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Sample records for 5-phosphate reductoisomerase mep

  1. Inhibition of green tea and the catechins against 1-deoxy-d-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway.

    Science.gov (United States)

    Hui, Xian; Liu, Hui; Tian, Fang-Lin; Li, Fei-Fei; Li, Heng; Gao, Wen-Yun

    2016-09-01

    1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR) is the first committed enzyme in the MEP terpenoid biosynthetic pathway and also a validated antimicrobial target. Green tea which is rich in polyphenolic components such as the catechins, possesses a plenty of pharmacological activities, in particular an antibacterial effect. To uncover the antibacterial mechanism of green tea and to seek new DXR inhibitors from natural sources, the DXR inhibitory activity of green tea and its main antimicrobial catechins were investigated in this study. The results show that the raw extract of green tea and its ethyl acetate fraction are able to suppress DXR activity explicitly. Further determination of the DXR inhibitory capacity of eight catechin compounds demonstrates that the most active compound is gallocatechin gallate that is able to inhibit around 50% activity of DXR at 25μM. Based on these data, the primary structure-activity relationship of the catechins against DXR is discussed. This study would be very helpful to elucidate the antimicrobial mechanism of green tea and the catechins and also would be very useful to direct the rational utilization of them as food additives. PMID:27439219

  2. Synthesis and evaluation of β-substituted fosmidomycin analogues as inhibitors of 1-deoxy-D-xylulose 5-phosphate reductoisomerase

    OpenAIRE

    Chofor, René; Sooriyaarachchi, Sanjeewani; Risseeuw, Martijn; Bergfors, Terese; Jones, T. Alwyn; Mowbray, Sherry L.; Van Calenbergh, Serge

    2015-01-01

    Blocking the MEP pathway for isoprenoid biosynthesis offers interesting prospects for inhibiting Plasmodia growth. Fosmidomycin (1) and its homologue FR900098 (2) potently inhibit 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr), a key enzyme in this pathway. Although fosmidomycin is a remarkably safe antimalarial agent, low oral absorption, short serum half-life and malaria recrudescence preclude its use in monotherapy. The development of more lipophilic Dxr inhibitors able to passively...

  3. 1-deoxy-D-xylulose-5-phosphate reductoisomerases, and methods of use

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, Rodney B. (Pullman, WA); Lange, Bernd M. (Pullman, WA)

    2002-07-16

    The present invention relates to isolated DNA sequences which code for the expression of plant 1-deoxy-D-xylulose-5-phosphate reductoisomerase protein, such as the sequence presented in SEQ ID NO:1 which encodes a 1-deoxy-D-xylulose-5-phosphate reductoisomerase protein from peppermint (Mentha x piperita). Additionally, the present invention relates to isolated plant 1-deoxy-D-xylulose-5-phosphate reductoisomerase protein. In other aspects, the present invention is directed to replicable recombinant cloning vehicles comprising a nucleic acid sequence which codes for a plant 1-deoxy-D-xylulose-5-phosphate reductoisomerase, to modified host cells transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence of the invention.

  4. 1-deoxy-d-xylulose-5-phosphate reductoisomerases and method of use

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, Rodney B. (Pullman, WA); Lange, Bernd M. (Pullman, WA)

    2001-01-01

    The present invention relates to isolated DNA sequences which code for the expression of plant 1-deoxy-D-xylulose-5-phosphate reductoisomerase protein, such as the sequence presented in SEQ ID NO:1 which encodes a 1-deoxy-D-xylulose-5-phosphate reductoisomerase protein from peppermint (Mentha x piperita). Additionally, the present invention relates to isolated plant 1-deoxy-D-xylulose-5-phosphate reductoisomerase protein. In other aspects, the present invention is directed to replicable recombinant cloning vehicles comprising a nucleic acid sequence which codes for a plant 1-deoxy-D-xylulose-5-phosphate reductoisomerase, to modified host cells transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence of the invention.

  5. Mechanism and inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase.

    Science.gov (United States)

    Murkin, Andrew S; Manning, Kathryn A; Kholodar, Svetlana A

    2014-12-01

    The non-mevalonate or 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway is responsible for generating isoprenoid precursors in plants, protozoa, and bacteria. Because this pathway is absent in humans, its enzymes represent potential targets for the development of herbicides and antibiotics. 1-Deoxy-d-xylulose (DXP) reductoisomerase (DXR) is a particularly attractive target that catalyzes the pathway's first committed step: the sequential isomerization and NADPH-dependent reduction of DXP to MEP. This article provides a comprehensive review of the mechanistic and structural investigations on DXR, including its discovery and validation as a drug target, elucidation of its chemical and kinetic mechanisms, characterization of inhibition by the natural antibiotic fosmidomycin, and identification of structural features that provide the molecular basis for inhibition of and catalysis. PMID:24998420

  6. Enhanced flux through the methylerythritol 4-phosphate pathway in Arabidopsis plants overexpressing deoxyxylulose 5-phosphate reductoisomerase.

    Science.gov (United States)

    Carretero-Paulet, Lorenzo; Cairó, Albert; Botella-Pavía, Patricia; Besumbes, Oscar; Campos, Narciso; Boronat, Albert; Rodríguez-Concepción, Manuel

    2006-11-01

    The methylerythritol 4-phosphate (MEP) pathway synthesizes the precursors for an astonishing diversity of plastid isoprenoids, including the major photosynthetic pigments chlorophylls and carotenoids. Since the identification of the first two enzymes of the pathway, deoxyxylulose 5-phoshate (DXP) synthase (DXS) and DXP reductoisomerase (DXR), they both were proposed as potential control points. Increased DXS activity has been shown to up-regulate the production of plastid isoprenoids in all systems tested, but the relative contribution of DXR to the supply of isoprenoid precursors is less clear. In this work, we have generated transgenic Arabidopsis thaliana plants with altered DXS and DXR enzyme levels, as estimated from their resistance to clomazone and fosmidomycin, respectively. The down-regulation of DXR resulted in variegation, reduced pigmentation and defects in chloroplast development, whereas DXR-overexpressing lines showed an increased accumulation of MEP- derived plastid isoprenoids such as chlorophylls, carotenoids, and taxadiene in transgenic plants engineered to produce this non-native isoprenoid. Changes in DXR levels in transgenic plants did not result in changes in DXS gene expression or enzyme accumulation, confirming that the observed effects on plastid isoprenoid levels in DXR-overexpressing lines were not an indirect consequence of altering DXS levels. The results indicate that the biosynthesis of MEP (the first committed intermediate of the pathway) limits the production of downstream isoprenoids in Arabidopsis chloroplasts, supporting a role for DXR in the control of the metabolic flux through the MEP pathway.

  7. 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase (IspC) from Mycobacterium tuberculosis: towards Understanding Mycobacterial Resistance to Fosmidomycin

    OpenAIRE

    Dhiman, Rakesh K.; Schaeffer, Merrill L.; Bailey, Ann Marie; Testa, Charles A.; Scherman, Hataichanok; Crick, Dean C.

    2005-01-01

    1-Deoxy-d-xylulose 5-phosphate reductoisomerase (IspC) catalyzes the first committed step in the mevalonate-independent isopentenyl diphosphate biosynthetic pathway and is a potential drug target in some pathogenic bacteria. The antibiotic fosmidomycin has been shown to inhibit IspC in a number of organisms and is active against most gram-negative bacteria but not gram positives, including Mycobacterium tuberculosis, even though the mevalonate-independent pathway is the sole isopentenyl dipho...

  8. Crystal structure of 1-deoxy-d-xylulose 5-phosphate reductoisomerase from the hyperthermophile Thermotoga maritima for insights into the coordination of conformational changes and an inhibitor binding.

    Science.gov (United States)

    Takenoya, Mihoko; Ohtaki, Akashi; Noguchi, Keiichi; Endo, Kiwamu; Sasaki, Yasuyuki; Ohsawa, Kanju; Yajima, Shunsuke; Yohda, Masafumi

    2010-06-01

    Isopentenyl diphosphate is a precursor of various isoprenoids and is produced by the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway in plastids of plants, protozoa and many eubacteria. A key enzyme in the MEP pathway, 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), has been shown to be the target of fosmidomycin, which works as an antimalarial, antibacterial and herbicidal compound. In this paper, we report studies of kinetics and the crystal structures of the thermostable DXR from the hyperthermophile Thermotoga maritima. Unlike the mesophilic DXRs, Thermotoga DXR (tDXR) showed activity only with Mg(2+) at its growth temperature. We solved the crystal structures of tDXR with and without fosmidomycin. The structure without fosmidomycin but unexpectedly bound with 2-methyl-2,4-pentanediol (MPD), revealing a new extra space available for potential drug design. This structure adopted the closed form by rigid domain rotation but without the flexible loop over the active site, which was considered as a novel conformation. Further, the conserved Asp residue responsible for cation binding seemed to play an important role in adjusting the position of fosmidomycin. Taken together, our kinetic and the crystal structures illustrate the binding mode of fosmidomycin that leads to its slow, tight binding according to the conformational changes of DXR.

  9. Molecular cloning, characterization and expression analysis of the gene encoding 1-deoxy-D-xylulose 5-phosphate reductoisomerase from Aquilaria sinensis (Lour.) Gilg

    Indian Academy of Sciences (India)

    Juan Liu; Yanhong Xu; Liang Liang; Jianhe Wei

    2015-06-01

    The major constituents of agarwood oils are sesquiterpenes that are obtained from isoprenoid precursors through the plastidial methylerythritol phosphate (MEP) pathway and the cytosolic mevalonate pathway. In this study, a novel full-length cDNA of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), which was the second key enzyme in the plastid MEP pathway of sesquiterpenes biosynthesis was isolated from the stem of Aquilaria sinensis (Lour.) Gilg by the methods of reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) technique for the first time, and named as AsDXR. The full-length cDNA of AsDXR was 1768 bp, containing a 1437 bp open reading frame (ORF) encoding a polypeptide of 478 amino acids with a molecular weight of 51.859 kD and the theoretical isoelectric point of 6.29. Comparative and bioinformatic analysis of the deduced AsDXR protein showed extensive homology with DXRs from other plant species, especially Theobroma cacao and Gossypium barbadense, and contained a conserved transit peptide for plastids, and extended pro-rich region and a highly conserved NADPH-binding motif owned by all plant DXRs. Southern blot analysis indicated that AsDXR belonged to a small gene family. Tissue expression pattern analysis revealed that AsDXR expressed strongly in root and stem, but weakly in leaf. Additionally, AsDXR expression was found to be activated by exogenous elicitor of MeJA (methyl jasmonate). The contents of three sesquiterpenes ($\\alpha$-guaiene, $\\alpha$-humulene and $\\delta$-guaiene) were significantly induced by MeJA. This study enables us to further elucidate the role of AsDXR in the biosynthesis of agarwood sesquiterpenes in A. sinensis at the molecular level.

  10. Alteration of the Flexible Loop in 1-Deoxy-d-xylulose-5-phosphate Reductoisomerase Boosts Enthalpy-Driven Inhibition by Fosmidomycin

    OpenAIRE

    Kholodar, Svetlana A.; Tombline, Gregory; Liu, Juan; Tan, Zhesen; Allen, C. Leigh; Gulick, Andrew M.; Murkin, Andrew S.

    2014-01-01

    1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR), which catalyzes the first committed step in the 2-C-methyl-d-erythritol 4-phosphate pathway of isoprenoid biosynthesis used by Mycobacterium tuberculosis and other infectious microorganisms, is absent in humans and therefore an attractive drug target. Fosmidomycin is a nanomolar inhibitor of DXR, but despite great efforts, few analogues with comparable potency have been developed. DXR contains a strictly conserved residue, Trp203, within ...

  11. Design of Potential Bisubstrate Inhibitors against Mycobacterium tuberculosis (Mtb) 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase (Dxr)—Evidence of a Novel Binding Mode

    OpenAIRE

    San Jose, Géraldine; Jackson, Emily R.; Uh, Eugene; Johny, Chinchu; Haymond, Amanda; Lundberg, Lindsay; Pinkham, Chelsea; Kehn-Hall, Kylene; Boshoff, Helena I.; Couch, Robin D.; Dowd, Cynthia S.

    2013-01-01

    In most bacteria, the nonmevalonate pathway is used to synthesize isoprene units. Dxr, the second step in the pathway, catalyzes the NADPH-dependent reductive isomerization of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol-4-phosphate (MEP). Dxr is inhibited by natural products fosmidomycin and FR900098, which bind in the DXP binding site. These compounds, while potent inhibitors of Dxr, lack whole cell activity against Mycobacterium tuberculosis (Mtb) due to their polarity. ...

  12. Cloning, Characterization, and Immunolocalization of a Mycorrhiza-Inducible 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase in Arbuscule-Containing Cells of Maize1

    Science.gov (United States)

    Hans, Joachim; Hause, Bettina; Strack, Dieter; Walter, Michael H.

    2004-01-01

    Colonization of plant roots by symbiotic arbuscular mycorrhizal fungi frequently leads to the accumulation of several apocarotenoids. The corresponding carotenoid precursors originate from the plastidial 2-C-methyl-d-erythritol 4-phosphate pathway. We have cloned and characterized 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), catalyzing the first committed step of the pathway, from maize (Zea mays). Functional identification was accomplished by heterologous expression of sequences coding for the mature protein in Escherichia coli. DXR is up-regulated in maize roots during mycorrhization as shown at transcript and protein levels, but is also abundant in leaves and young seedlings. Inspection of sequenced genomes and expressed sequence tag (EST) databases argue for a single-copy DXR gene. Immunolocalization studies in mycorrhizal roots using affinity-purified antibodies revealed a DXR localization in plastids around the main symbiotic structures, the arbuscules. DXR protein accumulation is tightly correlated with arbuscule development. The highest level of DXR protein is reached around maturity and initial senescence of these structures. We further demonstrate the formation of a DXR-containing plastidial network around arbuscules, which is highly interconnected in the mature, functional state of the arbuscules. Our findings imply a functional role of a still unknown nature for the apocarotenoids or their respective carotenoid precursors in the arbuscular life cycle. PMID:14764905

  13. Alteration of the flexible loop in 1-deoxy-D-xylulose-5-phosphate reductoisomerase boosts enthalpy-driven inhibition by fosmidomycin.

    Science.gov (United States)

    Kholodar, Svetlana A; Tombline, Gregory; Liu, Juan; Tan, Zhesen; Allen, C Leigh; Gulick, Andrew M; Murkin, Andrew S

    2014-06-01

    1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR), which catalyzes the first committed step in the 2-C-methyl-d-erythritol 4-phosphate pathway of isoprenoid biosynthesis used by Mycobacterium tuberculosis and other infectious microorganisms, is absent in humans and therefore an attractive drug target. Fosmidomycin is a nanomolar inhibitor of DXR, but despite great efforts, few analogues with comparable potency have been developed. DXR contains a strictly conserved residue, Trp203, within a flexible loop that closes over and interacts with the bound inhibitor. We report that while mutation to Ala or Gly abolishes activity, mutation to Phe and Tyr only modestly impacts kcat and Km. Moreover, pre-steady-state kinetics and primary deuterium kinetic isotope effects indicate that while turnover is largely limited by product release for the wild-type enzyme, chemistry is significantly more rate-limiting for W203F and W203Y. Surprisingly, these mutants are more sensitive to inhibition by fosmidomycin, resulting in Km/Ki ratios up to 19-fold higher than that of wild-type DXR. In agreement, isothermal titration calorimetry revealed that fosmidomycin binds up to 11-fold more tightly to these mutants. Most strikingly, mutation strongly tips the entropy-enthalpy balance of total binding energy from 50% to 75% and 91% enthalpy in W203F and W203Y, respectively. X-ray crystal structures suggest that these enthalpy differences may be linked to differences in hydrogen bond interactions involving a water network connecting fosmidomycin's phosphonate group to the protein. These results confirm the importance of the flexible loop, in particular Trp203, in ligand binding and suggest that improved inhibitor affinity may be obtained against the wild-type protein by introducing interactions with this loop and/or the surrounding structured water network.

  14. Design of Potential Bisubstrate Inhibitors against Mycobacterium tuberculosis (Mtb) 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase (Dxr)-Evidence of a Novel Binding Mode.

    Science.gov (United States)

    San Jose, Géraldine; Jackson, Emily R; Uh, Eugene; Johny, Chinchu; Haymond, Amanda; Lundberg, Lindsay; Pinkham, Chelsea; Kehn-Hall, Kylene; Boshoff, Helena I; Couch, Robin D; Dowd, Cynthia S

    2013-07-01

    In most bacteria, the nonmevalonate pathway is used to synthesize isoprene units. Dxr, the second step in the pathway, catalyzes the NADPH-dependent reductive isomerization of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol-4-phosphate (MEP). Dxr is inhibited by natural products fosmidomycin and FR900098, which bind in the DXP binding site. These compounds, while potent inhibitors of Dxr, lack whole cell activity against Mycobacterium tuberculosis (Mtb) due to their polarity. Our goal was to use the Mtb Dxr-fosmidomycin co-crystal structure to design bisubstrate ligands to bind to both the DXP and NADPH sites. Such compounds would be expected to demonstrate improved whole cell activity due to increased lipophilicity. Two series of compounds were designed and synthesized. Compounds from both series inhibited Mtb Dxr. The most potent compound (8) has an IC50 of 17.8 µM. Analysis shows 8 binds to Mtb Dxr via a novel, non-bisubstrate mechanism. Further, the diethyl ester of 8 inhibits Mtb growth making this class of compounds interesting lead molecules in the search for new antitubercular agents. PMID:23914289

  15. Cloning and expression regulation of 1-deoxy-D-xylulose-5-phosphate reductoisomerase cDNA from Alpinia officinarum%高良姜1-脱氧-D-木酮糖5-磷酸还原异构酶cDNA克隆与表达调控

    Institute of Scientific and Technical Information of China (English)

    张春荣; 杨全; 陈虎彪; 庞玉新; 唐晓敏; 程轩轩; 吴文雅; 陈诗敏

    2012-01-01

    The rhizome of Alpinia officinarum is a widely used Chinese herbal medicine. The essential oil in A. officinarum rhizome is mainly composed of 1 , 8-cineole and other monoterpenes, as the major bioactive ingredients. In plants, monoterpenes are synthesized through the methylerythritol phosphate ( MEP) pathway in the plastids, and 1-deoxy-D-xylulose 5-phosphate reductoisomerase ( DXR) is an enzyme catalyzing a committed step of the MEP pathway. In the present study, the full-length cDNA encoding DXR was cloned from the rhizome of A. officinarum, using homology-based RT-PCR and rapid amplification of cDNA ends (RACE) techniques. The new cDNA was designated as AoDXR and submitted to GenBank to be assigned with an accession number HQ874658. The full-length cDNA of AoDXR was 1 670 bp containing a 1 419 bp open reading frame encoding a polypeptide of 472 amino acids with a calculated molecular mass of 51. 48 kDa and an isoelectric point of 6. 15. Bioinformatic analyses revealed that AoDXR showed extensive homology with DXRs from other plant species and contained a conserved plastids transit peptide, a Pro-rich region and two highly conserved NADPH-binding motifs in its N-terminal region characterized by all plant DXRs. The phylogenetic analysis revealed that AoDXR belonged to angiosperm DXRs. The structural modeling of AoDXR showed that AoDXR had the typical V-shaped structure of DXR proteins. The tissue expression pattern analysis indicated that AoDXR expressed strongly in leaves, weak in rhizomes of A. officinarum. Exogenous methyl jasmonate ( MeJA) could enhance the expression of AoDXR and the production of 1, 8-cineole in A. officinarum rhizomes. The cloning and characterization of AoDXR will be helpful to reveal the molecular regulation mechanism of monoterpene biosynthesis in A. officinarum and provides a candidate gene for metabolic engineering in improving the medicinal quality of A. officinarum rhizome.%目的:克隆高良姜1-脱氧-D-木酮糖5-磷酸还原

  16. Differential Contribution of the First Two Enzymes of the MEP Pathway to the Supply of Metabolic Precursors for Carotenoid and Chlorophyll Biosynthesis in Carrot (Daucus carota).

    Science.gov (United States)

    Simpson, Kevin; Quiroz, Luis F; Rodriguez-Concepción, Manuel; Stange, Claudia R

    2016-01-01

    Carotenoids and chlorophylls are photosynthetic pigments synthesized in plastids from metabolic precursors provided by the methylerythritol 4-phosphate (MEP) pathway. The first two steps in the MEP pathway are catalyzed by the deoxyxylulose 5-phosphate synthase (DXS) and reductoisomerase (DXR) enzymes. While DXS has been recently shown to be the main flux-controlling step of the MEP pathway, both DXS and DXR enzymes have been proven to be able to promote an increase in MEP-derived products when overproduced in diverse plant systems. Carrot (Daucus carota) produces photosynthetic pigments (carotenoids and chlorophylls) in leaves and in light-exposed roots, whereas only carotenoids (mainly α- and β-carotene) accumulate in the storage root in darkness. To evaluate whether DXS and DXR activities influence the production of carotenoids and chlorophylls in carrot leaves and roots, the corresponding Arabidopsis thaliana genes were constitutively expressed in transgenic carrot plants. Our results suggest that DXS is limiting for the production of both carotenoids and chlorophylls in roots and leaves, whereas the regulatory role of DXR appeared to be minor. Interestingly, increased levels of DXS (but not of DXR) resulted in higher transcript abundance of endogenous carrot genes encoding phytoene synthase, the main rate-determining enzyme of the carotenoid pathway. These results support a central role for DXS on modulating the production of MEP-derived precursors to synthesize carotenoids and chlorophylls in carrot, confirming the pivotal relevance of this enzyme to engineer healthier, carotenoid-enriched products. PMID:27630663

  17. Differential Contribution of the First Two Enzymes of the MEP Pathway to the Supply of Metabolic Precursors for Carotenoid and Chlorophyll Biosynthesis in Carrot (Daucus carota)

    Science.gov (United States)

    Simpson, Kevin; Quiroz, Luis F.; Rodriguez-Concepción, Manuel; Stange, Claudia R.

    2016-01-01

    Carotenoids and chlorophylls are photosynthetic pigments synthesized in plastids from metabolic precursors provided by the methylerythritol 4-phosphate (MEP) pathway. The first two steps in the MEP pathway are catalyzed by the deoxyxylulose 5-phosphate synthase (DXS) and reductoisomerase (DXR) enzymes. While DXS has been recently shown to be the main flux-controlling step of the MEP pathway, both DXS and DXR enzymes have been proven to be able to promote an increase in MEP-derived products when overproduced in diverse plant systems. Carrot (Daucus carota) produces photosynthetic pigments (carotenoids and chlorophylls) in leaves and in light-exposed roots, whereas only carotenoids (mainly α- and β-carotene) accumulate in the storage root in darkness. To evaluate whether DXS and DXR activities influence the production of carotenoids and chlorophylls in carrot leaves and roots, the corresponding Arabidopsis thaliana genes were constitutively expressed in transgenic carrot plants. Our results suggest that DXS is limiting for the production of both carotenoids and chlorophylls in roots and leaves, whereas the regulatory role of DXR appeared to be minor. Interestingly, increased levels of DXS (but not of DXR) resulted in higher transcript abundance of endogenous carrot genes encoding phytoene synthase, the main rate-determining enzyme of the carotenoid pathway. These results support a central role for DXS on modulating the production of MEP-derived precursors to synthesize carotenoids and chlorophylls in carrot, confirming the pivotal relevance of this enzyme to engineer healthier, carotenoid-enriched products. PMID:27630663

  18. 烟草5-磷酸脱氧木酮糖还原异构酶基因(dxr)的克隆和表达分析%Cloning and Expression Analysis of 1-deoxy-D-xylulose-5-phosphate Reductoisomerases Gene (dxr) in Nicotina tabacum

    Institute of Scientific and Technical Information of China (English)

    朱晓宇; 王景; 赵二卫; 姚姗姗; 崔红

    2011-01-01

    以烟草(Nicotiana tabacum)栽培品种K326为材料,采用RT-PCR技术,克隆了萜类代谢关键酶烟草5-磷酸脱氧木酮糖还原异构酶(dxr)的cDNA片段.该基因编码区长1422 bp,编码473个氨基酸残基.利用Clustal W(1.82)和Bioedit软件,对烟草与番茄(Lycopersicon esculentum)、长春花(Catharanthus roseus)、金鱼草(A ntirrhinum majus)、薄荷(Mentha piperita)、玉米(Zea mays)、拟南芥(A rabidopsis thaliana)、念珠藻(Nostoc sp.)等物种dar基因的同源性进行分析,其氨基酸同源性分别达到93.6%、87.9%、86.3%、84.6%、84.2%、82.9%和53.5%.原核表达结果证明,该基因编码蛋白的分子量约为50 kD,与氨基酸序列估算相符合.组织表达特异性分析表明,dxr基因在烟草组织中的表达强弱为花>叶>茎>腺毛>种子>根,在花和叶片中的表达量占优势.该结果对烟草萜类代谢的分子调控和品质改良具有重要的参考价值.%Isoprenoid biosynthesis via mvalonate-independent pathway is very important to tobacco resistance and leaf quality. 1-deoxy-D-Xylulose-5-phosphate Reductoisomerases (dxr) is a key enzyme in biosynthesis of isopentenyl diphosphate, which is the precusor for monoterpenoid, diterpenoid and tetratepenoid compounds. To regulate the terpenoid metabolism pathway for tobacco improvement, some important genes such as dxr should be studied firstly. In this paper, dxr gene was cloned successfully from tobacco (Nicotiana tabacum) cultivar K326 leaf by RT-PCR. The cDNA code region was 1 422 bp long and encoding 437 amino acids. Sequence analysis by Clustal W declared that this fragment was highly homologous to dxr gene of other species. It shared 93.6% amino acid homologous to Lycopersicon esculentum, 87.9% to Catharanthus roseus, 86.3% to Antirrhinum majus,84.6% to Mentha piperita, 84.2% to Zea mays, 82.9% to Arabidopsis thaliana, and 53.5% to Nostoc sp.PCC7120. The expression vector pET21b-dxr was constructed and expressed in

  19. Metabolic engineering of essential oil yield and composition in mint by altering expression of deoxyxylulose phosphate reductoisomerase and menthofuran synthase

    OpenAIRE

    Mahmoud, Soheil S.; Croteau, Rodney B.

    2001-01-01

    Peppermint (Mentha × piperita L.) was independently transformed with a homologous sense version of the 1-deoxy-d-xylulose-5-phosphate reductoisomerase cDNA and with a homologous antisense version of the menthofuran synthase cDNA, both driven by the CaMV 35S promoter. Two groups of transgenic plants were regenerated in the reductoisomerase experiments, one of which remained normal in appearance and development; another was deficient in chlorophyll production and grew slowly. Transgenic plants ...

  20. Enzyme inhibitor studies reveal complex control of methyl-D-erythritol 4-phosphate (MEP) pathway enzyme expression in Catharanthus roseus.

    Science.gov (United States)

    Han, Mei; Heppel, Simon C; Su, Tao; Bogs, Jochen; Zu, Yuangang; An, Zhigang; Rausch, Thomas

    2013-01-01

    In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA) formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP) pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS), a new (type I) DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS) and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR)), respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms), DXR, and hydroxymethylbutenyl diphosphate synthase (HDS) were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation.

  1. Enzyme inhibitor studies reveal complex control of methyl-D-erythritol 4-phosphate (MEP pathway enzyme expression in Catharanthus roseus.

    Directory of Open Access Journals (Sweden)

    Mei Han

    Full Text Available In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS, a new (type I DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR, respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms, DXR, and hydroxymethylbutenyl diphosphate synthase (HDS were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation.

  2. Enzyme Inhibitor Studies Reveal Complex Control of Methyl-D-Erythritol 4-Phosphate (MEP) Pathway Enzyme Expression in Catharanthus roseus

    Science.gov (United States)

    Han, Mei; Heppel, Simon C.; Su, Tao; Bogs, Jochen; Zu, Yuangang; An, Zhigang; Rausch, Thomas

    2013-01-01

    In Catharanthus roseus, the monoterpene moiety exerts a strong flux control for monoterpene indole alkaloid (MIA) formation. Monoterpene synthesis depends on the methyl-D-erythritol 4-phosphate (MEP) pathway. Here, we have explored the regulation of this pathway in response to developmental and environmental cues and in response to specific enzyme inhibitors. For the MEP pathway entry enzyme 1-deoxy-D-xylulose 5-phosphate synthase (DXS), a new (type I) DXS isoform, CrDXS1, has been cloned, which, in contrast to previous reports on type II CrDXS, was not transcriptionally activated by the transcription factor ORCA3. Regulation of the MEP pathway in response to metabolic perturbations has been explored using the enzyme inhibitors clomazone (precursor of 5-ketochlomazone, inhibitor of DXS) and fosmidomycin (inhibitor of deoxyxylulose 5-phosphate reductoisomerase (DXR)), respectively. Young leaves of non-flowering plants were exposed to both inhibitors, adopting a non-invasive in vivo technique. Transcripts and proteins of DXS (3 isoforms), DXR, and hydroxymethylbutenyl diphosphate synthase (HDS) were monitored, and protein stability was followed in isolated chloroplasts. Transcripts for DXS1 were repressed by both inhibitors, whereas transcripts for DXS2A&B, DXR and HDS increased after clomazone treatment but were barely affected by fosmidomycin treatment. DXS protein accumulated in response to both inhibitors, whereas DXR and HDS proteins were less affected. Fosmidomycin-induced accumulation of DXS protein indicated substantial posttranscriptional regulation. Furthermore, fosmidomycin effectively protected DXR against degradation in planta and in isolated chloroplasts. Thus our results suggest that DXR protein stability may be affected by substrate binding. In summary, the present results provide novel insight into the regulation of DXS expression in C. roseus in response to MEP-pathway perturbation. PMID:23650515

  3. Liberia MEP WMS

    Data.gov (United States)

    US Agency for International Development — L-MEP WMS provides USAID, Implementing Partners, and L-MEP Staff the ability to view M view sector specific trend or base information; and answer questions about...

  4. Ketol-acid reductoisomerase enzymes and methods of use

    Science.gov (United States)

    Govindarajan, Sridhar; Li, Yougen; Liao, Der-Ing; O'Keefe, Daniel P.; Minshull, Jeremy Stephen; Rothman, Steven Cary; Tobias, Alexander Vincent

    2015-10-27

    Provided herein are polypeptides having ketol-aid reductoisomerase activity as well as microbial host cells comprising such polypeptides. Polypeptides provided herein may be used in biosynthetic pathways, including, but not limited to, isobutanol biosynthetic pathways.

  5. Ketol-acid reductoisomerase enzymes and methods of use

    Energy Technology Data Exchange (ETDEWEB)

    Govindarajan, Sridhar; Li, Yougen; Liao, Der-Ing; O' Keefe, Daniel P.; Minshull, Jeremy Stephen; Rothman, Steven Cary; Tobias, Alexander Vincent

    2016-07-12

    Provided herein are polypeptides having ketol-acid reductoisomerase activity as well as microbial host cells comprising such polypeptides. Polypeptides provided herein may be used in biosynthetic pathways, including, but not limited to, isobutanol biosynthetic pathways.

  6. 1-Deoxy-D-xylulose-5-phosphate synthase, a limiting enzyme for plastidic isoprenoid biosynthesis in plants.

    Science.gov (United States)

    Estévez, J M; Cantero, A; Reindl, A; Reichler, S; León, P

    2001-06-22

    The initial step of the plastidic 2C-methyl-D-erythritol 4-phosphate (MEP) pathway that produces isopentenyl diphosphate is catalyzed by 1-deoxy-d-xylulose-5-phosphate synthase. To investigate whether or not 1-deoxy-d-xylulose-5-phosphate synthase catalyzes a limiting step in the MEP pathway in plants, we produced transgenic Arabidopsis plants that over- or underexpress this enzyme. Compared with non-transgenic wild-type plants, the transgenic plants accumulate different levels of various isoprenoids such as chlorophylls, tocopherols, carotenoids, abscisic acid, and gibberellins. Phenotypically, the transgenic plants had slight alterations in growth and germination rates. Because the levels of several plastidic isoprenoids correlate with changes in 1-deoxy-D-xylulose-5-phosphate synthase levels, we conclude that this enzyme catalyzes one of the rate-limiting steps of the MEP biosynthetic pathway. Furthermore, since the product of the MEP pathway is isopentenyl diphosphate, our results suggest that in plastids the pool of isopentenyl diphosphate is limiting to isprenoid production.

  7. Genetics Home Reference: pyridoxal 5'-phosphate-dependent epilepsy

    Science.gov (United States)

    ... 5'-phosphate-dependent epilepsy pyridoxal 5'-phosphate-dependent epilepsy Enable Javascript to view the expand/collapse boxes. ... All Close All Description Pyridoxal 5'-phosphate-dependent epilepsy is a condition that involves seizures beginning soon ...

  8. Setting MEPS for electronic products

    International Nuclear Information System (INIS)

    When analysing price, performance and efficiency data for 15 consumer electronic and information and communication technology products, we found that in general price did not relate to the efficiency of the product. Prices of electronic products with comparable performance decreased over time. For products where the data allowed fitting the relationship, we found an exponential decrease in price with an average time constant of −0.30 [1/year], meaning that every year the product became 26% cheaper on average. The results imply that the classical approach of setting minimum efficiency performance standards (MEPS) by means of life cycle cost calculations cannot be applied to electronic products. Therefore, an alternative approach based on the improvement of efficiency over time and the variation in efficiency of products on the market, is presented. The concept of a policy action window can provide guidance for the decision on whether setting MEPS for a certain product is appropriate. If the (formal) procedure for setting MEPS takes longer than the policy action window, this means that the efficiency improvement will also be achieved without setting MEPS. We found short, i.e. less than three years, policy action windows for graphic cards, network attached storage products, network switches and televisions. - Highlights: • For electronic consumer products price does not relate to efficiency. • Average price decrease of selected electronic products is 26 % per year. • We give an alternative approach to life cycle cost calculations for setting MEPS. • The policy action window indicates whether setting MEPS is appropriate

  9. 21 CFR 582.5697 - Riboflavin-5-phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Riboflavin-5-phosphate. 582.5697 Section 582.5697 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5697 Riboflavin-5-phosphate. (a) Product. Riboflavin-5-phosphate. (b) Conditions of...

  10. Purification and characterization of ribitol-5-phosphate and xylitol-5-phosphate dehydrogenases from strains of Lactobacillus casei.

    OpenAIRE

    Hausman, S Z; London, J

    1987-01-01

    A simple three-step procedure is described which yields electrophoretically homogeneous preparations of ribitol-5-phosphate dehydrogenase and xylitol-5-phosphate dehydrogenase. The former enzyme is a 115,000-molecular-weight protein composed of two subunits of identical size and is specific for its substrate, ribitol. The xylitol-5-phosphate dehydrogenase exists as a tetrameric protein with a molecular weight of 180,000; this enzyme oxidizes the phosphate esters of both xylitol and D-arabitol...

  11. Mathematical modelling of the diurnal regulation of the MEP pathway in Arabidopsis.

    Science.gov (United States)

    Pokhilko, Alexandra; Bou-Torrent, Jordi; Pulido, Pablo; Rodríguez-Concepción, Manuel; Ebenhöh, Oliver

    2015-05-01

    Isoprenoid molecules are essential elements of plant metabolism. Many important plant isoprenoids, such as chlorophylls, carotenoids, tocopherols, prenylated quinones and hormones are synthesised in chloroplasts via the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway. Here we develop a mathematical model of diurnal regulation of the MEP pathway in Arabidopsis thaliana. We used both experimental and theoretical approaches to integrate mechanisms potentially involved in the diurnal control of the pathway. Our data show that flux through the MEP pathway is accelerated in light due to the photosynthesis-dependent supply of metabolic substrates of the pathway and the transcriptional regulation of key biosynthetic genes by the circadian clock. We also demonstrate that feedback regulation of both the activity and the abundance of the first enzyme of the MEP pathway (1-deoxy-D-xylulose 5-phosphate synthase, DXS) by pathway products stabilizes the flux against changes in substrate supply and adjusts the flux according to product demand under normal growth conditions. These data illustrate the central relevance of photosynthesis, the circadian clock and feedback control of DXS for the diurnal regulation of the MEP pathway.

  12. Reconciling Medical Expenditure Estimates from the MEPS...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Reconciling Medical Expenditure Estimates from the MEPS and NHEA, 2007, published in Volume 2, Issue 4 of the Medicare and Medicaid Research Review, provides a...

  13. SDE Plus, SDE and MEP. Annual review 2012; SDE+, SDE en MEP. Jaarbericht 2012

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-05-15

    This annual report describes the applications for SDE subsidy (renewable energy support scheme) in the period 2008-2012, the new SDE Plus which starts in 2013, and the MEP transition scheme (MEP stands for 'Environmental quality of electricity production', predecessor of SDE for the period 2003-2006) and applications from the MEP scheme [Dutch] Het jaarbericht 2012 voor de SDE+, SDE en MEP presenteert de resultaten van de regeling Stimulering Duurzame Energieproductie (SDE+ vanaf 2013 en SDE, 2008-2012) en de voorganger van de SDE, de subsidieregeling Milieukwaliteit van de Elektriciteitsproductie.

  14. Ribose 5-Phosphate Isomerase B Knockdown Compromises Trypanosoma brucei Bloodstream Form Infectivity

    OpenAIRE

    Inês Loureiro; Joana Faria; Christine Clayton; Sandra Macedo-Ribeiro; Nuno Santarém; Nilanjan Roy; Anabela Cordeiro-da-Siva; Joana Tavares

    2015-01-01

    Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, and catalyzes the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Trypanosomatids, including the agent of African sleeping sickness namely Trypanosoma brucei, have a type B ribose-5-phosphate isomerase. This enzyme is absent from humans, which have a structurally unrelated ribose 5-phosphate isomerase type A, and therefore has been proposed as an attractive dru...

  15. Four Thruster Microfluidic Electrospray Propulsion (MEP) Cubesat Board Demonstration Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Cubesat Microfluidic Electrospray Propulsion (MEP) system module prototype will be designed, built and tested to demonstrate that a four MEP thruster system can...

  16. Morton's foot and pyridoxal 5'-phosphate deficiency: genetically linked traits.

    Science.gov (United States)

    Nichols, Trent W; Gaiteri, Christopher

    2014-12-01

    Vitamin B6 is an essential vitamin needed for many chemical reactions in the human body. It exists as several vitamins forms but pyridoxal 5'-phosphate (PLP) is the phosphorylated form needed for transamination, deamination, and decarboxylation. PLP is important in the production of neurotransmitters, acts as a Schiff base and is essential in the metabolism of homocysteine, a toxic amino acid involved in cardiovascular disease, stroke, thrombotic and Alzheimer's disease. This report announces the connection between a deficit of PLP with a genetically linked physical foot form known as the Morton's foot. Morton's foot has been associated with fibromyalgia/myofascial pain syndrome. Another gene mutation methylenetetrahydrofolate reductase (MTHFr) is now being recognized much commonly than previous with chronic fatigue, chronic Lyme diseases and as "the missing link" in other chronic diseases. PLP deficiency also plays a role in impaired glucose tolerance and may play a much bigger role in the obesity, diabetes, fatty liver and metabolic syndrome. Without the Schiff-base of PLP acting as an electron sink, storing electrons and dispensing them in the mitochondria, free radical damage occurs! The recognition that a phenotypical expression (Morton's foot) of a gene resulting in deficiency of an important cofactor enzyme pyridoxal 5'-phosphate will hopefully alert physicians and nutritionist to these phenomena. Supplementation with PLP, L5-MTHF, B12 and trimethylglycine should be used in those patients with hyperhomocysteinemia and/or MTHFR gene mutation. PMID:25441836

  17. AutoCAD MEP 2009 Anpassad verktygspalett

    OpenAIRE

    Johansson, Magnus; Klasa, Thomas

    2009-01-01

    Rapporten handlar om examensprojektet som utförts av Magnus Johansson och Thomas Klasa under våren 2009. Man har under åtta veckors tid arbetat med att hjälpa företaget LBElkonsult AB i Mölndal med att ta fram en specialanpassad verktygspalett i datorprogrammet AutoCAD MEP 2009. I rapporten finns de olika steg som genomförts för att nå det önskade slutresultatet. Allt från förstudier och själva arbetet i AutoCAD MEP 2009 till finjusteringarna som avslutningsvis gjordes på den blivande slutpro...

  18. Inactive mutants of human pyridoxine 5'-phosphate oxidase: a possible role for a noncatalytic pyridoxal 5'-phosphate tight binding site.

    Science.gov (United States)

    Ghatge, Mohini S; Karve, Sayali S; David, Tanya M S; Ahmed, Mostafa H; Musayev, Faik N; Cunningham, Kendra; Schirch, Verne; Safo, Martin K

    2016-05-01

    Pyridoxal 5'-phosphate (PLP) is a cofactor for many vitamin B6-requiring enzymes that are important for the synthesis of neurotransmitters. Pyridoxine 5'-phosphate oxidase (PNPO) is one of two enzymes that produce PLP. Some 16 known mutations in human PNPO (hPNPO), including R95C and R229W, lead to deficiency of PLP in the cell and have been shown to cause neonatal epileptic encephalopathy (NEE). This disorder has no effective treatment, and is often fatal unless treated with PLP. In this study, we show that R95C hPNPO exhibits a 15-fold reduction in affinity for the FMN cofactor, a 71-fold decrease in affinity for the substrate PNP, a 4.9-fold decrease in specific activity, and a 343-fold reduction in catalytic activity, compared to the wild-type enzyme. We have reported similar findings for R229W hPNPO. This report also shows that wild-type, R95C and R229W hPNPO bind PLP tightly at a noncatalytic site and transfer it to activate an apo-B6 enzyme into the catalytically active holo-form. We also show for the first time that hPNPO forms specific interactions with several B6 enzymes with dissociation constants ranging from 0.3 to 12.3 μm. Our results suggest a possible in vivo role for the tight binding of PLP in hPNPO, whether wild-type or variant, by protecting the very reactive PLP, and transferring this PLP directly to activate apo-B6 enzymes. PMID:27419045

  19. Reconciling medical expenditure estimates from the MEPS and NHEA, 2002.

    Science.gov (United States)

    Sing, Merrile; Banthin, Jessica S; Selden, Thomas M; Cowan, Cathy A; Keehan, Sean P

    2006-01-01

    The Medical Expenditure Panel Survey (MEPS) and National Health Expenditure Accounts (NHEA) are often used for health care policy analysis and simulations because they contain comprehensive estimates of national health care expenditures. The NHEA are primarily based on aggregate provider revenue data, while MEPS is based on person-level data on health care expenditures. This article compares MEPS and NHEA expenditure estimates for 2002 and discusses the differences. When MEPS and the NHEA are adjusted to be on a consistent basis, their expenditure estimates differ by 13.8 percent.

  20. Molecular design, synthesis and biological activities of amidines as new ketol-acid reductoisomerase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Bao Lei Wang; Yong Hong Li; Jian Guo Wang; Yi Ma; Zheng Ming Li

    2008-01-01

    Diamidine (A) was identified in our in vitro bio-assay as a possible inhibitor of ketol-acid reductoisomerase (KARI) from the ACD database search based on the known three-dimensional crystal structure of KARI. An investigation on interaction of A on KARI active sites, led to the design and synthesis of 15 novel monoamidines. Some of those showed better biological activity than A on rice KARI (in vitro) and in greenhouse herbicidal tests (in vivo). The structure-biological activity relationship was investigated, which provides valuable information to further study of potential KARI inhibitors.

  1. Conversion of D-ribulose 5-phosphate to D-xylulose 5-phosphate : new insights from structural and biochemical studies on human RPE.

    Energy Technology Data Exchange (ETDEWEB)

    Liang, W.; Ouyang, S.; Shaw, N.; Joachimiak, A.; Zhang, R.; Liu, Z.; Biosciences Division; Chinese Academy of Sciences

    2011-02-01

    The pentose phosphate pathway (PPP) confers protection against oxidative stress by supplying NADPH necessary for the regeneration of glutathione, which detoxifies H{sub 2}O{sub 2} into H{sub 2}O and O{sub 2}. RPE functions in the PPP, catalyzing the reversible conversion of D-ribulose 5-phosphate to D-xylulose 5-phosphate and is an important enzyme for cellular response against oxidative stress. Here, using structural, biochemical, and functional studies, we show that human D-ribulose 5-phosphate 3-epimerase (hRPE) uses Fe{sup 2+} for catalysis. Structures of the binary complexes of hRPE with D-ribulose 5-phosphate and D-xylulose 5-phosphate provide the first detailed molecular insights into the binding mode of physiological ligands and reveal an octahedrally coordinated Fe{sup 2+} ion buried deep inside the active site. Human RPE folds into a typical ({beta}/{alpha}){sub 8} triosephosphate isomerase (TIM) barrel with a loop regulating access to the active site. Two aspartic acids are well positioned to carry out the proton transfers in an acid-base type of reaction mechanism. Interestingly, mutating Ser-10 to alanine almost abolished the enzymatic activity, while L12A and M72A mutations resulted in an almost 50% decrease in the activity. The binary complexes of hRPE reported here will aid in the design of small molecules for modulating the activity of the enzyme and altering flux through the PPP.

  2. A MEPS is a MEPS is a MEPS. Comparing Ecodesign and Top Runner schemes for setting product efficiency standards

    Energy Technology Data Exchange (ETDEWEB)

    Siderius, P.J.S. [NL Agency, Croeselaan 15, P.O. Box 8242, 3503 RE Utrecht (Netherlands); Nakagami, H. [Jyukankyo Research Institute, 3-29, Kioi-cho, Chiyoda-ku Tokyo, 102-0094 (Japan)

    2013-02-15

    Both Top Runner in Japan and Ecodesign in the European Union are schemes to set requirements on the energy efficiency (minimum efficiency performance standards, MEPS) of a variety of products. This article provides an overview of the main characteristics and results of both schemes and gives recommendations for improving them. Both schemes contribute significantly to the energy efficiency targets set by the European Commission and the Japanese government. Although it is difficult to compare the absolute levels of the requirements, comparison of the relative improvements and of the savings on household electricity consumption (11 % in Japan, 16 % in the EU) suggest they are in the same range. Furthermore, the time needed to set or review requirements is in both schemes considerable (between 5 and 6 years on average) and the manageability increasingly will become a challenge. The appeal of the Top Runner approach is that the most efficient product (Top Runner) sets the standard for all products at the next target year. Although the Ecodesign scheme includes the elements for a Top Runner approach, it could exploit this principle more explicitly. On the other hand, the Top Runner scheme could benefit by using a real minimum efficiency performance standard instead of a fleet average. This would make the monitoring and enforcement more simple and transparent, and would open the scheme for products where the market situation is less clear.

  3. The role of experience curves for setting MEPS for appliances

    International Nuclear Information System (INIS)

    Minimum efficiency performance standards (MEPS) are an important policy instrument to raise the efficiency of products. In most schemes the concept of life cycle costs (LCC) is used to guide setting the MEPS levels. Although a large body of literature shows that product cost is decreasing with increasing cumulative production, the experience curve, this is currently not used for setting MEPS. This article shows how to integrate the concept of the experience curve into LCC calculations for setting MEPS in the European Union and applies this to household laundry driers, refrigerator-freezers and televisions. The results indicate that for driers and refrigerator-freezers at least twice the energy savings compared to the current approach can be achieved. These products also show that energy label classes can successfully be used for setting MEPS. For televisions an experience curve is provided, showing a learning rate of 29%. However, television prices do not show a relation with energy efficiency but are to a large extent determined by the time the product is placed on the market. This suggests to policy makers that for televisions and other products with a short (re)design and market cycle timing is more important than the MEPS levels itself. - Highlights: • We integrate experience curves into life cycle cost calculations for MEPS. • For driers and refrigerators this results in at least twice the energy savings. • For flat panel televisions an experience curve is provided

  4. Structure of ribose 5-phosphate isomerase from the probiotic bacterium Lactobacillus salivarius UCC118

    International Nuclear Information System (INIS)

    The crystal structure of ribose 5-phosphate isomerase has been determined to 1.72 Å resolution and is presented with a brief comparison to other known ribose 5-phosphate isomerase A structures. The structure of ribose 5-phosphate isomerase from the probiotic bacterium Lactobacillus salivarius UCC188 has been determined at 1.72 Å resolution. The structure was solved by molecular replacement, which identified the functional homodimer in the asymmetric unit. Despite only showing 57% sequence identity to its closest homologue, the structure adopted the typical α and β d-ribose 5-phosphate isomerase fold. Comparison to other related structures revealed high homology in the active site, allowing a model of the substrate-bound protein to be proposed. The determination of the structure was expedited by the use of in situ crystallization-plate screening on beamline I04-1 at Diamond Light Source to identify well diffracting protein crystals prior to routine cryocrystallography

  5. Rv2607 from Mycobacterium tuberculosis is a pyridoxine 5'-phosphate oxidase with unusual substrate specificity.

    Directory of Open Access Journals (Sweden)

    Ellene H Mashalidis

    Full Text Available Despite intensive effort, the majority of the annotated Mycobacterium tuberculosis genome consists of genes encoding proteins of unknown or poorly understood function. For example, there are seven conserved hypothetical proteins annotated as homologs of pyridoxine 5'-phosphate oxidase (PNPOx, an enzyme that oxidizes pyridoxine 5'-phosphate (PNP or pyridoxamine 5'-phosphate (PMP to form pyridoxal 5'-phosphate (PLP. We have characterized the function of Rv2607 from Mycobacterium tuberculosis H37Rv and shown that it encodes a PNPOx that oxidizes PNP to PLP. The k(cat and K(M for this reaction were 0.01 s(-1 and 360 µM, respectively. Unlike many PNPOx enzymes, Rv2607 does not recognize PMP as a substrate.

  6. Medical Expenditure Panel Survey (MEPS) Summary Data Tables

    Data.gov (United States)

    U.S. Department of Health & Human Services — Summary Data Tables Data collected through MEPS are used to generate tables with frequently used summary statistics. These tables are available here for both the...

  7. Preparation and Purification of Xylitol-5-Phosphate from a Cell Extract of Lactobacillus casei Cl-16

    OpenAIRE

    Trahan, L.; Néron, S.; Bareil, M.

    1988-01-01

    A simple procedure which yields pure xylitol-5-phosphate is described. A cell extract of Lactobacillus casei Cl-16 from a 6-liter culture was used to synthesize up to 70 mg of xylitol-5-phosphate overnight from xylitol and phosphoenolpyruvate via a xylitol phosphoenolpyruvate:phosphotransferase system with a 53% yield. Centrifugation, filtration, precipitation as a barium salt, and ion-exchange batch chromatography permitted recovery of nearly 90% of the phosphorylated product synthesized. Th...

  8. Biosynthesis of riboflavin. Enzymatic formation of the xylene moiety from [14C]ribulose 5-phosphate.

    Science.gov (United States)

    Nielsen, P; Neuberger, G; Floss, H G; Bacher, A

    1984-02-14

    We have studied the enzymatic formation of the xylene ring of riboflavin using cell extracts from the flavinogenic yeast Candida guilliermondii. 5-Amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione or its 5'-phosphate could serve as substrates. In addition, a pentose phosphate or pentulose phosphate was required. Experiments with [14C]ribulose 5-phosphate gave evidence for the incorporation of the ribulose carbon atoms except C-4 into the xylene ring of the vitamin. PMID:6546684

  9. Host cells and methods for producing 1-deoxyxylulose 5-phosphate (DXP) and/or a DXP derived compound

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, James; Fortman, Jeffrey L.; Nishimoto, Minobu; Keasling, Jay D.

    2016-07-05

    The present invention provides for a genetically modified host cell capable of producing 1-deoxyxylulose 5-phosphate or 1-deoxy-D-xylulose 5-phosphate (DXP) (12), and optionally one or more DXP derived compounds, comprising: (a) a mutant RibB, or functional variant thereof, capable of catalyzing xylulose 5-phosphate and/or ribulose 5-phosphate to DXP, or (b) a YajO, or functional variant thereof, and a XylB, or functional variant thereof.

  10. Structural basis for Mep2 ammonium transceptor activation by phosphorylation.

    Science.gov (United States)

    van den Berg, Bert; Chembath, Anupama; Jefferies, Damien; Basle, Arnaud; Khalid, Syma; Rutherford, Julian C

    2016-04-18

    Mep2 proteins are fungal transceptors that play an important role as ammonium sensors in fungal development. Mep2 activity is tightly regulated by phosphorylation, but how this is achieved at the molecular level is not clear. Here we report X-ray crystal structures of the Mep2 orthologues from Saccharomyces cerevisiae and Candida albicans and show that under nitrogen-sufficient conditions the transporters are not phosphorylated and present in closed, inactive conformations. Relative to the open bacterial ammonium transporters, non-phosphorylated Mep2 exhibits shifts in cytoplasmic loops and the C-terminal region (CTR) to occlude the cytoplasmic exit of the channel and to interact with His2 of the twin-His motif. The phosphorylation site in the CTR is solvent accessible and located in a negatively charged pocket ∼30 Å away from the channel exit. The crystal structure of phosphorylation-mimicking Mep2 variants from C. albicans show large conformational changes in a conserved and functionally important region of the CTR. The results allow us to propose a model for regulation of eukaryotic ammonium transport by phosphorylation.

  11. Direct and indirect effects of RNA interference against pyridoxal kinase and pyridoxine 5'-phosphate oxidase genes in Bombyx mori.

    Science.gov (United States)

    Huang, ShuoHao; Yao, LiLi; Zhang, JianYun; Huang, LongQuan

    2016-08-01

    Vitamin B6 comprises six interconvertible pyridine compounds (vitamers), among which pyridoxal 5'-phosphate is a coenzyme involved in a high diversity of biochemical reactions. Humans and animals obtain B6 vitamers from diet, and synthesize pyridoxal 5'-phosphate by pyridoxal kinase and pyridoxine 5'-phosphate oxidase. Currently, little is known on how pyridoxal 5'-phosphate biosynthesis is regulated, and pyridoxal 5'-phosphate is supplied to meet their requirement in terms of cofactor. Bombyx mori is a large silk-secreting insect, in which protein metabolism is most active, and the vitamin B6 demand is high. In this study, we successfully down-regulated the gene expression of pyridoxal kinase and pyridoxine 5'-phosphate oxidase by body cavity injection of synthesized double-stranded small interfering RNA to 5th instar larvae of Bombyx mori, and analyzed the gene transcription levels of pyridoxal 5'-phosphate dependent enzymes, phosphoserine aminotransferase and glutamic-oxaloacetic transaminase. Results show that the gene expression of pyridoxal kinase and pyridoxine 5'-phosphate oxidase has a greater impact on the gene transcription of enzymes using pyridoxal 5'-phosphate as a cofactor in Bombyx mori. Our study suggests that pyridoxal 5'-phosphate biosynthesis and dynamic balance may be regulated by genetic networks.

  12. Direct and indirect effects of RNA interference against pyridoxal kinase and pyridoxine 5'-phosphate oxidase genes in Bombyx mori.

    Science.gov (United States)

    Huang, ShuoHao; Yao, LiLi; Zhang, JianYun; Huang, LongQuan

    2016-08-01

    Vitamin B6 comprises six interconvertible pyridine compounds (vitamers), among which pyridoxal 5'-phosphate is a coenzyme involved in a high diversity of biochemical reactions. Humans and animals obtain B6 vitamers from diet, and synthesize pyridoxal 5'-phosphate by pyridoxal kinase and pyridoxine 5'-phosphate oxidase. Currently, little is known on how pyridoxal 5'-phosphate biosynthesis is regulated, and pyridoxal 5'-phosphate is supplied to meet their requirement in terms of cofactor. Bombyx mori is a large silk-secreting insect, in which protein metabolism is most active, and the vitamin B6 demand is high. In this study, we successfully down-regulated the gene expression of pyridoxal kinase and pyridoxine 5'-phosphate oxidase by body cavity injection of synthesized double-stranded small interfering RNA to 5th instar larvae of Bombyx mori, and analyzed the gene transcription levels of pyridoxal 5'-phosphate dependent enzymes, phosphoserine aminotransferase and glutamic-oxaloacetic transaminase. Results show that the gene expression of pyridoxal kinase and pyridoxine 5'-phosphate oxidase has a greater impact on the gene transcription of enzymes using pyridoxal 5'-phosphate as a cofactor in Bombyx mori. Our study suggests that pyridoxal 5'-phosphate biosynthesis and dynamic balance may be regulated by genetic networks. PMID:27106120

  13. Structural mechanism of transcription regulation of the Staphylococcus aureus multidrug efflux operon mepRA by the MarR family repressor MepR.

    Science.gov (United States)

    Birukou, Ivan; Seo, Susan M; Schindler, Bryan D; Kaatz, Glenn W; Brennan, Richard G

    2014-02-01

    The multidrug efflux pump MepA is a major contributor to multidrug resistance in Staphylococcus aureus. MepR, a member of the multiple antibiotic resistance regulator (MarR) family, represses mepA and its own gene. Here, we report the structure of a MepR-mepR operator complex. Structural comparison of DNA-bound MepR with 'induced' apoMepR reveals the large conformational changes needed to allow the DNA-binding winged helix-turn-helix motifs to interact with the consecutive major and minor grooves of the GTTAG signature sequence. Intriguingly, MepR makes no hydrogen bonds to major groove nucleobases. Rather, recognition-helix residues Thr60, Gly61, Pro62 and Thr63 make sequence-specifying van der Waals contacts with the TTAG bases. Removing these contacts dramatically affects MepR-DNA binding activity. The wings insert into the flanking minor grooves, whereby residue Arg87, buttressed by Asp85, interacts with the O2 of T4 and O4' ribosyl oxygens of A23 and T4. Mutating Asp85 and Arg87, both conserved throughout the MarR family, markedly affects MepR repressor activity. The His14':Arg59 and Arg10':His35:Phe108 interaction networks stabilize the DNA-binding conformation of MepR thereby contributing significantly to its high affinity binding. A structure-guided model of the MepR-mepA operator complex suggests that MepR dimers do not interact directly and cooperative binding is likely achieved by DNA-mediated allosteric effects. PMID:24293644

  14. Mutations in Escherichia coli aceE and ribB Genes Allow Survival of Strains Defective in the First Step of the Isoprenoid Biosynthesis Pathway

    OpenAIRE

    Jordi Perez-Gil; Eva Maria Uros; Susanna Sauret-Güeto; Maria Lois, L.; James Kirby; Minobu Nishimoto; Baidoo, Edward E. K.; Jay D Keasling; Albert Boronat; Manuel Rodriguez-Concepcion

    2012-01-01

    A functional 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is required for isoprenoid biosynthesis and hence survival in Escherichia coli and most other bacteria. In the first two steps of the pathway, MEP is produced from the central metabolic intermediates pyruvate and glyceraldehyde 3-phosphate via 1-deoxy-D-xylulose 5-phosphate (DXP) by the activity of the enzymes DXP synthase (DXS) and DXP reductoisomerase (DXR). Because the MEP pathway is absent from humans, it was proposed as a pro...

  15. LuxS-independent formation of AI-2 from ribulose-5-phosphate

    Directory of Open Access Journals (Sweden)

    Hardie Kim R

    2008-06-01

    Full Text Available Abstract Background In many bacteria, the signal molecule AI-2 is generated from its precursor S-ribosyl-L-homocysteine in a reaction catalysed by the enzyme LuxS. However, generation of AI-2-like activity has also been reported for organisms lacking the luxS gene and the existence of alternative pathways for AI-2 formation in Escherichia coli has recently been predicted by stochastic modelling. Here, we investigate the possibility that spontaneous conversion of ribulose-5-phosphate could be responsible for AI-2 generation in the absence of luxS. Results Buffered solutions of ribulose-5-phosphate, but not ribose-5-phosphate, were found to contain high levels of AI-2 activity following incubation at concentrations similar to those reported in vivo. To test whether this process contributes to AI-2 formation by bacterial cells in vivo, an improved Vibrio harveyi bioassay was used. In agreement with previous studies, culture supernatants of E. coli and Staphylococcus aureus luxS mutants were found not to contain detectable levels of AI-2 activity. However, low activities were detected in an E. coli pgi-eda-edd-luxS mutant, a strain which degrades glucose entirely via the oxidative pentose phosphate pathway, with ribulose-5-phosphate as an obligatory intermediate. Conclusion Our results suggest that LuxS-independent formation of AI-2, via spontaneous conversion of ribulose-5-phosphate, may indeed occur in vivo. It does not contribute to AI-2 formation in wildtype E. coli and S. aureus under the conditions tested, but may be responsible for the AI-2-like activities reported for other organisms lacking the luxS gene.

  16. Expression of mep50 in adult and embryos of medaka fish (Oryzias latipes).

    Science.gov (United States)

    Cheng, Nana; Guo, Maomao; Chang, Pei; Zhang, Xueyan; Zhang, Runshuai; Qi, Chao; Zhong, Xueping; Zhou, Qingchun; Zhao, Haobin

    2016-06-01

    Protein arginine methylation is important for gene regulation and biological processes. Methylosome protein 50 (Mep50) is identified as a partner of protein arginine methyltransferase 5 (Prmt5), a major enzyme capable of symmetric dimethylation, in mammals and Xenopus. The isolation and characterization of medaka mep50 were reported in this paper. Medaka Mep50 is a homolog of human MEP50 with six WD40 domains. Medaka mep50 was ubiquitously expressed in the adult tissues and had maternal origin with continuous and dynamical expression during embryonic development detected by RT-PCR and in situ hybridization. A strong interaction of medaka Mep50 and Prmt5 was shown by yeast two hybridization. The expression pattern of mep50 is similar to that of prmt5 in medaka. The results suggested that medaka Mep50 could be a partner of Prmt5 and might play major roles in a variety of tissues in medaka. PMID:26749004

  17. Effect of exogenous hormones on transcription levels of pyridoxal 5'-phosphate biosynthetic enzymes in the silkworm (Bombyx mori).

    Science.gov (United States)

    Huang, ShuoHao; Yang, HuanHuan; Yao, LiLi; Zhang, JianYun; Huang, LongQuan

    2016-01-01

    Vitamin B6 includes 6 pyridine derivatives, among which pyridoxal 5'-phosphate is a coenzyme for over 140 enzymes. Animals acquire their vitamin B6 from food. Through a salvage pathway, pyridoxal 5'-phosphate is synthesized from pyridoxal, pyridoxine or pyridoxamine, in a series of reactions catalyzed by pyridoxal kinase and pyridoxine 5'-phosphate oxidase. The regulation of pyridoxal 5'-phospahte biosynthesis and pyridoxal 5'-phospahte homeostasis are at the center of study for vitamin B6 nutrition. How pyridoxal 5'-phosphate biosynthesis is regulated by hormones has not been reported so far. Our previous studies have shown that pyridoxal 5'-phosphate level in silkworm larva displays cyclic developmental changes. In the current study, effects of exogenous juvenile hormone and molting hormone on the transcription level of genes coding for the enzymes involved in the biosynthesis of pyridoxal 5'-phospahte were examined. Results show that pyridoxal kinase and pyridoxine 5'-phosphate oxidase are regulated at the transcription level by development and are responsive to hormones. Molting hormone stimulates the expression of genes coding for pyridoxal kinase and pyridoxine 5'-phosphate oxidase, and juvenile hormone appears to work against molting hormone. Whether pyridoxal 5'-phosphate biosynthesis is regulated by hormones in general is an important issue for further studies. PMID:26780217

  18. Phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ), a lipid signalling enigma.

    Science.gov (United States)

    Giudici, Maria-Luisa; Clarke, Jonathan H; Irvine, Robin F

    2016-05-01

    The phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are an important family of enzymes, whose physiological roles are being teased out by a variety of means. Phosphatidylinositol-5-phosphate 4-kinase γ (PI5P4Kγ) is especially intriguing as its in vitro activity is very low. Here we review what is known about this enzyme and discuss some recent advances towards an understanding of its physiology. Additionally, the effects of the ATP-competitive inhibitor I-OMe Tyrphostin AG-538 on all three mammalian PI5P4Ks was explored, including two PI5P4Kγ mutants with altered ATP- or PI5P-binding sites. The results suggest a strategy for targeting non-ATP binding sites on inositol lipid kinases. PMID:26710750

  19. Structural characterization of a ribose-5-phosphate isomerase B from the pathogenic fungus Coccidioides immitis

    Directory of Open Access Journals (Sweden)

    Leibly David J

    2011-10-01

    Full Text Available Abstract Background Ribose-5-phosphate isomerase is an enzyme that catalyzes the interconversion of ribose-5-phosphate and ribulose-5-phosphate. This family of enzymes naturally occurs in two distinct classes, RpiA and RpiB, which play an important role in the pentose phosphate pathway and nucleotide and co-factor biogenesis. Results Although RpiB occurs predominantly in bacteria, here we report crystal structures of a putative RpiB from the pathogenic fungus Coccidioides immitis. A 1.9 Å resolution apo structure was solved by combined molecular replacement and single wavelength anomalous dispersion (SAD phasing using a crystal soaked briefly in a solution containing a high concentration of iodide ions. RpiB from C. immitis contains modest sequence and high structural homology to other known RpiB structures. A 1.8 Å resolution phosphate-bound structure demonstrates phosphate recognition and charge stabilization by a single positively charged residue whereas other members of this family use up to five positively charged residues to contact the phosphate of ribose-5-phosphate. A 1.7 Å resolution structure was obtained in which the catalytic base of C. immitis RpiB, Cys76, appears to form a weakly covalent bond with the central carbon of malonic acid with a bond distance of 2.2 Å. This interaction may mimic that formed by the suicide inhibitor iodoacetic acid with RpiB. Conclusion The C. immitis RpiB contains the same fold and similar features as other members of this class of enzymes such as a highly reactive active site cysteine residue, but utilizes a divergent phosphate recognition strategy and may recognize a different substrate altogether.

  20. It takes two to tango: defining an essential second active site in pyridoxal 5'-phosphate synthase.

    Directory of Open Access Journals (Sweden)

    Cyril Moccand

    Full Text Available The prevalent de novo biosynthetic pathway of vitamin B6 involves only two enzymes (Pdx1 and Pdx2 that form an ornate multisubunit complex functioning as a glutamine amidotransferase. The synthase subunit, Pdx1, utilizes ribose 5-phosphate and glyceraldehyde 3-phosphate, as well as ammonia derived from the glutaminase activity of Pdx2 to directly form the cofactor vitamer, pyridoxal 5'-phosphate. Given the fact that a single enzyme performs the majority of the chemistry behind this reaction, a complicated mechanism is anticipated. Recently, the individual steps along the reaction co-ordinate are beginning to be unraveled. In particular, the binding of the pentose substrate and the first steps of the reaction have been elucidated but it is not known if the latter part of the chemistry, involving the triose sugar, takes place in the same or a disparate site. Here, we demonstrate through the use of enzyme assays, enzyme kinetics, and mutagenesis studies that indeed a second site is involved in binding the triose sugar and moreover, is the location of the final vitamin product, pyridoxal 5'-phosphate. Furthermore, we show that product release is triggered by the presence of a PLP-dependent enzyme. Finally, we provide evidence that a single arginine residue of the C terminus of Pdx1 is responsible for coordinating co-operativity in this elaborate protein machinery.

  1. Acetate selective fluorescent turn-on sensors derived using vitamin B6 cofactor pyridoxal-5-phosphate

    Science.gov (United States)

    Sharma, Darshna; Kuba, Aman; Thomas, Rini; Ashok Kumar, S. K.; Kuwar, Anil; Choi, Heung-Jin; Sahoo, Suban K.

    2016-03-01

    Two new Schiff base receptors have been synthesized by condensation of pyridoxal-5-phosphate with 2-aminophenol (L1) or aniline (L2). In DMSO, the receptors showed both chromogenic and 'turn-on' fluorescence responses selectively in the presence of AcO- and F-. However, in mixed DMSO-H2O medium, the receptors showed AcO- selective 'turn-on' fluorescence without any interference from other tested anions including F-. The detection limit for AcO- was found to be 7.37 μM and 22.9 μM using the receptors L1 and L2, respectively.

  2. Long-term effect of magnesium pyridoxal 5-phosphate glutamate in rabbits developing hypercholesterolemia.

    Science.gov (United States)

    Panagiotopoulos, T; Ketelsen, U P; Schmidt, A; Heuck, C C

    1986-08-01

    36 male rabbits were fed with a diet enriched with 20 g cholesterol/kg for a period of 8 weeks under a strict daily dietary control. Magnesium pyridoxal 5-phosphate glutamate (MPPG, Sedalipid) was supplemented to the diet at different quantities. Hypercholesterolemia developed later and less pronounced in animals receiving a medium or high dose of MPPG. Microscopical analysis indicated a protective effect of MPPG on calcium deposition in the aorta. The fatty acid pattern in serum showed only minor differences and was unchanged in liver extracts in animals supplemented with MPPG. This observation suggest that MPPG may act on the mechanism of cholesterol absorption in the intestine. PMID:3778558

  3. Functional and evolutionary analysis of DXL1, a non-essential gene encoding a 1-deoxy-D-xylulose 5-phosphate synthase like protein in Arabidopsis thaliana.

    Science.gov (United States)

    Carretero-Paulet, Lorenzo; Cairó, Albert; Talavera, David; Saura, Andreu; Imperial, Santiago; Rodríguez-Concepción, Manuel; Campos, Narciso; Boronat, Albert

    2013-07-15

    The synthesis of 1-deoxy-D-xylulose 5-phosphate (DXP), catalyzed by the enzyme DXP synthase (DXS), represents a key regulatory step of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis. In plants DXS is encoded by small multigene families that can be classified into, at least, three specialized subfamilies. Arabidopsis thaliana contains three genes encoding proteins with similarity to DXS, including the well-known DXS1/CLA1 gene, which clusters within subfamily I. The remaining proteins, initially named DXS2 and DXS3, have not yet been characterized. Here we report the expression and functional analysis of A. thaliana DXS2. Unexpectedly, the expression of DXS2 failed to rescue Escherichia coli and A. thaliana mutants defective in DXS activity. Coherently, we found that DXS activity was negligible in vitro, being renamed as DXL1 following recent nomenclature recommendation. DXL1 is targeted to plastids as DXS1, but shows a distinct expression pattern. The phenotypic analysis of a DXL1 defective mutant revealed that the function of the encoded protein is not essential for growth and development. Evolutionary analyses indicated that DXL1 emerged from DXS1 through a recent duplication apparently specific of the Brassicaceae lineage. Divergent selective constraints would have affected a significant fraction of sites after diversification of the paralogues. Furthermore, amino acids subjected to divergent selection and likely critical for functional divergence through the acquisition of a novel, although not yet known, biochemical function, were identified. Our results provide with the first evidences of functional specialization at both the regulatory and biochemical level within the plant DXS family.

  4. Da antiga à nova Filologia: o Projecto MEP-BPEDig.

    OpenAIRE

    Gonçalves, Maria Filomena; Banza, Ana Paula

    2013-01-01

    Neste artigo faz-se a descrição do projecto "Memória (Meta)linguística na Biblioteca Pública de Évora: Para uma Biblioteca Digital (MEP-BPEDig)", projecto que se centra em fontes existentes na bicentenária Biblioteca Pública de Évora. O projecto desenvolve-se no âmbito do CIDEHUS-UÉ e visa disponibilizar fontes relevantes para a História e Historiografia do Português.

  5. Evidence for a reactive cysteine at the nucleotide binding site of spinach ribulose-5-phosphate kinase

    International Nuclear Information System (INIS)

    Ribulose-5-phosphate kinase from spinach was rapidly inactivated by N-bromoacetylethanolamine phosphate in a bimolecular fashion with a k2 of 2.0 m-1 s-1 at 20C and pH 8.0. Ribulose 5-phosphate had little effect on the rate of inactivation, whereas complete protection was afforded by ADP or ATP. The extent of incorporation as determined with 14C-labeled reagent was about 1 molar equivalent per subunit in the presence of ATP with full retention of enzymatic activity, and about 2 molar equivalents per subunit in the completely inactivated enzyme. Amino acid analyses of enzyme derivatized with 14C-labeled reagent reveal that all of the covalently incorporated reagent was associated with cysteinyl residues. Hence, two sulfhydryls are reactive, but the inactivation correlates with alkylation of one cysteinyl residue at or near the enzyme's nucleotide binding site. The kinase was also extremely sensitive to the sulfhydryl reagents 5,5'-dithiobis(2-nitrobenzoic acid) and N-ethylmaleimide. The reactive sulfhydryl groups are likely to be those generated by reduction of a disulfide during activation. 20 references, 3 figures, 2 tables

  6. Identification of GutQ from Escherichia coli as a D-arabinose 5-phosphate isomerase.

    Science.gov (United States)

    Meredith, Timothy C; Woodard, Ronald W

    2005-10-01

    The glucitol operon (gutAEBDMRQ) of Escherichia coli encodes a phosphoenolpyruvate:sugar phosphotransferase system that metabolizes the hexitol D-glucitol (sorbitol). The functions for all but the last gene, gutQ, have been previously assigned. The high sequence similarity between GutQ and KdsD, a D-arabinose 5-phosphate isomerase (API) from the 3-deoxy-D-manno-octulosonate (KDO)-lipopolysaccharide (LPS) biosynthetic pathway, suggested a putative activity, but its role within the context of the gut operon remained unclear. Accordingly, the enzyme was cloned, overexpressed, and characterized. Recombinant GutQ was shown to indeed be a second copy of API from the E. coli K-12 genome with biochemical properties similar to those of KdsD, catalyzing the reversible aldol-ketol isomerization between D-ribulose 5-phosphate (Ru5P) and D-arabinose 5-phosphate (A5P). Genomic disruptions of each API gene were constructed in E. coli K-12. TCM11[(deltakdsD)] was capable of sustaining essential LPS synthesis at wild-type levels, indicating that GutQ functions as an API inside the cell. The gut operon remained inducible in TCM7[(deltagutQ)], suggesting that GutQ is not directly involved in d-glucitol catabolism. The conditional mutant TCM15[(deltagutQdeltakdsD)] was dependent on exogenous A5P both for LPS synthesis/growth and for upregulation of the gut operon. The phenotype was suppressed by complementation in trans with a plasmid encoding a functional copy of GutQ or by increasing the amount of A5P in the medium. As there is no obvious obligatory role for GutQ in the metabolism of d-glucitol and there is no readily apparent link between D-glucitol metabolism and LPS biosynthesis, it is suggested that A5P is not only a building block for KDO biosynthesis but also may be a regulatory molecule involved in expression of the gut operon.

  7. Ribose 5-phosphate isomerase inhibits LC3 processing and basal autophagy.

    Science.gov (United States)

    Heintze, Jacob; Costa, Joana R; Weber, Melanie; Ketteler, Robin

    2016-09-01

    Autophagy and cellular metabolism are tightly linked processes, but how individual metabolic enzymes regulate the process of autophagy is not well understood. This study implicates ribose-5-phosphate isomerase (RPIA), a key regulator of the pentose phosphate pathway, in the control of autophagy. We used a dual gene deletion strategy, combining shRNA-mediated knockdown studies with CRISPR/Cas9 genome editing. Knockdown of RPIA by shRNA or genomic deletion by CRISPR/Cas9 genome editing, results in an increase of ATG4B-mediated LC3 processing and in the appearance of LC3-positive autophagosomes in cells. Increased LC3 processing upon knockdown of RPIA can be reversed by treatment with the antioxidant N-acetyl cysteine. The results are consistent with a model in which RPIA suppresses autophagy and LC3 processing by modulation of redox signaling. PMID:27328773

  8. MESA/MEP at American River College: Year One Evaluation Report.

    Science.gov (United States)

    Lee, Beth S.; And Others

    In 1989, the Mathematics, Engineering, and Science Achievement (MESA)/Minority Engineering Program (MEP) was initiated at American River College. The MESA/MEP program recruits Black, Hispanic, and Native American students and provides assistance, encouragement, and enrichment programs to help them succeed in the fields of mathematics, engineering,…

  9. Binding and uptake of 125iodine-labelled, oxidized low density lipoprotein by macrophages: Comparison of the effects of α-tocopherol, probucol, pyridoxal-5'-phosphate and magnesium-pyridoxal-5'-phosphate-glutamate

    International Nuclear Information System (INIS)

    Specific and unspecific binding and uptake (internalization) by macrophages of 125iodine-labelled, copper-oxidized human low density lipoprotein is differently influenced by the anti-oxidants α-tocopherol (α-Toc), probucol (Prob), pyridoxal-5'-phosphate (PP) and the magnesium-pyridoxal-5'-phosphate glutamate complex (MPPG). Binding as well as internalization, mediated by the so-called 'scavenger receptor' is lower in the presence of MPPG whereas both specific binding and internalization are enhanced. The comparison of the effects in vitro allows a rating of the potentially anti-atherogenic and thus protective effects of the tested substances as follows: MPPG>PP>α-Toc>Prob. (orig.)

  10. Binding and uptake of 125iodine-labelled, oxidized low density lipoprotein by macrophages: comparison of the effects of alpha-tocopherol, probucol, pyridoxal-5'-phosphate and magnesium-pyridoxal-5'-phosphate-glutamate.

    Science.gov (United States)

    Selmer, D; Senekowitsch-Schmidtke, R; Schneider, W; Elstner, E F

    1997-01-01

    Specific and unspecific binding and uptake (internalization) by macrophages of 125iodine-labelled, copper-oxidized human low density lipoprotein is differently influenced by the anti-oxidants alpha-tocopherol (alpha-Toc), probucol (Prob), pyridoxal-5'-phosphate (PP) and the magnesium-pyridoxal-5'-phosphate glutamate complex (MPPG). Binding as well as internalization, mediated by the so-called "scavenger receptor" is lower in the presence of MPPG whereas both specific binding and internalization are enhanced. The comparison of the effects in vitro allows a rating of the potentially anti-atherogenic and thus protective effects of the tested substances as follows: MPPG > PP > alpha-Toc > Prob. PMID:9090072

  11. Binding and uptake of {sup 125}iodine-labelled, oxidized low density lipoprotein by macrophages: Comparison of the effects of {alpha}-tocopherol, probucol, pyridoxal-5`-phosphate and magnesium-pyridoxal-5`-phosphate-glutamate

    Energy Technology Data Exchange (ETDEWEB)

    Selmer, D. [Technische Univ. Muenchen, Freising-Weihenstephan (Germany). Lehrstuhl fuer Phytopathologie; Senekowitsch-Schmidtke, R. [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik; Schneider, W. [Steigerwald Arzneimittel, Darmstadt (Germany); Elstner, E.F. [Technische Univ. Muenchen, Freising-Weihenstephan (Germany). Lehrstuhl fuer Phytopathologie

    1997-01-01

    Specific and unspecific binding and uptake (internalization) by macrophages of {sup 125}iodine-labelled, copper-oxidized human low density lipoprotein is differently influenced by the anti-oxidants {alpha}-tocopherol ({alpha}-Toc), probucol (Prob), pyridoxal-5`-phosphate (PP) and the magnesium-pyridoxal-5`-phosphate glutamate complex (MPPG). Binding as well as internalization, mediated by the so-called `scavenger receptor` is lower in the presence of MPPG whereas both specific binding and internalization are enhanced. The comparison of the effects in vitro allows a rating of the potentially anti-atherogenic and thus protective effects of the tested substances as follows: MPPG>PP>{alpha}-Toc>Prob. (orig.)

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

    Science.gov (United States)

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

    2009-07-01

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

  13. Magnesium pyridoxal 5-phosphate glutamate reduces hyperlipidaemia in patients with chronic renal insufficiency.

    Science.gov (United States)

    Kirsten, R; Heintz, B; Nelson, K; Sieberth, H G; Oremek, G; Hasford, J; Speck, U

    1988-01-01

    Chronic renal insufficiency is often accompanied by hyperlipidaemia and subsequent coronary heart disease. Two groups of 15 patients with serum creatinine greater than 2 mg/100 ml and serum cholesterol less than 250 mg/100 ml were given 3 x 50 mg magnesium pyridoxal 5-phosphate glutamate (MPPG) or placebo for 12 weeks in a double-blind, randomised study. Total cholesterol in the MPPG group (282.4 mg.100 ml-1) was lower than in the placebo group (354.3 mg.100 ml-1) after 12 weeks of treatment. Triglycerides in the MPPG group were 265.1 mg.100 ml-1 compared to 361.9 mg.100 ml-1. After 12 weeks on MPPG the LDL/HDL ratio of 3.56 was lower than in the placebo group-6.83. Side effects in the MPPG group were similar to those in the placebo group. Thus, MPPG was an effective antihyperlipidaemic agent in patients with renal insufficiency. PMID:3383985

  14. Structural insight for substrate tolerance to 2-deoxyribose-5-phosphate aldolase from the pathogen Streptococcus suis.

    Science.gov (United States)

    Cao, Thinh-Phat; Kim, Joong-Su; Woo, Mi-Hee; Choi, Jin Myung; Jun, Youngsoo; Lee, Kun Ho; Lee, Sung Haeng

    2016-04-01

    2-deoxyribose-5-phosphate aldolase (DERA) is a class I aldolase that catalyzes aldol condensation of two aldehydes in the active site, which is particularly germane in drug manufacture. Structural and biochemical studies have shown that the active site of DERA is typically loosely packed and displays broader substrate specificity despite sharing conserved folding architecture with other aldolases. The most distinctive structural feature of DERA compared to other aldolases is short and flexible C-terminal region. This region is also responsible for substrate recognition. Therefore, substrate tolerance may be related to the C-terminal structural features of DERA. Here, we determined the crystal structures of full length and C-terminal truncated DERA from Streptococcus suis (SsDERA). In common, both contained the typical (α/β)8 TIM-barrel fold of class I aldolases. Surprisingly, C-terminal truncation resulting in missing the last α9 and β8 secondary elements, allowed DERA to maintain activity comparable to the fulllength enzyme. Specifically, Arg186 and Ser205 residues at the C-terminus appeared mutually supplemental or less indispensible for substrate phosphate moiety recognition. Our results suggest that DERA might adopt a shorter C-terminal region than conventional aldolases during evolution pathway, resulting in a broader range of substrate tolerance through active site flexibility. PMID:27033207

  15. Pyridoxal 5'-phosphate is a slow tight binding inhibitor of E. coli pyridoxal kinase.

    Directory of Open Access Journals (Sweden)

    Mohini S Ghatge

    Full Text Available Pyridoxal 5'-phosphate (PLP is a cofactor for dozens of B(6 requiring enzymes. PLP reacts with apo-B(6 enzymes by forming an aldimine linkage with the ε-amino group of an active site lysine residue, thus yielding the catalytically active holo-B(6 enzyme. During protein turnover, the PLP is salvaged by first converting it to pyridoxal by a phosphatase and then back to PLP by pyridoxal kinase. Nonetheless, PLP poses a potential toxicity problem for the cell since its reactive 4'-aldehyde moiety forms covalent adducts with other compounds and non-B(6 proteins containing thiol or amino groups. The regulation of PLP homeostasis in the cell is thus an important, yet unresolved issue. In this report, using site-directed mutagenesis, kinetic, spectroscopic and chromatographic studies we show that pyridoxal kinase from E. coli forms a complex with the product PLP to form an inactive enzyme complex. Evidence is presented that, in the inhibited complex, PLP has formed an aldimine bond with an active site lysine residue during catalytic turnover. The rate of dissociation of PLP from the complex is very slow, being only partially released after a 2-hour incubation with PLP phosphatase. Interestingly, the inactive pyridoxal kinase•PLP complex can be partially reactivated by transferring the tightly bound PLP to an apo-B(6 enzyme. These results open new perspectives on the mechanism of regulation and role of pyridoxal kinase in the Escherichia coli cell.

  16. Effect of magnesium pyridoxal 5-phosphate glutamate on vascular reactivity in experimental hypercholesterolemia.

    Science.gov (United States)

    Khayyal, M T; Khayyal, M A; Sharaf, H M; el-Sherbeeny, M; Okpanyi, S N; Schneider, W

    1998-01-01

    Hypercholesterolemia is known to affect the responsiveness of various blood vessels to endogenous and to exogenous vasoactive agents. Of particular interest is the increased responsiveness to vasoconstrictors, e.g., 5-hydroxy tryptamine and noradrenaline, and the decreased reactivity towards vasodilators, e.g., acetylcholine. This, together with the development of arteriosclerosis, could play an important role in the progression of many vascular complications, such as hypertension and coronary heart disease. Magnesium pyridoxal 5-phosphate glutamate (MPPG) has been shown to effectively reduce serum lipids in animals and in man, and to retard the progression of atherosclerotic lesions in experimental animals. It was therefore considered of interest to investigate the reactivity of both the aorta and the renal artery to different vasoactive substances in hypercholesterolemic rabbits under the influence of MPPG as well as the effect of such substances on the blood pressure of the anesthetized animals. The rabbits were fed a high cholesterol diet for 2 months, followed by MPPG for 1 month, while keeping the rabbits on the same diet. One batch of animals was used for blood pressure recording and testing drug effects, and another was used for testing the responsiveness of their aortae and renal arteries to the different mediators. In hypercholesterolemic rabbits, treatment with MPPG tended to normalize the increased responsiveness of the blood pressure to the vasoconstrictors: noradrenaline and angiotensin and the diminished sensitivity to histamine and acetylcholine. For the isolated arteries, however, MPPG did not significantly affect the responses to noradrenaline nor potassium chloride, but tended to normalize responses to clonidine and acetylcholine. It could be concluded from the present findings that the high cholesterol diet induces changes in vascular reactivity which are possibly related to endothelial and/or receptor sensitivity changes. Treatment with MPPG

  17. 78 FR 21109 - Manufacturing Extension Partnership (MEP) Center for Nebraska; Availability of Funds

    Science.gov (United States)

    2013-04-09

    ... National Institute of Standards and Technology Manufacturing Extension Partnership (MEP) Center for... applicants for funding projects that provide manufacturing extension services to primarily small- and medium... obtained by contacting Diane Henderson, National Institute of Standards and Technology,...

  18. 77 FR 12563 - Manufacturing Extension Partnership (MEP) Centers for South Dakota and Kentucky; Availability of...

    Science.gov (United States)

    2012-03-01

    ... National Institute of Standards and Technology Manufacturing Extension Partnership (MEP) Centers for South... eligible proposers for funding projects to provide manufacturing extension services to primarily small- and... Diane Henderson, National Institute of Standards and Technology, Manufacturing Extension...

  19. APPLICATION OF NEW TECHNOLOGY: MEPS AND LC-MS/MS FOR DETERMINATION OF THERAPEUTIC DRUGS

    OpenAIRE

    Said, Rana

    2010-01-01

    Bioanalysis most often requires an extraction procedure to isolate the target compounds from a complex matrix. The aim of this work was to evaluate microextraction in packed syringe (MEPS) performance as a sample preparation technique by developing new analytical methods for different categories of compounds utilizing MEPS in combination with LC-MS/MS. The overall goal was to provide high throughput methods that can offer automation, on-line coupling to mass spectrometry and...

  20. Hamsters vaccinated with Ace-mep-7 DNA vaccine produced protective immunity against Ancylostoma ceylanicum infection.

    Science.gov (United States)

    Wiśniewski, Marcin; Jaros, Sławomir; Bąska, Piotr; Cappello, Michael; Długosz, Ewa; Wędrychowicz, Halina

    2016-04-01

    Hookworms are intestinal nematodes that infect up to 740 million people, mostly in tropical and subtropical regions. Adult worms suck blood from damaged vessels in the gut mucosa, digesting hemoglobin using aspartic-, cysteine- and metalloproteases. Targeting aspartic hemoglobinases using drugs or vaccines is therefore a promising approach to ancylostomiasis control. Based on homology to metalloproteases from other hookworm species, we cloned the Ancylostoma ceylanicum metalloprotease 7 cDNA (Ace-mep-7). The corresponding Ace-MEP-7 protein has a predicted molecular mass of 98.8 kDa. The homology to metallopeptidases from other hookworm species and its predicted transmembrane region support the hypothesis that Ace-MEP-7 may be involved in hemoglobin digestion in the hookworm gastrointestinal tract, especially that our analyses show expression of Ace-mep-7 in the adult stage of the parasite. Immunization of Syrian golden hamsters with Ace-mep-7 cDNA resulted in 50% (p < 0.01) intestinal worm burden reduction. Additionally 78% (p < 0.05) egg count reduction in both sexes was observed. These results suggest that immunization with Ace-mep-7 may contribute to reduction in egg count released into the environment during the A. ceylanicum infection. PMID:26795262

  1. Experimental Evidence for a Revision in the Annotation of Putative Pyridoxamine 5'-Phosphate Oxidases P(N/MP from Fungi.

    Directory of Open Access Journals (Sweden)

    Tatiana Domitrovic

    Full Text Available Pyridoxinamine 5'-phosphate oxidases (P(N/MP oxidases that bind flavin mononucleotide (FMN and oxidize pyridoxine 5'-phosphate or pyridoxamine 5'-phosphate to form pyridoxal 5'-phosphate (PLP are an important class of enzymes that play a central role in cell metabolism. Failure to generate an adequate supply of PLP is very detrimental to most organisms and is often clinically manifested as a neurological disorder in mammals. In this study, we analyzed the function of YLR456W and YPR172W, two homologous genes of unknown function from S. cerevisiae that have been annotated as putative P(N/MP oxidases based on sequence homology. Different experimental approaches indicated that neither protein catalyzes PLP formation nor binds FMN. On the other hand, our analysis confirmed the enzymatic activity of Pdx3, the S. cerevisiae protein previously implicated in PLP biosynthesis by genetic and structural characterization. After a careful sequence analysis comparing the putative and confirmed P(N/MP oxidases, we found that the protein domain (PF01243 that led to the YLR456W and YPR172W annotation is a poor indicator of P(N/MP oxidase activity. We suggest that a combination of two Pfam domains (PF01243 and PF10590 present in Pdx3 and other confirmed P(N/MP oxidases would be a stronger predictor of this molecular function. This work exemplifies the importance of experimental validation to rectify genome annotation and proposes a revision in the annotation of at least 400 sequences from a wide variety of fungal species that are homologous to YLR456W and are currently misrepresented as putative P(N/MP oxidases.

  2. A unique arabinose 5-phosphate isomerase found within a genomic island associated with the uropathogenicity of Escherichia coli CFT073.

    Science.gov (United States)

    Mosberg, Joshua A; Yep, Alejandra; Meredith, Timothy C; Smith, Sara; Wang, Pan-Fen; Holler, Tod P; Mobley, Harry L T; Woodard, Ronald W

    2011-06-01

    Previous studies showed that deletion of genes c3405 to c3410 from PAI-metV, a genomic island from Escherichia coli CFT073, results in a strain that fails to compete with wild-type CFT073 after a transurethral cochallenge in mice and is deficient in the ability to independently colonize the mouse kidney. Our analysis of c3405 to c3410 suggests that these genes constitute an operon with a role in the internalization and utilization of an unknown carbohydrate. This operon is not found in E. coli K-12 but is present in a small number of pathogenic E. coli and Shigella boydii strains. One of the genes, c3406, encodes a protein with significant homology to the sugar isomerase domain of arabinose 5-phosphate isomerases but lacking the tandem cystathionine beta-synthase domains found in the other arabinose 5-phosphate isomerases of E. coli. We prepared recombinant c3406 protein, found it to possess arabinose 5-phosphate isomerase activity, and characterized this activity in detail. We also constructed a c3406 deletion mutant of E. coli CFT073 and demonstrated that this deletion mutant was still able to compete with wild-type CFT073 in a transurethral cochallenge in mice and could colonize the mouse kidney. These results demonstrate that the presence of c3406 is not essential for a pathogenic phenotype.

  3. Why Do MEPs Defect? An Analysis of Party Group Cohesion in the 5 th European Parliament

    Directory of Open Access Journals (Sweden)

    Thorsten Faas

    2002-03-01

    Full Text Available This study analyses party group cohesion and patterns of defections of national party delegations from party group lines in the present European Parliament, using a total of 1,370 roll call votes. The study confirms previous findings according to which party groups in the EP show (surprisingly high levels of cohesion. In addition and notwithstanding that, it reveals the circumstances under which MEPs and their national delegations are more likely to defect. Among other factors, it was analysed how the nature of the candidate selection process, the electoral system, and the relationships between MEPs and their home parties influence these defections. Assuming that MEPs have three different goals (re-election, office, and policy and want to first of all secure re-election, one can theoretically expect that those MEPs whose chances of re-election are more dependent on national parties than others’ (due to their specific candidate selection process or their relationship to their home party are more willing to vote against the party group line, if a conflict between party group and national party emerges. Empirically, this is confirmed. In other words, MEPs in general are very well aware of their specific situation. They know who deserves their primary attention and they act accordingly.

  4. Why Do MEPs Defect? An Analysis of Party Group Cohesion in the 5 th European Parliament

    Directory of Open Access Journals (Sweden)

    Thorsten Faas

    2002-03-01

    Full Text Available This study analyses party group cohesion and patterns of defections of national party delegations from party group lines in the present European Parliament, using a total of 1,370 roll call votes. The study confirms previous findings according to which party groups in the EP show (surprisingly high levels of cohesion. In addition and notwithstanding that, it reveals the circumstances under which MEPs and their national delegations are more likely to defect. Among other factors, it was analysed how the nature of the candidate selection process, the electoral system, and the relationships between MEPs and their home parties influence these defections. Assuming that MEPs have three different goals (re-election, office, and policy and want to first of all secure re-election, one can theoretically expect that those MEPs whose chances of re-election are more dependent on national parties than others (due to their specific candidate selection process or their relationship to their home party are more willing to vote against the party group line, if a conflict between party group and national party emerges. Empirically, this is confirmed. In other words, MEPs in general are very well aware of their specific situation. They know who deserves their primary attention and they act accordingly.

  5. MEP solution for a minimal climate model: success and limitation of a variational problem

    Directory of Open Access Journals (Sweden)

    S. Pascale

    2011-05-01

    Full Text Available Maximum Entropy Production conjecture (MEP is applied to a minimal four-box model of climate which accounts for both horizontal and vertical material heat fluxes. It is shown that, under condition of fixed insolation, a MEP solution is found with reasonably realistic temperature and heat fluxes, thus generalising results from independent two-box horizontal or vertical models. It is also shown that the meridional and the vertical entropy production terms are independently involved in the maximisation and thus MEP can be applied to each subsystem with fixed boundary conditions. We then extend the four-box model by increasing its number of degrees of freedom, and test its realism by comparing it with a GCM output. An order-of-magnitude evaluation of contributions to the material entropy production (≈50 mW m−2 K−1 due to horizontal and vertical processes within the climate system is carried out by using ad hoc temperature fields. It turns out that approximately 40 mW m−2 K−1 is the entropy production due to vertical heat transport and 5–7 mW m−2 K−1 to horizontal heat transport. A MEP solution is found which is fairly realistic as far as the horizontal large scale organisation of the surface climate is concerned whereas the vertical structure looks to be unrealistic and presents seriously unstable features. Finally a more general problem is investigated in which the longwave transmissivity is varied simultaneously with the temperature. This leads to a MEP solution characterised by a much warmer climate, with very vigorous vertical heat fluxes, in which the atmosphere is opaque to longwave radiation. A critical discussion about how to interpret MEP and how to apply it in a physically correct way concludes the paper.

  6. Characterization of three putative xylulose 5-phosphate/fructose 6-phosphate phosphoketolases in the cyanobacterium Anabaena sp. PCC 7120.

    Science.gov (United States)

    Moriyama, Takashi; Tajima, Naoyuki; Sekine, Kohsuke; Sato, Naoki

    2015-01-01

    Xylulose 5-phosphate/fructose 6-phosphate phosphoketolase (Xfp) is a key enzyme in the central carbohydrate metabolism in heterofermentative bacteria, in which enzymatic property of Xfps is well characterized. This is not the case in other microbes. The cyanobacterium Anabaena sp. PCC 7120 possesses three putative genes encoding Xfp, all1483, all2567, and alr1850. We purified three putative Xfps as recombinant proteins. The results of gel filtration indicated that these proteins form homomultimer complex. All1483 and All2567 showed phosphoketolase activity, whereas Alr1850 did not show the activity. Kinetic analyses demonstrated that substrates, fructose 6-phosphate and inorganic phosphate, are cooperatively bound to enzymes positively and negatively, respectively.

  7. Preliminary X-ray crystallographic analysis of the d-xylulose 5-phosphate phosphoketolase from Lactococcus lactis

    International Nuclear Information System (INIS)

    The expression, purification, preliminary crystallization and crystallographic analysis of phosphoketolase from L. lactis ssp. lactis (strain IL 1403) are reported. Phosphoketolases are thiamine diphosphate-dependent enzymes which play a central role in the pentose-phosphate pathway of heterofermentative lactic acid bacteria. They belong to the family of aldehyde-lyases and in the presence of phosphate ion cleave the carbon–carbon bond of the specific substrate d-xylulose 5-phosphate (or d-fructose 6-phosphate) to give acetyl phosphate and d-glyceraldehyde 3-phosphate (or d-erythrose 4-phosphate). Structural information about phosphoketolases is particularly important in order to fully understand their mechanism as well as the steric course of phosphoketolase-catalyzed reactions. Here, the purification, preliminary crystallization and crystallographic characterization of d-xylulose 5-phosphate phosphoketolase from Lactococcus lactis are reported. The presence of thiamine diphosphate during purification was essential for the enzymatic activity of the purified protein. The crystals belonged to the monoclinic space group P21. Diffraction data were obtained to a resolution of 2.2 Å

  8. Formation of xylitol and xylitol-5-phosphate and its impact on growth of d-xylose-utilizing Corynebacterium glutamicum strains.

    Science.gov (United States)

    Radek, Andreas; Müller, Moritz-Fabian; Gätgens, Jochem; Eggeling, Lothar; Krumbach, Karin; Marienhagen, Jan; Noack, Stephan

    2016-08-10

    Wild-type Corynebacterium glutamicum has no endogenous metabolic activity for utilizing the lignocellulosic pentose d-xylose for cell growth. Therefore, two different engineering approaches have been pursued resulting in platform strains harbouring a functional version of either the Isomerase (ISO) or the Weimberg (WMB) pathway for d-xylose assimilation. In a previous study we found for C. glutamicum WMB by-product formation of xylitol during growth on d-xylose and speculated that the observed lower growth rates are due to the growth inhibiting effect of this compound. Based on a detailed phenotyping of the ISO, WMB and the wild-type strain of C. glutamicum, we here show that this organism has a natural capability to synthesize xylitol from d-xylose under aerobic cultivation conditions. We furthermore observed the intracellular accumulation of xylitol-5-phosphate as a result of the intracellular phosphorylation of xylitol, which was particularly pronounced in the C. glutamicum ISO strain. Interestingly, low amounts of supplemented xylitol strongly inhibit growth of this strain on d-xylose, d-glucose and d-arabitol. These findings demonstrate that xylitol is a suitable substrate of the endogenous xylulokinase (XK, encoded by xylB) and its overexpression in the ISO strain leads to a significant phosphorylation of xylitol in C. glutamicum. Therefore, in order to circumvent cytotoxicity by xylitol-5-phosphate, the WMB pathway represents an interesting alternative route for engineering C. glutamicum towards efficient d-xylose utilization. PMID:27297548

  9. 34 CFR 200.89 - MEP allocations; Re-interviewing; Eligibility documentation; and Quality control.

    Science.gov (United States)

    2010-07-01

    ... determining eligibility and in conducting quality control procedures know the requirements for accurately... documentation; and Quality control. 200.89 Section 200.89 Education Regulations of the Offices of the Department...-interviewing; Eligibility documentation; and Quality control. (a) Allocation of funds under the MEP for...

  10. Cloning and Expression Analysis of MEP Pathway Enzyme-encoding Genes in Osmanthus fragrans

    Directory of Open Access Journals (Sweden)

    Chen Xu

    2016-09-01

    Full Text Available The 2-C-methyl-d-erythritol 4-phosphate (MEP pathway is responsible for the biosynthesis of many crucial secondary metabolites, such as carotenoids, monoterpenes, plastoquinone, and tocopherols. In this study, we isolated and identified 10 MEP pathway genes in the important aromatic plant sweet osmanthus (Osmanthus fragrans. Multiple sequence alignments revealed that 10 MEP pathway genes shared high identities with other reported proteins. The genes showed distinctive expression profiles in various tissues, or at different flower stages and diel time points. The qRT-PCR results demonstrated that these genes were highly expressed in inflorescences, which suggested a tissue-specific transcript pattern. Our results also showed that OfDXS1, OfDXS2, and OfHDR1 had a clear diurnal oscillation pattern. The isolation and expression analysis provides a strong foundation for further research on the MEP pathway involved in gene function and molecular evolution, and improves our understanding of the molecular mechanism underlying this pathway in plants.

  11. How Reproducible Are Transcranial Magnetic Stimulation-Induced MEPs in Subacute Stroke?

    NARCIS (Netherlands)

    Hoonhorst, Maurits H. W. J.; Kollen, Boudewijn J.; van den Berg, Peter S. P.; Emmelot, Cornelis H.; Kwakkel, Gert

    2014-01-01

    Purpose: Motor evoked potentials (MEPs) and total motor conduction time (TMCT) induced by transcranial magnetic stimulation (TMS) are used to make assumptions about the prognosis of motor outcome after stroke. Understanding the different sources of variability is fundamental to the concept of reliab

  12. Non-oxidative synthesis of pentose 5-phosphate from hexose 6-phosphate and triose phosphate by the L-type pentose pathway.

    Science.gov (United States)

    Williams, J F; Blackmore, P F

    1983-01-01

    1. Ribose 5-phosphate was non-oxidatively synthesized from glucose 6-phosphate and triose phosphate by an enzyme extract prepared from rat liver (RLEP). Analysis of the intermediates by GLC, ion-exchange chromatography and specific enzymatic analysis, revealed the presence of the following intermediates of the L-type pentose pathway: altro-heptulose 1,7-bisphosphate, arabinose 5-phosphate and D-glycero D-ido octulose 8-phosphate. 2. With either [1-14C] or [2-14C]glucose 6-phosphate as diagnostic substrates, the distribution of 14C in ribose 5-phosphate was determined. At early time intervals (0.5-8 hr), [1-14C]glucose 6-phosphate introduced 14C into C-1, C-3 and C-5 of ribose 5-phosphate, at 17 hr 14C was confined to C-1. With [2-14C]glucose 6-phosphate as substrate, 14C was confined to C-2, C-3 and C-5 of ribose 5-phosphate during early times (0.5-8 hr), while at 17 hr 14C was located in C-2. 3. The transketolase exchange reaction, [14C]ribose 5-phosphate + altro-heptulose 7-phosphate in equilibrium ribose 5-phosphate + [14C]altro-heptulose 7-phosphate, was demonstrated for the first time using purified transketolase, its activity was measured and it is proposed to play a major role in the relocation of 14C into C-3 and C-5 or ribose 5-phosphate during the prediction labelling experiments. 4. The coupled transketolase-transaldolase reactions, 2 fructose 6-phosphate in equilibrium altro-heptulose 7-phosphate + xylulose 5-phosphate and 2 altro-heptulose 7-phosphate in equilibrium fructose 6-phosphate + D-glycero D-altro octulose 8-phosphate were demonstrated with purified enzymes, but are concluded to play a minor role in the non-oxidative synthesis of pentose 5-phosphate and octulose phosphate by (RLEP). 5. The formation of gem diol and dimers of erythrose 4-phosphate is proposed to account in part for the failure to detect monomeric erythrose 4-phosphate in the carbon balance studies. 6. The equilibrium value for the pentose pathway acting by the reverse mode in

  13. Online political communication strategies: MEPs e-representation and self-representation

    OpenAIRE

    Lilleker, Darren; Koc-Michalska, Karolina

    2013-01-01

    Research into the communication strategies of legislators has a long history. The European Parliament offers an opportunity to add to understanding of how legislators prioritise styles of communication, with a comparative perspective across twenty-seven nations. Through content analysis of online communication we investigate how the Internet is used by MEPs. Our analysis assesses three communication strategies: homestyle, impression management and participatory. We find that a homestyle strat...

  14. Prior history of FDI muscle contraction: different effect on MEP amplitude and muscle activity.

    Science.gov (United States)

    Talis, V L; Kazennikov, O V; Castellote, J M; Grishin, A A; Ioffe, M E

    2014-03-01

    Motor evoked potentials (MEPs) in the right first dorsal interosseous (FDI) muscle elicited by transcranial magnetic stimulation of left motor cortex were assessed in ten healthy subjects during maintenance of a fixed FDI contraction level. Subjects maintained an integrated EMG (IEMG) level with visual feedback and reproduced this level by memory afterwards in the following tasks: stationary FDI muscle contraction at the level of 40 ± 5 % of its maximum voluntary contraction (MVC; 40 % task), at the level of 20 ± 5 % MVC (20 % task), and also when 20 % MVC was preceded by either no contraction (0-20 task), by stronger muscle contraction (40-20 task) or by no contraction with a previous strong contraction (40-0-20 task). The results show that the IEMG level was within the prescribed limits when 20 and 40 % stationary tasks were executed with and without visual feedback. In 0-20, 40-20, and 40-0-20 tasks, 20 % IEMG level was precisely controlled in the presence of visual feedback, but without visual feedback the IEMG and force during 20 % IEMG maintenance were significantly higher in the 40-0-20 task than those in 0-20 and 40-20 tasks. That is, without visual feedback, there were significant variations in muscle activity due to different prehistory of contraction. In stationary tasks, MEP amplitudes in 40 % task were higher than in 20 % task. MEPs did not differ significantly during maintenance of the 20 % level in tasks with different prehistory of muscle contraction with and without visual feedback. Thus, in spite of variations in muscle background activity due to different prehistory of contraction MEPs did not vary significantly. This dissociation suggests that the voluntary maintenance of IEMG level is determined not only by cortical mechanisms, as reflected by corticospinal excitability, but also by lower levels of CNS, where afferent signals and influences from other brain structures and spinal cord are convergent.

  15. Why Do MEPs Defect? An Analysis of Party Group Cohesion in the 5 th European Parliament

    OpenAIRE

    Thorsten Faas

    2002-01-01

    This study analyses party group cohesion and patterns of defections of national party delegations from party group lines in the present European Parliament, using a total of 1,370 roll call votes. The study confirms previous findings according to which party groups in the EP show (surprisingly) high levels of cohesion. In addition and notwithstanding that, it reveals the circumstances under which MEPs and their national delegations are more likely to defect. Among other factors, it was analys...

  16. Reconstruction and evaluation of the synthetic bacterial MEP pathway in Saccharomyces cerevisiae.

    Science.gov (United States)

    Partow, Siavash; Siewers, Verena; Daviet, Laurent; Schalk, Michel; Nielsen, Jens

    2012-01-01

    Isoprenoids, which are a large group of natural and chemical compounds with a variety of applications as e.g. fragrances, pharmaceuticals and potential biofuels, are produced via two different metabolic pathways, the mevalonate (MVA) pathway and the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Here, we attempted to replace the endogenous MVA pathway in Saccharomyces cerevisiae by a synthetic bacterial MEP pathway integrated into the genome to benefit from its superior properties in terms of energy consumption and productivity at defined growth conditions. It was shown that the growth of a MVA pathway deficient S. cerevisiae strain could not be restored by the heterologous MEP pathway even when accompanied by the co-expression of genes erpA, hISCA1 and CpIscA involved in the Fe-S trafficking routes leading to maturation of IspG and IspH and E. coli genes fldA and fpr encoding flavodoxin and flavodoxin reductase believed to be responsible for electron transfer to IspG and IspH. PMID:23285068

  17. The Integration of MEPs from Central and Eastern Europe into the European Parliament

    Directory of Open Access Journals (Sweden)

    Radko Hokovský

    2012-04-01

    Full Text Available This article evaluates the level of integration of Members of the European Parliament from Central and Eastern Europe in the European Parliament after the EU enlargements of 2004 and 2007. The main objective is to address the puzzle of how the European Parliament’s political groups could maintain or even increase their voting cohesion after the influx of a significantly large number of new MEPs coming from countries with different historical experience, socio-economic characteristics, and political and party systems. Three indicators of MEP integration are defined: integration into parliamentary leadership, integration into parliamentary work, and integration into voting patterns. The article uses data from the VoteWatch.eu website on MEPs’ activities and voting between the years 2004-2011, as well as data from official documents of the European Parliament and its political groups. Analysis of the data reveals that the new member states’ MEPs were significantly under-represented in parliamentary leadership and key legislative activities, despite the fact that their voting loyalty to their political groups was greater than that of their colleagues from older member states.

  18. Crosstalk between MAV and MEP pathways in vitro grape plants exposed to UV-B radiation

    International Nuclear Information System (INIS)

    The synthesis of terpenoids from IPP (isopentenyl diphosphate) proceeds in plants throughout two pathways, the MVA (mevalonic acid) in cytosol and the MEP (2-C-methyl-D-erythritol 4-phosphate) in plastids. Ultraviolet-B (UV-B) radiation induced the synthesis of terpenes in in vitro grape plants according to the fluence rate. Low intensity UV-B promoted the MVA pathway while high intensity UV-B stimulated the MEP pathway. Mevastatin is known to inhibit the enzyme HMG-CoA reductase blocking terpene synthesis in cytosol. In vitro plants growing 45 days under 16 h-photoperiod (100 μmol m-2 s-1) were fed at the apex with mevastatin and then exposed to an UV-B dose administrated at two intensities: low UV-B (8.25 μW cm-2,16 h) or high UV-B (33 μW cm-2,4 h). Methanol: chloroform extracts were analyzed by GC-EIMS and compared with controls without mevastatin. Levels of γ-Sitosterol and Stigmasterol were significantly increased under low intensity UV-B in the controls. The plants treated with the inhibitor showed a significant decrease of both sterols and a decrease in the plastidial terpenes but sterols were higher under UV-B. These results suggest an IPP crosstalk between the MAV and MEP pathways under restrictive conditions. (authors)

  19. Molecular cloning and enzymological characterization of pyridoxal 5'-phosphate independent aspartate racemase from hyperthermophilic archaeon Thermococcus litoralis DSM 5473.

    Science.gov (United States)

    Washio, Tsubasa; Kato, Shiro; Oikawa, Tadao

    2016-09-01

    We succeeded in expressing the aspartate racemase homolog gene from Thermococcus litoralis DSM 5473 in Escherichia coli Rosetta (DE3) and found that the gene encodes aspartate racemase. The aspartate racemase gene consisted of 687 bp and encoded 228 amino acid residues. The purified enzyme showed aspartate racemase activity with a specific activity of 1590 U/mg. The enzyme was a homodimer with a molecular mass of 56 kDa and did not require pyridoxal 5'-phosphate as a coenzyme. The enzyme showed aspartate racemase activity even at 95 °C, and the activation energy of the enzyme was calculated to be 51.8 kJ/mol. The enzyme was highly thermostable, and approximately 50 % of its initial activity remained even after incubation at 90 °C for 11 h. The enzyme showed a maximum activity at a pH of 7.5 and was stable between pH 6.0 and 7.0. The enzyme acted on L-cysteic acid and L-cysteine sulfinic acid in addition to D- and L-aspartic acids, and was strongly inhibited by iodoacetic acid. The site-directed mutagenesis of the enzyme showed that the essential cysteine residues were conserved as Cys83 and Cys194. D-Forms of aspartic acid, serine, alanine, and valine were contained in T. litoralis DSM 5473 cells. PMID:27438592

  20. Combinatorial engineering of 1-deoxy-D-xylulose 5-phosphate pathway using cross-lapping in vitro assembly (CLIVA method.

    Directory of Open Access Journals (Sweden)

    Ruiyang Zou

    Full Text Available The ability to assemble multiple fragments of DNA into a plasmid in a single step is invaluable to studies in metabolic engineering and synthetic biology. Using phosphorothioate chemistry for high efficiency and site specific cleavage of sequences, a novel ligase independent cloning method (cross-lapping in vitro assembly, CLIVA was systematically and rationally optimized in E. coli. A series of 16 constructs combinatorially expressing genes encoding enzymes in the 1-deoxy-D-xylulose 5-phosphate (DXP pathway were assembled using multiple DNA modules. A plasmid (21.6 kb containing 16 pathway genes, was successfully assembled from 7 modules with high efficiency (2.0 x 10(3 cfu/ µg input DNA within 2 days. Overexpressions of these constructs revealed the unanticipated inhibitory effects of certain combinations of genes on the production of amorphadiene. Interestingly, the inhibitory effects were correlated to the increase in the accumulation of intracellular methylerythritol cyclodiphosphate (MEC, an intermediate metabolite in the DXP pathway. The overexpression of the iron sulfur cluster operon was found to modestly increase the production of amorphadiene. This study demonstrated the utility of CLIVA in the assembly of multiple fragments of DNA into a plasmid which enabled the rapid exploration of biological pathways.

  1. Thermophilic Thermotoga maritima ribose-5-phosphate isomerase RpiB: optimized heat treatment purification and basic characterization.

    Science.gov (United States)

    Sun, Fangfang; Zhang, Xiao-Zhou; Myung, Suwan; Zhang, Y-H Percival

    2012-04-01

    The open reading frame TM1080 from Thermotoga maritima encoding ribose-5-phosphate isomerase type B (RpiB) was cloned and over-expressed in Escherichia coli BL21 (DE3). After optimization of cell culture conditions, more than 30% of intracellular proteins were soluble recombinant RpiB. High-purity RpiB was obtained by heat pretreatment through its optimization in buffer choice, buffer pH, as well as temperature and duration of pretreatment. This enzyme had the maximum activity at 70°C and pH 6.5-8.0. Under its suboptimal conditions (60°C and pH 7.0), k(cat) and K(m) values were 540s(-1) and 7.6mM, respectively; it had a half lifetime of 71h, resulting in its turn-over number of more than 2×10(8)mol of product per mol of enzyme. This study suggests that it is highly feasible to discover thermostable enzymes from exploding genomic DNA database of extremophiles with the desired stability suitable for in vitro synthetic biology projects and produce high-purity thermoenzymes at very low costs. PMID:22333529

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

    Science.gov (United States)

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

    2016-04-01

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

  3. Biosynthesis of ribose-5-phosphate and erythrose-4-phosphate in archaea: a phylogenetic analysis of archaeal genomes

    Directory of Open Access Journals (Sweden)

    Tim Soderberg

    2005-01-01

    Full Text Available A phylogenetic analysis of the genes encoding enzymes in the pentose phosphate pathway (PPP, the ribulose monophosphate (RuMP pathway, and the chorismate pathway of aromatic amino acid biosynthesis, employing data from 13 complete archaeal genomes, provides a potential explanation for the enigmatic phylogenetic patterns of the PPP genes in archaea. Genomic and biochemical evidence suggests that three archaeal species (Methanocaldococcus jannaschii, Thermoplasma acidophilum and Thermoplasma volcanium produce ribose-5-phosphate via the nonoxidative PPP (NOPPP, whereas nine species apparently lack an NOPPP but may employ a reverse RuMP pathway for pentose synthesis. One species (Halobacterium sp. NRC-1 lacks both the NOPPP and the RuMP pathway but may possess a modified oxidative PPP (OPPP, the details of which are not yet known. The presence of transketolase in several archaeal species that are missing the other two NOPPP genes can be explained by the existence of differing requirements for erythrose-4-phosphate (E4P among archaea: six species use transketolase to make E4P as a precursor to aromatic amino acids, six species apparently have an alternate biosynthetic pathway and may not require the ability to make E4P, and one species (Pyrococcus horikoshii probably does not synthesize aromatic amino acids at all.

  4. Large-Scale Domain Motions and Pyridoxal-5'-Phosphate Assisted Radical Catalysis in Coenzyme B12-Dependent Aminomutases

    Directory of Open Access Journals (Sweden)

    Amarendra Nath Maity

    2014-02-01

    Full Text Available Lysine 5,6-aminomutase (5,6-LAM and ornithine 4,5-aminomutase (4,5-OAM are two of the rare enzymes that use assistance of two vitamins as cofactors. These enzymes employ radical generating capability of coenzyme B12 (5'-deoxyadenosylcobalamin, dAdoCbl and ability of pyridoxal-5'-phosphate (PLP, vitamin B6 to stabilize high-energy intermediates for performing challenging 1,2-amino rearrangements between adjacent carbons. A large-scale domain movement is required for interconversion between the catalytically inactive open form and the catalytically active closed form. In spite of all the similarities, these enzymes differ in substrate specificities. 4,5-OAM is highly specific for D-ornithine as a substrate while 5,6-LAM can accept D-lysine and L-β-lysine. This review focuses on recent computational, spectroscopic and structural studies of these enzymes and their implications on the related enzymes. Additionally, we also discuss the potential biosynthetic application of 5,6-LAM.

  5. The effect of pyridoxal-5-phosphate on serum alanine aminotransferase activity in dogs suffering from canine babesiosis

    Directory of Open Access Journals (Sweden)

    E.C. Myburgh

    2009-09-01

    Full Text Available Accurate measurements of serum aminotransferase (ALT activity in dogs relies on the endogenous pro-enzyme pyridoxal 5-phosphate (P5P. The purpose of this study was to determine whether the exclusion of P5P from the analytical method causes an underestimation of serum ALT activity in dogs suffering from babesiosis and in those manifesting evidence of hepatocellular damage, and to determine if anorexia causes sufficient P5P depletion to affect in vitro serum ALT activity. One-hundred-and-twenty healthy control dogs and 105 Babesia-infected dogs were included in the study. Two methods for ALT measurement were used: Method 1 included P5P, and Method 2 excluded P5P from the reaction mixture. Higher serum ALT activity was measured with Method 1 in the Babesia-infected dogs (P < 0.001, as well as in 14 dogs with suspected hepatocellular damage (P = 0.03. Duration of anorexia had no effect, irrespective of the method used. Although inclusion of P5P to the reaction mixture consistently resulted in higher measured serum ALT activity, the differences were too small to have led to incorrect diagnoses in the Babesia-infected dogs suspected of liver disease.

  6. Poisoning pyridoxal 5-phosphate-dependent enzymes: a new strategy to target the malaria parasite Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Ingrid B Müller

    Full Text Available The human malaria parasite Plasmodium falciparum is able to synthesize de novo pyridoxal 5-phosphate (PLP, a crucial cofactor, during erythrocytic schizogony. However, the parasite possesses additionally a pyridoxine/pyridoxal kinase (PdxK to activate B6 vitamers salvaged from the host. We describe a strategy whereby synthetic pyridoxyl-amino acid adducts are channelled into the parasite. Trapped upon phosphorylation by the plasmodial PdxK, these compounds block PLP-dependent enzymes and thus impair the growth of P. falciparum. The novel compound PT3, a cyclic pyridoxyl-tryptophan methyl ester, inhibited the proliferation of Plasmodium very efficiently (IC(50-value of 14 microM without harming human cells. The non-cyclic pyridoxyl-tryptophan methyl ester PT5 and the pyridoxyl-histidine methyl ester PHME were at least one order of magnitude less effective or completely ineffective in the case of the latter. Modeling in silico indicates that the phosphorylated forms of PT3 and PT5 fit well into the PLP-binding site of plasmodial ornithine decarboxylase (PfODC, the key enzyme of polyamine synthesis, consistent with the ability to abolish ODC activity in vitro. Furthermore, the antiplasmodial effect of PT3 is directly linked to the capability of Plasmodium to trap this pyridoxyl analog, as shown by an increased sensitivity of parasites overexpressing PfPdxK in their cytosol, as visualized by GFP fluorescence.

  7. Application of a Colorimetric Assay to Identify Putative Ribofuranosylaminobenzene 5'-Phosphate Synthase Genes Expressed with Activity in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Bechard Matthew E.

    2003-01-01

    Full Text Available Tetrahydromethanopterin (H4MPT is a tetrahydrofolate analog originally discovered in methanogenic archaea, but later found in other archaea and bacteria. The extent to which H4MPT occurs among living organisms is unknown. The key enzyme which distinguishes the biosynthetic pathways of H4MPT and tetrahydrofolate is ribofuranosylaminobenzene 5'-phosphate synthase (RFAP synthase. Given the importance of RFAP synthase in H4MPT biosynthesis, the identification of putative RFAP synthase genes and measurement of RFAP synthase activity would provide an indication of the presence of H4MPT in untested microorganisms. Investigation of putative archaeal RFAP synthase genes has been hampered by the tendency of the resulting proteins to form inactive inclusion bodies in Escherichia coli. The current work describes a colorimetric assay for measuring RFAP synthase activity, and two modified procedures for expressing recombinant RFAP synthase genes to produce soluble, active enzyme. By lowering the incubation temperature during expression, RFAP synthase from Archaeoglobus fulgidus was produced in E. coli and purified to homogeneity. The production of active RFAP synthase from Methanothermobacter thermautotrophicus was achieved by coexpression of the gene MTH0830 with a molecular chaperone. This is the first direct biochemical identification of a methanogen gene that codes for an active RFAP synthase.

  8. Crystal Structure of 1-Deoxy-D-xylulose 5-Phosphate Synthase, A Crucial Enzyme for Isoprenoids Biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Xiang,S.; Usunow, G.; Busch, G.; Tong, L.

    2007-01-01

    Isopentenyl pyrophosphate (IPP) is a common precursor for the synthesis of all isoprenoids, which have important functions in living organisms. IPP is produced by the mevalonate pathway in archaea, fungi, and animals. In contrast, IPP is synthesized by a mevalonate-independent pathway in most bacteria, algae, and plant plastids. 1-Deoxy-D-xylulose 5-phosphate synthase (DXS) catalyzes the first and the rate-limiting step of the mevalonate-independent pathway and is an attractive target for the development of novel antibiotics, antimalarials, and herbicides. We report here the first structural information on DXS, from Escherichia coli and Deinococcus radiodurans, in complex with the coenzyme thiamine pyrophosphate (TPP). The structure contains three domains (I, II, and III), each of which bears homology to the equivalent domains in transketolase and the E1 subunit of pyruvate dehydrogenase. However, DXS has a novel arrangement of these domains as compared with the other enzymes, such that the active site of DXS is located at the interface of domains I and II in the same monomer, whereas that of transketolase is located at the interface of the dimer. The coenzyme TPP is mostly buried in the complex, but the C-2 atom of its thiazolium ring is exposed to a pocket that is the substrate-binding site. The structures identify residues that may have important roles in catalysis, which have been confirmed by our mutagenesis studies.

  9. Method of preparing highly active and thermostable preparations of liver uridin-kinase usable for enzymic synthesis of radioactive nucleoside-5'-phosphates

    International Nuclear Information System (INIS)

    A method is described of preparing a high-activity uridine kinase for the enzymic synthesis of radioactive nucleoside-5m-phosphates of the pyrimidine series. The preparation is separated from male rat liver after intraperitoneal application of 5'-azacytidine. Examples are given showing detailed procedures for the conversion of uridine and 6-azauridine to the corresponding 5'-phosphates. (L.K.)

  10. The role of 1-deoxy-d-xylulose-5-phosphate synthase and phytoene synthase gene family in citrus carotenoid accumulation.

    Science.gov (United States)

    Peng, Gang; Wang, Chunyan; Song, Song; Fu, Xiumin; Azam, Muhammad; Grierson, Don; Xu, Changjie

    2013-10-01

    Three 1-deoxy-D-xylulose-5-phosphate synthases (DXS) and three phytoene synthases (PSY) were identified in citrus, from Affymetrix GeneChip Citrus Genome Array, GenBank and public orange genome databases. Tissue-specific expression analysis of these genes was carried out on fruit peel and flesh, flower and leaf of Satsuma mandarin (Citrus unshiu Marc.) in order to determine their roles in carotenoid accumulation in different tissues. Expression of CitDXS1 and CitPSY1 was highest in all test tissues, while that of CitDXS2 and CitPSY2 was lower, and that of CitDXS3 and CitPSY3 undetectable. The transcript profiles of CitDXS1 and CitPSY1 paralleled carotenoid accumulation in flesh of Satsuma mandarin and orange (Citrus sinensis Osbeck) during fruit development, and CitPSY1 expression was also associated with carotenoid accumulation in peel, while the CitDXS1 transcript level was only weakly correlated with carotenoid accumulation in peel. Similar results were obtained following correlation analysis between expression of CitDXS1 and CitPSY1 and carotenoid accumulation in peel and flesh of 16 citrus cultivars. These findings identify CitPSY1 and CitDXS1 as the main gene members controlling carotenoid biosynthesis in citrus fruit. Furthermore, chromoplasts were extracted from flesh tissue of these citrus, and chromoplasts of different shape (spindle or globular), different size, and color depth were observed in different cultivars, indicating chromoplast abundance, number per gram tissue, size and color depth were closely correlated with carotenoid content in most cultivars. The relationship between carotenoid biosynthesis and chromoplast development was discussed.

  11. MEP Latencies Predict the Neuromodulatory Effect of cTBS Delivered to the Ipsilateral and Contralateral Sensorimotor Cortex.

    Directory of Open Access Journals (Sweden)

    Gan Huang

    Full Text Available Recently, it was shown that the highly variable after-effect of continuous theta-burst stimulation (cTBS of the primary motor cortex (M1 can be predicted by the latency of motor-evoked potentials (MEPs recorded before cTBS. This suggests that at least part of this inter-individual variability is driven by differences in the neuronal populations preferentially activated by transcranial magnetic stimulation (TMS.Here, we recorded MEPs, TMS-evoked brain potentials (TEPs and somatosensory-evoked potentials (SEPs to investigate the effects of cTBS delivered over the primary sensorimotor cortex on both the ipsilateral and contralateral M1, and the ipsilateral and contralateral primary somatosensory cortex (S1.We confirm that the after-effects of cTBS can be predicted by the latency of MEPs recorded before cTBS. Over the hemisphere onto which cTBS was delivered, short-latency MEPs at baseline were associated with an increase of MEP magnitude (i.e. an excitatory effect of cTBS whereas late-latency MEPs were associated with reduced MEPs (i.e. an inhibitory effect of cTBS. This relationship was reversed over the contralateral hemisphere, indicating opposite effects of cTBS on the responsiveness of the ipsilateral and contralateral M1. Baseline MEP latencies also predicted changes in the magnitude of the N100 wave of TEPs elicited by stimulation of the ipsilateral and contralateral hemisphere, indicating that this TEP component is specifically dependent on the state of M1. Finally, there was a reverse relationship between MEP latency and the effects of cTBS on the SEP waveforms (50-130 ms, indicating that after-effects of cTBS on S1 are opposite to those on M1.Taken together, our results confirm that the variable after-effects of cTBS can be explained by differences in the neuronal populations activated by TMS. Furthermore, our results show that this variability also determines remote effects of cTBS in S1 and the contralateral hemisphere, compatible with

  12. Synthesis and biological evaluation with plant cells of new fosmidomycin analogues containing a benzoxazolone or oxazolopyridinone ring.

    Science.gov (United States)

    Courtois, Martine; Mincheva, Zoia; Andreu, Françoise; Rideau, Marc; Viaud-Massuard, Marie-Claude

    2004-12-01

    Fosmidomycin, 3-(N-formyl-N-hydroxyamido) propylphosphonic acid sodium salt, is an efficient inhibitor of 1-deoxy-D-xylulose-5-phosphate (DOXP) reductoisomerase, the second enzyme of the 2C-methyl-D-erythritol-4-phosphate (MEP) pathway notably present in Plasmodium species. We have synthesized a new series of analogues of fosmidomycin, containing a benzoxazolone, benzoxazolethione or oxazolopyridinone ring. As the MEP pathway is involved in the biosynthesis of all isoprenoids, accumulation of ajmalicine in Catharanthus roseus cells was chosen as a marker of monoterpenoid indole alkaloid (MIA) production. None of the twelve studied phosphonic esters 3 and phosphonic acids 4 affected periwinkle cell growth, but some of them (3c, 3e, 3g and 3h) showed a significant inhibition of ajmalicine accumulation: 45-85% at 125 microM. Surprisingly, this effect disappeared by conversion of 3c and 3g into the corresponding acids 4c and 4g, respectively.

  13. Reduced neuronal expression of ribose-5-phosphate isomerase enhances tolerance to oxidative stress, extends lifespan, and attenuates polyglutamine toxicity in Drosophila

    OpenAIRE

    Wang, Ching-Tzu; Chen, Yi-Chun; Wang, Yi-Yun; Huang, Ming-Hao; Yen, Tzu-Li; Li, Hsun; Liang, Cyong-Jhih; Sang, Tzu-Kang; Cho, Si-Chih; Yuh, Chiou-Hwa; Wang, Chao-Yung; Brummel, Theodore J.; Wang, Horng-Dar

    2011-01-01

    Aging and age-related diseases can be viewed as the result of the lifelong accumulation of stress insults. The identification of mutant strains and genes which are responsive to stress and can alter longevity profiles provides new therapeutic targets for age-related diseases. Here we reported that a Drosophila strain with reduced expression of ribose-5-phosphate isomerase (rpi), EP2456, exhibits increased resistance to oxidative stress and enhanced lifespan. In addition, the strain also displ...

  14. TNF-α-induced down-regulation of CDX2 suppresses MEP1A expression in colitis

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Olsen, Anders Krüger; Holm, Thomas Lindebo;

    2012-01-01

    High levels of pro-inflammatory cytokines are linked to inflammatory bowel disease (IBD). The transcription factor Caudal-related homeobox transcription factor 2 (CDX2) plays a crucial role in differentiation of intestinal epithelium and regulates IBD-susceptibility genes, including meprin 1A (ME......A). The aim was to investigate the expression of CDX2 and MEP1A in colitis; to assess if they are regulated by tumor necrosis factor-α (TNF-α), and finally to reveal if CDX2 is involved in a TNF-α-induced down-regulation of MEP1A....

  15. Microcomputer Materials from MEP. An Annotated Directory of Packages of Interest to Further Education. An Occasional Paper.

    Science.gov (United States)

    Gilbert, Leslie

    Designed to disseminate information to the post-school sector of United Kingdom education, this directory provides information on 50 microcomputer software packages developed by the Microelectronics Education Program (MEP) and available through educational publishers. Subject areas represented include accountancy, biology, business education,…

  16. [Properties of 2,5-diamino-4-oxy-6-ribosylaminopyrimidine-5'- phosphate reductase, a enzyme of the second stage of flavinogenesis in Pichia guilliermondii yeasts].

    Science.gov (United States)

    Logvinenko, E M; Shavlovskiĭ, G M; Zakal'skiĭ, A E; Kontorovskaia, N Iu

    1989-01-01

    2,5-Diamino-4-oxy-6-ribosylaminopyrimidine-5'-phosphate reductase has been isolated from cells of Pichia guilliermondii and subjected to 20-fold purification by treating extracts with streptomycin sulphate, frationating proteins (NH4)2SO4 at 45-75% of saturation and chromatography on blue sepharose CL-6B. The use of gel filtration through Sephadex G-150 and chromatography on DEAE-cellulose proved to be less effective for the enzyme purification. It has been established that it is 2,5-diamino-4-oxy-6-ribosylaminopyrimidine-5-phosphate but not its dephosphorylated form that is the substrate of the given reductase; Km is equal to 7.10(-5) M. The reaction proceeds in the presence of NADPH or NADH. The enzyme affinity to NADPH (Km = 4.7.10(-5) M) is approximately one order higher than that to NADPH (Km = 5.5.10(-4) M). The enzyme manifests the optimum of action at pH 7.2 and the temperature of 37 degrees C; the molecular weight is 140 kD. EDTA as well as flavins in the concentration of 1.10(-3) M exert no effect on the reductase activity. The enzyme is labile at 4 degrees C and is inactivated in the frozen state at -15 degrees C. The 2.5-diamino-4-oxy-6-ribosylaminopyrimidine-5'-phosphate reductase has been also revealed in Torulopsis candida, Debaryomyces klöckeri, Schwanniomyces occidentalis, Eremothecium ashbyii (flavinogenic species) and Candida utilis. Aspergillus nidulans, Neurospora crassa (nonflavinogenic species). The synthesis of this enzyme contrary to other enzymes of the riboflavin biosynthesis is not regulated in flavinogenic yeast by iron ions. PMID:2511652

  17. [Properties of 2,5-diamino-4-oxy-6-ribosylaminopyrimidine-5'- phosphate reductase, a enzyme of the second stage of flavinogenesis in Pichia guilliermondii yeasts].

    Science.gov (United States)

    Logvinenko, E M; Shavlovskiĭ, G M; Zakal'skiĭ, A E; Kontorovskaia, N Iu

    1989-01-01

    2,5-Diamino-4-oxy-6-ribosylaminopyrimidine-5'-phosphate reductase has been isolated from cells of Pichia guilliermondii and subjected to 20-fold purification by treating extracts with streptomycin sulphate, frationating proteins (NH4)2SO4 at 45-75% of saturation and chromatography on blue sepharose CL-6B. The use of gel filtration through Sephadex G-150 and chromatography on DEAE-cellulose proved to be less effective for the enzyme purification. It has been established that it is 2,5-diamino-4-oxy-6-ribosylaminopyrimidine-5-phosphate but not its dephosphorylated form that is the substrate of the given reductase; Km is equal to 7.10(-5) M. The reaction proceeds in the presence of NADPH or NADH. The enzyme affinity to NADPH (Km = 4.7.10(-5) M) is approximately one order higher than that to NADPH (Km = 5.5.10(-4) M). The enzyme manifests the optimum of action at pH 7.2 and the temperature of 37 degrees C; the molecular weight is 140 kD. EDTA as well as flavins in the concentration of 1.10(-3) M exert no effect on the reductase activity. The enzyme is labile at 4 degrees C and is inactivated in the frozen state at -15 degrees C. The 2.5-diamino-4-oxy-6-ribosylaminopyrimidine-5'-phosphate reductase has been also revealed in Torulopsis candida, Debaryomyces klöckeri, Schwanniomyces occidentalis, Eremothecium ashbyii (flavinogenic species) and Candida utilis. Aspergillus nidulans, Neurospora crassa (nonflavinogenic species). The synthesis of this enzyme contrary to other enzymes of the riboflavin biosynthesis is not regulated in flavinogenic yeast by iron ions.

  18. Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Martin Ligr

    Full Text Available Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR and estrogen receptor (ER in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis.

  19. D-Ribulose 5-Phosphate 3-Epimerase: Functional and Structural Relationships to Members of the Ribulose-Phosphate Binding (beta/alpha)8-Barrel Superfamily

    International Nuclear Information System (INIS)

    The 'ribulose phosphate binding' superfamily defined by the Structural Classification of Proteins (SCOP) database is considered the result of divergent evolution from a common (β/α)8-barrel ancestor. The superfamily includes D-ribulose 5-phosphate 3-epimerase (RPE), orotidine 5'-monophosphate decarboxylase (OMPDC), and 3-keto-L-gulonate 6-phosphate decarboxylase (KGPDC), members of the OMPDC suprafamily, as well as enzymes involved in histidine and tryptophan biosynthesis that utilize phosphorylated metabolites as substrates. We now report studies of the functional and structural relationships of RPE to the members of the superfamily. As suggested by the results of crystallographic studies of the RPEs from rice and Plasmodium falciparum, the RPE from Streptococcus pyogenes is activated by Zn2+ which binds with a stoichiometry of one ion per polypeptide. Although wild type RPE has a high affinity for Zn2+ and inactive apoenzyme cannot be prepared, the affinity for Zn2+ is decreased by alanine substitutions for the two histidine residues that coordinate the Zn2+ ion (H34A and H67A); these mutant proteins can be prepared in an inactive, metal-free form and activated by exogenous Zn2+. The crystal structure of the RPE was solved at 1.8 Angstroms resolution in the presence of D-xylitol 5-phosphate, an inert analogue of the D-xylulose 5-phosphate substrate. This structure suggests that the 2,3-enediolate intermediate in the 1,1-proton transfer reaction is stabilized by bidentate coordination to the Zn2+ that also is liganded to His 34, Asp 36, His 67, and Asp 176; the carboxylate groups of the Asp residues are positioned also to function as the acid/base catalysts. Although the conformation of the bound analogue resembles those of ligands bound in the active sites of OMPDC and KGPDC, the identities of the active site residues that coordinate the essential Zn2+ and participate as acid/base catalysts are not conserved. We conclude that only the phosphate binding motif

  20. A higher number of TMS-elicited MEP from a combined hotspot improves intra- and inter-session reliability of the upper limb muscles in healthy individuals.

    Science.gov (United States)

    Bastani, Andisheh; Jaberzadeh, Shapour

    2012-01-01

    We aimed to determine, using transcranial magnetic stimulation (TMS), the number of elicited motor evoked potentials (MEPs) that induces the highest intra- and inter-sessions reliability for the extensor carpi radialis (ECR) and first dorsal interosseus (FDI) muscles. Twelve healthy subjects participated in this study on two separate days. Single pulse magnetic stimuli were triggered with Magstim 200(2) to obtain MEPs from the muscles of interest, with the subjects in a relaxed position. Reliability of MEP responses was investigated in three blocks of 5, 10 and 15 trials. The intra- and inter-session reliability of the MEPs' amplitudes and latencies were assessed using intraclass correlation coefficients (ICCs). Repeated measures ANOVA and paired t-tests revealed no significant time effect in the MEP amplitude and latency measurements (P>0.05). The ICCs indicated high intra-session reliability in the MEPs' amplitudes for the ECR and FDI muscles (0.77 to 0.99, 0.90 to 0.99, respectively) and latency (0.80 to 1.00, 0.75 to 0.97, respectively). The MEPs' amplitudes also had high inter-session reliability (0.84 to 0.97, 0.88 to 0.93, respectively), as did their latency (0.80 to 0.90, 0.75 to 0.97, respectively). Highest intra- and inter-session reliability was achieved for blocks of 10 and 15 trials. Our data suggest that intra- and inter-session comparisons should be performed using at least 10 MEPs in "combined hotspot" stimulation technique to ensure highest reliability.

  1. A higher number of TMS-elicited MEP from a combined hotspot improves intra- and inter-session reliability of the upper limb muscles in healthy individuals.

    Directory of Open Access Journals (Sweden)

    Andisheh Bastani

    Full Text Available We aimed to determine, using transcranial magnetic stimulation (TMS, the number of elicited motor evoked potentials (MEPs that induces the highest intra- and inter-sessions reliability for the extensor carpi radialis (ECR and first dorsal interosseus (FDI muscles. Twelve healthy subjects participated in this study on two separate days. Single pulse magnetic stimuli were triggered with Magstim 200(2 to obtain MEPs from the muscles of interest, with the subjects in a relaxed position. Reliability of MEP responses was investigated in three blocks of 5, 10 and 15 trials. The intra- and inter-session reliability of the MEPs' amplitudes and latencies were assessed using intraclass correlation coefficients (ICCs. Repeated measures ANOVA and paired t-tests revealed no significant time effect in the MEP amplitude and latency measurements (P>0.05. The ICCs indicated high intra-session reliability in the MEPs' amplitudes for the ECR and FDI muscles (0.77 to 0.99, 0.90 to 0.99, respectively and latency (0.80 to 1.00, 0.75 to 0.97, respectively. The MEPs' amplitudes also had high inter-session reliability (0.84 to 0.97, 0.88 to 0.93, respectively, as did their latency (0.80 to 0.90, 0.75 to 0.97, respectively. Highest intra- and inter-session reliability was achieved for blocks of 10 and 15 trials. Our data suggest that intra- and inter-session comparisons should be performed using at least 10 MEPs in "combined hotspot" stimulation technique to ensure highest reliability.

  2. Stability of pyridoxal-5-phosphate semicarbazone: applications in plasma vitamin B6 analysis and population surveys of vitamin B6 nutritional status.

    Science.gov (United States)

    Ubbink, J B; Serfontein, W J; de Villiers, L S

    1985-08-01

    The determination of pyridoxal-5-phosphate (PLP) and pyridoxal (PL) in plasma requires the availability of dark room facilities, due to the photosensitivity of these vitamin B6 vitamers. The fact that the semicarbazone forms of PL and PLP are more strongly fluorescent than the underivatized B6 vitamers has been exploited in plasma analyses, but it was not previously realised that these semicarbazone forms are also very stable even under conditions that lead to rapid decomposition of free PL and PLP. The stabilisation of PLP and PL obtained in this manner is sufficient and fully adequate to meet the practical requirements of clinical field studies. We report a high-performance liquid chromatographic method for plasma PLP and PL determinations based on precolumn semicarbazone formation and fluorescence detection. The method is sensitive enough for quantitative plasma PLP determinations even in B6-deficient patients. PMID:4055950

  3. Preparation of riboflavin 5' - phosphate sodium from crude riboflavin%利用核黄素粗品制备核黄素5'-磷酸钠

    Institute of Scientific and Technical Information of China (English)

    魏转; 周强; 孙文敬; 崔凤杰; 张铎; 余泗莲

    2011-01-01

    The objective of the present study was to investigate the feasibility of preparing riboflavin 5' - phosphate sodium from crude riboflavin. Riboflavin 5'-phosphate sodium was obtained with the yield of 68. 5% by reacting one mole of crude riboflavin with four moles of POC13 for 2 h at 35℃ , hydrolyzing the resulting mixture, and neutralizing with NaOH solution. The quality of obtained product met the requirements of US FCC (7 ). The phosphorylation reaction conditions of riboflavin was further optimized by one-factor-at-a-time experiment design, and results were: n ( POC13 ) / n ( VB2 ) 4. 6, n (POC13) /n (H20) 1.65, reaction time 2h, and reaction temperature 35 ± 1℃. Under the above condition, the yield of riboflavin 5'-phosphate sodium increased to above 73. 5%. This method significantly decreases production cost. In conclusion, preparation of riboflavin 5'-phosphate sodium from crude riboflavin was determined to be feasible e-conomically and technically.%探索利用核黄素粗品制备核黄素5'-磷酸钠的可行性.在吡啶和乙腈的混合溶剂中,使核黄素粗品与其4倍摩尔量的三氯氧磷35℃左右下反应2h,然后水解反应混合物,再用NaOH溶液中和,能够以68.5%以上的收率得到核黄素磷酸钠,产品质量符合美国FCC (7)要求.通过单因素试验,初步优化了核黄素5'-磷酸钠粗品磷酸化反应的条件,即:n (POCl3)/n(VB2)=4.6,n(POCl3)/n(H2O)=1.65,反应时间2h,反应温度35±1℃.在优化的磷酸化反应条件下,利用核黄素粗品制备核黄素5'-磷酸钠的收率平均可达73.5%以上,能够有效降低核黄素5'-磷酸钠的生产成本.研究结果表明,利用核黄素粗品制备核黄素5'-磷酸钠无论在经济上还是在技术上均是可行的.

  4. Phosphatidylinositol 5-phosphate 4-kinase type II beta is required for vitamin D receptor-dependent E-cadherin expression in SW480 cells

    International Nuclear Information System (INIS)

    Highlights: → We analyzed Phosphatidylinositol 5-phosphate kinase IIβ (PIPKIIβ) function in cancer. → PIPKIIβ is required for vitamin D receptor-mediated E-cadherin upregulation in SW480. → PIPKIIβ suppresses cellular motility through E-cadherin induction in SW480 cells. → Nuclear PIP2 but not plasma membrane-localized PIP2 mediates E-cadherin upregulation. -- Abstract: Numerous epidemiological data indicate that vitamin D receptor (VDR) signaling induced by its ligand or active metabolite 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) has anti-cancer activity in several colon cancers. 1α,25(OH)2D3 induces the epithelial differentiation of SW480 colon cancer cells expressing VDR (SW480-ADH) by upregulating E-cadherin expression; however, its precise mechanism remains unknown. We found that phosphatidylinositol-5-phosphate 4-kinase type II beta (PIPKIIβ) but not PIPKIIα is required for VDR-mediated E-cadherin induction in SW480-ADH cells. The syntenin-2 postsynaptic density protein/disc large/zona occludens (PDZ) domain and pleckstrin homology domain of phospholipase C-delta1 (PLCδ1 PHD) possess high affinity for phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) mainly localized to the nucleus and plasma membrane, respectively. The expression of syntenin-2 PDZ but not PLCδ1 PHD inhibited 1α,25(OH)2D3-induced E-cadherin upregulation, suggesting that nuclear PI(4,5)P2 production mediates E-cadherin expression through PIPKIIβ in a VDR-dependent manner. PIPKIIβ is also involved in the suppression of the cell motility induced by 1α,25(OH)2D3. These results indicate that PIPKIIβ-mediated PI(4,5)P2 signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation.

  5. Investigating the cortical regions involved in MEP modulation in tDCS

    Directory of Open Access Journals (Sweden)

    Ricardo eSalvador

    2015-10-01

    Full Text Available Transcranial magnetic stimulation (TMS is used in several studies to evaluate cortical excitability changes induced by transcranial direct current stimulation (tDCS of the primary motor cortex. Interpretation of these results, however, is hindered by the very different spatial distribution of the electric field (E-field induced by the two techniques and by the different target neurons that they might act upon. In this study we used the finite element method to calculate the E-field distribution induced by TMS and tDCS in a realistically shaped model of a human head. A model of a commercially available figure-8 coil was placed over a position above the identified hand knob (HK region. We also modelled two configurations of bipolar tDCS montages with one of the electrodes placed over the HK and a return electrode over the contralateral orbital region. The electrodes over the HK were either rectangular in shape, with an area of 35cm2 or cylindrical with an area of π cm2 (1 cm radius. To compare the E-field distribution in TMS and the two tDCS models, average values of the E-field’s magnitude as well as the polar and azimuthal angle were investigated in the HK region and premotor areas. The results show that both techniques induce fields with different magnitudes and directions in the HK: the field in tDCS is predominantly perpendicular to the cortical surface, contrary to what happens in TMS where the field is mostly parallel to it. In the premotor areas, the magnitude of the E-field induced in TMS was well below the accepted threshold for MEP generation, 100 V/m. In tDCS, the magnitude of the field in these areas was comparable to that induced at the HK with a significant component perpendicular to the cortical surface. These results indicate that tDCS and TMS target preferentially different neuronal structures at the HK. Besides, they show that premotor areas may play a role in the tDCS-induced after effects on motor cortex excitability.

  6. D-Ribulose 5-Phosphate 3-Epimerase: Functional and Structural Relationships to Members of the Ribulose-Phosphate Binding (beta/alpha)8-Barrel Superfamily

    Energy Technology Data Exchange (ETDEWEB)

    Akana,J.; Federov, A.; Federov, E.; Novak, W.; Babbitt, P.; Almo, S.; Gerlt, J.

    2006-01-01

    The 'ribulose phosphate binding' superfamily defined by the Structural Classification of Proteins (SCOP) database is considered the result of divergent evolution from a common ({beta}/{alpha}){sub 8}-barrel ancestor. The superfamily includes D-ribulose 5-phosphate 3-epimerase (RPE), orotidine 5'-monophosphate decarboxylase (OMPDC), and 3-keto-L-gulonate 6-phosphate decarboxylase (KGPDC), members of the OMPDC suprafamily, as well as enzymes involved in histidine and tryptophan biosynthesis that utilize phosphorylated metabolites as substrates. We now report studies of the functional and structural relationships of RPE to the members of the superfamily. As suggested by the results of crystallographic studies of the RPEs from rice and Plasmodium falciparum, the RPE from Streptococcus pyogenes is activated by Zn{sup 2+} which binds with a stoichiometry of one ion per polypeptide. Although wild type RPE has a high affinity for Zn{sup 2+} and inactive apoenzyme cannot be prepared, the affinity for Zn{sup 2+} is decreased by alanine substitutions for the two histidine residues that coordinate the Zn{sup 2+} ion (H34A and H67A); these mutant proteins can be prepared in an inactive, metal-free form and activated by exogenous Zn{sup 2+}. The crystal structure of the RPE was solved at 1.8 Angstroms resolution in the presence of D-xylitol 5-phosphate, an inert analogue of the D-xylulose 5-phosphate substrate. This structure suggests that the 2,3-enediolate intermediate in the 1,1-proton transfer reaction is stabilized by bidentate coordination to the Zn{sup 2+} that also is liganded to His 34, Asp 36, His 67, and Asp 176; the carboxylate groups of the Asp residues are positioned also to function as the acid/base catalysts. Although the conformation of the bound analogue resembles those of ligands bound in the active sites of OMPDC and KGPDC, the identities of the active site residues that coordinate the essential Zn{sup 2+} and participate as acid/base catalysts

  7. Mutations in Escherichia coli aceE and ribB genes allow survival of strains defective in the first step of the isoprenoid biosynthesis pathway.

    Directory of Open Access Journals (Sweden)

    Jordi Perez-Gil

    Full Text Available A functional 2-C-methyl-D-erythritol 4-phosphate (MEP pathway is required for isoprenoid biosynthesis and hence survival in Escherichia coli and most other bacteria. In the first two steps of the pathway, MEP is produced from the central metabolic intermediates pyruvate and glyceraldehyde 3-phosphate via 1-deoxy-D-xylulose 5-phosphate (DXP by the activity of the enzymes DXP synthase (DXS and DXP reductoisomerase (DXR. Because the MEP pathway is absent from humans, it was proposed as a promising new target to develop new antibiotics. However, the lethal phenotype caused by the deletion of DXS or DXR was found to be suppressed with a relatively high efficiency by unidentified mutations. Here we report that several mutations in the unrelated genes aceE and ribB rescue growth of DXS-defective mutants because the encoded enzymes allowed the production of sufficient DXP in vivo. Together, this work unveils the diversity of mechanisms that can evolve in bacteria to circumvent a blockage of the first step of the MEP pathway.

  8. 植物MEP途径的代谢调控机制%Multiple Regulation Mechanisms of MEP Pathway in Plant

    Institute of Scientific and Technical Information of China (English)

    张松涛; 陈红丽; 崔红; 杨惠娟; 刘国顺

    2012-01-01

    Terpenoids metabolism is one of the most important pathways of secondary metabolism in plant. The regulatory mechanisms that modulate this metabolic route will determine plant growth and development, resistance, quality and other aspects. The terpene precursors are synthesized by the 2-C-Methyl-D-E-rythritol-4-Phosphate (MEP) pathway in plant plastids. Recent studies have shown that, many genes involved in MEP pathway are not only regulated by multiple genes encoding and the transcript level,but also by post-transcriptional mechanism. Post-transcriptional regulation is a novel regulation mechanism described recently for this way and the mechanism is not clear. We review here various regulatory mechanisms of MEP pathway in plant, especially the mechanism and signal molecular that may be involved in post-transcriptional regulation,which may provide the theory basis for the research of regulation in this pathway.%萜类代谢途径是植物中最重要的次生代谢途径之一,对其有效的调控决定着植物的生长发育、抗性及品质等各个方面.植物中类萜合成的前体物在质体中是由2-C-甲基-D-赤藓糖醇-4-磷酸(2-C-Methyl-D-Erythritol-4-Phosphate,MEP)途径合成的,MEP途径中的许多基因除了受到多基因编码和转录水平的调节外,还受到转录后调节机制的调节,而转录后调节是一种新发现的调节方式,其机制还不是很清楚.该文重点对近年来国内外有关植物MEP途径的多种调节方式,尤其是转录后调节的调节机制及其可能参与的信号分子方面的研究进展进行综述,为植物的MEP途径的代谢调控提供参考.

  9. Phosphatidylinositol 5-phosphate 4-kinase type II beta is required for vitamin D receptor-dependent E-cadherin expression in SW480 cells

    Energy Technology Data Exchange (ETDEWEB)

    Kouchi, Zen, E-mail: zkouchi@toyaku.ac.jp [Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-city, Tokyo 192-0392 (Japan); Fujiwara, Yuki [Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-city, Tokyo 192-0392 (Japan); Yamaguchi, Hideki [Division of Metastasis and Invasion Signaling, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi-city, Saitama 332-0012 (Japan); Nakamura, Yoshikazu; Fukami, Kiyoko [Laboratory of Genome and Biosignals, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-city, Tokyo 192-0392 (Japan)

    2011-05-20

    Highlights: {yields} We analyzed Phosphatidylinositol 5-phosphate kinase II{beta} (PIPKII{beta}) function in cancer. {yields} PIPKII{beta} is required for vitamin D receptor-mediated E-cadherin upregulation in SW480. {yields} PIPKII{beta} suppresses cellular motility through E-cadherin induction in SW480 cells. {yields} Nuclear PIP{sub 2} but not plasma membrane-localized PIP{sub 2} mediates E-cadherin upregulation. -- Abstract: Numerous epidemiological data indicate that vitamin D receptor (VDR) signaling induced by its ligand or active metabolite 1{alpha},25-dihydroxyvitamin D{sub 3} (1{alpha},25(OH){sub 2}D{sub 3}) has anti-cancer activity in several colon cancers. 1{alpha},25(OH){sub 2}D{sub 3} induces the epithelial differentiation of SW480 colon cancer cells expressing VDR (SW480-ADH) by upregulating E-cadherin expression; however, its precise mechanism remains unknown. We found that phosphatidylinositol-5-phosphate 4-kinase type II beta (PIPKII{beta}) but not PIPKII{alpha} is required for VDR-mediated E-cadherin induction in SW480-ADH cells. The syntenin-2 postsynaptic density protein/disc large/zona occludens (PDZ) domain and pleckstrin homology domain of phospholipase C-delta1 (PLC{delta}1 PHD) possess high affinity for phosphatidylinositol-4,5-bisphosphate (PI(4,5)P{sub 2}) mainly localized to the nucleus and plasma membrane, respectively. The expression of syntenin-2 PDZ but not PLC{delta}1 PHD inhibited 1{alpha},25(OH){sub 2}D{sub 3}-induced E-cadherin upregulation, suggesting that nuclear PI(4,5)P{sub 2} production mediates E-cadherin expression through PIPKII{beta} in a VDR-dependent manner. PIPKII{beta} is also involved in the suppression of the cell motility induced by 1{alpha},25(OH){sub 2}D{sub 3}. These results indicate that PIPKII{beta}-mediated PI(4,5)P{sub 2} signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation.

  10. A split-ubiquitin two-hybrid screen for proteins physically interacting with the yeast amino acid transceptor Gap1 and ammonium transceptor Mep2.

    Directory of Open Access Journals (Sweden)

    Griet Van Zeebroeck

    Full Text Available Several nutrient permeases have been identified in yeast, which combine a transport and receptor function, and are called transceptors. The Gap1 general amino acid permease and the Mep2 ammonium permease mediate rapid activation by amino acids and by ammonium, respectively, of the protein kinase A (PKA pathway in nitrogen-starved cells. Their mode of action is not well understood. Both proteins are subject to complex controls governing their intracellular trafficking. Using a split-ubiquitin yeast two-hybrid screen with Gap1 or Mep2 as bait, we identified proteins putatively interacting with Gap1 and/or Mep2. They are involved in glycosylation, the secretory pathway, sphingolipid biosynthesis, cell wall biosynthesis and other processes. For several candidate interactors, determination of transport and signaling capacity, as well as localization of Gap1 or Mep2 in the corresponding deletion strains, confirmed a functional interaction with Gap1 and/or Mep2. Also common interacting proteins were identified. Transport and signaling were differentially affected in specific deletion strains, clearly separating the two functions of the transceptors and confirming that signaling does not require transport. We identified two new proteins, Bsc6 and Yir014w, that affect trafficking or downregulation of Gap1. Deletion of EGD2, YNL024c or SPC2 inactivates Gap1 transport and signaling, while its plasma membrane level appears normal.. Vma4 is required for Mep2 expression, while Gup1 appears to be required for proper distribution of Mep2 over the plasma membrane. Some of the interactions were confirmed by GST pull-down assay, using the C-terminal tail of Gap1 or Mep2 expressed in E.coli. Our results reveal the effectiveness of split-ubiquitin two-hybrid screening for identification of proteins functionally interacting with membrane proteins. They provide several candidate proteins involved in the transport and signaling function or in the complex trafficking

  11. An insight into the sequential, structural and phylogenetic properties of banana 1-aminocyclopropane-1-carboxylate synthase 1 and study of its interaction with pyridoxal-5'-phosphate and aminoethoxyvinylglycine.

    Science.gov (United States)

    Choudhury, Swarup Roy; Singh, Sanjay Kumar; Roy, Sujit; Sengupta, Dibyendu N

    2010-06-01

    In banana, ethylene production for ripening is accompanied by a dramatic increase in 1-aminocyclopropane-1-carboxylate (ACC) content, transcript level of Musa acuminata ACC synthase 1 (MA-ACS1) and the enzymatic activity of ACC synthase 1 at the onset of the climacteric period. MA-ACS1 catalyses the conversion of S-adenosyl-L-methionine (SAM) to ACC, the key regulatory step in ethylene biosynthesis. Multiple sequence alignments of 1-aminocyclopropane-1-carboxylate synthase (ACS) amino acid sequences based on database searches have indicated that MA-ACS1 is a highly conserved protein across the plant kingdom. This report describes an in silico analysis to provide the first important insightful information about the sequential, structural and phylogenetic characteristics of MA-ACS1. The three-dimensional structure of MA-ACS1, constructed based on homology modelling, in combination with the available data enabled a comparative mechanistic analysis of MA-ACS1 to explain the catalytic roles of the conserved and non-conserved active site residues. We have further demonstrated that, as in apple and tomato, banana- ACS1 (MA-ACS1) forms a homodimer and a complex with cofactor pyridoxal-5'-phosphate (PLP) and inhibitor aminoethoxyvinylglycine (AVG). We have also predicted that the residues from the PLP-binding pocket, essential for ligand binding, are mostly conserved across the MA-ACS1 structure and the competitive inhibitor AVG binds at a location adjacent to PLP.

  12. Method for Assaying the Lipid Kinase Phosphatidylinositol-5-phosphate 4-kinase α in Quantitative High-Throughput Screening (qHTS) Bioluminescent Format

    Science.gov (United States)

    Davis, Mindy I.; Sasaki, Atsuo T.; Simeonov, Anton

    2015-01-01

    Summary ipid kinases are important regulators of a variety of cellular processes and their dysregulation causes diseases such as cancer and metabolic diseases. Distinct lipid kinases regulate the seven different phosphorylated forms of phosphatidylinositol (PtdIns). Some lipid kinases utilize long-chain lipid substrates that have limited solubility in aqueous solutions, which can lead to difficulties in developing a robust and miniaturizable biochemical assay. The ability to prepare the lipid substrate and develop assays to identify modulators of lipid kinases is important and is the focus of this methods chapter. Herein, we describe a method to prepare a DMSO-based lipid mixture that enables the 1536-well screening of the lipid kinase phosphatidylinositol-5-phosphate 4-kinase α (PI5P4Kα) utilizing the D-myo-di16-PtIns(5)P substrate in quantitative high-throughput screening (qHTS) format using the ADP-Glo™ technology to couple the production of ADP to a bioluminescent readout. PMID:26552670

  13. Check-Testing of Manufacturer Self Reported Labeling Data& Compliance with MEPS

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Nan; Zhou, Nan; Zheng, Nina; Fridley, David; Wang, Ruohong; Egan, Christine

    2008-03-01

    China first adopted minimum energy performance standards (MEPS) in 1989. Today, there are standards for a wide range of domestic, commercial and selected industrial equipment. In 1999, China launched a voluntary endorsement label, which has grown to cover over 40 products including water-saving products. Further, in 2005, China started a mandatory energy information label that initially covered two products and in 2007 was extended to cover four products total including: air conditioners; household refrigerators; clothes washers; and unitary air conditioners. These programs have had an important impact in reducing the energy consumption of appliances in China. China has built up a strong infrastructure to develop and implement standards. Historically, however, the government's primary focus has been on the technical requirements for specifying efficiency performance. Less attention has been paid to monitoring and enforcement with a minimal commitment of resources and little expansion of administrative capacity in this area. Thus, market compliance with both mandatory standard and labeling programs has been questionable. Furthermore, actual energy savings have quite possibly been undermined as a result. The establishment of a regularized monitoring system for tracking compliance with the mandatory standard and energy information label programs in China is a major area for program improvement. Over the years, the Collaborative Labeling and Appliance Standards Program (CLASP) has partnered with several Chinese institutions to promote energy-efficient products in China. CLASP, together with its implementing partner Lawrence Berkeley National Laboratory (LBNL), has assisted China in developing and updating the above-mentioned standards and labeling programs. Because of the increasing need for the development of a monitoring system to track compliance with the standard, CLASP, with support from Japan's Ministry of Economy, Trade and Industry (METI) and the

  14. Purification, crystallization and X-ray crystallographic studies of a Bacillus cereus MepR-like transcription factor, BC0657.

    Science.gov (United States)

    Cho, Min Uk; Kim, Meong Il; Hong, Minsun

    2015-06-01

    Transcription factors of the MarR family respond to internal and external changes and regulate a variety of biological functions through ligand association with microorganisms. MepR belongs to the MarR family, and its mutations are associated with the development of multidrug resistance in Staphylococcus aureus, which has caused a growing health problem. In this study, a Bacillus cereus MepR-like transcription regulator, BC0657, was crystallized. The BC0657 crystals diffracted to 2.05 Å resolution and belonged to either space group P6(2)22 or P6(4)22, with unit-cell parameters a = 110.57, b = 110.57, c = 67.29 Å. There was one molecule per asymmetric unit. Future comparative structural studies on BC0657 would extend knowledge of ligand-induced transcriptional regulatory mechanisms in the MarR family and would make a significant contribution to the design of antibiotic drugs against multidrug-resistant bacteria.

  15. Properties and inhibition of the first two enzymes of the non-mevalonate pathway of isoprenoid biosynthesis.

    Science.gov (United States)

    Mueller, C; Schwender, J; Zeidler, J; Lichtenthaler, H K

    2000-12-01

    Enzymes of the 1-deoxy-D-xylulose 5-phosphate/2-C-methylerythritol 4-phosphate (DOXP/MEP) pathway are targets for new herbicides and antibacterial drugs. Until now, no inhibitors for the DOXP synthase have been known of. We show that one of the breakdown products of the herbicide clomazone affects the DOXP synthase. One inhibitor of the non-mevalonate pathway, fosmidomycin, blocks the DOXP reductoisomerase (DXR) of plants and bacteria. The I(50) values of plants are, however, higher than those found for the DXR of Escherichia coli. The DXR of plants, isolated from barley seedlings, shows a pH optimum of 8.1, which is typical for enzymes active in the chloroplast stroma.

  16. Structure of L-Xylulose-5-Phosphate 3-Epimerase (UlaE) from the Anaerobic L-Ascorbate Utilization Pathway of Escherichia coli: Identification of a Novel Phosphate Binding Motif within a TIM Barrel Fold

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Rong; Pineda, Marco; Ajamian, Eunice; Cui, Qizhi; Matte, Allan; Cygler, Miroslaw (McGill); (NRC-Canada)

    2009-01-15

    Three catabolic enzymes, UlaD, UlaE, and UlaF, are involved in a pathway leading to fermentation of L-ascorbate under anaerobic conditions. UlaD catalyzes a {beta}-keto acid decarboxylation reaction to produce L-xylulose-5-phosphate, which undergoes successive epimerization reactions with UlaE (L-xylulose-5-phosphate 3-epimerase) and UlaF (L-ribulose-5-phosphate 4-epimerase), yielding D-xylulose-5-phosphate, an intermediate in the pentose phosphate pathway. We describe here crystallographic studies of UlaE from Escherichia coli O157:H7 that complete the structural characterization of this pathway. UlaE has a triosephosphate isomerase (TIM) barrel fold and forms dimers. The active site is located at the C-terminal ends of the parallel {beta}-strands. The enzyme binds Zn{sup 2+}, which is coordinated by Glu155, Asp185, His211, and Glu251. We identified a phosphate-binding site formed by residues from the {beta}1/{alpha}1 loop and {alpha}3' helix in the N-terminal region. This site differs from the well-characterized phosphate-binding motif found in several TIM barrel superfamilies that is located at strands {beta}7 and {beta}8. The intrinsic flexibility of the active site region is reflected by two different conformations of loops forming part of the substrate-binding site. Based on computational docking of the L-xylulose 5-phosphate substrate to UlaE and structural similarities of the active site of this enzyme to the active sites of other epimerases, a metal-dependent epimerization mechanism for UlaE is proposed, and Glu155 and Glu251 are implicated as catalytic residues. Mutation and activity measurements for structurally equivalent residues in related epimerases supported this mechanistic proposal.

  17. Study of the factors affecting the performance of microextraction by packed sorbent (MEPS) using liquid scintillation counter and liquid chromatography-tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Altun, Zeki [Karlstad University, Faculty of Technology and Science, SE-651 88 Karlstad (Sweden); Abdel-Rehim, Mohamed [Karlstad University, Faculty of Technology and Science, SE-651 88 Karlstad (Sweden); Clinical Pharmacology and DMPK, AstraZeneca R and D Soedertaelje, SE-151 85 Soedertaelje (Sweden)], E-mail: Mohamed.Abdel-Rehim@Astrazeneca.com

    2008-12-23

    Microextraction by packed sorbent (MEPS) is a new technique for sample preparation that can be connected on-line with LC or GC. In MEPS, approximately 1-2 mg of the solid packing material is inserted into a syringe (100-250 {mu}L) as a plug. Sample preparation takes place on the packed bed. The bed can be packed or coated to provide selective and suitable sampling conditions. The new method is very promising for extraction of drugs and metabolites from biological samples. In this paper, some factors affecting the performance of MEPS such as recovery, carry-over, leakage, washing volume and elution volume were studied using C18 and hydroxylated polystyrene-divinylbenzene copolymer (ENV+) as sorbents. Radioactively labelled bupivacaine in plasma samples was used as test analyte. For the extraction of this drug, using methanol/water 95:5 (v/v) (0.25% ammonium hydroxide) was used as elution solvent. The analyte response increased with increasing the elution volume and it was linear upp up to 100 {mu}L utilizing liquid scintillation counter. Further, for concentrating the sample, we found that MEPS may be used such that the sample can be drawn through the needle, up and down, several times. The analyte leakage increases as the volume washing increases, though higher washing volumes may also result in cleaner extracts. To eliminate analyte carry-over, the sorbents were washed first with 3 x 250 {mu}L elution solution and then with 3 x 250 {mu}L washing solution. In addition, the reproducibility measurements show relatively good relative standard deviation (RSD) % values concerning analyte recovery and analyte leakage. The present study provides an understanding of basic aspects when optimizing methods for MEPS. In this study, MEPS was used off-line with liquid scintillation counter and on-line with LC-MS/MS.

  18. Comparative studies on the properties of tryptophanase and tyrosine phenol-lyase immobilized directly on Sepharose or by use of Sepharose-bound pyridoxal 5'-phosphate.

    Science.gov (United States)

    Fukui, S; Ikeda, S; Fujimura, M; Yamada, H; Kumagai, H

    1975-02-01

    Tryptophanase from Escherichia coli B/qt 7-A and tyrosine phenol-lyase (beta-tyrosinase) from Escherichia intermedia were immobilized on Sepharose 4B by several direct coupling reactions or through pyridoxal 5'-phosphate previously bound to Sepharose. The most active preparation of immobilized tryptophanase was obtained by coupling tetrameric apoenzyme to pyridoxal-P bound on Sepharose at the 6-position through a diazo linkage. This immobilization procedure involves the formation to Schiff base linkage between 4-formyl group of Sepharose-bound pyridoxal-P and the epsilon-amino group of the lysine residue at the active center of one subunit of tetrameric apo-tryptophanase, followed by the fixation of the Schiff base linkage by reduction with NaBH4. In the case of beta-tyrosinase having two catalytic centers, however, this method was not so suitable as the case of tryptophanase. Direct coupling of the apoenzyme to CNBr-activated Sepharose or to a bromoacetyl derivative of Sepharose gave better results. In each case, the affinity for substrate or coenzyme was scarcely influenced by the immobilization. When used repeatedly in a batch system or continuously in a flow system in the absence of added pyridoxal-P, immobilized holo-tryptophanase of holo-beta-tyrosinase gradually lost its original activity; however, supplement of pyridoxal-P to the reaction system restored its initial activity. From the kinetic analyses of these phenomena, the rate constants of coenzyme dissociation from immobilized tryptophanase and beta-tyrosinase were calculated. Upon immobilization, the pH optima of both enzymes shifted 0.5 to 1.0 pH unit to the alkaline side. Both immobilized enzymes showed higher thermal stability and resistance to a denaturing agent such as guinidine-HCl than their free counterpart. Furthermore, the reactivity of sulfhydryl group of beta-tyrosinase, in connection with its coenzyme-binding property, was conveniently studied by use of the immobilized enzyme.

  19. Systems-Wide Prediction of Enzyme Promiscuity Reveals a New Underground Alternative Route for Pyridoxal 5'-Phosphate Production in E. coli.

    Directory of Open Access Journals (Sweden)

    Matthew A Oberhardt

    2016-01-01

    Full Text Available Recent insights suggest that non-specific and/or promiscuous enzymes are common and active across life. Understanding the role of such enzymes is an important open question in biology. Here we develop a genome-wide method, PROPER, that uses a permissive PSI-BLAST approach to predict promiscuous activities of metabolic genes. Enzyme promiscuity is typically studied experimentally using multicopy suppression, in which over-expression of a promiscuous 'replacer' gene rescues lethality caused by inactivation of a 'target' gene. We use PROPER to predict multicopy suppression in Escherichia coli, achieving highly significant overlap with published cases (hypergeometric p = 4.4e-13. We then validate three novel predicted target-replacer gene pairs in new multicopy suppression experiments. We next go beyond PROPER and develop a network-based approach, GEM-PROPER, that integrates PROPER with genome-scale metabolic modeling to predict promiscuous replacements via alternative metabolic pathways. GEM-PROPER predicts a new indirect replacer (thiG for an essential enzyme (pdxB in production of pyridoxal 5'-phosphate (the active form of Vitamin B6, which we validate experimentally via multicopy suppression. We perform a structural analysis of thiG to determine its potential promiscuous active site, which we validate experimentally by inactivating the pertaining residues and showing a loss of replacer activity. Thus, this study is a successful example where a computational investigation leads to a network-based identification of an indirect promiscuous replacement of a key metabolic enzyme, which would have been extremely difficult to identify directly.

  20. Development of inhibitors of the 2C-methyl-D-erythritol 4-phosphate (MEP) pathway enzymes as potential anti-infective agents

    NARCIS (Netherlands)

    Masini, Tiziana; Hirsch, Anna K H

    2014-01-01

    Important pathogens such as Mycobacterium tuberculosis and Plasmodium falciparum, the causative agents of tuberculosis and malaria, respectively, and plants, utilize the 2C-methyl-D-erythritol 4-phosphate (MEP, 5) pathway for the biosynthesis of isopentenyl diphosphate (1) and dimethylallyl diphosph

  1. Novel bioassay for the discovery of inhibitors of the 2-C-Methyl-D-Erythritol 4-Phosphate (MEP) and terpenoid pathways leading to carotenoid biosynthesis

    Science.gov (United States)

    The 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway leads to the synthesis of isopentenyl-phosphate (IPP) in plastids. It is a major branch point providing precursors for the synthesis of carotenoids, tocopherols, plastoquinone and the phytyl chain of chlorophylls, as well as the hormones abscisi...

  2. Quantifying the Metabolites of the Methylerythritol 4-Phosphate (MEP) Pathway in Plants and Bacteria by Liquid Chromatography-Triple Quadrupole Mass Spectrometry.

    Science.gov (United States)

    González-Cabanelas, D; Hammerbacher, A; Raguschke, B; Gershenzon, J; Wright, L P

    2016-01-01

    The 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway occurs in the plastids of higher plants and in most economically important prokaryotes where it is responsible for the biosynthesis of the isoprenoid building blocks, isopentenyl diphosphate and dimethylallyl diphosphate. These five-carbon compounds are the substrates for the enormous variety of terpenoid products, including many essential metabolites and substances of commercial value. Increased knowledge of the regulation of the MEP pathway is critical to understanding many aspects of plant and microbial metabolism as well as in developing biotechnological platforms for producing these commercially valuable isoprenoids. To achieve this goal, researchers must have the ability to investigate the in vivo kinetics of the pathway by accurately measuring the concentrations of MEP pathway metabolites. However, the low levels of these metabolites complicate their accurate determination without suitable internal standards. This chapter describes a sensitive method to accurately determine the concentrations of MEP pathway metabolites occurring at trace amounts in biological samples using liquid chromatography coupled to triple quadrupole mass spectrometry. In addition, simple protocols are given for producing stable isotope-labeled internal standards for these analyses. PMID:27480689

  3. Novel bioassay for the discovery of inhibitors of the 2-C-methyl-D-erythritol 4-phosphate (MEP and terpenoid pathways leading to carotenoid biosynthesis.

    Directory of Open Access Journals (Sweden)

    Natália Corniani

    Full Text Available The 2-C-methyl-D-erythritol 4-phosphate (MEP pathway leads to the synthesis of isopentenyl diphosphate in plastids. It is a major branch point providing precursors for the synthesis of carotenoids, tocopherols, plastoquinone and the phytyl chain of chlorophylls, as well as the hormones abscisic acid and gibberellins. Consequently, disruption of this pathway is harmful to plants. We developed an in vivo bioassay that can measure the carbon flow through the carotenoid pathway. Leaf cuttings are incubated in the presence of a phytoene desaturase inhibitor to induce phytoene accumulation. Any compound reducing the level of phytoene accumulation is likely to interfere with either one of the steps in the MEP pathway or the synthesis of geranylgeranyl diphosphate. This concept was tested with known inhibitors of steps of the MEP pathway. The specificity of this in vivo bioassay was also verified by testing representative herbicides known to target processes outside of the MEP and carotenoid pathways. This assay enables the rapid screen of new inhibitors of enzymes preceding the synthesis of phytoene, though there are some limitations related to the non-specific effect of some inhibitors on this assay.

  4. Molecular evolution of B6 enzymes: Binding of pyridoxal-5'-phosphate and Lys41Arg substitution turn ribonuclease A into a model B6 protoenzyme

    Directory of Open Access Journals (Sweden)

    Marra Ersilia

    2008-06-01

    Full Text Available Abstract Background The pyridoxal-5'-phosphate (PLP-dependent or vitamin B6-dependent enzymes that catalyze manifold reactions in the metabolism of amino acids belong to no fewer than four evolutionarily independent protein families. The multiple evolutionary origin and the essential mechanistic role of PLP in these enzymes argue for the cofactor having arrived on the evolutionary scene before the emergence of the respective apoenzymes and having played a dominant role in the molecular evolution of the B6 enzyme families. Here we report on an attempt to re-enact the emergence of a PLP-dependent protoenzyme. The starting protein was pancreatic ribonuclease A (RNase, in which active-site Lys41 or Lys7 readily form a covalent adduct with PLP. Results We screened the PLP adduct of wild-type RNase and two variant RNases (K7R and K41R for catalytic effects toward L- and D-amino acids. RNase(K41R-PLP, in which the cofactor is bound through an imine linkage to Lys7, qualifies for a model proto-B6 enzyme by the following criteria: (1 covalent linkage of PLP (internal aldimine; (2 catalytic activity toward amino acids that depends on formation of an imine linkage with the substrate (external aldimine; (3 adjoining binding sites for the cofactor and amino acid moiety that facilitate the transimination reaction of the internal to the external aldimine and stabilize the resulting noncovalent complex of the coenzyme-substrate adduct with the protein; (4 reaction specificity, the only detectable reactions being racemization of diverse amino acids and β-decarboxylation of L-aspartate; (5 acceleration factors for racemization and β-decarboxylation of >103 over and above that of PLP alone; (6 ribonuclease activity that is 103-fold lower than that of wild-type RNase, attenuation of a pre-existing biological activity being indispensable for the further evolution as a PLP-dependent protoenzyme. Conclusion A single amino acid substitution (Lys41Arg and covalent

  5. The influence of magnesium-pyridoxal-5'-phosphate-glutamate in comparison with probucol, alpha-tocopherol and trolox on copper-induced oxidation of human low density lipoprotein in vitro.

    Science.gov (United States)

    Kögl, C; Schneider, W; Elstner, E F

    1994-06-15

    Low density lipoprotein (LDL) in the presence of magnesium-pyridoxal-5'-phosphate-glutamate (MPPG), pyridoxal-5'-phosphate (PP), alpha-tocopherol, probucol or trolox is more resistant against copper-induced oxidation as control-LDL in vitro. The efficiency of the drugs is: probucol > MPPG > trolox > alpha-tocopherol > PP. LDL oxidation is determined by its increasing negative surface charge, fragmentation of apolipoprotein B-100 and changes of the fatty acid content of LDL. The protection of the drugs depends on their concentration and incubation time. Different experiments point to the fact that copper-induced oxidation of LDL in vitro starts with the binding of copper at the apolipoprotein B-100, resulting in an increasing negative surface charge and fragmentation of the apolipoprotein B-100. Afterwards a decrease of LDL-bound linoleic acid (18:2) is measurable. PMID:8031313

  6. Elicitor induced activation of the methylerythritol phosphate pathway toward phytoalexins biosynthesis in rice.

    Science.gov (United States)

    Okada, Atsushi; Shimizu, Takafumi; Okada, Kazunori; Kuzuyama, Tomohisa; Koga, Jinichiro; Shibuya, Naoto; Nojiri, Hideaki; Yamane, Hisakazu

    2007-09-01

    Diterpenoid phytoalexins such as momilactones and phytocassanes are produced via geranylgeranyl diphosphate in suspension-cultured rice cells after treatment with a chitin elicitor. We have previously shown that the production of diterpene hydrocarbons leading to phytoalexins and the expression of related biosynthetic genes are activated in suspension-cultured rice cells upon elicitor treatment. To better understand the elicitor-induced activation of phytoalexin biosynthesis, we conducted microarray analysis using suspension-cultured rice cells collected at various times after treatment with chitin elicitor. Hierarchical cluster analysis revealed two types of early-induced expression (EIE-1, EIE-2) nodes and a late-induced expression (LIE) node that includes genes involved in phytoalexins biosynthesis. The LIE node contains genes that may be responsible for the methylerythritol phosphate (MEP) pathway, a plastidic biosynthetic pathway for isopentenyl diphosphate, an early precursor of phytoalexins. The elicitor-induced expression of these putative MEP pathway genes was confirmed by quantitative reverse-transcription PCR. 1-Deoxy-D: -xylulose 5-phosphate synthase (DXS), 1-deoxy-D: -xylulose 5-phosphate reductoisomerase (DXR), and 4-(cytidine 5'-diphospho)-2-C-methyl-D: -erythritol synthase (CMS), which catalyze the first three committed steps in the MEP pathway, were further shown to have enzymatic activities that complement the growth of E. coli mutants disrupted in the corresponding genes. Application of ketoclomazone and fosmidomycin, inhibitors of DXS and DXR, respectively, repressed the accumulation of diterpene-type phytoalexins in suspension cells treated with chitin elicitor. These results suggest that activation of the MEP pathway is required to supply sufficient terpenoid precursors for the production of phytoalexins in infected rice plants.

  7. Cross-talk between the cytosolic mevalonate and the plastidial methylerythritol phosphate pathways in tobacco bright yellow-2 cells.

    Science.gov (United States)

    Hemmerlin, Andréa; Hoeffler, Jean-François; Meyer, Odile; Tritsch, Denis; Kagan, Isabelle A; Grosdemange-Billiard, Catherine; Rohmer, Michel; Bach, Thomas J

    2003-07-18

    In plants, two pathways are utilized for the synthesis of isopentenyl diphosphate, the universal precursor for isoprenoid biosynthesis. The key enzyme of the cytoplasmic mevalonic acid (MVA) pathway is 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR). Treatment of Tobacco Bright Yellow-2 (TBY-2) cells by the HMGR-specific inhibitor mevinolin led to growth reduction and induction of apparent HMGR activity, in parallel to an increase in protein representing two HMGR isozymes. Maximum induction was observed at 24 h. 1-Deoxy-d-xylulose (DX), the dephosphorylated first precursor of the plastidial 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway, complemented growth inhibition by mevinolin in the low millimolar concentration range. Furthermore, DX partially re-established feedback repression of mevinolin-induced HMGR activity. Incorporation studies with [1,1,1,4-2H4]DX showed that sterols, normally derived from MVA, in the presence of mevinolin are synthesized via the MEP pathway. Fosmidomycin, an inhibitor of 1-deoxy-d-xylulose-5-phosphate reductoisomerase, the second enzyme of the MEP pathway, was utilized to study the reverse complementation. Growth inhibition by fosmidomycin of TBY-2 cells could be partially overcome by MVA. Chemical complementation was further substantiated by incorporation of [2-13C]MVA into plastoquinone, representative of plastidial isoprenoids. Best rates of incorporation of exogenous stably labeled precursors were observed in the presence of both inhibitors, thereby avoiding internal isotope dilution.

  8. Histone H2A and H4 N-terminal tails are positioned by the MEP50 WD repeat protein for efficient methylation by the PRMT5 arginine methyltransferase.

    Science.gov (United States)

    Burgos, Emmanuel S; Wilczek, Carola; Onikubo, Takashi; Bonanno, Jeffrey B; Jansong, Janina; Reimer, Ulf; Shechter, David

    2015-04-10

    The protein arginine methyltransferase PRMT5 is complexed with the WD repeat protein MEP50 (also known as Wdr77 or androgen coactivator p44) in vertebrates in a tetramer of heterodimers. MEP50 is hypothesized to be required for protein substrate recruitment to the catalytic domain of PRMT5. Here we demonstrate that the cross-dimer MEP50 is paired with its cognate PRMT5 molecule to promote histone methylation. We employed qualitative methylation assays and a novel ultrasensitive continuous assay to measure enzyme kinetics. We demonstrate that neither full-length human PRMT5 nor the Xenopus laevis PRMT5 catalytic domain has appreciable protein methyltransferase activity. We show that histones H4 and H3 bind PRMT5-MEP50 more efficiently compared with histone H2A(1-20) and H4(1-20) peptides. Histone binding is mediated through histone fold interactions as determined by competition experiments and by high density histone peptide array interaction studies. Nucleosomes are not a substrate for PRMT5-MEP50, consistent with the primary mode of interaction via the histone fold of H3-H4, obscured by DNA in the nucleosome. Mutation of a conserved arginine (Arg-42) on the MEP50 insertion loop impaired the PRMT5-MEP50 enzymatic efficiency by increasing its histone substrate Km, comparable with that of Caenorhabditis elegans PRMT5. We show that PRMT5-MEP50 prefers unmethylated substrates, consistent with a distributive model for dimethylation and suggesting discrete biological roles for mono- and dimethylarginine-modified proteins. We propose a model in which MEP50 and PRMT5 simultaneously engage the protein substrate, orienting its targeted arginine to the catalytic site.

  9. Map-Based Cloning of zb7 Encoding an IPP and DMAPP Synthase in the MEP Pathway of Maize

    Institute of Scientific and Technical Information of China (English)

    Xiao-Min Lu; Jin-Sheng Lai; Xiao-Jiao Hu; Yuan-Zeng Zhao; Wei-Bin Song; Mei Zhang; Zong-Liang Chen; Wei Chen; Yong-Bin Dong; Zhen-Hua Wang

    2012-01-01

    IspH is a key enzyme in the last step of the methyI-D-erythritol-4-phosphate (MEP) pathway.Loss of function of IspH can often result in complete yellow or albino phenotype in many plants.Here,we report the characterization of a recessive mutant of maize,zebra7 (zb7),showing transverse green/yellow striped leaves in young plants.The yellow bands of the mutant have decreased levels of chlorophylls and carotenoids with delayed chloroplast development.Low temperature suppressed mutant phenotype,while alternate light/dark cycle or high temperature enlarged the yellow section.Map-based cloning demonstrated that zb7 encodes the IspH protein with a mis-sense mutation in a conserved region.Transgenic silencing of Zb7 in maize resulted in complete albino plantlets that are aborted in a few weeks,confirming that Zb7 is important in the early stages of maize chloroplast development.Zb7 is constitutively expressed and its expression subject to a 16-h light/8-h dark cycle regulation.Our results suggest that the less effective or unstable IspH in zb7 mutant,together with its diurnal expression,are mechanistically accounted for the zebra phenotype.The increased IspH mRNA in the leaves of zb7 at the late development stage may explain the restoration of mutant phenotype in mature stages.

  10. Spared Primary Motor Cortex and the Presence of MEP in Cerebral Palsy Dictate the Responsiveness to tDCS During Gait Training

    Directory of Open Access Journals (Sweden)

    Luanda Collange Grecco

    2016-07-01

    Full Text Available The current priority of investigations involving transcranial direct current stimulation (tDCS and neurorehabilitation is to identify biomarkers associated with the positive results of the interventions such that respondent and non-respondent patients can be identified in the early phases of treatment. The aims were to determine whether; 1 present motor evoked potential (MEP and, 2 injuries involving the primary motor cortex, are associated with tDCS-enhancement in functional outcome following gait training in children with cerebral palsy (CP. We reviewed the data from our parallel, randomized, sham-controlled, double-blind studies. Fifty-six children with spastic CP received gait training (either treadmill training or virtual reality training and tDCS (active or sham. Univariate and multivariate logistic regression analyses were employed to identify clinical, neurophysiologic and neuroanatomic predictors associated with the responsiveness to treatment with tDCS. MEP presence during the initial evaluation and the subcortical injury were associated with positive effects in the functional results. The logistic regression revealed that present MEP was a significant predictor for the six-minute walk test (p=0.003 and gait speed (p=0.028, whereas the subcortical injury was a significant predictor of gait kinematics (p=0.013 and gross motor function (p = 0.021. In this preliminary study involving children with CP, two important prediction factors of good responses to anodal tDCS combined with gait training were identified. Apparently, MEP (integrity of the corticospinal tract and subcortical location of the brain injury exerted different influences on aspects related to gait, such as velocity and kinematics.

  11. Numerical simulation of 2D Silicon MESFET and MOSFET described by the MEP based energy-transport model with a mixed finite elements scheme

    OpenAIRE

    A. M. Anile; Marrocco, Americo; Romano, V; Sellier, J. M.

    2004-01-01

    The Mixed Finite Element approximation scheme presented in is used to simulate a consistent hydrodynamical model for electron transport in semiconductors, free of any fitting parameters, formulated on the basis of the maximum entropy principle (MEP) in \\cite{AnRo,Ro1,Ro2}.. 2D-MESFET and 2D-MOSFET Silicon devices are simulated in the parabolic band approximation. Comparison with the results obtained by the Stratton model are presented for completeness.

  12. Protein arginine methyltransferase Prmt5-Mep50 methylates histones H2A and H4 and the histone chaperone nucleoplasmin in Xenopus laevis eggs.

    Science.gov (United States)

    Wilczek, Carola; Chitta, Raghu; Woo, Eileen; Shabanowitz, Jeffrey; Chait, Brian T; Hunt, Donald F; Shechter, David

    2011-12-01

    Histone proteins carry information contained in post-translational modifications. Eukaryotic cells utilize this histone code to regulate the usage of the underlying DNA. In the maturing oocytes and eggs of the frog Xenopus laevis, histones are synthesized in bulk in preparation for deposition during the rapid early developmental cell cycles. During this key developmental time frame, embryonic pluripotent chromatin is established. In the egg, non-chromatin-bound histones are complexed with storage chaperone proteins, including nucleoplasmin. Here we describe the identification and characterization of a complex of the protein arginine methyltransferase 5 (Prmt5) and the methylosome protein 50 (Mep50) isolated from Xenopus eggs that specifically methylates predeposition histones H2A/H2A.X-F and H4 and the histone chaperone nucleoplasmin on a conserved motif (GRGXK). We demonstrate that nucleoplasmin (Npm), an exceedingly abundant maternally deposited protein, is a potent substrate for Prmt5-Mep50 and is monomethylated and symmetrically dimethylated at Arg-187. Furthermore, Npm modulates Prmt5-Mep50 activity directed toward histones, consistent with a regulatory role for Npm in vivo. We show that H2A and nucleoplasmin methylation appears late in oogenesis and is most abundant in the laid egg. We hypothesize that these very abundant arginine methylations are constrained to pre-mid blastula transition events in the embryo and therefore may be involved in the global transcriptional repression found in this developmental time frame.

  13. Merging Q-theory and MEP theory to explain some geographical variations seen in Russian soil C inventory data

    Science.gov (United States)

    Yurova, Alla

    2016-04-01

    Soils are as critical for understanding the ecosystem carbon cycle as plants are and here I critically evaluate some of the commonly used assumptions embedded into the soil organic matter dynamics process-based models. According to the biochemical concept (e.g. Mindermann, 1968) plant residues can be divided into liable and more recalcitrant fractions, each decomposing with a specific rate (increasing with temperature) and it is remains of recalcitrant compounds that accumulate to form soil organic matter. The application of this theory in regional to global biogeochemical models leads to conclusion that the high latitude soils stores the highest amount of carbon per square meter due to high percentage of recalcitrant compounds and low temperature. This contradicts with the Russian soil inventory data, demonstrating that within the large span of biomes present in Russia that is steepe that has the highest soil C storage. Here I take an alternative, most theoretical, viewpoint, called Q-theory (from q-quality) (Ågren and Bosatta, 1996) considering the changes in the continuous variable-the quality of the organic matter in the soil as a starting point. I then derive the novel equation for the entropy production of humification process and demonstrate how MEP theory works to explain geographical differences in soil C accumulation seen in Russian soil inventory data. Conceptually close to the work presented is a general theory of humification (Orlov, 1995) based on thermodynamic view on decomposition postulating that independently on acting factors and the soil type it is only the most thermodynamically stable components, such as humic substances, that will be produced and stored in the process of organic matter transformation This work was supported by RFBR grants 15-05-01368 A

  14. Spectroscopic (infrared, Raman, UV and NMR) analysis, Gaussian hybrid computational investigation (MEP maps/HOMO and LUMO) on cyclohexanone oxime

    Science.gov (United States)

    Ramalingam, S.; Karabacak, M.; Periandy, S.; Puviarasan, N.; Tanuja, D.

    2012-10-01

    In the present analysis, FT-IR/FT-Raman spectra of the cyclohexanone oxime (CHO, C6H11NO) are recorded. The observed vibrational frequencies are assigned and the computational calculations are carried out by HF and DFT (B3LYP and B3PW91) methods with 6-311++G(d,p) basis set and the corresponding results are tabulated. In order to yield good coherence with observed values, the calculated frequencies are scaled by appropriate scale factors. The complete assignments are performed on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method. The alternation of structure of cyclohexanone due to the substitution of NOH is investigated. The vibrational sequence pattern of the molecule related to the substitutions is analyzed. Comparison of the observed fundamental vibrational frequencies of CHO and calculated results by density functional (B3LYP and B3PW91) and HF methods indicates that B3LYP is superior to the scaled HF and B3PW91 approach for molecular vibrational problems. Moreover, 13C NMR and 1H NMR chemical shifts are calculated by using the gauge independent atomic orbital (GIAO) method with HF/B3LYP/B3PW91 methods and the same basis set. A study on the electronic properties; absorption wavelengths, excitation energy, dipole moment and frontier molecular orbital energies, are performed by HF and DFT methods. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. Besides frontier molecular orbitals (FMO), molecular electrostatic potential (MEP) was performed. NLO properties and Mulliken charges of the CHO was also calculated and interpreted. The thermodynamic properties (heat capacity, entropy, and enthalpy) of the title compound at different temperatures are calculated in gas phase.

  15. Effects of mutagenesis of aspartic acid residues in the putative phosphoribosyl diphosphate binding site of Escherichia coli phosphoribosyl diphosphate synthetase on metal ion specificity and ribose 5-phosphate binding

    DEFF Research Database (Denmark)

    Willemoës, Martin; Nilsson, Dan; Hove-Jensen, Bjarne

    1996-01-01

    an increase in KM for ribose 5-phosphate in the presence of at least one of the divalent metal ions Mg2+, Mn2+, Co2+, or Cd2+, with the most dramatic changes revealed by the D220E and D220F enzymes in the presence of Co2+ and the D221A enzyme in the presence of Mn2+ or Co2+. The D220F and D221A enzymes both...... showed large decreases in Vapp in the presence of the various divalent metal ions, except for the D221A enzyme in the presence of Co2+. Vapp of the D220E enzyme was similar to that of the wild-type enzyme in the presence of Mg2+, Mn2+, or Cd2+, whereas the Vapp was increased in the presence of Co2+. Vapp...... enzymes were dependent on the metal ion present, suggesting a function of the investigated aspartic acid residues both in the binding of ribose 5-phosphate, possibly via a divalent metal ion, and in the interaction with a divalent metal ion during catalysis...

  16. Overexpression of SrUGT85C2 from Stevia reduced growth and yield of transgenic Arabidopsis by influencing plastidial MEP pathway.

    Science.gov (United States)

    Guleria, Praveen; Masand, Shikha; Yadav, Sudesh Kumar

    2014-04-15

    The transcript expression of a gene SrUGT85C2 has been documented for direct relation with steviol glycoside content in Stevia plant. Steviol glycoside and gibberellin biosynthetic routes are divergent branches of methyl erythritol-4 phosphate (MEP) pathway. So, SrUGT85C2 might be an influencing gibberellin content. Hence in the present study, transgenic Arabidopsis thaliana overexpressing SrUGT85C2 cDNA from Stevia rebaudiana was developed to check its effect on gibberellin accumulation and related plant growth parameters. The developed transgenics showed a noteworthy decrease of 78-83% in GA3 content. Moreover, the transgenics showed a gibberellin deficient phenotype comprising stunted hypocotyl length, reduced shoot growth and a significant fall in relative water content. Transgenics also showed 17-37 and 64-76% reduction in chlorophyll a and chlorophyll b contents, respectively. Reduction in photosynthetic pigments could be responsible for the noticed significant decrease in plant biomass. Like steviol glycoside and gibberellin biosynthesis, chlorophyll biosynthesis also occurs from the precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) of MEP pathway in the plastids. The observed downregulated expression of genes encoding MEP pathway enzymes geranyl geranyl diphosphate synthase (GGDPS), copalyl diphosphate synthase (CDPS), kaurenoic acid oxidase (KAO), chlorophyll synthetase and chlorophyll a oxygenase in transgenics overexpressing SrUGT85C2 might be responsible for the reduction in gibberellins as well as chlorophyll. This study has documented for the first time the regulatory role of SrUGT85C2 in the biosynthesis of steviol glycoside, gibberellins and chlorophyll.

  17. Overexpression of SrUGT85C2 from Stevia reduced growth and yield of transgenic Arabidopsis by influencing plastidial MEP pathway.

    Science.gov (United States)

    Guleria, Praveen; Masand, Shikha; Yadav, Sudesh Kumar

    2014-04-15

    The transcript expression of a gene SrUGT85C2 has been documented for direct relation with steviol glycoside content in Stevia plant. Steviol glycoside and gibberellin biosynthetic routes are divergent branches of methyl erythritol-4 phosphate (MEP) pathway. So, SrUGT85C2 might be an influencing gibberellin content. Hence in the present study, transgenic Arabidopsis thaliana overexpressing SrUGT85C2 cDNA from Stevia rebaudiana was developed to check its effect on gibberellin accumulation and related plant growth parameters. The developed transgenics showed a noteworthy decrease of 78-83% in GA3 content. Moreover, the transgenics showed a gibberellin deficient phenotype comprising stunted hypocotyl length, reduced shoot growth and a significant fall in relative water content. Transgenics also showed 17-37 and 64-76% reduction in chlorophyll a and chlorophyll b contents, respectively. Reduction in photosynthetic pigments could be responsible for the noticed significant decrease in plant biomass. Like steviol glycoside and gibberellin biosynthesis, chlorophyll biosynthesis also occurs from the precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) of MEP pathway in the plastids. The observed downregulated expression of genes encoding MEP pathway enzymes geranyl geranyl diphosphate synthase (GGDPS), copalyl diphosphate synthase (CDPS), kaurenoic acid oxidase (KAO), chlorophyll synthetase and chlorophyll a oxygenase in transgenics overexpressing SrUGT85C2 might be responsible for the reduction in gibberellins as well as chlorophyll. This study has documented for the first time the regulatory role of SrUGT85C2 in the biosynthesis of steviol glycoside, gibberellins and chlorophyll. PMID:24518812

  18. Purification and characterization of pyridoxal-5'-phosphate hydrolase from tobacco%烟草磷酸吡哆醛水解酶的分离纯化与表征

    Institute of Scientific and Technical Information of China (English)

    马娅萍; 黄龙全; 张剑韵

    2012-01-01

    Pyridoxal-5'-phosphate hydrolase was purified from tobacco by ammonium sulfate,DEAE-Sepharose Fast Flow ion exchange chromatography,Sephadex G-100 gel filtration,SP Sephadex C-25 ion exchange chromatography. Further investigations of pyridoxal-5'-phosphate hydrolase, reported herein, lead to the conclusion that this enzyme was purified approximately 119. 6-fold, the recovery of 28. 49% activity, Sephadex G-100 gel filtration and SDS-PAGE showed that the molecular weight of the enzyme was 49. 6 kDa,and the molecular weight of subunit was approximately 25 kDa; The enzyme had an optimal temperature and pH at 50℃ and 5. 5, respectively. It was enhanced by Mg2+ ,Ca2+ and Mn2+ , yet inhibited by chelating agent EDTA , which inhibited effect was relieved after added Mg2+; under optimal conditions, the Km values for pyridoxal-5'-phosphate (PLP) and pyridoxamine-5 -phos-phate (PMP) were 0. 23 mmol/L,0. 56 mmol/L,respectively.%采用硫酸铵沉淀、DEAE-Sepharose Fast Flow阴离子交换、Sephadex G-100凝胶过滤和SP Sephadex C-25阳离子交换柱层析等步骤,对烟草磷酸吡哆醛水解酶进行了分离纯化.结果表明:该酶被纯化了119.6倍,得率为28.49%,经凝胶过滤和SDS-PAGE测得该酶的全分子量为49.6 kDa,亚基分子量约为25 kDa;该酶最适温度为50℃,最适反应pH为5.5;Mg2+、Ca2+、Mn2+等对该酶有激活作用,金属离子螯合剂EDTA对酶有抑制作用,加入Mg2+后抑制作用得到解除;在最适反应条件下,测得反应底物磷酸吡哆醛(PLP)和磷酸吡哆胺(PMP)的Km值分别为0.23 mmol/L和0.56 mmol/L.

  19. Lipophilic prodrugs of FR900098 are antimicrobial against Francisella novicida in vivo and in vitro and show GlpT independent efficacy.

    Directory of Open Access Journals (Sweden)

    Elizabeth S McKenney

    Full Text Available Bacteria, plants, and algae produce isoprenoids through the methylerythritol phosphate (MEP pathway, an attractive pathway for antimicrobial drug development as it is present in prokaryotes and some lower eukaryotes but absent from human cells. The first committed step of the MEP pathway is catalyzed by 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR/MEP synthase. MEP pathway genes have been identified in many biothreat agents, including Francisella, Brucella, Bacillus, Burkholderia, and Yersinia. The importance of the MEP pathway to Francisella is demonstrated by the fact that MEP pathway mutations are lethal. We have previously established that fosmidomycin inhibits purified MEP synthase (DXR from F. tularensis LVS. FR900098, the acetyl derivative of fosmidomycin, was found to inhibit the activity of purified DXR from F. tularensis LVS (IC(50=230 nM. Fosmidomycin and FR900098 are effective against purified DXR from Mycobacterium tuberculosis as well, but have no effect on whole cells because the compounds are too polar to penetrate the thick cell wall. Fosmidomycin requires the GlpT transporter to enter cells, and this is absent in some pathogens, including M. tuberculosis. In this study, we have identified the GlpT homologs in F. novicida and tested transposon insertion mutants of glpT. We showed that FR900098 also requires GlpT for full activity against F. novicida. Thus, we synthesized several FR900098 prodrugs that have lipophilic groups to facilitate their passage through the bacterial cell wall and bypass the requirement for the GlpT transporter. One compound, that we termed "compound 1," was found to have GlpT-independent antimicrobial activity. We tested the ability of this best performing prodrug to inhibit F. novicida intracellular infection of eukaryotic cell lines and the caterpillar Galleria mellonella as an in vivo infection model. As a lipophilic GlpT-independent DXR inhibitor, compound 1 has the potential to be a broad

  20. Improving peppermint essential oil yield and composition by metabolic engineering.

    Science.gov (United States)

    Lange, Bernd Markus; Mahmoud, Soheil Seyed; Wildung, Mark R; Turner, Glenn W; Davis, Edward M; Lange, Iris; Baker, Raymond C; Boydston, Rick A; Croteau, Rodney B

    2011-10-11

    Peppermint (Mentha × piperita L.) was transformed with various gene constructs to evaluate the utility of metabolic engineering for improving essential oil yield and composition. Oil yield increases were achieved by overexpressing genes involved in the supply of precursors through the 2C-methyl-D-erythritol 4-phosphate (MEP) pathway. Two-gene combinations to enhance both oil yield and composition in a single transgenic line were assessed as well. The most promising results were obtained by transforming plants expressing an antisense version of (+)-menthofuran synthase, which is critical for adjusting the levels of specific undesirable oil constituents, with a construct for the overexpression of the MEP pathway gene 1-deoxy-D-xylulose 5-phosphate reductoisomerase (up to 61% oil yield increase over wild-type controls with low levels of the undesirable side-product (+)-menthofuran and its intermediate (+)-pulegone). Elite transgenic lines were advanced to multiyear field trials, which demonstrated consistent oil yield increases of up to 78% over wild-type controls and desirable effects on oil composition under commercial growth conditions. The transgenic expression of a gene encoding (+)-limonene synthase was used to accumulate elevated levels of (+)-limonene, which allows oil derived from transgenic plants to be recognized during the processing of commercial formulations containing peppermint oil. Our study illustrates the utility of metabolic engineering for the sustainable agricultural production of high quality essential oils at a competitive cost.

  1. Apocarotenoid biosynthesis in arbuscular mycorrhizal roots: contributions from methylerythritol phosphate pathway isogenes and tools for its manipulation.

    Science.gov (United States)

    Walter, Michael H; Floss, Daniela S; Hans, Joachim; Fester, Thomas; Strack, Dieter

    2007-01-01

    During colonization by arbuscular mycorrhizal (AM) fungi plant roots frequently accumulate two types of apocarotenoids (carotenoid cleavage products). Both compounds, C(14) mycorradicin and C(13) cyclohexenone derivatives, are predicted to originate from a common C(40) carotenoid precursor. Mycorradicin is the chromophore of the "yellow pigment" responsible for the long-known yellow discoloration of colonized roots. The biosynthesis of apocarotenoids has been investigated with a focus on the two first steps of the methylerythritol phosphate (MEP) pathway catalyzed by 1-deoxy-D-xylulose 5-phosphate synthase (DXS) and 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR). In Medicago truncatula and other plants the DXS2 isogene appears to be specifically involved in the AM-mediated accumulation of apocarotenoids, whereas in the case of DXR a single gene contributes to both housekeeping and mycorrhizal (apo)carotenoid biosynthesis. Immunolocalization of DXR in mycorrhizal maize roots indicated an arbuscule-associated protein deposition, which occurs late in arbuscule development and accompanies arbuscule degeneration and breakdown. The DXS2 isogene is being developed as a tool to knock-down apocarotenoid biosynthesis in mycorrhizal roots by an RNAi strategy. Preliminary results from this approach provide starting points to suggest a new kind of function for apocarotenoids in mycorrhizal roots.

  2. 顶复门原虫类异戊二烯生物合成途径及其关键酶的研究进展%Advance in Isoprenoids Biosynthesis Pathway and DOXP Reductoisomerase in Apicomplexa

    Institute of Scientific and Technical Information of China (English)

    廖申权; 吴彩艳; 戚南山; 吕敏娜; 覃宗华; 孙铭飞

    2012-01-01

    顶复门原虫包括疟原虫(Plasmodium spp.)、刚地弓形虫(Toxoplasma gondii)、艾美耳球虫(Eimeria spp.)、锥虫(Trypanosoma spp.)、泰勒虫(Theileria spp.)及巴贝斯虫(Babesia spp.)等一大类引起严重人畜疾病的寄生性原虫.顶复门原虫利用2C-甲基-D-赤藓糖醇-4-磷酸(MEP)途径合成类异戊二烯前体物质,这些化合物对于维持顶复门原虫的生存具有十分重要的作用.1-脱氧-D-木酮糖-5-磷酸(DOXP)还原异构酶是MEP途径的关键酶,对其作用机理及抑制剂的筛选研究已取得重要进展.论文对顶复门原虫类异戊二烯的MEP途径,DOXP还原异构酶的作用机理及靶标研究进展进行综述.

  3. Slow-binding and competitive inhibition of 8-amino-7-oxopelargonate synthase, a pyridoxal-5'-phosphate-dependent enzyme involved in biotin biosynthesis, by substrate and intermediate analogs. Kinetic and binding studies.

    Science.gov (United States)

    Ploux, O; Breyne, O; Carillon, S; Marquet, A

    1999-01-01

    8-Amino-7-oxopelargonate synthase catalyzes the first committed step of biotin biosynthesis in micro-organisms and plants. Because inhibitors of this pathway might lead to antibacterials or herbicides, we have undertaken an inhibition study on 8-amino-7-oxopelargonate synthase using six different compounds. d-Alanine, the enantiomer of the substrate of this pyridoxal-5'-phosphate-dependent enzyme was found to be a competitive inhibitor with respect to l-alanine with a Ki of 0.59 mm. The fact that this inhibition constant was four times lower than the Km for l-alanine was interpreted as the consequence of the inversion-retention stereochemistry of the catalyzed reaction. Schiff base formation between l or d-alanine and pyridoxal-5'-phosphate, in the active site of the enzyme, was studied using ultraviolet/visible spectroscopy. It was found that l and d-alanine form an external aldimine with equilibrium constants K = 4.1 mm and K = 37.8 mm, respectively. However, the equilibrium constant for d-alanine aldimine formation dramatically decreased to 1.3 mm in the presence of saturating concentration of pimeloyl-CoA, the second substrate. This result strongly suggests that the binding of pimeloyl-CoA induces a conformational change in the active site, and we propose that this new topology is complementary to d-alanine and to the putative reaction intermediate since they both have the same configuration. (+/-)-8-Amino-7-oxo-8-phosphonononaoic acid (1), the phosphonate derivative of the intermediate formed during the reaction, was our most potent inhibitor with a Ki of 7 microm. This compound behaved as a reversible slow-binding inhibitor, competitive with respect to l-alanine. Kinetic investigation showed that this slow process was best described by a one-step mechanism (mechanism A) with the following rate constants: k1 = 0.27 x 103 m-1.s-1, k2 = 1.8 s-1 and half-life for dissociation t1/2 = 6.3 min. The binding of compound 1 to the enzyme was also studied using

  4. MEP incentive for onshore wind energy. Study on the robustness of the full load methodology and options for alternative differentiation of the incentive for onshore wind energy

    International Nuclear Information System (INIS)

    The proposed amendment to the Dutch Electricity Law of 1998, called 'environmental quality of electricity production' (MEP), provides operating support through a combination of feed-in tariffs and a reduced ecotax exemption. In order to prevent a free ride of windy locations, the feed-in tariff for onshore wind turbines is limited to a maximum of 18,000 full load hours. Several parties have expressed their concern that this system may possibly provide an incentive to increase the rated power in order to lengthen the period that the feed-in tariff is being received. This report reviews the risks of unintentional side effects of the proposed limitation of 18,000 full load hours. In addition, this report examines the possibilities for further differentiation of the feed-in tariff for onshore wind energy by reviewing methods of differentiation in a number of EU member states

  5. Effection of Pyridoxal- 5 '- phosphate on Determination of Alanine Aminotransferase activities%5'-磷酸吡哆醛对血清丙氨酸氨基转移酶活性测定的影响

    Institute of Scientific and Technical Information of China (English)

    朱柏林

    2012-01-01

    目的 研究丙氨酸氨基转移酶(Alanine Aminotraasferase,ALT) 检测试剂中 5'- 磷酸吡哆醛(Pyrldoxal - 5'-phosphate,PLP )的添加对血清ALT活性测定的影响.方法 以山东潍坊康华生物技术有限公司生产的丙氨酸氨基转移酶试剂(按照IFCC推荐方法配制,不含PLP)和在该品牌试剂中加入5'-磷酸吡哆醛溶液,分别用这两种试剂测定相同的新鲜临床标本280例,并对检测结果进行统计学比较.结果 使用含PLP的IFCC配方试剂较不含 PLP试剂的检测结果明显增高.结论 康华公司生产的丙氨酸氨基转移酶试剂添加PLP比较不添加PLP ALT活性增加近5%-40%,且两种试剂的ALT检测结果不能通过简单系数实现转换.

  6. Effects of mutagenesis of aspartic acid residues in the putative phosphoribosyl diphosphate binding site of Escherichia coli phosphoribosyl diphosphate synthetase on metal ion specificity and ribose-5-phosphate binding

    DEFF Research Database (Denmark)

    Willemoës, Martin; Nilsson, Dan; Hove-Jensen, Bjarne

    1996-01-01

    The three conserved aspartic acid residues of the 5-phospho-d-ribosyl a-1-diphosphate binding site (213-GRDCVLVDDMIDTGGT-228) of Escherichia coli phosphoribosyl diphosphate synthetase were studied by analysis of the mutant enzymes D220E, D220F, D221A, D224A, and D224S. The mutant enzymes showed...... an increase in KM for ribose 5-phosphate in the presence of at least one of the divalent metal ions Mg2+, Mn2+, Co2+, or Cd2+, with the most dramatic changes revealed by the D220E and D220F enzymes in the presence of Co2+ and the D221A enzyme in the presence of Mn2+ or Co2+. The D220F and D221A enzymes both...... showed large decreases in Vapp in the presence of the various divalent metal ions, except for the D221A enzyme in the presence of Co2+. Vapp of the D220E enzyme was similar to that of the wild-type enzyme in the presence of Mg2+, Mn2+, or Cd2+, whereas the Vapp was increased in the presence of Co2+. Vapp...

  7. Effects of mutagenesis of aspartic acid residues in the putative phosphoribosyl diphosphate binding site of Escherichia coli phosphoribosyl diphosphate synthetase on metal ion specificity and ribose 5-phosphate binding

    DEFF Research Database (Denmark)

    Willemoës, Martin; Nilsson, Dan; Hove-Jensen, Bjarne

    1996-01-01

    The three conserved aspartic acid residues of the 5-phospho-D-ribosyl α-1-diphosphate binding site (213-GRDCVLVDDMIDTGGT-228) of Escherichia coli phosphoribosyl diphosphate synthetase were studied by analysis of the mutant enzymes D220E, D220F, D221A, D224A, and D224S. The mutant enzymes showed...... an increase in KM for ribose 5-phosphate in the presence of at least one of the divalent metal ions Mg2+, Mn2+, Co2+, or Cd2+, with the most dramatic changes revealed by the D220E and D220F enzymes in the presence of Co2+ and the D221A enzyme in the presence of Mn2+ or Co2+. The D220F and D221A enzymes both...... showed large decreases in Vapp in the presence of the various divalent metal ions, except for the D221A enzyme in the presence of Co2+. Vapp of the D220E enzyme was similar to that of the wild-type enzyme in the presence of Mg2+, Mn2+, or Cd2+, whereas the Vapp was increased in the presence of Co2+. Vapp...

  8. Expression of the xylulose 5-phosphate phosphoketolase gene, xpkA, from Lactobacillus pentosus MD363 is induced by sugars that are fermented via the phosphoketolase pathway and is repressed by glucose mediated by CcpA and the mannose phosphoenolpyruvate phosphotransferase system

    NARCIS (Netherlands)

    Posthuma, C.C.; Bader, R.; Engelmann, R.; Postma, P.W.; Hengstenberg, W.; Pouwels, P.H.

    2002-01-01

    Purification of xylulose 5-phosphate phosphoketolase (XpkA), the central enzyme of the phosphoketolase pathway (PKP) in lactic acid bacteria, and cloning and sequence analysis of the encoding gene, xpkA, from Lactobacillus pentosus MD363 are described, xpkA encodes a 788-amino-acid protein with a ca

  9. Bisphosphonate inhibitors reveal a large elasticity of plastidic isoprenoid synthesis pathway in isoprene-emitting hybrid aspen.

    Science.gov (United States)

    Rasulov, Bahtijor; Talts, Eero; Kännaste, Astrid; Niinemets, Ülo

    2015-06-01

    Recently, a feedback inhibition of the chloroplastic 1-deoxy-D-xylulose 5-phosphate (DXP)/2-C-methyl-D-erythritol 4-phosphate (MEP) pathway of isoprenoid synthesis by end products dimethylallyl diphosphate (DMADP) and isopentenyl diphosphate (IDP) was postulated, but the extent to which DMADP and IDP can build up is not known. We used bisphosphonate inhibitors, alendronate and zoledronate, that inhibit the consumption of DMADP and IDP by prenyltransferases to gain insight into the extent of end product accumulation and possible feedback inhibition in isoprene-emitting hybrid aspen (Populus tremula × Populus tremuloides). A kinetic method based on dark release of isoprene emission at the expense of substrate pools accumulated in light was used to estimate the in vivo pool sizes of DMADP and upstream metabolites. Feeding with fosmidomycin, an inhibitor of DXP reductoisomerase, alone or in combination with bisphosphonates was used to inhibit carbon input into DXP/MEP pathway or both input and output. We observed a major increase in pathway intermediates, 3- to 4-fold, upstream of DMADP in bisphosphonate-inhibited leaves, but the DMADP pool was enhanced much less, 1.3- to 1.5-fold. In combined fosmidomycin/bisphosphonate treatment, pathway intermediates accumulated, reflecting cytosolic flux of intermediates that can be important under strong metabolic pull in physiological conditions. The data suggested that metabolites accumulated upstream of DMADP consist of phosphorylated intermediates and IDP. Slow conversion of the huge pools of intermediates to DMADP was limited by reductive energy supply. These data indicate that the DXP/MEP pathway is extremely elastic, and the presence of a significant pool of phosphorylated intermediates provides an important valve for fine tuning the pathway flux.

  10. Resistance of Francisella novicida to Fosmidomycin Associated with Mutations in the Glycerol-3-Phosphate Transporter

    Directory of Open Access Journals (Sweden)

    Ryan S Mackie

    2012-08-01

    Full Text Available The methylerythritol phosphate (MEP pathway is essential in most prokaryotes and some lower eukaryotes but absent from human cells, and is a validated target for antimicrobial drug development. The formation of MEP is catalyzed by 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR. MEP pathway genes have been identified in many Category A and B biothreat agents, including Francisella tularensis, which causes the zoonosis tularemia. Fosmidomycin inhibits purified Francisella DXR. This compound also inhibits the growth of F. tularensis NIH B38, F. novicida and F. tularensis subsp. holarctica LVS bacteria. Related compounds such as FR900098 and lipophilic prodrugs of FR900098 have been developed to improve the bioavailability of these DXR inhibitors. In disc-inhibition assays with these compounds, we observed breakthrough colonies of F. novicida in the presence of fosmidomycin, suggesting spontaneous development of fosmidomycin resistance (FosR. FosR bacteria had decreased sensitivity to both fosmidomycin and FR900098. The two most likely targets for the development of mutants would be the DXR enzyme or the glycerol-3-phosphate transporter (GlpT that allows entry of fosmidomycin into the bacteria. Sensitivity of FosR F. novicida bacteria to compound 1 was not abated suggesting that spontaneous resistance is not due to mutation of DXR. We thus predicted that the glpT transporter may be mutated leading to this resistant phenotype. Supporting this, transposon insertion mutants at the glpT locus were also found to be resistant to fosmidomycin. DNA sequencing of four different spontaneous FosR colonies demonstrated a variety of deletions in the glpT coding region. The overall frequency of FosR mutations in F. novicida was determined to be 6.3 x 10-8. Thus we conclude that one mechanism of resistance of F. novicida to fosmidomycin is caused by mutations in GlpT. This is the first description of mutations in Francisella leading to fosmidomycin

  11. Molecular structure, vibrational, UV, NMR, HOMO-LUMO, MEP, NLO, NBO analysis of 3,5 di tert butyl 4 hydroxy benzoic acid

    Science.gov (United States)

    Mathammal, R.; Sangeetha, K.; Sangeetha, M.; Mekala, R.; Gadheeja, S.

    2016-09-01

    In this study, we report a combined experimental and theoretical study on molecular structure and vibrational spectra of 3,5 di tert butyl 4 hydroxy benzoic acid. The properties of title compound have been evaluated by quantum chemical calculation (DFT) using B3LYP functional and 6-31 + G (d, p) as basis set. IR Spectra has been recorded using Fourier transform infrared spectroscopy (FT-IR) in the region 4000-400 cm-1. The vibrational assignment of the calculated normal modes has been made on the basis set. The isotropic chemical shifts computed by 13C and 1H NMR (Nuclear Magnetic Resonance) analyses also show good agreement with experimental observations. The theoretical UV-Vis spectrum of the compound are used to study the visible absorption maxima (λ max). The structure activity relationship have been interpreted by mapping electrostatic potential surface (MEP), which is valuable information for the quality control of medicines and drug receptor interactions. The Mullikan charges, HOMO (Highest Occupied Molecular Orbital) - LUMO (Lowest Unoccupied Molecular Orbital) energy are analyzed. HOMO-LUMO energy gap and other related molecular properties are also calculated. The Natural Bond Orbital (NBO) analysis is carried out to investigate the various intra and inter molecular interactions of molecular system. The Non-linear optical properties such as dipole moment (μ), polarizability (αtot) and molecular first order hyperpolarizability (β) of the title compound are computed with B3LYP/6-31 + G (d,p) level of theory.

  12. An animal homolog of plant Mep/Amt transporters promotes ammonia excretion by the anal papillae of the disease vector mosquito Aedes aegypti.

    Science.gov (United States)

    Chasiotis, Helen; Ionescu, Adrian; Misyura, Lidiya; Bui, Phuong; Fazio, Kimberly; Wang, Jason; Patrick, Marjorie; Weihrauch, Dirk; Donini, Andrew

    2016-05-01

    The transcripts of three putative ammonia (NH3/NH4 (+)) transporters, Rhesus-like glycoproteins AeRh50-1, AeRh50-2 and Amt/Mep-like AeAmt1 were detected in the anal papillae of larval Aedes aegypti Quantitative PCR studies revealed 12-fold higher transcript levels of AeAmt1 in anal papillae relative to AeRh50-1, and levels of AeRh50-2 were even lower. Immunoblotting revealed AeAmt1 in anal papillae as a pre-protein with putative monomeric and trimeric forms. AeAmt1 was immunolocalized to the basal side of the anal papillae epithelium where it co-localized with Na(+)/K(+)-ATPase. Ammonium concentration gradients were measured adjacent to anal papillae using the scanning ion-selective electrode technique (SIET) and used to calculate ammonia efflux by the anal papillae. dsRNA-mediated reductions in AeAmt1 decreased ammonia efflux at larval anal papillae and significantly increased ammonia levels in hemolymph, indicating a principal role for AeAmt1 in ammonia excretion. Pharmacological characterization of ammonia transport mechanisms in the anal papillae suggests that, in addition to AeAmt1, the ionomotive pumps V-type H(+)-ATPase and Na(+)/K(+)-ATPase as well as NHE3 are involved in ammonia excretion at the anal papillae.

  13. Clinical analysis of vitamin B(6): determination of pyridoxal 5'-phosphate and 4-pyridoxic acid in human serum by reversed-phase high-performance liquid chromatography with chlorite postcolumn derivatization.

    Science.gov (United States)

    Rybak, Michael E; Pfeiffer, Christine M

    2004-10-15

    A reversed-phase high-performance liquid chromatography (HPLC) method with fluorometric detection was developed for the routine determination of pyridoxal 5'-phosphate (PLP) and 4-pyridoxic acid (4-PA) in serum. Chlorite postcolumn derivatization was used to oxidize PLP to a more fluorescent carboxylic acid form. Sensitivity improved fourfold for PLP using chlorite postcolumn derivatization over traditional bisulfite postcolumn derivatization. The HPLC injection cycle was 15 min, facilitating a throughput of 60 patient samples (72 injections that included standards and quality control (QC) samples) in 18.5h. Method precision was evaluated using three serum QC pools with PLP and 4-PA concentrations of 11.5-34.8 nmol/L and 10.4-21.0 nmol/L, respectively. Within-run (n=7) repeatabilities were 0.6-1.2% for PLP and 0.9-1.8% for 4-PA. Run-to-run (n=23) reproducibilities were 3.6-6.7% for PLP and 3.7-5.6% for 4-PA. Relative detection (3sigma(0)) and quantitation (10sigma(0)) limits were 0.3 and 0.9 nmol/L, respectively, for both PLP and 4-PA using a 10-microl sample injection volume. Analytical recoveries ranged from 97 to 102%. Patient-matched serum and plasma specimens (n=25) were analyzed to evaluate specimen-type bias. Of the plasma types evaluated, heparinized plasma introduced the lowest relative bias for PLP (-5.3%) and minimal bias for 4-PA (-2.3%) compared with serum. Ethylenediaminetetraacetic acid (EDTA) plasma showed the lowest bias for 4-PA (0.7%) but a relatively high bias for PLP (13.0%) due to a chromatographic interference. Human serum samples from a non-representative population subset (n=303) were commensurate with values published for other vitamin B(6) HPLC methods. These values gave geometric means of 42.4 nmol/L for PLP and 27.3 nmol/L for 4-PA. Medians for PLP and 4-PA were 40.1 and 21.8 nmol/L, respectively. The high sensitivity, precision, and throughput of this method, combined with its minimal serum specimen (150 microl) and sample injection

  14. BAEP、BR及MEP联合检测在脑死亡诊断中的应用%Application of BAEP, BR and MEP combined detection for the diagnosis of brain death

    Institute of Scientific and Technical Information of China (English)

    朴虎男; 朴莲荀; 杜婷婷

    2012-01-01

    目的 探讨神经电生理在脑死亡判定中的应用价值.方法 通过瞬间反射(BR)、脑干听觉诱发电位(BAEP)、运动诱发电位(MEP)三项联合检查对22例脑死亡患者进行评定,并与GCS评分结果进行比较.结果 BAEP、BR和MEP三项联合检查对脑死亡判断准确率为100%,与GCS评分比较差异显著(P<0.05).结论 BAEP、BR和MEP三项联合检测对评价脑死亡患者的脑功能状态、预测预后提供了客观可靠的依据.%Objective To investigate the diagnosis value of neuro-electrophysiology detection for brain death. Methods Combined detection of brainstem auditory evoked potentials ( BAEP) , blink reflex (BR) united motor evoked potentials ( MEP) were used to access 22 brain death patients, and then compared with the Glasgow Coma Scale (GCS) scores. Results The accuracy of BAEP, BR and MEP combined detection was 100% , and which showed significant difference compared with GCS scores. Conclusion BAEP, BR united MEP testing can provide an objective indicator not only for e-valuating brain function of brain death, but also for estimating prognosis.

  15. Nuclear Polluters' Charter. Council directive 96/29/EURATOM (OJ L159 29th June 1996), the 'Basic Standards Directive'; briefing for MPs and MEPs

    International Nuclear Information System (INIS)

    The nuclear industry has huge 'back end' problems: acres of radioactive waste stacked up with no final disposal route; hundreds of thousands of tonnes of metals, glass, plastic, and concrete too 'hot' to re-use or dump. Sea dumping has been ruled out, Nirex's deep repository is back to square one, the waste mountain is growing, and hundreds of nuclear factories and power stations await decommissioning. But by May 2000 the UK and all member states are required to conform with a dangerously vague and permissive Directive, and deregulate much of this expensive, embarrassing, and harmful waste. Below certain very lax limits it will become a financial asset to be sold on the open market. What cannot be sold will be landfilled and incinerated without restriction. Ostensibly, the Directive is a 'harmonisation' of radiation exposure standards. It was promulgated by the European Commission under the Euratom Treaty of 1957. The European Parliament has no power over Euratom, and (with one exception) amendments advised by MEPs were ignored. The Directive effectively deregulates reuse, recycling, disposal, and incineration of radioactive materials below certain threshold levels. It specifically allows recycling of contaminated materials and drops a precautionary proviso used in earlier European legislation. Spokesmen from the nuclear industry, the regulators, and the Commission openly admit that there is nothing to stop hundreds of thousands of tonnes of radioactive materials from nuclear licensed sites - potentially, their entire inventory - being diluted into industrial feedstocks of recyclable materials and ending up in consumer goods, fertilisers or any product. The Commission's view is let the buyers beware if they don't want contaminated goods or raw materials. National radiation protection agencies which advise the Commission and national governments claim that there is no threat to health, according to internationally accepted radiation risk factors. But those same

  16. The effect of MEP pathway and other inhibitors on the intracellular localization of a plasma membrane-targeted, isoprenylable GFP reporter protein in tobacco BY-2 cells [v1; ref status: indexed, http://f1000r.es/yx

    Directory of Open Access Journals (Sweden)

    Michael Hartmann

    2013-08-01

    Full Text Available We have established an in vivo visualization system for the geranylgeranylation of proteins in a stably transformed tobacco BY-2 cell line, based on the expression of a dexamethasone-inducible GFP fused to the carboxy-terminal basic domain of the rice calmodulin CaM61, which naturally bears a CaaL geranylgeranylation motif (GFP-BD-CVIL. By using pathway-specific inhibitors it was demonstrated that inhibition of the methylerythritol phosphate (MEP pathway with known inhibitors like oxoclomazone and fosmidomycin, as well as inhibition of the protein geranylgeranyltransferase type 1 (PGGT-1, shifted the localization of the GFP-BD-CVIL protein from the membrane to the nucleus. In contrast, the inhibition of the mevalonate (MVA pathway with mevinolin did not affect the localization. During the present work, this test system has been used to examine the effect of newly designed inhibitors of the MEP pathway and inhibitors of sterol biosynthesis such as squalestatin, terbinafine and Ro48-8071. In addition, we also studied the impact of different post-prenylation inhibitors or those suspected to affect the transport of proteins to the plasma membrane on the localization of the geranylgeranylable fusion protein GFP-BD-CVIL.

  17. A novel strategy to isolate cell-envelope mutants resistant to phage infection: bacteriophage mEp213 requires lipopolysaccharides in addition to FhuA to enter Escherichia coli K-12.

    Science.gov (United States)

    Reyes-Cortés, Ruth; Martínez-Peñafiel, Eva; Martínez-Pérez, Francisco; de la Garza, Mireya; Kameyama, Luis

    2012-12-01

    We have developed a direct and efficient strategy, based on a three-step method, to select bacterial cell-envelope mutants resistant to bacteriophage infection. Escherichia coli K-12 strain W3110 underwent classical transposon mutagenesis followed by replica plating and selection for mutants resistant to infection by coliphage mEp213. To verify that phage resistance was due to mutations in the cell envelope, we transformed host cells with the viral genome using electroporation and selected those in which virions were subsequently detected in the supernatant. Among the nine mutants resistant to coliphage infection that we selected, six were in the fhuA gene, two were mutated in the waaC gene, and one was mutated in the gmhD gene. The latter two gene products are involved in the synthesis of lipopolysaccharide (LPS). The efficiency of plating and adsorption of phage mEp213 was affected in these mutants. We verified that LPS is required for the efficient infection of phage λ as well. We propose that this mutation-and-selection strategy can be used to find host factors involved in the initial steps of phage infection for any cognate pair of phage and bacteria.

  18. 经颅磁刺激运动诱发电位对脊髓损伤的评价及法医学意义%The Evaluation of SCI by TMS-MEP and Its Forensic Significance

    Institute of Scientific and Technical Information of China (English)

    杨蕾; 刘兴本; 朱镕霆; 徐晓明; 郑传斐; 周禹鑫

    2013-01-01

    目的 为脊髓损伤(spinal cord injury,SCI)的法医临床学鉴定寻找客观且准确的检查方法.方法 采用经颅磁刺激运动诱发电位(transcranial magnetic stimulation-motor evoked potential,TMS-MEP)测定68例SCI患者(颈段损伤23例,胸腰段损伤45例)拇短展肌和胫前肌的皮层起始潜伏期、N1峰潜伏期、中枢运动传导时间(central motor conduction time,CMCT)和波宽,并以30例正常人作为对照,比较两组差异. 结果 实验组随拇短展肌、胫前肌肌力下降或消失,皮层起始潜伏期、N1峰潜伏期、CMCT延长,波宽增宽,且实验组中的2、3级肌力者上述指标均高于对照组(P<0.05).结论 TMS-MEP检测可以直接、客观地反映脊髓锥体束的运动功能状态,为法医学鉴定提供更客观、准确的依据.%Objective To find an objective and accurate examination for evaluation of spinal cord injury (SCI) in forensic clinical medicine.Methods The onset latency of cortex,peak latency of N1,central motor conduction time (CMCT) and wave width of the abductor pollicis brevis and the anterior tibialis were calculated by transcranial magnetic stimulation-motor evoked potential (TMS-MEP).The data of 68 patients suffered from SCI including 23 cervical levels and 45 thoracolumbar levels were collected and compared with that of 30 normal controls.Results In experimental group,when the muscle strength of the abductor pollicis brevis or the anterior tibialis decreased or disappeared,the onset latency of cortex,the peak latency of N1,and CMCT prolonged and the wave width broadened.And these indexes of grade 2 and 3 muscle strength in experimental group were higher than that in the control group (P<0.05).Conclusion The TMS-MEP can determine directly and objectively the motor functional status of pyramidal tract of spinal cord in order to provide more accurate and objective evidences in forensic medicine.

  19. Spectroscopic (FT-IR and FT-Raman) investigation, first order hyperpolarizability, NBO, HOMO-LUMO and MEP analysis of 6-nitrochromone by ab initio and density functional theory calculations

    Science.gov (United States)

    Senthil kumar, J.; Jeyavijayan, S.; Arivazhagan, M.

    2015-02-01

    The vibrational spectral analysis is carried out using FT-Raman and FT-IR spectroscopy in the range 3500-50 cm-1 and 4000-400 cm-1, respectively, for 6-nitrochromone (6NC). The molecular structure, fundamental vibrational frequencies and intensity of the vibrational bands are interpreted with the aid of structure optimization and normal coordinates force field calculation based on ab initio HF and DFT gradient calculations employing the HF/6-311++G(d,p) and B3LYP/6-311++G(d,p) basis set. Stability of the molecule has been analyzed using NBO analysis. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. Thermodynamic properties like entropy, heat capacity, zero-point energy and Mulliken's charge analysis have been calculated for the 6NC. The complete assignments were performed on the basis of total energy distribution (TED) of the vibrational modes with scaled quantum mechanical (SQM) method. The MEP map shows the negative potential sites are on oxygen atoms as well as the positive potential sites are around the hydrogen atoms.

  20. Ornamental, Turf and Nursery Pests. MEP 308.

    Science.gov (United States)

    Morgan, Omar D.; And Others

    As part of a cooperative extension service series by the University of Maryland, this publication introduces the identification and control of common turf and plant pests that can be found in the urban environment. The first of the five sections defines "pest" and "weed" and generally introduces different kinds of pests such as insects, weeds, and…

  1. MEPs : ban hammer, sickle and swastika

    Index Scriptorium Estoniae

    2005-01-01

    Europarlamendi liikmete Vytautas Landsbergise ja Jozsef Szajeri avalduse kohaselt tuleks Euroopa Liidus ettevalmistatava seaduse raames, mis keelustaks natsisümboli - haakristi - kasutamise, keelata ka kommunismi sümboolika kasutamine

  2. Medical Expenditure Panel Survey (MEPS) Query Tool

    Data.gov (United States)

    U.S. Department of Health & Human Services — MEPSnet HC Query Tool MEPSnet/Household Component provides easy access to nationally representative statistics of health care use, expenditures, sources of payment,...

  3. Intracellular adenosine 3',5'-phosphate formation is essential for down-regulation of surface adenosine 3',5'-phosphate receptors in Dictyostelium

    OpenAIRE

    Van Haastert, Peter J. M.

    1994-01-01

    Dictyostelium discoideum cells contain cell surface cyclic AMP (cAMP) receptors that bind cAMP as a first messenger and intracellular cAMP receptors that bind cAMP as a second messenger. Prolonged incubation of Dictyostelium cells with cAMP induces a sequential process of phosphorylation, sequestration and down-regulation of the surface receptors. The role of intracellular cAMP in down-regulation of surface receptors was investigated. Down-regulation of receptors does not occur under conditio...

  4. 2C-Methyl-d-erythritol 4-phosphate enhances and sustains cyclodiphosphate synthase IspF activity.

    Science.gov (United States)

    Bitok, J Kipchirchir; Meyers, Caren Freel

    2012-10-19

    There is significant progress toward understanding catalysis throughout the essential MEP pathway to isoprenoids in human pathogens; however, little is known about pathway regulation. The present study begins by testing the hypothesis that isoprenoid biosynthesis is regulated via feedback inhibition of the fifth enzyme cyclodiphosphate synthase IspF by downstream isoprenoid diphosphates. Here, we demonstrate recombinant E. coli IspF is not inhibited by downstream metabolites isopentenyl diphosphate (IDP), dimethylallyl diphosphate (DMADP), geranyl diphosphate (GDP), and farnesyl diphosphate (FDP) under standard assay conditions. However, 2C-methyl-d-erythritol 4-phosphate (MEP), the product of reductoisomerase IspC and first committed MEP pathway intermediate, activates and sustains this enhanced IspF activity, and the IspF-MEP complex is inhibited by FDP. We further show that the methylerythritol scaffold itself, which is unique to this pathway, drives the activation and stabilization of active IspF. Our results suggest a novel feed-forward regulatory mechanism for 2C-methyl-d-erythritol 2,4-cyclodiphosphate (MEcDP) production and support an isoprenoid biosynthesis regulatory mechanism via feedback inhibition of the IspF-MEP complex by FDP. The results have important implications for development of inhibitors against the IspF-MEP complex, which may be the physiologically relevant form of the enzyme. PMID:22839733

  5. Comparability study of ALT detection by three biochemistry analyzer systems and the influence to ALT activity with the existence of coenzyme pyridoxal-5-phosphate.%辅酶磷酸吡哆醛的存在对三种生化检测系统测定丙氨酸氨基转移酶活性的影响及其可比性研究

    Institute of Scientific and Technical Information of China (English)

    张建忠; 沈春燕

    2011-01-01

    To study the difference and comparability of alanine aminotransferase (ALT) results detected by three biochemistry analyzer systems. Methods The ALT activities of 164 cases of patients and 152 cases of healthy adults were detected by DADE Dimension RXL system, Johnson Vitros-350 system that containing pyridoxal-5-phosphate in their reagents and HITACHI7170 system that not containing pyridoxal-5-phosphate in its reagents,respectively. According to the document EP9-A described by the NCCLS, two group parallel contrast tests had being established: In the first group, ALT detected by HITACHI7170 system was selected as the standard method and DADE Dimension RXL system as the empirical method. In the other group, ALT detected by DADE Dimension RXL system was selected as the standard method and Johnson Vitros-350 system as the empirical method. Results The assay resuits of ALT activity detected by DADE Dimension RXL and Johnson Vitros-350 systems were higher(20.2%~56.5%)than that detected by HITACHI7170 system and there was no significant difference between DADE Dimension RXL system and Johnson Vitros-350 system. The parallel contrast tests also showed that there was an obvious systematic error between HITACHI7170 system and DADE Dimension RXL system, but there was a good correlation between DADE Dimension RXL system and Vitros-350 system. Conclusion Because of the difference of methodology the results of ALT activity detected by DADE Dimension RXL and Johnson Vitros-350 biochemistry analyzer systems couldn't obtain consistency with those by HITACHI7170 system, but there was a higher consistency between DADE Dimension RXL system and Vitros-350 system.%目的 探讨不同生化检测系统间测定丙氨酸氨基转移酶(ALT)活性结果的差异及其可比性.方法 使用ALT试剂中含有磷酸吡哆醛的DADE Dimension RXL检测系统、强生Vitros-350检测系统以及ALT试剂中未含有磷酸吡哆醛HITACHI7170检测系统同时测试164例患者和152例

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

    OpenAIRE

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

    2009-01-01

    The structure of ribonuclease A in complex with uridine 5′-phosphate and uridine 5′-diphosphate has been determined at 1.4 Å resolution in order to facilitate the rational design of selective and potent inhibitors.

  7. Chemical modification of human muscle aldose reductase by pyridoxal 5'-phosphate

    International Nuclear Information System (INIS)

    Aldose reductase (ALR2) is a monomeric oxidoreductase (Mr, 37,000). This enzyme catalyzes the reduction of a wide variety of aliphatic and aromatic aldehydes to their corresponding alcohols. The ability to reduce D-glucose and utilize NADH distinguishes ALR2 from aldehyde reductase (ALR1) which is exclusively NADPH-dependent. As part of a study to determine active site residues critical for binding and catalysis they have investigated the behavior of ALR2 with pyridoxal phosphate (PLP). In contrast to ALR1, which is inactivated by PLP, the reaction of ALR2 with PLP results in a 2-3 fold activation with the incorporation of 1 mol of PLP/mol enzyme. However, despite a 3-fold increase in k/sub cat/, there is also a 13-14 fold increase in the Km for both coenzyme and substrate and catalytic efficiency (k/sub cat//Km) is actually decreased. Reaction of ALR2 with 3[H] PLP followed by digestion with endoproteinase Lys-C enabled the separation and purification by HPLC of a peptide containing a single pyridoxyllysine residue. The sequence of this 32 residue peptide is highly homologous with a peptide similarly obtained from pig and human ALR1 and is identical with one from pig ALR2. In all four enzymes, pig ALR1, ALR2; human ALR1, ALR2, a tetrapeptide containing the pyridoxylated lysine (I-P-K-S) shows absolute identity. Thus, despite differences in substrate and coenzyme specificity, the active site in both ALR1 and ALR2 is relatively conserved

  8. Studies on the Interaction of Riboflavin-5'-Phosphate with Protein with Special Attention to Bacterial Bioluminescence

    NARCIS (Netherlands)

    Gast, R.

    1978-01-01

    The central theme of this thesis is the interaction of FMN with proteins. For one of the proteins studied, the enzyme luciferase from bacteria, further investigations were done on the process of light emission.In chapter 2 and 3 studies are reported on the binding of FMN with relatively simple prote

  9. Medical Expenditure Panel Survey (MEPS) Restricted Data Files

    Data.gov (United States)

    U.S. Department of Health & Human Services — Restricted Data Files Available at the Data Centers Researchers and users with approved research projects can access restricted data files that have not been...

  10. Lithuanian MEP loses his immunity / Rokas M. Tracevskis

    Index Scriptorium Estoniae

    Tracevskis, Rokas M.

    2010-01-01

    7. septembril otsustas Euroopa Parlament parlamendisaadiku Viktor Uspaskihhi puutumatuse ära võtta, kuna teda kahtlustatakse Tööerakonna raamatupidamise võltsimises. Viktor Uspaskihhi poliitilisest tegevusest

  11. The non-mevalonate isoprenoid biosynthesis of plants as a test system for drugs against malaria and pathogenic bacteria.

    Science.gov (United States)

    Zeidler, J; Schwender, J; Mueller, C; Lichtenthaler, H K

    2000-12-01

    Two plant test systems are presented in the search for new inhibitors of the non-mevalonate isoprenoid pathway. A derivative of clomazone appears to be an inhibitor of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate (DOXP/MEP) pathway of isoprenoid formation.

  12. De novo fragment-based design of inhibitors of DXS guided by spin-diffusion-based NMR spectroscopy

    NARCIS (Netherlands)

    Masini, T.; Pilger, J.; Kroezen, B. S.; Illarionov, B.; Lottmann, P.; Fischer, M.; Griesinger, C.; Hirsch, A. K. H.

    2014-01-01

    We applied for the first time an innovative ligand-based NMR methodology (STI) to a medicinal-chemistry project aimed at the development of inhibitors for the enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS). DXS is the first enzyme of the 2C-methyl-D-erythritol-4-phosphate (MEP) pathway, presen

  13. Study on combined monitoring in cervical cord operation by median nerve brainstem somatosensory evoked potential (MN-BSEP) and short train transcranial electrical stimulation motor evoked potential (STTES-MEP)%正中神经脑干躯体感觉诱发电位和经颅短串电刺激运动诱发电位联合术中监护在颈髓手术中的应用

    Institute of Scientific and Technical Information of China (English)

    顾士欣; 徐启武; 陈炜; 车晓明

    2004-01-01

    目的研究在异丙酚全静脉麻醉方案下,联合应用正中神经脑干躯体感觉诱发电位(MN-BSEP)和经颅短串电刺激运动诱发电位(STTES-MEP)对颈髓手术实施术中监护的可行性.方法通过变换不同的刺激条件、记录条件、技术参数,分别摸索MN-BSEP和STTES-MEP的可靠检测方法,并按照总结得到的技术规范,选择我科15例接受颈髓手术的病人,进行术中联合监护,对照分析术前和术后脊髓功能的改变和诱发电位变化之间的关系.结果 MN-BSEP基本不受麻醉影响,术后的改变与术后病人感觉功能的转归情况相吻合;STTES-MEP与麻醉方案有关,在异丙酚麻醉下,可记录到清晰、稳定的运动诱发电位,其术后的变化与术后病人肌力的转归情况相吻合.结论选用异丙酚全静脉麻醉,联合应用MN-BSEP和STTES-MEP实现对颈髓功能的术中监护是可行的,其效果优于单纯应用体感诱发电位或运动诱发电位进行监护.

  14. Ribose-5-Phosphate Biosynthesis in Methanocaldococcus jannaschii Occurs in the Absence of a Pentose-Phosphate Pathway

    OpenAIRE

    Grochowski, Laura L.; Xu, Huimin; White, Robert H.

    2005-01-01

    Recent work has raised a question as to the involvement of erythrose-4-phosphate, a product of the pentose phosphate pathway, in the metabolism of the methanogenic archaea (R. H. White, Biochemistry 43:7618-7627, 2004). To address the possible absence of erythrose-4-phosphate in Methanocaldococcus jannaschii, we have assayed cell extracts of this methanogen for the presence of this and other intermediates in the pentose phosphate pathway and have determined and compared the labeling patterns ...

  15. A homogeneous, high-throughput assay for phosphatidylinositol 5-phosphate 4-kinase with a novel, rapid substrate preparation.

    Directory of Open Access Journals (Sweden)

    Mindy I Davis

    Full Text Available Phosphoinositide kinases regulate diverse cellular functions and are important targets for therapeutic development for diseases, such as diabetes and cancer. Preparation of the lipid substrate is crucial for the development of a robust and miniaturizable lipid kinase assay. Enzymatic assays for phosphoinositide kinases often use lipid substrates prepared from lyophilized lipid preparations by sonication, which result in variability in the liposome size from preparation to preparation. Herein, we report a homogeneous 1536-well luciferase-coupled bioluminescence assay for PI5P4Kα. The substrate preparation is novel and allows the rapid production of a DMSO-containing substrate solution without the need for lengthy liposome preparation protocols, thus enabling the scale-up of this traditionally difficult type of assay. The Z'-factor value was greater than 0.7 for the PI5P4Kα assay, indicating its suitability for high-throughput screening applications. Tyrphostin AG-82 had been identified as an inhibitor of PI5P4Kα by assessing the degree of phospho transfer of γ-(32P-ATP to PI5P; its inhibitory activity against PI5P4Kα was confirmed in the present miniaturized assay. From a pilot screen of a library of bioactive compounds, another tyrphostin, I-OMe tyrphostin AG-538 (I-OMe-AG-538, was identified as an ATP-competitive inhibitor of PI5P4Kα with an IC(50 of 1 µM, affirming the suitability of the assay for inhibitor discovery campaigns. This homogeneous assay may apply to other lipid kinases and should help in the identification of leads for this class of enzymes by enabling high-throughput screening efforts.

  16. Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV

    Science.gov (United States)

    Akil, Abdellah; Peng, Juan; Omrane, Mohyeddine; Gondeau, Claire; Desterke, Christophe; Marin, Mickaël; Tronchère, Hélène; Taveneau, Cyntia; Sar, Sokhavuth; Briolotti, Philippe; Benjelloun, Soumaya; Benjouad, Abdelaziz; Maurel, Patrick; Thiers, Valérie; Bressanelli, Stéphane; Samuel, Didier; Bréchot, Christian; Gassama-Diagne, Ama

    2016-01-01

    The accumulation of lipid droplets (LD) is frequently observed in hepatitis C virus (HCV) infection and represents an important risk factor for the development of liver steatosis and cirrhosis. The mechanisms of LD biogenesis and growth remain open questions. Here, transcriptome analysis reveals a significant upregulation of septin 9 in HCV-induced cirrhosis compared with the normal liver. HCV infection increases septin 9 expression and induces its assembly into filaments. Septin 9 regulates LD growth and perinuclear accumulation in a manner dependent on dynamic microtubules. The effects of septin 9 on LDs are also dependent on binding to PtdIns5P, which, in turn, controls the formation of septin 9 filaments and its interaction with microtubules. This previously undescribed cooperation between PtdIns5P and septin 9 regulates oleate-induced accumulation of LDs. Overall, our data offer a novel route for LD growth through the involvement of a septin 9/PtdIns5P signalling pathway. PMID:27417143

  17. Crystal Structure Analyses of the Fosmidomycin-Target Enzyme from Plasmodium Falciparum

    Science.gov (United States)

    Umeda, Tomonobu; Kusakabe, Yoshio; Tanaka, Nobutada

    The human malaria parasite Plasmodium falciparum is responsible for the death of more than a million people each year. Fosmidomycin has proved to be efficient in the treatment of P. falciparum malaria through the inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an enzyme of the non-mevalonate pathway of isoprenoid biosynthesis, which is absent in humans. Crystal structure analyses of P. falciparum DXR (PfDXR) revealed that (i) an intrinsic flexibility of the PfDXR molecule accounts for the induced-fit movement to accommodate the bound inhibitor in the active site, and (ii) a cis arrangement of the oxygen atoms of the hydroxamate group of the bound inhibitor is essential for tight binding of the inhibitor to the active site metal. We believe that our study will serve as a useful guide to develop more potent PfDXR inhibitors.

  18. Characterization of the Arabidopsis clb6 mutant illustrates the importance of posttranscriptional regulation of the methyl-D-erythritol 4-phosphate pathway.

    Science.gov (United States)

    Guevara-García, Arturo; San Román, Carolina; Arroyo, Analilia; Cortés, María Elena; de la Luz Gutiérrez-Nava, María; León, Patricia

    2005-02-01

    The biosynthesis of isopentenyl diphosphate and dimethylallyl diphosphate, the two building blocks for isoprenoid biosynthesis, occurs by two independent pathways in plants. The mevalonic pathway operates in the cytoplasm, and the methyl-d-erythritol 4-phosphate (MEP) pathway operates in plastids. Plastidic isoprenoids play essential roles in plant growth and development. Plants must regulate the biosynthesis of isoprenoids to fulfill metabolic requirements in specific tissues and developmental conditions. The regulatory events that modulate the plant MEP pathway are not well understood. In this article, we demonstrate that the CHLOROPLAST BIOGENESIS6 (CLB6) gene, previously shown to be required for chloroplast development, encodes 1-hydroxy-2-methyl-butenyl 4-diphosphate reductase, the last-acting enzyme of the MEP pathway. Comparative analysis of the expression levels of all MEP pathway gene transcripts and proteins in the clb6-1 mutant background revealed that posttranscriptional control modulates the levels of different proteins in this central pathway. Posttranscriptional regulation was also found during seedling development and during fosmidomycin inhibition of the pathway. Our results show that the first enzyme of the pathway, 1-deoxy-d-xylulose 5-phosphate synthase, is feedback regulated in response to the interruption of the flow of metabolites through the MEP pathway.

  19. OPEC – What Difference has it Made?: OIES paper: MEP 3

    OpenAIRE

    Fattouh, Bassam; Mahadeva, Lavan

    2013-01-01

    The main purpose of this paper is to review the evolution of OPEC models and to link this evolution to some key events in the oil market. Our main conclusion is that OPEC’s pricing power varies over time. There are many instances in which OPEC can lose the power to limit oil price movements – either up or down. Such changes in pricing power are brought about by market conditions and can occur both in weak and tight market conditions. Because of OPEC’s varying conduct, there is no single model...

  20. The Implications of the Arab Uprisings for Oil and Gas Markets: OIES paper: MEP 2

    OpenAIRE

    Fattouh, Bassam; Darbouche, Hakim

    2011-01-01

    The events that took place in the Arab world in the opening months of 2011 mark a watershed in the history of the Middle East and North Africa (MENA) region. Given the importance of MENA energy supplies in global economic terms, the political unrest witnessed by the region has caused widespread fears about the prospect of energy supply disruptions. With international oil and gas prices beginning to rise from 2010, there was serious concern among market and political actors that any further in...

  1. Energy Poverty in the Arab World: The Case of Yemen: OIES paper: MEP 1

    OpenAIRE

    Fattouh, Bassam; El-Katiri, Laura

    2011-01-01

    While much of the emphasis of the literature on energy poverty is on the prevalence of the phenomenon in sub-Saharan Africa and South Asia, little has been written about energy poverty in the Arab world. Traditionally having being seen as one of the world’s most energy rich regions, the Arab world has in recent years often been overlooked as a region which suffers severely from energy poverty itself. In 2002, about 65 million people in the Arab world had no access to electricity, and an addi...

  2. Monitoring- and Evaluation Program Near Shore Wind farm (MEP-NSW): Fish community

    NARCIS (Netherlands)

    Hal, van R.; Couperus, A.S.; Fassler, S.M.M.; Gastauer, S.; Griffioen, B.; Hintzen, N.T.; Teal, L.R.; Keeken, van O.A.; Winter, H.V.

    2012-01-01

    In 2006, the first Dutch offshore wind farm was built 10-18 km from the shore of Egmond aan Zee by a joint venture of Nuon and Shell Windenergy. A Monitoring and Evaluation Program accompanied the plans for the construction and exploitation of this farm. The program contained plans for the monitorin

  3. MEPS 2.0? EUROPARLIAMENTARIANS TALKING TO VOTERS IN THE INTERNET ERA

    Directory of Open Access Journals (Sweden)

    Stefano Braghiroli

    2010-09-01

    Full Text Available This paper systematically looks at the nature of MEPs’ internet-based “web tools” in the past EP legislature and at the extent to which their features reflect the complex nature of the EP environment (“Europeanization of communication”. To conduct this operation, a variety of structural and graphic features of MEPs’ websites have been identified, which have been made statistically analyzable, following a process of standardization and categorization, and were finally collected into a unique dataset. The preliminary figures obtained have been then controlled for a wide array of pluri-dimensional factors, operating both at micro-/individual-level and at macro-/country-level. Conceived as an explorative study towards clearer and more accurate understanding of MEPs’ internet-based communication styles and political strategies, our analysis aims at providing a stepping stone for further investigation in this direction.

  4. 75 FR 33766 - Manufacturing Extension Partnership (MEP) Availability of Funds for Projects To Develop Client...

    Science.gov (United States)

    2010-06-15

    ... or business model, the benefit of this integration and how the approach can expand service capability... project should further demonstrate in its proposed client engagement or business model, the benefit of... Funds for Projects To Develop Client Engagement or Business Models and Deployment Strategies...

  5. A STUDY OF FVC, PEFR AND MEP IN DIFFERENT TRIMESTERS OF PREGNANCY

    OpenAIRE

    2012-01-01

    Objective : Pregnancy is characterized by profound changes in the function of virtually every regulatory system in the human body. The events in pregnancy elicit one of the best examples of selective anatomical, physiological & biochemical adaptation that occur during pregnancy & profound changes in respiratory physiology is a part of the same process. Thus this study was designed to evaluate the pulmonary function tests in 1st, 2nd and 3rd trimesters of pregnancy & compare them w...

  6. Working at home: MEPs day-to-day practice of political representation in their constituency

    OpenAIRE

    Poyet, Corentin

    2015-01-01

    International audience In early 2000s, Simon Hix and his colleagues declared EP constitutes a good laboratory to test theories and hypotheses about legislative or party behavior. However, scholars mainly focused on roll-call votes analysis allowing them to investigate voting behavior, coalitions formation as well as activities in technical committees (Hix 2001; Hix, Noury and Roland 2007; Kreppel 2007; Mammoudh and Raunio 2003; McElroy 2006). In this paper, we propose to go further to anal...

  7. Airborne Survey Capacity Building of National Nuclear Safety Administration (MEP) in China

    International Nuclear Information System (INIS)

    Airborne survey is being paid more and attention in the nuclear radiation environment monitoring due to its unique advantages, especially monitoring due to its unique advantages, especially after the nuclear accident of Fukushima Japan. Thus, National Nuclear Safety Administration is strengthening to build airborne survey capacity. The administration has set up an advanced airborne survey system and established expert team. This airborne survey system here is fixed under a capable helicopter, which has a monitoring volume of 75.6 liters, independent advanced digital spectrometer and intelligent data processing functions. In this paper, a way that is applied for wireless data real-time transmission is presented, and our research works on calibration and the survey methods are also included. The airborne survey system can be widely used in the nuclear and radiation accidents monitoring and relative radiation monitoring in NORM. (author)

  8. 78 FR 34346 - Proposed Information Collection; Comment Request; NIST MEP Advanced Manufacturing Jobs and...

    Science.gov (United States)

    2013-06-07

    .... Estimated Time per Response: 15 minutes. Estimated Total Annual Burden Hours: 50. Estimated Total Annual... Commerce, as part of its continuing effort to reduce paperwork and respondent burden, invites the...

  9. Biosynthesis of β-carotene in engineered E. coli using the MEP and MVA pathways

    OpenAIRE

    Yang, Jianming; Guo, Lizhong

    2014-01-01

    Background β-carotene is a carotenoid compound that has been widely used not only in the industrial production of pharmaceuticals but also as nutraceuticals, animal feed additives, functional cosmetics, and food colorants. Currently, more than 90% of commercial β-carotene is produced by chemical synthesis. Due to the growing public concern over food safety, the use of chemically synthesized β-carotene as food additives or functional cosmetic agents has been severely controlled in recent years...

  10. Advanced In-Space Propulsion (AISP): Micro Electrospray Propulsion (MEP) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Propulsion technology is often critical for space missions. High-value missions could be done with very small spacecraft, even CubeSats, but these...

  11. 77 FR 12041 - Applications for New Awards; Migrant Education Program (MEP) Consortium Incentive Grants Program

    Science.gov (United States)

    2012-02-28

    ... notice of final requirements for this program, published in the Federal Register on March 3, 2004 (69 FR... FR 13217). Absolute Priorities: For FY 2012, these priorities are absolute priorities. Under 34 CFR... notice of final requirements published in the Federal Register on March 3, 2004 (69 FR 10110); and...

  12. Vitamin B6 nutritional status and cellular availability of pyridoxal 5'-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions.

    Science.gov (United States)

    Gregory, Jesse F; DeRatt, Barbara N; Rios-Avila, Luisa; Ralat, Maria; Stacpoole, Peter W

    2016-07-01

    The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the generation of H2S for signaling functions. Regulation of TS pathway kinetics involves stimulation of cystathionine β-synthase (CBS) by S-adenosylmethionine (SAM) and oxidants such as H2O2, and by Michaelis-Menten principles whereby substrate concentrations affect reaction rates. Although pyridoxal phosphate (PLP) serves as coenzyme for both CBS and cystathionine γ-lyase (CSE), CSE exhibits much greater loss of activity than CBS during PLP insufficiency. Thus, cellular and plasma cystathionine concentrations increase in vitamin B6 deficiency mainly due to the bottleneck caused by reduced CSE activity. Because of the increase in cystathionine, the canonical production of cysteine (homocysteine → cystathionine → cysteine) is largely maintained even during vitamin B6 deficiency. Typical whole body transsulfuration flux in humans is 3-7 μmol/h per kg body weight. The in vivo kinetics of H2S production via side reactions of CBS and CSE in humans are unknown but they have been reported for cultured HepG2 cells. In these studies, cells exhibit a pronounced reduction in H2S production capacity and rates of lanthionine and homolanthionine synthesis in deficiency. In humans, plasma concentrations of lanthionine and homolanthionine exhibit little or no mean change due to 4-wk vitamin B6 restriction, nor do they respond to pyridoxine supplementation of subjects in chronically low-vitamin B6 status. Wide individual variation in responses of the H2S biomarkers to such perturbations of human vitamin B6 status suggests that the resulting modulation of H2S production may have physiological consequences in a subset of people. Supported by NIH grant DK072398. This paper refers to data from studies registered at clinicaltrials.gov as NCT01128244 and NCT00877812. PMID:26765812

  13. An insight into the sequential, structural and phylogenetic properties of banana 1-aminocyclopropane-1-carboxylate synthase 1 and study of its interaction with pyridoxal-5'-phosphate and aminoethoxyvinylglycine

    Indian Academy of Sciences (India)

    Swarup Roy Choudhury; Sanjay Kumar Singh; Sujit Roy; Dibyendu N Sengupta

    2010-06-01

    In banana, ethylene production for ripening is accompanied by a dramatic increase in 1-aminocyclopropane-1-carboxylate (ACC) content, transcript level of Musa acuminata ACC synthase 1 (MA-ACS1) and the enzymatic activity of ACC synthase 1 at the onset of the climacteric period. MA-ACS1 catalyses the conversion of -adenosyl-L-methionine (SAM) to ACC, the key regulatory step in ethylene biosynthesis. Multiple sequence alignments of 1-aminocyclopropane-1-carboxylate synthase (ACS) amino acid sequences based on database searches have indicated that MA-ACS1 is a highly conserved protein across the plant kingdom. This report describes an in silico analysis to provide the first important insightful information about the sequential, structural and phylogenetic characteristics of MA-ACS1. The three-dimensional structure of MA-ACS1, constructed based on homology modelling, in combination with the available data enabled a comparative mechanistic analysis of MA-ACS1 to explain the catalytic roles of the conserved and non-conserved active site residues. We have further demonstrated that, as in apple and tomato, banana-ACS1 (MA-ACS1) forms a homodimer and a complex with cofactor pyridoxal-5′-phosphate (PLP) and inhibitor aminoethoxyvinylglycine (AVG). We have also predicted that the residues from the PLP-binding pocket, essential for ligand binding, are mostly conserved across the MA-ACS1 structure and the competitive inhibitor AVG binds at a location adjacent to PLP.

  14. De novo fragment-based design of inhibitors of DXS guided by spin-diffusion-based NMR spectroscopy.

    OpenAIRE

    Masini, T.; Pilger, J.; Kroezen, B.; Illarionov, B.; Lottmann, P.; Fischer, M.; Griesinger, C.; Hirsch, A.

    2014-01-01

    We applied for the first time an innovative ligand-based NMR methodology (STI) to a medicinal-chemistry project aimed at the development of inhibitors for the enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS). DXS is the first enzyme of the 2C-methyl-D-erythritol-4-phosphate (MEP) pathway, present in most bacteria (and not in humans) and responsible for the synthesis of the essential isoprenoid precursors. We designed de novo a first generation of fragments, using Deinococcus radiodurans D...

  15. The Arab Uprisings and MENA Political Instability – Implications for Oil & Gas Markets: OIES paper: MEP 8

    OpenAIRE

    El-Katiri, Laura; Fattouh, Bassam; Mallinson, Richard

    2014-01-01

    The political turmoil that has swept across many parts of the Middle East and North Africa (MENA) since the beginning of the Arab Spring in December 2010 and the tightening of international sanctions against Iran in 2012 have reignited the recurring debate about energy security and the reliability of MENA as an energy supplier. In this paper, we examine the impact of the past three years of political turmoil in MENA on oil and gas markets. We argue that although many disruptions did occur and...

  16. Enzymes in the Mycobacterium tuberculosis MEP and CoA Pathways Targeted for Structure-Based Drug Design

    OpenAIRE

    Björkelid, Christofer

    2012-01-01

    Tuberculosis, caused by the pathogenic bacteria Mycobacterium tuberculosis, is one of the most widespread and deadly infectious diseases today. Treatment of tuberculosis relies on antibiotics that were developed more than 50 years ago. These are now becoming ineffective due to the emergence of antibiotic resistant strains of the bacteria. The aim of the research in this thesis was to develop new antibiotics for tuberculosis treatment. To this end, we targeted enzymes from two essential biosyn...

  17. Guangxi Nanguo Copper’s150,000 t/a Copper Smelting Project was Approval by the MEP

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>In the middle of August,the environmental impact report for 150,000 t/a copper smelting project of Guangxi Nanguo Copper Industry Co.,Ltd received formal approval from the Ministry of Environmental Protection,signaling that this project’s environmental impact

  18. BIM-lean synergies in the management on MEP works in public facilities of intensive use – a case study

    OpenAIRE

    Clemente, José, 1720-1798; Cachadinha, Nuno

    2013-01-01

    21st Annual Conference of the International Group for Lean Construction – IGLC 21 – Fortaleza, Brazil AEC industry has been known for budget overruns and delays for a long time. One important reason for weak performances is the difficulty to visualize the production flow, and the deficient information transmission between the different stakeholders involved in a construction project. The use of 3D models plays a significant role in facilitating the implementation of Lean principles, ...

  19. Predicted essential proteins ofPlasmodium falciparum for potential drug targets

    Institute of Scientific and Technical Information of China (English)

    Qing-Feng He; Li Deng; Qin-Ying Xu; Zheng Shao

    2012-01-01

    ABSTRACT Objective:To identify novel drug targets for treatment ofPlasmodium falciparum.Methods:LocalBLASTP were used to find the proteins non-homologous to human essential proteins as novel drug targets. Functional domains of novel drug targets were identified by InterPro and Pfam,3D structures of potential drug targets were predicated by theSWISS-MODELworkspace. Ligands and ligand-binding sites of the proteins were searched byEf-seek.Results:Three essential proteins were identified that might be considered as potential drug targets.AAN37254.1 belonged to1-deoxy-D-xylulose5-phosphate reductoisomerase,CAD50499.1 belonged to chorismate synthase,CAD51220.1 belonged toFAD binging3 family, but the function of CAD51220.1 was unknown. The3D structures, ligands and ligand-binding sites ofAAN37254.1 andCAD50499.1 were successfully predicated.Conclusions:Two of these potential drug targets are key enzymes in2-C-methyl-d-erythritol4-phosphate pathway and shikimate pathway, which are absent in humans, so these two essential proteins are good potential drug targets. The function and3D structures ofCAD50499.1 is still unknown, it still need further study.

  20. Enhanced Production of Bioactive Isoprenoid Compounds from Cell Suspension Cultures of Artemisia annua L. Using β-Cyclodextrins

    Directory of Open Access Journals (Sweden)

    Francesca Rizzello

    2014-10-01

    Full Text Available Plant cell cultures as valuable tools for the production of specific metabolites can be greatly improved by the application of elicitors including cyclodextrins (CDs for enhancing the yields of the desired plant compounds. Here the effects of 2,6-dimethyl-β-cyclodextrins (DIMEB on the production of carotenoids and quinones from Artemisia annua L. cell suspension cultures were investigated. The addition of 50 mM DIMEB induced an early increase of intracellular carotenoid and quinone contents, which could be observed to a higher extent for lutein (10-fold, Q9 (3-fold and Q10 (2.5-fold. Real Time PCR analysis revealed that the expression of 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR gene in DIMEB treated cell cultures after three days was 2.5-fold higher than in untreated samples, thus suggesting that the DIMEB induced increase of carotenoids and quinones could be due to the induction of the plastidial isoprenoid biosynthetic route. In addition, the DIMEB treatment induced an enhanced release of carotenoids and quinones into the culture medium of A. annua cell suspension cultures possibly due to the ability of CDs to form inclusion complexes with hydrophobic molecules.

  1. The 2-C-methylerythritol 4-phosphate pathway in melon is regulated by specialized isoforms for the first and last steps.

    Science.gov (United States)

    Saladié, Montserrat; Wright, Louwrance P; Garcia-Mas, Jordi; Rodriguez-Concepcion, Manuel; Phillips, Michael A

    2014-09-01

    The 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway provides the precursors for the biosynthesis of plastidial isoprenoids, which include the carotenoid pigments of many fruits. We have analysed the genes encoding the seven enzymes of the MEP pathway in melon (Cucumis melo L.) and determined that the first one, 1-deoxyxylulose 5-phosphate synthase (DXS), and the last one, 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase (HDR), are represented in the genome as a small gene family and paralogous pair, respectively. In the case of DXS, three genes encode functional DXS activities which fall into previously established type I (CmDXS1) and II (CmDXS2a and CmDXS2b) categories, while a fourth DXS-like gene belonging to the type III group did not encode a protein with DXS activity. Their expression patterns and phylogenies suggest that CmDXS1 is functionally specialized for developmental and photosynthetic processes, while CmDXS2a and CmDXS2b are induced in flowers and ripening fruit of orange- (but not white-) fleshed varieties, coinciding with β-carotene accumulation. This is the first instance connecting type II DXS genes to specialized isoprenoid biosynthesis in the fruit of an agronomically important species. Two HDR paralogues were shown to encode functional enzymes, although only CmHDR1 was highly expressed in the tissues and developmental stages tested. Phylogenetic analysis showed that in cucurbits such as melon, these HDR paralogues probably arose through individual gene duplications in a common angiosperm ancestor, mimicking a prior division in gymnosperms, while other flowering plants, including apple, soy, canola, and poplar, acquired HDR duplicates recently as homoeologues through large-scale genome duplications. We report the influence of gene duplication history on the regulation of the MEP pathway in melon and the role of specialized MEP-pathway isoforms in providing precursors for β-carotene production in orange-fleshed melon varieties.

  2. 高效液相色谱分析法测定磷酸-5'-吡哆醛质量分数%Determination of Pyridoxal-5'-phosphate by High Performance Liquid Chromatography

    Institute of Scientific and Technical Information of China (English)

    胡鸣; 凌芳; 郑琦; 陈浩云; 干海平

    2016-01-01

    建立了磷酸-5'-吡哆醛的高效液相色谱定量检测方法.实验采用C18反相色谱柱(5μm,250 mm×4.6mm);流动相为乙腈-水,二者体积比为(10~30):(70~90);流速为1.0 mL/min;柱温为30℃;检测波长为388 nm;进样量为10.0 μL(将测定主成分质量分数的进样样品用水溶解并稀释成0.2 g/L).实验结果表明,磷酸-5'-吡哆醛的线性方程为y=7575.6x+4801.8,r=0.99995,检出限为0.2 g/L.

  3. 磷酸吡哆醛补救途径两个关键酶的研究进展%Research advance in two key enzymes involved in the pyridoxal 5'-phosphate salvage pathway

    Institute of Scientific and Technical Information of China (English)

    黄龙全; 张剑韵

    2015-01-01

    维生素B6(VB6)包括6个可相互转换的吡啶衍生物.其中,磷酸吡哆醛(PLP)作为140多种细胞酶的辅酶,在生物体内发挥重要作用.动物从食物中获得VB6,通过由吡哆醛激酶和磷酸吡哆醇氧化酶构成的补救途径合成PLP.PLP依赖酶的正常功能乃至人体最佳健康状态,依赖于细胞中PLP的平衡供给.然而,就PLP的动态平衡和调节机制以及PLP合成后的转移机制而言,目前还知之甚少,是一个富有挑战性的研究领域.为此,综述PLP补救途径两个关键酶的研究进展.

  4. Alanyl-lipid synthesis with microwave-induced organic reaction and its interaction with pyridoxal -5-phosphate on lipid surface%丙氨酰类脂的微波合成及其功能

    Institute of Scientific and Technical Information of China (English)

    石太德; 刘宝全; 王剑锋; 范圣第

    2009-01-01

    利用微波合成仪制备双十六烷基胺,通过DCC交联反应,得到叔丁氧甲酰丙氨酰双十六烷基胺,再通过酸水解制备出丙氨酰类脂.利用丙氨酰类脂的季铵盐衍生物(丙氨酰肽脂质)构建人工二分子膜,研究了磷酸吡哆醛(PLP)与丙氨酰类脂的相互作用.紫外-可见光谱检测发现,在330 nm 及415 nm 处有亚胺的特征吸收峰,表明PLP可以识别人工二分子膜上的丙氨酰类脂,丙氨酰类脂可以用作人工细胞信号转导的受体.

  5. 5'-磷酸吡哆醛影响血清丙氨酸氨基转移酶测定的研究%Effection of Pyridoxal -5'-phosphate on Determination of Alanine Aminotransferase activities

    Institute of Scientific and Technical Information of China (English)

    张宗彬; 鲍杰; 陈龙泉; 李传胜; 马洪波

    2007-01-01

    目的 研究丙氨酸氨基转移酶(Alanine Aminotraasferase,ALT)检测试剂中5'-磷酸吡哆醛(Pyrldoxal-5'-phos-phate,PLP)的添加对血清ALT活力测定的影响.方法 按IFCC推荐方法,自配ALT检测试剂(含PLP)和相应不添加PLP的检测试剂,分别用这两种试剂测定相同的新鲜临床标本,并对检测结果进行统计学比较.结果 使用含PLP的IFCC配方试剂较不含PLP试剂的检测结果明显增高.结论 健康人群和不同疾病人群由于个体差异,体内PLP含量不一,各组数据表明不含PLP配方试剂较IFCC配方检测结果明显偏低,因此两种配方的检测结果不能通过简单系数实现转换.

  6. Enhanced production of steviol glycosides in mycorrhizal plants: a concerted effect of arbuscular mycorrhizal symbiosis on transcription of biosynthetic genes.

    Science.gov (United States)

    Mandal, Shantanu; Upadhyay, Shivangi; Singh, Ved Pal; Kapoor, Rupam

    2015-04-01

    Stevia rebaudiana (Bertoni) produces steviol glycosides (SGs)--stevioside (stev) and rebaudioside-A (reb-A) that are valued as low calorie sweeteners. Inoculation with arbuscular mycorrhizal fungi (AMF) augments SGs production, though the effect of this interaction on SGs biosynthesis has not been studied at molecular level. In this study transcription profiles of eleven key genes grouped under three stages of the SGs biosynthesis pathway were compared. The transcript analysis showed upregulation of genes encoding 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway enzymes viz.,1-deoxy-D-xylulose 5-phospate synthase (DXS), 1-deoxy-D-xylulose 5-phospate reductoisomerase (DXR) and 2-C-methyl-D-erytrithol 2,4-cyclodiphosphate synthase (MDS) in mycorrhizal (M) plants. Zn and Mn are imperative for the expression of MDS and their enhanced uptake in M plants could be responsible for the increased transcription of MDS. Furthermore, in the second stage of SGs biosynthesis pathway, mycorrhization enhanced the transcription of copalyl diphosphate synthase (CPPS) and kaurenoic acid hydroxylase (KAH). Their expression is decisive for SGs biosynthesis as CPPS regulates flow of metabolites towards synthesis of kaurenoid precursors and KAH directs these towards steviol synthesis instead of gibberellins. In the third stage glucosylation of steviol to reb-A by four specific uridine diphosphate (UDP)-dependent glycosyltransferases (UGTs) occurs. While higher transcription of all the three characterized UGTs in M plants explains augmented production of SGs; higher transcript levels of UGT76G1, specifically improved reb-A to stev ratio implying increased sweetness. The work signifies that AM symbiosis upregulates the transcription of all eleven SGs biosynthesis genes as a result of improved nutrition and enhanced sugar concentration due to increased photosynthesis in M plants. PMID:25734328

  7. Effects of Gibberellic Acid on Primary Terpenoids and △9-Tetrahydrocannabinol in Cannabis sativa at Flowering Stage

    Institute of Scientific and Technical Information of China (English)

    Hakimeh Mansouri; Zahra Asrar; Mitra Mehrabani

    2009-01-01

    Plants synthesize an astonishing diversity of isoprenoids, some of which play essential roles in photosynthesis, respiration,and the regulation of growth and development. Two independent pathways for the biosynthesis of isoprenoid precursors coexist within the plant cell: the cytosolic mevalonic acid (MVA) pathway and the plastidial methylerythritol phosphate (MEP)pathway. However, little is known about the effects of plant hormones on the regulation of these pathways. In the present study we investigated the effect of gibberellic acid (GA3) on changes in the amounts of many produced terpenoids and the activity of the key enzymes, 1-deoxy-D-xylulose 5-phosphate synthase (DXS) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), in these pathways. Our results showed GA3 caused a decrease in DXS activity in both sexes that it wasaccompanied by a decrease in chlorophylls, carotenoids and △9-tetrahydrocannabinol (THC) contents and an increase in α-tocopherol content. The treated plants with GA3 showed an increase in HMGR activity. This increase in HMGR activity was followed by accumulation of stigmasterol and β-sitosterol in male and female plants and campestrol in male plants.The pattern of the changes in the amounts of sterols was exactly similar to the changes in the HMGR activity. These data suggest that GA3 can probably influence the MEP and MVA pathways oppositely, with stimulatory and inhibitory effects on the produced primary terpenoids in MVA and DXS pathways, respectively.

  8. Price Reform in Kuwait’s Electricity and Water Sector – Assessing the Net Benefits in the Presence of Congestion: OIES paper: MEP 9

    OpenAIRE

    Mahadeva, Lavan; Fattouh, Bassam

    2014-01-01

    Kuwait’s domestic electricity and water sector has been in disarray for several years, struggling with fast-rising demand for several decades as a result of rapid industrialization, population growth, rising living standards as well as due to the artificially low utility prices set by the government. We use a model-based methodology to compare the current pricing scheme against an alternative where consumer prices are raised to market levels and consumers are on average compensated by cash tr...

  9. A combination of whey protein and potassium bicarbonate supplements during head-down-tilt bed rest: Presentation of a multidisciplinary randomized controlled trial (MEP study)

    Science.gov (United States)

    Buehlmeier, Judith; Mulder, Edwin; Noppe, Alexandra; Frings-Meuthen, Petra; Angerer, Oliver; Rudwill, Floriane; Biolo, Gianni; Smith, Scott M.; Blanc, Stéphane; Heer, Martina

    2014-02-01

    Inactivity, as it appears during space flight and in bed rest, induces reduction of lean body and bone mass, glucose intolerance, and weakening of the cardiovascular system. Increased protein intake, whey protein in particular, has been proposed to counteract some of these effects, but has also been associated with negative effects on bone, likely caused by a correspondingly high ratio of acid to alkali precursors in the diet.

  10. Detection of biogenic amines in urine and plasma by liquid chromatography coupled to electrochemical detection HPLC-ED using microextraction in packed syringe MEPS

    OpenAIRE

    Oppolzer, David Jerónimo

    2012-01-01

    Biogenic amines are neurotransmitters involved in several physiological processes. Changes and disturbs in their function are associated to several neurological disorders or diseases, as well as consumption of psychotherapeutic or psychotropic drugs. The detection of these compounds in biological fluids is therefore of clinical and neurochemical interest. The goal of this work was to develop and validate and analytical method for the detection and quantification of the biogenic...

  11. Análisis energético de CYPECAD-MEP y CE3x en la edificación

    OpenAIRE

    Alarcón Blaya, Juan Antonio

    2014-01-01

    Con el objeto de promover la eficiencia energética de los edificios, la Directiva 2002/91/CE y posteriormente la Directiva 2010/31/UE, exigía a los Estados miembros el establecimiento de un procedimiento de certificación dirigido a los edificios, que pusiese a disposición del posible comprador o inquilino, una información objetiva sobre el consumo energético de la vivienda. El requisito de la eficiencia energética es alcanzar unos niveles óptimos de rentabilidad en la viv...

  12. Response and Defense Mechanisms of Taxus chinensis Leaves Under UV-A Radiation are Revealed Using Comparative Proteomics and Metabolomics Analyses.

    Science.gov (United States)

    Zheng, Wen; Komatsu, Setsuko; Zhu, Wei; Zhang, Lin; Li, Ximin; Cui, Lei; Tian, Jingkui

    2016-09-01

    Taxus chinensis var. mairei is a species endemic to south-eastern China and one of the natural sources for the anticancer medicine paclitaxel. To investigate the molecular response and defense mechanisms of T. chinensis leaves to enhanced ultraviolet-A (UV-A) radiation, gel-free/label-free and gel-based proteomics and gas chromatography-mass spectrometry (GC-MS) analyses were performed. The transmission electron microscopy results indicated damage to the chloroplast under UV-A radiation. Proteomics analyses in leaves and chloroplasts showed that photosynthesis-, glycolysis-, secondary metabolism-, stress-, and protein synthesis-, degradation- and activation-related systems were mainly changed under UV-A radiation. Forty-seven PSII proteins and six PSI proteins were identified as being changed in leaves and chloroplasts under UV-A treatment. This indicated that PSII was more sensitive to UV-A than PSI as the target of UV-A light. Enhanced glycolysis, with four glycolysis-related key enzymes increased, provided precursors for secondary metabolism. The 1-deoxy-d-xylulose-5-phosphate reductoisomerase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase were identified as being significantly increased during UV-A radiation, which resulted in paclitaxel enhancement. Additionally, mRNA expression levels of genes involved in the paclitaxel biosynthetic pathway indicated a down-regulation under UV-A irradiation and up-regulation in dark incubation. These results reveal that a short-term high dose of UV-A radiation could stimulate the plant stress defense system and paclitaxel production. PMID:27318281

  13. VOC emissions of Grey poplar leaves as affected by salt stress and different N sources.

    Science.gov (United States)

    Teuber, M; Zimmer, I; Kreuzwieser, J; Ache, P; Polle, A; Rennenberg, H; Schnitzler, J-P

    2008-01-01

    Nitrogen nutrition and salt stress experiments were performed in a greenhouse with hydroponic-cultured, salt-sensitive Grey poplar (Populus x canescens) plants to study the combined influence of different N sources (either 1 mm NO(3) (-) or NH(4)(+)) and salt (up to 75 mm NaCl) on leaf gas exchange, isoprene biosynthesis and VOC emissions. Net assimilation and transpiration proved to be highly sensitive to salt stress and were reduced by approximately 90% at leaf sodium concentrations higher than 1,800 microg Na g dry weight (dw)(-1). In contrast, emissions of isoprene and oxygenated VOC (i.e. acetaldehyde, formaldehyde and acetone) were unaffected. There was no significant effect of combinations of salt stress and N source, and neither NO(3)(-) or NH(4)(+) influenced the salt stress response in the Grey poplar leaves. Also, transcript levels of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (PcDXR) and isoprene synthase (PcISPS) did not respond to the different N sources and only responded slightly to salt application, although isoprene synthase (PcISPS) activity was negatively affected at least in one of two experiments, despite high isoprene emission rates. A significant salt effect was the strong reduction of leaf dimethylallyl diphosphate (DMADP) content, probably due to restricted availability of photosynthates for DMADP biosynthesis. Further consequences of reduced photosynthetic gas exchange and maintaining VOC emissions are a very high C loss, up to 50%, from VOC emissions related to net CO(2) uptake and a strong increase in leaf internal isoprene concentrations, with maximum mean values up to 6.6 microl x l(-1). Why poplar leaves maintain VOC biosynthesis and emission under salt stress conditions, despite impaired photosynthetic CO(2) fixation, is discussed. PMID:18211549

  14. Relative expression of genes of terpene metabolism in different tissues of Artemisia annua L

    Directory of Open Access Journals (Sweden)

    Lundgren Anneli

    2011-03-01

    Full Text Available Abstract Background Recently, Artemisia annua L. (annual or sweet wormwood has received increasing attention due to the fact that the plant produces the sesquiterpenoid endoperoxide artemisinin, which today is widely used for treatment of malaria. The plant produces relatively small amounts of artemisinin and a worldwide shortage of the drug has led to intense research in order to increase the yield of artemisinin. In order to improve our understanding of terpene metabolism in the plant and to evaluate the competition for precursors, which may influence the yield of artemisinin, we have used qPCR to estimate the expression of 14 genes of terpene metabolism in different tissues. Results The four genes of the artemisinin biosynthetic pathway (amorpha-4,11-diene synthase, amorphadiene-12-hydroxylase, artemisinic aldehyde ∆11(13 reductase and aldehyde dehydrogenase 1 showed remarkably higher expression (between ~40- to ~500-fold in flower buds and young leaves compared to other tissues (old leaves, stems, roots, hairy root cultures. Further, dihydroartemisinic aldehyde reductase showed a very high expression only in hairy root cultures. Germacrene A and caryophyllene synthase were mostly expressed in young leaves and flower buds while epi-cedrol synthase was highly expressed in old leaves. 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase exhibited lower expression in old leaves compared to other tissues. Farnesyldiphosphate synthase, squalene synthase, and 1-deoxy-D-xylulose-5-phosphate reductoisomerase showed only modest variation in expression in the different tissues, while expression of 1-deoxy-D-xylulose-5-phosphate synthase was 7-8-fold higher in flower buds and young leaves compared to old leaves. Conclusions Four genes of artemisinin biosynthesis were highly expressed in flower buds and young leaves (tissues showing a high density of glandular trichomes. The expression of dihydroartemisinic aldehyde reductase has been suggested to have a

  15. 75 FR 51449 - Notice of Proposed Information Collection Requests

    Science.gov (United States)

    2010-08-20

    ... Secondary Education Type of Review: Revision. Title: Migrant Education Program (MEP) Migrant Student... are collected and transferred between State migrant education programs (MEPs) as part of a larger mandated Migrant Student Information Exchange (MSIX). State educational agencies (SEAs) with MEPs...

  16. 75 FR 71675 - Notice of Submission for OMB Review

    Science.gov (United States)

    2010-11-24

    ... Review: Revision. Title of Collection: Migrant Education Program (MEP) Migrant Student Information... transferred between State migrant education programs (MEPs) as part of a larger mandated Migrant...

  17. Biosynthesis of sesquiterpenes in grape berry exocarp of Vitis vinifera L.: evidence for a transport of farnesyl diphosphate precursors from plastids to the cytosol.

    Science.gov (United States)

    May, Bianca; Lange, B Markus; Wüst, Matthias

    2013-11-01

    The participation of the mevalonic acid (MVA) and 1-deoxy-d-xylulose 5-phosphate/2-C-methyl-d-erythritol-4-phosphate (DOXP/MEP) pathways in sesquiterpene biosynthesis of grape berries was investigated. There is an increasing interest in this class of terpenoids, since the oxygenated sesquiterpene rotundone was identified as the peppery aroma impact compound in Australian Shiraz wines. To investigate precursor supply pathway utilization, in vivo feeding experiments were performed with the deuterium labeled, pathway specific, precursors [5,5-(2)H2]-1-deoxy-d-xylulose and [5,5-(2)H2]-mevalonic acid lactone. Head Space-Solid Phase Micro Extraction-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS) analysis of the generated volatile metabolites demonstrated that de novo sesquiterpene biosynthesis is mainly located in the grape berry exocarp (skin), with no detectable activity in the mesocarp (flesh) of the Lemberger variety. Interestingly, precursors from both the (primarily) cytosolic MVA and plastidial DOXP/MEP pathways were incorporated into grape sesquiterpenes in the varieties Lemberger, Gewürztraminer and Syrah. Our labeling data provide evidence for a homogenous, cytosolic pool of precursors for sesquiterpene biosynthesis, indicating that a transport of precursors occurs mostly from plastids to the cytosol. The labeling patterns of the sesquiterpene germacrene D were in agreement with a cyclization mechanism analogous to that of a previously cloned enantioselective (R)-germacrene D synthase from Solidago canadensis. This observation was subsequently confirmed by enantioselective GC-MS analysis demonstrating the exclusive presence of (R)-germacrene D, and not the (S)-enantiomer, in grape berries. PMID:23954075

  18. Changes in the transcriptional levels of pyridoxal kinase and pyridoxine-5'-phosphate oxidase post exogenous hormone treatment in the silkworm,Bombyx mori%外源激素处理后家蚕吡哆醛激酶和磷酸吡哆醇氧化酶转录水平的变化

    Institute of Scientific and Technical Information of China (English)

    杨欢欢; 姚丽丽; 张剑韵; 黄龙全

    2015-01-01

    [目的] 研究家蚕Bombyx mori经蜕皮激素(20-hydroxyecdysone,20-E)和保幼激素类似物(juvenile hormone analogue,JHA)处理后引起吡哆醛激酶(pyridoxal kinase,PLK)和磷酸吡哆醇氧化酶(pyridoxine-5'-phosphateoxidase,PNPO)的转录水平变化,为进一步研究激素对蚕体营养代谢等工作奠定基础.[方法]以20-E和JHA分别喂食不同发育时期(5龄第1,3和5天)的家蚕幼虫,以喂食蒸馏水的家蚕为对照,采用实时荧光定量PCR(real-time quantitative PCR)方法在处理后24和48 h对各组幼虫后部丝腺中PLP合成酶PLK和PNPO的转录水平进行分析.[结果]5龄第1天幼虫经20-E处理24和48 h后,PLK和PNPO的转录水平出现上调且与对照的差异达到极显著(P<0.01);5龄第3天幼虫经20-E处理,PLK的转录水平在48 h出现下调且与对照的差异达到显著(P<0.05),PNPO的转录水平在24和48 h均出现上调且与对照的差异达到极显著(P<0.01);5龄第5天幼虫经20-E处理后PLK和PNPO的转录水平无变化.5龄第1天幼虫经JHA处理后PLK和PNPO的转录水平未受到影响;5龄第3天幼虫经JHA处理后,PLK的转录水平在48 h出现显著下调且与对照的差异达到显著(P<0.05),PNPO的转录水平在24和48 h后均出现显著下调且与对照的差异达到极显著(P<0.05);5龄第5天幼虫经JHA处理24和48 h后,PLK和PNPO的转录水平出现下调且与对照的差异达到极显著(P<0.01).[结论]20-E和JHA显著影响家蚕5龄幼虫PLK和PNPO的转录水平,20-E提高5龄前期家蚕PLK和PNPO的转录水平,JHA降低5龄后期它们的转录水平,为深入研究激素对VB6的调控奠定基础.

  19. Clinical characteristics and genetic analysis of 2 children with pyridox (am)ine-5'-phosphate oxidase deficiency%磷酸吡哆醇(胺)氧化酶缺乏症2例的临床特征及基因突变分析

    Institute of Scientific and Technical Information of China (English)

    薛姣; 杨志仙; 张月华; 姜玉武

    2016-01-01

    目的 分析2例磷酸吡哆醇(胺)氧化酶(PNPO)缺乏症患儿的临床特征及PNPO基因突变特征.方法 患儿为2016年2月于北京大学第一医院儿科确诊的同卵双生兄弟,对其临床表现、诊治过程、血液生化、代谢筛查、脑电图、头颅磁共振成像(MRI)、癫痫相关基因(包括PNPO基因)检测结果等进行分析.结果 2例患儿为35+5周早产,有出生窒息史.均于出生24h内出现癫痫发作,多种抗癫痫药效不佳.EEG显示不典型高度失律或多灶性癫痫样放电;MRI均显示非特异性异常.病程中曾应用维生素B6单药或添加多种抗癫痫药物治疗,维生素B6单药治疗过程中最长1个月未出现发作.5岁左右时,在发作仍持续存在过程中逐渐停用所有抗癫痫药物,近1年仅口服维生素B6治疗,至6岁4个月时仍均有发作.血代谢筛查示精氨酸、天门冬氨酸、蛋氨酸水平降低;尿代谢筛查示香草酸水平明显升高,2例分别为正常值的49.78倍、36.60倍.患儿基因分析证实均携带PNPO基因复合杂合变异:c.445_448del(p.P150RfsX27)和c.481C> T(p.R161C),均为国际上尚未报道的位点.确诊后,换用磷酸吡哆醛(PLP)治疗,短暂随访中,发作先略增多,后逐渐减少至完全控制.智力运动发育情况均为重度落后.结论 2例患儿均以新生儿期难治性癫痫起病,维生素B6对癫痫发作有一定疗效.血、尿代谢筛查提示了PNPO缺乏症的可能,最终经基因检测首次在国内确诊了此症,应用PLP单药治疗后发作控制.

  20. Intraoperative monitoring study of ipsilateral motor evoked potentials in scoliosis surgery

    OpenAIRE

    Lo, Y. L.; Dan, Y. F.; Tan, Y. E.; Fook-Chong, S; Tan, S. B.; Tan, C T; Raman, S.

    2006-01-01

    Ipsilateral motor evoked potentials (MEPs) in spinal cord surgery intraoperative monitoring is not well studied. We show that ipsilateral MEPs have significantly larger amplitudes and were elicited with lower stimulation intensities than contralateral MEPs. The possible underlying mechanisms are discussed based on current knowledge of corticospinal pathways. Ipsilateral MEPs may provide additional information on the integrity of descending motor tracts during spinal surgery monitoring.

  1. A STUDY ON THE RELATIONSHIP BETWEEN MAGNETIC STIMULATION MEP AND THE NEUROPATHOLOGY OF THE CHRONIC COMPRESSED LESION OF CAT’S CERVICAL NERVE ROOTS AND THE SIGNIFICANCE OF ITS QUANTITATIVE DIAGNOSIS

    Institute of Scientific and Technical Information of China (English)

    杨大志; 郭玉霞; 陈君长; 赵龙柱; 王坤正; 杨哲; 李旭东; 袁国莲

    1999-01-01

    ThetechniqueofmagneticstimulationMEPhasprogressedrapidlysinceitcameintobeingin1985.Nowitisconsideredtobeabletoconfirmthelesio...

  2. FT-IR, NBO, HOMO-LUMO, MEP analysis and molecular docking study of Methyl N-({[2-(2-methoxyacetamido)-4-(phenylsulfanyl)phenyl]amino}[(methoxycarbonyl) imino]methyl)carbamate

    Science.gov (United States)

    Panicker, C. Yohannan; Varghese, Hema Tresa; Narayana, B.; Divya, K.; Sarojini, B. K.; War, Javeed Ahmad; Van Alsenoy, C.; Fun, H. K.

    2015-09-01

    The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of Methyl N-({[2-(2-methoxyacetamido)-4-(phenylsulfanyl) phenyl]amino} [(methoxycarbonyl)imino]methyl)carbamate have been investigated using HF and DFT levels of calculations. The geometrical parameters are in agreement with XRD data. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. Molecular electrostatic potential study was also performed. The first and second hyperpolarizability was calculated in order to find its role in nonlinear optics. Molecular docking studies are also reported. Prediction of Activity Spectra analysis of the title compound predicts anthelmintic and antiparasitic activity as the most probable activity with Pa (probability to be active) value of 0.808 and 0.797, respectively. Molecular docking studies show that both the phenyl groups and the carbonyl oxygens of the molecule are crucial for bonding and these results draw us to the conclusion that the compound might exhibit pteridine reductase inhibitory activity.

  3. Vibrational (FT-IR, FT-Raman) and UV-Visible spectroscopic studies, HOMO-LUMO, NBO, NLO and MEP analysis of Benzyl (imino (1H-pyrazol-1-yl) methyl) carbamate using DFT calculaions

    Science.gov (United States)

    Shankar Rao, Y. B.; Prasad, M. V. S.; Udaya Sri, N.; Veeraiah, V.

    2016-03-01

    This paper contains a combined experimental and theoretical study of vibrational and electronic properties of Benzyl(imino(1H-pyrazol-1-yl)methyl)carbamate (BPMC) molecule. The FT-IR and FT-Raman spectra of the title molecule in solid phase were recorded in the region 4000-400 cm-1 and 4000-50 cm-1, respectively. The UV absorption spectrum of the studied compound dissolved in ethanol was recorded in the range of 180-400 nm. The molecular geometries calculated using density functional theory (DFT) was compared with available experimental data. The vibrational spectra calculated at the B3LYP/6-31G(d,p) level were compared with the experimental spectra and assignment to each vibrational frequency was assigned on the basis of potential energy distribution (PED). The calculated electronic and nonlinear optical properties of the title molecule were reported. Furthermore, the thermodynamic properties of the molecule were discussed.

  4. Vibrational assignments, spectroscopic investigation (FT-IR and FT-Raman), NBO, MEP, HOMO‒LUMO analysis and intermolecular hydrogen bonding interactions of 7-fluoroisatin, 7-bromoisatin and 1-methylisatin ‒ A comparative study

    Science.gov (United States)

    Polat, Turgay; Bulut, Fatih; Arıcan, Ilknur; Kandemirli, Fatma; Yildirim, Gürcan

    2015-12-01

    In this comprehensive study, theoretical and experimental studies were carried out on 7-fluoroisatin, 7-bromoisatin and 1-methylisatin using FT-Raman and FT-IR spectra. The optimized geometrical parameters and theoretical vibrational frequencies were calculated by means of density functional theory (DFT/B3LYP) with 6-311++G(d,p) basis set based on scaled quantum mechanical (SQM) method for the first time. The relative abundances of the possible tautomers or conformers found were calculated with respect to the Boltzmann distribution. Moreover, the harmonic vibrational frequencies including IR and Raman intensities, thermodynamic and electronic parameters were computed in detail. The effects of substituents -F, ‒Br and -CH3 on the crucial characteristics pertaining to the title compound of isatin were investigated, and the obtained data were compared with each other. Natural bond orbital (NBO) analysis was applied to study the stability arising from charge delocalization along with the compound. The chemical reactivity parameters (chemical hardness and softness, electronegativity, chemical potential and electrophilicity index) were discussed clearly. The HOMO and LUMO energies determined showed that the serious charge transfer occurs in the title molecules studied. Furthermore, the size, shape, charge density distributions and chemical reactivity sites belonging to the molecules were obtained by mapping electron density isosurface with electrostatic potential surfaces (ESP). Additionally, the hydrogen-bonded complexes were simulated to describe the roles of intermolecular hydrogen bonding on the molecular structures and vibrational frequencies.

  5. Prevalence of use study for amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-methamphetamine (MDMA), and 3,4-methylenedioxy-ethylamphetamine (MDEA) in military entrance processing stations (MEPS) specimens.

    Science.gov (United States)

    Klette, Kevin L; Kettle, Aaron R; Jamerson, Matthew H

    2006-06-01

    The Roche Abuscreen Onlinetrade mark Amphetamine immunoassay (IA), modified to include sodium periodate, and the Microgenics DRI Ecstasy IA were used to determine the prevalence of amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) in urine specimens from applicants seeking to join the United States Armed Forces. Over a 4-month period, a total of 85,658 specimens were IA screened using the Department of Defense 500 ng/mL administrative cutoff level for AMP and MDMA. All presumptively positive specimens were confirmed using a solid-phase extraction procedure coupled with simultaneous analysis of AMP, MAMP, MDA, MDMA, and MDEA by fast gas chromatography-mass spectrometry using the same cutoff levels as the IA. The Roche Online Amphetamine IA identified 216 specimens as presumptively positive; of these, 70 specimens confirmed positive for AMP and 87 specimens confirmed positive for AMP and/or MAMP, resulting in a confirmation rate of 73%. The Microgenics DRI Ecstasy IA identified eight specimens as presumptively positive; of these, five specimens confirmed positive for MDMA and/or MDA, resulting in a confirmation rate of 63%. The total use prevalence for AMP, MAMP, MDA, MDMA, and/or MDEA in military entrance processing stations specimens over the testing period was determined to be 0.19%.

  6. Los textos literarios que asigna el MEP para el tercer ciclo de la educación general básica en Costa Rica: algunas reflexiones al respecto

    Directory of Open Access Journals (Sweden)

    Arias Orozco, Grettel

    2016-05-01

    Full Text Available En el presente artículo se detallan y analizan las principales modificaciones que presenta la lista de lecturas obligatorias propuesta en el año 2010 e implementada por el Ministerio de Educación Pública a partir del año 2011, en el Tercer Ciclo de la Educación General Básica costarricense. El estudio fue realizado a partir de la búsqueda bibliográfica de revistas especializadas, tesis de grado, libros, los Planes de Estudios de Español del 2005 y del año 2009, la lista de lecturas obligatorias implementada en el 2011, así como también gracias a entrevistas a especialistas en el área de la educación costarricense. Se concluye que las principales modificaciones responden a la dosificación, la categorización y la flexibilidad del listado de lecturas, pues la cantidad de textos y los géneros literarios que se estudian por nivel se modifican, así como también ahora se le brinda una gama de opciones al docente para que elija qué leer con su grupo estudiantil; no obstante, también se evidencia que ninguno de estos cambios ha sido debidamente fundamentado en la nueva propuesta. Finalmente, se destaca la incorporación de un corpus significativo de textos literarios que hacen referencia al personaje del presidente Juan Mora Porras, cuyo fin se vislumbra de carácter identitario e ideológico, pues su propósito es contrarrestar el desencanto político que ha aumentado en los últimos años e instaurarse como el nuevo referente del héroe nacional.

  7. Enhanced Diterpene Tanshinone Accumulation and Bioactivity of Transgenic Salvia miltiorrhiza Hairy Roots by Pathway Engineering.

    Science.gov (United States)

    Shi, Min; Luo, Xiuqin; Ju, Guanhua; Li, Leilei; Huang, Shengxiong; Zhang, Tong; Wang, Huizhong; Kai, Guoyin

    2016-03-30

    Tanshinones are health-promoting diterpenoids found in Salvia miltiorrhiza and have wide applications. Here, SmGGPPS (geranylgeranyl diphosphate synthase) and SmDXSII (1-deoxy-D-xylulose-5-phosphate synthase) were introduced into hairy roots of S. miltiorrhiza. Overexpression of SmGGPPS and SmDXSII in hairy roots produces higher levels of tanshinone than control and single-gene transformed lines; tanshinone production in the double-gene transformed line GDII10 reached 12.93 mg/g dry weight, which is the highest tanshinone content that has been achieved through genetic engineering. Furthermore, transgenic hairy root lines showed higher antioxidant and antitumor activities than control lines. In addition, contents of chlorophylls, carotenoids, indoleacetic acid, and gibberellins were significantly elevated in transgenic Arabidopsis thaliana plants. These results demonstrate a promising method to improve the production of diterpenoids including tanshinone as well as other natural plastid-derived isoprenoids in plants by genetic manipulation of the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway.

  8. Sequence Classification: 776671 [

    Lifescience Database Archive (English)

    Full Text Available ar zinc finger protein, Mog interacting, Ectopic P granules MEP-1, GEX (Gut on EXterior) Interacting protein GEI-2 (97.4 kD) (mep-1) || http://www.ncbi.nlm.nih.gov/protein/25152712 ...

  9. Mars Technology Project

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA’s Mars Exploration Program (MEP) calls for a series of highly ambitious missions over the next decade and beyond. The overall goals of the MEP must be...

  10. Host cells and methods for production of isobutanol

    Energy Technology Data Exchange (ETDEWEB)

    Anthony, Larry Cameron; He, Hongxian; Huang, Lixuan Lisa; Okeefe, Daniel P.; Kruckeberg, Arthur Leo; Li, Yougen; Maggio-Hall, Lori Ann; McElvain, Jessica; Nelson, Mark J.; Patnaik, Ranjan; Rothman, Steven Cary

    2016-08-23

    Provided herein are recombinant yeast host cells and methods for their use for production of isobutanol. Yeast host cells provided comprise an isobutanol biosynthetic pathway and at least one of reduced or eliminated aldehyde dehydrogenase activity, reduced or eliminated acetolactate reductase activity; or a heterologous polynucleotide encoding a polypeptide having ketol-acid reductoisomerase activity.

  11. The Carotenogenesis Pathway via the Isoprenoid-β-carotene Interference Approach in a New Strain of Dunaliella salina Isolated from Baja California Mexico

    Directory of Open Access Journals (Sweden)

    Luis Enrique Gutierrez-Millan

    2009-02-01

    Full Text Available D. salina is one of the recognized natural sources to produce β-carotene, and an useful model for studying the role of inhibitors and enhancers of carotenogenesis. However there is little information in D. salina regarding whether the isoprenoid substrate can be influenced by stress factors (carotenogenic or selective inhibitors which in turn may further contribute to elucidate the early steps of carotenogenesis and biosynthesis of β-carotene. In this study,Dunaliella salina (BC02 isolated from La Salina BC Mexico, was subjected to the method of isoprenoids-β-carotene interference in order to promote the interruption or accumulation of the programmed biosynthesis of carotenoids. When Carotenogenic and non-carotenogenic cells of D. salina BC02 were grown under photoautotrophicgrowth conditions in the presence of 200 µM fosmidomycin, carotenogenesis and the synthesis of β-carotene were interrupted after two days in cultured D. salina cells. This result is an indirect consequence of the inhibition of the synthesis of isoprenoids and activity of the recombinant DXR enzyme thereby preventing the conversionof 1-deoxy-D-xylulose 5-phosphate (DXP to 2-C-methyl-D-erythritol (MEP and consequently interrupts the early steps of carotenogenesis in D. salina. The effect at the level of proteins and RNA was not evident. Mevinolin treated D. salina cells exhibited carotenogenesis and β-carotene levels very similar to those of control cell cultures indicating that mevinolin not pursued any indirect action in the biosynthesis of isoprenoids and had no effect at the level of the HMG-CoA reductase, the key enzyme of the Ac/MVA pathway.

  12. Yeast Interacting Proteins Database: YNL189W, YDR487C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available synthase), required for riboflavin biosynthesis from ribulose-5-phosphate, also has an unrelated function in...esis from ribulose-5-phosphate, also has an unrelated function in mitochondrial respiration Rows with this p

  13. Bacterial population succession and adaptation affected by insecticide application and soil spraying history

    Directory of Open Access Journals (Sweden)

    Hideomi eItoh

    2014-08-01

    Full Text Available Although microbial communities have varying degrees of exposure to environmental stresses such as chemical pollution, little is known on how these communities respond to environmental disturbances and how past disturbance history affects these community-level responses. To comprehensively understand the effect of organophosphorus insecticide application on microbiota in soils with or without insecticide-spraying history, we investigated the microbial succession in response to the addition of fenitrothion (O,O-dimethyl O-(3-methyl-p-nitrophenyl phosphorothioate, abbreviated as MEP by culture-dependent experiments and deep sequencing of 16S rRNA genes. Despite similar microbial composition at the initial stage, microbial response to MEP application was remarkably different between soils with and without MEP-spraying history. MEP-degrading microbes more rapidly increased in the soils with MEP-spraying history, suggesting that MEP-degrading bacteria might already exist at a certain level and could quickly respond to MEP re-treatment in the soil. Culture-dependent and -independent evaluations revealed that MEP-degrading Burkholderia bacteria are predominant in soils after MEP application, limited members of which might play a pivotal role in MEP-degradation in soils. Notably, deep sequencing also revealed that some methylotrophs dramatically increased after MEP application, strongly suggesting that these bacteria play a role in the consumption and removal of methanol, a harmful derivative from MEP-degradation, for better growth of MEP-degrading bacteria. This comprehensive study demonstrated the succession and adaptation processes of microbial communities under MEP application, which were critically affected by past experience of insecticide-spraying.

  14. AcEST: DK954114 [AcEST

    Lifescience Database Archive (English)

    Full Text Available GN=Ncl PE=1 SV=3 35 0.36 sp|Q61SK8|MEP1_CAEBR MOG interacting and ectopic P-granules prot... 34 0.47 sp|Q9BY...>sp|Q61SK8|MEP1_CAEBR MOG interacting and ectopic P-granules protein 1 OS=Caenorhabditis briggsae GN=mep-1 P

  15. Evidence for the presence of a critical disulfide bond in the mouse EP3γ receptor

    OpenAIRE

    Downey, Jason D.; Sanders, Charles R.; Breyer, Richard M.

    2011-01-01

    To determine the contribution of cysteines to the function of the mouse E-prostanoid subtype 3 gamma (mEP3γ), we tested a series of cysteine-to-alanine mutants. Two of these mutants, C107A and C184A, showed no agonist-dependent activation in a cell-based reporter assay for mEP3γ, whereas none of the other cysteine-to-alanine mutations disrupted mEP3γ signal transduction. Total cell membranes prepared from HEK293 cells transfected with mEP3γ C107A or C184A had no detectable radioligand binding...

  16. Screening and determination of drugs in human saliva utilizing microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Abdel-Rehim, Abbi; Abdel-Rehim, Mohamed

    2013-09-01

    This study presents a new method for collecting and handling saliva samples using an automated analytical microsyringe and microextraction by packed syringe (MEPS). The screening and determination of lidocaine in human saliva samples utilizing MEPS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were carried out. An exact volume of saliva could be collected. The MEPS C8 -cartridge could be used for 50 extractions before it was discarded. The extraction recovery was about 60%. The pharmacokinetic curve of lidocaine in saliva using MEPS-LC-MS/MS is reported.

  17. Metabolic profiling of the methylerythritol phosphate pathway reveals the source of post-illumination isoprene burst from leaves.

    Science.gov (United States)

    Li, Ziru; Sharkey, Thomas D

    2013-02-01

    The methylerythritol phosphate (MEP) pathway in plants produces the prenyl precursors for all plastidic isoprenoids, including carotenoids and quinones. The MEP pathway is also responsible for synthesis of approximately 600 Tg of isoprene per year, the largest non-methane hydrocarbon flux into the atmosphere. There have been few studies of the regulation of the MEP pathway in plants under physiological conditions. In this study, we combined gas exchange techniques and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) and measured the profile of MEP pathway metabolites under different conditions. We report that in the MEP pathway, metabolites immediately preceding steps requiring reducing power were in high concentration. Inhibition of the MEP pathway by fosmidomycin caused deoxyxylulose phosphate accumulation in leaves as expected. Evidence is presented that accumulation of MEP pathway intermediates, primarily methylerythritol cyclodiphosphate, is responsible for the post-illumination isoprene burst phenomenon. Pools of intermediate metabolites stayed at approximately the same level 10 min after light was turned off, but declined eventually under prolonged darkness. In contrast, a strong inhibition of the second-to-last step of the MEP pathway caused suppression of isoprene emission in pure N(2). Our study suggests that reducing equivalents may be a key regulator of the MEP pathway and therefore isoprene emission from leaves. PMID:22831282

  18. Prevalence and Costs of Five Chronic Conditions in Children

    Science.gov (United States)

    Miller, Gabrielle F.; Coffield, Edward; Leroy, Zanie; Wallin, Robin

    2016-01-01

    The objective is to examine the prevalence and health-care costs associated with asthma, epilepsy, hypertension, food allergies, and diabetes in children aged 0-18 years. Prevalence was calculated using 2005-2012 Medical Expenditure Panel Survey (MEPS) data, a population-based, nationally representative sample. Using MEPS, two-part models…

  19. Botulinum Toxin Type A Injections in the Psoas Muscle of Children with Cerebral Palsy: Muscle Atrophy after Motor End Plate-Targeted Injections

    Science.gov (United States)

    Van Campenhout, Anja; Verhaegen, Ann; Pans, Steven; Molenaers, Guy

    2013-01-01

    MEP targeting during BoNT-A injections has been demonstrated to improve outcome. Two injection techniques of the psoas muscle--proximal MEP targeting versus a widely used more distal injection technique--are compared using muscle volume assessment by digital MRI segmentation as outcome measure. Method: 7 spastic diplegic children received…

  20. Stimulus-response characteristics of motor evoked potentials and silent periods in proximal and distal upper-extremity muscles.

    NARCIS (Netherlands)

    Kuijk, A.A. van; Anker, L.C.; Pasman, J.W.; Hendriks, J.C.M.; Elswijk, G.A.F. van; Geurts, A.C.H.

    2009-01-01

    OBJECTIVE: To compare stimulus-response characteristics of both motor evoked potentials (MEP) and silent periods (SP) induced by transcranial magnetic stimulation (TMS) in proximal and distal upper-extremity muscles. METHODS: Stimulus-response curves of MEPs and SPs were obtained from the biceps bra

  1. An Investigation of Groundwater Flow on a Coastal Barrier using Multi Electrode Profiling

    DEFF Research Database (Denmark)

    Poulsen, Søren Erbs; Christensen, Steen; Rasmussen, Keld Rømer;

    2008-01-01

    Preliminary geophysical and hydrogeological investigations indicate that multi-electrode profiling (MEP) can be used to monitor groundwater salinity on a coastal barrier where a shallow thin aquifer discharges to the North Sea. A monitoring system including five groups of piezometers and five MEP...

  2. AcEST: BP916380 [AcEST

    Lifescience Database Archive (English)

    Full Text Available 8|MEP1_CAEBR MOG interacting and ectopic P-granules prot... 31 2.9 sp|P15539|C11B2_MOUSE Cytochrome P450 11B...bjct: 117 QALIPQGADILPNPTGTAPGIIWEPRPDMTIFTFPGVPSE-MHRM 160 >sp|Q61SK8|MEP1_CAEBR MOG interacting and ectopic P-granules

  3. The European Parliament's Rejection of the Take-over Directive Proposal

    DEFF Research Database (Denmark)

    Steen Knudsen, Jette

    2003-01-01

    national characteristics: labour marketlegislation (national schemes to protect employees against dismissals) and corporategovernance issues. Labour market legislation can explain the UK and German MEP votesbut not the Swedish and French MEPs votes. These votes can be explained byemphasising measures...... against take-overs such as a high level of market capitalisation andunequal voting rights....

  4. Heterologous expression and characterization of bacterial 2-C-methyl-d-erythritol-4-phosphate pathway in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Carlsen, Simon; Ajikumar, Parayil Kumaran; Formenti, Luca Riccardo;

    2013-01-01

    the engineering of Escherichia coli genes encoding the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway into the genome of Saccharomyces cerevisiae and the characterization of intermediate metabolites synthesized by the MEP pathway in yeast. Our UPLC-MS analysis of the MEP pathway metabolites from engineered...... yeast showed that the pathway is active until the synthesis of 2-C-methyl-d-erythritol-2,4-cyclodiphosphate, but appears to lack functionality of the last two steps of the MEP pathway, catalyzed by the [4Fe–4S] iron sulfur cluster proteins encoded by ispG and ispH. In order to functionalize the last two...... steps of the MEP pathway, we co-expressed the genes for the E. coli iron sulfur cluster (ISC) assembly machinery. By deleting ERG13, thereby incapacitating the mevalonate pathway, in conjunction with labeling experiments with U–13C6 glucose and growth experiments, we found that the ISC assembly...

  5. An orthologue of the cor gene is involved in the exclusion of temperate lambdoid phages. Evidence that Cor inactivates FhuA receptor functions

    International Nuclear Information System (INIS)

    A new set of lambdoid phages (mEp) classified into different immunity groups was previously described. Phages mEp213, mEp237, and mEp410 were unable to grow in mEp167 lysogenic cells, presumably due to an exclusion mechanism expressed constitutively by the mEp167 repressed prophage. In this work, to analyze the exclusion phenomenon, we constructed a genomic library from mEp167 phage in a pPROEX derivative plasmid. A DNA fragment containing an open reading frame for a 77 amino acid polypeptide was selected by its ability to confer resistance to heteroimmune phage infection. This ORF shows high amino acid sequence identity with putative Cor proteins of phages HK022, φ80 and N15. Cells expressing the mEp167 cor gene from a plasmid (Cor+ phenotype) excluded 13 of 20 phages from different infection immunity groups. This exclusion was observed in both tonB- and tonB+ cells. Lambdoid mEp phages that were excluded in these cells were unable to infect cells defective in the outer membrane FhuA receptor (fhuA-). Thus, Cor-mediated exclusion was only observed in fhuA+ cells. Phage production after DNA transfection or the spontaneous induction of mEp prophage in Cor+ cells was not blocked. In addition, ferrichrome uptake, which is mediated by FhuA, was inhibited in Cor+ cells. Our results show that not only phage infection via FhuA but also a FhuA transport activity (ferrichrome uptake) are inhibited by Cor, presumably by inactivation of FhuA

  6. Francisella tularensis 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase: kinetic characterization and phosphoregulation.

    Directory of Open Access Journals (Sweden)

    Arthur Tsang

    Full Text Available Deliberate and natural outbreaks of infectious disease, the prevalence of antibiotic resistant strains, and the ease by which antibiotic resistant bacteria can be intentionally engineered all underscore the necessity of effective vaccines and continued development of novel antimicrobial/antiviral therapeutics. Isoprenes, a group of molecules fundamentally involved in a variety of crucial biological functions, are derived from either the mevalonic acid (MVA or methylerythritol phosphate (MEP pathway. While mammals utilize the MVA pathway, many bacteria utilize the MEP pathway, highlighting the latter as an attractive target for antibiotic development. In this report we describe the cloning and characterization of Francisella tularensis MEP cytidylyltransferase, a MEP pathway enzyme and potential target for antibiotic development. Size exclusion chromatography indicates the protein exists as a dimer in solution. Enzyme assays produced an apparentK(MEP(M = 178 μM, K(CTP(M = 73 μM , k(MEP(cat = 1(s-1, k(CTP(cat = 0.8( s-1, and a k(MEP(cat/ K(MEP(M = 3.4 x 10(5 M(-1 min(-1. The enzyme exhibits a strict preference for Mg(+2 as a divalent cation and CTP as the nucleotide. Titanium dioxide chromatography-tandem mass spectrometry identified Thr141 as a site of phosphorylation. T141D and T141E site-directed mutants are catalytically inactive, suggesting a mechanism for post-translational control of metabolic flux through the F. tularensis MEP pathway. Overall, our study suggests that MEP cytidylyltransferase is an excellent target for the development of novel antibiotics against F. tularensis.

  7. Binding of divalent magnesium by Escherichia coli phosphoribosyl diphosphate synthetase

    DEFF Research Database (Denmark)

    Willemoës, Martin; Hove-Jensen, Bjarne

    1997-01-01

    The mechanism of binding of the substrates Mg x ATP and ribose 5-phosphate as well as Mg2+ to the enzyme 5-phospho-D-ribosyl (alpha-1-diphosphate synthetase from Escherichia coli has been analyzed. By use of the competive inhibitors of ATP and ribose 5-phosphate binding, alpha,beta-methylene ATP ...

  8. Enzymatic synthesis of 3-deoxy-d-manno-octulosonic acid (KDO) and its application for LPS assembly.

    Science.gov (United States)

    Wen, Liuqing; Zheng, Yuan; Li, Tiehai; Wang, Peng George

    2016-06-15

    The studies of 3-deoxy-d-manno-octulosonic acid (KDO) have been hindered due to its limited availability. Herein, an efficient enzymatic system for the facile synthesis of KDO from easy-to-get starting materials is described. In this one-pot three-enzyme (OPME) system, d-ribulose 5-phosphate, which was prepared from d-xylose, was employed as starting materials. The reaction process involves the isomerization of d-ribulose 5-phosphate to d-arabinose 5-phosphate catalyzed by d-arabinose 5-phosphate isomerase (KdsD), the aldol condensation of d-arabinose 5-phosphate and phosphoenolpyruvate (PEP) catalyzed by KDO 8-phosphate synthetase (KdsA), and the hydrolysis of KDO-8-phosphate catalyzed by KDO 8-phosphate phosphatase (KdsC). By using this OPME system, 72% isolated yield was obtained. The obtained KDO was further transferred to lipid A by KDO transferase from Escherichia coli (WaaA). PMID:27173798

  9. Nucleic and amino acid sequences relating to a novel transketolase, and methods for the expression thereof

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, Rodney Bruce (Pullman, WA); Wildung, Mark Raymond (Colfax, WA); Lange, Bernd Markus (Pullman, WA); McCaskill, David G. (Pullman, WA)

    2001-01-01

    cDNAs encoding 1-deoxyxylulose-5-phosphate synthase from peppermint (Mentha piperita) have been isolated and sequenced, and the corresponding amino acid sequences have been determined. Accordingly, isolated DNA sequences (SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7) are provided which code for the expression of 1-deoxyxylulose-5-phosphate synthase from plants. In another aspect the present invention provides for isolated, recombinant DXPS proteins, such as the proteins having the sequences set forth in SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8. In other aspects, replicable recombinant cloning vehicles are provided which code for plant 1-deoxyxylulose-5-phosphate synthases, or for a base sequence sufficiently complementary to at least a portion of 1-deoxyxylulose-5-phosphate synthase DNA or RNA to enable hybridization therewith. In yet other aspects, modified host cells are provided that have been transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence encoding a plant 1-deoxyxylulose-5-phosphate synthase. Thus, systems and methods are provided for the recombinant expression of the aforementioned recombinant 1-deoxyxylulose-5-phosphate synthase that may be used to facilitate its production, isolation and purification in significant amounts. Recombinant 1-deoxyxylulose-5-phosphate synthase may be used to obtain expression or enhanced expression of 1-deoxyxylulose-5-phosphate synthase in plants in order to enhance the production of 1-deoxyxylulose-5-phosphate, or its derivatives such as isopentenyl diphosphate (BP), or may be otherwise employed for the regulation or expression of 1-deoxyxylulose-5-phosphate synthase, or the production of its products.

  10. TMS-induced motor evoked potentials in Wilson's disease: a systematic literature review.

    Science.gov (United States)

    Bembenek, Jan P; Kurczych, Katarzyna; Członkowska, Anna

    2015-04-01

    Wilson's disease (WD) is a metabolic brain disease resulting from improper copper metabolism. Although pyramidal symptoms are rarely observed, subclinical injury is highly possible as copper accumulates in all brain structures. The usefulness of motor evoked potentials (MEPs) in pyramidal tracts damage evaluation still appears to be somehow equivocal. We searched for original papers assessing the value of transcranial magnetic stimulation elicited MEPs with respect to motor function of upper and lower extremity in WD. We searched PubMed for original papers evaluating use of MEPs in WD using key words: "motor evoked potentials Wilson's disease" and "transcranial magnetic stimulation Wilson's disease." We found six articles using the above key words. One additional article and one case report were found while viewing the references lists. Therefore, we included eight studies. Number of patients in studies was low and their clinical characteristic was variable. There were also differences in methodology. Abnormal MEPs were confirmed in 20-70% of study participants. MEPs were not recorded in 7.6-66.7% of patients. Four studies reported significantly increased cortical excitability (up to 70% of patients). Prolonged central motor conduction time was observed in four studies (30-100% of patients). One study reported absent or prolonged central motor latency in 66.7% of patients. Although MEPs may be abnormal in WD, this has not been thoroughly assessed. Hence, further studies are indispensable to evaluate MEPs' usefulness in assessing pyramidal tract damage in WD.

  11. APPLICATION OF MAXIMUM ENTROPY PRINCIPLE METHOD TO THE STUDY OF WAVE CLIMATE STATISTICAL CHARACTERISTICS

    Institute of Scientific and Technical Information of China (English)

    XU Fu-min; XUE Hong-chao

    2004-01-01

    The Maximum Entropy Principle (MEP) method is elaborated, and the corresponding probability density evaluation method for the random fluctuation system is introduced, the goal of the article is to find the best fitting method for the wave climate statistical distribution. For the first time, a kind of new maximum entropy probability distribution (MEP distribution) expression is deduced in accordance with the second order moment of a random process. Different from all the fitting methods in the past, the MEP distribution can describe the probability distribution of any random fluctuation system conveniently and reasonably. If the moments of the random signal is limited to the second order, that is, the ratio of the root-mean-square value to the mean value of the random variable is obtained from the random sample, the corresponding MEP distribution can be computed according to the deduced expression in this essay. The concept of the wave climate is introduced here, and the MEP distribution is applied to fit the probability density distributions of the significant wave height and spectral peak period. Take the Mexico Gulf as an example, three stations at different locations, depths and wind wave strengths are chosen in the half-closed gulf, the significant wave height and spectral peak period distributions at each station are fitted with the MEP distribution, the Weibull distribution and the Log-normal distribution respectively, the fitted results are compared with the field observations, the results show that the MEP distribution is the best fitting method, and the Weibull distribution is the worst one when applied to the significant wave height and spectral peak period distributions at different locations, water depths and wind wave strengths in the Gulf. The conclusion shows the feasibility and reasonability of fitting wave climate statistical distributions with the deduced MEP distributions in this essay, and furthermore proves the great potential of MEP method to

  12. Synthesis, Structure and Biological Activities of Some Novel N-(4,6-Disubstituted-pyrimidin-2-yl)-N'-(trifluoromethylphenyl)-guanidine Derivatives

    Institute of Scientific and Technical Information of China (English)

    HE Feng-Qi; LIU Xing-Hai; WANG Bao-Lei; LI Yong-Hong; LI Zheng-Ming

    2008-01-01

    A novel series of guanidine derivatives were designed, synthesized and confirmed by FTIR, MS, 1H NMR and elemental analysis. The single crystal structure of 11b was determined by X-ray diffraction. Herbicidal activities of these guanidine derivatives were evaluated through barnyardgrass and rape cup tests, among which compounds lla, lib, and lie against Brassica campestris reached 71.2%, 86.7%, and 86.9% at 100 μg·mL-1 respectively. The preliminary ketol-acid reductoisomerase test showed that the synthesized compounds had weak activities.

  13. Accuracy of Medicare expenditures in the medical expenditure panel survey.

    Science.gov (United States)

    Zuvekas, Samuel H; Olin, Gary L

    2009-01-01

    This paper examines underreporting and underrepresentation of high expenditure cases in the Medical Expenditure Panel Survey (MEPS) and their implications for analyses. Our data come from a sample of Medicare beneficiaries in the MEPS who were matched to their Medicare claims and enrollment files, with supplemental data from the Medicare Current Beneficiary Survey (MCBS). Underreporting of expenditures affected all groups of Medicare beneficiaries in the matched sample, but uniformly so that behavioral analyses were largely unaffected. Straightforward adjustments to the MEPS expenditure estimates could align them with aggregate sources, such as the National Health Expenditure Accounts, while preserving underlying relationships between expenditures and key correlates.

  14. Labor Supply of Politicians

    DEFF Research Database (Denmark)

    Fisman, Raymond; Harmon, Nikolaj Arpe; Kamenica, Emir;

    2015-01-01

    Using data on Members of the European Parliament (MEPs), we examine the impact of salaries on the composition and the behavior of legislators. Employing a differences-in-differences approach, we exploit the introduction of a law that equalized MEPs’ salaries which had previously differed by as much...... as a factor of ten. Increasing salaries raises the fraction of MEPs who run for reelection but decreases the quality of elected MEPs (proxied by college quality). Salary has no discernible impact on effort or legislative output. Higher salaries induce more political competition....

  15. Connectivity analysis of suggestive brain areas involved in middle ear pressure regulation in humans

    DEFF Research Database (Denmark)

    SA, Sami; Gaihede, Michael

    2010-01-01

    HYPOTHESIS:: Middle ear pressure (MEP) is actively regulated by both the Eustachian tube and the mastoid air cell system. BACKGROUND:: MEP is a highly significant factor involved in many clinical conditions related to otitis media. Basic knowledge on its overall regulation remains insufficient...... of these distinct mechanisms were found. CONCLUSION:: The human mastoid as well as the Eustachian tube was capable of active counter-regulation of the MEP in short-term experimental pressure changes in healthy ears. Thus, these 2 systems seemed to function in a complementary way, where the mastoid was related...

  16. Toxoplasma gondii: mechanism of the parasitostatic action of 6-thioxanthine.

    Science.gov (United States)

    Pfefferkorn, E R; Bzik, D J; Honsinger, C P

    2001-12-01

    In contrast to the cytocidal effect of 6-thiopurines on mammalian cells, the action of 6-thioxanthine on Toxoplasma gondii was only parasitostatic. 6-Thioxanthine was a substrate of the parasite's hypoxanthine-guanine phosphoribosyltransferase. That enzyme converted 6-thioxanthine to 6-thioxanthosine 5'-phosphate which accumulated to near millimolar concentrations within parasites incubated intracellularly in medium containing the drug. 6-Thioxanthosine 5'-phosphate was the only detectable metabolite of 6-thioxanthine. The absence of 6-thioguanine nucleotides explains the lack of a parasitocidal effect because the incorporation of 6-thiodeoxyguanosine triphosphate into DNA is the mechanism of the lethal effect of 6-thiopurines on mammalian cells. Extracellular parasites that had accumulated a high concentration of 6-thioxanthosine 5'-phosphate incorporated more labeled hypoxanthine or xanthine into their nucleotide pools than did control parasites. The basis for this increased nucleobase salvage remains unexplained. It was not due to up-regulation of hypoxanthine-guanine phosphoribosyltransferase and could not be explained by reduced use of labeled nucleotides for nucleic acid synthesis. Extracellular parasites that had accumulated a high concentration of 6-thioxanthosine 5'-phosphate used labeled hypoxanthine almost entirely to make adenine nucleotides while control parasites made both adenine and guanine nucleotides. Both extracellular parasites that had accumulated a high concentration of 6-thioxanthosine 5'-phosphate and control parasites efficiently used labeled xanthine to make guanine nucleotides. These observations suggested that inosine 5'-phosphate-dehydrogenase was inhibited while guanosine 5'-phosphate synthase was not. Assay of inosine 5'-phosphate dehydrogenase in soluble extracts of T. gondii confirmed that 6-thioxanthosine 5'-phosphate was an inhibitor. We conclude that 6-thioxanthine blocks the growth of T. gondii by a depletion a guanine

  17. Medical Expenditure Panel Survey MEPSnet Insurance Component (MEPSnet/IC)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The MEPS-IC is an annual survey of establishments that collects information about employer-sponsored health insurance offerings in the United States. With...

  18. Corticospinal state variability and hemispheric asymmetries in motivational tendencies

    NARCIS (Netherlands)

    Schutter, D.J.L.G.; Hofman, D.; Hoppenbrouwers, S.S.; Kenemans, J.L.

    2011-01-01

    This transcranial magnetic stimulation (TMS) study examined interrelations between asymmetrical hemispheric differences in the degree of variability of corticospinal excitability levels and motivational tendencies. The relative standard deviation in motor evoked potentials (MEP) to single pulse TMS

  19. Possible impact of phthalates on infant reproductive health

    DEFF Research Database (Denmark)

    Poulsen, Grete Lottrup; Andersson, A-M; Leffers, H;

    2006-01-01

    discusses two recent studies on perinatal phthalate exposure, which indicated that human testicular development might be susceptible to phthalates. One study analysed phthalate monoesters in breast milk and reproductive hormone levels in infants. Five of six phthalates [monoethyl-(MEP), monobutyl- (MBP......) levels. MMP, MEP, MBP, MEHP and MiNP were positively correlated with the LH/testosterone ratio. Another study found a reduction of the anogenital index (AGI) in infant boys with increasing levels of MBP, MEP, monobenzyl- and mono-isobutyl phthalate in maternal urine samples during late-pregnancy. Boys...... with small AGI showed a high prevalence of cryptorchidism and small genital size. Taken together these studies suggest an antivirilizing effect of phthalates in infants. Most of these findings are in line with animal observations. However, the possible effects of MEP appear to be limited to humans. This may...

  20. Present and Last Glacial Maximum climates as states of maximum entropy production

    CERN Document Server

    Herbert, Corentin; Kageyama, Masa; Dubrulle, Berengere

    2011-01-01

    The Earth, like other planets with a relatively thick atmosphere, is not locally in radiative equilibrium and the transport of energy by the geophysical fluids (atmosphere and ocean) plays a fundamental role in determining its climate. Using simple energy-balance models, it was suggested a few decades ago that the meridional energy fluxes might follow a thermodynamic Maximum Entropy Production (MEP) principle. In the present study, we assess the MEP hypothesis in the framework of a minimal climate model based solely on a robust radiative scheme and the MEP principle, with no extra assumptions. Specifically, we show that by choosing an adequate radiative exchange formulation, the Net Exchange Formulation, a rigorous derivation of all the physical parameters can be performed. The MEP principle is also extended to surface energy fluxes, in addition to meridional energy fluxes. The climate model presented here is extremely fast, needs very little empirical data and does not rely on ad hoc parameterizations. We in...

  1. Gclust Server: 93355 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available 93355 SCE_YPR138C=MEP3 Cluster Sequences Related Sequences(238) 489 Ammonium permease of high capacity...s(238) Sequence length 489 Representative annotation Ammonium permease of high capacity

  2. Scout Missions and Future Exploration of the Martian Poles

    Science.gov (United States)

    McBride, K. S.

    2003-01-01

    NASA's Mars Exploration Program, (MEP) complemented by missions in operation by ESA and the Japanese space agency, is revolutionizing the study of Mars as a planet and potential home for life, past, present or future. Within the MEP there are a number of significant opportunities for the study of the Mars polar regions--from the ongoing Mars Global Surveyor and Odyssey missions, the upcoming Mars Reconnaissance Orbiter, and the soon-to-be-defined Mars Science Laboratory. As an internal complement to the Mars missions being developed by JPL for the MEP, Mars Scout investigations can provide substantial future opportunities to study the polar regions of Mars. These relatively small, PI-led missions provide substantial flexibility within the overall MEP, providing the capability to respond to scientific targets of opportunity in Mars science, with special-interest small missions, or to be developed to respond to instrument opportunities for missions developed by international partners.

  3. Mudel Euroopa Parlamendist = Модель Европейского Парламента / Irena Rihkrand

    Index Scriptorium Estoniae

    Rihkrand, Irena

    2009-01-01

    Simulatsioonimängust "Mudel Euroopa Parlamendist (MEP)", mille eesmärgiks on tutvustada noortele Euroopa Parlamenti, suurendada huvi ühiskondliku tegevuse vastu ja anda neile võimalus osaleda ühiskonna arengus

  4. Bilateral sensory deprivation of trigeminal afferent fibers on corticomotor control of human tongue musculature: A preliminary study

    DEFF Research Database (Denmark)

    Kothari, Mohit; Baad-Hansen, Lene; Svensson, Peter

    2016-01-01

    nerve affects the excitability of the tongue motor cortex (MI) as measured by TMS. Methods: The effect on MEPs after bilateral LA of the lingual nerve was studied, while the first dorsal interosseous (FDI) muscle served as a control in ten healthy participants. MEPs were measured on the right side...... of the tongue dorsum in four different conditions: (1) immediately prior to anaesthesia (baseline), (2) during bilateral LA block of the lingual nerve, (3) after anaesthesia had subjectively subsided (recovery) and (4) 3 hrs after bilateral lingual block injection. MEPs were assessed using stimulus......–response curves in steps of 10% of motor threshold (T). Eight stimuli were given at each stimulus level. Results: The amplitudes of the tongue MEPs were significantly influenced by the stimulus intensity (P

  5. Repeated tongue lift movement induces neuroplasticity in corticomotor control of tongue and jaw muscles in humans

    DEFF Research Database (Denmark)

    Komoda, Yoshihiro; Lida, Takashi; Kothari, Mohit;

    2015-01-01

    This study investigated the effect of repeated tongue lift training (TLT) on the excitability of the corticomotor representation of the human tongue and jaw musculature. Sixteen participants performed three series of TLT for 41min on each of 5 consecutive days. Each TLT series consisted of two....... EMG recordings from the left and right tongue dorsum and masseter muscles were made at three pressure levels (5kPa, 10kPa, 100% tongue lift), and tongue, masseter, and first dorsal interosseous (FDI) MEPs were measured. There were no significant day-to-day differences in the tongue pressure during...... maximum voluntary contractions. The amplitudes and thresholds of tongue and masseter MEPs after TLT on Day 5 were respectively higher and lower than before TLT on Day 1 (Ptongue and masseter MEP areas; no significant changes occurred in MEP onset...

  6. Medical Expenditure Panel Survey Household Component

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Medical Expenditure Panel Survey (MEPS) Household Component (HC) collects data from a sample of families and individuals in selected communities across the...

  7. Nanoindentation Studies of TNZ and Ti2448 Biomaterials After Magnetoelectropolishing

    Directory of Open Access Journals (Sweden)

    Hryniewicz T.

    2014-10-01

    Full Text Available This work presents the nanoindentation results of two newly developed titanium alloy biomaterials, TNZ and Ti2448, after different surface treatments. The investigations were performed on the samples, AR – as received, MP – after abrasive polishing, EP – after a standard electropolshing, and MEP – after magnetoelectropolishing. The electropolishing processes, both EP and MEP, were conducted in the same proprietary electrolyte based on concentrated sulfuric acid. The mechanical properties of the titanium alloys biomaterials demonstrated an evident dependence on the surface treatment method, with MEP samples revealing extremely different behaviour and mechanical properties. Such a different mechanical behaviour may mean completely different composition and thickness of the surface film formed on the studied samples after MEP

  8. 76 FR 22674 - Manufacturing Extension Partnership Advisory Board

    Science.gov (United States)

    2011-04-22

    ... National Institute of Standards and Technology Manufacturing Extension Partnership Advisory Board AGENCY... announces that the Manufacturing Extension Partnership (MEP) Advisory Board, National Institute of Standards... than May 2, 2011. FOR FURTHER INFORMATION CONTACT: Karen Lellock, Manufacturing Extension...

  9. 75 FR 50749 - Manufacturing Extension Partnership Advisory Board

    Science.gov (United States)

    2010-08-17

    ... National Institute of Standards and Technology Manufacturing Extension Partnership Advisory Board AGENCY... announces that the Manufacturing Extension Partnership (MEP) Advisory Board, National Institute of Standards... INFORMATION CONTACT: Karen Lellock, Manufacturing Extension Partnership, National Institute of Standards...

  10. 77 FR 20790 - Manufacturing Extension Partnership Advisory Board

    Science.gov (United States)

    2012-04-06

    ... National Institute of Standards and Technology Manufacturing Extension Partnership Advisory Board AGENCY... announces that the Manufacturing Extension Partnership (MEP) Advisory Board, National Institute of Standards... INFORMATION section below. FOR FURTHER INFORMATION CONTACT: Karen Lellock, Manufacturing Extension...

  11. 75 FR 19941 - Manufacturing Extension Partnership Advisory Board

    Science.gov (United States)

    2010-04-16

    ... National Institute of Standards and Technology Manufacturing Extension Partnership Advisory Board AGENCY... announces that the Manufacturing Extension Partnership (MEP) Advisory Board, National Institute of Standards..., 2010. FOR FURTHER INFORMATION CONTACT: Karen Lellock, Manufacturing Extension Partnership,...

  12. Master environmental plan for Fort Devens, Massachusetts

    Energy Technology Data Exchange (ETDEWEB)

    Biang, C.A.; Peters, R.W.; Pearl, R.H.; Tsai, S.Y. (Argonne National Lab., IL (United States). Energy Systems Div.)

    1991-11-01

    Argonne National Laboratory has prepared a master environmental plan (MEP) for Fort Devens, Massachusetts, for the US Army Toxic and Hazardous Materials Agency. The MEP is an assessment based on environmental laws and regulations of both the federal government and the Commonwealth of Massachusetts. The MEP assess the physical and environmental status of 58 potential hazardous waste sites, including 54 study areas (SAs) that pose a potential for releasing contamination into the environment and 4 areas of concern (AOCs) that are known to have substantial contamination. For each SA or AOC, this MEP describes the known history and environment, identifies additional data needs, and proposes possible response actions. Most recommended response actions consist of environmental sampling and monitoring and other characterization studies. 74 refs., 63 figs., 50 tabs.

  13. Steady state kinetic model for the binding of substrates and allosteric effectors to Escherichia coli phosphoribosyl-diphosphate synthase

    DEFF Research Database (Denmark)

    Willemoës, Martin; Hove-Jensen, Bjarne; Larsen, Sine

    2000-01-01

    saturation with ribose 5-phosphate leads to the binding of Mg2+ and substrates via a slow pathway where Pi binds to the enzyme last. The random mechanism for Pi binding was further supported by studies with competitive inhibitors of Mg2+, MgATP, and ribose 5-phosphate that all appeared noncompetitive when...... varying Pi at either saturating or unsaturating ribose 5-phosphate concentrations. Furthermore, none of the inhibitors induced inhibition at increasing Pi concentrations. Results from ADP inhibition of Pi activation suggest that these effectors compete for binding to a common regulatory site....

  14. Ehrlich-Schwoebel Effect for Organic Molecules: Direct Calculation of the Step Edge Barrier using Empirical Potentials

    OpenAIRE

    Fendrich, Markus; Krug, Joachim

    2007-01-01

    The step edge barrier of a prototypical organic semiconductor molecule, 3,4,9,10-perylene-tetracaboxylic-dianhydride (PTCDA) has been analysed by means of calculations based on emperical potentials. The minimum energy path (MEP) has been calculated for a single molecule on a substrate of three molecular layers between equivalent minimum energy positions within two neighboring unit cells. To determine the step edge barrier, we have calculated the MEP over a step to a fourth layer of molecules....

  15. The Mother Enrichment Program: A Genetic System for Facile Replicative Life Span Analysis in Saccharomyces cerevisiae

    OpenAIRE

    Lindstrom, Derek L.; Gottschling, Daniel E.

    2009-01-01

    The replicative life span (RLS) of Saccharomyces cerevisiae has been established as a model for the genetic regulation of longevity despite the inherent difficulty of the RLS assay, which requires separation of mother and daughter cells by micromanipulation after every division. Here we present the mother enrichment program (MEP), an inducible genetic system in which mother cells maintain a normal RLS—a median of 36 generations in the diploid MEP strain—while the proliferative potential of da...

  16. Lethal Mutations in the Isoprenoid Pathway of Salmonella enterica

    OpenAIRE

    Cornish, Rita M.; Roth, John R.; Poulter, C. Dale

    2006-01-01

    Essential isoprenoid compounds are synthesized using the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway in many gram-negative bacteria, some gram-positive bacteria, some apicomplexan parasites, and plant chloroplasts. The alternative mevalonate pathway is found in archaea and eukaryotes, including cytosolic biosynthesis in plants. The existence of orthogonal essential pathways in eukaryotes and bacteria makes the MEP pathway an attractive target for the development of antimicrobial agents....

  17. Cytidine derivatives as IspF inhibitors of Burkolderia pseudomallei

    OpenAIRE

    Zhang, Zheng; Jakkaraju, Sriram; Blain, Joy; Gogol, Kenneth; Zhao, Lei; Hartley, Robert C.; Karlsson, Courtney A.; Staker, Bart L.; Lance J Stewart; Myler, Peter J.; Clare, Michael; Begley, Darren W.; Horn, James R.; Hagen, Timothy J.

    2013-01-01

    Published biological data suggest that the methyl erythritol phosphate (MEP) pathway, a non-mevalonate isoprenoid biosynthetic pathway, is essential for certain bacteria and other infectious disease organisms. One highly conserved enzyme in the MEP pathway is 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (IspF). Fragment-bound complexes of IspF from Burkholderia pseudomallei were used to design and synthesize a series of molecules linking the cytidine moiety to different zinc pocket fr...

  18. Motorcycle exhaust particles induce airway inflammation and airway hyperresponsiveness in BALB/C mice.

    Science.gov (United States)

    Lee, Chen-Chen; Liao, Jiunn-Wang; Kang, Jaw-Jou

    2004-06-01

    A number of large studies have reported that environmental pollutants from fossil fuel combustion can cause deleterious effects to the immune system, resulting in an allergic reaction leading to respiratory tract damage. In this study, we investigated the effect of motorcycle exhaust particles (MEP), a major pollutant in the Taiwan urban area, on airway inflammation and airway hyperresponsiveness in laboratory animals. BALB/c mice were instilled intratracheally (i.t.) with 1.2 mg/kg and 12 mg/kg of MEP, which was collected from two-stroke motorcycle engines. The mice were exposed 3 times i.t. with MEP, and various parameters for airway inflammation and hyperresponsiveness were sequentially analyzed. We found that MEP would induce airway and pulmonary inflammation characterized by infiltration of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid (BALF) and inflammatory cell infiltration in lung. In addition, MEP treatment enhanced BALF interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) cytokine levels and serum IgE production. Bronchial response measured by unrestrained plethysmography with methacholine challenge showed that MEP treatment induced airway hyperresponsiveness (AHR) in BALB/c mice. The chemical components in MEP were further fractionated with organic solvents, and we found that the benzene-extracted fraction exerts a similar biological effect as seen with MEP, including airway inflammation, increased BALF IL-4, serum IgE production, and induction of AHR. In conclusion, we present evidence showing that the filter-trapped particles emitted from the unleaded-gasoline-fueled two-stroke motorcycle engine may induce proinflammatory and proallergic response profiles in the absence of exposure to allergen.

  19. Recurrent rearrangement during adaptive evolution in an interspecific yeast hybrid suggests a model for rapid introgression.

    Directory of Open Access Journals (Sweden)

    Barbara Dunn

    2013-03-01

    Full Text Available Genome rearrangements are associated with eukaryotic evolutionary processes ranging from tumorigenesis to speciation. Rearrangements are especially common following interspecific hybridization, and some of these could be expected to have strong selective value. To test this expectation we created de novo interspecific yeast hybrids between two diverged but largely syntenic Saccharomyces species, S. cerevisiae and S. uvarum, then experimentally evolved them under continuous ammonium limitation. We discovered that a characteristic interspecific genome rearrangement arose multiple times in independently evolved populations. We uncovered nine different breakpoints, all occurring in a narrow ~1-kb region of chromosome 14, and all producing an "interspecific fusion junction" within the MEP2 gene coding sequence, such that the 5' portion derives from S. cerevisiae and the 3' portion derives from S. uvarum. In most cases the rearrangements altered both chromosomes, resulting in what can be considered to be an introgression of a several-kb region of S. uvarum into an otherwise intact S. cerevisiae chromosome 14, while the homeologous S. uvarum chromosome 14 experienced an interspecific reciprocal translocation at the same breakpoint within MEP2, yielding a chimaeric chromosome; these events result in the presence in the cell of two MEP2 fusion genes having identical breakpoints. Given that MEP2 encodes for a high-affinity ammonium permease, that MEP2 fusion genes arise repeatedly under ammonium-limitation, and that three independent evolved isolates carrying MEP2 fusion genes are each more fit than their common ancestor, the novel MEP2 fusion genes are very likely adaptive under ammonium limitation. Our results suggest that, when homoploid hybrids form, the admixture of two genomes enables swift and otherwise unavailable evolutionary innovations. Furthermore, the architecture of the MEP2 rearrangement suggests a model for rapid introgression, a

  20. Does Remuneration Affect the Discipline and the Selection of Politicians? Evidence from Pay Harmonization in the European Parliament

    OpenAIRE

    Braendle, Thomas

    2013-01-01

    We study the harmonization of the base remuneration for the Members of the European Parliament (MEPs) who were previously paid like national parliamentarians implying large differences between the delegations from the 27 member countries. Based on detailed information on individual MEPs between 2004 and 2011, we find that the reform, which comes with an exceptional increase of, on average, 200 percent per national delegation, has a positive incentive effect on in-office effort as approximated...

  1. Estimate of Technical Potential for Minimum Efficiency Performance Standards in 13 Major World Economies

    Energy Technology Data Exchange (ETDEWEB)

    Letschert, Virginie [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Desroches, Louis-Benoit [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Ke, Jing [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); McNeil, Michael [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2012-07-01

    As part of the ongoing effort to estimate the foreseeable impacts of aggressive minimum efficiency performance standards (MEPS) programs in the world’s major economies, Lawrence Berkeley National Laboratory (LBNL) has developed a scenario to analyze the technical potential of MEPS in 13 major economies around the world1 . The “best available technology” (BAT) scenario seeks to determine the maximum potential savings that would result from diffusion of the most efficient available technologies in these major economies.

  2. An online electoral connection? How electoral systems condition representatives’ social media use

    OpenAIRE

    Obholzer, Lukas; Daniel, Williams T.

    2016-01-01

    This article analyses the impact of electoral institutions on the re-election campaigning and outreach strategies of Members of the European Parliament (MEPs) on the Twitter social media platform. Social media offers politicians a means to contact voters remotely and at low cost. We test the effect of diverse national proportional representation electoral institutions in European elections on a possible online electoral connection. We draw upon an original dataset of MEP Twitter activity befo...

  3. DXR Inhibition by Potent Mono- and Disubstituted Fosmidomycin Analogues

    OpenAIRE

    Jansson, Anna; Więckowska, Anna; Björkelid, Christofer; Yahiaoui, Samir; Sooriyaarachchi, Sanjeewani; Lindh, Martin; Bergfors, Terese; Dharavath, Shyamraj; Desroses, Matthieu; Suresh, Surisetti; Andaloussi, Mounir; Nikhil, Rautela; Sreevalli, Sharma; Srinivasa, Bachally R.; Larhed, Mats

    2013-01-01

    The antimalarial compound fosmidomycin targets DXR, the enzyme that catalyzes the first committed step in the MEP pathway producing the universally essential isoprenoid precursors, isopentenyl diphosphate and dimethylallyl diphosphate. The MEP pathway is used by a number of pathogens, including Mycobacterium tuberculosis and apicomplexan parasites, and differs from the classical mevalonate pathway that is essential in humans. Using a structure-based approach, we designed a number of analogues...

  4. The value of bilateral ipsilateral and contralateral motor evoked potential monitoring in scoliosis surgery

    OpenAIRE

    Lo, Y. L.; Dan, Y. F.; Teo, A; Tan, Y. E.; Yue, W. M.; Raman, S.; Tan, S. B.

    2007-01-01

    Intraoperative monitoring (IOM) of the motor pathways is a routine procedure for ensuring integrity of corticospinal tracts during scoliosis surgery. We have previously demonstrated presence of ipsilateral motor evoked potentials (MEPs) during IOM for scoliosis surgery, but its significance was uncertain. In this case series, we show concurrent ipsilateral and contralateral MEP amplitude changes obtained with cortical stimulation are of value in reducing false positive observations during IOM...

  5. ‘Normal Parliament’: Exploring the Organisation of Everyday Political Life in an MEP’s Office

    Directory of Open Access Journals (Sweden)

    Amy Busby

    2013-02-01

    Full Text Available The Lisbon Treaty has again enhanced the role and powers of the European Parliament [EP] and therefore increased the workload of individual MEPs. However many citizens remain unaware of what MEPs do and how they represent them. This paper reviews the academic literature and argues that we need to know more about how individual MEPs practise European politics inside this institution. Throughout, it argues that ethnography can play a key role in opening up this institutional black-box and enhancing our understanding of this profession by focusing on daily activities and backstage processes. It begins by exploring the working environment of MEPs, which is characterised by shortage of time, constant travelling, information overload, and highly technical issues. Secondly, it describes strategies MEPs employ to pursue their aims here, namely: specialisation, filtering, employing assistants, and information management. Thirdly, it draws comparisons with other professional fields to remind us the EP is a normal professional work environment. The contributions are twofold: the article provides a deeper, more nuanced, and more holistic understanding of (individual MEP behaviour; and also helps to demystify the profession and thus help alleviate the democratic deficit by beginning to close the gap between politicians and citizens.

  6. HIGH-VOLUME RESISTANCE TRAINING SESSION ACUTELY DIMINISHES RESPIRATORY MUSCLE STRENGTH

    Directory of Open Access Journals (Sweden)

    Daniel A. Hackett

    2012-03-01

    Full Text Available This study investigated the effect of a high-volume compared to a low-volume resistance training session on maximal inspiratory pressure (MIP and maximal expiratory pressure (MEP. Twenty male subjects with resistance training experience (6.2 ± 3.2 y, in a crossover trial, completed two resistance training protocols (high-volume: 5 sets per exercise; low-volume: 2 sets per exercise and a control session (no exercise on 3 separate occasions. MIP and MEP decreased by 13.6% (p < 0.01 and 14.7% (p < 0.01 respectively from pre-session MIP and MEP, following the high-volume session. MIP and MEP were unaffected following the low-volume or the control sessions. MIP returned to pre-session values after 40 minutes, whereas MEP remained significantly reduced after 60 minutes post-session by 9.2% compared to pre-session (p < 0.01. The findings suggest that the high-volume session significantly decreased MIP and MEP post-session, implicating a substantially increased demand on the respiratory muscles and that adequate recovery is mandatory following this mode of training.

  7. Identification of human erythroid lineage-committed progenitors.

    Science.gov (United States)

    Mori, Yasuo; Akashi, Koichi; Weissman, Irving L

    2016-05-01

    Elucidating the developmental pathway leading to erythrocytes and being able to isolate their progenitors is crucial to understanding and treating disorders of red cell imbalance such as anemia, myelodysplastic syndrome, and polycythemia vera. Endoglin (CD105) is a key marker for purifying mouse erythroid lineage-committed progenitors (EPs) from bone marrow. Herein, we show that human EPs can also be isolated from adult bone marrow. We identified three subfractions that possessed different expression patterns of CD105 and CD71 within the previously defined human megakaryocyte/erythrocyte progenitor (hMEP; Lineage-CD34(+)CD38(+)IL-3Rα(-)CD45RA(-)) population. Both CD71(-)CD105(-) and CD71(+)CD105(-) MEPs, at least in vitro, retained bipotency for the megakaryocyte (MegK) and erythrocyte (E) lineages, although the latter sub-population had a differentiation potential skewed toward the E-lineage. Notably, the differentiation output of the CD71(+)CD105(+) subset of cells within the MEP population was completely restricted to the E-lineage with the loss of MegK potential; thus, we termed CD71(+)CD105(-) MEPs and CD71(+)CD105(+) cells as E-biased MEPs (E-MEPs) and EPs, respectively. These previously unclassified populations may facilitate understanding of the molecular mechanisms governing human erythroid development and serve as potential therapeutic targets in disorders of the erythroid lineage. PMID:27263782

  8. Scaling of motor cortical excitability during unimanual force generation.

    Science.gov (United States)

    Perez, Monica A; Cohen, Leonardo G

    2009-10-01

    During performance of a unimanual force generation task primary motor cortices (M1s) experience clear functional changes. Here, we evaluated the way in which M1s interact during parametric increases in right wrist flexion force in healthy volunteers. We measured the amplitude and the slope of motor evoked potentials (MEP) recruitment curves to transcranial magnetic stimulation (TMS) in the left and right flexor carpi radialis (FCR) muscles at rest and during 10%, 30% and 70% of maximal wrist flexion force. At rest, no differences were observed in the amplitude and slope of MEP recruitment curves in the left and right FCR muscles. With increasing right wrist flexion force, MEP amplitudes increased in both FCR muscles, with larger amplitudes in the right FCR. We found a significant correlation between the left and right MEP amplitudes across conditions. The slope of right and left FCR MEP recruitment curve was significantly steeper at 70% of force compared to rest and 10% of force. A significant correlation between the slope of left and right FCR MEP amplitudes was found at 70% of force only. Our results indicate a differential scaling of excitability in the corticospinal system controlling right and left FCR muscles at increasing levels of unimanual force generation. Specifically, these data highlights that at strong levels of unimanual force the increases in motor cortical excitability with increasing TMS stimulus intensities follow a similar pattern in both M1s, while at low levels of force they do not.

  9. Longitudinal Evaluation of Residual Cortical and Subcortical Motor Evoked Potentials in Spinal Cord Injured Rats.

    Science.gov (United States)

    Redondo-Castro, Elena; Navarro, Xavier; García-Alías, Guillermo

    2016-05-15

    We have applied transcranial electrical stimulation to rats with spinal cord injury and selectively tested the motor evoked potentials (MEPs) conveyed by descending motor pathways with cortical and subcortical origin. MEPs were elicited by electrical stimulation to the brain and recorded on the tibialis anterior muscles. Stimulation parameters were characterized and changes in MEP responses tested in uninjured rats, in rats with mild or moderate contusion, and in animals with complete transection of the spinal cord. All injuries were located at the T8 vertebral level. Two peaks, termed N1 and N2, were obtained when changing from single pulse stimulation to trains of 9 pulses at 9 Hz. Selective injuries to the brain or spinal cord funiculi evidenced the subcortical origin of N1 and the cortical origin of N2. Animals with mild contusion showed small behavioral deficits and abolished N1 but maintained small amplitude N2 MEPs. Substantial motor deficits developed in rats with moderate contusion, and these rats had completely eliminated N1 and N2 MEPs. Animals with complete cord transection had abolished N1 and N2 and showed severe impairment of locomotion. The results indicate the reliability of MEP testing to longitudinally evaluate over time the degree of impairment of cortical and subcortical spinal pathways after spinal cord injuries of different severity. PMID:26560177

  10. Repeated tongue lift movement induces neuroplasticity in corticomotor control of tongue and jaw muscles in humans.

    Science.gov (United States)

    Komoda, Yoshihiro; Iida, Takashi; Kothari, Mohit; Komiyama, Osamu; Baad-Hansen, Lene; Kawara, Misao; Sessle, Barry; Svensson, Peter

    2015-11-19

    This study investigated the effect of repeated tongue lift training (TLT) on the excitability of the corticomotor representation of the human tongue and jaw musculature. Sixteen participants performed three series of TLT for 41 min on each of 5 consecutive days. Each TLT series consisted of two pressure levels (5 kPa and 10 kPa). All participants underwent transcranial magnetic stimulation (TMS) and electromyographic (EMG) recordings of motor evoked potentials (MEPs) in four sessions: (1) before TLT on Day 1 (baseline), (2) after TLT on Day 1, (3) before TLT on Day 5, and (4) after TLT on Day 5. EMG recordings from the left and right tongue dorsum and masseter muscles were made at three pressure levels (5 kPa, 10 kPa, 100% tongue lift), and tongue, masseter, and first dorsal interosseous (FDI) MEPs were measured. There were no significant day-to-day differences in the tongue pressure during maximum voluntary contractions. The amplitudes and thresholds of tongue and masseter MEPs after TLT on Day 5 were respectively higher and lower than before TLT on Day 1 (Ptongue and masseter MEP areas; no significant changes occurred in MEP onset latencies. FDI MEP parameters (amplitude, threshold, area, latency) were not significantly different between the four sessions. Our findings suggest that repeated TLT can trigger neuroplasticity reflected in increased excitability of the corticomotor representation of not only the tongue muscles but also the masseter muscles.

  11. GABAergic mechanisms contributing to categorical amygdala responses to chemosensory signals.

    Science.gov (United States)

    Westberry, Jenne M; Meredith, Michael

    2016-09-01

    Chemosensory stimuli from conspecific and heterospecific animals, elicit categorically different immediate-early gene response-patterns in medial amygdala in male hamsters and mice. We previously showed that conspecific signals activate posterior (MeP) as well as anterior medial amygdala (MeA), and especially relevant heterospecific signals such as chemosensory stimuli from potential predators also activate MeP in mice. Other heterospecific chemosignals activate MeA, but not MeP. Here we show that male hamster amygdala responds significantly differentially to different conspecific signals, by activating different proportions of cells of different phenotype, possibly leading to differential activation of downstream circuits. Heterospecific signals that fail to activate MeP do activate GABA-immunoreactive cells in the adjacent caudal main intercalated nucleus (mICNc) and elicit selective suppression of MeP cells bearing GABA-Receptors, suggesting GABA inhibition in MeP by GABAergic cells in mICNc. Overall, work presented here suggests that medial amygdala may discriminate between important conspecific social signals, distinguish them from the social signals of other species and convey that information to brain circuits eliciting appropriate social behavior. PMID:27329335

  12. Synergy between methylerythritol phosphate pathway and mevalonate pathway for isoprene production in Escherichia coli.

    Science.gov (United States)

    Yang, Chen; Gao, Xiang; Jiang, Yu; Sun, Bingbing; Gao, Fang; Yang, Sheng

    2016-09-01

    Isoprene, a key building block of synthetic rubber, is currently produced entirely from petrochemical sources. In this work, we engineered both the methylerythritol phosphate (MEP) pathway and the mevalonate (MVA) pathway for isoprene production in E. coli. The synergy between the MEP pathway and the MVA pathway was demonstrated by the production experiment, in which overexpression of both pathways improved the isoprene yield about 20-fold and 3-fold, respectively, compared to overexpression of the MEP pathway or the MVA pathway alone. The (13)C metabolic flux analysis revealed that simultaneous utilization of the two pathways resulted in a 4.8-fold increase in the MEP pathway flux and a 1.5-fold increase in the MVA pathway flux. The synergy of the dual pathway was further verified by quantifying intracellular flux responses of the MEP pathway and the MVA pathway to fosmidomycin treatment and mevalonate supplementation. Our results strongly suggest that coupling of the complementary reducing equivalent demand and ATP requirement plays an important role in the synergy of the dual pathway. Fed-batch cultivation of the engineered strain overexpressing the dual pathway resulted in production of 24.0g/L isoprene with a yield of 0.267g/g of glucose. The synergy of the MEP pathway and the MVA pathway also successfully increased the lycopene productivity in E. coli, which demonstrates that it can be used to improve the production of a broad range of terpenoids in microorganisms. PMID:27174717

  13. Ipsilesional motor-evoked potential absence in pediatric hemiparesis impacts tracking accuracy of the less affected hand.

    Science.gov (United States)

    Cassidy, Jessica M; Carey, James R; Lu, Chiahao; Krach, Linda E; Feyma, Tim; Durfee, William K; Gillick, Bernadette T

    2015-12-01

    This study analyzed the relationship between electrophysiological responses to transcranial magnetic stimulation (TMS), finger tracking accuracy, and volume of neural substrate in children with congenital hemiparesis. Nineteen participants demonstrating an ipsilesional motor-evoked potential (MEP) were compared with eleven participants showing an absent ipsilesional MEP response. Comparisons of finger tracking accuracy from the affected and less affected hands and ipsilesional/contralesional (I/C) volume ratio for the primary motor cortex (M1) and posterior limb of internal capsule (PLIC) were done using two-sample t-tests. Participants showing an ipsilesional MEP response demonstrated superior tracking performance from the less affected hand (p=0.016) and significantly higher I/C volume ratios for M1 (p=0.028) and PLIC (p=0.005) compared to participants without an ipsilesional MEP response. Group differences in finger tracking accuracy from the affected hand were not significant. These results highlight differentiating factors amongst children with congenital hemiparesis showing contrasting MEP responses: less affected hand performance and preserved M1 and PLIC volume. Along with MEP status, these factors pose important clinical implications in pediatric stroke rehabilitation. These findings may also reflect competitive developmental processes associated with the preservation of affected hand function at the expense of some function in the less affected hand. PMID:26426515

  14. Futile xylitol cycle in Lactobacillus casei.

    OpenAIRE

    Hausman, S Z; Thompson, J; London, J

    1984-01-01

    A futile xylitol cycle appears to be responsible for xylitol-mediated inhibition of growth of Lactobacillus casei Cl-16 at the expense of ribitol. The gratuitously induced xylitol-specific phosphoenolpyruvate-dependent phosphotransferase accumulates the pentitol as xylitol-5-phosphate, a phosphatase cleaves the latter, and an export system expels the xylitol. Operation of the cycle rapidly dissipates the ribitol-5-phosphate pool (and ultimately the energy supply of the cell), thereby producin...

  15. Comparison of Motor Inhibition in Variants of the Instructed-Delay Choice Reaction Time Task.

    Science.gov (United States)

    Quoilin, Caroline; Lambert, Julien; Jacob, Benvenuto; Klein, Pierre-Alexandre; Duque, Julie

    2016-01-01

    Using instructed-delay choice reaction time (RT) paradigms, many previous studies have shown that the motor system is transiently inhibited during response preparation: motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over the primary motor cortex are typically suppressed during the delay period. This effect has been observed in both selected and non-selected effectors, although MEP changes in selected effectors have been more inconsistent across task versions. Here, we compared changes in MEP amplitudes in three different variants of an instructed-delay choice RT task. All variants required participants to choose between left and right index finger movements but the responses were either provided "in the air" (Variant 1), on a regular keyboard (Variant 2), or on a response device designed to control from premature responses (Variant 3). The task variants also differed according to the visual layout (more concrete in Variant 3) and depending on whether participants received a feedback of their performance (absent in Variant 1). Behavior was globally comparable between the three variants of the task although the propensity to respond prematurely was highest in Variant 2 and lowest in Variant 3. MEPs elicited in a non-selected hand were similarly suppressed in the three variants of the task. However, significant differences emerged when considering MEPs elicited in the selected hand: these MEPs were suppressed in Variants 1 and 3 whereas they were often facilitated in Variant 2, especially in the right dominant hand. In conclusion, MEPs elicited in selected muscles seem to be more sensitive to small variations to the task design than those recorded in non-selected effectors, probably because they reflect a complex combination of inhibitory and facilitatory influences on the motor output system. Finally, the use of a standard keyboard seems to be particularly inappropriate because it encourages participants to respond promptly with no

  16. A microcalorimetric study of molecular interactions between immunoglobulin G and hydrophobic charge-induction ligand.

    Science.gov (United States)

    Yuan, Xiao-Ming; Lin, Dong-Qiang; Zhang, Qi-Lei; Gao, Dong; Yao, Shan-Jing

    2016-04-22

    Hydrophobic charge-induction chromatography (HCIC) with 4-mercaptoethyl-pyridine (MEP) as the ligand is a novel technology for antibody purification. In this study, isothermal titration calorimetry (ITC) was used to evaluate the molecular interactions between MEP ligand and immunoglobulin G (IgG). Three types of IgG molecules including human IgG (hIgG), bovine IgG (bIgG) and a monoclonal antibody (mAb) were investigated with human serum albumins (HSA) and bovine serum albumin (BSA) as the comparison. The thermodynamic parameters obtained from ITC were compared with the adsorption data. The results indicated that MEP binding to protein at neutral pH was entropy driven and induced by multimodal molecular interactions that was dominated by hydrophobic forces. The interactions between MEP and IgGs were stronger than that of albumins, which resulted in high binding affinity of IgGs. Moreover, the effects of pH and salt addition on MEP-hIgG binding were studied. The change of enthalpy increased obviously with the decrease of pH, which revealed that the electrostatic forces dominated the MEP-hIgG interactions at acidic condition and caused typical charge-induced elution of HCIC. Salt addition influenced both hydrophobic and electrostatic interactions. With the increase of salt concentration, the hydrophobic interactions decreased first and then increased, while the electrostatic interactions showed the opposite trend. This resulted in trade-off between the multimodal interactions, which caused the salt-tolerant property of MEP resin. In general, ITC studies revealed the molecular mechanism of three critical characteristics of HCIC, multimodal interactions, pH-dependent and salt-tolerant properties.

  17. Farnesol-mediated shift in the metabolic origin of prenyl groups used for protein prenylation in plants.

    Science.gov (United States)

    Huchelmann, Alexandre; Brahim, Mathieu Semir; Gerber, Esther; Tritsch, Denis; Bach, Thomas J; Hemmerlin, Andréa

    2016-08-01

    Little is known about how plant cells regulate the exchange of prenyl diphosphates between the two compartmentalized isoprenoid biosynthesis pathways. Prenylation of proteins is a suitable model to study such interactions between the plastidial methylerythritol phosphate (MEP) and the cytosolic mevalonate (MVA) pathways because prenyl moieties used to modify proteins rely on both origins. Tobacco cells expressing a prenylatable GFP were treated with specific MEP and/or MVA pathways inhibitors to block the formation of prenyl diphosphates and therefore the possibility to modify the proteins. Chemical complementation assays using prenyl alcohol precursors restore the prenylation. Indeed, geranylgeraniol (C20 prenyl alcohol) and to a lesser but significant level C15-farnesol restored the prenylation of a protein bearing a geranylgeranylation CaaX motif, which under standard conditions is modified by a MEP-derived prenyl group. However, the restoration takes place in different ways. While geranylgeraniol operates directly as a metabolic precursor, the C15-prenyl alcohol functions indirectly as a signal that leads to shift the metabolic origin of prenyl groups in modified proteins, here from the plastidial MEP pathway in favor of the cytosolic MVA pathway. Furthermore, farnesol interferes negatively with the MEP pathway in an engineered Escherichia coli strain synthesizing isoprenoids either starting from MVA or from MEP. Following the cellular uptake of a fluorescent analog of farnesol, we showed its close interaction with tobacco plastids and modification of plastid homeostasis. As a consequence, in tobacco farnesol supposedly inhibits the plastidial MEP pathway and activates the cytosolic MVA pathway, leading to the shift in the metabolic origin and thereby acts as a potential regulator of crosstalk between the two pathways. Together, those results suggest a new role for farnesol (or a metabolite thereof) as a central molecule for the regulation of isoprenoid

  18. Simultaneous Determination of Underivatized Vitamin B1 and B6 in Whole Blood by Reversed Phase Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry.

    Directory of Open Access Journals (Sweden)

    Johan Puts

    Full Text Available Vitamin B1 (thiamine-diphosphate and B6 (pyridoxal-5'phosphate are micronutrients. Analysis of these micronutrients is important to diagnose potential deficiency which often occurs in elderly people due to malnutrition, in severe alcoholism and in gastrointestinal compromise due to bypass surgery or disease. Existing High Performance Liquid Chromatography (HPLC based methods include the need for derivatization and long analysis time. We developed an Ultra High Performance Liquid Chromatography Tandem Mass spectrometry (UHPLC-MS/MS assay with internal standards for simultaneous measurement of underivatized thiamine-diphosphate and pyridoxal-5'phosphate without use of ion pairing reagent.Whole blood, deproteinized with perchloric acid, containing deuterium labelled internal standards thiamine-diphosphate(thiazole-methyl-D3 and pyridoxal-5'phosphate(methyl-D3, was analyzed by UHPLC-MS/MS. The method was validated for imprecision, linearity, recovery and limit of quantification. Alternate (quantitative method comparisons of the new versus currently used routine HPLC methods were established with Deming regression.Thiamine-diphosphate and pyridoxal-5'phosphate were measured within 2.5 minutes instrumental run time. Limits of detection were 2.8 nmol/L and 7.8 nmol/L for thiamine-diphosphate and pyridoxal-5'phosphate respectively. Limit of quantification was 9.4 nmol/L for thiamine-diphosphate and 25.9 nmol/L for pyridoxal-5'phosphate. The total imprecision ranged from 3.5-7.7% for thiamine-diphosphate (44-157 nmol/L and 6.0-10.4% for pyridoxal-5'phosphate (30-130 nmol/L. Extraction recoveries were 101-102% ± 2.5% (thiamine-diphosphate and 98-100% ± 5% (pyridoxal-5'phosphate. Deming regression yielded slopes of 0.926 and 0.990 in patient samples (n = 282 and national proficiency testing samples (n = 12 respectively, intercepts of +3.5 and +3 for thiamine-diphosphate (n = 282 and n = 12 and slopes of 1.04 and 0.84, intercepts of -2.9 and +20 for

  19. Dosimetric impact of mixed-energy volumetric modulated arc therapy plans for high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Shyam Pokharel

    2013-10-01

    Full Text Available Purpose: This study investigated the dosimetric impact of mixing low and high energy treatment plans for prostate cancer treated with volumetric modulated arc therapy (VMAT technique in the form of RapidArc.Methods: A cohort of 12 prostate cases involving proximal seminal vesicles and lymph nodes was selected for this retrospective study. For each prostate case, the single-energy plans (SEPs and mixed-energy plans (MEPs were generated.  First, the SEPs were created using 6 mega-voltage (MV energy for both the primary and boost plans. Second, the MEPs were created using 16 MV energy for the primary plan and 6 MV energy for the boost plan. The primary and boost MEPs used identical beam parameters and same dose optimization values as in the primary and boost SEPs for the corresponding case. The dosimetric parameters from the composite plans (SEPs and MEPs were evaluated. Results: The dose to the target volume was slightly higher (on average <1% in the SEPs than in the MEPs. The conformity index (CI and homogeneity index (HI values between the SEPs and MEPs were comparable. The dose to rectum and bladder was always higher in the SEPs (average difference up to 3.7% for the rectum and up to 8.4% for the bladder than in the MEPs. The mean dose to femoral heads was higher by about 0.8% (on average in the MEPs than in the SEPs. The number of monitor units and integral dose were higher in the SEPs compared to the MEPs by average differences of 9.1% and 5.5%, respectively.Conclusion: The preliminary results from this study suggest that use of mixed-energy VMAT plan for high-risk prostate cancer could potentially reduce the integral dose and minimize the dose to rectum and bladder, but for the higher femoral head dose.-----------------------------------------------Cite this article as:Pokharel S. Dosimetric impact of mixed-energy volumetric modulated arc therapy plans for high-risk prostate cancer. Int J Cancer Ther Oncol 2013;1(1:01011.DOI: http

  20. Development of a brief multidisciplinary education programme for patients with osteoarthritis

    Directory of Open Access Journals (Sweden)

    Moe Rikke H

    2011-11-01

    Full Text Available Abstract Background Osteoarthritis (OA is a prevalent progressive musculoskeletal disorder, leading to pain and disability. Patient information and education are considered core elements in treatment guidelines for OA; however, there is to our knowledge no evidence-based recommendation on the best approach, content or length on educational programmes in OA. Objective: to develop a brief, patient oriented disease specific multidisciplinary education programme (MEP to enhance self-management in patients with OA. Method Twelve persons (80% female mean age 59 years diagnosed with hand, hip or knee OA participated in focus group interviews. In the first focus group, six participants were interviewed about their educational needs, attitudes and expectations for the MEP. The interviews were transcribed verbatim and thereafter condensed. Based on results from focus group interviews, current research evidence, clinical knowledge and patients' experience, a multidisciplinary OA team (dietist, nurse, occupational therapist, pharmacist, physical therapist and rheumatologist and a patient representative developed a pilot-MEP after having attended a work-shop in health pedagogics. Finally, the pilot-MEP was evaluated by a second focus group consisting of four members from the first focus group and six other experienced patients, before final adjustments were made. Results The focus group interviews revealed four important themes: what is OA, treatment options, barriers and coping strategies in performing daily activities, and how to live with osteoarthritis. Identified gaps between patient expectations and experience with the pilot-programme were discussed and adapted into a final MEP. The final MEP was developed as a 3.5 hour educational programme provided in groups of 6-9 patients. All members from the multidisciplinary team are involved in the education programme, including a facilitator who during the provision of the programme ensures that the individual

  1. Surface modification of Ni–Ti alloys for stent application after magnetoelectropolishing

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Puneet; Musaramthota, Vishal; Munroe, Norman [Department of Mechanical and Materials Engineering, Florida International University, Miami, FL 33174 (United States); Datye, Amit [Department of Materials Science and Engineering, The University of Tennessee, Knoxville, TN 37916 (United States); Dua, Rupak [Department of Biomedical Engineering, Florida International University, Miami, FL 33174 (United States); Haider, Waseem [Mechanical Engineering, University of Texas-Pan American, TX (United States); McGoron, Anthony [Department of Biomedical Engineering, Florida International University, Miami, FL 33174 (United States); Rokicki, Ryszard [Electrobright, Macungie, PA 18062 (United States)

    2015-05-01

    The constant demand for new implant materials and the multidisciplinary design approaches for stent applications have expanded vastly over the past decade. The biocompatibility of these implant materials is a function of their surface characteristics such as morphology, surface chemistry, roughness, surface charge and wettability. These surface characteristics can directly influence the material's corrosion resistance and biological processes such as endothelialization. Surface morphology affects the thermodynamic stability of passivating oxides, which renders corrosion resistance to passivating alloys. Magnetoelectropolishing (MEP) is known to alter the morphology and composition of surface films, which assist in improving corrosion resistance of Nitinol alloys. This work aims at analyzing the surface characteristics of MEP Nitinol alloys by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The wettability of the alloys was determined by contact angle measurements and the mechanical properties were assessed by Nanoindentation. Improved mechanical properties were observed with the addition of alloying elements. Cyclic potentiodynamic polarization tests were performed to determine the corrosion susceptibility. Further, the alloys were tested for their cytotoxicity and cellular growth with endothelial cells. Improved corrosion resistance and cellular viability were observed with MEP surface treated alloys. - Highlights: • Magnetoelectropolishing (MEP) reduces the surface asperities of Nitinol alloys and formed stable oxides on the surface. • Improved corrosion resistance and reduced Nickel ion leaching were observed for MEP surfaces. • Ni–Ti alloyed with Cr showed improved mechanical properties. • Enhanced endothelial cell proliferation on ternary Nitinol alloys.

  2. Eating tools in hand activate the brain systems for eating action: a transcranial magnetic stimulation study.

    Science.gov (United States)

    Yamaguchi, Kaori; Nakamura, Kimihiro; Oga, Tatsuhide; Nakajima, Yasoichi

    2014-07-01

    There is increasing neuroimaging evidence suggesting that visually presented tools automatically activate the human sensorimotor system coding learned motor actions relevant to the visual stimuli. Such crossmodal activation may reflect a general functional property of the human motor memory and thus can be operating in other, non-limb effector organs, such as the orofacial system involved in eating. In the present study, we predicted that somatosensory signals produced by eating tools in hand covertly activate the neuromuscular systems involved in eating action. In Experiments 1 and 2, we measured motor evoked response (MEP) of the masseter muscle in normal humans to examine the possible impact of tools in hand (chopsticks and scissors) on the neuromuscular systems during the observation of food stimuli. We found that eating tools (chopsticks) enhanced the masseter MEPs more greatly than other tools (scissors) during the visual recognition of food, although this covert change in motor excitability was not detectable at the behavioral level. In Experiment 3, we further observed that chopsticks overall increased MEPs more greatly than scissors and this tool-driven increase of MEPs was greater when participants viewed food stimuli than when they viewed non-food stimuli. A joint analysis of the three experiments confirmed a significant impact of eating tools on the masseter MEPs during food recognition. Taken together, these results suggest that eating tools in hand exert a category-specific impact on the neuromuscular system for eating.

  3. Highlights of Magnetoelectropolishing

    Science.gov (United States)

    Hryniewicz, Tadeusz; Rokosz, Krzysztof

    2014-05-01

    The research work has been concerned on the studies and development of electrochemical polishing in the magnetic field (MEP) in comparison with the standard electropolishing methods performed without stirring (EP) and the process with the forced electrolyte mixing (MIX). Advanced techniques were used in the studies, to measure the effects of the surface treatment. They are as follows: scanning electron microscopy (SEM/EDS), X-ray Photoelectron Spectroscopy (XPS), Secondary Ion Mass Spectroscopy (SIMS), surface roughness, and nanoindentation measurements. For the corrosion studies, the electrochemical methods were used, such as: open circuit potential OCP, potentiodynamic curves PC, and electrochemical impedance spectroscopy EIS measurements. The MEP process is advised mainly due to the opportunity to enrich the surface layer with the chromium compounds (austenitic stainless steels), or titanium compounds (CP Ti Grade 2, Nitinol). The surface layers of biomaterials after MEP process contain much lower amount of carcinogenic compounds, like chromium VI oxidation stage (Cr6+) (austenitic stainless steels) and nickel compounds (austenitic stainless steel & Nitinol) versus those ones obtained after EP & MIX treatments. It is interesting that apart from the significant modification of the surface layer obtained after MEP, also mechanical properties, such as nanohardness, modulus of elasticity, and mechanical resistance to bending and torsion, undergo considerable advantageous changes. All they make the MEP process very promising for application in many clean industries, such as medical equipment and devices, electronics, food industry, etc.

  4. Eating tools in hand activate the brain systems for eating action: a transcranial magnetic stimulation study.

    Science.gov (United States)

    Yamaguchi, Kaori; Nakamura, Kimihiro; Oga, Tatsuhide; Nakajima, Yasoichi

    2014-07-01

    There is increasing neuroimaging evidence suggesting that visually presented tools automatically activate the human sensorimotor system coding learned motor actions relevant to the visual stimuli. Such crossmodal activation may reflect a general functional property of the human motor memory and thus can be operating in other, non-limb effector organs, such as the orofacial system involved in eating. In the present study, we predicted that somatosensory signals produced by eating tools in hand covertly activate the neuromuscular systems involved in eating action. In Experiments 1 and 2, we measured motor evoked response (MEP) of the masseter muscle in normal humans to examine the possible impact of tools in hand (chopsticks and scissors) on the neuromuscular systems during the observation of food stimuli. We found that eating tools (chopsticks) enhanced the masseter MEPs more greatly than other tools (scissors) during the visual recognition of food, although this covert change in motor excitability was not detectable at the behavioral level. In Experiment 3, we further observed that chopsticks overall increased MEPs more greatly than scissors and this tool-driven increase of MEPs was greater when participants viewed food stimuli than when they viewed non-food stimuli. A joint analysis of the three experiments confirmed a significant impact of eating tools on the masseter MEPs during food recognition. Taken together, these results suggest that eating tools in hand exert a category-specific impact on the neuromuscular system for eating. PMID:24835403

  5. Maximal respiratory static pressures in patients with different stages of COPD severity

    Directory of Open Access Journals (Sweden)

    Ricci Alberto

    2008-01-01

    Full Text Available Abstract Background In this study, we analyzed maximal inspiratory pressure (MIP and maximal expiratory pressure (MEP values in a stable COPD population compared with normal subjects. We evaluated the possible correlation between functional maximal respiratory static pressures and functional and anthropometric parameters at different stages of COPD. Furthermore, we considered the possible correlation between airway obstruction and MIP and MEP values. Subject and methods 110 patients with stable COPD and 21 age-matched healthy subjects were enrolled in this study. Patients were subdivided according to GOLD guidelines: 31 mild, 39 moderate and 28 severe. Results Both MIP and MEP were lower in patients with severe airway impairment than in normal subjects. Moreover, we found a correlation between respiratory muscle function and some functional and anthropometric parameters: FEV1 (forced expiratory volume in one second, FVC (forced vital capacity, PEF (peak expiratory flow, TLC (total lung capacity and height. MIP and MEP values were lower in patients with severe impairment than in patients with a slight reduction of FEV1. Conclusion The measurement of MIP and MEP indicates the state of respiratory muscles, thus providing clinicians with a further and helpful tool in monitoring the evolution of COPD.

  6. Can the hydrophilicity of functional monomers affect chemical interaction?

    Science.gov (United States)

    Feitosa, V P; Ogliari, F A; Van Meerbeek, B; Watson, T F; Yoshihara, K; Ogliari, A O; Sinhoreti, M A; Correr, A B; Cama, G; Sauro, S

    2014-02-01

    The number of carbon atoms and/or ester/polyether groups in spacer chains may influence the interaction of functional monomers with calcium and dentin. The present study assessed the chemical interaction and bond strength of 5 standard-synthesized phosphoric-acid ester functional monomers with different spacer chain characteristics, by atomic absorption spectroscopy (AAS), ATR-FTIR, thin-film x-ray diffraction (TF-XRD), scanning electron microscopy (SEM), and microtensile bond strength (μTBS). The tested functional monomers were 2-MEP (two-carbon spacer chain), 10-MDP (10-carbon), 12-MDDP (12-carbon), MTEP (more hydrophilic polyether spacer chain), and CAP-P (intermediate hydrophilicity ester spacer). The intensity of monomer-calcium salt formation measured by AAS differed in the order of 12-MDDP=10-MDP>CAP-P>MTEP>2-MEP. FTIR and SEM analyses of monomer-treated dentin surfaces showed resistance to rinsing for all monomer-dentin bonds, except with 2-MEP. TF-XRD confirmed the weaker interaction of 2-MEP. Highest µTBS was observed for 12-MDDP and 10-MDP. A shorter spacer chain (2-MEP) of phosphate functional monomers induced formation of unstable monomer-calcium salts, and lower chemical interaction and dentin bond strength. The presence of ester or ether groups within longer spacer carbon chains (CAP-P and MTEP) may affect the hydrophilicity, μTBS, and also the formation of monomer-calcium salts. PMID:24284259

  7. Immediate increases in quadriceps corticomotor excitability during an electromyography biofeedback intervention.

    Science.gov (United States)

    Pietrosimone, Brian; McLeod, Michelle M; Florea, David; Gribble, Phillip A; Tevald, Michael A

    2015-04-01

    The purpose of the study was to determine the effects of EMG-BF on vastus lateralis corticomotor excitability, measured via motor evoked potential (MEP) amplitudes elicited using Transcranial Magnetic Stimulation (TMS) during a maximal voluntary isometric contraction (MVIC). We also determined the effect of EMG-BF on isometric knee extensor strength. Fifteen healthy participants volunteered for this crossover study with two sessions held one-week apart. Participants were randomly assigned to condition order, during which five intervention MVICs were performed with or without EMG-BF. MEP amplitudes were collected with TMS during five knee extension contractions (5% of MVIC) at baseline and again during intervention MVICs within each session. During the control condition, participants were instructed to perform the same number of MVICs without any EMG-BF. Percent change scores were used to calculate the change in peak-to-peak MEP amplitudes that occurred during EMG-BF and Control MVICs compared to the baseline MEPs. Peak knee extension torque was recorded during MVICs prior to TMS for each condition. EMG-BF produced significantly increased MEP change scores and significantly greater torque than the control condition. The results of the current study suggest that EMG-BF may be a viable clinical method for targeting corticomotor excitability.

  8. Verification and intercomparison of mesoscale ensemble prediction systems in the Beijing 2008 Olympics Research and Development Project

    Science.gov (United States)

    Kunii, Masaru; Saito, Kazuo; Seko, Hiromu; Hara, Masahiro; Hara, Tabito; Yamaguchi, Munehiko; Gong, Jiandong; Charron, Martin; Du, Jun; Wang, Yong; Chen, Dehui

    2011-05-01

    During the period around the Beijing 2008 Olympic Games, the Beijing 2008 Olympics Research and Development Project (B08RDP) was conducted as part of the World Weather Research Program short-range weather forecasting research project. Mesoscale ensemble prediction (MEP) experiments were carried out by six organizations in near-real time, in order to share their experiences in the development of MEP systems. The purpose of this study is to objectively verify these experiments and to clarify the problems associated with the current MEP systems through the same experiences. Verification was performed using the MEP outputs interpolated into a common verification domain with a horizontal resolution of 15 km. For all systems, the ensemble spreads grew as the forecast time increased, and the ensemble mean improved the forecast errors compared with individual control forecasts in the verification against the analysis fields. However, each system exhibited individual characteristics according to the MEP method. Some participants used physical perturbation methods. The significance of these methods was confirmed by the verification. However, the mean error (ME) of the ensemble forecast in some systems was worse than that of the individual control forecast. This result suggests that it is necessary to pay careful attention to physical perturbations.

  9. Analogous corticocortical inhibition and facilitation in ipsilateral and contralateral human motor cortex representations of the tongue.

    Science.gov (United States)

    Muellbacher, W; Boroojerdi, B; Ziemann, U; Hallett, M

    2001-11-01

    How the human brain controls activation of the ipsilateral part of midline muscles is unknown. We studied corticospinal and corticocortical network excitability of both ipsilateral and contralateral motor representations of the tongue to determine whether they are under analogous or disparate inhibitory and facilitatory corticocortical control. Motor evoked potentials (MEPs) to unilateral focal transcranial magnetic stimulation (TMS) of the tongue primary motor cortex were recorded simultaneously from the ipsilateral and contralateral lingual muscles. Single-pulse TMS was used to assess motor threshold (MT) and MEP recruitment. Paired-pulse TMS was used to study intracortical inhibition (ICI) and intracortical facilitation (ICF) at various interstimulus intervals (ISIs) between the conditioning stimulus (CS) and the test stimulus (TS), and at different CS and TS intensities, respectively. Focal TMS invariably produced MEPs in both ipsilateral and contralateral lingual muscles. MT was lower and MEP recruitment was steeper when recorded from the contralateral muscle group. ICI and ICF were identical in the ipsilateral and contralateral representations, with inhibition occurring at short ISIs (2 and 3 ms) and facilitation occurring at longer ISIs (10 and 15 ms). Moreover, changing one stimulus parameter regularly produced analogous changes in MEP size bilaterally, revealing strong linear correlations between ipsilateral and contralateral ICI and ICF (P < 0.0001). These findings indicate that the ipsilateral and contralateral representations of the tongue are under analogous inhibitory and facilitatory control, possibly by a common intracortical network. PMID:11779968

  10. HIGHLIGHTS OF MAGNETOELECTROPOLISHING

    Directory of Open Access Journals (Sweden)

    Tadeusz eHryniewicz

    2014-05-01

    Full Text Available The research work has been concerned on the studies and development of electrochemical polishing in the magnetic field (MEP in comparison with the standard electropolishing methods performed without stirring (EP and the process with the forced electrolyte mixing (MIX. Advanced techniques were used in the studies, to measure the effects of the surface treatment. They are as follows: scanning electron microscopy (SEM/EDS, X-ray Photoelectron Spectroscopy (XPS, Secondary Ion Mass Spectroscopy (SIMS, surface roughness, and nanoindentation measurements. For the corrosion studies, the electrochemical methods were used, such as: open circuit potential OCP, potentiodynamic curves PC, and electrochemical impedance spectroscopy EIS measurements. The MEP process is advised mainly due to the opportunity to enrich the surface layer with the chromium compounds (austenitic stainless steels, or titanium compounds (CP Ti Grade 2, Nitinol. The surface layers of biomaterials after MEP process contain much lower amount of carcinogenic compounds, like chromium VI oxidation stage (Cr6+ (austenitic stainless steels and nickel compounds (austenitic stainless steel & Nitinol versus those ones obtained after EP & MIX treatments. It is interesting that apart from the significant modification of the surface layer obtained after MEP, also mechanical properties, such as nanohardness, modulus of elasticity, and mechanical resistance to bending and torsion, undergo considerable advantageous changes. All they make the MEP process very promising for application in many clean industries, such as medical equipment and devices, electronics, food industry, etc.

  11. Different Stimulation Frequencies Alter Synchronous Fluctuations in Motor Evoked Potential Amplitude of Intrinsic Hand Muscles-a TMS Study.

    Science.gov (United States)

    Sale, Martin V; Rogasch, Nigel C; Nordstrom, Michael A

    2016-01-01

    The amplitude of motor-evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) varies from trial-to-trial. Synchronous oscillations in cortical neuronal excitability contribute to this variability, however it is not known how different frequencies of stimulation influence MEP variability, and whether these oscillations are rhythmic or aperiodic. We stimulated the motor cortex with TMS at different regular (i.e., rhythmic) rates, and compared this with pseudo-random (aperiodic) timing. In 18 subjects, TMS was applied at three regular frequencies (0.05 Hz, 0.2 Hz, 1 Hz) and one aperiodic frequency (mean 0.2 Hz). MEPs (n = 50) were recorded from three intrinsic hand muscles of the left hand with different functional and anatomical relations. MEP amplitude correlation was highest for the functionally related muscle pair, less for the anatomically related muscle pair and least for the functionally- and anatomically-unrelated muscle pair. MEP correlations were greatest with 1 Hz, and least for stimulation at 0.05 Hz. Corticospinal neuron synchrony is higher with shorter TMS intervals. Further, corticospinal neuron synchrony is similar irrespective of whether the stimulation is periodic or aperiodic. These findings suggest TMS frequency is a crucial consideration for studies using TMS to probe correlated activity between muscle pairs.

  12. Design,Synthesis and Biological Activity of Ethyl 2-(N-Substituted-arylsulfonamido)-2-oxoacetate

    Institute of Scientific and Technical Information of China (English)

    WANG Bao-lei; WU Jing; HE Feng-qi; LI Yon-ghong; LI Zheng-ming

    2008-01-01

    Thirteen new ethyl 2-(N-substituted-arylsulfonamido)-2-oxoacetates(3a-3m),based on the structure of Ketol-acid reductoisomerase(KARI) inhibitor IpOHA,were designed and synthesized,Their structures were established on the basis of 1H NMR,IR,MS,and elemental analyses,The bioassay result reveals that the structural changes from hydroxyl group on the N atom of IpOHA to arylsulfonyl groups does not enhance the inhibitory activity of the compounds to KARI in vitro,Compounds 3c,3h,3k,and 3m are more effective than IpOHA against the monocotyledonous barnygrass at 100 μg/mL in herbicidal tests.

  13. Urinary excretion of phthalates and paraben after repeated whole-body topical application in humans

    DEFF Research Database (Denmark)

    Janjua, Nadeem Rezaq; Frederiksen, Hanne; Skakkebaek, Niels E;

    2008-01-01

    were given a whole body topical application of basic cream 2 mg/cm(2) (control week) and then a cream containing 2% (w/w) of DEP, DBP and BP each (treatment week) daily. Twenty-four-hour urine samples were collected. Urinary total, and unconjugated BP, monoethyl phthalate (MEP) and monobutyl phthalate...... (MBP) metabolites were analysed by Liquid Chromatography-Tandem Mass Spectroscopy (LC-MS/MS). All 26 subjects showed increased excretion of MEP, MBP and BP following topical application. Total MEP, MBP and BP (mean +/- SEM) excreted in urine in the treatment week were, respectively, 41 +/- 1.9, 11...... through dermal absorption, but there are no published data on absorption, metabolism, and excretion after dermal application. This study investigates urinary concentrations of BP and metabolites of DEP and DBP after topical application. In a 2-week single-blinded study, 26 healthy Caucasian male subjects...

  14. Phase-dependent modulation of corticospinal excitability during the observation of the initial phase of gait.

    Science.gov (United States)

    Takahashi, Makoto; Uchida, Natsuko; Yoshida, Mami; Liang, Nan; Nakazawa, Kimitaka; Sekikawa, Kiyokazu; Inamizu, Tsutomu; Hamada, Hironobu

    2014-12-01

    This study was undertaken to identify the temporal characteristics of corticospinal excitability of tibialis anterior muscle during the observation of the initial phase of gait. For this purpose, using transcranial magnetic stimulation, we recorded motor evoked potentials (MEPs) during the observation of the second step of an actor's first three steps of gait initiation with (complex gait) or without (normal gait) an obstacle and unstable surface. The results demonstrate that (1) MEPs during the observation of the initial phase of normal gait were significantly increased only at early swing phase, but not other phases (mid-swing, heel contact, mid-stance, and heel off) and (2) MEPs during the observation of the initial phase of complex gait were significantly increased at early swing and also at mid-swing and heel contact phases. These findings provide the first evidence that corticospinal excitability during the observation of gait, especially the initial phase, is modulated in phase- and motor-demanded-dependent manners.

  15. Methanolic extract of Pterocarpus santalinus induces apoptosis in HeLa cells.

    Science.gov (United States)

    Kwon, H J; Hong, Y K; Kim, K H; Han, C H; Cho, S H; Choi, J S; Kim, Byung-Woo

    2006-04-21

    Ptercarpus santalinus (Fabaceae) has been used as a folk remedy in Korea, and it has been shown to exhibit antiinflammations, antiulcers and anticancer effects. In this study, therefore, we report the cytotoxic activity and the mechanism of cell death exhibited by the methanol extract of Ptercarpus santalinus (MEPS) against human cervical adenocarcinoma cell line, HeLa. Treatment of HeLa cells with various concentrations of MEPS resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as determined by cell viability, chromatin condensation, DNA fragmentation and sub-G1 phase accumulation. In Western blot analysis, apoptosis in the HeLa cells was associated with the release of cytochrome C from mitochondria into the cytosol, activation of caspases-3, -8, -9 and proteolytic cleavage of PARP. These results suggest that MEPS exhibits antiproliferative effect on HeLa cells via apoptosis, and it may be a potential candidate in field of anticancer drug discovery. PMID:16326057

  16. Desarrollo profesional del docente de inglés en el área de evaluación de los aprendizajes

    OpenAIRE

    Calderón Mora, Roxy; Mora Ordoñez, Yinnia

    2015-01-01

    El presente artículo es el resultado de una investigación sobre capacitación docente en evaluación de los aprendizajes que se desarrolla bajo el Convenio Marco de Cooperación MEP-CONARE-INGLÉS en el período 2010-2011. La actividad de capacitación la diseña y ejecuta una comisión integrada por profesionales de las cuatro universidades y el MEP con el fin de fortalecer prácticas de mediación pedagógica y evaluación de los aprendizajes en la enseñanza del inglés con fondos aportados por el MEP. ...

  17. Removing External Degrees of Freedom from Transition-State Search Methods using Quaternions

    CERN Document Server

    Melander, Marko; Jonsson, Hannes

    2015-01-01

    In finite systems, such as nanoparticles and gas-phase molecules, calculations of minimum energy paths (MEPs) connecting initial and final states of transitions as well as searches for saddle points are complicated by the presence of external degrees of freedom, such as overall translation and rotation. A method based on quaternion algebra for removing the external degrees of freedom is described here and applied in calculations using two commonly used methods: the nudged elastic band (NEB) method for MEPs and the DIMER method for finding the minimum mode in minimum mode following searches of first-order saddle points. With the quaternion approach, fewer images in the NEB are needed to represent MEPs accurately. In both NEB and DIMER calculations of finite systems, the number of iterations required to reach convergence is significantly reduced. The algorithms have been implemented in the Atomic Simulation Environment (ASE) open source software.

  18. Removing External Degrees of Freedom from Transition-State Search Methods using Quaternions.

    Science.gov (United States)

    Melander, Marko; Laasonen, Kari; Jónsson, Hannes

    2015-03-10

    In finite systems, such as nanoparticles and gas-phase molecules, calculations of minimum energy paths (MEPs) connecting initial and final states of transitions as well as searches for saddle points are complicated by the presence of external degrees of freedom, such as overall translation and rotation. A method based on quaternion algebra for removing the external degrees of freedom is described here and applied in calculations using two commonly used methods: the nudged elastic band (NEB) method for MEPs and the DIMER method for finding the minimum mode in minimum mode following searches of first-order saddle points. With the quaternion approach, fewer images in the NEB are needed to represent MEPs accurately. In both NEB and DIMER calculations of finite systems, the number of iterations required to reach convergence is significantly reduced. The algorithms have been implemented in the Atomic Simulation Environment (ASE) open source software. PMID:26579757

  19. A chain-of-states acceleration method for the efficient location of minimum energy paths

    International Nuclear Information System (INIS)

    We describe a robust and efficient chain-of-states method for computing Minimum Energy Paths (MEPs) associated to barrier-crossing events in poly-atomic systems, which we call the acceleration method. The path is parametrized in terms of a continuous variable t ∈ [0, 1] that plays the role of time. In contrast to previous chain-of-states algorithms such as the nudged elastic band or string methods, where the positions of the states in the chain are taken as variational parameters in the search for the MEP, our strategy is to formulate the problem in terms of the second derivatives of the coordinates with respect to t, i.e., the state accelerations. We show this to result in a very simple and efficient method for determining the MEP. We describe the application of the method to a series of test cases, including two low-dimensional problems and the Stone-Wales transformation in C60

  20. A simple Chain-of-States method in acceleration space for the efficient location of Minimum Energy Paths

    CERN Document Server

    Hernandez, E R; Soler, J M

    2015-01-01

    We describe a robust and efficient chain-of-states method for computing Minimum Energy Paths~(MEPs) associated to barrier-crossing events in poly-atomic systems. The path is parametrized in terms of a continuous variable $t \\in [0,1]$ that plays the role of time. In contrast to previous chain-of-states algorithms such as the Nudged Elastic Band or String methods, where the positions of the states in the chain are taken as variational parameters in the search for the MEP, our strategy is to formulate the problem in terms of the second derivatives of the coordinates with respect to $t$, {\\em i.e.\\/} the state {\\em accelerations\\/}. We show this to result in a very transparent and efficient method for determining the MEP. We describe the application of the method in a series of test cases, including two low-dimensional problems and the Stone-Wales transformation in $\\mbox{C}_{60}$.

  1. How multiplicity determines entropy and the derivation of the maximum entropy principle for complex systems

    CERN Document Server

    Hanel, Rudolf; Gell-Mann, Murray

    2014-01-01

    The maximum entropy principle (MEP) is a method for obtaining the most likely distribution functions of observables from statistical systems, by maximizing entropy under constraints. The MEP has found hundreds of applications in ergodic and Markovian systems in statistical mechanics, information theory, and statistics. For several decades there exists an ongoing controversy whether the notion of the maximum entropy principle can be extended in a meaningful way to non-extensive, non-ergodic, and complex statistical systems and processes. In this paper we start by reviewing how Boltzmann-Gibbs-Shannon entropy is related to multiplicities of independent random processes. We then show how the relaxation of independence naturally leads to the most general entropies that are compatible with the first three Shannon-Khinchin axioms, the (c,d)-entropies. We demonstrate that the MEP is a perfectly consistent concept for non-ergodic and complex statistical systems if their relative entropy can be factored into a general...

  2. Comparison of clinical, magnetic resonance and evoked potentials data in a case of valproic-acid-related hyperammonemic coma

    Energy Technology Data Exchange (ETDEWEB)

    Hantson, Philippe [Universite Catholique de Louvain, Department of Intensive Care, Cliniques Saint-Luc, Brussels (Belgium); Grandin, Cecile; Duprez, Thierry [Universite Catholique de Louvain, Department of Neuroradiology, Cliniques Saint-Luc, Brussels (Belgium); Nassogne, Marie-Cecile [Universite Catholique de Louvain, Department of Pediatric Neurology, Cliniques Saint-Luc, Brussels (Belgium); Guerit, Jean-Michel [Universite Catholique de Louvain, Laboratory of Neurophysiology, Cliniques Saint-Luc, Brussels (Belgium)

    2005-01-01

    Magnetic resonance (MR) multimodality evoked potentials (MEPs) and clinical findings were correlated in a 47-year-old epileptic man in whom parenteral valproic acid (VPA) therapy induced severe comatose hyperammonemic encephalopathy without biological signs of hepatotoxicity (or hepatocytic dysfunction). Although the plasma VPA level remained within a normal therapeutic range, the ammoniemia increased to a toxic peak level at 411 {mu}mol/l 24 h after symptom onset, requiring VPA therapy discontinuation. Brain MR monitoring demonstrated early cytotoxic edema evolving into delayed vasogenic edema and final brain atrophy. Concomitantly to abnormalities within the brainstem on MR images, an increase in brainstem conduction at MEPs and clinical disturbance of brainstem reflexes were observed at the initial phase of the disease course. Later, the resolution of the MR and MEPs abnormalities paralleled the clinical recovery of the reflexes. (orig.)

  3. Development of a NASA 2018 Mars Landed Mission Concept

    Science.gov (United States)

    Wilson, M. G.; Salvo, C. G.; Abilleira, F.; Sengstacken, A. J.; Allwood, A. G.; Backes, P. G.; Lindemann, R. A.; Jordan, J. F.

    2010-01-01

    Fundamental to NASA's Mars Exploration Program (MEP) is an ongoing development of an integrated and coordinated set of possible future candidate missions that meet fundamental science and programmatic objectives of NASA and the Mars scientific community. In the current planning horizon of the NASA MEP, a landed mobile surface exploration mission launching in the 2018 Mars launch opportunity exists as a candidate project to meet MEP in situ science and exploration objectives. This paper describes the proposed mission science objectives and the mission implementation concept developed for the 2018 opportunity. As currently envisioned, this mission concept seeks to explore a yet-to-be-selected site with high preservation potential for physical and chemical biosignatures, evaluate paleoenvironmental conditions, characterize the potential for preservation of biosignatures, and access multiple sequences of geological units in a search for evidence of past life and/or prebiotic chemistry at a site on Mars.

  4. The Thermodynamics of Marine Biogeochemical Cycles: Lotka Revisited

    Science.gov (United States)

    Vallino, Joseph J.; Algar, Christopher K.

    2016-01-01

    Nearly 100 years ago, Alfred Lotka published two short but insightful papers describing how ecosystems may organize. Principally, Lotka argued that ecosystems will grow in size and that their cycles will spin faster via predation and nutrient recycling so as to capture all available energy, and that evolution and natural selection are the mechanisms by which this occurs and progresses. Lotka's ideas have often been associated with the maximum power principle, but they are more consistent with recent developments in nonequilibrium thermodynamics, which assert that complex systems will organize toward maximum entropy production (MEP). In this review, we explore Lotka's hypothesis within the context of the MEP principle, as well as how this principle can be used to improve marine biogeochemistry models. We need to develop the equivalent of a climate model, as opposed to a weather model, to understand marine biogeochemistry on longer timescales, and adoption of the MEP principle can help create such models.

  5. Chaotic motif sampler: detecting motifs from biological sequences by using chaotic neurodynamics

    Science.gov (United States)

    Matsuura, Takafumi; Ikeguchi, Tohru

    Identification of a region in biological sequences, motif extraction problem (MEP) is solved in bioinformatics. However, the MEP is an NP-hard problem. Therefore, it is almost impossible to obtain an optimal solution within a reasonable time frame. To find near optimal solutions for NP-hard combinatorial optimization problems such as traveling salesman problems, quadratic assignment problems, and vehicle routing problems, chaotic search, which is one of the deterministic approaches, has been proposed and exhibits better performance than stochastic approaches. In this paper, we propose a new alignment method that employs chaotic dynamics to solve the MEPs. It is called the Chaotic Motif Sampler. We show that the performance of the Chaotic Motif Sampler is considerably better than that of the conventional methods such as the Gibbs Site Sampler and the Neighborhood Optimization for Multiple Alignment Discovery.

  6. The Thermodynamics of Marine Biogeochemical Cycles: Lotka Revisited.

    Science.gov (United States)

    Vallino, Joseph J; Algar, Christopher K

    2016-01-01

    Nearly 100 years ago, Alfred Lotka published two short but insightful papers describing how ecosystems may organize. Principally, Lotka argued that ecosystems will grow in size and that their cycles will spin faster via predation and nutrient recycling so as to capture all available energy, and that evolution and natural selection are the mechanisms by which this occurs and progresses. Lotka's ideas have often been associated with the maximum power principle, but they are more consistent with recent developments in nonequilibrium thermodynamics, which assert that complex systems will organize toward maximum entropy production (MEP). In this review, we explore Lotka's hypothesis within the context of the MEP principle, as well as how this principle can be used to improve marine biogeochemistry models. We need to develop the equivalent of a climate model, as opposed to a weather model, to understand marine biogeochemistry on longer timescales, and adoption of the MEP principle can help create such models.

  7. Modulation of sensory inhibition of motor evoked potentials elicited by TMS prior to movement?

    DEFF Research Database (Denmark)

    Leukel, Christian; Lundbye-Jensen, Jesper; Nielsen, Jens Bo;

    Short latency afferent inhibition (SAI) refers to a decrement of the size of a motor evoked potential (MEP) by transcranial magnetic stimulation (TMS) after electrical stimulation of a peripheral afferent nerve (PNS) (Tokimura et al. 2000). Since SAI occurs when TMS is applied at the time...... to rest. In 9 healthy subjects (23 ± 3 years) MEPs were recorded in m. first dorsal interosseus (FDI) and m. abductor pollicis brevis (APB). To induce SAI, n. medianus was stimulated 20 ms prior to TMS over the motorcortex. In control trials, interstimulus intervals (ISIs) between afferent stimulation...... and TMS of 15, 25, 30, 35, and 40 ms were additionally tested. When moving, subjects were told to react to the afferent stimulus, and the delay between TMS and EMG onset was 343 ± 160 ms. When tested prior to movement, MEPs elicited with a delay of 20 ms after PNS were significantly greater (23 ± 9...

  8. Maggot excretion products from the blowfly Lucilia sericata contain contact phase/intrinsic pathway-like proteases with procoagulant functions.

    Science.gov (United States)

    Kahl, M; Gökçen, A; Fischer, S; Bäumer, M; Wiesner, J; Lochnit, G; Wygrecka, M; Vilcinskas, A; Preissner, K T

    2015-08-01

    For centuries, maggots have been used for the treatment of wounds by a variety of ancient cultures, as part of their traditional medicine. With increasing appearance of antimicrobial resistance and in association with diabetic ulcers, maggot therapy was revisited in the 1980s. Three mechanisms by which sterile maggots of the green bottle fly Lucilia sericata may improve healing of chronic wounds have been proposed: Biosurgical debridement, disinfecting properties, and stimulation of the wound healing process. However, the influence of maggot excretion products (MEP) on blood coagulation as part of the wound healing process has not been studied in detail. Here, we demonstrate that specific MEP-derived serine proteases from Lucilia sericata induce clotting of human plasma and whole blood, particularly by activating contact phase proteins factor XII and kininogen as well as factor IX, thereby providing kallikrein-bypassing and factor XIa-like activities, both in plasma and in isolated systems. In plasma samples deficient in contact phase proteins, MEP restored full clotting activity, whereas in plasma deficient in either factor VII, IX, X or II no effect was seen. The observed procoagulant/intrinsic pathway-like activity was mediated by (chymo-) trypsin-like proteases in total MEP, which were significantly blocked by C1-esterase inhibitor or other contact phase-specific protease inhibitors. No significant influence of MEP on platelet activation or fibrinolysis was noted. Together, MEP provides contact phase bypassing procoagulant activity and thereby induces blood clotting in the context of wound healing. Further characterisation of the active serine protease(s) may offer new perspectives for biosurgical treatment of chronic wounds. PMID:25948398

  9. Optimization of the IPP precursor supply for the production of lycopene, decaprenoxanthin and astaxanthin by Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Sabine A.E. Heider

    2014-08-01

    Full Text Available The biotechnologically relevant bacterium C. glutamicum, currently used for the million ton-scale production of amino acids for the food and feed industries, is pigmented due to synthesis of the rare cyclic C50 carotenoid decaprenoxanthin and its glucosides. The precursors of carotenoid biosynthesis, isopenthenyl pyrophosphate (IPP and its isomer dimethylallyl pyrophosphate (DMAPP, are synthesized in this organism via the methylerythritol phosphate (MEP or non-mevalonate pathway. Terminal pathway engineering in recombinant C. glutamicum permitted the production of various nonnative C50 and C40 carotenoids. Here, the role of engineering isoprenoid precursor supply for lycopene production by C. glutamicum was characterized. Overexpression of dxs encoding the enzyme that catalyzes the first committed step of the MEP-pathway by chromosomal promoter exchange in a prophage-cured, genome-reduced C. glutamicum strain improved lycopene formation. Similarly, an increased IPP supply was achieved by chromosomal integration of two artificial operons comprising MEP pathway genes under the control of a constitutive promoter. Combined overexpression of dxs and the other six MEP pathways genes in C. glutamicum strain LYC3-MEP was not synergistic with respect to improving lycopene accumulation. Based on C. glutamicum strain LYC3-MEP astaxanthin could be produced in the mg per g cell dry weight range when the endogenous genes crtE, crtB and crtI for conversion of geranylgeranyl pyrophosphate to lycopene were coexpressed with the genes for lycopene cyclase and β-carotene hydroxylase from Pantoea ananatis and carotene C(4 oxygenase from Brevundimonas aurantiaca.

  10. Abnormal motor cortex excitability during linguistic tasks in adductor-type spasmodic dysphonia.

    Science.gov (United States)

    Suppa, A; Marsili, L; Giovannelli, F; Di Stasio, F; Rocchi, L; Upadhyay, N; Ruoppolo, G; Cincotta, M; Berardelli, A

    2015-08-01

    In healthy subjects (HS), transcranial magnetic stimulation (TMS) applied during 'linguistic' tasks discloses excitability changes in the dominant hemisphere primary motor cortex (M1). We investigated 'linguistic' task-related cortical excitability modulation in patients with adductor-type spasmodic dysphonia (ASD), a speech-related focal dystonia. We studied 10 ASD patients and 10 HS. Speech examination included voice cepstral analysis. We investigated the dominant/non-dominant M1 excitability at baseline, during 'linguistic' (reading aloud/silent reading/producing simple phonation) and 'non-linguistic' tasks (looking at non-letter strings/producing oral movements). Motor evoked potentials (MEPs) were recorded from the contralateral hand muscles. We measured the cortical silent period (CSP) length and tested MEPs in HS and patients performing the 'linguistic' tasks with different voice intensities. We also examined MEPs in HS and ASD during hand-related 'action-verb' observation. Patients were studied under and not-under botulinum neurotoxin-type A (BoNT-A). In HS, TMS over the dominant M1 elicited larger MEPs during 'reading aloud' than during the other 'linguistic'/'non-linguistic' tasks. Conversely, in ASD, TMS over the dominant M1 elicited increased-amplitude MEPs during 'reading aloud' and 'syllabic phonation' tasks. CSP length was shorter in ASD than in HS and remained unchanged in both groups performing 'linguistic'/'non-linguistic' tasks. In HS and ASD, 'linguistic' task-related excitability changes were present regardless of the different voice intensities. During hand-related 'action-verb' observation, MEPs decreased in HS, whereas in ASD they increased. In ASD, BoNT-A improved speech, as demonstrated by cepstral analysis and restored the TMS abnormalities. ASD reflects dominant hemisphere excitability changes related to 'linguistic' tasks; BoNT-A returns these excitability changes to normal.

  11. Aberrant crossed corticospinal facilitation in muscles distant from a spinal cord injury.

    Directory of Open Access Journals (Sweden)

    Karen L Bunday

    Full Text Available Crossed facilitatory interactions in the corticospinal pathway are impaired in humans with chronic incomplete spinal cord injury (SCI. The extent to which crossed facilitation is affected in muscles above and below the injury remains unknown. To address this question we tested 51 patients with neurological injuries between C2-T12 and 17 age-matched healthy controls. Using transcranial magnetic stimulation we elicited motor evoked potentials (MEPs in the resting first dorsal interosseous, biceps brachii, and tibialis anterior muscles when the contralateral side remained at rest or performed 70% of maximal voluntary contraction (MVC into index finger abduction, elbow flexion, and ankle dorsiflexion, respectively. By testing MEPs in muscles with motoneurons located at different spinal cord segments we were able to relate the neurological level of injury to be above, at, or below the location of the motoneurons of the muscle tested. We demonstrate that in patients the size of MEPs was increased to a similar extent as in controls in muscles above the injury during 70% of MVC compared to rest. MEPs remained unchanged in muscles at and within 5 segments below the injury during 70% of MVC compared to rest. However, in muscles beyond 5 segments below the injury the size of MEPs increased similar to controls and was aberrantly high, 2-fold above controls, in muscles distant (>15 segments from the injury. These aberrantly large MEPs were accompanied by larger F-wave amplitudes compared to controls. Thus, our findings support the view that corticospinal degeneration does not spread rostral to the lesion, and highlights the potential of caudal regions distant from an injury to facilitate residual corticospinal output after SCI.

  12. Brain-robot interface driven plasticity: Distributed modulation of corticospinal excitability.

    Science.gov (United States)

    Kraus, Dominic; Naros, Georgios; Bauer, Robert; Leão, Maria Teresa; Ziemann, Ulf; Gharabaghi, Alireza

    2016-01-15

    Brain-robot interfaces (BRI) are studied as novel interventions to facilitate functional restoration in patients with severe and persistent motor deficits following stroke. They bridge the impaired connection in the sensorimotor loop by providing brain-state dependent proprioceptive feedback with orthotic devices attached to the hand or arm of the patients. The underlying neurophysiology of this BRI neuromodulation is still largely unknown. We investigated changes of corticospinal excitability with transcranial magnetic stimulation in thirteen right-handed healthy subjects who performed 40min of kinesthetic motor imagery receiving proprioceptive feedback with a robotic orthosis attached to the left hand contingent to event-related desynchronization of the right sensorimotor cortex in the β-band (16-22Hz). Neural correlates of this BRI intervention were probed by acquiring the stimulus-response curve (SRC) of both motor evoked potential (MEP) peak-to-peak amplitudes and areas under the curve. In addition, a motor mapping was obtained. The specificity of the effects was studied by comparing two neighboring hand muscles, one BRI-trained and one control muscle. Robust changes of MEP amplitude but not MEP area occurred following the BRI intervention, but only in the BRI-trained muscle. The steep part of the SRC showed an MEP increase, while the plateau of the SRC showed an MEP decrease. MEP mapping revealed a distributed pattern with a decrease of excitability in the hand area of the primary motor cortex, which controlled the BRI, but an increase of excitability in the surrounding somatosensory and premotor cortex. In conclusion, the BRI intervention induced a complex pattern of modulated corticospinal excitability, which may boost subsequent motor learning during physiotherapy. PMID:26505298

  13. Baroreceptor reflex during forced expiratory maneuvers in individuals with chronic spinal cord injury.

    Science.gov (United States)

    Legg Ditterline, Bonnie E; Aslan, Sevda C; Randall, David C; Harkema, Susan J; Ovechkin, Alexander V

    2016-07-15

    Pulmonary and cardiovascular dysfunctions are leading causes of morbidity and mortality in patients with chronic Spinal Cord Injury (SCI). Impaired respiratory motor function and decreased Baroreflex Sensitivity (BS) are predictors for the development of cardiopulmonary disease. This observational case-controlled clinical study was undertaken to investigate if respiratory motor control deficits in individuals with SCI affect their ability to perform the Valsalva maneuver, and to determine if a sustained Maximum Expiratory Pressure (MEP) effort can serve as an acceptable maneuver for determination of the BS in the event that the Valsalva maneuver cannot be performed. The BS outcomes (ms/mmHg) were obtained using continuous beat-to-beat arterial blood pressure (BP) and heart rate (HR) recordings during Valsalva or MEP maneuvers in thirty nine individuals with chronic C3-T12 SCI. Twenty one participants (54%) reported signs of intolerance during the Valsalva maneuver and only 15 individuals (39%) were able to complete this task. Cervical level of injury was a significant risk factor (p=0.001) for failing to complete the Valsalva maneuver, and motor-complete injury was a significant risk factor for symptoms of intolerance (p=0.04). Twenty eight participants (72%) were able to perform the MEP maneuver; the other 11 participants failed to exceed the standard airway pressure threshold of 27cm H2O. Neither level nor completeness of injury were significant risk factors for failure of MEP maneuver. When the required airway pressure was sustained, there were no significant differences between BS outcomes obtained during Valsalva and MEP maneuvers. The results of this study indicate that individuals with high-level and motor-complete SCI are at increased risk of not completing the Valsalva maneuver and that baroreflex-mediated responses can be evaluated by using sustained MEP maneuver when the Valsalva maneuver cannot be performed. PMID:27137412

  14. Normal Values of the Maximal Respiratory Pressures in Healthy People Older than 20 Years Old in the City of Manizales – Colombia

    Directory of Open Access Journals (Sweden)

    Lida Maritza Gil Obando

    2012-06-01

    Full Text Available The Maximal Inspiratory Pressure (MIP and Maximal Expiratory Pressure (MEP are global measures of the maximal strength of the respiratory muscles. Objectives :To determine the values of MIP and MEP in healthy subjects aged 20 years old from the urban area of Maniza­les, Colombia and to correlate them with sociodemographic and anthropometric variables. Methods: This is an observational descriptive study. The population of the study was 203.965 healthy people from Ma­nizales, a Colombian city located at 2150 meters above sea level. The sample size was 308 subjects, selected using simple random sampling. The maximal respiratory pressures were determined in the sample chosen and were then considered according to the variables of age, gender, size, weight, Body Mass Index (BMI, and BMI classification. Finally a predictive model was created. Results: The average MIP value among the subjects of the study was 75±27cmH20 and the MEP value was 96.4±36cmH20. Both averages were higher in men than in women. Predictive equations were established for the normal values of MIP and MEP in healthy subjects; the best model for MIP was the resultant one among age, gender and BMI classification and for the MEP among gender, weight and height. Conclusion: Maximal respiratory pressure values were lower among the population of Manizales than those found in in­ternational studies. Gender and anthropometric characteristics (weight, height and BMI classification are the explanatory variables that better support the average values of MIP and MEP in the predictive models proposed. 14.00 800x600 Normal 0 21 false false false ES-CO X-NONE X-NONE MicrosoftInternetExplorer4

  15. Brain-robot interface driven plasticity: Distributed modulation of corticospinal excitability.

    Science.gov (United States)

    Kraus, Dominic; Naros, Georgios; Bauer, Robert; Leão, Maria Teresa; Ziemann, Ulf; Gharabaghi, Alireza

    2016-01-15

    Brain-robot interfaces (BRI) are studied as novel interventions to facilitate functional restoration in patients with severe and persistent motor deficits following stroke. They bridge the impaired connection in the sensorimotor loop by providing brain-state dependent proprioceptive feedback with orthotic devices attached to the hand or arm of the patients. The underlying neurophysiology of this BRI neuromodulation is still largely unknown. We investigated changes of corticospinal excitability with transcranial magnetic stimulation in thirteen right-handed healthy subjects who performed 40min of kinesthetic motor imagery receiving proprioceptive feedback with a robotic orthosis attached to the left hand contingent to event-related desynchronization of the right sensorimotor cortex in the β-band (16-22Hz). Neural correlates of this BRI intervention were probed by acquiring the stimulus-response curve (SRC) of both motor evoked potential (MEP) peak-to-peak amplitudes and areas under the curve. In addition, a motor mapping was obtained. The specificity of the effects was studied by comparing two neighboring hand muscles, one BRI-trained and one control muscle. Robust changes of MEP amplitude but not MEP area occurred following the BRI intervention, but only in the BRI-trained muscle. The steep part of the SRC showed an MEP increase, while the plateau of the SRC showed an MEP decrease. MEP mapping revealed a distributed pattern with a decrease of excitability in the hand area of the primary motor cortex, which controlled the BRI, but an increase of excitability in the surrounding somatosensory and premotor cortex. In conclusion, the BRI intervention induced a complex pattern of modulated corticospinal excitability, which may boost subsequent motor learning during physiotherapy.

  16. Maggot excretion products from the blowfly Lucilia sericata contain contact phase/intrinsic pathway-like proteases with procoagulant functions.

    Science.gov (United States)

    Kahl, M; Gökçen, A; Fischer, S; Bäumer, M; Wiesner, J; Lochnit, G; Wygrecka, M; Vilcinskas, A; Preissner, K T

    2015-08-01

    For centuries, maggots have been used for the treatment of wounds by a variety of ancient cultures, as part of their traditional medicine. With increasing appearance of antimicrobial resistance and in association with diabetic ulcers, maggot therapy was revisited in the 1980s. Three mechanisms by which sterile maggots of the green bottle fly Lucilia sericata may improve healing of chronic wounds have been proposed: Biosurgical debridement, disinfecting properties, and stimulation of the wound healing process. However, the influence of maggot excretion products (MEP) on blood coagulation as part of the wound healing process has not been studied in detail. Here, we demonstrate that specific MEP-derived serine proteases from Lucilia sericata induce clotting of human plasma and whole blood, particularly by activating contact phase proteins factor XII and kininogen as well as factor IX, thereby providing kallikrein-bypassing and factor XIa-like activities, both in plasma and in isolated systems. In plasma samples deficient in contact phase proteins, MEP restored full clotting activity, whereas in plasma deficient in either factor VII, IX, X or II no effect was seen. The observed procoagulant/intrinsic pathway-like activity was mediated by (chymo-) trypsin-like proteases in total MEP, which were significantly blocked by C1-esterase inhibitor or other contact phase-specific protease inhibitors. No significant influence of MEP on platelet activation or fibrinolysis was noted. Together, MEP provides contact phase bypassing procoagulant activity and thereby induces blood clotting in the context of wound healing. Further characterisation of the active serine protease(s) may offer new perspectives for biosurgical treatment of chronic wounds.

  17. Urinary excretion and daily intake rates of diethyl phthalate in the general Canadian population.

    Science.gov (United States)

    Saravanabhavan, Gurusankar; Walker, Mike; Guay, Mireille; Aylward, Lesa

    2014-12-01

    We have analyzed the trends in the body-weight-adjusted urinary monoethyl phthalate (MEP) concentrations and the diethyl ethyl phthalate (DEP) daily intake estimates in the general Canadian population (aged 6-49 years) using the Canadian Health Measures Survey 2007-2009 dataset. The creatinine correction approach, as well as the urine volume approach in a simple one compartment model were used to calculate the daily urinary MEP excretion rates and DEP intake rates in individual survey participants. Using multiple regression models, we have estimated least square geometric means (LSGMs) of body-weight-adjusted MEP concentration, daily excretion and intake rates among different age groups and sex. We observed that body weight affects the trends in the MEP concentrations significantly among children (aged 6-11 years), adolescents (aged 12-19 years) and adults (aged 20-49 years). The body-weight-adjusted MEP concentrations in children were significantly higher than those in adults. On the other hand the DEP daily intakes in children were significantly lower than those in adults. We did not observe any differences in the DEP daily intake rates between males and females. Although the urinary MEP concentrations are correlated well with DEP daily intake estimates in the overall population, one should be cautious when directly using the urinary concentrations to compare the intake trends in the sub-populations (e.g. children vs. adults) as these trends are governed by additional physiological factors. The DEP daily intake calculated using the creatinine approach and that using the urine volume approach were similar to each other. The estimated geometric mean and 95th percentile of DEP daily intake in the general Canadian population are 2 and 20 μg/kg-bw/day, respectively. These daily intake estimates are significantly lower than the US Environmental Protection Agency's oral reference dose of 800 μg/kg-bw/day. PMID:25217994

  18. Transcranial magnetic stimulation with a half-sine wave pulse elicits direction-specific effects in human motor cortex

    Directory of Open Access Journals (Sweden)

    Jung Nikolai H

    2012-11-01

    Full Text Available Abstract Background Transcranial magnetic stimulation (TMS commonly uses so-called monophasic pulses where the initial rapidly changing current flow is followed by a critically dampened return current. It has been shown that a monophasic TMS pulse preferentially excites different cortical circuits in the human motor hand area (M1-HAND, if the induced tissue current has a posterior-to-anterior (PA or anterior-to-posterior (AP direction. Here we tested whether similar direction-specific effects could be elicited in M1-HAND using TMS pulses with a half-sine wave configuration. Results In 10 young participants, we applied half-sine pulses to the right M1-HAND which elicited PA or AP currents with respect to the orientation of the central sulcus. Measurements of the motor evoked potential (MEP revealed that PA half-sine stimulation resulted in lower resting motor threshold (RMT than AP stimulation. When stimulus intensity (SI was gradually increased as percentage of maximal stimulator output, the stimulus–response curve (SRC of MEP amplitude showed a leftward shift for PA as opposed to AP half-sine stimulation. Further, MEP latencies were approximately 1 ms shorter for PA relative to AP half-sine stimulation across the entire SI range tested. When adjusting SI to the respective RMT of PA and AP stimulation, the direction-specific differences in MEP latencies persisted, while the gain function of MEP amplitudes was comparable for PA and AP stimulation. Conclusions Using half-sine pulse configuration, single-pulse TMS elicits consistent direction-specific effects in M1-HAND that are similar to TMS with monophasic pulses. The longer MEP latency for AP half-sine stimulation suggests that PA and AP half-sine stimulation preferentially activates different sets of cortical neurons that are involved in the generation of different corticospinal descending volleys.

  19. Pre-stimulus Alpha Oscillations and Inter-subject Variability of Motor Evoked Potentials in Single- and Paired-Pulse TMS Paradigms

    Science.gov (United States)

    Iscan, Zafer; Nazarova, Maria; Fedele, Tommaso; Blagovechtchenski, Evgeny; Nikulin, Vadim V.

    2016-01-01

    Inter- and intra-subject variability of the motor evoked potentials (MEPs) to TMS is a well-known phenomenon. Although a possible link between this variability and ongoing brain oscillations was demonstrated, the results of the studies are not consistent with each other. Exploring this topic further is important since the modulation of MEPs provides unique possibility to relate oscillatory cortical phenomena to the state of the motor cortex probed with TMS. Given that alpha oscillations were shown to reflect cortical excitability, we hypothesized that their power and variability might explain the modulation of subject-specific MEPs to single- and paired-pulse TMS (spTMS, ppTMS, respectively). Neuronal activity was recorded with multichannel electroencephalogram. We used spTMS and two ppTMS conditions: intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI). Spearman correlations were calculated within and across subjects between MEPs and the pre-stimulus power of alpha oscillations in low (8–10 Hz) and high (10–12 Hz) frequency bands. Coefficient of quartile variation was used to measure variability. Across-subject analysis revealed no difference in the pre-stimulus alpha power among the TMS conditions. However, the variability of high-alpha power in spTMS condition was larger than in the SICI condition. In ICF condition pre-stimulus high-alpha power variability correlated positively with MEP amplitude variability. No correlation has been observed between the pre-stimulus alpha power and MEP responses in any of the conditions. Our results show that the variability of the alpha oscillations can be more predictive of TMS effects than the commonly used power of oscillations and we provide further support for the dissociation of high and low-alpha bands in predicting responses produced by the stimulation of the motor cortex. PMID:27774060

  20. Effect of Enzyme Inhibitors on Terpene Trilactones Biosynthesis and Gene Expression Profiling in Ginkgo biloba Cultured Cells.

    Science.gov (United States)

    Chen, Lijia; Tong, Hui; Wang, Mingxuan; Zhu, Jianhua; Zi, Jiachen; Song, Liyan; Yu, Rongmin

    2015-12-01

    The biosynthetic pathway of terpene trilactones of Ginkgo biloba is unclear. In this present study, suspension cultured cells of G. biloba were used to explore the regulation of the mevalonic acid (MVA) and methylerythritol 4-phosphate (MEP) pathways in response to specific enzyme inhibitors (lovastatin and clomazone). The results showed that the biosynthesis of bilobalide was more highly correlated with the MVA pathway, and the biosynthesis of ginkgolides was more highly correlated with the MEP pathway. Meanwhile, according to the results, it could be speculated that bilobalide might be a product of ginkgolide metabolism.

  1. Effect of surfactants on the morphology of FeSe films fabricated from a single source precursor by aerosol assisted chemical vapour deposition

    Indian Academy of Sciences (India)

    Raja Azadar Hussain; Amin Badshah; Naghma Haider; Malik Dilshad Khan; Bhajan Lal

    2015-03-01

    This article presents the fabrication of FeSe thin films from a single source precursor namely (1-(2-fluorobenzoyl)-3-(4-ferrocenyl-3-methylphenyl)selenourea (MeP2F)) by aerosol assisted chemical vapour deposition (AACVD). All the films were prepared via similar experimental conditions (temperature, flow rate, concentration, solvent system and reactor type) except the use of three different concentrations of two different surfactants i.e., triton and span. Seven thin films were characterized with PXRD, SEM, AFM, EDS and EDS mapping. The mechanism of the interaction of surfactant with MeP2F was determined with cyclic voltammetry (CV) and UV-Vis spectroscopy.

  2. Spinal inhibition of descending command to soleus motoneurons is removed prior to dorsiflexion

    DEFF Research Database (Denmark)

    Geertsen, Svend Sparre; van de Ruit, Mark; Grey, Michael James;

    2011-01-01

    investigated how afferent inputs from the tibialis anterior muscle modulate the corticospinal activation of soleus spinal motoneurons at rest, during static contraction and prior to movement. MEPs activated by transcranial magnetic stimulation (TMS) and Hoffmann-reflexes (H-reflexes) activated by electrical...... stimulation of the posterior tibial nerve (PTN) were conditioned by prior stimulation of the common peroneal nerve (CPN) at a variety of conditioning-test (CT) intervals.MEPs in the precontracted soleus muscle were inhibited when the TMS pulse was preceded by CPN stimulation with a CT interval of 35 ms...

  3. Röntgenstrukturanalyse von LytB aus Aquifex aeolicus und Plasmodium falciparum

    OpenAIRE

    Rekittke, Ingo

    2010-01-01

    Der MEP-Weg stellt auf Grund seiner besonderen Eigenschaften ein interessantes Ziel für die de novo Entwicklung antimikrobialer und herbizider Wirkstoffe dar. Mit Ausnahme der letzten beiden Enzyme GcpE und LytB ist der MEP-Weg schon strukturell geklärt. Um diese Lücke zu schliessen, wurden in dieser Arbeit Kristallisationsexperimente mit Aquifex aeolicus und Plasmodium falciparum LytB und Thermus thermophilus GcpE durchgeführt. Durch die im Rahmen dieser Arbeit durchgeführten Experimente ...

  4. Offsite Source Recovery Program (OSRP) Workshop Module: Tianjin, China, July 16-July 17, 2012

    International Nuclear Information System (INIS)

    Recovering and disposal of radioactive sources that are no longer in service in their intended capacity is an area of high concern Globally. A joint effort to recover and dispose of such sources was formed between the US Department of Energy and the Chinese Ministry of Environmental Protection (MEP), in preparation for the 2008 Beijing Olympics. LANL involvement in this agreement continues today under the DOE-Global Threat Reduction Initiative (GTRI) program. LANL will be presenting overview information on their Offsite Source Recovery (OSRP) and Source Disposal programs, in a workshop for the Ministry of Environmental Protection (MEP) at Tianjin, China, on July 16 and 17, 2012.

  5. Confronting Regulatory Cost and Quality Expectations. An Exploration of Technical Change in Minimum Efficiency Performance Standards

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Margaret [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Stanford Univ., CA (United States); Spurlock, C. Anna [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Yang, Hung-Chia [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-09-21

    The dual purpose of this project was to contribute to basic knowledge about the interaction between regulation and innovation and to inform the cost and benefit expectations related to technical change which are embedded in the rulemaking process of an important area of national regulation. The area of regulation focused on here is minimum efficiency performance standards (MEPS) for appliances and other energy-using products. Relevant both to U.S. climate policy and energy policy for buildings, MEPS remove certain product models from the market that do not meet specified efficiency thresholds.

  6. Synthesis of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate and kinetic studies of Mycobacterium tuberculosis IspF, a potential drug target

    OpenAIRE

    Narayanasamy, Prabagaran; Eoh, Hyungjin; Brennan, Patrick J.; Crick, Dean C.

    2010-01-01

    Many pathogenic bacteria utilize the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for the biosynthesis of isopentenyl diphosphate and dimethylallyl diphosphate, two major building blocks of isoprenoid compounds. The fifth enzyme in the MEP pathway, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) synthase (IspF), catalyzes the conversion of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to ME-CPP with a corresponding release of cytidine 5-monophosphate (CMP). Sinc...

  7. Comparison of Test Procedures and Energy Efficiency Criteria in Selected International Standards & Labeling Programs for Copy Machines, External Power Supplies, LED Displays, Residential Gas Cooktops and Televisions

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Nina [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Zhou, Nan [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Fridley, David [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2012-03-01

    This report presents a technical review of international minimum energy performance standards (MEPS), voluntary and mandatory energy efficiency labels and test procedures for five products being considered for new or revised MEPS in China: copy machines, external power supply, LED displays, residential gas cooktops and flat-screen televisions. For each product, an overview of the scope of existing international standards and labeling programs, energy values and energy performance metrics and description and detailed summary table of criteria and procedures in major test standards are presented.

  8. Delayed release particles from vascular endothelial growth factor for repairing spinal cord ischemic injury of rats

    Institute of Scientific and Technical Information of China (English)

    CHEN Yang; LI Feng; XIAO Jian-de; LI Zhen-yu; YANG Lei; LUO Xin-le

    2007-01-01

    Objective:To study the effect of delayed release particles from vascular endothelial growth factor (VEGF)on the reparation of ischemic injury of spinal cord in rats. Methods:The spinal cord ischemia model of rats was established.The delayed release particles from VEGF were injected via the intubation of spinal subarachnoid space.The rehabilitation was observed by the assessment of unfold claw reflection,space between toes,spinal evoked potential (SEP) and motor evoked potential (MEP). Results:VEGF prompted SEP and MEP appearance,improved the motor function of hind limbs. Conclusions:VEGF can promote the rehabilitation of spinal cord ischemic injury of rats.

  9. Offsite Source Recovery Program (OSRP) Workshop Module: Tianjin, China, July 16-July 17, 2012

    Energy Technology Data Exchange (ETDEWEB)

    Houlton, Robert J. [Los Alamos National Laboratory

    2012-07-11

    Recovering and disposal of radioactive sources that are no longer in service in their intended capacity is an area of high concern Globally. A joint effort to recover and dispose of such sources was formed between the US Department of Energy and the Chinese Ministry of Environmental Protection (MEP), in preparation for the 2008 Beijing Olympics. LANL involvement in this agreement continues today under the DOE-Global Threat Reduction Initiative (GTRI) program. LANL will be presenting overview information on their Offsite Source Recovery (OSRP) and Source Disposal programs, in a workshop for the Ministry of Environmental Protection (MEP) at Tianjin, China, on July 16 and 17, 2012.

  10. Early detection of pedicle screw-related spinal cord injury by continuous intraoperative neurophysiological monitoring (IONM).

    Science.gov (United States)

    Jahangiri, Faisal R; Sheryar, Muhammad; Al Behairy, Yaser

    2014-12-01

    Pedicle screw placement has a high risk of damaging the motor and sensory pathways due to the close proximity to the spinal cord and nerve roots. Early detection and prevention of injury can be achieved by utilizing Somatosensory Evoked Potentials (SSEP) and Transcranial electrical Motor Evoked Potentials (TCeMEP) during a scoliosis surgery. A 19-year-old female presented for correction of scoliosis. After intubation, electrodes were placed for upper and lower SSEPs, EMGs and TCeMEPs. Total intravenous anesthesia was used. Baseline SSEP and TCeMEP responses were present in all limbs. Eight pedicle screws were placed. After placing the last screw, TCeMEP signals were lost bilaterally in lower extremities. Surgery was paused. After removing all the screws TCeMEP responses returned to baseline in left lower limb but remained absent in right lower limb. A wake-up test was performed which was positive in her right leg. Blood pressure was increased and bolus of steroids was given. There was no improvement in right lower limb TCeMEP responses. Surgeon was advised to stop the surgery and proceed for MRI and follow-up. SSEP signals remained stable in all four-extremities. The surgical correction was cancelled. MRI revealed intramedullary spinal cord ischemic changes at T11. After extubation, patient was unable to move her right lower extremity with flaccid paralysis. She also complained about severe burning in her left lower extremity. The patient was taken for rehabilitation exercises. One week post-op, she was moving hip flexors and two weeks later had afull motor function, bilaterally. Real-time IONM was useful in early identification of spinal cord injury. Significant changes were seen in TCeMEP, without any change in SSEP. We highly recommend utilizing continuous TCeMEP and SSEP monitoring during pedicle screw placement for prevention of injury to the spinal cord. In this case, the patient would have been paralyzed post-operatively without the use of IONM. PMID

  11. Formation of nucleoside 5'-polyphosphates from nucleotides and trimetaphosphate.

    Science.gov (United States)

    Lohrmann, R

    1975-12-29

    When solutions of nucleoside 5'-phosphates and trimetaphosphate are dried out at room temperature, nucleoside 5'-polyphosphates are formed. The Mg++ ion shows a superior catalytic function in this reaction when compared with other divalent metal ions. Starting with nucleoside 5'-phosphates, Mg++ and trimetaphosphate, the predominant products in the nucleoside 5'-polyphosphate series pnN are p4N, P7N and p10N. Nucleoside 5'-diphosphates yield p5N and p8N, nucleoside 5'-triphosphates give p6N and p9N. The prebiological relevance of these reactions is discussed. PMID:1541

  12. Comparison study of selected geophysical and geotechnical parameters

    DEFF Research Database (Denmark)

    Nissen, Randi Warncke; Poulsen, Søren Erbs

    2015-01-01

    Successful foundation of constructions relies on accurate characterization of the geotechnical properties of the subsurface. By implementing data from geophysical surveys, the placement of geotechnical drillings can be significantly improved, potentially reducing the number of required drillings....... This case study is mainly to compare geophysical investigations (MEP/IP) with existing PACES data and information from geotechnical drillings....

  13. CYP7B1

    DEFF Research Database (Denmark)

    Roos, P; Svenstrup, K; Danielsen, E R;

    2014-01-01

    , electrophysiology, brain MRI and MR spectroscopy. RESULTS: One patient had saccadic pursuit eye movements in addition to a pure HSP phenotype. Motor evoked potential (MEP) examinations revealed prolonged central conduction time. MRI of the brain showed white matter hyperintensities (WMH) in one patient. MRS showed...

  14. Probing phosphorylation by non-mammalian isoprenoid biosynthetic enzymes using 1H–31P–31P correlation NMR spectroscopy†‡

    OpenAIRE

    Majumdar, Ananya; Shah, Meha H.; Bitok, J. Kipchirchir; Hassis-LeBeau, Maria E.; Freel Meyers, Caren L.

    2009-01-01

    The biogenesis of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) is accomplished by the methylerythritol phosphate (MEP) pathway in plants, bacteria and parasites, making it a potential target for the development of anti-infective agents and herbicides. The biosynthetic enzymes comprising this pathway catalyze intriguing chemical transformations on diphosphate scaffolds, offering an opportunity to generate novel analogs in this synthetically challenging compound class...

  15. Muscle potentials evoked by magnetic stimulation of the sciatic nerve in unilateral sciatic nerve dysfunction

    NARCIS (Netherlands)

    Van Soens, I.; Struys, M. M. R. F.; Van Ham, L. M. L.

    2010-01-01

    Magnetic stimulation of the sciatic nerve and subsequent recording of the muscle-evoked potential (MEP) was performed in eight dogs and three cats with unilateral sciatic nerve dysfunction. Localisation of the lesion in the sciatic nerve was based on the history, clinical neurological examination an

  16. Invisible Children: A Portrait of Migrant Education in the United States. Final Report.

    Science.gov (United States)

    National Commission of Migrant Education, Washington, DC.

    This report, the culmination of a 3-year examination of the federal Migrant Education Program (MEP), is based on research, public testimony, and interviews with migrant community members by the National Commission on Migrant Education. It discusses agricultural trends of the past 25 years and accompanying demographic changes in the migrant…

  17. 77 FR 41902 - Special Local Regulation and Safety Zone; America's Cup Sailing Events, San Francisco, CA

    Science.gov (United States)

    2012-07-17

    ... COTP Captain of the Port DHS Department of Homeland Security FR Federal Register MEP Marine Event... FR 4501. The Coast Guard provided a 90-day period for public comment on the proposed ] regulations... waterfront in the vicinity of the Golden Gate Bridge and Alcatraz Island. This rule will regulate the...

  18. Intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation for preservation of facial nerve function in patients with large acoustic neuroma

    Institute of Scientific and Technical Information of China (English)

    LIU Bai-yun; TIAN Yong-ji; LIU Wen; LIU Shu-ling; QIAO Hui; ZHANG Jun-ting; JIA Gui-jun

    2007-01-01

    Background Although various monitoring techniques have been used routinely in the treatment of the lesions in the skull base, iatrogenic facial paresis or paralysis remains a significant clinical problem. The aim of this study was to investigate the effect of intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation on preservation of facial nerve function.Method From January to November 2005, 19 patients with large acoustic neuroma were treated using intraoperative facial motor evoked potentials monitoring with transcranial electrical stimulation (TCEMEP) for preservation of facial nerve function. The relationship between the decrease of MEP amplitude after tumor removal and the postoperative function of the facial nerve was analyzed.Results MEP amplitude decreased more than 75% in 11 patients, of which 6 presented significant facial paralysis (H-B grade 3), and 5 had mild facial paralysis (H-B grade 2). In the other 8 patients, whose MEP amplitude decreased less than 75%, 1 experienced significant facial paralysis, 5 had mild facial paralysis, and 2 were normal.Conclusions Intraoperative TCEMEP can be used to predict postoperative function of the facial nerve. The decreased MEP amplitude above 75 % is an alarm point for possible severe facial paralysis.

  19. Alternative Methods for Defining Osteoarthritis and the Impact on Estimating Prevalence in a US Population-Based Survey

    Science.gov (United States)

    Cisternas, Miriam G.; Murphy, Louise; Sacks, Jeffrey J.; Solomon, Daniel H.; Pasta, David J.; Helmick, Charles G.

    2015-01-01

    Objective Provide a contemporary estimate of osteoarthritis (OA) by comparing accuracy and prevalence of alternative definitions of OA. Methods The Medical Expenditure Panel Survey (MEPS) household component (HC) records respondent-reported medical conditions as open-ended responses; professional coders translate these responses into ICD-9-CM codes for the medical conditions files. Using these codes and other data from the MEPS-HC medical conditions files, we constructed three case definitions of OA and assessed them against medical provider diagnoses of ICD-9-CM 715 [osteoarthrosis and allied disorders] in a MEPS subsample. The three definitions were: 1) strict = ICD-9-CM 715; 2) expanded = ICD-9-CM 715, 716 [other and unspecified arthropathies], OR 719 [other and unspecified disorders of joint]); and 3) probable = strict OR expanded + respondent-reported prior diagnosis of OA or other arthritis excluding rheumatoid arthritis (RA). Results Sensitivity and specificity of the three definitions were: strict – 34.6% and 97.5%; expanded – 73.8% and 90.5%; and probable – 62.9% and 93.5%. Conclusion The strict definition for OA (ICD-9-CM 715) excludes many individuals with OA. The probable definition of OA has the optimal combination of sensitivity and specificity relative to the two other MEPS-based definitions and yields a national annual estimate of 30.8 million adults with OA (13.4% of US adult population) for 2008 – 2011. PMID:26315529

  20. A highly efficient six-stroke internal combustion engine cycle with water injection for in-cylinder exhaust heat recovery

    Energy Technology Data Exchange (ETDEWEB)

    Conklin, James C.; Szybist, James P. [Oak Ridge National Laboratory, 2360 Cherahala Blvd, Knoxville, TN 37932 (United States)

    2010-04-15

    A concept adding two strokes to the Otto or Diesel engine cycle to increase fuel efficiency is presented here. It can be thought of as a four-stroke Otto or Diesel cycle followed by a two-stroke heat recovery steam cycle. A partial exhaust event coupled with water injection adds an additional power stroke. Waste heat from two sources is effectively converted into usable work: engine coolant and exhaust gas. An ideal thermodynamics model of the exhaust gas compression, water injection and expansion was used to investigate this modification. By changing the exhaust valve closing timing during the exhaust stroke, the optimum amount of exhaust can be recompressed, maximizing the net mean effective pressure of the steam expansion stroke (MEP{sub steam}). The valve closing timing for maximum MEP{sub steam} is limited by either 1 bar or the dew point temperature of the expansion gas/moisture mixture when the exhaust valve opens. The range of MEP{sub steam} calculated for the geometry of a conventional gasoline engine and is from 0.75 to 2.5 bars. Typical combustion mean effective pressures (MEP{sub combustion}) of naturally aspirated gasoline engines are up to 10 bar, thus this concept has the potential to significantly increase the engine efficiency and fuel economy. (author)

  1. Evaluation of the motor cortical excitability changes after ischemic stroke

    Directory of Open Access Journals (Sweden)

    D K Prashantha

    2013-01-01

    Full Text Available Background: We evaluated progressive changes in excitability of motor cortex following ischemic stroke using Transcranial Magnetic Stimulation (TMS. Materials and Methods: Thirty-one patients (24 men, 7 women; age 37.3 ± 8.2 years were recruited and TMS was performed using Magstim 200 stimulator and a figure-of-eight coil. Resting motor threshold (RMT was recorded from affected and unaffected hemispheres and motor evoked potential (MEP was recorded from contralateral FDI muscle. Central motor conduction time (CMCT was calculated using F wave method. All measurements were done at baseline (2 nd , 4 th , and 6 th week of stroke. Results: Affected hemisphere: MEP was recordable in 3 patients at baseline (all had prolonged CMCT. At 4 weeks, MEP was recordable in one additional patient and CMCT remained prolonged. At 6 weeks, CMCT normalized in one patient. RMT was recordable (increased in 3 patients at baseline, in one additional patient at 4 weeks, and reduced marginally in these patients at 6 weeks. Unaffected hemisphere: MEP was recordable in all patients at baseline, and reduced significantly over time (2 nd week 43.52 ± 9.60, 4 th week 38.84 ± 7.83, and 6 th week 36.85 ± 7.27; P < 0.001. The CMCT was normal and remained unchanged over time. Conclusion: The increase in excitability of the unaffected motor cortex suggests plasticity in the post-stroke phase.

  2. Comparison study of selected Geophysical and geotechnical parameters

    DEFF Research Database (Denmark)

    Nissen, Randi Warncke; Poulsen, Søren Erbs

    2015-01-01

    Successful foundation of constructions relies on accurate characterization of the geotechnical properties of the subsurface. By implementing data from geophysical surveys, the placement of geotechnical drillings can be significantly improved, potentially reducing the number of required drillings....... This case study is mainly to compare geophysical investigations (MEP/IP) with existing PACES data and information from geotechnical drillings....

  3. The Implementation of Rules on the Comprehensive Management of Heavy Metal Pollution will be Published This Year

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    <正>Sept 2nd, Xi’an - Zhou Shengxian, Minister of Environmental Protection, announced in the National Heavy Metal Pollution Management Conference that the MEP is cooperating with the SDPC, MIIT, MOF, MOA and MOH on the preparation of Implementing Rules on Com-prehensive Management

  4. Changes of evoked potential and expression of nestin in subventricular zones in rats after focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    GAO Jie; WANG Yong-tang; WANG Li-li; ZENG Ling; WU Ya-min; SHAO Yang

    2007-01-01

    Objective:To study the characteristics of latency of somatosensory evoked potential (SEP)and motor evoked potential (MEP) and the expression of nestin in subventricular zones (SVZ) after persistent focal cerebral ischemia in rats. Methods: The model of cerebral ischemia in rats was made by middle cerebral artery occlusion (MCAO). All animals of ischemia were sacrificed after 12 h, 1 d, 3 d, 7 d,and 14 d to observe the changes of latency of SEP and MEP and to detect the expression of nestin, with an immunohistochemical approach. Results: The latencies of P1 (positive wave 1), N1 (negative wave 1) and P2 (positive wave 2) in SEP were significantly prolonged after MCAO. The latencies of N1 and N2 waves in MEP were postponed gradually and no statistical difference of latency of N1 wave was found in rats at 7d and 14 d after MCAO. The expression of nestin increased at 12 h, and showed a significant augmentation at 3 d and peaked at 7 d, then declined slightly at 14 d after MCAO. Conclusion: The cerebral ischemia prolonged the latency of EP waves and the expression of nestin was up-regulated and reached the peak at 7d, showing the ischemia induced the proliferation of nervous stem cells. The SEP and MEP may evaluate the proliferation in SVZ after brain ischemia.

  5. Microsome biocolloids for rapid drug metabolism and inhibition assessment by LC-MS

    OpenAIRE

    Bajrami, Besnik; Krishnan, Sadagopan; Rusling, James F.

    2008-01-01

    Rat liver microsomes attached to nanoparticles were used for LC-MS studies of CYP3A and 2E1 enzymes in metabolism of N-nitroso compounds. Using these biocolloids, turnover rates were measured within 2 min. Inhibitor IC50 values for ketoconazole (KET) and 4-methylpyrazole (4-MEP) were estimated.

  6. Microsome biocolloids for rapid drug metabolism and inhibition assessment by LC-MS

    Science.gov (United States)

    Bajrami, Besnik; Krishnan, Sadagopan; Rusling, James F.

    2012-01-01

    Rat liver microsomes attached to nanoparticles were used for LC-MS studies of CYP3A and 2E1 enzymes in metabolism of N-nitroso compounds. Using these biocolloids, turnover rates were measured within 2 min. Inhibitor IC50 values for ketoconazole (KET) and 4-methylpyrazole (4-MEP) were estimated. PMID:19356087

  7. Rapid changes in corticospinal excitability during force field adaptation of human walking

    DEFF Research Database (Denmark)

    Barthélemy, Dorothy; Alain, S; Grey, Michael James;

    2012-01-01

    be explained by changes in background TA EMG activity. These effects seemed specific to walking, as similar changes in TA MEP were not seen when seated subjects were tested during static dorsiflexion. These observations suggest that the corticospinal tract contributes to the adaptation of walking...

  8. Experiment list: SRX203204 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic ser...ies (GRANULOCYTES and their precursors). 21711994,88.6,49.7,19612 GSM1032634: MEP H3K4me2; Mus musculus; ChI

  9. Electrostatic Potential as a Descriptor of Anti-Bacterial Activities of Some Anacardic Acid Derivatives: A Study Using Density Functional Theory

    CERN Document Server

    Tiwari, Manish K

    2015-01-01

    Structures and minimum molecular electrostatic potential (MEP) distributions in anacardic acid and some of its derivatives have been studied by full geometry optimization at the M06-2X/6-31G(d,p), WB97XD/6-31G(d,p) and B3LYP/6-31G(d,p) levels of density functional theory (DFT) in gas phase as well as in DMSO and aqueous solutions. Solvent effect was treated employing the integral equation formalism of the polarizable continuum model. Effects of modifications of the C1-side chain on the minimum MEP values in various regions were studied. Minimum MEP values near the oxygen atoms of the C2-OH group, oxygen or sulfur atoms of the C1-attached urea or thiourea groups and above or below the ring plane considered to be involved in interaction with the receptor were used to perform multiple linear regression. Experimentally observed anti-bacterial activities of these molecules against S. aureus are thus shown to be related to minimum MEP values in the above mentioned regions. Among the three DFT functionals used in th...

  10. Et undertrykt folk har altid ret

    DEFF Research Database (Denmark)

    Necef, Mehmet Ümit

    2012-01-01

    I midten af januar debatterede Søren Søndergaard, MEP, Folkebevægelsen mod EU, og Søren Espersen, udenrigsordfører, Dansk Folkeparti, i P1 Debat om, hvorvidt PKK-guerillaer er frihedskæmpere eller terrorister. Den danske debat minder om en lignende debat, der for blandt tyrkiske intellektuelle, men...

  11. 77 FR 58386 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Science.gov (United States)

    2012-09-20

    ... treated with diet, oral medications or insulin. 4. Authorization forms for the MEPS-MPC Provider and...,695,868 Production of Public Use Data Files..... 21,079,118 7,026,373 Project Management 4,233,739 1... HUMAN SERVICES Agency for Healthcare Research and Quality Agency Information Collection...

  12. A comparison of throwing kinematics between youth baseball players with and without a history of medial elbow pain.

    Science.gov (United States)

    Huang, Yung-Hsien; Wu, Ting-Yu; Learman, Kenneth E; Tsai, Yung-Shen

    2010-06-30

    Risk factors in throwing factors associated to little league elbow have not been adequately explored. Whether these factors also affect the players' performance is also important to elucidate while modifying throwing pattern to reduce injury. The purpose of this study was to compare the differences in throwing kinematics between youth baseball players with or without a history of medial elbow pain (MEP) and to determine the relationship between their throwing kinematics and ball speed. Fifteen players with previous MEP were matched with 15 healthy players by age, height and weight. Throwing kinematics was recorded by an electromagnetic motion analysis system. A foot switch was used for determining foot off and foot contact. Ball speed was recorded with a sports radar gun. The group with a history of MEP demonstrated less elbow flexion angle at maximum shoulder external rotation and had more lateral trunk tilt at ball release compared to the healthy group. The group with a history of MEP also had faster maximum upper torso rotation velocities, maximum pelvis rotation velocities and ball speeds. Maximum shoulder external rotation angle (r = 0.458, P = 0.011), elbow flexion angle at maximum shoulder external rotation (r = -0.637, P = 0.0003), and maximum upper torso rotation velocity (r = 0.562, P = 0.002) had significant correlation with ball speed. Findings of this study can be treated as elbow injury-related factors that clinicians and coaches can attend to when taking care of youth PMID:21793324

  13. Development and application of ultrasound-assisted microextraction to analysis of fenitrothion in environmental samples.

    Science.gov (United States)

    Takahashi, Fumiki; Kobayashi, Kanya; Jin, Jiye

    2016-10-01

    A microextraction technique based on ultrasonic emulsification and demulsification was developed for detecting pesticides at trace levels in environmental water samples. In this ultrasound-assisted microextraction (UAME), chloroform was emulsified with an aqueous sample solution containing trace fenitrothion (MEP) by ultrasonic irradiation (48 kHz) for 5 min. The emulsion was then demulsified by ultrasonic irradiation (2.4 MHz) for 10 min. This resulted in phase separation of the water and chloroform without centrifugation. The demulsified chloroform was collected by a microsyringe and submitted to gas chromatography-mass spectrometry. In conventional extraction with mechanical stirring, the extraction recovery (ER) of MEP was strongly dependent on the sample/chloroform volume ratio. However, in UAME, the ER was independent of the volume ratio and the ER was >80 % when the enrichment factor was 40. In UAME, MEP was rapidly extracted into the chloroform because of the large specific surface areas of the small chloroform droplets in the oil-in-water (O/W) emulsion. This gave a high extraction efficiency for MEP. UAME is a simple method requiring only a change in the ultrasound frequency and with no pretreatment steps that could contaminate the sample. The suitability of UAME was demonstrated by application to the detection of trace levels of pesticides in a spiked water sample from a fish tank. Graphical abstract Schematic diagram of the ultrasound-assisted microextraction (UAME) method.

  14. Application of multiple intraoperative monitoring techniques in microsurgery for anterior communicating aneurysms

    OpenAIRE

    Ni, De Wei; CHEN Liang; Xu, Geng; SONG Dong-lei; LEI, YU; Gu, Yu-Xiang

    2012-01-01

    Objective To evaluate the efficacy of combined multiple intraoperative monitoring techniques including transcranial Doppler (TCD), indocyanine green angiography (ICGA) and neuroelectrophysiological monitoring consisting of somatosensory evoked potential (SEP) and motor evoked potential (MEP) in the surgical management of anterior communicating aneurysm. Methods Clinical data were analyzed for the 23 patients who underwent microsurgery for anterior communicating aneurysms with assistance of co...

  15. Musical groove modulates motor cortex excitability: a TMS investigation.

    Science.gov (United States)

    Stupacher, Jan; Hove, Michael J; Novembre, Giacomo; Schütz-Bosbach, Simone; Keller, Peter E

    2013-07-01

    Groove is often described as a musical quality that can induce movement in a listener. This study examines the effects of listening to groove music on corticospinal excitability. Musicians and non-musicians listened to high-groove music, low-groove music, and spectrally matched noise, while receiving single-pulse transcranial magnetic stimulation (TMS) over the primary motor cortex either on-beat or off-beat. We examined changes in the amplitude of the motor-evoked potentials (MEPs), recorded from hand and arm muscles, as an index of activity within the motor system. Musicians and non-musicians rated groove similarly. MEP results showed that high-groove music modulated corticospinal excitability, whereas no difference occurred between low-groove music and noise. More specifically, musicians' MEPs were larger with high-groove than low-groove music, and this effect was especially pronounced for on-beat compared to off-beat pulses. These results indicate that high-groove music increasingly engages the motor system, and the temporal modulation of corticospinal excitability with the beat could stem from tight auditory-motor links in musicians. Conversely, non-musicians' MEPs were smaller for high-groove than low-groove music, and there was no effect of on- versus off-beat pulses, potentially stemming from suppression of overt movement. In sum, high-groove music engages the motor system, and previous training modulates how listening to music with a strong groove activates the motor system.

  16. Labor Supply of Politicians

    DEFF Research Database (Denmark)

    Fisman, Raymond; Harmon, Nikolaj Arpe; Kamenica, Emir;

    Using data on Members of the European Parliament (MEPs), we examine the impact of salaries on the composition and the behavior of legislators. Employing a differences-in-differences approach, we exploit the introduction of a law that equalized MEPs’ salaries which had previously differed by as mu...

  17. 77 FR 50083 - Submission for OMB Review; Comment Request

    Science.gov (United States)

    2012-08-20

    .... Burden Hours: 9,600. ] Needs and Uses: NIST MEP offers technical and business assistance to small- and... extent to which the Centers are meeting program goals and milestones. Affected Public: Business or other... information is used for the following purposes: (1) Program accountability, (2) reports to stakeholders,...

  18. Corticospinal Excitability during the Observation of Social Behavior

    Science.gov (United States)

    Bucchioni, Giulia; Cavallo, Andrea; Ippolito, Davide; Marton, Gianluca; Castiello, Umberto

    2013-01-01

    Evidence suggests that the observation of an action induces in the observers an enhancement of motor evoked potentials (MEPs) recorded by the observer's muscles corresponding to those involved in the observed action. Although this is a well-studied phenomenon, it remains still unclear how the viewer's motor facilitation is influenced by the social…

  19. Changes of Excitability in M1 Induced by Neuromuscular Electrical Stimulation Differ Between Presence and Absence of Voluntary Drive

    Science.gov (United States)

    Sugawara, Kenichi; Tanabe, Shigeo; Higashi, Toshio; Tsurumi, Takamasa; Kasai, Tatsuya

    2011-01-01

    The aim of this study is to investigate excitability changes in the human motor cortex induced by variable therapeutic electrical stimulations (TESs) with or without voluntary drive. We recorded motor-evoked potentials (MEPs) from extensor and flexor carpi radialis (FCR) muscles at rest and during FCR muscle contraction after the application of…

  20. Different motor learning effects on excitability changes of motor cortex in muscle contraction state.

    Science.gov (United States)

    Sugawara, Kenichi; Tanabe, Shigeo; Suzuki, Tomotaka; Higashi, Toshio

    2013-09-01

    We aimed to investigate whether motor learning induces different excitability changes in the human motor cortex (M1) between two different muscle contraction states (before voluntary contraction [static] or during voluntary contraction [dynamic]). For the same, using motor evoked potentials (MEPs) obtained by transcranial magnetic stimulation (TMS), we compared excitability changes during these two states after pinch-grip motor skill learning. The participants performed a force output tracking task by pinch grip on a computer screen. TMS was applied prior to the pinch grip (static) and after initiation of voluntary contraction (dynamic). MEPs of the following muscles were recorded: first dorsal interosseous (FDI), thenar muscle (Thenar), flexor carpi radialis (FCR), and extensor carpi radialis (ECR) muscles. During both the states, motor skill training led to significant improvement of motor performance. During the static state, MEPs of the FDI muscle were significantly facilitated after motor learning; however, during the dynamic state, MEPs of the FDI, Thenar, and FCR muscles were significantly decreased. Based on the results of this study, we concluded that excitability changes in the human M1 are differentially influenced during different voluntary contraction states (static and dynamic) after motor learning.

  1. Reduced surround inhibition in musicians.

    Science.gov (United States)

    Shin, Hae-Won; Kang, Suk Y; Hallett, Mark; Sohn, Young H

    2012-06-01

    To investigate whether surround inhibition (SI) in the motor system is altered in professional musicians, we performed a transcranial magnetic stimulation (TMS) study in 10 professional musicians and 15 age-matched healthy non-musicians. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1,000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the abductor digiti minimi (ADM) muscles were compared between the musicians and non-musicians with the primary analysis being the intervals between 3 and 80 ms (during the movement). A mixed-design ANOVA revealed a significant difference in normalized ADM MEPs during the index finger flexion between groups, with less SI in the musicians. This study demonstrated that the functional operation of SI is less strong in musicians than non-musicians, perhaps due to practice of movement synergies involving both muscles. Reduced SI, however, could lead susceptible musicians to be prone to develop task-specific dystonia.

  2. Co-digestion of animal manure and maize : is it sustainable, an update

    NARCIS (Netherlands)

    Zwart, K.B.; Kuikman, P.J.

    2011-01-01

    Co-digestion has attracted increased attention in The Netherlands as a result of a subsidy for electricity that is produced environmentally safe (MEP and SDE subsidy). Production of bio-energy by means of co-digestion turned financially profitable due to this financial support. Co-digestion is the s

  3. Characteristics and Antitumor Activity of Morchella esculenta Polysaccharide Extracted by Pulsed Electric Field

    Science.gov (United States)

    Liu, Chao; Sun, Yonghai; Mao, Qian; Guo, Xiaolei; Li, Peng; Liu, Yang; Xu, Na

    2016-01-01

    Polysaccharides from Morchella esculenta have been proven to be functional and helpful for humans. The purpose of this study was to investigate the chemical structure and anti-proliferating and antitumor activities of a Morchella esculenta polysaccharide (MEP) extracted by pulsed electric field (PEF) in submerged fermentation. The endo-polysaccharide was separated and purified by column chromatography and Gel permeation chromatography, and analyzed by gas chromatography. The MEP with an average molecular weight of 81,835 Da consisted of xylose, glucose, mannose, rhamnose and galactose at the ratio of 5.4:5.0:6.5:7.8:72.3. Structure of MEP was further analyzed by Fourier-transform infrared spectroscopy and 1H and 13C liquid-state nuclear magnetic resonance spectroscopy. Apoptosis tests proved that MEP could inhibit the proliferation and growth of human colon cancer HT-29 cells in a time- and dose-dependent manner within 48 h. This study provides more information on chemical structure of anti-proliferating polysaccharides isolated from Morchella esculenta. PMID:27338370

  4. Committee Representation in the European Parliament

    OpenAIRE

    McElroy, Gail

    2006-01-01

    Abstract The European Parliament (EP) possesses a highly specialized committee system, operating in a complex institutional and political environment, yet little empirical work has investigated how MEPs are assigned to EP committees and what consequences this process has for representation and policy-making. In this article I examine the growth of EP committees and committee membership since 1979, and addre...

  5. 77 FR 55811 - Manufacturing Extension Partnership Advisory Board On-line Open Meeting

    Science.gov (United States)

    2012-09-11

    ... National Institute of Standards and Technology Manufacturing Extension Partnership Advisory Board On-line... Manufacturing Extension Partnership (MEP) Advisory Board will hold an open, on-line meeting via webcast on... their remote location. Questions regarding the on-line meeting should be sent to the...

  6. 76 FR 23314 - Notice of Proposed Information Collection Requests

    Science.gov (United States)

    2011-04-26

    ... Education Type of Review: Extension. Title of Collection: Migrant Education Program (MEP) Migrant Student...) with Migrant Education Programs collect information from state and local education officials who desire access to the Migrant Student Information Exchange (MSIX) system. The form verifies the applicant's...

  7. 76 FR 51004 - Notice of Proposed Information Collection Requests

    Science.gov (United States)

    2011-08-17

    ...: Binational Migrant Education Program (BMEP) State MEP Director Survey. OMB Control Number: 1810-0670. Agency.... Abstract: This survey collects information from State Migrant Education Programs on their participation in the Binational Migrant Education Initiative to serve children who migrate between Mexico and the...

  8. 76 FR 64329 - Notice of Submission for OMB Review

    Science.gov (United States)

    2011-10-18

    ... Type of Review: Extension. Title of Collection: State MEP Director Survey Binational Migrant Education... Estimated Annual Burden Hours: 60. Abstract: This survey collects information from State Migrant Education Programs on their participation in the Binational Migrant Education Initiative to serve children...

  9. 78 FR 40084 - Proposed Requirement-Migrant Education Program Consortium Incentive Grant Program

    Science.gov (United States)

    2013-07-03

    ... Register on March 3, 2004 (69 FR 10110) (2004 Notice), and we have used these final requirements for CIG... final priority for the MEP CIG program in the Federal Register on March 12, 2008 (73 FR 13217), in which... CFR Chapter II Proposed Requirement--Migrant Education Program Consortium Incentive Grant...

  10. Validation of a homology model of Mycobacterium tuberculosis DXS : rationalization of observed activities of thiamine derivatives as potent inhibitors of two orthologues of DXS

    NARCIS (Netherlands)

    Masini, T; Lacy, B; Monjas, L; Hawksley, D; de Voogd, A R; Illarionov, B; Iqbal, A; Leeper, F J; Fischer, M; Kontoyianni, M; Hirsch, A K H

    2015-01-01

    The enzyme DXS catalyzes the first, rate-limiting step of the 2-C-methyl-d-erythritol-4-phosphate (MEP, ) pathway using thiamine diphosphate (ThDP) as cofactor; the DXS-catalyzed reaction constitutes also the first step in vitamin B1 and B6 metabolism in bacteria. DXS is the least studied among the

  11. 运动诱发电位联合体感诱发电位监测在颈动脉内膜切除术中的应用%Application of motor evoked potential in combination with somatosensory evoked potential monitoring during carotid endarterectomy

    Institute of Scientific and Technical Information of China (English)

    梁坤; 乔慧; 刘莉; 杨晓翠

    2016-01-01

    目的 评估运动诱发电位(MEP)联合体感诱发电位(SEP)术中监测颈动脉内膜切除术的优越性、可靠性及临床应用价值.方法 回顾性分析201 1年12月至2013年6月在首都医科大学附属北京天坛医院神经外科行颈动脉内膜切除术的45例颈动脉狭窄患者的临床资料.患者术中常规实施SEP和MEP监测,并分析术中SEP和MEP波幅和潜伏期的变化,分别比较SEP、MEP与MEP+ SEP联合监测的特异性与敏感性的差别,评估联合应用两种方法是否能提高监测的特异性.结果 45例患者中,有4例术后新发轻微的神经功能障碍,所有患者均无卒中、心肌梗死等术后严重并发症.单纯MEP监测的特异性为78% (32/41),单纯SEP监测的特异性为56% (23/41),MEP+SEP联合监测的特异性为95% (39/41).通过配对X2检验分析,单纯MEP监测或单纯SEP监测与MEP+ SEP联合监测相比,差异具有统计学意义(P <0.05);MEP+ SEP联合监测的特异性大大高于单一的监测方法.结论 对颈动脉内膜切除术进行MEP+ SEP联合监测,能大大降低“假阳性”的判断,以便更加精确地帮助术者操作.%Objective To evaluate the superiority,reliability and clinical application value of monitoring carotid endarterectomy in motor evoked potential (MEP) in combination with somatosensory evoked potential (SEP).Methods The clinical data of 45 patients with carotid endarterectomy treated at the Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University from December 2011 to June 2013 were analyzed retrospectively.The patients were monitored by the routine SEP and MEP,and the intraoperative changes of SEP and MEP amplitude and latency were analyzed.The differences of the specificity and sensitivity of SEP,MEP and SEP + MEP monitoring were compared respectively.Whether the combined application of the two methods could improve the specificity of monitoring was evaluated.Results In 45 patients,4 had mild

  12. Expression of the cytoplasmic mevalonate pathway in chloroplasts to reduce substrate limitations for cytoplasmically-produced terpenoid secondary products

    Science.gov (United States)

    All products of isoprenoid metabolism originate with the C5 non-allylic substrate, isopentenyl pyrophosphate (IPP). IPP is produced in plants by two distinct pathways, the mevalonate pathway (MEV) in the cytosol and the 2 C methyl-D-erythritol 4 phosphate (MEP) pathway in plastids. A multi-gene a...

  13. Effects of dietary protein level on growth, health and physiological parameters in growing-furring mink

    DEFF Research Database (Denmark)

    Damgaard, Birthe Marie; Larsen, Peter F.; Clausen, Tove

    2012-01-01

    The aim of the study was to investigate the effects of the dietary protein level and the feeding strategy on growth, health and physiological blood and liver parameters in growing-furring male mink. Effects of dietary protein levels ranging from 22% of metabolizable energy (MEp) to experimental p...

  14. Characteristics and Antitumor Activity of Morchella esculenta Polysaccharide Extracted by Pulsed Electric Field

    Directory of Open Access Journals (Sweden)

    Chao Liu

    2016-06-01

    Full Text Available Polysaccharides from Morchella esculenta have been proven to be functional and helpful for humans. The purpose of this study was to investigate the chemical structure and anti-proliferating and antitumor activities of a Morchella esculenta polysaccharide (MEP extracted by pulsed electric field (PEF in submerged fermentation. The endo-polysaccharide was separated and purified by column chromatography and Gel permeation chromatography, and analyzed by gas chromatography. The MEP with an average molecular weight of 81,835 Da consisted of xylose, glucose, mannose, rhamnose and galactose at the ratio of 5.4:5.0:6.5:7.8:72.3. Structure of MEP was further analyzed by Fourier-transform infrared spectroscopy and 1H and 13C liquid-state nuclear magnetic resonance spectroscopy. Apoptosis tests proved that MEP could inhibit the proliferation and growth of human colon cancer HT-29 cells in a time- and dose-dependent manner within 48 h. This study provides more information on chemical structure of anti-proliferating polysaccharides isolated from Morchella esculenta.

  15. Intraoperative monitoring during decompression of the spinal cord and spinal nerves using transcranial motor-evoked potentials: The law of twenty percent.

    Science.gov (United States)

    Tanaka, Satoshi; Hirao, Jun; Oka, Hidehiro; Akimoto, Jiro; Takanashi, Junko; Yamada, Junichi

    2015-09-01

    Motor-evoked potential (MEP) monitoring was performed during 196 consecutive spinal (79 cervical and 117 lumbar) surgeries for the decompression of compressive spinal and spinal nerve diseases. MEP monitoring in spinal surgery has been considered sensitive to predict postoperative neurological recovery. In this series, transcranial stimulation consisted of trains of five pulses at a constant voltage (200-600 V). For the normalization of MEP, we recorded compound muscle action potentials (CMAP) after peripheral nerve stimulation, usually on the median nerve at the wrist 2 seconds before or after each transcranial stimulation of the motor area, for all operations. The sensitivity and specificity of MEP monitoring was 100% and 97.4%, respectively, or 96.9% with or without CMAP compensation (if the threshold of postoperative motor palsy was defined as 20% relative amplitude rate [RAR]). The mean RAR after CMAP normalization, of the most affected muscle in the patient group with excellent postoperative results (recovery rate of a Japan Orthopedic Association score of more than 50%) was significantly higher than that in the other groups (p=0.0224). All patients with an amplitude increase rate (AIR) with CMAP normalization of more than 20% achieved neurological recovery postoperatively. Our results suggest that if the RAR is more than 20%, postoperative motor palsy can be avoided in spinal surgery. If the AIR with normalization by CMAP after peripheral nerve stimulation is more than 20%, neurological recovery can be expected in spinal surgery. PMID:26142049

  16. Analysis of Potential Energy Saving and CO2 Emission Reduction of Home Appliances and Commercial Equipments in China

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Nan; Fridley, David; McNeil, Michael; Zheng, Nina; Letschert, Virginie; Ke, Jing

    2011-04-01

    China has implemented a series of minimum energy performance standards (MEPS) for over 30 appliances, voluntary energy efficiency label for 40 products and a mandatory energy information label that covers 19 products to date. However, the impact of these programs and their savings potential has not been evaluated on a consistent basis. This paper uses modeling to estimate the energy saving and CO{sub 2} emission reduction potential of the appliances standard and labeling program for products for which standards are currently in place, under development or those proposed for development in 2010 under three scenarios that differ in the pace and stringency of MEPS development. In addition to a baseline 'Frozen Efficiency' scenario at 2009 MEPS level, the 'Continued Improvement Scenario' (CIS) reflects the likely pace of post-2009 MEPS revisions, and the likely improvement at each revision step. The 'Best Practice Scenario' (BPS) examined the potential of an achievement of international best practice efficiency in broad commercial use today in 2014. This paper concludes that under 'CIS', cumulative electricity consumption could be reduced by 9503 TWh, and annual CO{sub 2} emissions of energy used for all 37 products would be 16% lower than in the frozen efficiency scenario. Under a 'BPS' scenario for a subset of products, cumulative electricity savings would be 5450 TWh and annual CO{sub 2} emissions reduction of energy used for 11 appliances would be 35% lower.

  17. Normal cortical excitability in Myoclonus-Dystonia - A TMS study

    NARCIS (Netherlands)

    S.M.A. van der Salm; A.F. van Rootselaar; E.M.J. Foncke; J.H.T.M. Koelman; L.J. Bour; K.P. Bhatia; J.C. Rothwell; M.A.J. Tijssen

    2009-01-01

    OBJECTIVE: The aim of the present study is to investigate cortical excitability in patients with DYT 11 positive Myoclonus-Dystonia (M-D), using transcranial magnetic stimulation (TMS). METHODS: Silent period, motor evoked potential (MEP) recruitment curve, short interval intracortical inhibition (S

  18. Normal cortical excitability in Myoclonus-Dystonia - A TMS study

    NARCIS (Netherlands)

    van der Salm, S. M. A.; van Rootselaar, A. F.; Foncke, E. M. J.; Koelman, J. H. T. M.; Bour, L. J.; Bhatia, K. P.; Rothwell, J. C.; Tijssen, M. A. J.

    2009-01-01

    Objective: The aim of the present study is to investigate cortical excitability in patients with DYT 11 positive Myoclonus-Dystonia (M-D), using transcranial magnetic stimulation (TMS). Methods: Silent period, motor evoked potential (MEP) recruitment curve short interval intracortical, inhibition (S

  19. Comparison of TMS-induced arm activation and upper limb functional tests in hemiparetic stroke

    Directory of Open Access Journals (Sweden)

    Tarkka Ina M.

    2013-01-01

    Full Text Available Stroke has a major impact in the total cost of healthcare in the Western world as stroke is the most common cause of long-term disability [1]. In attempts to enhance motor recovery after stroke effective treatment strategies have been developed in recent years. Appropriate evaluation of the intervention programs requires comprehensive and accurate assessment of the residual abnormal function. In the present study we compare two well-known clinical functional scoring tests developed for the assessment of hemiparetic upper limb function due to stroke and navigated transcranial magnetic stimulation (nTMS, which measures involuntary target muscle response to cortical stimulation. The aim is to investigate the equivalence of these methods and thus add objective evidence of the limb function to strengthen evidence-based practice. In addition to functional tests, four muscles of both arms were studied in twenty chronic stroke patients. Those patients without motor evoked potentials (MEP to nTMS in the affected upper limb had significantly lower total score in Action Research Arm Test and Wolf Motor Function Test and longer performance time than those patients with MEP. Patients, in whom MEP in each of the four target muscles was elicitable, had better than average scores in clinical functional tests while patients, in whom no MEP was elicitable in any target muscle, had worse than average scores. Transcranial magnetic stimulation adds crucial information when clinical assessment based on voluntary activation by command is challenging, e.g. in patients suffering from cognitive deficits.

  20. Effects of Hand Vibration on Motor Output in Chronic Hemiparesis

    Directory of Open Access Journals (Sweden)

    Sibele de Andrade Melo

    2015-01-01

    Full Text Available Background. Muscle vibration has been shown to increase the corticospinal excitability assessed by transcranial magnetic stimulation (TMS and to change voluntary force production in healthy subjects. Objectives. To evaluate the effect of vibration on corticospinal excitability using TMS and on maximal motor output using maximal voluntary contraction (MVC in individuals with chronic hemiparesis. Methodology. Nineteen hemiparetic and 17 healthy control subjects participated in this study. Motor evoked potentials (MEPs and MVC during lateral pinch grip were recorded at first dorsal interosseous muscle in a single session before, during, and after one-minute trials of 80 Hz vibration of the thenar eminence. Results. In hemiparetic subjects, vibration increased MEP amplitudes to a level comparable to that of control subjects and triggered a MEP response in 4 of 7 patients who did not have a MEP at rest. Also, vibration increased the maximal rate of force production (dF/dtmax⁡ in both control and hemiparetic subjects but it did not increase MVC. Conclusion. Motor response generated with a descending cortical drive in chronic hemiparetic subjects can be increased during vibration. Vibration could be used when additional input is needed to reveal motor responses and to increase rate of force generation.

  1. Vertical and horizontal processes in the global atmosphere and the maximum entropy production conjecture

    Directory of Open Access Journals (Sweden)

    S. Pascale

    2012-01-01

    Full Text Available The objective of this paper is to reconsider the Maximum Entropy Production conjecture (MEP in the context of a very simple two-dimensional zonal-vertical climate model able to represent the total material entropy production due at the same time to both horizontal and vertical heat fluxes. MEP is applied first to a simple four-box model of climate which accounts for both horizontal and vertical material heat fluxes. It is shown that, under condition of fixed insolation, a MEP solution is found with reasonably realistic temperature and heat fluxes, thus generalising results from independent two-box horizontal or vertical models. It is also shown that the meridional and the vertical entropy production terms are independently involved in the maximisation and thus MEP can be applied to each subsystem with fixed boundary conditions. We then extend the four-box model by increasing its resolution, and compare it with GCM output. A MEP solution is found which is fairly realistic as far as the horizontal large scale organisation of the climate is concerned whereas the vertical structure looks to be unrealistic and presents seriously unstable features. This study suggest that the thermal meridional structure of the atmosphere is predicted fairly well by MEP once the insolation is given but the vertical structure of the atmosphere cannot be predicted satisfactorily by MEP unless constraints are imposed to represent the determination of longwave absorption by water vapour and clouds as a function of the state of the climate. Furthermore an order-of-magnitude estimate of contributions to the material entropy production due to horizontal and vertical processes within the climate system is provided by using two different methods. In both cases we found that approximately 40 mW m−2 K−1 of material entropy production is due to vertical heat transport and 5–7 mW m−2 K−1 to horizontal heat transport.

  2. 应用MEP、NCV联合诊断糖尿病性神经病%Diagnosis of diabetic neuropathy by motor evoked potentials and nerve conduction velocity

    Institute of Scientific and Technical Information of China (English)

    范秀玉; 邵会全; 董玉芳; 王晶; 魏淑芹

    2001-01-01

    Objective:To study the diagnostic value of Motor evokedpotentials(MEP) and nerve conduction velocity(NCV) in the lesions of motor nerve center,nerve root and peripheral nerve in patients with diabetes mellitus(DM).Methods: MEPs by electrostimulation of cerebral cortex and spinal cord and NCV were performed in 50 patients with DM.Results:The abnormality rate of MEPS was 82%(41/50).The main changes were the prolonged latency and unclear wave form.Central motor conduction time(CMCT) was prolonged in some patients.There was positive correlation between the course of disease and the abnormality rate of MEP.There was no significant relation between the result of MEP and the level of fasting blood sugar.The abnormality rate of NCV was 70%,the main changes were decreased motor conduction velocity(MCV) and sensory conduction velocity(SCV).Conclusions:MEP and NCVmight have an important role in the diagnosis of pyramid tract lesions,nerve root and peripheral nerve lesions,combination of the two methods may provide more complete and objective indexes for function of nevous system in patients with DM.%目的:探讨运动诱发电位(MEP)、神经传导速度(NCV)检测对糖尿病(DM)运动神经中枢及神经根、周围神经病变的诊断价值。方法:检测50例DM病人的MEP及NCV。结果:MEP异常率82%(41/50)。表现皮层、脊髓刺激MEP潜伏期延迟、波形分化欠佳,部分伴有中枢运动传导时间(CMCT)异常。MEP异常率与病程长短呈正相关;空腹血糖水平对MEP结果无明显影响。NCV异常率70%,主要表现运动神经传导速度(MCV)、感觉神经传导速度(SCV)减慢。结论:MEP、NCV检查对诊断DM的锥体束功能损害及神经根、周围神经病变有重要价值,二者结合可对DM的神经系统功能提供全面客观指标。

  3. A dynamic model to optimize municipal electric power systems by considering carbon emission trading under uncertainty

    International Nuclear Information System (INIS)

    In this study, a FFSP (full-infinite fuzzy stochastic programming) method is developed for planning MEPS (municipal electric power systems) associated with GHG (greenhouse gas) control under uncertainty. FFSP can deal with multiple uncertainties presented in terms of fuzzy sets, functional intervals, and random variables. FFSP is also applied to a case study of Beijing for managing MEPS, and reducing the GHG emission through introducing the EU ETS (European Union greenhouse gas emission trading scheme). The results indicate that reasonable solutions have been generated, which can be used for generating schemes of energy resources, electricity production/allocation, and capacity expansion under various economic costs and GHG reduction requirements. The case study demonstrates that FFSP can increase the abilities of reflecting complexities for dynamics of capacity expansion and interaction of multiple uncertainties in MEPS. The results allow in-depth analyses of trade-offs between GHG mitigation and economic objective as well as those between system cost and decision makers' satisfaction degree. Besides, this study can also provide an example to help China construct domestic carbon trading market at municipal scale for addressing the challenges of global climate change. - Highlights: • A dynamic optimization (FFSP) method is developed for tackling uncertainties. • FFSP is applied to planning MEPS (municipal electric power systems) of Beijing. • CET (Carbon emission trading) is introduced into MEPS for mitigating CO2 emissions. • Trade-offs occur between system cost and satisfaction degree under uncertainties. • Results can provide an example to construct domestic CET market in China

  4. Motor cortical plasticity in extrinsic hand muscles is determined by the resting thresholds of overlapping representations.

    Science.gov (United States)

    Mirdamadi, J L; Suzuki, L Y; Meehan, S K

    2016-10-01

    Knowledge of the properties that govern the effectiveness of transcranial magnetic stimulation (TMS) interventions is critical to clinical application. Extrapolation to clinical populations has been limited by high inter-subject variability and a focus on intrinsic muscles of the hand in healthy populations. Therefore, the current study assessed variability of continuous theta burst stimulation (cTBS), a patterned TMS protocol, across an agonist-antagonist pair of extrinsic muscles of the hand. Secondarily, we assessed whether concurrent agonist contraction could enhance the efficacy of cTBS. Motor evoked potentials (MEP) were simultaneously recorded from the agonist flexor (FCR) and antagonist extensor (ECR) carpi radialis before and after cTBS over the FCR hotspot. cTBS was delivered with the FCR relaxed (cTBS-Relax) or during isometric wrist flexion (cTBS-Contract). cTBS-Relax suppressed FCR MEPs evoked from the FCR hotspot. However, the extent of FCR MEP suppression was strongly correlated with the relative difference between FCR and ECR resting motor thresholds. cTBS-Contract decreased FCR suppression but increased suppression of ECR MEPs elicited from the FCR hotspot. The magnitude of ECR MEP suppression following cTBS-Contract was independent of the threshold-amplitude relationships observed with cTBS-Relax. Contraction alone had no effect confirming the effect of cTBS-Contract was driven by the interaction between neuromuscular activity and cTBS. Interactions across muscle representations should be taken into account when predicting cTBS outcomes in healthy and clinical populations. Contraction during cTBS may be a useful means of focusing aftereffects when differences in baseline excitability across overlapping agonist-antagonist cortical representations may mitigate the inhibitory effect of cTBS.

  5. Biomaterial Studies on AISI 316L Stainless Steel after Magnetoelectropolishing

    Directory of Open Access Journals (Sweden)

    Massimiliano Filippi

    2009-03-01

    Full Text Available The polarisation characteristics of the electropolishing process in a magnetic field (MEP – magnetoelectropolishing, in comparison with those obtained under standard/conventional process (EP conditions, have been obtained. The occurrence of an EP plateau has been observed in view of the optimization of MEP process. Up-to-date stainless steel surface studies always indicated some amount of free-metal atoms apart from the detected oxides and hydroxides. Such a morphology of the surface film usually affects the thermodynamic stability and corrosion resistance of surface oxide layer and is one of the most important features of stainless steels. With this new MEP process we can improve metal surface properties by making the stainless steel more resistant to halides encountered in a variety of environments. Furthermore, in this paper the stainless steel surface film study results have been presented. The results of the corrosion research carried out by the authors on the behaviour of the most commonly used material - medical grade AISI 316L stainless steel both in Ringer’s body fluid and in aqueous 3% NaCl solution have been investigated and presented earlier elsewhere, though some of these results, concerning the EIS Nyquist plots and polarization curves are also revealed herein. In this paper an attempt to explain this peculiar performance of 316L stainless steel has been undertaken. The SEM studies, Auger electron spectroscopy (AES and X-ray photoelectron spectroscopy (XPS were performed on 316L samples after three treatments: MP – abrasive polishing (800 grit size, EP – conventional electrolytic polishing, and MEP – magnetoelectropolishing. It has been found that the proposed magnetoelectropolishing (MEP process considerably modifies the morphology and the composition of the surface film, thus leading to improved corrosion resistance of the studied 316L SS.

  6. The Effect of Velocity of Joint Mobilization on Corticospinal Excitability in Individuals With a History of Ankle Sprain.

    Science.gov (United States)

    Fisher, Beth E; Piraino, Andrew; Lee, Ya-Yun; Smith, Jo Armour; Johnson, Sean; Davenport, Todd E; Kulig, Kornelia

    2016-07-01

    Study Design Controlled laboratory study. Background Joint mobilization and manipulation decrease pain and improve patient function. Yet, the processes underlying these changes are not well understood. Measures of corticospinal excitability provide insight into potential mechanisms mediated by the central nervous system. Objectives To investigate the differential effects of joint mobilization and manipulation at the talocrural joint on corticospinal excitability in individuals with resolved symptoms following ankle sprain. Methods Twenty-seven participants with a history of ankle sprain were randomly assigned to the control, joint mobilization, or thrust manipulation group. The motor-evoked potential (MEP) and cortical silent period (CSP) of the tibialis anterior and gastrocnemius were obtained with transcranial magnetic stimulation at rest and during active contraction of the tibialis anterior. The slopes of MEP/CSP input/output curves and the maximal MEP/CSP values were calculated to indicate corticospinal excitability. Behavioral measures, including ankle dorsiflexion and dynamic balance, were evaluated. Results A repeated-measures analysis of variance of the MEP slope showed a significant group-by-time interaction for the tibialis anterior at rest (P = .002) and during active contraction (P = .042). After intervention, the thrust manipulation group had an increase in corticospinal excitability, while the corticospinal excitability decreased in the mobilization group. The thrust manipulation group, but not other groups, also demonstrated a significant increase in the maximal MEP amplitude of the tibialis anterior after intervention. Conclusion The findings suggest that joint manipulation and mobilization have different effects on corticospinal excitability. The increased corticospinal excitability following thrust manipulation may provide a window for physical therapists to optimize muscle recruitment and subsequently movement. The trial was registered at

  7. Different Effects of Startling Acoustic Stimuli (SAS) on TMS-Induced Responses at Rest and during Sustained Voluntary Contraction.

    Science.gov (United States)

    Chen, Yen-Ting; Li, Shengai; Zhou, Ping; Li, Sheng

    2016-01-01

    Previous studies have shown that a habituated startling acoustic stimulus (SAS) can cause a transient suppression of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) during light muscle contraction. However, it is still unknown whether this phenomenon persists when at rest or during a sustained voluntary contraction task. Therefore, the purpose of this study was to determine whether a conditioning SAS has different effects. TMS was delivered to the hot spot for the left biceps on 11 subjects at rest both with and without a conditioning SAS. Of the 11subjects, 9 also had TMS delivered during isometric flexion of the left elbow, also with and without a conditioning SAS. TMS-induced MEPs, TMS-induced force, and silent periods were used to determine the effect of conditioning SAS. Consistent with previous findings, TMS-induced MEPs were smaller with a conditioning SAS (0.49 ± 0.37 mV) as compared without the SAS (0.69 ± 0.52 mV) at rest. However, a conditioning SAS during the voluntary contraction tasks resulted in a significant shortening of the MEP silent period (187.22 ± 22.99 ms with SAS vs. 200.56 ± 29.71 ms without SAS) without any changes in the amplitude of the MEP (1.37 ± 0.9 mV with SAS V.S. 1.32 ± 0.92 mV without SAS) or the TMS-induced force (3.11 ± 2.03 N-m with SAS V.S. 3.62 ± 1.33 N-m without SAS). Our results provide novel evidence that a conditioning SAS has different effects on the excitability of the motor cortex when at rest or during sustained voluntary contractions. PMID:27547181

  8. NUTRITIONAL STRATEGIES TO MITIGATE THE EFFECTS OF NEGATIVE ENERGY BALANCE ON REPRODUCTIVE PERFORMANCE OF EARLY POSTPARTUM DOES

    Directory of Open Access Journals (Sweden)

    Ondieki Gekara

    2012-01-01

    Full Text Available The objective of this study was to research nutritional strategies to mitigate the effects of Negative Energy Balance (NEB on reproductive performance of early postpartum does. Twenty seven does in their second week of lactation and their kids were randomly assigned to three levels of supplement diet, replicated three times. The diets were: (1 Low Energy/Protein supplement level (LEP; Control, (2 Medium Energy/Protein supplement level (MEP, or (3 High Energy/Protein supplement level (HEP. The LEP (control diet was fed at 0.95%, MEP at 1.50% and HEP at 1.90% of BW on a DM basis. The study lasted 28 days. Supplement level did not (p>0.10 reverse the expected loss in doe body condition during the early stages of lactation. The does lost on average 0.056 kg day-1 through the duration of the study. The average body condition score of the does at the start of the experiment was 1.80 (on a scale of 1-5 and 1.75 at the end. The HEP kids tended (p0.10 between HEP and MEP or MEP and LEP kids. The HEP kids gained 0.087 kg day-1; MEP kids gained 0.061 kg day-1 whereas LEP kids gained 0.022 kg day-1. In conclusion, something in addition to high energy/protein supplement level may be needed to mitigate the effects of NEB which is in part responsible for delayed return of ovulatory events in early postpartum does.

  9. Predictive value of intraoperative nerve monitoring for posterior lumbar interbody fusion%不同术中神经监测方法对后路腰椎椎间融合手术的预测作用

    Institute of Scientific and Technical Information of China (English)

    史图龙; 汪萌; 薛静; 彭江; 薛丽娟; 尚咏

    2015-01-01

    目的 比较体感诱发电位(somatosensory evoked potential,SEP)、运动诱发电位(motor evoked potential,MEP)和肌电图(electromyography,EMG)不同组合监测方式对腰椎后路椎板减压椎弓根螺钉固定椎体融合术(posterior lumbar interbody fusion,PLIF)术后结果的预测作用.方法 回顾性研究空军总医院骨科腰椎后路椎管减压融合术临床资料117例,其中66例行SEP+ EMG监测,51例采用MEP+ EMG监测.根据术中监测情况,并与术后结果疗效进行比较,并行统计学分析.结果 MEP+ EMG组手术时间明显少于SEP+ EMG组(P<0.05).SEP+ EMG组患者中,3例出现假阴性,8例为假阳性,1例出现监测信号引出不满意,共3例出现术后症状加重.在MEP+ EMG组中,2例未能引出信号,其中1例术后症状加重.两组监测方法对术后疗效准确性的比较有统计学意义(P<0.05).结论 MEP+ EMG监测反应灵敏,对腰椎融合术的手术结果及疗效有良好的预测作用,且对手术时间的影响更小.

  10. Modulation of corticospinal excitability during acquisition of action sequences by observation.

    Directory of Open Access Journals (Sweden)

    Masanori Sakamoto

    Full Text Available Excitability of the corticospinal pathway increases during observation of an action. However, how corticospinal excitability changes during observation of sequential actions in the course of acquiring novel skills (observational learning remains unexplored. To investigate this, we used a previously unpracticed sequence of ten hand postures. Participants were asked to repeat observation and replication of the sequence. This block of observation and replication was repeated 5 times. During observation of a given hand posture (OK sign, motor-evoked potentials (MEPs elicited by transcranial magnetic stimulation were recorded from hand muscles. In experiment 1, the OK sign appeared in the 9th position of the sequence. Almost all participants could replicate the OK sign only at the 5th block of the experiment. MEP amplitude was greater than that in the control, and decreased with the stages. This suggested that during observational learning of sequential hand postures MEP changed with the progress of the learning. To evaluate this idea, we performed two additional experiments. In experiment 2, the OK sign appeared in the 2nd position. Almost all participants replicated the OK sign even in the 1st block. The MEP amplitude did not change across stages. In experiment 3, the OK sign appeared in the 9th position, but the order of other signs was randomized in every stage. Many participants were not able to replicate the OK sign even during the 5th block of the experiment. The MEP amplitude did not change across stages. These results suggest that: (1 During observational learning modulation of corticospinal excitability is associated with the learning process. (2 Corticospinal excitability decreases as learning progresses.

  11. Distinct changes in cortical and spinal excitability following high-frequency repetitive TMS to the human motor cortex.

    Science.gov (United States)

    Quartarone, Angelo; Bagnato, Sergio; Rizzo, Vincenzo; Morgante, Francesca; Sant'angelo, Antonio; Battaglia, Fortunato; Messina, Corrado; Siebner, Hartwig Roman; Girlanda, Paolo

    2005-02-01

    It has been shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) to the human primary motor hand area (M1-HAND) can induce a lasting increase in corticospinal excitability. Here we recorded motor evoked potentials (MEPs) from the right first dorsal interosseus muscle to investigate how sub-threshold high-frequency rTMS to the M1-HAND modulates cortical and spinal excitability. In a first experiment, we gave 1500 stimuli of 5 Hz rTMS. At an intensity of 90% of active motor threshold, rTMS produced no effect on MEP amplitude at rest. Increasing the intensity to 90% of resting motor threshold (RMT), rTMS produced an increase in MEP amplitude. This facilitatory effect gradually built up during the course of rTMS, reaching significance after the administration of 900 stimuli. In a second experiment, MEPs were elicited during tonic contraction using weak anodal electrical or magnetic test stimuli. 1500 (but not 600) conditioning stimuli at 90% of RMT induced a facilitation of MEPs in the contracting FDI muscle. In a third experiment, 600 conditioning stimuli were given at 90% of RMT to the M1-HAND. Using two well-established conditioning-test paradigms, we found a decrease in short-latency intracortical inhibition (SICI), and a facilitation of the first peak of facilitatory I-waves interaction (SICF). There was no correlation between the relative changes in SICI and SICF. These results demonstrate that subthreshold 5 Hz rTMS can induce lasting changes in specific neuronal subpopulations in the human corticospinal motor system, depending on the intensity and duration of rTMS. Short 5 Hz rTMS (600 stimuli) at 90% of RMT can selectively shape the excitability of distinct intracortical circuits, whereas prolonged 5 Hz rTMS (> or =900 stimuli) provokes an overall increase in excitability of the corticospinal output system, including spinal motoneurones.

  12. Assessment of respiratory muscle strength in children according to the classification of body mass index

    Directory of Open Access Journals (Sweden)

    George Jung da Rosa

    2014-06-01

    Full Text Available OBJECTIVE: To assess and compare the respiratory muscle strength among eutrophic, overweight and obese school children, as well as to identify anthropometric and respiratory variables related to the results.METHODS: Cross-sectional survey with healthy schoolchildren aged 7-9 years old, divided into three groups: Normal weight, Overweight and Obese. The International Study of Asthma and Allergies in Childhood (ISAAC questionnaire was applied. The body mass index (BMI was evaluated, as well as the forced expiratory volume in one second (FEV1 with a portable digital device. The maximal inspiratory and expiratory pressures (MIP and MEP were measured by a digital manometer. Comparisons between the groups were made by Kruskal-Wallis test. Spearman's correlation coefficient was used to analyze the correlations among the variables.RESULTS: MIP of eutrophic school children was higher than MIP found in overweight (p=0.043 and obese (p=0.013 children. MIP was correlated with BMI percentile and weight classification (r=-0.214 and r=-0.256 and MEP was correlated with height (r=0.328. Both pressures showed strong correlation with each other in all analyses (r≥0.773, and less correlation with FEV1 (MIP - r=0.362 and MEP - r=0.494. FEV1 correlated with MEP in all groups (r: 0.429 - 0.569 and with MIP in Obese Group (r=0.565. Age was correlated with FEV1 (r=0.578, MIP (r=0.281 and MEP (r=0.328.CONCLUSIONS: Overweight and obese children showed lower MIP values, compared to eutrophic ones. The findings point to the influence of anthropometric variables on respiratory muscle strength in children.

  13. New Insight into the Time-Course of Motor and Sensory System Changes in Pain.

    Directory of Open Access Journals (Sweden)

    Siobhan M Schabrun

    Full Text Available Pain-related interactions between primary motor (M1 and primary sensory (S1 cortex are poorly understood. In particular, the time-course over which S1 processing and corticomotor output are altered in association with muscle pain is unclear. We aimed to examine the temporal profile of altered processing in S1 and altered corticomotor output with finer temporal resolution than has been used previously.In 10 healthy individuals we recorded somatosensory evoked potentials (SEPs and motor evoked potentials (MEPs in separate sessions at multiple time-points before, during and immediately after pain induced by hypertonic saline infusion in a hand muscle, and at 15 and 25 minutes follow-up.Participants reported an average pain intensity that was less in the session where SEPs were recorded (SEPs: 4.0 ± 1.6; MEPs: 4.9 ± 2.3. In addition, the time taken for pain to return to zero once infusion of hypertonic saline ceased was less for participants in the SEP session (SEPs: 4.7 ± 3.8 mins; MEPs 9.4 ± 7.4 mins. Both SEPs and MEPs began to reduce almost immediately after pain reached 5/10 following hypertonic saline injection and were significantly reduced from baseline by the second (SEPs and third (MEPs recording blocks during pain. Both parameters remained suppressed immediately after pain had resolved and at 15 and 25 minutes after the resolution of pain.These data suggest S1 processing and corticomotor output may be co-modulated in association with muscle pain. Interestingly, this is in contrast to previous observations. This discrepancy may best be explained by an effect of the SEP test stimulus on the corticomotor pathway. This novel finding is critical to consider in experimental design and may be potentially useful to consider as an intervention for the management of pain.

  14. Are somatosensory evoked potentials of the tibial nerve the most sensitive test in diagnosing multiple sclerosis?

    Directory of Open Access Journals (Sweden)

    Djuric S

    2010-01-01

    Full Text Available Background : Multiple sclerosis (MS is mostly diagnosed clinically, but the diagnosis has significantly improved through the use of brain magnetic resonance imaging (MRI, testing of cerebrospinal fluid, and multimodal evoked potentials (MEPs. Even though MRI is the superior method in diagnosing this illness, MEPs remain important because they can detect clinically silent lesions in the sensory and motor pathways of the central nervous system (CNS. Aim : The aim of the study is to test the diagnostic sensitivity of MEPs and MRI and the ratio of their sensitivity in patients with MS. Materials and Methods : The study subjects included 293 patients with MS with disease duration of two to six years: 249 patients with relapsing-remitting (RR MS and 44 with primary-progressive (PP MS. All patients were subjected to an MRI brain scan, visual evoked potentials (VEPs, median somatosensory evoked potentials (SEPs, tibial somatosensory evoked potentials (SEPs, and auditory evoked potentials (AEPs. Abnormal Findings Included : changed wave morphology, interside difference in wave amplitude, absolute and interwave latency increased by 2.5 SD as compared with the control group. The control group comprised of 35 healthy subjects. Results : In this study the most abnormal findings were tibial SEPs, median SEPs, and VEPs. Our results suggest different sensitivity of MEPs in patients suffering from different forms of MS. In RR-MS the sensitivity of tibial SEPs was statically significant (Fischer′s exact probability test as compared to other evoked potential modalities. Similarly VEPs were more sensitive as compared to AEPs. In the PP-MS, median SEPs have been found to be more sensitive than VEPs, while tibial SEPs have been found to be more sensitive than AEPs. There was no significant difference in the sensitivity of MRI and MEPs both the forms of MS. Conclusion : Tibial SEPs produce the most abnormal results and the highest sensitivity in the RR-MS. We

  15. Analysis of Potential Energy Saving and CO2 Emission Reduction of Home Appliances and Commercial Equipments in China

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Nan; Fridley, David; McNeill, Michael; Zheng, Nina; Letschert, Virginie; Ke, Jing; Saheb, Yamina

    2010-06-07

    China is now the world's largest producer and consumer of household appliances and commercial equipment. To address the growth of electricity use of the appliances, China has implemented a series of minimum energy performance standards (MEPS) for 30 appliances, and voluntary energy efficiency label for 40 products. Further, in 2005, China started a mandatory energy information label that covers 19 products to date. However, the impact of these standard and labeling programs and their savings potential has not been evaluated on a consistent basis. This research involved modeling to estimate the energy saving and CO{sub 2} emission reduction potential of the appliances standard and labeling program for products for which standards are currently in place, or under development and those proposed for development in 2010. Two scenarios that have been developed differ primarily in the pace and stringency of MEPS development. The 'Continued Improvement Scenario' (CIS) reflects the likely pace of post-2009 MEPS revisions, and the likely improvement at each revision step considering the technical limitation of the technology. The 'Best Practice Scenario' (BPS) examined the potential of an achievement of international best practice MEPS in 2014. This paper concludes that under the 'CIS' of regularly scheduled MEPS revisions to 2030, cumulative electricity consumption could be reduced by 9503 TWh, and annual CO{sub 2} emissions would be 16% lower than in the frozen efficiency scenario. Under a 'BPS' scenario for a subset of products, cumulative electricity savings would be 5450 TWh and annual CO{sub 2} emissions reduction would be 35% lower than in the frozen scenario.

  16. Intracortical inhibition and facilitation in different representations of the human motor cortex.

    Science.gov (United States)

    Chen, R; Tam, A; Bütefisch, C; Corwell, B; Ziemann, U; Rothwell, J C; Cohen, L G

    1998-12-01

    Intracortical inhibition and facilitation in different representations of the human motor cortex. J. Neurophysiol. 80: 2870-2881, 1998. Intracortical inhibition (ICI) and intracortical facilitation (ICF) of the human motor cortex can be studied with paired transcranial magnetic stimulation (TMS). Plastic changes and some neurological disorders in humans are associated with changes in ICI and ICF. Although well characterized in the hand representation, it is not known if ICI and ICF vary across different body part representations. Therefore we studied ICI and ICF in different motor representations of the human motor cortex. The target muscles were rectus abdominus (RA), biceps brachii (BB), abductor pollicis brevis (APB), quadriceps femoris (QF), and abductor hallucis (AH). For each muscle, we measured the rest and active motor thresholds (MTs), the motor-evoked potential (MEP) stimulus-response curve (MEP recruitment), ICI, and ICF. The effects of different interstimulus intervals (ISIs) were studied with a conditioning stimulus (CS) intensity of 80% active MT. The effects of different CS intensities were studied at ISI of 2 ms for ICI and ISI of 15 ms for ICF. MT was lowest for APB, followed by BB, AH, and QF, and was highest for RA. Except for BB, MEP recruitment was generally steeper for muscles with lower MT. ICI and ICF were present in all the motor representations tested. The stimulus intensity necessary to elicit ICI was consistently lower than that required to elicit ICF, suggesting that they are mediated by separate mechanisms. Despite wide differences in MT and MEP recruitment, the absolute CS intensities (expressed as percentage of the stimulator's output) required to elicit ICI and ICF appear unrelated to MT and MEP recruitment in the different muscles tested. These findings suggest that the intracortical mechanisms for inhibition and facilitation in different motor representations are not related to the strength of corticospinal projections. PMID

  17. Electrophysiological and MRI study on poor outcome after surgery for cervical myelopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kameyama, Osamu; Kawakita, Hirofumi; Ogawa, Ryokei [Kansai Medical Univ., Moriguchi, Osaka (Japan)

    1995-11-01

    Occasionally, the outcome from laminoplasty for cervical spondylosis is disappointing despite an adequate operation. Before surgery, it is difficult to diagnose the pathological extent of the involvement of the spinal cord. The purpose of this study is to determine the efficacy of magnetic resonance imaging (MRI) and of the motor evoked potentials (MEPs) for the indication of the surgery and prognosis. Retrospectively, we investigated the MEPs and the MRI of 31 patients in surgery for cervical myelopathy, involving 21 with cervical spondylosis and 10 with ossification of the posterior longitudinal ligamentum, and compared the findings from those with a poor outcome (n=3l) with the findings from those with a good outcome (n=32). The MEPs from the thenar muscle and the tibialis anterior were evoked by transcranial magnetic brain stimulation. In the poor-outcome patients, the spinal canal was narrow and lumbar spinal canal stenosis was seen in 5 cases which required lumbar laminectomy. Before operation, the MEPs from the thenar muscle could not be evoked in 5 cases while there was a remarkably prolonged central motor conduction time in the other 26 cases. MRI revealed the deformed spinal cord in the involved area, and the signal intensity of the involved spinal cord in the T2 weighted image was remarkably high. The signal intensity ratio was significantly higher in the poor-outcome patients than in the good-outcome patients. This study suggested that a high signal intensity in the T2 weighted image and a prolonged conduction time or absence of MEPs largely corresponded to the clinical and other investigative features of myelopathy responsible for a poor outcome. (author).

  18. Different Effects of Startling Acoustic Stimuli (SAS) on TMS-Induced Responses at Rest and during Sustained Voluntary Contraction.

    Science.gov (United States)

    Chen, Yen-Ting; Li, Shengai; Zhou, Ping; Li, Sheng

    2016-01-01

    Previous studies have shown that a habituated startling acoustic stimulus (SAS) can cause a transient suppression of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) during light muscle contraction. However, it is still unknown whether this phenomenon persists when at rest or during a sustained voluntary contraction task. Therefore, the purpose of this study was to determine whether a conditioning SAS has different effects. TMS was delivered to the hot spot for the left biceps on 11 subjects at rest both with and without a conditioning SAS. Of the 11subjects, 9 also had TMS delivered during isometric flexion of the left elbow, also with and without a conditioning SAS. TMS-induced MEPs, TMS-induced force, and silent periods were used to determine the effect of conditioning SAS. Consistent with previous findings, TMS-induced MEPs were smaller with a conditioning SAS (0.49 ± 0.37 mV) as compared without the SAS (0.69 ± 0.52 mV) at rest. However, a conditioning SAS during the voluntary contraction tasks resulted in a significant shortening of the MEP silent period (187.22 ± 22.99 ms with SAS vs. 200.56 ± 29.71 ms without SAS) without any changes in the amplitude of the MEP (1.37 ± 0.9 mV with SAS V.S. 1.32 ± 0.92 mV without SAS) or the TMS-induced force (3.11 ± 2.03 N-m with SAS V.S. 3.62 ± 1.33 N-m without SAS). Our results provide novel evidence that a conditioning SAS has different effects on the excitability of the motor cortex when at rest or during sustained voluntary contractions.

  19. Sequence Classification: 892238 [

    Lifescience Database Archive (English)

    Full Text Available nthase, an enzyme that catalyzes the second step in the biosynthesis of GMP from inosine 5'-phosphate (IMP); transcription is not sub...ject to regulation by guanine but is negatively regulated by nutrient starvation; Gua1p || http://www.ncbi.nlm.nih.gov/protein/6323873 ...

  20. SwissProt search result: AK106698 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK106698 002-114-D11 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 9e-20 ...

  1. SwissProt search result: AK061902 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061902 001-041-H06 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 3e-14 ...

  2. SwissProt search result: AK119895 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK119895 002-180-C05 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 5e-15 ...

  3. SwissProt search result: AK064089 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064089 002-100-D02 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 8e-25 ...

  4. SwissProt search result: AK107554 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107554 002-130-B02 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 2e-18 ...

  5. SwissProt search result: AK103526 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103526 J033131L11 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 4e-23 ...

  6. SwissProt search result: AK061521 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK061521 006-310-B05 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 6e-19 ...

  7. SwissProt search result: AK064221 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064221 002-104-G01 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 3e-16 ...

  8. SwissProt search result: AK067006 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK067006 J013093O09 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 3e-17 ...

  9. SwissProt search result: AK105961 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK105961 001-205-E02 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 3e-23 ...

  10. SwissProt search result: AK069342 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069342 J023013K12 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 4e-14 ...

  11. SwissProt search result: AK103774 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103774 J033143M23 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 1e-19 ...

  12. SwissProt search result: AK101194 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK101194 J033030J11 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 3e-16 ...

  13. SwissProt search result: AK064342 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK064342 002-107-H07 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 3e-18 ...

  14. SwissProt search result: AK109784 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109784 002-147-C09 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 3e-17 ...

  15. SwissProt search result: AK106518 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK106518 002-107-C02 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 6e-20 ...

  16. SwissProt search result: AK109450 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK109450 001-114-F08 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 1e-24 ...

  17. SwissProt search result: AK108373 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK108373 002-142-D10 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 4e-20 ...

  18. SwissProt search result: AK059748 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK059748 006-203-A07 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 5e-19 ...

  19. SwissProt search result: AK102879 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK102879 J033112G11 (Q8ZCX5) Phosphate import ATP-binding protein pstB 1 (EC 3.6.3.27) (Phosphate...-transporting ATPase 1) (ABC phosphate transporter 1) (Phosphate-specific transport component 1) PSTB1_YERPE 1e-18 ...

  20. AcEST: DK948936 [AcEST

    Lifescience Database Archive (English)

    Full Text Available GYGT+VQN L Sbjct: 582 IPIEVGRGRILLEGTEVALLGYGTMVQNCL 611 >tr|Q84ML9|Q84ML9_ANDPA 1-deoxy-D-xylulose-5-phosphate synthase OS=Andrograp...his paniculata GN=DXS1 PE=2 SV=1 Length = 691 Score = 38

  1. The transcriptional activators AraR and XlnR from Aspergillus niger regulate expression of pentose catabolic and pentose phosphate pathway genes

    NARCIS (Netherlands)

    Battaglia, Evy; Zhou, M.; de Vries, Ronald P; van den Brink, J.

    2014-01-01

    The pentose catabolic pathway (PCP) and the pentose phosphate pathway (PPP) are required for the conversion of pentose sugars in fungi and are linked via d-xylulose-5-phosphate. Previously, it was shown that the PCP is regulated by the transcriptional activators XlnR and AraR in Aspergillus niger. H

  2. A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast

    DEFF Research Database (Denmark)

    Andersen, Gorm; Andersen, Birgit; Dobritzsch, D.;

    2007-01-01

    to characterize the substrate specificity and kinetic parameters of the four enzymes. It was found that the cofactor pyridoxal 5'-phosphate is needed for enzymatic activity and alpha-ketoglutarate, and not pyruvate, as the amino group acceptor. SkPyd4p preferentially uses BAL as the amino group donor (V...

  3. Structural Determinants of the beta-Selectivity of a Bacterial Aminotransferase

    NARCIS (Netherlands)

    Wybenga, Gjalt G.; Crismaru, Ciprian G.; Janssen, Dick B.; Dijkstra, Bauke W.

    2012-01-01

    Chiral beta-amino acids occur as constituents of various natural and synthetic compounds with potentially useful bioactivities. The pyridoxal 5'-phosphate (PLP)-dependent S-selective transaminase from Mesorhizobium sp. strain LUK (MesAT) is a fold type I aminotransferase that can be used for the pre

  4. Mutation of His465 Alters the pH-dependent Spectroscopic Properties of Escherichia coli Glutamate Decarboxylase and Broadens the Range of Its Activity toward More Alkaline pH

    NARCIS (Netherlands)

    Pennacchietti, E.; Lammens, T.M.; Capitani, G.; Franssen, M.C.R.; John, R.A.; Bossa, F.; Biase, De D.

    2009-01-01

    Glutamate decarboxylase (GadB) from Escherichia coli is a hexameric, pyridoxal 5'-phosphate-dependent enzyme catalyzing CO2 release from the a-carboxyl group of l-glutamate to yield ¿-aminobutyrate. GadB exhibits an acidic pH optimum and undergoes a spectroscopically detectable and strongly cooperat

  5. A New Pyridoxal Derivative for Transamination of N-Terminus of Proteins%A New Pyridoxal Derivative for Transamination of N-Terminus of Proteins

    Institute of Scientific and Technical Information of China (English)

    张美娟; 张学梅; 李娟; 郭庆祥

    2011-01-01

    A new pyridoxal-5-phosphate (PLP) derivative FHMDP was developed for the transamination of different pep- tides with three most hindered amino acid residues (Leu, Ile, Val) as their N-terminus. Compared to the previously reported reactions of PLP derivatives, the N-terminus transamination could be accomplished efficiently with the new compound.

  6. Cloning and inactivation of a branched-chain-amino-acid aminotransferase gene from Staphylococcus carnosus and characterization of the enzyme

    DEFF Research Database (Denmark)

    Madsen, Søren M; Beck, Hans Christian; Ravn, Peter;

    2002-01-01

    the transamination of isoleucine, valine, leucine, and, to some extent, methionine using pyridoxal 5'-phosphate as a coenzyme. The ilvE mutant degraded less than 5% of the BCAAs, while the wild-type strain degraded 75 to 95%. Furthermore, the mutant strain produced approximately 100-fold less of the methyl...

  7. Structure of dimeric, recombinant Sulfolobus solfataricus phosphoribosyl diphosphate synthase

    DEFF Research Database (Denmark)

    Andersen, Rune W.; Lo Leggio, Leila; Hove-Jensen, Bjarne;

    2015-01-01

    PRPP synthase as a search model. The two amino acid sequences share 35 % identity. The resulting asymmetric unit consists of three separated dimers. The protein was co-crystallised in the presence of AMP and ribose 5-phosphate, but in the electron density map of the active site only AMP and a sulphate...

  8. Prediagnostic plasma vitamin B6 (pyridoxal 50-phosphate) and survival in patients with colorectal cancer

    Science.gov (United States)

    Higher plasma pyridoxal 5'-phosphate (PLP) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma PLP on survival of patients with colorectal cancer is unknown. We prospectively examined whether prediagnostic plasma PLP levels are associated with mortality...

  9. 40 CFR 63.601 - Definitions.

    Science.gov (United States)

    2010-07-01

    .... For the purposes of this subpart, HAP metals are expressed as particulate matter as measured by 40 CFR part 60, appendix A, Method 5. Phosphate rock calciner means the equipment used to remove moisture and... compounds, including the HAP hydrogen fluoride, as measured by reference methods specified in 40 CFR part...

  10. Discernment of lint trash in raw cotton using multivariate analysis of excitation-emission luminescence spectra

    Science.gov (United States)

    Excitation-Emission luminescence spectra of basic (pH 12.5) phosphate buffer solution extracts were used to distinguish among botanical components of trash within seed cotton. All components were separated from whole plants removed from a field in southern New Mexico. Unfolded Principal Component An...

  11. Structural Basis for Substrate Specificity in Phosphate Binding (beta/alpha)8-Barrels: D-Allulose 6-Phosphate 3-Epimerase from Escherichia coli K-12

    Energy Technology Data Exchange (ETDEWEB)

    Chan,K.; Fedorov, A.; Almo, S.; Gerlt, J.

    2008-01-01

    Enzymes that share the ({beta}/{alpha})8-barrel fold catalyze a diverse range of reactions. Many utilize phosphorylated substrates and share a conserved C-terminal ({beta}/a)2-quarter barrel subdomain that provides a binding motif for the dianionic phosphate group. We recently reported functional and structural studies of d-ribulose 5-phosphate 3-epimerase (RPE) from Streptococcus pyogenes that catalyzes the equilibration of the pentulose 5-phosphates d-ribulose 5-phosphate and d-xylulose 5-phosphate in the pentose phosphate pathway [J. Akana, A. A. Fedorov, E. Fedorov, W. R. P. Novack, P. C. Babbitt, S. C. Almo, and J. A. Gerlt (2006) Biochemistry 45, 2493-2503]. We now report functional and structural studies of d-allulose 6-phosphate 3-epimerase (ALSE) from Escherichia coli K-12 that catalyzes the equilibration of the hexulose 6-phosphates d-allulose 6-phosphate and d-fructose 6-phosphate in a catabolic pathway for d-allose. ALSE and RPE prefer their physiological substrates but are promiscuous for each other's substrate. The active sites (RPE complexed with d-xylitol 5-phosphate and ALSE complexed with d-glucitol 6-phosphate) are superimposable (as expected from their 39% sequence identity), with the exception of the phosphate binding motif. The loop following the eighth {beta}-strand in ALSE is one residue longer than the homologous loop in RPE, so the binding site for the hexulose 6-phosphate substrate/product in ALSE is elongated relative to that for the pentulose 5-phosphate substrate/product in RPE. We constructed three single-residue deletion mutants of the loop in ALSE, ?T196, ?S197 and ?G198, to investigate the structural bases for the differing substrate specificities; for each, the promiscuity is altered so that d-ribulose 5-phosphate is the preferred substrate. The changes in kcat/Km are dominated by changes in kcat, suggesting that substrate discrimination results from differential transition state stabilization. In both ALSE and RPE, the

  12. 经颅磁刺激对夜磨牙患者咬肌运动诱发电位的研究%The masseter motor-evoked potential after transcranial magnetic stimulation in patients with sleep bruxism

    Institute of Scientific and Technical Information of China (English)

    宋宇涵; 黄黄; 王继军; 郭茜; 刘伟才

    2014-01-01

    目的:比较夜磨牙患者与正常对照组经颅磁刺激(TMS)下产生的咬肌运动诱发电位(MEP)的异同。方法:纳入30名夜磨牙患者及30名健康志愿者,单脉冲TMS大脑皮层面部运动区域,记录咬肌MEP,分析比较2组MEP的各项参数。试验均在白天受试者清醒的状态下进行。结果:夜磨牙组咬肌MEP的激发阈值(130%AMT)为53%,对侧MEP(c-MEP)的潜伏期为(6.7±1.3)ms、波幅为0.19(0.15,0.29)mV,三叉神经根MEP(r-MEP)的潜伏期为(2.3±0.4)ms,中枢传导时间(CCT)为4.4(3.3,5.2)ms;正常对照组AMT为52(52,55)%,c-MEP的潜伏期为(6.4±0.7)ms、波幅为0.23(0.17,0.28) mV,r-MEP的潜伏期为(2.4±0.4)ms,CCT为4.0(3.4,4.4)ms,2组咬肌运动诱发电位各项参数均无统计学差别。结论:与正常人相比较,夜磨牙患者大脑皮层运动系统兴奋性未见明显改变。%Objective:To study the masseter motor evoked potential(MEP)in patients with sleep bruxism(SB)and in healthy con-trols.Methods:30 subjects with SB and 30 healthy controls were included.MEPs were obtained by transcranial magnetic stimulation (TMS).Tests were done during daytime when the subjects were awake.The data were statistically analysed.Results:In the patients AMT was 55(52,55)%,latency of c-MEP (6.7 ±1.3)ms,the amplitude of c-MEP 0.19(0.15,0.29)mV,latency of r-MEP (2.3 ±0.4)ms,the central conduction time(CCT)4.4(3.3,5.2)ms.In the control subjects AMT was 52(52,55)%,latency of c-MEP (6.4 ±0.7)ms,the amplitude of c-MEP 0.23(0.17,0.28)mV,latency of r-MEP (2.4 ±0.4)ms,CCT 4.0 (3.4,4.4) ms.No significant difference was found between the 2 groups in the measurements evoked by TMS.Conclusion:The MEP after TMS in patients with SB is similar to that of healthy subjects,indicating that the excitability of the cortical motor system is not changed in bruxism subjects,at least

  13. Urinary concentrations of parabens and their association with demographic factors: A population-based cross-sectional study.

    Science.gov (United States)

    Kang, Hui-Seung; Kyung, Min-Sik; Ko, Ahra; Park, Jae-Hong; Hwang, Myung-Sil; Kwon, Ji-Eun; Suh, Jin-Hyang; Lee, Hee-Seok; Moon, Gui Im; Hong, Jin-Hwan; Hwang, In Gyun

    2016-04-01

    Parabens are broad-spectrum antimicrobial agents used in a range of consumer products, including personal care products, cosmetics, and food. Recently, the widespread use of parabens has raised concerns about the potential health risks associated with their endocrine-disrupting effect. In the present study, 2541 urine samples were collected and analyzed by liquid chromatography-mass spectrometry for the determination of the concentrations of methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP) and butyl paraben (BuP). The detection rate and geometric mean concentrations of parabens in the general population followed the order MeP (97.7%; 116ng/mL)>EtP (97.2%; 24.7ng/mL)>PrP (96.7%; 11.0ng/mL)>BuP (83.5%; 1.13ng/mL). The composition profiles showed that MeP and EtP accounted for >90% of the urinary paraben concentration. We performed statistical analysis in order to evaluate differences between demographic variables and urinary concentrations. Our results showed that adjusted proportional change of MeP, PrP, and BuP in adults were 2.67-6.13 times higher in females than in males. The urinary concentrations of PrP in adults increased significantly with age. The adjusted proportional changes of MeP and PrP in adults were associated with increased body mass index (BMI). The adjusted proportional changes of BuP and PrP in children and adolescents were 1.44 and 1.69 times higher in females than in males. However, there was no clear association between paraben concentrations and demographic variables in the children and adolescents groups. The estimated daily intake (EDIurine) of MeP and EtP in adults were 301μg/kg bw/day, which is lower than the acceptable daily intake (ADI; 10mg/kg bw/day). In summary, our results revealed that the general population in Korea was exposed to parabens during 2009-2010, and most Koreans are exposed to parabens. The urinary levels of parabens varied by age group with demographic factors in the Korean population. The results of

  14. Structure of the (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase from Plasmodium falciparum.

    Science.gov (United States)

    Rekittke, Ingo; Olkhova, Elena; Wiesner, Jochen; Demmer, Ulrike; Warkentin, Eberhard; Jomaa, Hassan; Ermler, Ulrich

    2013-12-11

    Terpenoid precursor biosynthesis occurs in human and many pathogenic organisms via the mevalonate and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways, respectively. We determined the X-ray structure of the Fe/S containing (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase (LytB) of the pathogenic protozoa Plasmodium falciparum which catalyzes the terminal step of the MEP pathway. The cloverleaf fold and the active site of P. falciparum LytB corresponds to those of the Aquifex aeolicus and Escherichia coli enzymes. Its distinct electron donor [2Fe-2S] ferredoxin was modeled to its binding site by docking calculations. The presented structural data provide a platform for a rational search of anti-malarian drugs. PMID:24188825

  15. Remodeling the isoprenoid pathway in tobacco by expressing the cytoplasmic mevalonate pathway in chloroplasts.

    Science.gov (United States)

    Kumar, Shashi; Hahn, Frederick M; Baidoo, Edward; Kahlon, Talwinder S; Wood, Delilah F; McMahan, Colleen M; Cornish, Katrina; Keasling, Jay D; Daniell, Henry; Whalen, Maureen C

    2012-01-01

    Metabolic engineering to enhance production of isoprenoid metabolites for industrial and medical purposes is an important goal. The substrate for isoprenoid synthesis in plants is produced by the mevalonate pathway (MEV) in the cytosol and by the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway in plastids. A multi-gene approach was employed to insert the entire cytosolic MEV pathway into the tobacco chloroplast genome. Molecular analysis confirmed the site-specific insertion of seven transgenes and homoplasmy. Functionality was demonstrated by unimpeded growth on fosmidomycin, which specifically inhibits the MEP pathway. Transplastomic plants containing the MEV pathway genes accumulated higher levels of mevalonate, carotenoids, squalene, sterols, and triacyglycerols than control plants. This is the first time an entire eukaryotic pathway with six enzymes has been transplastomically expressed in plants. Thus, we have developed an important tool to redirect metabolic fluxes in the isoprenoid biosynthesis pathway and a viable multigene strategy for engineering metabolism in plants.

  16. Repetition-induced plasticity of motor representations of action sounds.

    Science.gov (United States)

    Bourquin, Nathalie M-P; Simonin, Alexandre; Clarke, Stephanie

    2013-01-01

    Action-related sounds are known to increase the excitability of motoneurones within the primary motor cortex (M1), but the role of this auditory input remains unclear. We investigated repetition priming-induced plasticity, which is characteristic of semantic representations, in M1 by applying transcranial magnetic stimulation pulses to the hand area. Motor evoked potentials (MEPs) were larger while subjects were listening to sounds related versus unrelated to manual actions. Repeated exposure to the same manual-action-related sound yielded a significant decrease in MEPs when right, hand area was stimulated; no repetition effect was observed for manual-action-unrelated sounds. The shared repetition priming characteristics suggest that auditory input to the right primary motor cortex is part of auditory semantic representations. PMID:23064984

  17. Increase in H-reflex gain following 1 week of immobilization

    DEFF Research Database (Denmark)

    Jensen, Jesper Lundbye; Sørensen, Mie; Nielsen, Jens Bo

    any changes in the flexion torque elicited by supramaximal stimulation of the median nerve. Both at rest and during tonic contraction the H-reflex increased significantly following immobilization without significant changes in Mmax. MEP amplitudes did not change significantly following immobilization...... the effect of 1 week of immobilization on transmission in the corticospinal pathway and the central part of the monosynaptic stretch reflex. In ten healthy volunteers the nondominant forearm, hand and fingers were immobilized by a cast for one week. EMG was obtained from m. Flexor Carpi Radialis (FCR......) and m. Abductor Pollicis Brevis (APB). Motor evoked potentials (MEPS) elicited by transcranial magnetic stimulation and H-reflexes were obtained at rest and during tonic contraction (10% of MVC) in both muscles. Maximal voluntary flexion torque decreased significantly following immobilization without...

  18. Induction of motor associative plasticity in the posterior parietal cortex-primary motor network

    DEFF Research Database (Denmark)

    Chao, Chi-Chao; Karabanov, Anke Ninija; Paine, Rainer;

    2015-01-01

    There is anatomical and functional connectivity between the primary motor cortex (M1) and posterior parietal cortex (PPC) that plays a role in sensorimotor integration. In this study, we applied corticocortical paired-associative stimuli to ipsilateral PPC and M1 (parietal ccPAS) in healthy right......-handed subjects to test if this procedure could modulate M1 excitability and PPC–M1 connectivity. One hundred and eighty paired transcranial magnetic stimuli to the PPC and M1 at an interstimulus interval (ISI) of 8 ms were delivered at 0.2 Hz. We found that parietal ccPAS in the left hemisphere increased...... the excitability of conditioned left M1 assessed by motor evoked potentials (MEPs) and the input–output curve. Motor behavior assessed by the Purdue pegboard task was unchanged compared with controls. At baseline, conditioning stimuli over the left PPC potentiated MEPs from left M1 when ISI was 8 ms...

  19. Effects of a multimodal exercise program on the functional capacity of Parkinson's disease patients considering disease severity and gender

    Directory of Open Access Journals (Sweden)

    Diego Orcioli-Silva

    2014-03-01

    Full Text Available The purpose of this study was to investigate the effects of a multimodal exercise program (MEP on the functional capacity of patients with Parkinson's disease (PD according to disease severity and gender. Fourteen patients with PD participated in the study and were distributed into groups according to 1 stage of disease and 2 gender. Functional capacity was evaluated before and after 6 months of intervention. The overall PD patient group improved their coordination and strength. Men and women improved in strength performance after exercise. Men also improved on coordination. For severity of disease, the unilateral group improved in strength, while the bilateral group improved in strength, balance, coordination and the UPDRS-functional score. In conclusion, a MEP is efficient in improving components of functional capacity in patients with PD, especially in strength. Gender may be considered in the exercise program. Individuals in the bilateral disease group appeared to benefit more from exercise.

  20. European symposium on precision medicine in allergy and airways diseases

    DEFF Research Database (Denmark)

    Muraro, A; Fokkens, W J; Pietikainen, S;

    2015-01-01

    On 14 October 2015, the European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS) and the European Medical Association (EMA) organized a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP...... Effectiveness Group (REG). MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, underlined the importance of the need for a better diagnostic and therapeutic approach for patients with Allergies and Chronic Airways Diseases, and encouraged a joint initiative to control....... This report summarizes the key messages delivered during the symposium by the speakers, including the EU Commissioner for Health and Food Safety Vitenys Andriukaitis. The Commissioner underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient...

  1. Transe maquínico: quando som e movimento se encontram na música eletrônica de pista

    OpenAIRE

    Pedro Peixoto Ferreira

    2008-01-01

    Desde sua emergência histórica em meados da década de 1970, a música eletrônica de pista (MEP) sempre teve como principal objetivo fazer as pessoas dançarem pela escolha criteriosa de músicas dançantes e dos melhores momentos e maneiras para reproduzi-las. Apesar do crescente interesse de pesquisadores de diversas áreas pelo estudo de assuntos relacionados à MEP, nota-se uma certa tendência de reduzi-la a idéias e conceitos forjados para o estudo de estilos musicais que não se baseiam na danç...

  2. Phthalates and parabens in personal care products from China: concentrations and human exposure.

    Science.gov (United States)

    Guo, Ying; Wang, Lei; Kannan, Kurunthachalam

    2014-01-01

    Our previous studies showed that populations in China are widely exposed to phthalates and parabens. Nevertheless, sources of Chinese exposure to phthalates and parabens are not well understood. In this study, we measured concentrations of nine phthalates and six parabens in five categories of personal care products (PCPs, N = 52) collected from Tianjin, China, and estimated human exposure doses to these compounds. The most frequently detected phthalates and parabens in PCPs were diethyl phthalate (DEP) (detection frequency 54 %), methyl paraben (MeP), and n-propyl paraben (PrP) (~75 %). The concentrations of DEP in PCPs ranged from not detected (ND; phthalates (45.5 μg/d). Hand and body lotions were the major contributors to exposures, and the daily exposure doses for DEP, MeP, and PrP from these products were 38.4, 10,200 and 4,890 μg, respectively.

  3. A study of transcranial magnetic stimulation in older (>3 years patients of malnutrition.

    Directory of Open Access Journals (Sweden)

    Karak B

    1999-07-01

    Full Text Available Transcranial magnetic stimulation was performed in 40 subjects. Twenty patients in the age group of 3 to 8 years and having different grades of malnutrition were included in the ′study group′ whereas 20 normal children having no complaints comprised the ′control group′. The coil of the magnetic stimulator was applied tangentially over the vertex to stimulate the cortex. The motor evoked potential (MEP was obtained using root stimulation by applying the coil at the cervical and lumbosacral spines. Recordings were made from the abductor pollicis brevis (APB and extensor digitorum brevis (EDB muscles of both sides. Cortical threshold, latency and amplitude of motor evoked potential and central conduction time were recorded. Malnourished children showed significantly increased cortical threshold, prolonged cortical latency and central conduction time and reduction in amplitude of MEP. Observed delay in central motor conduction in malnourished children suggests asymptomatic involvement of corticospinal pathways.

  4. Short-interval intracortical inhibition is modulated by high-frequency peripheral mixed nerve stimulation.

    Science.gov (United States)

    Murakami, Takenobu; Sakuma, Kenji; Nomura, Takashi; Nakashima, Kenji

    2007-06-01

    Cortical excitability can be modulated by manipulation of afferent input. We investigated the influence of peripheral mixed nerve stimulation on the excitability of the motor cortex. Motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in the right abductor pollicis brevis (APB), extensor carpi radialis (ECR) and first dorsal interosseous (FDI) muscles were evaluated using paired-pulse transcranial magnetic stimulation (TMS) before and after high-frequency peripheral mixed nerve stimulation (150 Hz, 30 min) over the right median nerve at the wrist. The MEP amplitude and SICI of the APB muscle decreased transiently 0-10 min after the intervention, whereas the ICF did not change. High-frequency peripheral mixed nerve stimulation reduced the excitability of the motor cortex. The decrement in the SICI, which reflects the function of GABA(A)ergic inhibitory interneurons, might compensate for the reduced motor cortical excitability after high-frequency peripheral mixed nerve stimulation.

  5. Intra-cortical excitability in healthy human subjects after tongue training

    DEFF Research Database (Denmark)

    Baad-Hansen, Lene; Blicher, Jakob; Lapitskaya, Natallia;

    2009-01-01

    ) and intra-cortical facilitatory (ICF) networks. This study examined changes in SICI and ICF in tongue motor cortex after tongue training in 11 healthy volunteers using ppTMS. Paired pulse TMS was applied to the 'hot-spot' for the tongue motor cortex and motor-evoked potentials (MEPs) were recorded from...... tongue muscles. In tongue motor cortex, bilateral SICI (P 0.063). The success rate improved during training (P ... to changes in single MEP amplitude (P 0.113). This first study of SICI/ICF after tongue training showed no training-related changes in intra-cortical inhibitory or facilitatory networks. However, there was an association between task performance and changes in corticomotor...

  6. Progression from respiratory dysfunction to failure in late-onset Pompe disease.

    Science.gov (United States)

    Berger, Kenneth I; Chan, Yinny; Rom, William N; Oppenheimer, Beno W; Goldring, Roberta M

    2016-08-01

    To identify determinants of respiratory disease progression in late-onset Pompe disease (LOPD), we studied relationships between pulmonary function, respiratory muscle strength, gas exchange, and respiratory control. Longitudinal evaluation of 22 LOPD patients (mean age 38 years) was performed at 6-month intervals for 6-24 months. Measurements included vital capacity (VC), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), tidal volume (VT), dead space (VD), and ventilatory response to CO2. Although reduction in VC correlated with MIP and MEP (p respiratory failure, is tightly linked to the degree of respiratory muscle weakness and severity of pulmonary dysfunction in LOPD patients. Reductions in CO2 clearance efficiency and ventilatory responsiveness may contribute to the development of chronic daytime hypercapnia.

  7. Theoretical Studies on Reaction Mechanisms of HNCS with NH (X3∑)

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The reaction mechanisms of HNCS with NH(X3∑) were theoretically investigated. The minimum energy paths (MEP) of the reaction were calculated by using the density functional theory(DFT) at the B3LYP/6-311 + + G** level. The equilibrium structural parameters, the harmonic vibrational frequencies, the total energies, and the zeropoint energies(ZPE) of all the species were calculated. The single-point energies along the MEP were further refined at the QCISD(T)/6-311 + + G** level. It was found that the mechanisms of the HNCS + NH(X3∑) reaction involve two channels producing the HNC + HNS and the N2H2 + CS products. Channel 1 plays a dominant role and the HNC + HNS are the main products. The reaction is exothermic.

  8. Outcome after total elbow arthroplasty

    DEFF Research Database (Denmark)

    Plaschke, Hans Christian; Thillemann, Theis M; Brorson, Stig;

    2015-01-01

    BACKGROUND: Total elbow arthroplasties (TEAs) are traditionally grouped into linked and unlinked design. The aim was to analyze the difference in clinical outcomes after TEA based on implant design and indication for surgery and to evaluate primary and revision TEAs. METHODS: A total of 167 TEAs...... (126 primary and 41 revision TEAs) in 141 patients were evaluated with patient-reported outcome measure by the Oxford Elbow Score (OES) and clinically assessed with the Mayo Elbow Performance Score (MEPS), range of motion (ROM), and standard radiographs. RESULTS: The mean follow-up was 10.5 years for...... primary and 7.5 years for revision TEAs. There was no difference in OES or MEPS between linked and unlinked primary TEAs. The OES score in the social-psychological domain was significantly lower in TEAs performed due to fracture (67) compared with rheumatoid arthritis (81; P = .025). ROM in extension...

  9. The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond.

    Science.gov (United States)

    Stopa, Nicole; Krebs, Jocelyn E; Shechter, David

    2015-06-01

    Post-translational arginine methylation is responsible for regulation of many biological processes. The protein arginine methyltransferase 5 (PRMT5, also known as Hsl7, Jbp1, Skb1, Capsuleen, or Dart5) is the major enzyme responsible for mono- and symmetric dimethylation of arginine. An expanding literature demonstrates its critical biological function in a wide range of cellular processes. Histone and other protein methylation by PRMT5 regulate genome organization, transcription, stem cells, primordial germ cells, differentiation, the cell cycle, and spliceosome assembly. Metazoan PRMT5 is found in complex with the WD-repeat protein MEP50 (also known as Wdr77, androgen receptor coactivator p44, or Valois). PRMT5 also directly associates with a range of other protein factors, including pICln, Menin, CoPR5 and RioK1 that may alter its subcellular localization and protein substrate selection. Protein substrate and PRMT5-MEP50 post-translation modifications induce crosstalk to regulate PRMT5 activity. Crystal structures of C. elegans PRMT5 and human and frog PRMT5-MEP50 complexes provide substantial insight into the mechanisms of substrate recognition and procession to dimethylation. Enzymological studies of PRMT5 have uncovered compelling insights essential for future development of specific PRMT5 inhibitors. In addition, newly accumulating evidence implicates PRMT5 and MEP50 expression levels and their methyltransferase activity in cancer tumorigenesis, and, significantly, as markers of poor clinical outcome, marking them as potential oncogenes. Here, we review the substantial new literature on PRMT5 and its partners to highlight the significance of understanding this essential enzyme in health and disease.

  10. The Natural Philosophy of Work

    Directory of Open Access Journals (Sweden)

    Stanley N. Salthe

    2007-06-01

    Full Text Available Work, by dissipative structures (DS, imposes delay on energy gradientdegradation. It diverts energy flow into DS maintenance while enhancing energy degradation.DS can be viewed as tradeoffs between enhancing entropy production maximization (themaximum entropy production principle, MEP by way of convective gradient degradation,and the need to maintain DS form, which is what mediates the convective dissipation. Thistradeoff frameworked the origin of living DS. In the Big Bang, the Universe departedincreasingly from an ordered state of low entropy. As a result the Second Law (locally, dS>or = 0 became an ever more powerful attractor, insuring that work could have only limitedenergy efficiency (utilization / throughput. That is, the ‘>’ in ‘dS > or = 0’ increased onaverage locally as the universe departed further from thermodynamic equilibrium. Energyefficiency becomes significant in the context of possible energy shortage, which impliesembodied agency, implying in turn the possibility of some stability into the future. Energyefficiency is needed in living DS which yet serve MEP by becoming relatively less energyefficient when striving. Biodiversity multiplies modes of energy consumption, alsofurthering MEP by compensating for the diversion of energy flow into the maintenance ofliving DS. Modular (hierarchical structure is very stable to perturbations, and also generatesthe variety requisite for adaptive flexibility, affording as well evolutionary access toincreased adjacent possibilities. Dynamical rate separation between hierarchical levelsstreamlines energy flows, enhancing orderly energy gradient degradation. I conjecture thatnew levels are interpolated when that fosters MEP overall. Of the three phases of energyflow -- low level conduction, mid level convection, and high level explosion -- orderlyconvection associates with DS form, constraining moderated energy flows, and defusingpotential

  11. Abnormal Modulation of Corticospinal Excitability in Adults with Asperger’s Syndrome

    OpenAIRE

    Oberman, Lindsay; Eldaief, Mark; Fecteau, Shirley; Ifert-Miller, Fritz; Tormos, Jose Maria; Pascual-Leone, Alvaro

    2012-01-01

    Most candidate genes and genetic abnormalities linked to autism spectrum disorders (ASD) are thought to play a role in developmental and experience-dependent plasticity. As a possible index of plasticity, we assessed the modulation of motor corticospinal excitability in individuals with Asperger’s Syndrome (AS) using transcranial magnetic stimulation (TMS). We measured the modulatory effects of Theta Burst Stimulation (TBS) on motor evoked potentials (MEPs) induced by single-pulse TMS in indi...

  12. Why all our top parties are doing voters a disservice by cramming the European Parliament ballot papers with the names of ‘no hope’ candidates

    OpenAIRE

    Dunleavy, Patrick; Hopkin, Jonathan; Kippin, Sean

    2014-01-01

    When British voters go to the polls on 22 May to elect MEPs to the European Parliament for another five years, they will face complex ballot papers with large number of candidates on them. The Democratic Audit team explain how the List PR system works and show how all the major parties follow practices that makes the ballot papers far more difficult for voters to understand than they could be.

  13. 7,7′-Bis[(aza-18-crown-6)carbonyl]thioindigo: Synthesis, Experimental, Theoretical Characterization and Biological Activities

    OpenAIRE

    Koparır, Metin

    2013-01-01

    This work presents the characterization of 7,7'-Bis[(aza-18-crown-6)carbonyl]thioindigo (I) by quantum chemical calculations and spectral techniques. The molecular geometry, frontier molecular orbitals (FMO), molecular electrostatic potentials (MEP) and nonlinear optical properties of I in the ground state have been calculated using the density functional method (B3LYP) with the 6−31G(d,p) basis set. The calculated results show that the optimized geometry can well reproduce the crystal struct...

  14. Age and muscle-dependent variations in corticospinal excitability during standing tasks.

    Directory of Open Access Journals (Sweden)

    Anthony Remaud

    Full Text Available In this study, we investigated how modulation in corticospinal excitability elicited in the context of standing tasks varies as a function of age and between muscles. Changes in motor evoked potentials (MEPs recorded in tibialis anterior (TA and gastrocnemius lateralis (GL were monitored while participants (young, n = 10; seniors, n = 11 either quietly stood (QS or performed a heel raise (HR task. In the later condition, transcranial magnetic stimulation (TMS pulses were delivered at three specific time points during the task: 1 250 ms before the "go" cue (preparatory (PREP phase, 2 100 ms before the heel rise (anticipatory postural adjustment (APA phase, and 3 200 ms after heel rise (execution (EXEC phase. In each task and each phase, variations in MEP characteristics were analysed for age and muscle-dependent effects. Variations in silent period (SP duration were also examined for certain phases (APA and EXEC. Our analysis revealed no major difference during QS, as participants exhibited very similar patterns of modulation in both TA and GL, irrespective of their age group. During the HR task, young adults exhibited a differential modulation in the PREP phase with enhanced responses in TA relative to GL, which was not seen in seniors. Finally, besides differences in MEP latency, age had little influence on MEP modulation during the APA and EXEC phases, where amplitude was largely a function of background muscle activity associated with each phase (i.e., APA: TA; EXEC: GL. No age or muscle effects were detected for SP measurements. Overall, our results revealed no major differences between young adults and healthy seniors in the ability to modulate corticospinal facilitation destined to ankle muscles during standing tasks, with maybe the exception of the ability to prime muscle synergies in the preparatory phase of action.

  15. Analysis of the Isoprenoid Biosynthesis Pathways in Listeria monocytogenes Reveals a Role for the Alternative 2-C-Methyl-d-Erythritol 4-Phosphate Pathway in Murine Infection▿

    OpenAIRE

    Begley, Máire; Bron, Peter A; Heuston, Sinead; Casey, Pat G.; Englert, Nadine; Wiesner, Jochen; Jomaa, Hassan; Gahan, Cormac G. M.; Hill, Colin

    2008-01-01

    Most bacteria synthesize isoprenoids through one of two essential pathways which provide the basic building block, isopentyl diphosphate (IPP): either the classical mevalonate pathway or the alternative non-mevalonate 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway. However, postgenomic analyses of the Listeria monocytogenes genome revealed that this pathogen possesses the genetic capacity to produce the complete set of enzymes involved in both pathways. The nonpathogenic species Listeria i...

  16. Francisella tularensis 2-C-Methyl-D-Erythritol 4-Phosphate Cytidylyltransferase: Kinetic Characterization and Phosphoregulation

    OpenAIRE

    Arthur Tsang; Heather Seidle; Safdar Jawaid; Weidong Zhou; Clint Smith; Couch, Robin D.

    2011-01-01

    Deliberate and natural outbreaks of infectious disease, the prevalence of antibiotic resistant strains, and the ease by which antibiotic resistant bacteria can be intentionally engineered all underscore the necessity of effective vaccines and continued development of novel antimicrobial/antiviral therapeutics. Isoprenes, a group of molecules fundamentally involved in a variety of crucial biological functions, are derived from either the mevalonic acid (MVA) or methylerythritol phosphate (MEP)...

  17. Identification of Novel Small Molecule Inhibitors of 4-diphosphocytidyl-2-C-methyl-D-erythritol (CDP-ME) kinase of Gram-negative bacteria

    OpenAIRE

    Tang, M; Odejinmi, SI; Allette, YM; Vankayalapati, H; Lai, K.

    2011-01-01

    The biosyntheses of isoprenoids is essential for the survival in all living organisms, and requires one of the two biochemical pathways: (a) Mevalonate (MVA) Pathway or (b) Methylerythritol Phosphate (MEP) Pathway. The latter pathway, which is used by all Gram-negative bacteria, some Gram-positive bacteria and a few apicomplexan protozoa, provides an attractive target for the development of new antimicrobials because of its absence in humans. In this report, we describe two different approach...

  18. Synthesis of Methylerythritol Phosphate Analogues and Their Evaluation as Alternate Substrates for IspDF and IspE from Agrobacterium tumefaciens

    OpenAIRE

    Krasutsky, Sergiy G.; Urbansky, Marek; Davis, Chad E.; Lherbet, Christian; Coates, Robert M.; Poulter, C. Dale

    2014-01-01

    The methylerythritol phosphate biosynthetic pathway, found in most Bacteria, some parasitic protists, and plant chloroplasts, converts d-glyceraldehyde phosphate and pyruvate to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), where it intersects with the mevalonate pathway found in some Bacteria, Archaea, and Eukarya, including the cytosol of plants. d-3-Methylerythritol-4-phosphate (MEP), the first pathway-specific intermediate in the pathway, is converted to IPP and DMA...

  19. Study on motor evoked potential of Arnoid-Chiari malformation%运动诱发电位在 Arnoid-Chiari畸形诊治中的应用价值

    Institute of Scientific and Technical Information of China (English)

    徐伟; 徐启武; 李盛昌

    2001-01-01

    Objective To study the electrical stimulation motor evokedpotentials in Arnoid-Chiari malformation.Methods Electrical stimulation motor evoked potentials were recorded in 30 cases with Arnoid-Chiari malformation proved by MRI.Results Abnormality rate of MEP was 96.7%,and the abnormal patterns mainly consisted of the delay of latency and the delay of central motor conduction time(CMCT). The change of MEP was connected with myodynamia and the type of Arnoid-Chiari malformation .Conclusions The change of MEP is more sensitive than clinical change, and can indicate the damage of the motor function objectively and quantitatively, and MEP can be used as an objective criterion for surgical effect, and can predict the recovery of motor function.%目的 探讨Arnoid-Chiari畸形(ACM)患者运动诱发电位(MEP)的变化规律。方法 经MRI证实的30例Arnoid-Chiari畸形患者接受电刺激运动诱发电位测试,对其中20例进行术后复查。结果 Arnoid-Chiari畸形患者MEP的中枢运动传导时间(CMCT)延长,异常率为96.7%(29/30),肌力减退愈重,MEP异常愈明显,Arnoid-Chiari畸形Ⅱ型的MEP异常较Ⅰ型更显著,MEP的改变与肌力的改变明显相关。结论 MEP改变比临床评定更为敏感,且能反映运动功能的损害程度;MEP可预测预后,能作为评定手术效果的客观指标。

  20. Left dorsal speech stream components and their contribution to phonological processing.

    Science.gov (United States)

    Murakami, Takenobu; Kell, Christian A; Restle, Julia; Ugawa, Yoshikazu; Ziemann, Ulf

    2015-01-28

    Models propose an auditory-motor mapping via a left-hemispheric dorsal speech-processing stream, yet its detailed contributions to speech perception and production are unclear. Using fMRI-navigated repetitive transcranial magnetic stimulation (rTMS), we virtually lesioned left dorsal stream components in healthy human subjects and probed the consequences on speech-related facilitation of articulatory motor cortex (M1) excitability, as indexed by increases in motor-evoked potential (MEP) amplitude of a lip muscle, and on speech processing performance in phonological tests. Speech-related MEP facilitation was disrupted by rTMS of the posterior superior temporal sulcus (pSTS), the sylvian parieto-temporal region (SPT), and by double-knock-out but not individual lesioning of pars opercularis of the inferior frontal gyrus (pIFG) and the dorsal premotor cortex (dPMC), and not by rTMS of the ventral speech-processing stream or an occipital control site. RTMS of the dorsal stream but not of the ventral stream or the occipital control site caused deficits specifically in the processing of fast transients of the acoustic speech signal. Performance of syllable and pseudoword repetition correlated with speech-related MEP facilitation, and this relation was abolished with rTMS of pSTS, SPT, and pIFG. Findings provide direct evidence that auditory-motor mapping in the left dorsal stream causes reliable and specific speech-related MEP facilitation in left articulatory M1. The left dorsal stream targets the articulatory M1 through pSTS and SPT constituting essential posterior input regions and parallel via frontal pathways through pIFG and dPMC. Finally, engagement of the left dorsal stream is necessary for processing of fast transients in the auditory signal.