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Sample records for femo cofactor maturation

  1. Theoretical calculations of valence states in Fe-Mo compounds

    International Nuclear Information System (INIS)

    Estrada, F; Navarro, O; Noverola, H; Suárez, J R; Avignon, M

    2014-01-01

    The half-metallic ferromagnetic double perovskite compound Sr 2 FeMoO 6 is considered as an important material for spintronic applications. It appears to be fundamental to understand the role of electronic parameters controlling the half-metallic ground state. Fe-Mo double perovskites usually present some degree of Fe/Mo disorder which generally increases with doping. In this work, we study the valence states of Fe-Mo cations in the off-stoichiometric system Sr 2 Fe 1+x Mo 1−x O 6 (−1 ≤ x ≤ 1/3) with disorder. Our results for Fe and Mo valence states are obtained using the Green functions and the renormalization perturbation expansion method. The model is based on a correlated electron picture with localized Fe-spins and conduction Mo-electrons interacting with the local spins via a double-exchange-type mechanism

  2. Fe-Mo alloy coatings as cathodes in chlorate production process

    Directory of Open Access Journals (Sweden)

    Gajić-Krstajić Ljiljana M.

    2016-01-01

    Full Text Available The aim of this study was to gain a better understanding of the feasibility of partial replacement of dichromate, Cr(VI, with phosphate buffer, focusing on the cathode reaction selectivity for hydrogen evolution on mild steel and Fe-Mo cathodes in undivided cell for chlorate production. To evaluate the ability of phosphate and Cr(VI additions to hinder hypochlorite and chlorate reduction, overall current efficiency (CE measurements in laboratory cell for chlorate production on stationary electrodes were performed. The concentration of hypochlorite was determined by a conventional potentiometric titration method using 0.01 mol dm-3 As2O3 solution as a titrant. The chlorate concentration was determined by excess of 1.0 mol dm-3 As2O3 solution and excess of arsenic oxide was titrated with 0.1 mol dm-3 KBrO3 solution in a strong acidic solution. Cathodic hypochlorite and chlorate reduction were suppressed efficiently by addition of 3 g dm-3 dichromate at both cathodes, except that Fe-Mo cathode exhibited higher catalytic activity for hydrogen evolution reaction (HER. The overvoltage for the HER was around 0.17 V lower on Fe-Mo cathode than on mild steel at the current density of 3 kA m-2. It was found that a dichromate content as low as 0.1 g dm-3 is sufficient for complete suppression of cathodic hypochlorite and chlorate reduction onto Fe-Mo catalyst in phosphate buffering system (3 g dm-3 Na2HPO4 + NaH2PO4. The overall current efficiency was practically the same as in the case of the presence of 3 g dm-3 dichromate buffer (98 %. However, for the mild steel cathode, the overall current efficiency for the chlorate production was somewhat lower in the above mentioned mixed phosphate + dichromate buffering system (95% than in the pure dichromate buffering solution (97.5%.

  3. Magnetic properties of Nd3(Fe,Mo)29 compound and its nitride

    International Nuclear Information System (INIS)

    Pan Hongge

    1998-01-01

    The iron-rich ternary intermetallic compound Nd 3 (Fe,Mo) 29 with the Nd 3 (Fe,Ti) 29 -type monoclinic structure and its nitride were prepared. After nitrogenation, the nitride retains the structure of the parent compound, but the unit-cell volume of the nitride is 5.9% greater than that of the parent compound. The Curie temperature of Nd 3 (Fe,Mo) 29 nitride is 70.9% higher than that of the parent compound and the saturation magnetization of the nitride is about 6.6% (at 4.2 K) and 23.7% (at 300 K) higher than that of the parent compound. The anisotropy of the nitride is similar to that of parent compound, which exhibits plane anisotropy. (orig.)

  4. Kinetics of the partial oxidation of methanol over a Fe-Mo catalyst

    NARCIS (Netherlands)

    Deshmukh, S.A.R.K.; Sint Annaland, van M.; Kuipers, J.A.M.

    2005-01-01

    The intrinsic steady-state kinetics of the partial oxidation of methanol to formaldehyde over a commercial Fe-Mo catalyst has been studied experimentally in a differentially operated reactor at temperatures of 230–260 °C, over a wide range of methanol and oxygen concentrations. The principal

  5. Kinetics of the partial oxidation of methanol over a Fe-Mo catalyst

    NARCIS (Netherlands)

    Deshmukh, S.A.R.K.; van Sint Annaland, M.; Kuipers, J.A.M.

    2005-01-01

    The intrinsic steady-state kinetics of the partial oxidation of methanol to formaldehyde over a commercial Fe-Mo catalyst has been studied experimentally in a differentially operated reactor at temperatures of 230¿260 °C, over a wide range of methanol and oxygen concentrations. The principal

  6. Proteolytic cleavage orchestrates cofactor insertion and protein assembly in [NiFe]-hydrogenase biosynthesis.

    Science.gov (United States)

    Senger, Moritz; Stripp, Sven T; Soboh, Basem

    2017-07-14

    Metalloenzymes catalyze complex and essential processes, such as photosynthesis, respiration, and nitrogen fixation. For example, bacteria and archaea use [NiFe]-hydrogenases to catalyze the uptake and release of molecular hydrogen (H 2 ). [NiFe]-hydrogenases are redox enzymes composed of a large subunit that harbors a NiFe(CN) 2 CO metallo-center and a small subunit with three iron-sulfur clusters. The large subunit is synthesized with a C-terminal extension, cleaved off by a specific endopeptidase during maturation. The exact role of the C-terminal extension has remained elusive; however, cleavage takes place exclusively after assembly of the [NiFe]-cofactor and before large and small subunits form the catalytically active heterodimer. To unravel the functional role of the C-terminal extension, we used an enzymatic in vitro maturation assay that allows synthesizing functional [NiFe]-hydrogenase-2 of Escherichia coli from purified components. The maturation process included formation and insertion of the NiFe(CN) 2 CO cofactor into the large subunit, endoproteolytic cleavage of the C-terminal extension, and dimerization with the small subunit. Biochemical and spectroscopic analysis indicated that the C-terminal extension of the large subunit is essential for recognition by the maturation machinery. Only upon completion of cofactor insertion was removal of the C-terminal extension observed. Our results indicate that endoproteolytic cleavage is a central checkpoint in the maturation process. Here, cleavage temporally orchestrates cofactor insertion and protein assembly and ensures that only cofactor-containing protein can continue along the assembly line toward functional [NiFe]-hydrogenase. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Formation of a homocitrate-free iron-molybdenum cluster on NifEN: implications for the role of homocitrate in nitrogenase assembly.

    Science.gov (United States)

    Fay, Aaron Wolfe; Blank, Michael Aaron; Yoshizawa, Janice Mariko; Lee, Chi Chung; Wiig, Jared Andrew; Hu, Yilin; Hodgson, Keith Owen; Hedman, Britt; Ribbe, Markus Walter

    2010-03-28

    Molybdenum (Mo)-dependent nitrogenase is a complex metalloprotein that catalyzes the biological reduction of dinitrogen (N(2)) to ammonia (NH(3)) at the molybdenum-iron cofactor (FeMoco) site of its molybdenum-iron (MoFe) protein component. Here we report the formation of a homocitrate-free, iron-molybdenum ("FeMo") cluster on the biosynthetic scaffold of FeMoco, NifEN. Such a NifEN-associated "FeMo" cluster exhibits EPR features similar to those of the NifEN-associated, fully-complemented "FeMoco", which originate from the presence of Mo in both cluster species; however, "FeMo" cluster and "FeMoco" display different temperature-dependent changes in the line shape and the signal intensity of their respective EPR features, which reflect the impact of homocitrate on the redox properties of these clusters. XAS/EXAFS analysis reveals that the Mo centers in both "FeMo" cluster and "FeMoco" are present in a similar coordination environment, although Mo in "FeMo" cluster is more loosely coordinated as compared to that in "FeMoco" with respect to the Mo-O distances in the cluster, likely due to the absence of homocitrate that normally serves as an additional ligand for the Mo in the cluster. Subsequent biochemical investigation of the "FeMo" cluster not only facilitates the determination of the sequence of events in the mobilization of Mo and homocitrate during FeMoco maturation, but also permits the examination of the role of homocitrate in the transfer of FeMoco between NifEN and MoFe protein. Combined outcome of these studies establishes a platform for future structural analysis of the interactions between NifEN and MoFe protein, which will provide useful insights into the mechanism of cluster transfer between the two proteins.

  8. Kinetics of Nif gene expression in a nitrogen-fixing bacterium.

    Science.gov (United States)

    Poza-Carrión, César; Jiménez-Vicente, Emilio; Navarro-Rodríguez, Mónica; Echavarri-Erasun, Carlos; Rubio, Luis M

    2014-02-01

    Nitrogen fixation is a tightly regulated trait. Switching from N2 fixation-repressing conditions to the N2-fixing state is carefully controlled in diazotrophic bacteria mainly because of the high energy demand that it imposes. By using quantitative real-time PCR and quantitative immunoblotting, we show here how nitrogen fixation (nif) gene expression develops in Azotobacter vinelandii upon derepression. Transient expression of the transcriptional activator-encoding gene, nifA, was followed by subsequent, longer-duration waves of expression of the nitrogenase biosynthetic and structural genes. Importantly, expression timing, expression levels, and NifA dependence varied greatly among the nif operons. Moreover, the exact concentrations of Nif proteins and their changes over time were determined for the first time. Nif protein concentrations were exquisitely balanced, with FeMo cofactor biosynthetic proteins accumulating at levels 50- to 100-fold lower than those of the structural proteins. Mutants lacking nitrogenase structural genes or impaired in FeMo cofactor biosynthesis showed overenhanced responses to derepression that were proportional to the degree of nitrogenase activity impairment, consistent with the existence of at least two negative-feedback regulatory mechanisms. The first such mechanism responded to the levels of fixed nitrogen, whereas the second mechanism appeared to respond to the levels of the mature NifDK component. Altogether, these findings provide a framework to engineer N2 fixation in nondiazotrophs.

  9. FEMO, A FLOW AND ENRICHMENT MONITOR FOR VERIFYING COMPLIANCE WITH INTERNATIONAL SAFEGUARDS REQUIREMENTS AT A GAS CENTRIFUGE ENRICHMENT FACILITY

    International Nuclear Information System (INIS)

    Gunning, John E.; Laughter, Mark D.; March-Leuba, Jose A.

    2008-01-01

    A number of countries have received construction licenses or are contemplating the construction of large-capacity gas centrifuge enrichment plants (GCEPs). The capability to independently verify nuclear material flows is a key component of international safeguards approaches, and the IAEA does not currently have an approved method to continuously monitor the mass flow of 235U in uranium hexafluoride (UF6) gas streams. Oak Ridge National Laboratory is investigating the development of a flow and enrichment monitor, or FEMO, based on an existing blend-down monitoring system (BDMS). The BDMS was designed to continuously monitor both 235U mass flow and enrichment of UF6 streams at the low pressures similar to those which exists at GCEPs. BDMSs have been installed at three sites-the first unit has operated successfully in an unattended environment for approximately 10 years. To be acceptable to GCEP operators, it is essential that the instrument be installed and maintained without interrupting operations. A means to continuously verify flow as is proposed by FEMO will likely be needed to monitor safeguards at large-capacity plants. This will enable the safeguards effectiveness that currently exists at smaller plants to be maintained at the larger facilities and also has the potential to reduce labor costs associated with inspections at current and future plants. This paper describes the FEMO design requirements, operating capabilities, and development work required before field demonstration.

  10. Expression and localization of tubulin cofactors TBCD and TBCE in human gametes.

    Science.gov (United States)

    Jiménez-Moreno, Victoria; Agirregoitia, Ekaitz

    2017-06-01

    The tubulin cofactors TBCD and TBCE play an essential role in regulation of the microtubule dynamics in a wide variety of somatic cells, but little information is known about the expression of these cofactors in human sperm and oocytes. In this study, we focused on the investigation of the presence of, and the differential distribution of, the tubulin cofactors TBCD and TBCE in human sperm and during human oocyte maturation. We performed expression assays for TBCD and TBCE by reverse transcription-polymerase chain reaction (RT-PCR), western blot and immunofluorescence and verified the presence of both cofactors in human gametes. TBCD and TBCE were located mainly in the middle region and in the tail of the sperm while in the oocyte the localization was cytosolic. The mRNA of both tubulin cofactors were present in the human oocytes but not in sperm cells. This finding gives a first insight into where TBCD and TBCE could carry out their function in the continuous changes that the cytoskeleton experiences during gametogenesis and also prior to fertilization.

  11. VTVH-MCD study of the Delta nifB Delta nifZ MoFe protein from Azotobacter vinelandii.

    Science.gov (United States)

    Cotton, Marcia S; Rupnik, Kresimir; Broach, Robyn B; Hu, Yilin; Fay, Aaron W; Ribbe, Markus W; Hales, Brian J

    2009-04-08

    NifZ is a member of a series of proteins associated with the maturation of the nitrogenase MoFe protein. An MCD spectroscopic study was undertaken on the Delta nifB Delta nifZ MoFe protein generated in the absence of both NifZ and NifB (deletion of NifB generates an apo-MoFe protein lacking the FeMo cofactor). Results presented here show that, in the absence of NifZ, only one of the two P-clusters of the MoFe protein is matured to the ultimate [8Fe-7S] structure. The other P-cluster site in the protein contains a [4Fe-4S] cluster pair, representing a P-cluster precursor that is electronically identical to the analogous clusters observed in the Delta nifH MoFe protein. These results suggest that the MoFe protein is synthesized in a stepwise fashion where NifZ is specifically required for the formation of the second P-cluster.

  12. The Role of System-Specific Molecular Chaperones in the Maturation of Molybdoenzymes in Bacteria

    Directory of Open Access Journals (Sweden)

    Meina Neumann

    2011-01-01

    Full Text Available Biogenesis of prokaryotic molybdoenzymes is a complex process with the final step representing the insertion of a matured molybdenum cofactor (Moco into a folded apoenzyme. Usually, specific chaperones of the XdhC family are required for the maturation of molybdoenzymes of the xanthine oxidase family in bacteria. Enzymes of the xanthine oxidase family are characterized to contain an equatorial sulfur ligand at the molybdenum center of Moco. This sulfur ligand is inserted into Moco while bound to the XdhC-like protein and before its insertion into the target enzyme. In addition, enzymes of the xanthine oxidase family bind either the molybdopterin (Mo-MPT form of Moco or the modified molybdopterin cytosine dinucleotide cofactor (MCD. In both cases, only the matured cofactor is inserted by a proofreading process of XdhC. The roles of these specific XdhC-like chaperones during the biogenesis of enzymes of the xanthine oxidase family in bacteria are described.

  13. Engineering redox balance through cofactor systems.

    Science.gov (United States)

    Chen, Xiulai; Li, Shubo; Liu, Liming

    2014-06-01

    Redox balance plays an important role in the production of enzymes, pharmaceuticals, and chemicals. To meet the demands of industrial production, it is desirable that microbes maintain a maximal carbon flux towards target metabolites with no fluctuations in redox. This requires functional cofactor systems that support dynamic homeostasis between different redox states or functional stability in a given redox state. Redox balance can be achieved by improving the self-balance of a cofactor system, regulating the substrate balance of a cofactor system, and engineering the synthetic balance of a cofactor system. This review summarizes how cofactor systems can be manipulated to improve redox balance in microbes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Cofactor engineering for advancing chemical biotechnology.

    Science.gov (United States)

    Wang, Yipeng; San, Ka-Yiu; Bennett, George N

    2013-12-01

    Cofactors provide redox carriers for biosynthetic reactions, catabolic reactions and act as important agents in transfer of energy for the cell. Recent advances in manipulating cofactors include culture conditions or additive alterations, genetic modification of host pathways for increased availability of desired cofactor, changes in enzyme cofactor specificity, and introduction of novel redox partners to form effective circuits for biochemical processes and biocatalysts. Genetic strategies to employ ferredoxin, NADH and NADPH most effectively in natural or novel pathways have improved yield and efficiency of large-scale processes for fuels and chemicals and have been demonstrated with a variety of microbial organisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Optimization Strategies for Hardware-Based Cofactorization

    Science.gov (United States)

    Loebenberger, Daniel; Putzka, Jens

    We use the specific structure of the inputs to the cofactorization step in the general number field sieve (GNFS) in order to optimize the runtime for the cofactorization step on a hardware cluster. An optimal distribution of bitlength-specific ECM modules is proposed and compared to existing ones. With our optimizations we obtain a speedup between 17% and 33% of the cofactorization step of the GNFS when compared to the runtime of an unoptimized cluster.

  16. Spin-polarized scanning tunneling microscopy of magnetic nanostructures at the example of bcc-Co/Fe(110), Fe/Mo(110), and copper phthalocyanine/Fe(1110); Spinpolarisierte Rastertunnelmikroskopie magnetischer Nanostrukturen am Beispiel von bcc-Co/Fe(110), Fe/Mo(110) und Kupfer-Phthalocyanin/Fe(110)

    Energy Technology Data Exchange (ETDEWEB)

    Methfessel, Torsten

    2010-12-09

    This thesis provides an introduction into the technique of spin-polarized scanning tunnelling microscopy and spectroscopy as an experimental method for the investigation of magnetic nanostructures. Experimental results for the spin polarized electronic structure depending on the crystal structure of ultrathin Co layers, and depending on the direction of the magnetization for ultrathin Fe layers are presented. High-resolution measurements show the position-dependent spin polarization on a single copper-phthalocyanine molecule deposited on a ferromagnetic surface. Co was deposited by molecular beam epitaxy on the (110) surface of the bodycentered cubic metals Cr and Fe. In contrast to previous reports in the literature only two layers of Co can be stabilized in the body-centered cubic (bcc) structure. The bcc-Co films on the Fe(110) surface show no signs of epitaxial distortions. Thicker layers reconstruct into a closed-packed structure (hcp / fcc). The bcc structure increases the spin-polarization of Co to P=62 % in comparison to hcp-Co (P=45 %). The temperature-dependent spin-reorientation of ultrathin Fe/Mo(110) films was investigated by spin-polarized spectroscopy. A reorientation of the magnetic easy axis from the [110] direction along the surface normal to the in-plane [001] axis is observed at T (13.2{+-}0.5) K. This process can be identified as a discontinuous reorientation transition, revealing two simultaneous minima of the free energy in a certain temperature range. The electronic structure of mono- and double-layer Fe/Mo(110) shows a variation with the reorientation of the magnetic easy axis and with the direction of the magnetization. The investigation of the spin-polarized charge transport through a copper-phthalocyanine molecule on the Fe/Mo(110) surface provides an essential contribution to the understanding of spin-transport at the interface between metal and organic molecule. Due to the interaction with the surface of the metal the HOMO-LUMO energy

  17. Analysis of steady-state creep of Fe-Mo alloys from the viewpoint of recovery

    International Nuclear Information System (INIS)

    Maruyama, K.; Karashima, S.; Oikawa, H.

    1979-01-01

    A theoretical equation to d evaluate the steady-state creep-rates, d epsilon/dtsub(s), based on a recovery creep model is derived: epsilonsub(s)/dt proportional to r/sigma 2 sub(a) x lambda 2 , where r is the recovery rate, which can be determined from results of stress-reduction tests, deltasub(a) the applied stress, and lambda the dislocation link-length. Two cases of recovery are considered, i.e., recovery of dislocation networks at sub-boundaries and that of three-dimensional networks within subgrains. The high-temperature steady-state creep of Fe-Mo solid solutions, creep characteristics of which have been reported to be well rationalized as viscous glide creep, is analyzed using this equation. It is shown that stress dependence of d epsilon/dtsub(s) is well explained from the viewpoint of recovery, in which the activation and the annihilation of dislocations at sub-boundaries are considered to take place. (orig.) [de

  18. Co-factor activated recombinant adenovirus proteinases

    Science.gov (United States)

    Anderson, Carl W.; Mangel, Walter F.

    1996-08-06

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  19. Replacing Electron Transport Cofactors with Hydrogenases

    KAUST Repository

    Laamarti, Rkia

    2016-12-01

    Enzymes have found applications in a broad range of industrial production processes. While high catalytic activity, selectivity and mild reaction conditions are attractive advantages of the biocatalysts, particularly costs arising from required cofactors pose a sever limitation. While cofactor-recycling systems are available, their use implies constraints for process set-up and conditions, which are a particular problem e.g. for solid-gas-phase reactions. Several oxidoreductases are able to directly exchange electrons with electrodes. Hence, the co-immobilization of both, an electron-utilizing and an electron-generating oxidoreductase on conductive nanoparticles should facilitate the direct electron flow from an enzymatic oxidation to a reduction reaction circumventing redox-cofactors requirements. In such a set-up, hydrogenases could generate and provide electrons directly form gaseous hydrogen. This thesis describes the co-immobilization of the oxygen tolerant hydrogenases from C. eutropha or C. metallidurans and cytochrome P450BM3 as test system. Conductive material in the form of carbon nanotubes (CNT) serves as a suitable support. A combination of the hydrogenase and the catalytic domain of P450BM3 immobilized on carbon nanotubes were tested for the oxidation of lauric acid in the presence of hydrogen instead of an electron-transport cofactor. The GC-MS analysis reveals the conversion of 4% of lauric acid (LA) into three products, which correspond to the hydroxylated lauric acid in three different positions with a total turnover (TON) of 34. The product distribution is similar to that obtained when using the wildtype P450BM3 with the nicotinamide adenine dinucleotide phosphate (NADPH) cofactor. Such electronic coupling couldn’t be achieved for the conversion of other substrates such as propane and cyclohexane, probably due to the high uncoupling rate within the heme-domain of cytochrome P450BM3 when unnatural substrates are introduced.

  20. Nuclear Receptor Cofactors in PPARγ-Mediated Adipogenesis and Adipocyte Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Emily Powell

    2007-01-01

    Full Text Available Transcriptional cofactors are integral to the proper function and regulation of nuclear receptors. Members of the peroxisome proliferator-activated receptor (PPAR family of nuclear receptors are involved in the regulation of lipid and carbohydrate metabolism. They modulate gene transcription in response to a wide variety of ligands, a process that is mediated by transcriptional coactivators and corepressors. The mechanisms by which these cofactors mediate transcriptional regulation of nuclear receptor function are still being elucidated. The rapidly increasing array of cofactors has brought into focus the need for a clear understanding of how these cofactors interact in ligand- and cell-specific manners. This review highlights the differential effects of the assorted cofactors regulating the transcriptional action of PPARγ and summarizes the recent advances in understanding the physiological functions of corepressors and coactivators.

  1. Feasibility of N2 Binding and Reduction to Ammonia on Fe-Deposited MoS2 2D Sheets: A DFT Study

    KAUST Repository

    Azofra Mesa, Luis

    2017-05-19

    Based on the structure of the nitrogenase FeMo cofactor (FeMoco), it is reported that Fe deposited on MoS2 2D sheets exhibits high selectivity towards the spontaneous fixation of N2 against chemisorption of CO2 and H2 O. DFT predictions also indicate the ability of this material to convert N2 into NH3 with a maximum energy input of 1.02 eV as an activation barrier for the first proton-electron pair transfer.

  2. Feasibility of N2 Binding and Reduction to Ammonia on Fe-Deposited MoS2 2D Sheets: A DFT Study

    KAUST Repository

    Azofra Mesa, Luis; Sun, Chenghua; Cavallo, Luigi; MacFarlane, Douglas R.

    2017-01-01

    Based on the structure of the nitrogenase FeMo cofactor (FeMoco), it is reported that Fe deposited on MoS2 2D sheets exhibits high selectivity towards the spontaneous fixation of N2 against chemisorption of CO2 and H2 O. DFT predictions also indicate the ability of this material to convert N2 into NH3 with a maximum energy input of 1.02 eV as an activation barrier for the first proton-electron pair transfer.

  3. The glmS ribozyme cofactor is a general acid-base catalyst.

    Science.gov (United States)

    Viladoms, Júlia; Fedor, Martha J

    2012-11-21

    The glmS ribozyme is the first natural self-cleaving ribozyme known to require a cofactor. The d-glucosamine-6-phosphate (GlcN6P) cofactor has been proposed to serve as a general acid, but its role in the catalytic mechanism has not been established conclusively. We surveyed GlcN6P-like molecules for their ability to support self-cleavage of the glmS ribozyme and found a strong correlation between the pH dependence of the cleavage reaction and the intrinsic acidity of the cofactors. For cofactors with low binding affinities, the contribution to rate enhancement was proportional to their intrinsic acidity. This linear free-energy relationship between cofactor efficiency and acid dissociation constants is consistent with a mechanism in which the cofactors participate directly in the reaction as general acid-base catalysts. A high value for the Brønsted coefficient (β ~ 0.7) indicates that a significant amount of proton transfer has already occurred in the transition state. The glmS ribozyme is the first self-cleaving RNA to use an exogenous acid-base catalyst.

  4. Lanthanide Cofactors for Triphosphorylation Ribozymes

    Science.gov (United States)

    Sweeney, K. J.; Müller, U. F.

    2017-07-01

    RNA world organisms could have used trimetaphosphate as energy source for thermodynamically unfavorable RNA polymerization. Using in vitro selection we show here that Lanthanides can serve as cofactors for ribozyme-catalyzed RNA triphosphorylation.

  5. A General Tool for Engineering the NAD/NADP Cofactor Preference of Oxidoreductases.

    Science.gov (United States)

    Cahn, Jackson K B; Werlang, Caroline A; Baumschlager, Armin; Brinkmann-Chen, Sabine; Mayo, Stephen L; Arnold, Frances H

    2017-02-17

    The ability to control enzymatic nicotinamide cofactor utilization is critical for engineering efficient metabolic pathways. However, the complex interactions that determine cofactor-binding preference render this engineering particularly challenging. Physics-based models have been insufficiently accurate and blind directed evolution methods too inefficient to be widely adopted. Building on a comprehensive survey of previous studies and our own prior engineering successes, we present a structure-guided, semirational strategy for reversing enzymatic nicotinamide cofactor specificity. This heuristic-based approach leverages the diversity and sensitivity of catalytically productive cofactor binding geometries to limit the problem to an experimentally tractable scale. We demonstrate the efficacy of this strategy by inverting the cofactor specificity of four structurally diverse NADP-dependent enzymes: glyoxylate reductase, cinnamyl alcohol dehydrogenase, xylose reductase, and iron-containing alcohol dehydrogenase. The analytical components of this approach have been fully automated and are available in the form of an easy-to-use web tool: Cofactor Specificity Reversal-Structural Analysis and Library Design (CSR-SALAD).

  6. Cofactory: Sequence-based prediction of cofactor specificity of Rossmann folds

    DEFF Research Database (Denmark)

    Geertz-Hansen, Henrik Marcus; Blom, Nikolaj; Feist, Adam

    2014-01-01

    Obtaining optimal cofactor balance to drive production is a challenge metabolically engineered microbial strains. To facilitate identification of heterologous enzymes with desirable altered cofactor requirements from native content, we have developed Cofactory, a method for prediction of enzyme...

  7. Molybdenum-cofactor deficiency: an easily missed cause of neonatal convulsions

    NARCIS (Netherlands)

    Slot, H. M.; Overweg-Plandsoen, W. C.; Bakker, H. D.; Abeling, N. G.; Tamminga, P.; Barth, P. G.; van Gennip, A. H.

    1993-01-01

    Intractable seizures in the neonatal period may be caused by molybdenum-cofactor deficiency, an inborn error which combines the deficiencies of sulphite oxidase and xanthine dehydrogenase. The neurological symptoms of molybdenum cofactor and isolated sulphite oxidase deficiencies are identical. Two

  8. Bleaching herbicide norflurazon inhibits phytoene desaturase by competition with the cofactors.

    Science.gov (United States)

    Breitenbach, J; Zhu, C; Sandmann, G

    2001-11-01

    Cofactor requirement was determined for the heterologous expressed phytoene desaturases from the cyanobacterium Synechococcus and the higher plant Gentiana lutea. The cyanobacterial enzyme is dependent on either NAD(P) or plastoquinone, whereas only quinones such as plastoquinone can function as a cofactor for the phytoene desaturase from G. lutea. Enzyme kinetic studies were carried out to determine a possible competition between the cofactors and the bleaching herbicide norflurazon. For the Synechococcus enzyme, competition between norflurazon and NADP, as well as plastoquinone, could be demonstrated. The K(m) values for these cofactors were 6.6 mM and 0.23 microM, respectively. Inhibition of the phytoene desaturase from G. lutea by norflurazon was also competitive with respect to plastoquinone. The K(m) values of both enzymes for plastoquinone were very close.

  9. Metabolic and Transcriptional Response to Cofactor Perturbations in Escherichia coli

    DEFF Research Database (Denmark)

    Holm, Anders Koefoed; Blank, L.M.; Oldiges, M.

    2010-01-01

    Metabolic cofactors such as NADH and ATP play important roles in a large number of cellular reactions, and it is of great interest to dissect the role of these cofactors in different aspects of metabolism. Toward this goal, we overexpressed NADH oxidase and the soluble F1-ATPase in Escherichia coli...... of redox and energy metabolism and should help in developing metabolic engineering strategies in E. coli....

  10. Enzyme cofactors: Double-edged sword for catalysis

    Science.gov (United States)

    Ivanov, Ivaylo

    2013-01-01

    The metal cofactors responsible for the activity of CDK2 -- a representative member of the kinase superfamily of enzymes -- have now been shown to also have inhibitory effects during the catalytic cycle.

  11. Metabolic impact of redox cofactor perturbations in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Hou, Jin; Lages, Nuno; Oldiges, M.

    2009-01-01

    to induce widespread changes in metabolism. We present a detailed analysis of the impact of perturbations in redox cofactors in the cytosol or mitochondria on glucose and energy metabolism in Saccharomyces cerevisiae to aid metabolic engineering decisions that involve cofactor engineering. We enhanced NADH...... oxidation by introducing NADH oxidase or alternative oxidase, its ATP-mediated conversion to NADPH using NADH kinase as well as the interconversion of NADH and NADPH independent of ATP by the soluble, non-proton-translocating bacterial transhydrogenase. Decreasing cytosolic NADH level lowered glycerol...

  12. Redox cofactor engineering in industrial microorganisms: strategies, recent applications and future directions.

    Science.gov (United States)

    Liu, Jiaheng; Li, Huiling; Zhao, Guangrong; Caiyin, Qinggele; Qiao, Jianjun

    2018-05-01

    NAD and NADP, a pivotal class of cofactors, which function as essential electron donors or acceptors in all biological organisms, drive considerable catabolic and anabolic reactions. Furthermore, they play critical roles in maintaining intracellular redox homeostasis. However, many metabolic engineering efforts in industrial microorganisms towards modification or introduction of metabolic pathways, especially those involving consumption, generation or transformation of NAD/NADP, often induce fluctuations in redox state, which dramatically impede cellular metabolism, resulting in decreased growth performance and biosynthetic capacity. Here, we comprehensively review the cofactor engineering strategies for solving the problematic redox imbalance in metabolism modification, as well as their features, suitabilities and recent applications. Some representative examples of in vitro biocatalysis are also described. In addition, we briefly discuss how tools and methods from the field of synthetic biology can be applied for cofactor engineering. Finally, future directions and challenges for development of cofactor redox engineering are presented.

  13. Investigation of the cofactor controlled substrate specificity of yeast inorganic pyrophosphatase

    International Nuclear Information System (INIS)

    Dunaway-Mariano, D.; Barry, R.J.; Brush, T.; Ting, S.J.

    1986-01-01

    The PPase reaction requires the participation of three metal ion cofactors. One metal ion binds to PP activating it for reaction and the other two bind to the enzyme activating it for catalysis. Of the metal ions tested only Mg 2+ , Zn 2+ , Co 2+ , Mn 2+ can perform all these roles. Most trivalent metal ions can function to activate the PP for reaction but cannot activate the enzyme for catalysis. The Mg 2+ activated enzyme is specific for M-PP and M-PPS complexes while the Zn 2+ activated enzyme also acts on metal complexes of PPP, PPPOR, PPOR and PPF. 18 O-Incorporation studies show that the substituted phosphoryl group of the unsymmetrical PP complexes always serves as the leaving group. To gain insight into the mechanism of the cofactor control over the substrate specificity the order of substrate/cofactor binding to the enzyme was examined. Dead end inhibition studies in which Cr(III)PP served as substrate and Mg 2+ as cofactor indicate that the mechanism is rapid equilibrium ordered (CrPP binds first) while dead end inhibitor induced activator inhibition studies with Mg 2+ and MgPP indicate that the kinetic mechanism is steady state preferred order. Cofactor-enzyme binding was studied as a function of substrate structure and the results obtained rule out interference of Mg 2+ binding by substrate analogs as an explanation for the different substrate specificities of the Zn 2+ and Mg 2+ activated enzymes

  14. Engineering cofactor flexibility enhanced 2,3-butanediol production in Escherichia coli.

    Science.gov (United States)

    Liang, Keming; Shen, Claire R

    2017-12-01

    Enzymatic reduction of acetoin into 2,3-butanediol (2,3-BD) typically requires the reduced nicotinamide adenine dinucleotide (NADH) or its phosphate form (NADPH) as electron donor. Efficiency of 2,3-BD biosynthesis, therefore, is heavily influenced by the enzyme specificity and the cofactor availability which varies dynamically. This work describes the engineering of cofactor flexibility for 2,3-BD production by simultaneous overexpression of an NADH-dependent 2,3-BD dehydrogenase from Klebsiella pneumoniae (KpBudC) and an NADPH-specific 2,3-BD dehydrogenase from Clostridium beijerinckii (CbAdh). Co-expression of KpBudC and CbAdh not only enabled condition versatility for 2,3-BD synthesis via flexible utilization of cofactors, but also improved production stereo-specificity of 2,3-BD without accumulation of acetoin. With optimization of medium and fermentation condition, the co-expression strain produced 92 g/L of 2,3-BD in 56 h with 90% stereo-purity for (R,R)-isoform and 85% of maximum theoretical yield. Incorporating cofactor flexibility into the design principle should benefit production of bio-based chemical involving redox reactions.

  15. Beyond the Protein Matrix : Probing Cofactor Variants in a Baeyer-Villiger Oxygenation Reaction

    NARCIS (Netherlands)

    Martinoli, Christian; Dudek, Hanna M.; Orru, Roberto; Edmondson, Dale E.; Fraaije, Marco W.; Mattevi, Andrea

    2013-01-01

    A general question in biochemistry is the interplay between the chemical properties of cofactors and the surrounding protein matrix. Here, the functions of NADP(+) and FAD are explored by investigation of a representative monooxygenase reconstituted with chemically modified cofactor analogues. Like

  16. Quantum localization and protein-assisted vibrational energy flow in cofactors

    International Nuclear Information System (INIS)

    Leitner, David M

    2010-01-01

    Quantum effects influence vibrational dynamics and energy flow in biomolecules, which play a central role in biomolecule function, including control of reaction kinetics. Lifetimes of many vibrational modes of proteins and their temperature dependence, as determined by quantum golden-rule-based calculations, exhibit trends consistent with experimental observation and distinct from estimates based on classical modeling. Particularly notable are quantum coherence effects that give rise to localization of vibrational states of sizable organic molecules in the gas phase. Even when such a molecule, for instance a cofactor, is embedded in a protein, remnants of quantum localization survive that influence vibrational energy flow and its dependence on temperature. We discuss these effects on the mode-damping rates of a cofactor embedded in a protein, using the green fluorescent protein chromophore as a specific example. We find that for cofactors of this size embedded in their protein and solvent environment at room temperature a golden-rule calculation often overestimates the mode-damping rate.

  17. Application of NAD(P)H oxidase for cofactor regeneration in dehydrogenase catalyzed oxidations

    DEFF Research Database (Denmark)

    Rehn, Gustav; Pedersen, Asbjørn Toftgaard; Woodley, John

    2016-01-01

    alcohol dehydrogenases. However, their effective use requires an effective regeneration of the oxidized nicotinamide cofactor (NAD(P)+), which is critical for the economic feasibility of the process. NAD(P)H oxidase is an enzyme class of particular interest for this cofactor regeneration since it enables...

  18. Insights into hydrocarbon formation by nitrogenase cofactor homologs.

    Science.gov (United States)

    Lee, Chi Chung; Hu, Yilin; Ribbe, Markus W

    2015-04-14

    The L-cluster is an all-iron homolog of nitrogenase cofactors. Driven by europium(II) diethylenetriaminepentaacetate [Eu(II)-DTPA], the isolated L-cluster is capable of ATP-independent reduction of CO and CN(-) to C1 to C4 and C1 to C6 hydrocarbons, respectively. Compared to its cofactor homologs, the L-cluster generates considerably more CH4 from the reduction of CO and CN(-), which could be explained by the presence of a "free" Fe atom that is "unmasked" by homocitrate as an additional site for methanation. Moreover, the elevated CH4 formation is accompanied by a decrease in the amount of longer hydrocarbons and/or the lengths of the hydrocarbon products, illustrating a competition between CH4 formation/release and C-C coupling/chain extension. These observations suggest the possibility of designing simpler synthetic clusters for hydrocarbon formation while establishing the L-cluster as a platform for mechanistic investigations of CO and CN(-) reduction without complications originating from the heterometal and homocitrate components. Nitrogenase is a metalloenzyme that is highly complex in structure and uniquely versatile in function. It catalyzes two reactions that parallel two important industrial processes: the reduction of nitrogen to ammonia, which parallels the Haber-Bosch process in ammonia production, and the reduction of carbon monoxide to hydrocarbons, which parallels the Fischer-Tropsch process in fuel production. Thus, the significance of nitrogenase can be appreciated from the perspective of the useful products it generates: (i) ammonia, the "fixed" nitrogen that is essential for the existence of the entire human population; and (ii) hydrocarbons, the "recycled" carbon fuel that could be used to directly address the worldwide energy shortage. This article provides initial insights into the catalytic characteristics of various nitrogenase cofactors in hydrocarbon formation. The reported assay system provides a useful tool for mechanistic

  19. Genome-scale consequences of cofactor balancing in engineered pentose utilization pathways in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Amit Ghosh

    Full Text Available Biofuels derived from lignocellulosic biomass offer promising alternative renewable energy sources for transportation fuels. Significant effort has been made to engineer Saccharomyces cerevisiae to efficiently ferment pentose sugars such as D-xylose and L-arabinose into biofuels such as ethanol through heterologous expression of the fungal D-xylose and L-arabinose pathways. However, one of the major bottlenecks in these fungal pathways is that the cofactors are not balanced, which contributes to inefficient utilization of pentose sugars. We utilized a genome-scale model of S. cerevisiae to predict the maximal achievable growth rate for cofactor balanced and imbalanced D-xylose and L-arabinose utilization pathways. Dynamic flux balance analysis (DFBA was used to simulate batch fermentation of glucose, D-xylose, and L-arabinose. The dynamic models and experimental results are in good agreement for the wild type and for the engineered D-xylose utilization pathway. Cofactor balancing the engineered D-xylose and L-arabinose utilization pathways simulated an increase in ethanol batch production of 24.7% while simultaneously reducing the predicted substrate utilization time by 70%. Furthermore, the effects of cofactor balancing the engineered pentose utilization pathways were evaluated throughout the genome-scale metabolic network. This work not only provides new insights to the global network effects of cofactor balancing but also provides useful guidelines for engineering a recombinant yeast strain with cofactor balanced engineered pathways that efficiently co-utilizes pentose and hexose sugars for biofuels production. Experimental switching of cofactor usage in enzymes has been demonstrated, but is a time-consuming effort. Therefore, systems biology models that can predict the likely outcome of such strain engineering efforts are highly useful for motivating which efforts are likely to be worth the significant time investment.

  20. Organic cofactors participated more frequently than transition metals in redox reactions of primitive proteins.

    Science.gov (United States)

    Ji, Hong-Fang; Chen, Lei; Zhang, Hong-Yu

    2008-08-01

    Protein redox reactions are one of the most basic and important biochemical actions. As amino acids are weak redox mediators, most protein redox functions are undertaken by protein cofactors, which include organic ligands and transition metal ions. Since both kinds of redox cofactors were available in the pre-protein RNA world, it is challenging to explore which one was more involved in redox processes of primitive proteins? In this paper, using an examination of the redox cofactor usage of putative ancient proteins, we infer that organic ligands participated more frequently than transition metals in redox reactions of primitive proteins, at least as protein cofactors. This is further supported by the relative abundance of amino acids in the primordial world. Supplementary material for this article can be found on the BioEssays website. (c) 2008 Wiley Periodicals, Inc.

  1. Separation of xylose and glucose using an integrated membrane system for enzymatic cofactor regeneration and downstream purification

    DEFF Research Database (Denmark)

    Morthensen, Sofie Thage; Sigurdardóttir, Sigyn Björk; Meyer, Anne S.

    2017-01-01

    Mixtures of xylose, glucose and pyruvate were fed to a membrane bioreactor equipped with a charged NF membrane (NTR 7450). Value-added products were obtained in the reactor via enzymatic cofactor-dependent catalysis of glucose to gluconic acid and pyruvate to lactic acid, respectively. The initial...... cofactor (NADH) concentration could be decreased to 10% of the stoichiometric value (relative to glucose) without compromising process time and substrate conversion via i) efficient cofactor regeneration and ii) high retention of cofactor (R=0.98) in the membrane bioreactor. Furthermore, accumulation...

  2. Cofactors in allergic reactions to food : physical exercise and alcohol are the most important

    NARCIS (Netherlands)

    Versluis, Astrid; van Os-Medendorp, Harmieke; Kruizinga, Astrid G; Blom, W Marty; Houben, Geert F; Knulst, André C

    2016-01-01

    INTRODUCTION: Involvement of cofactors, like physical exercise, alcohol consumption and use of several types of medication, are associated with more severe food allergic symptoms. However, there is limited evidence on how often cofactors play a role in food allergic reactions. The study aimed to get

  3. Insight into cofactor recognition in arylamine N-acetyltransferase enzymes

    DEFF Research Database (Denmark)

    Xu, Ximing; Li de la Sierra-Gallay, Inés; Kubiak, Xavier Jean Philippe

    2015-01-01

    Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes that catalyze the acetyl-CoA-dependent acetylation of arylamines. To better understand the mode of binding of the cofactor by this family of enzymes, the structure of Mesorhizobium loti NAT1 [(RHILO)NAT1] was determined...... for Bacillus anthracis NAT1 and Homo sapiens NAT2. Therefore, in contrast to previous data, this study shows that different orthologous NATs can bind their cofactors in a similar way, suggesting that the mode of binding CoA in this family of enzymes is less diverse than previously thought. Moreover......, it supports the notion that the presence of the `mammalian/eukaryotic insertion loop' in certain NAT enzymes impacts the mode of binding CoA by imposing structural constraints....

  4. Remaining challenges in cellular flavin cofactor homeostasis and flavoprotein biogenesis

    Science.gov (United States)

    Giancaspero, Teresa Anna; Colella, Matilde; Brizio, Carmen; Difonzo, Graziana; Fiorino, Giuseppina Maria; Leone, Piero; Brandsch, Roderich; Bonomi, Francesco; Iametti, Stefania; Barile, Maria

    2015-04-01

    The primary role of the water-soluble vitamin B2 (riboflavin) in cell biology is connected with its conversion into FMN and FAD, the cofactors of a large number of dehydrogenases, oxidases and reductases involved in energetic metabolism, epigenetics, protein folding, as well as in a number of diverse regulatory processes. The problem of localisation of flavin cofactor synthesis events and in particular of the FAD synthase (EC 2.7.7.2) in HepG2 cells is addressed here by confocal microscopy in the frame of its relationships with kinetics of FAD synthesis and delivery to client apo-flavoproteins. FAD synthesis catalysed by recombinant isoform 2 of FADS occurs via an ordered bi-bi mechanism in which ATP binds prior to FMN, and pyrophosphate is released before FAD. Spectrophotometric continuous assays of the reconstitution rate of apo-D-aminoacid oxidase with its cofactor, allowed us to propose that besides its FAD synthesising activity, hFADS is able to operate as a FAD "chaperone". The physical interaction between FAD forming enzyme and its clients was further confirmed by dot blot and immunoprecipitation experiments carried out testing as a client either a nuclear or a mitochondrial enzyme that is lysine specific demethylase 1 (LSD1, EC 1.-.-.-) and dimethylglycine dehydrogenase (Me2GlyDH, EC 1.5.8.4), respectively which carry out similar reactions of oxidative demethylation, assisted by tetrahydrofolate used to form 5,10-methylene-tetrahydrofolate. A direct transfer of the cofactor from hFADS2 to apo-dimethyl glycine dehydrogenase was also demonstrated. Thus, FAD synthesis and delivery to these enzymes are crucial processes for bioenergetics and nutri-epigenetics of liver cells.

  5. Redox-dependent substrate-cofactor interactions in the Michaelis-complex of a flavin-dependent oxidoreductase

    Science.gov (United States)

    Werther, Tobias; Wahlefeld, Stefan; Salewski, Johannes; Kuhlmann, Uwe; Zebger, Ingo; Hildebrandt, Peter; Dobbek, Holger

    2017-07-01

    How an enzyme activates its substrate for turnover is fundamental for catalysis but incompletely understood on a structural level. With redox enzymes one typically analyses structures of enzyme-substrate complexes in the unreactive oxidation state of the cofactor, assuming that the interaction between enzyme and substrate is independent of the cofactors oxidation state. Here, we investigate the Michaelis complex of the flavoenzyme xenobiotic reductase A with the reactive reduced cofactor bound to its substrates by X-ray crystallography and resonance Raman spectroscopy and compare it to the non-reactive oxidized Michaelis complex mimics. We find that substrates bind in different orientations to the oxidized and reduced flavin, in both cases flattening its structure. But only authentic Michaelis complexes display an unexpected rich vibrational band pattern uncovering a strong donor-acceptor complex between reduced flavin and substrate. This interaction likely activates the catalytic ground state of the reduced flavin, accelerating the reaction within a compressed cofactor-substrate complex.

  6. Co-factors necessary for PPAR mediated transactivation of endogenous target genes

    DEFF Research Database (Denmark)

    Grøntved, Lars; Nielsen, Ronni; Stunnenberg, Henk

    of endogenous target gene in different cell types are elusive. To mutually compare the ability of the PPAR subtypes to activate endogenous target genes in a given cell, PPARa, PPARb/d and PPARg2 were HA tagged and rapidly, equally and synchronously expressed using adenoviral delivery. Within a few hours after...... subtype specific activation of target genes. Accumulating evidence suggests that transcriptional co-factors can function as master regulators for nuclear receptors and impose promoter selectivity. To study co-factor necessity for PPAR mediated transactivation of endogenous target genes, specific co...

  7. Cytosolic iron chaperones: Proteins delivering iron cofactors in the cytosol of mammalian cells.

    Science.gov (United States)

    Philpott, Caroline C; Ryu, Moon-Suhn; Frey, Avery; Patel, Sarju

    2017-08-04

    Eukaryotic cells contain hundreds of metalloproteins that are supported by intracellular systems coordinating the uptake and distribution of metal cofactors. Iron cofactors include heme, iron-sulfur clusters, and simple iron ions. Poly(rC)-binding proteins are multifunctional adaptors that serve as iron ion chaperones in the cytosolic/nuclear compartment, binding iron at import and delivering it to enzymes, for storage (ferritin) and export (ferroportin). Ferritin iron is mobilized by autophagy through the cargo receptor, nuclear co-activator 4. The monothiol glutaredoxin Glrx3 and BolA2 function as a [2Fe-2S] chaperone complex. These proteins form a core system of cytosolic iron cofactor chaperones in mammalian cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Synthesis, delivery and regulation of eukaryotic heme and Fe-S cluster cofactors.

    Science.gov (United States)

    Barupala, Dulmini P; Dzul, Stephen P; Riggs-Gelasco, Pamela Jo; Stemmler, Timothy L

    2016-02-15

    In humans, the bulk of iron in the body (over 75%) is directed towards heme- or Fe-S cluster cofactor synthesis, and the complex, highly regulated pathways in place to accomplish biosynthesis have evolved to safely assemble and load these cofactors into apoprotein partners. In eukaryotes, heme biosynthesis is both initiated and finalized within the mitochondria, while cellular Fe-S cluster assembly is controlled by correlated pathways both within the mitochondria and within the cytosol. Iron plays a vital role in a wide array of metabolic processes and defects in iron cofactor assembly leads to human diseases. This review describes progress towards our molecular-level understanding of cellular heme and Fe-S cluster biosynthesis, focusing on the regulation and mechanistic details that are essential for understanding human disorders related to the breakdown in these essential pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Deducing the temporal order of cofactor function in ligand-regulated gene transcription: theory and experimental verification.

    Science.gov (United States)

    Dougherty, Edward J; Guo, Chunhua; Simons, S Stoney; Chow, Carson C

    2012-01-01

    Cofactors are intimately involved in steroid-regulated gene expression. Two critical questions are (1) the steps at which cofactors exert their biological activities and (2) the nature of that activity. Here we show that a new mathematical theory of steroid hormone action can be used to deduce the kinetic properties and reaction sequence position for the functioning of any two cofactors relative to a concentration limiting step (CLS) and to each other. The predictions of the theory, which can be applied using graphical methods similar to those of enzyme kinetics, are validated by obtaining internally consistent data for pair-wise analyses of three cofactors (TIF2, sSMRT, and NCoR) in U2OS cells. The analysis of TIF2 and sSMRT actions on GR-induction of an endogenous gene gave results identical to those with an exogenous reporter. Thus new tools to determine previously unobtainable information about the nature and position of cofactor action in any process displaying first-order Hill plot kinetics are now available.

  10. Cofactor Editing by the G-protein Metallochaperone Domain Regulates the Radical B12 Enzyme IcmF.

    Science.gov (United States)

    Li, Zhu; Kitanishi, Kenichi; Twahir, Umar T; Cracan, Valentin; Chapman, Derrell; Warncke, Kurt; Banerjee, Ruma

    2017-03-10

    IcmF is a 5'-deoxyadenosylcobalamin (AdoCbl)-dependent enzyme that catalyzes the carbon skeleton rearrangement of isobutyryl-CoA to butyryl-CoA. It is a bifunctional protein resulting from the fusion of a G-protein chaperone with GTPase activity and the cofactor- and substrate-binding mutase domains with isomerase activity. IcmF is prone to inactivation during catalytic turnover, thus setting up its dependence on a cofactor repair system. Herein, we demonstrate that the GTPase activity of IcmF powers the ejection of the inactive cob(II)alamin cofactor and requires the presence of an acceptor protein, adenosyltransferase, for receiving it. Adenosyltransferase in turn converts cob(II)alamin to AdoCbl in the presence of ATP and a reductant. The repaired cofactor is then reloaded onto IcmF in a GTPase-gated step. The mechanistic details of cofactor loading and offloading from the AdoCbl-dependent IcmF are distinct from those of the better characterized and homologous methylmalonyl-CoA mutase/G-protein chaperone system. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. DEAH-RHA helicase•Znf cofactor systems in kinetoplastid RNA editing and evolutionarily distant RNA processes

    Science.gov (United States)

    Cruz-Reyes, Jorge; Mooers, Blaine H.M.; Abu-Adas, Zakaria; Kumar, Vikas; Gulati, Shelly

    2016-01-01

    Multi-zinc finger proteins are an emerging class of cofactors in DEAH-RHA RNA helicases across highly divergent eukaryotic lineages. DEAH-RHA helicase•zinc finger cofactor partnerships predate the split of kinetoplastid protozoa, which include several human pathogens, from other eukaryotic lineages 100–400 Ma. Despite a long evolutionary history, the prototypical DEAH-RHA domains remain highly conserved. This short review focuses on a recently identified DEAH-RHA helicase•zinc finger cofactor system in kinetoplastid RNA editing, and its potential functional parallels with analogous systems in embryogenesis control in nematodes and antivirus protection in humans. PMID:27540585

  12. Time-resolved fluorescence analysis of the mobile flavin cofactor

    Indian Academy of Sciences (India)

    Conformational heterogeneity of the FAD cofactor in -hydroxybenzoate hydroxylase (PHBH) was investigated with time-resolved polarized flavin fluorescence. For binary enzyme/substrate (analogue) complexes of wild-type PHBH and Tyr222 mutants, crystallographic studies have revealed two distinct flavin conformations ...

  13. Optimal cofactor swapping can increase the theoretical yield for chemical production in Escherichia coli and Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    King, Zachary A.; Feist, Adam

    2014-01-01

    Maintaining cofactor balance is a critical function in microorganisms, but often the native cofactor balance does not match the needs of an engineered metabolic flux state. Here, an optimization procedure is utilized to identify optimal cofactor-specificity "swaps" for oxidoreductase enzymes...... specificity of central metabolic enzymes (especially GAPD and ALCD2x) is shown to increase NADPH production and increase theoretical yields for native products in E. coli and yeast-including l-aspartate, l-lysine, l-isoleucine, l-proline, l-serine, and putrescine-and non-native products in E. coli-including 1...

  14. Chemomimetic biocatalysis: exploiting the synthetic potential of cofactor-dependent enzymes to create new catalysts.

    Science.gov (United States)

    Prier, Christopher K; Arnold, Frances H

    2015-11-11

    Despite the astonishing breadth of enzymes in nature, no enzymes are known for many of the valuable catalytic transformations discovered by chemists. Recent work in enzyme design and evolution, however, gives us good reason to think that this will change. We describe a chemomimetic biocatalysis approach that draws from small-molecule catalysis and synthetic chemistry, enzymology, and molecular evolution to discover or create enzymes with non-natural reactivities. We illustrate how cofactor-dependent enzymes can be exploited to promote reactions first established with related chemical catalysts. The cofactors can be biological, or they can be non-biological to further expand catalytic possibilities. The ability of enzymes to amplify and precisely control the reactivity of their cofactors together with the ability to optimize non-natural reactivity by directed evolution promises to yield exceptional catalysts for challenging transformations that have no biological counterparts.

  15. S-Adenosyl-L-Homocysteine Hydrolase Inhibition by a Synthetic Nicotinamide Cofactor Biomimetic

    Directory of Open Access Journals (Sweden)

    Lyn L. Kailing

    2018-03-01

    Full Text Available S-adenosyl-L-homocysteine (SAH hydrolases (SAHases are involved in the regulation of methylation reactions in many organisms and are thus crucial for numerous cellular functions. Consequently, their dysregulation is associated with severe health problems. The SAHase-catalyzed reaction is reversible and both directions depend on the redox activity of nicotinamide adenine dinucleotide (NAD+ as a cofactor. Therefore, nicotinamide cofactor biomimetics (NCB are a promising tool to modulate SAHase activity. In the present in vitro study, we investigated 10 synthetic truncated NAD+ analogs against a SAHase from the root-nodulating bacterium Bradyrhizobium elkanii. Among this set of analogs, one was identified to inhibit the SAHase in both directions. Isothermal titration calorimetry (ITC and crystallography experiments suggest that the inhibitory effect is not mediated by a direct interaction with the protein. Neither the apo-enzyme (i.e., deprived of the natural cofactor, nor the holo-enzyme (i.e., in the NAD+-bound state were found to bind the inhibitor. Yet, enzyme kinetics point to a non-competitive inhibition mechanism, where the inhibitor acts on both, the enzyme and enzyme-SAH complex. Based on our experimental results, we hypothesize that the NCB inhibits the enzyme via oxidation of the enzyme-bound NADH, which may be accessible through an open molecular gate, leaving the enzyme stalled in a configuration with oxidized cofactor, where the reaction intermediate can be neither converted nor released. Since the reaction mechanism of SAHase is quite uncommon, this kind of inhibition could be a viable pharmacological route, with a low risk of off-target effects. The NCB presented in this work could be used as a template for the development of more potent SAHase inhibitors.

  16. CoFactor: Folate Requirement for Optimization of 5-Fluouracil Activity in Anticancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2010-01-01

    Full Text Available Intracellular reduced folate exists as a “pool” of more than 6 interconvertable forms. One of these forms, 5,10 methylenetetrahydrofolic acid (CH2THF, is the key one-carbon donor and reduced folate substrate for thymidylate synthase (TS. This pathway has been an important target for chemotherapy as it provides one of the necessary nucleotide substrates for DNA synthesis. The fluoropyrimidine 5-fluorouracil (5-FU exerts its main cytotoxic activity through TS inhibition. Leucovorin (5-formyltetrahydrofolate; LV has been used to increase the intracellular reduced folate pools and enhance TS inhibition. However, it must be metabolized within the cell through multiple intracellular enzymatic steps to form CH2THF. CoFactor (USAN fotrexorin calcium, (dl-5,10,-methylenepteroyl-monoglutamate calcium salt is a reduced folate that potentiates 5-FU cytotoxicity. According to early clinical trials, when 5-FU is modulated by CoFactor instead of LV, there is greater anti-tumor activity and less toxicity. This review presents the emerging role of CoFactor in colorectal and nongastrointestinal malignancies.

  17. [On the influence of local molecular environment on the redox potential of electron transfer cofactors in bacterial photosynthetic reaction centers].

    Science.gov (United States)

    Krasil'nikov, P M; Noks, P P; Rubin, A B

    2011-01-01

    The addition of cryosolvents (glycerol, dimethylsulfoxide) to a water solution containing bacterial photosynthetic reaction centers changes the redox potential of the bacteriochlorophyll dimer, but does not affect the redox potential of the quinone primary acceptor. It has been shown that the change in redox potential can be produced by changes of the electrostatic interactions between cofactors and the local molecular environment modified by additives entered into the solution. The degree of influence of a solvent on the redox potential of various cofactors is determined by degree of availability of these cofactors for molecules of solvent, which depends on the arrangement of cofactors in the structure of reaction centers.

  18. The MoxR ATPase RavA and its cofactor ViaA interact with the NADH:ubiquinone oxidoreductase I in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Keith S Wong

    Full Text Available MoxR ATPases are widespread throughout bacteria and archaea. The experimental evidence to date suggests that these proteins have chaperone-like roles in facilitating the maturation of dedicated protein complexes that are functionally diverse. In Escherichia coli, the MoxR ATPase RavA and its putative cofactor ViaA are found to exist in early stationary-phase cells at 37 °C at low levels of about 350 and 90 molecules per cell, respectively. Both proteins are predominantly localized to the cytoplasm, but ViaA was also unexpectedly found to localize to the cell membrane. Whole genome microarrays and synthetic lethality studies both indicated that RavA-ViaA are genetically linked to Fe-S cluster assembly and specific respiratory pathways. Systematic analysis of mutant strains of ravA and viaA indicated that RavA-ViaA sensitizes cells to sublethal concentrations of aminoglycosides. Furthermore, this effect was dependent on RavA's ATPase activity, and on the presence of specific subunits of NADH:ubiquinone oxidoreductase I (Nuo Complex, or Complex I. Importantly, both RavA and ViaA were found to physically interact with specific Nuo subunits. We propose that RavA-ViaA facilitate the maturation of the Nuo complex.

  19. A water-forming NADH oxidase from Lactobacillus pentosus and its potential application in the regeneration of synthetic biomimetic cofactors

    Directory of Open Access Journals (Sweden)

    Claudia eNowak

    2015-09-01

    Full Text Available The cell-free biocatalytic production of fine chemicals by oxidoreductases has continuously grown over the past years. Since especially dehydrogenases depend on the stoichiometric use of nicotinamide pyridine cofactors, an integrated efficient recycling system is crucial to allow process operation under economic conditions. Lately, the variety of cofactors for biocatalysis was broadened by the utilization of totally synthetic and cheap biomimetics. Though, to date the regeneration has been limited to chemical or electrochemical methods. Here, we report an enzymatic recycling by the flavoprotein NADH-oxidase from Lactobacillus pentosus (LpNox. Since this enzyme has not been described before, we first characterized it in regard to its optimal reaction parameters. We found that the heterologously overexpressed enzyme only contained 13 % FAD. In vitro loading of the enzyme with FAD, resulted in a higher specific activity towards its natural cofactor NADH as well as different nicotinamide derived biomimetics. Apart from the enzymatic recycling, which gives water as a by-product by transferring four electrons onto oxygen, unbound FAD can also catalyse the oxidation of biomimetic cofactors. Here a two electron process takes place yielding H2O2 instead. The enzymatic and chemical recycling was compared in regard to reaction kinetics for the natural and biomimetic cofactors. With LpNox and FAD, two recycling strategies for biomimetic cofactors are described with either water or hydrogen peroxide as a by-product.

  20. Cofactor-binding sites in proteins of deviating sequence: comparative analysis and clustering in torsion angle, cavity, and fold space.

    Science.gov (United States)

    Stegemann, Björn; Klebe, Gerhard

    2012-02-01

    Small molecules are recognized in protein-binding pockets through surface-exposed physicochemical properties. To optimize binding, they have to adopt a conformation corresponding to a local energy minimum within the formed protein-ligand complex. However, their conformational flexibility makes them competent to bind not only to homologous proteins of the same family but also to proteins of remote similarity with respect to the shape of the binding pockets and folding pattern. Considering drug action, such observations can give rise to unexpected and undesired cross reactivity. In this study, datasets of six different cofactors (ADP, ATP, NAD(P)(H), FAD, and acetyl CoA, sharing an adenosine diphosphate moiety as common substructure), observed in multiple crystal structures of protein-cofactor complexes exhibiting sequence identity below 25%, have been analyzed for the conformational properties of the bound ligands, the distribution of physicochemical properties in the accommodating protein-binding pockets, and the local folding patterns next to the cofactor-binding site. State-of-the-art clustering techniques have been applied to group the different protein-cofactor complexes in the different spaces. Interestingly, clustering in cavity (Cavbase) and fold space (DALI) reveals virtually the same data structuring. Remarkable relationships can be found among the different spaces. They provide information on how conformations are conserved across the host proteins and which distinct local cavity and fold motifs recognize the different portions of the cofactors. In those cases, where different cofactors are found to be accommodated in a similar fashion to the same fold motifs, only a commonly shared substructure of the cofactors is used for the recognition process. Copyright © 2011 Wiley Periodicals, Inc.

  1. On the Metal Cofactor in the Tyrosinase Family

    Directory of Open Access Journals (Sweden)

    Francisco Solano

    2018-02-01

    Full Text Available The production of pigment in mammalian melanocytes requires the contribution of at least three melanogenic enzymes, tyrosinase and two other accessory enzymes called the tyrosinase-related proteins (Trp1 and Trp2, which regulate the type and amount of melanin. The last two proteins are paralogues to tyrosinase, and they appeared late in evolution by triplication of the tyrosinase gene. Tyrosinase is a copper-enzyme, and Trp2 is a zinc-enzyme. Trp1 has been more elusive, and the direct identification of its metal cofactor has never been achieved. However, due to its enzymatic activity and similarities with tyrosinase, it has been assumed as a copper-enzyme. Recently, recombinant human tyrosinase and Trp1 have been expressed in enough amounts to achieve for the first time their crystallization. Unexpectedly, it has been found that Trp1 contains a couple of Zn(II at the active site. This review discusses data about the metal cofactor of tyrosinase and Trps. It points out differences in the studied models, and it proposes some possible points accounting for the apparent discrepancies currently appearing. Moreover, some proposals about the possible flexibility of the tyrosinase family to uptake copper or zinc are discussed.

  2. Synthesis, thermodynamic and transport properties of the compounds Sr3FeMO7-δ(M = Fe, Ni) in the temperature range of 400≤T≤1000oC

    International Nuclear Information System (INIS)

    Mogni, L; Prado, E; Caneiro, A

    2004-01-01

    The synthesis is presented for the mixed conductors Sr 3 FeMO 7-δ (M = Fe, Ni) belonging to the Ruddlesden Popper series A n+1 B n O3 n+1 with n = 2 using the acetates method. The samples were characterized using X-ray diffraction techniques, scanning electron microscopy and EDS. The variation of the chemical potential of oxygen was determined with the oxygen content of these compounds (7-δ) in a wide range of partial oxygen pressure 10 -5 ≤pO2≤ 1 atm and temperatures (673-1273 K). The electrical conductivity as a function of the temperature and the pO2 were measured by the four points method. Based on an analysis of the test data the effect of the cationic substitution of Fe by Ni on the thermodynamic, structural properties and on the structure of defects in the temperature range of interest for the electrochemical devices is discussed (WC)

  3. RNAi-Based Identification of Gene-Specific Nuclear Cofactor Networks Regulating Interleukin-1 Target Genes

    Directory of Open Access Journals (Sweden)

    Johanna Meier-Soelch

    2018-04-01

    Full Text Available The potent proinflammatory cytokine interleukin (IL-1 triggers gene expression through the NF-κB signaling pathway. Here, we investigated the cofactor requirements of strongly regulated IL-1 target genes whose expression is impaired in p65 NF-κB-deficient murine embryonic fibroblasts. By two independent small-hairpin (shRNA screens, we examined 170 genes annotated to encode nuclear cofactors for their role in Cxcl2 mRNA expression and identified 22 factors that modulated basal or IL-1-inducible Cxcl2 levels. The functions of 16 of these factors were validated for Cxcl2 and further analyzed for their role in regulation of 10 additional IL-1 target genes by RT-qPCR. These data reveal that each inducible gene has its own (quantitative requirement of cofactors to maintain basal levels and to respond to IL-1. Twelve factors (Epc1, H2afz, Kdm2b, Kdm6a, Mbd3, Mta2, Phf21a, Ruvbl1, Sin3b, Suv420h1, Taf1, and Ube3a have not been previously implicated in inflammatory cytokine functions. Bioinformatics analysis indicates that they are components of complex nuclear protein networks that regulate chromatin functions and gene transcription. Collectively, these data suggest that downstream from the essential NF-κB signal each cytokine-inducible target gene has further subtle requirements for individual sets of nuclear cofactors that shape its transcriptional activation profile.

  4. A live zebrafish-based screening system for human nuclear receptor ligand and cofactor discovery.

    Science.gov (United States)

    Tiefenbach, Jens; Moll, Pamela R; Nelson, Meryl R; Hu, Chun; Baev, Lilia; Kislinger, Thomas; Krause, Henry M

    2010-03-22

    Nuclear receptors (NRs) belong to a superfamily of transcription factors that regulate numerous homeostatic, metabolic and reproductive processes. Taken together with their modulation by small lipophilic molecules, they also represent an important and successful class of drug targets. Although many NRs have been targeted successfully, the majority have not, and one third are still orphans. Here we report the development of an in vivo GFP-based reporter system suitable for monitoring NR activities in all cells and tissues using live zebrafish (Danio rerio). The human NR fusion proteins used also contain a new affinity tag cassette allowing the purification of receptors with bound molecules from responsive tissues. We show that these constructs 1) respond as expected to endogenous zebrafish hormones and cofactors, 2) facilitate efficient receptor and cofactor purification, 3) respond robustly to NR hormones and drugs and 4) yield readily quantifiable signals. Transgenic lines representing the majority of human NRs have been established and are available for the investigation of tissue- and isoform-specific ligands and cofactors.

  5. A live zebrafish-based screening system for human nuclear receptor ligand and cofactor discovery.

    Directory of Open Access Journals (Sweden)

    Jens Tiefenbach

    2010-03-01

    Full Text Available Nuclear receptors (NRs belong to a superfamily of transcription factors that regulate numerous homeostatic, metabolic and reproductive processes. Taken together with their modulation by small lipophilic molecules, they also represent an important and successful class of drug targets. Although many NRs have been targeted successfully, the majority have not, and one third are still orphans. Here we report the development of an in vivo GFP-based reporter system suitable for monitoring NR activities in all cells and tissues using live zebrafish (Danio rerio. The human NR fusion proteins used also contain a new affinity tag cassette allowing the purification of receptors with bound molecules from responsive tissues. We show that these constructs 1 respond as expected to endogenous zebrafish hormones and cofactors, 2 facilitate efficient receptor and cofactor purification, 3 respond robustly to NR hormones and drugs and 4 yield readily quantifiable signals. Transgenic lines representing the majority of human NRs have been established and are available for the investigation of tissue- and isoform-specific ligands and cofactors.

  6. Protein Cofactors Are Essential for High-Affinity DNA Binding by the Nuclear Factor κB RelA Subunit.

    Science.gov (United States)

    Mulero, Maria Carmen; Shahabi, Shandy; Ko, Myung Soo; Schiffer, Jamie M; Huang, De-Bin; Wang, Vivien Ya-Fan; Amaro, Rommie E; Huxford, Tom; Ghosh, Gourisankar

    2018-05-22

    Transcription activator proteins typically contain two functional domains: a DNA binding domain (DBD) that binds to DNA with sequence specificity and an activation domain (AD) whose established function is to recruit RNA polymerase. In this report, we show that purified recombinant nuclear factor κB (NF-κB) RelA dimers bind specific κB DNA sites with an affinity significantly lower than that of the same dimers from nuclear extracts of activated cells, suggesting that additional nuclear cofactors might facilitate DNA binding by the RelA dimers. Additionally, recombinant RelA binds DNA with relatively low affinity at a physiological salt concentration in vitro. The addition of p53 or RPS3 (ribosomal protein S3) increases RelA:DNA binding affinity 2- to >50-fold depending on the protein and ionic conditions. These cofactor proteins do not form stable ternary complexes, suggesting that they stabilize the RelA:DNA complex through dynamic interactions. Surprisingly, the RelA-DBD alone fails to bind DNA under the same solution conditions even in the presence of cofactors, suggesting an important role of the RelA-AD in DNA binding. Reduced RelA:DNA binding at a physiological ionic strength suggests that multiple cofactors might be acting simultaneously to mitigate the electrolyte effect and stabilize the RelA:DNA complex in vivo. Overall, our observations suggest that the RelA-AD and multiple cofactor proteins function cooperatively to prime the RelA-DBD and stabilize the RelA:DNA complex in cells. Our study provides a mechanism for nuclear cofactor proteins in NF-κB-dependent gene regulation.

  7. Magnetostructural coupling behavior at the ferromagnetic transition in double-perovskite S r2FeMo O6

    Science.gov (United States)

    Yang, Dexin; Harrison, Richard J.; Schiemer, Jason A.; Lampronti, Giulio I.; Liu, Xueyin; Zhang, Fenghua; Ding, Hao; Liu, Yan'gai; Carpenter, Michael A.

    2016-01-01

    The ordered double-perovskite S r2FeMo O6 (SFMO) possesses remarkable room-temperature low-field colossal magnetoresistivity and transport properties which are related, at least in part, to combined structural and magnetic instabilities that are responsible for a cubic-tetragonal phase transition near 420 K. A formal strain analysis combined with measurements of elastic properties from resonant ultrasound spectroscopy reveal a system with weak biquadratic coupling between two order parameters belonging to Γ4+ and m Γ4+ of parent space group F m 3 ¯m . The observed softening of the shear modulus by ˜50% is due to the classical effects of strain/order parameter coupling at an improper ferroelastic (Γ4+) transition which is second order in character, while the ferromagnetic order parameter (m Γ4+ ) couples only with volume strain. The influence of a third order parameter, for ordering of Fe and Mo on crystallographic B sites, is to change the strength of coupling between the Γ4+ order parameter and the tetragonal shear strain due to the influence of changes in local strain heterogeneity at a unit cell scale. High anelastic loss below the transition point reveals the presence of mobile ferroelastic twin walls which become pinned by oxygen vacancies in a temperature interval near 340 K. The twin walls must be both ferroelastic and ferromagnetic, but due to the weak coupling between the magnetic and structural order parameters it should be possible to pull them apart with a weak magnetic field. These insights into the role of strain coupling and relaxational effects in a system with only weak coupling between three order parameters allow rationalization and prediction of how static and dynamic properties of the material might be tuned in thin film form by choice of strain contrast with a substrate.

  8. Oxygen diffusion pathways in a cofactor-independent dioxygenase

    Science.gov (United States)

    Di Russo, Natali V.; Condurso, Heather L.; Li, Kunhua; Bruner, Steven D.; Roitberg, Adrian E.

    2015-01-01

    Molecular oxygen plays an important role in a wide variety of enzymatic reactions. Through recent research efforts combining computational and experimental methods a new view of O2 diffusion is emerging, where specific channels guide O2 to the active site. The focus of this work is DpgC, a cofactor-independent oxygenase. Molecular dynamics simulations, together with mutagenesis experiments and xenon-binding data, reveal that O2 reaches the active site of this enzyme using three main pathways and four different access points. These pathways connect a series of dynamic hydrophobic pockets, concentrating O2 at a specific face of the enzyme substrate. Extensive molecular dynamics simulations provide information about which pathways are more frequently used. This data is consistent with the results of kinetic measurements on mutants and is difficult to obtain using computational cavity-location methods. Taken together, our results reveal that although DpgC is rare in its ability of activating O2 in the absence of cofactors or metals, the way O2 reaches the active site is similar to that reported for other O2-using proteins: multiple access channels are available, and the architecture of the pathway network can provide regio- and stereoselectivity. Our results point to the existence of common themes in O2 access that are conserved among very different types of proteins. PMID:26508997

  9. Probing the structural basis of oxygen binding in a cofactor-independent dioxygenase.

    Science.gov (United States)

    Li, Kunhua; Fielding, Elisha N; Condurso, Heather L; Bruner, Steven D

    2017-07-01

    The enzyme DpgC is included in the small family of cofactor-independent dioxygenases. The chemistry of DpgC is uncommon as the protein binds and utilizes dioxygen without the aid of a metal or organic cofactor. Previous structural and biochemical studies identified the substrate-binding mode and the components of the active site that are important in the catalytic mechanism. In addition, the results delineated a putative binding pocket and migration pathway for the co-substrate dioxygen. Here, structural biology is utilized, along with site-directed mutagenesis, to probe the assigned dioxygen-binding pocket. The key residues implicated in dioxygen trafficking were studied to probe the process of binding, activation and chemistry. The results support the proposed chemistry and provide insight into the general mechanism of dioxygen binding and activation.

  10. Rational modification of Corynebacterium glutamicum dihydrodipicolinate reductase to switch the nucleotide-cofactor specificity for increasing l-lysine production.

    Science.gov (United States)

    Xu, Jian-Zhong; Yang, Han-Kun; Liu, Li-Ming; Wang, Ying-Yu; Zhang, Wei-Guo

    2018-03-25

    l-lysine is an important amino acid in animals and humans and NADPH is a vital cofactor for maximizing the efficiency of l-lysine fermentation. Dihydrodipicolinate reductase (DHDPR), an NAD(P)H-dependent enzyme, shows a variance in nucleotide-cofactor affinity in bacteria. In this study, we rationally engineered Corynebacterium glutamicum DHDPR (CgDHDPR) to switch its nucleotide-cofactor specificity resulting in an increase in final titer (from 82.6 to 117.3 g L -1 ), carbon yield (from 0.35 to 0.44 g [g glucose] -1 ) and productivity (from 2.07 to 2.93 g L -1  hr -1 ) of l-lysine in JL-6 ΔdapB::Ec-dapB C115G,G116C in fed-batch fermentation. To do this, we comparatively analyzed the characteristics of CgDHDPR and Escherichia coli DHDPR (EcDHDPR), indicating that hetero-expression of NADH-dependent EcDHDPR increased l-lysine production. Subsequently, we rationally modified the conserved structure of cofactor-binding motif, and results indicated that introducing the mutation K11A or R13A in CgDHDPR and introducing the mutation R16A or R39A in EcDHDPR modifies the nucleotide-cofactor affinity of DHDPR. Lastly, the effects of these mutated DHDPRs on l-lysine production were investigated. The highest increase (26.2%) in l-lysine production was observed for JL-6 ΔdapB::Ec-dapB C115G,G116C , followed by JL-6 Cg-dapB C37G,G38C (21.4%) and JL-6 ΔdapB::Ec-dapB C46G,G47C (15.2%). This is the first report of a rational modification of DHDPR that enhances the l-lysine production and yield through the modulation of nucleotide-cofactor specificity. © 2018 Wiley Periodicals, Inc.

  11. Escherichia coli class Ib ribonucleotide reductase contains a dimanganese(III)-tyrosyl radical cofactor in vivo†

    Science.gov (United States)

    Cotruvo, Joseph A.; Stubbe, JoAnne

    2011-01-01

    Escherichia coli class Ib ribonucleotide reductase (RNR) converts nucleoside 5′-diphosphates to deoxynucleoside 5′-diphosphates in iron-limited and oxidative stress conditions. We have recently demonstrated in vitro that this RNR is active with both diferric-tyrosyl radical (FeIII2-Y•) and dimanganese(III)-Y• (MnIII2-Y•) cofactors in the β2 subunit, NrdF [Cotruvo J.A., Jr. and Stubbe J., Biochemistry (2010) 49, 1297–1309]. Here we demonstrate, by purification of this protein from its endogenous levels in an E. coli strain deficient in its five known iron uptake pathways and grown under iron-limited conditions, that the MnIII2-Y• cofactor is assembled in vivo. This is the first definitive determination of the active cofactor of a class Ib RNR purified from its native organism without overexpression. From 88 g of cell paste, 150 μg of NrdF was isolated with ~95% purity, with 0.2 Y•/β2, 0.9 Mn/β2, and a specific activity of 720 nmol/min/mg. In these conditions, the class Ib RNR is the primary active RNR in the cell. Our results strongly suggest that E. coli NrdF is an obligate manganese protein in vivo and that the MnIII2-Y• cofactor assembly pathway we have identified in vitro involving the flavodoxin-like protein NrdI, present inside the cell at catalytic levels, is operative in vivo. PMID:21250660

  12. Cofactor engineering to regulate NAD+/NADH ratio with its application to phytosterols biotransformation.

    Science.gov (United States)

    Su, Liqiu; Shen, Yanbing; Zhang, Wenkai; Gao, Tian; Shang, Zhihua; Wang, Min

    2017-10-30

    Cofactor engineering is involved in the modification of enzymes related to nicotinamide adenine dinucleotides (NADH and NAD + ) metabolism, which results in a significantly altered spectrum of metabolic products. Cofactor engineering plays an important role in metabolic engineering but is rarely reported in the sterols biotransformation process owing to its use of multi-catabolic enzymes, which promote multiple consecutive reactions. Androst-4-ene-3, 17-dione (AD) and androst-1, 4-diene-3, 17-dione (ADD) are important steroid medicine intermediates that are obtained via the nucleus oxidation and the side chain degradation of phytosterols by Mycobacterium. Given that the biotransformation from phytosterols to AD (D) is supposed to be a NAD + -dependent process, this work utilized cofactor engineering in Mycobacterium neoaurum and investigated the effect on cofactor and phytosterols metabolism. Through the addition of the coenzyme precursor of nicotinic acid in the phytosterols fermentation system, the intracellular NAD + /NADH ratio and the AD (D) production of M. neoaurum TCCC 11978 (MNR M3) were higher than in the control. Moreover, the NADH: flavin oxidoreductase was identified and was supposed to exert a positive effect on cofactor regulation and phytosterols metabolism pathways via comparative proteomic profiling of MNR cultured with and without phytosterols. In addition, the NADH: flavin oxidoreductase and a water-forming NADH oxidase from Lactobacillus brevis, were successfully overexpressed and heterologously expressed in MNR M3 to improve the intracellular ratio of NAD + /NADH. After 96 h of cultivation, the expression of these two enzymes in MNR M3 resulted in the decrease in intracellular NADH level (by 51 and 67%, respectively) and the increase in NAD + /NADH ratio (by 113 and 192%, respectively). Phytosterols bioconversion revealed that the conversion ratio of engineered stains was ultimately improved by 58 and 147%, respectively. The highest AD (D

  13. Involvement of the Cys-Tyr cofactor on iron binding in the active site of human cysteine dioxygenase.

    Science.gov (United States)

    Arjune, Sita; Schwarz, Guenter; Belaidi, Abdel A

    2015-01-01

    Sulfur metabolism has gained increasing medical interest over the last years. In particular, cysteine dioxygenase (CDO) has been recognized as a potential marker in oncology due to its altered gene expression in various cancer types. Human CDO is a non-heme iron-dependent enzyme, which catalyzes the irreversible oxidation of cysteine to cysteine sulfinic acid, which is further metabolized to taurine or pyruvate and sulfate. Several studies have reported a unique post-translational modification of human CDO consisting of a cross-link between cysteine 93 and tyrosine 157 (Cys-Tyr), which increases catalytic efficiency in a substrate-dependent manner. However, the reaction mechanism by which the Cys-Tyr cofactor increases catalytic efficiency remains unclear. In this study, steady-state kinetics were determined for wild type CDO and two different variants being either impaired or saturated with the Cys-Tyr cofactor. Cofactor formation in CDO resulted in an approximately fivefold increase in k cat and tenfold increase in k cat/K m over the cofactor-free CDO variant. Furthermore, iron titration experiments revealed an 18-fold decrease in K d of iron upon cross-link formation. This finding suggests a structural role of the Cys-Tyr cofactor in coordinating the ferrous iron in the active site of CDO in accordance with the previously postulated reaction mechanism of human CDO. Finally, we identified product-based inhibition and α-ketoglutarate and glutarate as CDO inhibitors using a simplified well plate-based activity assay. This assay can be used for high-throughput identification of additional inhibitors, which may contribute to understand the functional importance of CDO in sulfur amino acid metabolism and related diseases.

  14. Lineage-Specific Viral Hijacking of Non-canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity

    Directory of Open Access Journals (Sweden)

    Joshua R. Kane

    2015-05-01

    Full Text Available HIV-1 encodes the accessory protein Vif, which hijacks a host Cullin-RING ubiquitin ligase (CRL complex as well as the non-canonical cofactor CBFβ, to antagonize APOBEC3 antiviral proteins. Non-canonical cofactor recruitment to CRL complexes by viral factors, to date, has only been attributed to HIV-1 Vif. To further study this phenomenon, we employed a comparative approach combining proteomic, biochemical, structural, and virological techniques to investigate Vif complexes across the lentivirus genus, including primate (HIV-1 and simian immunodeficiency virus macaque [SIVmac] and non-primate (FIV, BIV, and MVV viruses. We find that CBFβ is completely dispensable for the activity of non-primate lentiviral Vif proteins. Furthermore, we find that BIV Vif requires no cofactor and that MVV Vif requires a novel cofactor, cyclophilin A (CYPA, for stable CRL complex formation and anti-APOBEC3 activity. We propose modular conservation of Vif complexes allows for potential exaptation of functions through the acquisition of non-CRL-associated host cofactors while preserving anti-APOBEC3 activity.

  15. Crystallization and preliminary X-ray analysis of tubulin-folding cofactor A from Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Lu, Lu; Nan, Jie; Mi, Wei; Wei, Chun-Hong; Li, Lan-Fen; Li, Yi

    2010-01-01

    Tubulin-folding cofactor A from A. thaliana has been crystallized and preliminarily analyzed using X-ray diffraction. Tubulin-folding cofactor A (TFC A) is a molecular post-chaperonin that is involved in the β-tubulin-folding pathway. It has been identified in many organisms including yeasts, humans and plants. In this work, Arabidopsis thaliana TFC A was expressed in Escherichia coli and purified to homogeneity. After thrombin cleavage, a well diffracting crystal was obtained by the sitting-drop vapour-diffusion method at 289 K. The crystal diffracted to 1.6 Å resolution using synchrotron radiation and belonged to space group I4 1 , with unit-cell parameters a = 55.0, b = 55.0, c = 67.4 Å

  16. Crystallization and preliminary crystallographic analysis of molybdenum-cofactor biosynthesis protein C from Thermus thermophilus

    International Nuclear Information System (INIS)

    Kanaujia, Shankar Prasad; Ranjani, Chellamuthu Vasuki; Jeyakanthan, Jeyaraman; Baba, Seiki; Chen, Lirong; Liu, Zhi-Jie; Wang, Bi-Cheng; Nishida, Masami; Ebihara, Akio; Shinkai, Akeo; Kuramitsu, Seiki; Shiro, Yoshitsugu; Sekar, Kanagaraj; Yokoyama, Shigeyuki

    2006-01-01

    The molybdenum-cofactor biosynthesis protein C from T. thermophilus has been crystallized in two different space groups, P2 1 and R32; the crystals diffracted to 1.9 and 1.75 Å resolution, respectively. The Gram-negative aerobic eubacterium Thermus thermophilus is an extremely important thermophilic microorganism that was originally isolated from a thermal vent environment in Japan. The molybdenum cofactor in this organism is considered to be an essential component required by enzymes that catalyze diverse key reactions in the global metabolism of carbon, nitrogen and sulfur. The molybdenum-cofactor biosynthesis protein C derived from T. thermophilus was crystallized in two different space groups. Crystals obtained using the first crystallization condition belong to the monoclinic space group P2 1 , with unit-cell parameters a = 64.81, b = 109.84, c = 115.19 Å, β = 104.9°; the crystal diffracted to a resolution of 1.9 Å. The other crystal form belonged to space group R32, with unit-cell parameters a = b = 106.57, c = 59.25 Å, and diffracted to 1.75 Å resolution. Preliminary calculations reveal that the asymmetric unit contains 12 monomers and one monomer for the crystals belonging to space group P2 1 and R32, respectively

  17. CD/MCD/VTVH-MCD Studies of Escherichia coli Bacterioferritin Support a Binuclear Iron Cofactor Site.

    Science.gov (United States)

    Kwak, Yeonju; Schwartz, Jennifer K; Huang, Victor W; Boice, Emily; Kurtz, Donald M; Solomon, Edward I

    2015-12-01

    Ferritins and bacterioferritins (Bfrs) utilize a binuclear non-heme iron binding site to catalyze oxidation of Fe(II), leading to formation of an iron mineral core within a protein shell. Unlike ferritins, in which the diiron site binds Fe(II) as a substrate, which then autoxidizes and migrates to the mineral core, the diiron site in Bfr has a 2-His/4-carboxylate ligand set that is commonly found in diiron cofactor enzymes. Bfrs could, therefore, utilize the diiron site as a cofactor rather than for substrate iron binding. In this study, we applied circular dichroism (CD), magnetic CD (MCD), and variable-temperature, variable-field MCD (VTVH-MCD) spectroscopies to define the geometric and electronic structures of the biferrous active site in Escherichia coli Bfr. For these studies, we used an engineered M52L variant, which is known to eliminate binding of a heme cofactor but to have very minor effects on either iron oxidation or mineral core formation. We also examined an H46A/D50A/M52L Bfr variant, which additionally disrupts a previously observed mononuclear non-heme iron binding site inside the protein shell. The spectral analyses define a binuclear and an additional mononuclear ferrous site. The biferrous site shows two different five-coordinate centers. After O2 oxidation and re-reduction, only the mononuclear ferrous signal is eliminated. The retention of the biferrous but not the mononuclear ferrous site upon O2 cycling supports a mechanism in which the binuclear site acts as a cofactor for the O2 reaction, while the mononuclear site binds the substrate Fe(II) that, after its oxidation to Fe(III), migrates to the mineral core.

  18. Site-Specific Bioconjugation of an Organometallic Electron Mediator to an Enzyme with Retained Photocatalytic Cofactor Regenerating Capacity and Enzymatic Activity

    Directory of Open Access Journals (Sweden)

    Sung In Lim

    2015-04-01

    Full Text Available Photosynthesis consists of a series of reactions catalyzed by redox enzymes to synthesize carbohydrates using solar energy. In order to take the advantage of solar energy, many researchers have investigated artificial photosynthesis systems mimicking the natural photosynthetic enzymatic redox reactions. These redox reactions usually require cofactors, which due to their high cost become a key issue when constructing an artificial photosynthesis system. Combining a photosensitizer and an Rh-based electron mediator (RhM has been shown to photocatalytically regenerate cofactors. However, maintaining the high concentration of cofactors available for efficient enzymatic reactions requires a high concentration of the expensive RhM; making this process cost prohibitive. We hypothesized that conjugation of an electron mediator to a redox enzyme will reduce the amount of electron mediators necessary for efficient enzymatic reactions. This is due to photocatalytically regenerated NAD(PH being readily available to a redox enzyme, when the local NAD(PH concentration near the enzyme becomes higher. However, conventional random conjugation of RhM to a redox enzyme will likely lead to a substantial loss of cofactor regenerating capacity and enzymatic activity. In order to avoid this issue, we investigated whether bioconjugation of RhM to a permissive site of a redox enzyme retains cofactor regenerating capacity and enzymatic activity. As a model system, a RhM was conjugated to a redox enzyme, formate dehydrogenase obtained from Thiobacillus sp. KNK65MA (TsFDH. A RhM-containing azide group was site-specifically conjugated to p-azidophenylalanine introduced to a permissive site of TsFDH via a bioorthogonal strain-promoted azide-alkyne cycloaddition and an appropriate linker. The TsFDH-RhM conjugate exhibited retained cofactor regenerating capacity and enzymatic activity.

  19. Elucidation of new condition-dependent roles for fructose-1,6-bisphosphatase linked to cofactor balances.

    Directory of Open Access Journals (Sweden)

    Du Toit W P Schabort

    Full Text Available The cofactor balances in metabolism is of paramount importance in the design of a metabolic engineering strategy and understanding the regulation of metabolism in general. ATP, NAD+ and NADP+ balances are central players linking the various fluxes in central metabolism as well as biomass formation. NADP+ is especially important in the metabolic engineering of yeasts for xylose fermentation, since NADPH is required by most yeasts in the initial step of xylose utilisation, including the fast-growing Kluyveromyces marxianus. In this simulation study of yeast metabolism, the complex interplay between these cofactors was investigated; in particular, how they may affect the possible roles of fructose-1,6-bisphosphatase, the pentose phosphate pathway, glycerol production and the pyruvate dehydrogenase bypass. Using flux balance analysis, it was found that the potential role of fructose-1,6-bisphosphatase was highly dependent on the cofactor specificity of the oxidative pentose phosphate pathway and on the carbon source. Additionally, the excessive production of ATP under certain conditions might be involved in some of the phenomena observed, which may have been overlooked to date. Based on these findings, a strategy is proposed for the metabolic engineering of a future xylose-fermenting yeast for biofuel production.

  20. Kinetics based reaction optimization of enzyme catalyzed reduction of formaldehyde to methanol with synchronous cofactor regeneration.

    Science.gov (United States)

    Marpani, Fauziah; Sárossy, Zsuzsa; Pinelo, Manuel; Meyer, Anne S

    2017-12-01

    Enzymatic reduction of carbon dioxide (CO 2 ) to methanol (CH 3 OH) can be accomplished using a designed set-up of three oxidoreductases utilizing reduced pyridine nucleotide (NADH) as cofactor for the reducing equivalents electron supply. For this enzyme system to function efficiently a balanced regeneration of the reducing equivalents during reaction is required. Herein, we report the optimization of the enzymatic conversion of formaldehyde (CHOH) to CH 3 OH by alcohol dehydrogenase, the final step of the enzymatic redox reaction of CO 2 to CH 3 OH, with kinetically synchronous enzymatic cofactor regeneration using either glucose dehydrogenase (System I) or xylose dehydrogenase (System II). A mathematical model of the enzyme kinetics was employed to identify the best reaction set-up for attaining optimal cofactor recycling rate and enzyme utilization efficiency. Targeted process optimization experiments were conducted to verify the kinetically modeled results. Repetitive reaction cycles were shown to enhance the yield of CH 3 OH, increase the total turnover number (TTN) and the biocatalytic productivity rate (BPR) value for both system I and II whilst minimizing the exposure of the enzymes to high concentrations of CHOH. System II was found to be superior to System I with a yield of 8 mM CH 3 OH, a TTN of 160 and BPR of 24 μmol CH 3 OH/U · h during 6 hr of reaction. The study demonstrates that an optimal reaction set-up could be designed from rational kinetics modeling to maximize the yield of CH 3 OH, whilst simultaneously optimizing cofactor recycling and enzyme utilization efficiency. © 2017 Wiley Periodicals, Inc.

  1. Catalase in peroxidase clothing: Interdependent cooperation of two cofactors in the catalytic versatility of KatG.

    Science.gov (United States)

    Njuma, Olive J; Ndontsa, Elizabeth N; Goodwin, Douglas C

    2014-02-15

    Catalase-peroxidase (KatG) is found in eubacteria, archaea, and lower eukaryotae. The enzyme from Mycobacterium tuberculosis has received the greatest attention because of its role in activation of the antitubercular pro-drug isoniazid, and the high frequency with which drug resistance stems from mutations to the katG gene. Generally, the catalase activity of KatGs is striking. It rivals that of typical catalases, enzymes with which KatGs share no structural similarity. Instead, catalatic turnover is accomplished with an active site that bears a strong resemblance to a typical peroxidase (e.g., cytochrome c peroxidase). Yet, KatG is the only member of its superfamily with such capability. It does so using two mutually dependent cofactors: a heme and an entirely unique Met-Tyr-Trp (MYW) covalent adduct. Heme is required to generate the MYW cofactor. The MYW cofactor allows KatG to leverage heme intermediates toward a unique mechanism for H2O2 oxidation. This review evaluates the range of intermediates identified and their connection to the diverse catalytic processes KatG facilitates, including mechanisms of isoniazid activation. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Quantification of methanogenic biomass by enzyme-linked immunosorbent assay and by analysis of specific methanogenic cofactors

    Energy Technology Data Exchange (ETDEWEB)

    Gorris, L G.M.; Kemp, H A; Archer, D B

    1987-01-01

    The reliability and accuracy with which enzyme-linked immunosorbent assay (ELISA) and an assay of methanogenic cofactors detect and quantify methanogenic species were investigated. Both assays required standardization with laboratory cultures of methanogenic bacteria and were applied to mixtures of pure cultures and samples from anaerobic digesters. ELISA was shown to be a simple method for detecting and quantifying individual methanogenic species. The range of species which can be assayed is limited by the range of antisera available but, potentially, ELISA can be applied to all methanogens. Although the cofactor assay is not species-specific it can distinguish hydrogenotrophic and acetotrophic methanogens and is quantitative.

  3. Correlation between dental maturity and cervical vertebral maturity.

    Science.gov (United States)

    Chen, Jianwei; Hu, Haikun; Guo, Jing; Liu, Zeping; Liu, Renkai; Li, Fan; Zou, Shujuan

    2010-12-01

    The aim of this study was to investigate the association between dental and skeletal maturity. Digital panoramic radiographs and lateral skull cephalograms of 302 patients (134 boys and 168 girls, ranging from 8 to 16 years of age) were examined. Dental maturity was assessed by calcification stages of the mandibular canines, first and second premolars, and second molars, whereas skeletal maturity was estimated by the cervical vertebral maturation (CVM) stages. The Spearman rank-order correlation coefficient was used to measure the association between CVM stage and dental calcification stage of individual teeth. The mean chronologic age of girls was significantly lower than that of boys in each CVM stage. The Spearman rank-order correlation coefficients between dental maturity and cervical vertebral maturity ranged from 0.391 to 0.582 for girls and from 0.464 to 0.496 for boys (P cervical vertebral maturation stage. The development of the mandibular second molar in females and that of the mandibular canine in males had the strongest correlations with cervical vertebral maturity. Therefore, it is practical to consider the relationship between dental and skeletal maturity when planning orthodontic treatment. Copyright © 2010 Mosby, Inc. All rights reserved.

  4. Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors

    OpenAIRE

    Montgomery, David C.; Sorum, Alexander W.; Guasch, Laura; Nicklaus, Marc C.; Meier, Jordan L.

    2015-01-01

    The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and developing therapeutic strategies to disrupt this process. Here, we describe a chemical approach to define the met...

  5. Dissociation of activated protein C functions by elimination of protein S cofactor enhancement.

    LENUS (Irish Health Repository)

    Harmon, Shona

    2008-11-07

    Activated protein C (APC) plays a critical anticoagulant role in vivo by inactivating procoagulant factor Va and factor VIIIa and thus down-regulating thrombin generation. In addition, APC bound to the endothelial cell protein C receptor can initiate protease-activated receptor-1 (PAR-1)-mediated cytoprotective signaling. Protein S constitutes a critical cofactor for the anticoagulant function of APC but is not known to be involved in regulating APC-mediated protective PAR-1 signaling. In this study we utilized a site-directed mutagenesis strategy to characterize a putative protein S binding region within the APC Gla domain. Three single amino acid substitutions within the APC Gla domain (D35T, D36A, and A39V) were found to mildly impair protein S-dependent anticoagulant activity (<2-fold) but retained entirely normal cytoprotective activity. However, a single amino acid substitution (L38D) ablated the ability of protein S to function as a cofactor for this APC variant. Consequently, in assays of protein S-dependent factor Va proteolysis using purified proteins or in the plasma milieu, APC-L38D variant exhibited minimal residual anticoagulant activity compared with wild type APC. Despite the location of Leu-38 in the Gla domain, APC-L38D interacted normally with endothelial cell protein C receptor and retained its ability to trigger PAR-1 mediated cytoprotective signaling in a manner indistinguishable from that of wild type APC. Consequently, elimination of protein S cofactor enhancement of APC anticoagulant function represents a novel and effective strategy by which to separate the anticoagulant and cytoprotective functions of APC for potential therapeutic gain.

  6. Maturity and maturity models in lean construction

    Directory of Open Access Journals (Sweden)

    Claus Nesensohn

    2014-03-01

    Full Text Available In recent years there has been an increasing interest in maturity models in management-related disciplines; which reflects a growing recognition that becoming more mature and having a model to guide the route to maturity can help organisations in managing major transformational change. Lean Construction (LC is an increasingly important improvement approach that organisations seek to embed. This study explores how to apply the maturity models to LC. Hence the attitudes, opinions and experiences of key industry informants with high levels of knowledge of LC were investigated. To achieve this, a review of maturity models was conducted, and data for the analysis was collected through a sequential process involving three methods. First a group interview with seven key informants. Second a follow up discussion with the same individuals to investigate some of the issues raised in more depth. Third an online discussion held via LinkedIn in which members shared their views on some of the results. Overall, we found that there is a lack of common understanding as to what maturity means in LC, though there is general agreement that the concept of maturity is a suitable one to reflect the path of evolution for LC within organisations.

  7. Panning for SNuRMs: using cofactor profiling for the rational discovery of selective nuclear receptor modulators.

    Science.gov (United States)

    Kremoser, Claus; Albers, Michael; Burris, Thomas P; Deuschle, Ulrich; Koegl, Manfred

    2007-10-01

    Drugs that target nuclear receptors are clinically, as well as commercially, successful. Their widespread use, however, is limited by an inherent propensity of nuclear receptors to trigger beneficial, as well as adverse, pharmacological effects upon drug activation. Hence, selective drugs that display reduced adverse effects, such as the selective estrogen receptor modulator (SERM) Raloxifene, have been developed by guidance through classical cell culture assays and animal trials. Full agonist and selective modulator nuclear receptor drugs, in general, differ by their ability to recruit certain cofactors to the receptor protein. Hence, systematic cofactor profiling is advancing into an approach for the rationally guided identification of selective NR modulators (SNuRMs) with improved therapeutic ratio.

  8. Solution Structure of LXXLL-related Cofactor Peptide of Orphan Nuclear Receptor FTZ-F1

    International Nuclear Information System (INIS)

    Yun, Ji Hye; Lee, Chul Jin; Jung, Jin Won; Lee, Weon Tae

    2012-01-01

    Functional interaction between Drosophila orphan receptor FTZ-F1 (NR5A3) and a segmentation gene product fushi tarazu (FTZ) is crucial for regulating genes related to define the identities of alternate segmental regions in the Drosophila embryo. FTZ binding to the ligand-binding domain (LBD) of FTZ-F1 is of essence in activating its transcription process. We determined solution structures of the cofactor peptide (FTZ PEP ) derived from FTZ by NMR spectroscopy. The cofactor peptide showed a nascent helical conformation in aqueous solution, however, the helicity was increased in the presence of TFE. Furthermore, FTZ PEP formed α- helical conformation upon FTZ-F1 binding, which provides a receptor bound structure of FTZ PEP . The solution structure of FTZ PEP in the presence of FTZ-F1 displays a long stretch of the α-helix with a bend in the middle of helix

  9. Solution Structure of LXXLL-related Cofactor Peptide of Orphan Nuclear Receptor FTZ-F1

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Ji Hye; Lee, Chul Jin; Jung, Jin Won; Lee, Weon Tae [Yonsei University, Seoul (Korea, Republic of)

    2012-02-15

    Functional interaction between Drosophila orphan receptor FTZ-F1 (NR5A3) and a segmentation gene product fushi tarazu (FTZ) is crucial for regulating genes related to define the identities of alternate segmental regions in the Drosophila embryo. FTZ binding to the ligand-binding domain (LBD) of FTZ-F1 is of essence in activating its transcription process. We determined solution structures of the cofactor peptide (FTZ{sup PEP}) derived from FTZ by NMR spectroscopy. The cofactor peptide showed a nascent helical conformation in aqueous solution, however, the helicity was increased in the presence of TFE. Furthermore, FTZ{sup PEP} formed α- helical conformation upon FTZ-F1 binding, which provides a receptor bound structure of FTZ{sup PEP}. The solution structure of FTZ{sup PEP} in the presence of FTZ-F1 displays a long stretch of the α-helix with a bend in the middle of helix.

  10. DNAJC21 Mutations Link a Cancer-Prone Bone Marrow Failure Syndrome to Corruption in 60S Ribosome Subunit Maturation.

    Science.gov (United States)

    Tummala, Hemanth; Walne, Amanda J; Williams, Mike; Bockett, Nicholas; Collopy, Laura; Cardoso, Shirleny; Ellison, Alicia; Wynn, Rob; Leblanc, Thierry; Fitzgibbon, Jude; Kelsell, David P; van Heel, David A; Payne, Elspeth; Plagnol, Vincent; Dokal, Inderjeet; Vulliamy, Tom

    2016-07-07

    A substantial number of individuals with bone marrow failure (BMF) present with one or more extra-hematopoietic abnormality. This suggests a constitutional or inherited basis, and yet many of them do not fit the diagnostic criteria of the known BMF syndromes. Through exome sequencing, we have now identified a subgroup of these individuals, defined by germline biallelic mutations in DNAJC21 (DNAJ homolog subfamily C member 21). They present with global BMF, and one individual developed a hematological cancer (acute myeloid leukemia) in childhood. We show that the encoded protein associates with rRNA and plays a highly conserved role in the maturation of the 60S ribosomal subunit. Lymphoblastoid cells obtained from an affected individual exhibit increased sensitivity to the transcriptional inhibitor actinomycin D and reduced amounts of rRNA. Characterization of mutations revealed impairment in interactions with cofactors (PA2G4, HSPA8, and ZNF622) involved in 60S maturation. DNAJC21 deficiency resulted in cytoplasmic accumulation of the 60S nuclear export factor PA2G4, aberrant ribosome profiles, and increased cell death. Collectively, these findings demonstrate that mutations in DNAJC21 cause a cancer-prone BMF syndrome due to corruption of early nuclear rRNA biogenesis and late cytoplasmic maturation of the 60S subunit. Copyright © 2016. Published by Elsevier Inc.

  11. Streptococcus sanguinis class Ib ribonucleotide reductase: high activity with both iron and manganese cofactors and structural insights.

    Science.gov (United States)

    Makhlynets, Olga; Boal, Amie K; Rhodes, Delacy V; Kitten, Todd; Rosenzweig, Amy C; Stubbe, JoAnne

    2014-02-28

    Streptococcus sanguinis is a causative agent of infective endocarditis. Deletion of SsaB, a manganese transporter, drastically reduces S. sanguinis virulence. Many pathogenic organisms require class Ib ribonucleotide reductase (RNR) to catalyze the conversion of nucleotides to deoxynucleotides under aerobic conditions, and recent studies demonstrate that this enzyme uses a dimanganese-tyrosyl radical (Mn(III)2-Y(•)) cofactor in vivo. The proteins required for S. sanguinis ribonucleotide reduction (NrdE and NrdF, α and β subunits of RNR; NrdH and TrxR, a glutaredoxin-like thioredoxin and a thioredoxin reductase; and NrdI, a flavodoxin essential for assembly of the RNR metallo-cofactor) have been identified and characterized. Apo-NrdF with Fe(II) and O2 can self-assemble a diferric-tyrosyl radical (Fe(III)2-Y(•)) cofactor (1.2 Y(•)/β2) and with the help of NrdI can assemble a Mn(III)2-Y(•) cofactor (0.9 Y(•)/β2). The activity of RNR with its endogenous reductants, NrdH and TrxR, is 5,000 and 1,500 units/mg for the Mn- and Fe-NrdFs (Fe-loaded NrdF), respectively. X-ray structures of S. sanguinis NrdIox and Mn(II)2-NrdF are reported and provide a possible rationale for the weak affinity (2.9 μM) between them. These streptococcal proteins form a structurally distinct subclass relative to other Ib proteins with unique features likely important in cluster assembly, including a long and negatively charged loop near the NrdI flavin and a bulky residue (Thr) at a constriction in the oxidant channel to the NrdI interface. These studies set the stage for identifying the active form of S. sanguinis class Ib RNR in an animal model for infective endocarditis and establishing whether the manganese requirement for pathogenesis is associated with RNR.

  12. O-, N-Atoms-Coordinated Mn Cofactors within a Graphene Framework as Bioinspired Oxygen Reduction Reaction Electrocatalysts.

    Science.gov (United States)

    Yang, Yang; Mao, Kaitian; Gao, Shiqi; Huang, Hao; Xia, Guoliang; Lin, Zhiyu; Jiang, Peng; Wang, Changlai; Wang, Hui; Chen, Qianwang

    2018-05-28

    Manganese (Mn) is generally regarded as not being sufficiently active for the oxygen reduction reaction (ORR) compared to other transition metals such as Fe and Co. However, in biology, manganese-containing enzymes can catalyze oxygen-evolving reactions efficiently with a relative low onset potential. Here, atomically dispersed O and N atoms coordinated Mn active sites are incorporated within graphene frameworks to emulate both the structure and function of Mn cofactors in heme-copper oxidases superfamily. Unlike previous single-metal catalysts with general M-N-C structures, here, it is proved that a coordinated O atom can also play a significant role in tuning the intrinsic catalytic activities of transition metals. The biomimetic electrocatalyst exhibits superior performance for the ORR and zinc-air batteries under alkaline conditions, which is even better than that of commercial Pt/C. The excellent performance can be ascribed to the abundant atomically dispersed Mn cofactors in the graphene frameworks, confirmed by various characterization methods. Theoretical calculations reveal that the intrinsic catalytic activity of metal Mn can be significantly improved via changing local geometry of nearest coordinated O and N atoms. Especially, graphene frameworks containing the Mn-N 3 O 1 cofactor demonstrate the fastest ORR kinetics due to the tuning of the d electronic states to a reasonable state. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Molybdenum cofactor deficiency: Identification of a patient with homozygote mutation in the MOCS3 gene

    NARCIS (Netherlands)

    Huijmans, Jan G. M.; Schot, Rachel; de Klerk, Johannis B. C.; Williams, Monique; de Coo, René F. M.; Duran, Marinus; Verheijen, Frans W.; van Slegtenhorst, Marjon; Mancini, Grazia M. S.

    2017-01-01

    We describe the clinical presentation and 17 years follow up of a boy, born to consanguineous parents and presenting with intellectual disability (ID), autism, "marfanoid" dysmorphic features, and moderate abnormalities of sulfite metabolism compatible with molybdenum cofactor deficiency, but normal

  14. Live Cell Discovery of Microbial Vitamin Transport and Enzyme-Cofactor Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Lindsey N.; Koech, Phillip K.; Plymale, Andrew E.; Landorf, Elizabeth V.; Konopka, Allan; Collart, Frank; Lipton, Mary S.; Romine, Margaret F.; Wright, Aaron T.

    2016-02-02

    The rapid completion of microbial genomes is inducing a conundrum in functional gene discovery. Novel methods are critically needed to shorten the gap between characterizing a microbial genome and experimentally validating bioinformatically-predicted functions. Of particular importance are transport mechanisms, used to shuttle nutrients and metabolites across cell mem-branes, such as B vitamins, which are indispensable to metabolic reactions crucial to the survival of diverse microbes ranging from members of environmental microbial communities to human pathogens. Methods to accurately assign function and specificity for a wide range of experimentally unidentified and/or predicted membrane-embedded transport proteins, and characterization of intra-cellular enzyme-cofactor/nutrient associations are needed to enable a significantly improved understanding of microbial biochemis-try and physiology, how microbes associate with others, and how they sense and respond to environmental perturbations. Chemical probes derived from B vitamins B1, B2, and B7 have allowed us to experimentally address the aforementioned needs by identifying B vitamin transporters and intracellular protein-cofactor associations through live cell labeling of the filamentous anoxygenic pho-toheterotroph, Chloroflexus aurantiacus J-10-fl, known for both B vitamin biosynthesis and environmental salvage. Our probes provide a unique opportunity to directly link cellular activity and protein function back to ecosystem and/or host dynamics by iden-tifying B vitamin transport and disposition mechanisms required for survival.

  15. Structural evidence for the partially oxidized dipyrromethene and dipyrromethanone forms of the cofactor of porphobilinogen deaminase: structures of the Bacillus megaterium enzyme at near-atomic resolution

    International Nuclear Information System (INIS)

    Azim, N.; Deery, E.; Warren, M. J.; Wolfenden, B. A. A.; Erskine, P.; Cooper, J. B.; Coker, A.; Wood, S. P.; Akhtar, M.

    2014-01-01

    The enzyme porphobilinogen deaminase (PBGD; hydroxymethylbilane synthase; EC 2.5.1.61) catalyses a key early step in the biosynthesis of tetrapyrroles in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole. Two near-atomic resolution structures of PBGD from B. megaterium are reported that demonstrate the time-dependent accumulation of partially oxidized forms of the cofactor, including one that possesses a tetrahedral C atom in the terminal pyrrole ring. The enzyme porphobilinogen deaminase (PBGD; hydroxymethylbilane synthase; EC 2.5.1.61) catalyses an early step of the tetrapyrrole-biosynthesis pathway in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole. The enzyme possesses a dipyrromethane cofactor, which is covalently linked by a thioether bridge to an invariant cysteine residue (Cys241 in the Bacillus megaterium enzyme). The cofactor is extended during the reaction by the sequential addition of the four substrate molecules, which are released as a linear tetrapyrrole product. Expression in Escherichia coli of a His-tagged form of B. megaterium PBGD has permitted the X-ray analysis of the enzyme from this species at high resolution, showing that the cofactor becomes progressively oxidized to the dipyrromethene and dipyrromethanone forms. In previously solved PBGD structures, the oxidized cofactor is in the dipyromethenone form, in which both pyrrole rings are approximately coplanar. In contrast, the oxidized cofactor in the B. megaterium enzyme appears to be in the dipyrromethanone form, in which the C atom at the bridging α-position of the outer pyrrole ring is very clearly in a tetrahedral configuration. It is suggested that the pink colour of the freshly purified protein is owing to the presence of the dipyrromethene form of the cofactor which, in the structure reported here, adopts the same conformation as the fully reduced dipyrromethane form

  16. Absorption and emission spectroscopic characterization of BLUF protein Slr1694 from Synechocystis sp. PCC6803 with roseoflavin cofactor.

    Science.gov (United States)

    Zirak, P; Penzkofer, A; Mathes, T; Hegemann, P

    2009-11-09

    The wild-type BLUF protein Slr1694 from Synechocystis sp. PCC6803 (BLUF=blue-light sensor using FAD) has flavin adenosine dinucleotide (FAD) as natural cofactor. This light sensor causes positive phototaxis of the marine cyanobacterium. In this study the FAD cofactor of the wild-type Slr1694 was replaced by roseoflavin (RoF) and the roseoflavin derivatives RoFMN and RoFAD during heterologous expression in a riboflavin auxotrophic E. coli strain. An absorption and emission spectroscopic characterization of the cofactor-exchanged-Slr1694 (RoSlr) was carried out both under dark conditions and under illuminated conditions. The behaviour of RoF embedded in RoSlr in aqueous solution at pH 8 is compared with the behaviour of RoF in aqueous solution. The fluorescence of RoF and RoSlr is quenched by photo-induced twisted intra-molecular charge transfer at room temperature with stronger effect for RoF. The fluorescence quenching is diminished at liquid nitrogen temperature. Light exposure of RoSlr causes irreversible conversion of the protein embedded roseoflavins to 8-methylamino-flavins, 8-dimethylamino-lumichrome and 8-methylamino-lumichrome.

  17. Reorientational properties of fluorescent analogues of the protein kinase C cofactors diacylglycerol and phorbol ester.

    NARCIS (Netherlands)

    Pap, E.H.W.; Ketelaars, M.; Borst, J.W.; Hoek, van A.; Visser, A.J.W.G.

    1996-01-01

    The reorientational properties of the fluorescently labelled protein kinase C (PKC) cofactors diacylglycerol (DG) and phorbol ester (PMA) in vesicles and mixed micelles have been investigated using time-resolved polarised fluorescence. The sn-2 acyl chain of DG was replaced by diphenylhexatriene-

  18. Crystal Structure of the Thermus thermophilus 16 S rRNA Methyltransferase RsmC in Complex with Cofactor and Substrate Guanosine

    Energy Technology Data Exchange (ETDEWEB)

    Demirci, H.; Gregory, S; Dahlberg, A; Jogl, G

    2008-01-01

    Post-transcriptional modification is a ubiquitous feature of ribosomal RNA in all kingdoms of life. Modified nucleotides are generally clustered in functionally important regions of the ribosome, but the functional contribution to protein synthesis is not well understood. Here we describe high resolution crystal structures for the N{sup 2}-guanine methyltransferase RsmC that modifies residue G1207 in 16 S rRNA near the decoding site of the 30 S ribosomal subunit. RsmC is a class I S-adenosyl-l-methionine-dependent methyltransferase composed of two methyltransferase domains. However, only one S-adenosyl-l-methionine molecule and one substrate molecule, guanosine, bind in the ternary complex. The N-terminal domain does not bind any cofactor. Two structures with bound S-adenosyl-l-methionine and S-adenosyl-l-homocysteine confirm that the cofactor binding mode is highly similar to other class I methyltransferases. Secondary structure elements of the N-terminal domain contribute to cofactor-binding interactions and restrict access to the cofactor-binding site. The orientation of guanosine in the active site reveals that G1207 has to disengage from its Watson-Crick base pairing interaction with C1051 in the 16 S rRNA and flip out into the active site prior to its modification. Inspection of the 30 S crystal structure indicates that access to G1207 by RsmC is incompatible with the native subunit structure, consistent with previous suggestions that this enzyme recognizes a subunit assembly intermediate.

  19. Cervical carcinogenesis: the role of co-factors and generation of reactive oxygen species Carcinogénesis cervical: co-factores y antioxidantes

    Directory of Open Access Journals (Sweden)

    Anna Giuliano

    2003-01-01

    Full Text Available Several HPV co-factors have been proposed, some more or less consistently associated with cervical dysplasia and cancer risk. More research, using prospective cohort designs, is needed to further describe where in carcinogenesis these factors are working and to assess the biological mechanism of these factors. In addition, further research is needed to define the role of various hormonal contraceptive formulations in promoting cervical carcinogenesis. While many interesting scientific questions remain to be answered, results from the numerous epidemiological studies conducted to date indicate that cervical dysplasia and cancer may be reduced if the oxidant antioxidant ratio is shifted to more of and antioxidant profile. In addition to cervical cancer screening, a reduction in cervical cancer incidence may be accomplished by reducing tobacco use, increasing nutritional status, and utilizing barrier contraception to prevent infection with other sexually acquired infections.Diversos co-factores de riesgo han sido asociados consistentemente con displasia cervical y cáncer invasor. Es necesario un mayor número de investigaciones que utilicen diseños de cohorte prospectivos para describir el proceso de carcinogénesis y el mecanismo biológico de cada uno de estos factores. Adicionalmente, futuras investigaciones serán necesarias para definir el papel de los anticonceptivos hormonales en la promoción de la carcinogénesis cervical. Mientras que muchas preguntas científicas interesantes permanecen sin ser respondidas, resultados de numerosos estudios epidemiológicos que se desarrollan actualmente, indican que la displasia cervical y cáncer podrán ser reducidos si la tasa de oxidantes-antioxidantes es cambiada a más de un perfil antioxidante. Además de la detección oportuna de cáncer cervical, puede lograrse una reducción de la incidencia de esta enfermedad disminuyendo el consumo de tabaco, incrementando el estatus nutricional, y

  20. Maturity group classification and maturity locus genotyping of early-maturing soybean varieties from high-latitude cold regions.

    Science.gov (United States)

    Jia, Hongchang; Jiang, Bingjun; Wu, Cunxiang; Lu, Wencheng; Hou, Wensheng; Sun, Shi; Yan, Hongrui; Han, Tianfu

    2014-01-01

    With the migration of human beings, advances of agricultural sciences, evolution of planting patterns and global warming, soybeans have expanded to both tropical and high-latitude cold regions (HCRs). Unlike other regions, HCRs have much more significant and diverse photoperiods and temperature conditions over seasons or across latitudes, and HCR soybeans released there show rich diversity in maturity traits. However, HCR soybeans have not been as well classified into maturity groups (MGs) as other places. Therefore, it is necessary to identify MGs in HCRs and to genotype the maturity loci. Local varieties were collected from the northern part of Northeast China and the far-eastern region of Russia. Maturity group reference (MGR) soybeans of MGs MG000, MG00, and MG0 were used as references during field experiments. Both local varieties and MGR soybeans were planted for two years (2010-2011) in Heihe (N 50°15', E 127°27', H 168.5 m), China. The days to VE (emergence), R1 (beginning bloom) and R7 (beginning maturity) were recorded and statistically analyzed. Furthermore, some varieties were further genotyped at four molecularly-identified maturity loci E1, E2, E3 and E4. The HCR varieties were classified into MG0 or even more early-maturing. In Heihe, some varieties matured much earlier than MG000, which is the most early-maturing known MG, and clustered into a separate group. We designated the group as MG0000, following the convention of MGs. HCR soybeans had relatively stable days to beginning bloom from emergence. The HCR varieties diversified into genotypes of E1, E2, E3 and E4. These loci had different effects on maturity. HCRs diversify early-maturing MGs of soybean. MG0000, a new MG that matures much earlier than known MGs, was developed. HCR soybean breeding should focus more on shortening post-flowering reproductive growth. E1, E2, E3, and E4 function differentially.

  1. Kinetics based reaction optimization of enzyme catalysed reduction of formaldehyde to methanol with synchronous cofactor regeneration

    DEFF Research Database (Denmark)

    Marpani, Fauziah Binti; Sárossy, Zsuzsa; Pinelo, Manuel

    2017-01-01

    regeneration of the reducing equivalents during reaction is required. Herein, we report the optimization of the enzymatic conversion of formaldehyde (CHOH) to CH3 OH by alcohol dehydrogenase, the final step of the enzymatic redox reaction of CO2 to CH3 OH, with kinetically synchronous enzymatic cofactor...... regeneration using either glucose dehydrogenase (System I) or xylose dehydrogenase (System II). A mathematical model of the enzyme kinetics was employed to identify the best reaction set-up for attaining optimal cofactor recycling rate and enzyme utilization efficiency. Targeted process optimization...... experiments were conducted to verify the kinetically modelled results. Repetitive reaction cycles were shown to enhance the yield of CH3 OH, increase the total turnover number (TTN) and the biocatalytic productivity rate (BPR) value for both system I and II whilst minimizing the exposure of the enzymes...

  2. A toxic imbalance of Hsp70s in Saccharomyces cerevisiae is caused by competition for cofactors.

    Science.gov (United States)

    Keefer, Kathryn M; True, Heather L

    2017-09-01

    Molecular chaperones are responsible for managing protein folding from translation through degradation. These crucial machines ensure that protein homeostasis is optimally maintained for cell health. However, 'too much of a good thing' can be deadly, and the excess of chaperones can be toxic under certain cellular conditions. For example, overexpression of Ssa1, a yeast Hsp70, is toxic to cells in folding-challenged states such as [PSI+]. We discovered that overexpression of the nucleotide exchange factor Sse1 can partially alleviate this toxicity. We further argue that the basis of the toxicity is related to the availability of Hsp70 cofactors, such as Hsp40 J-proteins and nucleotide exchange factors. Ultimately, our work informs future studies about functional chaperone balance and cautions against therapeutic chaperone modifications without a thorough examination of cofactor relationships. © 2017 John Wiley & Sons Ltd.

  3. Improving metabolic efficiency of the reverse beta-oxidation cycle by balancing redox cofactor requirement.

    Science.gov (United States)

    Wu, Junjun; Zhang, Xia; Zhou, Peng; Huang, Jiaying; Xia, Xiudong; Li, Wei; Zhou, Ziyu; Chen, Yue; Liu, Yinghao; Dong, Mingsheng

    2017-11-01

    Previous studies have made many exciting achievements on pushing the functional reversal of beta-oxidation cycle (r-BOX) to more widespread adoption for synthesis of a wide variety of fuels and chemicals. However, the redox cofactor requirement for the efficient operation of r-BOX remains unclear. In this work, the metabolic efficiency of r-BOX for medium-chain fatty acid (C 6 -C 10 , MCFA) production was optimized by redox cofactor engineering. Stoichiometric analysis of the r-BOX pathway and further experimental examination identified NADH as a crucial determinant of r-BOX process yield. Furthermore, the introduction of formate dehydrogenase from Candida boidinii using fermentative inhibitor byproduct formate as a redox NADH sink improved MCFA titer from initial 1.2g/L to 3.1g/L. Moreover, coupling of increasing the supply of acetyl-CoA with NADH to achieve fermentative redox balance enabled product synthesis at maximum titers. To this end, the acetate re-assimilation pathway was further optimized to increase acetyl-CoA availability associated with the new supply of NADH. It was found that the acetyl-CoA synthetase activity and intracellular ATP levels constrained the activity of acetate re-assimilation pathway, and 4.7g/L of MCFA titer was finally achieved after alleviating these two limiting factors. To the best of our knowledge, this represented the highest titer reported to date. These results demonstrated that the key constraint of r-BOX was redox imbalance and redox engineering could further unleash the lipogenic potential of this cycle. The redox engineering strategies could be applied to acetyl-CoA-derived products or other bio-products requiring multiple redox cofactors for biosynthesis. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  4. Structural insights into the cofactor-assisted substrate recognition of yeast methylglyoxal/isovaleraldehyde reductase Gre2.

    Science.gov (United States)

    Guo, Peng-Chao; Bao, Zhang-Zhi; Ma, Xiao-Xiao; Xia, Qingyou; Li, Wei-Fang

    2014-09-01

    Saccharomyces cerevisiae Gre2 (EC1.1.1.283) serves as a versatile enzyme that catalyzes the stereoselective reduction of a broad range of substrates including aliphatic and aromatic ketones, diketones, as well as aldehydes, using NADPH as the cofactor. Here we present the crystal structures of Gre2 from S. cerevisiae in an apo-form at 2.00Å and NADPH-complexed form at 2.40Å resolution. Gre2 forms a homodimer, each subunit of which contains an N-terminal Rossmann-fold domain and a variable C-terminal domain, which participates in substrate recognition. The induced fit upon binding to the cofactor NADPH makes the two domains shift toward each other, producing an interdomain cleft that better fits the substrate. Computational simulation combined with site-directed mutagenesis and enzymatic activity analysis enabled us to define a potential substrate-binding pocket that determines the stringent substrate stereoselectivity for catalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Human HOX Proteins Use Diverse and Context-Dependent Motifs to Interact with TALE Class Cofactors.

    Science.gov (United States)

    Dard, Amélie; Reboulet, Jonathan; Jia, Yunlong; Bleicher, Françoise; Duffraisse, Marilyne; Vanaker, Jean-Marc; Forcet, Christelle; Merabet, Samir

    2018-03-13

    HOX proteins achieve numerous functions by interacting with the TALE class PBX and MEIS cofactors. In contrast to this established partnership in development and disease, how HOX proteins could interact with PBX and MEIS remains unclear. Here, we present a systematic analysis of HOX/PBX/MEIS interaction properties, scanning all paralog groups with human and mouse HOX proteins in vitro and in live cells. We demonstrate that a previously characterized HOX protein motif known to be critical for HOX-PBX interactions becomes dispensable in the presence of MEIS in all except the two most anterior paralog groups. We further identify paralog-specific TALE-binding sites that are used in a highly context-dependent manner. One of these binding sites is involved in the proliferative activity of HOXA7 in breast cancer cells. Together these findings reveal an extraordinary level of interaction flexibility between HOX proteins and their major class of developmental cofactors. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Sequencing and functional analysis of the nifENXorf1orf2 gene cluster of Herbaspirillum seropedicae.

    Science.gov (United States)

    Klassen, G; Pedrosa, F O; Souza, E M; Yates, M G; Rigo, L U

    1999-12-01

    A 5.1-kb DNA fragment from the nifHDK region of H. seropedicae was isolated and sequenced. Sequence analysis showed the presence of nifENXorf1orf2 but nifTY were not present. No nif or consensus promoter was identified. Furthermore, orf1 expression occurred only under nitrogen-fixing conditions and no promoter activity was detected between nifK and nifE, suggesting that these genes are expressed from the upstream nifH promoter and are parts of a unique nif operon. Mutagenesis studies indicate that nifN was essential for nitrogenase activity whereas nifXorf1orf2 were not. High homology between the C-terminal region of the NifX and NifB proteins from H. seropedicae was observed. Since the NifX and NifY proteins are important for FeMo cofactor (FeMoco) synthesis, we propose that alternative proteins with similar activities exist in H. seropedicae.

  7. Oxidation of the FAD cofactor to the 8-formyl-derivative in human electron-transferring flavoprotein

    Science.gov (United States)

    Augustin, Peter; Toplak, Marina; Fuchs, Katharina; Gerstmann, Eva Christine; Prassl, Ruth; Winkler, Andreas; Macheroux, Peter

    2018-01-01

    The heterodimeric human (h) electron-transferring flavoprotein (ETF) transfers electrons from at least 13 different flavin dehydrogenases to the mitochondrial respiratory chain through a non-covalently bound FAD cofactor. Here, we describe the discovery of an irreversible and pH-dependent oxidation of the 8α-methyl group to 8-formyl-FAD (8f-FAD), which represents a unique chemical modification of a flavin cofactor in the human flavoproteome. Furthermore, a set of hETF variants revealed that several conserved amino acid residues in the FAD-binding pocket of electron-transferring flavoproteins are required for the conversion to the formyl group. Two of the variants generated in our study, namely αR249C and αT266M, cause glutaric aciduria type II, a severe inherited disease. Both of the variants showed impaired formation of 8f-FAD shedding new light on the potential molecular cause of disease development. Interestingly, the conversion of FAD to 8f-FAD yields a very stable flavin semiquinone that exhibited slightly lower rates of electron transfer in an artificial assay system than hETF containing FAD. In contrast, the formation of 8f-FAD enhanced the affinity to human dimethylglycine dehydrogenase 5-fold, indicating that formation of 8f-FAD modulates the interaction of hETF with client enzymes in the mitochondrial matrix. Thus, we hypothesize that the FAD cofactor bound to hETF is subject to oxidation in the alkaline (pH 8) environment of the mitochondrial matrix, which may modulate electron transport between client dehydrogenases and the respiratory chain. This discovery challenges the current concepts of electron transfer processes in mitochondria. PMID:29301933

  8. Pharmacoepidemiological assessment of adherence and influencing co-factors among primary open-angle glaucoma patients-An observational cohort study.

    Directory of Open Access Journals (Sweden)

    Stefanie Frech

    Full Text Available The goal of this study was to assess the adherence of primary open-angle glaucoma (POAG patients to medication, and to determine co-factors influencing adherence, using a representative sample of members of the largest German public health insurer. The observational cohort study was based on a longitudinal data set from 2010-2013 and included 250,000 insured persons aged 50 and older with 10,120 diagnosed POAG patients. Uni- and multivariate analysis was performed to investigate several aspects of glaucoma, such as prevalence, adherence, and co-factors influencing adherence. The main outcome measured adherence with prescriptions filled within a year. Multivariate panel regression analysis was used to determine the co-factors influencing this adherence. Prevalence of POAG was 3.36% [CI: 3.28-3.43%], with 2.91% [CI: 2.81-3.01%] for males and 3.71% [CI: 3.61-3.81%] for females, increasing with age. The mean level of adherence in terms of prescriptions filled was 66.5% [CI: 65.50-67.60%]. The results of this analysis revealed a significant influence of age, duration of the disease, care need, distance to death, and multimorbidity as co-factors of non-adherence, whereas gender had no influence. The analysis provided detailed information about POAG health care aspects concerning prevalence and adherence. The most endangered risk groups for non-adherence were patients aged 50-59, patients older than 80 years, patients with a longer duration of POAG, patients with care needs, and patients with three or more severe diseases in addition to glaucoma. To know the predictors responsible for an increased risk to develop POAG is of importance for all persons involved in health care management. Therefore effective strategies to increase awareness of patients and medical care personnel about non-adherence and the importance of a regular and continuous medication to avoid further nerve fiber damage and possible blindness have to be developed.

  9. Switching an O2 sensitive glucose oxidase bioelectrode into an almost insensitive one by cofactor redesign.

    Science.gov (United States)

    Tremey, Emilie; Suraniti, Emmanuel; Courjean, Olivier; Gounel, Sébastien; Stines-Chaumeil, Claire; Louerat, Frédéric; Mano, Nicolas

    2014-06-04

    In the 5-8 mM glucose concentration range, of particular interest for diabetes management, glucose oxidase bioelectrodes are O2 dependent, which decrease their efficiencies. By replacing the natural cofactor of glucose oxidase, we succeeded in turning an O2 sensitive bioelectrode into an almost insensitive one.

  10. How Diverse are the Protein-Bound Conformations of Small-Molecule Drugs and Cofactors?

    Science.gov (United States)

    Friedrich, Nils-Ole; Simsir, Méliné; Kirchmair, Johannes

    2018-03-01

    Knowledge of the bioactive conformations of small molecules or the ability to predict them with theoretical methods is of key importance to the design of bioactive compounds such as drugs, agrochemicals and cosmetics. Using an elaborate cheminformatics pipeline, which also evaluates the support of individual atom coordinates by the measured electron density, we compiled a complete set (“Sperrylite Dataset”) of high-quality structures of protein-bound ligand conformations from the PDB. The Sperrylite Dataset consists of a total of 10,936 high-quality structures of 4548 unique ligands. Based on this dataset, we assessed the variability of the bioactive conformations of 91 small molecules—each represented by a minimum of ten structures—and found it to be largely independent of the number of rotatable bonds. Sixty-nine molecules had at least two distinct conformations (defined by an RMSD greater than 1 Å). For a representative subset of 17 approved drugs and cofactors we observed a clear trend for the formation of few clusters of highly similar conformers. Even for proteins that share a very low sequence identity, ligands were regularly found to adopt similar conformations. For cofactors, a clear trend for extended conformations was measured, although in few cases also coiled conformers were observed. The Sperrylite Dataset is available for download from http://www.zbh.uni-hamburg.de/sperrylite_dataset.

  11. Assessment of cortical maturation with prenatal MRI. Part I: normal cortical maturation

    Energy Technology Data Exchange (ETDEWEB)

    Fogliarini, Celine [Faculte Timone, Centre de Resonance Magnetique Biologique et Medicale, Marseille (France); Chaumoitre, Katia [Hopital Nord, Department of Radiology, Marseille (France); Chapon, Frederique; Levrier, Olivier; Girard, Nadine [Hopital Timone, Department of Neuroradiology, Marseille Cedex 5 (France); Fernandez, Carla; Figarella-Branger, Dominique [Hopital Timone, Department of Pathology, Marseille (France)

    2005-08-01

    Cortical maturation, especially gyral formation, follows a temporospatial schedule and is a good marker of fetal maturation. Although ultrasonography is still the imaging method of choice to evaluate fetal anatomy, MRI has an increasingly important role in the detection of brain abnormalities, especially of cortical development. Knowledge of MRI techniques in utero with the advantages and disadvantages of some sequences is necessary, in order to try to optimize the different magnetic resonance sequences to be able to make an early diagnosis. The different steps of cortical maturation known from histology represent the background necessary for the understanding of maturation in order to be then able to evaluate brain maturation through neuroimaging. Illustrations of the normal cortical maturation are given for each step accessible to MRI for both the cerebral hemispheres and the posterior fossa. (orig.)

  12. Assessment of cortical maturation with prenatal MRI. Part I: normal cortical maturation

    International Nuclear Information System (INIS)

    Fogliarini, Celine; Chaumoitre, Katia; Chapon, Frederique; Levrier, Olivier; Girard, Nadine; Fernandez, Carla; Figarella-Branger, Dominique

    2005-01-01

    Cortical maturation, especially gyral formation, follows a temporospatial schedule and is a good marker of fetal maturation. Although ultrasonography is still the imaging method of choice to evaluate fetal anatomy, MRI has an increasingly important role in the detection of brain abnormalities, especially of cortical development. Knowledge of MRI techniques in utero with the advantages and disadvantages of some sequences is necessary, in order to try to optimize the different magnetic resonance sequences to be able to make an early diagnosis. The different steps of cortical maturation known from histology represent the background necessary for the understanding of maturation in order to be then able to evaluate brain maturation through neuroimaging. Illustrations of the normal cortical maturation are given for each step accessible to MRI for both the cerebral hemispheres and the posterior fossa. (orig.)

  13. ORGANIZATIONAL PROJECT MANAGEMENT MATURITY

    Directory of Open Access Journals (Sweden)

    Yana Derenskaya

    2017-11-01

    Full Text Available The present article is aimed at developing a set of recommendations for achieving a higher level of organizational project maturity at a given enterprise. Methodology. For the purposes of the current research, the available information sources on the components of project management system are analysed; the essence of “organizational maturity” and the existing models of organizational maturity are studied. The method of systemic and structural analysis, as well as the method of logical generalization, are employed in order to study the existing models of organizational maturity, to describe levels of organizational maturity, and finally to develop a set of methodological recommendations for achieving a higher level of organizational project maturity at a given enterprise. The results of the research showed that the core elements of project management system are methodological, organizational, programtechnical, and motivational components. Project management encompasses a wide range of issues connected with organizational structure, project team, communication management, project participants, etc. However, the fundamental basis for developing project management concept within a given enterprise starts with defining its level of organizational maturity. The present paper describes various models of organizational maturity (staged, continuous, petal-shaped and their common types (H. Кеrzner Organizational Maturity Model, Berkeley PM Maturity Model, Organizational Project Management Maturity Model, Portfolio, Program & Project Management Maturity Model. The analysis of available theoretic works showed that the notion “organizational project maturity” refers to the capability of an enterprise to select projects and manage them with the intention of achieving its strategic goals in the most effective way. Importantly, the level of maturity can be improved by means of formalizing the acquired knowledge, regulating project-related activities

  14. Purification, crystallization and preliminary crystallographic analysis of a multiple cofactor-dependent DNA ligase from Sulfophobococcus zilligii

    International Nuclear Information System (INIS)

    Supangat, Supangat; An, Young Jun; Sun, Younguk; Kwon, Suk-Tae; Cha, Sun-Shin

    2010-01-01

    A recombinant multiple cofactor-dependent DNA ligase from S. zilligii has been purified and crystallized. X-ray diffraction data were collected to 2.9 Å resolution and the crystals belonged to space group P1. A recombinant DNA ligase from Sulfophobococcus zilligii that shows multiple cofactor specificity (ATP, ADP and GTP) was expressed in Escherichia coli and purified under reducing conditions. Crystals were obtained by the microbatch crystallization method at 295 K in a drop containing 1 µl protein solution (10 mg ml −1 ) and an equal volume of mother liquor [0.1 M HEPES pH 7.5, 10%(w/v) polyethylene glycol 10 000]. A data set was collected to 2.9 Å resolution using synchrotron radiation. The crystals belonged to space group P1, with unit-cell parameters a = 63.7, b = 77.1, c = 77.8 Å, α = 83.4, β = 82.4, γ = 74.6°. Assuming the presence of two molecules in the unit cell, the solvent content was estimated to be about 53.4%

  15. Assessing healthcare process maturity: challenges of using a business process maturity model

    NARCIS (Netherlands)

    Tarhan, A.; Turetken, O.; van den Biggelaar, F.J.H.M.

    2015-01-01

    Doi: 10.4108/icst.pervasivehealth.2015.259105 The quality of healthcare services is influenced by the maturity of healthcare processes used to develop it. A maturity model is an instrument to assess and continually improve organizational processes. In the last decade, a number of maturity models

  16. Diagnostic assessment of skeletal maturity through dental maturation in Hispanic growing individuals

    Directory of Open Access Journals (Sweden)

    Alejandra Cisternas

    2017-01-01

    Full Text Available Background: The aim of this study was to explore dental maturation as a diagnostic test for skeletal maturation. Materials and Methods: Six hundred and fifty-seven growing individuals were classified according to their cervical vertebral maturity and dental maturity, both determined in lateral cephalograms and panoramic radiographs, respectively. The correlation between cervical and dental stages was established for each gender. A receiver operating characteristic curve analysis was made, and sensitivity and specificity values were established. Results: Correlation was found between cervical and dental maturation for females (r = 0.73; P<0.001 and males (r = 0.60; P<0.001. Sensitivity for dental Stage F, as an indicator of a postmaturation peak stage, was 87.21% for females and 97.1% for males, whereas specificity for the same stage was 82.92% and 72.3% for females and males, respectively. Conclusions: Dental maturation evaluation could contribute determining whether a patient is in a pre- or post-growth spurt stage.

  17. Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia.

    Science.gov (United States)

    Malm, Sven; Jusko, Monika; Eick, Sigrun; Potempa, Jan; Riesbeck, Kristian; Blom, Anna M

    2012-01-01

    Infection with the Gram-negative pathogen Prevotella intermedia gives rise to periodontitis and a growing number of studies implies an association of P. intermedia with rheumatoid arthritis. The serine protease Factor I (FI) is the central inhibitor of complement degrading complement components C3b and C4b in the presence of cofactors such as C4b-binding protein (C4BP) and Factor H (FH). Yet, the significance of complement inhibitor acquisition in P. intermedia infection and FI binding by Gram-negative pathogens has not been addressed. Here we show that P. intermedia isolates bound purified FI as well as FI directly from heat-inactivated human serum. FI bound to bacteria retained its serine protease activity as shown in degradation experiments with (125)I-labeled C4b. Since FI requires cofactors for its activity we also investigated the binding of purified cofactors C4BP and FH and found acquisition of both proteins, which retained their activity in FI mediated degradation of C3b and C4b. We propose that FI binding by P. intermedia represents a new mechanism contributing to complement evasion by a Gram-negative bacterial pathogen associated with chronic diseases.

  18. Correlation between Dental Maturity by Demirjian Method and Skeletal Maturity by Cervical Vertebral Maturity Method using Panoramic Radiograph and Lateral Cephalogram

    Directory of Open Access Journals (Sweden)

    Madhusudhanan Mallika Mini

    2017-01-01

    Full Text Available Introduction: Radiographs are effective tools in assessing the stages of bone maturation in dentistry. The cervical vertebral maturation method is a proven effective tool in assessing the adolescent growth spurt than hand-wrist radiographs in an individual. Assessment of dental calcification stages are a reliable method for determining dental maturity. Panoramic imaging can be used as the primary imaging modality for assessing maturity if a correlation can be found out between tooth calcification stages and cervical vertebral maturation stages. This study was conducted to determine the correlation between dental maturity stage and cervical vertebral maturity stage and to estimate predictor variables for cervical vertebral maturation stages (CVMS stratified by gender in a tertiary hospital setting. Materials and Methods: A descriptive study was conducted among patients accessing orthodontic care in radiology outpatient clinic, Oral Medicine and Radiology department, Government Dental College Thiruvananthapuram for a period of 15 months. Participants were selected between the ages of 8 and 16 years. Panoramic radiographs and lateral cephalograms were used to determine dental maturity stages using Demirjian method and CVMS using Bacetti and Franchi method, respectively. Results: One hundred patients (males = 46, females = 54 were included in the study; the spearman rank order correlation revealed significant relationship. The correlation ranged from 0.61 to 0.74 for females and 0.48 to 0.51 for males. Second premolar showed highest correlation and canine the lowest for both females and males. Stage G of mandibular second premolar signifies the pubertal growth period in this study population. By ordinal regression model, G stage of second premolar was found to be a significant predictor in males and stage H followed by G and F in females for the age group of 12–14 years. Conclusion: Dental maturation stages were significantly correlated with CVMS

  19. Characterization of water-forming NADH oxidases for co-factor regeneration

    DEFF Research Database (Denmark)

    Rehn, Gustav; Pedersen, Asbjørn Toftgaard; J. Charnock, Simon

    an environmentaland economic perspective [1]. Alcohol dehydrogenases (ADH) offer one such alternative. However, the reaction requires the oxidized nicotinamide co-factor (NAD+) that must be recycled due to its high cost contribution. One regeneration method that offers certain advantages is the oxidation of NADH......Traditional chemical methods for alcohol oxidation are often associated with issues such as high consumption of expensive oxidizing agents, generation of metal waste and the use of environmentally undesirable organic solvents. Developing green, selective catalysts is therefore important from...... using water forming NADH oxidases (NOX-2). The implementation of the ADH/NOX system for alcohol oxidation, however, requires consideration of several different issues. Enzyme activity and stability at relevant pH and temperature conditions, but also the tolerance to the substrates and products present...

  20. Quantum mechanics/molecular mechanics studies on the mechanism of action of cofactor pyridoxal 5'-phosphate in ornithine 4,5-aminomutase.

    Science.gov (United States)

    Pang, Jiayun; Scrutton, Nigel S; Sutcliffe, Michael J

    2014-09-01

    A computational study was performed on the experimentally elusive cyclisation step in the cofactor pyridoxal 5'-phosphate (PLP)-dependent D-ornithine 4,5-aminomutase (OAM)-catalysed reaction. Calculations using both model systems and a combined quantum mechanics/molecular mechanics approach suggest that regulation of the cyclic radical intermediate is achieved through the synergy of the intrinsic catalytic power of cofactor PLP and the active site of the enzyme. The captodative effect of PLP is balanced by an enzyme active site that controls the deprotonation of both the pyridine nitrogen atom (N1) and the Schiff-base nitrogen atom (N2). Furthermore, electrostatic interactions between the terminal carboxylate and amino groups of the substrate and Arg297 and Glu81 impose substantial "strain" energy on the orientation of the cyclic intermediate to control its trajectory. In addition the "strain" energy, which appears to be sensitive to both the number of carbon atoms in the substrate/analogue and the position of the radical intermediates, may play a key role in controlling the transition of the enzyme from the closed to the open state. Our results provide new insights into several aspects of the radical mechanism in aminomutase catalysis and broaden our understanding of cofactor PLP-dependent reactions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Assessment of the optimum degree of Sr{sub 3}Fe{sub 2}MoO{sub 9} electron-doping through oxygen removal: An X-ray powder diffraction and {sup 57}Fe Moessbauer spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Carlos A.; Viola, Maria del C. [Area de Quimica General e Inorganica, Departamento de Quimica, Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera, 5700 San Luis (Argentina); Pedregosa, Jose C., E-mail: jpedreg@unsl.edu.ar [Area de Quimica General e Inorganica, Departamento de Quimica, Facultad de Quimica, Bioquimica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera, 5700 San Luis (Argentina); Mercader, Roberto C., E-mail: mercader@fisica.unlp.edu.ar [Departamento de Fisica, IFLP-CONICET, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, C.C. 67, 1900 La Plata (Argentina)

    2010-10-15

    We describe the preparation and structural characterization by X-ray powder diffraction (XRPD) and Moessbauer spectroscopy of three electron-doped perovskites Sr{sub 3}Fe{sub 2}MoO{sub 9-{delta}} with Fe/Mo = 2 obtained from Sr{sub 3}Fe{sub 2}MoO{sub 9}. The compounds were synthesized by topotactic reduction with H{sub 2}/N{sub 2} (5/95) at 600, 700 and 800 {sup o}C. Above 800 {sup o}C the Fe/Mo ratio changes from Fe/Mo = 2-1 < Fe/Mo < 2. The structural refinements of the XRPD data for the reduced perovskites were carried out by the Rietveld profile analysis method. The crystal structure of these phases is cubic, space group Fm3-bar m, with cationic disorder at the two different B sites that can be populated in variable proportions by the Fe atoms. The Moessbauer spectra allowed determining the evolution of the different species formed after the treatments at different temperatures and confirm that Fe ions in the samples reduced at 600, 700 and 800 {sup o}C are only in the high-spin Fe{sup 3+} electronic state.

  2. Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type A : a prospective cohort study

    NARCIS (Netherlands)

    Schwahn, Bernd C.; Van Spronsen, Francjan J.; Belaidi, Abdel A.; Bowhay, Stephen; Christodoulou, John; Derks, Terry G.; Hennermann, Julia B.; Jameson, Elisabeth; Koenig, Kai; McGregor, Tracy L.; Font-Montgomery, Esperanza; Santamaria-Araujo, Jose A.; Santra, Saikat; Vaidya, Mamta; Vierzig, Anne; Wassmer, Evangeline; Weis, Ilona; Wong, Flora Y.; Veldman, Alex; Schwarz, Guenter

    2015-01-01

    Background Molybdenum cofactor deficiency (MoCD) is characterised by early, rapidly progressive postnatal encephalopathy and intractable seizures, leading to severe disability and early death. Previous treatment attempts have been unsuccessful. After a pioneering single treatment we now report the

  3. Protein S binding to human endothelial cells is required for expression of cofactor activity for activated protein C

    NARCIS (Netherlands)

    Hackeng, T. M.; Hessing, M.; van 't Veer, C.; Meijer-Huizinga, F.; Meijers, J. C.; de Groot, P. G.; van Mourik, J. A.; Bouma, B. N.

    1993-01-01

    An important feedback mechanism in blood coagulation is supplied by the protein C/protein S anticoagulant pathway. In this study we demonstrate that the binding of human protein S to cultured human umbilical vein endothelial cells (HUVECs) is required for the expression of cofactor activity of

  4. Discovery and validation of information theory-based transcription factor and cofactor binding site motifs.

    Science.gov (United States)

    Lu, Ruipeng; Mucaki, Eliseos J; Rogan, Peter K

    2017-03-17

    Data from ChIP-seq experiments can derive the genome-wide binding specificities of transcription factors (TFs) and other regulatory proteins. We analyzed 765 ENCODE ChIP-seq peak datasets of 207 human TFs with a novel motif discovery pipeline based on recursive, thresholded entropy minimization. This approach, while obviating the need to compensate for skewed nucleotide composition, distinguishes true binding motifs from noise, quantifies the strengths of individual binding sites based on computed affinity and detects adjacent cofactor binding sites that coordinate with the targets of primary, immunoprecipitated TFs. We obtained contiguous and bipartite information theory-based position weight matrices (iPWMs) for 93 sequence-specific TFs, discovered 23 cofactor motifs for 127 TFs and revealed six high-confidence novel motifs. The reliability and accuracy of these iPWMs were determined via four independent validation methods, including the detection of experimentally proven binding sites, explanation of effects of characterized SNPs, comparison with previously published motifs and statistical analyses. We also predict previously unreported TF coregulatory interactions (e.g. TF complexes). These iPWMs constitute a powerful tool for predicting the effects of sequence variants in known binding sites, performing mutation analysis on regulatory SNPs and predicting previously unrecognized binding sites and target genes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Influence of common mucosal co-factors on HIV infection in the female genital tract.

    Science.gov (United States)

    Ferreira, Victor H; Kafka, Jessica K; Kaushic, Charu

    2014-06-01

    Women constitute almost half of HIV-infected population globally, and the female genital tract (FGT) accounts for approximately 40% of all new HIV infections worldwide. The FGT is composed of upper and lower parts, distinct in their morphological and functional characteristics. Co-factors in the genital microenvironment, such as presence of hormones, semen, and other sexually transmitted infections, can facilitate or deter HIV infection and play a critical role in determining susceptibility to HIV. In this review, we examine some of these co-factors and their potential influence. Presence of physical and chemical barriers such as epithelial tight junctions, mucus, and anti-microbial peptides can actively block and inhibit viral replication, presenting a significant deterrent to HIV. Upon exposure, HIV and other pathogens first encounter the genital epithelium: cells that express a wide repertoire of pattern recognition receptors that can recognize and directly initiate innate immune responses. These and other interactions in the genital tract can lead to direct and indirect inflammation and enhance the number of local target cells, immune activation, and microbial translocation, all of which promote HIV infection and replication. Better understanding of the dynamics of HIV transmission in the female genital tract would be invaluable for improving the design of prophylactic strategies against HIV. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Structures of Saccharomyces cerevisiae D-arabinose dehydrogenase Ara1 and its complex with NADPH: implications for cofactor-assisted substrate recognition.

    Science.gov (United States)

    Hu, Xiao-Qian; Guo, Peng-Chao; Ma, Jin-Di; Li, Wei-Fang

    2013-11-01

    The primary role of yeast Ara1, previously mis-annotated as a D-arabinose dehydrogenase, is to catalyze the reduction of a variety of toxic α,β-dicarbonyl compounds using NADPH as a cofactor at physiological pH levels. Here, crystal structures of Ara1 in apo and NADPH-complexed forms are presented at 2.10 and 2.00 Å resolution, respectively. Ara1 exists as a homodimer, each subunit of which adopts an (α/β)8-barrel structure and has a highly conserved cofactor-binding pocket. Structural comparison revealed that induced fit upon NADPH binding yielded an intact active-site pocket that recognizes the substrate. Moreover, the crystal structures combined with computational simulation defined an open substrate-binding site to accommodate various substrates that possess a dicarbonyl group.

  7. Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma.

    Science.gov (United States)

    Crawford, Lisa J; Anderson, Gordon; Johnston, Cliona K; Irvine, Alexandra E

    2016-10-25

    Multiple Myeloma (MM) is a haematological neoplasm characterised by the clonal proliferation of malignant plasma cells in the bone marrow. The success of proteasome inhibitors in the treatment of MM has highlighted the importance of the ubiquitin proteasome system (UPS) in the pathogenesis of this disease. In this study, we analysed gene expression of UPS components to identify novel therapeutic targets within this pathway in MM. Here we demonstrate how this approach identified previously validated and novel therapeutic targets. In addition we show that FZR1 (Fzr), a cofactor of the multi-subunit E3 ligase complex anaphase-promoting complex/cyclosome (APC/C), represents a novel therapeutic target in myeloma. The APC/C associates independently with two cofactors, Fzr and Cdc20, to control cell cycle progression. We found high levels of FZR1 in MM primary cells and cell lines and demonstrate that expression is further increased on adhesion to bone marrow stromal cells (BMSCs). Specific knockdown of either FZR1 or CDC20 reduced viability and induced growth arrest of MM cell lines, and resulted in accumulation of APC/CFzr substrate Topoisomerase IIα (TOPIIα) or APC/CCdc20 substrate Cyclin B. Similar effects were observed following treatment with proTAME, an inhibitor of both APC/CFzr and APC/CCdc20. Combinations of proTAME with topoisomerase inhibitors, etoposide and doxorubicin, significantly increased cell death in MM cell lines and primary cells, particularly if TOPIIα levels were first increased through pre-treatment with proTAME. Similarly, combinations of proTAME with the microtubule inhibitor vincristine resulted in enhanced cell death. This study demonstrates the potential of targeting the APC/C and its cofactors as a therapeutic approach in MM.

  8. Biochemical and genetic characterization of three molybdenum cofactor hydroxylases in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Hoff, Tine; Frandsen, Gitte Inselmann; Rocher, Anne

    1998-01-01

    Aldehyde oxidases and xanthine dehydrogenases/oxidases belong to the molybdenum cofactor dependent hydroxylase class of enzymes. Zymograms show that Arabidopsis thaliana has at least three different aldehyde oxidases and one xanthine oxidase. Three different cDNA clones encoding putative aldehyde...... oxidases (AtAO1, 2, 3) were isolated. An aldehyde oxidase is the last step in abscisic acid (ABA) biosynthesis. AtAO1 is mainly expressed in seeds and roots which might reflect that it is involved in ABA biosynthesis....

  9. High Content Analysis of Hippocampal Neuron-Astrocyte Co-cultures Shows a Positive Effect of Fortasyn Connect on Neuronal Survival and Postsynaptic Maturation.

    Science.gov (United States)

    van Deijk, Anne-Lieke F; Broersen, Laus M; Verkuyl, J Martin; Smit, August B; Verheijen, Mark H G

    2017-01-01

    Neuronal and synaptic membranes are composed of a phospholipid bilayer. Supplementation with dietary precursors for phospholipid synthesis -docosahexaenoic acid (DHA), uridine and choline- has been shown to increase neurite outgrowth and synaptogenesis both in vivo and in vitro . A role for multi-nutrient intervention with specific precursors and cofactors has recently emerged in early Alzheimer's disease, which is characterized by decreased synapse numbers in the hippocampus. Moreover, the medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect (FC), improves memory performance in early Alzheimer's disease patients, possibly via maintaining brain connectivity. This suggests an effect of FC on synapses, but the underlying cellular mechanism is not fully understood. Therefore, we investigated the effect of FC (consisting of DHA, eicosapentaenoic acid (EPA), uridine, choline, phospholipids, folic acid, vitamins B12, B6, C and E, and selenium), on synaptogenesis by supplementing it to primary neuron-astrocyte co-cultures, a cellular model that mimics metabolic dependencies in the brain. We measured neuronal developmental processes using high content screening in an automated manner, including neuronal survival, neurite morphology, as well as the formation and maturation of synapses. Here, we show that FC supplementation resulted in increased numbers of neurons without affecting astrocyte number. Furthermore, FC increased postsynaptic PSD95 levels in both immature and mature synapses. These findings suggest that supplementation with FC to neuron-astrocyte co-cultures increased both neuronal survival and the maturation of postsynaptic terminals, which might aid the functional interpretation of FC-based intervention strategies in neurological diseases characterized by neuronal loss and impaired synaptic functioning.

  10. High Content Analysis of Hippocampal Neuron-Astrocyte Co-cultures Shows a Positive Effect of Fortasyn Connect on Neuronal Survival and Postsynaptic Maturation

    Directory of Open Access Journals (Sweden)

    Anne-Lieke F. van Deijk

    2017-08-01

    Full Text Available Neuronal and synaptic membranes are composed of a phospholipid bilayer. Supplementation with dietary precursors for phospholipid synthesis –docosahexaenoic acid (DHA, uridine and choline– has been shown to increase neurite outgrowth and synaptogenesis both in vivo and in vitro. A role for multi-nutrient intervention with specific precursors and cofactors has recently emerged in early Alzheimer's disease, which is characterized by decreased synapse numbers in the hippocampus. Moreover, the medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect (FC, improves memory performance in early Alzheimer's disease patients, possibly via maintaining brain connectivity. This suggests an effect of FC on synapses, but the underlying cellular mechanism is not fully understood. Therefore, we investigated the effect of FC (consisting of DHA, eicosapentaenoic acid (EPA, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C and E, and selenium, on synaptogenesis by supplementing it to primary neuron-astrocyte co-cultures, a cellular model that mimics metabolic dependencies in the brain. We measured neuronal developmental processes using high content screening in an automated manner, including neuronal survival, neurite morphology, as well as the formation and maturation of synapses. Here, we show that FC supplementation resulted in increased numbers of neurons without affecting astrocyte number. Furthermore, FC increased postsynaptic PSD95 levels in both immature and mature synapses. These findings suggest that supplementation with FC to neuron-astrocyte co-cultures increased both neuronal survival and the maturation of postsynaptic terminals, which might aid the functional interpretation of FC-based intervention strategies in neurological diseases characterized by neuronal loss and impaired synaptic functioning.

  11. Study of behaviour during a quench treatment of ferrite delta of binary and pseudo-binary alloys

    International Nuclear Information System (INIS)

    Champin, B.

    1970-01-01

    Focusing of Fe-Cr and Fe-Mo alloys (and extending results to different binary alloys like Fe-W, Fe-Al and Fe-Si, and even to some ternary systems such as Fe-Cr-Ni and Fe-Mo-Ni), and after having recalled some previous results and presented experimental materials and processes, this research thesis describes the behaviour of the considered alloys, reports a detailed study of Fe-Mo alloys (influence of carbon content), a bibliographical study of the gamma-to-delta transformation, the study of hybrid alloys (behaviour, partial transformations, diffusion), the study of other types of alloys (hyper-quench of delta ferrite of Fe-Mo alloys, adsorption and diffusion). It discusses the case of two-phase structures, and the mechanism and kinetics of the delta-to-gamma transformation

  12. Novel maturity parameters for mature to over-mature source rocks and oils based on the distribution of phenanthrene series compounds

    Directory of Open Access Journals (Sweden)

    Zixiang Wang

    2016-03-01

    Two additional novel and an optimized maturation parameters based on the distribution of phenanthrene series compounds are proposed and their relationships to EasyRo% (x are established: log(MPs/P = 0.19x + 0.08 (0.9% < EasyRo% < 2.1%; log(MPs/P = 0.64x − 0.86 (2.1% < EasyRo% < 3.4%; log(DMPs/TMPs = 0.71x − 0.55 (0.9% < EasyRo% < 3.4%; log(MTR = 0.84x − 0.75 (0.9% < EasyRo% < 3.4%. These significant positive correlations are strong argument for using log(MPs/P, log(DMPs/TMPs and log(MTR as maturity parameters, especially for mature to over-mature source rocks.

  13. Potential role of Arabidopsis PHP as an accessory subunit of the PAF1 transcriptional cofactor.

    Science.gov (United States)

    Park, Sunchung; Ek-Ramos, Maria Julissa; Oh, Sookyung; van Nocker, Steven

    2011-08-01

    Paf1C is a transcriptional cofactor that has been implicated in various transcription-associated mechanisms spanning initiation, elongation and RNA processing, and is important for multiple aspects of development in Arabidopsis. Our recent studies suggest Arabidopsis Paf1C is crucial for proper regulation of genes within H3K27me3-enriched chromatin, and that a protein named PHP may act as an accessory subunit of Paf1C that promotes this function.

  14. La mitocondria como fábrica de cofactores: biosíntesis de grupo hemo, centros Fe-S y nucleótidos de flavina (FMN/FAD

    Directory of Open Access Journals (Sweden)

    Alexa Villavicencio-Queijeiro

    2012-01-01

    Full Text Available Los cofactores hemo, centros Fe-S y los nucleótidos de flavina (FMN y FAD son esenciales para muchos organismos, existen un gran número de proteínas que dependen de ellos para llevar a cabo sus funciones biológicas. Estos cofactores han sido reconocidos como esenciales para las reacciones de óxido-reducción, pero también están involucrados en otros procesos celulares como la catálisis química, la regulación, la señalización y la detección de señales intra y extra celulares. Diversos grupos de investigación han contribuido al establecimiento de las rutas bioquímicas por las que se sintetizan estos cofactores, así como a la forma en que se transportan y regulan en los diferentes organismos. Todo este conocimiento ha permitido asociar algunas enfermedades con defectos metabólicos en estas rutas de biosíntesis, así como plantear nuevas estrategias terapéuticas y algunas aplicaciones biotecnológicas.

  15. Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function

    DEFF Research Database (Denmark)

    Ek, J; Grarup, N; Urhammer, S A

    2001-01-01

    Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) are known to cause a rare subtype of maturity-onset diabetes of the young (MODY5), which is associated with early-onset progressive non-diabetic renal dysfunction. To investigate whether...... mutations in HNF-1 are implicated in the pathogenesis of MODY or late-onset diabetes with and without nephropathy in Danish Caucasians we examined the HNF-1beta (TCF2) and the dimerization cofactor of HNF-1 (DCoH, PCBD) genes for mutations in 11 MODY probands, 28 type 2 diabetic patients with nephropathy...... comprising the DCoH gene revealed a previously described A-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects....

  16. Correlation of Improved Version of Cervical Vertebral Maturation Indicator with Other Growth Maturity Indicators

    Directory of Open Access Journals (Sweden)

    Tripti Tikku

    2013-01-01

    Conclusion: The correlation between middle phalanx of 3rd finger (MP3 and cervical vertebral maturation method (CVMI and CVMS was higher as compared to the correlation of either of the cervical vertebral maturation method or MP3 with dental maturation indicator.

  17. The structure of tubulin-binding cofactor A from Leishmania major infers a mode of association during the early stages of microtubule assembly

    Energy Technology Data Exchange (ETDEWEB)

    Barrack, Keri L.; Fyfe, Paul K.; Hunter, William N., E-mail: w.n.hunter@dundee.ac.uk [University of Dundee, Dow Street, Dundee DD1 5EH, Scotland (United Kingdom)

    2015-04-21

    The structure of a tubulin-binding cofactor from L. major is reported and compared with yeast, plant and human orthologues. Tubulin-binding cofactor A (TBCA) participates in microtubule formation, a key process in eukaryotic biology to create the cytoskeleton. There is little information on how TBCA might interact with β-tubulin en route to microtubule biogenesis. To address this, the protozoan Leishmania major was targeted as a model system. The crystal structure of TBCA and comparisons with three orthologous proteins are presented. The presence of conserved features infers that electrostatic interactions that are likely to involve the C-terminal tail of β-tubulin are key to association. This study provides a reagent and template to support further work in this area.

  18. Developing maturity grids for assessing organisational capabilities

    DEFF Research Database (Denmark)

    Maier, Anja; Moultrie, James; Clarkson, P John

    2009-01-01

    Keyword: Maturity Model,Maturity Grid,Maturity Matrix,Organisational Capabilities,Benchmarking,New Product Development,Perfirmance Assessment......Keyword: Maturity Model,Maturity Grid,Maturity Matrix,Organisational Capabilities,Benchmarking,New Product Development,Perfirmance Assessment...

  19. Engineering Cofactor Preference of Ketone Reducing Biocatalysts: A Mutagenesis Study on a γ-Diketone Reductase from the Yeast Saccharomyces cerevisiae Serving as an Example

    Directory of Open Access Journals (Sweden)

    Michael Katzberg

    2010-04-01

    Full Text Available The synthesis of pharmaceuticals and catalysts more and more relies on enantiopure chiral building blocks. These can be produced in an environmentally benign and efficient way via bioreduction of prochiral ketones catalyzed by dehydrogenases. A productive source of these biocatalysts is the yeast Saccharomyces cerevisiae, whose genome also encodes a reductase catalyzing the sequential reduction of the γ-diketone 2,5-hexanedione furnishing the diol (2S,5S-hexanediol and the γ-hydroxyketone (5S-hydroxy-2-hexanone in high enantio- as well as diastereoselectivity (ee and de >99.5%. This enzyme prefers NADPH as the hydrogen donating cofactor. As NADH is more stable and cheaper than NADPH it would be more effective if NADH could be used in cell-free bioreduction systems. To achieve this, the cofactor binding site of the dehydrogenase was altered by site-directed mutagenesis. The results show that the rational approach based on a homology model of the enzyme allowed us to generate a mutant enzyme having a relaxed cofactor preference and thus is able to use both NADPH and NADH. Results obtained from other mutants are discussed and point towards the limits of rationally designed mutants.

  20. A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev

    International Nuclear Information System (INIS)

    Fang Jianhua; Kubota, Satoshi; Yang Bin; Zhou Naiming; Zhang Hui; Godbout, Roseline; Pomerantz, Roger J.

    2004-01-01

    HIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells, which allows formation of infectious HIV-1 virions. We have identified a putative DEAD box (Asp-Glu-Ala-Asp) RNA helicase, DDX1, as a cellular co-factor of Rev, through yeast and mammalian two-hybrid systems using the N-terminal motif of Rev as 'bait'. DDX1 is not a functional homolog of HIV-1 Rev, but down-regulation of DDX1 resulted in an alternative splicing pattern of Rev-responsive element (RRE)-containing mRNA, and attenuation of Gag p24 antigen production from HLfb rev(-) cells rescued by exogenous Rev. Co-transfection of a DDX1 expression vector with HIV-1 significantly increased viral production. DDX1 binding to Rev, as well as to the RRE, strongly suggest that DDX1 affects Rev function through the Rev-RRE axis. Moreover, down-regulation of DDX1 altered the steady state subcellular distribution of Rev, from nuclear/nucleolar to cytoplasmic dominance. These findings indicate that DDX1 is a critical cellular co-factor for Rev function, which maintains the proper subcellular distribution of this lentiviral regulatory protein. Therefore, alterations in DDX1-Rev interactions could induce HIV-1 persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV-1 strategies and therapeutics

  1. Refining the reaction mechanism of O2 towards its co-substrate in cofactor-free dioxygenases

    Directory of Open Access Journals (Sweden)

    Pedro J. Silva

    2016-12-01

    Full Text Available Cofactor-less oxygenases perform challenging catalytic reactions between singlet co-substrates and triplet oxygen, in spite of apparently violating the spin-conservation rule. In 1-H-3-hydroxy-4-oxoquinaldine-2,4-dioxygenase, the active site has been suggested by quantum chemical computations to fine tune triplet oxygen reactivity, allowing it to interact rapidly with its singlet substrate without the need for spin inversion, and in urate oxidase the reaction is thought to proceed through electron transfer from the deprotonated substrate to an aminoacid sidechain, which then feeds the electron to the oxygen molecule. In this work, we perform additional quantum chemical computations on these two systems to elucidate several intriguing features unaddressed by previous workers. These computations establish that in both enzymes the reaction proceeds through direct electron transfer from co-substrate to O2 followed by radical recombination, instead of minimum-energy crossing points between singlet and triplet potential energy surfaces without formal electron transfer. The active site does not affect the reactivity of oxygen directly but is crucial for the generation of the deprotonated form of the co-substrates, which have redox potentials far below those of their protonated forms and therefore may transfer electrons to oxygen without sizeable thermodynamic barriers. This mechanism seems to be shared by most cofactor-less oxidases studied so far.

  2. Neutrino mass matrices with two vanishing cofactors and Fritzsch texture for charged lepton mass matrix

    Science.gov (United States)

    Wang, Weijian; Guo, Shu-Yuan; Wang, Zhi-Gang

    2016-04-01

    In this paper, we study the cofactor 2 zero neutrino mass matrices with the Fritzsch-type structure in charged lepton mass matrix (CLMM). In the numerical analysis, we perform a scan over the parameter space of all the 15 possible patterns to get a large sample of viable scattering points. Among the 15 possible patterns, three of them can accommodate the latest lepton mixing and neutrino mass data. We compare the predictions of the allowed patterns with their counterparts with diagonal CLMM. In this case, the severe cosmology bound on the neutrino mass set a strong constraint on the parameter space, rendering two patterns only marginally allowed. The Fritzsch-type CLMM will have impact on the viable parameter space and give rise to different phenomenological predictions. Each allowed pattern predicts the strong correlations between physical variables, which is essential for model selection and can be probed in future experiments. It is found that under the no-diagonal CLMM, the cofactor zeros structure in neutrino mass matrix is unstable as the running of renormalization group (RG) from seesaw scale to the electroweak scale. A way out of the problem is to propose the flavor symmetry under the models with a TeV seesaw scale. The inverse seesaw model and a loop-induced model are given as two examples.

  3. People Capability Maturity Model. SM.

    Science.gov (United States)

    1995-09-01

    tailored so it consumes less time and resources than a traditional software process assessment or CMU/SEI-95-MM-02 People Capability Maturity Model...improved reputation or customer loyalty. CMU/SEI-95-MM-02 People Capability Maturity Model ■ L5-17 Coaching Level 5: Optimizing Activity 1...Maturity Model CMU/SEI-95-MM-62 Carnegie-Mellon University Software Engineering Institute DTIC ELECTE OCT 2 7 1995 People Capability Maturity

  4. Acute TNF-induced repression of cell identity genes is mediated by NFκB-directed redistribution of cofactors from super-enhancers

    DEFF Research Database (Denmark)

    Schmidt, Søren Fisker; Larsen, Bjørk Ditlev; Loft, Anne

    2015-01-01

    The proinflammatory cytokine tumor necrosis factor (TNF) plays a central role in low-grade adipose tissue inflammation and development of insulin resistance during obesity. In this context, nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) is directly involved and required for the...... specifically repressing super-enhancer-associated cell identity genes....... binding to the associated enhancers but rather loss of cofactors and enhancer RNA (eRNA) selectively from high-occupancy sites within super-enhancers. Based on these data, we have developed models that, with high accuracy, predict which enhancers and genes are repressed by TNF in adipocytes. We show...... that these models are applicable to other cell types where TNF represses genes associated with super-enhancers in a highly cell-type-specific manner. Our results propose a novel paradigm for NFκB-mediated repression, whereby NFκB selectively redistributes cofactors from high-occupancy enhancers, thereby...

  5. Expression, purification, crystallization and preliminary phasing of the heteromerization domain of the tRNA-export and aminoacylation cofactor Arc1p from yeast

    International Nuclear Information System (INIS)

    Simader, Hannes; Suck, Dietrich

    2006-01-01

    The heteromerization domain of an aminoacyl-tRNA synthetase cofactor from yeast was crystallized, complete selenomethionine MAD data were collected to 2.8 Å resolution and preliminary phasing reveals the presence of 20 monomers in the asymmetric unit. Eukaryotic aminoacyl-tRNA synthetases (aaRSs) must be integrated into an efficient tRNA-export and shuttling machinery. This is reflected by the presence of additional protein–protein interaction domains and a correspondingly higher degree of complex formation in eukaryotic aaRSs. However, the structural basis of interaction between eukaryotic aaRSs and associated protein cofactors has remained elusive. The N-terminal heteromerization domain of the tRNA aminoacylation and export cofactor Arc1p has been cloned from yeast, expressed and purified. Crystals have been obtained belonging to space group C2, with unit-cell parameters a = 222.32, b = 89.46, c = 126.79 Å, β = 99.39°. Calculated Matthews coefficients are compatible with the presence of 10–25 monomers in the asymmetric unit. A complete multiple-wavelength anomalous dispersion data set has been collected from a selenomethionine-substituted crystal at 2.8 Å resolution. Preliminary phasing reveals the presence of 20 monomers organized in five tetramers per asymmetric unit

  6. IT Governance Maturity: Developing a Maturity Model Using the Delphi Method

    NARCIS (Netherlands)

    Smits, Daniël; van Hillegersberg, Jos

    2015-01-01

    To advance in maturity, organizations should pay attention to both the hard and soft sides of IT governance (ITG). The hard side is related to processes and structure, the soft side to social aspects like behavior and organizational culture. This paper describes a study to develop an ITG maturity

  7. MatureBayes: a probabilistic algorithm for identifying the mature miRNA within novel precursors.

    Directory of Open Access Journals (Sweden)

    Katerina Gkirtzou

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are small, single stranded RNAs with a key role in post-transcriptional regulation of thousands of genes across numerous species. While several computational methods are currently available for identifying miRNA genes, accurate prediction of the mature miRNA remains a challenge. Existing approaches fall short in predicting the location of mature miRNAs but also in finding the functional strand(s of miRNA precursors. METHODOLOGY/PRINCIPAL FINDINGS: Here, we present a computational tool that incorporates a Naive Bayes classifier to identify mature miRNA candidates based on sequence and secondary structure information of their miRNA precursors. We take into account both positive (true mature miRNAs and negative (same-size non-mature miRNA sequences examples to optimize sensitivity as well as specificity. Our method can accurately predict the start position of experimentally verified mature miRNAs for both human and mouse, achieving a significantly larger (often double performance accuracy compared with two existing methods. Moreover, the method exhibits a very high generalization performance on miRNAs from two other organisms. More importantly, our method provides direct evidence about the features of miRNA precursors which may determine the location of the mature miRNA. We find that the triplet of positions 7, 8 and 9 from the mature miRNA end towards the closest hairpin have the largest discriminatory power, are relatively conserved in terms of sequence composition (mostly contain a Uracil and are located within or in very close proximity to the hairpin loop, suggesting the existence of a possible recognition site for Dicer and associated proteins. CONCLUSIONS: This work describes a novel algorithm for identifying the start position of mature miRNA(s produced by miRNA precursors. Our tool has significantly better (often double performance than two existing approaches and provides new insights about the potential use

  8. Crystallographic investigation of the cooperative interaction between trimethoprim, reduced cofactor and dihydrofolate reductase

    International Nuclear Information System (INIS)

    Champness, J.N.; Stammers, D.K.; Beddell, C.R.

    1986-01-01

    The structure of the complex between E. coli form I dihydrofolate reductase, the antibacterial trimethoprim and NADPH has been determined by X-ray crystallography. The inhibitor and cofactor are in mutual contact. A flexible chain segment which includes Met 20 is in contact with the inhibitor in the presence of NADPH, but more distant in its absence. By contrast, the inhibitor conformation is little changed with NADPH present. The authors discuss these observations with regard to the mutually cooperative binding of these ligands to the protein, and to the associated enhancement of inhibitory selectivity shown by trimethoprim for bacterial as opposed to vertebrate enzyme. (Auth.)

  9. Bioinformatic evidence for a widely distributed, ribosomally produced electron carrier precursor, its maturation proteins, and its nicotinoprotein redox partners

    Directory of Open Access Journals (Sweden)

    Haft Daniel H

    2011-01-01

    Full Text Available Abstract Background Enzymes in the radical SAM (rSAM domain family serve in a wide variety of biological processes, including RNA modification, enzyme activation, bacteriocin core peptide maturation, and cofactor biosynthesis. Evolutionary pressures and relationships to other cellular constituents impose recognizable grammars on each class of rSAM-containing system, shaping patterns in results obtained through various comparative genomics analyses. Results An uncharacterized gene cluster found in many Actinobacteria and sporadically in Firmicutes, Chloroflexi, Deltaproteobacteria, and one Archaeal plasmid contains a PqqE-like rSAM protein family that includes Rv0693 from Mycobacterium tuberculosis. Members occur clustered with a strikingly well-conserved small polypeptide we designate "mycofactocin," similar in size to bacteriocins and PqqA, precursor of pyrroloquinoline quinone (PQQ. Partial Phylogenetic Profiling (PPP based on the distribution of these markers identifies the mycofactocin cluster, but also a second tier of high-scoring proteins. This tier, strikingly, is filled with up to thirty-one members per genome from three variant subfamilies that occur, one each, in three unrelated classes of nicotinoproteins. The pattern suggests these variant enzymes require not only NAD(P, but also the novel gene cluster. Further study was conducted using SIMBAL, a PPP-like tool, to search these nicotinoproteins for subsequences best correlated across multiple genomes to the presence of mycofactocin. For both the short chain dehydrogenase/reductase (SDR and iron-containing dehydrogenase families, aligning SIMBAL's top-scoring sequences to homologous solved crystal structures shows signals centered over NAD(P-binding sites rather than over substrate-binding or active site residues. Previous studies on some of these proteins have revealed a non-exchangeable NAD cofactor, such that enzymatic activity in vitro requires an artificial electron acceptor such

  10. Academic Achievement of High School Students in Relation to Their Anxiety, Emotional Maturity and Social Maturity

    Science.gov (United States)

    Puar, Surjit Singh

    2013-01-01

    The present study has been designed to investigate the non-cognitive variables like anxiety, emotional maturity and social maturity and their relationship with academic achievement and also to see the locale-wise differences on the basis of their anxiety, emotional maturity and social maturity. The study was conducted over a sample of 400 (200…

  11. Leveraging People-Related Maturity Issues for Achieving Higher Maturity and Capability Levels

    Science.gov (United States)

    Buglione, Luigi

    During the past 20 years Maturity Models (MM) become a buzzword in the ICT world. Since the initial Crosby's idea in 1979, plenty of models have been created in the Software & Systems Engineering domains, addressing various perspectives. By analyzing the content of the Process Reference Models (PRM) in many of them, it can be noticed that people-related issues have little weight in the appraisals of the capabilities of organizations while in practice they are considered as significant contributors in traditional process and organizational performance appraisals, as stressed instead in well-known Performance Management models such as MBQA, EFQM and BSC. This paper proposes some ways for leveraging people-related maturity issues merging HR practices from several types of maturity models into the organizational Business Process Model (BPM) in order to achieve higher organizational maturity and capability levels.

  12. Income poverty, poverty co-factors, and the adjustment of children in elementary school.

    Science.gov (United States)

    Ackerman, Brian P; Brown, Eleanor D

    2006-01-01

    Since 1990, there have been great advances in how developmental researchers construct poverty. These advances are important because they may help inform social policy at many levels and help frame how American culture constructs poverty for children, both symbolically and in the opportunities children and families get to escape from poverty. Historically, developmental perspectives have embodied social address and main effects models, snapshot views of poverty effects at single points in time, and a rather narrow focus on income as the symbolic marker of the ecology of disadvantage. More recent views, in contrast, emphasize the diverse circumstances of disadvantaged families and diverse outcomes of disadvantaged children, the multiple sources of risk and the multiple determinants of poor outcomes for these children, dynamic aspects of that ecology, and change as well as continuity in outcome trajectories. The advances also consist of more powerful frames for understanding the ecology of disadvantage and the risk it poses for child outcomes. Most developmental researchers still tend to frame causal variables ultimately in terms of the dichotomy between social causation and social selection views, with a primary emphasis on the former. In part, this framing has reflected limitations of sample size and design, because the theoretical and empirical power of reciprocal selection models is clear (Kim et al., 2003). The conceptual advances that prompt such models include widespread acknowledgement of third variable problems in interpreting effects, of the clear need for multivariate approaches, and the need to pursue mechanisms and moderators of the relations between causal candidates and child outcomes. In the context of these advances, one of the core goals of our research program has been to construct robust representations of environmental adversity for disadvantaged families. Most of our research focuses on contextual co-factors at a family level (e.g., maternal

  13. Zinc is the metal cofactor of Borrelia burgdorferi peptide deformylase.

    Science.gov (United States)

    Nguyen, Kiet T; Wu, Jen-Chieh; Boylan, Julie A; Gherardini, Frank C; Pei, Dehua

    2007-12-15

    Peptide deformylase (PDF, E.C. 3.5.1.88) catalyzes the removal of N-terminal formyl groups from nascent ribosome-synthesized polypeptides. PDF contains a catalytically essential divalent metal ion, which is tetrahedrally coordinated by three protein ligands (His, His, and Cys) and a water molecule. Previous studies revealed that the metal cofactor is a Fe2+ ion in Escherichia coli and many other bacterial PDFs. In this work, we found that PDFs from two iron-deficient bacteria, Borrelia burgdorferi and Lactobacillus plantarum, are stable and highly active under aerobic conditions. The native B. burgdorferi PDF (BbPDF) was purified 1200-fold and metal analysis revealed that it contains approximately 1.1 Zn2+ ion/polypeptide but no iron. Our studies suggest that PDF utilizes different metal ions in different organisms. These data have important implications in designing PDF inhibitors and should help address some of the unresolved issues regarding PDF structure and catalytic function.

  14. Maturity Models Development in IS Research

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan; Vatrapu, Ravi; Andersen, Kim Normann

    2015-01-01

    Maturity models are widespread in IS research and in particular, IT practitioner communities. However, theoretically sound, methodologically rigorous and empirically validated maturity models are quite rare. This literature review paper focuses on the challenges faced during the development...... literature reveals that researchers have primarily focused on developing new maturity models pertaining to domain-specific problems and/or new enterprise technologies. We find rampant re-use of the design structure of widely adopted models such as Nolan’s Stage of Growth Model, Crosby’s Grid, and Capability...... Maturity Model (CMM). Only recently have there been some research efforts to standardize maturity model development. We also identify three dominant views of maturity models and provide guidelines for various approaches of constructing maturity models with a standard vocabulary. We finally propose using...

  15. La mitocondria como fábrica de cofactores: biosíntesis de grupo hemo, centros Fe-S y nucleótidos de flavina (FMN/FAD)

    OpenAIRE

    Alexa Villavicencio-Queijeiro

    2012-01-01

    Los cofactores hemo, centros Fe-S y los nucleótidos de flavina (FMN y FAD) son esenciales para muchos organismos, existen un gran número de proteínas que dependen de ellos para llevar a cabo sus funciones biológicas. Estos cofactores han sido reconocidos como esenciales para las reacciones de óxido-reducción, pero también están involucrados en otros procesos celulares como la catálisis química, la regulación, la señalización y la detección de señales intra y extra celulares. Diversos grupos d...

  16. Substrate- and Cofactor-independent Inhibition of Histone Demethylase KDM4C

    DEFF Research Database (Denmark)

    Leurs, Ulrike; Lohse, Brian; Rand, Kasper Dyrberg

    2014-01-01

    Inhibition of histone demethylases has within recent years advanced into a new strategy for treating cancer and other diseases. Targeting specific histone demethylases can be challenging as the active sites of KDM1A-B and KDM-4A-D histone demethylases, respectively, are highly conserved. Most...... inhibitors developed up-to-date target either the cofactor- or substrate-binding sites of these enzymes, resulting in a lack of selectivity and off-target effects. This study describes the discovery of the first peptide-based inhibitors of KDM4 histone demethylases that do not share the histone peptide...... sequence, or inhibit through substrate competition. Through screening of DNA-encoded peptide libraries against KDM1 and -4 histone demethylases by phage display, two cyclic peptides targeting the histone demethylase KDM4C were identified and developed as inhibitors by amino acid replacement, truncation...

  17. Modeling non-maturing liabilities

    OpenAIRE

    von Feilitzen, Helena

    2011-01-01

    Non‐maturing liabilities, such as savings accounts, lack both predetermined maturity and reset dates due to the fact that the depositor is free to withdraw funds at any time and that the depository institution is free to change the rate. These attributes complicate the risk management of such products and no standardized solution exists. The problem is important however since non‐maturing liabilities typically make up a considerable part of the funding of a bank. In this report different mode...

  18. Testing remotely operated module technique for Wackersdorf reprocessing plant at Lahde test rig

    International Nuclear Information System (INIS)

    Leister, P.; Schroeder, G.; Boehme, G.

    1986-01-01

    The FEMO technique represents a plant concept which makes it possible to carry out the repair of high and medium activity wet chemical stages of the process by remote handling without direct access by staff. For this purpose, the apparatus of this step of the process is arranged modularly in large cells, so that movable large handling devices such as cranes and manipulator systems can replace process components subject to wear via the process modules. The machine room of the former coal-fired power station Heyden I at Lahde was, after removal of the turbines and generators, converted to a hall in which the following test areas were accommodated: FEMO cell section with 10 positions for module, cell wall mock-up and wall penetration, module mounting area, module measuring position, workplace for service area, training position, welding position and FEMO control position. (orig./HP) [de

  19. Markers, Cofactors and Staging Systems in the Study of HIV Disease Progression: A Review

    Directory of Open Access Journals (Sweden)

    MC Portela

    1997-07-01

    Full Text Available This paper is aimed at providing a comprehensive review of markers, cofactors and staging systems used for HIV disease, focusing on some aspects that nowadays could even be considered historical, and advancing in current issues such as the prognostic value of viral load measurements, viral genotypic and phenotypic characterization, and new HIV disease treatment protocols. CD4+ cell values, combined with the new viral markers mentioned are promising as a parsimonious predictor set for defining both severity and progression. An adequate predictor of patient resource use for planning purposes still needs to be defined

  20. Synthesis and characterization of sulfur-voided cubanes. Structural analogues for the MoFe(3)S(3) subunit in the nitrogenase cofactor.

    Science.gov (United States)

    Coucouvanis, Dimitri; Han, Jaehong; Moon, Namdoo

    2002-01-16

    A new class of Mo/Fe/S clusters with the MoFe(3)S(3) core has been synthesized in attempts to model the FeMo-cofactor in nitrogenase. These clusters are obtained in reactions of the (Cl(4)-cat)(2)Mo(2)Fe(6)S(8)(PR(3))(6) [R = Et (I), (n)Pr (II)] clusters with CO. The new clusters include those preliminarily reported: (Cl(4)-cat)MoFe(3)S(3)(PEt(3))(2)(CO)(6) (III), (Cl(4)-cat)(O)MoFe(3)S(3)(PEt(3))(3)(CO)(5) (IV), (Cl(4)-cat)(Pyr)MoFe(3)S(3)(PEt(3))(2)(CO)(6) (VI), and (Cl(4)-cat)(Pyr)MoFe(3)S(3)(P(n)Pr(3))(3)(CO)(4) (VIII). In addition the new (Cl(4)-cat)(O)MoFe(3)S(3)(P(n)Pr(3))(3)(CO)(5) cluster (IVa), the (Cl(4)-cat)(O)MoFe(3)S(3)(PEt(3))(2)(CO)(6)cluster (V), the (Cl(4)-cat)(O)MoFe(3)S(3)(P(n)Pr(3))(2)(CO)(6) cluster (Va), the (Cl(4)-cat)(Pyr)MoFe(3)S(3)(P(n)Pr(3))(2)(CO)(6) cluster (VIa), and the (Cl(4)-cat)(P(n)Pr(3))MoFe(3)S(3)(P(n)Pr(3))(2)(CO)(6) cluster (VII) also are reported. Clusters III-VIII have been structurally and spectroscopically characterized. EPR, zero-field (57)Fe-Mössbauer spectroscopic characterizations, and magnetic susceptibility measurements have been used for a tentative assignment of the electronic and oxidation states of the MoFe(3)S(3) sulfur-voided cuboidal clusters. A structural comparison of the clusters with the MoFe(3)S(3) subunit of the FeMo-cofactor has led to the suggestion that the storage of reducing equivalents into M-M bonds, and their use in the reduction of substrates, may occur with the FeMo-cofactor, which also appears to have M-M bonding. On the basis of this argument, a possible N(2)-binding and reduction mechanism on the FeMoco-cofactor is proposed.

  1. Slab replacement maturity guidelines.

    Science.gov (United States)

    2014-04-01

    This study investigated the use of maturity method to determine early age strength of concrete in slab : replacement application. Specific objectives were (1) to evaluate effects of various factors on the compressive : maturity-strength relationship ...

  2. Specificity of anti-phospholipid antibodies in infectious mononucleosis: a role for anti-cofactor protein antibodies

    Science.gov (United States)

    Sorice, M; Pittoni, V; Griggi, T; Losardo, A; Leri, O; Magno, M S; Misasi, R; Valesini, G

    2000-01-01

    The antigen specificity of anti-phospholipid antibodies in infectious mononucleosis (IM) was studied using ELISA for the detection of anti-β2-glycoprotein I (β2-GPI), anti-annexin V, anti-protein S and anti-prothrombin antibodies and TLC immunostaining for the detection of anti-phospholipid antibodies. This technique enabled us to look at antibodies reacting to ‘pure’ phospholipid antigens in the absence of protein contamination. Sera from 46 patients with IM, 18 with systemic lupus erythematosus (SLE), 21 with primary anti-phospholipid antibody syndrome (PAPS), 50 with Helicobacter pylori infection and 30 healthy blood donors were tested. This study highlights anti-phospholipid antibodies in patients with IM as specific ‘pure’ anti-cardiolipin antibodies, while in PAPS and SLE patients anti-phosphatidylserine and anti-phosphatidylethanolamine antibodies were also found. This investigation also shows that the anti-cardiolipin antibodies found in IM can be present with anti-cofactor protein antibodies. The higher prevalence of anti-cofactor antibodies found in IM sera than in Helicobacter pylori sera may be due to the immunostimulatory effect and/or the polyclonal activation often observed in course of Epstein–Barr virus infection. However, anti-β2-GPI and, to a lesser extent, anti-prothrombin antibodies occur with a significantly lower prevalence in IM than in PAPS patients. This finding suggests that these antibodies should be regarded as the expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins. PMID:10792380

  3. Maturity effects in energy futures

    Energy Technology Data Exchange (ETDEWEB)

    Serletis, Apostolos (Calgary Univ., AB (CA). Dept. of Economics)

    1992-04-01

    This paper examines the effects of maturity on future price volatility and trading volume for 129 energy futures contracts recently traded in the NYMEX. The results provide support for the maturity effect hypothesis, that is, energy futures prices to become more volatile and trading volume increases as futures contracts approach maturity. (author).

  4. Correlation between Cervical Vertebral Maturation Stages and Dental Maturation in a Saudi Sample

    Directory of Open Access Journals (Sweden)

    Nayef H Felemban

    2017-01-01

    Full Text Available Background: The aim of the present study was to compare the cervical vertebra maturation stages method and dental maturity using tooth calcification stages. Methods: The current study comprised of 405 subjects selected from orthodontic patients of Saudi origin coming to clinics of the specialized dental centers in western region of Saudi Arabia. Dental age was assessed according to the developmental stages of upper and lower third molars and skeletal maturation according to the cervical vertebrae maturation stage method. Statistical analysis was done using Kruskal-Wallis H, Mann-Whitney U test, Chi-Square test; t-test and Spearman correlation coefficient for inter group comparison. Results: The females were younger than males in all cervical stages. The CS1-CS2 show the period before the peak of growth, during CS3-CS5 it’s the pubertal growth spurt and CS6 is the period after the peak of the growth. The mean age and standard deviation for cervical stages of CS2, CS3 and CS4 were 12.09 ±1.72 years, 13.19 ±1.62 and 14.88 ±1.52 respectively. The Spearman correlation coefficients between cervical vertebrae and dental maturation were between 0.166 and 0.612, 0.243 and 0.832 for both sexes for upper and lower third molars. The significance levels for all coefficients were equal at 0.01 and 0.05. Conclusion: The results of this study showed that the skeletal maturity increased with the increase in dental ages for both genders. An early rate of skeletal maturation stage was observed in females. This study needs further analysis using a larger sample covering the entire dentition.

  5. Identification of an Isothiocyanate on the HypEF Complex Suggests a Route for Efficient Cyanyl-Group Channeling during [NiFe]-Hydrogenase Cofactor Generation.

    Directory of Open Access Journals (Sweden)

    Sven T Stripp

    Full Text Available [NiFe]-hydrogenases catalyze uptake and evolution of H2 in a wide range of microorganisms. The enzyme is characterized by an inorganic nickel/ iron cofactor, the latter of which carries carbon monoxide and cyanide ligands. In vivo generation of these ligands requires a number of auxiliary proteins, the so-called Hyp family. Initially, HypF binds and activates the precursor metabolite carbamoyl phosphate. HypF catalyzes removal of phosphate and transfers the carbamate group to HypE. In an ATP-dependent condensation reaction, the C-terminal cysteinyl residue of HypE is modified to what has been interpreted as thiocyanate. This group is the direct precursor of the cyanide ligands of the [NiFe]-hydrogenase active site cofactor. We present a FT-IR analysis of HypE and HypF as isolated from E. coli. We follow the HypF-catalyzed cyanation of HypE in vitro and screen for the influence of carbamoyl phosphate and ATP. To elucidate on the differences between HypE and the HypEF complex, spectro-electrochemistry was used to map the vibrational Stark effect of naturally cyanated HypE. The IR signature of HypE could ultimately be assigned to isothiocyanate (-N=C=S rather than thiocyanate (-S-C≡N. This has important implications for cyanyl-group channeling during [NiFe]-hydrogenase cofactor generation.

  6. Maturity models in supply chain sustainability

    DEFF Research Database (Denmark)

    Correia, Elisabete; Carvalho, Helena; Azevedo, Susana G.

    2017-01-01

    A systematic literature review of supply chain maturity models with sustainability concerns is presented. The objective is to give insights into methodological issues related to maturity models, namely the research objectives; the research methods used to develop, validate and test them; the scope...... of maturity levels. The comprehensive review, analysis, and synthesis of the maturity model literature represent an important contribution to the organization of this research area, making possible to clarify some confusion that exists about concepts, approaches and components of maturity models...

  7. Iron binary and ternary coatings with molybdenum and tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Yar-Mukhamedova, Gulmira, E-mail: gulmira-alma-ata@mail.ru [Institute Experimental and Theoretical Physics Al-Farabi Kazakh National University, 050038, Al-Farabi av., 71, Almaty (Kazakhstan); Ved, Maryna; Sakhnenko, Nikolay; Karakurkchi, Anna; Yermolenko, Iryna [National Technical University “Kharkov Polytechnic Institute”, Kharkov (Ukraine)

    2016-10-15

    Highlights: • High quality coatings of double Fe-Mo and ternary Fe-Mo-W electrolytic alloys can be produced both in a dc and a pulsed mode. • Application of unipolar pulsed current allows receiving an increased content of the alloying components and their more uniform distribution over the surface. • It is established that Fe-Mo and Fe-Mo-W coatings have an amorphous structure and exhibit improved corrosion resistance and microhardness as compared with the steel substrate due to the inclusion molybdenum and tungsten. - Abstract: Electrodeposition of Fe-Mo-W and Fe-Mo layers from a citrate solution containing iron(III) on steel and iron substrates is compared. The utilization of iron(III) compounds significantly improved the electrolyte stability eliminating side anodic redox reactions. The influence of concentration ratios and electrodeposition mode on quality, chemical composition, and functional properties of the alloys is determined. It has been found that alloys deposited in pulse mode have more uniform surface morphology and chemical composition and contain less impurities. Improvement in physical and mechanical properties as well as corrosion resistance of Fe-Mo and Fe-Mo-W deposits when compared with main alloy forming metals is driven by alloying components chemical passivity as well as by alloys amorphous structure. Indicated deposits can be considered promising materials in surface hardening technologies and repair of worn out items.

  8. Biocatalytic hydroxylation of n-butane with in situ cofactor regeneration at low temperature and under normal pressure

    Directory of Open Access Journals (Sweden)

    Svenja Staudt

    2012-02-01

    Full Text Available The hydroxylation of n-alkanes, which proceeds in the presence of a P450-monooxygenase advantageously at temperatures significantly below room temperature, is described. In addition, an enzymatic hydroxylation of the “liquid gas” n-butane with in situ cofactor regeneration, which does not require high-pressure conditions, was developed. The resulting 2-butanol was obtained as the only regioisomer, at a product concentration of 0.16 g/L.

  9. Maturity Models

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan; Vatrapu, Ravi

    2016-01-01

    Recent advancements in set theory and readily available software have enabled social science researchers to bridge the variable-centered quantitative and case-based qualitative methodological paradigms in order to analyze multi-dimensional associations beyond the linearity assumptions, aggregate...... effects, unicausal reduction, and case specificity. Based on the developments in set theoretical thinking in social sciences and employing methods like Qualitative Comparative Analysis (QCA), Necessary Condition Analysis (NCA), and set visualization techniques, in this position paper, we propose...... and demonstrate a new approach to maturity models in the domain of Information Systems. This position paper describes the set-theoretical approach to maturity models, presents current results and outlines future research work....

  10. Relative contributions of decay accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 in the protection of melanocytes from homologous complement

    NARCIS (Netherlands)

    Venneker, G. T.; Vodegel, R. M.; Okada, N.; Westerhof, W.; Bos, J. D.; Asghar, S. S.

    1998-01-01

    Complement regulatory molecules, membrane cofactor protein (MCP), decay accelerating factor (DAF) and CD59, protect body cells from autologous complement. They have wide tissue distribution but nothing is known about the expression of these molecules on human melanocytes. Since melanocytes are lysed

  11. Naturally Engineered Maturation of Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Gaetano J. Scuderi

    2017-05-01

    Full Text Available Ischemic heart disease remains one of the most prominent causes of mortalities worldwide with heart transplantation being the gold-standard treatment option. However, due to the major limitations associated with heart transplants, such as an inadequate supply and heart rejection, there remains a significant clinical need for a viable cardiac regenerative therapy to restore native myocardial function. Over the course of the previous several decades, researchers have made prominent advances in the field of cardiac regeneration with the creation of in vitro human pluripotent stem cell-derived cardiomyocyte tissue engineered constructs. However, these engineered constructs exhibit a functionally immature, disorganized, fetal-like phenotype that is not equivalent physiologically to native adult cardiac tissue. Due to this major limitation, many recent studies have investigated approaches to improve pluripotent stem cell-derived cardiomyocyte maturation to close this large functionality gap between engineered and native cardiac tissue. This review integrates the natural developmental mechanisms of cardiomyocyte structural and functional maturation. The variety of ways researchers have attempted to improve cardiomyocyte maturation in vitro by mimicking natural development, known as natural engineering, is readily discussed. The main focus of this review involves the synergistic role of electrical and mechanical stimulation, extracellular matrix interactions, and non-cardiomyocyte interactions in facilitating cardiomyocyte maturation. Overall, even with these current natural engineering approaches, pluripotent stem cell-derived cardiomyocytes within three-dimensional engineered heart tissue still remain mostly within the early to late fetal stages of cardiomyocyte maturity. Therefore, although the end goal is to achieve adult phenotypic maturity, more emphasis must be placed on elucidating how the in vivo fetal microenvironment drives cardiomyocyte

  12. Cofactor and CO2 donor regulation involved in reductive routes for polymalic acid production by Aureobasidium pullulans CCTCC M2012223.

    Science.gov (United States)

    Zou, Xiang; Tu, Guangwei; Zan, Zhanquan

    2014-10-01

    Polymalic acid (PMA) is a water-soluble polyester with many attractive properties for biomedical application. Its monomer L-malic acid is widely used in the food industry and also a potential C4 platform chemical. Cofactor and CO2 donor involved in the reductive routes were investigated for PMA production by Aureobasidium pullulans. Biotin as the key cofactor of pyruvate carboxylase was favor for the PMA biosynthesis. Na2CO3 as CO2 donor can obviously improved PMA titer when compared with no CO2 supplier NaOH, and also exhibit more advantages than the other donor CaCO3 because of its water-soluble characteristic. A combinational process with addition of biotin 70 mg/L and Na2CO3 as the CO2 donor was scaled-up in 50 L fermentor, achieving the high product 34.3 g/L of PMA and productivity of 0.41 g/L h. This process provides an efficient and economical way for PMA and malic acid production, and is promising for industrial application.

  13. Emissive Synthetic Cofactors: An Isomorphic, Isofunctional, and Responsive NAD+ Analogue.

    Science.gov (United States)

    Rovira, Alexander R; Fin, Andrea; Tor, Yitzhak

    2017-11-08

    The synthesis, photophysics, and biochemical utility of a fluorescent NAD + analogue based on an isothiazolo[4,3-d]pyrimidine core (N tz AD + ) are described. Enzymatic reactions, photophysically monitored in real time, show N tz AD + and N tz ADH to be substrates for yeast alcohol dehydrogenase and lactate dehydrogenase, respectively, with reaction rates comparable to that of the native cofactors. A drop in fluorescence is seen as N tz AD + is converted to N tz ADH, reflecting a complementary photophysical behavior to that of the native NAD + /NADH. N tz AD + and N tz ADH serve as substrates for NADase, which selectively cleaves the nicotinamide's glycosidic bond yielding tz ADP-ribose. N tz AD + also serves as a substrate for ribosyl transferases, including human adenosine ribosyl transferase 5 (ART5) and Cholera toxin subunit A (CTA), which hydrolyze the nicotinamide and transfer tz ADP-ribose to an arginine analogue, respectively. These reactions can be monitored by fluorescence spectroscopy, in stark contrast to the corresponding processes with the nonemissive NAD + .

  14. Dynamic mechanistic modeling of the multienzymatic one-pot reduction of dehydrocholic acid to 12-keto ursodeoxycholic acid with competing substrates and cofactors.

    Science.gov (United States)

    Sun, Boqiao; Hartl, Florian; Castiglione, Kathrin; Weuster-Botz, Dirk

    2015-01-01

    Ursodeoxycholic acid (UDCA) is a bile acid which is used as pharmaceutical for the treatment of several diseases, such as cholesterol gallstones, primary sclerosing cholangitis or primary biliary cirrhosis. A potential chemoenzymatic synthesis route of UDCA comprises the two-step reduction of dehydrocholic acid to 12-keto-ursodeoxycholic acid (12-keto-UDCA), which can be conducted in a multienzymatic one-pot process using 3α-hydroxysteroid dehydrogenase (3α-HSDH), 7β-hydroxysteroid dehydrogenase (7β-HSDH), and glucose dehydrogenase (GDH) with glucose as cosubstrate for the regeneration of cofactor. Here, we present a dynamic mechanistic model of this one-pot reduction which involves three enzymes, four different bile acids, and two different cofactors, each with different oxidation states. In addition, every enzyme faces two competing substrates, whereas each bile acid and cofactor is formed or converted by two different enzymes. First, the kinetic mechanisms of both HSDH were identified to follow an ordered bi-bi mechanism with EBQ-type uncompetitive substrate inhibition. Rate equations were then derived for this mechanism and for mechanisms describing competing substrates. After the estimation of the model parameters of each enzyme independently by progress curve analyses, the full process model of a simple batch-process was established by coupling rate equations and mass balances. Validation experiments of the one-pot multienzymatic batch process revealed high prediction accuracy of the process model and a model analysis offered important insight to the identification of optimum reaction conditions. © 2015 American Institute of Chemical Engineers.

  15. Co-ordinate variations in methylmalonyl-CoA mutase and methionine synthase, and the cobalamin cofactors in human glioma cells during nitrous oxide exposure and the subsequent recovery phase.

    Science.gov (United States)

    Riedel, B; Fiskerstrand, T; Refsum, H; Ueland, P M

    1999-07-01

    We investigated the co-ordinate variations of the two cobalamin (Cbl)-dependent enzymes, methionine synthase (MS) and methylmalonyl-CoA mutase (MCM), and measured the levels of their respective cofactors, methylcobalamin (CH3Cbl) and adenosylcobalamin (AdoCbl) in cultured human glioma cells during nitrous oxide exposure and during a subsequent recovery period of culture in a nitrous oxide-free atmosphere (air). In agreement with published data, MS as the primary target of nitrous oxide was inactivated rapidly (initial rate of 0.06 h(-1)), followed by reduction of CH3Cbl (to ordinate distribution of Cbl cofactors during depletion and repletion.

  16. Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors.

    Science.gov (United States)

    Montgomery, David C; Sorum, Alexander W; Guasch, Laura; Nicklaus, Marc C; Meier, Jordan L

    2015-08-20

    The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and developing therapeutic strategies to disrupt this process. Here, we describe a chemical approach to define the metabolic regulation of lysine acetyltransferase (KAT) enzymes. Using a novel chemoproteomic probe, we identify a previously unreported interaction between palmitoyl coenzyme A (palmitoyl-CoA) and KAT enzymes. Further analysis reveals that palmitoyl-CoA is a potent inhibitor of KAT activity and that fatty acyl-CoA precursors reduce cellular histone acetylation levels. These studies implicate fatty acyl-CoAs as endogenous regulators of histone acetylation, and suggest novel strategies for the investigation and metabolic modulation of epigenetic signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Proteolytic activation transforms heparin cofactor II into a host defense molecule.

    Science.gov (United States)

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Tollefsen, Douglas M; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

    2013-06-15

    The abundant serine proteinase inhibitor heparin cofactor II (HCII) has been proposed to inhibit extravascular thrombin. However, the exact physiological role of this plasma protein remains enigmatic. In this study, we demonstrate a previously unknown role for HCII in host defense. Proteolytic cleavage of the molecule induced a conformational change, thereby inducing endotoxin-binding and antimicrobial properties. Analyses employing representative peptide epitopes mapped these effects to helices A and D. Mice deficient in HCII showed increased susceptibility to invasive infection by Pseudomonas aeruginosa, along with a significantly increased cytokine response. Correspondingly, decreased levels of HCII were observed in wild-type animals challenged with bacteria or endotoxin. In humans, proteolytically cleaved HCII forms were detected during wounding and in association with bacteria. Thus, the protease-induced uncovering of cryptic epitopes in HCII, which transforms the molecule into a host defense factor, represents a previously unknown regulatory mechanism in HCII biology and innate immunity.

  18. 7 CFR 51.1904 - Maturity classification.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Maturity classification. 51.1904 Section 51.1904... STANDARDS) United States Consumer Standards for Fresh Tomatoes Size and Maturity Classification § 51.1904 Maturity classification. Tomatoes which are characteristically red when ripe, but are not overripe or soft...

  19. Niveles plasmáticos e interacciones del sistema cofactor 2 de la heparina-trombina-dermatan sulfato

    OpenAIRE

    Rossi, Eleonora Beatriz

    1999-01-01

    El Cofactor II de la Heparina (HCII) es un inhibidor fisiológico del sistema de coagulación, miembro de la familia de serpinas. Inhibe específicamente trombina, una enzima clave del sistema hemostático. La capacidad del HCII de inhibir trombina es potenciada mas de 1000 veces por la presencia de glicosaminoglicano el Dermatán Sulfato (DS),. Aún no está claramente definido el papel que desempeña el HCII en la fisiología de la Hemostasia, postulándose su deficiencia corno leve factor de riesgo ...

  20. Cervical vertebral maturation as a biologic indicator of skeletal maturity.

    Science.gov (United States)

    Santiago, Rodrigo César; de Miranda Costa, Luiz Felipe; Vitral, Robert Willer Farinazzo; Fraga, Marcelo Reis; Bolognese, Ana Maria; Maia, Lucianne Cople

    2012-11-01

    To identify and review the literature regarding the reliability of cervical vertebrae maturation (CVM) staging to predict the pubertal spurt. The selection criteria included cross-sectional and longitudinal descriptive studies in humans that evaluated qualitatively or quantitatively the accuracy and reproducibility of the CVM method on lateral cephalometric radiographs, as well as the correlation with a standard method established by hand-wrist radiographs. The searches retrieved 343 unique citations. Twenty-three studies met the inclusion criteria. Six articles had moderate to high scores, while 17 of 23 had low scores. Analysis also showed a moderate to high statistically significant correlation between CVM and hand-wrist maturation methods. There was a moderate to high reproducibility of the CVM method, and only one specific study investigated the accuracy of the CVM index in detecting peak pubertal growth. This systematic review has shown that the studies on CVM method for radiographic assessment of skeletal maturation stages suffer from serious methodological failures. Better-designed studies with adequate accuracy, reproducibility, and correlation analysis, including studies with appropriate sensitivity-specificity analysis, should be performed.

  1. Correlation between chronological age, cervical vertebral maturation and Fishman's skeletal maturity indicators in southern Chinese.

    Science.gov (United States)

    Alkhal, Hessa Abdulla; Wong, Ricky W K; Rabie, A Bakr M

    2008-07-01

    To investigate the correlation between chronological age, cervical vertebral maturation (CVM), and Fishman's hand-wrist skeletal maturity indicators in southern Chinese. Four hundred contemporary hand-wrist and lateral cephalometric radiographs of southern Chinese subjects were randomly selected and analyzed. The female subjects were between 10 and 15 years of age, and the male subjects were between 12 and 17 years of age; all subjects were within the circumpubertal period. The CVM was assessed using the method developed by Baccetti and coworkers, but the hand-wrist maturation was assessed using the method developed by Fishman. These two methods and the chronological age were correlated using the Spearman rank correlation analysis. The CVM was significantly correlated with the hand-wrist skeletal age (Spearman r male = 0.9206, female = 0.9363). All patients in the cervical maturation stage (CS3) of CVM were discovered to be in the skeletal maturational indicator (SMI2 or SMI3) stages of hand-wrist maturation (HWM), which was around the peak of the growth spurt. Low correlations were found between the CVM and chronological age (male r = 0.7577; female r = 0.7877) and between the HWM and chronological age (male r = 0.7492; female r = 0.7758). CVM is a valid indicator of skeletal growth during the circumpubertal and has a high correlation with the HWM for the southern Chinese population. However, the low correlations found between the chronological age and both CVM and HWM showed that the chronological age was not suitable to measure skeletal maturity.

  2. Set-Theoretic Approach to Maturity Models

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan

    Despite being widely accepted and applied, maturity models in Information Systems (IS) have been criticized for the lack of theoretical grounding, methodological rigor, empirical validations, and ignorance of multiple and non-linear paths to maturity. This PhD thesis focuses on addressing...... these criticisms by incorporating recent developments in configuration theory, in particular application of set-theoretic approaches. The aim is to show the potential of employing a set-theoretic approach for maturity model research and empirically demonstrating equifinal paths to maturity. Specifically...... methodological guidelines consisting of detailed procedures to systematically apply set theoretic approaches for maturity model research and provides demonstrations of it application on three datasets. The thesis is a collection of six research papers that are written in a sequential manner. The first paper...

  3. Cofactor requirement of HpyAV restriction endonuclease.

    Directory of Open Access Journals (Sweden)

    Siu-Hong Chan

    Full Text Available BACKGROUND: Helicobacter pylori is the etiologic agent of common gastritis and a risk factor for gastric cancer. It is also one of the richest sources of Type II restriction-modification (R-M systems in microorganisms. PRINCIPAL FINDINGS: We have cloned, expressed and purified a new restriction endonuclease HpyAV from H. pylori strain 26695. We determined the HpyAV DNA recognition sequence and cleavage site as CCTTC 6/5. In addition, we found that HpyAV has a unique metal ion requirement: its cleavage activity is higher with transition metal ions than in Mg(++. The special metal ion requirement of HpyAV can be attributed to the presence of a HNH catalytic site similar to ColE9 nuclease instead of the canonical PD-X-D/EXK catalytic site found in many other REases. Site-directed mutagenesis was carried out to verify the catalytic residues of HpyAV. Mutation of the conserved metal-binding Asn311 and His320 to alanine eliminated cleavage activity. HpyAV variant H295A displayed approximately 1% of wt activity. CONCLUSIONS/SIGNIFICANCE: Some HNH-type endonucleases have unique metal ion cofactor requirement for optimal activities. Homology modeling and site-directed mutagenesis confirmed that HpyAV is a member of the HNH nuclease family. The identification of catalytic residues in HpyAV paved the way for further engineering of the metal binding site. A survey of sequenced microbial genomes uncovered 10 putative R-M systems that show high sequence similarity to the HpyAV system, suggesting lateral transfer of a prototypic HpyAV-like R-M system among these microorganisms.

  4. Tentative characterization of precursor compounds and co-factors of pigment formation in production of 'wu mi' from Vaccinium bracteatum Thunb. Leaves.

    Science.gov (United States)

    Fan, Mingcong; Fan, Yihui; Huang, Weiping; Wang, Li; Li, Yan; Qian, Haifeng; Zhang, Hui; Qi, Xiguang

    2018-10-01

    Vaccinium bracteatum leaves (VBTL) are traditionally used in China to dye rice grains, which assume a deep blue color, named 'Wu mi'. Information on the mechanism of pigment formation is limited. In this study, CIELAB color space parameters were used to represent the color of 'Wu mi'. Precursor compounds of pigments formed during the dyeing process were identified by UPLC Q-TOF MS analysis. The changes in co-factors for pigment formation in VBTL were measured at different growth stages. The L ∗ and b ∗ values of dyed rice increased as the leaves aged, whereas a ∗ values showed irregular changes. Six compounds were tentatively identified as pigment precursors by UPLC Q-TOF MS analysis. The pH and β-glucosidase activity at different growth stages of VBTL were indicated to be crucial co-factors for pigment formation. A tentative hypothesis is presented that iridoid glycosides are hydrolyzed by acids and β-glucosidases to form a dialdehyde structure that binds covalently with amino residues of lysine side chains in rice protein molecules. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Halogens are key cofactors in building of collagen IV scaffolds outside the cell.

    Science.gov (United States)

    Brown, Kyle L; Hudson, Billy G; Voziyan, Paul A

    2018-05-01

    The purpose of this review is to highlight recent advances in understanding the molecular assembly of basement membranes, as exemplified by the glomerular basement membrane (GBM) of the kidney filtration apparatus. In particular, an essential role of halogens in the basement membrane formation has been discovered. Extracellular chloride triggers a molecular switch within non collagenous domains of collagen IV that induces protomer oligomerization and scaffold assembly outside the cell. Moreover, bromide is an essential cofactor in enzymatic cross-linking that reinforces the stability of scaffolds. Halogenation and halogen-induced oxidation of the collagen IV scaffold in disease states damage scaffold function. Halogens play an essential role in the formation of collagen IV scaffolds of basement membranes. Pathogenic damage of these scaffolds by halogenation and halogen-induced oxidation is a potential target for therapeutic interventions.

  6. Sustaining Exploration in Mature Basins

    International Nuclear Information System (INIS)

    Bayo, A.

    2002-01-01

    Exploration is a business like any other business driven by opportunity, resources and expectation of profit. Therefore, exploration will thrive anywhere the opportunities are significant, the resources are available and the outlook for profit (or value creation) is good. To sustain exploration activities anywhere, irrespective of the environment, there must be good understanding of the drivers of these key investment criteria. This paper will examine these investment criteria as they relate to exploration business and address the peculiarity of exploration in mature basin. Mature basins are unique environment that lends themselves a mix of fears, paradigms and realities, particularly with respect to the perception of value. To sustain exploration activities in a mature basin, we need to understand these perceptions relative to the true drivers of profitability. Exploration in the mature basins can be as profitable as exploration in emerging basins if the dynamics of value definition-strategic and fiscal values are understood by operators, regulators and co ventures alike. Some suggestions are made in this presentation on what needs to be done in addressing these dynamic investment parameters and sustaining exploration activities in mature basins

  7. Cofactor specificity switch in Shikimate dehydrogenase by rational design and consensus engineering.

    Science.gov (United States)

    García-Guevara, Fernando; Bravo, Iris; Martínez-Anaya, Claudia; Segovia, Lorenzo

    2017-08-01

    Consensus engineering has been used to design more stable variants using the most frequent amino acid at each site of a multiple sequence alignment; sometimes consensus engineering modifies function, but efforts have mainly been focused on studying stability. Here we constructed a consensus Rossmann domain for the Shikimate dehydrogenase enzyme; separately we decided to switch the cofactor specificity through rational design in the Escherichia coli Shikimate dehydrogenase enzyme and then analyzed the effect of consensus mutations on top of our design. We found that consensus mutations closest to the 2' adenine moiety increased the activity in our design. Consensus engineering has been shown to result in more stable proteins and our findings suggest it could also be used as a complementary tool for increasing or modifying enzyme activity during design. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Characterization of a "TRAMP-like" co-factor of the human RNA exosome

    DEFF Research Database (Denmark)

    Christensen, Marianne Skovgaard; Kristiansen, Maiken Søndergaard; Lubas, Michal Szymon

    Genome-wide studies in yeast, plants and humans have revealed numerous new transcripts in what was previously thought to be silent DNA or junk DNA. One class of non-coding transcript discovered recently is the PROMoter uPstream Transcripts (PROMPTs), which is only seen upon depletion of the RNA...... exosome, the major 3’-5’ exonuclease complex in human cells. PROMPTs have a lot in common with the yeast Cryptic Unstable Transcripts (CUTs), which are degraded by the concerted effort of the exosome, and its co-factor complex TRAMP (Trf4p/Air1p/Mtr4p). We have identified human proteins with functional...... similarities to components of the yeast TRAMP complex, and show that these are involved in the degradation of PROMPTs. While, these proteins form transient complexes with the exosome, our preliminary results also indicate that complex formation can occur directly with catalytic components of the exosome...

  9. Conformational control of cofactors in nature: The effect of methoxy group orientation on the electronic structure of ubisemiquinone

    Science.gov (United States)

    De Almeida, Wagner B.; O'Malley, Patrick J.

    2018-03-01

    Ubiquinone is the key electron and proton transfer agent in biology. Its mechanism involves the formation of its intermediate one-electron reduced form, the ubisemiquinone radical. This is formed in a protein-bound form which permits the semiquinone to vary its electronic and redox properties. This can be achieved by hydrogen bonding acceptance by one or both oxygen atoms or as we now propose by restricted orientations for the methoxy groups of the headgroup. We show how the orientation of the two methoxy groups of the quinone headgroup affects the electronic structure of the semiquinone form and demonstrate a large dependence of the ubisemiquinone spin density distribution on the orientation each methoxy group takes with respect to the headgroup ring plane. This is shown to significantly modify associated hyperfine couplings which in turn needs to be accounted for in interpreting experimental values in vivo. The study uncovers the key potential role the methoxy group orientation can play in controlling the electronic structure and spin density of ubisemiquinone and provides an electronic-level insight into the variation in electron affinity and redox potential of ubiquinone as a function of the methoxy orientation. Taken together with the already known influence of cofactor conformation on heme and chlorophyll electronic structure, it reveals a more widespread role for cofactor conformational control of electronic structure and associated electron transfer in biology.

  10. Mechanism of the reaction of ebselen with endogenous thiols : dihydrolipoate is a better cofactor than glutathione in the peroxidase activity of ebselen

    NARCIS (Netherlands)

    Haenen, G R; De Rooij, B M; Vermeulen, N P; Bast, A

    The therapeutic effect of ebselen has been linked to its peroxidase activity. In the present study, the peroxidase activity of ebselen toward H2O2 with the endogenous thiols GSH and dihydrolipoate [L(SH)2] as cofactors was determined. When GSH was used, peroxide removal was described by a ter uni

  11. Bicarbonate Transport During Enamel Maturation.

    Science.gov (United States)

    Yin, Kaifeng; Paine, Michael L

    2017-11-01

    Amelogenesis (tooth enamel formation) is a biomineralization process consisting primarily of two stages (secretory stage and maturation stage) with unique features. During the secretory stage, the inner epithelium of the enamel organ (i.e., the ameloblast cells) synthesizes and secretes enamel matrix proteins (EMPs) into the enamel space. The protein-rich enamel matrix forms a highly organized architecture in a pH-neutral microenvironment. As amelogenesis transitions to maturation stage, EMPs are degraded and internalized by ameloblasts through endosomal-lysosomal pathways. Enamel crystallite formation is initiated early in the secretory stage, however, during maturation stage the more rapid deposition of calcium and phosphate into the enamel space results in a rapid expansion of crystallite length and mineral volume. During maturation-stage amelogenesis, the pH value of enamel varies considerably from slightly above neutral to acidic. Extracellular acid-base balance during enamel maturation is tightly controlled by ameloblast-mediated regulatory networks, which include significant synthesis and movement of bicarbonate ions from both the enamel papillary layer cells and ameloblasts. In this review we summarize the carbonic anhydrases and the carbonate transporters/exchangers involved in pH regulation in maturation-stage amelogenesis. Proteins that have been shown to be instrumental in this process include CA2, CA6, CFTR, AE2, NBCe1, SLC26A1/SAT1, SLC26A3/DRA, SLC26A4/PDS, SLC26A6/PAT1, and SLC26A7/SUT2. In addition, we discuss the association of miRNA regulation with bicarbonate transport in tooth enamel formation.

  12. Whose Maturity is it Anyway?

    DEFF Research Database (Denmark)

    Lasrado, Lester Allan; Vatrapu, Ravi; Mukkamala, Raghava Rao

    2017-01-01

    This paper presents results from an ongoing empirical study that seeks to understand the influence of different quantitative methods on the design and assessment of maturity models. Although there have been many academic publications on maturity models, there exists a significant lack of understa...

  13. Maturity of the PWR

    International Nuclear Information System (INIS)

    Bacher, P.; Rapin, M.; Aboudarham, L.; Bitsch, D.

    1983-03-01

    Figures illustrating the predominant position of the PWR system are presented. The question is whether on the basis of these figures the PWR can be considered to have reached maturity. The following analysis, based on the French program experience, is an attempt to pinpoint those areas in which industrial maturity of the PWR has been attained, and in which areas a certain evolution can still be expected to take place

  14. Metabolic Profiles in Ovine Carotid Arteries with Developmental Maturation and Long-Term Hypoxia.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available Long-term hypoxia (LTH is an important stressor related to health and disease during development. At different time points from fetus to adult, we are exposed to hypoxic stress because of placental insufficiency, high-altitude residence, smoking, chronic anemia, pulmonary, and heart disorders, as well as cancers. Intrauterine hypoxia can lead to fetal growth restriction and long-term sequelae such as cognitive impairments, hypertension, cardiovascular disorders, diabetes, and schizophrenia. Similarly, prolonged hypoxic exposure during adult life can lead to acute mountain sickness, chronic fatigue, chronic headache, cognitive impairment, acute cerebral and/or pulmonary edema, and death.LTH also can lead to alteration in metabolites such as fumarate, 2-oxoglutarate, malate, and lactate, which are linked to epigenetic regulation of gene expression. Importantly, during the intrauterine life, a fetus is under a relative hypoxic environment, as compared to newborn or adult. Thus, the changes in gene expression with development from fetus to newborn to adult may be as a consequence of underlying changes in the metabolic profile because of the hypoxic environment along with developmental maturation. To examine this possibility, we examined the metabolic profile in carotid arteries from near-term fetus, newborn, and adult sheep in both normoxic and long-term hypoxic acclimatized groups.Our results demonstrate that LTH differentially regulated glucose metabolism, mitochondrial metabolism, nicotinamide cofactor metabolism, oxidative stress and antioxidants, membrane lipid hydrolysis, and free fatty acid metabolism, each of which may play a role in genetic-epigenetic regulation.

  15. Intra-follicular interactions affecting mammalian oocyte maturation

    NARCIS (Netherlands)

    van Tol, H.T.A.|info:eu-repo/dai/nl/313871817

    2009-01-01

    Nuclear oocyte maturation is defined as reinitiation and progression of the first meiotic division and subsequently formation of the methaphase II (MII) plate. Concomitantly with nuclear maturation, cytoplasmic maturation which is essential for proper fertilization and early embryo development is

  16. Growth indicators in orthodontic patients. Part 1: comparison of cervical vertebral maturation and hand-wrist skeletal maturation.

    Science.gov (United States)

    Litsas, G; Ari-Demirkaya, A

    2010-12-01

    The purpose of this study was to predict the skeletal maturation status based on the assessment of cervical vertebrae from lateral cephalometric radiographs and to compare these findings with the skeletal maturity of the same individuals judged from the hand-wrist radiographs. Lateral cephalometric and left hand-wrist radiographs of 393 Caucasian children from 8 to 18 years old were evaluated. On the hand-wrist radiographs the classification of Bjork [1972] and Grave and Brown [1976] was used to assess skeletal maturity (HWSS). Cervical vertebral maturation was also evaluated on lateral cephalometric radiographs using the improved CVMS method described by Baccetti, Franchi, and McNamara [2002]. These methods were correlated using the chi-square test. The chi-square test showed that skeletal maturational values obtained by the CVMS method were significantly correlated with the skeletal values obtained from the hand-wrist analysis for both genders (pmaturity.

  17. Maturity acceleration of Italian dried sausage by Staphylococcus carnosus - Relationship between maturity and flavor compounds

    DEFF Research Database (Denmark)

    Stahnke, Louise Heller; Holck, A.; Jensen, Anni

    2002-01-01

    . Sausages with S. carnosus 833 matured more than 2 wk faster than control sausages. Maturity correlated significantly with higher amounts of branched-chain aldehydes and alcohols and both branched- and straight-chain methyl ketones-compounds arising from the breakdown of the amino acids leucine, isoleucine...

  18. A PACS maturity model: a systematic meta-analytic review on maturation and evolvability of PACS in the hospital enterprise.

    NARCIS (Netherlands)

    Wetering, R. van de; Batenburg, R.

    2009-01-01

    INTRODUCTION: With PACS and medical imaging technology maturing, the importance of organizational maturity and effective deployment of PACS in the hospital enterprise are becoming significant. OBJECTIVE: The objective of this paper is twofold. Firstly, PACS literature on maturity and evolvability in

  19. PROJECT MANAGEMENT MATURITY: AN ASSESSMENT OF MATURITY FOR DEVELOPING PILOT PLANTS

    Directory of Open Access Journals (Sweden)

    H.K. Mittermaier

    2012-01-01

    Full Text Available

    ENGLISH ABSTRACT: Despite the current economic climate, the South African mining and engineering industry is experiencing a very promising future, with a large number of capital projects in the offing. It is inevitable that pilot plant development will form part of this future as a risk mitigation technique. This study found that, even though the terms ‘pilot plant’ and ‘project management maturity’ are familiar within the industry, no link between these two could be found in the literature. A number of maturity models exist; and one developed by PMSolutions was selected to perform an assessment of the current level of project management maturity within the South African mining and engineering industry pertaining to the development of pilot plants. The Delphi technique was used to determine the views of experts in the South African mining, mineral processing, petrochemical, nuclear, and mechanical sectors regarding this maturity. A significant difference was observed between the current level of maturity and the required level of maturity in all but one of the nine knowledge areas defined by the Project Management Institute. The two knowledge areas of project time and risk management showed significant differences between current and required maturity levels, and were identified as key areas for improvement.

    AFRIKAANSE OPSOMMING: Ten spyte van die huidige ekonomiese klimaat ondervind die Suid-Afrikaanse mynbou- en ingenieursbedryf ’n baie bemoedigende toekoms, met ’n groot aantal kapitaalprojekte in die vooruitsig. Ten einde risiko’s te verlaag, sal die ontwikkeling van loodsaanlegte noodwendig deel van hierdie toekoms uitmaak. Daar is gevind dat, alhoewel die terme ‘loodsaanleg’ en ‘projekbestuur volwassenheid’ in die nywerheid bekend is, geen skakeling van hierdie twee terme in die literatuur opgespoor kon word nie. ’n Aantal volwassenheid modelle bestaan; en een wat deur PMSolutions ontwikkel is, is gekies om

  20. Rice Bran Metabolome Contains Amino Acids, Vitamins & Cofactors, and Phytochemicals with Medicinal and Nutritional Properties.

    Science.gov (United States)

    Zarei, Iman; Brown, Dustin G; Nealon, Nora Jean; Ryan, Elizabeth P

    2017-12-01

    Rice bran is a functional food that has shown protection against major chronic diseases (e.g. obesity, diabetes, cardiovascular disease and cancer) in animals and humans, and these health effects have been associated with the presence of bioactive phytochemicals. Food metabolomics uses multiple chromatography and mass spectrometry platforms to detect and identify a diverse range of small molecules with high sensitivity and precision, and has not been completed for rice bran. This study utilized global, non-targeted metabolomics to identify small molecules in rice bran, and conducted a comprehensive search of peer-reviewed literature to determine bioactive compounds. Three U.S. rice varieties (Calrose, Dixiebelle, and Neptune), that have been used for human dietary intervention trials, were assessed herein for bioactive compounds that have disease control and prevention properties. The profiling of rice bran by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) identified 453 distinct phytochemicals, 209 of which were classified as amino acids, cofactors & vitamins, and secondary metabolites, and were further assessed for bioactivity. A scientific literature search revealed 65 compounds with health properties, 16 of which had not been previously identified in rice bran. This suite of amino acids, cofactors & vitamins, and secondary metabolites comprised 46% of the identified rice bran metabolome, which substantially enhanced our knowledge of health-promoting rice bran compounds provided during dietary supplementation. Rice bran metabolite profiling revealed a suite of biochemical molecules that can be further investigated and exploited for multiple nutritional therapies and medical food applications. These bioactive compounds may also be biomarkers of dietary rice bran intake. The medicinal compounds associated with rice bran can function as a network across metabolic pathways and this

  1. TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins

    KAUST Repository

    Schaefer, Ulf; Schmeier, Sebastian; Bajic, Vladimir B.

    2010-01-01

    The initiation and regulation of transcription in eukaryotes is complex and involves a large number of transcription factors (TFs), which are known to bind to the regulatory regions of eukaryotic DNA. Apart from TF-DNA binding, protein-protein interaction involving TFs is an essential component of the machinery facilitating transcriptional regulation. Proteins that interact with TFs in the context of transcription regulation but do not bind to the DNA themselves, we consider transcription co-factors (TcoFs). The influence of TcoFs on transcriptional regulation and initiation, although indirect, has been shown to be significant with the functionality of TFs strongly influenced by the presence of TcoFs. While the role of TFs and their interaction with regulatory DNA regions has been well-studied, the association between TFs and TcoFs has so far been given less attention. Here, we present a resource that is comprised of a collection of human TFs and the TcoFs with which they interact. Other proteins that have a proven interaction with a TF, but are not considered TcoFs are also included. Our database contains 157 high-confidence TcoFs and additionally 379 hypothetical TcoFs. These have been identified and classified according to the type of available evidence for their involvement in transcriptional regulation and their presence in the cell nucleus. We have divided TcoFs into four groups, one of which contains high-confidence TcoFs and three others contain TcoFs which are hypothetical to different extents. We have developed the Dragon Database for Human Transcription Co-Factors and Transcription Factor Interacting Proteins (TcoF-DB). A web-based interface for this resource can be freely accessed at http://cbrc.kaust.edu.sa/tcof/ and http://apps.sanbi.ac.za/tcof/. © The Author(s) 2010.

  2. TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins

    KAUST Repository

    Schaefer, Ulf

    2010-10-21

    The initiation and regulation of transcription in eukaryotes is complex and involves a large number of transcription factors (TFs), which are known to bind to the regulatory regions of eukaryotic DNA. Apart from TF-DNA binding, protein-protein interaction involving TFs is an essential component of the machinery facilitating transcriptional regulation. Proteins that interact with TFs in the context of transcription regulation but do not bind to the DNA themselves, we consider transcription co-factors (TcoFs). The influence of TcoFs on transcriptional regulation and initiation, although indirect, has been shown to be significant with the functionality of TFs strongly influenced by the presence of TcoFs. While the role of TFs and their interaction with regulatory DNA regions has been well-studied, the association between TFs and TcoFs has so far been given less attention. Here, we present a resource that is comprised of a collection of human TFs and the TcoFs with which they interact. Other proteins that have a proven interaction with a TF, but are not considered TcoFs are also included. Our database contains 157 high-confidence TcoFs and additionally 379 hypothetical TcoFs. These have been identified and classified according to the type of available evidence for their involvement in transcriptional regulation and their presence in the cell nucleus. We have divided TcoFs into four groups, one of which contains high-confidence TcoFs and three others contain TcoFs which are hypothetical to different extents. We have developed the Dragon Database for Human Transcription Co-Factors and Transcription Factor Interacting Proteins (TcoF-DB). A web-based interface for this resource can be freely accessed at http://cbrc.kaust.edu.sa/tcof/ and http://apps.sanbi.ac.za/tcof/. © The Author(s) 2010.

  3. Maturation of the human fetal startle response: evidence for sex-specific maturation of the human fetus.

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M; Sandman, Curt A

    2009-10-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks' GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks' GA, females however, presented with a mature FHR startle response by 31 weeks' GA. The results indicate that there are different rates of maturation in the male and female fetuses that may have implications for sex-specific programming influences.

  4. Assessment of skeletal maturation using mandibular second molar maturation stages.

    Science.gov (United States)

    Goyal, S; Goyal, S; Gugnani, N

    2014-01-01

    To investigate the relationship between cervical vertebrae maturation and mandibular second molar calcification stages. The study was designed as a retrospective, descriptive and crosssectional research project. Pre-treatment lateral cephalograms and panoramic radiographs of 99 males and 110 females in the age range of 7 to 18 years 7 months were evaluated with Demirjian Index (DI) and cervical vertebrae maturation indicators (CVMI) of Hassel and Farman. A null hypothesis was proposed that there is no relation between CVMI and DI. A highly significant association (Pearson's contingency coefficient 0.713 for males and 0.863 for females) was found between DI and CVMI. In males, the DI stage E corresponded to stage 2 of CVMI (pre-peak of pubertal growth spurt) and DI stages F and G corresponded to stages 3 and 4 of CVMI (peak of pubertal growth spurt). DI stage H was associated with stages 5 and 6 of CVMI (end of pubertal growth spurt). In females, the DI stages C, D corresponded to CVMI stages 1, 2; DI stages E, F with CVMI stages 3, 4; DI stages G, H with CVMI stages 5, 6. Mandibular second molar calcification stages can be used as indicators for assessment of skeletal maturity.

  5. A Set Theoretical Approach to Maturity Models

    DEFF Research Database (Denmark)

    Lasrado, Lester; Vatrapu, Ravi; Andersen, Kim Normann

    2016-01-01

    characterized by equifinality, multiple conjunctural causation, and case diversity. We prescribe methodological guidelines consisting of a six-step procedure to systematically apply set theoretic methods to conceptualize, develop, and empirically derive maturity models and provide a demonstration......Maturity Model research in IS has been criticized for the lack of theoretical grounding, methodological rigor, empirical validations, and ignorance of multiple and non-linear paths to maturity. To address these criticisms, this paper proposes a novel set-theoretical approach to maturity models...

  6. A maturity model for blockchain adoption

    OpenAIRE

    Wang, Huaiqing; Chen, Kun; Xu, Dongming

    2016-01-01

    Background: The rapid development of the blockchain technology and its various applications has rendered it important to understand the guidelines for adopting it. Methods: The comparative analysis method is used to analyze different dimensions of the maturity model, which is mainly based on the commonly used capability maturity model. Results: The blockchain maturity model and its adoption process have been discussed and presented. Conclusions: This study serves as a guide to institutions to...

  7. Structural basis of thermal stability of the tungsten cofactor synthesis protein MoaB from Pyrococcus furiosus.

    Directory of Open Access Journals (Sweden)

    Nastassia Havarushka

    Full Text Available Molybdenum and tungsten cofactors share a similar pterin-based scaffold, which hosts an ene-dithiolate function being essential for the coordination of either molybdenum or tungsten. The biosynthesis of both cofactors involves a multistep pathway, which ends with the activation of the metal binding pterin (MPT by adenylylation before the respective metal is incorporated. In the hyperthermophilic organism Pyrococcus furiosus, the hexameric protein MoaB (PfuMoaB has been shown to catalyse MPT-adenylylation. Here we determined the crystal structure of PfuMoaB at 2.5 Å resolution and identified key residues of α3-helix mediating hexamer formation. Given that PfuMoaB homologues from mesophilic organisms form trimers, we investigated the impact on PfuMoaB hexamerization on thermal stability and activity. Using structure-guided mutagenesis, we successfully disrupted the hexamer interface in PfuMoaB. The resulting PfuMoaB-H3 variant formed monomers, dimers and trimers as determined by size exclusion chromatography. Circular dichroism spectroscopy as well as chemical cross-linking coupled to mass spectrometry confirmed a wild-type-like fold of the protomers as well as inter-subunits contacts. The melting temperature of PfuMoaB-H3 was found to be reduced by more than 15 °C as determined by differential scanning calorimetry, thus demonstrating hexamerization as key determinant for PfuMoaB thermal stability. Remarkably, while a loss of activity at temperatures higher than 50 °C was observed in the PfuMoaB-H3 variant, at lower temperatures, we determined a significantly increased catalytic activity. The latter suggests a gain in conformational flexibility caused by the disruption of the hexamerization interface.

  8. Integrating biocompatible chemistry and manipulating cofactor partitioning in metabolically engineeredLactococcus lactisfor fermentative production of (3S)-acetoin

    DEFF Research Database (Denmark)

    Liu, Jianming; Solem, Christian; Jensen, Peter Ruhdal

    2016-01-01

    Biocompatible chemistry (BC), i.e. non-enzymatic chemical reactions compatible with living organisms, is increasingly used in conjunction with metabolically engineered microorganisms for producing compounds that do not usually occur naturally. Here we report production of one such compound, (3S......)-acetoin, a valuable precursor for chiral synthesis, using a metabolically engineered Lactococcus lactis strain growing under respiratory conditions with ferric iron serving as a BC component. The strain used has all competing product pathways inactivated, and an appropriate cofactor balance is achieved by fine...

  9. Mature students' perspectives of studying radiography

    International Nuclear Information System (INIS)

    Williams, M.; Decker, S.

    2009-01-01

    The study set out to explore the experiences of all final year mature students on a diagnostic radiography course, in one United Kingdom University. The aims were to identify any difficulties they may have had and to make recommendations to improve mature students' learning experiences with the hope of lowering attrition rates in this group. A qualitative study involving one-to-one audio recorded interviews was utilised. Analysis of the transcripts of interviews suggested that the group believed that their maturity and previous experiences helped them in the clinical environment and put them in a good position, when asked, to counsel younger students. However for some of the mature students these experiential skills did not extend fully into seeking appropriate support for themselves. The mature students were found to be highly motivated but there was a conflict between balancing clinical and academic aspects of studying as well as balancing studying with home life. The group was found to be unprepared for the volume of academic work and its detrimental effect on family life as they sacrificed other aspects of their lives in order to complete the course. It is recommended that forewarning and forearming prospective mature students be considered by radiography education providers. Setting up and utilising an on-line forum providing a 24/7 peer support environment would aid in coping with academic, clinical or personal problems

  10. Molybdenum cofactor deficiency causes translucent integument, male-biased lethality, and flaccid paralysis in the silkworm Bombyx mori.

    Science.gov (United States)

    Fujii, Tsuguru; Yamamoto, Kimiko; Banno, Yutaka

    2016-06-01

    Uric acid accumulates in the epidermis of Bombyx mori larvae and renders the larval integument opaque and white. Yamamoto translucent (oya) is a novel spontaneous mutant with a translucent larval integument and unique phenotypic characteristics, such as male-biased lethality and flaccid larval paralysis. Xanthine dehydrogenase (XDH) that requires a molybdenum cofactor (MoCo) for its activity is a key enzyme for uric acid synthesis. It has been observed that injection of a bovine xanthine oxidase, which corresponds functionally to XDH and contains its own MoCo activity, changes the integuments of oya mutants from translucent to opaque and white. This finding suggests that XDH/MoCo activity might be defective in oya mutants. Our linkage analysis identified an association between the oya locus and chromosome 23. Because XDH is not linked to chromosome 23 in B. mori, MoCo appears to be defective in oya mutants. In eukaryotes, MoCo is synthesized by a conserved biosynthesis pathway governed by four loci (MOCS1, MOCS2, MOCS3, and GEPH). Through a candidate gene approach followed by sequence analysis, a 6-bp deletion was detected in an exon of the B. mori molybdenum cofactor synthesis-step 1 gene (BmMOCS1) in the oya strain. Moreover, recombination was not observed between the oya and BmMOCS1 loci. These results indicate that the BmMOCS1 locus is responsible for the oya locus. Finally, we discuss the potential cause of male-biased lethality and flaccid paralysis observed in the oya mutants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Roles of Fe-S proteins: from cofactor synthesis to iron homeostasis to protein synthesis.

    Science.gov (United States)

    Pain, Debkumar; Dancis, Andrew

    2016-06-01

    Fe-S cluster assembly is an essential process for all cells. Impairment of Fe-S cluster assembly creates diseases in diverse and surprising ways. In one scenario, the loss of function of lipoic acid synthase, an enzyme with Fe-S cluster cofactor in mitochondria, impairs activity of various lipoamide-dependent enzymes with drastic consequences for metabolism. In a second scenario, the heme biosynthetic pathway in red cell precursors is specifically targeted, and iron homeostasis is perturbed, but lipoic acid synthesis is unaffected. In a third scenario, tRNA modifications arising from action of the cysteine desulfurase and/or Fe-S cluster proteins are lost, which may lead to impaired protein synthesis. These defects can then result in cancer, neurologic dysfunction or type 2 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Relocalization of human chromatin remodeling cofactor TIP48 in mitosis

    International Nuclear Information System (INIS)

    Sigala, Barbara; Edwards, Mina; Puri, Teena; Tsaneva, Irina R.

    2005-01-01

    TIP48 is a highly conserved eukaryotic AAA + protein which is an essential cofactor for several complexes involved in chromatin acetylation and remodeling, transcriptional and developmental regulation and nucleolar organization and trafficking. We show that TIP48 abundance in HeLa cells did not change during the cell cycle, nor did its distribution in various biochemical fractions. However, we observed distinct changes in the subcellular localization of TIP48 during M phase using immunofluorescence microscopy. Our studies demonstrate that in interphase cells TIP48 was found mainly in the nucleus and exhibited a distinct localization in the nuclear periphery. As the cells entered mitosis, TIP48 was excluded from the condensing chromosomes but showed association with the mitotic apparatus. During anaphase, some TIP48 was detected in the centrosome colocalizing with tubulin but the strongest staining appeared in the mitotic equator associated with the midzone central spindle. Accumulation of TIP48 in the midzone and the midbody was observed in late telophase and cytokinesis. This redeployment of TIP48 during anaphase and cytokinesis was independent of microtubule assembly. The relocation of endogenous TIP48 to the midzone/midbody under physiological conditions suggests a novel and distinct function for TIP48 in mitosis and possible involvement in the exit of mitosis

  13. Relationship between cervical vertebral maturation and mandibular growth.

    Science.gov (United States)

    Ball, Gina; Woodside, Donald; Tompson, Bryan; Hunter, W Stuart; Posluns, James

    2011-05-01

    The cervical vertebrae have been proposed as a method of determining biologic maturity. The purposes of this study were to establish a pattern of mandibular growth and to relate this pattern to the stages of cervical vertebral maturation. Cephalometric radiographs, taken annually from ages 9 to 18 years, were evaluated for 90 boys from the Burlington Growth Center, Toronto, Ontario, Canada. Mandibular lengths were measured from articulare to gnathion, and incremental growth was determined. Cervical vertebral maturation stages were assessed by using a 6-stage method. Advanced, average, and delayed maturation groups were established. The prepubertal mandibular growth minimum velocity occurred during cervical stages 1 through 4 (P = 0.7327). Peak mandibular growth velocity occurred most frequently during stage 4 in all 3 maturation groups, with a statistical difference in the average and delayed groups (P cervical stages 1 through 6 does not occur annually; time spent in each stage varies depending on the stage and the maturation group. Cervical vertebral maturation stages cannot accurately identify the mandibular prepubertal growth minimum and therefore cannot predict the onset of the peak in mandibular growth. The cervical vertebral maturation stages should be used with other methods of biologic maturity assessment when considering both dentofacial orthopedic treatment and orthognathic surgery. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  14. Effects of Crocin Supplementation during In Vitro Maturation of Mouse Oocytes on Glutathione Synthesis and Cytoplasmic Maturation

    Directory of Open Access Journals (Sweden)

    Elham Mokhber Maleki

    2016-05-01

    Full Text Available Background: Crocin is an active ingredient of saffron (Crocus sativus L. and its antioxidant properties have been previously investigated. This carotenoid scavenges free radicals and stimulates glutathione (GSH synthesis; consequently, it may protect cells against oxidative stress. The aim of this research is to protect oocytes from oxidative stress by the addition of a natural source antioxidant. Materials and Methods: In the present in vitro experimental study, we collected cumulus oocyte complexes (COCs from mouse ovaries of euthanized, 6-8 week-old female Naval Medical Research Institute (NMRI mice. Oocytes were subjected to in vitro maturation (IVM in the presence of either crocin (5 or 10 μg/ml, 5 mM buthionine-[S-R]- sulfoximine (BSO, or the combination of crocin plus BSO. Oocytes that matured in vitro in a medium without crocin or BSO supplements were considered as controls. Following 16-18 hours of IVM, matured oocytes (n=631 were fertilized by capacitated sperm from NMRI male mice, and cultured in vitro for up to 96 hours to assess preimplantation embryonic development. The levels of GSH in metaphase II (MII oocytes after IVM (n=240 were also assessed by the 5, 5-dithio-bis (2-nitrobenzoic acid (DTNB-GSH reductase recycling assay. Results: Supplementation of IVM media with 10 μg/ml crocin significantly (P<0.05 increased nuclear maturation, preimplantation development and GSH concentrations compared with the control group. Maturation of oocytes in IVM medium supplemented with BSO alone or the combination of 5 μg/ml crocin and BSO drastically decreased GSH concentrations and subsequently resulted in low rates of maturation, fertilization and blastocyst development. However, the combination of 10 μg/ml crocin with 5 mM BSO increased the level of nuclear maturation which was comparable to the control group. Conclusion: Supplementation of IVM media with crocin can improve nuclear maturation rates and subsequent developmental potential

  15. The allosteric HIV-1 integrase inhibitor BI-D affects virion maturation but does not influence packaging of a functional RNA genome.

    Directory of Open Access Journals (Sweden)

    Nikki van Bel

    Full Text Available The viral integrase (IN is an essential protein for HIV-1 replication. IN inserts the viral dsDNA into the host chromosome, thereby aided by the cellular co-factor LEDGF/p75. Recently a new class of integrase inhibitors was described: allosteric IN inhibitors (ALLINIs. Although designed to interfere with the IN-LEDGF/p75 interaction to block HIV DNA integration during the early phase of HIV-1 replication, the major impact was surprisingly found on the process of virus maturation during the late phase, causing a reverse transcription defect upon infection of target cells. Virus particles produced in the presence of an ALLINI are misformed with the ribonucleoprotein located outside the virus core. Virus assembly and maturation are highly orchestrated and regulated processes in which several viral proteins and RNA molecules closely interact. It is therefore of interest to study whether ALLINIs have unpredicted pleiotropic effects on these RNA-related processes. We confirm that the ALLINI BI-D inhibits virus replication and that the produced virus is non-infectious. Furthermore, we show that the wild-type level of HIV-1 genomic RNA is packaged in virions and these genomes are in a dimeric state. The tRNAlys3 primer for reverse transcription was properly placed on this genomic RNA and could be extended ex vivo. In addition, the packaged reverse transcriptase enzyme was fully active when extracted from virions. As the RNA and enzyme components for reverse transcription are properly present in virions produced in the presence of BI-D, the inhibition of reverse transcription is likely to reflect the mislocalization of the components in the aberrant virus particle.

  16. The allosteric HIV-1 integrase inhibitor BI-D affects virion maturation but does not influence packaging of a functional RNA genome.

    Science.gov (United States)

    van Bel, Nikki; van der Velden, Yme; Bonnard, Damien; Le Rouzic, Erwann; Das, Atze T; Benarous, Richard; Berkhout, Ben

    2014-01-01

    The viral integrase (IN) is an essential protein for HIV-1 replication. IN inserts the viral dsDNA into the host chromosome, thereby aided by the cellular co-factor LEDGF/p75. Recently a new class of integrase inhibitors was described: allosteric IN inhibitors (ALLINIs). Although designed to interfere with the IN-LEDGF/p75 interaction to block HIV DNA integration during the early phase of HIV-1 replication, the major impact was surprisingly found on the process of virus maturation during the late phase, causing a reverse transcription defect upon infection of target cells. Virus particles produced in the presence of an ALLINI are misformed with the ribonucleoprotein located outside the virus core. Virus assembly and maturation are highly orchestrated and regulated processes in which several viral proteins and RNA molecules closely interact. It is therefore of interest to study whether ALLINIs have unpredicted pleiotropic effects on these RNA-related processes. We confirm that the ALLINI BI-D inhibits virus replication and that the produced virus is non-infectious. Furthermore, we show that the wild-type level of HIV-1 genomic RNA is packaged in virions and these genomes are in a dimeric state. The tRNAlys3 primer for reverse transcription was properly placed on this genomic RNA and could be extended ex vivo. In addition, the packaged reverse transcriptase enzyme was fully active when extracted from virions. As the RNA and enzyme components for reverse transcription are properly present in virions produced in the presence of BI-D, the inhibition of reverse transcription is likely to reflect the mislocalization of the components in the aberrant virus particle.

  17. 7 CFR 1421.101 - Maturity dates.

    Science.gov (United States)

    2010-01-01

    ... filed and disbursed except, for transferred marketing assistance loan collateral. The maturity date for transferred marketing assistance loan collateral will be the maturity date applicable to the original loan... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS GRAINS AND SIMILARLY HANDLED COMMODITIES-MARKETING...

  18. A Systematic Literature Review of Agile Maturity Model Research

    Directory of Open Access Journals (Sweden)

    Vaughan Henriques

    2017-02-01

    Full Text Available Background/Aim/Purpose: A commonly implemented software process improvement framework is the capability maturity model integrated (CMMI. Existing literature indicates higher levels of CMMI maturity could result in a loss of agility due to its organizational focus. To maintain agility, research has focussed attention on agile maturity models. The objective of this paper is to find the common research themes and conclusions in agile maturity model research. Methodology: This research adopts a systematic approach to agile maturity model research, using Google Scholar, Science Direct, and IEEE Xplore as sources. In total 531 articles were initially found matching the search criteria, which was filtered to 39 articles by applying specific exclusion criteria. Contribution:: The article highlights the trends in agile maturity model research, specifically bringing to light the lack of research providing validation of such models. Findings: Two major themes emerge, being the coexistence of agile and CMMI and the development of agile principle based maturity models. The research trend indicates an increase in agile maturity model articles, particularly in the latter half of the last decade, with concentrations of research coinciding with version updates of CMMI. While there is general consensus around higher CMMI maturity levels being incompatible with true agility, there is evidence of the two coexisting when agile is introduced into already highly matured environments. Future Research:\tFuture research direction for this topic should include how to attain higher levels of CMMI maturity using only agile methods, how governance is addressed in agile environments, and whether existing agile maturity models relate to improved project success.

  19. Customer-Provider Strategic Alignment: A Maturity Model

    Science.gov (United States)

    Luftman, Jerry; Brown, Carol V.; Balaji, S.

    This chapter presents a new model for assessing the maturity of a ­customer-provider relationship from a collaborative service delivery perspective: the Customer-Provider Strategic Alignment Maturity (CPSAM) Model. This model builds on recent research for effectively managing the customer-provider relationship in IT service outsourcing contexts and a validated model for assessing alignment across internal IT service units and their business customers within the same organization. After reviewing relevant literature by service science and information systems researchers, the six overarching components of the maturity model are presented: value measurements, governance, partnership, communications, human resources and skills, and scope and architecture. A key assumption of the model is that all of the components need be addressed to assess and improve customer-provider alignment. Examples of specific metrics for measuring the maturity level of each component over the five levels of maturity are also presented.

  20. Maturation of the human fetal startle response: Evidence for sex-specific maturation of the human fetus1

    Science.gov (United States)

    Buss, Claudia; Davis, Elysia Poggi; Class, Quetzal A.; Gierczak, Matt; Pattillo, Carol; Glynn, Laura M.; Sandman, Curt A.

    2009-01-01

    Despite the evidence for early fetal experience exerting programming influences on later neurological development and health risk, very few prospective studies of human fetal behavior have been reported. In a prospective longitudinal study, fetal nervous system maturation was serially assessed by monitoring fetal heart rate (FHR) responses to vibroacoustic stimulation (VAS) in 191 maternal/fetal dyads. Responses were not detected at 26 weeks gestational age (GA). Sex-specific, age-characteristic changes in the FHR response to VAS were observed by 31 weeks’ GA. Males showed larger responses and continued to exhibit maturational changes until 37 weeks’ GA, females however, presented with a mature FHR startle response by 31 weeks’ GA. The results indicate that there are different rates of maturation in the male and female fetus that may have implications for sex-specific programming influences. PMID:19726143

  1. NMR analysis of the dynamic exchange of the NS2B cofactor between open and closed conformations of the West Nile virus NS2B-NS3 protease.

    Directory of Open Access Journals (Sweden)

    Xun-Cheng Su

    Full Text Available BACKGROUND: The two-component NS2B-NS3 proteases of West Nile and dengue viruses are essential for viral replication and established targets for drug development. In all crystal structures of the proteases to date, the NS2B cofactor is located far from the substrate binding site (open conformation in the absence of inhibitor and lining the substrate binding site (closed conformation in the presence of an inhibitor. METHODS: In this work, nuclear magnetic resonance (NMR spectroscopy of isotope and spin-labeled samples of the West Nile virus protease was used to investigate the occurrence of equilibria between open and closed conformations in solution. FINDINGS: In solution, the closed form of the West Nile virus protease is the predominant conformation irrespective of the presence or absence of inhibitors. Nonetheless, dissociation of the C-terminal part of the NS2B cofactor from the NS3 protease (open conformation occurs in both the presence and the absence of inhibitors. Low-molecular-weight inhibitors can shift the conformational exchange equilibria so that over 90% of the West Nile virus protease molecules assume the closed conformation. The West Nile virus protease differs from the dengue virus protease, where the open conformation is the predominant form in the absence of inhibitors. CONCLUSION: Partial dissociation of NS2B from NS3 has implications for the way in which the NS3 protease can be positioned with respect to the host cell membrane when NS2B is membrane associated via N- and C-terminal segments present in the polyprotein. In the case of the West Nile virus protease, discovery of low-molecular-weight inhibitors that act by breaking the association of the NS2B cofactor with the NS3 protease is impeded by the natural affinity of the cofactor to the NS3 protease. The same strategy can be more successful in the case of the dengue virus NS2B-NS3 protease.

  2. A correlative study of dental age and skeletal maturation.

    Science.gov (United States)

    Sachan, Kiran; Sharma, Vijay Prakash; Tandon, Pradeep

    2011-01-01

    Skeletal age had been assessed by comparison between maturation of hand-wrist with stages of cervical vertebrae or canine calcification stages in past and this had been closely related to craniofacial growth. The importance of pubertal growth spurt in various types of orthodontic therapies is already established. Hence, this study was aimed to evaluate the relationship of skeletal maturity by hand-wrist with cervical vertebral maturation indicators and canine calcification stages. The study consisted of randomly selected 90 children from Lucknow population with 45 males (age range 10-13 years) and 45 females (age range 9-12 years). Lateral Cephalogram, hand-wrist x-ray, and periapical x-rays of maxillary and mandibular right canines were taken. Mean, standard deviation was calculated of different groups. Correlation was made among cervical vertebral maturation, hand wrist maturation, and canine calcification stages at various age groups. There was strong correlation between skeletal maturation indicator and cervical vertebral maturation indicator for both male (0.849) and female (0.932), whereas correlation between skeletal maturation indicator and canine calcification was good for both male and female (0.635, 0.891). It was concluded that cervical vertebral maturation indicator and canine calcification stages can also be used for assessing skeletal maturity.

  3. Maturation of sugar maple seed

    Science.gov (United States)

    Clayton M., Jr. Carl; Albert G., Jr. Snow; Albert G. Snow

    1971-01-01

    The seeds of a sugar maple tree (Acer saccharum Marsh.) do not mature at the same time every year. And different trees mature their seeds at different times. So time of year is not a reliable measure of when seeds are ripe. Better criteria are needed. In recent studies we have found that moisture content and color are the best criteria for judging when sugar maple...

  4. Assessing organisational governance maturity: A retail industry case study

    Directory of Open Access Journals (Sweden)

    Hendrik Marius Wessels

    2016-05-01

    Full Text Available For any business to operate effectively, a governance framework that operates at the relevant maturity level is required. An organisational governance maturity framework is a tool that leadership can use to determine governance maturity. This study aims to determine whether the organisational governance maturity framework (developed by Wilkinson can be applied to the selected retail industry organisation to assess the maturity of the organisation’s governance, limited to the ‘leadership’ attribute. Firstly, a high-level literature review on ethical leadership, ethical decision-making, ethical foundation and culture (‘tone at the top’, and organisational governance and maturity was conducted. Secondly, a Johannesburg Stock Exchange (JSE listed South African-based company was selected for the empirical part of the study using a single case study research design. The empirical results confirmed that the organisational governance maturity framework can be used to determine the maturity level of organisational governance for the selected attribute of ‘leadership’

  5. Towards a Sustainable Design for Maturity Measurement Marketplace

    DEFF Research Database (Denmark)

    Lasrado, Lester; Vatrapu, Ravi; Kærsgaard, Henrik Bjerre

    2016-01-01

    In this research-in-progress paper, we propose a solution in form of an IT artefact to address both theoretical and practical challenges faced by maturity model designers. We identify and list out the existing challenges & criticisms of maturity models research through an extensive literature...... review, followed by semi-structured interviews with four maturity model designers. We also explore different motivations of building a maturity model, and using them further scope the boundaries of our solution....

  6. The crystal structure of escherichia coli MoaB suggests a probable role in molybdenum cofactor synthesis

    International Nuclear Information System (INIS)

    Sanishvili, R.; Beasley, S.; Skarina, T; Glesne, D; Joachimiak, A; Edwards, A; Savchenko, A.; Univ. Health Network; Univ. of Toronto

    2004-01-01

    The crystal structure of Escherichia coli MoaB was determined by multiwavelength anomalous diffraction phasing and refined at 1.6 Angstrom resolution. The molecule displayed a modified Rossman fold. MoaB is assembled into a hexamer composed of two trimers. The monomers have high structural similarity with two proteins, MogA and MoeA, from the molybdenum cofactor synthesis pathway in E. Coli, as well as with domains of mammalian gephyrin and plant Cnx1, which are also involved in molybdopterin synthesis. Structural comparison between these proteins and the amino acid conservation patterns revealed a putative active site in MoaB. The structural analysis of this site allowed to advance several hypothesis which can be tested in further studies

  7. Game Maturity Model for Health Care.

    Science.gov (United States)

    de Boer, Jan C; Adriani, Paul; van Houwelingen, Jan Willem; Geerts, A

    2016-04-01

    This article introduces the Game Maturity Model for the healthcare industry as an extension to the general Game Maturity Model and describes the usage by two case studies of applied health games. The Game Maturity Model for healthcare provides a practical and value-adding method to assess existing games and to determine strategic considerations for application of applied health games. Our forecast is that within 5 years the use and development of applied games will have a role in our daily lives and the way we organize health care that will be similar to the role social media has today.

  8. A novel conserved isoform of the ubiquitin ligase UFD2a/UBE4B is expressed exclusively in mature striated muscle cells.

    Directory of Open Access Journals (Sweden)

    Andrew L Mammen

    Full Text Available Yeast Ufd2p was the first identified E4 multiubiquitin chain assembly factor. Its vertebrate homologues later referred to as UFD2a, UBE4B or E4B were also shown to have E3 ubiquitin ligase activity. UFD2a function in the brain has been well established in vivo, and in vitro studies have shown that its activity is essential for proper condensation and segregation of chromosomes during mitosis. Here we show that 2 alternative splice forms of UFD2a, UFD2a-7 and -7/7a, are expressed sequentially during myoblast differentiation of C2C12 cell cultures and during cardiotoxin-induced regeneration of skeletal muscle in mice. UFD2a-7 contains an alternate exon 7, and UFD2a-7/7a, the larger of the 2 isoforms, contains an additional novel exon 7a. Analysis of protein or mRNA expression in mice and zebrafish revealed that a similar pattern of isoform switching occurs during developmental myogenesis of cardiac and skeletal muscle. In vertebrates (humans, rodents, zebrafish, UFD2a-7/7a is expressed only in mature striated muscle. This unique tissue specificity is further validated by the conserved presence of 2 muscle-specific splicing regulatory motifs located in the 3' introns of exons 7 and 7a. UFD2a interacts with VCP/p97, an AAA-type ATPase implicated in processes whose functions appear to be regulated, in part, through their interaction with one or more of 15 previously identified cofactors. UFD2a-7/7a did not interact with VCP/p97 in yeast 2-hybrid experiments, which may allow the ATPase to bind cofactors that facilitate its muscle-specific functions. We conclude that the regulated expression of these UFD2a isoforms most likely imparts divergent functions that are important for myogenisis.

  9. Vegetative propagation of mature and juvenile northern red oak

    Science.gov (United States)

    James J. Zaczek; K. C. Steiner; C. W., Jr. Heuser

    1993-01-01

    Rooting trials were established to evaluate rooting success of cuttings from mature and juvenile, grafted and ungrafted northern red oak (NRO). Buds from 4 mature NRO ortets and juvenile seedlings were grafted onto juvenile and mature rootstock. Cuttings were collected from the grafts and from juvenile and mature shoots developed in situ and...

  10. Decision-Making Style and Vocational Maturity.

    Science.gov (United States)

    Phillips, Susan D.; Strohmer, Douglas C.

    1982-01-01

    Examined the relationship between decision-making style, scholastic achievement, and vocational maturity for college students (N=64). Results did not support the hypothesized relationship between rationality and attitudinal and cognitive maturity. Scholastic achievement and lack of dependent decision style were found to be moderately predictive of…

  11. Color back projection for fruit maturity evaluation

    Science.gov (United States)

    Zhang, Dong; Lee, Dah-Jye; Desai, Alok

    2013-12-01

    In general, fruits and vegetables such as tomatoes and dates are harvested before they fully ripen. After harvesting, they continue to ripen and their color changes. Color is a good indicator of fruit maturity. For example, tomatoes change color from dark green to light green and then pink, light red, and dark red. Assessing tomato maturity helps maximize its shelf life. Color is used to determine the length of time the tomatoes can be transported. Medjool dates change color from green to yellow, and the orange, light red and dark red. Assessing date maturity helps determine the length of drying process to help ripen the dates. Color evaluation is an important step in the processing and inventory control of fruits and vegetables that directly affects profitability. This paper presents an efficient color back projection and image processing technique that is designed specifically for real-time maturity evaluation of fruits. This color processing method requires very simple training procedure to obtain the frequencies of colors that appear in each maturity stage. This color statistics is used to back project colors to predefined color indexes. Fruit maturity is then evaluated by analyzing the reprojected color indexes. This method has been implemented and used for commercial production.

  12. Putative endogenous filovirus VP35-like protein potentially functions as an IFN antagonist but not a polymerase cofactor.

    Directory of Open Access Journals (Sweden)

    Tatsunari Kondoh

    Full Text Available It has been proposed that some non-retroviral RNA virus genes are integrated into vertebrate genomes. Endogenous filovirus-like elements (EFLs have been discovered in some mammalian genomes. However, their potential roles in ebolavirus infection are unclear. A filovirus VP35-like element (mlEFL35 is found in the little brown bat (Myotis lucifugus genome. Putative mlEFL35-derived protein (mlEFL35p contains nearly full-length amino acid sequences corresponding to ebolavirus VP35. Ebola virus VP35 has been shown to bind double-stranded RNA, leading to inhibition of type I interferon (IFN production, and is also known as a viral polymerase cofactor that is essential for viral RNA transcription/replication. In this study, we transiently expressed mlEFL35p in human kidney cells and investigated its biological functions. We first found that mlEFL35p was coimmunoprecipitated with itself and ebolavirus VP35s but not with the viral nucleoprotein. Then the biological functions of mlEFL35p were analyzed by comparing it to ebolavirus VP35s. We found that the expression of mlEFL35p significantly inhibited human IFN-β promoter activity as well as VP35s. By contrast, expression of mlEFL35p did not support viral RNA transcription/replication and indeed slightly decrease the reporter gene expression in a minigenome assay. These results suggest that mlEFL35p potentially acts as an IFN antagonist but not a polymerase cofactor.

  13. Thiamin diphosphate in biological chemistry: new aspects of thiamin metabolism, especially triphosphate derivatives acting other than as cofactors.

    Science.gov (United States)

    Bettendorff, Lucien; Wins, Pierre

    2009-06-01

    Prokaryotes, yeasts and plants synthesize thiamin (vitamin B1) via complex pathways. Animal cells capture the vitamin through specific high-affinity transporters essential for internal thiamin homeostasis. Inside the cells, thiamin is phosphorylated to higher phosphate derivatives. Thiamin diphosphate (ThDP) is the best-known thiamin compound because of its role as an enzymatic cofactor. However, in addition to ThDP, at least three other thiamin phosphates occur naturally in most cells: thiamin monophosphate, thiamin triphosphate (ThTP) and the recently discovered adenosine thiamin triphosphate. It has been suggested that ThTP has a specific neurophysiological role, but recent data favor a much more basic metabolic function. During amino acid starvation, Escherichia coli accumulate ThTP, possibly acting as a signal involved in the adaptation of the bacteria to changing nutritional conditions. In animal cells, ThTP can phosphorylate some proteins, but the physiological significance of this mechanism remains unknown. Adenosine thiamin triphosphate, recently discovered in E. coli, accumulates during carbon starvation and might act as an alarmone. Among the proteins involved in thiamin metabolism, thiamin transporters, thiamin pyrophosphokinase and a soluble 25-kDa thiamin triphosphatase have been characterized at the molecular level, in contrast to thiamin mono- and diphosphatases whose specificities remain to be proven. A soluble enzyme catalyzing the synthesis of adenosine thiamin triphosphate from ThDP and ADP or ATP has been partially characterized in E. coli, but the mechanism of ThTP synthesis remains elusive. The data reviewed here illustrate the complexity of thiamin biochemistry, which is not restricted to the cofactor role of ThDP.

  14. Pa2G4 is a novel Six1 co-factor that is required for neural crest and otic development☆

    Science.gov (United States)

    Neilson, Karen M.; Abbruzzesse, Genevieve; Kenyon, Kristy; Bartolo, Vanessa; Krohn, Patrick; Alfandari, Dominique; Moody, Sally A.

    2016-01-01

    Mutations in SIX1 and in its co-factor, EYA1, underlie Branchiootorenal Spectrum disorder (BOS), which is characterized by variable branchial arch, otic and kidney malformations. However, mutations in these two genes are identified in only half of patients. We screened for other potential co-factors, and herein characterize one of them, Pa2G4 (aka Ebp1/Plfap). In human embryonic kidney cells, Pa2G4 binds to Six1 and interferes with the Six1-Eya1 complex. In Xenopus embryos, knock-down of Pa2G4 leads to down-regulation of neural border zone, neural crest and cranial placode genes, and concomitant expansion of neural plate genes. Gain-of-function leads to a broader neural border zone, expanded neural crest and altered cranial placode domains. In loss-of-function assays, the later developing otocyst is reduced in size, which impacts gene expression. In contrast, the size of the otocyst in gain-of-function assays is not changed but the expression domains of several otocyst genes are reduced. Together these findings establish an interaction between Pa2G4 and Six1, and demonstrate that it has an important role in the development of tissues affected in BOS. Thereby, we suggest that pa2g4 is a potential candidate gene for BOS. PMID:27940157

  15. Down-regulation of viral replication by adenoviral-mediated expression of siRNA against cellular cofactors for hepatitis C virus

    International Nuclear Information System (INIS)

    Zhang Jing; Yamada, Osamu; Sakamoto, Takashi; Yoshida, Hiroshi; Iwai, Takahiro; Matsushita, Yoshihisa; Shimamura, Hideo; Araki, Hiromasa; Shimotohno, Kunitada

    2004-01-01

    Small interfering RNA (siRNA) is currently being evaluated not only as a powerful tool for functional genomics, but also as a potentially promising therapeutic agent for cancer and infectious diseases. Inhibitory effect of siRNA on viral replication has been demonstrated in multiple pathogenic viruses. However, because of the high sequence specificity of siRNA-mediated RNA degradation, antiviral efficacy of siRNA directed to viral genome will be largely limited by emergence of escape variants resistant to siRNA due to high mutation rates of virus, especially RNA viruses such as poliovirus and hepatitis C virus (HCV). To investigate the therapeutic feasibility of siRNAs specific for the putative cellular cofactors for HCV, we constructed adenovirus vectors expressing siRNAs against La, polypyrimidine tract-binding protein (PTB), subunit gamma of human eukaryotic initiation factors 2B (eIF2Bγ), and human VAMP-associated protein of 33 kDa (hVAP-33). Adenoviral-mediated expression of siRNAs markedly diminished expression of the endogenous genes, and silencing of La, PTB, and hVAP-33 by siRNAs substantially blocked HCV replication in Huh-7 cells. Thus, our studies demonstrate the feasibility and potential of adenoviral-delivered siRNAs specific for cellular cofactors in combating HCV infection, which can be used either alone or in combination with siRNA against viral genome to prevent the escape of mutant variants and provide additive or synergistic anti-HCV effects

  16. Long Maturity Forward Rates

    DEFF Research Database (Denmark)

    Christiansen, Charlotte

    2001-01-01

    The paper aims to improve the knowledge of the empirical properties of the long maturity region of the forward rate curve. Firstly, the theoretical negative correlation between the slope at the long end of the forward rate curve and the term structure variance is recovered empirically and found...... to be statistically significant. Secondly, the expectations hypothesis is analyzed for the long maturity region of the forward rate curve using "forward rate" regressions. The expectations hypothesis is numerically close to being accepted but is statistically rejected. The findings provide mixed support...... for the affine term structure model....

  17. Public Sector IS Maturity Models

    DEFF Research Database (Denmark)

    Zinner Henriksen, Helle; Andersen, Kim Normann; Medaglia, Rony

    2011-01-01

    Online applications and processing of tax forms, driver licenses, and construction permits are examples of where policy attention and research have been united in efforts aiming to categorize the maturity level of e-services. Less attention has been attributed to policy areas with continuous online...... citizenpublic interaction, such as in public education. In this paper we use a revised version of the Public Sector Process Rebuilding (PPR) maturity model for mapping 200 websites of public primary schools in Denmark. Findings reveal a much less favorable picture of the digitization of the Danish public sector...... compared to the high ranking it has received in the international benchmark studies. This paper aims at closing the gap between the predominant scope of maturity models and the frequency of citizen-public sector interaction, and calls for increased attention to the activities of government where the scale...

  18. Service Quality and Process Maturity Assessment

    Directory of Open Access Journals (Sweden)

    Serek Radomir

    2013-12-01

    Full Text Available This article deals with service quality and the methods for its measurement and improvements to reach the so called service excellence. Besides older methods such as SERVQUAL and SERPERF, there are also shortly described capability maturity models based on which the own methodology is developed and used for process maturity assessment in organizations providing technical services. This method is equally described and accompanied by examples on pictures. The verification of method functionality is explored on finding a correlation between service employee satisfaction and average process maturity in a service organization. The results seem to be quite promising and open an arena for further studies.

  19. Genotype x environmental interaction for mature size and rate of maturing for Angus, Brahman, and reciprocal-cross cows grazing bermudagrass or endophyte infected fescue.

    Science.gov (United States)

    Sandelin, B A; Brown, A H; Brown, M A; Johnson, Z B; Kellogg, D W; Stelzleni, A M

    2002-12-01

    Mature weight and rate of maturing were estimated in 177 Angus, Brahman, and reciprocal-cross cows grazing bermudagrass or endophyte-infected tall fescue over a 4-yr period to evaluate genotype x environment interactions. Data were collected every 28 d until cows were approximately 18 mo of age and then at prebreeding, postcalving, and weaning of calf. All cows with weight data to at least 42 mo of age were included in the analysis. Mature weight and rate of maturing were estimated using the three-parameter growth curve model described by Brody (1945). Data were pooled over year and analyzed by the general linear model procedure of SAS. Included in the models for mature weight and rate of maturing were the independent variables of genotype, environment, and genotype x environment interaction. There was a genotype x environment interaction (P < 0.01) for mature body weight (BW) but not for rate of maturing. Angus cows grazing fescue pastures had greater (P < 0.01) mean mature BW than Angus x Brahman cows grazing bermudagrass (611 +/- 17 vs 546 +/- 16 kg). Angus x Brahman cows grazing bermudagrass had lower (P < 0.05) mean mature BW than Brahman x Angus cows grazing bermudagrass or endophyte-infected fescue and Brahman cows grazing bermudagrass (546 +/- 16 vs 624 +/- 19, 614 +/- 22 and 598 +/- 20 kg, respectively). Brahman cows grazing endophyte-infected fescue had smaller (P < 0.05) mean mature BW than all genotype x forage combinations except for Angus x Brahman cows grazing bermudagrass. Angus cows had a smaller (P < 0.05) mean rate of maturing than Angus x Brahman and Brahman x Angus cows (0.039 +/- 0.002 vs 0.054 +/- 0.002 and 0.049 +/- 0.002%/mo, respectively), respectively, and Angus x Brahman cows had a larger (P < 0.05) mean rate of maturing than Brahman x Angus and Brahman cows (0.054 +/- 0.002 vs 0.049 +/- 0.002 and 0.041 +/- 0.002 %/mo, respectively). There was a direct breed x forage interaction (P < 0.05) for mature BW. These data suggest that the

  20. Induction and inhibition of oocyte maturation by EDCs in zebrafish

    Directory of Open Access Journals (Sweden)

    Tokumoto Mika

    2005-12-01

    Full Text Available Abstract Background Oocyte maturation in lower vertebrates is triggered by maturation-inducing hormone (MIH, which acts on unidentified receptors on the oocyte surface and induces the activation of maturation-promoting factor (MPF in the oocyte cytoplasm. We previously described the induction of oocyte maturation in fish by an endocrine-disrupting chemical (EDC, diethylstilbestrol (DES, a nonsteroidal estrogen. Methods In this study, stimulatory and inhibitory effects of EDCs and natural steroids on oocyte maturation were examined in zebrafish. For effective agents, some details about the mechanism in induction or inhibition of maturation were examined. Possible groups of DES interacting with the MIH receptor are discussed based on relative potency of steroids to induce maturation. Results Among agents tested, tamoxifen (TAM and its metabolite 4-hydroxytamoxifen (4-OHT showed stimulatory activity similar to DES. The time courses of the change in germinal vesicle breakdown and an intracellular molecular event (the synthesis of cyclin B induced by TAM were indistinguishable from those induced by MIH. In contrast, pentachlorophenol (PCP had a potent inhibitory effect on MIH-induced oocyte maturation. PCP inhibited not only MIH-induced maturation but also DES- and TAM-induced maturation. Methoxychlor also inhibited maturation when oocytes were pre-treated with this agent. Conclusion These results suggest that EDCs act as agonists or antagonists in the induction of oocyte maturation in fish.

  1. On the occurrence of nuclei in mature sieve elements.

    Science.gov (United States)

    Event, R F; Davis, J D; Tucker, C M; Alfieri, F J

    1970-12-01

    The secondary phloem of 3 species of the Taxodiaceae and 13 species of woody dicotyledons was examined for the occurrence of nuclei in mature sieve elements. Nuclei were found in all mature sieve cells of Metasequoia glyptostroboides, Sequoia sempervirens and Taxodium distichum, and in some mature sieve-tube members in 12 of the 13 species of woody dicotyledons. Except for nuclei of sieve cells undergoing cessation of function, the nuclei in mature sieve cells of M. glyptostroboides, S. sempervirens and T. distichum were normal in appearance. The occurrence and morphology of nuclei in mature sieve-tube members of the woody dicotyledons were quite variable. Only 3 species, Robinia pseudoacacia, Ulmus americana and Vitis riparia, contained some mature sieve elements with apparently normal nuclei.

  2. A model-independent view of the mature organization

    Energy Technology Data Exchange (ETDEWEB)

    Hanna, M.; Langston, D.

    1996-12-31

    Over the last 10 years, industry has been dealing with the issues of process and organizational maturity. This focus on process is driven by the success that manufacturing organizations have had implementing the management principles of W. Edwards Deming and Joseph M. Juran. The organizational-maturity focus is driven by organizations striving to be ISO 9000 compliant or to achieve a specific level on one of the maturity models. Unfortunately, each of the models takes a specific view into what is a very broad arena. That is to say, each model addresses only a specific subset of the characteristics of maturity. This paper attempts to extend beyond these specific views to answer the general question, What is a mature organization and its relationship to Quantitative management and statistical process control?

  3. Analysis of business process maturity and organisational performance relations

    Directory of Open Access Journals (Sweden)

    Kalinowski T. Bartosz

    2016-12-01

    Full Text Available The paper aims to present results of the study on business process maturity in relation to organisational performance. A two-phase methodology, based on literature review and survey was used. The literature is a source of knowledge about business process maturity and organisational performance, whereas the research on process maturity vs organisational performance in Polish Enterprises provides findings based on 84 surveyed companies. The main areas of the research covered: identification and analysis of maturity related variables and identification of organisational performance perspectives and its relation to process maturity. The study shows that there is a significant positive relation between process maturity and organisational performance. Although there are research on such relation available, they are scarce and have some significant limitations in terms of research sample or the scope of maturity or organisational performance covered. This publication is part of a project funded by the National Science Centre awarded by decision number DEC-2011/01/D/HS4/04070.

  4. Maturation arrest of human oocytes at germinal vesicle stage

    Directory of Open Access Journals (Sweden)

    Zhi Qin Chen

    2010-01-01

    Full Text Available Maturation arrest of human oocytes may occur at various stages of the cell cycle. A total failure of human oocytes to complete meiosis is rarely observed during assisted conception cycles. We describe here a case of infertile couples for whom all oocytes repeatedly failed to mature at germinal vesicle (GV stage during in vitro fertilization/Intra cytoplasmic sperm injection (IVF/ICSI. The patient underwent controlled ovarian stimulation followed by oocyte retrieval and IVF/ICSI. The oocytes were stripped off cumulus cells prior to the ICSI procedure and their maturity status was defined. The oocyte maturation was repeatedly arrested at the GV. Oocyte maturation arrest may be the cause of infertility in this couple. The recognition of oocyte maturation arrest as a specific medical condition may contribute to the characterization of the currently known as "oocyte factor." The cellular and genetic mechanisms causing oocyte maturation arrest should be the subject for further investigation.

  5. Breeding of cocksfoot cultivars with different maturity

    Directory of Open Access Journals (Sweden)

    Babić Snežana

    2017-01-01

    Full Text Available One of the most important criteria in breeding process of perennial grasses is maturity. Cultivars with different maturity play a very important role in utilization of perennial grasses, by providing the ability to create a mixture of different aspects utilization and time. The first grass species in Serbia whose breeding program involved this criterion was cocksfoot (Dactylis glomerata L.. In general cocksfoot is early to medium-early in maturity in comparison with other grasses and legumes, and that is mayor problem since in the optimum phase for cutting, cocksfoot is often earlier then other species in mixtures. As a result of this work, in the previous period, two cultivars of different maturity were released, Kruševačka 24 (K-24 and Kruševačka 25 (K-25. K-24 is medium and K-25 is late in maturity. New material is adapted to local agro-ecological conditions and productive in the same time. In breeding process of both cultivars initial material originated from autochthonous populations collected in eastern and central Serbia. Material from the wild flora is selected based on medium and late maturity which is already adapted and has good productivity. We applied the standard method of phenotypic recurrent selection with the creation of synthetic varieties by polycross.

  6. Phenylalanine ammonia lyase catalyzed synthesis of amino acids by an MIO-cofactor independent pathway.

    Science.gov (United States)

    Lovelock, Sarah L; Lloyd, Richard C; Turner, Nicholas J

    2014-04-25

    Phenylalanine ammonia lyases (PALs) belong to a family of 4-methylideneimidazole-5-one (MIO) cofactor dependent enzymes which are responsible for the conversion of L-phenylalanine into trans-cinnamic acid in eukaryotic and prokaryotic organisms. Under conditions of high ammonia concentration, this deamination reaction is reversible and hence there is considerable interest in the development of PALs as biocatalysts for the enantioselective synthesis of non-natural amino acids. Herein the discovery of a previously unobserved competing MIO-independent reaction pathway, which proceeds in a non-stereoselective manner and results in the generation of both L- and D-phenylalanine derivatives, is described. The mechanism of the MIO-independent pathway is explored through isotopic-labeling studies and mutagenesis of key active-site residues. The results obtained are consistent with amino acid deamination occurring by a stepwise E1 cB elimination mechanism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Determinants of relative skeletal maturity in South African children.

    Science.gov (United States)

    Hawley, Nicola L; Rousham, Emily K; Johnson, William; Norris, Shane A; Pettifor, John M; Cameron, Noël

    2012-01-01

    The variation of skeletal maturity about chronological age is a sensitive indicator of population health. Age appropriate or advanced skeletal maturity is a reflection of adequate environmental and social conditions, whereas delayed maturation suggests inadequate conditions for optimal development. There remains a paucity of data, however, to indicate which specific biological and environmental factors are associated with advancement or delay in skeletal maturity. The present study utilises longitudinal data from the South African Birth to Twenty (Bt20) study to indentify predictors of relative skeletal maturity (RSM) in early adolescence. A total of 244 black South African children (n=131 male) were included in this analysis. Skeletal maturity at age 9/10 years was assessed using the Tanner and Whitehouse III RUS technique. Longitudinal data on growth, socio-economic position and pubertal development were entered into sex-specific multivariable general linear regression models with relative skeletal maturity (skeletal age-chronological age) as the outcome. At 9/10 years of age males showed an average of 0.66 years delay in skeletal maturation relative to chronological age. Females showed an average of 1.00 year delay relative to chronological age. In males, being taller at 2 years (pdetermining the rate of skeletal maturation during childhood independently of current stature. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. A comparison of skeletal maturation in patients with tooth agenesis and unaffected controls assessed by the cervical vertebral maturation (CVM) index.

    Science.gov (United States)

    Casey, Christine; Gill, Daljit S; Jones, Steven P

    2013-12-01

    The aims of this study were to (1) investigate if there is a difference in skeletal maturation between tooth agenesis and control patients and (2) whether skeletal maturation is affected by the severity of tooth agenesis. The cervical vertebral maturation (CVM) index can be used to assess skeletal maturation. A retrospective cross-sectional study. Eastman Dental Hospital, London, UK. A total of 360 cephalograms of patients aged 9-17 years (164 males and 196 females) allocated to four subgroups (mild, moderate and severe tooth agenesis patients, and controls) were assessed retrospectively. There were 90 patients in each of the four subgroups. The skeletal maturation of each subject was assessed both quantitatively and qualitatively using the CVM index. All patients in the study were either currently receiving treatment or had been discharged from the hospital. There was no statistically significant relationship between skeletal maturation and the presence of tooth agenesis. Furthermore, there was no statistically significant relationship between the skeletal maturity of patients and different severities of tooth agenesis. The data obtained from this group of patients and using this measurement tool alone does not supply sufficient reason to reject the null hypothesis. However, it suggests that it is possible that no difference exists between the groups.

  9. Maturity of hospital information systems: Most important influencing factors.

    Science.gov (United States)

    Vidal Carvalho, João; Rocha, Álvaro; Abreu, António

    2017-07-01

    Maturity models facilitate organizational management, including information systems management, with hospital organizations no exception. This article puts forth a study carried out with a group of experts in the field of hospital information systems management with a view to identifying the main influencing factors to be included in an encompassing maturity model for hospital information systems management. This study is based on the results of a literature review, which identified maturity models in the health field and relevant influencing factors. The development of this model is justified to the extent that the available maturity models for the hospital information systems management field reveal multiple limitations, including lack of detail, absence of tools to determine their maturity and lack of characterization for stages of maturity structured by different influencing factors.

  10. Ovarian follicle maturation and ovulation: An integrated perspective

    Science.gov (United States)

    Patino, R.; Thomas, P.; Yoshizaki, G.

    2003-01-01

    Numerous studies with teleosts have addressed the regulation and mechanisms of oocyte maturation, but largely at the exclusion of ovulation. A smaller but still considerable number of studies have focused on ovulation, and ignored maturation. Consequently, little is known about the mechanistic linkages between these two events. New information is presented here indicating that luteinizing hormone regulates the acquisition not only of oocyte maturational competence, but also ovulatory competence. The thesis is presented that maturation and ovulation are closely integrated and overlapping events that are best viewed conceptually and experimentally as parts of a functional whole. ?? 2004 Kluwer Academic Publishers.

  11. Mall shopping preferences and patronage of mature shoppers

    Directory of Open Access Journals (Sweden)

    Gabriel G. Rousseau

    2014-04-01

    Research purpose: The purpose of this study was to investigate the buying behaviour of mature consumers (older than 55 in Port Elizabeth shopping malls. Motivation for the study: The perception of mature shoppers as old people with limited financial resources is untrue. This study investigates the behaviours of mature shoppers. Research design, approach and method: A model guided the investigation. The authors facilitated four focus groups to gain insight into mature consumers’ buying behaviours. A field survey followed with a sample of mall shoppers (n = 680. The authors performed content analysis of the focus group material and used SPSS and AMOS programs to analyse the data quantitatively. Main findings: Focus group interviews revealed specific buying behaviours of mature shoppers. The survey showed significant relationships between various determinants that influence respondents’ buying behaviours with adequate model fit indices. These results confirmed the convergent and discriminant validity of the model that comprises mall shopping anticipation, experience and patronage. Practical/managerial implications: Mature shoppers’ expectations exceeded their experiences, suggesting dissatisfaction with some aspects of their experiences. Retailers and shopping mall managers need to redesign malls if they wish to cater for the segment of ageing shoppers and their spending power. Contribution/value-add: The study contributes to the research available in South Africa on service at shopping malls that cater for mature consumers.

  12. Physical activity and biological maturation: a systematic review

    Directory of Open Access Journals (Sweden)

    Eliane Denise Araújo Bacil

    2015-03-01

    Full Text Available OBJECTIVE: To analyze the association between physical activity (PA and biological maturation in children and adolescents. DATA SOURCE: We performed a systematic review in April 2013 in the electronic databases of PubMed/MEDLINE, SportDiscus, Web of Science and LILACS without time restrictions. A total of 628 potentially relevant articles were identified and 10 met the inclusion criteria for this review: cross-sectional or longitudinal studies, published in Portuguese, English or Spanish, with schoolchildren aged 9-15 years old of both genders. DATA SYNTHESIS: Despite the heterogeneity of the studies, there was an inverse association between PA and biological maturation. PA decreases with increased biological and chronological age in both genders. Boys tend to be more physically active than girls; however, when controlling for biological age, the gender differences disappear. The association between PA and timing of maturation varies between the genders. Variation in the timing of biological maturation affects the tracking of PA in early adolescent girls. This review suggests that mediators (BMI, depression, low self-esteem, and concerns about body weight can explain the association between PA and biological maturation. CONCLUSIONS: There is an association between PA and biological maturation. PA decreases with increasing biological age with no differences between genders. As for the timing of biological maturation, this association varies between genders.

  13. Age of biological maturity of Malaysian girls by ethnicity.

    Science.gov (United States)

    Noor Laily Abu Bakar; Prasanta K Majumdar; Tan Boon Ann

    1983-01-01

    This study estimates the age of biological maturity, defined as the end of adolescent sterility, of Malaysian girls by employing an indiredt methodology. Biological maturity usually occurs about 3 years after puberty. Adolescent subfecundity is due to anovulatory cycles or to short luteal phases among menarchial girls. In this study, age at biological maturity is estimated by considering retrospective fertility and family survey data on marriage, 1st birt, and contraceptive use. The waiting time for the biologically mature females to conceive is 3.0 months; 3.2 months among the Malays, 2.7 months among the Chinese, and 2.8 months among the Indians. The maximum age of attaining biological maturity is 20 for all ethnic groups except Indians (19 years). The maximum age is estimated by considering females whose 1st pregnancy ended in a live birth and who have been living most of the time with their husbands since marriage, with no contraceptive usage. The expected age of biological maturity at birth is 15.6 years; 15.3 years for the Malays, 15.4 years for the Chinese, and 14.8 years for the Indians. The means age of attaining biological maturity coincides with the expected age of attaining biological maturity at birth.

  14. Effects of posttreatment skeletal maturity measured with the cervical vertebral maturation method on incisor alignment relapse.

    Science.gov (United States)

    Fudalej, Piotr; Rothe, Laura E; Bollen, Anne-Marie

    2008-08-01

    Our aim was to test the hypothesis that relapse of incisor alignment is associated with skeletal maturity at the end of treatment, as assessed with the cervical vertebral maturation (CVM) method. This was a case-control study with information from the postretention database at the University of Washington. Mandibular incisor irregularity (II) at least 10 years out of retention (T3) was used to define the subjects (II >6 mm, relapse group) and the controls (II 0.05). Pretreatment II and postretention time were found to be correlated with long-term incisor stability (P = 0.007 and 0.034, respectively). Sex was not related to relapse (P = 0.33). Maturity of craniofacial structures at the end of treatment evaluated with the CVM method is not associated with long-term stability of incisor alignment.

  15. Maturity Model for Advancing Smart Grid Interoperability

    Energy Technology Data Exchange (ETDEWEB)

    Knight, Mark; Widergren, Steven E.; Mater, J.; Montgomery, Austin

    2013-10-28

    Abstract—Interoperability is about the properties of devices and systems to connect and work properly. Advancing interoperability eases integration and maintenance of the resulting interconnection. This leads to faster integration, lower labor and component costs, predictability of projects and the resulting performance, and evolutionary paths for upgrade. When specifications are shared and standardized, competition and novel solutions can bring new value streams to the community of stakeholders involved. Advancing interoperability involves reaching agreement for how things join at their interfaces. The quality of the agreements and the alignment of parties involved in the agreement present challenges that are best met with process improvement techniques. The GridWise® Architecture Council (GWAC) sponsored by the United States Department of Energy is supporting an effort to use concepts from capability maturity models used in the software industry to advance interoperability of smart grid technology. An interoperability maturity model has been drafted and experience is being gained through trials on various types of projects and community efforts. This paper describes the value and objectives of maturity models, the nature of the interoperability maturity model and how it compares with other maturity models, and experiences gained with its use.

  16. Maturity grids as tools for change management

    DEFF Research Database (Denmark)

    Maier, Anja; Moultrie, James; Clarkson, P John

    2011-01-01

    A maturity grid is a change management tool. Levels of maturity are assigned against aspects of an area under study, thus creating a grid. Text descriptions at the resulting intersections describe the typical behaviour exhibited by a firm for each area under study and from the basis...... for the assessment scale. It is a flexible assessment technique that is used by practitioners in industry, consultants and researchers in academia for diagnostic, reflective and improvement purposes. A large number of maturity grids have been proposed to assess a range of capabilities including quality management...

  17. Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites

    Science.gov (United States)

    Mortusewicz, Oliver; Roth, Wera; Li, Na; Cardoso, M. Cristina; Meisterernst, Michael; Leonhardt, Heinrich

    2008-01-01

    The multifunctional nuclear protein positive cofactor 4 (PC4) is involved in various cellular processes including transcription, replication, and chromatin organization. Recently, PC4 has been identified as a suppressor of oxidative mutagenesis in Escherichia coli and Saccharomyces cerevisiae. To investigate a potential role of PC4 in mammalian DNA repair, we used a combination of live cell microscopy, microirradiation, and fluorescence recovery after photobleaching analysis. We found a clear accumulation of endogenous PC4 at DNA damage sites introduced by either chemical agents or laser microirradiation. Using fluorescent fusion proteins and specific mutants, we demonstrated that the rapid recruitment of PC4 to laser-induced DNA damage sites is independent of poly(ADP-ribosyl)ation and γH2AX but depends on its single strand binding capacity. Furthermore, PC4 showed a high turnover at DNA damages sites compared with the repair factors replication protein A and proliferating cell nuclear antigen. We propose that PC4 plays a role in the early response to DNA damage by recognizing single-stranded DNA and may thus initiate or facilitate the subsequent steps of DNA repair. PMID:19047459

  18. Genetic transformation of mature citrus plants.

    Science.gov (United States)

    Cervera, Magdalena; Juárez, José; Navarro, Luis; Peña, Leandro

    2005-01-01

    Most woody fruit species have long juvenile periods that drastically prolong the time required to analyze mature traits. Evaluation of characteristics related to fruits is a requisite to release any new variety into the market. Because of a decline in regenerative and transformation potential, genetic transformation procedures usually employ juvenile material as the source of plant tissue, therefore resulting in the production of juvenile plants. Direct transformation of mature material could ensure the production of adult transgenic plants, bypassing in this way the juvenile phase. Invigoration of the source adult material, establishment of adequate transformation and regeneration conditions, and acceleration of plant development through grafting allowed us to produce transgenic mature sweet orange trees flowering and bearing fruits in a short time period.

  19. Skeletal maturity assessment using mandibular canine calcification stages

    Directory of Open Access Journals (Sweden)

    Vildana Džemidžić

    2016-11-01

    Full Text Available Objective. The aims of this study were: to investigate the relationship between mandibular canine calcification stages and skeletal maturity; and to evaluate whether the mandibular canine calcification stages may be used as a reliable diagnostic tool for skeletal maturity assessment. Materials and methods. This study included 151 subjects: 81 females and 70 males, with ages ranging from 9 to 16 years (mean age: 12.29±1.86 years. The inclusion criteria for subjects were as follows: age between 9 and 16 years; good general health without any hormonal, nutritional, growth or dental development problems. Subjects who were undergoing or had previously received orthodontic treatment were not included in this study. The calcification stages of the left permanent mandibular canine were assessed according to the method of Demirjian, on panoramic radiographs. Assessment of skeletal maturity was carried out using the cervical vertebral maturation index (CVMI, as proposed by the Hassel-Farman method, on lateral cephalograms. The correlation between the calcification stages of mandibular canine and skeletal maturity was estimated separately for male and female subjects. Results. Correlation coefficients between calcification stages of mandibular canine and skeletal maturity were 0.895 for male and 0.701 for female subjects. Conclusions. A significant correlation was found between the calcification stages of the mandibular canine and skeletal maturity. The calcification stages of the mandibular canine show a satisfactory diagnostic performance only for assessment of pre-pubertal growth phase.

  20. Catalyst design for carbon nanotube growth using atomistic modeling

    International Nuclear Information System (INIS)

    Pint, Cary L; Bozzolo, Guillermo; Hauge, Robert

    2008-01-01

    The formation and stability of bimetallic catalyst particles, in the framework of carbon nanotube growth, is studied using the Bozzolo-Ferrante-Smith (BFS) method for alloys. Monte Carlo-Metropolis simulations with the BFS method are utilized in order to predict and study equilibrium configurations for nanoscale catalyst particles which are directly relevant to the catalyst state prior to growth of carbon nanotubes. At the forefront of possible catalyst combinations is the popular Fe-Mo bimetallic catalyst, which we have recently studied experimentally. We explain our experimental results, which indicate that the growth observed is dependent on the order of co-catalyst deposition, in the straightforward interpretation of BFS strain and chemical energy contributions toward the formation of Fe-Mo catalyst prior to growth. We find that the competition between the formation of metastable inner Mo cores and clusters of surface-segregated Mo atoms in Fe-Mo catalyst particles influences catalyst formation, and we investigate the role of Mo concentration and catalyst particle size in this process. Finally, we apply the same modeling approach to other prominent bimetallic catalysts and suggest that this technique can be a powerful tool to understand and manipulate catalyst design for highly efficient carbon nanotube growth

  1. Aspects of remote maintenance in an FRG reprocessing plant from the manufacturer's viewpoint

    International Nuclear Information System (INIS)

    Zeitzchel, G.; Tennie, M.; Saal, G.

    1986-01-01

    In April 1986 a consortium led by Kraftwerk Union AG was commissioned by the German society for nuclear fuel reprocessing (DWK) to build the first West German commercial reprocessing plant for spent fuel assemblies. The main result of the planning efforts regarding remote maintenance operations inside the main process building was the introduction of FEMO technology (FEMO is an acronym based on German for remote handling modular technique). According to this technology the two cells in which the actual reprocessing (which is based on the PUREX technique) takes place are provided with frames to accommodate the process components (tanks, pumps, agitators, etc.), each frame together with the components which it supports forming one module. The two cells are inaccessible and windowless. For handling operations each cell is equipped with an overhead crane and a crane-like manipulator carrier system (MTS) with power manipulator. Viewing of the operations from outside the cells is made possible by television (TV) cameras installed at the crane, the MTS, and the manipulator. This paper addresses some examples of problems that still need to be solved in connection with FEMO handling. In particular, the need for close cooperation between the equipment operator, the component designer, the process engineer, the planning engineer, and the licensing authorities will be demonstrated

  2. Identification and Characterization of the Novel p97 co-factors, Rep8 and ASPL

    DEFF Research Database (Denmark)

    Klausen, Louise Kjær

    to the ER membrane with the UBX domain situated in the cytosol. Mouse Rep8 is highly tissue-specific and abundant in gonads. In tests, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Additional precipitation experiments revealed that Rep8......The highly conserved and ubiquitin-specific AAA ATPase p97 acts on ubiquitylated substrates in diverse cellular mechanisms such as chromatin-associated degradation, fusion of homotypic membranes and ER-associated degradation. Different p97 cofactors associate with the ATPase, thereby constituting...... that ASPL localizes to the ER membrane and in vitro ASPL leads to disassembly of the p97 hexameric ATPase. Rep8 was found to interact with p97 both in vitro and in vivo, and the binding was mediated through the N-domain of p97 and the UBX domain of Rep8. Localization studies showed that Rep8 localizes...

  3. Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes.

    Science.gov (United States)

    Annis, Ryan P; Swahari, Vijay; Nakamura, Ayumi; Xie, Alison X; Hammond, Scott M; Deshmukh, Mohanish

    2016-12-01

    Apoptotic cell death is critical for the early development of the nervous system, but once the nervous system is established, the apoptotic pathway becomes highly restricted in mature neurons. However, the mechanisms underlying this increased resistance to apoptosis in these mature neurons are not completely understood. We have previously found that members of the miR-29 family of microRNAs (miRNAs) are induced with neuronal maturation and that overexpression of miR-29 was sufficient to restrict apoptosis in neurons. To determine whether endogenous miR-29 alone was responsible for the inhibition of cytochrome c release in mature neurons, we examined the status of the apoptotic pathway in sympathetic neurons deficient for all three miR-29 family members. Unexpectedly, we found that the apoptotic pathway remained largely restricted in miR-29-deficient mature neurons. We therefore probed for additional mechanisms by which mature neurons resist apoptosis. We identify miR-24 as another miRNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR-29 by targeting a similar repertoire of prodeath BH3-only genes. Overall, our results reveal that mature neurons engage multiple redundant brakes to restrict the apoptotic pathway and ensure their long-term survival. © 2016 Federation of European Biochemical Societies.

  4. Maturity Models in Supply Chain Sustainability: A Systematic Literature Review

    Directory of Open Access Journals (Sweden)

    Elisabete Correia

    2017-01-01

    Full Text Available A systematic literature review of supply chain maturity models with sustainability concerns is presented. The objective is to give insights into methodological issues related to maturity models, namely the research objectives; the research methods used to develop, validate and test them; the scope; and the main characteristics associated with their design. The literature review was performed based on journal articles and conference papers from 2000 to 2015 using the SCOPUS, Emerald Insight, EBSCO and Web of Science databases. Most of the analysed papers have as main objective the development of maturity models and their validation. The case study is the methodology that is most widely used by researchers to develop and validate maturity models. From the sustainability perspective, the scope of the analysed maturity models is the Triple Bottom Line (TBL and environmental dimension, focusing on a specific process (eco-design and new product development and without a broad SC perspective. The dominant characteristics associated with the design of the maturity models are the maturity grids and a continuous representation. In addition, results do not allow identifying a trend for a specific number of maturity levels. The comprehensive review, analysis, and synthesis of the maturity model literature represent an important contribution to the organization of this research area, making possible to clarify some confusion that exists about concepts, approaches and components of maturity models in sustainability. Various aspects associated with the maturity models (i.e., research objectives, research methods, scope and characteristics of the design of models are explored to contribute to the evolution and significance of this multidimensional area.

  5. Cervical vertebral and dental maturity in Turkish subjects.

    Science.gov (United States)

    Başaran, Güvenç; Ozer, Törün; Hamamci, Nihal

    2007-04-01

    The aim of this study was to investigate the relationships between the stages of calcification of teeth and the cervical vertebral maturity stages in Turkish subjects. A retrospective cross-sectional study was designed. The final study population consisted of 590 Turkish subjects. Statistical analysis of the data was performed with computer software. Spearman rank order correlation coefficients were used to assess the relationship between cervical vertebral and dental maturation. For a better understanding of the relationship between cervical vertebral maturation indexes and dental age, percentage distributions of the studied teeth were also calculated. Strict correlations were found between dental and cervical vertebral maturation of Turkish subjects. For males, the sequence from lowest to the highest was third molar, central incisor, canine, first premolar, second premolar, first molar, and second molar. For females, the sequence from lowest to the highest was third molar, canine, second premolar, first premolar, central incisor, first molar, and second molar. Dental maturation stages can be used as a reliable indicator of facial growth.

  6. MD3M: The Master Data Management Maturity Model

    NARCIS (Netherlands)

    Spruit, Marco|info:eu-repo/dai/nl/297391879; Pietzka, Katharina

    2015-01-01

    This research aims to assess the master data maturity of an organization. It is based on thorough literature study to derive the main concepts and best practices in master data maturity assessment. A maturity matrix relating 13 focus areas and 65 capabilities was designed and validated. Furthermore,

  7. Assessing the Harvest Maturity of Brazilian Mangoes

    NARCIS (Netherlands)

    Pereira, T.; Tijskens, L.M.M.; Vanoli, M.; Rizzolo, A.; Eccher Zerbini, P.C.; Torricelli, A.; Filgueiras, H.; Spinelli, L.

    2010-01-01

    No clear criterion exists to determine the optimum time to harvest mango. Some empirical relations are used to assess maturity, such as shoulder development. Moreover, as a result of the typical growing conditions in tropical climates, a huge variation in maturity and ripeness exists, seriously

  8. Transcriptional Programs Controlling Perinatal Lung Maturation

    Science.gov (United States)

    Xu, Yan; Wang, Yanhua; Besnard, Valérie; Ikegami, Machiko; Wert, Susan E.; Heffner, Caleb; Murray, Stephen A.; Donahue, Leah Rae; Whitsett, Jeffrey A.

    2012-01-01

    The timing of lung maturation is controlled precisely by complex genetic and cellular programs. Lung immaturity following preterm birth frequently results in Respiratory Distress Syndrome (RDS) and Broncho-Pulmonary Dysplasia (BPD), which are leading causes of mortality and morbidity in preterm infants. Mechanisms synchronizing gestational length and lung maturation remain to be elucidated. In this study, we designed a genome-wide mRNA expression time-course study from E15.5 to Postnatal Day 0 (PN0) using lung RNAs from C57BL/6J (B6) and A/J mice that differ in gestational length by ∼30 hr (B6controlling lung maturation. We identified both temporal and strain dependent gene expression patterns during lung maturation. For time dependent changes, cell adhesion, vasculature development, and lipid metabolism/transport were major bioprocesses induced during the saccular stage of lung development at E16.5–E17.5. CEBPA, PPARG, VEGFA, CAV1 and CDH1 were found to be key signaling and transcriptional regulators of these processes. Innate defense/immune responses were induced at later gestational ages (E18.5–20.5), STAT1, AP1, and EGFR being important regulators of these responses. Expression of RNAs associated with the cell cycle and chromatin assembly was repressed during prenatal lung maturation and was regulated by FOXM1, PLK1, chromobox, and high mobility group families of transcription factors. Strain dependent lung mRNA expression differences peaked at E18.5. At this time, mRNAs regulating surfactant and innate immunity were more abundantly expressed in lungs of B6 (short gestation) than in A/J (long gestation) mice, while expression of genes involved in chromatin assembly and histone modification were expressed at lower levels in B6 than in A/J mice. The present study systemically mapped key regulators, bioprocesses, and transcriptional networks controlling lung maturation, providing the basis for new therapeutic strategies to enhance lung function in preterm

  9. Maturation of human oocytes in vitro

    Directory of Open Access Journals (Sweden)

    Mojca Čižek-Sajko

    2007-01-01

    Full Text Available Background: Immature oocyte retrieval followed by in vitro maturation is a promising infertility treatment option. In patients with morphologically normal ovaries and regular menstrual cycles and in patients with polycystic ovary syndrome (PCOS we attempted to assess the success of oocyte in vitro maturation in in vitro fertilization (IVF procedures.Methods: Retrospectively we analyzed 87 IVF procedures with in vitro maturation of oocytes carried out in 73 infertile couples treated at the Maribor Teaching Hospital. We compared the success following three different hormone priming protocols: regular cycling patients with normal ovaries and without hormone priming (Group A, n = 27; patients with PCOS and hormone priming with follitropin (follicle stimulating hormone, FSH (Group B, n = 22; patients with PCOS and hormone priming with human chorionic gonadotrophin (hCG (Group C, n = 38. Success of the procedure was evaluated on the basis of the ability of oocytes to mature, fertilize and develop into embryos, and on the basis of the quality of embryos and their ability to implant in the uterus.Results: In regular cycling patients with normal ovaries (n = 27 we obtained a significantly lower number of immature oocytes (3.2 ± 2.5 compared with patients with PCOS and FSH priming (11.7 ± 7.2 or those with PCOS and hCG priming (10.4 ± 7.2. The oocyte maturation rate, the fertilization rate and the embryo cleavage rate were as follows: in Group A 57.7 %, 63.2 % and 91.7 %, in Group B 57.6 %, 66.2 % and 90.0 %, and in Group C 58.0 %, 66.2 % and 91.0 % (the differences between groups were not statistically significant. Six pregnancies were recorded only in patients with PCOS. The pregnancy rate per embryo transfer was 1/20 (5.0 % in patients with FSH priming, and 5/33 (15.2 % in patients with hCG priming.Conclusions: Oocyte in vitro maturation is successful in patients with normal ovaries and regular menstrual cycle as well as in those with polycystic

  10. Determinants of loan maturity in small business lending

    Directory of Open Access Journals (Sweden)

    Ashiqur Rahman

    2017-06-01

    Full Text Available This paper investigates the determinants of loan maturity of small and medium enterprises (SMEs in the context of Visegrad countries: Czech Republic, Slovak Republic, Poland, and Hungary. The data of instead of for this paper was obtained from the Business Environment and Enterprise Performance Survey (BEEPS, which is a joint project of the European Bank for Reconstruction and Development and the World Bank. By using a binary logistic model, we have found that loan maturity is shorter for older and mature firms, firms owned by female and firms experiencing a shortage of liquidity. At the same time, we have also found that firms having concentrated ownership structure and more tangible assets can borrow for a longer period. In addition to that, we have found evidence that loan maturity is longer for the firms located closer to a bank branch. We also provide empirical support for the assumption that bank low competition is associated with longer maturity. From the obtained results, we may recommend SMEs to borrow from banks that are within their vicinity since this may increase the maturity of loans. Policy makers are recommended to implement policies so that to alleviate gender-related discrimination and take initiatives to moderate the level of competition at this market.

  11. Comparative transcriptome analyses of a late-maturing mandarin mutant and its original cultivar reveals gene expression profiling associated with citrus fruit maturation

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2017-05-01

    Full Text Available Characteristics of late maturity in fruit are good agronomic traits for extending the harvest period and marketing time. However, underlying molecular basis of the late-maturing mechanism in fruit is largely unknown. In this study, RNA sequencing (RNA-Seq technology was used to identify differentially expressed genes (DEGs related to late-maturing characteristics from a late-maturing mutant ‘Huawan Wuzishatangju’ (HWWZSTJ (Citrus reticulata Blanco and its original line ‘Wuzishatangju’ (WZSTJ. A total of approximately 17.0 Gb and 84.2 M paried-end reads were obtained. DEGs were significantly enriched in the pathway of photosynthesis, phenylpropanoid biosynthesis, carotenoid biosynthesis, chlorophyll and abscisic acid (ABA metabolism. Thirteen candidate transcripts related to chlorophyll metabolism, carotenoid biosynthesis and ABA metabolism were analyzed using real-time quantitative PCR (qPCR at all fruit maturing stages of HWWZSTJ and WZSTJ. Chlorophyllase (CLH and divinyl reductase (DVR from chlorophyll metabolism, phytoene synthase (PSY and capsanthin/capsorubin synthase (CCS from carotenoid biosynthesis, and abscisic acid 8′-hydroxylase (AB1 and 9-cis-epoxycarotenoid dioxygenase (NCED1 from ABA metabolism were cloned and analyzed. The expression pattern of NCED1 indicated its role in the late-maturing characteristics of HWWZSTJ. There were 270 consecutive bases missing in HWWZSTJ in comparison with full-length sequences of NCED1 cDNA from WZSTJ. Those results suggested that NCED1 might play an important role in the late maturity of HWWZSTJ. This study provides new information on complex process that results in the late maturity of Citrus fruit at the transcriptional level.

  12. Maturity In The Petrochemical Industry Features, Motives And Combating

    International Nuclear Information System (INIS)

    Farag, H.; El Messirie, A.

    2004-01-01

    Petrochemicals give the highest value from crude oil and natural gas but suffers from maturity like any other business. Petrochemicals companies are promoting their business in the direction from oil and gas commodities. Specialities and life science. Reasons of maturity are expired patents, low demand, over capacity, intense competition. Actions to combat maturity are to restructure capacity achieving mega sizes, do downstream, and restructuring business practices. Strategies followed by some companies to combat maturity include exit, focus on core business and exploit a competitive advantage

  13. Patterns of pulmonary maturation in normal and abnormal pregnancy.

    Science.gov (United States)

    Goldkrand, J W; Slattery, D S

    1979-03-01

    Fetal pulmonary maturation may be a variable event depending on various feto-maternal environmental and biochemical influences. The patterns of maturation were studied in 211 amniotic fluid samples from 123 patients (normal 55; diabetes 23; Rh sensitization 19; preeclampsia 26). The phenomenon of globule formation from the amniotic fluid lipid extract and is relation to pulmonary maturity was utilized for this analysis. Validation of this technique is presented. A normal curve was constructed from 22 to 42 weeks; gestation and compared to the abnormal pregnancies. Patients with class A, B, and C diabetes and Rh-sensitized pregnancies had delayed pulmonary maturation. Patients with class D diabetes and preclampsia paralleled the normal course of maturation. A discussion of these results and their possible cause is presented.

  14. early maturing mutants in Indica rice and their traits

    International Nuclear Information System (INIS)

    Chen Xiulan; He Zhentian; Han Yuepeng; Liu Xueyu; Yang Hefeng; Xu Chenwu; Gu Shiliang

    1998-01-01

    The correlation and genetic parameters of eleven agronomic characters of 50 early mature lines induced from late mature cultivar, IR 1529-68-3-2 were studied by morphological classification and correlation and regression analysis. The results showed that: 1. The early mutants could be divided into two ecotype: early mature type and medium mature type of mid-maturity rice. 2. The 1000-grain weight of early mutants negatively correlated with the length of growing period. 3. According to direct path coefficients, the relation with heading period of early mutants was in order of 1000-grain-weight>plant height>seed sterility. 4.The higher heritability in broad sense were found in plant height, 1000 grain weight and heading period of the early mutants

  15. Digital Maturity of the Firm's Business Model

    DEFF Research Database (Denmark)

    Groskovs, Sergejs; Vemula, Sreekanth

    We propose a digital maturity assessment model as an instrument for researchers and a strategic tool for managers. Existing literature lacks a conceptually clear way to measure the construct of digital maturity at the level of the firms business model. Our proposed instrument thus opens avenues f...

  16. Chromatin maturation depends on continued DNA-replication

    International Nuclear Information System (INIS)

    Schlaeger, E.J.; Puelm, W.; Knippers, R.

    1983-01-01

    The structure of [ 3 H]thymidine pulse-labeled chromatin in lymphocytes differs from that of non-replicating chromatin by several operational criteria which are related to the higher nuclease sensitivity of replicating chromatin. These structural features of replicating chromatin rapidly disappear when the [ 3 H]thymidine pulse is followed by a chase in the presence of an excess of non-radioactive thymidine. However, when the rate of DNA replication is reduced, as in cycloheximide-treated lymphocytes, chromatin maturation is retarded. No chromatin maturation is observed when nuclei from pulse-labeled lymphocytes are incubated in vitro in the absence of DNA precursors. In contrast, when these nuclei are incubated under conditions known to be optimal for DNA replication, the structure of replicating chromatin is efficiently converted to that of 'mature', non-replicating chromatin. The authors conclude that the properties of nascent DNA and/or the distance from the replication fork are important factors in chromatin maturation. (Auth.)

  17. 7 CFR 1427.174 - Maturity of seed cotton loans.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Maturity of seed cotton loans. 1427.174 Section 1427.174 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION... Maturity of seed cotton loans. Seed cotton loans mature on demand by CCC but no later than May 31 following...

  18. Chemical composition, at consuming ripeness level of tomatoes irradiated at mature green and greenish yellow stages of maturity

    Science.gov (United States)

    Al-Wandawi, H. K.; Abdul-Rahman, M. H.; Al-Shaickley, K. A.

    Tomatoes (Lycopersicon esculentum L.,var.Monte carlo) have been Y-irradiated (100-400Krad) and left to ripen to consuming ripeness. The results revealed that in fruits irradiated with 100,200 and 300 krad at mature-green, 48 hour after harvesting and at greenish yellow stages of maturity, 24 hours after harvesting, the levels of ascorbic acid were accounted to 62, 51, 27% and 84, 59, 34% of control samples respectively. In fruits irradiated with 200 krad at mature-green stage and 48 hours after harvesting and in fruits irradiated with 400 krad at greenish yellow stage and 48 hours after harvesting, the levels of lycopene were 279 and 246% of that of control samples; while the lowest levels of lycopene were in fruits irradiated with 400 krad and at mature-green and greenish yellow stages and 48 hours after harvesting where lycopene accounted to 11 and 24% respectively when compared to control samples . on the other hand, radiation had no significant effect on PH, titrable acidity and °Brix of tomatoes.

  19. Chemical composition, at consuming ripeness level of tomatoes irradiated at mature green and greenish yellow stages of maturity

    International Nuclear Information System (INIS)

    Al-Wandawi, H.K.; Abdul-Rahman, M.H.; Al-Shaickley, K.A.

    1983-01-01

    Tomatoes (Lycopersicon esculentum L., var. Monte Carlo) have been γ-irradiated (100 to 400 krad) and left to ripen to consuming ripeness. The results revealed that in fruits irradiated with 100, 200 and 300 krad at mature-green, 48 hours after harvesting and at greenish yellow stages of maturity, 24 hours after harvesting, the levels of ascorbic acid were accounted to 62, 51, 27% and 84, 59, 34% of control samples respectively. In fruits irradiated with 200 krad at mature-green stage and 48 hours after harvesting and in fruits irradiated with 400 krad at greenish yellow stage and 48 hours after harvesting, the levels of lycopene were 279 and 246% of that of control samples; while the lowest levels of lycopene were in fruits irradiated with 400 krad and at mature-green and greenish yellow stages and 48 hours after harvesting where lycopene accounted to 11 and 24% respectively when compared to control samples. On the other hand, radiation had no significant effect on PH, titrable acidity and deg Brix of tomatoes. (author)

  20. Association between frontal sinus morphology and cervical vertebral maturation for the assessment of skeletal maturity.

    Science.gov (United States)

    Mahmood, Hafiz Taha; Shaikh, Attiya; Fida, Mubassar

    2016-10-01

    Various methods have been proposed to evaluate a patient's developmental status. However, most of them lacked precision and failed to give a reliable estimate of skeletal maturity. The aims of this study were to evaluate the association between frontal sinus morphology and cervical vertebral maturation for the assessment of skeletal maturity and to determine its validity in assessing the different stages of the adolescent growth spurt. A cross-sectional study was performed on the pretreatment lateral cephalograms of 252 subjects aged 8 to 21 years. The sample was divided into 6 groups based on the cervical vertebral maturation stages. The frontal sinus index was calculated by dividing the frontal sinus height and width, and the cervical stages were evaluated on the same radiograph. The Kruskal-Wallis test was applied to compare frontal sinus index values at different cervical stages, and the post hoc Dunnett T3 test was applied to compare frontal sinus index values between adjacent cervical stages for each sex. The Kendall tau-b values were computed to assess the correlation between the cervical stages and the sinus index. A P value of ≤0.05 was considered statistically significant. The height and width of the frontal sinus were significantly larger in the male subjects than in the females. A significant association was found between the frontal sinus height and width and cervical stages (P ≤0.001) in both sexes. However, the changes in the frontal sinus index across the different cervical stages were found to be significant (P ≤0.001) in male subjects only. Similarly, a weak negative correlation was found between the sinus index and the cervical stages in male subjects (tau-b = -0.271; P cervical stages. The frontal sinus index cannot be used to identify the prepubertal, pubertal, and postpubertal stages of the adolescent growth spurt. Therefore, it cannot be used as a reliable maturity indicator. Copyright © 2016 American Association of

  1. A maturity model for industrial supply chains

    NARCIS (Netherlands)

    Hameri, A.P.; McKay, K.N.; Wiers, V.C.S.

    2013-01-01

    This article takes an evolutionary view of supply chains to suggest a series of distinct, contextual phases for supply chain execution and what maturity might mean at each phase. For example, what is best practice in a mature industry might not be best practice in a pioneering situation.Three

  2. Moving towards maturity in business model definitions

    DEFF Research Database (Denmark)

    Nielsen, Christian; Lund, Morten; Bukh, Per Nikolaj

    2014-01-01

    The field of business models has, as is the case with all emerging fields of practice, slowly matured through the development of frameworks, models, concepts and ideas over the last 15 years. New concepts, theories and models typically transcend a series of maturity phases. For the concept of Bus...

  3. Insulin-like growth factor I: a biologic maturation indicator.

    Science.gov (United States)

    Ishaq, Ramy Abdul Rahman; Soliman, Sanaa Abou Zeid; Foda, Manal Yehya; Fayed, Mona Mohamed Salah

    2012-11-01

    Determination of the maturation level and the subsequent evaluation of growth potential during preadolescence and adolescence are important for optimal orthodontic treatment planning and timing. This study was undertaken to evaluate the applicability of insulin-like growth factor I (IGF-I) blood level as a maturation indicator by correlating it to the cervical vertebral maturation index. The study was conducted with 120 subjects, equally divided into 60 males (ages, 10-18 years) and 60 females (ages, 8-16 years). A lateral cephalometric radiograph and a blood sample were taken from each subject. For each subject, cervical vertebral maturation and IGF-I serum level were assessed. Mean values of IGF-I in each stage of cervical vertebral maturation were calculated, and the means in each stage were statistically compared with those of the other stages. The IGF-I mean value at each cervical vertebral maturation stage was statistically different from the mean values at the other stages. The highest mean values were observed in stage 4, followed by stage 5 in males and stage 3 in females. IGF-I serum level is a reliable maturation indicator that could be applied in orthodontic diagnosis. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  4. Antibody Affinity Maturation in Fishes—Our Current Understanding

    Directory of Open Access Journals (Sweden)

    Brad G. Magor

    2015-07-01

    Full Text Available It has long been believed that fish lack antibody affinity maturation, in part because they were thought to lack germinal centers. Recent research done on sharks and bony fishes indicates that these early vertebrates are able to affinity mature their antibodies. This article reviews the functionality of the fish homologue of the immunoglobulin (Ig mutator enzyme activation-induced cytidine deaminase (AID. We also consider the protein and molecular evidence for Ig somatic hypermutation and antibody affinity maturation. In the context of recent evidence for a putative proto-germinal center in fishes we propose some possible reasons that observed affinity maturation in fishes often seems lacking and propose future work that might shed further light on this process in fishes.

  5. A lack of cerebral lateralization in schizophrenia is within the normal variation in brain maturation but indicates late, slow maturation.

    Science.gov (United States)

    Saugstad, L F

    1999-10-19

    The planum temporale (PT) bias, PT leftward, PT symmetry, and PT rightward reversal and sidedness preference, consistent right-handedness, ambilaterality, and consistent left-handedness are placed on a continuum mirroring the normal variation in rate of brain maturation. Maturational rate declines as we pass from PT leftward bias and consistent right-handedness to PT reversal and consistent left-handedness. Concomitantly, we expect an increased prevalence of males due to their pubertal age being about 2 years later than that of females, and a shift in cognitive profile from higher verbal scores than performance scores on the WAIS to higher performance than verbal scores. Three disorders fulfilling the criteria of late CNS maturation apart from the corresponding cognitive profile were studied: infantile autism (IA), schizophrenia (S), and developmental dyslexia (DD). These disorders have in common deficits in cognition, perception, and somatomotor function. The deficits range from an arrest in brain development (which is evident in infancy superimposed on late maturation in IA) to overall delayed brain and somatic development in S (culminating in postpubertal psychotic episodes and persistent and generalized residual deficits). Finally, reading inability, problems in perception (vision and hearing) and in motor coordination, particularly between the two hemispheres, characterize DD. Enhancing brain maturation and the prevalence of 'normal' cerebral asymmetry--laterality is preferable if we want to reduce the risk of developing the above-mentioned disorders. It is suggested that in the past environmental challenges have favored early maturation, with its abundant neuronal population, arborization and excessive density of synapses and cerebral excitability which has powered evolution through the mechanism of natural selection. Early maturation is obtainable through optimal nutrition, including a satisfactory amount of marine fat (PUFA), before and during pregnancy and

  6. Grammar Maturity Model

    NARCIS (Netherlands)

    Zaytsev, V.; Pierantonio, A.; Schätz, B.; Tamzalit, D.

    2014-01-01

    The evolution of a software language (whether modelled by a grammar or a schema or a metamodel) is not limited to development of new versions and dialects. An important dimension of a software language evolution is maturing in the sense of improving the quality of its definition. In this paper, we

  7. Tomato seeds maturity detection system based on chlorophyll fluorescence

    Science.gov (United States)

    Li, Cuiling; Wang, Xiu; Meng, Zhijun

    2016-10-01

    Chlorophyll fluorescence intensity can be used as seed maturity and quality evaluation indicator. Chlorophyll fluorescence intensity of seed coats is tested to judge the level of chlorophyll content in seeds, and further to judge the maturity and quality of seeds. This research developed a detection system of tomato seeds maturity based on chlorophyll fluorescence spectrum technology, the system included an excitation light source unit, a fluorescent signal acquisition unit and a data processing unit. The excitation light source unit consisted of two high power LEDs, two radiators and two constant current power supplies, and it was designed to excite chlorophyll fluorescence of tomato seeds. The fluorescent signal acquisition unit was made up of a fluorescence spectrometer, an optical fiber, an optical fiber scaffolds and a narrowband filter. The data processing unit mainly included a computer. Tomato fruits of green ripe stage, discoloration stage, firm ripe stage and full ripe stage were harvested, and their seeds were collected directly. In this research, the developed tomato seeds maturity testing system was used to collect fluorescence spectrums of tomato seeds of different maturities. Principal component analysis (PCA) method was utilized to reduce the dimension of spectral data and extract principal components, and PCA was combined with linear discriminant analysis (LDA) to establish discriminant model of tomato seeds maturity, the discriminant accuracy was greater than 90%. Research results show that using chlorophyll fluorescence spectrum technology is feasible for seeds maturity detection, and the developed tomato seeds maturity testing system has high detection accuracy.

  8. Guidelines for assessing the knowledge management maturity of organizations

    Directory of Open Access Journals (Sweden)

    C. J. Kruger

    2007-11-01

    Full Text Available In a recent article Kruger and Snyman hypothesized that progressions in knowledge management maturity (from a strategic perspective are directly related to an increased ability to speed up the strategic cycle of imitation, consolidation and innovation. The arguments proposed, however, neglected to supply the reader with a practical toolkit or even a roadmap (a time-related matrix, or questionnaire to successfully measure succession in knowledge management maturity. This article builds on the previous one and proposes a questionnaire consisting of six sections, containing 101 descriptive questions, to enable organizations to test and assess their knowledge management maturity empirically. The development of an instrument to measure knowledge management maturity required adhering to a research design that combined theoretical propositions with practical experimentation. As a point of departure, a knowledge management maturity matrix consisting of seven maturity levels was formulated. All questions contained within the matrix were benchmarked against a survey questionnaire developed by the public management service of the OECD (PUMA and were also pre-tested and validated. This process of refinement led to the formulation of the Knowledge Management Maturity Questionnaire. To avoid any taint of this research being based only on theoretical propositions, the questionnaire was tested by 178 master students of the University of Pretoria, South Africa, in nine different industries. The proposed questionnaire provides a bridge between theoretical propositions and practical usability, not only enabling knowledge management practitioners to assess the level of knowledge management maturity reached successfully but, more importantly, also serving as a guideline to institutionalize further and future knowledge management endeavours.

  9. Sequential Analysis of Global Gene Expression Profiles in Immature and In vitro Matured Bovine Oocytes: Potential Molecular Markers of Oocyte Maturation

    LENUS (Irish Health Repository)

    Mamo, Solomon

    2011-03-16

    Abstract Background Without intensive selection, the majority of bovine oocytes submitted to in vitro embryo production (IVP) fail to develop to the blastocyst stage. This is attributed partly to their maturation status and competences. Using the Affymetrix GeneChip Bovine Genome Array, global mRNA expression analysis of immature (GV) and in vitro matured (IVM) bovine oocytes was carried out to characterize the transcriptome of bovine oocytes and then use a variety of approaches to determine whether the observed transcriptional changes during IVM was real or an artifact of the techniques used during analysis. Results 8489 transcripts were detected across the two oocyte groups, of which ~25.0% (2117 transcripts) were differentially expressed (p < 0.001); corresponding to 589 over-expressed and 1528 under-expressed transcripts in the IVM oocytes compared to their immature counterparts. Over expression of transcripts by IVM oocytes is particularly interesting, therefore, a variety of approaches were employed to determine whether the observed transcriptional changes during IVM were real or an artifact of the techniques used during analysis, including the analysis of transcript abundance in oocytes in vitro matured in the presence of α-amanitin. Subsets of the differentially expressed genes were also validated by quantitative real-time PCR (qPCR) and the gene expression data was classified according to gene ontology and pathway enrichment. Numerous cell cycle linked (CDC2, CDK5, CDK8, HSPA2, MAPK14, TXNL4B), molecular transport (STX5, STX17, SEC22A, SEC22B), and differentiation (NACA) related genes were found to be among the several over-expressed transcripts in GV oocytes compared to the matured counterparts, while ANXA1, PLAU, STC1and LUM were among the over-expressed genes after oocyte maturation. Conclusion Using sequential experiments, we have shown and confirmed transcriptional changes during oocyte maturation. This dataset provides a unique reference resource

  10. Cone and Seed Maturation of Southern Pines

    Science.gov (United States)

    James P. Barnett

    1976-01-01

    If slightly reduced yields and viability are acceptable, loblolly and slash cone collections can begin 2 to 3 weeks before maturity if the cones are stored before processing. Longleaf(P. palestris Mill.) pine cones should be collected only when mature, as storage decreased germination of seeds from immature cones. Biochemical analyses to determine reducing sugar...

  11. Analyzing Project Management Maturity Level in Indonesia

    Directory of Open Access Journals (Sweden)

    Eliot Simangunsong

    2013-04-01

    Full Text Available Project management has been generally known and increasingly used by many organizations to gain competitive advantage. In this context, many studies have proposed maturity models to evaluate how project management knowledge has been deployed effectively and efficiently in or- ganization. As a developing country, Indonesia needs many development projects managed by government and private companies in different industries. Here, a study to assess project manage- ment maturity level in Indonesian businesses may bring insight about current business practices, which is important to speed up country development and business sustainability. Adapting the Project Management Maturity Model (ProMMM, a survey instrument has been developed and ap- plied to professionals from Jakarta and surrounding area. The result of analysis shows that con- struction and primary industry have a higher maturity level compare to manufacturing and servic- es. It is to be noted, however, that the level of project management understanding is low across in- dustries. This indicates that more quality project management training or certification is required to improve overall project management knowledge in Indonesia.

  12. Mature teratoma of the posterior mediastinum

    International Nuclear Information System (INIS)

    Kurosaki, Y.; Tanaka, Y.O.; Itai, Y.

    1998-01-01

    The vast majority of germ cell tumors in the thorax arise at or near the thymus. We report a case of a 41-year-old man with mature teratoma of the posterior mediastinum. He was asymptomatic and was incidentally found to have a posterior mediastinal mass. Computed tomography was helpful in suggesting a diagnosis of mature teratoma by demonstrating the presence of fat and calcification. The differential diagnosis included neurogenic tumors, liposarcoma, and extramedullary hematopoiesis. (orig.)

  13. Mature Oocyte Cryopreservation for Fertility Preservation.

    Science.gov (United States)

    Liang, Tina; Motan, Tarek

    2016-01-01

    In recent decades, advances in cancer treatment have led to a dramatic improvement in long term survival. This has led to an increasing focus on quality of life after surviving cancer treatment, with fertility being an important aspect. Given the known reproductive risks of cancer therapies, there has been a growing interest in the field of fertility preservation (also referred to as oncofertility). Mature oocyte cryopreservation is no longer considered experimental and has become a realistic option for reproductive aged women prior to undergoing cancer treatment. Additionally, as cryopreservation techniques improve, mature oocyte cryopreservation is increasing being marketed to healthy women without cancer wishing to delay child bearing, also termed "social egg freezing". This chapter provides a review of the current technology, use, and outcomes of mature oocyte cryopreservation. It also outlines the ethical debate surrounding social egg freezing and directions for future research in female fertility preservation.

  14. POSTTREATMENT NEUROBLASTOMA MATURATION TO GANGLIONIC CELL TUMOR

    Directory of Open Access Journals (Sweden)

    M. V. Ryzhova

    2012-01-01

    Full Text Available Tumor cells can differentiate into more mature forms in undifferentiated or poorly differentiated tumors, such as medulloblastomas with increased nodularity, as well as neuroblastomas. The authors describe 2 cases of neuroblastoma maturation into ganglioneuroblastoma 5 months after chemotherapy in a 2-year-old girl and 3 years after radiotherapy in a 16-year-old girl.

  15. Information system maturity and the hospitality enterprise performance

    Directory of Open Access Journals (Sweden)

    Daniela Garbin Pranicevic

    2015-01-01

    Full Text Available The purpose of this paper is to empirically evaluate the relationship between the maturity of hotels’ information systems and their performance. This study uses customized models of information system (IS maturity and hotel performance measurement. Since we wanted to include the intangible aspects of performance, we opted for an adapted application of the Balanced Scorecard model. In the empirical part of the paper, fundamental constructs of the model are verified, while the individual items are further evaluated by employing discriminant analysis to distinguish hotels with relatively low and high performance levels. The findings demonstrate the existence of a significant and positive relationship between IS maturity and two dimensions of performance in the hospitality industry – process quality and guest relationships. The level of employee development and financial performance do not seem to be related to IS maturity. Although representative, the sample is relatively small, and the primary data were collected in a single country. The paper provides a framework of IS maturity items in the hospitality industry which seem to contribute to hotels’ business performances. As such, it can serve as a practical framework relevant for IT management in tourism and hospitality. The paper addresses a topic already discussed in a range of industries, although it does not seem to have been empirically evaluated by many studies of the tourism and hospitality industry. In addition, a new theoretical model of IT maturity in tourism and hospitality is proposed.

  16. CT findings of overian teratomas : mature versus immature

    International Nuclear Information System (INIS)

    Kim, Jong Chul; Kim, Young Wol

    1996-01-01

    To differentiate mature and immature ovarian teratomas, using CT findings. The CT findings of ten mature ovarian teratomas (in one patient, bilateral) and ten which were immature were compared, using statistical analysis. Images were evaluated for size, margins, architecture, contents (mural nodules, fat, calcification), septa, local invasion and distant metastasis. These findings were compared with pathologic findings. Of the ten mature tumors, nine were well defined and predominantly cystic in internal architecture, and one was mixed. Mural nodules were found in six tumor, fat in all, distinct calcification in seven, and regular septa in three lesions. Of the ten immature humors, eight had irregular margins. Seven were predominantly solid in internal architecture and irregularly enhanced, two were mixed, and one was mainly cystic. Fat was detected in five lesions, indistinct scattered calcification in six, irregular septa in three, and local invasion of distant metastasis in four patients. Compared with mature ovarian teratomas, those that are immature tend to show CT findings of marginal irregularity, solid mass with irregular enhacement, scattered indistinct calcifications, septal irregularity, local invasion or distant metastasis. Our experience suggests that these findings may be helpful in differentiation of mature and immature ovarian teratomas

  17. Indeks Penilaian Kematangan (Maturity Manajemen Keamanan Layanan TI

    Directory of Open Access Journals (Sweden)

    Farroh Sakinah

    2014-09-01

    Full Text Available Pemanfaatan Teknologi Informasi (TI dalam mendukung terselenggaranya pelayanan yang optimal menjadi kebutuhan utama organisasi saat ini. Jaminan pengelolaan layanan dan keamanan yang baik menjadi salah satu tolok ukurnya. Pengimplementasian sebuah standar menjadi salah satu solusinya meskipun penggunaan satu buah standar dirasa belum maksimal melihat cakupan yang disediakan kurang luas sehingga diadakannya upaya penggabungan beberapa standar dengan harapan standar-standar tersebut dapat saling melengkapi. Pengimplementasian beberapa standar ini dapat dimonitoring tingkat kematangannya (maturity dengan menggunakan alat ukur penilaian kematangan (maturity. Alat ukur kematangan (maturity manajemen keamanan layanan ini merupakan gabungan pemetaan dari control objective IT Governance COBIT 4.1 yang dipenuhi kebutuhan manajemen layanannya sesuai dengan Service Management di dalam ITIL v3 (Information Technology Infrastructure Library. Selanjutnya kebutuhan manajemen layanan ini diukur dengan maturity level COBIT 4.1 dan disesuaikan dengan framework ISO 27000 untuk memaksimalkan manajemen keamanan informasi.

  18. Methodology for Diagnostics of the Company Management and Technological Maturity

    Directory of Open Access Journals (Sweden)

    Olena Martynyuk

    2017-12-01

    Full Text Available Approaches to the measurement and assessment of the company technological maturity level and management maturity apart, formulated in scientific researches and practical recommendations, significantly differ according to their purpose, content and depth of the factors analysis. Studies of the company technological maturity and possibility for implementing business processes and certain IT technologies have become more advanced in some degree. The general idea of forming a model of diagnostics of the management and technological maturity is based on the determination of prevailing company system influence components. Management techniques are a nucleus of the model, and the innovation level of management techniques is an energy impulse inciting to development. Basing on the analysis performed, the author created a concept of levels of the company management and technological maturity considering the main parameters of the company management and technological maturity. A composite algorithm was proposed for determining the level of managerial technological maturity (LMTM, end exposition of a complex of management techniques to ensure the company dynamic progress based on determining a level of the management and technological maturity. The advantages and disadvantages are determined by the methodology. The performed approbation has confirmed the approach validity and its usefulness. The approbation shows the reliability and unambiguity of interpreting results. To use it for bigger enterprises and corporations, it is not even necessary to change identification parameters.

  19. Mature teratoma of the posterior mediastinum

    Energy Technology Data Exchange (ETDEWEB)

    Kurosaki, Y.; Tanaka, Y.O.; Itai, Y. [Department of Radiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki-ken 305 (Japan)

    1998-02-01

    The vast majority of germ cell tumors in the thorax arise at or near the thymus. We report a case of a 41-year-old man with mature teratoma of the posterior mediastinum. He was asymptomatic and was incidentally found to have a posterior mediastinal mass. Computed tomography was helpful in suggesting a diagnosis of mature teratoma by demonstrating the presence of fat and calcification. The differential diagnosis included neurogenic tumors, liposarcoma, and extramedullary hematopoiesis. (orig.) With 2 figs., 18 refs.

  20. ASSOCIATION BETWEEN DENTAL AND SKELETAL MATURATION STAGES IN CROATIAN SUBJECTS.

    Science.gov (United States)

    Srkoc, Tamara; Mestrović, Senka; Anić-Milosević, Sandra; Slaj, Mladen

    2015-12-01

    This study investigated the relationships between the stages of calcification of teeth and cervical vertebral maturation. The sample consisted of 295 subjects (129 male and 166 female), mean age 13.36 ± 2.65 (range 7-18) years. Dental age was evaluated from panoramic radiographs according to the method of Demirjian. Cervical vertebral maturation was determined on lateral cephalometric radiographs using cervical vertebrae maturation stages (CVS). For assessing the relationship between cervical vertebral and dental maturation, percentage distributions of the stages of calcification for each studied tooth were calculated. Only in the first CVS stage, boys and girls were of the same age. In all other stages (CVS 2-CVS 6) girls were by 0.98 (range 0.23-1.86) younger than boys. Gender differences in the mineralization pattern were also observed. It was found that dental maturation was finished earlier in female subjects. The highest correlation coefficient between dental and skeletal maturity was found for second premolars. Mineralization pattern of second premolars could be considered as a guideline for prediction of the pubertal growth spurt. Dental maturation stages might be clinically useful as a reliable indicator of facial growth.

  1. Radium retention in mature beagles injected at 5 years of age

    International Nuclear Information System (INIS)

    Lloyd, R.D.; Bruenger, F.W.; Jones, C.W.; Taylor, G.N.; Mays, C.W.

    1982-01-01

    Retention of 226 Ra was substantially lower in mature beagles injected at 5 years of age compared to corresponding values for 1 1/2-year-old young adult beagles. As with young adults, average retention in mature dogs given about 10 μCi/kg exceeded that of mature dogs given 4 μCi/kg or less. Measured 222 Rn/ 226 Ra ratios in bone were similar in mature and young adults. About 66% of the injected radium was excreted by mature dogs during the first 3 weeks, about 2/3 of the total excretion appearing in the feces. Distribution of 226 Ra within the skeleton was similar in mature and young adult beagles

  2. Radiation induced early maturing mutants in barley

    International Nuclear Information System (INIS)

    Kumar, R.; Chauhan, S.V.S.; Sharma, R.P.

    1978-01-01

    In M 2 generation, two early maturing plants were screened from a single spike progeny of a plant obtained from 20 kR of gamma-ray irradiation of a six-rowed barley (Hordeum vulgare L. var. Jyoti). Their true breeding nature was confirmed in M 3 generation. These mutants flower and mature 38 and 22 days earlier than those of control. (auth.)

  3. In vitro maturation of human oocytes for assisted reproduction.

    Science.gov (United States)

    Jurema, Marcus W; Nogueira, Daniela

    2006-11-01

    To describe and evaluate the current practice of in vitro maturation of oocytes for assisted reproduction. Review of the available and relevant literature regarding in vitro maturation of oocytes. In vitro maturation of human oocytes retrieved from antral ovarian follicles is an emerging procedure quickly being incorporated into the realm of assisted reproductive technologies. This new technology has several potential advantages over traditional controlled ovarian hyperstimulation for IVF, such as reduction of costs by minimizing gonadotropin and GnRH analogue use, elimination of ovarian hyperstimulation syndrome, and simplicity of protocol. In vitro maturation of oocytes for assisted reproduction in human beings still is undergoing refinement but currently is providing efficacy and safety outcome comparable to that of traditional IVF in recent selected studies. Implementing in vitro maturation into an established IVF practice is feasible and requires only a few simple adjustments. Crucial to the advancement and optimization of the technology is a better understanding of how to maximize immature oocyte developmental competence and endometrial receptivity.

  4. A Comparison of Skeletal Maturation assessed from MP3 and Its Correlation with Dental Maturation

    Directory of Open Access Journals (Sweden)

    Vishnu Vardhan Reddy

    2014-01-01

    Full Text Available To compare the various ossification stages of middle phalanges of third finger (MP3 and developmental stages of 2nd mandibular molar during the entire process of pubertal growth spurt. Evaluate the feasibility of recording MP3 stages using standard dental X-ray film. The mandibular 2nd molar exhibited highly significant correlation for both the males and females. This study showed a good correlation between the MP3 and dental maturity indicators. Therefore, 2nd molar tooth could be used as maturity indicator for the entire period of pubertal growth spurt. It can be used as an adjunct to the hand and wrist radiograph.

  5. Toward the Decision Tree for Inferring Requirements Maturation Types

    Science.gov (United States)

    Nakatani, Takako; Kondo, Narihito; Shirogane, Junko; Kaiya, Haruhiko; Hori, Shozo; Katamine, Keiichi

    Requirements are elicited step by step during the requirements engineering (RE) process. However, some types of requirements are elicited completely after the scheduled requirements elicitation process is finished. Such a situation is regarded as problematic situation. In our study, the difficulties of eliciting various kinds of requirements is observed by components. We refer to the components as observation targets (OTs) and introduce the word “Requirements maturation.” It means when and how requirements are elicited completely in the project. The requirements maturation is discussed on physical and logical OTs. OTs Viewed from a logical viewpoint are called logical OTs, e.g. quality requirements. The requirements of physical OTs, e.g., modules, components, subsystems, etc., includes functional and non-functional requirements. They are influenced by their requesters' environmental changes, as well as developers' technical changes. In order to infer the requirements maturation period of each OT, we need to know how much these factors influence the OTs' requirements maturation. According to the observation of actual past projects, we defined the PRINCE (Pre Requirements Intelligence Net Consideration and Evaluation) model. It aims to guide developers in their observation of the requirements maturation of OTs. We quantitatively analyzed the actual cases with their requirements elicitation process and extracted essential factors that influence the requirements maturation. The results of interviews of project managers are analyzed by WEKA, a data mining system, from which the decision tree was derived. This paper introduces the PRINCE model and the category of logical OTs to be observed. The decision tree that helps developers infer the maturation type of an OT is also described. We evaluate the tree through real projects and discuss its ability to infer the requirements maturation types.

  6. The maturation and germination of Phytophthora ramorum Chlamydospores

    Science.gov (United States)

    Aaron L. Smith; Everett M. Hansen

    2008-01-01

    Chlamydospores are a distinctive feature of Phytophthora ramorum. They are formed quickly in agar, and within colonized leaves. We followed their development and maturation in vitro and in vivo, and studied conditions affecting their germination. Cell walls of mature P. ramorum chlamydospores...

  7. Study of Kerogen Maturity using Transmission Fourier Transform Infrared Spectroscopy (FTIR)

    Science.gov (United States)

    Dang, S. T.

    2014-12-01

    Maturity of kerogen in shale governs the productivity and generation hydrocarbon type. There are generally two accepted methods to measure kerogen maturity; one is the measurement of vitrinite reflectance, %Ro, and another is the measurement of Tmax through pyrolysis. However, each of these techniques has its own limits; vitrinite reflectance measurement cannot be applied to marine shale and pre-Silurian shales, which lack plant materials. Furthermore, %Ro, requires the isolation and identification of vitrinite macerals and statistical measurements of at least 50 macerals. Tmax measurement is questionable for mature and post-mature samples. In addition, there are questions involving the effects of solvents on Tmax determinations. Fourier Transmission Infrared Spectroscopy, FTIR, can be applied for both qualitative and quantitative assessment on organics maturity in shale. The technique does not require separating organic matter or identifying macerals. A CH2/CH3 index, RCH, calculated from FTIR spectra is more objective than other measurements. The index increases with maturity (both natural maturation and synthetic maturation through hydrous and dry pyrolysis). The new maturity index RCH can be calibrated to vitrinite reflectance which allows the definition of the following values for levels of maturity: 1) immature—RCH > 1.6±0.2; 2) oil window-- 1.6±0.2 1.3±0.3; 3) wet gas window--1.3±0.3 1.13±0.05; and 4) dry gas window RCH < 1.13±0.05.

  8. FeS2-doped MoS2 nanoflower with the dominant 1T-MoS2 phase as an excellent electrocatalyst for high-performance hydrogen evolution

    International Nuclear Information System (INIS)

    Zhao, Xue; Ma, Xiao; Lu, Qingqing; Li, Qun; Han, Ce; Xing, Zhicai; Yang, Xiurong

    2017-01-01

    Well-established methods to improve the hydrogen evolution reaction (HER) performances include, but are not limited to, tailoring the morphology and electronic structure of transition metal dichalcogenides (TMDs), and doping of earth abundant chemicals such as iron pyrite FeS 2 into existing TMDs. In this work, MoS 2 nanoflowers with the majority being octahedral MoS 2 (1T-MoS 2 ) and doped with FeS 2 were prepared and applied to HER. The as-prepared catalysts were characterized by X-ray absorption fine structure at the K-edge of Mo, S, and Fe to probe the local electronic structures. The resulting nanomaterial was identified to be FeS 2 doped MoS 2 nanoflower (denoted as Fe-MoS 2 NF) with 66% 1T-MoS 2 which was the metallic phase and could drastically boost the HER properties. The Fe-MoS 2 NF exhibited high HER performance with a Tafel slope of 82 mV dec −1 and it needs 136 mV to achieve a current density of 10 mA cm −2 . The synthesis of Fe-MoS 2 NF with refined morphology and active electronic structure is expected to open a new era for improving the catalytic activity and stability of MoS 2 .

  9. Detection of optimum maturity of maize using image processing and ...

    African Journals Online (AJOL)

    A CCD camera for image acquisition of the different green colorations of the maize leaves at maturity was used. Different color features were extracted from the image processing system (MATLAB) and used as inputs to the artificial neural network that classify different levels of maturity. Keywords: Maize, Maturity, CCD ...

  10. Correlation between cervical vertebral and dental maturity in Iranian subjects.

    Science.gov (United States)

    Heravi, Farzin; Imanimoghaddam, Mahrokh; Rahimi, Hoda

    2011-12-01

    Determination of the skeletal maturation is extremely important in clinical orthodontics. Cervical vertebral maturation is an effective diagnostic tool for determining the adolescent growth spurt. The aim of this study was to investigate the correlation between the stages of calcification of teeth and the cervical vertebral maturity stages.

  11. Quercetin Efficacy on in vitro Maturation of Porcine Oocytes

    Directory of Open Access Journals (Sweden)

    Delia Orlovschi

    2014-05-01

    Full Text Available The present study proposed to examine the effects of a polyphenol (quercetin on in vitro maturated parameters. Quercetin it has been extensively studied by researchers on animals over the 35 years. It is a plant derived flavonoid from fruits and vegetables that has antioxidant action as a free radical scavenger. Immature porcine oocytes were untreated and treated with 5, 15, 25, 35 µg/ml quercetin during in vitro maturation. After then the mature oocytes were fertilized. It was observed that cumulus cell expansion of COCs cultured in maturation media supplemented with 5 µg/ml quercetin in grad 3 could be very significantly increased (p<0.001. In grad 4 could be significantly between different levels of quercetin (5 vs. 25, 5 vs. 35, p<0.001. The rates of embryos cultured in medium supplemented with different levels of quercetin did not presented significantly statistically different. The presence of 25 µg/ml quercetin in the maturation medium increased the percentage of embryos in the morula stage compared with the control. In the morula stage all the concentrations of quercetin resulted percentages increased to control. This results shows that quercetin added during in vitro maturation has a positive effect on future embryos development.

  12. 7 CFR 915.332 - Florida avocado maturity regulation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Florida avocado maturity regulation. 915.332 Section... SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE AVOCADOS GROWN IN SOUTH FLORIDA Container and Pack Regulations § 915.332 Florida avocado maturity regulation. (a...

  13. X-ray absorption spectroscopy on the calcium cofactor to the manganese cluster in photosynthetic oxygen evolution

    Energy Technology Data Exchange (ETDEWEB)

    Cinco, Roehl M. [Univ. of California, Berkeley, CA (United States)

    1999-12-01

    Along with Mn, calcium and chloride ions are necessary cofactors for oxygen evolution in Photosystem II (PS II). To further test and verify whether Ca is close to the Mn cluster, the authors substituted strontium for Ca and probed from the Sr point of view for any nearby Mn. The extended X-ray absorption fine structure (EXAFS) of Sr-reactivated PS II indicates major differences between the intact and NH2OH-treated samples. In intact samples, the Fourier transform of the Sr EXAFS shows a Fourier peak that is missing in inactive samples. This peak II is best simulated by two Mn neighbors at a distance of 3.5 Angstrom, confirming the proximity of Ca (Sr) cofactor to the Mn cluster. In addition, polarized Sr EXAFS on oriented Sr-reactivated samples shows this peak II is dichroic: large magnitude at 10 degrees (angle between the PS II membrane normal and the x-ray electric field vector) and small at 80 degrees. Analysis of the dichroism yields the relative angle between the Sr-Mn vector and membrane normal (23 degrees ± 4 degrees), and the isotropic coordination number for these layered samples. X-ray absorption spectroscopy has also been employed to assess the degree of similarity between the manganese cluster in PS II and a family of synthetic manganese complexes containing the distorted cubane [Mn4O3X] core (X = benzoate, acetate, methoxide, hydroxide, azide, fluoride, chloride or bromide). In addition, Mn4O3Cl complexes containing three or six terminal Cl ligands at three of the Mn were included in this study. The EXAFS method detects the small changes in the core structures as X is varied in this series, and serves to exclude these distorted cubanes of C3v symmetry as a topological model for the Mn catalytic cluster. The sulfur K-edge x-ray absorption near-edge structure (XANES) spectra for the amino acids cysteine, methionine, their corresponding oxidized forms cystine and methionine sulfoxide, and

  14. Effect of melatonin on maturation capacity and fertilization of Nili ...

    African Journals Online (AJOL)

    This study evaluated the effect of melatonin supplementation of in vitro maturation media on in vitro maturation (IVM) and in vitro fertilization (IVF) rate of buffalo oocytes. Cumulus oocytes complexes (COCs) were aspirated from follicles of 2-8 mm diameter. In experiment I, COCs were matured in IVM medium supplemented ...

  15. As Technologies for Nucleotide Therapeutics Mature, Products Emerge.

    Science.gov (United States)

    Beierlein, Jennifer M; McNamee, Laura M; Ledley, Fred D

    2017-12-15

    The long path from initial research on oligonucleotide therapies to approval of antisense products is not unfamiliar. This lag resembles those encountered with monoclonal antibodies, gene therapies, and many biological targets and is consistent with studies of innovation showing that technology maturation is a critical determinant of product success. We previously described an analytical model for the maturation of biomedical research, demonstrating that the efficiency of targeted and biological development is connected to metrics of technology growth. The present work applies this model to characterize the advance of oligonucleotide therapeutics. We show that recent oligonucleotide product approvals incorporate technologies and targets that are past the established point of technology growth, as do most of the oligonucleotide products currently in phase 3. Less mature oligonucleotide technologies, such as miRNAs and some novel gene targets, have not passed the established point and have not yielded products. This analysis shows that oligonucleotide product development has followed largely predictable patterns of innovation. While technology maturation alone does not ensure success, these data show that many oligonucleotide technologies are sufficiently mature to be considered part of the arsenal for therapeutic development. These results demonstrate the importance of technology assessment in strategic management of biomedical technologies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Origin of the Proton-transfer Step in the Cofactor-free (1H)-3-Hydroxy-4-oxoquinaldine 2,4-Dioxygenase

    Science.gov (United States)

    Hernandez-Ortega, Aitor; Quesne, Matthew G.; Bui, Soi; Heuts, Dominic P. H. M.; Steiner, Roberto A.; Heyes, Derren J.; de Visser, Sam P.; Scrutton, Nigel S.

    2014-01-01

    Dioxygenases catalyze a diverse range of chemical reactions that involve the incorporation of oxygen into a substrate and typically use a transition metal or organic cofactor for reaction. Bacterial (1H)-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) belongs to a class of oxygenases able to catalyze this energetically unfavorable reaction without any cofactor. In the quinaldine metabolic pathway, HOD breaks down its natural N-heteroaromatic substrate using a mechanism that is still incompletely understood. Experimental and computational approaches were combined to study the initial step of the catalytic cycle. We have investigated the role of the active site His-251/Asp-126 dyad, proposed to be involved in substrate hydroxyl group deprotonation, a critical requirement for subsequent oxygen reaction. The pH profiles obtained under steady-state conditions for the H251A and D126A variants show a strong pH effect on their kcat and kcat/Km constants, with a decrease in kcat/Km of 5500- and 9-fold at pH 10.5, respectively. Substrate deprotonation studies under transient-state conditions show that this step is not rate-limiting and yield a pKa value of ∼7.2 for WT HOD. A large solvent isotope effect was found, and the pKa value was shifted to ∼8.3 in D2O. Crystallographic and computational studies reveal that the mutations have a minor effect on substrate positioning. Computational work shows that both His-251 and Asp-126 are essential for the proton transfer driving force of the initial reaction. This multidisciplinary study offers unambiguous support to the view that substrate deprotonation, driven by the His/Asp dyad, is an essential requirement for its activation. PMID:24482238

  17. Protonation/reduction dynamics at the [4Fe-4S] cluster of the hydrogen-forming cofactor in [FeFe]-hydrogenases.

    Science.gov (United States)

    Senger, Moritz; Mebs, Stefan; Duan, Jifu; Shulenina, Olga; Laun, Konstantin; Kertess, Leonie; Wittkamp, Florian; Apfel, Ulf-Peter; Happe, Thomas; Winkler, Martin; Haumann, Michael; Stripp, Sven T

    2018-01-31

    The [FeFe]-hydrogenases of bacteria and algae are the most efficient hydrogen conversion catalysts in nature. Their active-site cofactor (H-cluster) comprises a [4Fe-4S] cluster linked to a unique diiron site that binds three carbon monoxide (CO) and two cyanide (CN - ) ligands. Understanding microbial hydrogen conversion requires elucidation of the interplay of proton and electron transfer events at the H-cluster. We performed real-time spectroscopy on [FeFe]-hydrogenase protein films under controlled variation of atmospheric gas composition, sample pH, and reductant concentration. Attenuated total reflection Fourier-transform infrared spectroscopy was used to monitor shifts of the CO/CN - vibrational bands in response to redox and protonation changes. Three different [FeFe]-hydrogenases and several protein and cofactor variants were compared, including element and isotopic exchange studies. A protonated equivalent (HoxH) of the oxidized state (Hox) was found, which preferentially accumulated at acidic pH and under reducing conditions. We show that the one-electron reduced state Hred' represents an intrinsically protonated species. Interestingly, the formation of HoxH and Hred' was independent of the established proton pathway to the diiron site. Quantum chemical calculations of the respective CO/CN - infrared band patterns favored a cysteine ligand of the [4Fe-4S] cluster as the protonation site in HoxH and Hred'. We propose that proton-coupled electron transfer facilitates reduction of the [4Fe-4S] cluster and prevents premature formation of a hydride at the catalytic diiron site. Our findings imply that protonation events both at the [4Fe-4S] cluster and at the diiron site of the H-cluster are important in the hydrogen conversion reaction of [FeFe]-hydrogenases.

  18. A Drosophila Model to Image Phagosome Maturation

    Directory of Open Access Journals (Sweden)

    Douglas A. Brooks

    2013-03-01

    Full Text Available Phagocytosis involves the internalization of extracellular material by invagination of the plasma membrane to form intracellular vesicles called phagosomes, which have functions that include pathogen degradation. The degradative properties of phagosomes are thought to be conferred by sequential fusion with endosomes and lysosomes; however, this maturation process has not been studied in vivo. We employed Drosophila hemocytes, which are similar to mammalian professional macrophages, to establish a model of phagosome maturation. Adult Drosophila females, carrying transgenic Rab7-GFP endosome and Lamp1-GFP lysosome markers, were injected with E. coli DH5α and the hemocytes were collected at 15, 30, 45 and 60 minutes after infection. In wild-type females, E. coli were detected within enlarged Rab7-GFP positive phagosomes at 15 to 45 minutes after infection; and were also observed in enlarged Lamp1-GFP positive phagolysosomes at 45 minutes. Two-photon imaging of hemocytes in vivo confirmed this vesicle morphology, including enlargement of Rab7-GFP and Lamp1-GFP structures that often appeared to protrude from hemocytes. The interaction of endosomes and lysosomes with E. coli phagosomes observed in Drosophila hemocytes was consistent with that previously described for phagosome maturation in human ex vivo macrophages. We also tested our model as a tool for genetic analysis using 14-3-3e mutants, and demonstrated altered phagosome maturation with delayed E. coli internalization, trafficking and/or degradation. These findings demonstrate that Drosophila hemocytes provide an appropriate, genetically amenable, model for analyzing phagosome maturation ex vivo and in vivo.

  19. Relationship between Problem-Solving Ability and Career Maturity ...

    African Journals Online (AJOL)

    This study investigated the relationship between problem-solving ability and career maturity of secondary school students in Ibadan, Oyo State, Nigeria. 230 final year secondary school students completed self-report measures of problem solving and career maturity. Multiple regression analysis was used to analyse the data ...

  20. Mature age job seekers : The role of proactivity

    NARCIS (Netherlands)

    Zacher, Hannes; Bock, Angelika

    2014-01-01

    Purpose - In the context of demographic and economic changes, helping mature age job seekers find employment is imperative. The purpose of this paper is to examine mature age job seekers' proactive personality as a moderator of the relationship between age and job search intensity; and to examine

  1. [Maturation diagnosis in full term hypotrophic fetuses].

    Science.gov (United States)

    Scharnke, H D; Gartzke, J; Fleischer, G; Isbruch, E

    1977-01-01

    Foam-Test by Clements is a valuable method for determining the foetus maturity of lungs. We introduce this test along with other parameters for the maturity-diagnosis since one year. In 15% result, the Foam-Test was not applicable because of blood, or meconic amniotic fluid, other wise wrong negative and in 0% wrong positive results. By unmatured child, there was doubtable results with Foam-Test. Since it is important to determine the early delivery of unmatured children, particularly the case of foetus maturity of lungs must be exact, we therefore decided to use the Lecithin/Sphingomyelinquotients in some cases. The results of Lecithin/Sphingomyelinquotient in unmatured children are almost with the approximated date under two. From this, one must deduce from these children, that the intrauterine unmatured lungs lately took place.

  2. Towards a Maturity Modeling Approach for the Implementation of Industrial Internet

    DEFF Research Database (Denmark)

    Menon, Karan; Kärkkäinen, Hannu; Lasrado, Lester Allan

    2016-01-01

    guidelines for industrial internet maturity model for mass production manufacturing industries which use heavy equipment. The detailed research design presented here uses ADR methodology to enable the construction of the ensemble artefact. The industrial internet maturity model will be tested, developed......This Research-in-Progress paper facilitates the design and provides guidelines for the development of a maturity model to achieve a coordinated, systematic and stepwise adoption of industrial internet, thus enabling the industrial internet to be used to its full potential in manufacturing...... enterprises. Using analogous maturity models from the fields of supply chain management and product lifecycle maturity among others, this paper explains why a maturity model approach would facilitate the step-by-step implementation of industrial internet. The paper goes on to provide systematic design...

  3. Trade-Offs of Flowering and Maturity Synchronisation for Pineapple Quality.

    Directory of Open Access Journals (Sweden)

    V Nicodème Fassinou Hotegni

    Full Text Available In the pineapple sector of Benin, poor fruit quality prevents pineapple producers to enter the European market. We investigated effects of common cultural practices, flowering and maturity synchronisation, (1 to quantify the trade-offs of flowering and maturity synchronisation for pineapple quality and the proportion of fruits exportable to European markets, and (2 to determine the effect of harvesting practice on quality attributes. Four on-farm experiments were conducted during three years using cultivars Sugarloaf and Smooth Cayenne. A split-split plot design was used in each experiment, with flowering induction practice as main factor (artificial or natural flowering induction, maturity induction practice as split factor (artificial or natural maturity induction and harvesting practice as the split-split factor (farmers' harvest practice or individual fruit harvesting at optimum maturity. Artificial flowering induction gave fruits with lower infructescence weight, higher ratio crown: infructescence length, and a lower proportion of fruits exportable to European markets than natural flowering induction. The costs of the improvements by natural flowering induction were huge: the longer durations from planting to flowering induction and harvesting, the higher number of harvestings of the fruits increasing the labour cost and the lower proportion of plants producing fruits compared with crops from artificially flowering-induced plants. Artificial maturity induction decreased the total soluble solids concentration in the fruits compared with natural maturity induction thus decreasing the proportion of fruits exportable to European markets, at a benefit of only a slightly shorter time from flowering induction to harvesting. Harvesting individual fruits at optimum maturity gave fruits with higher total soluble solids in naturally maturity induced fruits compared with the farmers' harvest practice. Given the huge costs of natural flowering induction

  4. Chemical composition, at consuming ripeness level of tomatoes irradiated at mature green and greenish yellow stages of maturity. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Al-Wandawi, H.K.; Abdul-Rahman, M.H.; Al-Shaickley, K.A. (Iraq Atomic Energy Commission, Baghdad. Nuclear Research Inst.)

    1983-01-01

    Tomatoes (Lycopersicon esculentum L., var. Monte Carlo) have been ..gamma..-irradiated (100 to 400 krad) and left to ripen to consuming ripeness. The results revealed that in fruits irradiated with 100, 200 and 300 krad at mature-green, 48 hours after harvesting and at greenish yellow stages of maturity, 24 hours after harvesting, the levels of ascorbic acid were accounted to 62, 51, 27% and 84, 59, 34% of control samples respectively. In fruits irradiated with 200 krad at mature-green stage and 48 hours after harvesting and in fruits irradiated with 400 krad at greenish yellow stage and 48 hours after harvesting, the levels of lycopene were 279 and 246% of that of control samples; while the lowest levels of lycopene were in fruits irradiated with 400 krad and at mature-green and greenish yellow stages and 48 hours after harvesting where lycopene accounted to 11 and 24% respectively when compared to control samples. On the other hand, radiation had no significant effect on PH, titrable acidity and deg Brix of tomatoes.

  5. Evaluating the Organizational Interoperability Maturity Level in ICT Research Center

    Directory of Open Access Journals (Sweden)

    Manijeh Haghighinasab

    2011-03-01

    Full Text Available Interoperability refers to the ability to provide services and to accept services from other systems or devices. Collaborative enterprises face additional challenges to interoperate seamlessly within a networked organization. The major task here is to assess the maturity level of interoperating organizations. For this purpose the maturity models for enterprise were reviewed based on vendors’ reliability and advantages versus disadvantages. Interoperability maturity model was deduced from ATHENA project as European Integrated Project in 2005, this model named as EIMM was examined in Iran information and Communication Institute as a leading Telecommunication organization. 115 questionnaires were distributed between staff of 4 departments: Information Technology, Communication Technology, Security and Strategic studies regarding six areas of concern: Enterprise Modeling, Business Strategy Process, Organization and Competences, Products and Services, Systems and Technology, Legal Environment, Security and Trust at five maturity levels: Performed, Modeled , Integrated, Interoperable and Optimizing maturity. The findings showed different levels of maturity in this Institute. To achieve Interoperability level, appropriate practices are proposed for promotion to the higher levels.

  6. Maturing interorganisational information systems

    NARCIS (Netherlands)

    Plomp, M.G.A.|info:eu-repo/dai/nl/313946809

    2012-01-01

    This thesis consists of nine chapters, divided over five parts. PART I is an introduction and the last part contains the conclusions. The remaining, intermediate parts are: PART II: Developing a maturity model for chain digitisation. This part contains two related studies concerning the development

  7. Non-Destructive Technique for Determining Mango Maturity

    OpenAIRE

    Salengke; Mursalim

    2013-01-01

    Mango (Mangifera indica L.) is an important tropical fruit that has great potential in international markets. Currently, major markets for mango include North America, Europe, and Japan. The acceptance of exported mango in destination countries depends largely on eating quality, which is affected by maturity at harvest. Mango maturity can be judged visually, based on skin color, or determined chemically based on soluble solids content, acid content, and solids:acid ratio....

  8. EMOTIONAL MATURITY OF PERSONALITY: THE PRACTICAL PROBLEM OF PSYCHOLOGICAL DIAGNOSIS

    Directory of Open Access Journals (Sweden)

    O. I. Afonina

    2013-03-01

    Full Text Available In the dif?cult conditions of the contemporary society which are far from being favorable to maintain one’s emotional and physical health the problem of development and achievement of emotional maturity as a factor of the well-being is getting more signi?cant. Based on the theoretical concepts of different scientists who de?ned the construct of emotional maturity three groups of psychological methods for assessing emotional maturity are analyzed. The ?rst group includes the methods that are used to assess emotional maturity explicitly and have a theoretical or empirical veri?cation. The second group includes the methods that are intended to assess emotional maturity as a separate scale complimented by other scales, related to evaluating other aspects of emotionality in  the  structure  of  the  personality.  The  third  group  includes  the  methods  in  which  emotional maturity is mentioned in the description of other psychic phenomena, or in the interpretation of certain factors (scales. Psychodiagnostic methods studying different parameters depending on the theoretical concepts of the authors about the structure and content of the emotional maturity of the personality make references to concepts of emotional development, consciousness, cognitive and volitional capacities of the personality and the coping strategies the individual prefer to use. The problem of developing valid and reliable psychodiagnostic methods of studying emotional maturity of the adult personality as a holistic phenomenon still awaits attention and retains its signi?cance.

  9. Correlation between dental and cervical vertebral maturation in Iranian females.

    Science.gov (United States)

    Valizadeh, Solmaz; Eil, Nakissa; Ehsani, Sara; Bakhshandeh, Hooman

    2012-12-01

    Considerable variations in the development stage among patients of the same chronological age have led to introduce the concept of the developmental age based on the maturation of different organs such as cervical vertebrae or teeth. The purpose of this study was to investigate the correlation between the stages of tooth calcification and the cervical vertebral maturation in Iranian females. Four hundred females (age range, 8 to 14 years) participated in the study. To determine the dental maturational stage, calcification of the mandibular teeth except for third molars were rated according to the method suggested by Demirjian et al. To evaluate the stage of skeletal maturation, cervical vertebral morphologic changes were assessed on lateral cephalometric radiographs according to the method explained by Baccetti et al. Correlations between bone maturation and teeth calcification were showed by Spearman's correlation and Kendall's tau-b coefficients. The relevant associations were investigated by ordinal logistic regression models. Correlations between the two stages were observed in the first and second premolars, canine and central incisors. All these correlations were significant. The association between cervical vertebral maturation and tooth calcification was greatest in the lateral incisor (odds ratio (OR) = 11, 95% confidence interval (CI): 6.6-18.3). However, considering the 95% CI for OR, no significant difference was detected among the second molar, first molar and lateral incisor. The relationship between calcification of teeth and maturation of cervical bones was significant. Bone maturation can be predicted by using teeth calcification stages, especially in the second molar, first molar and lateral incisor.

  10. Predicting technology operational availability using technical maturity assessment

    International Nuclear Information System (INIS)

    Kenley, C.R.; Creque, T.R.

    1998-01-01

    A technical maturity assessment method was performed by systems engineers in collaboration with an advisory panel composed of team members from different Department of Energy sites and from different engineering and science disciplines. Various stabilization technologies were assessed annually as to their relative maturity and availability for use in stabilizing nuclear materials. After three years of assessments, several of the technologies are now components of operational systems. A regression analysis of the historical assessments was performed, and it was concluded that the numerical technical maturity score produced by a team of experts can provide a powerful predictor of the time remaining until the operational application of technologies

  11. Non-matured arteriovenous fistulae for haemodialysis: diagnosis, endovascular and surgical treatment

    Directory of Open Access Journals (Sweden)

    Marko Malovrh

    2010-04-01

    Full Text Available Non-maturation is a feature of autologous vascular access. The autologous arteriovenous fistula needs time to mature and for the vein to enlarge to a size where it can be needled for dialysis. A fistula that fails early is one that either never develops adequately to support dialysis or fails within the first three months of its use. Two variables are required for fistula maturation. Firstly, the fistula should have adequate blood flow to support dialysis and secondly, it should have enough size to allow for successful repetitive cannulation. Three main reasons for maturation failure are: arterial and venous problems and the presence of accessory veins. Early diagnostics and intervention for fistula maturation minimizes catheter use and its associated complications. The identification of immature fistulae is relatively simple. Physical examination has been highlighted to be a valuable tool in assessing fistula. Any fistula that fails to mature adequately and demonstrates abnormal physical findings should be studied aggressively. Ultrasonography can successfully identify candidates who fail to meet the recently developed criteria for immature fistulae. In recent years, digital subtraction angiography and contrast-enhanced magnetic resonance angiography has been introduced for assessment of dysfunctional haemodialysis conduits, including immature fistulae. A great majority of non-matured fistulae can be successfully salvaged using percutaneous techniques. In addition to endovascular techniques, surgical intervention can also be an option. This paper reviews the process of fistula maturation and presents information regarding how to obtain a mature fistula.

  12. Revaluation of maturity and stability indices for compost ...

    African Journals Online (AJOL)

    BOD/COD ratio of compost was studied in conjunction with C/N ratio as commonly maturity index. Carbonaceous materials as well as nitrogenous materials declined in open-air conditions during 20 weeks. C/N ratio was correlated with BOD/COD, a couple parameters to qualify the compost was mature and stable.

  13. Self-Esteem and Emotional Maturity in College Students.

    Science.gov (United States)

    Leung, Jupian J.; Sand, Margaret C.

    1981-01-01

    Determined if self-esteem is related to emotional maturity. Scores from 200 male and female college students on Coopersmith's Self-Esteem Inventory and on the Washburne Social-Adjustment Inventory were correlated. Students high in self-esteem were found to be more emotionally mature than students low in self-esteem. (Author)

  14. Mature consumers’ relationship with their perfume

    Directory of Open Access Journals (Sweden)

    Lindsey DRYLIE-CAREY

    2018-01-01

    Full Text Available Glamorous and stylish, perfume is an evocative product that provokes a stimulus of the senses. It is suggested that the basis for consumer choice for this product should be based on olfactory preference, however the process related decision-making has been shown to be more complex. The mature consumer purchase decision making in this product category is often associated with long standing, established, luxury fragrance brands. In addition, at the frontline of the perfume sales process are fragrance consultants, who possess invaluable information on consumer involvement with perfume products and brands. Hence, this paper investigates CBR (consumer brand relationship and the subsequent perfume purchase behaviour of mature female consumers from a dual (industry and consumer perspective. Results indicate that important perceptual differences related to brand relationships with perfume exist between fragrance consultants and experts on one hand and consumers on the other. This research promotes a deeper understanding of current consumer approach and issues surrounding female mature purchasing behaviour for this unique category of product, and complements the growing body of literature related to luxury brands.

  15. Towards an energy management maturity model

    International Nuclear Information System (INIS)

    Antunes, Pedro; Carreira, Paulo; Mira da Silva, Miguel

    2014-01-01

    Energy management is becoming a priority as organizations strive to reduce energy costs, conform to regulatory requirements, and improve their corporate image. Despite the upsurge of interest in energy management standards, a gap persists between energy management literature and current implementation practices. This gap can be traced to the lack of an incremental improvement roadmap. In this paper we propose an Energy Management Maturity Model that can be used to guide organizations in their energy management implementation efforts to incrementally achieve compliance with energy management standards such as ISO 50001. The proposed maturity model is inspired on the Plan-Do-Check-Act cycle approach for continual improvement, and covers well-understood fundamental energy management activities common across energy management texts. The completeness of our proposal is then evaluated by establishing an ontology mapping against ISO 50001. - Highlights: • Real-world energy management activities are not aligned with the literature. • An Energy Management Maturity Model is proposed to overcome this alignment gap. • The completeness and relevance of proposed model are validated

  16. Role of WNT signaling in epididymal sperm maturation.

    Science.gov (United States)

    Cheng, Jin-Mei; Tang, Ji-Xin; Li, Jian; Wang, Yu-Qian; Wang, Xiu-Xia; Zhang, Yan; Chen, Su-Ren; Liu, Yi-Xun

    2018-02-01

    Spermatozoa maturation, a process required for spermatozoa to acquire progressive motility and the ability to fertilize ova, primarily occurs in the caput and corpus of the epididymis. Despite considerable efforts, the factor(s) promoting epididymal sperm maturation remains unclear. Recently, WNT signaling has been implicated in epididymal sperm maturation. To further investigate WNT signaling function in epididymal sperm maturation, we generated Wntless conditional knockout mice (Wls cKO), Wls flox/flox ; Lcn5-Cre. In these mice, WNTLESS (WLS), a conserved membrane protein required for all WNT protein secretion, was specifically disrupted in the principal cells of the caput epididymidis. Immunoblot analysis showed that WLS was significantly reduced in the caput epididymidis of Wls cKO mice. In the caput epididymidis of Wls cKO mice, WNT 10A and WNT 2b, which are typically secreted by the principal cells of the caput epididymis, were not secreted. Interestingly, sperm motility analysis showed that the WLS deficiency in the caput epididymidis had no effect on sperm motility. Moreover, fertility tests showed that Wls cKO male mice had normal fertility. These results indicate that the disruption of WLS in principal cells of the caput epididymidis inhibits WNT protein secretion but has no effect on sperm motility and male fertility, suggesting that WNT signaling in the caput epididymidis may be dispensable for epididymal sperm maturation in mice.

  17. Maturation evolution of chardonnay grape for juice preparation

    Directory of Open Access Journals (Sweden)

    Bender Angelica

    2016-01-01

    Full Text Available This study aims to evaluate the evolution of the maturation of the “Chardonnay” grape variety for the preparation of juices and its adequacy to the current legislation. Grapes from the 2015 harvest from São Lourenço do Sul-RS were used. The experimental design was completely randomized in a factorial design, with the treatment factor being the maturation stages. The physicochemical analysis of titratable acidity, soluble solids, relative density, total sugar, alcohol content, volatile acidity and SS/TA ratio were carried out in EPAGRI – Agricultural Research and Rural Extension Company of Santa Catarina, in the Videira Experimental Station (Videira SC/Brazil. Statistical analysis of the maturation stages was given by linear regression models. When comparing the maturation points of 17∘Brix and 19∘Brix to 15∘Brix, volatile acidity and alcohol content did not fit to the model, while the other tested variables fit properly. Elaborated juices had a decrease in titratable acidity and percentage increments for soluble solids, SS/TA ratio and total sugars for the harvest points at 17 and 19∘Brix. For 15∘Brix and 17∘Brix, nonconformity was observed with the identity and quality standards in relation to soluble solids and SS/TA ratio and relative density. At maturation point 19∘Brix all variables were found to be consistent.

  18. Capability maturity models for offshore organisational management.

    Science.gov (United States)

    Strutt, J E; Sharp, J V; Terry, E; Miles, R

    2006-12-01

    The goal setting regime imposed by the UK safety regulator has important implications for an organisation's ability to manage health and safety related risks. Existing approaches to safety assurance based on risk analysis and formal safety assessments are increasingly considered unlikely to create the step change improvement in safety to which the offshore industry aspires and alternative approaches are being considered. One approach, which addresses the important issue of organisational behaviour and which can be applied at a very early stage of design, is the capability maturity model (CMM). The paper describes the development of a design safety capability maturity model, outlining the key processes considered necessary to safety achievement, definition of maturity levels and scoring methods. The paper discusses how CMM is related to regulatory mechanisms and risk based decision making together with the potential of CMM to environmental risk management.

  19. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    International Nuclear Information System (INIS)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang; Liu, Chao; Zhang, Hui

    2015-01-01

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  20. RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Chao, E-mail: liuchao9@mail.sysu.edu.cn [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Zhang, Hui [Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China)

    2015-12-15

    Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

  1. Best practices show the way to information security maturity

    CSIR Research Space (South Africa)

    Lessing, MM

    2008-09-01

    Full Text Available A Security Maturity Model (SMM) provides an organisation with a distinct Information Security framework. Organisations that conform to these models are likely to pursue satisfactory Information Security. Additionally, the use of Security Maturity...

  2. Amniocentesis for fetal lung maturity: will it become obsolete?

    Science.gov (United States)

    Varner, Stephen; Sherman, Craig; Lewis, David; Owens, Sheri; Bodie, Frankie; McCathran, C Eric; Holliday, Nicolette

    2013-01-01

    AMNIOCENTESIS FOR FETAL LUNG MATURITY HAS HISTORICALLY BEEN PERFORMED FOR MANY REASONS: uterine and placental complications, maternal comorbidities, fetal issues, and even obstetric problems. Even though the risks associated with third trimester amniocentesis are extremely low, complications have been documented, including preterm labor, placental abruptions, intrauterine rupture, maternal sepsis, fetal heart rate abnormalities, and fetal-maternal hemorrhage. This review presents the types of tests for fetal lung maturity, presents the indications and tests utilized, and discusses recommendations for when amniocentesis for fetal lung maturity may be appropriate.

  3. Methylation changes associated with early maturation stages in the Atlantic salmon

    Directory of Open Access Journals (Sweden)

    Pérez-Figueroa Andrés

    2011-10-01

    Full Text Available Abstract Background Early maturation in the Atlantic salmon is an interesting subject for numerous research lines. Prior to sea migration, parr can reach sexual maturation and successfully fertilize adult female eggs during the reproductive season. These individuals are known as precocious parr, mature parr or "sneakers". Reasons for early maturation are unknown and this transitory stage is usually considered to be a threshold trait. Here, we compare methylation patterns between mature and immature salmon parr from two different rivers in order to infer if such methylation differences may be related to their maturation condition. First we analyzed genetic differences between rivers by means of AFLPs. Then, we compared the DNA methylation differences between mature and immature parrs, using a Methylation-Sensitive Amplified Polymorphism (MSAP, which is a modification of the AFLPs method by making use of the differential sensitivity of a pair of restriction enzymes isoschizomeres to cytosine methylation. The tissues essayed included brain, liver and gonads. Results AFLPs statistical analysis showed that there was no significant differentiation between rivers or a significant differentiation between maturation states in each river. MSAP statistical analysis showed that among the three tissues sampled, the gonads had the highest number of significant single-locus variation among populations with 74 loci followed by brain with 70 and finally liver with only 12. Principal components analysis (PCA of the MSAP profiles revealed different profiles among different tissues (liver, brain and testis clearly separating maturation states in the testis tissue when compared to the liver. Conclusions Our results reveal that genetically-similar mature and immature salmon parr present high levels of DNA methylation variation in two of the three analyzed tissues. We hypothesize that early maturation may be mostly mediated by epigenetic processes rather than by

  4. Assessing Organizational Capabilities: Reviewing and Guiding the Development of Maturity Grids

    DEFF Research Database (Denmark)

    Maier, Anja; Moultrie, James; Clarkson, P John

    2012-01-01

    Managing and improving organizational capabilities is a significant and complex issue for many companies. To support management and enable improvement, performance assessments are commonly used. One way of assessing organizational capabilities is by means of maturity grids. Whilst maturity grids...... than twenty maturity grids places particular emphasis on embedded assumptions about organizational change in the formulation of the maturity ratings. The suggested roadmap encompasses four phases: planning, development, evaluation and maintenance. Each phase discusses a number of decision points...

  5. Correlation Between Dental and Cervical Vertebral Maturation in Iranian Females

    Science.gov (United States)

    Valizadeh, Solmaz; Eil, Nakissa; Ehsani, Sara; Bakhshandeh, Hooman

    2012-01-01

    Background Considerable variations in the development stage among patients of the same chronological age have led to introduce the concept of the developmental age based on the maturation of different organs such as cervical vertebrae or teeth. Objectives The purpose of this study was to investigate the correlation between the stages of tooth calcification and the cervical vertebral maturation in Iranian females. Patients and Methods Four hundred females (age range, 8 to 14 years) participated in the study. To determine the dental maturational stage, calcification of the mandibular teeth except for third molars were rated according to the method suggested by Demirjian et al. To evaluate the stage of skeletal maturation, cervical vertebral morphologic changes were assessed on lateral cephalometric radiographs according to the method explained by Baccetti et al. Correlations between bone maturation and teeth calcification were showed by Spearman's correlation and Kendall’s tau-b coefficients. The relevant associations were investigated by ordinal logistic regression models. Results Correlations between the two stages were observed in the first and second premolars, canine and central incisors. All these correlations were significant. The association between cervical vertebral maturation and tooth calcification was greatest in the lateral incisor (odds ratio (OR) = 11, 95% confidence interval (CI): 6.6-18.3). However, considering the 95% CI for OR, no significant difference was detected among the second molar, first molar and lateral incisor. Conclusion The relationship between calcification of teeth and maturation of cervical bones was significant. Bone maturation can be predicted by using teeth calcification stages, especially in the second molar, first molar and lateral incisor. PMID:23599706

  6. Changes in polyphenolics during maturation of Java plum (Syzygium cumini Lam.).

    Science.gov (United States)

    Lestario, Lydia Ninan; Howard, Luke R; Brownmiller, Cindi; Stebbins, Nathan B; Liyanage, Rohana; Lay, Jackson O

    2017-10-01

    Java plum (Syzygium cumini Lam.) is a rich source of polyphenolics with many purported health benefits, but the effect of maturation on polyphenolic content is unknown. Freeze-dried samples of Java plum from seven different maturity stages were analyzed for anthocyanin, flavonol, flavanonol and hydrolysable tannin composition by HPLC. Anthocyanins were first detected at the green-pink stage of maturity and increased throughout maturation with the largest increase occurring from the dark purple to black stages of maturation. Levels of gallotannins, ellagitannins, flavonols, gallic acid and ellagic acid were highest at early stages of maturation and decreased as the fruit ripened. For production of antioxidant-rich nutraceutical ingredients, fruit should be harvested immature to obtain extracts rich in hydrolysable tannins and flavonols. The exceptional anthocyanin content of black fruit may prove useful as a source of a natural colorant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. SOUL System Maturation, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Busek Co. Inc. proposes to advance the maturity of an innovative Spacecraft on Umbilical Line (SOUL) System suitable for a wide variety of applications of interest...

  8. SOUL System Maturation, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Busek Co. Inc. proposes to advance the maturity of an innovative Spacecraft on Umbilical Line (SOUL) System suitable for a wide variety of applications of interest...

  9. The Self--The Global Factor of Emotional Maturity.

    Science.gov (United States)

    Landau, Erika

    1998-01-01

    The relationship between emotional maturity and the developing self in the gifted individual is examined. Emotional maturity is seen to involve the integration of intrapersonal and interpersonal aspects of the personality. The developing self is thought to be more than the sum of its components and becomes a global factor in the development of a…

  10. 7 CFR 944.31 - Avocado import maturity regulation.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Avocado import maturity regulation. 944.31 Section 944...; IMPORT REGULATIONS § 944.31 Avocado import maturity regulation. (a) Pursuant to section 8e [7 U.S.C. 608e...—Fruits; Import Regulations, the importation into the United States of any avocados, except the Hass...

  11. Melatonin accelerates maturation inducing hormone (MIH): induced oocyte maturation in carps.

    Science.gov (United States)

    Chattoraj, Asamanja; Bhattacharyya, Sharmistha; Basu, Dipanjan; Bhattacharya, Shelley; Bhattacharya, Samir; Maitra, Saumen Kumar

    2005-02-01

    The present communication is an attempt to demonstrate the influence of melatonin on the action of maturation inducing hormone (MIH) on the maturation of oocytes in carps. The oocytes from gravid female major carp Labeo rohita were isolated and incubated separately in Medium 199 containing (a) only MIH (1 microg/ml), (b) only melatonin (at concentrations of 50, 100 or 500 pg/ml), and (c) both melatonin and MIH, but at different time intervals. In the latter group, melatonin was added to the incubating medium either (i) 4 h before addition of MIH, (ii) 2 h before addition of MIH, (iii) co-administered with MIH (0 h interval) or (iv) 2 h after addition of MIH. In each case, oocytes were further incubated for 4, 8, 12 or 16 h post- administration of MIH, and the effects of treatment on oocyte maturation were evaluated by considering the rate (%) of germinal vesicle breakdown (GVBD). Incubation of oocytes in a medium containing only melatonin did not result in GVBD of any oocyte. Nearly all the oocytes underwent GVBD when incubated with MIH for 16 h. Administration of melatonin along with MIH (at 0 h interval) or 2 h after addition of MIH did not result in any significant change in the rate of GVBD compared to that in a medium containing only MIH. However, it was quite interesting to observe that incubation of oocytes with melatonin especially 4 h prior to addition of MIH in the medium, led to an accelerated rate of GVBD in the oocytes. Experiments with the oocytes of another major carp Cyprinus carpio following an identical schedule depicted similar results except a difference in the optimum melatonin dose. In L. rohita, 50 pg/ml melatonin had maximum acceleratory effect on MIH-induced GVBD of oocytes, while it was 100 pg/ml in C. carpio. Further study revealed that pre-incubation with melatonin accelerates the action of MIH on the formation of a complex of two proteins (MPF), a regulatory component called cyclin B and the catalytic component protein kinase known as

  12. Altruism and mature care: some rival moral considerations in care ethics.

    Science.gov (United States)

    Hem, Marit Helene; Halvorsen, Kristin; Nortvedt, Per

    2014-11-01

    We discuss Carol Gilligan's original concept of mature care in the light of the altruistic approach to caring and good clinical judgment. In particular, we highlight how the concept of mature care can capture important challenges in today's nursing. Further, we illuminate how mature care might differ normatively from an altruistic approach to caring and the traditional prudential virtues in nursing. We also discuss similarities between mature care and virtue ethics. For nursing and nurses' identity, in today's health care system that is increasingly pressured to 'produce' health, we believe it is important to both developing further theories on mature care and having normative discussions about care. © The Author(s) 2014.

  13. Tubulin cofactor B regulates microtubule densities during microglia transition to the reactive states

    International Nuclear Information System (INIS)

    Fanarraga, M.L.; Villegas, J.C.; Carranza, G.; Castano, R.; Zabala, J.C.

    2009-01-01

    Microglia are highly dynamic cells of the CNS that continuously survey the welfare of the neural parenchyma and play key roles modulating neurogenesis and neuronal cell death. In response to injury or pathogen invasion parenchymal microglia transforms into a more active cell that proliferates, migrates and behaves as a macrophage. The acquisition of these extra skills implicates enormous modifications of the microtubule and actin cytoskeletons. Here we show that tubulin cofactor B (TBCB), which has been found to contribute to various aspects of microtubule dynamics in vivo, is also implicated in microglial cytoskeletal changes. We find that TBCB is upregulated in post-lesion reactive parenchymal microglia/macrophages, in interferon treated BV-2 microglial cells, and in neonate amoeboid microglia where the microtubule densities are remarkably low. Our data demonstrate that upon TBCB downregulation both, after microglia differentiation to the ramified phenotype in vivo and in vitro, or after TBCB gene silencing, microtubule densities are restored in these cells. Taken together these observations support the view that TBCB functions as a microtubule density regulator in microglia during activation, and provide an insight into the understanding of the complex mechanisms controlling microtubule reorganization during microglial transition between the amoeboid, ramified, and reactive phenotypes

  14. Primordial Pb, radiogenic Pb and lunar soil maturity

    International Nuclear Information System (INIS)

    Reed, G.W. Jr.; Jovanovic, S.

    1978-01-01

    The soil maturity index I/sub s//FeO does not apply to either 204 Pb/sub r/ or C/sub hyd/; both are directly correlated with the submicron Fe 0 (I/sub s/) content. They act as an index of soil maturity which is independent of soil composition. In contrast to primordial Pb, radiogenic Pb is lost during soil maturation. Radiogenic Pb is present in mineral grains and may be lost by solar wind sputtering (or volatilization) and not resupplied. 204 Pb coating grain surfaces acts as a reservoir to provide the 204 Pb being extracted in the Fe 0 formation process. Venting or some other volatile source may replenish the surface 204 Pb. 1 figure

  15. Predictive Capability Maturity Model for computational modeling and simulation.

    Energy Technology Data Exchange (ETDEWEB)

    Oberkampf, William Louis; Trucano, Timothy Guy; Pilch, Martin M.

    2007-10-01

    The Predictive Capability Maturity Model (PCMM) is a new model that can be used to assess the level of maturity of computational modeling and simulation (M&S) efforts. The development of the model is based on both the authors experience and their analysis of similar investigations in the past. The perspective taken in this report is one of judging the usefulness of a predictive capability that relies on the numerical solution to partial differential equations to better inform and improve decision making. The review of past investigations, such as the Software Engineering Institute's Capability Maturity Model Integration and the National Aeronautics and Space Administration and Department of Defense Technology Readiness Levels, indicates that a more restricted, more interpretable method is needed to assess the maturity of an M&S effort. The PCMM addresses six contributing elements to M&S: (1) representation and geometric fidelity, (2) physics and material model fidelity, (3) code verification, (4) solution verification, (5) model validation, and (6) uncertainty quantification and sensitivity analysis. For each of these elements, attributes are identified that characterize four increasing levels of maturity. Importantly, the PCMM is a structured method for assessing the maturity of an M&S effort that is directed toward an engineering application of interest. The PCMM does not assess whether the M&S effort, the accuracy of the predictions, or the performance of the engineering system satisfies or does not satisfy specified application requirements.

  16. Developing the Value Management Maturity Model (VM3©

    Directory of Open Access Journals (Sweden)

    Saipol Bari Abd Karim

    2013-06-01

    Full Text Available Value management (VM practices have been expanded and became a well-received technique globally. Organisations are now progressing towards a better implementation of VM and should be assessing their strengths and weaknesses in order to move forward competitively. There is a need to benchmark the existing VM practices to reflect their maturing levels which is currently not available. This paper outlines the concept of Value Management Maturity Model (VM3' as a structured plan of maturity and performance growth for businesses. It proposes five levels of maturity and each level has its own criteria or attributes to be achieved before progressing to a higher level. The framework for VM3' has been developed based on the review of literatures related to VM and maturity models (MM. Data is collected through questionnaire surveys to organisations that have implemented VM methodology. Additionally, semi-structured interviews were conducted to select individuals involved in implementing VM. The questions were developed to achieve the research objectives; investigating the current implementation of VM and, exploring the organisation's MM knowledge and practices. However, this research was limited to VM implementation in the Malaysian government's projects and programmes. VM3' introduces a new paradigm in VM as it provides a rating method for capabilities or performance. It is advocated that this VM3' framework is still being refined in the advance stage in order to provide a comprehensive and well accepted method to provide ratings for organisations' maturity.

  17. Quality Management Systems Implementation Compared With Organizational Maturity in Hospital.

    Science.gov (United States)

    Moradi, Tayebeh; Jafari, Mehdi; Maleki, Mohammad Reza; Naghdi, Seyran; Ghiasvand, Hesam

    2015-07-27

    A quality management system can provide a framework for continuous improvement in order to increase the probability of customers and other stakeholders' satisfaction. The test maturity model helps organizations to assess the degree of maturity in implementing effective and sustained quality management systems; plan based on the current realities of the organization and prioritize their improvement programs. We aim to investigate and compare the level of organizational maturity in hospitals with the status of quality management systems implementation. This analytical cross sectional study was conducted among hospital administrators and quality experts working in hospitals with over 200 beds located in Tehran. In the first step, 32 hospitals were selected and then 96 employees working in the selected hospitals were studied. The data were gathered using the implementation checklist of quality management systems and the organization maturity questionnaire derived from ISO 10014. The content validity was calculated using Lawshe method and the reliability was estimated using test - retest method and calculation of Cronbach's alpha coefficient. The descriptive and inferential statistics were used to analyze the data using SPSS 18 software. According to the table, the mean score of organizational maturity among hospitals in the first stage of quality management systems implementation was equal to those in the third stage and hypothesis was rejected (p-value = 0.093). In general, there is no significant difference in the organizational maturity between the first and third level hospitals (in terms of implementation of quality management systems). Overall, the findings of the study show that there is no significant difference in the organizational maturity between the hospitals in different levels of the quality management systems implementation and in fact, the maturity of the organizations cannot be attributed to the implementation of such systems. As a result, hospitals

  18. Debt Maturity: Is Long-Term Debt Optimal?

    OpenAIRE

    Laura Alfaro; Fabio Kanczuk

    2007-01-01

    We model and calibrate the arguments in favor and against short-term and long-term debt. These arguments broadly include: maturity premium, sustainability, and service smoothing. We use a dynamic equilibrium model with tax distortions and government outlays uncertainty, and model maturity as the fraction of debt that needs to be rolled over every period. In the model, the benefits of defaulting are tempered by higher future interest rates. We then calibrate our artificial economy and solve fo...

  19. Relationship between viticultural climatic indices and grape maturity in Australia

    Science.gov (United States)

    Jarvis, C.; Barlow, E.; Darbyshire, R.; Eckard, R.; Goodwin, I.

    2017-10-01

    Historical temperature data and maturity records were analyzed for 45 vineyard blocks in 15 winegrowing regions across Australia in order to evaluate the suitability of common viticultural indices to estimate date of grape maturity. Five temperature-based viticultural indices (mean January temperature, mean growing season temperature, growing degree days, biologically effective degree days, Huglin Index) along with four springtime temperature indices (mean and maximum temperature summations for September, October, and November; growing degree days and biologically effective degree days modified to include September) were compared to maturity data in order to investigate index relationship to observed maturity timing. Daily heat summations for the months of September, October, and November showed the best correlation to day of year of maturity, suggesting that springtime temperatures are important relative to the timing of grape maturity. Mean January temperature, a commonly used index, had the poorest correlation with day of year of maturity of all the indices included in this study. Indices that included the month of April had poorer correlation than indices that shifted the months included in the growing season to be from September to March inclusive. Calculated index values for the past 30 years for every region included in this study showed increasing temporal trends to various degrees, indicating that all regions studied are experiencing warming temperatures during the growing season. These results emphasize the need to reevaluate viticultural indices in the context of a changing climate.

  20. Maturation of the adolescent brain

    Directory of Open Access Journals (Sweden)

    Arain M

    2013-04-01

    Full Text Available Mariam Arain, Maliha Haque, Lina Johal, Puja Mathur, Wynand Nel, Afsha Rais, Ranbir Sandhu, Sushil Sharma Saint James School of Medicine, Kralendijk, Bonaire, The Netherlands Abstract: Adolescence is the developmental epoch during which children become adults – intellectually, physically, hormonally, and socially. Adolescence is a tumultuous time, full of changes and transformations. The pubertal transition to adulthood involves both gonadal and behavioral maturation. Magnetic resonance imaging studies have discovered that myelinogenesis, required for proper insulation and efficient neurocybernetics, continues from childhood and the brain's region-specific neurocircuitry remains structurally and functionally vulnerable to impulsive sex, food, and sleep habits. The maturation of the adolescent brain is also influenced by heredity, environment, and sex hormones (estrogen, progesterone, and testosterone, which play a crucial role in myelination. Furthermore, glutamatergic neurotransmission predominates, whereas gamma-aminobutyric acid neurotransmission remains under construction, and this might be responsible for immature and impulsive behavior and neurobehavioral excitement during adolescent life. The adolescent population is highly vulnerable to driving under the influence of alcohol and social maladjustments due to an immature limbic system and prefrontal cortex. Synaptic plasticity and the release of neurotransmitters may also be influenced by environmental neurotoxins and drugs of abuse including cigarettes, caffeine, and alcohol during adolescence. Adolescents may become involved with offensive crimes, irresponsible behavior, unprotected sex, juvenile courts, or even prison. According to a report by the Centers for Disease Control and Prevention, the major cause of death among the teenage population is due to injury and violence related to sex and substance abuse. Prenatal neglect, cigarette smoking, and alcohol consumption may also

  1. Dual utilization of NADPH and NADH cofactors enhances xylitol production in engineered Saccharomyces cerevisiae.

    Science.gov (United States)

    Jo, Jung-Hyun; Oh, Sun-Young; Lee, Hyeun-Soo; Park, Yong-Cheol; Seo, Jin-Ho

    2015-12-01

    Xylitol, a natural sweetener, can be produced by hydrogenation of xylose in hemicelluloses. In microbial processes, utilization of only NADPH cofactor limited commercialization of xylitol biosynthesis. To overcome this drawback, Saccharomyces cerevisiae D452-2 was engineered to express two types of xylose reductase (XR) with either NADPH-dependence or NADH-preference. Engineered S. cerevisiae DWM expressing both the XRs exhibited higher xylitol productivity than the yeast strain expressing NADPH-dependent XR only (DWW) in both batch and glucose-limited fed-batch cultures. Furthermore, the coexpression of S. cerevisiae ZWF1 and ACS1 genes in the DWM strain increased intracellular concentrations of NADPH and NADH and improved maximum xylitol productivity by 17%, relative to that for the DWM strain. Finally, the optimized fed-batch fermentation of S. cerevisiae DWM-ZWF1-ACS1 resulted in 196.2 g/L xylitol concentration, 4.27 g/L h productivity and almost the theoretical yield. Expression of the two types of XR utilizing both NADPH and NADH is a promising strategy to meet the industrial demands for microbial xylitol production. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo.

    Science.gov (United States)

    Papareddy, Praveen; Kalle, Martina; Singh, Shalini; Mörgelin, Matthias; Schmidtchen, Artur; Malmsten, Martin

    2014-05-01

    Host defense peptides are key components of the innate immune system, providing multi-facetted responses to invading pathogens. Here, we describe that the peptide GKS26 (GKSRIQRLNILNAKFAFNLYRVLKDQ), corresponding to the A domain of heparin cofactor II (HCII), ameliorates experimental septic shock. The peptide displays antimicrobial effects through direct membrane disruption, also at physiological salt concentration and in the presence of plasma and serum. Biophysical investigations of model lipid membranes showed the antimicrobial action of GKS26 to be mirrored by peptide incorporation into, and disordering of, bacterial lipid membranes. GKS26 furthermore binds extensively to bacterial lipopolysaccharide (LPS), as well as its endotoxic lipid A moiety, and displays potent anti-inflammatory effects, both in vitro and in vivo. Thus, for mice challenged with ip injection of LPS, GKS26 suppresses pro-inflammatory cytokines, reduces vascular leakage and infiltration in lung tissue, and normalizes coagulation. Together, these findings suggest that GKS26 may be of interest for further investigations as therapeutic against severe infections and septic shock. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Effects of mixing and covering with mature compost on gaseous emissions during composting.

    Science.gov (United States)

    Luo, Wen Hai; Yuan, Jing; Luo, Yi Ming; Li, Guo Xue; Nghiem, Long D; Price, William E

    2014-12-01

    This study investigated effects of mature compost on gaseous emissions during composting using pig manure amended with corn stalks. Apart from a control treatment, three treatments were conducted with the addition of 5% (wet weight of raw materials) of mature compost: (a) mixing raw materials with mature compost at the beginning of composting; (b) covering raw materials with mature compost throughout the experimental period; and (c) covering raw materials with mature compost at the start of composting, but incorporating it into composting pile on day 6 of composting. Mature compost used for the last treatment was inoculated with 2% (wet weight) of raw materials of strain M5 (a methanotrophic bacterium) solution. During 30-d of composting, three treatments with the addition of mature compost could reduce CH4 emission by 53-64% and N2O emission by 43-71%. However, covering with mature compost throughout the experimental period increased cumulative NH3 emission by 61%, although it could reduce 34% NH3 emission in the first 3d. Inoculating strain M5 in mature compost covered on the top of composting pile within first 6d enhanced CH4 oxidation, but simultaneously increased N2O emission. In addition, mixing with mature compost could improve compost maturity. Given the operational convenience in practice, covering with mature compost and then incorporating it into composting pile is a suitable approach to mitigate gaseous emissions during composting. Copyright © 2014. Published by Elsevier Ltd.

  4. ICoNOs MM: The IT-enabled Collaborative Networked Organizations Maturity Model

    NARCIS (Netherlands)

    Santana Tapia, R.G.

    2009-01-01

    The focus of this paper is to introduce a comprehensive model for assessing and improving maturity of business-IT alignment (B-ITa) in collaborative networked organizations (CNOs): the ICoNOs MM. This two dimensional maturity model (MM) addresses five levels of maturity as well as four domains to

  5. The Relationship between Emotional Maturity, Intelligence and Creativity in Gifted Children.

    Science.gov (United States)

    Landau, Erika; Weissler, Kineret

    1998-01-01

    This study examined the relationships among emotional maturity, intelligence, and creativity in 221 gifted children at a special school in Israel. Emotional maturity was defined as the strength and courage to actualize individual abilities within the frame of social demands. Highly intelligent and emotionally mature children were more creative…

  6. Intraovarian markers of follicular and oocyte maturation.

    Science.gov (United States)

    Pellicer, A; Diamond, M P; DeCherney, A H; Naftolin, F

    1987-08-01

    The use of ovulation induction for multiple follicular growth in in vitro fertilization (IVF) has introduced the problem of follicular asynchrony. As a consequence of the asynchrony, the parameters most commonly used by IVF groups to assess follicular and oocyte quality within those follicles are not sufficiently sensitive or specific. Thus, each follicle must be considered separately, and specific markers of follicular and/or oocyte maturation must be sought from within the follicle. In this review we analyze previous reports of potential markers of follicular and oocyte maturation. In regards to the follicular fluid constituents, the level of estradiol in follicular fluid correlates with fertilization and pregnancy in stimulated cycles. Other steroids are only helpful when specific stimulation protocols are used. The level of some follicular proteins such as alpha-1-antitrypsin and fibrinogen also correlates with fertilization and pregnancy outcome. Cyclic AMP levels in follicular fluid are significantly reduced in follicles leading to conception. Regulators of oocyte maturation, such as the Oocyte Maturation Inhibitor (OMI) or the Meiosis Inducing Substance (MIS) have also been correlated with IVF outcome, but their exact structure remains still unknown. In addition, other sophisticated parameters, such as chemotactic activity of human leukocytes, or simple methods, such as the presence of intrafollicular echoes, have also been used as successful markers in predicting IVF outcome.

  7. Jealousy and Moral Maturity.

    Science.gov (United States)

    Mathes, Eugene W.; Deuger, Donna J.

    Jealousy may be perceived as either good or bad depending upon the moral maturity of the individual. To investigate this conclusion, a study was conducted testing two hypothesis: a positive relationship exists between conventional moral reasoning (reference to norms and laws) and the endorsement and level of jealousy; and a negative relationship…

  8. Mechanosensitivity of dental pulp stem cells is related to their osteogenic maturity.

    Science.gov (United States)

    Kraft, David C E; Bindslev, Dorthe A; Melsen, Birte; Abdallah, Basem M; Kassem, Moustapha; Klein-Nulend, Jenneke

    2010-02-01

    For engineering bone tissue, mechanosensitive cells are needed for bone (re)modelling. Local bone mass and architecture are affected by mechanical loading, which provokes a cellular response via loading-induced interstitial fluid flow. We studied whether human dental pulp-derived mesenchymal stem cells (PDSCs) portraying mature (PDSC-mature) or immature (PDSC-immature) bone cell characteristics are responsive to pulsating fluid flow (PFF) in vitro. We also assessed bone formation by PDSCs on hydroxyapatite-tricalcium phosphate granules after subcutaneous implantation in mice. Cultured PDSC-mature exhibited higher osteocalcin and alkaline phosphatase gene expression and activity than PDSC-immature. Pulsating fluid flow (PFF) stimulated nitric oxide production within 5 min by PDSC-mature but not by PDSC-immature. In PDSC-mature, PFF induced prostaglandin E(2) production, and cyclooxygenase 2 gene expression was higher than in PDSC-immature. Implantation of PDSC-mature resulted in more osteoid deposition and lamellar bone formation than PDSC-immature. We conclude that PDSCs with a mature osteogenic phenotype are more responsive to pulsating fluid shear stress than osteogenically immature PDSCs and produce more bone in vivo. These data suggest that PDSCs with a mature osteogenic phenotype might be preferable for bone tissue engineering to restore, for example, maxillofacial defects, because they might be able to perform mature bone cell-specific functions during bone adaptation to mechanical loading in vivo.

  9. Social and moral maturity of high-school students

    Directory of Open Access Journals (Sweden)

    Silvana Gasar

    2005-02-01

    Full Text Available The level of social and moral maturity of high-school students was examined. There were almost no significant differences between the students of two different educational programs. In general, the students' level of social and moral maturity is satisfyingly high, but their social skills are not quite appropriately developed. The results of behaviour in school situations reveal a quite unpleasant picture of interpersonal relations, which is probably a reflection of social relations in society. The absence of correlations between both components of maturity and social skills shows the gap between human's reasoning and behaviour. Students know, which behaviour is moral and socially adapted, but they do not always act in congruence with that, because existing social relations often encourage different behaviour.

  10. Posttesticular sperm maturation, infertility, and hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Marjorie Whitfield

    2015-01-01

    Full Text Available Cholesterol is a key molecule in the mammalian physiology of especial particular importance for the reproductive system as it is the common precursor for steroid hormone synthesis. Cholesterol is also a recognized modulator of sperm functions, not only at the level of gametogenesis. Cholesterol homeostasis regulation is crucial for posttesticular sperm maturation, and imbalanced cholesterol levels may particularly affect these posttesticular events. Metabolic lipid disorders (dyslipidemia affect male fertility but are most of the time studied from the angle of endocrine/testicular consequences. This review will focus on the deleterious effects of a particular dyslipidemia, i.e., hypercholesterolemia, on posttesticular maturation of mammalian spermatozoa.

  11. Ecological and evolutionary patterns of freshwater maturation in Pacific and Atlantic salmonines

    Science.gov (United States)

    Sloat, Matthew R.; Fraser, Dylan J.; Dunham, Jason B.; Falke, Jeffery A.; Jordan, Chris E.; McMillan, John R.; Ohms, Haley A.

    2014-01-01

    Reproductive tactics and migratory strategies in Pacific and Atlantic salmonines are inextricably linked through the effects of migration (or lack thereof) on age and size at maturity. In this review, we focus on the ecological and evolutionary patterns of freshwater maturation in salmonines, a key process resulting in the diversification of their life histories. We demonstrate that the energetics of maturation and reproduction provides a unifying theme for understanding both the proximate and ultimate causes of variation in reproductive schedules among species, populations, and the sexes. We use probabilistic maturation reaction norms to illustrate how variation in individual condition, in terms of body size, growth rate, and lipid storage, influences the timing of maturation. This useful framework integrates both genetic and environmental contributions to conditional strategies for maturation and, in doing so, demonstrates how flexible life histories can be both heritable and subject to strong environmental influences. We review evidence that the propensity for freshwater maturation in partially anadromous species is predictable across environmental gradients at geographic and local spatial scales. We note that growth is commonly associated with the propensity for freshwater maturation, but that life-history responses to changes in growth caused by temperature may be strikingly different than changes caused by differences in food availability. We conclude by exploring how contemporary management actions can constrain or promote the diversity of maturation phenotypes in Pacific and Atlantic salmonines and caution against underestimating the role of freshwater maturing forms in maintaining the resiliency of these iconic species.

  12. Aerobic fitness, maturation, and training experience in youth basketball.

    Science.gov (United States)

    Carvalho, Humberto M; Coelho-e-Silva, Manuel J; Eisenmann, Joey C; Malina, Robert M

    2013-07-01

    Relationships among chronological age (CA), maturation, training experience, and body dimensions with peak oxygen uptake (VO2max) were considered in male basketball players 14-16 y of age. Data for all players included maturity status estimated as percentage of predicted adult height attained at the time of the study (Khamis-Roche protocol), years of training, body dimensions, and VO2max (incremental maximal test on a treadmill). Proportional allometric models derived from stepwise regressions were used to incorporate either CA or maturity status and to incorporate years of formal training in basketball. Estimates for size exponents (95% CI) from the separate allometric models for VO2max were height 2.16 (1.23-3.09), body mass 0.65 (0.37-0.93), and fat-free mass 0.73 (0.46-1.02). Body dimensions explained 39% to 44% of variance. The independent variables in the proportional allometric models explained 47% to 60% of variance in VO2max. Estimated maturity status (11-16% of explained variance) and training experience (7-11% of explained variance) were significant predictors with either body mass or estimated fat-free mass (P ≤ .01) but not with height. Biological maturity status and training experience in basketball had a significant contribution to VO2max via body mass and fat-free fat mass and also had an independent positive relation with aerobic performance. The results highlight the importance of considering variation associated with biological maturation in aerobic performance of late-adolescent boys.

  13. Involvement of PLA2, COX and LOX in Rhinella arenarum oocyte maturation.

    Science.gov (United States)

    Ortiz, Maria Eugenia; Bühler, Marta Inés; Zelarayán, Liliana Isabel

    2014-11-01

    In Rhinella arenarum, progesterone is the physiological nuclear maturation inducer that interacts with the oocyte surface and starts a cascade of events that leads to germinal vesicle breakdown (GVBD). Polyunsaturated fatty acids and their metabolites produced through cyclooxygenase (COX) and lipoxygenase (LOX) pathways play an important role in reproductive processes. In amphibians, to date, the role of arachidonic acid (AA) metabolites in progesterone (P4)-induced oocyte maturation has not been clarified. In this work we studied the participation of three enzymes involved in AA metabolism - phospholipase A2 (PLA2), COX and LOX in Rhinella arenarum oocyte maturation. PLA2 activation induced maturation in Rhinella arenarum oocytes in a dose-dependent manner. Oocytes when treated with 0.08 μM melittin showed the highest response (78 ± 6% GVBD). In follicles, PLA2 activation did not significantly induce maturation at the assayed doses (12 ± 3% GVBD). PLA2 inhibition with quinacrine prevented melittin-induced GVBD in a dose-dependent manner, however PLA2 inactivation did not affect P4-induced maturation. This finding suggests that PLA2 is not the only phospholipase involved in P4-induced maturation in this species. P4-induced oocyte maturation was inhibited by the COX inhibitors indomethacin and rofecoxib (65 ± 3% and 63 ± 3% GVBD, respectively), although COX activity was never blocked by their addition. Follicles showed a similar response following the addition of these inhibitors. Participation of LOX metabolites in maturation seems to be correlated with seasonal variation in ovarian response to P4. During the February to June period (low P4 response), LOX inhibition by nordihydroguaiaretic acid or lysine clonixinate increased maturation by up to 70%. In contrast, during the July to January period (high P4 response), LOX inhibition had no effect on hormone-induced maturation.

  14. Neuropsychological relationship between maturity and presence-absence of crawling behavior

    OpenAIRE

    Suárez, Alejandra; Lozada, Carlos

    2017-01-01

    Neuropsychological maturity is the level of organization and maturational development that allows the development of behavioral and cognitive age-appropriate individual functions, crawling behavior is the first harmonic motion in which the baby uses his head and his both lower extremities as superior, to support and move, it allows the establishment of connections between brain hemispheres, leading to the intercom that simplifies the work of the brain and promotes the maturation of the cognit...

  15. Water relations in culture media influence maturation of avocado somatic embryos.

    Science.gov (United States)

    Márquez-Martín, Belén; Sesmero, Rafael; Quesada, Miguel A; Pliego-Alfaro, Fernando; Sánchez-Romero, Carolina

    2011-11-15

    Application of transformation and other biotechnological tools in avocado (Persea americana Mill.) is hampered by difficulties in obtaining mature somatic embryos capable of germination at an acceptable rate. In this work, we evaluated the effect of different compounds affecting medium water relations on maturation of avocado somatic embryos. Culture media were characterized with respect to gel strength, water potential and osmotic potential. Improved production of mature somatic embryos was achieved with gelling agent concentrations higher than those considered standard. The osmotic agents such as sorbitol and PEG did not have positive effects on embryo maturation. The number of w-o mature somatic embryos per culture was positively correlated with medium gel strength. Gel strength was significantly affected by gelling agent type as well as by gelling agent and PEG concentration. Medium water potential was influenced by sorbitol concentration; incorporation of PEG to a culture medium did not affect medium water potential. The highest maturation results were achieved on a medium gelled with 10 gl(-1) agar. Moreover, these somatic embryos had improved germination rates. These results corroborate the role of water restriction as a key factor controlling maturation of somatic embryos. Copyright © 2011 Elsevier GmbH. All rights reserved.

  16. Iron valence in double-perovskite (Ba,Sr,Ca)2FeMoO6: isovalent substitution effect

    International Nuclear Information System (INIS)

    Yasukawa, Y.; Linden, J.; Chan, T.S.; Liu, R.S.; Yamauchi, H.; Karppinen, M.

    2004-01-01

    In the Fe-Mo based B-site ordered double-perovskite, A 2 FeMoO 6.0 , with iron in the mixed-valence II/III state, the valence value of Fe is not precisely fixed at 2.5 but may be fine-tuned by means of applying chemical pressure at the A-cation site. This is shown through a systematic 57 Fe Moessbauer spectroscopy study using a series of A 2 FeMoO 6.0 [A=(Ba,Sr) or (Sr,Ca)] samples with high degree of Fe/Mo order, the same stoichiometric oxygen content and also almost the same grain size. The isomer shift values and other hyperfine parameters obtained from the Moessbauer spectra confirm that Fe remains in the mixed-valence state within the whole range of A constituents. However, upon increasing the average cation size at the A site the precise valence of Fe is found to decrease such that within the A=(Ba,Sr) regime the valence of Fe is closer to II, while within the A=(Sr,Ca) regime it is closer to the actual mixed-valence II/III state. As the valence of Fe approaches II, the difference in charges between Fe and Mo increases, and parallel with this the degree of Fe/Mo order increases. Additionally, for the less-ordered samples an increased tendency of clustering of the antisite Fe atoms is deduced from the Moessbauer data

  17. Slab replacement maturity guidelines : [summary].

    Science.gov (United States)

    2014-04-01

    Concrete sets in hours at moderate temperatures, : but the bonds that make concrete strong continue : to mature over days to years. However, for : replacement concrete slabs on highways, it is : crucial that concrete develop enough strength : within ...

  18. Comparative study of the nutritional composition of matured green ...

    African Journals Online (AJOL)

    peppery fruit”. The fruit serve as a stimulant and eaten raw. It is still green when matured and turn from yellow to red if left for sometime after reaching maturity. Dennettia tripetala is one of the most cherished stimulants. However, there is lack of ...

  19. Communication between Thiamin Cofactors in the Escherichia coli Pyruvate Dehydrogenase Complex E1 Component Active Centers EVIDENCE FOR A DIRECT PATHWAY BETWEEN THE 4′-AMINOPYRIMIDINE N1′ ATOMS

    Energy Technology Data Exchange (ETDEWEB)

    Nemeria, Natalia S; Arjunan, Palaniappa; Chandrasekhar, Krishnamoorthy; Mossad, Madouna; Tittmann, Kai; Furey, William; Jordan, Frank [Pitt; (Goettingen); (VA); (Rutgers)

    2010-11-03

    Kinetic, spectroscopic, and structural analysis tested the hypothesis that a chain of residues connecting the 4{prime}-aminopyrimidine N1{prime} atoms of thiamin diphosphates (ThDPs) in the two active centers of the Escherichia coli pyruvate dehydrogenase complex E1 component provides a signal transduction pathway. Substitution of the three acidic residues (Glu{sup 571}, Glu{sup 235}, and Glu{sup 237}) and Arg{sup 606} resulted in impaired binding of the second ThDP, once the first active center was filled, suggesting a pathway for communication between the two ThDPs. (1) Steady-state kinetic and fluorescence quenching studies revealed that upon E571A, E235A, E237A, and R606A substitutions, ThDP binding in the second active center was affected. (2) Analysis of the kinetics of thiazolium C2 hydrogen/deuterium exchange of enzyme-bound ThDP suggests half-of-the-sites reactivity for the E1 component, with fast (activated site) and slow exchanging sites (dormant site). The E235A and E571A variants gave no evidence for the slow exchanging site, indicating that only one of two active sites is filled with ThDP. (3) Titration of the E235A and E237A variants with methyl acetylphosphonate monitored by circular dichroism suggested that only half of the active sites were filled with a covalent predecarboxylation intermediate analog. (4) Crystal structures of E235A and E571A in complex with ThDP revealed the structural basis for the spectroscopic and kinetic observations and showed that either substitution affects cofactor binding, despite the fact that Glu{sup 235} makes no direct contact with the cofactor. The role of the conserved Glu{sup 571} residue in both catalysis and cofactor orientation is revealed by the combined results for the first time.

  20. E-learning process maturity level: a conceptual framework

    Science.gov (United States)

    Rahmah, A.; Santoso, H. B.; Hasibuan, Z. A.

    2018-03-01

    ICT advancement is a sure thing with the impact influencing many domains, including learning in both formal and informal situations. It leads to a new mindset that we should not only utilize the given ICT to support the learning process, but also improve it gradually involving a lot of factors. These phenomenon is called e-learning process evolution. Accordingly, this study attempts to explore maturity level concept to provide the improvement direction gradually and progression monitoring for the individual e-learning process. Extensive literature review, observation, and forming constructs are conducted to develop a conceptual framework for e-learning process maturity level. The conceptual framework consists of learner, e-learning process, continuous improvement, evolution of e-learning process, technology, and learning objectives. Whilst, evolution of e-learning process depicted as current versus expected conditions of e-learning process maturity level. The study concludes that from the e-learning process maturity level conceptual framework, it may guide the evolution roadmap for e-learning process, accelerate the evolution, and decrease the negative impact of ICT. The conceptual framework will be verified and tested in the future study.

  1. Relative Skeletal Maturation and Population Ancestry in Nonobese Children and Adolescents.

    Science.gov (United States)

    McCormack, Shana E; Chesi, Alessandra; Mitchell, Jonathan A; Roy, Sani M; Cousminer, Diana L; Kalkwarf, Heidi J; Lappe, Joan M; Gilsanz, Vicente; Oberfield, Sharon E; Shepherd, John A; Mahboubi, Soroosh; Winer, Karen K; Kelly, Andrea; Grant, Struan Fa; Zemel, Babette S

    2017-01-01

    More rapid skeletal maturation in African-American (AA) children is recognized and generally attributed to an increased prevalence of obesity. The objective of the present study was to evaluate the effects of population ancestry on relative skeletal maturation in healthy, non-obese children and adolescents, accounting for body composition and sexual maturation. To do this, we leveraged a multiethnic, mixed-longitudinal study with annual assessments for up to 7 years (The Bone Mineral Density in Childhood Study and its ancillary cohort) conducted at five US clinical centers. Participants included 1592 children, skeletally immature (45% females, 19% AA) who were aged 5 to 17 years at study entry. The primary outcome measure was relative skeletal maturation as assessed by hand-wrist radiograph. Additional covariates measured included anthropometrics, body composition by dual-energy X-ray absorptiometry (DXA), and Tanner stage of sexual maturation. Using mixed effects longitudinal models, without covariates, advancement in relative skeletal maturation was noted in self-reported AA girls (∼0.33 years, p ancestry groups showed independent positive associations of height, lean mass, fat mass, and puberty with relative skeletal maturation. The effect of ancestry was attenuated but persistent after accounting for covariates: for girls, 0.19 years (ancestry by self-report, p = 0.02) or 0.29 years (ancestry by admixture, p = 0.004); and for boys, 0.20 years (ancestry by self-report, p = 0.004), or 0.29 years (ancestry by admixture, p = 0.004). In summary, we conclude that advancement in relative skeletal maturation was associated with AA ancestry in healthy, non-obese children, independent of growth, body composition, and puberty. Further research into the mechanisms underlying this observation may provide insights into the regulation of skeletal maturation. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and

  2. A novel cofactor-binding mode in bacterial IMP dehydrogenases explains inhibitor selectivity.

    Science.gov (United States)

    Makowska-Grzyska, Magdalena; Kim, Youngchang; Maltseva, Natalia; Osipiuk, Jerzy; Gu, Minyi; Zhang, Minjia; Mandapati, Kavitha; Gollapalli, Deviprasad R; Gorla, Suresh Kumar; Hedstrom, Lizbeth; Joachimiak, Andrzej

    2015-02-27

    The steadily rising frequency of emerging diseases and antibiotic resistance creates an urgent need for new drugs and targets. Inosine 5'-monophosphate dehydrogenase (IMP dehydrogenase or IMPDH) is a promising target for the development of new antimicrobial agents. IMPDH catalyzes the oxidation of IMP to XMP with the concomitant reduction of NAD(+), which is the pivotal step in the biosynthesis of guanine nucleotides. Potent inhibitors of bacterial IMPDHs have been identified that bind in a structurally distinct pocket that is absent in eukaryotic IMPDHs. The physiological role of this pocket was not understood. Here, we report the structures of complexes with different classes of inhibitors of Bacillus anthracis, Campylobacter jejuni, and Clostridium perfringens IMPDHs. These structures in combination with inhibition studies provide important insights into the interactions that modulate selectivity and potency. We also present two structures of the Vibrio cholerae IMPDH in complex with IMP/NAD(+) and XMP/NAD(+). In both structures, the cofactor assumes a dramatically different conformation than reported previously for eukaryotic IMPDHs and other dehydrogenases, with the major change observed for the position of the NAD(+) adenosine moiety. More importantly, this new NAD(+)-binding site involves the same pocket that is utilized by the inhibitors. Thus, the bacterial IMPDH-specific NAD(+)-binding mode helps to rationalize the conformation adopted by several classes of prokaryotic IMPDH inhibitors. These findings offer a potential strategy for further ligand optimization. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. A Novel Cofactor-binding Mode in Bacterial IMP Dehydrogenases Explains Inhibitor Selectivity*

    Science.gov (United States)

    Makowska-Grzyska, Magdalena; Kim, Youngchang; Maltseva, Natalia; Osipiuk, Jerzy; Gu, Minyi; Zhang, Minjia; Mandapati, Kavitha; Gollapalli, Deviprasad R.; Gorla, Suresh Kumar; Hedstrom, Lizbeth; Joachimiak, Andrzej

    2015-01-01

    The steadily rising frequency of emerging diseases and antibiotic resistance creates an urgent need for new drugs and targets. Inosine 5′-monophosphate dehydrogenase (IMP dehydrogenase or IMPDH) is a promising target for the development of new antimicrobial agents. IMPDH catalyzes the oxidation of IMP to XMP with the concomitant reduction of NAD+, which is the pivotal step in the biosynthesis of guanine nucleotides. Potent inhibitors of bacterial IMPDHs have been identified that bind in a structurally distinct pocket that is absent in eukaryotic IMPDHs. The physiological role of this pocket was not understood. Here, we report the structures of complexes with different classes of inhibitors of Bacillus anthracis, Campylobacter jejuni, and Clostridium perfringens IMPDHs. These structures in combination with inhibition studies provide important insights into the interactions that modulate selectivity and potency. We also present two structures of the Vibrio cholerae IMPDH in complex with IMP/NAD+ and XMP/NAD+. In both structures, the cofactor assumes a dramatically different conformation than reported previously for eukaryotic IMPDHs and other dehydrogenases, with the major change observed for the position of the NAD+ adenosine moiety. More importantly, this new NAD+-binding site involves the same pocket that is utilized by the inhibitors. Thus, the bacterial IMPDH-specific NAD+-binding mode helps to rationalize the conformation adopted by several classes of prokaryotic IMPDH inhibitors. These findings offer a potential strategy for further ligand optimization. PMID:25572472

  4. Diversity and Functional Analysis of the FeMo-Cofactor Maturase NifB

    Directory of Open Access Journals (Sweden)

    Simon Arragain

    2017-11-01

    Full Text Available One of the main hurdles to engineer nitrogenase in a non-diazotrophic host is achieving NifB activity. NifB is an extremely unstable and oxygen sensitive protein that catalyzes a low-potential SAM-radical dependent reaction. The product of NifB activity is called NifB-co, a complex [8Fe-9S-C] cluster that serves as obligate intermediate in the biosyntheses of the active-site cofactors of all known nitrogenases. Here we study the diversity and phylogeny of naturally occurring NifB proteins, their protein architecture and the functions of the distinct NifB domains in order to understand what defines a catalytically active NifB. Focus is on NifB from the thermophile Chlorobium tepidum (two-domain architecture, the hyperthermophile Methanocaldococcus infernus (single-domain architecture and the mesophile Klebsiella oxytoca (two-domain architecture, showing in silico characterization of their nitrogen fixation (nif gene clusters, conserved NifB motifs, and functionality. C. tepidum and M. infernus NifB were able to complement an Azotobacter vinelandii (ΔnifB mutant restoring the Nif+ phenotype and thus demonstrating their functionality in vivo. In addition, purified C. tepidum NifB exhibited activity in the in vitro NifB-dependent nitrogenase reconstitution assay. Intriguingly, changing the two-domain K. oxytoca NifB to single-domain by removal of the C-terminal NifX-like extension resulted in higher in vivo nitrogenase activity, demonstrating that this domain is not required for nitrogen fixation in mesophiles.

  5. Ntdin, a tobacco senescence-associated gene, is involved in molybdenum cofactor biosynthesis.

    Science.gov (United States)

    Yang, Seung Hwan; Berberich, Thomas; Miyazaki, Atsushi; Sano, Hiroshi; Kusano, Tomonobu

    2003-10-01

    To date, dozens of genes have been reported to be up-regulated with senescence in higher plants. Radish din1 and its ortholog sen1 of Arabidopsis are known as such, but their function is not clear yet. Here we have isolated their counterpart cDNA from tobacco and designated it as NTDIN: Its product, Ntdin, a 185 amino acid polypeptide with 56.8% and 54.2% identity to Atsen1 and Rsdin1, respectively, is localized in chloroplasts. Transcripts of Ntdin are induced by sulfate or nitrate but not by phosphate, suggesting its involvement in sulfur and nitrogen metabolism. A database search revealed that Ntdin shows similarity with the C-terminal region of Nicotiana plumbaginifolia Cnx5, which functions in molybdenum cofactor (Moco) biosynthesis. Transgenic tobacco plants with suppressed Ntdin are more tolerant to chlorate, a substrate analog of nitrate reductase, than controls, implying low nitrate reductase activity in the transgenic plants due to a deficiency of Moco. Indeed, enzymatic activities of two molybdoenzymes, nitrate reductase and xanthine dehydrogenase, in transgenic plants are found to be significantly lower than in control plants. Direct measurement of Moco contents reveals that those transgenic plants contain about 5% Moco of those of the control plants. Abscisic acid and indole-3-acidic acid, whose biosynthetic pathways require Moco, up-regulated Ntdin expression. Taken together, it is concluded that Ntdin functions in a certain step in Moco biosynthesis.

  6. Farmakologisk behandling af præmatur ejakulation

    DEFF Research Database (Denmark)

    Kuhlmann, Ida Berglund; Hedegaard, Ulla; Christensen, Mette Marie H

    2017-01-01

    Forfatterne anbefaler lokalanæstesi med lidokain og/eller prilokain som førstevalg. Andet valg til behandling vil være dapoxetin, som er en korttidsvirkende SSRI med indikationen præmatur ejakulation. Som tredje valg kan overvejes SSRI'et sertralin......Forfatterne anbefaler lokalanæstesi med lidokain og/eller prilokain som førstevalg. Andet valg til behandling vil være dapoxetin, som er en korttidsvirkende SSRI med indikationen præmatur ejakulation. Som tredje valg kan overvejes SSRI'et sertralin...

  7. Digital Maturity of the Firm's Business Model

    DEFF Research Database (Denmark)

    Groskovs, Sergejs; Vemula, Sreekanth

    We propose a digital maturity assessment model as an instrument for researchers and a strategic tool for managers. Existing literature lacks a conceptually clear way to measure the construct of digital maturity at the level of the firms business model. Our proposed instrument thus opens avenues...... for research into questions related to antecedents, process, and performance outcomes of the digitalization of business activities. The assessment follows the logic of first decomposing the business model into the underlying value creation activities and then evaluating the levels of automation...

  8. Evaluation of sexual maturity among adolescent male sickle cell ...

    African Journals Online (AJOL)

    Tanner staging and testicular volume assessment were both used as models for evaluating stages of sexual maturation among SCA patients and their normal counterparts matched for age and socioeconomic status. Results. SCA patients showed delayed onset and completion of sexual maturation. TV of subjects was ...

  9. Nicotine supplementation blocks oocyte maturation in Rattus norvegicus

    Directory of Open Access Journals (Sweden)

    Meitria Syahadatina Noor

    2013-08-01

    Full Text Available Background Indonesia has the third largest tobacco consumption in the world after China and India. Nicotine as the main component of cigarette smoke has negative effects on the reproductive system, such as oocyte maturation, ovulation, and fertilization, and increasing the diploidy of oocytes. The goal of this research was to evaluate the effect of nicotine on oocyte maturation in Rattus norvegicus. Methods This was an experimental study with post test only control group design. The subjects were 40 rats selected homogenously and randomly. They were divided into a control group (receiving carboxy-methyl-cellulose sodium and 3 treatment groups (I-III receiving nicotine subcutaneously for 7 days at dosages of 21 mg/kgBW, 41 kg/kgBW and 84/kgBW, respectively. The observations comprised oocyte maturation stage, viz. germinal vesicle (GV, germinal vesicle breakdown (GVBD, metaphase I and metaphase II. Data were analyzed by one-way Anova with á=0.05, followed by Tukey’s HSD test. Results One-way Anova showed significant differences in oocyte maturation in all groups. Tukey’s HSD test showed that for GV, the differing groups were control and I, control and II, I and III. For GVBD, the differing groups were control and I, I and II, I and III. For metaphase I, the differing groups were control with I, II, and III, I and II, I and III. For metaphase II, the differing groups were control versus I, II, and III, I and II, I and III. Conclusion Low dose of nicotine is capable of affecting oocyte maturation in Rattus norvegicus.

  10. Cord blood mesenchymal stem cells propel human dendritic cells to an intermediate maturation state and boost interleukin-12 production by mature dendritic cells.

    NARCIS (Netherlands)

    Berk, L.C.J. van den; Roelofs, H.; Huijs, T.; Siebers-Vermeulen, K.G.C.; Raymakers, R.A.P.; Kogler, G.; Figdor, C.G.; Torensma, R.

    2009-01-01

    Pathogen-derived entities force the tissue-resident dendritic cells (DCs) towards a mature state, followed by migration to the draining lymph node to present antigens to T cells. Bone marrow mesenchymal stem cells (MSCs) modulate the differentiation, maturation and function of DCs. In umbilical cord

  11. In vivo and in vitro pollen maturation in Lilium: influence of carbohydrates

    Directory of Open Access Journals (Sweden)

    Christophe Clement

    2014-01-01

    Full Text Available The purpose of this study was to develop a protocol for in vitro conform pollen maturation, as a model to study the involvement of carbohydrates on pollen maturation in Lilium. In vivo and in vitro pollen maturations were followed and compared by transmission electron microscopy, and several in vitro parameters were tested in terms of carbohydrate physiology. In vivo, pollen maturation was initiated at the vacuolated microspore stage, and consisted of two successive phases. The first phase was characterized by reactivation of microspore organelles, followed by microspore mitosis, starch synthesis and vacuole breakdown. During the second phase, starch was progressively degraded whereas lipid and phytine reserves accumulated. In vivo, pollen maturation occured within 14 days and pollen germination rate was 73.6 ± 2.2%. We then attempted to realise in vitro pollen maturation starting from the vacuolated microspore stage. The best results were obtained with flower buds cultivated at 26oC, in 100 µmol/m2/s light, with a 16h/8h photoperiod on a modified Heller's medium supplemented with NAA (10-2 mg/l and sucrose (M/6. In these conditions, pollen maturation occured within 7 days only. In vitro matured pollen is cytologically comparable to in vivo developed pollen grains and the germination rate was 72.4 ± 3.7%. When flower buds were cultivated in the dark, the germination rate decreased, but this could be compensated by providing high sucrose concentrations (1M in the medium. Further, photosynthesis inhibitors had the same effect on pollen maturation than the darkness, strongly suggesting that photosynthesis occurs in the flower bud and is important for pollen maturation in Lilium.

  12. Maturation of pig oocytes in vitro in a medium with pyruvate

    Directory of Open Access Journals (Sweden)

    H. Gonzales-Figueroa

    2005-06-01

    Full Text Available The aim of in vitro maturation oocyte systems is to produce oocytes of comparable quality to those derived in vivo. The present study was designed to examine the surface morphological changes of the cumulus-oocyte complex (COC and nuclear maturation in a culture system containing pyruvate. Ovaries were obtained from a slaughterhouseand transported to the laboratory within 2 h at 35-39ºC,and rinsed three times in 0.9% NaCl. The COCs were harvested from the ovaries and in vitro maturation was evaluated in San Marcos (SM medium, a chemically defined culture system containing 22.3 mM sodium pyruvate. Oocytes were cultured in SM, SM + porcine follicular fluid (pFF and in SM + pFF + gonadotropins (eCG and hCG for 20-22 h and then without hormonal supplements for an additional 20-22 h. After culture, the degree of cumulus expansion and frequency of nuclear maturation were determined. Oocytes matured in SM (40.9% and SM + pFF (42.9% showed moderate cumulus expansion, whereas oocytes matured in SM + pFF + gonadotropins (54.6% showed high cumulus expansion. The maturation rate of cultured oocytes, measured in function of the presence of the polar corpuscle, did not differ significantly between SM (40.9 ± 3.6% and SM + pFF (42.9 ± 3.7%. These results indicate that pig oocytes can be successfully matured in a chemically definedmedium and suggest a possible bifunctional role of pyruvate as an energy substrate and as an antioxidant protecting oocytes against the stress of the in vitro environment.

  13. Thermal mud maturation: organic matter and biological activity.

    Science.gov (United States)

    Centini, M; Tredici, M R; Biondi, N; Buonocore, A; Maffei Facino, R; Anselmi, C

    2015-06-01

    Many of the therapeutic and cosmetic treatments offered in spas are centred on mud therapy, to moisturize the skin and prevent skin ageing and rheumatic diseases. Thermal mud is a complex matrix composed of organic and inorganic elements which contribute to its functions. It is a natural product derived from the long mixing of clay and thermal water. During its maturation, organic substances are provided by the microalgae, which develop characteristic of the composition of thermal water. The aim of this study was to identify methods for introducing objective parameters as a basis for characterizing thermal mud and assessing its efficacy. Samples of thermal mud were collected at the Saturnia spa, where there are several sulphureous pools. The maturation of the mud was evaluated by organic component determination using extractive methods and chromatographic analysis (HPLC, GC-MS, SPME). We also studied the radical scavenging activity of mud samples at different stages of maturation, in a homogeneous phase, using several tests (DPPH, ORAC, ABTS). We identified several classes of compounds: saturated and unsaturated fatty acids, hydroxyl acids, dicarboxylic acids, ketoacids, alcohols and others. SPME analysis showed the presence of various hydrocarbons compounds (C(11) -C(17)) and long-chain alcohols (C(12) -C(16)). Six or seven months seemed appropriate to complete the process of maturation, and the main effect of maturation time was the increase of lipids. Six-month mud showed the highest activity. The hydrophilic extract was more active than the lipophilic extract. The results indicate that maturation of thermal mud can be followed on the basis of the changes in its organic composition and antioxidant properties along the time. They also highlight the need to develop reference standards for thermal muds in relation to assess their use for therapeutic and cosmetic purposes. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  14. Effect of fertilization on the physiological maturation of sesame seeds

    Directory of Open Access Journals (Sweden)

    Erivan Isídio Ferreira

    2017-06-01

    Full Text Available Fertilization and harvest time may influence the formation and maturation processes, as well as the physiological quality of seeds. This study aimed at evaluating the effect of fertilization on the physiological maturation of sesame seeds. The following variables were evaluated: fruit color, dry mass and water content of fruits and seeds, germination, first germination count, germination speed, emergence and emergence speed. No significant fertilization effect was observed on fruit maturation for water content or dry mass. However, there was significance for these variables in the seeds. The harvest time had a significant effect on water content and dry mass of fruits and seeds. For the variables that evaluated the seed viability and vigor, both the fertilization and harvest time influenced the physiological maturation. The physiological maturity of the sesame seeds, whose plants were grown with and without fertilization, was reached between 52 and 54 days after anthesis, when the fruits were classified as yellow-greenish 7.5 Y 8/6 and yellow to yellow-red 10.R 4/6.

  15. Pricing constant maturity credit default swaps under jumo dynamics

    NARCIS (Netherlands)

    Jönsson, H.; Schoutens, W.

    2009-01-01

    In this paper we discuss the pricing of Constant Maturity Credit Default Swaps (CMCDS) under single sided jump models. The CMCDS offers default protection in exchange for a floating premium which is periodically reset and indexed to the market spread on a CDS with constant maturity tenor written on

  16. Regulation of oocyte maturation in fish.

    Science.gov (United States)

    Nagahama, Yoshitaka; Yamashita, Masakane

    2008-06-01

    A period of oocyte growth is followed by a process called oocyte maturation (the resumption of meiosis) which occurs prior to ovulation and is a prerequisite for successful fertilization. Our studies using fish models have revealed that oocyte maturation is a three-step induction process involving gonadotropin (LH), maturation-inducing hormone (MIH), and maturation-promoting factor (MPF). LH acts on the ovarian follicle layer to produce MIH (17alpha, 20beta-dihydroxy-4-pregnen-3-one, 17alpha, 20beta-DP, in most fishes). The interaction of ovarian thecal and granulosa cell layers (two-cell type model), is required for the synthesis of 17alpha,20beta-DP. The dramatic increase in the capacity of postvitellogenic follicles to produce 17alpha,20beta-DP in response to LH is correlated with decreases in P450c17 (P450c17-I) and P450 aromatase (oP450arom) mRNA and increases in the novel form of P450c17 (P450c17-II) and 20beta-hydroxysteroid dehydrogenase (20beta-HSD) mRNA. Transcription factors such as Ad4BP/SF-1, Foxl2, and CREB may be involved in the regulation of expression of these steroidogenic enzymes. A distinct family of G-protein-coupled membrane-bound MIH receptors has been shown to mediate non-genomic actions of 17alpha, 20beta-DP. The MIH signal induces the de novo synthesis of cyclin B from the stored mRNA, which activates a preexisting 35 kDa cdc2 kinase via phosphorylation of its threonine 161 by cyclin-dependent kinase activating kinase, thus producing the 34 kDa active cdc2 (active MPF). Upon egg activation, MPF is inactivated by degradation of cyclin B. This process is initiated by the 26S proteasome through the first cut in its NH(2) terminus at lysine 57.

  17. MRI quantitative assessment of brain maturation and prognosis in premature infants using total maturation score

    International Nuclear Information System (INIS)

    Qi Ying; Wang Xiaoming

    2009-01-01

    Objective: To quantitatively assess brain maturation and prognosis in premature infants on conventional MRI using total maturation score (TMS). Methods: Nineteen cases of sequelae of white matter damage (WMD group )and 21 cases of matched controls (control group) in premature infants confirmed by MRI examinations were included in the study. All cases underwent conventional MR imaging approximately during the perinatal period after birth. Brain development was quantitatively assessed using Childs AM's validated scoring system of TMS by two sophisticated radiology physicians. Interobserver agreement and reliability was evaluated by using intraclass correlation (ICC). Linear regression analysis between TMS and postmenstrual age (PMA) was made(Y: TMS, X: PMA). Independent-sample t test of the two groups' TMS was made. Results: Sixteen of 19 cases revealed MRI abnormalities. Lesions showing T 1 and T 2 shortening tended to occur in clusters or a linear pattern in the deep white matter of the centrum semiovale, periventricular white matter. Diffusion-weighted MR image (DWI) showed 3 cases with greater lesions and 4 cases with new lesions in corpus callosum. There was no abnormality in control group on MRI and DWI. The average numbers of TMS between the two observers were 7.13±2.27, 7.13±2.21. Interobservcer agreement was found to be high (ICC=0.990, P 2 =0.6401,0.5156 respectively, P 0.05). Conclusion: Conventional MRI is able to quantify the brain maturation and prognosis of premature infants using TMS. (authors)

  18. Maturity Gonad Sea Cucumber Holothuria scabra Under The Month Cycle

    Science.gov (United States)

    Penina Tua Rahantoknam, Santi

    2017-10-01

    Gonad maturity level of the sea cucumber Holothuria scabra is important to note for selection of parent ready spawn. Sea cucumbers are giving a reaction to the treatment of excitatory spawn mature individuals only. For the determination of the level of maturity of gonads of sea cucumbers, the necessary observation of the gonads are microscopic, macroscopic and gonad maturity gonado somatic indeks (GSI). GSI value is important to know the changes that occur in the gonads quantitatively, so that time can be presumed spawning (Effendie, 1997). Reproductive cycle can be determined by observing the evolution of GSI. The study of sea cucumbers Holothuria scabra gonad maturity conducted in Langgur, Southeast Maluku. Observations were made at every cycle of the moon is the full moon phase (BP) and new moon (BB) in the period January 29, 2017 until July 23, 2017. Observations H. scabra gonad maturity level is done with surgery, observation and calculation GSI gonad histology. GSI highest value obtained in May that full moon cycle at 90% of individuals that are in the spawning stage (phase 5), then 70% of the individuals that are in the spawning stage (phase 5) in March that the full moon cycle. The results obtained show that the peak spawning H. scabra period January 2017 to July 2017 occurred on the full moon cycle in May.

  19. How to manage sustainable supply chain? The issue of maturity

    Directory of Open Access Journals (Sweden)

    Agata Rudnicka

    2016-12-01

    Full Text Available Background: The issue of managing sustainability in supply chain seems to be more and more complex. There are many aspects that need to be taken into consideration when planning, implementing and monitoring environmental and social conditions of supply chains. Despite many works, already published, on the concept of sustainable development (SD is seems that the issue of assessment and especially the issue of maturity in the light of the SD concept is still not developed enough. Methods: The general aim of the paper is the analysis of the maturity issue in the context of sustainability. The main objective is to conceptualize the idea of maturity in sustainable supply chain. Beside the literature research the own proposition of theoretical model was described. Results: The article describes the issue of maturity as an element of managing sustainable development in the supply chain. The author presented a theoretical model of the maturity. Moreover the author gave some recommendations how to manage the sustainability issues in supply chain in more mature approach and introduced some useful tools among which are: certification, code of conduct and code of ethics, audits, projects etc. Conclusions: The issue of maturity seems to be very useful for proper understanding the idea of sustainable development in supply chain. The developed model can be used as self-assessment method to check at which level of implementation the idea of SD is analyzed in supply chain. Furthermore, the next phase of the planned research in form of practical verification of the model was advised as well as a research of identification of new factors and tools in analyzed area.

  20. EMOTIONAL MATURITY OF PERSONALITY: THE PRACTICAL PROBLEM OF PSYCHOLOGICAL DIAGNOSIS

    OpenAIRE

    O. I. Afonina

    2013-01-01

    In the dif?cult conditions of the contemporary society which are far from being favorable to maintain one’s emotional and physical health the problem of development and achievement of emotional maturity as a factor of the well-being is getting more signi?cant. Based on the theoretical concepts of different scientists who de?ned the construct of emotional maturity three groups of psychological methods for assessing emotional maturity are analyzed. The ?rst group includes the methods that are u...

  1. Role of intensive training in the growth and maturation of artistic gymnasts.

    Science.gov (United States)

    Malina, Robert M; Baxter-Jones, Adam D G; Armstrong, Neil; Beunen, Gaston P; Caine, Dennis; Daly, Robin M; Lewis, Richard D; Rogol, Alan D; Russell, Keith

    2013-09-01

    Short stature and later maturation of youth artistic gymnasts are often attributed to the effects of intensive training from a young age. Given limitations of available data, inadequate specification of training, failure to consider other factors affecting growth and maturation, and failure to address epidemiological criteria for causality, it has not been possible thus far to establish cause-effect relationships between training and the growth and maturation of young artistic gymnasts. In response to this ongoing debate, the Scientific Commission of the International Gymnastics Federation (FIG) convened a committee to review the current literature and address four questions: (1) Is there a negative effect of training on attained adult stature? (2) Is there a negative effect of training on growth of body segments? (3) Does training attenuate pubertal growth and maturation, specifically, the rate of growth and/or the timing and tempo of maturation? (4) Does training negatively influence the endocrine system, specifically hormones related to growth and pubertal maturation? The basic information for the review was derived from the active involvement of committee members in research on normal variation and clinical aspects of growth and maturation, and on the growth and maturation of artistic gymnasts and other youth athletes. The committee was thus thoroughly familiar with the literature on growth and maturation in general and of gymnasts and young athletes. Relevant data were more available for females than males. Youth who persisted in the sport were a highly select sample, who tended to be shorter for chronological age but who had appropriate weight-for-height. Data for secondary sex characteristics, skeletal age and age at peak height velocity indicated later maturation, but the maturity status of gymnasts overlapped the normal range of variability observed in the general population. Gymnasts as a group demonstrated a pattern of growth and maturation similar to

  2. The Influence of Debt Maturity Structure on Accounting Conservatism

    Institute of Scientific and Technical Information of China (English)

    Zhao Huiqing; Chen Xinguo

    2015-01-01

    According to the related data of A-share listed companies in 2009-2013,through extension model based on Basu's surplus - the stock return rate model ,this paper studies that the debt maturity structure influences on accounting conservatism. The empirical study finds that the amount of debt affects significantly the prudence,that is,the greater the amount of the debt contract con- cluded, the stronger role of accounting conservatism is ; Debt maturity have significant relationship with accounting conservatism. For the shorter debt maturity, the enterprise is easier to choose more prudent accounting policy, and when the period is longer, accounting conservatism is relatively weaker.

  3. Survival and maturation rates of the African rodent Mastomys natalensis

    DEFF Research Database (Denmark)

    Sluydts, Vincent; Crespin, Laurent; Davis, Stephen

    2008-01-01

    the model fit. On the other hand we showed that maturation rates were correlated negatively with density the previous month and positively to cumulative rainfall over the past three months. Survival estimates of both adults and subadults varied seasonally, with higher estimates during the increase phase......Survival and maturation rates of female Mastomys natalensis were analysed based on a ten-year onthly capture-recapture data set. We investigated whether direct and delayed density dependent and independent (rainfall) variables accounted for the considerable variation in demographic traits....... It was estimated that seasonal and annual covariates accounted for respectively 29 and 26% of the total variation in maturation rates and respectively 17 and 11% of the variation in survival rates. Explaining the between-year differences in maturation rates with annual past rainfall or density did not improve...

  4. Structural and Maturational Covariance in Early Childhood Brain Development.

    Science.gov (United States)

    Geng, Xiujuan; Li, Gang; Lu, Zhaohua; Gao, Wei; Wang, Li; Shen, Dinggang; Zhu, Hongtu; Gilmore, John H

    2017-03-01

    Brain structural covariance networks (SCNs) composed of regions with correlated variation are altered in neuropsychiatric disease and change with age. Little is known about the development of SCNs in early childhood, a period of rapid cortical growth. We investigated the development of structural and maturational covariance networks, including default, dorsal attention, primary visual and sensorimotor networks in a longitudinal population of 118 children after birth to 2 years old and compared them with intrinsic functional connectivity networks. We found that structural covariance of all networks exhibit strong correlations mostly limited to their seed regions. By Age 2, default and dorsal attention structural networks are much less distributed compared with their functional maps. The maturational covariance maps, however, revealed significant couplings in rates of change between distributed regions, which partially recapitulate their functional networks. The structural and maturational covariance of the primary visual and sensorimotor networks shows similar patterns to the corresponding functional networks. Results indicate that functional networks are in place prior to structural networks, that correlated structural patterns in adult may arise in part from coordinated cortical maturation, and that regional co-activation in functional networks may guide and refine the maturation of SCNs over childhood development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Endogenous laminin is required for human airway smooth muscle cell maturation

    Directory of Open Access Journals (Sweden)

    Tran Thai

    2006-09-01

    Full Text Available Abstract Background Airway smooth muscle (ASM contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. Methods Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. Results Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. Conclusion While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the

  6. 7 CFR 51.2841 - Mature.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing Practices), DEPARTMENT OF AGRICULTURE REGULATIONS AND STANDARDS UNDER THE AGRICULTURAL MARKETING ACT OF 1946... considered mature when harvested in accordance with good commercial practice at a stage which will not result...

  7. The geochemical record of the ancient nitrogen cycle, nitrogen isotopes, and metal cofactors.

    Science.gov (United States)

    Godfrey, Linda V; Glass, Jennifer B

    2011-01-01

    The nitrogen (N) cycle is the only global biogeochemical cycle that is driven by biological functions involving the interaction of many microorganisms. The N cycle has evolved over geological time and its interaction with the oxygen cycle has had profound effects on the evolution and timing of Earth's atmosphere oxygenation (Falkowski and Godfrey, 2008). Almost every enzyme that microorganisms use to manipulate N contains redox-sensitive metals. Bioavailability of these metals has changed through time as a function of varying redox conditions, and likely influenced the biological underpinnings of the N cycle. It is possible to construct a record through geological time using N isotopes and metal concentrations in sediments to determine when the different stages of the N cycle evolved and the role metal availability played in the development of key enzymes. The same techniques are applicable to understanding the operation and changes in the N cycle through geological time. However, N and many of the redox-sensitive metals in some of their oxidation states are mobile and the isotopic composition or distribution can be altered by subsequent processes leading to erroneous conclusions. This chapter reviews the enzymology and metal cofactors of the N cycle and describes proper utilization of methods used to reconstruct evolution of the N cycle through time. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Prevalence of Anti Human Herpes Virus-6 IgG and its Receptor in Acute Leukemia (Membrane Cofactor Protein: MCP, CD46)

    International Nuclear Information System (INIS)

    Assem, M.M; El-Sharkawy, N.M.; Tarek, H.; Kamel, A.M.; Gad, W.H.; El-Rouby, M.N.; Ghaleb, F.M.

    2005-01-01

    CD46 is a membrane cofactor protein, which acts as a cofactor for factor I proteolytic cleavage of C3, so it protects the cells expressing it on their surface from autologous complement attack. It has been recently described as a receptor for HHV-6. Also, it has been shown to be highly expressed on malignant cells as compared to normal cells, thus playing a major role by which these cells, either cells of haematological malignancy or cells of other body cancers, can protect themselves against complement attack so they can survive and metastasize. Patients and methods: This study has been done to detect the sero prevalence of HHV-6 among 47 Egyptian adult cases of acute leukemia using the anti-HHV-6 IgG ELISA serological technique. CD46 receptor expression and immuno phenotyping technique were performed using FCM. Twenty nine of the cases were ANLL, while 18 were ALL cases. Sixteen age- and sex-matched control cases were also studied for both anti-HHV-6 IgG and CD46 receptor expression. HHV-6 IgG antibodies were encountered in 29 (100%), 14 (77.8%) and 12 (75%) of the ANLL, ALL and the control group, cases, respectively. CD46 expression was encountered in 21 (72.4%) of the ANLL cases and in 10 (55.6%) of the ALL cases. Concordance between HHV6 sero positivity and CD46 expression was encountered in 31 cases (29 positive and 2 negative). Dis concordance was encountered in 16 cases with 14 showing HHV-6 IgG sero positivity with no CD46 expression and 2 showing the reverse. The lack of significant correlation between CD46 expression and sero positivity would exclude CD46 expression as a cause of contracting HHV-6 infection in leukemic patients

  9. On the improvement of IT process maturity: assessment, recommendation and validation

    Directory of Open Access Journals (Sweden)

    Dirgahayu Teduh

    2018-01-01

    Full Text Available The use of information technology (IT in enterprises must be governed and managed appropriately using IT processes. The notion of IT process maturity is useful to measure the actual performance and to define the desired performance of IT processes. Improvements are necessary when there are gaps between the actual and desired performance. Most literatures focus on IT process maturity assessment. They do not address how to improve IT process maturity. This paper proposes an approach to enterprise IT process maturity improvement for COBIT processes. The approach consists of three activities, i.e. IT process maturity assessment, recommendation, and validation. Assessment is to recognise the process’ control objectives maturity. From the assessment results, recommendation identifies control objectives that must be improved and then suggests improvement actions. The prescriptive nature of the control objectives facilitates in suggesting those actions. Recommendations for managements are defined by abstracting similar actions. Validation checks whether the recommendations match with the enterprise needs and capability. It includes a scale for validation, in which enterprise’s capability is categorized into (i not capable, (ii capable with great efforts, and (iii fully capable. The paper illustrates the approach with a case study.

  10. Abscisic Acid and the Maturation of Cacao Embryos in Vitro 1

    Science.gov (United States)

    Pence, Valerie Creaser

    1992-01-01

    Abscisic acid (ABA) was tested for its ability to affect development of immature zygotic embryos of cacao (Theobroma cacao) in vitro, by adding exogenous ABA, fluridone, or mefluidide to cultured embryos. Endogenous ABA levels, measured by enzyme-linked immunosorbent assay, were increased by exogenous ABA or by culture on sucrose increasing to 21%, and were decreased by fluridone and, to a lesser extent, by mefluidide. The effects of these on maturation were measured as effects on anthocyanins, lipids, and fatty acid saturation, all of which increase with maturation of the cacao embryo. Maturation was stimulated by increasing sucrose and, to a lesser degree, the addition of ABA, but decreasing endogenous ABA by treating with fluridone significantly inhibited all maturation parameters. Although desiccation tolerance does not develop in cacao embryos, these results suggest that ABA and sucrose are both needed for the initiation of events associated with maturation in vitro. PMID:16668805

  11. Plasticity in probabilistic reaction norms for maturation in a salmonid fish.

    Science.gov (United States)

    Morita, Kentaro; Tsuboi, Jun-ichi; Nagasawa, Toru

    2009-10-23

    The relationship between body size and the probability of maturing, often referred to as the probabilistic maturation reaction norm (PMRN), has been increasingly used to infer genetic variation in maturation schedule. Despite this trend, few studies have directly evaluated plasticity in the PMRN. A transplant experiment using white-spotted charr demonstrated that the PMRN for precocious males exhibited plasticity. A smaller threshold size at maturity occurred in charr inhabiting narrow streams where more refuges are probably available for small charr, which in turn might enhance the reproductive success of sneaker precocious males. Our findings suggested that plastic effects should clearly be included in investigations of variation in PMRNs.

  12. Peak height velocity as an alternative for maturational classification associated with motor performance

    Directory of Open Access Journals (Sweden)

    Leonardo Trevizan Costa

    2009-01-01

    Full Text Available Adolescence is a phase characterized by important physical and maturational alterations, with individuals of the same chronological age, but who are more mature, may present sportive advantages because of greater force gain and additional muscle mass. Thus, in studies evaluating motor skills of children and adolescents, maturational classification should be an efficient and easily applicable tool in order to facilitate the interpretation of the true relationship between maturation and motor performance. Therefore, the objective of this study was to compare the relationship between motor performance and different types of classification of biological maturation in 209 boys aged to 17 years (11.59 ± 2.57 practicing soccer. Anthropometric variables were obtained according to the ISAK criteria. Biological maturation was determined based on age at peak height velocity (PHV and also by self-assessment of sexual maturation (genitalia and pubic hair. Motor performance was evaluated by sit-and-reach tests, horizontal jump, modified push-ups, 50-m run, and 9/12-min run/walk. The results showed progression in the variables analyzed as the subjects reached maturity. Correlation analysis and the egression values indicated higher consistency for the PHV classification, which better explained motor performance according to maturational status, exceeding the values obtained by comparison according to age or sexual maturation. Thus, the use of PHV as a classification instrument is preferably recommended for youngsters with haracteristics similar to those of the present sample.

  13. The Responsible Research and Innovation (RRI) Maturity Model

    DEFF Research Database (Denmark)

    Stahl, Bernd; Obach, Michael; Yaghmaei, Emad

    2017-01-01

    Responsible research and innovation (RRI) is an approach to research and innovation governance aiming to ensure that research purpose, process and outcomes are acceptable, sustainable and even desirable. In order to achieve this ambitious aim, RRI must be relevant to research and innovation...... in industry. In this paper, we discuss a way of understanding and representing RRI that resonates with private companies and lends itself to practical implementation and action. We propose the development of an RRI maturity model in the tradition of other well-established maturity models, linked...... with a corporate research and development (R&D) process. The foundations of this model lie in the discourse surrounding RRI and selected maturity models from other domains as well as the results of extensive empirical investigation. The model was tested in three industry environments and insights from these case...

  14. The AGU Data Management Maturity Model Initiative

    Science.gov (United States)

    Bates, J. J.

    2015-12-01

    In September 2014, the AGU Board of Directors approved two initiatives to help the Earth and space sciences community address the growing challenges accompanying the increasing size and complexity of data. These initiatives are: 1) Data Science Credentialing: development of a continuing education and professional certification program to help scientists in their careers and to meet growing responsibilities and requirements around data science; and 2) Data Management Maturity (DMM) Model: development and implementation of a data management maturity model to assess process maturity against best practices, and to identify opportunities in organizational data management processes. Each of these has been organized within AGU as an Editorial Board and both Boards have held kick off meetings. The DMM model Editorial Board will recommend strategies for adapting and deploying a DMM model to the Earth and space sciences create guidance documents to assist in its implementation, and provide input on a pilot appraisal process. This presentation will provide an overview of progress to date in the DMM model Editorial Board and plans for work to be done over the upcoming year.

  15. Evaluation of portable near infrared spectrophotometer to stage maturity in channel catfish

    Science.gov (United States)

    Gonadal maturity of channel catfish varies within the same cohort of fish. Female channel catfish with superior maturity need to be identified and staged for higher success to induce spawn wit ovulating hormones to produce channel x blue hybrid catfish fry in hatcheries. Maturation is not synchron...

  16. Mechanosensitivity of dental pulp stem cells is related to their osteogenic maturity

    DEFF Research Database (Denmark)

    Kraft, David C E; Bindslev, Dorthe A; Melsen, Birte

    2010-01-01

    -mature exhibited higher osteocalcin and alkaline phosphatase gene expression and activity than PDSC-immature. Pulsating fluid flow (PFF) stimulated nitric oxide production within 5 min by PDSC-mature but not by PDSC-immature. In PDSC-mature, PFF induced prostaglandin E(2) production, and cyclooxygenase 2 gene...

  17. Vision-based judgment of tomato maturity under growth conditions ...

    African Journals Online (AJOL)

    To determine the picking time of tomato and design the control strategy for the harvesting robot, the judgment of tomato maturity under natural conditions is ... Hue-mean and red-green color-difference image mean can be used as a criterion for the judgment of tomato maturity, and the tests indicated that the redgreen mean ...

  18. Variations in fatty acid composition during maturation of cumin ...

    African Journals Online (AJOL)

    Changes in fatty acids were studied during maturation of cumin (Cuminum cyminum L.) seeds cultivated in the North-Eastern region of Tunisia (Menzel Temim). The fruits matured in 49 Days after flowering (DAF). The first results show a rapid oil accumulation started in newly formed fruits (8.2%) and continued until their full ...

  19. Isolation and characterization of populations of mature and immature rat colonocytes

    International Nuclear Information System (INIS)

    Ahnen, D.J.; Reed, T.A.; Bozdech, J.M.

    1988-01-01

    A nonenzymatic method is described for the isolation of viable populations of mature and immature rat colonocytes. Histology was used to monitor colonocyte dissociation and to systematically characterize the amount of cross-contamination between populations of mature luminal cells and immature crypt cells. The mature coloncytes were 87 ± 9% pure with respect to contamination from cells from the lower half of the colonic crypt, and the immature populations were 98% pure with respect to contamination with cells from the upper half of the colonic crypt. Neither population contained significant numbers of cells from the lamina propria. Cell viability and synthetic function were maintained from 10-12 h in short-term culture. Alkaline phosphatase activity was 1.59 ± 0.01-fold higher in the mature cells than in the immature cells, and in vivo [ 3 H]thymidine incorporation was 2.9 ± 0.4-fold greater in the immature than the mature populations. These studies demonstrate that highly enriched populations of mature and immature rat colonocytes that maintain viability and synthetic function in short-term culture can be prepared. The intrinsic rate of protein synthesis is higher in immature colonocytes, and a shift to synthesis of a higher percentage of fucoproteins occurs during colonocyte differentiation. In contrast to result in the small intestine, only modest gradients of differentiation markers and cell surface protein expression were observed between mature and immature colonocytes

  20. Asymptotic weight and maturing rate in mice selected for body conformation

    Directory of Open Access Journals (Sweden)

    Di Masso Ricardo J.

    2000-01-01

    Full Text Available Growth patterns of four lines of mice selected for body conformation were analyzed with the logistic function, in order to provide baseline information about the relationship between asymptotic weight and maturing rate of body weight. Two lines were divergently selected favoring the phenotypic correlation between body weight and tail length (agonistic selection: CBi+, high body weight and long tail; CBi-, low body weight and short tail, whereas the other two lines were generated by a disruptive selection performed against the correlation between the aforementioned traits (antagonistic selection: CBi/C, high body weight and short tail; CBi/L, low body weight and long tail. The logistic parameters A (asymptotic weight and k (maturing rate behaved in CBi/C and CBi- mice and in CBi+ females as expected in terms of the negative genetic relationship between mature size and earliness of maturing. An altered growth pattern was found in CBi/L mice and in CBi+ males, because in the former genotype, selected for low body weight, the time taken to mature increased, whereas in the latter, selected for high body weight, there was a non-significant increase in the same trait. In accordance with the selective criterion, different sources of genetic variation for body weight could be exploited: one inversely associated with earliness of maturing (agonistic selection, and the other independent of maturing rate (antagonistic selection, showing that genetic variation of A is partly independent of k.

  1. 7 CFR 51.767 - Mature.

    Science.gov (United States)

    2010-01-01

    ... Florida Citrus Industry, Part 1, Chapter 20-13 Market Classification, Maturity Standards and Processing or... 2065-S, 14th and Independence Ave., Washington, DC 20250 or at the National Archives and Records...: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. ...

  2. 7 CFR 51.1158 - Mature.

    Science.gov (United States)

    2010-01-01

    ... Citrus Industry, Part 1, Chapter 20-13 Market Classification, Maturity Standards and Processing or... 2065-S, 14th and Independence Ave., Washington, DC 20250 or at the National Archives and Records...: http://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. ...

  3. Motivational Maturity and Helping Behavior

    Science.gov (United States)

    Haymes, Michael; Green, Logan

    1977-01-01

    Maturity in conative development (type of motivation included in Maslow's needs hierarchy) was found to be predictive of helping behavior in middle class white male college students. The effects of safety and esteem needs were compared, and the acceptance of responsibility was also investigated. (GDC)

  4. Blood pressure and sexual maturity in adolescents: the Heartfelt Study.

    Science.gov (United States)

    Cho, S D; Mueller, W H; Meininger, J C; Liehr, P; Chan, W

    2001-01-01

    This study investigates sexual maturity as a predictor of resting blood pressures independent of other known predictors, in 179 boys and 204 girls 11-16 years of age from the Heartfelt Study. The sample included youth of African (n = 140), Mexican (n = 117), and European and "other" (n = 126) backgrounds. Sexual maturity was assessed during clinical examination of three standard indicators for each sex. Systolic and diastolic blood pressures were higher in children of maturity stages IV and V, compared to stages I-III, in each gender/ethnic group (P maturity for their age group, had significantly higher systolic blood pressures (but not diastolic) than the less advanced in linear models that included height, body mass index (BMI), ethnicity, and age as co-predictors. Diastolic blood pressures were predicted by height in boys and by age and the BMI in girls. This analysis, using a very conservative approach, suggests that sexual maturity provides important and independent information on systolic blood pressure in adolescents. Further investigation of its role in 24-hr blood pressures and in blood pressures taken during physical and emotional stress, is recommended.

  5. Pharmaceutical Options for Triggering of Final Oocyte Maturation in ART

    Directory of Open Access Journals (Sweden)

    Juan Carlos Castillo

    2014-01-01

    Full Text Available Since the pioneering days of in vitro fertilization, hCG has been the gold standard to induce final follicular maturation. We herein reviewed different pharmaceutical options for triggering of final oocyte maturation in ART. The new upcoming agent seems to be GnRHa with its potential advantages over hCG trigger. GnRHa triggering elicits a surge of gonadotropins resembling the natural midcycle surge of gonadotropins, without the prolonged action of hCG, resulting in the retrieval of more mature oocytes and a significant reduction in or elimination of OHSS as compared to hCG triggering. The induction of final follicular maturation using GnRHa represents a paradigm shift in the ovulation triggering concept in ART and, thus, a way to develop a safer IVF procedure. Kisspeptins are key central regulators of the neuroendocrine mechanisms of human reproduction, who have been shown to effectively elicit an LH surge and to induce final oocyte maturation in IVF cycles. This new trigger concept may, therefore, offer a completely new, “natural” pharmacological option for ovulation induction. Whether kisspeptins will be the future agent to trigger ovulation remains to be further explored.

  6. Association of a multi-synthetase complex with translating ribosomes in the archaeon Thermococcus kodakarensis

    DEFF Research Database (Denmark)

    Raina, Medha; Elgamal, Sara; Santangelo, Thomas J

    2012-01-01

    -dependent methyltransferase 144, GTP cyclohydrolase 398, DNA topoisomerase VI subunit A 209, DNA topoisomerase VI subunit B 192, Type A Flavoprotein 911, NAD(P)H:rubredoxin oxidoreductase (Fatty acid metabolism) 120, NAD(P)H:rubredoxin oxidoreductase 120, cofactor-independent phosphoglycerate mutase 909, bis(5'-adenosyl...... subunit 2 255, glycerol kinase 257, phosphomannomutase-related protein 321, ribose-5-phosphate isomerase A 107, phosphate transport regulator 193, isopentenyl pyrophosphate isomerase (mevanolate Pathway) 500, amino acid kinase 203, NADH:polysulfide oxidoreductase 203, 5'-methylthioadenosine phosphorylase......, cysteine desulfurase 521, hydrogenase maturation protein HypF 235, iron-molybdenum cofactor-binding protein 192, ATPase 260, 4Fe-4S cluster-binding protein 254, phosphopyruvate hydratase 650, fructose-1,6-bisphosphatase 140, aspartate carbamoyltransferase catalytic subunit 158, Bipolar DNA helicase 448...

  7. Ergonomic sustainability based on the ergonomic maturity level measurement.

    Science.gov (United States)

    Vidal, Mario Cesar; Guizze, Carmen Lucia Campos; Bonfatti, Renato José; Silva e Santos, Marcello

    2012-01-01

    This paper aims at the application of an ergonomic maturity model (EMM), in order to assess the ergonomic sustainability outreach of ergonomic actions. This proposition was motivated by the widespread sensation that the development of the discipline, its educational devices and related practices depends on the attitude of ergonomics practitioners rather than environmental macroergonomic conditions. Maturity modeling in this paper is undertaken as a tool for ergonomic practitioners. Thus, its foundations were uprooted from diverse fields: Clinic Psychology, Quality Management and Project Management. The paper brings about a detailled explanation of this ergonomic maturity tool. The empirical part is fulfilled by the examination - using the EMM - of four emblematic cases excerpted from our research lab ergonomic portfolio.

  8. Characterization of monocyte-derived dendritic cells maturated with IFN-alpha

    DEFF Research Database (Denmark)

    Svane, I M; Nikolajsen, K; Walter, M R

    2006-01-01

    Dendritic cells (DC) are promising candidates for cancer immunotherapy. These cells can be generated from peripheral blood monocytes cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). In order to obtain full functional capacity, maturation is required......, maturation with IFN-alpha has only a small effect on induction of autologous T-cell stimulatory capacity of the DC. However, an increase in DC allogeneic T-cell stimulatory capacity was observed. These data suggest that IFN-alpha has a potential as a maturation agent used in DC-based cancer vaccine trials...

  9. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    Yeast surface display is an effective tool for antibody affinity maturation because yeast can be used as an all-in-one workhorse to assemble, display and screen diversified antibody libraries. By employing the natural ability of yeast Saccharomyces cerevisiae to efficiently recombine multiple DNA...... laboratory conditions. A particular emphasis was put on using molecular techniques in conjunction with microenvironmental measurements (O2, pH, irradiance), a combination that is rarely found but provides a much more detailed understanding of “cause and effect” in complex natural systems...

  10. Scrub-Successional Bird Community Dynamics in Young and Mature Pine-Wiregrass Savannahs

    International Nuclear Information System (INIS)

    Krementz, D.G.; Christie, J.S.

    2001-01-01

    We investigated how management for habitat conditions to support the endangered red-cockaded woodpecker effects the biodiversity of the breeding bird community associated with those habitats. Habitat is created by thinning, burning and mid-story control of hardwoods in mature longleaf stands. In addition, similar habitat structurally can be found in recently harvested areas. We tested the hypothesis that diversity and abundance, as well as survival and reproduction would be greater in mature stands. However, mature stands used for recruitment always had fewer species (36/31) than recently harvested areas (54/55). All species that occurred in recruitment stands also occurred in mature stands. No differences in survival rates were found between mature and recent cuts for Bachman's sparrow and indigo bunting

  11. Shared Sulfur Mobilization Routes for tRNA Thiolation and Molybdenum Cofactor Biosynthesis in Prokaryotes and Eukaryotes

    Directory of Open Access Journals (Sweden)

    Silke Leimkühler

    2017-01-01

    Full Text Available Modifications of transfer RNA (tRNA have been shown to play critical roles in the biogenesis, metabolism, structural stability and function of RNA molecules, and the specific modifications of nucleobases with sulfur atoms in tRNA are present in pro- and eukaryotes. Here, especially the thiomodifications xm5s2U at the wobble position 34 in tRNAs for Lys, Gln and Glu, were suggested to have an important role during the translation process by ensuring accurate deciphering of the genetic code and by stabilization of the tRNA structure. The trafficking and delivery of sulfur nucleosides is a complex process carried out by sulfur relay systems involving numerous proteins, which not only deliver sulfur to the specific tRNAs but also to other sulfur-containing molecules including iron–sulfur clusters, thiamin, biotin, lipoic acid and molybdopterin (MPT. Among the biosynthesis of these sulfur-containing molecules, the biosynthesis of the molybdenum cofactor (Moco and the synthesis of thio-modified tRNAs in particular show a surprising link by sharing protein components for sulfur mobilization in pro- and eukaryotes.

  12. Evolutionistic or revolutionary paths? A PACS maturity model for strategic situational planning.

    Science.gov (United States)

    van de Wetering, Rogier; Batenburg, Ronald; Lederman, Reeva

    2010-07-01

    While many hospitals are re-evaluating their current Picture Archiving and Communication System (PACS), few have a mature strategy for PACS deployment. Furthermore, strategies for implementation, strategic and situational planning methods for the evolution of PACS maturity are scarce in the scientific literature. Consequently, in this paper we propose a strategic planning method for PACS deployment. This method builds upon a PACS maturity model (PMM), based on the elaboration of the strategic alignment concept and the maturity growth path concept previously developed in the PACS domain. First, we review the literature on strategic planning for information systems and information technology and PACS maturity. Secondly, the PMM is extended by applying four different strategic perspectives of the Strategic Alignment Framework whereupon two types of growth paths (evolutionistic and revolutionary) are applied that focus on a roadmap for PMM. This roadmap builds a path to get from one level of maturity and evolve to the next. An extended method for PACS strategic planning is developed. This method defines eight distinctive strategies for PACS strategic situational planning that allow decision-makers in hospitals to decide which approach best suits their hospitals' current situation and future ambition and what in principle is needed to evolve through the different maturity levels. The proposed method allows hospitals to strategically plan for PACS maturation. It is situational in that the required investments and activities depend on the alignment between the hospital strategy and the selected growth path. The inclusion of both strategic alignment and maturity growth path concepts make the planning method rigorous, and provide a framework for further empirical research and clinical practice.

  13. Enterprise Risk Management Implementation Maturity in Non Bank and Financial Companies

    Directory of Open Access Journals (Sweden)

    Subagio Tjahjono

    2017-07-01

    Full Text Available Previous studies of ERM implementation mostly using dummy variable to figure out relation with its determinant. Until today, studies that using risk management maturity as real variable are limited. Therefore, this study intends to determine the maturity level of ERM implementation in non-financial companies listed on Indonesia Stock Exchange during period 2015 and influence of firm’s total assets, total employee, leverage and public ownership to the ERM maturity. The method use are qualitative and multiple regression analysis. The result of data analysis showed that ERM implementation in selected sample during 2015 are still low (majority in initial and repeatable level. In addition, from determinant factors only total asset that have significant influence to the ERM maturity. This result implies that non-financial listed companies are vulnerable to risks. Management should consider future benefit of a mature ERM, not only to comply with regulation.DOI: 10.15408/etk.v16i2.5440 

  14. Maturity and medical students' ease of transition into the clinical environment.

    Science.gov (United States)

    Shacklady, Jaine; Holmes, Eileen; Mason, Graham; Davies, Ioan; Dornan, Tim

    2009-07-01

    Medical education has been characterized in terms of points of transition, which are accentuated by lack of relevant prior experience and can lead to extreme positive and negative emotions. Quantify the effect of maturity on medical students' transitions into the clinical environment and identify how experiences of transition might be improved. Eleven weeks after entering the clinical environment, 29 mature students (age over 21 at entry, median age 22) in a horizontally-integrated, predominantly undergraduate entry, problem-based curriculum offering little early clinical exposure and 58 matched non-mature students (median age 18 years) rated their experiences of transition and wrote free text comments about them. 62% of mature students compared with 24% of controls described 'good transitions' (odds ratio [OR] for a good transition 6.1; p = 0.002) and mature students were more likely than controls to describe how they drew on their previous years in medical school (OR 2.7, p = 0.04) and their wider life experiences in making the transition (OR 3.9, p = 0.01). They were less likely to feel confused or daunted. Whether mature or not, prior workplace experience, having learned the theory of medicine by PBL, and being confident in their knowledge and skills helped students' transitions. Both mature and non-mature students valued the support of teachers and peers and would have valued clinical experience earlier. The fact that just a few extra years of life experience made such a large difference to students' experiences of transition illustrates how important social factors are in the personal development of medical students. In respondents' views, early clinical experience and early skills training could ease students' passage into the clerkship phase of their education.

  15. Five-Factor Personality Traits as Predictor of Career Maturity

    Science.gov (United States)

    Atli, Abdullah

    2017-01-01

    Purpose: This study aims to determine the predictive strength of personality traits based on the five-factor theory on the level of career maturity Research Methods: The sample of the study included a total of 429 high school students, 248 females (57.8%) and 181 males (42.2%). The study utilized the "Career Maturity Scale" to determine…

  16. Preparation of ferrocyanide molybdate and their selective uptake properties for palladium and cesium ions

    Energy Technology Data Exchange (ETDEWEB)

    Hitoshi, Mimura; Ayumi, Asakura; Yan, Wu; Yuichi, Niibori; Masaki, Ozawa [Tohoku Univ., Dept. of Quantum Science and Engineering Graduate School of Engineering (Japan)

    2007-07-01

    The selective separation of heat-generating nuclide (Cs) and platinum group metal (Pd) containing in high-level liquid wastes (HLLW) is an important subject for the advancement of nuclear fuel cycle. Selective uptake of these nuclides was accomplished by using insoluble ferrocyanide molybdates (FeMo-[1-4]). The uptake properties of Pd{sup 2+} and Cs{sup +} for MoFe-[1-4] in the presence of 1 M HNO{sub 3} were examined by batch method. Relatively high uptake percentages of Pd{sup 2+} and Cs{sup +} above 90% were obtained within 30 min. The uptake percentage above 90% was kept in the presence of 0.1-3 M HNO{sub 3}. The uptake selectivity of Pd{sup 2+} was higher than that of Cs{sup +}; the separation factor of Pd{sup 2+} to Cs{sup +} increased with coexisting HNO{sub 3} concentration and was estimated to be 15 at 3 M HNO{sub 3}. The uptake of Pd{sup 2+} and Cs{sup +} on FeMo-[1-4] followed a Langmuir-type adsorption equation, and the uptake capacities of Pd{sup 2+} and Cs{sup +} were estimated to be [0.17-0.28] and [1.68-2.24] mmol/g, respectively. The uptake is mainly governed by the ion-exchange reaction between exchangeable cations (Na{sup +} and K{sup +}) and target cations (Pd{sup 2+} and Cs{sup +}). Further, the selective uptake of Pd{sup 2+} and Cs{sup +} was confirmed by using simulated HLLW (28 components, SW-11, JAEA); the uptake equilibrium attained within 30 min and the uptake percentages of Pd{sup 2+} and Cs{sup +} were 99 and 85 %, respectively. In order to granulate the fine powders of FeMo exchangers, the alginate gel polymer was used as an immobilizing matrix for the micro-encapsulation. The uptake percentages of Pd{sup 2+} and Cs{sup +} for FeMo-3 micro-capsule were above 80% even in the presence of 3 M HNO{sub 3}. Thus the molybdate can be converted to the ion-exchanger having high selectivity towards Pd{sup 2+} and Cs{sup +} in HLLW. This conversion method leads to the volume reduction of wastes and the utilization of useful nuclides. (authors)

  17. Regulators of growth plate maturation

    NARCIS (Netherlands)

    Emons, Joyce Adriana Mathilde

    2010-01-01

    Estrogen is known to play an important role in longitudinal bone growth and growth plate maturation, but the mechanism by which estrogens exert their effect is not fully understood. In this thesis this role is further explored. Chapter 1 contains a general introduction to longitudinal bone growth

  18. Nuclear magnetic resonance studies on maturation of skeletal muscle

    International Nuclear Information System (INIS)

    Yuasa, Tatsuhiko; Kuwahara, Takeo; Ohno, Takao; Miyatake, Tadashi.

    1982-01-01

    The water proton relaxation time ( 1 H-T 1 ) of the maturing chick pectoral muscle and the 23 Na concentration in the muscular tissue were determined by NMR spectrometry. 1 H-T 1 was determined on 12-day-old chick embryos, 19- and 20-day-old embryos and chicks aged 8, 15 and 22 days. 23 Na concentration was determined on 12-14 day-old chick embryos, 19-day-old embryos and 4-6 day-old and 20-day-old chicks. 1 H-T 1 gradually decreased with maturation; 2.082 +- 0.091 sec, 1.605 +- 0.106 sec, 1.321 +- 0.107 sec, 1.108 +- 0.038 sec and 1.087 +- 0.053 sec. The 23 Na level showed similar decreases; 59.5 +- 3.51 μEq/gm, 49.0 +- 4.95 μEq/gm, 47.5 +- 3.87 μEq/gm and 10.3 +- 2.13 μEq/gm. The water content in the skeletal muscle decreased with maturation, and 1 H-T 1 and the water content showed an exponential relationship. Comparison between the 23 Na concentration of muscle tissues determined by NMR and the Na + concentration by flame photometry revealed a decrease of the detection rate of 23 Na by NMR from 81.9 % to 54.7 % with maturation. It was conjectured that as well as the mode of existence of water proton, that of 23 Na in the tissue was subject to changes occurring with maturation of the skeletal muscle. (Chiba, N.)

  19. ADHD symptoms and maturity - a follow-up study in school children.

    Science.gov (United States)

    Gustafsson, P; Holmström, E; Besjakov, J; Karlsson, M K

    2010-10-01

    To test the hypothesis that there is a subgroup of children with attention deficit hyperactivity disorder (ADHD) who show a decline in ADHD-symptoms that is associated with signs of biological maturation, a phenomenon referred to as a 'maturation catch-up'. The parents of 147 children who were given an examination in grades one and two 1999-2000 that included assessment of ADHD-symptoms and estimation of skeletal bone-age by use of hand radiographs (which was repeated in the eighth grade), were contacted 2008-2009 and were asked to answer questions concerning ADHD-symptoms and behavioural maturity in their children. The response frequency was 67%. A complete dataset was achieved in 57 children. A reduction of Conners scores for ADHD-symptoms of eight or more between the evaluations was defined as a marked reduction in symptoms. When the children with a marked symptom reduction (n = 6) were compared with children without such a reduction (n = 51), we found a significant difference in skeletal maturation (p theory that there is a group of children with ADHD-symptoms who have a biological maturational-lag who will show a decrease in their ADHD-symptoms as they show a maturation catch-up with increasing age. © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.

  20. Physical chemistry and microscopic characteristics of matured beef peccary (Tayassu tajacu

    Directory of Open Access Journals (Sweden)

    Hugo Rangel Fernandes

    2015-06-01

    Full Text Available ABSTRACT. Fernandes H.R., Oliveira L.C., Ribeiro S.C.A. & Lourenço L.F.H. [Physical chemistry and microscopic characteristics of matured beef peccary (Tayassu tajacu.] Características físicas e microscópicas da carne maturada de caititu (Tayassu tajacu. Revista Brasileira de Medicina Veterinária, 37(2:167-172, 2015. Universidade do Estado do Pará, Travessa Enéas Pinheiro, 2626, Marco, Belém, PA 66113-200, Brasil. Email: suziar@yahoo.com The objective of this article was to analyze the physical and microscopic matured beef peccary. Were performed analyses of shear force, water holding capacity, weight loss by cooking and scanning electron microscopy in matured beef. The matured beef presented values of shear force between 3.76 and 5.26 %, water activity between 0,96 to 0,98 and weight loss by cooking between 19,46 and 21,17%. Therefore, it was found that the matured beef peccary, were considered soft according to analysis of shear force. The matured beef at 0ºC for 12 days was considered the best product for having less weight loss by cooking and softness according to analysis of shear force and scanning electron microscopy.

  1. Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function.

    Science.gov (United States)

    Spencer, William C; Deneris, Evan S

    2017-01-01

    The brain serotonin (5-hydroxytryptamine; 5-HT) system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF) Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory networks controlling

  2. Peripheral T-Cell Reactivity to Heat Shock Protein 70 and Its Cofactor GrpE from Tropheryma whipplei Is Reduced in Patients with Classical Whipple's Disease.

    Science.gov (United States)

    Trotta, Lucia; Weigt, Kathleen; Schinnerling, Katina; Geelhaar-Karsch, Anika; Oelkers, Gerrit; Biagi, Federico; Corazza, Gino Roberto; Allers, Kristina; Schneider, Thomas; Erben, Ulrike; Moos, Verena

    2017-08-01

    Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward Tropheryma whipplei in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from T. whipplei was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-γ) were determined in T cells by flow cytometry. Upon stimulation with total bacterial lysate or recombinant GrpE or Hsp70 of T. whipplei , the proportions of activated effector CD4 + T cells, determined as CD40L + IFN-γ + , were significantly lower in patients with CWD than in healthy controls; CD8 + T cells of untreated CWD patients revealed an enhanced activation toward unspecific stimulation and T. whipplei -specific degranulation, although CD69 + IFN-γ + CD8 + T cells were reduced upon stimulation with T. whipplei lysate and recombinant T. whipplei -derived proteins. Hsp70 and its cofactor GrpE are immunogenic in healthy individuals, eliciting effective responses against T. whipplei to control bacterial spreading. The lack of specific T-cell responses against these T. whipplei -derived proteins may contribute to the pathogenesis of CWD. Copyright © 2017 American Society for Microbiology.

  3. Asset management maturity in public infrastructure: the case of Rijkswaterstaat

    NARCIS (Netherlands)

    Volker, L.; Ligtvoet, A.; van den Boomen, M.; Wessels, Peter; van der Lei, T.E.; Herder, P.M.

    2013-01-01

    In times of restructuring governmental policies and resources, the
    need for strategic asset management is growing. Maturity models offer
    organisations a structure to assist them in improving their asset management
    performance. We present the results of a repeated maturity measurement

  4. Measuring chain digitisation maturity: an assessment of Dutch retail branches.

    NARCIS (Netherlands)

    Plomp, M.; Batenburg, R.

    2010-01-01

    The purpose of this article is to develop a validated measurement model and typology for chain digitisation maturity, defined as the degree of interorganisational collaboration through ICT. Design/methodology/approach: Through a literature (meta) study, 22 existing maturity models are found and

  5. Constructing service-oriented architecture adoption maturity matrix using Kano model

    Science.gov (United States)

    Hamzah, Mohd Hamdi Irwan; Baharom, Fauziah; Mohd, Haslina

    2017-10-01

    Commonly, organizations adopted Service-Oriented Architecture (SOA) because it can provide a flexible reconfiguration and can reduce the development time and cost. In order to guide the SOA adoption, previous industry and academia have constructed SOA maturity model. However, there is a limited number of works on how to construct the matrix in the previous SOA maturity model. Therefore, this study is going to provide a method that can be used in order to construct the matrix in the SOA maturity model. This study adapts Kano Model to construct the cross evaluation matrix focused on SOA adoption IT and business benefits. This study found that Kano Model can provide a suitable and appropriate method for constructing the cross evaluation matrix in SOA maturity model. Kano model also can be used to plot, organize and better represent the evaluation dimension for evaluating the SOA adoption.

  6. Lending to Small Businesses : The Role of Loan Maturity in Adressing Information Problems

    OpenAIRE

    Ortiz-Molina, H.; Penas, M.F.

    2004-01-01

    We investigate what determines the maturity of loans to small, informationally opaque businesses.We find that longer maturities are associated with collateral pledges, better financial condition, good credit history, and less informational opacity of the borrower.However, we do not find a positive association between stronger firm-creditor relationships (which can attenuate these information asymmetries) and longer maturities.The evidence suggests that creditors use shorter maturities to indu...

  7. Impaired response of mature adipocytes of diabetic mice to hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seok Jong, E-mail: seok-hong@northwestern.edu; Jin, Da P.; Buck, Donald W.; Galiano, Robert D.; Mustoe, Thomas A., E-mail: tmustoe@nmh.org

    2011-10-01

    Adipose tissue contains various cells such as infiltrated monocytes/macrophages, endothelial cells, preadipocytes, and adipocytes. Adipocytes have an endocrine function by secreting adipokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-{alpha}, leptin, and adiponectin. Dysregulation of adipokines in adipose tissues leads to a chronic low-grade inflammation which could result in atherosclerosis, hypertension, and type 2 diabetes. A sustained inflammatory state, which is characterized by prolonged persistence of macrophages and neutrophils, is found in diabetic wounds. In addition, subcutaneous adipocytes are enormously increased in amount clinically in type 2 diabetes. However, the function of subcutaneous adipocytes, which play an important role in injured tissue subjected to hypoxia, has not been well characterized in vitro due to the difficulty of maintaining mature adipocytes in culture using conventional methods because of their buoyancy. In this study, we established a novel in vitro culture method of mature adipocytes by enclosing them in a hyaluronan (HA) based hydrogel to study their role in response to stress such as hypoxia. BrdU labeling and Ki67 immunostaining experiments showed that hydrogel enclosed mature adipocytes proliferate in vitro. Both mRNA and protein expression analyses for hypoxia regulated genes, such as vascular endothelial growth factor (VEGF) and heme oxygenase 1 (HO1), showed that mature adipocytes of wild type mice respond to hypoxia. In contrast, mature adipocytes of diabetic db/db and TallyHo mice did not efficiently respond to hypoxia. Our studies suggest that mature adipocytes are functionally active cells, and their abnormal function to hypoxia can be one of underlining mechanisms in type 2 diabetes.

  8. Geospatial Information System Capability Maturity Models

    Science.gov (United States)

    2017-06-01

    To explore how State departments of transportation (DOTs) evaluate geospatial tool applications and services within their own agencies, particularly their experiences using capability maturity models (CMMs) such as the Urban and Regional Information ...

  9. Pristipomoides filamentosus Size at Maturity Study

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains information used to help determine median size at 50% maturity for the bottomfish species, Pristipomoides filamentosus in the Main Hawaiian...

  10. 7 CFR 51.1823 - Mature.

    Science.gov (United States)

    2010-01-01

    ... Industry, Part 1, Chapter 20-13 Market Classification, Maturity Standards and Processing or Packing... Independence Ave., Washington, DC 20250 or at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202-741-6030, or go to: http://www.archives.gov...

  11. Sexual maturation in the Sumatran rhinoceros (Dicerorhinus sumatrensis).

    Science.gov (United States)

    Roth, Terri L; Reinhart, Paul R; Romo, John S; Candra, Dedi; Suhaery, Andriansyah; Stoops, Monica A

    2013-01-01

    To help save the Sumatran rhino from extinction, the captive breeding program must capitalize on each rhino's reproductive lifespan. Doing so requires knowing when calves are sexually mature. The goal of this study was to monitor physiological changes associated with sexual maturation in two captive born calves (one male and one female) to determine the approximate age of maturity for both sexes of this species. Fecal testosterone metabolites were monitored in the male calf from 6 months to 7 years of age, and fecal pregnane metabolites were measured in the female calf from 6 months to 5.5 years of age. In addition, rectal ultrasonography was employed to monitor changes in ovarian activity from 2 to 5.5 years of age. The male calf's fecal testosterone concentrations reached levels comparable to those detected in samples from adult males when he was 6-6.5 years of age. The first pre-ovulatory sized follicle was observed on the ovaries of the female calf when she was 4.75 years old, but fecal pregnane metabolite concentrations only reached maximum mean concentrations and variability when she was 5-5.5 years of age. Results from this study indicate that male and female Sumatran rhino calves are sexually mature at 6-6.5 and 5-5.5 years of age, respectively. © 2013 Wiley Periodicals, Inc.

  12. Efficient Maturation and Cytokine Production of Neonatal DCs Requires Combined Proinflammatory Signals

    Directory of Open Access Journals (Sweden)

    Doreen Krumbiegel

    2005-01-01

    Full Text Available Specific functional properties of dendritic cells (DCs have been suspected as being responsible for the impaired specific immune responses observed in human neonates. To analyze stimulatory requirements for the critical transition from immature, antigen-processing DCs to mature, antigen-presenting DCs, we investigated the effect of different proinflammatory mediators and antigens on phenotype and cytokine secretion of human neonatal DCs derived from hematopoietic progenitor cells (HPCs. Whereas single proinflammatory mediators were unable to induce the maturation of neonatal DCs, various combinations of IFNγ, CD40L, TNFα, LPS and antigens, induced the maturation of neonatal DCs documented by up-regulation of HLA-DR, CD83 and CD86. Combinations of proinflammatory mediators also increased cytokine secretion by neonatal DCs. Especially combined stimulation with LPS and IFNγ proved to be very efficient in inducing maturation and cytokine synthesis of neonatal DCs. In conclusion, neonatal DCs can be stimulated to express maturation as well as costimulatory surface molecules. However, induction of maturation requires combined stimulation with multiple proinflammatory signals.

  13. In vitro atrazine exposure affects the phenotypic and functional maturation of dendritic cells

    International Nuclear Information System (INIS)

    Pinchuk, Lesya M.; Lee, Sang-Ryul; Filipov, Nikolay M.

    2007-01-01

    Recent data suggest that some of the immunotoxic effects of the herbicide atrazine, a very widely used pesticide, may be due to perturbations in dendritic cell (DC) function. As consequences of atrazine exposure on the phenotypic and functional maturation of DC have not been studied, our objective was, using the murine DC line, JAWSII, to determine whether atrazine will interfere with DC maturation. First, we characterized the maturation of JAWSII cells in vitro by inducing them to mature in the presence of growth factors and selected maturational stimuli in vitro. Next, we exposed the DC cell line to a concentration range of atrazine and examined its effects on phenotypic and functional maturation of DC. Atrazine exposure interfered with the phenotypic and functional maturation of DC at non-cytotoxic concentrations. Among the phenotypic changes caused by atrazine exposure was a dose-dependent removal of surface MHC-I with a significant decrease being observed at 1 μM concentration. In addition, atrazine exposure decreased the expression of the costimulatory molecule CD86 and it downregulated the expression of the CD11b and CD11c accessory molecules and the myeloid developmental marker CD14. When, for comparative purposes, we exposed primary thymic DC to atrazine, MHC-I and CD11c expression was also decreased. Phenotypic changes in JAWSII DC maturation were associated with functional inhibition of maturation as, albeit at higher concentrations, receptor-mediated antigen uptake was increased by atrazine. Thus, our data suggest that atrazine directly targets DC maturation and that toxicants such as atrazine that efficiently remove MHC-I molecules from the DC surface are likely to contribute to immune evasion

  14. Effect of Kaempferol on in vitro Maturation of Porcine Oocytes

    Directory of Open Access Journals (Sweden)

    Delia Orlovschi

    2014-10-01

    Full Text Available We investigated the effects of kaempferol on porcine oocytes in vitro maturation. Kaempferol is one the most studied flavonoids and is in research attention on animal cells until 1979. Flavonoids are known as polyphenolic compounds synthesized by the plants. Cumulus-oocyte complexes aspirated from the ovaries were maturated in vitro, fertilized and embryos were cultured in a defined conditioned medium with 5, 15, 25, 35 µg/ml or without kaempferol supplementation. During in vitro maturation with highest kaempferol concentration (35 µg/ml distinct significantly increase the rate of cumulus cell expansion in grad 4 (42.74 vs. 50.96%, p<0.01. The same, addition of 5 µg/ml kaempferol to the in vitro maturation medium increase significantly the rate of expansion compared to 25 µg/ml (42.20 vs. 48.67%, p<0.05 and increase distinct significantly the rate of expansion compared to 35 µg/ml (42.20 vs. 50.96%, p<0.01. Kaempferol supplementation (15 µg/ml vs. 35 µg/ml of the in vitro fertilization medium led to a significant increase in the rate of 4-8 cells formation (0.69 vs. 4.96%, p<0.05. In conclusion, these results demonstrate that supplementation with kaempferol during in vitro maturation improved the developmental competence of porcine oocytes.

  15. 7 CFR 1710.115 - Final maturity.

    Science.gov (United States)

    2010-01-01

    ... Basic Policies § 1710.115 Final maturity. (a) RUS is authorized to make loans and loan guarantees with a... due, in part, to obsolescence. Operating loans to finance working capital required for the initial...

  16. Measurement of Food Safety Culture using Survey and Maturity Profiling Tools

    OpenAIRE

    Jespersen, Lone; Griffiths, Mansel; Maclaurin, Tanya; Chapman, Ben; Wallace, Carol A.

    2016-01-01

    Organizational culture is defined by dimensions and characteristics that can be used to measure food safety culture in food manufacturing through a food safety maturity model. Maturity models from quality, health care, and information technology have been used since early 1970 and this work presents a novel food safety culture maturity model with five capability areas and food safety pinpointed behaviours specific to functions and levels in a food manufacturing company. A survey tool linked t...

  17. Spheno-Occipital Synchondrosis Fusion Correlates with Cervical Vertebrae Maturation.

    Directory of Open Access Journals (Sweden)

    María José Fernández-Pérez

    Full Text Available The aim of this study was to determine the relationship between the closure stage of the spheno-occipital synchondrosis and the maturational stage of the cervical vertebrae (CVM in growing and young adult subjects using cone beam computed tomography (CBCT. CBCT images with an extended field of view obtained from 315 participants (148 females and 167 males; mean age 15.6 ±7.3 years; range 6 to 23 years were analyzed. The fusion status of the synchondrosis was determined using a five-stage scoring system; the vertebral maturational status was evaluated using a six-stage stratification (CVM method. Ordinal regression was used to study the ability of the synchondrosis stage to predict the vertebral maturation stage. Vertebrae and synchondrosis had a strong significant correlation (r = 0.89 that essential was similar for females (r = 0.88 and males (r = 0.89. CVM stage could be accurately predicted from synchondrosis stage by ordinal regression models. Prediction equations of the vertebral stage using synchondrosis stage, sex and biological age as predictors were developed. Thus this investigation demonstrated that the stage of spheno-occipital synchondrosis, as determined in CBCT images, is a reasonable indicator of growth maturation.

  18. Intracellular vesicle acidification promotes maturation of infectious poliovirus particles.

    Directory of Open Access Journals (Sweden)

    Alexsia L Richards

    Full Text Available The autophagic pathway acts as part of the immune response against a variety of pathogens. However, several pathogens subvert autophagic signaling to promote their own replication. In many cases it has been demonstrated that these pathogens inhibit or delay the degradative aspect of autophagy. Here, using poliovirus as a model virus, we report for the first time bona fide autophagic degradation occurring during infection with a virus whose replication is promoted by autophagy. We found that this degradation is not required to promote poliovirus replication. However, vesicular acidification, which in the case of autophagy precedes delivery of cargo to lysosomes, is required for normal levels of virus production. We show that blocking autophagosome formation inhibits viral RNA synthesis and subsequent steps in the virus cycle, while inhibiting vesicle acidification only inhibits the final maturation cleavage of virus particles. We suggest that particle assembly, genome encapsidation, and virion maturation may occur in a cellular compartment, and we propose the acidic mature autophagosome as a candidate vesicle. We discuss the implications of our findings in understanding the late stages of poliovirus replication, including the formation and maturation of virions and egress of infectious virus from cells.

  19. Spheno-Occipital Synchondrosis Fusion Correlates with Cervical Vertebrae Maturation.

    Science.gov (United States)

    Fernández-Pérez, María José; Alarcón, José Antonio; McNamara, James A; Velasco-Torres, Miguel; Benavides, Erika; Galindo-Moreno, Pablo; Catena, Andrés

    2016-01-01

    The aim of this study was to determine the relationship between the closure stage of the spheno-occipital synchondrosis and the maturational stage of the cervical vertebrae (CVM) in growing and young adult subjects using cone beam computed tomography (CBCT). CBCT images with an extended field of view obtained from 315 participants (148 females and 167 males; mean age 15.6 ±7.3 years; range 6 to 23 years) were analyzed. The fusion status of the synchondrosis was determined using a five-stage scoring system; the vertebral maturational status was evaluated using a six-stage stratification (CVM method). Ordinal regression was used to study the ability of the synchondrosis stage to predict the vertebral maturation stage. Vertebrae and synchondrosis had a strong significant correlation (r = 0.89) that essential was similar for females (r = 0.88) and males (r = 0.89). CVM stage could be accurately predicted from synchondrosis stage by ordinal regression models. Prediction equations of the vertebral stage using synchondrosis stage, sex and biological age as predictors were developed. Thus this investigation demonstrated that the stage of spheno-occipital synchondrosis, as determined in CBCT images, is a reasonable indicator of growth maturation.

  20. Effect of maturity stages, variety and storage environment on sugar ...

    African Journals Online (AJOL)

    This study clearly demonstrated the importance of integrated agro-technology of combining cultivar, maturity stage and storage environment in shelf life improvement of tomato by reducing the rate of ripening and utilization of sugar, reducing water loss and maintaining marketability. Key words: Tomato, maturity stage, ...

  1. Regeneration of tropical maize lines ( Zea mays l .) from mature ...

    African Journals Online (AJOL)

    The use of immature zygotic embryos as an explant for maize regeneration has been hampered by the strictly limited suitable duration of immature embryos for culture. In contrast, mature zygotic embryos harvested from dry seeds are ubiquitous. However, generally mature embryos and especially tropical maize genotypes ...

  2. Adult maturational processes and the facilitating environment.

    Science.gov (United States)

    Acklin, M W

    1986-09-01

    The psychoanalytic theory of religion has been seriously limited in its development, largely owing to Freud's emphasis on religion's neurotic elements and an overemphasis on the infantile origins of religious development. This paper offers a conceptual framework and advances the thesis, based on contemporary psychoanalytic, developmental theory, that 1) Erikson's concept of epigenesis has applicability across the life span; 2) that beyond-the-self identity is constituent to human maturation and self-completion; 3) that successful adult maturation requires a mirroring-facilitating environment; and 4) that religious values, meanings, images, and communities play an essential role-as-elements of the facilitating environment of later life.

  3. The diagnostic performance of chronologic age in the assessment of skeletal maturity.

    Science.gov (United States)

    Baccetti, Tiziano; Franchi, Lorenzo; De Toffol, Laura; Ghiozzi, Bruno; Cozza, Paola

    2006-01-01

    The aim of this study was to analyze the relationship between chronologic age the and individual skeletal maturity as assessed by means of the cervical vertebral maturation (CVM) method during the circumpubertal period. The evaluated sample of 600 subjects consisted of 100 subjects (50 males and 50 females) for each of 6 age groups, from 9 years through 14 years of age. Individual skeletal maturity for all subjects was determined by using the CVM method. The relationship between chronologic age and the most prevalent CVM stage at each age group was evaluated statistically by means of indicators of diagnostic test performance that specify the ability of a diagnostic test to identify a condition. The diagnostic performance of chronologic age for the detection of the onset of the adolescent peak in skeletal maturation was very low both in males and in females. In male subjects, the chronologic age of 9 years +/- 6 months presented with strong diagnostic power for the identification of a pre-pubertal stage in skeletal maturation. In female subjects, the chronologic age of 14 years +/- 6 months corresponded with a strong probability of a postpubertal stage in skeletal maturation. In males, chronologic age can identify a pre-pubertal stage of skeletal development, and in females a post-pubertal stage. In both males and females, chronologic age cannot recognize the onset of the adolescent peak in skeletal maturation.

  4. Use of NAA to determine nutritive elements in immature and mature soybeans

    International Nuclear Information System (INIS)

    Iskander, F.Y.

    1986-01-01

    During the maturation of soybeans, several changes in the chemical composition take place. However, data available relating mineral and vitamin content to maturation stage are limited and show a wide range of values. There are several factors that affect the mineral content of soybeans. These factors include, but are not limited to, soil composition, application of fertilizers, environmental conditions, and genetic factors. For the samples examined in this study all the aforementioned factors, except genetic, were kept unchanged. Neutron activation analysis (NAA) was employed to measure calcium, iron, potassium, magnesium, manganese, and zinc in three soybean varieties at three maturation stages. Samples from three soybean varieties were investigated. The three maturation stages were defined as immature, green mature, and dry mature. The concentration of calcium, iron, potassium, magnesium, manganese, and zinc in the three soybean varieties at different maturation stages are shown. The concentration of some nutritive elements (for example, calcium, iron, manganese, and zinc) in soybeans are much higher than in other grain cereals such as wheat and corn. However, it is questionable whether too much nutritional importance be given to these elements in soybeans since phytate content in soybeans is much higher than that of wheat or corn, and it has been postulated that low bioavailability of the aforementioned elements are related to phytate content

  5. A maturity model to assess organisational readiness for change

    OpenAIRE

    Zephir, Olivier; Minel, Stéphanie; Chapotot, Emilie

    2011-01-01

    International audience; The presented model which is developed in a European project allows project management teams to assess the organisational maturity to integrate new practices under structural or technological change. Maturity for change is defined here as workforce capability to operate effectively in transformed processes. This methodology is addressed to tackle organisational readiness to fulfil business objectives through technological and structural improvements. The tool integrate...

  6. Results of measurement procedure of innovation maturity of business

    Directory of Open Access Journals (Sweden)

    O. A. Kozlova

    2010-09-01

    Full Text Available In this article the basic approaches of innovation maturity of business has been applied. The realization procedure of innovation maturity as an example of organizations of Perm’s region has been call attention. The preliminary potential assessments of perception of plans innovations will give optimize selection innovative strategy for organization and increase the effectiveness of business for microeconomics and region’s level.

  7. Is the cervical vertebral maturation (CVM) method effective enough to replace the hand-wrist maturation (HWM) method in determining skeletal maturation?-A systematic review.

    Science.gov (United States)

    Szemraj, Agnieszka; Wojtaszek-Słomińska, Anna; Racka-Pilszak, Bogna

    2018-05-01

    Chronological age provides only general information on the development of a child/adolescent. However, the biological age of the patient is more significant. One of the methods is the determination of the bone age based on the development of the hand and wrist bones. In 1972 a method for assessing cervical vertebral maturation on the cephalometric radiographs was introduced (CVM method). As a result, additional patient radiation was eliminated. Currently, this type of radiograph is routinely applied in orthodontic treatment. The aim of the study was to assess the usefulness of the CVM method and to verify the assumption, according to which the CVM method modified by Baccetti et al. may replace the method for the assessment of skeletal maturation based on a hand-wrist X-ray, which is known as the hand-wrist maturation (HWM) method. The present study reviewed the literature between 2006 and 2016. In the first stage of selection 905 articles were obtained. Finally, 10 articles were enrolled for the review. All of the studies presented a high level of correlation between the examined methods. In eight articles the researchers admitted that the CVM classification could replace the HWM method, known as the "gold standard". In two studies , the researchers suggested considering the CVM method an additional method despite its compatibility and usefulness. The lowest correlation coefficient was 0.616 and the highest 0.937. The assessment of the skeletal age with the CVM is done on a cephalometric radiograph, routinely used in orthodontic practice, which makes it easy to apply. The determination of features of only C2, C3 and C4 vertebrae is possible even if the patient wears an X-ray protective thyroid collar. Therefore, the radiation dose is minimized. The CVM method shows a high level of correlation with the HWM method. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Mature Students Speak Up: Career Exploration and the Working Alliance

    Science.gov (United States)

    Pott, Terilyn

    2015-01-01

    This exploratory study was undertaken to learn more about how mature students perceive the career counselling process in a post-secondary institution. Through the use of critical incident technique this study examined how three mature students interpret their relationship between themselves and their counsellors. Significant factors identified as…

  9. Pharmaceutical Options for Triggering of Final Oocyte Maturation in ART

    DEFF Research Database (Denmark)

    Castillo, Juan Carlos; Humaidan, Peter; Bernabéu, Rafael

    2014-01-01

    Since the pioneering days of in vitro fertilization, hCG has been the gold standard to induce final follicular maturation. We herein reviewed different pharmaceutical options for triggering of final oocyte maturation in ART. The new upcoming agent seems to be GnRHa with its potential advantages o...

  10. Effect of melatonin on in vitro maturation of bovine oocytes ...

    African Journals Online (AJOL)

    ... Vs 17.67, 15.68, 16.53). In conclusion in this experiment, melatonin cannot improve cumulus cell expansion and nuclear maturation of bovine oocytes. When concentrations is high, melatonin may affect bovine oocytes meiotic maturation at metaphase-1 stage, but it is improbable melatonin be toxic for bovine oocytes.

  11. Experiences with the Capability Maturity Model in a research environment

    NARCIS (Netherlands)

    Velden, van der M.J.; Vreke, J.; Wal, van der B.; Symons, A.

    1996-01-01

    The project described here was aimed at evaluating the Capability Maturity Model (CMM) in the context of a research organization. Part of the evaluation was a standard CMM assessment. It was found that CMM could be applied to a research organization, although its five maturity levels were considered

  12. Composition, physicochemical properties and thermal inactivation kinetics of polyphenol oxidase and peroxidase from coconut (Cocos nucifera) water obtained from immature, mature and overly-mature coconut.

    Science.gov (United States)

    Tan, Thuan-Chew; Cheng, Lai-Hoong; Bhat, Rajeev; Rusul, Gulam; Easa, Azhar Mat

    2014-01-01

    Composition, physicochemical properties and enzyme inactivation kinetics of coconut water were compared between immature (IMC), mature (MC) and overly-mature coconuts (OMC). Among the samples studied, pH, turbidity and mineral contents for OMC water was the highest, whereas water volume, titratable acidity, total soluble solids and total phenolics content for OMC water were the lowest. Maturity was found to affect sugar contents. Sucrose content was found to increase with maturity, and the reverse trend was observed for fructose and glucose. Enzyme activity assessment showed that polyphenol oxidase (PPO) in all samples was more heat resistant than peroxidase (POD). Compared to IMC and MC, PPO and POD from OMC water showed the lowest thermal resistance, with D83.3°C=243.9s (z=27.9°C), and D83.3°C=129.9s (z=19.5°C), respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Cigarette Smoke Decreases the Maturation of Lung Myeloid Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    Elena Arellano-Orden

    Full Text Available Conflicting data exist on the role of pulmonary dendritic cells (DCs and their maturation in patients with chronic obstructive pulmonary disease (COPD. Herein, we investigated whether disease severity and smoking status could affect the distribution and maturation of DCs in lung tissues of patients undergoing elective pneumectomy or lobectomy for suspected primary lung cancer.A total of 75 consecutive patients were included. Spirometry testing was used to identify COPD. Lung parenchyma sections anatomically distant from the primary lesion were examined. We used flow cytometry to identify different DCs subtypes-including BDCA1-positive myeloid DCs (mDCs, BDCA3-positive mDCs, and plasmacytoid DCs (pDCs-and determine their maturation markers (CD40, CD80, CD83, and CD86 in all participants. We also identified follicular DCs (fDCs, Langerhans DCs (LDCs, and pDCs in 42 patients by immunohistochemistry.COPD was diagnosed in 43 patients (16 current smokers and 27 former smokers, whereas the remaining 32 subjects were classified as non-COPD (11 current smokers, 13 former smokers, and 8 never smokers. The number and maturation of DCs did not differ significantly between COPD and non-COPD patients. However, the results of flow cytometry indicated that maturation markers CD40 and CD83 of BDCA1-positive mDCs were significantly decreased in smokers than in non-smokers (P = 0.023 and 0.013, respectively. Immunohistochemistry also revealed a lower number of LDCs in COPD patients than in non-COPD subjects.Cigarette smoke, rather than airflow limitation, is the main determinant of impaired DCs maturation in the lung.

  14. Development and maturation of Escherichia coli K-12 biofilms

    DEFF Research Database (Denmark)

    Reisner, A.; Haagensen, J.A.J.; Schembri, Mark

    2003-01-01

    The development and maturation of E. coli biofilms in flow-chambers was investigated. We found that the presence of transfer constitutive IncF plasmids induced biofilm development forming structures resembling those reported for Pseudomonas aeruginosa . The development occurred in a step...... occurred in conjugation pilus proficient plasmid-carrying strains. The final shapes of the expanding structures in the mature biofilm seem to be determined by the pilus configuration, as various mutants affected in the processing and activity of the transfer pili displayed differently structured biofilms....... We further provide evidence that flagella, type 1 fimbriae, curli and Ag43 are all dispensable for the observed biofilm maturation. In addition, our results indicate that cell-to-cell signalling mediated by autoinducer 2 (AI-2) is not required for differentiation of E. coli within a biofilm community...

  15. THE POSSIBILITIES TO DETERMINE FETAL MATURITY BY ULTRASOUND DIAGNOSTICS

    Directory of Open Access Journals (Sweden)

    S. N. Lysenko

    2015-01-01

    Full Text Available Background: Extragenital disorders in a pregnant patient, as well as complications of pregnancy often necessitate preterm delivery, when the state of the fetus is one of the criteria determining terms and type of delivery. In connection with this, the physician faces the challenge of accurate assessment of fetal maturity. Aim: To identify ultrasound signs of functional fetal maturity. Materials and methods: 120 pregnant patients were assessed at 35 to 40 weeks of gestation. Beyond a standard fetometry, we assessed interhemispheric cerebellar size, the biggest size of the Beclard’s nucleus, the ratio of cortical to medullar substance of fetal adrenal glands (adrenal coefficient, the ration between ultrasound density of lungs, liver and ultrasound density of fetal urine (histogram analysis. Results: Up to 36 weeks of gestation, the interhemispheric cerebellar size was below 52 mm, starting from 37 weeks, above 53 mm and from week 40 on, above 58 mm. All newborns, which had their interhemispheric cerebellar size ≥ 53 mm antenatally, were assessed as being mature at birth (p < 0.05. All newborns, which had Beclard’s nucleus size ≥ 5 mm antenatally, were assessed as being mature at birth (p < 0.05. At 35–35.6 weeks of gestation, mean adrenal coefficients in all cases exceeded 1. Starting with full 36 weeks of gestation onwards, this parameter decreased to 0.94 and showed a steady decrease thereafter. There were no signs of functional immaturity or respiratory distress among newborns with antenatal adrenal coefficient of ≤ 0.99 (p < 0.05. The ratio between ultrasound density of lungs to ultrasound density of bladder contents increases up to 37 weeks of gestation and remains stable up to 40 weeks. The ratio of liver density to the same substrate is non-significantly lower due to lower ultrasound density of the liver itself. The ratio of ultrasound density of the lung to that of the liver up to 36 weeks was at least 1.41 and decreased

  16. Chronologic age and skeletal maturation of the cervical vertebrae and hand-wrist: is there a relationship?

    Science.gov (United States)

    Uysal, Tancan; Ramoglu, Sabri Ilhan; Basciftci, Faruk Ayhan; Sari, Zafer

    2006-11-01

    The aims of this study were (1) to investigate the relationship between chronologic age and maturation of cervical vertebrae, (2) to identify the relationship between chronologic age and maturation stage evaluated by hand-wrist radiographs, and (3) to determine whether the maturation of cervical vertebrae correlates with maturation indicated by hand-wrist radiographs in a Turkish population. The samples were derived from lateral cephalometric and hand-wrist radiographs of 503 subjects (213 male, 290 female; ages, 5.3-24.1 years). Cervical vertebral development was evaluated by the method of Hassel and Farman. Skeletal maturation of each hand-wrist radiograph was determined according to the method described by Björk and Grave, and Brown's system. The Spearman rank-order correlation coefficients were estimated separately for males and females to measure the relationships among chronologic age, cervical vertebral maturation, and the skeletal maturation measured at the hand-wrist. The Spearman correlation coefficients were 0.72 (P cervical vertebrae skeletal maturation, and 0.79 (P maturation via hand-wrist radiographs. The correlation coefficient between hand-wrist and cervical-vertebrae maturation was 0.86 (P cervical-vertebrae maturation stages are clinically useful maturity indicators of the pubertal growth period Turkish subjects.

  17. Structural Evolution of Kerogen and Bitumen during Thermal Maturation examined by Fourier-Transform Infrared Spectroscopy

    Science.gov (United States)

    Craddock, P. R.; Le Doan, T. V.; Pomerantz, A.

    2014-12-01

    Kerogen—the organic matter that is solid and insoluble in organic solvents—is a key component of organic-rich mudstones. The composition of kerogen affects the storage and transport of hydrocarbons in these unconventional resources and is known to change with thermal maturity. We report here using FTIR spectroscopy, the compositional characteristics of kerogen as a function of thermal maturity, together with the compositional characteristics of the organic phase, bitumen—the organic matter that is solid, but soluble in organic solvents. Kerogen is consumed during thermal maturation, whereas bitumen is an intermediary formed at low maturity from kerogen and consumed at higher maturities in formation of oil and gas. Bitumen relative to kerogen has higher aliphatic content, lower aromatic content, and lower abundance of oxygenated functions. At low maturity (vitrinite reflectance equivalent VRe ~ 0.5-0.9 %), the average length of aliphatic chains in bitumen increases during bitumen formation. At higher thermal maturities (VRe > 1.0-1.3 %), average aliphatic chain length decreases as bitumen is consumed. This evolution contrasts to that in kerogen, where aliphatic chain lengths shorten during all stages of maturation. Breakdown of kerogen appears to be driven by cleavage of oxygen functions at low maturity and removal of aliphatic carbons at higher maturities. These aliphatic-rich fragments may comprise the bitumen, and may in part explain the solubility of bitumen in organic solvents. Bitumen shows evidence of oxidation at low thermal maturity, a phenonemom not documented for kerogen. Bitumen maturation and degradation at higher thermal maturity is driven by cleavage and loss of aliphatic carbons, and is coincident with the maximum generation of oil and gas. The aromatic content of bitumen and of kerogen both increase during maturation as a consequence of the loss of aliphatic carbon. The oil and gas generation potential of the residual organic matter thus

  18. The role of psychological maturity in direct and indirect aggressiveness in Spanish adolescents.

    Science.gov (United States)

    Morales-Vives, Fabia; Camps, Elisa; Lorenzo-Seva, Urbano; Vigil-Colet, Andreu

    2014-01-01

    Understanding which factors are related to different kinds of aggressive behaviors in adolescents might help to improve violence-prevention programs for schools and families. Although some studies show that adolescents who are less psychologically mature tend to display more behavioral problems, few studies have been performed on the relationship between aggressive behavior and psychological maturity in adolescence, and no studies have focused specifically on indirect aggression. For this reason, the current research tests the role of psychological maturity in direct and indirect aggressiveness in a sample of 193 Spanish adolescents (49% boys and 51% girls) between 14 and 18 years old (M = 16.1, SD = 1.18). The results show that psychological maturity is related to both kinds of aggressiveness. In fact, less mature adolescents tend to show higher levels of direct aggression (r = -.22, p self-reliance and identity: self-reliance is the main predictor of indirect aggression (p < .01) and identity is the main predictor of direct aggression (p < .01). Moreover, overall psychological maturity is more related to indirect aggression in men than in women (p < .05), so the increase in psychological maturity implies a greater decrease of indirect aggression in men.

  19. Cost uncertainty for different levels of technology maturity

    International Nuclear Information System (INIS)

    DeMuth, S.F.; Franklin, A.L.

    1996-01-01

    It is difficult at best to apply a single methodology for estimating cost uncertainties related to technologies of differing maturity. While highly mature technologies may have significant performance and manufacturing cost data available, less well developed technologies may be defined in only conceptual terms. Regardless of the degree of technical maturity, often a cost estimate relating to application of the technology may be required to justify continued funding for development. Yet, a cost estimate without its associated uncertainty lacks the information required to assess the economic risk. For this reason, it is important for the developer to provide some type of uncertainty along with a cost estimate. This study demonstrates how different methodologies for estimating uncertainties can be applied to cost estimates for technologies of different maturities. For a less well developed technology an uncertainty analysis of the cost estimate can be based on a sensitivity analysis; whereas, an uncertainty analysis of the cost estimate for a well developed technology can be based on an error propagation technique from classical statistics. It was decided to demonstrate these uncertainty estimation techniques with (1) an investigation of the additional cost of remediation due to beyond baseline, nearly complete, waste heel retrieval from underground storage tanks (USTs) at Hanford; and (2) the cost related to the use of crystalline silico-titanate (CST) rather than the baseline CS100 ion exchange resin for cesium separation from UST waste at Hanford

  20. Space Mission Concept Development Using Concept Maturity Levels

    Science.gov (United States)

    Wessen, Randii R.; Borden, Chester; Ziemer, John; Kwok, Johnny

    2013-01-01

    Over the past five years, pre-project formulation experts at the Jet Propulsion Laboratory (JPL) has developed and implemented a method for measuring and communicating the maturity of space mission concepts. Mission concept development teams use this method, and associated tools, prior to concepts entering their Formulation Phases (Phase A/B). The organizing structure is Concept Maturity Level (CML), which is a classification system for characterizing the various levels of a concept's maturity. The key strength of CMLs is the ability to evolve mission concepts guided by an incremental set of assessment needs. The CML definitions have been expanded into a matrix form to identify the breadth and depth of analysis needed for a concept to reach a specific level of maturity. This matrix enables improved assessment and communication by addressing the fundamental dimensions (e.g., science objectives, mission design, technical risk, project organization, cost, export compliance, etc.) associated with mission concept evolution. JPL's collaborative engineering, dedicated concept development, and proposal teams all use these and other CML-appropriate design tools to advance their mission concept designs. This paper focuses on mission concept's early Pre-Phase A represented by CMLs 1- 4. The scope was limited due to the fact that CMLs 5 and 6 are already well defined based on the requirements documented in specific Announcement of Opportunities (AO) and Concept Study Report (CSR) guidelines, respectively, for competitive missions; and by NASA's Procedural Requirements NPR 7120.5E document for Projects in their Formulation Phase.

  1. Differences in growth, fillet quality, and fatty acid metabolism-related gene expression between juvenile male and female rainbow trout.

    Science.gov (United States)

    Manor, Meghan L; Cleveland, Beth M; Kenney, P Brett; Yao, Jianbo; Leeds, Tim

    2015-04-01

    Sexual maturation occurs at the expense of stored energy and nutrients, including lipids; however, little is known regarding sex effects on nutrient regulatory mechanisms in rainbow trout prior to maturity. Thirty-two, 14-month-old, male and female rainbow trout were sampled for growth, carcass yield, fillet composition, and gene expression of liver, white muscle, and visceral adipose tissue. Growth parameters, including gonadosomatic index, were not affected by sex. Females had higher percent separable muscle yield, but there were no sex effects on fillet proximate composition. Fillet shear force indicated females produce firmer fillets than males. Male livers had greater expression of three cofactors within the mTOR signaling pathway that act to inhibit TORC1 assembly; mo25, rictor, and pras40. Male liver also exhibited increased expression of β-oxidation genes cpt1b and ehhadh. These findings are indicative of increased mitochondrial β-oxidation in male liver. Females exhibited increased expression of the mTOR cofactor raptor in white muscle and had higher expression levels of several genes within the fatty acid synthesis pathway, including gpat, srebp1, scd1, and cd36. Female muscle also had increased expression of β-oxidation genes cpt1d and cpt2. Increased expression of both fatty acid synthesis and β-oxidation genes suggests female muscle may have greater fatty acid turnover. Differences between sexes were primarily associated with variation of gene expression within the mTOR signaling pathway. Overall, data suggest there is differential regulation of gene expression in male and female rainbow trout tissues prior to the onset of sexual maturity that may lead to nutrient repartitioning during maturation.

  2. Attributions, future time perspective and career maturity in nursing undergraduates: correlational study design.

    Science.gov (United States)

    Cheng, Cheng; Yang, Liu; Chen, Yuxia; Zou, Huijing; Su, Yonggang; Fan, Xiuzhen

    2016-01-25

    Career maturity is an important parameter as nursing undergraduates prepare for their future careers. However, little is known regarding the relationships between attributions, future time perspective and career maturity among nursing undergraduates. The purpose of this study was to investigate the degree of career maturity and its relationship with attributions and future time perspective. A cross-sectional survey was designed. This survey was administered to 431 Chinese nursing undergraduates. Independent-sample t-tests and one-way ANOVA were performed to examine the mean differences between categories of binary and categorical demographic characteristics, respectively. Pearson correlations and multiple linear regressions were used to test the relationships between attributions, future time perspective and career maturity. The degree of career maturity was moderate among nursing undergraduates and that internal attributions of academic achievement, future efficacy and future purpose consciousness were positively associated with career maturity (all p time perspective and to facilitate their transition from school to clinical practice.

  3. Growth goals, maturity, and well-being.

    Science.gov (United States)

    Bauer, Jack J; McAdams, Dan P

    2004-01-01

    In 2 studies (125 college students and 51 adults), 2 forms of growth goals (exploratory and intrinsic) were compared with 2 forms of personality development (social-cognitive maturity and social-emotional well-being). Participants whose narratives of major life goals emphasized conceptual exploration were especially likely to have high levels of maturity (measured as ego development; J. Loevinger, 1976), whereas those whose goals emphasized intrinsic interests (K. M. Sheldon & T. Kasser, 1995) were especially likely to have high levels of well-being. Participants who had coherent hierarchies of growth goals on the levels of major life goals and everyday goals were especially likely to have high levels of personality development. Finally, growth goals accounted for some relationships between age and personality development. Growth goals are discussed in terms of intentional self-development and specific developmental paths. (c) 2003 APA

  4. Analyzing Project Management Maturity Level in Indonesia

    Directory of Open Access Journals (Sweden)

    Eliot Simangunsong

    2013-05-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Project management has been generally known and increasingly used by many organizations to gain competitive advantage. In this context, many studies have proposed maturity models to evaluate how project management knowledge has been deployed effectively and efficiently in organization. As a developing country, Indonesia needs many development projects managed by government and private companies in different industries. Here, a study to assess project management maturity level in Indonesian businesses may bring insight about current business practices, which is important to speed up country development and business sustainability.  Adapting the Project Management Maturity Model (ProMMM, a survey instrument has been developed and applied to professionals from Jakarta and surrounding area.  The result of analysis shows that construction and primary industry have a higher maturity level compare to manufacturing and services.  It is to be noted, however, that the level of project management understanding is low across industries.  This indicates that more quality project management training or certification is required to improve overall project management knowledge in Indonesia. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  5. Can we set a global threshold age to define mature forests?

    Directory of Open Access Journals (Sweden)

    Philip Martin

    2016-02-01

    Full Text Available Globally, mature forests appear to be increasing in biomass density (BD. There is disagreement whether these increases are the result of increases in atmospheric CO2 concentrations or a legacy effect of previous land-use. Recently, it was suggested that a threshold of 450 years should be used to define mature forests and that many forests increasing in BD may be younger than this. However, the study making these suggestions failed to account for the interactions between forest age and climate. Here we revisit the issue to identify: (1 how climate and forest age control global forest BD and (2 whether we can set a threshold age for mature forests. Using data from previously published studies we modelled the impacts of forest age and climate on BD using linear mixed effects models. We examined the potential biases in the dataset by comparing how representative it was of global mature forests in terms of its distribution, the climate space it occupied, and the ages of the forests used. BD increased with forest age, mean annual temperature and annual precipitation. Importantly, the effect of forest age increased with increasing temperature, but the effect of precipitation decreased with increasing temperatures. The dataset was biased towards northern hemisphere forests in relatively dry, cold climates. The dataset was also clearly biased towards forests <250 years of age. Our analysis suggests that there is not a single threshold age for forest maturity. Since climate interacts with forest age to determine BD, a threshold age at which they reach equilibrium can only be determined locally. We caution against using BD as the only determinant of forest maturity since this ignores forest biodiversity and tree size structure which may take longer to recover. Future research should address the utility and cost-effectiveness of different methods for determining whether forests should be classified as mature.

  6. Late maturation of adult-born neurons in the temporal dentate gyrus.

    Science.gov (United States)

    Snyder, Jason S; Ferrante, Sarah C; Cameron, Heather A

    2012-01-01

    Hippocampal function varies along its septotemporal axis, with the septal (dorsal) pole more frequently involved in spatial learning and memory and the temporal (ventral) pole playing a greater role in emotional behaviors. One feature that varies across these subregions is adult neurogenesis. New neurons are more numerous in the septal hippocampus but are more active in the temporal hippocampus during water maze training. However, many other aspects of adult neurogenesis remain unexplored in the context of septal versus temporal subregions. In addition, the dentate gyrus contains another functionally important anatomical division along the transverse axis, with the suprapyramidal blade showing greater experience-related activity than the infrapyramidal blade. Here we ask whether new neurons differ in their rates of survival and maturation along the septotemporal and transverse axes. We found that neurogenesis is initially higher in the infrapyramidal than suprapyramidal blade, but these cells are less likely to survive, resulting in similar densities of neurons in the two blades by four weeks. Across the septotemporal axis, neurogenesis was higher in septal than temporal pole, while the survival rate of new neurons did not differ. Maturation was assessed by immunostaining for the neuronal marker, NeuN, which increases in expression level with maturation, and for the immediate-early gene, Arc, which suggests a neuron is capable of undergoing activity-dependent synaptic plasticity. Maturation occurred approximately 1-2 weeks earlier in the septal pole than in the temporal pole. This suggests that septal neurons may contribute to function sooner; however, the prolonged maturation of new temporal neurons may endow them with a longer window of plasticity during which their functions could be distinct from those of the mature granule cell population. These data point to subregional differences in new neuron maturation and suggest that changes in neurogenesis could alter

  7. RESULTS OF IN VITRO MATURATION OF MEIOTICALLY IMMATURE HUMAN OOCYTES IN A SIMPLE MEDIUM

    Directory of Open Access Journals (Sweden)

    Borut Kovačič

    2002-12-01

    Full Text Available Background. Among oocytes obtained during aspiration of preovulatory ovarian follicles in hormonally stimulated cycles, we ascertained the percentage of immature oocytes with the nucleus in the metaphase (M I oocytes or even in the prophase (GV oocytes of the first meiotic division and their capacity to mature in vitro in a simple medium without hormonal supplements.Methods. In 818 women, stimulated by gonadotropin releasing hormone agonist (GnRHa and gonadotropins, aspiration of preovulatory size follicles yielded 4972 oocytes. From these we denuded cells of cumulus oophorus and corona, meiotic maturity was evaluated under a microscope. Cells in the metaphase of the second meiotic division (M II oocytes and those maturing after 5 hours were used clinically in the intracytoplasmic sperm injection (ICSI procedure. Immature cells were left in the simple medium. The degree of their nuclear maturity was evaluated after one and after two days of culture. In vitro maturation was clinically used also in 14 cycles with no mature oocytes.Results. Among 4731 oocytes with denuded corona and cumulus, 4199 (88.8% were mature M II oocytes, 295 (6.2% immature M I oocytes and 237 (5% immature GV oocytes. Under in vitro conditions, 68.7% (90/131 GV oocytes attained maturity. Among M I oocytes, 63.6% (136/214 cells matured already after 5 hours and 26.6% (57/214 until the next day. In all 14 women with only immature oocytes, the embryos for embryotransfer were obtained after in vitro maturation and ICSI procedure. The result was four pregnancies and two deliveries.Conclusions. Immature oocytes, obtained in hormonally stimulated cycles, may become clinically applicable if left to mature in vitro in a simple medium without supplementation of growth factors and hormones.

  8. Acoustic and Petrophysical Evolution of Organic-Rich Chalk Following Maturation Induced by Unconfined Pyrolysis

    Science.gov (United States)

    Shitrit, Omri; Hatzor, Yossef H.; Feinstein, Shimon; Vinegar, Harold J.

    2017-12-01

    Thermal maturation is known to influence the rock physics of organic-rich rocks. While most studies were performed on low-porosity organic-rich shales, here we examine the effect of thermal maturation on a high-porosity organic-rich chalk. We compare the physical properties of native state immature rock with the properties at two pyrolysis-simulated maturity levels: early-mature and over-mature. We further evaluate the applicability of results from unconfined pyrolysis experiments to naturally matured rock properties. Special attention is dedicated to the elastic properties of the organic phase and the influence of bitumen and kerogen contents. Rock physics is studied based on confined petrophysical measurements of porosity, density and permeability, and measurements of bedding-normal acoustic velocities at estimated field stresses. Geochemical parameters like total organic carbon (TOC), bitumen content and thermal maturation indicators are used to monitor variations in density and volume fraction of each phase. We find that porosity increases significantly upon pyrolysis and that P wave velocity decreases in accordance. Solids density versus TOC relationships indicate that the kerogen increases its density from 1.43 to 1.49 g/cc at the immature and early-mature stages to 2.98 g/cc at the over-mature stage. This density value is unusually high, although increase in S wave velocity and backscatter SEM images of the over-mature samples verify that the over-mature kerogen is significantly denser and stiffer. Using the petrophysical and acoustic properties, the elastic moduli of the rock are estimated by two Hashin-Shtrikman (HS)-based models: "HS + BAM" and "HS kerogen." The "HS + BAM" model is calibrated to the post-pyrolysis measurements to describe the mechanical effect of the unconfined pyrolysis on the rock. The absence of compaction in the pyrolysis process causes the post-pyrolysis samples to be extremely porous. The "HS kerogen" model, which simulates a

  9. Adenocarcinomas arising from primary retroperitoneal mature teratomas: CT and MR imaging

    International Nuclear Information System (INIS)

    Wang, Li-Jen; Wong, Yon-Cheong; Chu, Sheng-Hsien; Ng, Kwai-Fong

    2002-01-01

    An adenocarcinoma arising from mature teratoma is one form of teratoma with malignant transformation. It is extremely rare but highly malignant. The authors report two patients with adenocarcinomas arising from primary retroperitoneal teratomas. The CT and MRI findings of the tumors are presented with emphasis on imaging features implying the presence of malignant transformation and differing from those of pure benign mature teratoma. Correct diagnosis of the presence of malignant transformation from a benign mature teratoma can be made as early as possible by awareness of the imaging features. (orig.)

  10. Zulliger (CS in Assessing the Relational Maturity of Children

    Directory of Open Access Journals (Sweden)

    Anna Elisa Villemor-Amaral

    Full Text Available Abstract Relational maturity is an important aspect to be considered in the evaluation of children. Its development in children is considered related to sex and chronological age. The present study aimed to seek evidence of validity for the Zulliger test (Comprehensive System - CS in the evaluation of maturity for interpersonal relationships in children. A total of 566 children, both sexes, of which 52.8% were girls, were submitted to the Zulliger test (CS. For comparison according to age, a subsample was extracted, composed of two groups of six and 12-year-olds, totaling 115 children. The analysis revealed statistically significant differences in the variables H, (H, A, Ad, (A, M, FC and AG. Results show findings in favor of using the Zulliger test (CS in the evaluation of maturity for interpersonal relationships in children.

  11. Bentonite maturation with 'Águas de Lindóia' water (SP)

    Energy Technology Data Exchange (ETDEWEB)

    Torrecilha, Jefferson K.; Silva, Paulo S.C., E-mail: jeffkoy@usp.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    This study aims to characterize the artificial peloid obtained by maturing bentonite with Águas de Lindóia water for periods of three, six and nine months. The pH, moisture, organic matter content, loss on ignition and swelling power of matured and non-matured samples were measured for physicochemical characterization. The elemental concentration was determined by instrumental neutron activation analysis. Results showed that water adsorption capacity, organic matter and swelling power is related to the maturation time and no significant differences occurs in the elemental concentration except for Na. (author)

  12. DmsD, a Tat system specific chaperone, interacts with other general chaperones and proteins involved in the molybdenum cofactor biosynthesis

    OpenAIRE

    Li, Haiming; Chang, Limei; Howell, Jenika M.; Turner, Raymond J.

    2010-01-01

    Many bacterial oxidoreductases depend on the Tat translocase for correct cell localization. Substrates for the Tat translocase possess twin-arginine leaders. System specific chaperones or redox enzyme maturation proteins (REMPs) are a group of proteins implicated in oxidoreductase maturation. DmsD is a REMP discovered in Escherichia coli, which interacts with the twin-arginine leader sequence of DmsA, the catalytic subunit of DMSO reductase. In this study, we identified several potential inte...

  13. Mature cystic teratoma of the pancreas in a child

    International Nuclear Information System (INIS)

    Yu, C.W.; Liu, K.L.; Li, Y.W.; Lin, W.C.

    2003-01-01

    A cystic pancreatic tumour is rare in a child and a mature cystic teratoma of the pancreas is even rarer. This is the first demonstration of the CT appearance of such a tumour in a child. We present a 2-year-old boy who presented with a palpable abdominal mass. Abdominal CT revealed a huge cystic mass in the upper abdomen. Pathology disclosed a mature cystic teratoma originating from the pancreas. (orig.)

  14. How Enterprise Architecture Maturity Enables Post-merger IT Integration

    DEFF Research Database (Denmark)

    Törmer, Robert Lorenz; Henningsson, Stefan

    2017-01-01

    advances the argument that a company’s pre-existing Enterprise Architecture decisively shapes the capability to implement post-merger IT integration and subsequently realize benefits from M&A. Our multiple-case study investigates three acquisition cases and develops an explanatory theory of how Enterprise...... Architecture maturity enables the implementation of distinct integration strategies. The results do not only enrich the academic literature on M&A, but also show the strategic value of Enterprise Architecture maturity....

  15. Facilitating Oak and Hickory Regeneration in Mature Central Hardwood Forests

    Directory of Open Access Journals (Sweden)

    Eric J. Holzmueller

    2014-12-01

    Full Text Available Advanced oak and hickory regeneration is often absent in mature oak-hickory forests in the Central Hardwood Region of the United States. Prescribed fire and thinning, alone and combined, are commonly prescribed silvicultural treatments that are recommended to initiate the regeneration process. This study examined the regeneration response in three mature oak stands following four treatments: (1 thin, (2 burn, (3 thinning and burning, or (4 no treatment (control. Ten years after initial treatment, results indicate that oak and hickory seedlings had greater height and diameter in the thinning and burning treatment compared to the control and that this treatment may help facilitate desirable regeneration in mature oak-hickory forests.

  16. Effect of chronological age of beef steers of different maturity types ...

    African Journals Online (AJOL)

    Effect of chronological age of beef steers of different maturity types on their growth ... and carcass studies have been conducted in the sourveld regions of the country. ... different beef maturity types which differ in body frame size were used, viz.

  17. Business process maturity assessment : state of the art and key characteristics

    NARCIS (Netherlands)

    Tarhan, A.; Turetken, O.; Ilisu, F.

    2015-01-01

    Business processes are basic enablers in sustaining an organization's existence in delivering high-quality products and services. A maturity model is an instrument to assess and continually improve business processes. For example, Capability Maturity Model Integration for Development (CMMI-Dev) in

  18. The influence of sex steroids on structural brain maturation in adolescence

    NARCIS (Netherlands)

    Koolschijn, P.C.M.P.; Peper, J.S.; Crone, E.A.

    2014-01-01

    Puberty reflects a period of hormonal changes, physical maturation and structural brain reorganization. However, little attention has been paid to what extent sex steroids and pituitary hormones are associated with the refinement of brain maturation across adolescent development. Here we used

  19. Improved Method for the Incorporation of Heme Cofactors into Recombinant Proteins Using Escherichia coli Nissle 1917.

    Science.gov (United States)

    Fiege, Kerstin; Querebillo, Christine Joy; Hildebrandt, Peter; Frankenberg-Dinkel, Nicole

    2018-05-15

    Recombinant production of heme proteins in Escherichia coli is often limited by the availability of heme in the host. Therefore, several methods, including the reconstitution of heme proteins after production but prior to purification or the HPEX system, conferring the ability to take up external heme have been developed and used in the past. Here we describe the use of the apathogenic E. coli strain Nissle 1917 (EcN) as a suitable host for the recombinant production of heme proteins. EcN has an advantage over commonly used lab strains in that it is able to take up heme from the environment through the heme receptor ChuA. Expression of several heme proteins from different prokaryotic sources led to high yield and quantitative incorporation of the cofactor when heme was supplied in the growth medium. Comparative UV-vis and resonance Raman measurements revealed that the method employed has significant influence on heme coordination with the EcN system representing the most native situation. Therefore, the use of EcN as a host for recombinant heme protein production represents an inexpensive and straightforward method to facilitate further investigations of structure and function.

  20. Predicting individual brain maturity using dynamic functional connectivity

    Directory of Open Access Journals (Sweden)

    Jian eQin

    2015-07-01

    Full Text Available Neuroimaging-based functional connectivity (FC analyses have revealed significant developmental trends in specific intrinsic connectivity networks linked to cognitive and behavioral maturation. However, knowledge of how brain functional maturation is associated with FC dynamics at rest is limited. Here, we examined age-related differences in the temporal variability of FC dynamics with data publicly released by the Nathan Kline Institute (NKI (n=183, ages 7-30 and showed that dynamic inter-region interactions can be used to accurately predict individual brain maturity across development. Furthermore, we identified a significant age-dependent trend underlying dynamic inter-network FC, including increasing variability of the connections between the visual network, default mode network (DMN and cerebellum as well as within the cerebellum and DMN and decreasing variability within the cerebellum and between the cerebellum and DMN as well as the cingulo-opercular network. Overall, the results suggested significant developmental changes in dynamic inter-network interaction, which may shed new light on the functional organization of typical developmental brains.