0/C. These boreholes were followed by a pair of wells, completed in 1981, the deepest of which penetrated the Precambrian basement to a vertical depth of 4.39 km at a temperature of 320/sup 0/C.

  6. Synthesis of crystalline silicate ZSM-11

    SciTech Connect

    Beck, J.S.; Schlenker, J.D.

    1993-05-25

    A method for synthesizing crystalline material exhibiting a characteristic X-ray diffraction pattern including d-spacing maxima values is described, in Angstroms, as follows: 11.2 [plus minus] 0.2, 10.1 [plus minus] 0.2; 6.73 [plus minus] 0.2; 5.61 [plus minus] 0.1; 5.03 [plus minus] 0.1; 4.62 [plus minus] 0.1; 4.39 [plus minus] 0.08; 3.86 [plus minus] 0.07; 3.73 [plus minus] 0.07; 3.49 [plus minus] 0.07; (3.07, 3.00 [plus minus] 0.05); 2.01 [plus minus] 0.02; which comprises (i) preparing a mixture capable of forming said material, said mixture comprising sources of alkali or alkaline earth metal (M), an oxide of trivalent element (X), an oxide of tetravalent element (Y), water and C[sub n]N[sup +](CH[sub 3])[sub 3], wherein n = 9, 10, 11 or 12, directing agent (R), and having a composition in terms of mole ratios within the following ranges: X[sub 2]O[sub 3]/YO[sub 2] - 0 to .05; H[sub 2]O/YO[sub 2] - 10 to 200; OH[sup [minus

  7. Synthesis of crystalline ceramics for actinide immobilisation

    SciTech Connect

    Burakov, B.; Gribova, V.; Kitsay, A.; Ojovan, M.; Hyatt, N.C.; Stennett, M.C.

    2007-07-01

    Methods for the synthesis of ceramic wasteforms for the immobilization of actinides are common to those for non-radioactive ceramics: hot uniaxial pressing (HUP); hot isostatic pressing (HIP); cold pressing followed by sintering; melting (for some specific ceramics, such as garnet/perovskite composites). Synthesis of ceramics doped with radionuclides is characterized with some important considerations: all the radionuclides should be incorporated into crystalline structure of durable host-phases in the form of solid solutions and no separate phases of radionuclides should be present in the matrix of final ceramic wasteform; all procedures of starting precursor preparation and ceramic synthesis should follow safety requirements of nuclear industry. Synthesis methods that avoid the use of very high temperatures and pressures and are easily accomplished within the environment of a glove-box or hot cell are preferable. Knowledge transfer between the V. G. Khlopin Radium Institute (KRI, Russia) and Immobilisation Science Laboratory (ISL, UK) was facilitated in the framework of a joint project supported by UK Royal Society. In order to introduce methods of precursor preparation and ceramic synthesis we selected well-known procedures readily deployable in radiochemical processing plants. We accounted that training should include main types of ceramic wasteforms which are currently discussed for industrial applications. (authors)

  8. Laser ceramics with disordered crystalline structure

    NASA Astrophysics Data System (ADS)

    Bagayev, S. N.; Osipov, V. V.; Pestryakov, E. V.; Solomonov, V. I.; Shitov, V. A.; Maksimov, R. N.; Orlov, A. N.; Petrov, V. V.

    2015-01-01

    New ceramic materials based on yttrium oxide Y2O3 with isovalent (Yb2O3, Nd2 O3, and Lu2O3) and heterovalent (ZrO2 and HfO2) components are synthesized, and their spectroscopic properties are investigated. Possible channels of losses in the gain of stimulated radiation in the radiative transitions of Nd3+ and Yb3+ ions in ceramics with heterovalent additives are studied. The results of measurements of Y2O3 ceramics doped with zirconium and hafnium ions, the emission bandwidth and the lifetimes of the 4F3/2 and 2F5/2 levels of Nd3+ and Yb3+ ions, respectively, are presented. It is shown that the nonradiative population of the 4F3/2 levels of neodymium ions is due to their dipole-dipole interaction with Zr3+ and Hf3+ ions. Laser generation in [(Yb0.01Lu0.24Y0.75)2O3]0.88(ZrO2)0.12 ceramics with disordered crystalline structure was achieved at a wavelength of 1034 nm with a differential efficiency of 29%.

  9. Crystalline Organic Cavitands As Microcavity Materials

    NASA Astrophysics Data System (ADS)

    Kane, Christopher Michael

    There has been much interest in inefficiently packed molecular materials and their applications in gas storage, separations, catalysis, etc. Such known materials include metal-organic frameworks (MOFs), polymers of intrinsic microporosity (PIMs), container molecule materials, etc. One way to design inefficiently packed materials is to construct them from compounds that are incapable of close-packing, that is rigid scaffolds with enforced cavities that cannot be filled by self-packing. Cavitand molecules, tetrameric macrocycles derived from calix[4]resorcinarene derivatives, are well known for their propensity to form crystalline inclusion compounds with small molecules; for example, of the 169 examples of calix[4]resorcinarene scaffolds found in the Cambridge Structural Database (CSD), no guest-free forms exist. The guest-free forms of various cavitands, synthesized by literature methods, have been obtained as single crystals by sublimation. Gas inclusion compounds of these cavitands have also been isolated and studied by single crystal x-ray diffraction, thermogravimetric analysis, and 1 H NMR. Furthermore, some cavitand derivatives have shown promise as media for industrial separations (Kr vs. Xe, MeCl vs. DME, Propene vs. Propane).

  10. Bacterial Transport Experiments in Fractured Crystalline Bedrock

    USGS Publications Warehouse

    Becker, M.W.; Metge, D.W.; Collins, S.A.; Shapiro, A.M.; Harvey, R.W.

    2003-01-01

    The efficiency of contaminant biodegradation in ground water depends, in part, on the transport properties of the degrading bacteria. Few data exist concerning the transport of bacteria in saturated bedrock, particularly at the field scale. Bacteria and microsphere tracer experiments were conducted in a fractured crystalline bedrock under forced-gradient conditions over a distance of 36 m. Bacteria isolated from the local ground water were chosen on the basis of physicochemical and physiological differences (shape, cell-wall type, motility), and were differentially stained so that their transport behavior could be compared. No two bacterial strains transported in an identical manner, and microspheres produced distinctly different breakthrough curves than bacteria. Although there was insufficient control in this field experiment to completely separate the effects of bacteria shape, reaction to Gram staining, cell size, and motility on transport efficiency, it was observed that (1) the nonmotile, mutant strain exhibited better fractional recovery than the motile parent strain; (2) Gram-negative rod-shaped bacteria exhibited higher fractional recovery relative to the Gram-positive rod-shaped strain of similar size; and (3) coccoidal (spherical-shaped) bacteria transported better than all but one strain of the rod-shaped bacteria. The field experiment must be interpreted in the context of the specific bacterial strains and ground water environment in which they were conducted, but experimental results suggest that minor differences in the physical properties of bacteria can lead to major differences in transport behavior at the field scale.

  11. Thermal Conductivities of Crystalline Organic Semiconductors

    NASA Astrophysics Data System (ADS)

    Brill, Joseph

    2014-03-01

    As applications for organic semiconductors grow, it is becoming increasingly important to know their thermal conductivities, k. For example, for sub-micron electronic devices, values of k>k0 ~ 5 mW/cm/K are needed, while values kcrystalline organic semiconductors using frequency[2] and position dependent[3] ac-calorimetry; the thermal conductivities are then determined from the specific heats measured with differential scanning calorimetry. For rubrene, which has k

  12. Bacterial transport experiments in fractured crystalline bedrock.

    PubMed

    Becker, Matthew W; Metge, David W; Collins, Samantha A; Shapiro, Allen M; Harvey, Ronald W

    2003-01-01

    The efficiency of contaminant biodegradation in ground water depends, in part, on the transport properties of the degrading bacteria. Few data exist concerning the transport of bacteria in saturated bedrock, particularly at the field scale. Bacteria and microsphere tracer experiments were conducted in a fractured crystalline bedrock under forced-gradient conditions over a distance of 36 m. Bacteria isolated from the local ground water were chosen on the basis of physicochemical and physiological differences (shape, cell-wall type, motility), and were differentially stained so that their transport behavior could be compared. No two bacterial strains transported in an identical manner, and microspheres produced distinctly different breakthrough curves than bacteria. Although there was insufficient control in this field experiment to completely separate the effects of bacteria shape, reaction to Gram staining, cell size, and motility on transport efficiency, it was observed that (1) the nonmotile, mutant strain exhibited better fractional recovery than the motile parent strain; (2) Gram-negative rod-shaped bacteria exhibited higher fractional recovery relative to the Gram-positive rod-shaped strain of similar size; and (3) coccoidal (spherical-shaped) bacteria transported better than all but one strain of the rod-shaped bacteria. The field experiment must be interpreted in the context of the specific bacterial strains and ground water environment in which they were conducted, but experimental results suggest that minor differences in the physical properties of bacteria can lead to major differences in transport behavior at the field scale.

  13. Viscoelastic damping in crystalline composites and alloys

    NASA Astrophysics Data System (ADS)

    Ranganathan, Raghavan; Ozisik, Rahmi; Keblinski, Pawel

    We use molecular dynamics simulations to study viscoelastic behavior of model Lennard-Jones (LJ) crystalline composites subject to an oscillatory shear deformation. The two crystals, namely a soft and a stiff phase, individually show highly elastic behavior and a very small loss modulus. On the other hand, when the stiff phase is included within the soft matrix as a sphere, the composite exhibits significant viscoelastic damping and a large phase shift between stress and strain. In fact, the maximum loss modulus in these model composites was found to be about 20 times greater than that given by the theoretical Hashin-Shtrikman upper bound. We attribute this behavior to the fact that in composites shear strain is highly inhomogeneous and mostly accommodated by the soft phase, corroborated by frequency-dependent Grüneisen parameter analysis. Interestingly, the frequency at which the damping is greatest scales with the microstructural length scale of the composite. Finally, a critical comparison between damping properties of these composites with ordered and disordered alloys and superlattice structures is made.

  14. Physics of liquid and crystalline plasmas: Future perspectives

    NASA Astrophysics Data System (ADS)

    Morfill, G. E.

    It has been shown that under certain conditions "complex plasmas" (plasma containing ions, electrons and charged microspheres) may undergo spontaneous phase changes to become liquid and crystalline, without recombination of the charge components. Hence these systems may be regarded as new plasma states "condensed plasmas". The ordering forces are mainly electrostatic, but dipolar effects, anisotropic pressure due shielding, ion flow focussing etc. may all play a role, too. Complex plasmas are of great interest from a fundamental research point of view because the individual particles of one plasma component (the charged microspheres) can be visualised and hence the plasma can be studied at the kinetic level. Also, the relevant time scales (e.g. 1/plasma frequency) are of order 0.1 sec, the plasma processes occur practically in "slow motion". We will discuss some physical processes (e.g. wave propagation, shocks, phase transitions) of these systems and outline the potential of the research for the understanding of strongly coupled systems. Technologically, it is expected that colloidal plasmas will also become very important, because both plasma technology and colloid technology are widely developed already. In this overview first the basic forces between the particles are discussed, then the phase transitions, the lattice structures and results from active experiments will be presented. Finally the future perspectives will be discussed, from the scientific potential point of view and the experimental approaches in the laboratory and in space. Experiments under microgravity conditions are of great importance, because the microspheres are 10's of billions times heavier than the ions.

  15. Sequence analysis of four acidic beta-crystallin subunits of amphibian lenses: phylogenetic comparison between beta- and gamma-crystallins.

    PubMed

    Lu, S F; Pan, F M; Chiou, S H

    1996-04-16

    beta-Crystallins composed of the most heterogeneous group of subunit chains among the three major crystallin families of vertebrates, i.e. alpha-, beta- and gamma-crystallins, are less well understood at the structural and functional levels than the other two. They comprise a multigene family with at least three basic (betaB1-3) and four acidic (betaA1-4) subunit polypeptides. In order to facilitate the determination of the primary sequences of all these ubiquitous crystallin subunits present in all vertebrate species, cDNA mixture was synthesized from the poly(A)+ mRNA isolated from bullfrog eye lenses. We report here a protocol of Rapid Amplification of cDNA Ends (RACE) was used to amplify cDNAs encoding beta-crystallin acidic subunit polypeptides by polymerase chain reaction (PCR). Four complete full-length reading frames with two each of 597 and 648 base pairs, which cover four deduced protein sequences of 198 (betaA1-1 and betaA1-2) and 215 (betaA3-1 and betaA3-2) amino acids including the universal initiating methionine, were revealed by nucleotide sequencing. They show about 96-98% sequence similarity among themselves and 76-80%, 80-83% to the homologous betaA1/A3 crystallins of bovine and human species respectively, revealing the close structural relationship among acidic subunits of all beta-crystallins even from remotely related species. In this study a phylogenetic comparison based on amino-acid sequences of various betaA1/A3 crystallins plus the major basic beta-crystallin (betaBp) and gamma-crystallin from different vertebrate species is made using a combination of distance matrix and approximate parsimony methods, which correctly groups these betaA crystallin chains together as one family distinct from basic beta-crystallins and gamma-crystallin and further corroborates the supposition that beta- and gamma-crystallins form a superfamily with a common ancestry.

  16. Intracellular adenosine 5'-triphosphate, adenosine 5'-diphosphate, and adenosine 5'-monophosphate detection by short-end injection capillary electrophoresis using methylcellulose as the effective electroosmostic flow suppressor.

    PubMed

    Zinellu, Angelo; Sotgia, Salvatore; Pasciu, Valeria; Madeddu, Manuela; Leoni, Giovanni Giuseppe; Naitana, Salvatore; Deiana, Luca; Carru, Ciriaco

    2008-07-01

    We present a new rapid CE method to measure adenine nucleotides adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine 5'-monophosphate (AMP) in cells. The short-end injection mode allows a decrease in the analysis time by injecting samples at the outlet end of a silica capillary closest to the detection window, reducing the migration distance. Moreover, the use of methylcellulose (MC) as run buffer additive to suppress EOF permits to further reduce the migration times of analytes. Thus, when a capillary with an effective length of 10.2 cm was used with a 60 mmol/L sodium acetate buffer pH 3.80 in the presence of 0.01% of MC, the migration time of analytes were 1.35 min for ATP, 1.85 min for ADP, and 4.64 min for AMP. These conditions gave a good reproducibility for intra- and interassay (CV <4 and 8%, respectively) and all the procedure demonstrated an excellent analytical recovery (from 98.3 to 99 %). The method suitability was proved both on red blood cells and in spermatozoa. We compared our proposed method to a spectrophotometric assay, by measuring ATP levels in 40 spermatozoa samples. The obtained data were analyzed by the Passing and Bablok regression and Bland-Altman test. PMID:18551716

  17. The role of metal ion binding in generating 8-hydroxy-2'-deoxyguanosine from the nucleoside 2'-deoxyguanosine and the nucleotide 2'-deoxyguanosine-5'-monophosphate.

    PubMed

    Noblitt, Scott D; Huehls, Amelia M; Morris, Daniel L

    2007-03-01

    The metal ions Cu(II), Fe(II), and Cr(III) were allowed to react with H(2)O(2) in the presence of either the mononucleoside 2'-deoxyguanosine (dG) or the mononucleotide 2'-deoxyguanosine-5'-monophosphate (dGMP). The percentage of reacted dG or dGMP that formed the oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was monitored. Oxidative damage from reactions involving Cu(II) appear dependent on an interaction between copper and N7 on the guanine base. Any interactions involving the phosphate group have little additional effect on overall oxidative damage or 8-OH-dG production. Reactions involving Fe(II) seem very dependent on an interaction that may involve both N7 on the guanine base and the phosphate group. This interaction may slow oxidation of Fe(II) to Fe(III) in solution, keeping iron in a readily available form to undergo the Fenton reaction. Chromium(III) appears to interact with the phosphate group of dGMP, resulting in significant overall oxidative damage. However, production of 8-OH-dG appears to be very dependent on the ability of Cr(III) to interact with N7 on the guanine base, an interaction that seems to be weak for both the mononucleoside and mononucleotide. PMID:17234269

  18. Mechanism for regulating the distribution of glucose carbon between the Embden-Meyerhof and hexose-monophosphate pathways in Streptococcus faecalis.

    PubMed

    Brown, A T; Wittenberger, C L

    1971-05-01

    Glucose-adapted Streptococcus faecalis produced little if any (14)CO(2) from glucose-1-(14)C, although high levels of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44) were detected in cell-free extracts. Metabolism of glucose through the oxidative portion of the hexose-monophosphate pathway was shown to be regulated in this organism by the specific inhibitory interaction of the Embden-Meyerhof intermediate, fructose-1, 6-diphosphate (FDP), with 6-phosphogluconate dehydrogenase. Glucose-6-phosphate dehydrogenase activity was unaffected by FDP. The S. faecalis 6-phosphogluconate dehydrogenase was partially purified from crude extracts by standard fractionation procedures and certain kinetic parameters of the FDP-mediated inhibition were investigated. The negative effector was shown to cause a decrease in V(max) and an increase in the apparent K(m) for both 6-phosphogluconate and nicotinamide adenine dinucleotide phosphate (NADP). These effects were apparently a consequence of the ligand interacting with the enzyme at a site distinct from either the substrate or the coenzyme sites. Among the evidence supporting this was the fact that beta-mercaptoethanol blocked completely FDP inhibition, but had no effect on catalytic activity. The possibility that the regulation of 6-phosphogluconate dehydrogenase activity by FDP might be of some general significance was suggested by the observation that this enzyme from several other sources was also sensitive to FDP.

  19. Enhanced Production of Adenosine Triphosphate by Pharmacological Activation of Adenosine Monophosphate-Activated Protein Kinase Ameliorates Acetaminophen-Induced Liver Injury.

    PubMed

    Hwang, Jung Hwan; Kim, Yong-Hoon; Noh, Jung-Ran; Choi, Dong-Hee; Kim, Kyoung-Shim; Lee, Chul-Ho

    2015-10-01

    The hepatic cell death induced by acetaminophen (APAP) is closely related to cellular adenosine triphosphate (ATP) depletion, which is mainly caused by mitochondrial dysfunction. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of low energy status. AMPK regulates metabolic homeostasis by stimulating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. We found that the decrease in active phosphorylation of AMPK in response to APAP correlates with decreased ATP levels, in vivo. Therefore, we hypothesized that the enhanced production of ATP via AMPK stimulation can lead to amelioration of APAP-induced liver failure. A769662, an allosteric activator of AMPK, produced a strong synergistic effect on AMPK Thr172 phosphorylation with APAP in primary hepatocytes and liver tissue. Interestingly, activation of AMPK by A769662 ameliorated the APAP-induced hepatotoxicity in C57BL/6N mice treated with APAP at a dose of 400 mg/kg intraperitoneally. However, mice treated with APAP alone developed massive centrilobular necrosis, and APAP increased their serum alanine aminotransferase and aspartate aminotransferase levels. Furthermore, A769662 administration prevented the loss of intracellular ATP without interfering with the APAP-mediated reduction of mitochondrial dysfunction. In contrast, inhibition of glycolysis by 2-deoxy-glucose eliminated the beneficial effects of A769662 on APAP-mediated liver injury. In conclusion, A769662 can effectively protect mice against APAP-induced liver injury through ATP synthesis by anaerobic glycolysis. Furthermore, stimulation of AMPK may have potential therapeutic application for APAP overdose. PMID:26434492

  20. Rotation around the glycosidic bond as driving force of proton transfer in protonated 2‧-deoxyriboadenosine monophosphate (dAMP)

    NASA Astrophysics Data System (ADS)

    Shishkin, Oleg V.; Dopieralski, Przemyslaw; Palamarchuk, Gennady V.; Latajka, Zdzislaw

    2010-04-01

    Theoretical investigation of the conformation of 2'-deoxyriboadenosine monophosphate protonated at the N7 atom and stabilized by a very strong C8-H⋯O-P hydrogen bond indicates that this hydrogen bond may be disrupted by rotation of the adenine moiety around the glycosidic bond. A B3LYP/aug-cc-pVDZ scan of the relaxed potential energy surface demonstrates that this rotation is a multi-stage process, accompanying proton transfer from the N7 atom of adenine to the oxygen atom of the phosphate group with a change of conformation of the nucleotide from south/anti to north/syn conformation. Car-Parrinello molecular dynamics simulation indicates that rotation around the glycosidic bond is the preferred way for relaxation of the molecular geometry of this conformer. Both processes, i.e. conformational transition and proton transfer, are strongly coupled. However, the conformer containing a strong C-H⋯O hydrogen bond also corresponds to a local minimum on the Gibbs free energy surface. A specific property of this hydrogen bond is the large variation of the H⋯O distance (ranging from 1.3 to 2.2 Å), which is not caused by proton movement between the carbon and oxygen atoms, but rather by relative motions of the adenine and phosphate moieties.

  1. Enhanced Production of Adenosine Triphosphate by Pharmacological Activation of Adenosine Monophosphate-Activated Protein Kinase Ameliorates Acetaminophen-Induced Liver Injury.

    PubMed

    Hwang, Jung Hwan; Kim, Yong-Hoon; Noh, Jung-Ran; Choi, Dong-Hee; Kim, Kyoung-Shim; Lee, Chul-Ho

    2015-10-01

    The hepatic cell death induced by acetaminophen (APAP) is closely related to cellular adenosine triphosphate (ATP) depletion, which is mainly caused by mitochondrial dysfunction. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of low energy status. AMPK regulates metabolic homeostasis by stimulating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. We found that the decrease in active phosphorylation of AMPK in response to APAP correlates with decreased ATP levels, in vivo. Therefore, we hypothesized that the enhanced production of ATP via AMPK stimulation can lead to amelioration of APAP-induced liver failure. A769662, an allosteric activator of AMPK, produced a strong synergistic effect on AMPK Thr172 phosphorylation with APAP in primary hepatocytes and liver tissue. Interestingly, activation of AMPK by A769662 ameliorated the APAP-induced hepatotoxicity in C57BL/6N mice treated with APAP at a dose of 400 mg/kg intraperitoneally. However, mice treated with APAP alone developed massive centrilobular necrosis, and APAP increased their serum alanine aminotransferase and aspartate aminotransferase levels. Furthermore, A769662 administration prevented the loss of intracellular ATP without interfering with the APAP-mediated reduction of mitochondrial dysfunction. In contrast, inhibition of glycolysis by 2-deoxy-glucose eliminated the beneficial effects of A769662 on APAP-mediated liver injury. In conclusion, A769662 can effectively protect mice against APAP-induced liver injury through ATP synthesis by anaerobic glycolysis. Furthermore, stimulation of AMPK may have potential therapeutic application for APAP overdose.

  2. Mulberry leaf polyphenol extract induced apoptosis involving regulation of adenosine monophosphate-activated protein kinase/fatty acid synthase in a p53-negative hepatocellular carcinoma cell.

    PubMed

    Yang, Tzi-Peng; Lee, Huei-Jane; Ou, Ting-Tsz; Chang, Ya-Ju; Wang, Chau-Jong

    2012-07-11

    The polyphenols in mulberry leaf possess the ability to inhibit cell proliferation, invasion, and metastasis of tumors. It was reported that the p53 status plays an important role in switching apoptosis and the cell cycle following adenosine monophosphate-activated protein kinase (AMPK) activation. In this study, we aimed to detect the effect of the mulberry leaf polyphenol extract (MLPE) on inducing cell death in p53-negative (Hep3B) and p53-positive (Hep3B with transfected p53) hepatocellular carcinoma cells and also to clarify the role of p53 in MLPE-treated cells. After treatment of the Hep3B cells with MLPE, apoptosis was induced via the AMPK/PI3K/Akt and Bcl-2 family pathways. Transient transfection of p53 into Hep3B cells led to switching autophagy instead of apoptosis by MLPE treatment. We demonstrated that acridine orange staining and protein expressions of LC-3 and beclin-1 were increased in p53-transfected cells. These results implied induction of apoptosis or autophagy in MLPE-treated hepatocellular carcinoma cells can be due to the p53 status. We also found MLPE can not only activate AMPK but also diminish fatty acid synthase, a molecular target for cancer inhibition. At present, our results indicate MLPE can play an active role in mediating the cell death of hepatocellular carcinoma cells and the p53 might play an important role in regulating the death mechanisms.

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

    SciTech Connect

    K Smith; C Shanahan; E Moore; A Simon; S Strobel

    2011-12-31

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

  4. Measuring the dynamics of cyclic adenosine monophosphate level in living cells induced by low-level laser irradiation using bioluminescence resonance energy transfer

    NASA Astrophysics Data System (ADS)

    Huang, Yimei; Zheng, Liqin; Yang, Hongqin; Chen, Jiangxu; Wang, Yuhua; Li, Hui; Xie, Shusen; Zeng, Haishan

    2015-05-01

    Several studies demonstrated that the cyclic adenosine monophosphate (cAMP), an important second messenger, is involved in the mechanism of low-level laser irradiation (LLLI) treatment. However, most of these studies obtained the cAMP level in cell culture extracts or supernatant. In this study, the cAMP level in living cells was measured with bioluminescence resonance energy transfer (BRET). The effect of LLLI on cAMP level in living cells with adenosine receptors blocked was explored to identify the role of adenosine receptors in LLLI. The results showed that LLLI increased the cAMP level. Moreover, the rise of cAMP level was light dose dependent but wavelength independent for 658-, 785-, and 830-nm laser light. The results also exhibited that the adenosine receptors, a class of G protein-coupled receptor (GPCR), modulated the increase of cAMP level induced by LLLI. The cAMP level increased more significantly when the A3 adenosine receptors (A3R) were blocked by A3R antagonist compared with A1 adenosine receptor or A2a adenosine receptor blocked in HEK293T cells after LLLI, which was in good agreement with the adenosine receptors' expressions. All these results suggested that measuring the cAMP level with BRET could be a useful technique to study the role of GPCRs in living cells under LLLI.

  5. Pharmacokinetics of IDX184, a liver-targeted oral prodrug of 2'-methylguanosine-5'-monophosphate, in the monkey and formulation optimization for human exposure.

    PubMed

    Pan-Zhou, Xin-Ru; Mayes, Benjamin A; Rashidzadeh, Hassan; Gasparac, Rahela; Smith, Steven; Bhadresa, Sanjeev; Gupta, Kusum; Cohen, Marita Larsson; Bu, Charlie; Good, Steven S; Moussa, Adel; Rush, Roger

    2016-10-01

    IDX184 is a phosphoramidate prodrug of 2'-methylguanosine-5'-monophosphate, developed to treat patients infected with hepatitis C virus. A mass balance study of radiolabeled IDX184 and pharmacokinetic studies of IDX184 in portal vein-cannulated monkeys revealed relatively low IDX184 absorption but higher exposure of IDX184 in the portal vein than in the systemic circulation, indicating >90 % of the absorbed dose was subject to hepatic extraction. Systemic exposures to the main metabolite, 2'-methylguanosine (2'-MeG), were used as a surrogate for liver levels of the pharmacologically active entity 2'-MeG triphosphate, and accordingly, systemic levels of 2'-MeG in the monkey were used to optimize formulations for further clinical development of IDX184. Capsule formulations of IDX184 delivered acceptable levels of 2'-MeG in humans; however, the encapsulation process introduced low levels of the genotoxic impurity ethylene sulfide (ES), which necessitated formulation optimization. Animal pharmacokinetic data guided the development of a tablet with trace levels of ES and pharmacokinetic performance equal to that of the clinical capsule in the monkey. Under fed conditions in humans, the new tablet formulation showed similar exposure to the capsule used in prior clinical trials. PMID:25898809

  6. Increased inosine 5{prime}-monophosphate dehydrogenase gene expression in replicating cells: A response to growth factors, not to changes in cell cycle parameters

    SciTech Connect

    Tsutani, Hiroshi; Collart, F.R.; Glesne, D.A.; Huberman, E. |

    1997-07-01

    The authors have analyzed levels of inosine 5{prime}-monophosphate dehydrogenase (IMPDH; E.C. 1.1.1.205) type II mRNA levels in a human melanoma cell line, SK-MEL-131, and a Chinese hamster ovary cell line synchronously progressing through the cell cycle following treatment with aphidicolin. Following release from the aphidicolin block at the G{sub 1}-S phase boundary, the type II IMPDH gene was found to be constitutively expressed at a similar level during all stages of the cell cycle. To analyze growth regulation, as opposed to cell cycle regulation, stable SK-MEL-131 transfectants that express a type II IMPDH-promoted heterologous construct were assayed following deprivation of serum growth factors and after restimulation with fresh serum. Serum deprivation resulted in down-regulation of both steady state type II IMPDH mRNA levels and promoter activity, while restimulation with serum resulted in up-regulation of these parameters. These findings support the conclusion that the increase in IMPDH type II gene expression in replicating cells is mainly due to growth factor regulation rather than changes in cell cycle parameters and that this regulation is mediated primarily by a transcriptional mechanism. The increased level of IMPDH expression and activity found in many tumors may therefore also be due to a transcriptionally mediated response to growth factors.

  7. Uric acid induces oxidative stress and growth inhibition by activating adenosine monophosphate-activated protein kinase and extracellular signal-regulated kinase signal pathways in pancreatic β cells.

    PubMed

    Zhang, Yongneng; Yamamoto, Tetsuya; Hisatome, Ichiro; Li, Youfeng; Cheng, Weijie; Sun, Ning; Cai, Bozhi; Huang, Tianliang; Zhu, Yuzhang; Li, Zhi; Jing, Xubin; Zhou, Rui; Cheng, Jidong

    2013-08-15

    Hyperuricaemia is a disorder of purine metabolism, and is strongly associated with insulin resistance and abnormal glucose metabolism. As the producer of insulin, pancreatic β cells might be affected by elevated serum uric acid levels and contribute to the disregulated glucose metabolism. In this study, we investigated the effect of high uric acid on rat pancreatic β cell function. Under high uric acid condition, proliferation of pancreatic β cells was inhibited, production of reactive oxygen species increased, and glucose stimulated insulin secretion was also compromised. Further examination on signal transduction pathways revealed that uric acid-induced ROS is involved in the activation of adenosine monophosphate-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK). Pharmacological inhibition of ERK activation rescued β cells from growth inhibition. More importantly, activation of ERK induced by uric acid is significantly diminished by AMPK inhibitor, indicating ERK as a downstream target of AMPK in response to high uric acid condition. We also investigated the transportation channel for uric acid into pancreatic β cells. While major urate transporter URAT1 is not expressed in β cells, organic anion transporter (OAT) inhibitor successfully blocked the activation of ERK by uric acid. Our data indicate that high uric acid levels induce oxidative damage and inhibit growth of rat pancreatic β cells by activating the AMPK and ERK signal pathways. Hyperuricemia may contribute to abnormal glucose metabolism by causing oxidative damage and function inhibition of pancreatic β cells.

  8. Pharmacokinetics of IDX184, a liver-targeted oral prodrug of 2'-methylguanosine-5'-monophosphate, in the monkey and formulation optimization for human exposure.

    PubMed

    Pan-Zhou, Xin-Ru; Mayes, Benjamin A; Rashidzadeh, Hassan; Gasparac, Rahela; Smith, Steven; Bhadresa, Sanjeev; Gupta, Kusum; Cohen, Marita Larsson; Bu, Charlie; Good, Steven S; Moussa, Adel; Rush, Roger

    2016-10-01

    IDX184 is a phosphoramidate prodrug of 2'-methylguanosine-5'-monophosphate, developed to treat patients infected with hepatitis C virus. A mass balance study of radiolabeled IDX184 and pharmacokinetic studies of IDX184 in portal vein-cannulated monkeys revealed relatively low IDX184 absorption but higher exposure of IDX184 in the portal vein than in the systemic circulation, indicating >90 % of the absorbed dose was subject to hepatic extraction. Systemic exposures to the main metabolite, 2'-methylguanosine (2'-MeG), were used as a surrogate for liver levels of the pharmacologically active entity 2'-MeG triphosphate, and accordingly, systemic levels of 2'-MeG in the monkey were used to optimize formulations for further clinical development of IDX184. Capsule formulations of IDX184 delivered acceptable levels of 2'-MeG in humans; however, the encapsulation process introduced low levels of the genotoxic impurity ethylene sulfide (ES), which necessitated formulation optimization. Animal pharmacokinetic data guided the development of a tablet with trace levels of ES and pharmacokinetic performance equal to that of the clinical capsule in the monkey. Under fed conditions in humans, the new tablet formulation showed similar exposure to the capsule used in prior clinical trials.

  9. Developmental Competence of Vitrified-Warmed Bovine Oocytes at the Germinal-Vesicle Stage is Improved by Cyclic Adenosine Monophosphate Modulators during In Vitro Maturation

    PubMed Central

    Ezoe, Kenji; Yabuuchi, Akiko; Tani, Tetsuya; Mori, Chiemi; Miki, Tetsuya; Takayama, Yuko; Beyhan, Zeki; Kato, Yoko; Okuno, Takashi; Kobayashi, Tamotsu; Kato, Keiichi

    2015-01-01

    Cryopreservation of mature oocytes and embryos has provided numerous benefits in reproductive medicine. Although successful cryopreservation of germinal-vesicle stage (GV) oocytes holds promise for further advances in reproductive biology and clinical embryology fields, reports regarding cryopreservation of immature oocytes are limited. Oocyte survival and maturation rates have improved since vitrification is being performed at the GV stage, but the subsequent developmental competence of GV oocytes is still low. The purpose of this study was to evaluate the effects of supplementation of the maturation medium with cyclic adenosine monophosphate (cAMP) modulators on the developmental competence of vitrified-warmed GV bovine oocytes. GV oocytes were vitrified-warmed and cultured to allow for oocyte maturation, and then parthenogenetically activated or fertilized in vitro. Our results indicate that addition of a cAMP modulator forskolin (FSK) or 3-isobutyl-1-methylxanthine (IBMX) to the maturation medium significantly improved the developmental competence of vitrified-warmed GV oocytes. We also demonstrated that vitrification of GV oocytes led to a decline in cAMP levels and maturation-promoting factor (MPF) activity in the oocytes during the initial and final phases of maturation, respectively. Nevertheless, the addition of FSK or IBMX to the maturation medium significantly elevated cAMP levels and MPF activity during IVM. Taken together, our results suggest that the cryopreservation-associated meiotic and developmental abnormalities observed in GV oocytes may be ameliorated by an artificial increase in cAMP levels during maturation culture after warming. PMID:25965267

  10. Enhanced Production of Adenosine Triphosphate by Pharmacological Activation of Adenosine Monophosphate-Activated Protein Kinase Ameliorates Acetaminophen-Induced Liver Injury

    PubMed Central

    Hwang, Jung Hwan; Kim, Yong-Hoon; Noh, Jung-Ran; Choi, Dong-Hee; Kim, Kyoung-Shim; Lee, Chul-Ho

    2015-01-01

    The hepatic cell death induced by acetaminophen (APAP) is closely related to cellular adenosine triphosphate (ATP) depletion, which is mainly caused by mitochondrial dysfunction. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of low energy status. AMPK regulates metabolic homeostasis by stimulating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. We found that the decrease in active phosphorylation of AMPK in response to APAP correlates with decreased ATP levels, in vivo. Therefore, we hypothesized that the enhanced production of ATP via AMPK stimulation can lead to amelioration of APAP-induced liver failure. A769662, an allosteric activator of AMPK, produced a strong synergistic effect on AMPK Thr172 phosphorylation with APAP in primary hepatocytes and liver tissue. Interestingly, activation of AMPK by A769662 ameliorated the APAP-induced hepatotoxicity in C57BL/6N mice treated with APAP at a dose of 400 mg/kg intraperitoneally. However, mice treated with APAP alone developed massive centrilobular necrosis, and APAP increased their serum alanine aminotransferase and aspartate aminotransferase levels. Furthermore, A769662 administration prevented the loss of intracellular ATP without interfering with the APAP-mediated reduction of mitochondrial dysfunction. In contrast, inhibition of glycolysis by 2-deoxy-glucose eliminated the beneficial effects of A769662 on APAP-mediated liver injury. In conclusion, A769662 can effectively protect mice against APAP-induced liver injury through ATP synthesis by anaerobic glycolysis. Furthermore, stimulation of AMPK may have potential therapeutic application for APAP overdose. PMID:26434492

  11. Medium optimization for the production of cyclic adenosine 3',5'-monophosphate by Microbacterium sp. no. 205 using response surface methodology.

    PubMed

    Chen, Xiao-Chun; Bai, Jian-Xin; Cao, Jia-Ming; Li, Zhen-Jiang; Xiong, Jian; Zhang, Lei; Hong, Yuan; Ying, Han-Jie

    2009-01-01

    Response surface methodology was employed to optimize medium composition for the production of cyclic adenosine 3',5'-monophosphate (cAMP) with Microbacterium sp. no. 205. A fractional factorial design (2(11-7)) was applied to evaluate the effects of different components in the medium. K(2)HPO(4), MgSO(4) and NaF were found to significantly influence on the cAMP production. The steepest ascent method was used to access the optimal region of the medium composition. The concentrations of the three factors were optimized subsequently using central composite design and response surface methodology. The optimal medium composition to achieve the optimal cAMP production was determined (g/L): K(2)HPO(4), 12.78; MgSO(4), 3.53 and NaF, 0.18. The corresponding cAMP concentration was 8.50 g/L, which was about 1.8-fold increase compared with that using the original medium. Validation experiments were also carried out to prove the adequacy and the accuracy of the model obtained. The cAMP fermentation in 5L fermenter reached 9.87 g/L. PMID:18778935

  12. Quantification of residual crystallinity in ball milled commercially sourced lactose monohydrate by thermo-analytical techniques and terahertz spectroscopy.

    PubMed

    Smith, Geoff; Hussain, Amjad; Bukhari, Nadeem Irfan; Ermolina, Irina

    2015-05-01

    The quantification of crystallinity is necessary in order to be able to control the milling process. The use of thermal analysis for this assessment presents certain challenges, particularly in the case of crystal hydrates. In this study, the residual crystallinity on ball milling of lactose monohydrate (LMH), for periods up to 90min, was evaluated by thermo-analytical techniques (TGA, DSC) and terahertz spectroscopy (THz). In general, the results from one of the DSC analysis and the THz measurements agree showing a monotonous decrease in relative residual crystallinity with milling time (∼80% reduction after 60min milling) and a slight increase at the 90min time point. However, the estimates from TGA and two other methods of analyzing DSC curve do not agree with the former techniques and show variability with significantly higher estimates for crystallinity. It was concluded that, the thermal techniques require more complex treatment of the data in the evaluation of changes in crystallinity of a milled material (in particular to account for the de-vitrification and mutarotation of the material that inevitably occurs during the measurement cycle) while the analysis of THz data is more straightforward, with the measurement having no impact on the native state of the material. PMID:25784570

  13. Highly selective electrodeposition of sub-10 nm crystalline noble metallic nanorods inside vertically aligned multiwall carbon nanotubes.

    PubMed

    Wang, Xuyang; Wang, Ranran; Wu, Qiang; Zhang, Xiaohua; Yang, Zhaohui; Guo, Jun; Chen, Muzi; Tang, Minghua; Cheng, Yajun; Chu, Haibin

    2016-07-01

    In this paper crystalline noble metallic nanorods including Au and Ag with sub-10 nm diameter, are encapsulated within prealigned and open-ended multiwall carbon nanotubes (MWCNTs) through an electrodeposition method. As the external surface of CNTs has been insulated by the epoxy the CNT channel becomes the only path for the mass transport as well as the nanoreactor for the metal deposition. Highly crystallized Au and Ag2O nanorods parallel to the radial direction of CNTs are confirmed by high-resolution transmission electron microscopy, energy dispersive x-ray spectroscopy and x-ray powder diffraction spectroscopy. The Ag2O nanorods are formed by air oxidation on the Ag metals and show a single crystalline structure with (111) planes. The Au nanorods exhibit a complex crystalline structure including twin-crystal and lattice dislocation with (111) and (200) planes. These crystalline noble metallic nanostructures may have important applications for nanocatalysts for fuel cells as well as nanoelectronic and nanophotonic devices. This method is deemed to benefit the precise deposition of other crystalline nanostructures inside CNTs with a small diameter.

  14. High-temperature hydrothermal synthesis of crystalline mesoporous TiO2 with superior photo catalytic activities

    NASA Astrophysics Data System (ADS)

    Liu, Fujian; Liu, Chun-Lin; Hu, Baowei; Kong, Wei-Ping; Qi, Chen-Ze

    2012-07-01

    Mesoporous titanium dioxide with crystalline mesopore walls (M-TiO2-ns) have been successfully synthesized through the self-assembly of poly 4-Vinylpyridine template and tetrabutyl titanate precursor based on their complex bond interaction under high temperature (180 °C) hydrothermal conditions. X-ray diffraction shows that M-TiO2-ns have highly crystalline mesopore walls with anatase phase characters; N2 sorption-desorption isotherms, SEM and TEM images show that M-TiO2-ns have high BET surface areas (85 and 120 m2/g, respectively), large pore volumes (0.32 and 0.34 cm3/g, respectively) and crystalline mesopore walls, which exhibit monolithic morphology with crystal sizes around 3-5 μm. Interestingly, M-TiO2-ns exhibit much higher catalytic activities and good recyclability in both induced reduction of decabromodiphenyl and oxidation of Rhodamine B under UV light than those of nonporous crystalline TiO2 and M-TiO2 templated by hydrocarbon surfactant of F127, which is even comparable with that of commercial P25. Combination of the unique characters such as crystallinity, stable mesostructure, large BET surface areas and superior photo catalytic activities make M-TiO2-ns a kind of potentially important material for removing of organic pollutions in environment through green photo irradiation processes.

  15. Highly selective electrodeposition of sub-10 nm crystalline noble metallic nanorods inside vertically aligned multiwall carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Wang, Xuyang; Wang, Ranran; Wu, Qiang; Zhang, Xiaohua; Yang, Zhaohui; Guo, Jun; Chen, Muzi; Tang, Minghua; Cheng, Yajun; Chu, Haibin

    2016-07-01

    In this paper crystalline noble metallic nanorods including Au and Ag with sub-10 nm diameter, are encapsulated within prealigned and open-ended multiwall carbon nanotubes (MWCNTs) through an electrodeposition method. As the external surface of CNTs has been insulated by the epoxy the CNT channel becomes the only path for the mass transport as well as the nanoreactor for the metal deposition. Highly crystallized Au and Ag2O nanorods parallel to the radial direction of CNTs are confirmed by high-resolution transmission electron microscopy, energy dispersive x-ray spectroscopy and x-ray powder diffraction spectroscopy. The Ag2O nanorods are formed by air oxidation on the Ag metals and show a single crystalline structure with (111) planes. The Au nanorods exhibit a complex crystalline structure including twin-crystal and lattice dislocation with (111) and (200) planes. These crystalline noble metallic nanostructures may have important applications for nanocatalysts for fuel cells as well as nanoelectronic and nanophotonic devices. This method is deemed to benefit the precise deposition of other crystalline nanostructures inside CNTs with a small diameter.

  16. A Systematic Search for the Spectra with Features of Crystalline Silicates in the Spitzer IRS Enhanced Products

    NASA Astrophysics Data System (ADS)

    Chen, Rui; Luo, Ali; Liu, Jiaming; Jiang, Biwei

    2016-06-01

    The crystalline silicate features are mainly reflected in infrared bands. The Spitzer Infrared Spectrograph (IRS) collected numerous spectra of various objects and provided a big database to investigate crystalline silicates in a wide range of astronomical environments. We apply the manifold ranking algorithm to perform a systematic search for the spectra with crystalline silicate features in the Spitzer IRS Enhanced Products available. In total, 868 spectra of 790 sources are found to show the features of crystalline silicates. These objects are cross-matched with the SIMBAD database as well as with the Large Sky Area Multi-object Fiber Spectroscopic Telescope (LAMOST)/DR2. The average spectrum of young stellar objects shows a variety of features dominated either by forsterite or enstatite or neither, while the average spectrum of evolved objects consistently present dominant features of forsterite in AGB, OH/IR, post-AGB, and planetary nebulae. They are identified optically as early-type stars, evolved stars, galaxies and so on. In addition, the strength of spectral features in typical silicate complexes is calculated. The results are available through CDS for the astronomical community to further study crystalline silicates.

  17. Hypoxanthine-guanine phosphoribosyltransferase and inosine 5′-monophosphate dehydrogenase activities in three mammalian species: aquatic (Mirounga angustirostris), semi-aquatic (Lontra longicaudis annectens) and terrestrial (Sus scrofa)

    PubMed Central

    Barjau Pérez-Milicua, Myrna; Zenteno-Savín, Tania; Crocker, Daniel E.; Gallo-Reynoso, Juan P.

    2015-01-01

    Aquatic and semiaquatic mammals have the capacity of breath hold (apnea) diving. Northern elephant seals (Mirounga angustirostris) have the ability to perform deep and long duration dives; during a routine dive, adults can hold their breath for 25 min. Neotropical river otters (Lontra longicaudis annectens) can hold their breath for about 30 s. Such periods of apnea may result in reduced oxygen concentration (hypoxia) and reduced blood supply (ischemia) to tissues. Production of adenosine 5′-triphosphate (ATP) requires oxygen, and most mammalian species, like the domestic pig (Sus scrofa), are not adapted to tolerate hypoxia and ischemia, conditions that result in ATP degradation. The objective of this study was to explore the differences in purine synthesis and recycling in erythrocytes and plasma of three mammalian species adapted to different environments: aquatic (northern elephant seal) (n = 11), semiaquatic (neotropical river otter) (n = 4), and terrestrial (domestic pig) (n = 11). Enzymatic activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was determined by spectrophotometry, and activity of inosine 5′-monophosphate dehydrogenase (IMPDH) and the concentration of hypoxanthine (HX), inosine 5′-monophosphate (IMP), adenosine 5′-monophosphate (AMP), adenosine 5′-diphosphate (ADP), ATP, guanosine 5′-diphosphate (GDP), guanosine 5′-triphosphate (GTP), and xanthosine 5′-monophosphate (XMP) were determined by high-performance liquid chromatography (HPLC). The activities of HGPRT and IMPDH and the concentration of HX, IMP, AMP, ADP, ATP, GTP, and XMP in erythrocytes of domestic pigs were higher than in erythrocytes of northern elephant seals and river otters. These results suggest that under basal conditions (no diving, sleep apnea or exercise), aquatic, and semiaquatic mammals have less purine mobilization than their terrestrial counterparts. PMID:26283971

  18. Identification of tryptophan oxidation products in bovine alpha-crystallin.

    PubMed Central

    Finley, E. L.; Dillon, J.; Crouch, R. K.; Schey, K. L.

    1998-01-01

    Oxidation is known to affect the structure, activity, and rate of degradation of proteins, and is believed to contribute to a variety of pathological conditions. Metal-catalyzed oxidation (MCO) is a primary oxidizing system in many cell types. In this study, the oxidative effects of a MCO system (the Fenton reaction) on the structure of the tryptophan residues of alpha-crystallin were determined. Tandem mass spectrometry (MS/MS) was utilized to identify specific tryptophan and methionine oxidation products in the bovine alpha-crystallin sequence. After oxidative exposure, alpha-crystallin was digested with trypsin, and the resulting peptides were fractionated by reverse-phase HPLC. Structural analysis by mass spectrometry revealed that tryptophan 9 of alphaA- and tryptophan 60 of alphaB-crystallin were each converted into hydroxytryptophans (HTRP), N-formylkynurenine (NFK), and kynurenine (KYN). However, only HTRP and KYN formation were detected at residue 9 of alphaB-crystallin. Oxidation of methionine 1 of alphaA- and methionine 1 and 68 of alphaB-crystallin was also detected. The products NFK and KYN are of particular importance in the lens, as they themselves are photosensitizers that can generate reactive oxygen species (ROS) upon UV light absorption. The unambiguous identification of HTRP, NFK, and KYN in intact alpha-crystallin represents the first structural proof of the formation of these products in an intact protein, and provides a basis for detailed structural analysis of oxidized proteins generated in numerous pathological conditions. PMID:9828005

  19. Classification of topological crystalline insulators based on representation theory

    NASA Astrophysics Data System (ADS)

    Dong, Xiao-Yu; Liu, Chao-Xing

    2016-01-01

    Topological crystalline insulators define a new class of topological insulator phases with gapless surface states protected by crystalline symmetries. In this work, we present a general theory to classify topological crystalline insulator phases based on the representation theory of space groups. Our approach is to directly identify possible nontrivial surface states in a semi-infinite system with a specific surface, of which the symmetry property can be described by 17 two-dimensional space groups. We reproduce the existing results of topological crystalline insulators, such as mirror Chern insulators in the p m or p m m groups, Cn v topological insulators in the p 4 m ,p 31 m , and p 6 m groups, and topological nonsymmorphic crystalline insulators in the p g and p m g groups. Aside from these existing results, we also obtain the following results: (1) there are two integer mirror Chern numbers (Z2) in the p m group but only one (Z ) in the c m or p 3 m 1 group for both the spinless and spinful cases; (2) for the p m m (c m m ) groups, there is no topological classification in the spinless case but Z4 (Z2) classifications in the spinful case; (3) we show how topological crystalline insulator phase in the p g group is related to that in the p m group; (4) we identify topological classification of the p 4 m ,p 31 m , and p 6 m for the spinful case; (5) we find topological nonsymmorphic crystalline insulators also existing in p g g and p 4 g groups, which exhibit new features compared to those in p g and p m g groups. We emphasize the importance of the irreducible representations for the states at some specific high-symmetry momenta in the classification of topological crystalline phases. Our theory can serve as a guide for the search of topological crystalline insulator phases in realistic materials.

  20. Optical Dephasing by Defects in Crystalline Solids

    NASA Astrophysics Data System (ADS)

    Jang, Ki-Wan

    Two pulse photon echo (TPPE) and hole burning techniques are used in the study of the effect of defects on the optical dephasing in crystalline materials for various types of defects. From a optical dephasing study of the ^7F_0 rightarrow ^5D_0 transition of Eu^ {3+} ions doped in a number of crystalline fibers of rm Y_2O_3 prepared by three different crystal-growth techniques, it is shown that the optical dephasing rate, 1/T _{m} (T_{m}: phase memory time), of crystals prepared by laser heated pedestal growth (LHPG) or arc-imaging furnace at 1.4K is up to two orders of magnitude faster than that of a crystal grown by the flame fusion and that its linear temperature dependence is similar to that in highly disordered system such as glass. However, other optical spectroscopic properties such as the lifetime, or inhomogeneous linewidth are similar to that of the flame fusion crystal. Nevertheless, the fact that the optical dephasing depends linearly on temperature suggests that the optical dephasing may be attributed to disorder present in the samples resulting in an additional dephasing due to local configurational changes. In relation to defects in samples, the study of the optical dephasing of the ^7F _0 rightarrow ^5D_0 transition of Eu^{3+} ions doped in the disordered system rm Y_{2-x}Sc_{x}O_3 (2% Eu, x = 0.04, 0.3, 1 and 0.2% Eu, x = 0.04) shows that the optical dephasing and its temperature behavior are similar to that in the flame fusion crystal and that the optical dephasing is uncorrelated with the inhomogeneous linewidth of the samples studied. This means that Sc ^{3+} ions may remove the TLS type of the optical dephasing observed in pure rm Y_2O_3 fibers, perhaps by stabilizing the stoichiometry. The optical dephasing in YSZ with a high concentration of defects due to oxygen vacancies is faster, by up to three orders of magnitude, than that of YScO_3 (x = 1) in spite of a similar inhomogeneous linewidth. Hole spectra via a hole burning experiment shows

  1. Purity assessment of commercially available crystalline deoxynivalenol.

    PubMed

    Krska, Rudolf; Szente, Elisabeth; Freudenschuss, Martin; Hametner, Christian; Zöllner, Peter

    2004-01-01

    Deoxynivalenol (DON) obtained from 2 commercial sources was characterized, and its purity was determined. The structural identity of DON was confirmed by 1H and 13C-nuclear magnetic resonance (NMR) spectroscopy, gas chromatography with mass spectrometric (GC/MS) detection, and infrared/attenuated total reflectance (IR/ATR) spectroscopy. NMR spectra showed shifts that varied from previously published data. However, we established a complete, unambiguous assignment for all signals. Chromatograms obtained by GC/MS were almost identical for both investigated samples and confirmed the structure of DON. Likewise, IR/ATR spectra verified the identity of DON. The degree of purity was determined by liquid chromatography (LC) with a variable wavelength detector, LC/MS/MS, GC with electron-capture detection (GC-ECD), and ultraviolet (UV) spectrophotometry. The purity check using LC showed a single peak in both chromatograms. With LC/MS/MS measurements, we could detect small amounts of impurities in the crystalline DON from both sources. In data obtained by GC-ECD, no differences in purity were observed. The UV measurements showed an absorption maximum at 217 nm. The mean epsilon(m) of the extinction coefficients was calculated as 6727 (L/cm/mol) for DON (Sigma) and 6825 (L/cm/mol) for DON (Biopure). Finally, the purity of DON from the 2 commercial sources was calculated as >96 and >98%, respectively. Although the DON produced by both providers can be considered sufficiently pure for routine analysis of trichothecenes in food and feed, this work again demonstrated that the impurity of the solid mycotoxin constitutes the greatest contribution to the overall uncertainty of a mycotoxin calibrant.

  2. Thermal diffusivity of some crystalline rocks

    SciTech Connect

    Drury, M.J.

    1987-01-01

    Thermal diffusivity data at room temperature and uniaxial pressure of 1 MPa are reported for five sets of crystalline rocks - granite, granodiorite, gabbro, basalt and gneiss. Diffusivity ranges between approximately 0.6 and 1.9 mm/sup 2//s, the lower end of the range being appropriate for basic rocks and the upper end for quartz-bearing acidic rocks. The scatter in diffusivity for each data set is significantly more than that of thermal conductivity, because the diffusivity of water is typically less than 10% of the diffusivity of most common minerals, whereas water conductivity is 25 - 30% of the conductivity of the minerals. For a sample set of uniform mineralogy in which porosity varies, a greater variation of diffusivity than of conductivity is therefore expected. For three of the sets sufficient mineralogical data were available to permit the assessment of methods of estimating thermal diffusivity from mineral content. All models tested yielded higher mean values of diffusivity than the means of the measured values. No model was found to be able to predict diffusivity to better than approximately 20%, but if that accuracy is sufficient, a simple geometrical model, for which only quartz content must be known, is adequate. The diffusivity data have been combined with measurements of thermal conductivity and density to provide estimates of specific heat. These all tend to be higher than those reported in the literature. For some rocks, such as the basalts, this can be explained in terms of relatively high water content and the very high specific heat of water compared with that of most common minerals. For the granites and granodiorites, the new specific heat data redefine the previously published means and ranges, by increasing the data base by approximately an order of magnitude.

  3. Unilateral Crystalline Vitreoretinopathy: A Rare Entity Associated with Intraocular Inflammation

    PubMed Central

    Harshey, Kaustubh B.; Srinivasan, Karthik; Rengappa, Ramakrishnan; Ramasamy, Kim

    2015-01-01

    A 31-year-old Indian male presented with floaters and diminution of vision in the right eye. Ocular examination showed features of old anterior uveitis with posterior subcapsular cataract and fine, refractile crystals in the vitreous cavity and on the retinal surface. A thorough workup for all known causes of crystalline retinopathy was inconclusive. Unilateral crystalline retinopathy has been sparingly reported. This is the first report of unilateral, crystalline vitreoretinopathy in the absence of any demonstrable and known cause for intraocular crystals. PMID:26688764

  4. Unilateral Crystalline Vitreoretinopathy: A Rare Entity Associated with Intraocular Inflammation.

    PubMed

    Harshey, Kaustubh B; Srinivasan, Karthik; Rengappa, Ramakrishnan; Ramasamy, Kim

    2015-01-01

    A 31-year-old Indian male presented with floaters and diminution of vision in the right eye. Ocular examination showed features of old anterior uveitis with posterior subcapsular cataract and fine, refractile crystals in the vitreous cavity and on the retinal surface. A thorough workup for all known causes of crystalline retinopathy was inconclusive. Unilateral crystalline retinopathy has been sparingly reported. This is the first report of unilateral, crystalline vitreoretinopathy in the absence of any demonstrable and known cause for intraocular crystals. PMID:26688764

  5. Reductive electrosynthesis of crystalline metal-organic frameworks.

    PubMed

    Li, Minyuan; Dincă, Mircea

    2011-08-24

    Electroreduction of oxoanions affords hydroxide equivalents that induce selective deposition of crystalline metal-organic frameworks (MOFs) on conductive surfaces. The method is illustrated by cathodic electrodeposition of Zn(4)O(BDC)(3) (MOF-5; BDC = 1,4-benzenedicarboxylate), which is deposited at room temperature in only 15 min under cathodic potential. Although many crystalline phases are known in the Zn(2+)/BDC(2-) system, MOF-5 is the only observed crystalline MOF phase under these conditions. This fast and mild method of synthesizing MOFs is amenable to direct surface functionalization and could impact applications requiring conformal coatings of microporous MOFs, such as gas separation membranes and electrochemical sensors.

  6. Silylene-diethynyl-arylene polymers having liquid crystalline properties

    DOEpatents

    Barton, T.J.; Yiwei Ding.

    1993-09-07

    The present invention provides linear organosilicon polymers including diethynyl-(substituted)arylene units, and a process for their preparation. These novel polymers possess useful properties including electrical conductivity, liquid crystallinity, and/or photoluminescence. These polymers possess good solubility in organic solvents. A preferred example is produced according to the following reaction scheme. ##STR1## These polymers can be solvent-cast to yield excellent films and can also be pulled into fibers from concentrated solutions. All possess substantial crystallinity as revealed by DSC analysis and observation through a polarizing microscope, and possess liquid crystalline properties.

  7. Comparison of the incremental and hierarchical methods for crystalline neon.

    PubMed

    Nolan, S J; Bygrave, P J; Allan, N L; Manby, F R

    2010-02-24

    We present a critical comparison of the incremental and hierarchical methods for the evaluation of the static cohesive energy of crystalline neon. Both of these schemes make it possible to apply the methods of molecular electronic structure theory to crystalline solids, offering a systematically improvable alternative to density functional theory. Results from both methods are compared with previous theoretical and experimental studies of solid neon and potential sources of error are discussed. We explore the similarities of the two methods and demonstrate how they may be used in tandem to study crystalline solids.

  8. Diffraction enhanced X-ray imaging of mammals crystalline lens

    NASA Astrophysics Data System (ADS)

    Antunes, A.; Hönnicke, M. G.; Safatle, A. M. V.; Cusatis, C.; Moraes Barros, P. S.; Morelhão, S. L.

    2005-08-01

    Crystalline lenses are transparent biological materials where the organization of the lens fibers can also be affected by changes at molecular level, and therefore the structure and morphology of the tissue can be correlated to the loss of transparency of the lens. In this work, internal structure of mammal lenses regarding the long-range ordering of the fibers are investigated by diffraction enhanced X-ray imaging (DEI) radiography. Moreover, DEI and absorption X-ray synchrotron radiographs for healthy and cataractous crystalline lenses are compared. Significant differences in healthy and cataractous crystalline lenses are observed.

  9. The mode of action and the structure of a herbicide in complex with its target: binding of activated hydantocidin to the feedback regulation site of adenylosuccinate synthetase.

    PubMed Central

    Fonné-Pfister, R; Chemla, P; Ward, E; Girardet, M; Kreuz, K E; Honzatko, R B; Fromm, H J; Schär, H P; Grütter, M G; Cowan-Jacob, S W

    1996-01-01

    (+)-Hydantocidin, a recently discovered natural spironucleoside with potent herbicidal activity, is shown to be a proherbicide that, after phosphorylation at the 5' position, inhibits adenylosuccinate synthetase, an enzyme involved in de novo purine synthesis. The mode of binding of hydantocidin 5'-monophosphate to the target enzyme was analyzed by determining the crystal structure of the enzyme-inhibitor complex at 2.6-A resolution. It was found that adenylosuccinate synthetase binds the phosphorylated compound in the same fashion as it does adenosine 5'-monophosphate, the natural feedback regulator of this enzyme. This work provides the first crystal structure of a herbicide-target complex reported to date. Images Fig. 4 Fig. 5 PMID:8790347

  10. Variations in Crystalline Structures and Electrical Properties of Single Crystalline Boron Nitride Nanosheets.

    PubMed

    Aldalbahi, Ali; Zhou, Andrew Feng; Feng, Peter

    2015-01-01

    We report the studies of (1) the basic mechanism underlying the formation of defect-free, single crystalline boron nitride nanosheets (BNNSs) synthesized using pulsed laser plasma deposition (PLPD) technique, (2) the variation in the crystalline structure at the edges of the hexagonal boron nitride (h-BN) nanosheets, and (3) the basic electrical properties related to the BNNSs tunneling effect and electrical breakdown voltage. The nanoscale morphologies of BNNSs are characterized using scanning electron microscope (SEM) and high-resolution transmission electron microscope (HRTEM). The results show that each sample consisted of a number of transparent BNNSs that partially overlapped one another. Varying the deposition duration yielded different thicknesses of sample but did not affect the morphology, structure, and thickness of individual BNNSs pieces. Analysis of the SEM and HRTEM data revealed changes in the spatial period of the B3-N3 hexagonal structures and the interlayer distance at the edge of the BNNSs, which occurred due to the limited number of atomic layers and was confirmed further by x-ray diffraction (XRD) study. The experimental results clearly indicate that the values of the electrical conductivities of the super-thin BNNSs and the effect of temperature relied strongly on the direction of observation. PMID:26563901

  11. Variations in Crystalline Structures and Electrical Properties of Single Crystalline Boron Nitride Nanosheets

    PubMed Central

    Aldalbahi, Ali; Zhou, Andrew Feng; Feng, Peter

    2015-01-01

    We report the studies of (1) the basic mechanism underlying the formation of defect-free, single crystalline boron nitride nanosheets (BNNSs) synthesized using pulsed laser plasma deposition (PLPD) technique, (2) the variation in the crystalline structure at the edges of the hexagonal boron nitride (h-BN) nanosheets, and (3) the basic electrical properties related to the BNNSs tunneling effect and electrical breakdown voltage. The nanoscale morphologies of BNNSs are characterized using scanning electron microscope (SEM) and high-resolution transmission electron microscope (HRTEM). The results show that each sample consisted of a number of transparent BNNSs that partially overlapped one another. Varying the deposition duration yielded different thicknesses of sample but did not affect the morphology, structure, and thickness of individual BNNSs pieces. Analysis of the SEM and HRTEM data revealed changes in the spatial period of the B3–N3 hexagonal structures and the interlayer distance at the edge of the BNNSs, which occurred due to the limited number of atomic layers and was confirmed further by x-ray diffraction (XRD) study. The experimental results clearly indicate that the values of the electrical conductivities of the super-thin BNNSs and the effect of temperature relied strongly on the direction of observation. PMID:26563901

  12. Crystalline-crystalline phase transformation in two-dimensional In2Se3 thin layers.

    PubMed

    Tao, Xin; Gu, Yi

    2013-08-14

    We report, for the first time, the fabrication of single-crystal In2Se3 thin layers using mechanical exfoliation and studies of crystalline-crystalline (α → β) phase transformations as well as the corresponding changes of the electrical properties in these thin layers. Particularly, using electron microscopy and correlative in situ micro-Raman and electrical measurements, we show that, in contrast to bulk single crystals, the β phase can persist in single-crystal thin layers at room temperature (RT). The single-crystal nature of the layers before and after the phase transition allows for unambiguous determination of changes in the electrical resistivity. Specifically, the β phase has an electrical resistivity about 1-2 orders of magnitude lower than the α phase. Furthermore, we find that the temperature of the α → β phase transformation increases by as much as 130 K with the layer thickness decreasing from ~87 nm to ~4 nm. These single-crystal thin layers are ideal for studying the scaling behavior of the phase transformations and associated changes of the electrical properties. For these In2Se3 thin layers, the accessibility of the β phase at RT, with distinct electrical properties than the α phase, provides the basis for multilevel phase-change memories in a single material system.

  13. Highly viscous liquid crystalline mixtures: the alternative to liquid crystalline elastomers

    NASA Astrophysics Data System (ADS)

    Shibaev, Petr; Schlesier, Cristina; Newman, Leah; McDonald, Scott

    2012-02-01

    Novel highly viscous liquid crystalline materials based on mixtures of glass forming oligomers and low molar mass liquid crystals were recently designed [1, 2] and studied. In this communication the novel data are presented, the analysis and discussion are extended. It is shown that viscoelastic properties of the materials are due to the physical entanglements between cyclic oligomers and low molar mass mesogens, not due to the chemical crosslinks between molecular moities. However, the mechanical properties of these viscoelastic materials resemble those of chemically crosslinked elastomers (elasticity and reversibility of deformations). The properties of chiral and non-chiral materials loaded with ferromagnetic nanoparticles are discussed in detail. Cholesteric materials undergo gigantic color changes in the wide spectral range under the deformation that allows distant detection of deformation and determination the anisotropy of deformation and its type. The materials doped with laser dyes become mechanically tunable lasers themselves and emit coherent light while pumped by external laser. A simple model is suggested to account for the observed effects; physical properties of the novel materials and liquid crystalline elastomers are compared and discussed. [4pt] [1] P.V. Shibaev, C. Schlesier, R. Uhrlass, S. Woodward, E. Hanelt, Liquid Crystals, 37:12, 1601-1604 [0pt] [2] P.V. Shibaev, P. Riverra, D. Teter, S. Marsico, M. Sanzari, V. Ramakrishnan, E. Hanelt, Optics Express, 16, 2965 (2008)

  14. Uridine diphosphate galactose-4-epimerase. Uridine monophosphate-dependent reduction by alpha- and beta-D-glucose.

    PubMed

    Kang, U G; Nolan, L D; Frey, P A

    1975-09-25

    Rates of UMP-dependent reduction of the DPN+ associated with Escherichia coli UDP-galactose-4-epimerase at 27 degrees and 0.2 M ionic strength in 0.1 M Tris-HCl buffer, pH 8.5, are reported. The reaction exhibits excellent pseudo-first order behavior when D-glucose is at anomeric equilibrium. The effects of [UMP] and [glucose] on the observed first order rate constants are consistent with the following equation. The symbols phi are empirical parameters. (See article). The data indicate that the pathway involves random equilibrium binding of UMP and glucose followed by rate-limiting decomposition of the ternary complex to epimerase-DNPH. The binding parameters indicate that the principal activating effect of UMP is not simply to increase the affinity of the enzyme for glucose. UMP appears to increase the reactivity or availability of enzyme-bound DPN+. The kinetic isotope effect for the reaction of D-]1-2H]glucose (kH/kD) is 4.2, which confirms that C-1 is oxidized and that hydride transfer is rate limiting. Both of the purified anomers, alpha- and beta-D-glucose, reduce the enzyme-bound DPN+. As indicated by the deviations from pseudo-first order kinetics because of concurrent mutarotation, the beta anomer is the more reactive, reacting about 4 to 5 times faster than the alpha anomer at concentrations well below saturation. Is is suggested that the lack of stereo-specificity in this reaction may be attributed to the two anomers being productively bound with their opposite faces projecting toward C-4 of bound DPN+. Nonstereospecific oxidation of alpha- and beta-D-glucose may be a model for the mechanism of UDP-hexose epimerization, which also involves nonstereospecific hydride transfer.

  15. 3'5'-cyclic adenosine monophosphate-dependent up-regulation of phosphodiesterase type 3A in porcine cumulus cells.

    PubMed

    Sasseville, Maxime; Côté, Nancy; Vigneault, Christian; Guillemette, Christine; Richard, François J

    2007-04-01

    The means by which cumulus cells react to gonadotropin stimulation and regulate the subsequent production and degradation of cAMP are largely unknown. In this article, we report that cyclic nucleotide phosphodiesterase (PDE) type 3A (Pde3a) is transcriptionally regulated in porcine cumulus cells by a cAMP-dependent pathway during in vitro maturation (IVM). cAMP-PDE activity was increased in the cumulus-oocyte complex (COC) after 10 h of IVM, and 78% of this increase was sensitive to a Pde3-specific inhibitor, cilostamide. Although no variation was observed in the oocyte, cilostamide-sensitive cAMP-PDE activity increased in the cumulus cells after IVM. This was supported by Western blotting, which showed that the intensity of a 135-kDa anti-Pde3a immunoreactive band was increased in COC after IVM. The Pde3a mRNA level was up-regulated 28-fold in the COC after 4 h of IVM and remained high up to 12 h. The mRNA up-regulation and increased activity were inhibited by an RNA synthesis inhibitor, alpha-amanitin. The cilostamide-sensitive increase in PDE activity was inhibited by a protein synthesis inhibitor, cycloheximide. Pregnant mare serum gonadotropin (PMSG) caused dose-dependent activation of Pde3. The PMSG-dependent increase in Pde3 activity and Pde3a mRNA were mimicked by the adenylyl cyclase activator forskolin or prostaglandin E2. PMSG-dependent Pde3 activation was inhibited by the protein kinase A-specific inhibitor H89. Collectively, our results show for the first time that degradation of the intracellular cyclic nucleotide by Pde3a is transcriptionally up-regulated via a cAMP-dependent pathway in cumulus cells, suggesting that it has a functional role during the ovulatory gonadotropin surge.

  16. Lack of low-grade metamorphism in the Triassic formations of the Argana basin, Morocco: an illite crystallinity re-evaluation

    NASA Astrophysics Data System (ADS)

    Leikine, M.; Medina, F.; Ahmamou, M.

    1996-05-01

    Analysis of mineral assemblages and illite crystallinity of the Arganan Triassic formations show that: i) mixed-layers are present across almost all of the section; and ii) values of illite crystallinity are quite dispersed and lie mostly in the diagenetic zone, with no gradient related to burial. It is therefore concluded that, contrary to ideas proposed recently, there is no evidence for very low-grade metamorphism related to crustal thinning during the early rifting of the Central Atlantic. Fluctuations of illite crystallinity values are interpreted as due to complex interactions of detrital heritage and several factors governing illitization and improvement of illite crystallinity. The increase in temperature during burial constitutes only one of them.

  17. Spectroscopic studies on the riboflavin-sensitized conformational changes of calf lens alpha-crystallin.

    PubMed

    Andley, U P

    1988-04-01

    The change in conformation of calf lens alpha-crystallin by oxidation in the presence of the photosensitizer riboflavin and light has been investigated. Near-UV circular dichroism (CD) spectrum, absorption spectrum, tryptophan fluorescence yield and fluorescence lifetime of the SH-specific fluorescent probe, N-iodoacetyl-N'-(5-sulfo-1-naphtyl) ethylenediamine (1,5-IAEDANS), were significantly altered by irradiation in the presence of RF. In the initial stages of photolysis (1-2 hr), a slight degradation of the protein to lower molecular weight peptides was observed. Upon increased photolysis, intersubunit cross-linking to dimers and other high molecular weight species was observed. To determine the effects of cross-linking on the accessibility of the cysteine residues of the protein, lifetime quenching studies on the IAEDANS-labeled alpha-crystallin were performed. A decrease in the quenching constant (kappa q) in the photolysed sample indicates that the labeled SH groups are less susceptible to collisional quenching, which requires contact between the quencher and the excited state of the fluorophore, due to steric inhibition in the cross-linked protein. Cross-linking and the rate of loss of tryptophan fluorescence of alpha-crystallin diminished under anaerobic conditions and increased when D2O was used in the medium for irradiation. Use of inhibitors and quenchers of active species of oxygen suggests that photo-oxidation probably occurs via the action of singlet oxygen as well as substrate-sensitizer complexation.

  18. High-Fidelity Replica Molding of Glassy Liquid Crystalline Polymer Microstructures.

    PubMed

    Zhao, Hangbo; Wie, Jeong Jae; Copic, Davor; Oliver, C Ryan; Orbaek White, Alvin; Kim, Sanha; Hart, A John

    2016-03-01

    Liquid crystalline polymers have recently been engineered to exhibit complex macroscopic shape adaptivity, including optically- and thermally driven bending, self-sustaining oscillation, torsional motion, and three-dimensional folding. Miniaturization of these novel materials is of great interest for both fundamental study of processing conditions and for the development of shape-changing microdevices. Here, we present a scalable method for high-fidelity replica molding of glassy liquid crystalline polymer networks (LCNs), by vacuum-assisted replica molding, along with magnetic field-induced control of the molecular alignment. We find that an oxygen-free environment is essential to establish high-fidelity molding with low surface roughness. Identical arrays of homeotropic and polydomain LCN microstructures are fabricated to assess the influence of molecular alignment on the elastic modulus (E = 1.48 GPa compared to E = 0.54 GPa), and side-view imaging is used to quantify the reversible thermal actuation of individual LCN micropillars by high-resolution tracking of edge motion. The methods and results from this study will be synergistic with future advances in liquid crystalline polymer chemistry, and could enable the scalable manufacturing of stimuli-responsive surfaces for applications including microfluidics, tunable optics, and surfaces with switchable wetting and adhesion. PMID:26943057

  19. Geology, hydrology, and mineral resources of crystalline rock areas of the northeastern United States

    SciTech Connect

    Harrison, W.; Edgar, D.; Barosh, P.; Ebel, J.; Kuecher, G.; Tisue, M.; Tsai, S.; Winters, M.; Flower, M.; Sood, M.

    1983-10-01

    This report, which includes a series of maps, is a compendium of the available information on several topics of importance in defining the geologic setting of crystalline rocks in Maine, New Hampshire, Vermont, northeastern New York (the Adirondack Mountains), Massachusetts, Rhode Island, Connecticut, southeastern New York, northern New Jersey, and southeastern Pennsylvania. Crystalline rocks are defined herein as bodies of medium- to coarse-grained igneous and high-grade metamorphic rocks. The study was undertaken to provide background information to assist in evaluating the geologic suitability of such rocks for isolating high-level radioactive waste. Topics covered include the geologic history of the region; patterns of earthquake occurrence, earthquake magnitudes and horizontal ground accelerations, crustal stress, regional fault domains, and Holocene faulting and vertical crustal movements; surface processes, anticipated climatic changes, and possible effects of renewed glaciation; landforms and surficial deposits; regional surface-water and ground-water hydrology; and the commercial potential of rock and mineral prospects and mines located within or near crystalline-rock complexes. 68 figures, 35 tables.

  20. A large multigene family codes for the polypeptides of the crystalline trichocyst matrix in Paramecium.

    PubMed Central

    Madeddu, L; Gautier, M C; Vayssié, L; Houari, A; Sperling, L

    1995-01-01

    The secretory granules (trichocysts) of Paramecium are characterized by a highly constrained shape that reflects the crystalline organization of their protein contents. Yet the crystalline trichocyst content is composed not of a single protein but of a family of related polypeptides that derive from a family of precursors by protein processing. In this paper we show that a multigene family, of unusually large size for a unicellular organism, codes for these proteins. The family is organized in subfamilies; each subfamily codes for proteins with different primary structures, but within the subfamilies several genes code for nearly identical proteins. For one subfamily, we have obtained direct evidence that the different members are coexpressed. The three subfamilies we have characterized are located on different macronuclear chromosomes. Typical 23-29 nucleotide Paramecium introns are found in one of the regions studied and the intron sequences are more variable than the surrounding coding sequences, providing gene-specific markers. We suggest that this multigene family may have evolved to assure a microheterogeneity of structural proteins necessary for morphogenesis of a complex secretory granule core with a constrained shape and dynamic properties: genetic analysis has shown that correct assembly of the crystalline core is necessary for trichocyst function. Images PMID:7579685