Science.gov

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. Surface complexation modeling of uranium(VI) sorbed onto lanthanum monophosphate.

    PubMed

    Ordoñez-Regil, E; Drot, R; Simoni, E

    2003-07-15

    Sorption/desorption are basic processes in the field of contaminant transport. In order to develop mechanistically accurate thermodynamic sorption models, the simulation of retention data has to take into account molecular scale informations provided by structural investigations. In this way, the uranyl sorption constants onto lanthanum monophosphate (LaPO(4)) were determined on the basis of a previously published structural investigation. The surface complexation modeling of U(VI) retention onto LaPO(4) has been performed using the constant capacitance model included in the FITEQLv3.2 program. The electrical behavior of the solid surface was investigated using electrophoretic measurements and potentiometric titration experiments. The point of zero charge was found to be 3.5 and surface complexation modeling has made it possible to calculate the surface acidity constants. The fitting procedure was done with respect to the spectroscopic results, which have shown that LaPO(4) presents two kinds of reactive surface sites (lanthanum atoms and phosphate groups). The uranyl sorption edges were determined for two surface coverages: 40 and 20% of the surface sites that are occupied, assuming complete sorption. The modeling of these experimental data was realized by considering two uranyl species ("free" uranyl and uranyl nitrate complex) sorbed only onto phosphate surface groups according to the previously published structural investigation. The obtained sorption constants present similar values for both surface complexes and make it possible to fit both sorption edges: logK(U)=9.4 for z.tbnd;P(OH)(2)+UO(2)(2+)<-->z.tbnd;P(OH)(2)UO(2)(2+) and logK(UN)=9.7 for z.tbnd;P(OH)(2)+UO(2)NO(3)(+)<-->z.tbnd;P(OH)(2)UO(2)NO(3)(+). PMID:12909028

  4. Complexes of Cu(II) Ions and Noncovalent Interactions in Systems with L-Aspartic Acid and Cytidine-5'-Monophosphate

    PubMed Central

    Bregier-Jarzebowska, Romualda; Gasowska, Anna; Lomozik, Lechosław

    2008-01-01

    Interactions between aspartic acid (Asp) and cytidine-5-monophosphate (CMP) in metal-free systems as well as the coordination of Cu(II) ions with the above ligands were studied. The composition and overall stability constants of the species formed in those systems were determined by the potentiometric method, and the interaction centres in the ligands were identified by the spectral methods UV-Vis, EPR, NMR, and IR. In metal-free systems, the formation of adducts, in which each ligand has both positive and negative reaction centres, was established. The main reaction centres in Asp are the oxygen atoms of carboxyl groups and the nitrogen atom of the amine group, while the main reaction centre in CMP at low pH is the N(3) atom. With increasing pH, the efficiency of the phosphate group of the nucleotide in the interactions significantly increases, and the efficiency of carboxyl groups in Asp decreases. The noncovalent reaction centres in the ligands are simultaneously the potential sites of metal-ion coordination. The mode of coordination in the complexes formed in the ternary systems was established. The sites of coordination depend clearly on the solution pH. In the molecular complexes ML⋯L, metallation involves the oxygen atoms of the carboxyl groups of the amino acid, while the protonated nucleotide is in the outer coordination sphere and interacts noncovalently with the anchoring CuHx(Asp) species. The influence of the metal ions on the weak interactions between the biomolecules was established. PMID:18682818

  5. Bacillus anthracis Inosine 5′-Monophosphate Dehydrogenase in Action: The First Bacterial Series of Structures of Phosphate Ion-, Substrate-, and Product-Bound Complexes

    PubMed Central

    Makowska-Grzyska, Magdalena; Kim, Youngchang; Wu, Ruiying; Wilton, Rosemarie; Gollapalli, Deviprasad R.; Wang, Ximi K.; Zhang, Rongguang; Jedrzejczak, Robert; Mack, Jamey C.; Maltseva, Natalia; Mulligan, Rory; Binkowski, T. Andrew; Gornicki, Piotr; Kuhn, Misty L.; Anderson, Wayne F.; Hedstrom, Lizbeth; Joachimiak, Andrzej

    2013-01-01

    Inosine 5′-monophosphate dehydrogenase (IMPDH) catalyzes the first unique step of the GMP branch of the purine nucleotide biosynthetic pathway. This enzyme is found in organisms of all three kingdoms. IMPDH inhibitors have broad clinical applications in cancer treatment, as antiviral drugs and as immunosuppressants, and have also displayed antibiotic activity. We have determined three crystal structures of Bacillus anthracis IMPDH, in a phosphate ion-bound (termed “apo”) form and in complex with its substrate, inosine 5′-monophosphate (IMP), and product, xanthosine 5′-monophosphate (XMP). This is the first example of a bacterial IMPDH in more than one state from the same organism. Furthermore, for the first time for a prokaryotic enzyme, the entire active site flap, containing the conserved Arg-Tyr dyad, is clearly visible in the structure of the apoenzyme. Kinetic parameters for the enzymatic reaction were also determined, and the inhibitory effect of XMP and mycophenolic acid (MPA) has been studied. In addition, the inhibitory potential of two known Cryptosporidium parvum IMPDH inhibitors was examined for the B. anthracis enzyme and compared with those of three bacterial IMPDHs from Campylobacter jejuni, Clostridium perfringens, and Vibrio cholerae. The structures contribute to the characterization of the active site and design of inhibitors that specifically target B. anthracis and other microbial IMPDH enzymes. PMID:22788966

  6. A crystalline σ complex of copper.

    PubMed

    Gualco, Pauline; Amgoune, Abderrahmane; Miqueu, Karinne; Ladeira, Sonia; Bourissou, Didier

    2011-03-30

    Over the last decades, our understanding of σ-bond activation at transition metals has progressed considerably from both fundamental and synthetic points of view thanks to the preparation and characterization of a variety of σ complexes. Here we report the synthesis and structural analysis of the first σ complex involving a coinage metal. The copper(I) complex 2 derived from the diphosphine-disilane [Ph(2)P(C(6)H(4))Me(2)Si-SiMe(2)(C(6)H(4))PPh(2)] (1) has been isolated and crystallographically characterized. The coordination of the Si-Si σ bond to copper was thoroughly analyzed by quantum-chemical methods. PMID:21381745

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. A gadolinium(iii) complex that shows room-temperature phosphorescence in the crystalline state.

    PubMed

    Nakai, Hidetaka; Kitagawa, Kazuhiro; Seo, Juncheol; Matsumoto, Takahiro; Ogo, Seiji

    2016-07-19

    This paper presents a gadolinium(iii) complex that shows blue phosphorescence in the crystalline state at room temperature under air atmosphere; color of the crystals can be changed to pale-green from blue by doping of 1-naphthol. PMID:27221814

  15. 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.

  16. Thermodynamic functions of formation of n-alkane complexes with crystalline urea

    SciTech Connect

    Tolmachev, V.V.; Semenov, L.V.; Gaile, A.A.; Proskuryakov, V.A.

    1987-07-10

    For optimization of the conditions of deparaffination of petroleum fractions with the aid of urea, with the composition of the feedstock taken into account, it is important to know the equilibrium constants of formation of complexes of urea with n-alkanes differing in the number of carbon atoms in their molecules, as functions of temperature. In this investigation they obtained experimental data necessary for calculating the thermodynamic functions of formation of n-alkane complexes with crystalline urea up to the decomposition temperature, using Kirchhoff's equations.

  17. 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.

  18. 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.

  19. A liquid crystalline supramolecular complex of C60 with a cyclotriveratrylene derivative

    PubMed

    Felder; Heinrich; Guillon; Nicoud; Nierengarten

    2000-10-01

    Cyclotriveratrylene (CTV) derivatives substituted with 9 (1) or 18 (2) long alkyl chains have been prepared. Whereas no liquid crystalline behavior has been observed for 1, the CTV derivative 2 has mesomorphic properties. Indeed, at room temperature compound 2 exhibits a nematic phase characterized by cybotactic groups with a local lamello-columnar order. Both CTV derivatives 1 and 2 are able to form supramolecular complexes with C60 in the solid state. In both cases, the 2:1 host-guest species have been obtained as brown compounds. No liquid crystalline behavior was observed for the supramolecular complex [C60 is included in (1)2]. In contrast, observation of the brown product obtained from C60 and the CTV derivative 2 directly after preparation by polarized optical microscopy revealed a fluid birefringent phase at room temperature. When the sample is heated above 70 degrees C, the birefringence of the texture under the microscope disappears and the X-ray diffraction pattern is transformed into a pattern characteristic of a cubic phase. For the first time in thermotropic liquid crystals, the space group of this cubic phase can be assigned as I4(1)32. PMID:11072814

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

    DOE PAGESBeta

    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

  1. 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

  2. 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

  3. 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. PMID:26053762

  4. 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.

  5. 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 ...

  6. Optical enrichment of dansyl-rac-amino acids by formation of crystalline inclusion complexes with cyclodextrins.

    PubMed

    Jin, H L; Stalcup, A; Armstrong, D W

    1989-01-01

    Optical enrichment from racemic dansyl-leucine, dansyl-norleucine, and dansyl-phenylalanine with both beta- and gamma-cyclodextrins in water is reported. Initial crystallization yielded the dansyl-L-Leucine isomer complexed in excess with beta-cyclodextrin with an optical purity of 62-78% depending on experimental conditions. The optical purities obtained for L-norleucine and L-phenylalanine were 71 and 64%, respectively. The optical purity can be increased with continued recrystallization. The dansyl-D-leucine isomer was obtained in the mother liquor with an optical purity of 54-93% depending on experimental conditions. The optical purities obtained for D-norleucine and D-phenylalanine were 72 and 58%. The optical purity of the isomer depended on the molar ratio of host:guest and the pH value of the solution. Optimum enrichment of both enantiomers was achieved with host:guest ratios of 2:1 and 3:1. Although maximum crystalline yield of the dansyl-leucine/CD inclusion complex was obtained at a pH of 3.5, optical purity of both enantiomers was less than that obtained at other pHs. The influence of the molar ratio of host:guest and the pH value of the solution are discussed. This method is suitable for large-scale enantiomeric separations. PMID:2642042

  7. 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.

  8. 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.

  9. Encapsulation of CO2 into amorphous and crystalline α-cyclodextrin powders and the characterization of the complexes formed.

    PubMed

    Ho, Thao M; Howes, Tony; Bhandari, Bhesh R

    2015-11-15

    Carbon dioxide complexation was undertaken into solid matrices of amorphous and crystalline α-cyclodextrin (α-CD) powders, under various pressures (0.4-1.6 MPa) and time periods (4-96 h). The results show that the encapsulation capacity of crystalline α-CD was significantly lower than that of amorphous α-CD at low pressure and short time (0.4-0.8 MPa and 4-24 h), but was markedly enhanced with an increase of pressure and prolongation of encapsulation time. For each pressure level tested, the time required to reach a near equilibrium encapsulation capacity of the crystalline powder was around 48 h, which was much longer than that of the amorphous one, which only required about 8h. The inclusion complex formation of both types of α-CD powders was confirmed by the appearance of a CO2 peak on the FTIR and NMR spectra. Moreover, inclusion complexes were also characterized by DSC, TGA, SEM and X-ray analyses. PMID:25977044

  10. 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

  11. 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

  12. 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

  13. 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

  14. New crystalline complex metal oxides created by unit-synthesis and their catalysis based on porous and redox properties.

    PubMed

    Zhang, Zhenxin; Ishikawa, Satoshi; Tsuboi, Yuta; Sadakane, Masahiro; Murayama, Toru; Ueda, Wataru

    2016-07-01

    The development of new complex metal oxides having structural complexity suitable for solid-state catalysis is of great importance in fundamental catalysis research and practical applications. However, examples of these materials are rare. Herein, we report two types of crystalline complex metal oxides with new structures and their catalytic properties. The first one is an all-inorganic ε-Keggin polyoxometalate-based material with intrinsic microporosity. The framework of the material is formed by the assembly of ε-Keggin polyoxomolybdate units with metal ion linkers in a diamondoid topology. The micropores of the material can be opened without change of the structures, and the material adsorbs small molecules. This material has both redox properties and acidity and can be applied to O2 adsorption, selective oxidation of methacrolein, and hydrolysis of cellobiose. The other material is a crystalline metal oxide based on molecular nanowires. The hexagonal POM units stack along the c axis to form prismatic clusters as molecular wires. The molecular wires further assemble in a hexagonal fashion to form the crystals, and NH4(+) and water are present in between the molecular wires. The material is active as an acid catalyst for cellobiose conversion. PMID:27146122

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

    NASA Astrophysics Data System (ADS)

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

    1988-03-01

    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.

  16. Crystalline sulfur dioxide: Crystal field splittings, absolute band intensities, and complex refractive indices derived from infra-red spectra

    NASA Astrophysics Data System (ADS)

    Khanna, R. K.; Zhao, Guizhi; Ospina, M. J.; Pearl, J. C.

    The infra-red absorption spectra of thin crystalline films of sulfur dioxide at 90 K are reported in the 2700-450 cm -1 region. The observed multiplicity of the bands in the regions of fundamental modes is attributed to crystal field effects, including factor group and LO—TO splittings, and naturally present minor 34S, 36S and 18O substituted 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.

  17. 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.

  18. 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

  19. Post-Translational Regulation of the Glucose-6-Phosphatase Complex by Cyclic Adenosine Monophosphate Is a Crucial Determinant of Endogenous Glucose Production and Is Controlled by the Glucose-6-Phosphate Transporter.

    PubMed

    Soty, Maud; Chilloux, Julien; Delalande, François; Zitoun, Carine; Bertile, Fabrice; Mithieux, Gilles; Gautier-Stein, Amandine

    2016-04-01

    The excessive endogenous glucose production (EGP) induced by glucagon participates in the development of type 2 diabetes. To further understand this hormonal control, we studied the short-term regulation by cyclic adenosine monophosphate (cAMP) of the glucose-6-phosphatase (G6Pase) enzyme, which catalyzes the last reaction of EGP. In gluconeogenic cell models, a 1-h treatment by the adenylate cyclase activator forskolin increased G6Pase activity and glucose production independently of any change in enzyme protein amount or G6P content. Using specific inhibitors or protein overexpression, we showed that the stimulation of G6Pase activity involved the protein kinase A (PKA). Results of site-directed mutagenesis, mass spectrometry analyses, and in vitro phosphorylation experiments suggested that the PKA stimulation of G6Pase activity did not depend on a direct phosphorylation of the enzyme. However, the temperature-dependent induction of both G6Pase activity and glucose release suggested a membrane-based mechanism. G6Pase is composed of a G6P transporter (G6PT) and a catalytic unit (G6PC). Surprisingly, we demonstrated that the increase in G6PT activity was required for the stimulation of G6Pase activity by forskolin. Our data demonstrate the existence of a post-translational mechanism that regulates G6Pase activity and reveal the key role of G6PT in the hormonal regulation of G6Pase activity and of EGP. PMID:26958868

  20. The effect of PEG molecular weights on the thermal stability and dissolution behaviors of griseofulvin-PEG crystalline inclusion complexes.

    PubMed

    Yang, Xiaotong; Zhong, Zhi; Huang, Yanbin

    2016-07-11

    Co-crystals formed between small molecular drugs and hydrophilic co-formers have shown great potential to optimize the dissolution profiles of drug substances. So far most of the co-formers used are small molecules. However, linear polymers are also able to form drug-polymer crystalline inclusion complexes (ICs). In contrast to the small molecular co-formers, molecular weight of the polymer co-formers can be easily changed without disrupting the IC crystal structure, and hence represents an interesting approach to tune the IC properties. In this study, we investigated the effect of PEG molecular weights on the thermal stability and dissolution behavior of Gris-PEG ICs. It was found that the thermal stability of Gris-PEG IC crystals first increased with PEG molecular weight, and then reached a plateau value, while an optimized PEG molecular weight existed for the dissolution profile. The experimental results were explained by the formation of two types of crystal defects during the IC growth in PEG melt: the void defects and the grain boundary defects. This is the first study on the pharmaceutical profiles of drug-polymer crystalline inclusion complexes. PMID:27173824

  1. Quantification of Outer-Sphere Macrochelate Formation in the Ternary cis-Diammine-Platinum(II)-Bis-2'-deoxyguanosine 5'-Monophosphate Complex, cis-(NH(3))(2)Pt(dGMP)(2)(2)(-), and Formation of Quaternary Mixed Metal Ion Species with Magnesium(II), Copper(II), or Zinc(II) in Aqueous Solution.

    PubMed

    Song, Bin; Oswald, Gerda; Zhao, Jing; Lippert, Bernhard; Sigel, Helmut

    1998-09-21

    The acid-base properties of cis-(NH(3))(2)Pt(dG)(2)(2)(-), where both dG(2)(-) (=2'-deoxyguanosine 5'-monophosphate) are N7-coordinated to the same Pt(II) [the complex is abbreviated as Pt(dG)(2)(2)(-)], are summarized [on the basis of potentiometric pH titration data from B. Song et al. (Metal-Based Drugs 1996, 3, 131-141)] and a micro acidity constant scheme is developed which allows quantification of the intrinsic acidity of the two P(O)(2)(OH)(-) groups present in this ternary complex (I = 0.1 M, NaNO(3); 25 degrees C). On the basis of comparisons with the corresponding acid-base properties of cis-(NH(3))(2)Pt(dCMP.H-N3)(2) [(dCMP.H)(-) = phosphate-monoprotonated 2'-deoxycytidine 5'-monophosphate] it is concluded that intramolecular, outer-sphere macrochelates form via Pt(NH(3)).O(3)P hydrogen bonds. The formation degree of these macrochelates is quantified; it amounts in aqueous solution in each case (in its lower limit) to about 40% for the various possibilities which exist for the formation of these chelates in the cis-(NH(3))(2)Pt(dG)(2) complexes. The stability constants of the mixed metal ion complexes, M[Pt(H;dG)(dG)](+) and M[Pt(dG)(2)], were also determined via potentiometric pH titrations. On the basis of previous measurements with simple phosphate monoesters and phosphonate derivatives, i.e., R-PO(3)(2)(-) with R being a noncoordinating residue (Sigel, H.; et al., Helv. Chim. Acta 1992, 75, 2634-2656), it is shown that the stability of the two mixed metal ion complexes is largely governed by the basicity of the phosphate groups (as quantified via the mentioned microconstants) indicating that the effect of the N7-bound Pt(II) on the phosphate-metal ion binding properties is relatively small. These results suggest that, e.g., a metal ion bound to a nucleobase residue in a nucleotide or in a nucleic acid affects only slightly the metal ion binding capabilities of its phosphate residue or its phosphate backbone. PMID:11670649

  2. 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

  3. 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

  4. 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.

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

    NASA Astrophysics Data System (ADS)

    Bhargavi, R.; Nair, Geetha G.; Krishna Prasad, S.; Majumdar, R.; Bag, Braja G.

    2014-10-01

    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.

  6. 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.

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

    PubMed

    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

    2015-12-01

    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(Tren(TIPS) )}2 (μ-η(2) :η(2) -As2 H2 )] (3, Tren(TIPS) =N(CH2 CH2 NSiPr(i) 3 )3 ; Pr(i) =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

  8. 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

  9. 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

  10. Investigation of Water Nucleation on Designed Single Crystalline Oxide Surfaces - a Step Towards Understanding the Complex Behavior of Atmospheric Aerosols

    NASA Astrophysics Data System (ADS)

    Du, Y.; Wang, B.; Lyubinetsky, I.; Laskin, A.; Kulkarni, G.; Knopf, D. A.; Guenther, A. B.

    2014-12-01

    The interaction between water molecules and solid surfaces during water/ice nucleation is of extreme importance in physical, biological, geological, and environmental research. Aerosols in the atmosphere, including inorganic mineral dust particles and organic compounds from biogenic and anthropogenic sources, are recognized to be effective ice nuclei (IN) that lead to the formation of ice crystals. These ice crystals play important roles in climate through their interactions with solar and terrestrial radiation. However, a detailed understanding is hampered by the fact that the aerosols vary in size, chemical composition, morphology, crystal orientation, and local defects. In EMSL, some of those challenges can be addressed by utilizing state-of-the-art synthesis and characterization capabilities. By using molecular beam epitaxy (MBE), we are able to synthesis materials, such as TiO2 and Fe2O3, that are commonly found in mineral dusts in their single crystalline thin film form with controlled surface termination. Fundamental studies on these designed surfaces allow us to vary some of the variables independently so that a concrete cause and effect relationship can be established. In this study, we grow epitaxial rutile TiO2(110) and anatase TiO2(001) films and investigate water adsorption and water nucleation processes on these surfaces by ultra-high vacuum scanning tunneling microscopy (STM) and environmental scanning electron microscopy (E-SEM). The surface reaction dynamics revealed can be of critical importance in understanding the water/ice nucleation process on complex aerosols.

  11. 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

  12. Evidence for intramolecular aromatic-ring stacking in the physiological pH range of the monodeprotonated xanthine residue in mixed-ligand complexes containing xanthosinate 5'-monophosphate (XMP).

    PubMed

    Sigel, Helmut; Operschall, Bert P; Massoud, Salah S; Song, Bin; Griesser, Rolf

    2006-12-14

    The stability constants of the mixed-ligand complexes formed between Cu(Arm)2+ [Arm = 2,2'-bipyridine (Bpy) or 1,10-phenanthroline (Phen)], and the di- or trianion of xanthosine 5'-monophosphoric acid [= XMP(2-) or (XMP - H)(3-)] were determined by potentiometric pH titration in aqueous solution (25 degrees C; I = 0.1 M, NaNO3). Those for the monoanion, i.e., the Cu(Arm)(H;XMP)+ complexes, could only be estimated; for these species it is concluded that the metal ion is overwhelmingly bound at N7 and the proton resides at the phosphate group. Similarly, in the Cu(Arm)(XMP)+/- [= Cu(Arm)(X - H.MP.H)+/-] complexes Cu(Arm)2+ is also at N7 but the xanthine residue has lost a proton whereas the phosphate group still carries one, i.e., stacking plays, if at all, only a very minor role, yet, the N7-bound Cu(Arm)2+ appears to form an outer-sphere macrochelate with P(O)2(OH)-, its formation degree being about 60%. All this is different in the Cu(Arm)(XMP - H)- complexes, which are formed by the (XMP - H)(3-) species, that occur at the physiological pH of 7.5 and for which previously evidence has been provided that in a tautomeric equilibrium the xanthine moiety loses a proton either from (N1)H or (N3)H. In Cu(Arm)(XMP - H)- the phosphate group is the primary binding site for Cu(Arm)2+ and the observed increased complex stability is mainly due to intramolecular stack (st) formation between the aromatic-ring systems of Phen or Bpy and the monodeprotonated xanthine residue of (XMP - H)(3-); e.g., the stacked Cu(Phen)(XMP - H) isomer occurs with approximately 76%. Regarding biological systems the most important result is that at physiological pH the xanthine moiety has lost a proton from the (N1)H/(N3)H sites forming (XMP - H)(3-) and that its anionic xanthinate residue is able to undergo aromatic-ring stacking. PMID:17117222

  13. Lanthanum inhibition of Vibrio cholerae and Escherichia coli enterotoxin-induced enterosorption and its effects on intestinal mucosa cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate levels.

    PubMed Central

    Leitch, G J; Amer, M S

    1975-01-01

    Several trivalent cations, including lanthanum (La3+), inhibited the secretion (enterosorption) induced by the enterotoxins of Vibrio cholerae and Escherichia coli in the rabbit ileum in vivo. High concentrations (greater than 10 mM) of La3+ were required to inhibit cholera enterotoxin (CE)-induced enterosorption, probably because of the adsorption of the La3+ often potentiated the CE-induced enterosorption. If luminal La3+ exposure followed CE exposure, some recovery of the enterosorptive response was observed. The longer the lag between the CE exposure and the La3+ exposure, the greater was the recovery of the enterosorptive response. Lanthanum inhibited HCO3- secretion more than Cl- secretion. By altering the luminal fluid pH at the time of La3+ exposure, it was found that La3+ was adsorbed to negatively charged luminal sites, having an apparent pK between 2.5 and 3.0. Although La3+ antagonized the enterosorptive response to CE, it mimicked rather than antagonized the cyclic adenosine 3',5'-monophosphate elevation and cyclic guanosine 3',5'-monophosphate depression induced by the toxin. It is therefore concluded that the La3+ inhibition of the CE-induced enterosorption must have occurred at a site following the generation of the cyclic nucleotides. Cholera enterotoxin caused complex time-dependent changes in the mucosal cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate levels, as revealed by studying tissue cyclic adenosine 3',5'-monophosphate/cyclic guanosine 3',5'-monophosphate ratios. The possible roles these two cyclic nucleotides may play in the pathogenesis of the cholera diarrhea are discussed. PMID:164410

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

    PubMed

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

    1989-09-01

    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

  15. Cyclic adenosine monophosphate phosphodiesterase in brain: effect on anxiety.

    PubMed

    Beer, B; Chasin, M; Clody, D E; Vogel, J R

    1972-04-28

    Drugs that reduce anxiety may be mediated by cyclic adenosine monophosphate in the brain because (i) potent anxiety-reducing drugs are also potent inhibitors of brain phosphodiesterase activity; (ii) dibutyryl cyclic adenosine monophosphate has the ability to reduce anxiety; (iii) the methylxanthines show significant anxiety-reducing effects; (iv) theophylline and chlordiazepoxide produce additive anxiety-reducing activity; and (v) there is a significant correlation between the anxiety-reducing property of drugs and their ability to inhibit phosphodiesterase activity in the brain. PMID:4402069

  16. Hydrolytic effects of scaffolding proteins CbpB and CbpC on crystalline cellulose mediated by the major cellulolytic complex from Clostridium cellulovorans.

    PubMed

    Jeon, Sang Duck; Kim, Su Jung; Park, Sung Hyun; Choi, Gi-Wook; Han, Sung Ok

    2015-09-01

    The role of the scaffolding proteins, cellulose binding protein B and C (CbpB and CbpC, respectively) were identified in cellulolytic complex (cellulosome) of Clostridium cellulovorans for efficient degradation of cellulose. Recombinant CbpB and CbpC directly anchored to the cell surface of C. cellulovorans. In addition, CbpB and CbpC showed increased hydrolytic activity on crystalline cellulose incubated with exoglucanase S (ExgS) and endoglucanase Z (EngZ) compared with the activity of free enzymes. Moreover, the results showed synergistic effects of crystalline cellulose hydrolytic activity (1.8- to 2.2-fold) when CbpB and CbpC complex with ExgS and EngZ are incubated with cellulolytic complex containing mini-CbpA. The results suggest C. cellulovorans critically uses CbpB and CbpC, which can directly anchor cells for the hydrolysis of cellulosic material with the major cellulosome complex. PMID:25748018

  17. Single-walled carbon nanotube-induced crystallinity on the electropolymeric film of tetraaminophthalocyaninatonickel(II) complex: Impact on the rate of heterogeneous electron transfer

    NASA Astrophysics Data System (ADS)

    Pillay, Jeseelan; Ozoemena, Kenneth I.

    2007-06-01

    We present a fundamental investigation on the impact of single-walled carbon nanotube (SWCNT) on the film structure and redox behaviour of tetraaminophthalocyaninatonickel(II) complex (NiTAPc) electropolymer immobilized on a basal plane pyrolytic graphite electrode (BPPGE). SWCNT induces crystallinity on the NiTAPc electropolymeric film structure and increases its apparent electron transfer rate constant ( kapp). We proved that there is potential advantage of using electrode based on the SWCNT- poly-NiTAPc hybrid for catalytic and sensing applications as it enhances the catalytic current for the detection of nitric oxide more than twice compared to bare BPPGE, BPPGE-SWCNT and other electrodes without SWCNTs.

  18. 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

  19. 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. PMID:25907694

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

    DOE PAGESBeta

    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

  1. 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

  2. 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.

  3. The crystal structure and mechanism of orotidine 5'-monophosphate decarboxylase.

    PubMed

    Appleby, T C; Kinsland, C; Begley, T P; Ealick, S E

    2000-02-29

    The crystal structure of Bacillus subtilis orotidine 5'-monophosphate (OMP) decarboxylase with bound uridine 5'-monophosphate has been determined by multiple wavelength anomalous diffraction phasing techniques and refined to an R-factor of 19.3% at 2.4 A resolution. OMP decarboxylase is a dimer of two identical subunits. Each monomer consists of a triosephosphate isomerase barrel and contains an active site that is located across one end of the barrel and near the dimer interface. For each active site, most of the residues are contributed by one monomer with a few residues contributed from the adjacent monomer. The most highly conserved residues are located in the active site and suggest a novel catalytic mechanism for decarboxylation that is different from any previously proposed OMP decarboxylase mechanism. The uridine 5'-monophosphate molecule is bound to the active site such that the phosphate group is most exposed and the C5-C6 edge of the pyrimidine base is most buried. In the proposed catalytic mechanism, the ground state of the substrate is destabilized by electrostatic repulsion between the carboxylate of the substrate and the carboxylate of Asp60. This repulsion is reduced in the transition state by shifting negative charge from the carboxylate to C6 of the pyrimidine, which is close to the protonated amine of Lys62. We propose that the decarboxylation of OMP proceeds by an electrophilic substitution mechanism in which decarboxylation and carbon-carbon bond protonation by Lys62 occur in a concerted reaction. PMID:10681442

  4. 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

  5. Time- and Space-Resolved SAXS Experiments Inform on Phase Transition Kinetics in Hydrated, Liquid-Crystalline Films of Polyion-Surfactant Ion "Complex Salts".

    PubMed

    Li, Joaquim; Gustavsson, Charlotte; Piculell, Lennart

    2016-05-24

    Detailed time- and space-resolved SAXS experiments show the variation with hydration of liquid crystalline structures in ethanol-cast 5-80 μm thick films of polyion-surfactant ion "complex salts" (CS). The CS were dodecyl- (C12) or hexadecyl- (C16) trimethylammonium surfactants with polyacrylate (DP 25 or 6000) counter-polyions. The experiments were carried out on vertical films in humid air above a movable water bath, so that gradients of hydration were generated, which could rapidly be altered. Scans over different positions along a film, kept fixed relative to the bath, showed that the surfactant aggregates of the various liquid-crystalline CS structures grow in cross-sectional area with decreasing hydration. This behavior is attributed to the low water content. Studies of films undergoing rapid dehydration, made possible by the original experimental setup, gave strong evidence that some of the investigated systems remain kinetically trapped for minutes in a nonequilibrium Pm3n micellar cubic phase before switching to the equilibrium P6mm 2D hexagonal phase. Both the length of the polyion and the length of the surfactant hydrocarbon "tail" affect the kinetics of the phase transition. The slowness of the cubic-to-hexagonal structural transition is attributed to the fact that it requires major rearrangements of the polyions and surfactant ions relative to each other. By contrast, other structure changes, such as between the hexagonal and rectangular phases, were observed to occur much more rapidly. PMID:27153140

  6. Novel crystalline phase and first-order phase transitions of human insulin complexed with two distinct phenol derivatives.

    PubMed

    Valmas, A; Magiouf, K; Fili, S; Norrman, M; Schluckebier, G; Beckers, D; Degen, T; Wright, J; Fitch, A; Gozzo, F; Giannopoulou, A E; Karavassili, F; Margiolaki, I

    2015-04-01

    The primary focus of the present work is the study of the effects that two ligands and the crystallization pH have on the crystalline forms of human insulin. For this purpose, human insulin (HI) was co-crystallized with two distinct phenolic derivatives: the organic ligands meta-cresol (m-cresol) and 4-nitrophenol. The formation of polycrystalline precipitates was then followed by means of structural characterization of the individual specimens in terms of unit-cell symmetry and parameters. In both cases, two different polymorphs were identified via X-ray powder diffraction measurements, the first of hexagonal symmetry (R3 space group) at higher pH values and the second of monoclinic symmetry (space group P21) with unit-cell parameters a = 87.4282 (5), b = 70.5020 (3), c = 48.3180 (4) Å, β = 106.8958 (4)°, the latter of which to our knowledge has never been observed before. PMID:25849393

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. HspB5/αB-crystallin increases dendritic complexity and protects the dendritic arbor during heat shock in cultured rat hippocampal neurons.

    PubMed

    Bartelt-Kirbach, Britta; Moron, Margarethe; Glomb, Maximilian; Beck, Clara-Maria; Weller, Marie-Pascale; Golenhofen, Nikola

    2016-10-01

    The small heat shock protein ΗspΒ5 (αB-crystallin) exhibits generally cytoprotective functions and possesses powerful neuroprotective capacity in the brain. However, little is known about the mode of action of ΗspΒ5 or other members of the HspB family particularly in neurons. To get clues of the neuronal function of HspBs, we overexpressed several HspBs in cultured rat hippocampal neurons and investigated their effect on neuronal morphology and stress resistance. Whereas axon length and synapse density were not affected by any HspB, dendritic complexity was enhanced by HspB5 and, to a lesser extent, by HspB6. Furthermore, we could show that this process was dependent on phosphorylation, since a non-phosphorylatable mutant of HspB5 did not show this effect. Rarefaction of the dendritic arbor is one hallmark of several neurodegenerative diseases. To investigate if HspB5, which is upregulated at pathophysiological conditions, might be able to protect dendrites during such situations, we exposed HspB5 overexpressing neuronal cultures to heat shock. HspB5 prevented heat shock-induced rarefaction of dendrites. In conclusion, we identified regulation of dendritic complexity as a new function of HspB5 in hippocampal neurons. PMID:27085702

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

    PubMed

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

    2012-12-01

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

  13. Paleoproterozoic sequences and magmatic complexes of the Losevo suture zone of the Voronezh crystalline massif: Geological position, material composition, geochemistry, and paleogeodynamics

    NASA Astrophysics Data System (ADS)

    Terentiev, R. A.

    2014-03-01

    In order to resolve the contradictions associated with uncertainty in the identification of the material composition, subdivision, and conditions of formation of the Paleoproterozoic intrusive, metavolcanogenic, and metasedimentary sequences of the Losevo suture zone of the Voronezh crystalline massif, this work presents geological, petrographic, petrochemical, and geochemical features of these sequences. The stratigraphic and magmatic scheme of the central part of the Losevo suture zone is clarified. In particular, the Paleoproterozoic Losevo Series is divided into two sequences: Strelitsa (marginal sea) and Podgornoe (island arc). A new hypabyssal Novo-Voronezh metagabbro-diabase complex, comagmatic to metatholeiites of the Podgornoe sequence, is distinguished. The isotope age of the Strelitsa sequence is assumed to be 2172 ± 17 Ma on the basis of the results of age dating of zircon cores from the Usman plagiogranites, intruding this sequence. The upper age boundary of the Strelitsa sequence corresponds to the age of premetamorphic gabbro of the Rozhdestvenskoe complex, comagmatic to metavolcanites (2120 ± 11-2158 ± 43 Ma). The age of the Usman plagiogranite complex is clarified. On the basis of geological-structural and petrographic-mineralogical analyses of metavolcanogenic rocks, lithological analysis of metasedimentary formations, and new geochemical data obtained from metavolcanites and metamorphosed deposits, the pattern of paleogeodynamic evolution of the Losevo suture zone in the first half of the Paleoproterozoic is proposed. The next stages are distinguished: (1) intrusion of tholeiites of transition T-MORB type in spreading zones and deposition of terrigenous strata in the marginal sea basins; (2) intrusion of Nb-depleted tholeiites and plagiorhyolites, the geochemical characteristics indicating their formation in the subduction setting; (3) intrusion of gabbroids of the Rozhdestvenskoe complex; (4) formation of an island arc synchronously with

  14. 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

  15. An improved method for the enzymatic transformation of nucleosides into 5'-monophosphates.

    PubMed

    Barai, Vladimir N; Kvach, Sergei V; Zinchenko, Anatoli I; Mikhailopulo, Igor A

    2004-12-01

    An improved method to transform nucleosides into 5'-monophosphates using nucleoside phosphotransferase from Erwinia herbicola is reported. The method is based on the shift in the equilibrium state of the reaction to the formation of desired product due to its precipitation by Zn2+. Under optimal conditions, the extent of nucleoside transformations into nucleoside-5'-monophosphates were 41-91% (mol). PMID:15672226

  16. Supercell-size convergence of formation energies and gap levels of vacancy complexes in crystalline silicon in density functional theory calculations

    NASA Astrophysics Data System (ADS)

    Dabrowski, J.; Kissinger, G.

    2015-10-01

    Results for supercell-size convergence of formation energies and charge transition levels of vacancy complexes Vn(1 ≤n ≤11 ) in crystalline Si are reported for the ab initio density functional theory (DFT) with generalized gradient approximation (GGA) pseudopotentials. When extrapolated to the dilute limit, the formation energy of an uncharged vacancy becomes 3.74 ±0.1 eV , and the binding energy of an uncharged divacancy becomes 1.9 ±0.2 eV . Stable Vn clusters are built on the basis of sixfold rings (n ≤6 ) and of octahedral voids (n ≥7 ) . If the well-known underestimate of the band gap by the DFT and the accuracy of extrapolations are taken into account, the extrapolated levels are in good agreement with experiment. We discuss the implications for simulation of vacancy clustering during thermal quenching, for interpretation of deep-level spectroscopy and electron paramagnetic resonance in irradiated Si, and for cell and Brillouin-zone sampling choice when DFT-related methods beyond local-density approximation or GGA are used.

  17. 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.

  18. 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

  19. Alkali metal crystalline polymer electrolytes.

    PubMed

    Zhang, Chuhong; Gamble, Stephen; Ainsworth, David; Slawin, Alexandra M Z; Andreev, Yuri G; Bruce, Peter G

    2009-07-01

    Polymer electrolytes have been studied extensively because uniquely they combine ionic conductivity with solid yet flexible mechanical properties, rendering them important for all-solid-state devices including batteries, electrochromic displays and smart windows. For some 30 years, ionic conductivity in polymers was considered to occur only in the amorphous state above Tg. Crystalline polymers were believed to be insulators. This changed with the discovery of Li(+) conductivity in crystalline poly(ethylene oxide)(6):LiAsF(6). However, new crystalline polymer electrolytes have proved elusive, questioning whether the 6:1 complex has particular structural features making it a unique exception to the rule that only amorphous polymers conduct. Here, we demonstrate that ionic conductivity in crystalline polymers is not unique to the 6:1 complex by reporting several new crystalline polymer electrolytes containing different alkali metal salts (Na(+), K(+) and Rb(+)), including the best conductor poly(ethylene oxide)(8):NaAsF(6) discovered so far, with a conductivity 1.5 orders of magnitude higher than poly(ethylene oxide)(6):LiAsF(6). These are the first crystalline polymer electrolytes with a different composition and structures to that of the 6:1 Li(+) complex. PMID:19543313

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

    PubMed

    Floyd, E E; Jones, M E

    1985-08-01

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

  1. Quantification of the abundance and mean residence time of carbon associated with metal-humus complexes, short-range-order Al and Fe hydroxides, and crystalline Fe oxyhydroxides across a suite of ecosystems

    NASA Astrophysics Data System (ADS)

    Heckman, K. A.; Lawrence, C. R.

    2013-12-01

    Stabilization of SOM (soil organic matter) is regulated in part by sorption and desorption reactions happening at mineral surfaces, as well as precipitation and dissolution of metal-humus complexes. Fe and Al hydroxides play a particularly significant role in SOM stabilization in soils due to their ubiquitous distribution and their highly reactive surface properties. Fe and Al hydroxides exist in soils across a wide spectrum of crystallinity, ranging from dissolved Fe and Al cations which combine with organics to form metal-humus precipitates to the more crystalline end members, goethite and gibbsite, which sorb SOM through a variety of molecular interactions. Though the importance of these sorption and precipitation reactions has long been recognized, the distribution of SOM among Fe and Al hydroxides of differing crystallinity has not been well quantified, nor has the timescales over which these stabilization mechanisms operate. In an attempt to measure the distribution of organic C among i) Al- and Fe-humus complexes ii) short-range-order Al and Fe hydroxide surfaces and iii) crystalline Fe oxyhydroxide surfaces, a suite of selective dissolutions were applied to soils of four different geneses (a tropical forest Andisol, a temperate forest basaltic Mollisol, a mediterranean coastal prairie Mollisol, and a northern mixed hardwood forest Spodosol. The traditional reactants used in selective dissolutions were replaced with carbon-free analogues so that the carbon released along with the Fe and Al at each stage of the selective dissolution process could be examined. Selective dissolutions were performed sequentially: Na-pyrophosphate (Al- and Fe-humus complexes) followed by hydroxylamine (short-range-order Al and Fe hydroxides) followed by dithionite/HCl (crystalline Fe hydroxides). C, Al, and Fe concentrations, as well as Δ14C were measured for the solutions yielded by each stage of the selective dissolution process. Δ14C data were used to estimate a MRT (mean

  2. Characterising fracture systems within fractured crystalline reservoirs: the Lewisian Gneiss Complex, Scotland as an onshore analogue for the Clair Field basement

    NASA Astrophysics Data System (ADS)

    Franklin, B.; Martin, J. C.; Holdsworth, R. E.; McCaffrey, K.; Krabbendam, M.; Conway, A.; Jones, R.

    2011-12-01

    Exotic hydrocarbon reservoirs, such as crystalline basement, are increasingly a target for hydrocarbon exploration in the development of new and existing fields. The Clair field lies in the Faroe-Shetland Basin, with reservoirs in Devonian- Carboniferous clastics overlying and onlapping a basement high that was upfaulted in the Mesozoic. This basement is known to control fluid flow and the structural development of the field due to its highly fractured nature. Consequently, it is important to characterise fault networks to assess the connected volume within the basement rocks. Fault-fracture systems in the regional basement complex of NW Scotland, the Leiwsian Gneiss Complex, and in overlying Mesozoic cover sequences have been characterised as an analogue for the Clair Field. Variations in lithology, metamorphic grade and tectonic setting all influence the fault network characteristics in the Scottish mainland and Hebridean islands. This study included analysis of regional NEXTMap° digital elevation models of surface outcrops together with studies of seismic attribute maps of the Clair top basement horizon in the subsurface. The aim here was to characterise and compare the large scale fault patterns, including orientation, density and spacing attributes. Fieldwork has been undertaken onshore in order to characterise fault systems and the tectonic history within Lewisian Gneiss and sedimentary cover sequences at meso- to micro-scales. This involves 1-D line sample analysis, photomosaic analysis and terrestrial laser scanning (LIDAR) to allow analysis of the fault networks in different dimensions. 1-dimensional and 2-dimensional analyses of regional and outcrop scale data show that NE-SW is a predominant fault trend within the Lewisian in both the onshore and offshore datasets. Spacing data onshore show mainly power-law distributions. These distributions allow us to infer that the outcrop data show scale-invariance for spacing and can therefore be used as an

  3. 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

  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. PMID:18180152

  5. Deoxypyrimidine monophosphate bypass therapy for thymidine kinase 2 deficiency

    PubMed Central

    Garone, Caterina; Garcia-Diaz, Beatriz; Emmanuele, Valentina; Lopez, Luis C; Tadesse, Saba; Akman, Hasan O; Tanji, Kurenai; Quinzii, Catarina M; Hirano, Michio

    2014-01-01

    Autosomal recessive mutations in the thymidine kinase 2 gene (TK2) cause mitochondrial DNA depletion, multiple deletions, or both due to loss of TK2 enzyme activity and ensuing unbalanced deoxynucleotide triphosphate (dNTP) pools. To bypass Tk2 deficiency, we administered deoxycytidine and deoxythymidine monophosphates (dCMP+dTMP) to the Tk2 H126N (Tk2−/−) knock-in mouse model from postnatal day 4, when mutant mice are phenotypically normal, but biochemically affected. Assessment of 13-day-old Tk2−/− mice treated with dCMP+dTMP 200 mg/kg/day each (Tk2−/−200dCMP/dTMP) demonstrated that in mutant animals, the compounds raise dTTP concentrations, increase levels of mtDNA, ameliorate defects of mitochondrial respiratory chain enzymes, and significantly prolong their lifespan (34 days with treatment versus 13 days untreated). A second trial of dCMP+dTMP each at 400 mg/kg/day showed even greater phenotypic and biochemical improvements. In conclusion, dCMP/dTMP supplementation is the first effective pharmacologic treatment for Tk2 deficiency. Subject Categories Genetics, Gene Therapy & Genetic Disease; Metabolism PMID:24968719

  6. 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. PMID:18443613

  7. Phosphatidylinositol 3-Monophosphate Is Involved in Toxoplasma Apicoplast Biogenesis

    PubMed Central

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

    2011-01-01

    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

  8. 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

  9. Examination of carbon associated with metal-humus complexes, short-range-order Al and Fe oxides, and crystalline Al and Fe oxides: Differences in carbon abundance and mean residence time

    NASA Astrophysics Data System (ADS)

    Heckman, K. A.; Lawrence, C. R.

    2012-12-01

    Transport of SOM (soil organic matter) between soils and aquatic systems is regulated in part by sorption and desorption reactions happening at mineral surfaces, as well as precipitation and dissolution of metal-humus complexes. Fe and Al hydroxides play a particularly significant role in SOM stabilization in soils due to their ubiquitous distribution and their highly reactive surface properties. Fe and Al hydroxides exist in soils across a wide spectrum of crystallinity, ranging from dissolved Fe and Al cations which combine with organics to form metal-humus precipitates to the more crystalline end members, goethite and gibbsite, which sorb SOM through a variety of molecular interactions. Though the importance of these sorption and precipitation reactions has long been recognized, the distribution of SOM among Fe and Al hydroxides of differing crystallinity has not been well quantified, nor has the timescales over which these stabilization mechanisms operate. In an attempt to measure the distribution of organic C among i) Al- and Fe-humus complexes ii) short-range-order Al and Fe oxide surfaces and iii) crystalline Al and Fe oxide surfaces, a suite of selective dissolutions were applied to soils of four different geneses (a tropical forest andosol, a temperate basaltic mollisol, a grassland alfisol, and a northern pine spodosol. The traditional reactants used in selective dissolutions were replaced with carbon-free analogues so that the carbon released along with the Fe and Al at each stage of the selective dissolution process could be examined. Selective dissolutions were performed sequentially: Na-pyrophosphate (Al- and Fe-humus complexes) followed by hydroxyl-amine (short-range-order Al and Fe hydroxides) followed by dithionite/HCl (crystalline Al and Fe hydroxides). Carbon concentration, δ13C, and Δ14C were measured for the solutions yielded by each stage of the selective dissolution process. Δ14C were used to estimate a MRT (mean residence time) for SOM

  10. 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.

  11. 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

  12. Structural and functional characterization of the Mycobacterium tuberculosis uridine monophosphate kinase: insights into the allosteric regulation†

    PubMed Central

    Labesse, Gilles; Benkali, Khaled; Salard-Arnaud, Isabelle; Gilles, Anne-Marie; Munier-Lehmann, Hélène

    2011-01-01

    Nucleoside Monophosphate Kinases (NMPKs) family are key enzymes in nucleotide metabolism. Bacterial UMPKs depart from the main superfamily of NMPKs. Having no eukaryotic counterparts they represent attractive therapeutic targets. They are regulated by GTP and UTP, while showing different mechanisms in Gram(+), Gram(–) and archaeal bacteria. In this work, we have characterized the mycobacterial UMPK (UMPKmt) combining enzymatic and structural investigations with site-directed mutagenesis. UMPKmt exhibits cooperativity toward ATP and an allosteric regulation by GTP and UTP. The crystal structure of the complex of UMPKmt with GTP solved at 2.5 Å, was merely identical to the modelled apo-form, in agreement with SAXS experiments. Only a small stretch of residues was affected upon nucleotide binding, pointing out the role of macromolecular dynamics rather than major structural changes in the allosteric regulation of bacterial UMPKs. We further probe allosteric regulation by site-directed mutagenesis. In particular, a key residue involved in the allosteric regulation of this enzyme was identified. PMID:21149268

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

    PubMed Central

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

    2010-01-01

    Summary The e (P4) phosphatase from Haemophilus influenzae functions in a vestigial NAD+ utilization pathway by dephosphorylating NMN to nicotinamide riboside. P4 is also the prototype of class C acid phosphatases, 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 NMN, 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 hydrogen-bonding edge of the base. The span between the hydrophobic box and phosphoryl site is optimal for recognizing nucleoside monophosphates, which explains the general preference for this class of substrate. The base makes no hydrogen bonds with the enzyme, which is consistent with observed lack of base specificity. Two solvent-filled pockets flanking the ribose are key to the dual recognition of 5′- 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 and C acid phosphatases share a common strategy for nucleotide recognition. PMID:20934434

  14. Characterization of a monoclonal antibody to thymidine glycol monophosphate

    SciTech Connect

    Chen, B.X.; Hubbard, K.; Ide, H.; Wallace, S.S.; Erlanger, B.F. )

    1990-11-01

    A monoclonal antibody specific for thymine glycol (TG) in irradiated or OsO4-treated DNA was obtained by immunizing with thymidine glycol monophosphate (TMP-glycol) conjugated to bovine serum albumin by a carbodiimide procedure. Screening by dot-immunobinding and enzyme-linked immunosorbant assay (ELISA) procedures gave eight clones that bound OsO4- treated DNA. One of them, 2.6F.6B.6C, an IgG2a kappa, was characterized further. Hapten inhibition studies with OsO4-treated DNA showed that the antibody was specific for TMP-glycol. Among the various inhibitors tested, inhibition was in the order TMP-glycol greater than 5,6-dihydrothymidine phosphate greater than TMP greater than thymidine glycol greater than TG. Inhibition by 5,6-dihydrothymidine, thymidine, thymine, AMP, and CMP was negligible. In OsO4-treated DNA, as few as 0.5 TG per 10,000 bp were detectable by direct ELISA. Inhibition assays could detect as few as 1.5 TG per 10,000 bp. The antibody was equally reactive with native or denatured DNA containing TG. Among the X-irradiated homopolymers dC, dA, dG, and dT, only dT reacted with the antibody. Using an ELISA, the antibody could detect damage in irradiated DNA at the level of 20 Gy. Thus the antibody is of potential use in assays for DNA damage caused by X rays or other agents that damage DNA by free radical interactions.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Kinetics and mechanism of the acid-catalyzed hydrolysis of a hypermodified nucleoside wyosine and its 5'-monophosphate.

    PubMed Central

    Golankiewicz, B; Zielonacka-Lis, E; Folkman, W

    1985-01-01

    The rates of acid-catalyzed hydrolysis of a hypermodified nucleoside, wyosine and its 5'-monophosphate were determined at various pH, temperature and buffer concentrations. The results show that despite distinct differences in structure and the glycosyl bond stability, the hydrolysis of wyosine proceeds via cleavage of the C-N bond by A-1 mechanism, analogously to simple nucleosides. Unlike majority of other monophosphates studied so far, wyosine 5'-monophosphate is not more stable than respective nucleoside. PMID:4000960

  20. Mitochondrial Oxidative Stress Corrupts Coronary Collateral Growth by Activating Adenosine Monophosphate Activated Kinase-α Signaling

    PubMed Central

    Pung, Yuh Fen; Sam, Wai Johnn; Stevanov, Kelly; Enrick, Molly; Chen, Chwen-Lih; Kolz, Christopher; Thakker, Prashanth; Hardwick, James P.; Chen, Yeong-Renn; Dyck, Jason R.B.; Yin, Liya; Chilian, William M.

    2015-01-01

    Objective Our goal was to determine the mechanism by which mitochondrial oxidative stress impairs collateral growth in the heart. Approach and Results Rats were treated with rotenone (mitochondrial complex I inhibitor that increases reactive oxygen species production) or sham-treated with vehicle and subjected to repetitive ischemia protocol for 10 days to induce coronary collateral growth. In control rats, repetitive ischemia increased flow to the collateral-dependent zone; however, rotenone treatment prevented this increase suggesting that mitochondrial oxidative stress compromises coronary collateral growth. In addition, rotenone also attenuated mitochondrial complex I activity and led to excessive mitochondrial aggregation. To further understand the mechanistic pathway(s) involved, human coronary artery endothelial cells were treated with 50 ng/ mL vascular endothelial growth factor, 1 µmol/L rotenone, and rotenone/vascular endothelial growth factor for 48 hours. Vascular endothelial growth factor induced robust tube formation; however, rotenone completely inhibited this effect (P<0.05 rotenone versus vascular endothelial growth factor treatment). Inhibition of tube formation by rotenone was also associated with significant increase in mitochondrial superoxide generation. Immunoblot analyses of human coronary artery endothelial cells with rotenone treatment showed significant activation of adenosine monophosphate activated kinase (AMPK)-α and inhibition of mammalian target of rapamycin and p70 ribosomal S6 kinase. Activation of AMPK-α suggested impairments in energy production, which was reflected by decrease in O2 consumption and bioenergetic reserve capacity of cultured cells. Knockdown of AMPK-α (siRNA) also preserved tube formation during rotenone, suggesting the negative effects were mediated by the activation of AMPK-α. Conversely, expression of a constitutively active AMPK-α blocked tube formation. Conclusions We conclude that activation of AMPK

  1. Evaluation of the metal-ion-coordinating differences between the 2'-, 3'- and 5'-monophosphates of adenosine.

    PubMed

    Massoud, S S; Sigel, H

    1989-02-01

    The stability constants of the 1:1 complexes formed between Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+ or Cd2+ and 2'AMP2-, 3'AMP2- or 5'AMP2- were determined by potentiometric pH titration in aqueous solution (I = 0.1 M, NaNO3; 25 degrees C). The experimental conditions were carefully selected such that self-association of the nucleotides and their complexes is negligibly small; i.e. it was made certain that the properties of the monomeric divalent-metal-ion--AMP [M(AMP)] complexes were studied. Based on recent measurements with simple phosphate monoesters, R-MP2- where R is a non-coordinating residue [Massoud, S. S. & Sigel, H. (1988) Inorg. Chem. 27, 1447-1453], it is shown that all the M(AMP) complexes of the alkaline earth ions, with the possible exception of Mg(5'AMP), have exactly the stability expected for a sole-phosphate coordination of the metal ion. The same property is revealed for the complexes with Mn2+, Co2+, Zn2+ or Cd2+ and 3'AMP2-; in case of Ni(3'AMP) and Cu(3'AMP) a slight stability increase just at the edge of the experimental-error limits is indicated. This slight stability increase is attributed to the formation of a macrochelate (possibly with N-3); in fact, additional information confirms macrochelation for Cu(3'AMP). About 45% of Cu(2'AMP) exists in aqueous solution as a macrochelate (probably involving N-3); the other M(2'AMP) complexes (M2+ = Mn2+, Co2+, Ni2+, Zn2+, Cd2+) form (if at all) only traces of a base-backbound species. Most pronounced is macrochelate formation with 5'AMP2-: all mentioned 3d ions and Zn2+ or Cd2+ form to some extent macrochelates via N-7 (the structures of these closed species are indicated). In case of M(5'AMP) the base-binding site is certain: replacement of N-7 by a CH unit (tubercidin 5'-monophosphate) eliminates any increased complex stability, whereas formation of the 1,N6-etheno bridge to form 1,N6-ethenoadenosine 5'-monophosphate results in the phenanthroline-like N-6,N-7 site which

  2. 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.

  3. Spectroscopic, thermal and voltammetric studies of crystalline complex trans- N, N'-bis(salicylidene)-1',2'-cyclohexanediamine with Cu(II)

    NASA Astrophysics Data System (ADS)

    Aslantas, Mehmet; Tümer, Mehmet; Şahin, Ertan

    2008-11-01

    The dimeric complex, [C 20H 20CuN 2O 2] 2, has been prepared and characterized by thermal analysis, IR spectroscopy and single-crystal X-ray diffraction techniques. The Cu atom in the binuclear complex exists in a distorted square-pyramidal configuration, defined by three O atoms and two N atoms. The crystal structure is stabilized by intermolecular C-H⋯O hydrogen bonding interaction. The electrochemical property of the complex was investigated in CH 2Cl 2 by cyclic voltammetry at 100 mV s -1 scan rate.

  4. Solvent exchange and discrimination in crystalline state. Formation and properties of copper(II) complexes containing 2,3-bis(isonicotinoyloxy)naphthalene

    NASA Astrophysics Data System (ADS)

    Cho, Yoonjung; Kim, Jeong Gyun; Noh, Tae Hwan; Jung, Ok-Sang

    2013-09-01

    Self-assembly of copper(II) nitrate with 2,3-bis(isonicotinoyloxy)naphthalene (L) in a mixture of acetonitrile and dichloromethane produces a 30-membered discrete metallacyclodimer, [Cu(NO3)2(L)]2, while the self-assembly in a mixture of N,N-dimethylformamide and CH2Cl2 and a mixture of N,N-dimethylformamide and dioxane yields 1D coordination polymers consisting of [Cu(NO3)2(L)2]ṡ4CH2Cl2 and [Cu(NO3)2(L)2]ṡ3dioxane, respectively. Recrystallizations of [Cu(NO3)2(L)]2 from N,N-dimethylformamide/CH2Cl2 and N,N-dimethylformamide/dioxane lead to [Cu(NO3)2(L)2]ṡ4CH2Cl2 and [Cu(NO3)2(L)2]ṡ3dioxane, respectively. Constructions of the two skeletons, metallacyclodimer and 1D coordination polymer, are determined by solvents rather than synthetic methodologies. For [Cu(NO3)2(L)2]ṡ4CH2Cl2 and [Cu(NO3)2(L)2]ṡ3dioxane, exchange of the solvate molecules in the crystalline solids is carried out, and the 1D skeletal structure discriminates dioxane and CH2Cl2 molecules.

  5. Coordination properties of adenosine-5'-monophosphate and related ligands towards Me2Sn(IV)2+ in aqueous solution.

    PubMed

    Jankovics, H; Nagy, L; Buzás, N; Pellerito, L; Barbieri, R

    2002-09-30

    The coordination of Me2Sn(IV)2+ to adenosine-5'-monophosphate (AMP) and the related compounds D-ribose-5-phosphate (R5P), D-glucose-1-phosphate (G1P) and D-glucose-6-phosphate (G6P) in aqueous solution was investigated by means of potentiometric titration, and 1H-, 31P-NMR and Mössbauer spectroscopic methods in the pH range 2-11 (I=0.1 M NaClO4, 298 K). The complex of AMP and Me2Sn(IV)2+ precipitated at low pH was characterised by elemental analysis, FT-IR and Mössbauer spectroscopic methods. From a comparison of the pK values obtained in the presence and absence of metal ion and the stability constants for the different systems, the coordination of [N] is excluded, while bidentate coordination of the phosphate group is presumed. Mössbauer spectroscopic measurements recorded in the glassy state confirmed bidentate coordination of the phosphate and the formation of mixed hydroxo complexes in the weakly acidic, neutral and strongly basic pH range. With increasing pH, the phosphate groups were replaced by the deprotonated alcoholic [O] atoms of the sugar moiety. The solid complex proved to be tbp structure with bidentate phosphate coordination. PMID:12230988

  6. 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.

  7. Encapsulation of CO2 into amorphous alpha-cyclodextrin powder at different moisture contents - Part 2: Characterization of complexed powders and determination of crystalline structure.

    PubMed

    Ho, Thao M; Howes, Tony; Jack, Kevin S; Bhandari, Bhesh R

    2016-09-01

    This study aims to characterize CO2-α-cyclodextrin (α-CD) inclusion complexes produced from amorphous α-CD powder at moisture contents (MC) close to or higher than the critical level of crystallization (e.g. 13, 15 and 17% MC on wet basis, w.b.) at 0.4 and 1.6MPa pressure for 72h. The results of (13)C NMR, SEM, DSC and X-ray analyses showed that these MC levels were high enough to induce crystallization of CO2-α-CD complexed powders during encapsulation, by which amount of CO2 encapsulated by amorphous α-CD powder was significantly increased. The formation of inclusion complexes were well confirmed by results of FTIR and (13)C NMR analyses through an appearance of a peak associated with CO2 on the FTIR (2334cm(-1)) and NMR (125.3ppm) spectra. Determination of crystal packing patterns of CO2-α-CD complexed powders showed that during crystallization, α-CD molecules were arranged in cage-type structure in which CO2 molecules were entrapped in isolated cavities. PMID:27041303

  8. 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

  9. Human monocyte killing of Staphylococcus aureus: modulation by agonists of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-monophosphate.

    PubMed Central

    O'Dorisio, M S; Vandenbark, G R; LoBuglio, A F

    1979-01-01

    This study was designed to test whether cyclic nucleotides play a role in the regulation of bacterial killing by human monocytes. Agents were tested for their ability to activate monocyte adenylate or guanylate cyclase in cell-free preparations, to increase cyclic adenosine 3',5'-monophosphate (cAMP) or cyclic guanosine 3',5'-monophosphate (cGMP) in intact human monocytes, and to modulate monocyte-induced killing of Staphylococcus aureus in vitro. Prostaglandin E1 and cholera toxin activated monocyte adenylate cyclase and inhibited monocyte killing of S. aureus. An adenylate cyclase inhibitor, RMI 12330A, reversed the prostaglandin E1-mediated inhibition of bacterial killing, thus implicating cAMP as the intracellular mediator of this inhibition. In contrast, monocyte cGMP levels were increased 5- and 17-fold by 5-hydroxytryptamine and N-methyl-N' -nitro-N-nitrosoguanidine, respectively, but neither agent was effective in modulating monocyte bactericidal activity. Thus, modulation of bactericidal activity in human monocytes did not conform to the yin/yang theory of opposing actions by cAMP and cGMP, for although monocyte-mediated killing of S. aureus was inhibited by cAMP agonists, it was not enhanced by cGMP agonists. PMID:44704

  10. 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

  11. 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. PMID:19498234

  12. 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

  13. L-theanine elicits an umami taste with inosine 5'-monophosphate.

    PubMed

    Narukawa, Masataka; Morita, Kanako; Hayashi, Yukako

    2008-11-01

    We investigated the taste synergy between L-theanine and the flavour enhancer, inosine 5'-monophosphate (IMP), by using a human sensory evaluation. When L-theanine was added to IMP, only the umami taste was enhanced. We then investigated this synergistic effect of L-theanine in mice by gustatory nerve recording. We confirmed the synergism between L-theanine and IMP for the umami taste. PMID:18997398

  14. Triamterene crystalline nephropathy.

    PubMed

    Nasr, Samih H; Milliner, Dawn S; Wooldridge, Thomas D; Sethi, Sanjeev

    2014-01-01

    Medications can cause a tubulointerstitial insult leading to acute kidney injury through multiple mechanisms. Acute tubular injury, a dose-dependent process, occurs due to direct toxicity on tubular cells. Acute interstitial nephritis characterized by interstitial inflammation and tubulitis develops from drugs that incite an allergic reaction. Other less common mechanisms include osmotic nephrosis and crystalline nephropathy. The latter complication is rare but has been associated with several drugs, such as sulfadiazine, indinavir, methotrexate, and ciprofloxacin. Triamterene crystalline nephropathy has been reported only rarely, and its histologic characteristics are not well characterized. We report 2 cases of triamterene crystalline nephropathy, one of which initially was misdiagnosed as 2,8-dihydroxyadenine crystalline nephropathy. PMID:23958399

  15. 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

  16. 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

  17. The crystalline sponge method updated.

    PubMed

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

    2016-03-01

    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

  18. Crystalline Silica Primer

    USGS Publications Warehouse

    Staff- Branch of Industrial Minerals

    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.

  19. Analysis of Nucleotide 5'-Monophosphates in Infant Formulas by HPLC-UV: Collaborative Study, Final Action 2011.20.

    PubMed

    Gill, Brendon D; Indyk, Harvey E

    2015-01-01

    A collaborative study was conducted on AOAC First Action Method 2011.20: 5'-Mononucleotides in Infant Formula and Adult/Pediatric Nutritional Formula. After the successful analysis of National Institute of Standards and Technology (NIST) 1849a Standard Reference Material (SRM) as a practice sample, 12 laboratories participated in the analysis of duplicate samples of six different infant formula products. The samples were dissolved in high-salt solution to inhibit protein and fat interactions, with the nucleotides [uridine 5'-monophosphate (UMP), inosine 5'-monophosphate (IMP), adenosine 5'-monophosphate (AMP), guanosine 5'-monophosphate (GMP), and cytidine 5'-monophosphate (CMP)] separated from the sample matrix by strong-anion exchange SPE, followed by chromatographic analysis using a C18 stationary phase with gradient elution, UV detection, and quantitation by an internal standard technique using thymidine 5'-monophosphate. For nucleotide-supplemented products, precision is within the Standard Method Performance RequirementsSM (SMPR) 2011.008 target reproducibility limit of ≤11%, with the reproducibility RSD (RSDR) estimated at 7.1-8.7% for CMP, 7.9-9.0% for UMP, 2.8-7.7% for GMP, 5.5-10.3% for IMP, and 2.7-6.2% for AMP, and Horwitz ratio (HorRat) values of 0.9-1.0 for CMP, 0.9-1.0 for UMP, 0.3-0.7 for GMP, 0.6-1.0 for IMP, and 0.3-0.7 for AMP. PMID:26268980

  20. Molecular aggregation in crystalline 1:1 complexes of hydrophobic D- and L-amino acids. I. The L-isoleucine series.

    PubMed

    Dalhus; Görbitz

    1999-06-01

    The amino acid L-isoleucine has been cocrystallized with seven selected D-amino acids including D-methionine [L-isoleucine-D-methionine (1/1), C(6)H(13)NO(2).C(5)H(11)NO(2)S, amino-acid side chain R = -CH(2)-CH(2)-S-CH(3)] and a homologous series from D-alanine [L-isoleucine-D-alanine (1/1), C(6)H(13)NO(2).C(3)H(7)NO(2), R = -CH(3)] through D-alpha-aminobutyric acid [L-isoleucine-D-alpha-aminobutyric acid (1/1), C(6)H(13)NO(2).C(4)H(9)NO(2), R = -CH(2)-CH(3)] and D-norvaline [L-isoleucine-D-norvaline (1/1), C(6)H(13)NO(2).C(5)H(11)NO(2), R = -CH(2)-CH(2)-CH(3)] to D-norleucine [L-isoleucine-D-norleucine (1/1), C(6)H(13)NO(2).C(6)H(13)NO(2), R = -CH(2)-CH(2)-CH(2)-CH(3)] with linear side chains, and D-valine [L-isoleucine-D-valine (1/1), C(6)H(13)NO(2).C(5)H(11)NO(2), R = -CH-(CH(3))(2)] and D-leucine [L-isoleucine-D-leucine (1/1), C(6)H(13)NO(2).C(6)H(13)NO(2), R = -CH(2)-CH-(CH(3))(2)] with branched side chains. All the crystal structures are divided into distinct hydrophilic and hydrophobic layers. In the five complexes with amino acids with linear side chains the polar parts of the D- and L-amino acids are related by pseudo-glide-plane symmetry, and four of them have remarkably similar molecular arrangements. The D-valine and D-leucine complexes, on the other hand, are structurally quite different with the polar parts of the D- and L-amino acids related by pseudo-inversion. Differences in the hydrogen-bond pattern in the two molecular arrangements are discussed. PMID:10927385

  1. Factors influencing α-crystallin association with phospholipid vesicles

    PubMed Central

    Cobb, Brian A.; Petrash, J. Mark

    2010-01-01

    Purpose Lens lipids undergo a number of changes with age, including an overall increase in phospholipid acyl chain saturation and a decrease in length. In addition, the amount of membrane bound α-crystallin increases dramatically with age and with the onset of cataract. The aim of this study was to determine if a link exists between age and cataract associated changes in lens lipids and the changes in α-crystallin membrane association. Methods Protein-free lipid vesicles composed of a wide variety of synthetic and lens-derived lipid vesicles were formed by sonication. These vesicles were used with fluorescent native and recombinant α-crystallin conjugates in vesicle binding assays. Vesicles were collected by centrifugation and bound α-crystallin was quantified with fluorescence intensity measurements. Results α-Crystallin complexes showed remarkably similar binding profiles for all lipid vesicles tested, regardless of lipid origin, phospholipid head group, acyl chain length or saturation, and inclusion of cholesterol. In addition, recombinant α-crystallin complexes bind to these vesicles in a manner that is essentially indistinguishable from that of native human and bovine α-crystallins. Unlike α-crystallin binding to lens membranes containing intrinsic proteins, binding of α-crystallin to protein-free vesicles was very high capacity and unsaturable. Conclusions We conclude from these data that the binding of α-crystallin to lens membranes is not lipid-specific. Furthermore, protein post-translational changes, such as phosphorylation, do not appear to alter α-crystallin binding to these vesicles. Given the linearity of the binding curves, we propose that the only limiting factor for normal α-crystallin membrane binding is available surface area on the bilayer. Finally, the present data suggests that increased in vivo membrane association of α-crystallin is not a result of lipid changes, but more likely a result of non-lipid factors such as the

  2. 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

  3. Bicyclol promotes toll-like 2 receptor recruiting inosine 5'-monophosphate dehydrogenase II to exert its anti-inflammatory effect.

    PubMed

    Zhang, You-Wen; Guo, Yan-Shen; Bao, Xiu-Qi; Sun, Hua; Zhang, Dan

    2016-05-01

    The aim was to investigate potential targets and anti-inflammatory mechanisms of bicyclol, which has been extensively used in clinic for decades in China. Tar-Fis-Dock, virtual molecular docking system, showed that inosine 5'-monophosphate dehydrogenase II (IMPDH II) has the highest probability of binding to bicyclol. To investigate the possible role of IMPDH II in mechanisms of bicyclol, recombinant enzyme models, mice splenic lymphocytes, and human lymphocytes were used. Bicyclol (1-5 μM) significantly inhibited the proliferation of mice splenic lymphocytes stimulated by concanavalin A (conA). However, bicyclol did not show inhibitory effects on proliferation of human peripheral blood mononuclear cells (hPBMC) induced by phytohemagglutinin (PHA). IMPDH II enzyme kinetic model showed that bicyclol only had a slight regulatory effect on IMPDH II enzyme activity. These results revealed that bicyclol may be not a conventional inhibitor of IMPDH II. Further studies showed that bicyclol could promote recruitment of IMPDH II by active toll-like 2 receptor (TLR2) complex. Such effects lead to the reduction of nuclear factor κB (NF-κB) expression, increase in I-κB expression, and decrease in cytokine release, including tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). It may be a new mechanism of bicyclol for its anti-inflammatory effect. PMID:26744808

  4. Computer-assisted combinatorial design of bicyclic thymidine analogs as inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase.

    PubMed

    Frecer, Vladimir; Seneci, Pierfausto; Miertus, Stanislav

    2011-01-01

    Thymidine monophosphate kinase (TMPK(mt)) is an essential enzyme for nucleotide metabolism in Mycobacterium tuberculosis, and thus an attractive target for novel antituberculosis agents. In this work, we have explored the chemical space around the 2',3'-bicyclic thymidine nucleus by designing and in silico screening of a virtual focused library selected via structure based methods to identify more potent analogs endowed with favorable ADME-related properties. In all the library members we have exchanged the ribose ring of the template with a cyclopentane moiety that is less prone to enzymatic degradation. In addition, we have replaced the six-membered 2',3'-ring by a number of five-membered and six-membered heterocyclic rings containing alternative proton donor and acceptor groups, to exploit the interaction with the carboxylate groups of Asp9 and Asp163 as well as with several cationic residues present in the vicinity of the TMPK(mt) binding site. The three-dimensional structure of the TMPK(mt) complexed with 5-hydroxymethyl-dUMP, an analog of dTMP, was employed to develop a QSAR model, to parameterize a scoring function specific for the TMPK(mt) target and to select analogues which display the highest predicted binding to the target. As a result, we identified a small highly focused combinatorial subset of bicyclic thymidine analogues as virtual hits that are predicted to inhibit the mycobacterial TMPK in the submicromolar concentration range and to display favorable ADME-related properties. PMID:21082329

  5. 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.

  6. 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.

  7. Bisthienylethene Th2im and its complex (Th2imH)2[ReCl6]: crystalline-phase photochromism, and photochemical regulation of luminescence and magnetic properties.

    PubMed

    Gong, Dan-Ping; Chen, Jun-Feng; Zhao, Yue; Cao, Deng-Ke

    2016-02-16

    Molecular assembly of bisthienylethene Th2im () and [ReCl6](2-) anions leads to the complex (Th2imH)2[ReCl6] (), in which a [ReCl6](2-) anion connects two equivalent Th2imH(+) cations through ClN/C hydrogen bonds. Crystal structures of and indicate that two thiophene groups of each Th2im/Th2imH(+) molecule adopt a photoactive antiparallel conformation. Thus, two compounds show crystalline-phase photochromism (CPP), i.e. reversible structural transformation between the open form and the closed form upon alternately irradiating the sample with UV light (365 nm) and visible light (574 nm for , 624 nm for ). It was found that the CPP behaviors of and could regulate their luminescence and/or magnetic properties. Their solid-state emissions (433, 448, 482, 531 and 570 nm for , and 460, 489, 535 and 593 nm for ) exhibited weaker intensities after UV irradiation with 365 nm light. Besides CPP and luminescence, compound shows field-induced slow magnetic relaxation. Before and after UV irradiation, this compound revealed different magnetic behaviors, including the differences in the shape of the χMT vs. T plot, D parameter, and the values of the relaxation barrier Ueff and the preexponential factor τ0. PMID:26790478

  8. Human UMP-CMP kinase 2, a novel nucleoside monophosphate kinase localized in mitochondria.

    PubMed

    Xu, Yunjian; Johansson, Magnus; Karlsson, Anna

    2008-01-18

    Enzyme deficiency in the salvage pathway of deoxyribonucleotide synthesis in mitochondria can cause mtDNA depletion syndromes. We have identified a human mitochondrial UMP-CMP kinase (UMP-CMPK, cytidylate kinase; EC 2.7.4.14), designated as UMP-CMP kinase 2 (UMP-CMPK2). The C-terminal domain of this 449-amino acid protein contains all consensus motifs of a nucleoside monophosphate kinase. Phylogenetic analysis showed that UMP-CMPK2 belonged to a novel nucleoside monophosphate kinase family, which was closer to thymidylate kinase than to cytosolic UMP-CMP kinase. Subcellular localization with green fluorescent protein fusion proteins illustrated that UMP-CMPK2 was localized in the mitochondria of HeLa cells and that the mitochondrial targeting signal was included in the N-terminal 22 amino acids. The enzyme was able to phosphorylate dUMP, dCMP, CMP, and UMP with ATP as phosphate donor, but the kinetic properties were different compared with the cytosolic UMP-CMPK. Its efficacy to convert dUMP was highest, followed by dCMP, whereas CMP and UMP were the poorest substrates. It also phosphorylated the monophosphate forms of the nucleoside analogs ddC, dFdC, araC, BVDU, and FdUrd, which suggests that UMP-CMPK2 may be involved in mtDNA depletion caused by long term treatment with ddC or other pyrimidine analogs. UMP-CMPK2 mRNA expression was exclusively detected in chronic myelogenous leukemia K-562 and lymphoblastic leukemia MOLT-4 among eight studied cancer cell lines. Particular high expression in leukemia cells, dominant expression in bone marrow, and tight correlation with macrophage activation and inflammatory response suggest that UMP-CMPK2 may have other functions in addition to the supply of substrates for mtDNA synthesis. PMID:17999954

  9. 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

  10. Postirradiation administration of adenosine monophosphate combined with dipyridamole reduces early cellular damage in mice

    SciTech Connect

    Bohacek, J.; Hosek, B.; Pospisil, M. )

    1993-01-01

    The administration of dipyridamole and adenosine 5'-monophosphate (AMP) to mice 5 to 25 min after 1 Gy of total-body gamma irradiation was found to decrease cellular damage, as indicated by the thymidine level in plasma and the amount of saline soluble polynucleotides in the thymus. The drug combination used did not influence similar cytotoxic effects of hydrocortisone. Furthermore, it was shown that the addition of dipyridamole and AMP to in vitro irradiated suspensions of thymocytes enhanced the rejoining processes of DNA strand breaks. Receptor-mediated action of extracellular adenosine may be responsible for the therapeutic effects observed.

  11. 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. PMID:27018895

  12. 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.

  13. Determination of the lowest-energy oxidation site in nucleotides: 2'-deoxythymidine 5'-monophosphate anion.

    PubMed

    Rubio, Mercedes; Roca-Sanjuan, Daniel; Merchan, Manuela; Serrano-Andrés, Luis

    2006-06-01

    High level ab initio computations anticipate nucleobases as the most favorable sites for oxidation in nucleotides. At the CASPT2 level, the lowest ionization channel for the 2'-deoxythymidine 5'-monophosphate anion is related to a pi-orbital of the thymine base. The present findings lead to revision of the recent assignments of the photodetachment photoelectron spectra of mononucleotide anions in the gas phase and support the classical view of the nucleobase being the main actor in the oxidation process of both nucleosides and nucleotides. PMID:16722723

  14. 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.

  15. Crystalline bipyridinium radical complexes and uses thereof

    DOEpatents

    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.

  16. 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

  17. 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

  18. 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

  19. Structural defects in crystalline silicon

    NASA Technical Reports Server (NTRS)

    Sirtl, E.

    1985-01-01

    The basic photovoltaic properties of a given crystalline silicon specimen seem to be governed by density and nature of two to three dimensional lattice defects. These are mainly generated by primary growth conditions as grain boundaries of more or less intrinsic character or second phase precipitates from supersaturated solutions of carbon or oxygen. Considerably high values of both solubility and diffusivity in connection with their abundance in common refractory material systems account for the predominance of the two particular elements. Unsaturated dislocations of different types very often can be seen as a consequence of the existence of more dimensional defects as described initially. The final performance of a solar cell is dependent of the concentration and distribution of recombination active centers in the different regions of this device. Typical representatives are fast diffusing transition metals in form of either single atoms or simple complexes. Their avoidance, annihilation, or removal is of great concern in different fields of electronic materials development.

  20. 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.

  1. 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.

  2. Crystalline titanate catalyst supports

    SciTech Connect

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

    1991-12-31

    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.

  3. 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.

  4. THz-Spectroscopy on High Density Polyethylene with Different Crystallinity

    NASA Astrophysics Data System (ADS)

    Sommer, Stefan; Raidt, Thomas; Fischer, Bernd M.; Katzenberg, Frank; Tiller, Jörg C.; Koch, Martin

    2016-02-01

    The different crystallinity states of high density polyethylene (PE-HD) are investigated using THz time-domain spectroscopy by exploiting the complex permittivity at a frequency range from 0.5 up to 3.5 THz. We found that samples with different crystallinity can be distinguished by comparing the material specific refractive index ( n) or rather the linked complex part of the permittivity (∈ ' '). Correlating the calorimetrically determined degrees of crystallinity with the absolute values of the refractive index and the specific absorption peak at 2.18 THz, respectively, suggests in both cases a linear correlation.

  5. Colliding Crystalline Beams

    SciTech Connect

    Wei, Jie; Sessler, A.M.

    1998-06-01

    The understanding of crystalline beams has advanced to the point where one can now, with reasonable confidence, undertake an analysis of the luminosity of colliding crystalline beams. Such a study is reported here. It is necessary to observe the criteria, previously stated, for the creation and stability of crystalline beams. This requires, firstly, the proper design of a lattice. Secondly, a crystal must be formed, and this can usually be done at various densities. Thirdly, the crystals in a colliding-beam machine are brought into collision. We study all of these processes using the molecular dynamics (MD) method. The work parallels what was done previously, but the new part is to study the crystal-crystal interaction in collision. We initially study the zero-temperature situation. If the beam-beam force (or equivalent tune shift) is too large then over-lapping crystals can not be created (rather two spatially separated crystals are formed). However, if the beam-beam force is less than but comparable to that of the space-charge forces between the particles, we find that overlapping crystals can be formed and the beam-beam tune shift can be of the order of unity. Operating at low but non-zero temperature can increase the luminosity by several orders of magnitude over that of a usual collider. The construction of an appropriate lattice, and the development of adequately strong coding, although theoretically achievable, is a challenge in practice.

  6. COLLIDING CRYSTALLINE BEAMS.

    SciTech Connect

    WEI, J.

    1998-06-26

    The understanding of crystalline beams has advanced to the point where one can now, with reasonable confidence, undertake an analysis of the luminosity of colliding crystalline beams. Such a study is reported here. It is necessary to observe the criteria, previously stated, for the creation and stability of crystalline beams. This requires, firstly, the proper design of a lattice. Secondly, a crystal must be formed, and this can usually be done at various densities. Thirdly, the crystals in a colliding-beam machine are brought into collision. We study all of these processes using the molecular dynamics (MD) method. The work parallels what was done previously, but the new part is to study the crystal-crystal interaction in collision. We initially study the zero-temperature situation. If the beam-beam force (or equivalent tune shift) is too large then overlapping crystals can not be created (rather two spatially separated crystals are formed). However, if the beam-beam force is less than but comparable to that of the space-charge forces between the particles, we find that overlapping crystals can be formed and the beam-beam tune shift can be of the order of unity. Operating at low but non-zero temperature can increase the luminosity by several orders of magnitude over that of a usual collider. The construction of an appropriate lattice, and the development of adequately strong cooling, although theoretically achievable, is a challenge in practice.

  7. Fractured unconventional reservoirs in the Crystalline Basement

    NASA Astrophysics Data System (ADS)

    Plotnikova, Irina

    2015-04-01

    wells penetrating the crystalline basement rocks with cumulative thickness 8,216 m were studies. The cumulative thickness of formations with potential reservoir properties in these wells was 375.6 m (or 4.6 percent from cumulative thickness of the crystalline basement profile). In total, 82 intervals were identified using well log data. Comparison of these intervals with the results of tests using KII-146 showed that reliability of reservoir zone differentiation in 16 wells in question was 69%. First of all, it should be noted that the studied wells included those ones where the recommended optimal well logging complex had not been applied. Besides, borehole conditions of tests with KII-146 were not optimal in all wells. Evidently, all these factors impacted the reliability of test results. Nevertheless, practically 70-percent confirmation of reservoir zone differentiation in the crystalline basement profile based on well log data allows using well log information for the analysis of regularities of the crystalline basement reservoir distribution by section and area.

  8. 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

  9. Enzyme Architecture: Deconstruction of the Enzyme-Activating Phosphodianion Interactions of Orotidine 5′-Monophosphate Decarboxylase

    PubMed Central

    2015-01-01

    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 kcat and Km 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 (kcat)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 (Km)obs. PMID:24958125

  10. 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

  11. Neomycin inhibits the phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate stimulation of plasma membrane ATPase activity

    SciTech Connect

    Chen, Qiuyun; Boss, W.F. )

    1991-05-01

    The inositol phospholipids, phosphatidylinositol monophosphate (PIP) and phosphatidylinositol bisphosphate (PIP{sub 2}), have been shown to increase the vanadate-sensitive ATPase activity of plant plasma membranes. In this paper, the authors show the effect of various concentrations of phosphatidyinositol, PIP, and PIP{sub 2} on the plasma membrane vanadate-sensitive ATPase activity. PIP and PIP{sub 2} at concentrations at 10 nanomoles per 30 microgram membrane protein per milliliter of reaction mixture caused a twofold and 1.8-fold increase in the ATPase activity, respectively. The effect of these negatively charged phospholipids on the ATPase activity was inhibited by adding the positively charged aminoglycoside, neomycin. Neomycin did not affect the endogenous plasma membrane ATPase activity in the absence of exogenous lipids.

  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. 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

  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. Corticosteroid-Responsive Pulmonary Toxicity Associated with Fludarabine Monophosphate: A Case Report

    PubMed Central

    Rudzianskiene, Milda; Griniute, Rasa; Juozaityte, Elona; Inciura, Arturas; Rudzianskas, Viktoras; Emilia Kiavialaitis, Greta

    2012-01-01

    Fludarabine monophosphate is an effective drug for the treatment of lymphoid malignancies. Myelosuppression, opportunistic infections, and autoimmune hemolytic anemia are the most common side effects of fludarabine. Herein we report a 55-year-old female that presented with fever and dyspnea after completing her third cycle of FMD (fludarabine, mitoxantrone, and dexamethasone) chemotherapy for stage IV non-Hodgkin follicular lymphoma. Chest X-ray revealed bilateral pneumofibrotic changes and chest CT showed bilateral diffuse interstitial changes with fibrotic alterations. No evidence of infectious agents was noted. The patient had a reduced carbon monoxide transfer factor (45%). Her symptoms and radiographic findings resolved following treatment with prednisolone. The literature contains several cases of fludarabine-associated interstitial pulmonary toxicity that responded to steroid therapy. Fludarabine-induced pulmonary toxicity is reversible with cessation of the drug and administration of glucocorticosteroids. Conflict of interest:None declared. PMID:24385727

  16. Structural Determinants for Inhibitory Ligands of Orotidine-5′-Monophosphate Decarboxylase

    PubMed Central

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

    2011-01-01

    In recent years, orotidine-5′-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. PMID:20452222

  17. 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

  18. 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

  19. 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

  20. Site-selective DNA hydrolysis by Ce(IV)-EDTA with the use of one oligonucleotide additive bearing two monophosphates.

    PubMed

    Chen, Wen; Komiyama, Makoto

    2005-10-01

    Two deoxyuridine derivatives each bearing a monophosphate group at the 5-position with a C3 linker, were incorporated into an oligonucleotide. By using this modified oligonucleotide, a bulge was formed at a predetermined position in a DNA substrate, and two monophosphate groups were placed at both junctions of the bulge. Upon treatment of the mixture with Ce(IV)-EDTA at pH 7.0, the phosphodiester linkages at the bulge site were selectively and efficiently hydrolyzed. The monophosphate groups introduced into the bulge site greatly accelerated site-selective DNA scission. Compared with the previously reported two-additive system, which combines two oligonucleotide additives each with a monophosphate at their termini, the present one-additive system is simpler and more convenient. Furthermore, site-selective DNA hydrolysis by using this one-additive system is successful even at high reaction temperatures (e.g., 55 degrees C). This reflects the thermodynamic stability of the duplexes formed between the substrate and the additive DNA. PMID:16196014

  1. 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.

  2. Mutation of Archaeal Isopentenyl Phosphate Kinase Highlights Mechanism and Guides Phosphorylation of Additional Isoprenoid Monophosphates

    PubMed Central

    2010-01-01

    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 Mg2+-dependent reaction producing IPP. Here, we describe crystal structures of IPK from M. jannaschii refined to nominal resolutions of 2.0−2.8 Å. 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 Nε2 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

  3. 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.

  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. Nanocomposites with Crystalline Polymers

    NASA Astrophysics Data System (ADS)

    Kumar, Sanat

    2015-03-01

    The creation of ordered (layered) biomimetic materials typically follows a series of steps: first mix nanoparticles with water, organize the NPs by ice templating, evaporate the ice and then back fill with metal or polymer. We propose a simple method exploiting the in situ self-assembly of a crystalline polymer in the presence of nanoparticles to facilitate this process, and provide a completely new pathway for the synthesis of biomimetic materials. A suite of complementary experimental tools are used in this analysis. In parallel, we are developing theoretical tools to a priori predict the morphologies adopted by semicrystalline polymers. The convergence of these novel experimental and theoretical developments in the venerable field of semicrystalline polymers could lead to new applications for this largest class of commercially relevant polymeric materials. With Jacques Jestin, Brian Benicewicz, Dan Zhao, Longxi Zhao

  6. 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.

  7. Single crystalline magnetite nanotubes.

    PubMed

    Liu, Zuqin; Zhang, Daihua; Han, Song; Li, Chao; Lei, Bo; Lu, Weigang; Fang, Jiye; Zhou, Chongwu

    2005-01-12

    We descried a method to synthesize single crystalline Fe3O4 nanotubes by wet-etching the MgO inner cores of MgO/Fe3O4 core-shell nanowires. Homogeneous Fe3O4 nanotubes with controllable length, diameter, and wall thickness have been obtained. Resistivity of the Fe3O4 nanotubes was estimated to be approximately 4 x 10-2 Omega cm at room temperature. Magnetoresistance of approximately 1% was observed at T = 77 K when a magnetic field of B = 0.7 T was applied. The synthetic strategy presented here may be extended to a variety of materials such as YBCO, PZT, and LCMO which should provide ideal candidates for fundamental studies of superconductivity, piezoelectricity, and ferromagnetism in nanoscale structures. PMID:15631421

  8. Control ion transport by tuning the crystalline morphology in polyethylene oxide-based solid electrolyte

    NASA Astrophysics Data System (ADS)

    Cheng, Shan; Li, Christopher; Smith, Derrick

    2013-03-01

    The crystalline structure of polyethylene oxide (PEO) strongly affects the ion transport in solid PEO-Lithium salt electrolytes. Four possible phases can exist in a PEO-LiClO4 electrolyte membrane, e.g. crystalline PEO, amorphous PEO, amorphous PEO-Li complex and crystalline PEO-Li complex. It has been widely accepted so far that ion can transport through either amorphous PEO phase or PEO-Li crystalline complex phase. The ion conduction mechanism of the former is based on ion hopping as well as PEO segment motion. In the latter case two PEO chains form cylindrical channels within which Lithium cation can transport. In this presentation, we will show that tuning the crystalline morphology can optimize ion conduction. This can be achieved by controlling the orientation of the PEO lamellae as well as PEO-Li crystalline complex to optimize the ion conducting pathways.

  9. Mathematical models for the shape analysis of human crystalline lens

    NASA Astrophysics Data System (ADS)

    Giovanzana, Stefano; Talu, Stefan

    2012-01-01

    The objective of this paper is to present an analysis of mathematical models of the human crystalline lens. Seven existing models presented in the literature were investigated: conic, figuring conicoid, generalized conic, Hermans conic patch, Kasprzak hyperbolic cosine, Urs 10th-order Fourier series and Giovanzana parametric models. The analyzed models describe the shape for a data set of human crystalline lenses with ages from 6 to 82 years. The results highlight the difficulty and complexity of the task of choosing the most appropriate model for the crystalline lens shape.

  10. Increasing the conductivity of crystalline polymer electrolytes.

    PubMed

    Christie, Alasdair M; Lilley, Scott J; Staunton, Edward; Andreev, Yuri G; Bruce, Peter G

    2005-01-01

    Polymer electrolytes consist of salts dissolved in polymers (for example, polyethylene oxide, PEO), and represent a unique class of solid coordination compounds. They have potential applications in a diverse range of all-solid-state devices, such as rechargeable lithium batteries, flexible electrochromic displays and smart windows. For 30 years, attention was focused on amorphous polymer electrolytes in the belief that crystalline polymer:salt complexes were insulators. This view has been overturned recently by demonstrating ionic conductivity in the crystalline complexes PEO6:LiXF6 (X = P, As, Sb); however, the conductivities were relatively low. Here we demonstrate an increase of 1.5 orders of magnitude in the conductivity of these materials by replacing a small proportion of the XF6- anions in the crystal structure with isovalent N(SO2CF3)2- ions. We suggest that the larger and more irregularly shaped anions disrupt the potential around the Li+ ions, thus enhancing the ionic conductivity in a manner somewhat analogous to the AgBr(1-x)I(x) ionic conductors. The demonstration that doping strategies can enhance the conductivity of crystalline polymer electrolytes represents a significant advance towards the technological exploitation of such materials. PMID:15635406

  11. Radiolysis of crystalline nickel oxalates

    NASA Astrophysics Data System (ADS)

    Basahel, S. N.; Diefallah, El-H. M.; El-Fass, M. M.; Al-Sabban, E. A.

    Radiolysis of crystalline K 2Ni(C 2O 4) 2);6H 2O, K 2Ni(C 2O 4) 2 and Ni(C 2O 4));2H 2O has been investigated. The results showed that in K 2Ni(C 2O 4) 2);6H 2O, the initial G(Ni 3+) has a value of 3.75 and drops to about 1.27 when the dose approaches 1.2 × 10 22 eV g -1. The decrease in G(Ni 3+) with increasing radiation dose is accompanied with an increase in G(Ni 2+). In the irradiated anhydrated complex, the results however show an increase in G(Ni 3+) and a decrease in G(Ni 2+) with increasing radiation dose. The radiolysis of Ni(C 2O 4)·2H 2O showed an increase in G(Ni 3+) with increasing radiation dose. A mechanism has been suggested to explain the observed results.

  12. Compartmentalized Cyclic Adenosine 3′,5′-Monophosphate at the Plasma Membrane Clusters PDE3A and Cystic Fibrosis Transmembrane Conductance Regulator into Microdomains

    PubMed Central

    Penmatsa, Himabindu; Zhang, Weiqiang; Yarlagadda, Sunitha; Li, Chunying; Conoley, Veronica G.; Yue, Junming; Bahouth, Suleiman W.; Buddington, Randal K.; Zhang, Guangping; Nelson, Deborah J.; Sonecha, Monal D.; Manganiello, Vincent; Wine, Jeffrey J.

    2010-01-01

    Formation of multiple-protein macromolecular complexes at specialized subcellular microdomains increases the specificity and efficiency of signaling in cells. In this study, we demonstrate that phosphodiesterase type 3A (PDE3A) physically and functionally interacts with cystic fibrosis transmembrane conductance regulator (CFTR) channel. PDE3A inhibition generates compartmentalized cyclic adenosine 3′,5′-monophosphate (cAMP), which further clusters PDE3A and CFTR into microdomains at the plasma membrane and potentiates CFTR channel function. Actin skeleton disruption reduces PDE3A–CFTR interaction and segregates PDE3A from its interacting partners, thus compromising the integrity of the CFTR-PDE3A–containing macromolecular complex. Consequently, compartmentalized cAMP signaling is lost. PDE3A inhibition no longer activates CFTR channel function in a compartmentalized manner. The physiological relevance of PDE3A–CFTR interaction was investigated using pig trachea submucosal gland secretion model. Our data show that PDE3A inhibition augments CFTR-dependent submucosal gland secretion and actin skeleton disruption decreases secretion. PMID:20089840

  13. Topological Crystalline Insulators

    NASA Astrophysics Data System (ADS)

    Hsieh, Timothy

    2015-03-01

    Topological crystalline insulators (TCI) are new phases of matter in which nontrivial band topology and crystal symmetry unite to protect metallic states on the boundary. Remarkably, TCIs have been predicted and observed in the conveniently simple rocksalt SnTe class of IV-VI semiconductors. Despite the simple crystal structure, the interplay between topology and crystal symmetry in these materials have led to a rich variety of new phenomena, including the coexistence of massless and massive Dirac fermions arising from ferroelectric distortion and strain-induced flat band superconductivity. These new physical mechanisms are not only of intrinsic interest but may also find application in new transistor devices. After discussing the topological nature and potential uses of IV-VI family TCIs, I will present recent predictions of TCIs in several anti-perovskite materials. The origin of TCI in this new class of materials is strikingly different and involves the band inversion of two J = 3/2 quartets of Dirac fermions, which together form a ``Dirac octet.'' As interactions play a significant role in many anti-perovskites, this prediction serves as first step toward realizing TCIs in strongly correlated systems. This work is supported by NSF Graduate Research Fellowship No. 0645960 and DOE Office of Basic Energy Sciences, Division of Materials Sciences and Engineering under Award DE-SC0010526.

  14. Syntheses of 5'-Nucleoside Monophosphate Derivatives with Unique Aminal, Hemiaminal, and Hemithioaminal Functionalities: A New Class of 5'-Peptidyl Nucleotides.

    PubMed

    De, Swarup; Groaz, Elisabetta; Margamuljana, Lia; Herdewijn, Piet

    2016-06-01

    A number of synthetically useful transformations have been developed to generate novel 5'-peptidyl nucleoside monophosphate analogues that incorporate sensitive phosphoaminal, -hemiaminal or -hemithioaminal functionalities. The strategies adopted entailed the coupling between dipeptides, which enclose a reactive Cα-functionalized glycine residue and phosphate or phosphorothioate moieties. These developments led to potentially powerful and general methodologies for the preparation of α-phosphorylated pseudopeptides as well as nucleoside monophosphate mimics. The resulting conjugates are of interest for a variety of important applications, which range from drug development to synthetic biology, as pronucleotides or artificial building blocks for the enzymatic synthesis of xenobiotic information systems. The potential of all dipeptide-TMP conjugates as pyrophosphate mimics in the DNA polymerization reaction was tested, and the influence of the nature of the linker was evaluated by in vitro chain elongation assay in the presence of wild-type microbial DNA polymerases. PMID:27136602

  15. 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

  16. Myricetin is a novel inhibitor of human inosine 5'-monophosphate dehydrogenase with anti-leukemia activity.

    PubMed

    Pan, Huiling; Hu, Qian; Wang, Jingyuan; Liu, Zehui; Wu, Dang; Lu, Weiqiang; Huang, Jin

    2016-09-01

    Human inosine 5'-monophosphate dehydrogenase (hIMPDH) is a rate-limiting enzyme in the de novo biosynthetic pathway of purine nucleotides, playing crucial roles in cellular proliferation, differentiation, and transformation. Dysregulation of hIMPDH expression and activity have been found in a variety of human cancers including leukemia. In this study, we found that myricetin, a naturally occurring phytochemical existed in berries, wine and tea, was a novel inhibitor of human type 1 and type 2 IMPDH (hIMPDH1/2) with IC50 values of 6.98 ± 0.22 μM and 4.10 ± 0.14 μM, respectively. Enzyme kinetic analysis using Lineweaver-Burk plot revealed that myricetin is a mix-type inhibitor for hIMPDH1/2. Differential scanning fluorimetry and molecular docking simulation data demonstrate that myricetin is capable of binding with hIMPDH1/2. Myricetin treatment exerts potent anti-proliferative and pro-apoptotic effects on K562 human leukemia cells in a dose-dependent manner. Importantly, cytotoxicity of myricetin on K562 cells were markedly attenuated by exogenous addition of guanosine, a salvage pathway of maintaining intracellular pool of guanine nucleotides. Taking together, these results indicate that natural product myricetin exhibits potent anti-leukemia activity by interfering with purine nucleotides biosynthetic pathway through the suppression of hIMPDH1/2 catalytic activity. PMID:27378425

  17. Selective and potent urea inhibitors of Cryptosporidium parvum inosine 5′ monophosphate dehydrogenase

    PubMed Central

    Gorla, Suresh Kumar; Kavitha, Mandapati; Zhang, Minjia; Liu, Xiaoping; Sharling, Lisa; Gollapalli, Deviprasad R.; Striepen, Boris; Hedstrom, Lizbeth; Cuny, Gregory D.

    2012-01-01

    Cryptosporidium parvum and related species are zoonotic intracellular parasites of the intestine. Cryptosporidium is a leading cause of diarrhea in small children around the world. Infection can cause severe pathology in children and immunocompromised patients. This waterborne parasite is resistant to common methods of water treatment and therefore a prominent threat to drinking and recreation water even in countries with strong water safety systems. The drugs currently used to combat these organisms are ineffective. Genomic analysis revealed that the parasite relies solely on inosine-5′-monophosphate dehydrogenase (IMPDH) for the biosynthesis of guanine nucleotides. Herein, we report a selective urea-based inhibitor of C. parvum IMPDH (CpIMPDH) identified by high throughput screening. We performed a SAR study of these inhibitors with some analogues exhibiting high potency (IC50 < 2 nM) against CpIMPDH, excellent selectivity > 1000-fold versus human IMPDH type 2 and good stability in mouse liver microsomes. A subset of inhibitors also displayed potent antiparasitic activity in a Toxoplasma gondii model. PMID:22950983

  18. [Cyclic Guanosine Monophosphate as a Mediator in Processes of Stress Signaling Transduction in Higher Plants].

    PubMed

    Dubovskaya, L V; Bakakina, Y S; Volotovski, I D

    2015-01-01

    Currently, biophysical mechanisms of stress signaling transduction became an object of consideration of researchers in connection with the urgent necessity to develop new techniques to enhance the sustainability and productivity of agricultural crops. The development of sensitive methods for the determination of cyclic guanosine monophosphate (cGMP) and comparative analysis of cGMP-dependent events in biological systems has contributed to progress in the understanding of the functioning of cGMP in plant cells. Currently, it is shown that cGMP as a secondary mediator is involved in such vital processes of growth and development of plants as seed germination, cell division, development of chloroplasts, flowering and regulation of stomatal movements. This review summarizes the available data in the literature about the role of cGMP in the responses of plant organisms to the action of stress factors of abiotic and biotic nature and its interaction with other intracellular mediators. With the use of existing ideas about the biophysical mechanisms of stress in plants, the basic elements of cGMP-dependent signal transduction system in a plant cell are considered. PMID:26394467

  19. Radiolysis in aqueous solution of dinucleoside monophosphates by high-energy electrons and fission neutrons.

    PubMed

    Vaishnav, Y N; Swenberg, C E

    1993-01-01

    The radiation chemistry in aqueous solution of the dinucleoside monophosphate d-[CpT] and its sequence isomer d-[TpC] in air or nitrogen was examined using different qualities and quantities of radiations. High-performance liquid chromatography and gas chromatography-mass spectrometry were used to analyze the high-energy electron (13.2 MeV) exposure products or fission-neutron exposure products of d-[CpT] and d-[TpC]. A comparison of product profiles obtained from irradiated d-[CpT] and d-[TpC] suggests that, at relatively low radiation doses (50-250 Gy), products are formed by N-glycosidic or phosphodiester bond-cleavage, while at higher doses (500-1000 Gy) additional products were detected as a consequence of ring-modification mechanisms. The plots of radiation dose-yield and corresponding calculated G values of the released undamaged bases and nucleosides from d-[CpT] and d-[TpC] suggest a base-sequence dependence and a quality- and quantity-dependent response to ionizing radiation. Although the product quantities formed from sequence isomers were slightly different, we found no qualitative differences in the product formed at the lowest doses examined. PMID:8434108

  20. A Screening Pipeline for Antiparasitic Agents Targeting Cryptosporidium Inosine Monophosphate Dehydrogenase

    PubMed Central

    Sharling, Lisa; Liu, Xiaoping; Gollapalli, Deviprasad R.; Maurya, Sushil K.; Hedstrom, Lizbeth; Striepen, Boris

    2010-01-01

    Background The protozoan parasite Cryptosporidium parvum is responsible for significant disease burden among children in developing countries. In addition Cryptosporidiosis can result in chronic and life-threatening enteritis in AIDS patients, and the currently available drugs lack efficacy in treating these severe conditions. The discovery and development of novel anti-cryptosporidial therapeutics has been hampered by the poor experimental tractability of this pathogen. While the genome sequencing effort has identified several intriguing new targets including a unique inosine monophosphate dehydrogenase (IMPDH), pursuing these targets and testing inhibitors has been frustratingly difficult. Methodology and Principal Findings Here we have developed a pipeline of tools to accelerate the in vivo screening of inhibitors of C. parvum IMPDH. We have genetically engineered the related parasite Toxoplasma gondii to serve as a model of C. parvum infection as the first screen. This assay provides crucial target validation and a large signal window that is currently not possible in assays involving C. parvum. To further develop compounds that pass this first filter, we established a fluorescence-based assay of host cell proliferation, and a C. parvum growth assay that utilizes automated high-content imaging analysis for enhanced throughput. Conclusions and Significance We have used these assays to evaluate C. parvum IMPDH inhibitors emerging from our ongoing medicinal chemistry effort and have identified a subset of 1,2,3-triazole ethers that exhibit excellent in vivo selectivity in the T. gondii model and improved anti-cryptosporidial activity. PMID:20706578

  1. Inosine monophosphate dehydrogenase expression: transcriptional regulation of the type I and type II genes.

    PubMed

    Zimmermann, A; Gu, J J; Spychala, J; Mitchell, B S

    1996-01-01

    Inosine 5'-monophosphate dehydrogenase (IMPDH) is an essential rate-limiting enzyme in the de novo guanine nucleotide synthetic pathway that catalyzes the conversion of IMP to XMP. Enzyme activity is accounted for by the expression of two distinct but closely related genes termed IMPDH I and II. Increased IMPDH activity has been linked to both cellular proliferation and neoplastic transformation and generally ascribed to an increase in the expression of the type II gene. We have characterized the type I and type II genes and identified elements important in the transcriptional regulation of both genes. The type II IMPDH gene contains a 466 bp 5' flanking region spanning the translation start site that contains several transcription factor binding sites and mediates increased transcription of a CAT reporter gene in peripheral blood T lymphocytes when these cells are induced to proliferate. The single functional IMPDH type I gene contains exon-intron boundaries and exon structures that are nearly identical to those in the type II gene. In contrast to the type II gene, however, it contains two putative promoter sites, each with the potential for transcriptional regulation. We conclude that these two genes most probably arose from an early gene duplication event and that their highly conserved structures and differential regulation at the transcriptional level argue strongly for a significant role for each gene in cellular metabolism, growth, and differentiation. PMID:8869741

  2. Cyclic diguanylate monophosphate directly binds to human siderocalin and inhibits its antibacterial activity

    PubMed Central

    Li, Weihui; Cui, Tao; Hu, Lihua; Wang, Ziqing; Li, Zongqiang; He, Zheng-Guo

    2015-01-01

    Cyclic diguanylate monophosphate (c-di-GMP) is a well-conserved second messenger in bacteria. During infection, the innate immune system can also sense c-di-GMP; however, whether bacterial pathogens utilize c-di-GMP as a weapon to fight against host defense for survival and possible mechanisms underlying this process remain poorly understood. Siderocalin (LCN2) is a key antibacterial component of the innate immune system and sequesters bacterial siderophores to prevent acquisition of iron. Here we show that c-di-GMP can directly target the human LCN2 protein to inhibit its antibacterial activity. We demonstrate that c-di-GMP specifically binds to LCN2. In addition, c-di-GMP can compete with bacterial ferric siderophores to bind LCN2. Furthermore, c-di-GMP can significantly reduce LCN2-mediated inhibition on the in vitro growth of Escherichia coli. Thus, LCN2 acts as a c-di-GMP receptor. Our findings provide insight into the mechanism by which bacteria utilize c-di-GMP to interfere with the innate immune system for survival. PMID:26390966

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

    PubMed

    Manganiello, V; Evans, W H; Stossel, T P; Mason, R J; Vaughan, M

    1971-12-01

    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

  4. A Mixed-Valent Molybdenum Monophosphate with a Layer Structure: KMo 3P 2O 14

    NASA Astrophysics Data System (ADS)

    Guesdon, A.; Borel, M. M.; Leclaire, A.; Grandin, A.; Raveau, B.

    1994-03-01

    A new mixed-valent molybdenum monophosphate with a layer structure KMo 3P 2O 14 has been isolated. It crystallizes in the space group P2 1/ m with a = 8.599(2) Å, b = 6.392(2) Å, c = 10.602(1) Å, and β = 111.65(2)°. The layers [Mo 3P 2O 14] ∞ are parallel to (100) and consist of [MoPO 8] ∞ chains running along limitb→ , in which one MoO 6 octahedron alternates with one PO 4 tetrahedron. In fact, four [MoPO 8] ∞ chains share the corners of their polyhedra and the edges of their octahedra, forming [Mo 4P 4O 24] ∞ columns which are linked through MoO 5 bipyramids along limitc→. The K + ions interleaved between these layers are surrounded by eight oxygens, forming bicapped trigonal prisms KO 8. Besides the unusual trigonal bipyramids MoO 5, this structure is also characterized by a tendency to the localization of the electrons, since one octahedral site is occupied by Mo(V), whereas the other octahedral site and the trigonal bipyramid are occupied by Mo(VI). The similarity of this structure with pure octahedral layer structures suggests the possibility of generating various derivatives, and of ion exchange properties.

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

    PubMed

    Norberg, J; Nilsson, L

    1994-08-01

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

  6. 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

  7. A putative role for inosine 5' monophosphate dehydrogenase (IMPDH) in Leishmania amazonensis programmed cell death.

    PubMed

    Pitaluga, A N; Moreira, M E C; Traub-Csekö, Y M

    2015-02-01

    Leishmania amazonensis undergoes apoptosis-like programmed cell death (PCD) under heat shock conditions. We identified a potential role for inosine 5' monophosphate dehydrogenase (IMPDH) in L. amazonensis PCD. Trypanosomatids do not have a "de novo" purine synthesis pathway, relying on the salvage pathway for survival. IMPDH, a key enzyme in the purine nucleotide pathway, is related to cell growth and apoptosis. Since guanine nucleotide depletion triggers cell cycle arrest and apoptosis in several organisms we analyzed the correlation between IMPDH and apoptosis-like death in L. amazonensis. The L. amazonensis IMPDH inhibition effect on PCD was evaluated through gene expression analysis, mitochondrial depolarization and detection of Annexin-V labeled parasites. We demonstrated a down-regulation of impdh expression under heat shock treatment, which mimics the natural mammalian host infection. Also, IMPDH inhibitors ribavirin and mycophenolic acid (MPA) prevented cell growth and generated an apoptosis-like phenotype in sub-populations of L. amazonensis promastigotes. Our results are in accordance with previous results showing that a subpopulation of parasites undergoes apoptosis-like cell death in the nutrient poor environment of the vector gut. Here, we suggest the involvement of purine metabolism in previously observed apoptosis-like cell death during Leishmania infection. PMID:25499513

  8. 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

  9. Stimulation of cyclic adenosine monophosphate accumulation causes breakdown of the blood-retinal barrier.

    PubMed

    Sen, H A; Campochiaro, P A

    1991-06-01

    Pigmented rabbits were given an intravitreous injection of 0.1 ml of various concentrations of test drug, and vitreous fluorophotometry was done 6 and 24 hr after injection. Dibutyryl cyclic adenosine monophosphate (AMP) and 8-bromo-cyclic AMP caused reversible intravitreous fluorescein leakage only at relatively high concentrations. Adrenergic agents that are effective stimulators of adenylate cyclase (epinephrine, isoproterenol, and norepinephrine) caused transient intravitreous fluorescein leakage (2.3-3.1-fold above baseline) that was significantly greater than that caused by phenylephrine (1.1-fold above baseline), an adrenergic agent that is a poor stimulator of adenylate cyclase. Prostaglandins E1 and E2, which are good stimulators of adenylate cyclase, caused striking disruption of the blood-ocular barriers, and prostaglandins that are not good stimulators of adenylate cyclase had little or no effect on these barriers. The magnitude of the prostaglandin E1 effect (9.3-fold above baseline) was similar to that of N-ethylcarboxamidoadenosine (NECA), the most potent adenosine agonist, and was greater than one would predict based on its effect on adenylate cyclase in vitro. Prostaglandin E1, like NECA, also caused retinal vasodilation and hemorrhages. These data suggest that stimulation of intracellular cyclic AMP accumulation may be a common feature of mediators that cause breakdown of the blood-retinal barrier, but there may be another as yet unexplained feature shared by PGE1 and NECA that makes them particularly effective and capable of causing retinal vasodilation and hemorrhages. PMID:1647374

  10. Preliminary X-ray crystallographic analysis of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase.

    PubMed

    Whitby, F G; Huete-Perez, J; Luecke, H; Wang, C C

    1995-12-01

    Inosine-5'-monophosphate dehydrogenase (IMPDH) from the protozoan parasite Tritrichomonas foetus has been expressed in E. coli and crystallized. Crystals were grown to 0.1 mm in each dimension in 18 to 72 h using ammonium sulfate and low-molecular-weight polyethylene glycols. The crystals belong to the cubic space group P432 with unit cell edge = 157.25 A. The enzyme is a homotetramer with each monomer having a molecular weight of 55,534 Da. There is one monomer per asymmetric unit, based on a volume/mass ratio of 2.7 A3/Da and self-rotation analysis. The crystals are adequately stable to allow a complete data set to be collected from a single crystal. Complete native data sets have been collected to 2.3 A resolution at 4 degrees C using synchrotron radiation. High-quality complete data extending to 3.0 A resolution have been collected from crystals of four putative derivatives, and the data appear to be isomorphous with that of the native crystals in each case. Efforts to solve the derivatives for use in MIR phasing are underway. PMID:8749858

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

    PubMed Central

    Trevillyan, J M; Pall, M L

    1979-01-01

    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. PMID:220213

  12. 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

  13. 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

  14. 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})

  15. Circumstellar Crystalline Silicates: Evolved Stars

    NASA Astrophysics Data System (ADS)

    Tartar, Josh; Speck, A. K.

    2008-05-01

    One of the most exciting developments in astronomy in the last 15 years was the discovery of crystalline silicate stardust by the Short Wavelength Spectrometer (SWS) on board of ISO; discovery of the crystalline grains was indeed one of the biggest surprises of the ISO mission. Initially discovered around AGB stars (evolved stars in the range of 0.8 > M/M¤>8) at far-infrared (IR) wavelengths, crystalline silicates have since been seen in many astrophysical environments including young stellar objects (T Tauri and Herbig Ae/Be), comets and Ultra Luminous Infrared Galaxies. Low and intermediate mass stars (LIMS) comprise 95% of the contributors to the ISM, so study of the formation of crystalline silicates is critical to our understanding of the ISM, which is thought to be primarily amorphous (one would expect an almost exact match between the composition of AGB dust shells and the dust in the ISM). Whether the crystalline dust is merely undetectable or amorphized remains a mystery. The FORCAST instrument on SOFIA as well as the PACS instrument on Herschel will provide exciting observing opportunities for the further study of crystalline silicates.

  16. Level of 5-fluorodeoxyuridine 5'-monophosphate in cancerous tissue in patients with gastric cancer under preoperative administration of TS-1. A preliminary study.

    PubMed

    Yamamoto, S; Kubota, K

    2005-09-01

    Metabolizing enzymes such as thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) have long been known to be useful for predicting response and outcome in patients receiving 5-fluorouracil (5-FU). However, few studies have examined the cancerous tissue levels of 5-fluorodeoxyuridine 5'-monophosphate (FdUMP), a metabolite of 5-FU that has an important role in inhibiting DNA synthesis. In this study, for the first time to our knowledge, we measured concentrations of FdUMP in tumor specimens and surrounding non-cancerous tissue obtained at operation in 10 patients with gastric cancer who received TS-1 before surgery (80 mg/m2, 3 days). The FdUMP level in the cancerous tissue was significantly higher than that in the non-cancerous tissue (153.0 +/- 85.7 pmol/g tissue vs. 53.0 +/- 47.0 pmol/g tissue)(p = 0.0046). Furthermore, the TS level in tumor was significantly higher than that in non-cancerous tissue (6.362 +/- 5.106 pmol/g tissue vs. 2.092 +/- 2.050 pmol/g tissue) (p = 0.0310). The mean ratios of TS-bound FdUMP to TS and FdUMP concentrations in the cancerous tissues were 45.9% and 2.00%, respectively. Our results demonstrate that in cancerous tissue, TS-1 may produce high FdUMP concentration and suppress about half FdUMP concentration by forming ternary complexes. PMID:16270533

  17. 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.

  18. 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

  19. The effects of cyclic adenosine 3',5'-monophosphate and other adenine nucleotides on body temperature.

    PubMed Central

    Dascombe, M J; Milton, A S

    1975-01-01

    1. Adenosine 3',5'-monophosphate (cAMP), its dibutyryl derivative (Db-cAMP) and other adenine nucleotides have been micro-injected into the hypothalamic region of the unanaesthetized cat and the effects on body temperature, and on behavioural and autonomic thermoregulatory activities observed. 2. Db-cAMP and cAMP both produced hypothermia when applied to the pre-optic anterior hypothalamus. With Db-cAMP the hypothermia was shown to be dose dependent between 50 and 500 mug (0-096-0-96 mumole). 3. AMP, ADP and ATP also produced hypothermia when injected into the pre-optic anterior hypothalamus. 4. The order of relative potencies of the adenine nucleotides with respect both to the hypothermia produced and to the autonomic thermoregulatory effects observed were similar. Db-cAMP was most potent and cAMP least. 5. Micro-injection into the pre-optic anterior hypothalamus of many substances including saline produced in most cats a non-specific rise in body temperature apparently the result of tissue damage. Intraperitoneal injection of 4-acetamidophenol (paracetamol 50 mg/kg) reduced or abolished this febrile response. 6. The hypothermic effect of the adenine nucleotides has been compared with the effects produced in these same cats by micro-injections of noradrenaline, 5-hydroxytryptamine, a mixture of acetylcholine and physostigmine (1:1), EDTA and excess Ca2+ ions. 7. It is concluded that as Db-cAMP and cAMP both produce hypothermia, it is unlikely that endogenous cAMP in the pre-optic anterior hypothalamus mediates the hyperthermic responses to pyrogens and prostaglandins. PMID:170396

  20. The effects of cyclic adenosine 3',5'-monophosphate and other adenine nucleotides on body temperature.

    PubMed

    Dascombe, M J; Milton, A S

    1975-08-01

    1. Adenosine 3',5'-monophosphate (cAMP), its dibutyryl derivative (Db-cAMP) and other adenine nucleotides have been micro-injected into the hypothalamic region of the unanaesthetized cat and the effects on body temperature, and on behavioural and autonomic thermoregulatory activities observed. 2. Db-cAMP and cAMP both produced hypothermia when applied to the pre-optic anterior hypothalamus. With Db-cAMP the hypothermia was shown to be dose dependent between 50 and 500 mug (0-096-0-96 mumole). 3. AMP, ADP and ATP also produced hypothermia when injected into the pre-optic anterior hypothalamus. 4. The order of relative potencies of the adenine nucleotides with respect both to the hypothermia produced and to the autonomic thermoregulatory effects observed were similar. Db-cAMP was most potent and cAMP least. 5. Micro-injection into the pre-optic anterior hypothalamus of many substances including saline produced in most cats a non-specific rise in body temperature apparently the result of tissue damage. Intraperitoneal injection of 4-acetamidophenol (paracetamol 50 mg/kg) reduced or abolished this febrile response. 6. The hypothermic effect of the adenine nucleotides has been compared with the effects produced in these same cats by micro-injections of noradrenaline, 5-hydroxytryptamine, a mixture of acetylcholine and physostigmine (1:1), EDTA and excess Ca2+ ions. 7. It is concluded that as Db-cAMP and cAMP both produce hypothermia, it is unlikely that endogenous cAMP in the pre-optic anterior hypothalamus mediates the hyperthermic responses to pyrogens and prostaglandins. PMID:170396

  1. 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

  2. Triazole-containing monophosphate mRNA cap analogs as effective translation inhibitors

    PubMed Central

    Piecyk, Karolina; Lukaszewicz, Maciej; Darzynkiewicz, Edward

    2014-01-01

    Synthetic analogs of the 5′ end of mRNA (cap structure) are widely used in molecular studies on mechanisms of cellular processes such as translation, intracellular transport, splicing, and turnover. The best-characterized cap binding protein is translation initiation factor 4E (eIF4E). Recognition of the mRNA cap by eIF4E is a critical, rate-limiting step for efficient translation initiation and is considered a major target for anticancer therapy. Here, we report a facile methodology for the preparation of N2-triazole-containing monophosphate cap analogs and present their biological evaluation as inhibitors of protein synthesis. Five analogs possessing this unique hetero-cyclic ring spaced from the m7-guanine of the cap structure at a distance of one or three carbon atoms and/or additionally substituted by various groups containing the benzene ring were synthesized. All obtained compounds turned out to be effective translation inhibitors with IC50 similar to dinucleotide triphosphate m7GpppG. As these compounds possess a reduced number of phosphate groups and, thereby, a negative charge, which may support their cell penetration, this type of cap analog might be promising in terms of designing new potential therapeutic molecules. In addition, an exemplary dinucleotide from a corresponding mononucleotide containing benzyl substituted 1,2,3-triazole was prepared and examined. The superior inhibitory properties of this analog (10-fold vs. m7GpppG) suggest the usefulness of such compounds for the preparation of mRNA transcripts with high translational activity. PMID:25150228

  3. Inosine monophosphate dehydrogenase variability in renal transplant patients on long-term mycophenolate mofetil therapy

    PubMed Central

    Chiarelli, Laurent R; Molinaro, Mariadelfina; Libetta, Carmelo; Tinelli, Carmine; Cosmai, Laura; Valentini, Giovanna; Canton, Antonio Dal; Regazzi, Mario

    2010-01-01

    AIMS Long-term mycophenolate mofetil (MMF) therapy may induce inosine 5′-monophosphate dehydrogenase (IMPDH) activity in peripheral blood mononuclear cells (PBMCs), thus decreasing MMF immunosuppressive properties. Pharmacodynamic monitoring was used to investigate whether biological activity is altered after long-term therapy. METHODS IMPDH activity was measured in PBMC samples from 54 stable kidney transplant patients, already on MMF (for at least 3 months), before (t0) and 2 h after (t2) MMF morning dose administration; levels were monitored for up to 15 months, together with total mycophenolic acid (MPA) and free MPA concentrations. RESULTS During the 15 months' monitoring, t0 IMPDH activity in transplant recipients increased from 5.9 ± 3.7 nmol h−1 mg−1[95% confidence interval (CI) 4.9, 6.9] to 9.0 ± 3.9 nmol h−1 mg−1 (95% CI 7.2, 10.8), with an intra- and interpatient variability of 28% and 42%. Five patients experienced acute rejection during the follow-up: t0 IMPDH activity was increased during rejection vs. nonrejection, and the trend was significantly higher in rejecting than in nonrejecting subjects for the whole monitoring period. CONCLUSIONS Even though a correlation has been found between IMPDH activity and rejection, its efficacy as a predictive tool in long-term transplant outcomes may be affected by high interpatient variability; on the other hand, continuous monitoring of the IMPDH trend could make an effective prognostic parameter of rejection. Other trials also including pre-transplant data on both IMPDH expression and activity are warranted to better assess their role as biomarkers for MPA effect in clinical practice. PMID:20078611

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. On the interaction of caffeine with nucleic acids. III. 1H NMR studies of caffeine--5'-adenosine monophosphate and caffeine-poly(riboadenylate) interactions.

    PubMed

    Fritzsche, H; Petri, I; Schütz, H; Weller, K; Sedmera, P; Lang, H

    1980-02-01

    1) The self-association of both caffeine (Cf) and 5'-adenosine monophosphate (AMP) in aqueous solution has been reinvestigated by 1H NMR. The self-association process is characterized by an isodesmic model. The apparent self-association constants of the vertical stacking process are KCf = (10.6 +/- 1.0) M-1 and KAMP = (1.67 +/- 0.17) M-1. The arrangement of the monomeric units in the stacked aggregates is discussed in terms of isoshielding curves theoretically calculated by Giessner-Prettre and Pullman. Models are proposed which are consistent with these and further previous NMR data. 2) The interaction of Cf and AMP has been studied by 1H NMR. The apparent association constant of the complex Cf-AMP is KC-A = (7.3 +/- 1.2) M-1. Two models of the mutual arrangement of AMP and Cf in the complex are proposed on the basis of the calculated isoshielding curves considering both ring current and local atomic diamagnetic anisotropy effects. 3) The interaction of Cf and poly(riboadenylate), (rA)n, is indicated by a downfield shift of the H-8 line but an upfield shifts of the H-2 line in the 1H NMR spectra of (rA)n. The concentration dependence of the 1H NMR shifts of both Cf and (rA)n can be explained by the existence of two binding mechanisms. We suggest (i) partial insertion of Cf between adjacent base residues of ordered single-stranded regions of (rA)n and (ii) outside binding of Cf in form of monomeric Cf as well as of self-associated aggregates. The complex geometry of insertion proposed on the basis of the calculated isoshielding curves is characterized by a stronger overlapping of the Cf ring and the H-2 proton of (rA)n as compared to the H-8 proton. PMID:7357061

  9. ESR Measurement Of Crystallinity In Semicrystalline Polymers

    NASA Technical Reports Server (NTRS)

    Kim, Soon Sam; Tsay, Fun-Dow

    1989-01-01

    Photogenerated free radicals decay at different rates in crystalline and amorphous phases. Degree of crystallinity in polymer having both crystalline and amorphous phases measured indirectly by technique based in part on electron-spin-resonance (ESR) spectroscopy. Accuracy of crystallinity determined by new technique equals or exceeds similar determinations by differential scanning calorimetry, wide-angle x-ray scattering, or measurement of density.

  10. Nanostructures having crystalline and amorphous phases

    SciTech Connect

    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.

  11. 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.

  12. 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.

  13. [Circular dichroism of DNA liquid-crystalline dispersion particles].

    PubMed

    Semenov, S V; Yevdokimov, Yu M

    2015-01-01

    The optical activity of DNA liquid-crystalline dispersions is being investigated based on a theory for absorption of electromagnetic waves by large molecular aggregates. The impact on the dispersions-optical properties, exerted by the interaction between the complexes of nucleic acid molecules and nanoparticles, is being considered. PMID:26016021

  14. Cyclic adenosine 3', 5'-monophosphate in cerebrospinal fluid during thermoregulation and fever.

    PubMed Central

    Dascombe, M J; Milton, A S

    1976-01-01

    1. Samples of cerebrospinal fluid (c.s.f.) have been taken from the cisterna magna of unanaesthetized cats, whilst rectal temperature was recorded, during exposure of the animals to various ambient temperatures and during fever induced by pyrogen. The concentration of adenosine 3', 5'-monophosphate (cyclic AMP) in samples of c.s.f. has been assayed. 2. Cats exposed to low ambient temperatures (-2 to +2 degrees C) for 3 h maintained body temperature by both behavioural and autonomic heat gain activity. Exposure of cats to high ambient temperatures (44 - 45 degrees C) for 3.5 h caused a rise in body temperatures of about 2.5 degrees C, despite behavioural and autonomic heat loss activity. Neither cold nor heat stress had a significant effect on c.s.f. cyclic AMP. 3. Fever induced by intravenous Shigella dysenteriae (2 and 20 mug/kg) was associated with a dose-related increase in the concentration of cyclic AMP in c.s.f. Paracetamol (75 mg/kg) injected I.P. before the onset of fever, suppressed the increase in both temperature and c.s.f. cyclic AMP in response to pyrogen. Paracetamol (50 and 100 mg/kg), injected after the onset of fever, caused a fall in temperature, which was not associated with a decrease in the concentration of cyclic AMP in c.s.f. 4. Fever induced in cats by intravenous Shigella dysenteriae (20 mug/kg) was associated with an increase in the concentration of cyclic AMP in plasma as well as in c.s.f. 5. The sodium salt of cyclic AMP (0.1-10 mg/kg) injected I.V. into unanaesthetized cats caused a dose-related hypothermia, which was associated with autonomic heat loss activity and a dose-related increase in the concentration of cyclic AMP in cisternal c.s.f., which was not mimicked by adenosine. 6. It is concluded that the raised concentrations of cyclic AMP in c.s.f., in response to pyrogen I.V., do not mediate fever in the cat and that the concentration of cyclic AMP in cisternal c.s.f. may be affected by changes in the plasma concentration of the

  15. 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.

  16. 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.

  17. CRYSTALLINE BEAMS AT HIGH ENERGIES.

    SciTech Connect

    WEI, J.; OKAMOTO, H.; YURI, Y.; SESSLER, A.; MACHIDA, S.

    2006-06-23

    Previously it was shown that by crystallizing each of the two counter-circulating beams, a much larger beam-beam tune shift can be tolerated during the beam-beam collisions; thus a higher luminosity can be reached for colliding beams [1]. On the other hand, crystalline beams can only be formed at energies below the transition energy ({gamma}{sub T}) of the accelerators [2]. In this paper, we investigate the formation of crystals in a high-{gamma}{sub T} lattice that also satisfies the maintenance condition for a crystalline beam [3].

  18. A Facile and Sensitive Method for Quantification of Cyclic Nucleotide Monophosphates in Mammalian Organs: Basal Levels of Eight cNMPs and Identification of 2',3'-cIMP

    PubMed Central

    Jia, Xin; Fontaine, Benjamin M.; Strobel, Fred; Weinert, Emily E.

    2014-01-01

    A sensitive, versatile and economical method to extract and quantify cyclic nucleotide monophosphates (cNMPs) using LC-MS/MS, including both 3',5'-cNMPs and 2',3'-cNMPs, in mammalian tissues and cellular systems has been developed. Problems, such as matrix effects from complex biological samples, are addressed and have been optimized. This protocol allows for comparison of multiple cNMPs in the same system and was used to examine the relationship between tissue levels of cNMPs in a panel of rat organs. In addition, the study reports the first identification and quantification of 2',3'-cIMP. The developed method will allow for quantification of cNMPs levels in cells and tissues with varying disease states, which will provide insight into the role(s) and interplay of cNMP signalling pathways. PMID:25513747

  19. 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...

  20. The cystathionine-β-synthase domains on the guanosine 5''-monophosphate reductase and inosine 5'-monophosphate dehydrogenase enzymes from Leishmania regulate enzymatic activity in response to guanylate and adenylate nucleotide levels.

    PubMed

    Smith, Sabrina; Boitz, Jan; Chidambaram, Ehzilan Subramanian; Chatterjee, Abhishek; Ait-Tihyaty, Maria; Ullman, Buddy; Jardim, Armando

    2016-06-01

    The Leishmania guanosine 5'-monophosphate reductase (GMPR) and inosine 5'-monophosphate dehydrogenase (IMPDH) are purine metabolic enzymes that function maintaining the cellular adenylate and guanylate nucleotide. Interestingly, both enzymes contain a cystathionine-β-synthase domain (CBS). To investigate this metabolic regulation, the Leishmania GMPR was cloned and shown to be sufficient to complement the guaC (GMPR), but not the guaB (IMPDH), mutation in Escherichia coli. Kinetic studies confirmed that the Leishmania GMPR catalyzed a strict NADPH-dependent reductive deamination of GMP to produce IMP. Addition of GTP or high levels of GMP induced a marked increase in activity without altering the Km values for the substrates. In contrast, the binding of ATP decreased the GMPR activity and increased the GMP Km value 10-fold. These kinetic changes were correlated with changes in the GMPR quaternary structure, induced by the binding of GMP, GTP, or ATP to the GMPR CBS domain. The capacity of these CBS domains to mediate the catalytic activity of the IMPDH and GMPR provides a regulatory mechanism for balancing the intracellular adenylate and guanylate pools. PMID:26853689

  1. 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

  2. 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.

  3. Liquid Crystalline Networks Composed of Pentagonal, Square, and Triangular Cylinders

    NASA Astrophysics Data System (ADS)

    Chen, Bin; Zeng, Xiangbing; Baumeister, Ute; Ungar, Goran; Tschierske, Carsten

    2005-01-01

    T-shaped molecules are designed in such a way that they self-organize into nanoscale liquid crystalline honeycombs based on polygons with any chosen number of sides. One of the phases reported here is a periodic organization of identical pentagonal cylinders; the other one is a structure composed of square-shaped and triangular cylinders in the ratio 2:1. These two different packing motifs represent duals of the same topological class. The generalization of the concept applied here allows the prediction of a whole range of unusual complex liquid crystalline phases.

  4. Ductile crystalline-amorphous nanolaminates.

    PubMed

    Wang, Yinmin; Li, Ju; Hamza, Alex V; Barbee, Troy W

    2007-07-01

    It is known that the room-temperature plastic deformation of bulk metallic glasses is compromised by strain softening and shear localization, resulting in near-zero tensile ductility. The incorporation of metallic glasses into engineering materials, therefore, is often accompanied by complete brittleness or an apparent loss of useful tensile ductility. Here we report the observation of an exceptional tensile ductility in crystalline copper/copper-zirconium glass nanolaminates. These nanocrystalline-amorphous nanolaminates exhibit a high flow stress of 1.09 +/- 0.02 GPa, a nearly elastic-perfectly plastic behavior without necking, and a tensile elongation to failure of 13.8 +/- 1.7%, which is six to eight times higher than that typically observed in conventional crystalline-crystalline nanolaminates (<2%) and most other nanocrystalline materials. Transmission electron microscopy and atomistic simulations demonstrate that shear banding instability no longer afflicts the 5- to 10-nm-thick nanolaminate glassy layers during tensile deformation, which also act as high-capacity sinks for dislocations, enabling absorption of free volume and free energy transported by the dislocations; the amorphous-crystal interfaces exhibit unique inelastic shear (slip) transfer characteristics, fundamentally different from those of grain boundaries. Nanoscale metallic glass layers therefore may offer great benefits in engineering the plasticity of crystalline materials and opening new avenues for improving their strength and ductility. PMID:17592136

  5. 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.

  6. Lens Aging: Effects of Crystallins

    PubMed Central

    Sharma, K. Krishna; Santhoshkumar, Puttur

    2009-01-01

    The primary function of the eye lens is to focus light on the retina. The major proteins in the lens—a, b, and g-crystallins—are constantly subjected to age-related changes such as oxidation, deamidation, truncation, glycation, and methylation. Such age-related modifications are cumulative and affect crystallin structure and function. With time, the modified crystallins aggregate, causing the lens to increasingly scatter light on the retina instead of focusing light on it and causing the lens to lose its transparency gradually and become opaque. Age-related lens opacity, or cataract, is the major cause of blindness worldwide. We review deamidation, and glycation that occur in the lenses during aging keeping in mind the structural and functional changes that these modifications bring about in the proteins. In addition, we review proteolysis and discuss recent observations on how crystallin fragments generated in vivo, through their anti-chaperone activity may cause crystallin aggregation in aging lenses. We also review hyperbaric oxygen treatment induced guinea pig and ‘humanized’ ascorbate transporting mouse models as suitable options for studies on age-related changes in lens proteins. PMID:19463898

  7. Potential of mean force calculations of the stacking-unstacking process in single-stranded deoxyribodinucleoside monophosphates.

    PubMed Central

    Norberg, J; Nilsson, L

    1995-01-01

    The free energy of the stacking-unstacking process of deoxyribodinucleoside monophosphates in aqueous solution has been investigated by potential of mean force calculations along a reaction coordinate, defined by the distance between the glycosidic nitrogen atoms of the bases. The stacking-unstacking process of a ribodinucleoside monophosphate was observed to be well characterized by this coordinate, which has the advantage that it allows for a dynamical backbone and flexible bases. All 16 naturally occurring DNA dimers composed of the adenine, cytosine, guanine, or thymine bases in both the 5' and the 3' positions were studied. From the free-energy profiles we observed the deepest minima for the stacked states of the purine-purine dimers, but good stacking was also observed for the purine-pyrimidine and pyrimidine-purine dimers. Substantial stacking ability was found for the dimers composed of a thymine base and a purine base and also for the deoxythymidylyl-3',5'-deoxythymidine dimer. Very poor stacking was observed for the dCpdC dimer. Conformational properties and solvent accessibility are discussed for the stacked and unstacked dimers. The potential of mean force profiles of the stacking-unstacking process for the DNA dimers are compared with the RNA dimers. PMID:8599635

  8. Enhanced Antitumor Activity of Monophosphate Ester Prodrugs of Gemcitabine: In Vitro and In Vivo Evaluation.

    PubMed

    Qi, Huixin; Lu, Jia; Li, Jiajun; Wang, Meiyu; Xu, Yunting; Wang, Yedong; Zhang, Hongjian

    2016-09-01

    The prodrug strategy has been explored frequently for a number of marked drugs to obtain better pharmaceutical properties and efficacy and safety profiles. For gemcitabine, a nucleoside analog that has been used widely as a chemotherapeutic agent for the treatment of a variety of cancers, the protection of the amino group from extensive deamination and increase of permeability have been used for oral prodrug development. In the present study, several novel and proprietary monophosphate ester prodrugs of gemcitabine representing different "tail" structures were evaluated for their antiproliferation activities in various tumor cell lines. As compared to LY2334737, a prototype oral prodrug of gemcitabine, the monophosphate ester prodrugs exhibited superior in vitro antiproliferation activity. Among those, compound-3 emerged as a promising prodrug candidate. Data revealed that cellular concentrations of compound-3 were correlated well with its antiproliferation activity and its cellular uptake did not involve human equilibrative nucleoside transporter, suggesting a potential to treat gemcitabine resistant tumors. Compound-3 demonstrated equal or better antitumor efficacy after oral administration as compared to intraperitoneally injected gemcitabine. Taken together, compound-3 has the potential for further development as an orally active antitumor agent. PMID:26994559

  9. A New Subfamily of Polyphosphate Kinase 2 (Class III PPK2) Catalyzes both Nucleoside Monophosphate Phosphorylation and Nucleoside Diphosphate Phosphorylation

    PubMed Central

    Motomura, Kei; Hirota, Ryuichi; Okada, Mai; Ikeda, Takeshi; Ishida, Takenori

    2014-01-01

    Inorganic polyphosphate (polyP) is a linear polymer of tens to hundreds of phosphate (Pi) residues linked by “high-energy” phosphoanhydride bonds as in ATP. PolyP kinases, responsible for the synthesis and utilization of polyP, are divided into two families (PPK1 and PPK2) due to differences in amino acid sequence and kinetic properties. PPK2 catalyzes preferentially polyP-driven nucleotide phosphorylation (utilization of polyP), which is important for the survival of microbial cells under conditions of stress or pathogenesis. Phylogenetic analysis suggested that the PPK2 family could be divided into three subfamilies (classes I, II, and III). Class I and II PPK2s catalyze nucleoside diphosphate and nucleoside monophosphate phosphorylation, respectively. Here, we demonstrated that class III PPK2 catalyzes both nucleoside monophosphate and nucleoside diphosphate phosphorylation, thereby enabling us to synthesize ATP from AMP by a single enzyme. Moreover, class III PPK2 showed broad substrate specificity over purine and pyrimidine bases. This is the first demonstration that class III PPK2 possesses both class I and II activities. PMID:24532069

  10. Planar Flow Casting: Crystalline and Non-crystalline Ribbon Formation

    NASA Astrophysics Data System (ADS)

    Mattson, Joseph; Theisen, Eric; Steen, Paul

    2015-11-01

    Planar flow casting (PFC) is a single-stage continuous casting process used in the production of thin metallic sheets. Molten metal is ejected from a reservoir and forced through a small gap to freeze against a translating substrate. The process is typically `feed limited' which means that an imposed pressure drop determines the flow rate of metal to the solidification front, and thus the ultimate thickness of the solid sheet. Depending on the molten alloy, the substrate heat sink can provide sufficient cooling rates to produce a glassy (amorphous) metal. Otherwise, a crystalline solid is the result. In this talk, by relating ribbon thickness to residence time for both amorphous and crystalline products, we address the question: to what extent is processing `blind' to the solidification mechanism? Support from National Science Foundation (Awards 1400964 and 0966045); Metglas Inc.

  11. Taste perception of monosodium glutamate and inosine monophosphate by 129P3/J and C57BL/6ByJ mice.

    PubMed

    Murata, Yuko; Beauchamp, Gary K; Bachmanov, Alexander A

    2009-10-19

    Our previous studies have shown that in long-term two-bottle preference tests, mice from the C57BL/6ByJ (B6) inbred strain drink more monosodium glutamate (MSG) and inosine monophosphate (IMP) than mice from the 129P3/J (129) inbred strain. The goal of this study was to examine whether this variation in consumption could be attributed to strain differences in perception of the taste quality of MSG and IMP. We developed a conditioned taste aversion (CTA) in B6 and 129 mice to 100 mM MSG or 10 mM IMP and used a brief-access taste assay to examine CTA generalization. B6 and 129 mice did not differ in the generalization patterns following CTA to MSG: mice from both strains generalized CTA from MSG to NaCl. In contrast, strain differences in the generalization patterns were evident following the CTA to IMP: while mice from both strains generalized CTA from IMP to MSG, 129 mice tended to have stronger CTA generalization to saccharin and d-tryptophan, both of which are perceived as sweet by humans. These data suggest that the strain differences in MSG consumption are not due to variation in perception of the taste quality of MSG. Instead, the differential intake of IMP likely reflects strain differences in the way the taste quality of IMP is perceived. Our data suggest that mice perceive MSG and IMP as complex taste stimuli: some taste components are shared between these two substances, but their relative intensity seems to be different for MSG and IMP. The amiloride-sensitive salt taste component is more prevalent in MSG than in IMP taste, and in B6 compared with 129 mice. PMID:19666040

  12. 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

  13. Self-adjustable crystalline inorganic nanocoils.

    PubMed

    Wang, Peng-peng; Yang, Yong; Zhuang, Jing; Wang, Xun

    2013-05-01

    Biomacromolecules such as proteins, although extremely complex in microstructure, can crystallize into macro-sized crystals after self-adjusting their shapes, based on which the structure of biology is built. Inorganic nanowires/nanoribbons with a similar one-dimensional topology but much simpler structures can hardly be as flexible as macromolecules when constructing superlattice structures because of their inherent rigidity. Here we report the synthesis of crystalline indium sulfide nanoribbon-based nanocoils that are formed by spontaneous self-coiling of ultrathin nanoribbons. The nanostructures are flexible and appear as relatively random coils because of their ultrathin ribbon structures (~0.9 nm in thickness) with high aspect ratios. Moreover, the nanocoils can self-adjust their shapes and assemble into two-dimensional superlattices and three-dimensional supercrystals in solution. The ultrathin nanocoils are expected to bring new insights into the use of flexible nanocrystals as building blocks for constructing superstructures. PMID:23611283

  14. 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).

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Crystalline 1H-1,2,3-triazol-5-ylidenes

    DOEpatents

    Bertrand, Guy; Gulsado-Barrios, Gregorio; Bouffard, Jean; Donnadieu, Bruno

    2016-08-02

    The present invention provides novel and stable crystalline 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes. The present invention also provides methods of making 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes. The present invention also provides methods of using 1H-1,2,3 triazolium carbenes and metal complexes of 1H-1,2,3 triazolium carbenes in catalytic reactions.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. Regulation of Maltodextrin Phosphorylase Synthesis in Escherichia coli by Cyclic Adenosine 3′, 5′-Monophosphate and Glucose1

    PubMed Central

    Chao, Julie; Weathersbee, Carolyn J.

    1974-01-01

    Cyclic adenosine 3′, 5′-monophosphate (AMP) stimulates maltodextrin phosphorylase synthesis in Escherichia coli cells induced with maltose. A maximal effect occurs at 2 to 3 mM cyclic AMP. The action of cyclic AMP is specific, inasmuch as adenosine triphosphate, 3′-AMP, 5′-AMP, adenosine, and dibutyryl cyclic AMP are inactive. Glucose, α-methyl glucoside, 2-deoxyglucose, and pyridoxal 5′-phosphate repress maltodextrin phosphorylase synthesis. This repression is reversed by cyclic AMP. The action of cyclic AMP appears to be at the transcriptional level, since cyclic AMP fails to stimulate phosphorylase production in induced cells in which messenger ribonucleic acid synthesis has been arrested by rifampin or by inducer removal. The two other enzymes involved in the metabolism of maltose, amylomaltase and maltose permease, are also induced in this strain of E. coli and affected by glucose and cyclic AMP in a manner similar to phosphorylase. PMID:4358043

  5. 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.

  6. Adenosine 3',5'-monophosphate in relation to inhibition of cervical smooth muscle activity in early pregnant women.

    PubMed

    Norström, A; Bryman, I

    1991-08-01

    Contractile activity was registered in strips of cervical tissue obtained by needle biopsy from women in the first trimester of pregnancy. Dibutyryl cyclic adenosine-3',5'-monophosphate (5 x 10(-6) mol/l), isobutyryl methylxanthine (10(-4) mol/l), and forskolin (10(-5)-10(-4) mol/l), the latter two drugs known to increase the levels of endogenous cAMP, inhibited spontaneous muscle activity. The levels of tissue cAMP were determined in strips during relaxation induced by prostaglandin E2 or purified porcine relaxin and compared with cAMP levels in strips from the same women during contractile activity. Exposure to prostaglandin E2 but not to relaxin was followed by increased levels of cAMP. It is suggested that cAMP has a role as a second messenger in the prostaglandin E2-mediated relaxation of cervical smooth muscle. PMID:1654721

  7. Disruption of Nucleotide Homeostasis by the Antiproliferative Drug 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside Monophosphate (AICAR).

    PubMed

    Ceschin, Johanna; Hürlimann, Hans Caspar; Saint-Marc, Christelle; Albrecht, Delphine; Violo, Typhaine; Moenner, Michel; Daignan-Fornier, Bertrand; Pinson, Benoît

    2015-09-25

    5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside monophosphate (AICAR) is a natural metabolite with potent anti-proliferative and low energy mimetic properties. At high concentration, AICAR is toxic for yeast and mammalian cells, but the molecular basis of this toxicity is poorly understood. Here, we report the identification of yeast purine salvage pathway mutants that are synthetically lethal with AICAR accumulation. Genetic suppression revealed that this synthetic lethality is in part due to low expression of adenine phosphoribosyl transferase under high AICAR conditions. In addition, metabolite profiling points to the AICAR/NTP balance as crucial for optimal utilization of glucose as a carbon source. Indeed, we found that AICAR toxicity in yeast and human cells is alleviated when glucose is replaced by an alternative carbon source. Together, our metabolic analyses unveil the AICAR/NTP balance as a major factor of AICAR antiproliferative effects. PMID:26283791

  8. Sum-frequency generation spectroscopy of self-assembled structures of Guanosine 5‧-monophosphate on mica

    NASA Astrophysics Data System (ADS)

    Kunstelj, Klemen; Spindler, Lea; Federiconi, Francesco; Bonn, Mischa; Drevenšek-Olenik, Irena; Čopič, Martin

    2008-12-01

    The structure and ordering of Guanosine 5'-monophosphate (GMP) films self-assembled on mica from GMP salt solutions were studied by infrared-visible sum-frequency generation spectroscopy (IR-VIS SFG) and atomic force microscopy (AFM). We find that the surface self-assembly of GMP can be tuned through the concentration of the GMP solution as well as the nature of the counter ion. At low concentrations of the ammonium and the sodium GMP salt solutions, the self-assembled films are very similar, while at higher concentrations the SFG signal of ammonium GMP samples is dominated by a contribution not originating from azimuthally symmetric layers, which signifies that a helical bulk structure might be present.

  9. 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

  10. 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