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Sample records for hybrid polyketide-terpenoid metabolites

  1. Hybrid isoprenoid secondary metabolite production in terrestrial and marine actinomycetes.

    Science.gov (United States)

    Gallagher, Kelley A; Fenical, William; Jensen, Paul R

    2010-12-01

    Terpenoids are among the most ubiquitous and diverse secondary metabolites observed in nature. Although actinomycete bacteria are one of the primary sources of microbially derived secondary metabolites, they rarely produce compounds in this biosynthetic class. The terpenoid secondary metabolites that have been discovered from actinomycetes are often in the form of biosynthetic hybrids called hybrid isoprenoids (HIs). HIs include significant structural diversity and biological activity and thus are important targets for natural product discovery. Recent screening of marine actinomycetes has led to the discovery of a new lineage that is enriched in the production of biologically active HI secondary metabolites. These strains represent a promising resource for natural product discovery and provide unique opportunities to study the evolutionary history and ecological functions of an unusual group of secondary metabolites. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Hesseltin A, a novel antiviral metabolite from Penicillium hesseltinei

    DEFF Research Database (Denmark)

    Phipps, Richard Kerry; Petersen, B.O.; Christensen, K.B.;

    2004-01-01

    Hesseltin A(1), a novel compound of mixed polyketide-terpenoid origins was isolated from the filamentous fungus Penicillium hesseltinei. The structure and stereochemistry were determined from extensive one- and two-dimensional NMR and mass spectral data.......Hesseltin A(1), a novel compound of mixed polyketide-terpenoid origins was isolated from the filamentous fungus Penicillium hesseltinei. The structure and stereochemistry were determined from extensive one- and two-dimensional NMR and mass spectral data....

  3. Metabolite variation in hybrid corn grain from a large-scale multisite study

    Institute of Scientific and Technical Information of China (English)

    Mingjie Chen; R Shyama Prasad Rao; Yiming Zhang; Cathy Zhong; Jay J Thelen

    2016-01-01

    Metabolite composition is strongly affected by genotype, environment, and interactions between genotype and environment, although the extent of variation caused by these factors may depend upon the type of metabolite. To characterize the complexity of genotype, environment, and their interaction in hybrid seeds, 50 genetically diverse non-genetically modified (GM) maize hybrids were grown in six geographically diverse locations in North America. Polar metabolites from 553 harvested corn grain samples were isolated and analyzed by gas chromatography–mass spectrometry and 45 metabolites detected in all samples were used to generate a data matrix for statistical analysis. There was moderate variation among biological replicates and across genotypes and test sites. The genotype effects were detected by univariate and Hierarchical clustering analyses (HCA) when environmental effects were excluded. Overall, environment exerted larger effects than genotype, and polar metabolite accumulation showed a geographic effect. We conclude that it is possible to increase seed polar metabolite content in hybrid corn by selection of appropriate inbred lines and growing regions.

  4. Metabolite variation in hybrid corn grain from a large-scale multisite study

    Directory of Open Access Journals (Sweden)

    Mingjie Chen

    2016-06-01

    Full Text Available Metabolite composition is strongly affected by genotype, environment, and interactions between genotype and environment, although the extent of variation caused by these factors may depend upon the type of metabolite. To characterize the complexity of genotype, environment, and their interaction in hybrid seeds, 50 genetically diverse non-genetically modified (GM maize hybrids were grown in six geographically diverse locations in North America. Polar metabolites from 553 harvested corn grain samples were isolated and analyzed by gas chromatography–mass spectrometry and 45 metabolites detected in all samples were used to generate a data matrix for statistical analysis. There was moderate variation among biological replicates and across genotypes and test sites. The genotype effects were detected by univariate and Hierarchical clustering analyses (HCA when environmental effects were excluded. Overall, environment exerted larger effects than genotype, and polar metabolite accumulation showed a geographic effect. We conclude that it is possible to increase seed polar metabolite content in hybrid corn by selection of appropriate inbred lines and growing regions.

  5. Investigating the drought-stress response of hybrid poplar genotypes by metabolite profiling.

    Science.gov (United States)

    Barchet, Genoa L H; Dauwe, Rebecca; Guy, Robert D; Schroeder, William R; Soolanayakanahally, Raju Y; Campbell, Malcolm M; Mansfield, Shawn D

    2014-11-01

    Drought stress is perhaps the most commonly encountered abiotic stress plants experience in the natural environment, and it is one of the most important factors limiting plant productivity. Here, we employed untargeted metabolite profiling to examine four drought-stressed hybrid poplar (Populus spp.) genotypes for their metabolite content, using gas chromatography coupled to mass spectrometry. The primary objective of these analyses was to characterize the metabolite profile of poplar trees to assess relative drought resistance and to investigate the underlying biochemical mechanisms employed by the genotypes to combat drought. Metabolite profiling identified key metabolites that increased or decreased in relative abundance upon exposure to drought stress. Overall, amino acids, the antioxidant phenolic compounds catechin and kaempferol, as well as the osmolytes raffinose and galactinol exhibited increased abundance under drought stress, whereas metabolites involved in photorespiration, redox regulation and carbon fixation showed decreased abundance under drought stress. One clone in particular, Okanese, displayed unique responses to the imposed drought conditions. This clone was found to have higher leaf water potential, but lower growth rate relative to the other clones tested. Okanese also had lower accumulation of osmolytes such as raffinose, galactinol and proline, but higher overall levels of antioxidants such as catechin and dehydroascorbic acid. As such, it was proposed that osmotic adjustment as a mechanism for drought avoidance in this clone is not as well developed in comparison with the other clones investigated in this study, and that a possible alternative mechanism for the enhanced drought avoidance displayed by Okanese may be due to differential allocation of resources or better retention of water.

  6. 2-Aminoacetophenone Is the Main Volatile Phase I Skatole Metabolite in Pietrain × Baden-Württemberg Hybrid Type Boars.

    Science.gov (United States)

    Gerlach, Christoph; Elsinghorst, Paul W; Schmarr, Hans-Georg; Wüst, Matthias

    2016-02-10

    Skatole metabolites have been considered as putative contributors to boar taint. Recently, 2-aminoacetophenone, a volatile phase I skatole metabolite, was identified in back fat samples from boars of Pietrain × Baden-Württemberg hybrid type. This paper addresses the question of the physiological origin of the observed 2-aminoacetophenone in these pigs. Microsomal fractions from nine boars were isolated, and formation of skatole metabolites was subsequently analyzed by stable-isotope dilution analysis (SIDA) using headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME/GC-MS). Significant breed-related differences in phase I skatole metabolism were observed, explaining the high levels of 2-aminoacetophenone in Pietrain × Baden-Württemberg hybrid type boars.

  7. Neurotoxicity of isoniazid and its metabolites in cultures of mouse dorsal root ganglion neurons and hybrid neuronal cell line.

    Science.gov (United States)

    Sanfeliu, C; Wright, J M; Kim, S U

    1999-12-01

    Isoniazid (INH) is one of the anti-tuberculosis drugs widely prescribed for patients since the early 1950s. It is relatively nontoxic but some patients develop peripheral neuropathy attributed to a disturbance of vitamin B6 metabolism. Some isoniazid metabolites are hepatotoxic but little is known about their neurotoxic property. Isoniazid and its metabolites including acetylisoniazid, acetylhydrazine, diacetylhydrazine, isonicotinic acid and hydrazine were examined for their potential neurotoxic effects in cultured mouse dorsal root ganglion (DRG) neurons and mouse neuroblastoma x DRG neuron hybrid cell line N18D3. Isoniazid did not cause neurotoxicity at exposures up to 7 days. Hydrazine was found to be the most toxic metabolite with LC50 values of 2.7 mM and 0.3 mM after 7 days of exposure in DRG neurons and N18D3 hybrid neurons, respectively. Other metabolites including acetylisoniazid, acetylhydrazine, diacetylhydrazine and isonicotinic acid had moderate to minor neurotoxic effects on N18D3 hybrid neurons. Pyridoxine, which is used in clinical practice to prevent or ameliorate the isoniazid-induced neuropathy, did not consistently reverse the neurotoxicity of any of the metabolites in the cell cultures, but some interaction with hydrazine cannot be ruled out. Pyridoxine itself was found to be neurotoxic both in DRG neurons and N18D3 hybrid neurons, in agreement with human peripheral sensory neuropathy caused by prolonged overdosage. The enzymes catalase and superoxide dismutase and the antioxidant agent selenium showed some protection against hydrazine neurotoxicity, suggesting an involvement of the generation of reactive oxygen species in the pathogenesis of isoniazid neuropathy. Both mouse DRG neurons and N18D3 mouse hybrid neurons were shown to be useful culture systems for elucidating the neurotoxicity mechanisms of agents causing sensory neuropathies and general neurotoxic effects in the nervous system.

  8. Biosynthesis-Based Quantitative Analysis of 151 Secondary Metabolites of Licorice To Differentiate Medicinal Glycyrrhiza Species and Their Hybrids.

    Science.gov (United States)

    Song, Wei; Qiao, Xue; Chen, Kuan; Wang, Ying; Ji, Shuai; Feng, Jin; Li, Kai; Lin, Yan; Ye, Min

    2017-03-07

    Secondary metabolites are usually the bioactive components of medicinal plants. The difference in the secondary metabolisms of closely related plant species and their hybrids has rarely been addressed. In this study, we conducted a holistic secondary metabolomics analysis of three medicinal Glycyrrhiza species (G. uralensis, G. glabra, and G. inflata), which are used as the popular herbal medicine licorice. The Glycyrrhiza species (genotype) for 95 batches of samples were identified by DNA barcodes of the internal transcribed spacer and trnV-ndhC regions, and the chemotypes were revealed by LC/UV- or LC/MS/MS-based quantitative analysis of 151 bioactive secondary metabolites, including 17 flavonoid glycosides, 24 saponins, and 110 free phenolic compounds. These compounds represented key products in the biosynthetic pathways of licorice. For the 76 homozygous samples, the three Glycyrrhiza species showed significant biosynthetic preferences, especially in coumarins, chalcones, isoflavanes, and flavonols. In total, 27 species-specific chemical markers were discovered. The 19 hybrid samples indicated that hybridization could remarkably alter the chemical composition and that the male parent contributed more to the offspring than the female parent did. This is hitherto the largest-scale targeted secondary metabolomics study of medicinal plants and the first report on uniparental inheritance in plant secondary metabolism. The results are valuable for biosynthesis, inheritance, and quality control studies of licorice and other medicinal plants.

  9. Unambiguous Metabolite Identification in High-Throughput Metabolomics by Hybrid 1H-NMR/ESI-MS1 Approach

    Energy Technology Data Exchange (ETDEWEB)

    2016-10-18

    The invention improves accuracy of metabolite identification by combining direct infusion ESI-MS with one-dimensional 1H-NMR spectroscopy. First, we apply a standard 1H-NMR metabolite identification protocol by matching the chemical shift, J-coupling and intensity information of experimental NMR signals against the NMR signals of standard metabolites in a metabolomics reference libraries. This generates a list of candidate metabolites. The list contains both false positive and ambiguous identifications. The software tool (the invention) takes the list of candidate metabolites, generated from NMRbased metabolite identification, and then calculates, for each of the candidate metabolites, the monoisotopic mass-tocharge (m/z) ratios for each commonly observed ion, fragment and adduct feature. These are then used to assign m/z ratios in experimental ESI-MS spectra of the same sample. Detection of the signals of a given metabolite in both NMR and MS spectra resolves the ambiguities, and therefore, significantly improves the confidence of the identification.

  10. Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.

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    Cécile Pierre-Eugene

    Full Text Available BACKGROUND: In diabetic patients, the pharmacokinetics of injected human insulin does not permit optimal control of glycemia. Fast and slow acting insulin analogues have been developed, but they may have adverse properties, such as increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors (IR/IGF1R, present in most tissues, have been proposed to transmit biological effects close to those of IGF1R. However, the study of hybrid receptors is difficult because of the presence of IR and IGF1R homodimers. Our objective was to perform the first study on the pharmacological properties of the five marketed insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of insulin analogues on IR/IGF1R hybrids, we used our previously developed Bioluminescence Resonance Energy Transfer (BRET assay that permits specific analysis of the pharmacological properties of hybrid receptors. Moreover, we have developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol-3 phosphate (PIP(3 production in living cells. Using this assay, we performed a detailed pharmacological analysis of PIP(3 production induced by IGF1, insulin and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells. RESULTS: Among the five insulin analogues tested, only glargine stimulated IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close to that of IGF1. Glargine more efficiently stimulated PIP(3 production in MCF-7 cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine metabolites M1 and M2 showed lower potency for hybrid receptors stimulation, PIP(3 production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7 cells, compared to insulin. CONCLUSION: Glargine, possibly acting through IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2 display lower potency than insulin for the stimulation of proliferative/anti-apoptotic pathways in

  11. Isolation and identification of novel genes involved in artemisinin production from flowers of Artemisia annua using suppression subtractive hybridization and metabolite analysis.

    Science.gov (United States)

    Liu, Shuoqian; Tian, Na; Li, Juan; Huang, Jianan; Liu, Zhonghua

    2009-11-01

    Malaria is a global health problem that threatens 300-500 million people and kills more than one million people annually. Artemisinin is highly effective against multidrug-resistant Plasmodium falciparum and it has been widely used as part of the artemisinin-based combination therapies against malaria. To elucidate the biosynthetic pathway of artemisinin and to clone related genes in Artemisia annua, differentially expressed genes between blooming flowers and flower buds were isolated and characterized by a combined approach of suppression subtractive hybridization (SSH) and metabolite analysis. A total of 350 cDNA clones from a subtractive cDNA library were randomly picked, sequenced and analyzed and 253 high-quality sequences were obtained. BLASTX comparisons indicated that about 9.9 % of the clones encoded enzymes involved in isoprenoid (including artemisinin) biosynthesis. The expression of 4 gene transcripts involved in artemisinin biosynthesis was examined by RT-PCR and the results confirmed the higher expression of these transcripts in blooming flowers than in flower buds. In addition, 2 putative transcript factors transparenta testa glabra 1 (TTG1) and ENHANCER OF GLABRA3 (GL3), which promote trichome initiation, were presented in the library. Finally, this study demonstrated that the increase of expression level of the putative TTG1 gene correlated with the improvement of glandular trichome density and artemisinin production in A. annua leaves. The subtractive cDNA library described in the present study provides important candidate genes for future research in order to increase the artemisinin content in A. annua.

  12. Isolation and Biosynthetic Analysis of Haliamide, a New PKS-NRPS Hybrid Metabolite from the Marine Myxobacterium Haliangium ochraceum

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    Yuwei Sun

    2016-01-01

    Full Text Available Myxobacteria of marine origin are rare and hard-to-culture microorganisms, but they genetically harbor high potential to produce novel antibiotics. An extensive investigation on the secondary metabolome of the unique marine myxobacterium Haliangium ochraceum SMP-2 led to the isolation of a new polyketide-nonribosomal peptide hybrid product, haliamide (1. Its structure was elucidated by spectroscopic analyses including NMR and HR-MS. Haliamide (1 showed cytotoxicity against HeLa-S3 cells with IC50 of 12 μM. Feeding experiments were performed to identify the biosynthetic building blocks of 1, revealing one benzoate, one alanine, two propionates, one acetate and one acetate-derived terminal methylene. The biosynthetic gene cluster of haliamide (hla, 21.7 kbp was characterized through the genome mining of the producer, allowing us to establish a model for the haliamide biosynthesis. The sulfotransferase (ST-thioesterase (TE domains encoded in hlaB appears to be responsible for the terminal alkene formation via decarboxylation.

  13. Analysis of 44 drugs of abuse and metabolites in wastewater and river water using a hybrid quadrupole time-of-flight tandem mass spectrometry

    Science.gov (United States)

    Andres-Costa, M. Jesus; Andreu, Vicente; Picó, Yolanda

    2016-04-01

    The presence of drugs of abuse in the aquatic environment has been recognized as an important issue for the ecosystem due their possible negative effect on it (Richardson, 2011). Incomplete removal of these substances during wastewater treatment could be one of the causes of their release in the environment (Zuccato and Castiglioni, 2009). Pollution by illicit drug residues at very low concentrations is generalized in populated areas, with potential risks for human health and the environment (Zuccato, 2008; Castiglioni et al 2007).The aim of this study was to screen and quantify 44 drugs of abuse and metabolites of wastewater samples using a hybrid quadrupole time-of-flight tandem mass spectrometry and furthermore carry out a post-target screening to identify additional compounds present in the water samples. Wastewater samples were collected from the influent and effluent of three wastewater treatment plants (WWTPs) in Valencia and river water samples form Turia River Basin. Illicit drugs were extracted by solid-phase extraction (SPE). The chromatography was performed with an Agilent 1260 Infinity ultra high performance liquid chromatography (UHPLC). The UHPLC system was coupled to a hybrid quadrupole time-of-flight ABSciex Triple TOFTM 5600. All analytes were analyzed in positive mode. Acquiring full scan MS data was employed for quantification of drugs of abuse, and automatic data dependent information product ion spectra (IDA-MS/MS) was checked for identifying emerging illicit drugs and other compounds in water samples. The use of a database containing 1212 compounds achieved high confidence results for a wide number of contaminants. In the present study, the presence of compounds that belong to amphetamines group (amphetamine, methamphetamine, ephedrine, MDMA, MDA and MDEA), tryptamines (bufotenine), pirrolidinophenone group (α-PVP and 4'-MePHP), arylcyclohexylamines (ketamine), cocainics (cocaine, benzoylecgonine, cocaethylene and ecgonine methyl ester) and

  14. Comparison of triple quadrupole, hybrid linear ion trap triple quadrupole, time-of-flight and LTQ-Orbitrap mass spectrometers in drug discovery phase metabolite screening and identification in vitro--amitriptyline and verapamil as model compounds.

    Science.gov (United States)

    Rousu, Timo; Herttuainen, Jukka; Tolonen, Ari

    2010-04-15

    Liquid chromatography in combination with mass spectrometry (LC/MS) is a superior analytical technique for metabolite profiling and identification studies performed in drug discovery and development laboratories. In the early phase of drug discovery the analytical approach should be both time- and cost-effective, thus providing as much data as possible with only one visit to the laboratory, without the need for further experiments. Recent developments in mass spectrometers have created a situation where many different mass spectrometers are available for the task, each with their specific strengths and drawbacks. We compared the metabolite screening properties of four main types of mass spectrometers used in analytical laboratories, considering both the ability to detect the metabolites and provide structural information, as well as the issues related to time consumption in laboratory and thereafter in data processing. Human liver microsomal incubations with amitriptyline and verapamil were used as test samples, and early-phase 'one lab visit only' approaches were used with all instruments. In total, 28 amitriptyline and 69 verapamil metabolites were found and tentatively identified. Time-of-flight mass spectrometry (TOFMS) was the only approach detecting all of them, shown to be the most suitable instrument for elucidating as comprehensive metabolite profile as possible leading also to lowest overall time consumption together with the LTQ-Orbitrap approach. The latter however suffered from lower detection sensitivity and false negatives, and due to slow data acquisition rate required slower chromatography. Approaches with triple quadrupole mass spectrometry (QqQ) and hybrid linear ion trap triple quadrupole mass spectrometry (Q-Trap) provided the highest amount of fragment ion data for structural elucidation, but, in addition to being unable to produce very high-important accurate mass data, they suffered from many false negatives, and especially with the Qq

  15. Unambiguous metabolite identification in high-throughput metabolomics by hybrid 1D 1 H NMR/ESI MS 1 approach: Hybrid 1D 1 H NMR/ESI MS 1 metabolomics method

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Lawrence R. [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99354 USA; Hoyt, David W. [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99354 USA; Walker, S. Michael [Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence KS 66045 USA; Ward, Joy K. [Department of Ecology and Evolutionary Biology, University of Kansas, Lawrence KS 66045 USA; Nicora, Carrie D. [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99354 USA; Bingol, Kerem [Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland WA 99354 USA

    2016-09-16

    We present a novel approach to improve accuracy of metabolite identification by combining direct infusion ESI MS1 with 1D 1H NMR spectroscopy. The new approach first applies standard 1D 1H NMR metabolite identification protocol by matching the chemical shift, J-coupling and intensity information of experimental NMR signals against the NMR signals of standard metabolites in metabolomics library. This generates a list of candidate metabolites. The list contains false positive and ambiguous identifications. Next, we constrained the list with the chemical formulas derived from high-resolution direct infusion ESI MS1 spectrum of the same sample. Detection of the signals of a metabolite both in NMR and MS significantly improves the confidence of identification and eliminates false positive identification. 1D 1H NMR and direct infusion ESI MS1 spectra of a sample can be acquired in parallel in several minutes. This is highly beneficial for rapid and accurate screening of hundreds of samples in high-throughput metabolomics studies. In order to make this approach practical, we developed a software tool, which is integrated to Chenomx NMR Suite. The approach is demonstrated on a model mixture, tomato and Arabidopsis thaliana metabolite extracts, and human urine.

  16. Morphine metabolites

    DEFF Research Database (Denmark)

    Christrup, Lona Louring

    1997-01-01

    , morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...

  17. Discrimination of wild types and hybrids of Duboisia myoporoides and Duboisia leichhardtii at different growth stages using (1)H NMR-based metabolite profiling and tropane alkaloids-targeted HPLC-MS analysis.

    Science.gov (United States)

    Ullrich, Sophie Friederike; Averesch, Nils J H; Castellanos, Leonardo; Choi, Young Hae; Rothauer, Andreas; Kayser, Oliver

    2016-11-01

    Duboisia species, which belong to the family of Solanaceae, are commercially cultivated in large scale, as they are main source of the pharmaceutically-used active compound scopolamine. In this study, (1)H NMR-based metabolite profiling linking primary with secondary metabolism and additional quantification via HPCL-MS with special focus on the tropane alkaloids were applied to compare leaf and root extracts of three wild types and two hybrids of Duboisia myoporoides and D. leichhardtii at different developmental stages grown under controlled conditions in climate chambers and under agricultural field plantation. Based on the leaf extracts, a clear distinction between the Duboisia hybrids and the wild types Duboisia myoporoides and D. leichhardtii using principal component analysis of (1)H NMR data was observed. The average content in scopolamine in the hybrids of Duboisia cultivated in climate chambers increased significantly from month 3-6 after potting of the rooted cuttings, however not so for the examined wild types. The Duboisia hybrids grown in climate chambers showed higher growth and contained more sugars and amino acids than Duboisia hybrids grown in the field, which in contrast showed an enhanced flux towards tropane alkaloids as well as flavonoids. For a more detailed analysis of tropane alkaloids, an appropriate HPLC-MS method was developed and validated. The measurements revealed large differences in the alkaloid pattern within the different genotypes under investigation, especially regarding the last enzymatic step, the conversion from hyoscamine to scopolamine by the hyoscyamine 6β-hydroxylase. Scopolamine was found in highest concentrations in Duboisia hybrids (20.04 ± 4.05 and 17.82 ± 3.52 mg/g dry wt) followed by Duboisia myoporoides (12.71 ± 2.55 mg/g dry wt), both showing a high selectivity for scopolamine in contrast to Duboisia leichhardtii (3.38 ± 0.59 and 5.09 ± 1.24 mg/g dry wt) with hyoscyamine being the

  18. Identification of a hybrid PKS-NRPS required for the biosynthesis of NG-391 and NG-393 metabolites in Metarhizium anisopliae

    Science.gov (United States)

    A 19,818 kb genomic region harboring six predicted ORFs was identified in M. anisopliae ARSEF 2575. The ORF4 CDS, putatively encoding a hybrid polyketide synthase/nonribosomal peptide synthetase (PKS-NRPS) was targeted using Agrobacterium-mediated gene knockout. Homologous, but not heterolog...

  19. Facile synthesis of boronate-decorated polyethyleneimine-grafted hybrid magnetic nanoparticles for the highly selective enrichment of modified nucleosides and ribosylated metabolites.

    Science.gov (United States)

    Li, Hua; Shan, Yuanhong; Qiao, Lizhen; Dou, Abo; Shi, Xianzhe; Xu, Guowang

    2013-12-03

    Ribosylated metabolites, especially modified nucleosides, have been extensively evaluated as cancer-related biomarkers. Boronate adsorbents are considered to be promising materials for extracting them from complex matrices. However, the enrichment of ribosylated metabolites in low abundance is still a challenge due to the limited capacity and selectivity of the existing boronate adsorbents. In this study, a novel type of magnetic nanoparticles named Fe3O4@SiO2@PEI-FPBA was synthesized by grafting polyethyleneimine (PEI) onto the surface of Fe3O4@SiO2 before modification by boronate groups. The high density of the amino groups on the PEI chains supplied a large number of binding sites for boronate groups. Thus, the adsorption capacity (1.34 ± 0.024 mg/g) of the nanoparticles, which is 6- to 7-fold higher than that of analogous materials, was greatly improved. The unreacted secondary amines and tertiary amines of the PEI enhanced the aqueous solubility of the nanoparticles, which could efficiently reduce nonspecific adsorption. The nanoparticles were able to capture 1,2 cis-diol nucleosides from 1000-fold interferences. Moreover, the flexible chains of PEI were favorable for effective enrichment and quick equilibration (nanoparticles. Among them, 43 were identified to be nucleosides and other ribosylated metabolites. Nine low abundance modified nucleosides were detected for the first time. In conclusion, Fe3O4@SiO2@PEI-FPBA is an attractive candidate material for the highly selective enrichment of 1,2-cis-diol compounds.

  20. Volatile Metabolites

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    Daryl D. Rowan

    2011-11-01

    Full Text Available Volatile organic compounds (volatiles comprise a chemically diverse class of low molecular weight organic compounds having an appreciable vapor pressure under ambient conditions. Volatiles produced by plants attract pollinators and seed dispersers, and provide defense against pests and pathogens. For insects, volatiles may act as pheromones directing social behavior or as cues for finding hosts or prey. For humans, volatiles are important as flavorants and as possible disease biomarkers. The marine environment is also a major source of halogenated and sulfur-containing volatiles which participate in the global cycling of these elements. While volatile analysis commonly measures a rather restricted set of analytes, the diverse and extreme physical properties of volatiles provide unique analytical challenges. Volatiles constitute only a small proportion of the total number of metabolites produced by living organisms, however, because of their roles as signaling molecules (semiochemicals both within and between organisms, accurately measuring and determining the roles of these compounds is crucial to an integrated understanding of living systems. This review summarizes recent developments in volatile research from a metabolomics perspective with a focus on the role of recent technical innovation in developing new areas of volatile research and expanding the range of ecological interactions which may be mediated by volatile organic metabolites.

  1. Metabolite identification of seven active components of Huan-Nao-Yi-Cong-Fang in rat plasma using high-performance liquid chromatography combined with hybrid ion trap/time-of-flight mass spectrometry.

    Science.gov (United States)

    Wang, Minchao; Lu, Yanzhen; Liu, Jiangang; Li, Hao; Wei, Yun

    2016-02-01

    Huan-Nao-Yi-Cong-Fang (HNYCF) is a potential prescription in treating Alzheimer's disease. Seven constituents [ferulic acid (FA), 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (THSG), berberine hydrochloride (BHCl), emodin, ginsenoside Rg1 (Rg1), ginsenoside Re (Re) and ginsenoside Rb1 (Rb1)] have been used as quality chemical markers of HNYCF owing to their biological significance and high contents in crude plant materials. This study explored the metabolites of the seven bioactive components in rat plasma to give useful data for further study of the action mechanism of HNYCF. LC/MS-IT-TOF was used to simultaneously characterize the metabolites of the seven components. Using the combination of MetID Solution 1.0 software and accurate mass measurements, the metabolites of HNYCF were reliably characterized. Their structures were elucidated based on the accurate MS(2) spectra and comparisons of their changes in accurate molecular masses and fragment ions with those of parent compounds. A total of five parent active compounds (BHCl, emodin, Rg1, Rb1 and Re) and 10 metabolites were found from the rat plasma 2 h after oral administration of HNYCF dosage, of which two metabolites of emodin were observed for the first time. The proposed metabolic pathways of the bioactive components in the rat plasma are helpful for further studies on the pharmacokinetics and real active compound forms of this drug.

  2. Enhanced metabolite generation

    Science.gov (United States)

    Chidambaram, Devicharan [Middle Island, NY

    2012-03-27

    The present invention relates to the enhanced production of metabolites by a process whereby a carbon source is oxidized with a fermentative microbe in a compartment having a portal. An electron acceptor is added to the compartment to assist the microbe in the removal of excess electrons. The electron acceptor accepts electrons from the microbe after oxidation of the carbon source. Other transfers of electrons can take place to enhance the production of the metabolite, such as acids, biofuels or brewed beverages.

  3. Secondary metabolites from Ganoderma.

    Science.gov (United States)

    Baby, Sabulal; Johnson, Anil John; Govindan, Balaji

    2015-06-01

    Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites.

  4. Understanding and classifying metabolite space and metabolite-likeness.

    Directory of Open Access Journals (Sweden)

    Julio E Peironcely

    Full Text Available While the entirety of 'Chemical Space' is huge (and assumed to contain between 10(63 and 10(200 'small molecules', distinct subsets of this space can nonetheless be defined according to certain structural parameters. An example of such a subspace is the chemical space spanned by endogenous metabolites, defined as 'naturally occurring' products of an organisms' metabolism. In order to understand this part of chemical space in more detail, we analyzed the chemical space populated by human metabolites in two ways. Firstly, in order to understand metabolite space better, we performed Principal Component Analysis (PCA, hierarchical clustering and scaffold analysis of metabolites and non-metabolites in order to analyze which chemical features are characteristic for both classes of compounds. Here we found that heteroatom (both oxygen and nitrogen content, as well as the presence of particular ring systems was able to distinguish both groups of compounds. Secondly, we established which molecular descriptors and classifiers are capable of distinguishing metabolites from non-metabolites, by assigning a 'metabolite-likeness' score. It was found that the combination of MDL Public Keys and Random Forest exhibited best overall classification performance with an AUC value of 99.13%, a specificity of 99.84% and a selectivity of 88.79%. This performance is slightly better than previous classifiers; and interestingly we found that drugs occupy two distinct areas of metabolite-likeness, the one being more 'synthetic' and the other being more 'metabolite-like'. Also, on a truly prospective dataset of 457 compounds, 95.84% correct classification was achieved. Overall, we are confident that we contributed to the tasks of classifying metabolites, as well as to understanding metabolite chemical space better. This knowledge can now be used in the development of new drugs that need to resemble metabolites, and in our work particularly for assessing the metabolite

  5. Production of Metabolites

    DEFF Research Database (Denmark)

    2011-01-01

    A recombinant micro-organism such as Saccharomyces cerevisiae which produces and excretes into culture medium a stilbenoid metabolite product when grown under stilbenoid production conditions, which expresses in above native levels a ABC transporter which transports said stilbenoid out of said...... micro-organism cells to the culture medium. The genome of the Saccharomyces cerevisiae produces an auxotrophic phenotype which is compensated by a plasmid which also expresses one or more of said enzymes constituting said metabolic pathway producing said stilbenoid, an expression product of the plasmid...

  6. Hybrid Baryons

    CERN Document Server

    Page, P R

    2003-01-01

    We review the status of hybrid baryons. The only known way to study hybrids rigorously is via excited adiabatic potentials. Hybrids can be modelled by both the bag and flux-tube models. The low-lying hybrid baryon is N 1/2^+ with a mass of 1.5-1.8 GeV. Hybrid baryons can be produced in the glue-rich processes of diffractive gamma N and pi N production, Psi decays and p pbar annihilation.

  7. Identification of Metabolites of the Fungicide Penconazole in Human Urine.

    Science.gov (United States)

    Mercadante, R; Polledri, E; Scurati, S; Moretto, A; Fustinoni, S

    2016-07-18

    Penconazole (PEN) is a fungicide used in agriculture that has been classified as hazardous to humans and the environment. The objective of this work was to identify PEN urinary metabolites in humans and propose a biomarker for PEN exposure. Five urine samples were collected from agricultural workers who worked with and were exposed to PEN. Samples were analyzed by liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry, with the source operating in the electrospray ionization mode. Metabolites previously identified in animal studies were searched as possible metabolites in humans. Candidate metabolites were first identified by multiple reaction monitoring following the protonated molecular ions that generated the protonated triazole moiety, which is expected to be present in all PEN metabolites; second, the isotopic patterns of the molecular ions were checked for consistency with the presence of two chlorine atoms; third, the full mass spectra were evaluated for consistency with the molecular structure. Seven different oxidized metabolites were found, both in the free and glucuronide conjugate forms. The major metabolite was the monohydroxyl-derivative PEN-OH (median molar fraction approximately 0.92 as a sum of free and glucuronide conjugated form). The product of further oxidation was the carboxyl-derivate PEN-COOH (median molar fraction approximately 0.03). After hydrolysis with β-glucuronidase, the free compounds were quantified in the presence of deuterated PEN as an internal standard; PEN-OH levels ranged from 230 to 460 μg/L, and PEN-COOH levels ranged from 5.2 to 16.7 μg/L. We propose a pathway for PEN metabolism in humans and suggest PEN-OH, after hydrolysis of glucuronide conjugates, as a biomarker for monitoring human exposure to PEN.

  8. Hybrid vehicles

    Energy Technology Data Exchange (ETDEWEB)

    West, J.G.W. [Electrical Machines (United Kingdom)

    1997-07-01

    The reasons for adopting hybrid vehicles result mainly from the lack of adequate range from electric vehicles at an acceptable cost. Hybrids can offer significant improvements in emissions and fuel economy. Series and parallel hybrids are compared. A combination of series and parallel operation would be the ideal. This can be obtained using a planetary gearbox as a power split device allowing a small generator to transfer power to the propulsion motor giving the effect of a CVT. It allows the engine to run at semi-constant speed giving better fuel economy and reduced emissions. Hybrid car developments are described that show the wide range of possible hybrid systems. (author)

  9. Rethinking cycad metabolite research.

    Science.gov (United States)

    Snyder, Laura R; Marler, Thomas E

    2011-01-01

    Cycads are among the most ancient of extant Spermatophytes, and are known for their numerous pharmacologically active compounds. One compound in particular, β-methylamino-L-alanine (BMAA), has been implicated as the cause of amyotrophic lateral sclerosis/Parkinson dementia complex (ALS/PDC) on Guam. Previous studies allege that BMAA is produced exclusively by cyanobacteria, and is transferred to cycads through the symbiotic relationship between these cyanobacteria and the roots of cycads. We recently published data showing that Cycas micronesica seedlings grown without endophytic cyanobacteria do in fact increase in BMAA, invalidating the foundation of the BMAA hypothesis. We use this example to suggest that the frenzy centered on BMAA and other single putative toxins has hindered progress. The long list of cycad-specific compounds may have important roles in signaling or communication, but these possibilities have been neglected during decades of attempts to force single metabolites into a supposed anti-herbivory function. We propose that an unbiased, comprehensive approach may be a more appropriate means of proceeding with cycad biochemistry research.

  10. Synthesis Of Labeled Metabolites

    Science.gov (United States)

    Martinez, Rodolfo A.; Silks, III, Louis A.; Unkefer, Clifford J.; Atcher, Robert

    2004-03-23

    The present invention is directed to labeled compounds, for example, isotopically enriched mustard gas metabolites including: [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1,1'-sulfonylbis[2-(methylthio); [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1-[[2-(methylsulfinyl)ethyl]sulfonyl]-2-(methylthio); [1,1',2,2'-.sup.13 C.sub.4 ]ethane, 1,1'-sulfonylbis[2-(methylsulfinyl)]; and, 2,2'-sulfinylbis([1,2-.sup.13 C.sub.2 ]ethanol of the general formula ##STR1## where Q.sup.1 is selected from the group consisting of sulfide (--S--), sulfone (--S(O)--), sulfoxide (--S(O.sub.2)--) and oxide (--O--), at least one C* is .sup.13 C, X is selected from the group consisting of hydrogen and deuterium, and Z is selected from the group consisting of hydroxide (--OH), and --Q.sup.2 --R where Q.sup.2 is selected from the group consisting of sulfide (--S--), sulfone(--S(O)--), sulfoxide (--S(O.sub.2)--) and oxide (--O--), and R is selected from the group consisting of hydrogen, a C.sub.1 to C.sub.4 lower alkyl, and amino acid moieties, with the proviso that when Z is a hydroxide and Q.sup.1 is a sulfide, then at least one X is deuterium.

  11. Metabolite Space of Rheumatoid Arthritis

    OpenAIRE

    van Wietmarschen, Herman; van der Greef, Jan

    2012-01-01

    Metabolites play numerous roles in the healthy and diseased body, ranging from regulating physiological processes to providing building blocks for the body. Therefore, understanding the role of metabolites is important in elucidating the etiology and pathology of diseases and finding targets for new treatment options. Rheumatoid arthritis is a complex chronic disease for which new disease management strategies are needed. The aim of this review is to bring together and integrate information a...

  12. Secondary metabolites from marine microorganisms

    Directory of Open Access Journals (Sweden)

    KELECOM ALPHONSE

    2002-01-01

    Full Text Available After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

  13. The identification of lobeglitazone metabolites in rat liver microsomes and the kinetics of the in vivo formation of the major metabolite M1 in rats.

    Science.gov (United States)

    Lee, Jong-Hwa; Ahn, Sung Hoon; Maeng, Han-Joo; Lee, Wooin; Kim, Dae-Duk; Chung, Suk-Jae

    2015-11-10

    The objective of this study was to elucidate the chemical structure of the metabolites derived from lobeglitazone (LB) during its incubation with rat liver microsomes and to characterize the kinetics of formation of the major metabolite M1 in vivo. Using high performance liquid chromatography coupled with a hybrid quadrupole linear ion trap, the metabolites were derived from LB during its incubation with rat liver microsomes. From various fragmentation patterns obtained from the metabolites, LB was biotransformed into 5 metabolites in the incubation, in which demethylation and hydroxylation appeared to be the principle metabolic pathways in vitro; Amongst the five primary metabolites, M1, a demethylated derivative of LB, appeared to be the major metabolite of LB, based on a comparison on the peak intensities in the ion chromatogram. In a study of the in vivo kinetics of formation of M1 in rats, the rate of formation of M1 from LB was determined to be 0.252 and 0.216mL/min/kg at doses of 0.5mg/kg and 2mg/kg of LB, respectively, suggesting that the kinetics of M1 formation were linear in the dose range tested. Considering the fact that LB is primarily eliminated by hepatic metabolism in rats, the formation of M1 accounts for approximately 7.50-9.76% of the overall elimination of LB in rats.

  14. Anticancer properties of Monascus metabolites.

    Science.gov (United States)

    Yang, Tao; Liu, Junwen; Luo, Feijun; Lin, Qinlu; Rosol, Thomas J; Deng, Xiyun

    2014-08-01

    This review provides up-to-date information on the anticancer properties of Monascus-fermented products. Topics covered include clinical evidence for the anticancer potential of Monascus metabolites, bioactive Monascus components with anticancer potential, mechanisms of the anticancer effects of Monascus metabolites, and existing problems as well as future perspectives. With the advancement of related fields, the development of novel anticancer Monascus food products and/or pharmaceuticals will be possible with the ultimate goal of decreasing the incidence and mortality of malignancies in humans.

  15. Understanding and classifying metabolite space and Metabolite-Likeness

    NARCIS (Netherlands)

    Peironcely, J.E.; Reijmers, T.; Coulier, L.; Bender, A.; Hankemeier, T.

    2011-01-01

    While the entirety of 'Chemical Space' is huge (and assumed to contain between 1063 and 10200 'small molecules'), distinct subsets of this space can nonetheless be defined according to certain structural parameters. An example of such a subspace is the chemical space spanned by endogenous metabolite

  16. Hybrid Metaheuristics

    CERN Document Server

    2013-01-01

    The main goal of this book is to provide a state of the art of hybrid metaheuristics. The book provides a complete background that enables readers to design and implement hybrid metaheuristics to solve complex optimization problems (continuous/discrete, mono-objective/multi-objective, optimization under uncertainty) in a diverse range of application domains. Readers learn to solve large scale problems quickly and efficiently combining metaheuristics with complementary metaheuristics, mathematical programming, constraint programming and machine learning. Numerous real-world examples of problems and solutions demonstrate how hybrid metaheuristics are applied in such fields as networks, logistics and transportation, bio-medical, engineering design, scheduling.

  17. Identification of in vitro metabolites of ethylphenidate by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry

    OpenAIRE

    Negreira, Noelia; Erratico, Claudio; Nuijs, van, Alexander L.N.; Covaci, Adrian

    2016-01-01

    Abstract: Ethylphenidate is a new potent synthetic psychoactive drug, structurally related to methylphenidate. Using human liver microsomes and cytosol, we have investigated for the first time the Phase-I and Phase-II in vitro metabolism of ethylphenidate. The structure of the metabolites was elucidated by hybrid quadrupole time-of-flight mass spectrometry. Overall, seven Phase-I, but no Phase-II metabolites were detected. Ethylphenidate underwent hydroxylation forming two primary mono-hydrox...

  18. Primary expectations of secondary metabolites

    Science.gov (United States)

    My program examines the plant secondary metabolites (i.e. phenolics) important for human health, and which impart the organoleptic properties that are quality indicators for fresh and processed foods. Consumer expectations such as appearance, taste, or texture influence their purchasing decisions; a...

  19. The secondary metabolite bioinformatics portal

    DEFF Research Database (Denmark)

    Weber, Tilmann; Kim, Hyun Uk

    2016-01-01

    . In this context, this review gives a summary of tools and databases that currently are available to mine, identify and characterize natural product biosynthesis pathways and their producers based on ‘omics data. A web portal called Secondary Metabolite Bioinformatics Portal (SMBP at http...

  20. Genetically Encoded Sensors for Metabolites

    Science.gov (United States)

    Deuschle, Karen; Fehr, Marcus; Hilpert, Melanie; Lager, Ida; Lalonde, Sylvie; Looger, Loren L.; Okumoto, Sakiko; Persson, Jörgen; Schmidt, Anja; Frommer, Wolf B.

    2009-01-01

    Background Metabolomics, i.e., the multiparallel analysis of metabolite changes occurring in a cell or an organism, has become feasible with the development of highly efficient mass spectroscopic technologies. Functional genomics as a standard tool helped to identify the function of many of the genes that encode important transporters and metabolic enzymes over the past few years. Advanced expression systems and analysis technologies made it possible to study the biochemical properties of the corresponding proteins in great detail. We begin to understand the biological functions of the gene products by systematic analysis of mutants using systematic PTGS/RNAi, knockout and TILLING approaches. However, one crucial set of data especially relevant in the case of multicellular organisms is lacking: the knowledge of the spatial and temporal profiles of metabolite levels at cellular and subcellular levels. Methods We therefore developed genetically encoded nanosensors for several metabolites to provide a basic set of tools for the determination of cytosolic and subcellular metabolite levels in real time by using fluorescence microscopy. Results Prototypes of these sensors were successfully used in vitro and also in vivo, i.e., to measure sugar levels in fungal and animal cells. Conclusions One of the future goals will be to expand the set of sensors to a wider spectrum of substrates by using the natural spectrum of periplasmic binding proteins from bacteria and by computational design of proteins with altered binding pockets in conjunction with mutagenesis. This toolbox can then be applied for four-dimensional imaging of cells and tissues to elucidate the spatial and temporal distribution of metabolites as a discovery tool in functional genomics, as a tool for high-throughput, high-content screening for drugs, to test metabolic models, and to analyze the interplay of cells in a tissue or organ. PMID:15688353

  1. Hybrid intermediaries

    OpenAIRE

    Cetorelli, Nicola

    2014-01-01

    I introduce the concept of hybrid intermediaries: financial conglomerates that control a multiplicity of entity types active in the "assembly line" process of modern financial intermediation, a system that has become known as shadow banking. The complex bank holding companies of today are the best example of hybrid intermediaries, but I argue that financial firms from the "nonbank" space can just as easily evolve into conglomerates with similar organizational structure, thus acquiring the cap...

  2. Hybrid composites

    CSIR Research Space (South Africa)

    Jacob John, Maya

    2009-04-01

    Full Text Available effect was observed for the elongation at break of the hybrid composites. The impact strength of the hybrid composites increased with the addition of glass fibres. The tensile and impact properties of thermoplastic natural rubber reinforced short... panels made from conventional structural materials. Figure 3 illustrates the performance of cellular biocomposite panels against conventional systems used for building and residential construction, namely a pre- cast pre-stressed hollow core concrete...

  3. Metabolite profiles of common Stemphylium species

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Solfrizzo, Michelle; Visconti, Angelo

    1995-01-01

    Thirty-three isolates of Stemphylium spp. have been analysed for their metabolite profiles. Five metabolites, stemphylin, stemphyloxin II, stemphyperylenol, stemphol and a stemphol related compound, have been detected by high-performance liquid chromatography and thin-layer chromatography...

  4. Pharmacokinetics of Tyrosol Metabolites in Rats

    OpenAIRE

    Da-Hye Lee; Yang-Ji Kim; Min Jung Kim; Jiyun Ahn; Tae-Youl Ha; Sang Hee Lee; Young Jin Jang; Chang Hwa Jung

    2016-01-01

    Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol-derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Two tyrosol metabolites (M1 and M2) were detected in the plasma. M1 was identified as...

  5. 10 CFR 26.163 - Cutoff levels for drugs and drug metabolites.

    Science.gov (United States)

    2010-01-01

    ... metabolites Cutoff level Marijuana metabolites 50 Cocaine metabolites 300 Opiate metabolites 2000... Levels for Drugs and Drug Metabolites Drug or metabolites Cutoff level(ng/mL) Marijuana metabolite 1...

  6. Fungal metabolites with anticancer activity.

    Science.gov (United States)

    Evidente, Antonio; Kornienko, Alexander; Cimmino, Alessio; Andolfi, Anna; Lefranc, Florence; Mathieu, Véronique; Kiss, Robert

    2014-05-01

    Covering: 1964 to 2013. Natural products from bacteria and plants have played a leading role in cancer drug discovery resulting in a large number of clinically useful agents. In contrast, the investigations of fungal metabolites and their derivatives have not led to a clinical cancer drug in spite of significant research efforts revealing a large number of fungi-derived natural products with promising anticancer activity. Many of these natural products have displayed notable in vitro growth-inhibitory properties in human cancer cell lines and select compounds have been demonstrated to provide therapeutic benefits in mouse models of human cancer. Many of these compounds are expected to enter human clinical trials in the near future. The present review discusses the reported sources, structures and biochemical studies aimed at the elucidation of the anticancer potential of these promising fungal metabolites.

  7. Secondary metabolites from Eremostachys laciniata

    DEFF Research Database (Denmark)

    Calis, Ihsan; Güvenc, Aysegül; Armagan, Metin;

    2008-01-01

    From the aerial parts of Eremostachys laciniata (Lamiaceae), a new acidic iridoid glucoside, 5-desoxysesamosidic acid (1) was isolated in addition to thirteen known iridoid glucosides, 5-desoxysesamoside (2), sesamoside (3), 6β-hydroxy-7-epi-loganin (4), chlorotuberoside (5), 5-deoxypulchelloside...... elucidated from spectroscopic (UV, IR, 1D- and 2D-NMR) and ESI-MS evidence, as well as from their specific optical rotation. The presence of these metabolites of three different classes strongly supports the close relationship of the genera Eremostachys and Phlomis.......), and forsythoside B (18), and five flavone derivatives, luteolin (19), luteolin 7-O-β-D-glucopyranoside (20), luteolin 7-O-(6''-O-β-D-apiofuranosyl)-β-D-glucopyranoside (21), apigenin 7-O-β-D-glucopyranoside (22), and apigenin 7-O-(6''-O-p-coumaroyl)-β-D-glucopyranoside (23). The structures of the metabolites were...

  8. Beyond Polymaxenolide: Cembrane-Africanane Terpenoids from the Hybrid Soft Coral Sinularia maxima x S. polydactyla

    Science.gov (United States)

    The effects of natural hybridization on secondary metabolite production and diversification have only recently been studied in plants and have essentially been overlooked in marine organisms. Chemical investigation of the hybrid soft coral Sinularia maxima × S. polydactyla resulted in the isolation ...

  9. Metabolite

    Science.gov (United States)

    Kumar V, Abbas AK, Aster JC. Cellular responses to stress and toxic insults: Adaptation, injury, and death. In: Kumar V, Abbas AK, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease . 9th ed. Philadelphia, PA: ...

  10. Epigenome targeting by probiotic metabolites

    Directory of Open Access Journals (Sweden)

    Licciardi Paul V

    2010-12-01

    Full Text Available Abstract Background The intestinal microbiota plays an important role in immune development and homeostasis. A disturbed microbiota during early infancy is associated with an increased risk of developing inflammatory and allergic diseases later in life. The mechanisms underlying these effects are poorly understood but are likely to involve alterations in microbial production of fermentation-derived metabolites, which have potent immune modulating properties and are required for maintenance of healthy mucosal immune responses. Probiotics are beneficial bacteria that have the capacity to alter the composition of bacterial species in the intestine that can in turn influence the production of fermentation-derived metabolites. Principal among these metabolites are the short-chain fatty acids butyrate and acetate that have potent anti-inflammatory activities important in regulating immune function at the intestinal mucosal surface. Therefore strategies aimed at restoring the microbiota profile may be effective in the prevention or treatment of allergic and inflammatory diseases. Presentation of the hypothesis Probiotic bacteria have diverse effects including altering microbiota composition, regulating epithelial cell barrier function and modulating of immune responses. The precise molecular mechanisms mediating these probiotic effects are not well understood. Short-chain fatty acids such as butyrate are a class of histone deacetylase inhibitors important in the epigenetic control of host cell responses. It is hypothesized that the biological function of probiotics may be a result of epigenetic modifications that may explain the wide range of effects observed. Studies delineating the effects of probiotics on short-chain fatty acid production and the epigenetic actions of short-chain fatty acids will assist in understanding the association between microbiota and allergic or autoimmune disorders. Testing the hypothesis We propose that treatment with

  11. Metabolite Profiling of Red Sea Corals

    KAUST Repository

    Ortega, Jovhana Alejandra

    2016-12-01

    Looking at the metabolite profile of an organism provides insights into the metabolomic state of a cell and hence also into pathways employed. Little is known about the metabolites produced by corals and their algal symbionts. In particular, corals from the central Red Sea are understudied, but interesting study objects, as they live in one of the warmest and most saline environments and can provide clues as to the adjustment of corals to environmental change. In this study, we applied gas chromatography – mass spectrometry (GC–MS) metabolite profiling to analyze the metabolic profile of four coral species and their associated symbionts: Fungia granulosa, Acropora hemprichii, Porites lutea, and Pocillopora verrucosa. We identified and quantified 102 compounds among primary and secondary metabolites across all samples. F. granulosa and its symbiont showed a total of 59 metabolites which were similar to the 51 displayed by P. verrucosa. P. lutea and A. hemprichii both harbored 40 compounds in conjunction with their respective isolated algae. Comparing across species, 28 metabolites were exclusively present in algae, while 38 were exclusive to corals. A principal component and cluster analyses revealed that metabolite profiles clustered between corals and algae, but each species harbored a distinct catalog of metabolites. The major classes of compounds were carbohydrates and amino acids. Taken together, this study provides a first description of metabolites of Red Sea corals and their associated symbionts. As expected, the metabolites of coral hosts differ from their algal symbionts, but each host and algal species harbor a unique set of metabolites. This corroborates that host-symbiont species pairs display a fine-tuned complementary metabolism that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing

  12. GPCR-Mediated Signaling of Metabolites

    DEFF Research Database (Denmark)

    Husted, Anna Sofie; Trauelsen, Mette; Rudenko, Olga

    2017-01-01

    in adipose tissue, the liver, and the endocrine pancreas. Importantly, distinct metabolite GPCRs act as efficient pro- and anti-inflammatory regulators of key immune cells, and signaling metabolites may thus function as important drivers of the low-grade inflammation associated with insulin resistance...... and obesity. The concept of key metabolites as ligands for specific GPCRs has broadened our understanding of metabolic signaling significantly and provides a number of novel potential drug targets....

  13. Metabolites from Alternaria Fungi and Their Bioactivities

    Directory of Open Access Journals (Sweden)

    Ligang Zhou

    2013-05-01

    Full Text Available Alternaria is a cosmopolitan fungal genus widely distributing in soil and organic matter. It includes saprophytic, endophytic and pathogenic species. At least 268 metabolites from Alternaria fungi have been reported in the past few decades. They mainly include nitrogen-containing metabolites, steroids, terpenoids, pyranones, quinones, and phenolics. This review aims to briefly summarize the structurally different metabolites produced by Alternaria fungi, as well as their occurrences, biological activities and functions. Some considerations related to synthesis, biosynthesis, production and applications of the metabolites from Alternaria fungi are also discussed.

  14. Pharmaceutical metabolite profiling using quadrupole/ion mobility spectrometry/time-of-flight mass spectrometry.

    Science.gov (United States)

    Chan, Eric C Y; New, Lee Sun; Yap, Chun Wei; Goh, Lin Tang

    2009-02-01

    The use of hybrid quadrupole ion mobility spectrometry time-of-flight mass spectrometry (Q/IMS/TOFMS) in the metabolite profiling of leflunomide (LEF) and acetaminophen (APAP) is presented. The IMS drift times (T(d)) of the drugs and their metabolites were determined in the IMS/TOFMS experiments and correlated with their exact monoisotopic masses and other in silico generated structural properties, such as connolly molecular area (CMA), connolly solvent-excluded volume (CSEV), principal moments of inertia along the X, Y and Z Cartesian coordinates (MI-X, MI-Y and MI-Z), inverse mobility and collision cross-section (CCS). The correlation of T(d) with these parameters is presented and discussed. IMS/TOF tandem mass spectrometry experiments (MS(2) and MS(3)) were successfully performed on the N-acetyl-p-benzoquinoneimine glutathione (NAPQI-GSH) adduct derived from the in vitro microsomal metabolism of APAP. As comparison, similar experiments were also performed using hybrid triple quadrupole linear ion trap mass spectrometry (QTRAPMS) and quadrupole time-of-flight mass spectrometry (QTOFMS). The abilities to resolve the product ions of the metabolite within the drift tube and fragment the ion mobility resolved product ions in the transfer travelling wave-enabled stacked ring ion guide (TWIG) demonstrated the potential applicability of the Q/IMS/TOFMS technique in pharmaceutical metabolite profiling.

  15. Hybrid microelectronic technology

    Science.gov (United States)

    Moran, P.

    Various areas of hybrid microelectronic technology are discussed. The topics addressed include: basic thick film processing, thick film pastes and substrates, add-on components and attachment methods, thin film processing, and design of thick film hybrid circuits. Also considered are: packaging hybrid circuits, automating the production of hybrid circuits, application of hybrid techniques, customer's view of hybrid technology, and quality control and assurance in hybrid circuit production.

  16. Dialkyl Phosphate Urinary Metabolites and Chromosomal Abnormalities in Human Sperm

    Science.gov (United States)

    Figueroa, Zaida I.; Young, Heather A.; Meeker, John D.; Martenies, Sheena E.; Barr, Dana Boyd; Gray, George; Perry, Melissa J.

    2015-01-01

    Background The past decade has seen numerous human health studies seeking to characterize the impacts of environmental exposures, such as organophosphate (OP) insecticides, on male reproduction. Despite an extensive literature on OP toxicology, many hormone-mediated effects on the testes are not well understood. Objectives This study investigated environmental exposures to OPs and their association with the frequency of sperm chromosomal abnormalities (i.e., disomy) among adult men. Methods Men (n=159) from a study assessing the impact of environmental exposures on male reproductive health were included in this investigation. Multi-probe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was used to determine XX18, YY18, XY18 and total disomy in sperm nuclei. Urine was analyzed using gas chromatography coupled with mass spectrometry for concentrations of dialkyl phosphate (DAP) metabolites of OPs [dimethylphosphate (DMP); dimethylthiophosphate (DMTP); dimethyldithiophosphate (DMDTP); diethylphosphate (DEP); diethylthiophosphate (DETP); and diethyldithiophosphate (DEDTP)]. Poisson regression was used to model the association between OP exposures and disomy measures. Incidence rate ratios (IRRs) were calculated for each disomy type by exposure quartiles for most metabolites, controlling for age, race, BMI, smoking, specific gravity, total sperm concentration, motility, and morphology. Results A significant positive trend was seen for increasing IRRs by exposure quartiles of DMTP, DMDTP, DEP and DETP in XX18, YY18, XY18 and total disomy. A significant inverse association was observed between DMP and total disomy. Findings for total sum of DAP metabolites concealed individual associations as those results differed from the patterns observed for each individual metabolite. Dose-response relationships appeared nonmonotonic, with most of the increase in disomy rates occurring between the second and third exposure quartiles and without additional

  17. Correcting ligands, metabolites, and pathways

    Directory of Open Access Journals (Sweden)

    Vriend Gert

    2006-11-01

    Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

  18. Synthetic cannabinoids: analysis and metabolites.

    Science.gov (United States)

    Elsohly, Mahmoud A; Gul, Waseem; Wanas, Amira S; Radwan, Mohamed M

    2014-02-27

    Cannabimimetics (commonly referred to as synthetic cannabinoids), a group of compounds encompassing a wide range of chemical structures, have been developed by scientists with the hope of achieving selectivity toward one or the other of the cannabinoid receptors CB1 and CB2. The goal was to have compounds that could possess high therapeutic activity without many side effects. However, underground laboratories have used the information generated by the scientific community to develop these compounds for illicit use as marijuana substitutes. This chapter reviews the different classes of these "synthetic cannabinoids" with particular emphasis on the methods used for their identification in the herbal products with which they are mixed and identification of their metabolites in biological specimens.

  19. Microsomal metabolism of trenbolone acetate metabolites ...

    Science.gov (United States)

    Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbolone, 17-trenbolone and trendione), little is known about other metabolites formed in vivo and subsequently discharged into the environment, with some evidence suggesting these unknown metabolites comprise a majority of the TBA mass dosed to the animal. Here, we explored the metabolism of the three known TBA metabolites using rat liver microsome studies. All TBA metabolites are transformed into a complex mixture of monohydroxylated products. Based on product characterization, the majority are more polar than the parent metabolites but maintain their characteristic trienone backbone. A minor degree of interconversion between known metabolites was also observed, as were higher order hydroxylated products with a greater extent of reaction. Notably, the distribution and yield of products were generally comparable across a series of variably induced rat liver microsomes, as well as during additional studies with human and bovine liver microsomes. Bioassays conducted with mixtures of these transformation products suggest that androgen receptor (AR) binding activity is diminished as a result of the microsomal treatment, suggesting that the transformation products are generally less potent than

  20. Riboselector: riboswitch-based synthetic selection device to expedite evolution of metabolite-producing microorganisms.

    Science.gov (United States)

    Jang, Sungho; Yang, Jina; Seo, Sang Woo; Jung, Gyoo Yeol

    2015-01-01

    Many successful metabolic engineering projects have utilized evolutionary approaches, which consist of generating phenotypic diversity and screening for desired phenotype. Since conventional screening methods suffer from low throughput and limited target metabolites, a universal high-throughput screening platform for selection of improved strains should be developed to facilitate evolution of metabolite high producer. Recently, riboswitches have received attention as attractive sensor-actuator hybrids that can control gene expression in response to intracellular metabolite concentration. Our group developed a riboswitch-based selection device called "Riboselector" which can give a growth advantage to metabolite-overproducing strains by modulating expression of a selectable marker gene. We applied the device to expedite evolution of lysine producing Escherichia coli, and the selected strain showed a dramatic improvement of lysine production compared to its parental strain. Moreover, a tryptophan-responsive Riboselector was also developed using synthetic tryptophan aptamer. In this chapter, we provide a step-by-step overview of developing synthetic RNA devices comprising a riboswitch and a selection module that specifically sense inconspicuous metabolites and enrich high producer strains out of library.

  1. Hybrid Gear

    Science.gov (United States)

    Handschuh, Robert F. (Inventor); Roberts, Gary D. (Inventor)

    2016-01-01

    A hybrid gear consisting of metallic outer rim with gear teeth and metallic hub in combination with a composite lay up between the shaft interface (hub) and gear tooth rim is described. The composite lay-up lightens the gear member while having similar torque carrying capability and it attenuates the impact loading driven noise/vibration that is typical in gear systems. The gear has the same operational capability with respect to shaft speed, torque, and temperature as an all-metallic gear as used in aerospace gear design.

  2. Hybrid Qualifications

    DEFF Research Database (Denmark)

    has turned out as a major focus of European education and training policies and certainly is a crucial principle underlying the European Qualifications Framework (EQF). In this context, «hybrid qualifications» (HQ) may be seen as an interesting approach to tackle these challenges as they serve «two...... masters», i.e. by producing skills for the labour market and enabling individuals to progress more or less directly to higher education. The specific focus of this book is placed on conditions, structures and processes which help to combine VET with qualifications leading into higher education...

  3. [Biologically active metabolites of the marine actinobacteria].

    Science.gov (United States)

    Sobolevskaia, M P; Kuznetsova, T A

    2010-01-01

    This review systematically data on the chemical structure and biological activity of metabolites of obligate and facultative marine actinobacteria, published from 2000 to 2007. We discuss some structural features of the five groups of metabolites related to macrolides and compounds containing lactone, quinone and diketopiperazine residues, cyclic peptides, alkaloids, and compounds of mixed biosynthesis. Survey shows a large chemical diversity of metabolites actinobacteria isolated from marine environment. It is shown that, along with metabolites, identical to previously isolated from terrestrial actinobacteria, marine actinobacteria synthesize unknown compounds not found in other natural sources, including micro organisms. Perhaps the biosynthesis of new chemotypes bioactive compounds in marine actinobacteria is one manifestation of chemical adaptation of microorganisms to environmental conditions at sea. Review stresses the importance of the chemical study of metabolites of marine actinobacteria. These studies are aimed at obtaining new data on marine microorganisms producers of biologically active compounds and chemical structure and biological activity of new low-molecular bioregulators of natural origin.

  4. Metabolite Profiling and Classification of DNA-Authenticated Licorice Botanicals.

    Science.gov (United States)

    Simmler, Charlotte; Anderson, Jeffrey R; Gauthier, Laura; Lankin, David C; McAlpine, James B; Chen, Shao-Nong; Pauli, Guido F

    2015-08-28

    Raw licorice roots represent heterogeneous materials obtained from mainly three Glycyrrhiza species. G. glabra, G. uralensis, and G. inflata exhibit marked metabolite differences in terms of flavanones (Fs), chalcones (Cs), and other phenolic constituents. The principal objective of this work was to develop complementary chemometric models for the metabolite profiling, classification, and quality control of authenticated licorice. A total of 51 commercial and macroscopically verified samples were DNA authenticated. Principal component analysis and canonical discriminant analysis were performed on (1)H NMR spectra and area under the curve values obtained from UHPLC-UV chromatograms, respectively. The developed chemometric models enable the identification and classification of Glycyrrhiza species according to their composition in major Fs, Cs, and species specific phenolic compounds. Further key outcomes demonstrated that DNA authentication combined with chemometric analyses enabled the characterization of mixtures, hybrids, and species outliers. This study provides a new foundation for the botanical and chemical authentication, classification, and metabolomic characterization of crude licorice botanicals and derived materials. Collectively, the proposed methods offer a comprehensive approach for the quality control of licorice as one of the most widely used botanical dietary supplements.

  5. Intuitionistic hybrid logic

    DEFF Research Database (Denmark)

    Braüner, Torben

    2011-01-01

    Intuitionistic hybrid logic is hybrid modal logic over an intuitionistic logic basis instead of a classical logical basis. In this short paper we introduce intuitionistic hybrid logic and we give a survey of work in the area.......Intuitionistic hybrid logic is hybrid modal logic over an intuitionistic logic basis instead of a classical logical basis. In this short paper we introduce intuitionistic hybrid logic and we give a survey of work in the area....

  6. Continuity Controlled Hybrid Automata

    OpenAIRE

    Bergstra, J. A.; Middelburg, C.A.

    2004-01-01

    We investigate the connections between the process algebra for hybrid systems of Bergstra and Middelburg and the formalism of hybrid automata of Henzinger et al. We give interpretations of hybrid automata in the process algebra for hybrid systems and compare them with the standard interpretation of hybrid automata as timed transition systems. We also relate the synchronized product operator on hybrid automata to the parallel composition operator of the process algebra. It turns out that the f...

  7. Hybridized tetraquarks

    Directory of Open Access Journals (Sweden)

    A. Esposito

    2016-07-01

    Full Text Available We propose a new interpretation of the neutral and charged X,Z exotic hadron resonances. Hybridized-tetraquarks are neither purely compact tetraquark states nor bound or loosely bound molecules but rather a manifestation of the interplay between the two. While meson molecules need a negative or zero binding energy, its counterpart for h-tetraquarks is required to be positive. The formation mechanism of this new class of hadrons is inspired by that of Feshbach metastable states in atomic physics. The recent claim of an exotic resonance in the Bs0π± channel by the D0 Collaboration and the negative result presented subsequently by the LHCb Collaboration are understood in this scheme, together with a considerable portion of available data on X,Z particles. Considerations on a state with the same quantum numbers as the X(5568 are also made.

  8. Hybridized Tetraquarks

    CERN Document Server

    Esposito, A.; Polosa, A.D.

    2016-01-01

    We propose a new interpretation of the neutral and charged X, Z exotic hadron resonances. Hybridized-tetraquarks are neither purely compact tetraquark states nor bound or loosely bound molecules. The latter would require a negative or zero binding energy whose counterpart in h-tetraquarks is a positive quantity. The formation mechanism of this new class of hadrons is inspired by that of Feshbach metastable states in atomic physics. The recent claim of an exotic resonance in the Bs pi+- channel by the D0 collaboration and the negative result presented subsequently by the LHCb collaboration are understood in this scheme, together with a considerable portion of available data on X, Z particles. Considerations on a state with the same quantum numbers as the X(5568) are also made.

  9. Fluxomics with ratiometric metabolite dyes.

    Science.gov (United States)

    Chaudhuri, Bhavna; Niittylä, Totte; Hörmann, Friederike; Frommer, Wolf B

    2007-03-01

    Today's major excitement in biology centers on signaling: How can a cell or organism measure the myriad of environmental cues, integrate it, and acclimate to the new conditions? Hormonal signals and second messengers are in the focus of most of these studies, e.g., regulation of glucose transporter GLUT4 cycling by insulin, or regulation of plant growth by auxin or brassinosteroids.1-3 In comparison, we generally assume that we know almost everything about basic metabolism since it has been studied for many decades; for example we know since the early 80s that allosteric regulation by fructose-2,6-bisphophate plays an important role in regulating glycolysis in plants and animals.4 This may be the reason why studies of metabolism appear to be a bit out of fashion. But if we look to other organisms such as E. coli or yeast, we rapidly realize that metabolism is controlled by complex interconnected signaling networks, and that we understand little of these signaling networks in humans and plants.5,6 As it turns out, the cell registers many metabolites, and flux through the pathways is regulated using complex signaling networks that involve calcium as well as hormones.

  10. Secondary Metabolites from Rubiaceae Species

    Directory of Open Access Journals (Sweden)

    Daiane Martins

    2015-07-01

    Full Text Available This study describes some characteristics of the Rubiaceae family pertaining to the occurrence and distribution of secondary metabolites in the main genera of this family. It reports the review of phytochemical studies addressing all species of Rubiaceae, published between 1990 and 2014. Iridoids, anthraquinones, triterpenes, indole alkaloids as well as other varying alkaloid subclasses, have shown to be the most common. These compounds have been mostly isolated from the genera Uncaria, Psychotria, Hedyotis, Ophiorrhiza and Morinda. The occurrence and distribution of iridoids, alkaloids and anthraquinones point out their chemotaxonomic correlation among tribes and subfamilies. From an evolutionary point of view, Rubioideae is the most ancient subfamily, followed by Ixoroideae and finally Cinchonoideae. The chemical biosynthetic pathway, which is not so specific in Rubioideae, can explain this and large amounts of both iridoids and indole alkaloids are produced. In Ixoroideae, the most active biosysthetic pathway is the one that produces iridoids; while in Cinchonoideae, it produces indole alkaloids together with other alkaloids. The chemical biosynthetic pathway now supports this botanical conclusion.

  11. Discovery of novel metabolites from marine actinomycetes.

    Science.gov (United States)

    Lam, Kin S

    2006-06-01

    Recent findings from culture-dependent and culture-independent methods have demonstrated that indigenous marine actinomycetes exist in the oceans and are widely distributed in different marine ecosystems. There is tremendous diversity and novelty among the marine actinomycetes present in marine environments. Progress has been made to isolate novel actinomycetes from samples collected at different marine environments and habitats. These marine actinomycetes produce different types of new secondary metabolites. Many of these metabolites possess biological activities and have the potential to be developed as therapeutic agents. Marine actinomycetes are a prolific but underexploited source for the discovery of novel secondary metabolites.

  12. Metabolism and metabolites of polychlorinated biphenyls.

    Science.gov (United States)

    Grimm, Fabian A; Hu, Dingfei; Kania-Korwel, Izabela; Lehmler, Hans-Joachim; Ludewig, Gabriele; Hornbuckle, Keri C; Duffel, Michael W; Bergman, Åke; Robertson, Larry W

    2015-03-01

    Abstract The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity, and thereby on the assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general, and in humans in particular. The aim of this document is to provide an overview of PCB metabolism, and to identify the metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and sulfated metabolites, especially those that persist in human blood. Potential intracellular targets and health risks are also discussed.

  13. Secondary metabolites of slime molds (myxomycetes).

    Science.gov (United States)

    Dembitsky, Valery M; Rezanka, Tomás; Spízek, Jaroslav; Hanus, Lumír O

    2005-04-01

    The compounds reported from the slime molds (myxomycetes) species are described. Almost 100 natural compounds including their chemical structures and biological activities are described in this review article. Only metabolites with a well-defined structure are included.

  14. Secondary metabolites of cyanobacteria Nostoc sp.

    Science.gov (United States)

    Kobayashi, Akio; Kajiyama, Shin-Ichiro

    1998-03-01

    Cyanobacteria attracted much attention recently because of their secondary metabolites with potent biological activities and unusual structures. This paper reviews some recent studies on the isolation, structural, elucidation and biological activities of the bioactive compounds from cyanobacteria Nostoc species.

  15. Streptopyrrole: An antimicrobial metabolite from Streptomyces armeniacus

    DEFF Research Database (Denmark)

    Breinholt, J.; Gürtler, Hanne; Kjær, Anders

    1998-01-01

    A colourless, crystalline metabolite, C14H12ClNO4, named streptopyrrole, has been isolated from submerged fermentation cultures of Streptomyces armeniacus by extraction, followed by chromatographic purification. Its tricyclic molecular framework, seemingly without natural product precedents...

  16. Antibacterial activity of secondary metabolites isolated from ...

    African Journals Online (AJOL)

    Aghomotsegin

    2015-10-28

    Oct 28, 2015 ... The metabolites were determined and extracted for GC analysis using the method of ... Gas chromatography-mass spectrometry (GC-MS) analysis. Bioactive ..... Ostry V (2008). Alternaria mycotoxins: an overview of chemical.

  17. Detecting beer intake by unique metabolite patterns

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian

    2016-01-01

    Evaluation of health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern...... representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were...... assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum...

  18. Continuity Controlled Hybrid Automata

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2004-01-01

    We investigate the connections between the process algebra for hybrid systems of Bergstra and Middelburg and the formalism of hybrid automata of Henzinger et al. We give interpretations of hybrid automata in the process algebra for hybrid systems and compare them with the standard interpretation of

  19. Continuity controlled Hybrid Automata

    NARCIS (Netherlands)

    Bergstra, J.A.; Middelburg, C.A.

    2008-01-01

    We investigate the connections between the process algebra for hybrid systems of Bergstra and Middelburg and the formalism of hybrid automata of Henzinger et al. We give interpretations of hybrid automata in the process algebra for hybrid systems and compare them with the standard interpretation of

  20. Tailoring specialized metabolite production in streptomyces.

    Science.gov (United States)

    Hiltner, Jana K; Hunter, Iain S; Hoskisson, Paul A

    2015-01-01

    Streptomycetes are prolific producers of a plethora of medically useful metabolites. These compounds are made by complex secondary (specialized) metabolic pathways, which utilize primary metabolic intermediates as building blocks. In this review we discuss the evolution of specialized metabolites and how expansion of gene families in primary metabolism has lead to the evolution of diversity in these specialized metabolic pathways and how developing a better understanding of expanded primary metabolic pathways can help enhance synthetic biology approaches to industrial pathway engineering.

  1. Synthesis of the major metabolites of Tolvaptan

    Institute of Scientific and Technical Information of China (English)

    Wei Li Wan; Jian Bo Wu; Fan Lei; Xiao Long Li; Li Hai; Yong Wu

    2012-01-01

    Tolvaptan is a nonpeptide arginine vasopressin (AVP) V2-receptor antagonist and used in the treatment of heart failure,cirrhosis,syndrome of inappropriate antidiuretic hormone secretion or other high-volume capacity of hyponatremia.The metabolites of tolvaptan are mainly produced by CYP3A4,including two major compounds named DM-4103 and DM-4107.Herein,the chemical synthesis of those two metabolites is described in this article for further study.

  2. The Significance of Lichens and Their Metabolites

    Science.gov (United States)

    Huneck, S.

    Lichens, symbiontic organisms of fungi and algae, synthesize numerous metabolites, the "lichen substances," which comprise aliphatic, cycloaliphatic, aromatic, and terpenic compounds. Lichens and their metabolites have a manifold biological activity: antiviral, antibiotic, antitumor, allergenic, plant growth inhibitory, antiherbivore, and enzyme inhibitory. Usnic acid, a very active lichen substance is used in pharmaceutical preparations. Large amounts of Pseudevernia furfuracea and Evernia prunastri are processed in the perfume industry, and some lichens are sensitive reagents for the evaluation of air pollution.

  3. Secondary metabolites in bryophytes: an ecological aspect.

    Science.gov (United States)

    Xie, Chun-Feng; Lou, Hong-Xiang

    2009-03-01

    Bryophytes frequently grow in an unfavorable environment as the earliest land plants, and inevitably biosynthesize secondary metabolites against biotic or abiotic stress. They not only defend against the plant competition, microbial attack, and insect or animal predation, but also function in UV protection, drought tolerance, and freezing survival. This review covers the ecological aspect of secondary metabolites in bryophytes and is taxonomically presented according to the ecological significances.

  4. Flux balance analysis accounting for metabolite dilution.

    Science.gov (United States)

    Benyamini, Tomer; Folger, Ori; Ruppin, Eytan; Shlomi, Tomer

    2010-01-01

    Flux balance analysis is a common method for predicting steady-state flux distributions within metabolic networks, accounting for the growth demand for the synthesis of a predefined set of essential biomass precursors. Ignoring the growth demand for the synthesis of intermediate metabolites required for balancing their dilution leads flux balance analysis to false predictions in some cases. Here, we present metabolite dilution flux balance analysis, which addresses this problem, resulting in improved metabolic phenotype predictions.

  5. Pharmacokinetics of Tyrosol Metabolites in Rats

    Directory of Open Access Journals (Sweden)

    Da-Hye Lee

    2016-01-01

    Full Text Available Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol-derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS. Two tyrosol metabolites (M1 and M2 were detected in the plasma. M1 was identified as tyrosol-4-sulfate (T4S with an [M − H]− ion at m/z 217. While M2 showed an [M − H]− ion at m/z 151.0, its metabolite was not identified. Pharmacokinetic analysis of T4S and M2 showed rapid uptake after oral administration of tyrosol within 1 h. The metabolites were rapidly distributed in most organs and tissues and eliminated within 4 h. The greatest T4S deposition by tissue weight was observed in the liver, followed by the kidney and spleen, while M2 was most concentrated in the kidney followed by the liver and spleen. These findings indicate that T4S and M2 were distributed mainly in tissues with an abundant blood supply and were rapidly excreted in urine.

  6. Pharmacokinetics of Tyrosol Metabolites in Rats.

    Science.gov (United States)

    Lee, Da-Hye; Kim, Yang-Ji; Kim, Min Jung; Ahn, Jiyun; Ha, Tae-Youl; Lee, Sang Hee; Jang, Young Jin; Jung, Chang Hwa

    2016-01-21

    Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol-derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Two tyrosol metabolites (M1 and M2) were detected in the plasma. M1 was identified as tyrosol-4-sulfate (T4S) with an [M - H](-) ion at m/z 217. While M2 showed an [M - H](-) ion at m/z 151.0, its metabolite was not identified. Pharmacokinetic analysis of T4S and M2 showed rapid uptake after oral administration of tyrosol within 1 h. The metabolites were rapidly distributed in most organs and tissues and eliminated within 4 h. The greatest T4S deposition by tissue weight was observed in the liver, followed by the kidney and spleen, while M2 was most concentrated in the kidney followed by the liver and spleen. These findings indicate that T4S and M2 were distributed mainly in tissues with an abundant blood supply and were rapidly excreted in urine.

  7. Hairy root culture for mass-production of high-value secondary metabolites.

    Science.gov (United States)

    Srivastava, Smita; Srivastava, Ashok K

    2007-01-01

    Plant cell cultivations are being considered as an alternative to agricultural processes for producing valuable phytochemicals. Since many of these products (secondary metabolites) are obtained by direct extraction from plants grown in natural habitat, several factors can alter their yield. The use of plant cell cultures has overcome several inconveniences for the production of these secondary metabolites. Organized cultures, and especially root cultures, can make a significant contribution in the production of secondary metabolites. Most of the research efforts that use differentiated cultures instead of cell suspension cultures have focused on transformed (hairy) roots. Agrobacterium rhizogenes causes hairy root disease in plants. The neoplastic (cancerous) roots produced by A. rhizogenes infection are characterized by high growth rate, genetic stability and growth in hormone free media. These genetically transformed root cultures can produce levels of secondary metabolites comparable to that of intact plants. Hairy root cultures offer promise for high production and productivity of valuable secondary metabolites (used as pharmaceuticals, pigments and flavors) in many plants. The main constraint for commercial exploitation of hairy root cultivations is the development and scaling up of appropriate reactor vessels (bioreactors) that permit the growth of interconnected tissues normally unevenly distributed throughout the vessel. Emphasis has focused on designing appropriate bioreactors suitable to culture the delicate and sensitive plant hairy roots. Recent reactors used for mass production of hairy roots can roughly be divided as liquid-phase, gas-phase, or hybrid reactors. The present review highlights the nature, applications, perspectives and scale up of hairy root cultures for the production of valuable secondary metabolites.

  8. Milk metabolites and their genetic variability.

    Science.gov (United States)

    Wittenburg, D; Melzer, N; Willmitzer, L; Lisec, J; Kesting, U; Reinsch, N; Repsilber, D

    2013-04-01

    The composition of milk is crucial to evaluate milk performance and quality measures. Milk components partly contribute to breeding scores, and they can be assessed to judge metabolic and energy status of the cow as well as to serve as predictive markers for diseases. In addition to the milk composition measures (e.g., fat, protein, lactose) traditionally recorded during milk performance test via infrared spectroscopy, novel techniques, such as gas chromatography-mass spectrometry, allow for a further analysis of milk into its metabolic components. Gas chromatography-mass spectrometry is suitable for measuring several hundred metabolites with high throughput, and thus it is applicable to study sources of genetic and nongenetic variation of milk metabolites in dairy cows. Heritability and mode of inheritance of metabolite measurements were studied in a linear mixed model approach including expected (pedigree) and realized (genomic) relationship between animals. The genetic variability of 190 milk metabolite intensities was analyzed from 1,295 cows held on 18 farms in Mecklenburg-Western Pomerania, Germany. Besides extensive pedigree information, genotypic data comprising 37,180 single nucleotide polymorphism markers were available. Goodness of fit and significance of genetic variance components based on likelihood ratio tests were investigated with a full model, including marker- and pedigree-based genetic effects. Broad-sense heritability varied from zero to 0.699, with a median of 0.125. Significant additive genetic variance was observed for highly heritable metabolites, but dominance variance was not significantly present. As some metabolites are particularly favorable for human nutrition, for instance, future research should address the identification of locus-specific genetic effects and investigate metabolites as the molecular basis of traditional milk performance test traits.

  9. Identification of in vitro metabolites of ethylphenidate by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Negreira, Noelia; Erratico, Claudio; van Nuijs, Alexander L N; Covaci, Adrian

    2016-01-05

    Ethylphenidate is a new potent synthetic psychoactive drug, structurally related to methylphenidate. Using human liver microsomes and cytosol, we have investigated for the first time the Phase-I and Phase-II in vitro metabolism of ethylphenidate. The structure of the metabolites was elucidated by hybrid quadrupole time-of-flight mass spectrometry. Overall, seven Phase-I, but no Phase-II metabolites were detected. Ethylphenidate underwent hydroxylation forming two primary mono-hydroxylated metabolites and, subsequently, dehydration and ring opening with an additional hydroxylation, forming secondary metabolites. The involvement of different human cytochrome P450 (CYP) enzymes in the formation of ethylphenidate metabolites was investigated using a panel of human recombinant CYPs (rCYPs). rCYP2C19 was the most active recombinant enzyme involved in the formation of all seven ethylphenidate metabolites detected, although other rCYPs (rCYP1A2, rCYP2B6, rCYPC9, rCYP2D6, and rCYP3A4, but not rCYP2E1) played a role in the metabolism of ethylphenidate. All metabolites identified in the present study can be considered as potential specific biomarkers of ethylphenidate in toxicological studies. Additionally, ritalinic acid and methylphenidate were formed by non-enzymatic hydrolysis and trans-esterification, and, therefore, they cannot be considered as (oxidative) metabolites of ethylphenidate. The presence of methylphenidate and ritalinic acid cannot be exclusively associated to the use of ethylphenidate, since methylphenidate is a drug itself and ritanilic acid can be formed from both ethylphenidate and methylphenidate.

  10. [Secondary Metabolites from Marine Microorganisms. I. Secondary Metabolites from Marine Actinomycetes].

    Science.gov (United States)

    Orlova, T I; Bulgakova, V G; Polin, A N

    2015-01-01

    Review represents data on new active metabolites isolated from marine actinomycetes published in 2007 to 2014. Marine actinomycetes are an unlimited source of novel secondary metabolites with various biological activities. Among them there are antibiotics, anticancer compounds, inhibitors of biochemical processes.

  11. Performance of the linear ion trap Orbitrap mass analyzer for qualitative and quantitative analysis of drugs of abuse and relevant metabolites in sewage water

    NARCIS (Netherlands)

    Bijlsma, L.; Emke, E.; Hernández, F.; de Voogt, P.

    2013-01-01

    This work illustrates the potential of liquid chromatography coupled to a hybrid linear ion trap Fourier Transform Orbitrap mass spectrometer for the simultaneous identification and quantification of 24 drugs of abuse and relevant metabolites in sewage water. The developed methodology consisted of a

  12. Pharmaceutically active secondary metabolites of marine actinobacteria.

    Science.gov (United States)

    Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

    2014-04-01

    Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

  13. Metabolite Profiling of Italian Tomato Landraces with Different Fruit Types

    Directory of Open Access Journals (Sweden)

    Svetlana eBaldina

    2016-05-01

    Full Text Available Increased interest towards traditional tomato varieties is fueled by the need to rescue desirable organoleptic traits and to improve the quality of fresh and processed tomatoes in the market. In addition, the phenotypic and genetic variation preserved in tomato landraces represents a means to understand the genetic basis of traits related to health and organoleptic aspects and improve them in modern varieties. To establish a framework for this approach, we studied the content of several metabolites in a panel of Italian tomato landraces categorized into three broad fruit type classes (flattened/ribbed, pear/oxheart, round/elongate. Three modern hybrids, corresponding to the three fruit shape typologies, were included as reference. Red ripe fruits were morphologically characterized and biochemically analyzed for their content in glycoalkaloids, phenols, amino acids and Amadori products. The round/elongate types showed a higher content in glycoalkaloids, whereas flattened types had higher levels of phenolic compounds. Flattened tomatoes were also rich in total amino acids and in particular in glutamic acid. Multivariate analysis of amino acid content clearly separated the three classes of fruit types. Making allowance of the very low number of genotypes, phenotype-marker relationships were analyzed after retrieving single nucleotide polymorphisms (SNPs among the landraces available in the literature. Sixty-six markers were significantly associated with the studied traits. The positions of several of these SNPs showed correspondence with already described genomic regions and QTLs supporting the reliability of the association. Overall the data indicated that significant changes in quality-related metabolites occur depending on the genetic background in traditional tomato germplasm, frequently according to specific fruit shape categories. Such a variability is suitable to harness association mapping for metabolic quality traits using this germplasm

  14. Metabolites from mangrove endophytic fungus Dothiorella sp.

    Institute of Scientific and Technical Information of China (English)

    XUQingyan; WANGJianfeng; HUANGYaojian; ZHENGZhonghui; SONGSiyang; ZHANGYongmin; SUWenjin

    2004-01-01

    Mangroves are special woody plant communities in the intertidal zone of tropical and subtropical coasts. They prove to be a natural microorganisms and new metabolites storage. In the study of mangrove endophytic fungi metabolites, four new compounds, Compounds 1, 2, 3 and 4, as well as a known octaketide, cytosporone B (5), are isolated from an endophytic fungus, Dothiorella sp., HTF3. They all show cytotoxic activities. The elucidation of these structures is mainly based on 1D/2D NMR and ESI-MS spectral analyses.

  15. Keanekaragaman metabolit sekunder Genus Artocarpus (Moraceae

    Directory of Open Access Journals (Sweden)

    ALIEFMAN HAKIM

    2011-11-01

    Full Text Available Hakim A. 2011. Keanekaragaman metabolit sekunder Genus Artocarpus (Moraceae. Bioteknologi 8: 86-98. Beberaapa spesies dari genus Artocarpus (Moraceae telah diteliti kandungan bahan alamnya. Metabolit sekunder yang berhasil diisolasi dari genus Artocarpus terdiri dari terpenoid, flavonoid, stilbenoid, arilbenzofuran, neolignan, dan adduct Diels-Alder. Kelompok flavonoid merupakan senyawa yang paling banyak ditemukan dari tumbuhan Artocarpus. Senyawa flavonoid yang telah berhasil diisolasi dari tumbuhan Artocarpus memiliki kerangka yang beragam seperti calkon, flavanon, flavan-3-ol, flavon sederhana, prenilflavon, oksepinoflavon, piranoflavon, dihidrobenzosanton, furanodi hidrobenzosanton, piranodihidrobenzosanton, kuinonosanton, siklolopentenosanton, santonolid, dihidrosanton.

  16. Network analysis of metabolite GWAS hits

    DEFF Research Database (Denmark)

    Matone, Alice; Scott-Boyer, Marie-Pier; Carayol, Jerome

    2016-01-01

    . Altered plasma metabolites concentration could partly explain weight loss maintenance mechanisms. In the present work, a systems biology approach has been applied to investigate the potential mechanisms involved in weight loss maintenance within the Diogenes weight-loss intervention study. METHODS...... were associated with successful weight maintenance and with several SNPs within CPS1 (cis-eQTL). In order to contextualize these results, a gene-metabolite interaction network of CPS1 and glycine has been built and analyzed, showing functional enrichment in genes involved in lipid metabolism and one...

  17. From hybrid swarms to swarms of hybrids

    Science.gov (United States)

    The introgression of modern humans (Homo sapiens) with Neanderthals 40,000 YBP after a half-million years of separation, may have led to the best example of a hybrid swarm on earth. Modern trade and transportation in support of the human hybrids has continued to introduce additional species, genotyp...

  18. The Hybrid Museum: Hybrid Economies of Meaning

    DEFF Research Database (Denmark)

    Vestergaard, Vitus

    2013-01-01

    this article shows that there are two different museum mindsets where the second mindset leans towards participatory practices. It is shown how a museum can support a hybrid economy of meaning that builds on both a user generated economy of meaning and an institutional economy of meaning and adds value to both....... Such a museum is referred to as a hybrid museum....

  19. Hydraulic Hybrid Vehicles

    Science.gov (United States)

    EPA and the United Parcel Service (UPS) have developed a hydraulic hybrid delivery vehicle to explore and demonstrate the environmental benefits of the hydraulic hybrid for urban pick-up and delivery fleets.

  20. Hybrid Management in Hospitals

    DEFF Research Database (Denmark)

    Byrkjeflot, Haldor; Jespersen, Peter Kragh

    2010-01-01

    Artiklen indeholder et litteraturbaseret studium af ledelsesformer i sygehuse, hvor sundhedsfaglig ledelse og generel ledelse mikses til hybride ledelsesformer......Artiklen indeholder et litteraturbaseret studium af ledelsesformer i sygehuse, hvor sundhedsfaglig ledelse og generel ledelse mikses til hybride ledelsesformer...

  1. Residue depletion of albendazole and its metabolites in aquacultured yellow perch (Perca flavescens).

    Science.gov (United States)

    Yu, D; Evans, E R; Hasbrouck, N; Reimschuessel, R; Shaikh, B

    2012-12-01

    Metabolism and residue depletion studies are conducted to determine the marker residue (MR) of a drug in a target tissue of food animals. The MR is used to monitor potential unauthorized use of drugs. The current work is a continuation of our efforts to study metabolism and depletion profiles of albendazole in multiple finfish species to determine a common MR. The results of this study suggest that albendazole sulfone metabolite could potentially serve as MR for albendazole in yellow perch muscle, similar to channel catfish and hybrid striped bass as reported previously by us.

  2. Resin Catalyst Hybrids

    Institute of Scientific and Technical Information of China (English)

    S. Asaoka

    2005-01-01

    @@ 1Introduction: What are resin catalyst hybrids? There are typically two types of resin catalyst. One is acidic resin which representative is polystyrene sulfonic acid. The other is basic resin which is availed as metal complex support. The objective items of this study on resin catalyst are consisting of pellet hybrid, equilibrium hybrid and function hybrid of acid and base,as shown in Fig. 1[1-5].

  3. Mesoscale hybrid calibration artifact

    Science.gov (United States)

    Tran, Hy D.; Claudet, Andre A.; Oliver, Andrew D.

    2010-09-07

    A mesoscale calibration artifact, also called a hybrid artifact, suitable for hybrid dimensional measurement and the method for make the artifact. The hybrid artifact has structural characteristics that make it suitable for dimensional measurement in both vision-based systems and touch-probe-based systems. The hybrid artifact employs the intersection of bulk-micromachined planes to fabricate edges that are sharp to the nanometer level and intersecting planes with crystal-lattice-defined angles.

  4. Realizing the Hybrid Library.

    Science.gov (United States)

    Pinfield, Stephen; Eaton, Jonathan; Edwards, Catherine; Russell, Rosemary; Wissenburg, Astrid; Wynne, Peter

    1998-01-01

    Outlines five projects currently funded by the United Kingdom's Electronic Libraries Program (eLib): HyLiFe (Hybrid Library of the Future), MALIBU (MAnaging the hybrid Library for the Benefit of Users), HeadLine (Hybrid Electronic Access and Delivery in the Library Networked Environment), ATHENS (authentication scheme), and BUILDER (Birmingham…

  5. Homoploid hybrid expectations

    Science.gov (United States)

    Homoploid hybrid speciation occurs when a stable, fertile, and reproductively isolated lineage results from hybridization between two distinct species without a change in ploidy level. Reproductive isolation between a homoploid hybrid species and its parents is generally attained via chromosomal re...

  6. Hybrid armature projectile

    Science.gov (United States)

    Hawke, Ronald S.; Asay, James R.; Hall, Clint A.; Konrad, Carl H.; Sauve, Gerald L.; Shahinpoor, Mohsen; Susoeff, Allan R.

    1993-01-01

    A projectile for a railgun that uses a hybrid armature and provides a seed block around part of the outer surface of the projectile to seed the hybrid plasma brush. In addition, the hybrid armature is continuously vaporized to replenish plasma in a plasma armature to provide a tandem armature and provides a unique ridge and groove to reduce plasama blowby.

  7. Intraply Hybrid Composite Design

    Science.gov (United States)

    Chamis, C. C.; Sinclair, J. H.

    1986-01-01

    Several theoretical approaches combined in program. Intraply hybrid composites investigated theoretically and experimentally at Lewis Research Center. Theories developed during investigations and corroborated by attendant experiments used to develop computer program identified as INHYD (Intraply Hybrid Composite Design). INHYD includes several composites micromechanics theories, intraply hybrid composite theories, and integrated hygrothermomechanical theory. Equations from theories used by program as appropriate for user's specific applications.

  8. Hybrid quantum information processing

    Energy Technology Data Exchange (ETDEWEB)

    Furusawa, Akira [Department of Applied Physics, School of Engineering, The University of Tokyo (Japan)

    2014-12-04

    I will briefly explain the definition and advantage of hybrid quantum information processing, which is hybridization of qubit and continuous-variable technologies. The final goal would be realization of universal gate sets both for qubit and continuous-variable quantum information processing with the hybrid technologies. For that purpose, qubit teleportation with a continuousvariable teleporter is one of the most important ingredients.

  9. Sequence-based analysis of secondary-metabolite biosynthesis in marine actinobacteria.

    Science.gov (United States)

    Gontang, Erin A; Gaudêncio, Susana P; Fenical, William; Jensen, Paul R

    2010-04-01

    A diverse collection of 60 marine-sediment-derived Actinobacteria representing 52 operational taxonomic units was screened by PCR for genes associated with secondary-metabolite biosynthesis. Three primer sets were employed to specifically target adenylation domains associated with nonribosomal peptide synthetases (NRPSs) and ketosynthase (KS) domains associated with type I modular, iterative, hybrid, and enediyne polyketide synthases (PKSs). In total, two-thirds of the strains yielded a sequence-verified PCR product for at least one of these biosynthetic types. Genes associated with enediyne biosynthesis were detected in only two genera, while 88% of the ketosynthase sequences shared greatest homology with modular PKSs. Positive strains included representatives of families not traditionally associated with secondary-metabolite production, including the Corynebacteriaceae, Gordoniaceae, Intrasporangiaceae, and Micrococcaceae. In four of five cases where phylogenetic analyses of KS sequences revealed close evolutionary relationships to genes associated with experimentally characterized biosynthetic pathways, secondary-metabolite production was accurately predicted. Sequence clustering patterns were used to provide an estimate of PKS pathway diversity and to assess the biosynthetic richness of individual strains. The detection of highly similar KS sequences in distantly related strains provided evidence of horizontal gene transfer, while control experiments designed to amplify KS sequences from Salinispora arenicola strain CNS-205, for which a genome sequence is available, led to the detection of 70% of the targeted PKS pathways. The results provide a bioinformatic assessment of secondary-metabolite biosynthetic potential that can be applied in the absence of fully assembled pathways or genome sequences. The rapid identification of strains that possess the greatest potential to produce new secondary metabolites along with those that produce known compounds can be used

  10. Sequence-Based Analysis of Secondary-Metabolite Biosynthesis in Marine Actinobacteria ▿ ‡

    Science.gov (United States)

    Gontang, Erin A.; Gaudêncio, Susana P.; Fenical, William; Jensen, Paul R.

    2010-01-01

    A diverse collection of 60 marine-sediment-derived Actinobacteria representing 52 operational taxonomic units was screened by PCR for genes associated with secondary-metabolite biosynthesis. Three primer sets were employed to specifically target adenylation domains associated with nonribosomal peptide synthetases (NRPSs) and ketosynthase (KS) domains associated with type I modular, iterative, hybrid, and enediyne polyketide synthases (PKSs). In total, two-thirds of the strains yielded a sequence-verified PCR product for at least one of these biosynthetic types. Genes associated with enediyne biosynthesis were detected in only two genera, while 88% of the ketosynthase sequences shared greatest homology with modular PKSs. Positive strains included representatives of families not traditionally associated with secondary-metabolite production, including the Corynebacteriaceae, Gordoniaceae, Intrasporangiaceae, and Micrococcaceae. In four of five cases where phylogenetic analyses of KS sequences revealed close evolutionary relationships to genes associated with experimentally characterized biosynthetic pathways, secondary-metabolite production was accurately predicted. Sequence clustering patterns were used to provide an estimate of PKS pathway diversity and to assess the biosynthetic richness of individual strains. The detection of highly similar KS sequences in distantly related strains provided evidence of horizontal gene transfer, while control experiments designed to amplify KS sequences from Salinispora arenicola strain CNS-205, for which a genome sequence is available, led to the detection of 70% of the targeted PKS pathways. The results provide a bioinformatic assessment of secondary-metabolite biosynthetic potential that can be applied in the absence of fully assembled pathways or genome sequences. The rapid identification of strains that possess the greatest potential to produce new secondary metabolites along with those that produce known compounds can be used

  11. Human pharmacokinetics of proguanil and its metabolites

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Ravn, P; Rønn, A;

    1987-01-01

    The pharmacokinetics of proguanil and its metabolites cycloguanil and p-chlorophenylbiguanide were studied in five healthy volunteers taking 200 mg orally for 14 days. A highly sensitive and specific high-performance liquid chromatographic assay was applied, clearly identifying all three compound...

  12. Clinical chemistry of serotonin and metabolites

    NARCIS (Netherlands)

    Kema, IP; de Vries, EGE; Muskiet, FAJ

    2000-01-01

    Analyses of serotonin and other 5-hydroxyindoles, such as its precursor 5-hydroxytryptophan and major metabolite 5-hydroxyindoleacetic acid (5-HIAA), are indispensable for the elucidation of their (patho)physiological roles. In clinical chemistry attention is mainly focused on the diagnosis and foll

  13. Clinical chemistry of serotonin and metabolites

    NARCIS (Netherlands)

    Kema, IP; de Vries, EGE; Muskiet, FAJ

    2000-01-01

    Analyses of serotonin and other 5-hydroxyindoles, such as its precursor 5-hydroxytryptophan and major metabolite 5-hydroxyindoleacetic acid (5-HIAA), are indispensable for the elucidation of their (patho)physiological roles. In clinical chemistry attention is mainly focused on the diagnosis and

  14. Antiinflammatory and immunomodulating properties of fungal metabolites

    NARCIS (Netherlands)

    Lull Noguera, C.; Wichers, H.J.; Savelkoul, H.F.J.

    2005-01-01

    We discuss current information on the ability of extracts and isolated metabolites from mushrooms to modulate immune responses. This can result in a more enhanced innate and acquired disease resistance. The major immunomodulating effects of these active substances derived from mushrooms include mito

  15. A review: trichloroethylene metabolites: potential cardiac teratogens.

    Science.gov (United States)

    Johnson, P D; Dawson, B V; Goldberg, S J

    1998-08-01

    This review is a a series of the authors' studies designed to test the hypothesis that administration of trichloroethylene (TCE), dichloroethylene (DCE), their metabolites, and related compounds are responsible for fetal cardiac teratogenesis when given to pregnant rats during organogenesis. Identification of teratogenic compounds will allow more accurate assessment of environmental contaminants and public health risks. Epidemiologic studies and previous teratogenic studies using chick embryos and fetal rats have reported an increased number of congenital cardiac defects when exposed to TCE or DCE during fetal development. Metabolites of TCE and DCE studied in the drinking-water exposure study include trichloroacetic acid TCAA), monochloroacetic acid, trichloroethanol, carboxymethylcysteine, trichloroacetaldehyde, dichloroacetaldehyde, and dichlorovinyl cysteine. Varying doses of each were given in drinking water to pregnant rats during the period of fetal heart development. Rats receiving 2730 ppm TCAA in drinking water were the only metabolite group demonstrating a significant increase in the number of cardiac defects in fetuses on a per-litter basis (p = 0.0004 Wilcoxon test and p =0.0015 exact permutation test). Maternal and fetal variables showed no statistically significant differences between treated and untreated groups. When treated with TCAA the increased cardiac defects, as compared to controls, do not preclude the involvement of other metabolites as cardiac teratogens, but indicates TCAA as a specific cardiac teratogen. Further studies of drinking-water exposure and potential mechanisms of action on the developing heart are proceeding.

  16. The Membrane Gradostat Reactor: Secondary metabolite production ...

    African Journals Online (AJOL)

    SERVER

    2007-05-16

    May 16, 2007 ... gies are now well accepted and cost effective (Wiesner and Chellam ... uce these secondary metabolites continuously were .... and ammonium sources in the feed and permeates reco- .... when the solutions were fed through the lumen of the .... Progress from batch culture to a membrane bioreactor for the.

  17. The hydrogen hybrid option

    Energy Technology Data Exchange (ETDEWEB)

    Smith, J.R.

    1993-10-15

    The energy efficiency of various piston engine options for series hybrid automobiles are compared with conventional, battery powered electric, and proton exchange membrane (PEM) fuel cell hybrid automobiles. Gasoline, compressed natural gas (CNG), and hydrogen are considered for these hybrids. The engine and fuel comparisons are done on a basis of equal vehicle weight, drag, and rolling resistance. The relative emissions of these various fueled vehicle options are also presented. It is concluded that a highly optimized, hydrogen fueled, piston engine, series electric hybrid automobile will have efficiency comparable to a similar fuel cell hybrid automobile and will have fewer total emissions than the battery powered vehicle, even without a catalyst.

  18. 呋喃西林代谢物在杂交鳢(斑鳢♀×乌鳢♂)体内的残留消除规律研究%Studies on the Residue and Degradation Rules of Nitrofurazone Metabolites in Hybrid Snakehead(Channa maculata (♀) × Channa argus (♂))

    Institute of Scientific and Technical Information of China (English)

    刘书贵; 吴仕辉; 郑光明; 王群; 戴晓欣; 宋怿; 刘毅辉; 马兵

    2013-01-01

    在模拟养殖条件下,对杂交鳢(斑鳢Channa maculata♀×乌鳢Channa argus♂)体内呋喃西林代谢物氨基脲(Semicarbazide,SEM)的残留及消除规律进行了研究.在(30.5±0.5)℃水温条件下,用质量浓度为2 mg/L呋喃西林药浴杂交鳢苗种2d.药浴期间于0.5、1、2、4、8、12、24、48 h取样,停止药浴后于0.5、1、2、4、8、12、24、48、96、192、288、384、480、720、960、1 200、1 440、1 920、2 400、2 880 h取样,采用液-质联用(HPLC-MS)方法测定杂交鳢肌肉中SEM的含量.结果显示,药浴期间0.5~48 h,肌肉中SEM质量分数从(32.58±2.82) μg/kg逐渐升高至(175.92±18.49) μg/kg;药浴结束后的SEM质量分数经测定于1h达到最高,为(108.00 ±5.86) μg/kg;药浴结束后2~ 48h,苗种体内SEM质量分数维持在(53.60 ±4.90) ~ (69.21 ±5.71)μg/kg,48 h后显著下降,至60d后已低于检测限0.25 μg/kg.鱼体肌肉中SEM的平均消除速率为0.089 μg/(kg.h).结果显示,在该试验条件下,鱼体内SEM可在60 d后代谢消除.%In this paper, the residues and depuration of semicarbazide ( SEM) in hybrid snakeheads (Channa maculata (♀×) × Channa argus (♂ ) ) were tested. Hybrid snakeheads were drug-bathed 2 days with 2 mg/L nitrofurazone at temperatures of (30. 5 ± 0. 5) ℃. During drug-bath, the samples were collected at 0.5,1,2,4,8,12,24,48 h,and at 0.5,1,2,4,8,12,24,48,96,192,288,384,480,720, 960,1 200,1 440,1 920,2 400,2 880 h after drug-bath, and the SEM residues in muscle were measured by high performance liquid chromatography tandem mass spectrometry ( HPLC-MS). The results showed that the SEM residue from 0. 5 to 48 h in hybrid snakehead muscle increased gradually from (32. 58 ± 2. 82) to( 175. 92 ± 18. 49) μg/kg during drug-bath. SEM residue was found to be the highest, (108. 00 ± 5.86) ±g/kg at 1 h after drug-bath. The residues ranged between (53. 60 ± 4. 90) and (69. 21 ±5.71) μ/kg from 2 to 48 h after drug-bath but significantly decreased

  19. Effect of Genetics, Environment, and Phenotype on the Metabolome of Maize Hybrids Using GC/MS and LC/MS.

    Science.gov (United States)

    Tang, Weijuan; Hazebroek, Jan; Zhong, Cathy; Harp, Teresa; Vlahakis, Chris; Baumhover, Brian; Asiago, Vincent

    2017-06-28

    We evaluated the variability of metabolites in various maize hybrids due to the effect of environment, genotype, phenotype as well as the interaction of the first two factors. We analyzed 480 forage and the same number of grain samples from 21 genetically diverse non-GM Pioneer brand maize hybrids, including some with drought tolerance and viral resistance phenotypes, grown at eight North American locations. As complementary platforms, both GC/MS and LC/MS were utilized to detect a wide diversity of metabolites. GC/MS revealed 166 and 137 metabolites in forage and grain samples, respectively, while LC/MS captured 1341 and 635 metabolites in forage and grain samples, respectively. Univariate and multivariate analyses were utilized to investigate the response of the maize metabolome to the environment, genotype, phenotype, and their interaction. Based on combined percentages from GC/MS and LC/MS datasets, the environment affected 36% to 84% of forage metabolites, while less than 7% were affected by genotype. The environment affected 12% to 90% of grain metabolites, whereas less than 27% were affected by genotype. Less than 10% and 11% of the metabolites were affected by phenotype in forage and grain, respectively. Unsupervised PCA and HCA analyses revealed similar trends, i.e., environmental effect was much stronger than genotype or phenotype effects. On the basis of comparisons of disease tolerant and disease susceptible hybrids, neither forage nor grain samples originating from different locations showed obvious phenotype effects. Our findings demonstrate that the combination of GC/MS and LC/MS based metabolite profiling followed by broad statistical analysis is an effective approach to identify the relative impact of environmental, genetic and phenotypic effects on the forage and grain composition of maize hybrids.

  20. Hybridization and extinction.

    Science.gov (United States)

    Todesco, Marco; Pascual, Mariana A; Owens, Gregory L; Ostevik, Katherine L; Moyers, Brook T; Hübner, Sariel; Heredia, Sylvia M; Hahn, Min A; Caseys, Celine; Bock, Dan G; Rieseberg, Loren H

    2016-08-01

    Hybridization may drive rare taxa to extinction through genetic swamping, where the rare form is replaced by hybrids, or by demographic swamping, where population growth rates are reduced due to the wasteful production of maladaptive hybrids. Conversely, hybridization may rescue the viability of small, inbred populations. Understanding the factors that contribute to destructive versus constructive outcomes of hybridization is key to managing conservation concerns. Here, we survey the literature for studies of hybridization and extinction to identify the ecological, evolutionary, and genetic factors that critically affect extinction risk through hybridization. We find that while extinction risk is highly situation dependent, genetic swamping is much more frequent than demographic swamping. In addition, human involvement is associated with increased risk and high reproductive isolation with reduced risk. Although climate change is predicted to increase the risk of hybridization-induced extinction, we find little empirical support for this prediction. Similarly, theoretical and experimental studies imply that genetic rescue through hybridization may be equally or more probable than demographic swamping, but our literature survey failed to support this claim. We conclude that halting the introduction of hybridization-prone exotics and restoring mature and diverse habitats that are resistant to hybrid establishment should be management priorities.

  1. Spoof Plasmon Hybridization

    CERN Document Server

    Zhang, Jingjing; Luo, Yu; Shen, Xiaopeng; Maier, Stefan A; Cui, Tie Jun

    2016-01-01

    Plasmon hybridization between closely spaced nanoparticles yields new hybrid modes not found in individual constituents, allowing for the engineering of resonance properties and field enhancement capabilities of metallic nanostructure. Experimental verifications of plasmon hybridization have been thus far mostly limited to optical frequencies, as metals cannot support surface plasmons at longer wavelengths. Here, we introduce the concept of 'spoof plasmon hybridization' in highly conductive metal structures and investigate experimentally the interaction of localized surface plasmon resonances (LSPR) in adjacent metal disks corrugated with subwavelength spiral patterns. We show that the hybridization results in the splitting of spoof plasmon modes into bonding and antibonding resonances analogous to molecular orbital rule and plasmonic hybridization in optical spectrum. These hybrid modes can be manipulated to produce enormous field enhancements (larger than 5000) by tuning the separation between disks or alte...

  2. Spatial distribution of metabolites in the human lens.

    Science.gov (United States)

    Tamara, Semen O; Yanshole, Lyudmila V; Yanshole, Vadim V; Fursova, Anjella Zh; Stepakov, Denis A; Novoselov, Vladimir P; Tsentalovich, Yuri P

    2016-02-01

    Spatial distribution of 34 metabolites along the optical and equatorial axes of the human lens has been determined. For the majority of metabolites, the homogeneous distribution has been observed. That suggests that the rate of the metabolite transformation in the lens is low due to the general metabolic passivity of the lens fiber cells. However, the redox processes are active in the lens; as a result, some metabolites, including antioxidants, demonstrate the "nucleus-depleted" type of distribution, whereas secondary UV filters show the "nucleus-enriched" type. The metabolite concentrations at the lens poles and equator are similar for all metabolites under study. The concentric pattern of the "nucleus-depleted" and "nucleus-enriched" distributions testifies that the metabolite distribution inside the lens is mostly governed by a passive diffusion, relatively free along the fiber cells and retarded in the radial direction across the cells. No significant difference in the metabolite distribution between the normal and cataractous human lenses was found.

  3. Discovering the secondary metabolite potential encoded within entomopathogenic fungi.

    Science.gov (United States)

    Gibson, Donna M; Donzelli, Bruno G G; Krasnoff, Stuart B; Keyhani, Nemat O

    2014-10-01

    This highlight discusses the secondary metabolite potential of the insect pathogens Metarhizium and Beauveria, including a bioinformatics analysis of secondary metabolite genes for which no products are yet identified.

  4. Antioxidant status, immune system, blood metabolites and carcass ...

    African Journals Online (AJOL)

    Antioxidant status, immune system, blood metabolites and carcass characteristic of broiler ... African Journal of Biotechnology ... rhizome powder (TP) on performance, blood metabolite, immune system, antioxidant status, and relative weight of ...

  5. The role of natural chlorinated hydroquinone metabolites in ligninolytic fungi

    NARCIS (Netherlands)

    Teunissen, P.J.M.

    1999-01-01

    Ligninolytic Basidiomycetes have been reported to produce a wide variety of chloroaromatic compounds as secondary metabolites, which are structurally similar to environmental pollutants. Among these are chlorinated hydroquinone metabolites (CHM), such as 2-chloro-1,4-dimethoxybenzene

  6. Marine Fish Hybridization

    KAUST Repository

    He, Song

    2017-04-01

    Natural hybridization is reproduction (without artificial influence) between two or more species/populations which are distinguishable from each other by heritable characters. Natural hybridizations among marine fishes were highly underappreciated due to limited research effort; it seems that this phenomenon occurs more often than is commonly recognized. As hybridization plays an important role in biodiversity processes in the marine environment, detecting hybridization events and investigating hybridization is important to understand and protect biodiversity. The first chapter sets the framework for this disseration study. The Cohesion Species Concept was selected as the working definition of a species for this study as it can handle marine fish hybridization events. The concept does not require restrictive species boundaries. A general history and background of natural hybridization in marine fishes is reviewed during in chapter as well. Four marine fish hybridization cases were examed and documented in Chapters 2 to 5. In each case study, at least one diagnostic nuclear marker, screened from among ~14 candidate markers, was found to discriminate the putative hybridizing parent species. To further investigate genetic evidence to support the hybrid status for each hybrid offspring in each case, haploweb analysis on diagnostic markers (nuclear and/or mitochondrial) and the DAPC/PCA analysis on microsatellite data were used. By combining the genetic evidences, morphological traits, and ecological observations together, the potential reasons that triggered each hybridization events and the potential genetic/ecology effects could be discussed. In the last chapter, sequences from 82 pairs of hybridizing parents species (for which COI barcoding sequences were available either on GenBank or in our lab) were collected. By comparing the COI fragment p-distance between each hybridizing parent species, some general questions about marine fish hybridization were discussed: Is

  7. Qualitative and quantitative determination of drotaverine metabolites in rat bile.

    Science.gov (United States)

    Vargay, Z; Simon, G; Winter, M; Szüts, T

    1980-01-01

    After oral and intravenous administration of drotaverin-14C its metabolites were determined in rat bile. Three major metabolites were identified by tlc. All the metabolites appeared in conjugated form. No unchanged drotaverine was detectable in the bile, except after treatment with doses much in excess of the therapeutic range. The ratio of major metabolites to unchanged product was determined by two-dimensional densitometry using a Telechrom Video Densitometer.

  8. Non-peptide metabolites from the genus Bacillus.

    Science.gov (United States)

    Hamdache, Ahlem; Lamarti, Ahmed; Aleu, Josefina; Collado, Isidro G

    2011-04-25

    Bacillus species produce a number of non-peptide metabolites that display a broad spectrum of activity and structurally diverse bioactive chemical structures. Biosynthetic, biological, and structural studies of these metabolites isolated from Bacillus species are reviewed. This contribution also includes a detailed study of the activity of the metabolites described, especially their role in biological control mechanisms.

  9. SPE-NMR metabolite sub-profiling of urine

    NARCIS (Netherlands)

    Jacobs, D.M.; Spiesser, L.; Garnier, M.; Roo, de N.; Dorsten, van F.; Hollebrands, B.; Velzen, van E.; Draijer, R.; Duynhoven, van J.P.M.

    2012-01-01

    NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has b

  10. SPE-NMR metabolite sub-profiling of urine

    NARCIS (Netherlands)

    Jacobs, D.M.; Spiesser, L.; Garnier, M.; Roo, de N.; Dorsten, van F.; Hollebrands, B.; Velzen, van E.; Draijer, R.; Duynhoven, van J.P.M.

    2012-01-01

    NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has

  11. An RNA isolation system for plant tissues rich in secondary metabolites

    Directory of Open Access Journals (Sweden)

    Bhardwaj Pardeep K

    2011-03-01

    Full Text Available Abstract Background Secondary metabolites are reported to interfere with the isolation of RNA particularly with the recipes that use guanidinium-based salt. Such interference was observed in isolation of RNA with medicinal plants rheum (Rheum australe and arnebia (Arnebia euchroma. A rapid and less cumbersome system for isolation of RNA was essential to facilitate any study related to gene expression. Findings An RNA isolation system free of guanidinium salt was developed that successfully isolated RNA from rheum and arnebia. The method took about 45 min and was successfully evaluated on twenty one tissues with varied secondary metabolites. The A260/280 ratio ranged between 1.8 - 2.0 with distinct 28 S and 18 S rRNA bands visible on a formaldehyde-agarose gel. Conclusions The present manuscript describes a rapid protocol for isolation of RNA, which works well with all the tissues examined so far. The remarkable feature was the success in isolation of RNA with those tissues, wherein the most commonly used methods failed. Isolated RNA was amenable to downstream applications such as reverse transcription-polymerase chain reaction (RT-PCR, differential display (DD, suppression subtractive hybridization (SSH library construction, and northern hybridization.

  12. Artificially decreased vapour pressure deficit in field conditions modifies foliar metabolite profiles in birch and aspen.

    Science.gov (United States)

    Lihavainen, Jenna; Keinänen, Markku; Keski-Saari, Sarita; Kontunen-Soppela, Sari; Sõber, Anu; Oksanen, Elina

    2016-07-01

    Relative air humidity (RH) is expected to increase in northern Europe due to climate change. Increasing RH reduces the difference of water vapour pressure deficit (VPD) between the leaf and the atmosphere, and affects the gas exchange of plants. Little is known about the effects of decreased VPD on plant metabolism, especially under field conditions. This study was conducted to determine the effects of artificially decreased VPD on silver birch (Betula pendula Roth.) and hybrid aspen (Populus tremula L.×P. tremuloides Michx.) foliar metabolite and nutrient profiles in a unique free air humidity manipulation (FAHM) field experiment during the fourth season of humidity manipulation, in 2011. Long-term exposure to decreased VPD modified nutrient homeostasis in tree leaves, as demonstrated by a lower N concentration and N:P ratio in aspen leaves, and higher Na concentration and lower K:Na ratio in the leaves of both species in decreased VPD than in ambient VPD. Decreased VPD caused a shift in foliar metabolite profiles of both species, affecting primary and secondary metabolites. Metabolic adjustment to decreased VPD included elevated levels of starch and heptulose sugars, sorbitol, hemiterpenoid and phenolic glycosides, and α-tocopherol. High levels of carbon reserves, phenolic compounds, and antioxidants under decreased VPD may modify plant resistance to environmental stresses emerging under changing climate.

  13. Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”

    Science.gov (United States)

    Gomes, Nelson G. M.; Dasari, Ramesh; Chandra, Sunena; Kiss, Robert; Kornienko, Alexander

    2016-01-01

    Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors’ opinion should be pursued due to their most promising anticancer activities. PMID:27213412

  14. Marine Invertebrate Metabolites with Anticancer Activities: Solutions to the “Supply Problem”

    Directory of Open Access Journals (Sweden)

    Nelson G. M. Gomes

    2016-05-01

    Full Text Available Marine invertebrates provide a rich source of metabolites with anticancer activities and several marine-derived agents have been approved for the treatment of cancer. However, the limited supply of promising anticancer metabolites from their natural sources is a major hurdle to their preclinical and clinical development. Thus, the lack of a sustainable large-scale supply has been an important challenge facing chemists and biologists involved in marine-based drug discovery. In the current review we describe the main strategies aimed to overcome the supply problem. These include: marine invertebrate aquaculture, invertebrate and symbiont cell culture, culture-independent strategies, total chemical synthesis, semi-synthesis, and a number of hybrid strategies. We provide examples illustrating the application of these strategies for the supply of marine invertebrate-derived anticancer agents. Finally, we encourage the scientific community to develop scalable methods to obtain selected metabolites, which in the authors’ opinion should be pursued due to their most promising anticancer activities.

  15. Comparison of the secondary metabolites in Penicillium chrysogenum between pilot and industrial penicillin G fermentations.

    Science.gov (United States)

    Cao, Ying-Xiu; Qiao, Bin; Lu, Hua; Chen, Yao; Yuan, Ying-Jin

    2011-02-01

    The disparity of secondary metabolites in Penicillium chrysogenum between two scales of penicillin G fermentation (50 L as pilot process and 150,000 L as industrial one) was investigated by ion-pair reversed-phase liquid chromatography tandemed with hybrid quadrupole time-of-flight mass spectrometry. In industrial process, the pools of intracellular L-α-aminoadipyl-L-cysteinyl-D-valine (LLD-ACV) and isopenicillin N (IPN) were remarkably less than that in the pilot one, which indicated that the productivity of penicillin G might be higher in the large scale of fermentation. This conclusion was supported by the higher intracellular penicillin G concentration as well as its higher yield per unit biomass in industrial cultivation. The different changing tendencies of IPN, 6-aminopenicillanic acid and 6-oxopiperide-2-carboxylic acid between two processes also suggested the same conclusion. The higher content of intracellular LLD-ACV in pilot process lead to a similarly higher concentration of bis-δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine, which had an inhibitory effect on ACV synthetase and also subdued the activity of IPN synthetase. The interconversion of secondary metabolites and the influence they put on enzymes would intensify the discrepancy between two fermentations more largely. These findings provided new insight into the changes and regulation of secondary metabolites in P. chrysogenum under different fermentation sizes.

  16. Novel bioactive metabolites of dipyrone (metamizol).

    Science.gov (United States)

    Rogosch, Tobias; Sinning, Christian; Podlewski, Agnes; Watzer, Bernhard; Schlosburg, Joel; Lichtman, Aron H; Cascio, Maria G; Bisogno, Tiziana; Di Marzo, Vincenzo; Nüsing, Rolf; Imming, Peter

    2012-01-01

    Dipyrone is a common antipyretic drug and the most popular non-opioid analgesic in many countries. In spite of its long and widespread use, molecular details of its fate in the body are not fully known. We administered dipyrone orally to mice. Two unknown metabolites were found, viz. the arachidonoyl amides of the known major dipyrone metabolites, 4-methylaminoantipyrine (2) and 4-aminoantipyrine (3). They were identified by ESI-LC-MS/MS after extraction from the CNS, and comparison with reference substances prepared synthetically. The arachidonoyl amides were positively tested for cannabis receptor binding (CB(1) and CB(2)) and cyclooxygenase inhibition (COX-1 and COX-2 in tissues and as isolated enzymes), suggesting that the endogenous cannabinoid system may play a role in the effects of dipyrone against pain. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Biologically Active Metabolites Synthesized by Microalgae

    Science.gov (United States)

    de Morais, Michele Greque; Vaz, Bruna da Silva; de Morais, Etiele Greque; Costa, Jorge Alberto Vieira

    2015-01-01

    Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences. PMID:26339647

  18. Deep Sea Actinomycetes and Their Secondary Metabolites

    Directory of Open Access Journals (Sweden)

    Kui Hong

    2017-05-01

    Full Text Available Deep sea is a unique and extreme environment. It is a hot spot for hunting marine actinomycetes resources and secondary metabolites. The novel deep sea actinomycete species reported from 2006 to 2016 including 21 species under 13 genera with the maximum number from Microbacterium, followed by Dermacoccus, Streptomyces and Verrucosispora, and one novel species for the other 9 genera. Eight genera of actinomycetes were reported to produce secondary metabolites, among which Streptomyces is the richest producer. Most of the compounds produced by the deep sea actinomycetes presented antimicrobial and anti-cancer cell activities. Gene clusters related to biosynthesis of desotamide, heronamide, and lobophorin have been identified from the deep sea derived Streptomyces.

  19. The neurotoxicity of pyridinium metabolites of haloperidol

    Directory of Open Access Journals (Sweden)

    Agnieszka Górska

    2015-10-01

    Full Text Available Haloperydol is a butyrophenone, typical neuroleptic agent characterized as a high antipsychotics effects in the treatment of schizophrenia and in palliative care to alleviation many syndromes, such as naursea, vomiting and delirium. Clinical problems occurs during and after administration of the drug are side effects, particularly extrapyrramidal symptoms (EPS. The neurotoxicity of haloperydol may be initiated by the cationic metabolites of haloperydol, HPP+, RHPP+, formed by oxidation and reduction pathways. These metabolites are transported by human organic cation transporters (hOCT to several brain structures for exapmle, in substantia nigra, striatum, caudate nucleus, hippocampus. After reaching the dopaminergic neurons inhibits mitochondrial complex I, evidence for free radical involvement, thus leading to neurodegeneration.

  20. Metabolite production by differnt Ulocladium species

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Hollensted, Morten

    2008-01-01

    Ulocladium, which is phylogenetically related to Alternaria, contains species that are food spoilers and plant pathogens, but also species that have potential as enzyme producers and bio-control agents. Ulocladium spp. are often found on dead vegetation, in soil, air and dust, but also on food...... and feedstuffs and on water-damaged building materials. The aim was to study the morphological and chemical diversity within the genus Ulocladium. Cultures of 52 Ulocladium strains were identified morphologically, and then extracted and analyzed using automated Chemical Image Analysis. Production of individual...... metabolites was correlated to species identity and source of isolation (substratum). Chemical analyses corroborated the morphological identifications and showed the existence of several species species-specific metabolites, of which most were known Compounds. The production of curvularins was specific...

  1. Biologically Active Metabolites Synthesized by Microalgae

    Directory of Open Access Journals (Sweden)

    Michele Greque de Morais

    2015-01-01

    Full Text Available Microalgae are microorganisms that have different morphological, physiological, and genetic traits that confer the ability to produce different biologically active metabolites. Microalgal biotechnology has become a subject of study for various fields, due to the varied bioproducts that can be obtained from these microorganisms. When microalgal cultivation processes are better understood, microalgae can become an environmentally friendly and economically viable source of compounds of interest, because production can be optimized in a controlled culture. The bioactive compounds derived from microalgae have anti-inflammatory, antimicrobial, and antioxidant activities, among others. Furthermore, these microorganisms have the ability to promote health and reduce the risk of the development of degenerative diseases. In this context, the aim of this review is to discuss bioactive metabolites produced by microalgae for possible applications in the life sciences.

  2. Differences in urinary trichloroethylene metabolites of animals.

    Directory of Open Access Journals (Sweden)

    Ogata,Masana

    1979-12-01

    Full Text Available Differences in urinary excretion of trichloroethylene were studied in rabbits, rats and mice. Trichloretylene (1 m mole/kg was injected intra-peritoneally, then urinary trichloroacetic acid and trichloroethanol glucuronide were measured. The results were: 1. The ratio of total excretion of trichloroethylene metabolites to the administered trichloroethylene decreased in the order of mice, rats and rabbits. 2. The ratio of total trichloroethanol to trichloroacetic acid in urine decreased in the order of rabbits (69.2, mice (12.8 and rats (2.3. The high ratio in rabbits was due to the extremely small amount of trichloroacetic acid in the urine. 3. Differences in these two urinary metabolites in the three kinds of animals and in human subjects were discussed.

  3. Transgenic hybrid poplar for sustainable and scalable production of the commodity/specialty chemical, 2-phenylethanol.

    Directory of Open Access Journals (Sweden)

    Michael A Costa

    Full Text Available Fast growing hybrid poplar offers the means for sustainable production of specialty and commodity chemicals, in addition to rapid biomass production for lignocellulosic deconstruction. Herein we describe transformation of fast-growing transgenic hybrid poplar lines to produce 2-phenylethanol, this being an important fragrance, flavor, aroma, and commodity chemical. It is also readily converted into styrene or ethyl benzene, the latter being an important commodity aviation fuel component. Introducing this biochemical pathway into hybrid poplars marks the beginnings of developing a platform for a sustainable chemical delivery system to afford this and other valuable specialty/commodity chemicals at the scale and cost needed. These modified plant lines mainly sequester 2-phenylethanol via carbohydrate and other covalently linked derivatives, thereby providing an additional advantage of effective storage until needed. The future potential of this technology is discussed. MALDI metabolite tissue imaging also established localization of these metabolites in the leaf vasculature.

  4. Henkin and Hybrid Logic

    DEFF Research Database (Denmark)

    Blackburn, Patrick Rowan; Huertas, Antonia; Manzano, Maria;

    2014-01-01

    Leon Henkin was not a modal logician, but there is a branch of modal logic that has been deeply influenced by his work. That branch is hybrid logic, a family of logics that extend orthodox modal logic with special proposition symbols (called nominals) that name worlds. This paper explains why...... Henkin’s techniques are so important in hybrid logic. We do so by proving a completeness result for a hybrid type theory called HTT, probably the strongest hybrid logic that has yet been explored. Our completeness result builds on earlier work with a system called BHTT, or basic hybrid type theory...... is due to the first-order perspective, which lies at the heart of Henin’s best known work and hybrid logic....

  5. Indoor fungi and their ciliostatic metabolites.

    Science.gov (United States)

    Piecková, Elena; Kunová, Zuzana

    2002-01-01

    According to epidemiological studies, it is possible that some secondary metabolites of indoor airborne fungi could be responsible for health troubles which occupants suffer from. In our previous experiments, a model with tracheal rings of 1-day-old chicks in vitro was shown to be a very suitable method to study the ciliostatic chloroform-extractable endo- and/or exometabolites of filamentous fungi. In this study we isolated the filamentous fungi from walls of "mouldy" dwellings and schools (cultivation on dichloran 18% glycerol agar at 25 and 37 degrees C for 10 d) in Slovakia. We studied the ciliostatic effect of the chloroform-extractable endo- and exometabolites of 96 representative isolates (stationary cultivation on the liquid medium with 2% of yeast extract and 10% of sucrose at 25 degrees C for 10 days) on the cilia movement in tracheal organ cultures of 1-day-old chickens in vitro after 24, 48 and 72 hrs (incubation in the minimal essential medium according to Eagle with Earl s salts and 20 microg of extract of metabolites dissolved in dimethylsulfoxide per 1 mL). Strains of Penicillium Link: Fr. sp., Aspergillus versicolor (Vuill.) Tiraboschi, A. flavus Link, Cladosporium sphaerospermum Penzig and C. cladosporioides (Fres.) de Vries were isolated most frequently. Two A. flavus isolates were able to produce aflatoxins B1, B2, G1, G2 in vitro after cultivation on the liquid medium with 20% sucrose and 2% yeast extract. This is the first isolation of aflatoxigenic A. flavus strains from dwellings in Slovakia. All frequently isolated strains produced secondary metabolites with the strongest ciliostatic activity -- their exo- and endometabolites stopped tracheal ciliary movement in chicks till 24 h. There are some toxic fungal metabolites in the indoor air not only with the ability to destroy ciliary movement in the upper airways in vitro but, probably, during long-lasting exposure to cause general intoxication of macroorganism via lung tissue.

  6. Three new metabolites from Botrytis cinerea.

    Science.gov (United States)

    Wang, Tian-Shan; Zhou, Jin-Yan; Tan, Hong

    2008-01-01

    Three new metabolites, gamma-abscisolactone (1), botrytisic acids A (3) and B (4) were isolated from the fermentation broth of Botrytis cinerea TB-3-H8. Their structures were elucidated on the basis of MS, IR, UV, and NMR spectroscopic data. Compound 2 was isolated from natural resource for the first time. The structure of 1 was further confirmed by single-crystal X-ray diffraction (CCDC-265897).

  7. A review: trichloroethylene metabolites: potential cardiac teratogens.

    OpenAIRE

    Johnson, P. D.; Dawson, B V; Goldberg, S J

    1998-01-01

    This review is a a series of the authors' studies designed to test the hypothesis that administration of trichloroethylene (TCE), dichloroethylene (DCE), their metabolites, and related compounds are responsible for fetal cardiac teratogenesis when given to pregnant rats during organogenesis. Identification of teratogenic compounds will allow more accurate assessment of environmental contaminants and public health risks. Epidemiologic studies and previous teratogenic studies using chick embryo...

  8. [Actinomycetes from mangrove and their secondary metabolites].

    Science.gov (United States)

    Hong, Kui

    2013-11-04

    Mangroves are woody plants located in tropical and subtropical intertidal coastal regions. Driven by the discovery of novel natural products from marine environment, mangrove is becoming a hot spot for actinomycetes resources collection and secondary metabolites (natural products) identification as well as their biosynthesis mechanism investigation. Salinaspora A produced by a Salinispora strain isolated from Bahamas mangrove environment, is in the first clinical trial. Till the time of writing this paper, 24 genera of 11 families and 8 suborders under the actinomycetale have been reported from mangrove, among which 3 are new genera, and 31 are new species. At the same time, secondary metabolites were identified from the mangrove actinomycetes culture, including alkanoids and quinines, azalomycins, antimycins, bezamides and quinazolines, divergolides, indole derivatives, kandenols, macrocyclic dilactones, and the attractive structures, such as the Streptocarbazoles, the multicyclic indolsesquiterpenes, and xiamycin presented unique structures. Their biosynthetic mechanism has also been investigated. Most of the metabolites were isolated from streptomycetes, with a few from Micromonospora and Saccharopolyspora.

  9. Natural metabolites for parasitic weed management.

    Science.gov (United States)

    Vurro, Maurizio; Boari, Angela; Evidente, Antonio; Andolfi, Anna; Zermane, Nadjia

    2009-05-01

    Compounds of natural origin, such as phytotoxins produced by fungi or natural amino acids, could be used in parasitic weed management strategies by interfering with the early growth stages of the parasites. These metabolites could inhibit seed germination or germ tube elongation, so preventing attachment to the host plant, or, conversely, stimulate seed germination in the absence of the host, contributing to a reduction in the parasite seed bank. Some of the fungal metabolites assayed were very active even at very low concentrations, such as some macrocyclic trichothecenes, which at 0.1 microM strongly suppressed the germination of Orobanche ramosa L. seeds. Interesting results were also obtained with some novel toxins, such as phyllostictine A, highly active in reducing germ tube elongation and seed germination both of O. ramosa and of Cuscuta campestris Yuncker. Among the amino acids tested, methionine and arginine were particularly interesting, as they were able to suppress seed germination at concentrations lower than 1 mM. Some of the fungal metabolites tested were also able to stimulate the germination of O. ramosa seeds. The major findings in this research field are described and discussed.

  10. Phthalate Metabolites, Consumer Habits and Health Effects

    Directory of Open Access Journals (Sweden)

    Peter Wallner

    2016-07-01

    Full Text Available Phthalates are multifunctional chemicals used in a wide variety of consumer products. The aim of this study was to investigate whether levels of urinary phthalate metabolites in urine samples of Austrian mothers and their children were associated with consumer habits and health indicators. Within an Austrian biomonitoring survey, urine samples from 50 mother-child pairs of five communities (two-stage random stratified sampling were analysed. The concentrations of 14 phthalate metabolites were determined, and a questionnaire was administered. Monoethyl phthalate (MEP, mono-n-butyl phthalate (MnBP, mono-isobutyl phthalate (MiBP, monobenzyl phthalate (MBzP, mono-(2-ethylhexyl phthalate (MEHP, mono-(2-ethyl-5-hydroxyhexyl phthalate (5OH-MEHP, mono-(2-ethyl-5-oxohexyl phthalate (5oxo-MEHP, mono-(5-carboxy-2-ethylpentyl phthalate (5cx-MEPP, and 3-carboxy-mono-propyl phthalate (3cx-MPP could be quantified in the majority of samples. Significant correlations were found between the use of hair mousse, hair dye, makeup, chewing gum, polyethylene terephthalate (PET bottles and the diethyl phthalate (DEP metabolite MEP. With regard to health effects, significant associations of MEP in urine with headache, repeated coughing, diarrhoea, and hormonal problems were observed. MBzP was associated with repeated coughing and MEHP was associated with itching.

  11. Phthalate Metabolites, Consumer Habits and Health Effects

    Science.gov (United States)

    Wallner, Peter; Kundi, Michael; Hohenblum, Philipp; Scharf, Sigrid; Hutter, Hans-Peter

    2016-01-01

    Phthalates are multifunctional chemicals used in a wide variety of consumer products. The aim of this study was to investigate whether levels of urinary phthalate metabolites in urine samples of Austrian mothers and their children were associated with consumer habits and health indicators. Within an Austrian biomonitoring survey, urine samples from 50 mother-child pairs of five communities (two-stage random stratified sampling) were analysed. The concentrations of 14 phthalate metabolites were determined, and a questionnaire was administered. Monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-(5-carboxy-2-ethylpentyl) phthalate (5cx-MEPP), and 3-carboxy-mono-propyl phthalate (3cx-MPP) could be quantified in the majority of samples. Significant correlations were found between the use of hair mousse, hair dye, makeup, chewing gum, polyethylene terephthalate (PET) bottles and the diethyl phthalate (DEP) metabolite MEP. With regard to health effects, significant associations of MEP in urine with headache, repeated coughing, diarrhoea, and hormonal problems were observed. MBzP was associated with repeated coughing and MEHP was associated with itching. PMID:27428989

  12. Optimizing metabolite production using periodic oscillations.

    Directory of Open Access Journals (Sweden)

    Steven W Sowa

    2014-06-01

    Full Text Available Methods for improving microbial strains for metabolite production remain the subject of constant research. Traditionally, metabolic tuning has been mostly limited to knockouts or overexpression of pathway genes and regulators. In this paper, we establish a new method to control metabolism by inducing optimally tuned time-oscillations in the levels of selected clusters of enzymes, as an alternative strategy to increase the production of a desired metabolite. Using an established kinetic model of the central carbon metabolism of Escherichia coli, we formulate this concept as a dynamic optimization problem over an extended, but finite time horizon. Total production of a metabolite of interest (in this case, phosphoenolpyruvate, PEP is established as the objective function and time-varying concentrations of the cellular enzymes are used as decision variables. We observe that by varying, in an optimal fashion, levels of key enzymes in time, PEP production increases significantly compared to the unoptimized system. We demonstrate that oscillations can improve metabolic output in experimentally feasible synthetic circuits.

  13. BSA Hybrid Synthesized Polymer

    Institute of Scientific and Technical Information of China (English)

    Zong Bin LIU; Xiao Pei DENG; Chang Sheng ZHAO

    2006-01-01

    Bovine serum albumin (BSA), a naturally occurring biopolymer, was regarded as a polymeric material to graft to an acrylic acid (AA)-N-vinyl pyrrolidone (NVP) copolymer to form a biomacromolecular hybrid polymer. The hybrid polymer can be blended with polyethersulfone (PES) to increase the hydrophilicity of the PES membrane, which suggested that the hybrid polymer might have a wide application in the modification of biomaterials.

  14. Hybrid Action Systems

    DEFF Research Database (Denmark)

    Ronkko, Mauno; Ravn, Anders P.

    1997-01-01

    a differential action, which allows differential equations as primitive actions. The extension allows us to model hybrid systems with both continuous and discrete behaviour. The main result of this paper is an extension of such a hybrid action system with parallel composition. The extension does not change...... the original meaning of the parallel composition, and therefore also the ordinary action systems can be composed in parallel with the hybrid action systems....

  15. HYBRID VEHICLE CONTROL SYSTEM

    Directory of Open Access Journals (Sweden)

    V. Dvadnenko

    2016-06-01

    Full Text Available The hybrid vehicle control system includes a start–stop system for an internal combustion engine. The system works in a hybrid mode and normal vehicle operation. To simplify the start–stop system, there were user new possibilities of a hybrid car, which appeared after the conversion. Results of the circuit design of the proposed system of basic blocks are analyzed.

  16. Nanoscale Organic Hybrid Electrolytes

    KAUST Repository

    Nugent, Jennifer L.

    2010-08-20

    Nanoscale organic hybrid electrolytes are composed of organic-inorganic hybrid nanostructures, each with a metal oxide or metallic nanoparticle core densely grafted with an ion-conducting polyethylene glycol corona - doped with lithium salt. These materials form novel solvent-free hybrid electrolytes that are particle-rich, soft glasses at room temperature; yet manifest high ionic conductivity and good electrochemical stability above 5V. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Hybrid radiator cooling system

    Science.gov (United States)

    France, David M.; Smith, David S.; Yu, Wenhua; Routbort, Jules L.

    2016-03-15

    A method and hybrid radiator-cooling apparatus for implementing enhanced radiator-cooling are provided. The hybrid radiator-cooling apparatus includes an air-side finned surface for air cooling; an elongated vertically extending surface extending outwardly from the air-side finned surface on a downstream air-side of the hybrid radiator; and a water supply for selectively providing evaporative cooling with water flow by gravity on the elongated vertically extending surface.

  18. Hybrid Unifying Variable Supernetwork Model

    Institute of Scientific and Technical Information of China (English)

    LIU; Qiang; FANG; Jin-qing; LI; Yong

    2015-01-01

    In order to compare new phenomenon of topology change,evolution,hybrid ratio and network characteristics of unified hybrid network theoretical model with unified hybrid supernetwork model,this paper constructed unified hybrid variable supernetwork model(HUVSM).The first layer introduces a hybrid ratio dr,the

  19. Large Unifying Hybrid Supernetwork Model

    Institute of Scientific and Technical Information of China (English)

    LIU; Qiang; FANG; Jin-qing; LI; Yong

    2015-01-01

    For depicting multi-hybrid process,large unifying hybrid network model(so called LUHNM)has two sub-hybrid ratios except dr.They are deterministic hybrid ratio(so called fd)and random hybrid ratio(so called gr),respectively.

  20. Hybrid Rocket Technology

    National Research Council Canada - National Science Library

    Sankaran Venugopal; K K Rajesh; V Ramanujachari

    2011-01-01

    With their unique operational characteristics, hybrid rockets can potentially provide safer, lower-cost avenues for spacecraft and missiles than the current solid propellant and liquid propellant systems...

  1. Hybrid FOSS Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Armstrong researchers are continuing their efforts to further develop FOSS technologies. A hybrid FOSS technique (HyFOSS) employs conventional continuous grating...

  2. From hybrid swarms to swarms of hybrids

    Science.gov (United States)

    Stohlgren, Thomas J.; Szalanski, Allen L; Gaskin, John F.; Young, Nicholas E.; West, Amanda; Jarnevich, Catherine S.; Tripodi, Amber

    2015-01-01

    Science has shown that the introgression or hybridization of modern humans (Homo sapiens) with Neanderthals up to 40,000 YBP may have led to the swarm of modern humans on earth. However, there is little doubt that modern trade and transportation in support of the humans has continued to introduce additional species, genotypes, and hybrids to every country on the globe. We assessed the utility of species distributions modeling of genotypes to assess the risk of current and future invaders. We evaluated 93 locations of the genus Tamarix for which genetic data were available. Maxent models of habitat suitability showed that the hybrid, T. ramosissima x T. chinensis, was slightly greater than the parent taxa (AUCs > 0.83). General linear models of Africanized honey bees, a hybrid cross of Tanzanian Apis mellifera scutellata and a variety of European honey bee including A. m. ligustica, showed that the Africanized bees (AUC = 0.81) may be displacing European honey bees (AUC > 0.76) over large areas of the southwestern U.S. More important, Maxent modeling of sub-populations (A1 and A26 mitotypes based on mDNA) could be accurately modeled (AUC > 0.9), and they responded differently to environmental drivers. This suggests that rapid evolutionary change may be underway in the Africanized bees, allowing the bees to spread into new areas and extending their total range. Protecting native species and ecosystems may benefit from risk maps of harmful invasive species, hybrids, and genotypes.

  3. Cardiac hybrid imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gaemperli, Oliver [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); University Hospital Zurich, Nuclear Cardiology, Cardiovascular Center, Zurich (Switzerland); Kaufmann, Philipp A. [University Hospital Zurich, Cardiac Imaging, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2014-05-15

    Hybrid cardiac single photon emission computed tomography (SPECT)/CT imaging allows combined assessment of anatomical and functional aspects of cardiac disease. In coronary artery disease (CAD), hybrid SPECT/CT imaging allows detection of coronary artery stenosis and myocardial perfusion abnormalities. The clinical value of hybrid imaging has been documented in several subsets of patients. In selected groups of patients, hybrid imaging improves the diagnostic accuracy to detect CAD compared to the single imaging techniques. Additionally, this approach facilitates functional interrogation of coronary stenoses and guidance with regard to revascularization procedures. Moreover, the anatomical information obtained from CT coronary angiography or coronary artery calcium scores (CACS) adds prognostic information over perfusion data from SPECT. The use of cardiac hybrid imaging has been favoured by the dissemination of dedicated hybrid systems and the release of dedicated image fusion software, which allow simple patient throughput for hybrid SPECT/CT studies. Further technological improvements such as more efficient detector technology to allow for low-radiation protocols, ultra-fast image acquisition and improved low-noise image reconstruction algorithms will be instrumental to further promote hybrid SPECT/CT in research and clinical practice. (orig.)

  4. Hybrid intelligent engineering systems

    CERN Document Server

    Jain, L C; Adelaide, Australia University of

    1997-01-01

    This book on hybrid intelligent engineering systems is unique, in the sense that it presents the integration of expert systems, neural networks, fuzzy systems, genetic algorithms, and chaos engineering. It shows that these new techniques enhance the capabilities of one another. A number of hybrid systems for solving engineering problems are presented.

  5. A Hybrid Imagination

    DEFF Research Database (Denmark)

    Jamison, Andrew; Christensen, Steen Hyldgaard; Botin, Lars

    contexts, or sites, for mixing scientific knowledge and technical skills from different fields and social domains into new combinations, thus fostering what the authors term a “hybrid imagination”. Such a hybrid imagination is especially important today, as a way to counter the competitive and commercial...

  6. Hybrid trajectory spaces

    NARCIS (Netherlands)

    Collins, P.J.

    2005-01-01

    In this paper, we present a general framework for describing and studying hybrid systems. We represent the trajectories of the system as functions on a hybrid time domain, and the system itself by its trajectory space, which is the set of all possible trajectories. The trajectory space is given a na

  7. Editorial: Hybrid Systems

    DEFF Research Database (Denmark)

    Olderog, Ernst-Rüdiger; Ravn, Anders Peter

    2007-01-01

    An introduction to three papers in a special issue on Hybrid Systems. These paper were first presented at an IFIP WG 2.2 meeting in Skagen 2005.......An introduction to three papers in a special issue on Hybrid Systems. These paper were first presented at an IFIP WG 2.2 meeting in Skagen 2005....

  8. Regulatory Roles of Metabolites in Cell Signaling Networks

    Institute of Scientific and Technical Information of China (English)

    Feng Li; Wei Xu; Shimin Zhao

    2013-01-01

    Mounting evidence suggests that cellular metabolites,in addition to being sources of fuel and macromolecular substrates,are actively involved in signaling and epigenetic regulation.Many metabolites,such as cyclic AMP,which regulates phosphorylation/dephosphorylation,have been identified to modulate DNA and histone methylation and protein stability.Metabolite-driven cellular regulation occurs through two distinct mechanisms:proteins allosterically bind or serve as substrates for protein signaling pathways,and metabolites covalently modify proteins to regulate their functions.Such novel protein metabolites include fumarate,succinyl-CoA,propionyl-CoA,butyryl-CoA and crontonyl-CoA.Other metabolites,including α-ketoglutarate,succinate and fumarate,regulate epigenetic processes and cell signaling via protein binding.Here,we summarize recent progress in metabolite-derived post-translational protein modification and metabolite-binding associated signaling regulation.Uncovering metabolites upstream of cell signaling and epigenetic networks permits the linkage of metabolic disorders and human diseases,and suggests that metabolite modulation may be a strategy for innovative therapeutics and disease prevention techniques.

  9. Hybrid reactors. [Fuel cycle

    Energy Technology Data Exchange (ETDEWEB)

    Moir, R.W.

    1980-09-09

    The rationale for hybrid fusion-fission reactors is the production of fissile fuel for fission reactors. A new class of reactor, the fission-suppressed hybrid promises unusually good safety features as well as the ability to support 25 light-water reactors of the same nuclear power rating, or even more high-conversion-ratio reactors such as the heavy-water type. One 4000-MW nuclear hybrid can produce 7200 kg of /sup 233/U per year. To obtain good economics, injector efficiency times plasma gain (eta/sub i/Q) should be greater than 2, the wall load should be greater than 1 MW.m/sup -2/, and the hybrid should cost less than 6 times the cost of a light-water reactor. Introduction rates for the fission-suppressed hybrid are usually rapid.

  10. Hybrid propulsion technology program

    Science.gov (United States)

    1990-01-01

    Technology was identified which will enable application of hybrid propulsion to manned and unmanned space launch vehicles. Two design concepts are proposed. The first is a hybrid propulsion system using the classical method of regression (classical hybrid) resulting from the flow of oxidizer across a fuel grain surface. The second system uses a self-sustaining gas generator (gas generator hybrid) to produce a fuel rich exhaust that was mixed with oxidizer in a separate combustor. Both systems offer cost and reliability improvement over the existing solid rocket booster and proposed liquid boosters. The designs were evaluated using life cycle cost and reliability. The program consisted of: (1) identification and evaluation of candidate oxidizers and fuels; (2) preliminary evaluation of booster design concepts; (3) preparation of a detailed point design including life cycle costs and reliability analyses; (4) identification of those hybrid specific technologies needing improvement; and (5) preperation of a technology acquisition plan and large scale demonstration plan.

  11. Endogenous cross-talk of fungal metabolites.

    Directory of Open Access Journals (Sweden)

    Kevin J Sheridan

    2015-01-01

    Full Text Available Non-ribosomal peptide synthesis in fungi requires a ready supply of proteogenic and non-proteogenic amino acids which are subsequently incorporated into the nascent non-ribosomal peptide via a thiotemplate mechanism catalysed by non-ribosomal peptide synthetases. Substrate amino acids can be modified prior to or during incorporation into the non-ribosomal peptide, or following incorporation into an early stage amino acid-containing biosynthetic intermediate. These post-incorporation modifications involve a range of additional enzymatic activities including but not exclusively, monooxygenases, methyltransferases, epimerases, oxidoreductases and glutathione transferases which are essential to effect biosynthesis of the final non-ribosomal peptide. Likewise, polyketide biosynthesis is directly by polyketide synthase megaenzymes and cluster-encoded ancilliary decorating enzymes. Additionally, a suite of additional primary metabolites, for example: CoA, acetyl CoA, S-adenosylmethionine, glutathione, NADPH, malonyl CoA and molecular oxygen, amongst others are required for non-ribosomal peptide and polyketide synthesis. Clearly these processes must involve exquisite orchestration to facilitate the simultaneous biosynthesis of different types of non-ribosomal peptides, polyketides, and related metabolites requiring identical or similar biosynthetic precursors or co-factors. Moreover, the near identical structures of many natural products within a given family (e.g., ergot alkaloids, along with localization to similar regions within fungi (e.g., conidia suggests that cross-talk may exist, in terms of biosynthesis and functionality. Finally, we speculate if certain biosynthetic steps involved in non-ribosomal peptide and polyketide synthesis play a role in cellular protection or environmental adaptation, and wonder if these enzymatic reactions are of equivalent importance to the actual biosynthesis of the final metabolite.

  12. Metabolic prediction of important agronomic traits in hybrid rice (Oryza sativa L.).

    Science.gov (United States)

    Dan, Zhiwu; Hu, Jun; Zhou, Wei; Yao, Guoxin; Zhu, Renshan; Zhu, Yingguo; Huang, Wenchao

    2016-02-24

    Hybrid crops have contributed greatly to improvements in global food and fodder production over the past several decades. Nevertheless, the growing population and changing climate have produced food crises and energy shortages. Breeding new elite hybrid varieties is currently an urgent task, but present breeding procedures are time-consuming and labour-intensive. In this study, parental metabolic information was utilized to predict three polygenic traits in hybrid rice. A complete diallel cross population consisting of eighteen rice inbred lines was constructed, and the hybrids' plant height, heading date and grain yield per plant were predicted using 525 metabolites. Metabolic prediction models were built using the partial least square regression method, with predictive abilities ranging from 0.858 to 0.977 for the hybrid phenotypes, relative heterosis, and specific combining ability. Only slight changes in predictive ability were observed between hybrid populations, and nearly no changes were detected between reciprocal hybrids. The outcomes of prediction of the three highly polygenic traits demonstrated that metabolic prediction was an accurate (high predictive abilities) and efficient (unaffected by population genetic structures) strategy for screening promising superior hybrid rice. Exploitation of this pre-hybridization strategy may contribute to rice production improvement and accelerate breeding programs.

  13. Marine metabolites: The sterols of soft coral

    Digital Repository Service at National Institute of Oceanography (India)

    Sarma, N.S.; Krishna, M.S.; Pasha, Sk.G.; Rao, T.S.P.; Venkateswarlu, Y.; Parameswaran, P.S.

    stream_size 141933 stream_content_type text/plain stream_name Chem_Rev_109_2803.pdf.txt stream_source_info Chem_Rev_109_2803.pdf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 Marine Metabolites... nuclear structure or of the “usual” C 8 or C 9 side chain. The side chains of corals can have from nil to eleven carbons. Their structures are given in Figures 1-5inthe sequence of increasing number of carbon atomsstwo, three, four, five, and seven carbon...

  14. New Secondary Metabolites from Quercus coccifera L.

    Directory of Open Access Journals (Sweden)

    Didem Şöhretoğlu

    2014-07-01

    Full Text Available Three new secondary metabolites kermesoside (1, cocciferoside (2 and (--8-chlorocatechin (3, were isolated from the the stems with barks of Quercus coccifera along with five known phenolic compounds, 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl-propan-1-one (4 and 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl-propan-1-one (5, trans-resveratrol-3-O-β-glucopyranoside (6 lyoniresinol-9-O-β-xylopyranoside (7, lyoniresinol-9-O-β-glucopyranoside (8. The structure elucidation of the isolated compounds was performed by spectroscopic methods (UV, 1D- and 2D- NMR and HR-MS.

  15. Using Hairy Roots for Production of Valuable Plant Secondary Metabolites.

    Science.gov (United States)

    Tian, Li

    2015-01-01

    Plants synthesize a wide variety of natural products, which are traditionally termed secondary metabolites and, more recently, coined specialized metabolites. While these chemical compounds are employed by plants for interactions with their environment, humans have long since explored and exploited plant secondary metabolites for medicinal and practical uses. Due to the tissue-specific and low-abundance accumulation of these metabolites, alternative means of production in systems other than intact plants are sought after. To this end, hairy root culture presents an excellent platform for producing valuable secondary metabolites. This chapter will focus on several major groups of secondary metabolites that are manufactured by hairy roots established from different plant species. Additionally, the methods for preservations of hairy roots will also be reviewed.

  16. Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

    Science.gov (United States)

    Schäberle, Till F

    2016-01-01

    Summary Myxobacteria are famous for their ability to produce most intriguing secondary metabolites. Till recently, only terrestrial myxobacteria were in the focus of research. In this review, however, we discuss marine-derived myxobacteria, which are particularly interesting due to their relatively recent discovery and due to the fact that their very existence was called into question. The to-date-explored members of these halophilic or halotolerant myxobacteria are all grouped into the suborder Nannocystineae. Few of them were chemically investigated revealing around 11 structural types belonging to the polyketide, non-ribosomal peptide, hybrids thereof or terpenoid class of secondary metabolites. A most unusual structural type is represented by salimabromide from Enhygromyxa salina. In silico analyses were carried out on the available genome sequences of four bacterial members of the Nannocystineae, revealing the biosynthetic potential of these bacteria. PMID:27340488

  17. A hybrid approach to urine drug testing using high-resolution mass spectrometry and select immunoassays.

    Science.gov (United States)

    McMillin, Gwendolyn A; Marin, Stephanie J; Johnson-Davis, Kamisha L; Lawlor, Bryan G; Strathmann, Frederick G

    2015-02-01

    The major objective of this research was to propose a simplified approach for the evaluation of medication adherence in chronic pain management patients, using liquid chromatography time-of-flight (TOF) mass spectrometry, performed in parallel with select homogeneous enzyme immunoassays (HEIAs). We called it a "hybrid" approach to urine drug testing. The hybrid approach was defined based on anticipated positivity rates, availability of commercial reagents for HEIAs, and assay performance, particularly analytical sensitivity and specificity for drug(s) of interest. Subsequent to implementation of the hybrid approach, time to result was compared with that observed with other urine drug testing approaches. Opioids, benzodiazepines, zolpidem, amphetamine-like stimulants, and methylphenidate metabolite were detected by TOF mass spectrometry to maximize specificity and sensitivity of these 37 drug analytes. Barbiturates, cannabinoid metabolite, carisoprodol, cocaine metabolite, ethyl glucuronide, methadone, phencyclidine, propoxyphene, and tramadol were detected by HEIAs that performed adequately and/or for which positivity rates were very low. Time to result was significantly reduced compared with the traditional approach. The hybrid approach to urine drug testing provides a simplified and analytically specific testing process that minimizes the need for secondary confirmation. Copyright© by the American Society for Clinical Pathology.

  18. Exploring laser-guided metal deposition through a microbe metabolite

    OpenAIRE

    2009-01-01

    Purpose: The purpose of the paper is to describe exploring laser-guided metal deposition through a microbe metabolite.Design/methodology/approach: A maskless micro-fabrication of laser-guided deposition process through the metabolite of Acidophilic bacteria Thiobacillus ferrooxidans (T.f.) is explored.Findings: The authors have conducted an analysis of the metal deposition process using the point thermal-source of the Nd:YAG laser through the metabolite of Acidophilic bacteria Thiobacillus. A...

  19. Differences between human plasma and serum metabolite profiles.

    Directory of Open Access Journals (Sweden)

    Zhonghao Yu

    Full Text Available BACKGROUND: Human plasma and serum are widely used matrices in clinical and biological studies. However, different collecting procedures and the coagulation cascade influence concentrations of both proteins and metabolites in these matrices. The effects on metabolite concentration profiles have not been fully characterized. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the concentrations of 163 metabolites in plasma and serum samples collected simultaneously from 377 fasting individuals. To ensure data quality, 41 metabolites with low measurement stability were excluded from further analysis. In addition, plasma and corresponding serum samples from 83 individuals were re-measured in the same plates and mean correlation coefficients (r of all metabolites between the duplicates were 0.83 and 0.80 in plasma and serum, respectively, indicating significantly better stability of plasma compared to serum (p = 0.01. Metabolite profiles from plasma and serum were clearly distinct with 104 metabolites showing significantly higher concentrations in serum. In particular, 9 metabolites showed relative concentration differences larger than 20%. Despite differences in absolute concentration between the two matrices, for most metabolites the overall correlation was high (mean r = 0.81±0.10, which reflects a proportional change in concentration. Furthermore, when two groups of individuals with different phenotypes were compared with each other using both matrices, more metabolites with significantly different concentrations could be identified in serum than in plasma. For example, when 51 type 2 diabetes (T2D patients were compared with 326 non-T2D individuals, 15 more significantly different metabolites were found in serum, in addition to the 25 common to both matrices. CONCLUSIONS/SIGNIFICANCE: Our study shows that reproducibility was good in both plasma and serum, and better in plasma. Furthermore, as long as the same blood preparation procedure is

  20. Novel pyrazine metabolites found in polymyxin biosynthesis by Paenibacillus polymyxa

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Hansen, Anne M; Lauritsen, Frants R

    2003-01-01

    A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2...... supplementation. The other pyrazine metabolites, all related pyrazines with either one, two or three alkyl substituents, were identified by means of their mass spectral data and/or co-elution with authentic standards....

  1. Metabolite Profiles of Lactic Acid Bacteria in Grass Silage▿

    OpenAIRE

    Broberg, Anders; Jacobsson, Karin; Ström, Katrin; Schnürer, Johan

    2007-01-01

    The metabolite production of lactic acid bacteria (LAB) on silage was investigated. The aim was to compare the production of antifungal metabolites in silage with the production in liquid cultures previously studied in our laboratory. The following metabolites were found to be present at elevated concentrations in silos inoculated with LAB strains: 3-hydroxydecanoic acid, 2-hydroxy-4-methylpentanoic acid, benzoic acid, catechol, hydrocinnamic acid, salicylic acid, 3-phenyllactic acid, 4-hydro...

  2. In vivo metabolite compartmentalization probed using intracellular GdDTPA

    DEFF Research Database (Denmark)

    Peters, David Alberg; Rowland, Ian

    Fast trans-membrane water exchange enables in- tracellular relaxation enhancement of water by contrast agents in the extracellular space. For me- tabolites not in fast exchange across membranes, intracellular metabolite relaxation enhancement will only occur if the contrast agent and metabolite a...... are in the same compartment. Extracellular contrast has utilized electroporation methods to deliver GdDTPA into the cytosol of rat muscle in vivo in order to probe the intracellular compart- mentalization of MR-visible metabolites....

  3. Benzene metabolites induce apoptosis in lymphocytes.

    Science.gov (United States)

    Martínez-Velázquez, M; Maldonado, V; Ortega, A; Meléndez-Zajgla, J; Albores, A

    2006-08-01

    Benzene is an important environmental pollutant with important health implications. Exposure to this aromatic hydrocarbon is associated with hematotoxicity, and bone marrow carcinogenic effects. It has been shown that benzene induces oxidative stress, cell cycle alterations, and programmed cell death in cultured cells. Hepatic metabolism of benzene is thought to be a prerequisite for its bone marrow toxicity. Nevertheless, there are no reports on the cellular effects of reactive intermediates derived from hepatic metabolism of benzene. Thus, the goal of this project was to determine the cellular alterations of benzene metabolites produced by the cultured hepatic cell line HepG2. Supernatants collected from these cells were applied to a culture of freshly isolated lymphocytes. A higher decrease in cell viability was found in cells exposed to these supernatants than to unmetabolized benzene. This viability decrease was due to apoptosis, as determined by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) assay and internucleosomal fragmentation of DNA. When supernatants were analyzed by HPLC, we found that not all the hydrocarbon was biotransformed, since a 28 microM concentration (37%) remained. The only metabolite found in the culture medium was muconic acid. The present results show that muconic acid derived from benzene metabolism is able to cooperate with the pollutant for the induction of apoptosis in rat lymphocytes.

  4. Urinary estrogen metabolites and breast cancer

    DEFF Research Database (Denmark)

    Dallal, Cher M; Stone, Roslyn A; Cauley, Jane A

    2013-01-01

    Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1......), and their ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using...... premenopausal 2:16a-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16a-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvs...

  5. Regulation of Vascular and Renal Function by Metabolite Receptors*

    Science.gov (United States)

    Peti-Peterdi, János; Kishore, Bellamkonda K.; Pluznick, Jennifer L.

    2016-01-01

    To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis—from salt and water balance to metabolism—by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families—(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and (c) short-chain fatty acid receptors—we emphasize the unique and important roles that these receptors play in renal and vascular physiology and pathophysiology. PMID:26667077

  6. Regulation of Vascular and Renal Function by Metabolite Receptors.

    Science.gov (United States)

    Peti-Peterdi, János; Kishore, Bellamkonda K; Pluznick, Jennifer L

    2016-01-01

    To maintain metabolic homeostasis, the body must be able to monitor the concentration of a large number of substances, including metabolites, in real time and to use that information to regulate the activities of different metabolic pathways. Such regulation is achieved by the presence of sensors, termed metabolite receptors, in various tissues and cells of the body, which in turn convey the information to appropriate regulatory or positive or negative feedback systems. In this review, we cover the unique roles of metabolite receptors in renal and vascular function. These receptors play a wide variety of important roles in maintaining various aspects of homeostasis-from salt and water balance to metabolism-by sensing metabolites from a wide variety of sources. We discuss the role of metabolite sensors in sensing metabolites generated locally, metabolites generated at distant tissues or organs, or even metabolites generated by resident microbes. Metabolite receptors are also involved in various pathophysiological conditions and are being recognized as potential targets for new drugs. By highlighting three receptor families-(a) citric acid cycle intermediate receptors, (b) purinergic receptors, and

  7. Global metabolite analysis of yeast: evaluation of sample preparation methods

    DEFF Research Database (Denmark)

    Villas-Bôas, Silas Granato; Højer-Pedersen, Jesper; Åkesson, Mats Fredrik;

    2005-01-01

    , which is the analysis of a large number of metabolites with very diverse chemical and physical properties. This work reports the leakage of intracellular metabolites observed during quenching yeast cells with cold methanol solution, the efficacy of six different methods for the extraction...... of intracellular metabolites, and the losses noticed during sample concentration by lyophilization and solvent evaporation. A more reliable procedure is suggested for quenching yeast cells with cold methanol solution, followed by extraction of intracellular metabolites by pure methanol. The method can be combined...

  8. Hybrid electric vehicles TOPTEC

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-06-21

    This one-day TOPTEC session began with an overview of hybrid electric vehicle technology. Updates were given on alternative types of energy storage, APU control for low emissions, simulation programs, and industry and government activities. The keynote speech was about battery technology, a key element to the success of hybrids. The TOPEC concluded with a panel discussion on the mission of hybrid electric vehicles, with a perspective from industry and government experts from United States and Canada on their view of the role of this technology.

  9. Hybrid systems with constraints

    CERN Document Server

    Daafouz, Jamal; Sigalotti, Mario

    2013-01-01

    Control theory is the main subject of this title, in particular analysis and control design for hybrid dynamic systems.The notion of hybrid systems offers a strong theoretical and unified framework to cope with the modeling, analysis and control design of systems where both continuous and discrete dynamics interact. The theory of hybrid systems has been the subject of intensive research over the last decade and a large number of diverse and challenging problems have been investigated. Nevertheless, many important mathematical problems remain open.This book is dedicated mainly to

  10. Hybrid Bloch Brane

    CERN Document Server

    Bazeia, D; Losano, L

    2016-01-01

    This work reports on models described by two real scalar fields coupled with gravity in the five-dimensional spacetime, with a warped geometry involving one infinite extra dimension. Through a mechanism that smoothly changes a thick brane into a hybrid brane, one investigates the appearance of hybrid branes hosting internal structure, characterized by the splitting on the energy density and the volcano potential, induced by the parameter which controls interactions between the two scalar fields. In particular, we investigate distinct symmetric and asymmetric hybrid brane scenarios.

  11. Hybrid Bloch brane

    Energy Technology Data Exchange (ETDEWEB)

    Bazeia, D.; Lima, Elisama E.M.; Losano, L. [Universidade Federal da Paraiba, Departamento de Fisica, Joao Pessoa, PB (Brazil)

    2017-02-15

    This work reports on models described by two real scalar fields coupled with gravity in the five-dimensional spacetime, with a warped geometry involving one infinite extra dimension. Through a mechanism that smoothly changes a thick brane into a hybrid brane, one investigates the appearance of hybrid branes hosting internal structure, characterized by the splitting on the energy density and the volcano potential, induced by the parameter which controls interactions between the two scalar fields. In particular, we investigate distinct symmetric and asymmetric hybrid brane scenarios. (orig.)

  12. Hybrid silicon evanescent devices

    Directory of Open Access Journals (Sweden)

    Alexander W. Fang

    2007-07-01

    Full Text Available Si photonics as an integration platform has recently been a focus of optoelectronics research because of the promise of low-cost manufacturing based on the ubiquitous electronics fabrication infrastructure. The key challenge for Si photonic systems is the realization of compact, electrically driven optical gain elements. We review our recent developments in hybrid Si evanescent devices. We have demonstrated electrically pumped lasers, amplifiers, and photodetectors that can provide a low-cost, scalable solution for hybrid integration on a Si platform by using a novel hybrid waveguide architecture, consisting of III-V quantum wells bonded to Si waveguides.

  13. Performance of the linear ion trap Orbitrap mass analyzer for qualitative and quantitative analysis of drugs of abuse and relevant metabolites in sewage water

    OpenAIRE

    Bijlsma, Lubertus; Emke, Erik; Hernández Hernández, Félix; Voogt, Pim de

    2013-01-01

    This work illustrates the potential of liquid chromatography coupled to a hybrid linear ion trap Fourier Transform Orbitrap mass spectrometer for the simultaneous identification and quantification of 24 drugs of abuse and relevant metabolites in sewage water. The developed methodology consisted of automatic solid-phase extraction using Oasis HLB cartridges, chromatographic separation of the targeted drugs, full-scan accurate mass data acquisition under positive electrospray ionization mode ov...

  14. A metabolomic strategy to screen the prototype components and metabolites of Qingkailing injection in rat urine by high-performance liquid chromatography with tandem mass spectrometry.

    Science.gov (United States)

    Guo, Mingxing; Zhang, Li; Liu, Haiyu; Qin, Lingling; Zhang, Zhixin; Bai, Xu; Gao, Xiaoyan

    2014-10-01

    Xenobiotic metabolome identification of Chinese herbal formula in biological systems is a very challenging task. Qingkailing injection is a typical Chinese herbal injection, which is wildly used clinically in China. However, the holistic metabolic fate of the ingredient from Qingkailing injection remains unclear. In this work, a metabolomic strategy for comprehensively elucidating Qingkailing injection derived prototype components and metabolites in rat urine conducted by hybrid linear ion trap high-resolution mass spectrometry was developed. High-performance liquid chromatography coupled with hybrid linear ion trap high-resolution mass spectrometry was developed to obtain the urine profiling between the control group and Qingkailing injection treated group. Orthogonal partial least squares discriminate analysis was applied to distinguish the exogenous and the endogenous. In the S-plot, 37 xenobiotics derived from Qingkailing injection were found in urine, including 18 prototype compounds and 19 metabolites. The characterization of the prototype components and metabolites in rat's urine provided essential data for further pharmacological studies of Qingkailing injection. Our results indicated that the metabolomic approach was an effective tool to discover, screen, and analyze the multiple prototype components and their metabolites from complicated traditional Chinese preparations in vivo.

  15. Host plant secondary metabolite profiling shows a complex, strain-dependent response of maize to plant growth-promoting rhizobacteria of the genus Azospirillum.

    Science.gov (United States)

    Walker, Vincent; Bertrand, Cédric; Bellvert, Floriant; Moënne-Loccoz, Yvan; Bally, René; Comte, Gilles

    2011-01-01

    Most Azospirillum plant growth-promoting rhizobacteria (PGPR) benefit plant growth through source effects related to free nitrogen fixation and/or phytohormone production, but little is known about their potential effects on plant physiology. These effects were assessed by comparing the early impacts of three Azospirillum inoculant strains on secondary metabolite profiles of two different maize (Zea mays) cultivars. After 10d of growth in nonsterile soil, maize methanolic extracts were analyzed by reverse-phase high-performance liquid chromatography (RP-HPLC) and secondary metabolites identified by liquid chromatography/mass spectrometry (LC/MS) and nuclear magnetic resonance (NMR). Seed inoculation resulted in increased shoot biomass (and also root biomass with one strain) of hybrid PR37Y15 but had no stimulatory effect on hybrid DK315. In parallel, Azospirillum inoculation led to major qualitative and quantitative modifications of the contents of secondary metabolites, especially benzoxazinoids, in the maize plants. These modifications depended on the PGPR strain×plant cultivar combination. Thus, Azospirillum inoculation resulted in early, strain-dependent modifications in the biosynthetic pathways of benzoxazine derivatives in maize in compatible interactions. This is the first study documenting a PGPR effect on plant secondary metabolite profiles, and suggests the establishment of complex interactions between Azospirillum PGPR and maize. © The Authors (2010). Journal compilation © New Phytologist Trust (2010).

  16. Chaotic mixer improves microarray hybridization.

    Science.gov (United States)

    McQuain, Mark K; Seale, Kevin; Peek, Joel; Fisher, Timothy S; Levy, Shawn; Stremler, Mark A; Haselton, Frederick R

    2004-02-15

    Hybridization is an important aspect of microarray experimental design which influences array signal levels and the repeatability of data within an array and across different arrays. Current methods typically require 24h and use target inefficiently. In these studies, we compare hybridization signals obtained in conventional static hybridization, which depends on diffusional target delivery, with signals obtained in a dynamic hybridization chamber, which employs a fluid mixer based on chaotic advection theory to deliver targets across a conventional glass slide array. Microarrays were printed with a pattern of 102 identical probe spots containing a 65-mer oligonucleotide capture probe. Hybridization of a 725-bp fluorescently labeled target was used to measure average target hybridization levels, local signal-to-noise ratios, and array hybridization uniformity. Dynamic hybridization for 1h with 1 or 10ng of target DNA increased hybridization signal intensities approximately threefold over a 24-h static hybridization. Similarly, a 10- or 60-min dynamic hybridization of 10ng of target DNA increased hybridization signal intensities fourfold over a 24h static hybridization. In time course studies, static hybridization reached a maximum within 8 to 12h using either 1 or 10ng of target. In time course studies using the dynamic hybridization chamber, hybridization using 1ng of target increased to a maximum at 4h and that using 10ng of target did not vary over the time points tested. In comparison to static hybridization, dynamic hybridization reduced the signal-to-noise ratios threefold and reduced spot-to-spot variation twofold. Therefore, we conclude that dynamic hybridization based on a chaotic mixer design improves both the speed of hybridization and the maximum level of hybridization while increasing signal-to-noise ratios and reducing spot-to-spot variation.

  17. Hybrid polymer microspheres

    Science.gov (United States)

    Rembaum, A.

    1980-01-01

    Techniques have been successfully tested for bonding polymeric spheres, typically 0.1 micron in diameter, to spheres with diameter up to 100 microns. Hybrids are being developed as improved packing material for ion-exchange columns, filters, and separators.

  18. Hybrid adsorptive membrane reactor

    Science.gov (United States)

    Tsotsis, Theodore T. (Inventor); Sahimi, Muhammad (Inventor); Fayyaz-Najafi, Babak (Inventor); Harale, Aadesh (Inventor); Park, Byoung-Gi (Inventor); Liu, Paul K. T. (Inventor)

    2011-01-01

    A hybrid adsorbent-membrane reactor in which the chemical reaction, membrane separation, and product adsorption are coupled. Also disclosed are a dual-reactor apparatus and a process using the reactor or the apparatus.

  19. Hybrid photon detectors

    CERN Document Server

    D'Ambrosio, C

    2003-01-01

    Hybrid photon detectors detect light via vacuum photocathodes and accelerate the emitted photoelectrons by an electric field towards inversely polarized silicon anodes, where they are absorbed, thus producing electron-hole pairs. These, in turn, are collected and generate electronic signals on their ohmic contacts. This review first describes the characteristic properties of the main components of hybrid photon detectors: light entrance windows, photocathodes, and silicon anodes. Then, essential relations describing the trajectories of photoelectrons in electric and magnetic fields and their backscattering from the silicon anodes are derived. Depending on their anode configurations, three families of hybrid photon detectors are presented: hybrid photomultiplier tubes with single anodes for photon counting with high sensitivity and for gamma spectroscopy; multi-anode photon detector tubes with anodes subdivided into square or hexagonal pads for position-sensitive photon detection; imaging silicon pixel array t...

  20. Functional hybrid materials

    National Research Council Canada - National Science Library

    Fahmi, Amir; Pietsch, Torsten; Mendoza, Cesar; Cheval, Nicolas

    2009-01-01

    .... This paper describes our group's achievements towards the development of multifunctional nanostructures via self-assembly of hybrid systems based on the block copolymer PS-b-P4VP and inorganic nanoparticles (NPs...

  1. Hybrid Rocket Technology

    Directory of Open Access Journals (Sweden)

    Sankaran Venugopal

    2011-04-01

    Full Text Available With their unique operational characteristics, hybrid rockets can potentially provide safer, lower-cost avenues for spacecraft and missiles than the current solid propellant and liquid propellant systems. Classical hybrids can be throttled for thrust tailoring, perform in-flight motor shutdown and restart. In classical hybrids, the fuel is stored in the form of a solid grain, requiring only half the feed system hardware of liquid bipropellant engines. The commonly used fuels are benign, nontoxic, and not hazardous to store and transport. Solid fuel grains are not highly susceptible to cracks, imperfections, and environmental temperature and are therefore safer to manufacture, store, transport, and use for launch. The status of development based on the experience of the last few decades indicating the maturity of the hybrid rocket technology is given in brief.Defence Science Journal, 2011, 61(3, pp.193-200, DOI:http://dx.doi.org/10.14429/dsj.61.518

  2. Nitrous Paraffin Hybrid Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The Nitrous Oxide Paraffin Hybrid engine (N2OP) is a proposed technology designed to provide small launch vehicles with high specific impulse, indefinitely storable...

  3. Hybrid adsorptive membrane reactor

    Science.gov (United States)

    Tsotsis, Theodore T.; Sahimi, Muhammad; Fayyaz-Najafi, Babak; Harale, Aadesh; Park, Byoung-Gi; Liu, Paul K. T.

    2011-03-01

    A hybrid adsorbent-membrane reactor in which the chemical reaction, membrane separation, and product adsorption are coupled. Also disclosed are a dual-reactor apparatus and a process using the reactor or the apparatus.

  4. Hybridity in Disgrace

    Institute of Scientific and Technical Information of China (English)

    刘建平

    2015-01-01

    John Maxwell Coetzee's masterpiece-Disgrace is the representative work about post colonialism.The novel describes a series of disgraceful events happened between the white and the black in the post apartheid South Africa.The famous literature theory-hybridity of Homi K.Bhabha is the very key theory to analyze the work.In post apartheid South Africa,hybridity is the only way for the white and the black to coexist.

  5. Hybrid Baryon Signatures

    CERN Document Server

    Page, P R

    2000-01-01

    We discuss whether a low-lying hybrid baryon should be defined as a three quark - gluon bound state or as three quarks moving on an excited adiabatic potential. We show that the latter definition becomes exact, not only for very heavy quarks, but also for specific dynamics. We review the literature on the signatures of hybrid baryons, with specific reference to strong hadronic decays, electromagnetic couplings, diffractive production and production in psi decay.

  6. Hybrid vertical cavity laser

    DEFF Research Database (Denmark)

    Chung, Il-Sug; Mørk, Jesper

    2010-01-01

    A new hybrid vertical cavity laser structure for silicon photonics is suggested and numerically investigated. It incorporates a silicon subwavelength grating as a mirror and a lateral output coupler to a silicon ridge waveguide.......A new hybrid vertical cavity laser structure for silicon photonics is suggested and numerically investigated. It incorporates a silicon subwavelength grating as a mirror and a lateral output coupler to a silicon ridge waveguide....

  7. Requirements for Hybrid Cosimulation

    Science.gov (United States)

    2014-08-16

    hybrid cosimulation version of the Functional Mockup Interface (FMI) standard. A cosimulation standard de nes interfaces that enable diverse simulation...cosimulation standards, and specifically provides guidance for development of a hybrid cosimulation version of the Functional Mockup Interface (FMI) standard...V. Peetz, and S. Wolf. The functional mockup interface for tool independent exchange of simulation models. In Proc. of the 8-th International

  8. Secondary metabolites: applications on cultural heritage.

    Science.gov (United States)

    Sasso, S; Scrano, L; Bonomo, M G; Salzano, G; Bufo, S A

    2013-01-01

    Biological sciences and related bio-technology play a very important role in research projects concerning protection and preservation of cultural heritage for future generations. In this work secondary metabolites of Burkholderia gladioli pv. agaricicola (Bga) ICMP 11096 strain and crude extract of glycoalkaloids from Solanaceae plants, were tested against a panel of microorganisms isolated from calcarenite stones of two historical bridges located in Potenza and in Campomaggiore (Southern Italy). The isolated bacteria belong to Bacillus cereus and Arthrobacter agilis species, while fungi belong to Aspergillus, Penicillium, Coprinellus, Fusarium, Rhizoctonio and Stemphylium genera. Bga broth (unfiltered) and glycoalkaloids extracts were able to inhibit the growth of all bacterial isolates. Bga culture was active against fungal colonies, while Solanaceae extract exerted bio-activity against Fusarium and Rhizoctonia genera.

  9. [Electrochemical reduction of pentaerythrityltetranitrate (PETN) and metabolites].

    Science.gov (United States)

    Hess, U; Brosig, H; König, G; Stoeter, M; Stalleicken, D

    2002-07-01

    The reduction-cascade of PETN is described as a combination of cyclic-voltammetric measurements and analytical results together with synthesis of PETN-metabolites; furthermore the electroreduction of pentaerythityldinitrate (PEDN) in the presence and absence of cystine as well as cystine and electrogenerated superoxide-radicalanions to elucidate the interaction of PETN with thiol-species. PETN was recognized as precursor for a initial radicalic process, followed by intermediate formation of pentaerythityltrinitratealdehyde (PENA) inside a self-reducing nitrate-system with NO as final product, which may explain its special position in comparison with other pharmaceutically applied nitratestructures. It could be proved, that a cystine-pool reacts as a selective moderator inside the reduction of PEDN without being interfered by O2.-, yielding pentaerythitylmononitrate (PEMN) meanwhile in the absence of cystine only pentaerythrite (PE) is formed.

  10. Encapsulates for Food Bioconversions and Metabolite Production

    Science.gov (United States)

    Breguet, Véronique; Vojinovic, Vojislav; Marison, Ian W.

    The control of production costs in the food industry must be very strict as a result of the relatively low added value of food products. Since a wide variety of enzymes and/or cells are employed in the food industry for starch processing, cheese making, food preservation, lipid hydrolysis and other applications, immobilization of the cells and/or enzymes has been recognized as an attractive approach to improving food processes while minimizing costs. This is due to the fact that biocatalyst immobilization allows for easier separation/purification of the product and reutilization of the biocatalyst. The advantages of the use of immobilized systems are many, and they have a special relevance in the area of food technology, especially because industrial processes using immobilized biosystems are usually characterized by lower capital/energy costs and better logistics. The main applications of immobilization, related to the major processes of food bioconversions and metabolite production, will be described and discussed in this chapter.

  11. Low-molecular-weight metabolite systems chemistry

    Directory of Open Access Journals (Sweden)

    Franz eHadacek

    2015-03-01

    Full Text Available Low-molecular-weight metabolites (LMWMs comprise primary or central and a plethora of intermediary or secondary metabolites, all of which are characterized by a molecular weight below 900 Dalton. The latter are especially prominent in sessile higher organisms, such as plants, corals, sponges and fungi, but are produced by all types of microbial organisms too. Common to all of these carbon molecules are oxygen, nitrogen and, to a lesser extent, sulfur, as heteroatoms. The latter can contribute as electron donators or acceptors to cellular redox chemistry and define the potential of the molecule to enter charge-transfer complexes. Furthermore, they allow LMWMs to serve as organic ligands in coordination complexes of various inorganic metals as central atoms. Especially the transition metals Fe, Cu and Mn can catalyze one electron reduction of molecular oxygen, which results in formation of free radical species and reactive follow-up reaction products. As antioxidants LMWMs can scavenge free radicals. Depending on the chemical environment, the same LMWMs can act as pro-oxidants by reducing molecular oxygen. The cellular regulation of redox homeostasis, a balance between oxidation and reduction, is still far from being understood. Charge-transfer and coordination complex formation with metals shapes LMWMs into gel-like matrices in the cytosol. The quasi-polymer structure is lost usually during the isolation procedure. In the gel state, LMWMs possess semiconductor properties. Also proteins and membranes are semiconductors. Together they can represent biotransistor components that can be part of a chemoelectrical signaling system that coordinates systems chemistry by initiating cell differentiation or tissue homeostasis, the activated and the resting cell state, when it is required. This concept is not new and dates back to Albert Szent-Györgyi.

  12. Production of unusual dispiro metabolites in Pestalotiopsis virgatula endophyte cultures

    DEFF Research Database (Denmark)

    Kesting, Julie Regitze; Olsen, Lars; Stærk, Dan;

    2011-01-01

    The endophytic fungus Pestalotiopsis virgatula, derived from the plant Terminalia chebula and previously found to produce a large excess of a single metabolite when grown in the minimal M1D medium, was induced to produce a variety of unusual metabolites by growing in potato dextrose broth medium...

  13. Fatty acid metabolites in rapidly proliferating breast cancer.

    Directory of Open Access Journals (Sweden)

    Joseph T O'Flaherty

    Full Text Available PURPOSE: Breast cancers that over-express a lipoxygenase or cyclooxygenase are associated with poor survival possibly because they overproduce metabolites that alter the cancer's malignant behaviors. However, these metabolites and behaviors have not been identified. We here identify which metabolites among those that stimulate breast cancer cell proliferation in vitro are associated with rapidly proliferating breast cancer. EXPERIMENTAL DESIGN: We used selective ion monitoring-mass spectrometry to quantify in the cancer and normal breast tissue of 27 patients metabolites that stimulate (15-, 12-, 5-hydroxy-, and 5-oxo-eicosatetraenoate, 13-hydroxy-octadecaenoate [HODE] or inhibit (prostaglandin [PG]E2 and D2 breast cancer cell proliferation. We then related their levels to each cancer's proliferation rate as defined by its Mib1 score. RESULTS: 13-HODE was the only metabolite strongly, significantly, and positively associated with Mib1 scores. It was similarly associated with aggressive grade and a key component of grade, mitosis, and also trended to be associated with lymph node metastasis. PGE2 and PGD2 trended to be negatively associated with these markers. No other metabolite in cancer and no metabolite in normal tissue had this profile of associations. CONCLUSIONS: Our data fit a model wherein the overproduction of 13-HODE by 15-lipoxygenase-1 shortens breast cancer survival by stimulating its cells to proliferate and possibly metastasize; no other oxygenase-metabolite pathway, including cyclooxygenase-PGE2/D2 pathways, uses this specific mechanism to shorten survival.

  14. UV-guided isolation of fungal metabolites by HSCCC

    DEFF Research Database (Denmark)

    Dalsgaard, P.W.; Nielsen, K.F.; Larsen, Thomas Ostenfeld

    2005-01-01

    Analytical standardised reversed phase liquid chromatography (RPLC) data can be helpful in finding a suitable solvent combination for isolation of fungal metabolites by high-speed counter current chromatography. Analysis of the distribution coefficient (K-D) of fungal metabolites in a series of b...

  15. Circulating acetaminophen metabolites are toxicokinetic biomarkers of acute liver injury.

    Science.gov (United States)

    Vliegenthart, Adb; Kimmitt, R A; Seymour, J H; Homer, N Z; Clarke, J I; Eddleston, M; Gray, A; Wood, D M; Dargan, P I; Cooper, J G; Antoine, D J; Webb, D J; Lewis, S C; Bateman, D N; Dear, J W

    2017-04-01

    Acetaminophen (paracetamol-APAP) is the most common cause of drug-induced liver injury in the Western world. Reactive metabolite production by cytochrome P450 enzymes (CYP-metabolites) causes hepatotoxicity. We explored the toxicokinetics of human circulating APAP metabolites following overdose. Plasma from patients treated with acetylcysteine (NAC) for a single APAP overdose was analyzed from discovery (n = 116) and validation (n = 150) patient cohorts. In the discovery cohort, patients who developed acute liver injury (ALI) had higher CYP-metabolites than those without ALI. Receiver operator curve (ROC) analysis demonstrated that at hospital presentation CYP-metabolites were more sensitive/specific for ALI than alanine aminotransferase (ALT) activity and APAP concentration (optimal CYP-metabolite receiver operating characteristic area under the curve (ROC-AUC): 0.91 (95% confidence interval (CI) 0.83-0.98); ALT ROC-AUC: 0.67 (0.50-0.84); APAP ROC-AUC: 0.50 (0.33-0.67)). This enhanced sensitivity/specificity was replicated in the validation cohort. Circulating CYP-metabolites stratify patients by risk of liver injury prior to starting NAC. With development, APAP metabolites have potential utility in stratified trials and for refinement of clinical decision-making. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  16. Synthesis of an Albendazole Metabolite: Characterization and HPLC Determination

    Science.gov (United States)

    Mahler, Graciela; Davyt, Danilo; Gordon, Sandra; Incerti, Marcelo; Nunez, Ivana; Pezaroglo, Horacio; Scarone, Laura; Serra, Gloria; Silvera, Mauricio; Manta, Eduardo

    2008-01-01

    In this laboratory activity, students are introduced to the synthesis of an albendazole metabolite obtained by a sulfide oxidation reaction. Albendazole as well as its metabolite, albendazole sulfoxide, are used as anthelmintic drugs. The oxidation reagent is H[subscript 2]O[subscript 2] in acetic acid. The reaction is environmental friendly,…

  17. A Latex Metabolite Benefits Plant Fitness under Root Herbivore Attack

    NARCIS (Netherlands)

    Huber, M.; Epping, Janina; Schulze Gronover, C.; Fricke, Julia; Aziz, Zohra; Brillatz, Théo; Swyers, Michael; Kollner, T.G.; Vogel, H.; Hammerbacher, Almuth; Triebwasser-Freese, Daniella; Robert, Christelle A.M.; Verhoeven, K.J.F.; Preite, V.; Gershenzon, J.; Erb, M.

    2016-01-01

    Plants produce large amounts of secondary metabolites in their shoots and roots and store them in specialized secretory structures. Although secondary metabolites and their secretory structures are commonly assumed to have a defensive function, evidence that they benefit plant fitness under herbivor

  18. Leach and mold resistance of essential oil metabolites

    Science.gov (United States)

    Carol A. Clausen; Vina W. Yang

    2011-01-01

    Purified primary metabolites from essential oils were previously shown to be bioactive inhibitors of mold fungi on unleached Southern pine sapwood, either alone or in synergy with a second metabolite. This study evaluated the leachability of these compounds in Southern pine that was either dip- or vacuum-treated. Following laboratory leach tests, specimens were...

  19. Between Metabolite Relationships: an essential aspect of metabolic change.

    NARCIS (Netherlands)

    Jansen, J.J.; Szymanska, E.; Hoefsloot, H.C.J.; Jacobs, D.M.; Strassburg, K.; Smilde, A.K.

    2012-01-01

    Not only the levels of individual metabolites, but also the relations between the levels of different metabolites may indicate (experimentally induced) changes in a biological system. Component analysis methods in current ‘standard’ use for metabolomics, such as Principal Component Analysis (PCA),

  20. Natural occurrence of fungi and fungal metabolites in moldy tomatoes

    DEFF Research Database (Denmark)

    Andersen, B.; Frisvad, Jens Christian

    2004-01-01

    . extracted, and analyzed for fungal metabolites. Extracts from pure cultures were compared with extracts from the moldy tomatoes and fungal metabolite standards in two HPLC systems with DAD and FLD detection. The results showed that Penicillium tularense, Stemphylium eturmiunum. and S. cf. lycopersici were...

  1. Synthesis of an Albendazole Metabolite: Characterization and HPLC Determination

    Science.gov (United States)

    Mahler, Graciela; Davyt, Danilo; Gordon, Sandra; Incerti, Marcelo; Nunez, Ivana; Pezaroglo, Horacio; Scarone, Laura; Serra, Gloria; Silvera, Mauricio; Manta, Eduardo

    2008-01-01

    In this laboratory activity, students are introduced to the synthesis of an albendazole metabolite obtained by a sulfide oxidation reaction. Albendazole as well as its metabolite, albendazole sulfoxide, are used as anthelmintic drugs. The oxidation reagent is H[subscript 2]O[subscript 2] in acetic acid. The reaction is environmental friendly,…

  2. Gene probes for the detection of 6-deoxyhexose metabolism in secondary metabolite-producing streptomycetes.

    Science.gov (United States)

    Stockmann, M; Piepersberg, W

    1992-01-01

    DNA probes were designed from the streptomycin production genes strDELM of Streptomyces griseus involved in the biosynthesis of the 6-deoxyhexose (6DOH) dihydrostreptose which could detect the genomic fragments coding for 6DOH formation in other actinomycetes strains. In about 70% of the 43 strains tested at least one signal could be detected with strD-, strE- or strLM-specific probes. Evidence is presented that the hybridizing genes are mostly clustered and probably engaged in the formation of secondary metabolites. Because of the wide-spread use of 6DOH constituents in natural products these probes should allow to detect a vast array of different secondary metabolic gene clusters in actinomycetes.

  3. Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite.

    Science.gov (United States)

    Fisch, Katja M; Bakeer, Walid; Yakasai, Ahmed A; Song, Zhongshu; Pedrick, Jennifer; Wasil, Zahida; Bailey, Andrew M; Lazarus, Colin M; Simpson, Thomas J; Cox, Russell J

    2011-10-19

    The mechanism of programming of iterative highly reducing polyketide synthases remains one of the key unsolved problems of secondary metabolism. We conducted rational domain swaps between the polyketide synthases encoding the biosynthesis of the closely related compounds tenellin and desmethylbassianin. Expression of the hybrid synthetases in Aspergillus oryzae led to the production of reprogrammed compounds in which the changes to the methylation pattern and chain length could be mapped to the domain swaps. These experiments reveal for the first time the origin of programming in these systems. Domain swaps combined with coexpression of two cytochrome P450 encoding genes from the tenellin biosynthetic gene cluster led to the resurrection of the extinct metabolite bassianin.

  4. Importance of MS selectivity and chromatographic separation in LC-MS/MS-based methods when investigating pharmaceutical metabolites in water. Dipyrone as a case of study.

    Science.gov (United States)

    Ibáñez, M; Gracia-Lor, E; Sancho, J V; Hernández, F

    2012-08-01

    Pharmaceuticals are emerging contaminants of increasing concern because of their presence in the aquatic environment and potential to reach drinking-water sources. After human and/or veterinary consumption, pharmaceuticals can be excreted in unchanged form, as the parent compound, and/or as free or conjugated metabolites. Determination of most pharmaceuticals and metabolites in the environment is commonly made by liquid chromatography (LC) coupled to mass spectrometry (MS). LC coupled to tandem MS is the technique of choice nowadays in this field. The acquisition of two selected reaction monitoring (SRM) transitions together with the retention time is the most widely accepted criterion for a safe quantification and confirmation assay. However, scarce attention is normally paid to the selectivity of the selected transitions as well as to the chromatographic separation. In this work, the importance of full spectrum acquisition high-resolution MS data using a hybrid quadrupole time-of-flight analyser and/or a suitable chromatographic separation (to reduce the possibility of co-eluting interferences) is highlighted when investigating pharmaceutical metabolites that share common fragment ions. For this purpose, the analytical challenge associated to the determination of metabolites of the widely used analgesic dipyrone (also known as metamizol) in urban wastewater is discussed. Examples are given on the possibilities of reporting false positives of dypirone metabolites by LC-MS/MS under SRM mode due to a wrong assignment of identity of the compounds detected. Copyright © 2012 John Wiley & Sons, Ltd.

  5. The application of a new microfluidic device for the simultaneous identification and quantitation of midazolam metabolites obtained from a single micro-litre of chimeric mice blood.

    Science.gov (United States)

    Gallagher, Richard; Dillon, Leonard; Grimsley, Aidan; Murphy, Jim; Samuelsson, Kristin; Douce, David

    2014-06-15

    Improvements in the design of low-flow highly sensitive chromatographic ion source interfaces allow the detection and characterisation of drugs and metabolites from smaller sample volumes. This in turn improves the ethical treatment of animals by reducing both the number of animals needed and the blood sampling volumes required. A new microfluidic device combining an ultra-high pressure liquid chromatography (UHPLC) analytical column with a nano-flow electrospray source is described. All microfluidic, gas and electrical connections are automatically engaged when the ceramic microfluidic device is inserted into the source enclosure. The system was used in conjunction with a hybrid quadrupole-time-of-flight mass spectrometer. The improved sensitivity of the system is highlighted in its application in the quantification and qualification of midazolam and its metabolites detected in whole blood from chimeric and wild-type mice. Metabolite identification and full pharmacokinetic profiles were obtained from a single micro-litre of whole blood at each sampling time and significant pharmacokinetic differences were observed between the two types of mice. Improvements in the enhanced ionisation efficiency from the microfluidic device in conjunction with nanoUHPLC/MS was sufficiently sensitive for the identification and quantification of midazolam metabolites from a single micro-litre of whole blood. Detection of metabolites not previously recorded from the chimeric mouse in vivo model was made. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Mass spectrometric evaluation of mephedrone in vivo human metabolism: identification of phase I and phase II metabolites, including a novel succinyl conjugate.

    Science.gov (United States)

    Pozo, Óscar J; Ibáñez, María; Sancho, Juan V; Lahoz-Beneytez, Julio; Farré, Magí; Papaseit, Esther; de la Torre, Rafael; Hernández, Félix

    2015-02-01

    In recent years, many new designer drugs have emerged, including the group of cathinone derivatives. One frequently occurring drug is mephedrone; although mephedrone was originally considered as a "legal high" product, it is currently banned in most Western countries. Despite the banning, abuse of the drug and seizures are continuously reported. Although the metabolism of mephedrone has been studied in rats or in vitro using human liver microsomes, to the best of our knowledge, no dedicated study with human volunteers has been performed for studying the in vivo metabolism of mephedrone in humans. Therefore, the aim of this study was to establish the actual human metabolism of mephedrone and to compare it with other models. For this purpose, urine samples of two healthy volunteers, who ingested 200 mg mephedrone orally, were taken before administration and 4 hours after substance intake. The discovery and identification of the phase I and phase II metabolites of mephedrone were based on ultra-high-performance liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry, operating in the so-called MS(E) mode. Six phase I metabolites and four phase II metabolites were identified, four of them not previously reported in the literature. The structure of four of the detected metabolites was confirmed by synthesis of the suggested compounds. Remarkably, a mephedrone metabolite conjugated with succinic acid has been identified and confirmed by synthesis. According to the reviewed literature, this is the first time that this type of conjugate is reported for human metabolism.

  7. Development of cell metabolite analysis on microfluidic platform

    Institute of Scientific and Technical Information of China (English)

    Luyao Lin; Jin-Ming Lin

    2015-01-01

    abstract Cell metabolite analysis is of great interest to analytical chemists and physiologists, with some meta-bolites having been identified as important indicators of major diseases such as cancer. A high-throughput and sensitive method for drug metabolite analysis will largely promote the drug discovery industry. The basic barrier of metabolite analysis comes from the interference of complex components in cell biological system and low abundance of target substances. As a powerful tool in biosample analysis, microfluidic chip enhances the sensitivity and throughput by integrating multiple functional units into one chip. In this review, we discussed three critical steps of establishing functional microfluidic platform for cellular metabolism study. Cell in vitro culture model, on chip sample pretreatment, and microchip combined detectors were described in details and demonstrated by works in five years. And a brief summary was given to discuss the advantages as well as challenges of applying microchip method in cell metabolite and biosample analysis.

  8. Urinary pesticide metabolites in school students from northern Thailand.

    Science.gov (United States)

    Panuwet, Parinya; Prapamontol, Tippawan; Chantara, Somporn; Barr, Dana B

    2009-05-01

    We evaluated exposure to pesticides among secondary school students aged 12-13 years old in Chiang Mai Province, Thailand. Pesticide-specific urinary metabolites were used as biomarkers of exposure for a variety of pesticides, including organophosphorus insecticides, synthetic pyrethroid insecticides and selected herbicides. We employed a simple solid-phase extraction with analysis using isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). A total of 207 urine samples from Thai students were analyzed for 18 specific pesticide metabolites. We found 14 metabolites in the urine samples tested; seven of them were detected with a frequency > or=17%. The most frequently detected metabolites were 2-[(dimethoxyphosphorothioyl) sulfanyl] succinic acid (malathion dicarboxylic acid), para-nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TPCY; metabolite of chlorpyrifos), 2,4-dichlorophenoxyacetic acid (2,4-D), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (c-DCCA and t-DCCA; metabolite of permethrin) and 3-phenoxybenzoic acid (3-PBA; metabolite of pyrethroids). The students were classified into 4 groups according to their parental occupations: farmers (N=60), merchants and traders (N=39), government and company employees (N=52), and laborers (N=56). Children of farmers had significantly higher urinary concentrations of pyrethroid insecticide metabolites than did other children (p<0.05). Similarly, children of agricultural families had significantly higher pyrethroid metabolite concentrations. Males had significantly higher values of PNP (Mann-Whitney test, p=0.009); however, no other sex-related differences were observed. Because parental occupation and agricultural activities seemed to have little influence on pesticide levels, dietary sources were the likely contributors to the metabolite levels observed.

  9. Identification of metabolites with anticancer properties by computational metabolomics

    Directory of Open Access Journals (Sweden)

    Bowen Nathan J

    2008-06-01

    Full Text Available Abstract Background Certain endogenous metabolites can influence the rate of cancer cell growth. For example, diacylglycerol, ceramides and sphingosine, NAD+ and arginine exert this effect by acting as signaling molecules, while carrying out other important cellular functions. Metabolites can also be involved in the control of cell proliferation by directly regulating gene expression in ways that are signaling pathway-independent, e.g. by direct activation of transcription factors or by inducing epigenetic processes. The fact that metabolites can affect the cancer process on so many levels suggests that the change in concentration of some metabolites that occurs in cancer cells could have an active role in the progress of the disease. Results CoMet, a fully automated Computational Metabolomics method to predict changes in metabolite levels in cancer cells compared to normal references has been developed and applied to Jurkat T leukemia cells with the goal of testing the following hypothesis: Up or down regulation in cancer cells of the expression of genes encoding for metabolic enzymes leads to changes in intracellular metabolite concentrations that contribute to disease progression. All nine metabolites predicted to be lowered in Jurkat cells with respect to lymphoblasts that were examined (riboflavin, tryptamine, 3-sulfino-L-alanine, menaquinone, dehydroepiandrosterone, α-hydroxystearic acid, hydroxyacetone, seleno-L-methionine and 5,6-dimethylbenzimidazole, exhibited antiproliferative activity that has not been reported before, while only two (bilirubin and androsterone of the eleven tested metabolites predicted to be increased or unchanged in Jurkat cells displayed significant antiproliferative activity. Conclusion These results: a demonstrate that CoMet is a valuable method to identify potential compounds for experimental validation, b indicate that cancer cell metabolism may be regulated to reduce the intracellular concentration of

  10. Characterizing protein modifications by reactive metabolites using magnetic bead bioreactors and LC-MS/MS.

    Science.gov (United States)

    Li, Dandan; Fu, You-Jun; Rusling, James F

    2015-03-18

    We report here label-free metabolite-protein adduct detection and identification employing magnetic beads coated with metabolic enzymes as bioreactors to generate metabolites and possible metabolite-protein adducts for analysis by liquid chromatography-tandem mass spectrometry.

  11. The Hybrids of Postmodernism

    Directory of Open Access Journals (Sweden)

    Dana BĂDULESCU

    2014-09-01

    Full Text Available Hybridization is a fundamental characteristic of postmodernism, included by Ihab Hassan in his “catena” of features. This paper looks into the hybrids of postmodernism, which are the result of migration, displacement and uprooting, the re-visitation of myths, folklore and legends, or projections of their author’s imagination. The hybrids used as examples here are drawn from several novels written by Salman Rushdie, especially The Satanic Verses, two short stories, one by Márquez and the other by Donald Barthelme, Borges’s Book of Imaginary Beings, Cărtărescu’s Encyclopaedia of Dragons and Michelle Cliff’s No Telephone to Heaven. Diverse as they may be, these hybrids emphasize a defining characteristic of postmodernism, which is its pluralism. I conclude that the hybrids of postmodernism are aesthetically or politically subversive. Besides, what makes them difficult to grasp is their unfixed and protean nature. They ask for high leaps of the imagination, a total suspension of disbelief and a complete surrender to the powerful seduction of imagination on the reader’s part.

  12. Research on Hybrid Vehicle Drivetrain

    Science.gov (United States)

    Xie, Zhongzhi

    Hybrid cars as a solution to energy saving, emission reduction measures, have received widespread attention. Motor drive system as an important part of the hybrid vehicles as an important object of study. Based on the hybrid electric vehicle powertrain control system for permanent magnet synchronous motor as the object of study. Can be applied to hybrid car compares the characteristics of traction motors, chose permanent magnet synchronous Motors as drive motors for hybrid vehicles. Building applications in hybrid cars in MATLAB/Simulink simulation model of permanent-magnet synchronous motor speed control system and analysis of simulation results.

  13. Metabolic and Phenotypic Responses of Greenhouse-Grown Maize Hybrids to Experimentally Controlled Drought Stress

    Institute of Scientific and Technical Information of China (English)

    Sandra Witt; Luis Galici; Jan Lisec; Jill Cairns; Axel Tiessen; Jose Luis Araus; Natalia Palacios-Rojas; Alisdair R.Fernie

    2012-01-01

    Adaptation to abiotic stresses like drought is an important acquirement of agriculturally relevant crops like maize.Development of enhanced drought tolerance in crops grown in climatic zones where drought is a very dominant stress factor therefore plays an essential role in plant breeding.Previous studies demonstrated that corn yield potential and enhanced stress tolerance are associated traits.In this study,we analyzed six different maize hybrids for their ability to deal with drought stress in a greenhouse experiment.We were able to combine data from morphophysiological parameters measured under well-watered conditions and under water restriction with metabolic data from different organs.These different organs possessed distinct metabolite compositions,with the leaf blade displaying the most considerable metabolome changes following water deficiency.Whilst we could show a general increase in metabolite levels under drought stress,including changes in amino acids,sugars,sugar alcohols,and intermediates of the TCA cycle,these changes were not differential between maize hybrids that had previously been designated based on field trial data as either drought-tolerant or susceptible.The fact that data described here resulted from a greenhouse experiment with rather different growth conditions compared to natural ones in the field may explain why tolerance groups could not be confirmed in this study.We were,however,able to highlight several metabolites that displayed conserved responses to drought as well as metabolites whose levels correlated well with certain physiological traits.

  14. for hybrid dynamical systems

    Directory of Open Access Journals (Sweden)

    Wassim M. Haddad

    2001-01-01

    Full Text Available In this paper we develop a unified dynamical systems framework for a general class of systems possessing left-continuous flows; that is, left-continuous dynamical systems. These systems are shown to generalize virtually all existing notions of dynamical systems and include hybrid, impulsive, and switching dynamical systems as special cases. Furthermore, we generalize dissipativity, passivity, and nonexpansivity theory to left-continuous dynamical systems. Specifically, the classical concepts of system storage functions and supply rates are extended to left-continuous dynamical systems providing a generalized hybrid system energy interpretation in terms of stored energy, dissipated energy over the continuous-time dynamics, and dissipated energy over the resetting events. Finally, the generalized dissipativity notions are used to develop general stability criteria for feedback interconnections of left-continuous dynamical systems. These results generalize the positivity and small gain theorems to the case of left-continuous, hybrid, and impulsive dynamical systems.

  15. Hybrid Action Systems

    DEFF Research Database (Denmark)

    Rönnkö, M.; Ravn, Anders Peter; Sere, K.

    2003-01-01

    In this paper we investigate the use of action systems with differential actions in the specifcation of hybrid systems. As the main contribution we generalize the definition of a differential action, allowing the use of arbitrary relations over model variables and their time-derivatives in modell......In this paper we investigate the use of action systems with differential actions in the specifcation of hybrid systems. As the main contribution we generalize the definition of a differential action, allowing the use of arbitrary relations over model variables and their time...... parallel composition. Moreover, as the strength of the action system formalism is the support for stepwise development by refinement, we investigate refinement involving a differential action. We show that, due to the predicate transformer semantics, standard action refinement techniques apply also...... to the differential action, thus, allowing stepwise development of hybrid systems Udgivelsesdato: JAN 1...

  16. Conditional Hybrid Nonclassicality

    Science.gov (United States)

    Agudelo, E.; Sperling, J.; Costanzo, L. S.; Bellini, M.; Zavatta, A.; Vogel, W.

    2017-09-01

    We derive and implement a general method to characterize the nonclassicality in compound discrete- and continuous-variable systems. For this purpose, we introduce the operational notion of conditional hybrid nonclassicality which relates to the ability to produce a nonclassical continuous-variable state by projecting onto a general superposition of discrete-variable subsystem. We discuss the importance of this form of quantumness in connection with interfaces for quantum communication. To verify the conditional hybrid nonclassicality, a matrix version of a nonclassicality quasiprobability is derived and its sampling approach is formulated. We experimentally generate an entangled, hybrid Schrödinger cat state, using a coherent photon-addition process acting on two temporal modes, and we directly sample its nonclassicality quasiprobability matrix. The introduced conditional quantum effects are certified with high statistical significance.

  17. Porosity in hybrid materials

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, D.W.; Beaucage, G.; Loy, D. [Sandia National Labs., Albuquerque, NM (United States)

    1995-12-31

    Multicomponent, or hybrid composites are emerging as precursors to porous materials. Sacrifice of an ephemeral phase can be used to generate porosity, the nature of which depends on precursor structure. Retention of an organic constituent, on the other hand, can add desirable toughness to an otherwise brittle ceramic. We use small-angle x-ray and neutron scattering to examine porosity in both simple and hybrid materials. We find that microphase separation controls porosity in almost all systems studied. Pore distributions are controlled by the detailed bonding within and between phases as well as the flexibility of polymeric constituents. Thus hybridization opens new regions of pore distributions not available in simple systems. We look at several sacrificial concepts and show that it is possible to generate multimodal pore size distributions due to the complicated phase structure in the precursor.

  18. Photoproduction of Hybrid Mesons

    CERN Document Server

    Barnes, T

    1998-01-01

    In this contribution I discuss prospects for photoproducing hybrid mesons at CEBAF, based on recent model results and experimental indications of possible hybrids. One excellent opportunity appears to be a search for the I=1, JPC=2+-, neutral "(b2)o" hybrid in (a2 pi)o through diffractive photoproduction. Other notable possibilities accessible through pi+ or pio exchange photoproduction are I=1, JPC=1-+, charged "pi1+" in f1 pi+, (b1 pi)+ and (rho pi)+; piJ(1770)+ in f2 pi+ and (b1 pi)+; pi(1800)+ in f0 pi+, f2 pi+, omega rho+ and (rho pi)+; a1 in f1 pi+ and f2 pi+; and omega in (rho pi)o, omega eta and (K1 K)o.

  19. Smart hybrid rotary damper

    Science.gov (United States)

    Yang, C. S. Walter; DesRoches, Reginald

    2014-03-01

    This paper develops a smart hybrid rotary damper using a re-centering smart shape memory alloy (SMA) material as well as conventional energy-dissipating metallic plates that are easy to be replaced. The ends of the SMA and steel plates are inserted in the hinge. When the damper rotates, all the plates bend, providing energy dissipating and recentering characteristics. Such smart hybrid rotary dampers can be installed in structures to mitigate structural responses and to re-center automatically. The damaged energy-dissipating plates can be easily replaced promptly after an external excitation, reducing repair time and costs. An OpenSEES model of a smart hybrid rotary was established and calibrated to reproduce the realistic behavior measured from a full-scale experimental test. Furthermore, the seismic performance of a 3-story moment resisting model building with smart hybrid rotary dampers designed for downtown Los Angeles was also evaluated in the OpenSEES structural analysis software. Such a smart moment resisting frame exhibits perfect residual roof displacement, 0.006", extremely smaller than 18.04" for the conventional moment resisting frame subjected to a 2500 year return period ground motion for the downtown LA area (an amplified factor of 1.15 on Kobe earthquake). The smart hybrid rotary dampers are also applied into an eccentric braced steel frame, which combines a moment frame system and a bracing system. The results illustrate that adding smart hybrid rotaries in this braced system not only completely restores the building after an external excitation, but also significantly reduces peak interstory drifts.

  20. Using Molecular Networking for Microbial Secondary Metabolite Bioprospecting

    Directory of Open Access Journals (Sweden)

    Kevin Purves

    2016-01-01

    Full Text Available The oceans represent an understudied resource for the isolation of bacteria with the potential to produce novel secondary metabolites. In particular, actinomyces are well known to produce chemically diverse metabolites with a wide range of biological activities. This study characterised spore-forming bacteria from both Scottish and Antarctic sediments to assess the influence of isolation location on secondary metabolite production. Due to the selective isolation method used, all 85 isolates belonged to the phyla Firmicutes and Actinobacteria, with the majority of isolates belonging to the genera Bacillus and Streptomyces. Based on morphology, thirty-eight isolates were chosen for chemical investigation. Molecular networking based on chemical profiles (HR-MS/MS of fermentation extracts was used to compare complex metabolite extracts. The results revealed 40% and 42% of parent ions were produced by Antarctic and Scottish isolated bacteria, respectively, and only 8% of networked metabolites were shared between these locations, implying a high degree of biogeographic influence upon secondary metabolite production. The resulting molecular network contained over 3500 parent ions with a mass range of m/z 149–2558 illustrating the wealth of metabolites produced. Furthermore, seven fermentation extracts showed bioactivity against epithelial colon adenocarcinoma cells, demonstrating the potential for the discovery of novel bioactive compounds from these understudied locations.

  1. Using Molecular Networking for Microbial Secondary Metabolite Bioprospecting.

    Science.gov (United States)

    Purves, Kevin; Macintyre, Lynsey; Brennan, Debra; Hreggviðsson, Guðmundur Ó; Kuttner, Eva; Ásgeirsdóttir, Margrét E; Young, Louise C; Green, David H; Edrada-Ebel, Ruangelie; Duncan, Katherine R

    2016-01-08

    The oceans represent an understudied resource for the isolation of bacteria with the potential to produce novel secondary metabolites. In particular, actinomyces are well known to produce chemically diverse metabolites with a wide range of biological activities. This study characterised spore-forming bacteria from both Scottish and Antarctic sediments to assess the influence of isolation location on secondary metabolite production. Due to the selective isolation method used, all 85 isolates belonged to the phyla Firmicutes and Actinobacteria, with the majority of isolates belonging to the genera Bacillus and Streptomyces. Based on morphology, thirty-eight isolates were chosen for chemical investigation. Molecular networking based on chemical profiles (HR-MS/MS) of fermentation extracts was used to compare complex metabolite extracts. The results revealed 40% and 42% of parent ions were produced by Antarctic and Scottish isolated bacteria, respectively, and only 8% of networked metabolites were shared between these locations, implying a high degree of biogeographic influence upon secondary metabolite production. The resulting molecular network contained over 3500 parent ions with a mass range of m/z 149-2558 illustrating the wealth of metabolites produced. Furthermore, seven fermentation extracts showed bioactivity against epithelial colon adenocarcinoma cells, demonstrating the potential for the discovery of novel bioactive compounds from these understudied locations.

  2. Antimicrobial Activity of Metabolites of Various Strains of Lactobacillus acidophilus

    Directory of Open Access Journals (Sweden)

    Hassan Pyar Ali Hassan

    2011-01-01

    Full Text Available The antimicrobial activity of metabolites of eight strains of Lactobacillus acidophilus (FTDC 2804, FTDC 0785, FTDC 8592, FTDC 1295, FTDC 4793, FTDC 4462, FTDC 0582 and FTDC 2916 against  Staphylococcus aureus (gram positive and Escherichia coli (gram negative, was examined and compared using agar well diffusion method.  Lactobacillus acidophilus was cultivated in two different types of dairy growth medium namely, full cream milk and skim milk. The results showed that the metabolites of all the eight strains had significant antimicrobial effect based on zone of inhibition results when compared to control. There was a statistically significant difference in the zone of inhibition data for Staphylococcus aureus and Escherichia coli among the metabolites of the eight strains cultivated in the two different growth medium. Certain L. acidophilus strains were more effective against  Staphylococcus aureus, while other strains were more effective against  Escherichia coli. On the other hand, the growth medium had no significant influence on the antimicrobial effect of metabolites of seven strains except  L. acidophilus FTDC 4462 against Escherichia coli. As for  Staphylococcus aureus, the growth medium only affected the antimicrobial effect of metabolite of strain  L. acidophilus FTDC 1295, but did not affect the antimicrobial effect of metabolites of the other seven strains. It can be concluded that L. acidophilus cultivated in dairy products produced metabolites with antimicrobial property, which could provide beneficial medicinal values to human.

  3. Metabolites of alectinib in human: their identification and pharmacological activity

    Directory of Open Access Journals (Sweden)

    Mika Sato-Nakai

    2017-07-01

    Full Text Available Two metabolites (M4 and M1b in plasma and four metabolites (M4, M6, M1a and M1b in faeces were detected through the human ADME study following a single oral administration of [14C]alectinib, a small-molecule anaplastic lymphoma kinase inhibitor, to healthy subjects. In the present study, M1a and M1b, which chemical structures had not been identified prior to the human ADME study, were identified as isomers of a carboxylate metabolite oxidatively cleaved at the morpholine ring. In faeces, M4 and M1b were the main metabolites, which shows that the biotransformation to M4 and M1b represents two main metabolic pathways for alectinib. In plasma, M4 was a major metabolite and M1b was a minor metabolite. The contribution to in vivo pharmacological activity of these circulating metabolites was assessed from their in vitro pharmacological activity and plasma protein binding. M4 had a similar cancer cell growth inhibitory activity and plasma protein binding to that of alectinib, suggesting its contribution to the antitumor activity of alectinib, whereas the pharmacological activity of M1b was insignificant.

  4. Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

    Science.gov (United States)

    Zhong, Jian-Jiang; Xiao, Jian-Hui

    Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

  5. Development of competitive immunoassays to hydroxyl containing fungicide metabolites.

    Science.gov (United States)

    Gough, Kevin C; Jarvis, Shila; Maddison, Ben C

    2011-01-01

    This paper describes the isolation of monoclonal antibodies and the development of competitive immunoassays to pesticide metabolites of the fungicides imazalil, carbendazim and thiabendazole. The metabolite specific hydroxyl residues were used as the reactive group with which to link the metabolite to the carrier proteins Keyhole Limpet Haemocyanin (KLH) and Bovine Serum Albumin (BSA). In each case immune responses in mice were raised and monoclonal antibodies were produced. Antibodies were developed into competitive ELISAs to the appropriate metabolite. The antibody raised to a metabolite of imazalil was optimised into a competitive ELISA format which had an assay IC50 of 7.5 μg/L and a limit of detection (LOD) of 1.1 μg/L. A single antibody isolated against the metabolite of carbendazim had assay IC50s of 3.2 and 2.7 μg/L for the metabolites of carbendazim and thiabendazole respectively with an LOD of 0.38 μg/L for both. These sensitive immunoassays may have application in the monitoring of human exposure to these fungicide residues either by occupational or non-occupational routes.

  6. Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites

    Directory of Open Access Journals (Sweden)

    Miroslava Cuperlovic-Culf

    2016-09-01

    Full Text Available Fusarium head blight (FHB, primarily caused by Fusarium graminearum, is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum, such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.

  7. 10 CFR 26.133 - Cutoff levels for drugs and drug metabolites.

    Science.gov (United States)

    2010-01-01

    ... cutoff levels. Otherwise, the following cutoff levels must be used for initial testing of urine specimens... Cocaine metabolites 300 Opiate metabolites 2000 Phencyclidine (PCP) 25 Amphetamines 1000...

  8. Analog and hybrid computing

    CERN Document Server

    Hyndman, D E

    2013-01-01

    Analog and Hybrid Computing focuses on the operations of analog and hybrid computers. The book first outlines the history of computing devices that influenced the creation of analog and digital computers. The types of problems to be solved on computers, computing systems, and digital computers are discussed. The text looks at the theory and operation of electronic analog computers, including linear and non-linear computing units and use of analog computers as operational amplifiers. The monograph examines the preparation of problems to be deciphered on computers. Flow diagrams, methods of ampl

  9. Hybrid Weyl semimetal

    Science.gov (United States)

    Li, Fei-Ye; Luo, Xi; Dai, Xi; Yu, Yue; Zhang, Fan; Chen, Gang

    2016-09-01

    We construct a tight-binding model realizing one pair of Weyl nodes and three distinct Weyl semimetals. In the type-I (type-II) Weyl semimetal, both nodes belong to type-I (type-II) Weyl nodes. In addition, there exists a third type, previously undiscovered and dubbed "hybrid Weyl semimetal", in which one Weyl node is of type I while the other is of type II. For the hybrid Weyl semimetal, we further demonstrate the bulk Fermi surfaces and the topologically protected surface states, analyze the unique Landau-level structure and quantum oscillation, and discuss the conditions for possible material realization.

  10. Toyota hybrid synergy drive

    Energy Technology Data Exchange (ETDEWEB)

    Gautschi, H.

    2008-07-01

    This presentation made at the Swiss 2008 research conference on traffic by Hannes Gautschi, director of service and training at the Toyota company in Switzerland, takes a look at Toyota's hybrid drive vehicles. The construction of the vehicles and their combined combustion engines and electric generators and drives is presented and the combined operation of these components is described. Braking and energy recovery are discussed. Figures on the performance, fuel consumption and CO{sub 2} output of the hybrid vehicles are compared with those of conventional vehicles.

  11. Toyota hybrid synergy drive

    Energy Technology Data Exchange (ETDEWEB)

    Gautschi, H.

    2008-07-01

    This presentation made at the Swiss 2008 research conference on traffic by Hannes Gautschi, director of service and training at the Toyota company in Switzerland, takes a look at Toyota's hybrid drive vehicles. The construction of the vehicles and their combined combustion engines and electric generators and drives is presented and the combined operation of these components is described. Braking and energy recovery are discussed. Figures on the performance, fuel consumption and CO{sub 2} output of the hybrid vehicles are compared with those of conventional vehicles.

  12. THERMALLY CLEAVABLE HYBRID MATERIALS

    Directory of Open Access Journals (Sweden)

    Constantin Gaina

    2011-12-01

    Full Text Available Thermally cleavable hybrid materials were prepared by the Diels-Alder cycloaddition reaction of poly(vinyl furfural to N phenylmaleimido-N’-(triethoxysilylpropylurea followed by the sol-gel condensation reaction of trietoxysilyl groups with water and acetic acid. Thermal and dynamic mechanical analysis, dielectric and FTIR spectroscopy were used to characterize the structure and properties of the composites. The size of the inorganic silica particles in the hybrid material varied dependent on the silica content. The DSC study of the prepared materials revealed that the cleavage process of the formed cycloadducts takes place at temperatures varying between 143-165°C and is an endothermic process.

  13. The hybrid BCI

    Directory of Open Access Journals (Sweden)

    Gert Pfurtscheller

    2010-04-01

    Full Text Available Nowadays, everybody knows what a hybrid car is. A hybrid car normally has 2 engines, its main purpose being to enhance energy efficiency and reduce CO2 output. Similarly, a typical hybrid brain-computer interface (BCI is also composed of 2 BCIs or at least one BCI and another system. Such a hybrid BCI, like any BCI, must fulfil the following four criteria: (i the device must rely on signals recorded directly from the brain; (ii there must be at least one recordable brain signal that the user can intentionally modulate to effect goal-directed behaviour; (iii real time processing; and (iv the user must obtain feedback. This paper introduces some hybrid BCIs which have already been published or are currently in development or validation, and some concepts for future work. The BCIs described classify 2 EEG patterns: One is the event-related (desynchronisation (ERD, ERS of sensorimotor rhythms, and the other is the steady-state visual evoked potential (SSVEP. The hybrid BCI can either have more than one input whereby the inputs are typically processed simultaneously or operate 2 systems sequentially, whereby the first system can act as a “brain switch”. In the case of self-paced operation of a SSVEP-based hand orthosis control with an motor imagery-based switch it was possible to reduce the rate of false positives during resting periods by about 50% compared to the SSVEP BCI alone. It is shown that such a brain switch can also rely on hemodynamic changes measured through near-infrared spectroscopy (NIRS. Another interesting approach is a hybrid BCI with simultaneous operations of ERD- and SSVEP-based BCIs. Here it is important to prove the existing promising offline simulation results with online experiments. Hybrid BCIs can also use one brain signal and another input. Such an additional input can be a physiological signal like the heart rate but also a signal from an external device like, an eye gaze control system.

  14. Selected Secondary Plant Metabolites for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2015-01-01

    Full Text Available Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases. As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics, either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of action of natural products is expected to open new perspectives in coming years for their use alone or in combination therapies in oncology. Two major strategies to identify novel drug candidates from nature are the bioactivity-guided fractionation of medicinal plant extracts to isolate cytotoxic chemicals and the identification of small molecules inhibiting specific targets in cancer cells. In the present review, we report on our own efforts to unravel the molecular modes of action of phytochemicals in cancer cells and focus on resveratrol, betulinic acid, artesunate, dicentrine and camptothecin derivatives.

  15. Glutamine and glutamate as vital metabolites

    Directory of Open Access Journals (Sweden)

    Newsholme P.

    2003-01-01

    Full Text Available Glucose is widely accepted as the primary nutrient for the maintenance and promotion of cell function. This metabolite leads to production of ATP, NADPH and precursors for the synthesis of macromolecules such as nucleic acids and phospholipids. We propose that, in addition to glucose, the 5-carbon amino acids glutamine and glutamate should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine/glutamate are many, i.e., they are substrates for protein synthesis, anabolic precursors for muscle growth, they regulate acid-base balance in the kidney, they are substrates for ureagenesis in the liver and for hepatic and renal gluconeogenesis, they act as an oxidative fuel for the intestine and cells of the immune system, provide inter-organ nitrogen transport, and act as precursors of neurotransmitter synthesis, of nucleotide and nucleic acid synthesis and of glutathione production. Many of these functions are interrelated with glucose metabolism. The specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells are discussed in the context of glucose requirements and cell function.

  16. Dichlorodiphenyltrichloroethane (DDT), DDT Metabolites and Pregnancy Outcomes

    Science.gov (United States)

    Kezios, Katrina L.; Liu, Xinhua; Cirillo, Piera M.; Cohn, Barbara A.; Kalantzi, Olga I.; Wang, Yunzhu; Petreas, Myrto X.; Park, June-Soo; Factor-Litvak, Pam

    2012-01-01

    Organochlorine pesticides (OCPs) are persistent endocrine disruptors. OCPs cross the placenta; this prenatal exposure has been associated with adverse pregnancy outcomes. We investigated associations between prenatal exposure to OCPs and gestational age and birth weight in 600 infants born between 1960 and 1963. The primary OCP was 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p′-DDT), its primary metabolite, 1,1′-dichloro-2,2'-bis(p-chlorophenyl)ethylene(p,p′-DDE) and the contaminant, 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)-ethane (o,p′-DDT). Regression analysis indicated that for each natural log unit increase in p,p′-DDT, birth weight increased by 274 grams (95% CI 122, 425) when controlling for p,p′-DDE and o,p′-DDT. At a given level of p,p′-DDT exposure, o,p′-DDT and p,p′-DDE were associated with decreased birth weight. p,p′-DDE was negatively associated with length of gestation, controlling for p,p′-DDT and o,p′-DDT. These findings suggest opposing associations between exposure to p,p′-DDT and p,p′-DDE and birth weight. We did not find evidence to support mediation by maternal thyroid hormone status nor that the association differed by sex. PMID:23142753

  17. Dietary Metabolites and Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Sho Hasegawa

    2017-04-01

    Full Text Available Dietary contents and their metabolites are closely related to chronic kidney disease (CKD progression. Advanced glycated end products (AGEs are a type of uremic toxin produced by glycation. AGE accumulation is not only the result of elevated glucose levels or reduced renal clearance capacity, but it also promotes CKD progression. Indoxyl sulfate, another uremic toxin derived from amino acid metabolism, accumulates as CKD progresses and induces tubulointerstitial fibrosis and glomerular sclerosis. Specific types of amino acids (d-serine or fatty acids (palmitate are reported to be closely associated with CKD progression. Promising therapeutic targets associated with nutrition include uremic toxin absorbents and inhibitors of AGEs or the receptor for AGEs (RAGE. Probiotics and prebiotics maintain gut flora balance and also prevent CKD progression by enhancing gut barriers and reducing uremic toxin formation. Nrf2 signaling not only ameliorates oxidative stress but also reduces elevated AGE levels. Bardoxolone methyl, an Nrf2 activator and NF-κB suppressor, has been tested as a therapeutic agent, but the phase 3 clinical trial was terminated owing to the high rate of cardiovascular events. However, a phase 2 trial has been initiated in Japan, and the preliminary analysis reveals promising results without an increase in cardiovascular events.

  18. Arachidonic acid metabolites in pathogenic yeasts

    Directory of Open Access Journals (Sweden)

    Ells Ruan

    2012-08-01

    Full Text Available Abstract Although most of what is known about the biology and function of arachidonic acid metabolites comes from the study of mammalian biology, these compounds can also be produced by lower eukaryotes, including yeasts and other fungi. It is also in this group of organisms that the least is known about the metabolic pathways leading to the production of these compounds as well as the functions of these compounds in the biology of fungi and yeasts. This review will deal with the discovery of oxylipins from polyunsaturated fatty acids, and more specifically the arachidonic acid derived eicosanoids, such as 3-hydroxy eicosatetraenoic acid, prostaglandin F2α and prostaglandin E2, in yeasts starting in the early 1990s. This review will also focus on what is known about the metabolic pathways and/or proteins involved in the production of these compounds in pathogenic yeasts. The possible roles of these compounds in the biology, including the pathology, of these organisms will be discussed.

  19. Transformation of tamoxifen and its major metabolites during water chlorination: Identification and in silico toxicity assessment of their disinfection byproducts.

    Science.gov (United States)

    Negreira, Noelia; Regueiro, Jorge; López de Alda, Miren; Barceló, Damià

    2015-11-15

    The selective estrogen receptor modulator tamoxifen is the most commonly used drug for the treatment and prevention of breast cancer. Tamoxifen is considered as a pro-drug since it is known to exert its pharmacological effect through its major active metabolites, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen, which are mainly excreted in the urine in the days following administration. In the present work, the reactivity of tamoxifen and its major active metabolites in free chlorine-containing water was investigated for the first time. Under the studied chlorination conditions, tamoxifen was fairly stable whereas its metabolites were quickly degraded. A total of thirteen chlorinated byproducts were tentatively identified by ultra-high performance liquid chromatography coupled to high-resolution hybrid quadrupole-Orbitrap tandem mass spectrometry. Time-course profiles of the identified byproducts were followed in real wastewater samples under conditions that simulate wastewater disinfection. A preliminary assessment of their acute aquatic toxicity at two trophic levels by means of quantitative structure-activity relationship models showed that the identified byproducts were up to 110-fold more toxic than the parent compounds.

  20. Medicinal chemistry of drugs with active metabolites following conjugation.

    Science.gov (United States)

    Kalász, Huba; Petroianu, Georg; Hosztafi, Sándor; Darvas, Ferenc; Csermely, Tamás; Adeghate, Ernest; Siddiq, Afshan; Tekes, Kornélia

    2013-10-01

    Authorities of Drug Administration in the United States of America approved about 5000 drugs for use in the therapy or management of several diseases. About two hundred of these drugs have active metabolites and the knowledge of their medicinal chemistry is important both in medical practice and pharmaceutical research. This review gives a detailed description of the medicinal chemistry of drugs with active metabolites generated after conjugation. This review focused on glucuronide-, acetyl-, sulphate- and phosphate-conjugation of drugs, converting the drug into an active metabolite. This conversion essentially changed the lipophilicity of the drug.

  1. A Mathematical Approach to Hybridization

    Science.gov (United States)

    Matthews, P. S. C.; Thompson, J. J.

    1975-01-01

    Presents an approach to hybridization which exploits the similarities between the algebra of wave functions and vectors. This method will account satisfactorily for the number of orbitals formed when applied to hybrids involving the s and p orbitals. (GS)

  2. Glycoalkaloids as biomarkers for recognition of cultivated, wild, and somatic hybrids of potato.

    Science.gov (United States)

    Savarese, Salvatore; Andolfi, Anna; Cimmino, Alessio; Carputo, Domenico; Frusciante, Luigi; Evidente, Antonio

    2009-04-01

    Cultivated and wild potato species synthesize a wide variety of steroidal glycoalkaloids (GAs). During breeding programs, species genomes are often put together through either sexual or somatic hybridization. Therefore, the determination of the GA composition of hybrids is very important in that it may affect either human consumption, or resistance to pathogen and pests. Here, we report the results of GA analysis performed on wild Solanum bulbocastanum, haploids of cultivated potato S. tuberosum and their interspecific somatic hybrids. GAs were extracted from tubers and analyzed by HPLC. HPLC Profile of S. tuberosum haploids showed, as expected, the presence of alpha-solanine and alpha-chaconine. The profile of S. bulbocastanum extract showed lack of alpha-solanine and alpha-chaconine, and the presence of four GAs. The GA pattern of the somatic hybrids was the sum of their parents' profile. This represents a noteworthy tool for their unequivocal recognition. Interestingly, two hybrids produced not only GAs of both parents but also new compounds to be further investigated. This provided evidence that somatic hybridization induced the synthesis of new metabolites. The nature of the probable unidentified GAs associated to S. bulbocastanum and its somatic hybrids was ascertained by chemical degradation and spectroscopic analysis of their aglycones and sugar moieties. Our results suggest their close relation with GAs of both wild and cultivated potato species.

  3. Metabolite profiling reveals abiotic stress tolerance in Tn5 mutant of Pseudomonas putida.

    Directory of Open Access Journals (Sweden)

    Vasvi Chaudhry

    Full Text Available Pseudomonas is an efficient plant growth-promoting rhizobacteria (PGPR; however, intolerance to drought and high temperature limit its application in agriculture as a bioinoculant. Transposon 5 (Tn5 mutagenesis was used to generate a stress tolerant mutant from a PGPR Pseudomonas putida NBRI1108 isolated from chickpea rhizosphere. A mutant NBRI1108T, selected after screening of nearly 10,000 transconjugants, exhibited significant tolerance towards high temperature and drought. Southern hybridization analysis of EcoRI and XhoI restricted genomic DNA of NBRI1108T confirmed that it had a single Tn5 insertion. The metabolic changes in the polar and non-polar extracts of NBRI1108 and NBRI1108T were examined using 1H, 31P nuclear magnetic resonance (NMR spectroscopy and gas chromatography-mass spectrometry (GC-MS. Thirty six chemically diverse metabolites consisting of amino acids, fatty acids and phospholipids were identified and quantified. Insertion of Tn5 influenced amino acid and phospholipid metabolism and resulted in significantly higher concentration of aspartic acid, glutamic acid, glycinebetaine, glycerophosphatidylcholine (GPC and putrescine in NBRI1108T as compared to that in NBRI1108. The concentration of glutamic acid, glycinebetaine and GPC increased by 34%, 95% and 100%, respectively in the NBRI1108T as compared to that in NBRI1108. High concentration of glycerophosphatidylethanolamine (GPE and undetected GPC in NBRI1108 indicates that biosynthesis of GPE may have taken place via the methylation pathway of phospholipid biosynthesis. However, high GPC and low GPE concentration in NBRI1108T suggest that methylation pathway and phosphatidylcholine synthase (PCS pathway of phospholipid biosynthesis are being followed in the NBRI1108T. Application of multivariate principal component analysis (PCA on the quantified metabolites revealed clear variations in NBRI1108 and NBRI1108T in polar and non-polar metabolites. Identification of abiotic

  4. Metabolite profiling reveals abiotic stress tolerance in Tn5 mutant of Pseudomonas putida.

    Science.gov (United States)

    Chaudhry, Vasvi; Bhatia, Anil; Bharti, Santosh Kumar; Mishra, Shashank Kumar; Chauhan, Puneet Singh; Mishra, Aradhana; Sidhu, Om Prakash; Nautiyal, Chandra Shekhar

    2015-01-01

    Pseudomonas is an efficient plant growth-promoting rhizobacteria (PGPR); however, intolerance to drought and high temperature limit its application in agriculture as a bioinoculant. Transposon 5 (Tn5) mutagenesis was used to generate a stress tolerant mutant from a PGPR Pseudomonas putida NBRI1108 isolated from chickpea rhizosphere. A mutant NBRI1108T, selected after screening of nearly 10,000 transconjugants, exhibited significant tolerance towards high temperature and drought. Southern hybridization analysis of EcoRI and XhoI restricted genomic DNA of NBRI1108T confirmed that it had a single Tn5 insertion. The metabolic changes in the polar and non-polar extracts of NBRI1108 and NBRI1108T were examined using 1H, 31P nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS). Thirty six chemically diverse metabolites consisting of amino acids, fatty acids and phospholipids were identified and quantified. Insertion of Tn5 influenced amino acid and phospholipid metabolism and resulted in significantly higher concentration of aspartic acid, glutamic acid, glycinebetaine, glycerophosphatidylcholine (GPC) and putrescine in NBRI1108T as compared to that in NBRI1108. The concentration of glutamic acid, glycinebetaine and GPC increased by 34%, 95% and 100%, respectively in the NBRI1108T as compared to that in NBRI1108. High concentration of glycerophosphatidylethanolamine (GPE) and undetected GPC in NBRI1108 indicates that biosynthesis of GPE may have taken place via the methylation pathway of phospholipid biosynthesis. However, high GPC and low GPE concentration in NBRI1108T suggest that methylation pathway and phosphatidylcholine synthase (PCS) pathway of phospholipid biosynthesis are being followed in the NBRI1108T. Application of multivariate principal component analysis (PCA) on the quantified metabolites revealed clear variations in NBRI1108 and NBRI1108T in polar and non-polar metabolites. Identification of abiotic stress

  5. Hybrid Ventilation Air Flow Process

    DEFF Research Database (Denmark)

    Heiselberg, Per Kvols

    The scope of this annex is therefore to obtain better knowledge of the use of hybrid ventilation technologies. The annex focus on development of control strategies for hybrid ventilation, on development of methods to predict hybrid ventilation performance in office buildings and on implementation...

  6. (Hybrid) Baryons Symmetries and Masses

    CERN Document Server

    Page, P R

    1999-01-01

    We construct (hybrid) baryons in the flux-tube model of Isgur and Paton. In the limit of adiabatic quark motion, we build proper eigenstates of orbital angular momentum and construct the flavour, spin and J^P of hybrid baryons from the symmetries of the system. The lowest mass hybrid baryon is estimated at approximately 2 GeV.

  7. Improved hybrid rocket fuel

    Science.gov (United States)

    Dean, David L.

    1995-01-01

    McDonnell Douglas Aerospace, as part of its Independent R&D, has initiated development of a clean burning, high performance hybrid fuel for consideration as an alternative to the solid rocket thrust augmentation currently utilized by American space launch systems including Atlas, Delta, Pegasus, Space Shuttle, and Titan. It could also be used in single stage to orbit or as the only propulsion system in a new launch vehicle. Compared to solid propellants based on aluminum and ammonium perchlorate, this fuel is more environmentally benign in that it totally eliminates hydrogen chloride and aluminum oxide by products, producing only water, hydrogen, nitrogen, carbon oxides, and trace amounts of nitrogen oxides. Compared to other hybrid fuel formulations under development, this fuel is cheaper, denser, and faster burning. The specific impulse of this fuel is comparable to other hybrid fuels and is between that of solids and liquids. The fuel also requires less oxygen than similar hybrid fuels to produce maximum specific impulse, thus reducing oxygen delivery system requirements.

  8. Workshop on hybrid rice

    Institute of Scientific and Technical Information of China (English)

    TANZhijun

    1994-01-01

    FAO, in collaboration with FEDEARROZ in Colombia and EMBRAPA / CNPAF in Brail, organized a workshop on the Establishment of a Coorperative Research Network on Hybrid Rice in Latin America and the Caribbean held from Mar 16 to 18, 1994 at EMBRAPA/CNPAF in Brazil. Dr MAO Changxiang,

  9. Teelt van hybride wintertarwerassen

    NARCIS (Netherlands)

    Timmer, R.D.; Paauw, J.G.M.

    2003-01-01

    Om de mogelijkheden van de teelt van hybride wintertarwerassen onder Nederlandse omstandigheden in beeld te brengen zijn er van 2000-2002 proeven uitgevoerd op het PPO-proefbedrijf te Lelystad. In deze proeven zijn een 4-tal hybriderassen (Hybnos, Hyno-braba, Hyno-esta, Mercury) vergeleken met een s

  10. Organics go hybrid

    Science.gov (United States)

    Lanzani, Guglielmo; Petrozza, Annamaria; Caironi, Mario

    2017-01-01

    From displays to solar cells, the field of organic optoelectronics has come a long way over the past 50 years, but the realization of an electrically pumped organic laser remains elusive. The answer may lie with hybrid organic-inorganic materials called perovskites.

  11. Hybrid-secure MPC 

    DEFF Research Database (Denmark)

    Lucas, Christoph; Raub, Dominik; Maurer, Ueli

    2010-01-01

    Most protocols for distributed, fault-tolerant computation, or multi-party computation (MPC), provide security guarantees in an all-or-nothing fashion. In contrast, a hybrid-secure protocol provides different security guarantees depending on the set of corrupted parties and the computational powe...

  12. Indexical Hybrid Tense Logic

    DEFF Research Database (Denmark)

    Blackburn, Patrick Rowan; Jørgensen, Klaus Frovin

    2012-01-01

    In this paper we explore the logic of now, yesterday, today and tomorrow by combining the semantic approach to indexicality pioneered by Hans Kamp [9] and refined by David Kaplan [10] with hybrid tense logic. We first introduce a special now nominal (our @now corresponds to Kamp’s original now...

  13. Nuclear hybrid energy infrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Vivek; Tawfik, Magdy S.

    2015-02-01

    The nuclear hybrid energy concept is becoming a reality for the US energy infrastructure where combinations of the various potential energy sources (nuclear, wind, solar, biomass, and so on) are integrated in a hybrid energy system. This paper focuses on challenges facing a hybrid system with a Small Modular Reactor at its core. The core of the paper will discuss efforts required to develop supervisory control center that collects data, supports decision-making, and serves as an information hub for supervisory control center. Such a center will also be a model for integrating future technologies and controls. In addition, advanced operations research, thermal cycle analysis, energy conversion analysis, control engineering, and human factors engineering will be part of the supervisory control center. Nuclear hybrid energy infrastructure would allow operators to optimize the cost of energy production by providing appropriate means of integrating different energy sources. The data needs to be stored, processed, analyzed, trended, and projected at right time to right operator to integrate different energy sources.

  14. Hybrid printed electronics

    NARCIS (Netherlands)

    Koetse, M.; Smits, E.; Rubingh, E.; Teunissen, P.; Kusters, R.; Abbel, R.; Brand, J. van den

    2016-01-01

    Although many electronic functionalities can be realized by printed or organic electronics, short-term marketable products often require robust, reproducible, and nondisturbing technologies. In this chapter we show how hybrid electronics, a combination of printed circuitry, thin-film electronics,

  15. Distinguishing enzymes using metabolome data for the hybrid dynamic/static method

    Directory of Open Access Journals (Sweden)

    Nakayama Yoichi

    2007-05-01

    Full Text Available Abstract Background In the process of constructing a dynamic model of a metabolic pathway, a large number of parameters such as kinetic constants and initial metabolite concentrations are required. However, in many cases, experimental determination of these parameters is time-consuming. Therefore, for large-scale modelling, it is essential to develop a method that requires few experimental parameters. The hybrid dynamic/static (HDS method is a combination of the conventional kinetic representation and metabolic flux analysis (MFA. Since no kinetic information is required in the static module, which consists of MFA, the HDS method may dramatically reduce the number of required parameters. However, no adequate method for developing a hybrid model from experimental data has been proposed. Results In this study, we develop a method for constructing hybrid models based on metabolome data. The method discriminates enzymes into static modules and dynamic modules using metabolite concentration time series data. Enzyme reaction rate time series were estimated from the metabolite concentration time series data and used to distinguish enzymes optimally for the dynamic and static modules. The method was applied to build hybrid models of two microbial central-carbon metabolism systems using simulation results from their dynamic models. Conclusion A protocol to build a hybrid model using metabolome data and a minimal number of kinetic parameters has been developed. The proposed method was successfully applied to the strictly regulated central-carbon metabolism system, demonstrating the practical use of the HDS method, which is designed for computer modelling of metabolic systems.

  16. Hybrid keyword search auctions

    KAUST Repository

    Goel, Ashish

    2009-01-01

    Search auctions have become a dominant source of revenue generation on the Internet. Such auctions have typically used per-click bidding and pricing. We propose the use of hybrid auctions where an advertiser can make a per-impression as well as a per-click bid, and the auctioneer then chooses one of the two as the pricing mechanism. We assume that the advertiser and the auctioneer both have separate beliefs (called priors) on the click-probability of an advertisement. We first prove that the hybrid auction is truthful, assuming that the advertisers are risk-neutral. We then show that this auction is superior to the existing per-click auction in multiple ways: 1. We show that risk-seeking advertisers will choose only a per-impression bid whereas risk-averse advertisers will choose only a per-click bid, and argue that both kind of advertisers arise naturally. Hence, the ability to bid in a hybrid fashion is important to account for the risk characteristics of the advertisers. 2. For obscure keywords, the auctioneer is unlikely to have a very sharp prior on the click-probabilities. In such situations, we show that having the extra information from the advertisers in the form of a per-impression bid can result in significantly higher revenue. 3. An advertiser who believes that its click-probability is much higher than the auctioneer\\'s estimate can use per-impression bids to correct the auctioneer\\'s prior without incurring any extra cost. 4. The hybrid auction can allow the advertiser and auctioneer to implement complex dynamic programming strategies to deal with the uncertainty in the click-probability using the same basic auction. The per-click and per-impression bidding schemes can only be used to implement two extreme cases of these strategies. As Internet commerce matures, we need more sophisticated pricing models to exploit all the information held by each of the participants. We believe that hybrid auctions could be an important step in this direction. The

  17. Metabolite Signatures of Metabolic Risk Factors and their Longitudinal Changes

    NARCIS (Netherlands)

    Yin, X.; Subramanian, S.; Willinger, C.M.; Chen, G.; Juhasz, P.; Courchesne, P.; Chen, B.H.; Li, X.; Hwang, S.J.; Fox, C.S.; O'Donnell, C.J.; Muntendam, P.; Fuster, V.; Bobeldijk-Pastorova, I.; Sookoian, S.C.; Pirola, C.J.; Gordon, N.; Adourian, A.; Larson, M.G.; Levy, D.

    2016-01-01

    Context: Metabolic dysregulation underlies key metabolic risk factors—obesity, dyslipidemia, and dysglycemia. Objective: To uncover mechanistic links between metabolomic dysregulation and metabolic risk by testing metabolite associations with risk factors cross-sectionally and with risk factor

  18. β-Orcinol Metabolites from the Lichen Hypotrachyna revoluta

    Directory of Open Access Journals (Sweden)

    Panagiota Papadopoulou

    2007-05-01

    Full Text Available Four new β-orcinol metabolites, hypotrachynic acid (1, deoxystictic acid (2, cryptostictinolide (3 and 8 ́-methylconstictic acid (4 along with the metabolites 8 ́-methylstictic acid (5, 8 ́-methylmenegazziaic acid (6, stictic acid (7, 8 ́-ethylstictic acid (8 and atranorin (9, that have been previously described, were isolated for the first time from the tissue extracts of the lichen Hypotrachyna revoluta (Flörke Hale. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analyses. Radical scavenging activity (RSA of the metabolites isolated in adequate amounts, was evaluated using luminol chemiluminescence and comparison with Trolox®.

  19. Metabolite Signatures of Metabolic Risk Factors and their Longitudinal Changes

    NARCIS (Netherlands)

    Yin, X.; Subramanian, S.; Willinger, C.M.; Chen, G.; Juhasz, P.; Courchesne, P.; Chen, B.H.; Li, X.; Hwang, S.J.; Fox, C.S.; O'Donnell, C.J.; Muntendam, P.; Fuster, V.; Bobeldijk-Pastorova, I.; Sookoian, S.C.; Pirola, C.J.; Gordon, N.; Adourian, A.; Larson, M.G.; Levy, D.

    2016-01-01

    Context: Metabolic dysregulation underlies key metabolic risk factors—obesity, dyslipidemia, and dysglycemia. Objective: To uncover mechanistic links between metabolomic dysregulation and metabolic risk by testing metabolite associations with risk factors cross-sectionally and with risk factor chang

  20. Ruta graveolens Extracts and Metabolites against Spodoptera frugiperda.

    Science.gov (United States)

    Ayil-Gutiérrez, Benjamin A; Villegas-Mendoza, Jesús M; Santes-Hernndez, Zuridai; Paz-González, Alma D; Mireles-Martínez, Maribel; Rosas-García, Ninfa M; Rivera, Gildardo

    2015-11-01

    The biological activity of Ruta graveolens leaf tissue extracts obtained with different solvents (ethyl acetate, ethanol, and water) and metabolites (psoralen, 2- undecanone and rutin) against Spodoptera frugiperda was evaluated. Metabolites levels in extracts were quantified by HPLC and GC. Ethyl acetate and ethanol extracts showed 94% and 78% mortality, respectively. Additionally, psoralen metabolite showed a high mortality as cypermethrin. Metabolite quantification in extracts shows the presence of 2-undecanone (87.9 µmoles mg(-1) DW), psoralen (3.6 µmoles mg(-1) DW) and rutin (0.001 pmoles mg(-1) DW). We suggest that these concentrations of 2-undecanone and psoralen in R. graveolens leaf tissue extracts could be responsible for S. frugiperda mortality.

  1. Detection of mastitis pathogens by analysis of volatile bacterial metabolites

    NARCIS (Netherlands)

    Hettinga, K.A.; Valenberg, van H.J.F.; Lam, T.J.G.M.; Hooijdonk, van A.C.M.

    2008-01-01

    The ability to detect mastitis pathogens based on their volatile metabolites was studied. Milk samples from cows with clinical mastitis, caused by Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus uberis, Streptococcus dysgalactiae, and Escherichia coli were collected. In

  2. Metabolite essentiality elucidates robustness of Escherichia coli metabolism

    CERN Document Server

    Kim, Pan-Jun; Kim, Tae Yong; Lee, Kwang Ho; Jeong, Hawoong; Lee, Sang Yup; Park, Sunwon

    2007-01-01

    Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by using redundant or alternative pathways. Thus, only a limited number of genes have been identified to be lethal to the cell. In this regard, the reaction-centric gene deletion study has a limitation in understanding the metabolic robustness. Here, we report the use of flux-sum, which is the summation of all incoming or outgoing fluxes around a particular metabolite under pseudo-steady state conditions, as a good conserved property for elucidating such robustness of E. coli from the metabolite point of view. The functional behavior, as well as the structural and evolutionary properties of metabolites essential to the cell survival, was investigated by means of a constraints-based flux analysis under perturbed conditions. The essential metabolites are capable of maintaining a...

  3. Comparison of the selected secondary metabolite content present in ...

    African Journals Online (AJOL)

    Comparison of the selected secondary metabolite content present in the ... and gravimetric methods, to the effect of quantitative comparison of their phenolic, ... The extracts were also qualitatively analyzed so as to evaluate the presence of ...

  4. Induced sclerotium formation exposes new bioactive metabolites from Aspergillus sclerotiicarbonarius.

    Science.gov (United States)

    Petersen, Lene M; Frisvad, Jens C; Knudsen, Peter B; Rohlfs, Marko; Gotfredsen, Charlotte H; Larsen, Thomas O

    2015-10-01

    Sclerotia are known to be fungal survival structures, and induction of sclerotia may prompt production of otherwise undiscovered metabolites. Aspergillus sclerotiicarbonarius (IBT 28362) was investigated under sclerotium producing conditions, which revealed a highly altered metabolic profile. Four new compounds were isolated from cultivation under sclerotium formation conditions and their structures elucidated using different analytical techniques (HRMS, UV, 1D and 2D NMR). This included sclerolizine, an alkylated and oxidized pyrrolizine, the new emindole analog emindole SC and two new carbonarins; carbonarins I and J. We have identified the three latter as true sclerotial metabolites. All metabolites were tested for antifungal and antiinsectan activity, and sclerolizine and carbonarin I displayed antifungal activity against Candida albicans, while all four showed antiinsectan activity. These results demonstrate induction of sclerotia as an alternative way of triggering otherwise silent biosynthetic pathways in filamentous fungi for the discovery of novel bioactive secondary metabolites.

  5. High Resolution Screening of biologically active compounds and metabolites

    NARCIS (Netherlands)

    Kool, J.

    2007-01-01

    High Resolution Screening of biologically active compounds and metabolites Jeroen Kool Biotransformation enzymes play a crucial role in the metabolism of both endogenous compounds and xenobiotics. Usually, the detoxication of these compounds by biotransformation enzymes results in harmless metab

  6. Fusarial toxins: secondary metabolites of Fusarium fungi.

    Science.gov (United States)

    Nesic, Ksenija; Ivanovic, Snezana; Nesic, Vladimir

    2014-01-01

    Exposure to mycotoxins occurs worldwide, even though there are geographic and climatic differences in the amounts produced and occurrence of these substances.Mycotoxins are secondary chemical metabolites of different fungi. They are natural contaminants of cereals, so their presence is often inevitable. Among many genera that produce mycotoxins, Fusarium fungi are the most widespread in cereal-growing areas of the planet. Fusarium fungi produce a diversity of mycotoxin types, whose distributions are also diverse. What is produced and where it is produced is influenced primarily by environmental conditions, and crop production and storage methods. The amount of toxin produced depends on physical (viz., moisture, relative humidity, temperature, and mechanical damage), chemical (viz., carbon dioxide,oxygen, composition of substrate, insecticides and fungicides), and biological factors (viz., plant variety, stress, insects, spore load, etc.). Moisture and temperature have a major influence on mold growth rate and mycotoxin production.Among the most toxic and prevalent fusaria) toxins are the following: zearalenone,fumonisins, moniliformin and trichothecenes (T-2/HT-2 toxin, deoxynivalenol,diacetoxyscirpenol, nivalenol). Zearalenone (ZEA; ZON, F-2 toxin) isaphy to estrogenic compound, primarily a field contaminant, which exhibits estrogenic activity and has been implicated in numerous mycotoxicoses of farm animals,especially pigs. Recently, evidence suggests that ZEA has potential to stimulate the growth of human breast cancer cells. Fumonisins are also cancer-promoting metabolites,of which Fumonisin 8 I (FBI) is the most important. Moniliformin (MON) isalso highly toxic to both animals and humans. Trichothecenes are classified as gastrointestinal toxins, dermatotoxins, immunotoxins, hematotoxins, and gene toxins.T-2 and HT-2 toxin, and diacetoxyscirpenol (DAS, anguidine) are the most toxic mycotoxins among the trichothecene group. Deoxynivalenol (DON, vomitoxin) and

  7. Acrolein metabolites, diabetes and insulin resistance.

    Science.gov (United States)

    Feroe, Aliya G; Attanasio, Roberta; Scinicariello, Franco

    2016-07-01

    Acrolein is a dietary and environmental pollutant that has been associated in vitro to dysregulate glucose transport. We investigated the association of urinary acrolein metabolites N-acetyl-S-(3-hydroxypropyl)-l-cysteine (3-HPMA) and N-acetyl-S-(carboxyethyl)-l-cysteine (CEMA) and their molar sum (∑acrolein) with diabetes using data from investigated 2027 adults who participated in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). After excluding participants taking insulin or other diabetes medication we, further, investigated the association of the compounds with insulin resistance (n=850), as a categorical outcome expressed by the homeostatic model assessment (HOMA-IR>2.6). As secondary analyses, we investigated the association of the compounds with HOMA-IR, HOMA-β, fasting insulin and fasting plasma glucose. The analyses were performed using urinary creatinine as independent variable in the models, and, as sensitivity analyses, the compounds were used as creatinine corrected variables. Diabetes as well as insulin resistance (defined as HOMA-IR>2.6) were positively associated with the 3-HPMA, CEMA and ∑Acrolein with evidence of a dose-response relationship (pCEMA compared to the lowest quartile were significantly associated with higher HOMA-IR, HOMA-β and fasting insulin with a dose-response relationship. The highest 3rd quartile of 3-HPMA and ∑Acrolein were positively and significantly associated with HOMA-IR, HOMA-β and fasting insulin. These results suggest a need of further studies to fully understand the implications of acrolein with type 2 diabetes and insulin.

  8. Metabolic Enzymes of Cocaine Metabolite Benzoylecgonine.

    Science.gov (United States)

    Chen, Xiabin; Zheng, Xirong; Zhan, Max; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

    2016-08-19

    Cocaine is one of the most addictive drugs without a U.S. Food and Drug Administration (FDA)-approved medication. Enzyme therapy using an efficient cocaine-metabolizing enzyme is recognized as the most promising approach to cocaine overdose treatment. The actual enzyme, known as RBP-8000, under current clinical development for cocaine overdose treatment is our previously designed T172R/G173Q mutant of bacterial cocaine esterase (CocE). The T172R/G173Q mutant is effective in hydrolyzing cocaine but inactive against benzoylecgonine (a major, biologically active metabolite of cocaine). Unlike cocaine itself, benzoylecgonine has an unusually stable zwitterion structure resistant to further hydrolysis in the body and environment. In fact, benzoylecgonine can last in the body for a very long time (a few days) and, thus, is responsible for the long-term toxicity of cocaine and a commonly used marker for drug addiction diagnosis in pre-employment drug tests. Because CocE and its mutants are all active against cocaine and inactive against benzoylecgonine, one might simply assume that other enzymes that are active against cocaine are also inactive against benzoylecgonine. Here, through combined computational modeling and experimental studies, we demonstrate for the first time that human butyrylcholinesterase (BChE) is actually active against benzoylecgonine, and that a rationally designed BChE mutant can not only more efficiently accelerate cocaine hydrolysis but also significantly hydrolyze benzoylecgonine in vitro and in vivo. This sets the stage for advanced studies to design more efficient mutant enzymes valuable for the development of an ideal cocaine overdose enzyme therapy and for benzoylecgonine detoxification in the environment.

  9. Choline metabolites: gene by diet interactions.

    Science.gov (United States)

    Smallwood, Tangi; Allayee, Hooman; Bennett, Brian J

    2016-02-01

    The review highlights recent advances in our understanding of the interactions between genetic polymorphisms in genes that metabolize choline and the dietary requirements of choline and how these interactions relate to human health and disease. The importance of choline as an essential nutrient has been well established, but our appreciation of the interaction between our underlying genetic architecture and dietary choline requirements is only beginning. It has been shown in both human and animal studies that choline deficiencies contribute to diseases such as nonalcoholic fatty liver disease and various neurodegenerative diseases. An adequate supply of dietary choline is important for optimum development, highlighted by the increased maternal requirements during fetal development and in breast-fed infants. We discuss recent studies investigating variants in PEMT and MTHFR1 that are associated with a variety of birth defects. In addition to genetic interactions, we discuss several recent studies that uncover changes in fetal global methylation patterns in response to maternal dietary choline intake that result in changes in gene expression in the offspring. In contrast to the developmental role of adequate choline, there is now an appreciation of the role choline has in cardiovascular disease through the gut microbiota-mediated metabolite trimethylamine N-oxide. This pathway highlights some of our understanding of how the microbiome affects nutrient processing and bioavailability. Finally, to better characterize the genetic architecture regulating choline requirements, we discuss recent results focused on identifying polymorphisms that regulate choline and its derivative products. Here we discuss recent studies that have advanced our understanding of how specific alleles in key choline metabolism genes are related to dietary choline requirements and human disease.

  10. Bioactive Metabolites from Spilanthes acmella Murr.

    Directory of Open Access Journals (Sweden)

    Virapong Prachayasittikul

    2009-02-01

    Full Text Available Spilanthes acmella Murr. (Compositae has been used as a traditional medicine for toothache, rheumatism and fever. Its extracts had been shown to exhibit vasorelaxant and antioxidant activities. Herein, its antimicrobial, antioxidant and cytotoxic activities were evaluated. Agar dilution method assays against 27 strains of microorganisms were performed. Results showed that fractions from the chloroform and methanol extracts inhibited the growth of many tested organisms, e.g. Corynebacterium diphtheriae NCTC 10356 with minimum inhibitory concentration (MIC of 64-256 mg/mL and Bacillus subtilis ATCC 6633 with MIC of 128-256 mg/mL. The tested fractions all exhibited antioxidant properties in both DPPH and SOD assays. Potent radical scavenging activity was observed in the DPPH assay. No cytotoxic effects of the extracts against KB and HuCCA-1 cell lines were evident. Bioassay-guided isolation resulted in a diverse group of bioactive compounds such as phenolics [vanillic acid (2, trans-ferulic acid (5 and trans-isoferulic acid (6], coumarin (scopoletin, 4 and triterpenoids like 3-acetylaleuritolic acid (1, b-sitostenone (3, stigmasterol and stigmasteryl-3-O-b-D-glucopyranosides, in addition to a mixture of stigmasteryl-and b-sitosteryl-3-O-b-D-glucopyranosides. The compounds 1–6 represent bioactive metabolites of S. acmella Murr. that were never previously reported. Our findings demonstrate for the first time the potential benefits of this medicinal plant as a rich source of high therapeutic value compounds for medicines, cosmetics, supplements and as a health food.

  11. Biologically active secondary metabolites from Asphodelus microcarpus.

    Science.gov (United States)

    Ghoneim, Mohammed M; Ma, Guoyi; El-Hela, Atef A; Mohammad, Abd-Elsalam I; Kottob, Saeid; El-Ghaly, Sayed; Cutler, Stephen J; Ross, Samir A

    2013-08-01

    Bioassay guided fractionation of the ethanolic extract of Asphodelus microcarpus Salzm.et Vivi (Asphodelaceae) resulted in the isolation of one new metabolite, 1,6-dimethoxy-3-methyl-2-naphthoic acid (1) as well as nine known compounds: asphodelin (2), chrysophanol (3), 8-methoxychrysophanol (4), emodin (5), 2-acetyl-1,8-dimethoxy-3-methylnaphthalene (6), 10-(chrysophanol-7'-yl)-10-hydroxychrysophanol-9-anthrone (7), aloesaponol-III-8-methyl ether (8), ramosin (9) and aestivin (10). The compounds were identified by 1D and 2D NMR and HRESIMS. Compounds 3, 6 and 10 were isolated for the first time from this species. Compounds 3 and 4 showed moderate to weak antileishmanial activity with IC50 values of 14.3 and 35.1 microg/mL, respectively. Compound 4 exhibited moderate antifungal activity against Cryptococcus neoformans with an IC50 value of 15.0 microg/mL, while compounds 5, 7 and 10 showed good to potent activity against methicillin resistant Staphylococcus aureus (MRSA) with IC50 values of 6.6, 9.4 microg/mL and 1.4 microg/mL respectively. Compounds 5, 8 and 9 displayed good activity against S. aureus with IC50 values of 3.2, 7.3 and 8.5 microg/mL, respectively. Compounds 7 and 9 exhibited a potent cytotoxic activity against leukemia LH60 and K562 cell lines. Compound 10 showed potent antimalarial activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with IC50 values in the range of 0.8-0.7 microg/mL without showing any cytotoxicity to mammalian cells.

  12. Metabolites of Hypoxic Cardiomyocytes Induce the Migration of Cardiac Fibroblasts.

    Science.gov (United States)

    Shi, Huairui; Zhang, Xuehong; He, Zekun; Wu, Zhiyong; Rao, Liya; Li, Yushu

    2017-01-01

    The migration of cardiac fibroblasts to the infarct region plays a major role in the repair process after myocardial necrosis or damage. However, few studies investigated whether early hypoxia in cardiomyocytes induces the migration of cardiac fibroblasts. The purpose of this study was to assess the role of metabolites of early hypoxic cardiomyocytes in the induction of cardiac fibroblast migration. Neonatal rat heart tissue was digested with a mixture of trypsin and collagenase at an appropriate ratio. Cardiomyocytes and cardiac fibroblasts were cultured via differential adhesion. The cardiomyocyte cultures were subjected to hypoxia for 2, 4, 6, 8, 10, and 12 h. The supernatants of the cardiomyocyte cultures were collected to determine the differences in cardiac fibroblast migration induced by hypoxic cardiomyocyte metabolites at various time points using a Transwell apparatus. Meanwhile, ELISA was performed to measure TNF-α, IL-1β and TGF-β expression levels in the cardiomyocyte metabolites at various time points. The metabolites of hypoxic cardiomyocytes significantly induced the migration of cardiac fibroblasts. The induction of cardiac fibroblast migration was significantly enhanced by cardiomyocyte metabolites in comparison to the control after 2, 4, and 6 h of hypoxia, and the effect was most significant after 2 h. The expression levels of TNF-α, IL-1β, IL-6, and TGF-β were substantially increased in the metabolites of cardiomyocytes, and neutralization with anti-TNF-α and anti-IL-1β antibodies markedly reduced the induction of cardiac fibroblast migration by the metabolites of hypoxic cardiomyocytes. The metabolites of early hypoxic cardiomyocytes can induce the migration of cardiac fibroblasts, and TNF-α and IL-1β may act as the initial chemotactic inducers. © 2017 The Author(s) Published by S. Karger AG, Basel.

  13. Phytotoxic metabolites produced by Botryosphaeriaceae involved in grapevine trunk diseases

    OpenAIRE

    Basso, Sara; Andolfi, Anna; Maddau, Lucia; Linaldeddu, Benedetto Teodoro; Deidda, Antonio; Serra, Salvatorica; Cimmino, Alessio; Evidente, Antonio

    2013-01-01

    Fungi belonging to the Botryosphaeriaceae family are well known as cosmopolitan pathogens, saprophytes and endophytes and occur on a wide range of hosts including grapevine. More recently, a new species of Lasiodiplodia was isolated from declining grapevines in Sardinia (Italy). This still undescribed species showed to produce in liquid culture several phytotoxic secondary metabolites. In this communication the chemical and biological characterization of these bioactive secondary metabolit...

  14. Neural Signaling Metabolites May Modulate Energy Use in Hibernation.

    Science.gov (United States)

    Drew, Kelly L; Frare, Carla; Rice, Sarah A

    2017-01-01

    Despite an epidemic in obesity and metabolic syndrome limited means exist to effect adiposity or metabolic rate other than life style changes. Here we review evidence that neural signaling metabolites may modulate thermoregulatory pathways and offer novel means to fine tune energy use. We extend prior reviews on mechanisms that regulate thermogenesis and energy use in hibernation by focusing primarily on the neural signaling metabolites adenosine, AMP and glutamate.

  15. Ants exhibit asymmetric hybridization in a mosaic hybrid zone.

    Science.gov (United States)

    Purcell, Jessica; Zahnd, Sacha; Athanasiades, Anouk; Türler, Rebecca; Chapuisat, Michel; Brelsford, Alan

    2016-10-01

    Research on hybridization between species provides unparalleled insights into the pre- and postzygotic isolating mechanisms that drive speciation. In social organisms, colony-level incompatibilities may provide additional reproductive barriers not present in solitary species, and hybrid zones offer an opportunity to identify these barriers. Here, we use genotyping-by-sequencing to sequence hundreds of markers in a hybrid zone between two socially polymorphic ant species, Formica selysi and Formica cinerea. We characterize the zone, determine the frequency of hybrid workers, infer whether hybrid queens or males are produced and investigate whether hybridization is influenced by colony social organization. We also compare cuticular hydrocarbon profiles and aggression levels between the two species. The hybrid zone exhibits a mosaic structure. The asymmetric distribution of hybrids skewed towards F. cinerea suggests a pattern of unidirectional nuclear gene flow from F. selysi into F. cinerea. The occurrence of backcrossed individuals indicates that hybrid queens and/or males are fertile, and the presence of the F. cinerea mitochondrial haplotype in 97% of hybrids shows that successful F1 hybrids will generally have F. cinerea mothers and F. selysi fathers. We found no evidence that social organization contributes to speciation, because hybrids occur in both single-queen and multiple-queen colonies. Strongly differentiated cuticular hydrocarbon profiles and heightened interspecific aggression further reveal that species recognition cues are both present and perceived. The discovery of fertile hybrids and asymmetrical gene flow is unusual in ants, and this hybrid zone will therefore provide an ideal system with which to investigate speciation in social insects.

  16. Extracellular Metabolites from Industrial Microalgae and Their Biotechnological Potential.

    Science.gov (United States)

    Liu, Lu; Pohnert, Georg; Wei, Dong

    2016-10-20

    Industrial microalgae, as a big family of promising producers of renewable biomass feedstock, have been commercially exploited for functional food, living feed and feed additives, high-value chemicals in nutraceuticals, cosmeceuticals, and chemical reagents. Recently, microalgae have also been considered as a group that might play an important role in biofuel development and environmental protection. Almost all current products of industrial microalgae are derived from their biomass; however, large amounts of spent cell-free media are available from mass cultivation that is mostly unexploited. In this contribution we discuss that these media, which may contain a remarkable diversity of bioactive substances are worthy to be recovered for further use. Obviously, the extracellular metabolites from industrial microalgae have long been neglected in the development of production methods for valuable metabolites. With the advances in the last ten years, more and more structures and properties from extracellular metabolites have been identified, and the potential utilization over wide fields is attracting attention. Some of these extracellular metabolites can be potentially used as drugs, antioxidants, growth regulators or metal chelators. The purpose of this review is to provide an overview of the known extracellular metabolites from industrial microalgae which might be of commercial interest. The attention mainly focuses on the reports of extracellular bioactive metabolites and their potential application in biotechnology.

  17. Extracellular Metabolites from Industrial Microalgae and Their Biotechnological Potential

    Science.gov (United States)

    Liu, Lu; Pohnert, Georg; Wei, Dong

    2016-01-01

    Industrial microalgae, as a big family of promising producers of renewable biomass feedstock, have been commercially exploited for functional food, living feed and feed additives, high-value chemicals in nutraceuticals, cosmeceuticals, and chemical reagents. Recently, microalgae have also been considered as a group that might play an important role in biofuel development and environmental protection. Almost all current products of industrial microalgae are derived from their biomass; however, large amounts of spent cell-free media are available from mass cultivation that is mostly unexploited. In this contribution we discuss that these media, which may contain a remarkable diversity of bioactive substances are worthy to be recovered for further use. Obviously, the extracellular metabolites from industrial microalgae have long been neglected in the development of production methods for valuable metabolites. With the advances in the last ten years, more and more structures and properties from extracellular metabolites have been identified, and the potential utilization over wide fields is attracting attention. Some of these extracellular metabolites can be potentially used as drugs, antioxidants, growth regulators or metal chelators. The purpose of this review is to provide an overview of the known extracellular metabolites from industrial microalgae which might be of commercial interest. The attention mainly focuses on the reports of extracellular bioactive metabolites and their potential application in biotechnology. PMID:27775594

  18. Metabolite Profiles of Lactic Acid Bacteria in Grass Silage▿

    Science.gov (United States)

    Broberg, Anders; Jacobsson, Karin; Ström, Katrin; Schnürer, Johan

    2007-01-01

    The metabolite production of lactic acid bacteria (LAB) on silage was investigated. The aim was to compare the production of antifungal metabolites in silage with the production in liquid cultures previously studied in our laboratory. The following metabolites were found to be present at elevated concentrations in silos inoculated with LAB strains: 3-hydroxydecanoic acid, 2-hydroxy-4-methylpentanoic acid, benzoic acid, catechol, hydrocinnamic acid, salicylic acid, 3-phenyllactic acid, 4-hydroxybenzoic acid, (trans, trans)-3,4-dihydroxycyclohexane-1-carboxylic acid, p-hydrocoumaric acid, vanillic acid, azelaic acid, hydroferulic acid, p-coumaric acid, hydrocaffeic acid, ferulic acid, and caffeic acid. Among these metabolites, the antifungal compounds 3-phenyllactic acid and 3-hydroxydecanoic acid were previously isolated in our laboratory from liquid cultures of the same LAB strains by bioassay-guided fractionation. It was concluded that other metabolites, e.g., p-hydrocoumaric acid, hydroferulic acid, and p-coumaric acid, were released from the grass by the added LAB strains. The antifungal activities of the identified metabolites in 100 mM lactic acid were investigated. The MICs against Pichia anomala, Penicillium roqueforti, and Aspergillus fumigatus were determined, and 3-hydroxydecanoic acid showed the lowest MIC (0.1 mg ml−1 for two of the three test organisms). PMID:17616609

  19. Extracellular Metabolites from Industrial Microalgae and Their Biotechnological Potential

    Directory of Open Access Journals (Sweden)

    Lu Liu

    2016-10-01

    Full Text Available Industrial microalgae, as a big family of promising producers of renewable biomass feedstock, have been commercially exploited for functional food, living feed and feed additives, high-value chemicals in nutraceuticals, cosmeceuticals, and chemical reagents. Recently, microalgae have also been considered as a group that might play an important role in biofuel development and environmental protection. Almost all current products of industrial microalgae are derived from their biomass; however, large amounts of spent cell-free media are available from mass cultivation that is mostly unexploited. In this contribution we discuss that these media, which may contain a remarkable diversity of bioactive substances are worthy to be recovered for further use. Obviously, the extracellular metabolites from industrial microalgae have long been neglected in the development of production methods for valuable metabolites. With the advances in the last ten years, more and more structures and properties from extracellular metabolites have been identified, and the potential utilization over wide fields is attracting attention. Some of these extracellular metabolites can be potentially used as drugs, antioxidants, growth regulators or metal chelators. The purpose of this review is to provide an overview of the known extracellular metabolites from industrial microalgae which might be of commercial interest. The attention mainly focuses on the reports of extracellular bioactive metabolites and their potential application in biotechnology.

  20. Urinary and biliary metabolites of daidzin and daidzein in rats.

    Science.gov (United States)

    Yasuda, T; Kano, Y; Saito, K; Ohsawa, K

    1994-10-01

    Examination was made of the urinary and biliary excretion of metabolites of daidzin and daidzein, the major components of roots of Pueraria lobata Ohwi (Leguminosae) in rats. The urine of rats administered daidzin orally contained four major metabolites, daidzein 7,4'-di-O-sulfate (M-1), daidzein 7-O-beta-D-glucuronide (M-2), daidzein 4'-O-sulfate (M-3), daidzein (M-4), as determined from spectroscopic and chemical data. The urine of rats treated with daidzein contained M-2--M-4 in the above metabolites. Total cumulative amounts of the four metabolites excreted in the urine at 48 h following the oral administration of daidzin and daidzein were approximately 4.8% and 4.6% of the doses administered, respectively. The bile of rats administered daidzin orally contained M-1--M-4. Daidzein 7-O-beta-D-glucuronide 4'-O-sulfate (M-5), a major biliary metabolite, was identified by the high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectra. At least daidzin appeared to be hydrolyzed to aglycone after absorption in the body, and as a part of metabolites, M-1--M-4 having free hydroxyl, glucuronided or sulfated hydroxyls at the C-7 position, may then be excreted in the urine and bile.

  1. DHEA metabolites activate estrogen receptors alpha and beta

    Science.gov (United States)

    Michael Miller, Kristy K.; Al-Rayyan, Numan; Ivanova, Margarita M.; Mattingly, Kathleen A.; Ripp, Sharon L.; Klinge, Carolyn M.; Prough, Russell A.

    2012-01-01

    Dehydroepiandrosterone (DHEA) levels were reported to associate with increased breast cancer risk in postmenopausal women, but some carcinogen-induced rat mammary tumor studies question this claim. The purpose of this study was to determine how DHEA and its metabolites affect estrogen receptors α or β (ERα or ERβ) -regulated gene transcription and cell proliferation. In transiently transfected HEK-293 cells, androstenediol, DHEA, and DHEA-S activated ERα. In ERβ transfected HepG2 cells, androstenedione, DHEA, androstenediol, and 7-oxo DHEA stimulated reporter activity. ER antagonists ICI 182,780 (fulvestrant) and 4-hydroxytamoxifen, general P450 inhibitor miconazole, and aromatase inhibitor exemestane inhibited activation by DHEA or metabolites in transfected cells. ERβ-selective antagonist R,R-THC (R,R-cis-diethyl tetrahydrochrysene) inhibited DHEA and DHEA metabolite transcriptional activity in ERβ-transfected cells. Expression of endogenous estrogen-regulated genes: pS2, progesterone receptor, cathepsin D1, and nuclear respiratory factor-1 was increased by DHEA and its metabolites in an ER-subtype, gene, and cell-specific manner. DHEA metabolites, but not DHEA, competed with 17β-estradiol for ERα and ERβ binding and stimulated MCF-7 cell proliferation, demonstrating that DHEA metabolites interact directly with ERα and ERβ in vitro, modulating estrogen target genes in vivo. PMID:23123738

  2. Biotechnologically produced secondary plant metabolites for cancer treatment and prevention.

    Science.gov (United States)

    Korkina, Liudmila; Kostyuk, Vladimir

    2012-01-01

    Secondary metabolites of higher plants exert numerous effects on tumorigenesis, on tumor cells in vitro, tumors in experimental animals in vivo, interact with anti-cancer drugs, thus affecting positively or negatively their efficacy, and protect normal tissues of the host organism against adverse effects of anti-cancer therapies. The industrial development of pharmaceutical and nutraceutical products based on secondary plant metabolites is limited due to the following: (i) limited availability of their natural sources, (ii) concern about rare extinguishing plants, (iii) unavoidable contamination of plant extracts with environmental pollutants, (iv) seasonal variations in plant harvesting, (v) poor standardization of the final product due to variable conditions for plant growth, and (vi) difficulties of secondary metabolite extraction from the parts of grown plant. There is now steadily growing interest in the biotechnological approach to produce secondary metabolites using plant cell or plant tissue cultures. In the present review, biosynthesis of secondary metabolites and their role(s) in plant physiology will be briefly discussed; the biotechnological approach to active substances production in the plant cell and plant tissue cultures will be described; examples and mechanisms of cancer preventive and anti-cancer action of some biotechnologically produced plant metabolites will be provided; and future perspectives for biotechnologically produced plant-derived substances in the combined protocols for cancer treatment will be suggested.

  3. Metabolites of Siamenoside I and Their Distributions in Rats

    Directory of Open Access Journals (Sweden)

    Xue-Rong Yang

    2016-01-01

    Full Text Available Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography-electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MSn method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo.

  4. Modulation of antimicrobial metabolites production by the fungus Aspergillus parasiticus

    Directory of Open Access Journals (Sweden)

    Adriana A.P. Bracarense

    2014-01-01

    Full Text Available Biosynthesis of active secondary metabolites by fungi occurs as a specific response to the different growing environments. Changes in this environment alter the chemical and biological profiles leading to metabolites diversification and consequently to novel pharmacological applications. In this work, it was studied the influence of three parameters (fermentation length, medium composition and aeration in the biosyntheses of antimicrobial metabolites by the fungus Aspergillus parasiticus in 10 distinct fermentation periods. Metabolism modulation in two culturing media, CYA and YES was evaluated by a 2² full factorial planning (ANOVA and on a 2³ factorial planning, role of aeration, medium composition and carbohydrate concentration were also evaluated. In overall, 120 different extracts were prepared, their HPLC profiles were obtained and the antimicrobial activity against A. flavus, C. albicans, E. coli and S. aureus of all extracts was evaluated by microdilution bioassay. Yield of kojic acid, a fine chemical produced by the fungus A. parasiticus was determined in all extracts. Statistical analyses pointed thirteen conditions able to modulate the production of bioactive metabolites by A. parasiticus. Effect of carbon source in metabolites diversification was significant as shown by the changes in the HPLC profiles of the extracts. Most of the extracts presented inhibition rates higher than that of kojic acid as for the extract obtained after 6 days of fermentation in YES medium under stirring. Kojic acid was not the only metabolite responsible for the activity since some highly active extracts showed to possess low amounts of this compound, as determined by HPLC.

  5. Lichen secondary metabolites affect growth of Physcomitrella patens by allelopathy.

    Science.gov (United States)

    Goga, Michal; Antreich, Sebastian J; Bačkor, Martin; Weckwerth, Wolfram; Lang, Ingeborg

    2017-05-01

    Lichen secondary metabolites can function as allelochemicals and affect the development and growth of neighboring bryophytes, fungi, vascular plants, microorganisms, and even other lichens. Lichen overgrowth on bryophytes is frequently observed in nature even though mosses grow faster than lichens, but there is still little information on the interactions between lichens and bryophytes.In the present study, we used extracts from six lichen thalli containing secondary metabolites like usnic acid, protocetraric acid, atranorin, lecanoric acid, nortistic acid, and thamnolic acid. To observe the influence of these metabolites on bryophytes, the moss Physcomitrella patens was cultivated for 5 weeks under laboratory conditions and treated with lichen extracts. Toxicity of natural mixtures of secondary metabolites was tested at three selected doses (0.001, 0.01, and 0.1 %). When the mixture contained substantial amounts of usnic acid, we observed growth inhibition of protonemata and reduced development of gametophores. Significant differences in cell lengths and widths were also noticed. Furthermore, usnic acid had a strong effect on cell division in protonemata suggesting a strong impact on the early stages of bryophyte development by allelochemicals contained in the lichen secondary metabolites.Biological activities of lichen secondary metabolites were confirmed in several studies such as antiviral, antibacterial, antitumor, antiherbivore, antioxidant, antipyretic, and analgetic action or photoprotection. This work aimed to expand the knowledge on allelopathic effects on bryophyte growth.

  6. Analytical strategy to investigate 3,4-methylenedioxypyrovalerone (MDPV) metabolites in consumers' urine by high-resolution mass spectrometry.

    Science.gov (United States)

    Ibáñez, María; Pozo, Óscar J; Sancho, Juan V; Orengo, Teresa; Haro, Gonzalo; Hernández, Félix

    2016-01-01

    The potential of high-resolution mass spectrometry (HRMS) for the investigation of human in vivo metabolism of 3,4-methylenedioxypyrovalerone (MDPV) using urine collected from a consumer (this is, in non-controlled experiments) has been investigated. As a control sample was not available, the common approach based on the comparison of a control/blank sample and samples collected after drug intake could not be used. Alternatively, an investigation based on common fragmentation pathways was applied, assuming that most metabolites share some fragments with the parent drug. An extension of this approach was also applied based on the fragmentation pathway of those metabolites identified in urine samples in the first step. The use of MS(E) experiments (sequential acquisition of mass spectra at low and high collision energy) has been crucial to this aim as it allowed promoting fragmentation in the collision cell without any previous precursor ion selection. MDPV belongs to the group of new psychoactive substances (NPS), being known as the "cannibal drug". This substance is being abused more and more and is associated with dangerous side effects. The human metabolites (both phase I and phase II) were detected and tentatively identified by accurate mass full-spectrum measurements using ultra-high performance liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Following this strategy, up to 10 phase I metabolites, together with some glucuronides and sulphates, were detected and tentative structures were proposed. Several compounds identified in this work have not been previously reported in the literature.

  7. Associations between vitamin D-binding protein isotypes, circulating 25(OH)D levels, and vitamin D metabolite uptake in colon cancer cells.

    Science.gov (United States)

    Hibler, Elizabeth A; Jacobs, Elizabeth T; Stone, Angelika Dampf; Sardo, Christine L; Galligan, Michael A; Jurutka, Peter W

    2014-04-01

    Vitamin D metabolites have been extensively studied as cancer chemopreventive agents. Gc-globulin (GC) isotypes, based on rs7041 and rs4588 diplotypes, have varying affinities for 1α,25-dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxyvitamin D (25(OH)D), which may affect circulating metabolite concentration as well as delivery at the cellular level. We evaluated associations between GC isotype and circulating vitamin D metabolite concentrations in 403 ursodeoxycholic acid (UDCA) clinical trial participants. Metabolite uptake was evaluated in human colon cancer (HCT-116) cells treated with ethanol vehicle, 1,25(OH)2D, or 25(OH)D, and with plasma from individuals with known GC isotype. Mammalian-2-hybrid and vitamin D-responsive element-based luciferase assays were used to measure the vitamin D receptor pathway activation as a marker for metabolite uptake. Regression analysis demonstrated significantly lower serum 25(OH)D concentration for clinical trial participants with 1F_2, 1S_2, or 2_2 isotypes (P OH)D uptake varied less by GC isotype only at the higher concentration tested (P = 0.05), while 1,25(OH)2D uptake differed markedly by GC isotype across concentration and assay (P OH)2D treatment and, while activation varied less with 25(OH)D, the 2_2 isotype demonstrated increased induction at the lower concentration. These results suggest that vitamin D metabolite concentration and delivery to colon cells may vary not only by GC isotype, but also that certain isotypes may more effectively deliver 1,25(OH)2D versus 25(OH)D. Overall, these results may help identify populations at risk for cancer and potential recipients of targeted chemoprevention.

  8. Metabolomic changes during cellular transformation monitored by metabolite-metabolite correlation analysis and correlated with gene expression.

    Science.gov (United States)

    Madhu, Basetti; Narita, Masako; Jauhiainen, Alexandra; Menon, Suraj; Stubbs, Marion; Tavaré, Simon; Narita, Masashi; Griffiths, John R

    To investigate metabolic changes during cellular transformation, we used a (1)H NMR based metabolite-metabolite correlation analysis (MMCA) method, which permits analysis of homeostatic mechanisms in cells at the steady state, in an inducible cell transformation model. Transcriptomic data were used to further explain the results. Transformed cells showed many more metabolite-metabolite correlations than control cells. Some had intuitively plausible explanations: a shift from glycolysis to amino acid oxidation after transformation was accompanied by a strongly positive correlation between glucose and glutamine and a strongly negative one between lactate and glutamate; there were also many correlations between the branched chain amino acids and the aromatic amino acids. Others remain puzzling: after transformation strong positive correlations developed between choline and a group of five amino acids, whereas the same amino acids showed negative correlations with phosphocholine, a membrane phospholipid precursor. MMCA in conjunction with transcriptome analysis has opened a new window into the metabolome.

  9. Sertraline and Its Metabolite Desmethylsertraline, but not Bupropion or Its Three Major Metabolites, Have High Affinity for P-Glycoprotein

    OpenAIRE

    Wang, Jun-Sheng; Zhu, Hao-Jie; Gibson, Bryan Bradford; Markowitz, John Seth; Donovan, Jennifer Lyn; DeVane, Carl Lindsay

    2008-01-01

    The ATP-binding cassette (ABC) transporter protein subfamily Bl line (ABCBl) transporter P-glycoprotein (P-gp) plays an important role in the blood–brain barrier limiting a broad spectrum of substrates from entering the central nervous system. In the present study, the transport activity of P-gp for sertraline, desmethylsertralin, bupropion, and the major metabolites of bupropion, threo-amino alcohol (TB), erythro-amino alchhol (EB), and hydroxy metabolite (HB) was studied using an ATPase ass...

  10. Energy Efficiency Comparison between Hydraulic Hybrid and Hybrid Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Jia-Shiun Chen

    2015-05-01

    Full Text Available Conventional vehicles tend to consume considerable amounts of fuel, which generates exhaust gases and environmental pollution during intermittent driving cycles. Therefore, prospective vehicle designs favor improved exhaust emissions and energy consumption without compromising vehicle performance. Although pure electric vehicles feature high performance and low pollution characteristics, their limitations are their short driving range and high battery costs. Hybrid electric vehicles (HEVs are comparatively environmentally friendly and energy efficient, but cost substantially more compared with conventional vehicles. Hydraulic hybrid vehicles (HHVs are mainly operated using engines, or using alternate combinations of engine and hydraulic power sources while vehicles accelerate. When the hydraulic system accumulator is depleted, the conventional engine reengages; concurrently, brake-regenerated power is recycled and reused by employing hydraulic motor–pump modules in circulation patterns to conserve fuel and recycle brake energy. This study adopted MATLAB Simulink to construct complete HHV and HEV models for backward simulations. New European Driving Cycles were used to determine the changes in fuel economy. The output of power components and the state-of-charge of energy could be retrieved. Varying power component models, energy storage component models, and series or parallel configurations were combined into seven different vehicle configurations: the conventional manual transmission vehicle, series hybrid electric vehicle, series hydraulic hybrid vehicle, parallel hybrid electric vehicle, parallel hydraulic hybrid vehicle, purely electric vehicle, and hydraulic-electric hybrid vehicle. The simulation results show that fuel consumption was 21.80% lower in the series hydraulic hybrid vehicle compared to the series hybrid electric vehicle; additionally, fuel consumption was 3.80% lower in the parallel hybrid electric vehicle compared to the

  11. Severe drought stress is affecting selected primary metabolites, polyphenols, and volatile metabolites in grapevine leaves (Vitis vinifera cv. Pinot noir).

    Science.gov (United States)

    Griesser, Michaela; Weingart, Georg; Schoedl-Hummel, Katharina; Neumann, Nora; Becker, Manuel; Varmuza, Kurt; Liebner, Falk; Schuhmacher, Rainer; Forneck, Astrid

    2015-03-01

    Extreme weather conditions with prolonged dry periods and high temperatures as well as heavy rain events can severely influence grapevine physiology and grape quality. The present study evaluates the effects of severe drought stress on selected primary metabolites, polyphenols and volatile metabolites in grapevine leaves. Among the 11 primary metabolites, 13 polyphenols and 95 volatiles which were analyzed, a significant discrimination between control and stressed plants of 7 primary metabolites, 11 polyphenols and 46 volatile metabolites was observed. As single parameters are usually not specific enough for the discrimination of control and stressed plants, an unsupervised (PCA) and a supervised (PLS-DA) multivariate approach were applied to combine results from different metabolic groups. In a first step a selection of five metabolites, namely citric acid, glyceric acid, ribose, phenylacetaldehyde and 2-methylbutanal were used to establish a calibration model using PLS regression to predict the leaf water potential. The model was strong enough to assign a high number of plants correctly with a correlation of 0.83. The PLS-DA provides an interesting approach to combine data sets and to provide tools for the specific evaluation of physiological plant stresses.

  12. Phoxonic Hybrid Superlattice.

    Science.gov (United States)

    Alonso-Redondo, Elena; Huesmann, Hannah; El Boudouti, El-Houssaine; Tremel, Wolfgang; Djafari-Rouhani, Bahram; Butt, Hans-Juergen; Fytas, George

    2015-06-17

    We studied experimentally and theoretically the direction-dependent elastic and electromagnetic wave propagation in a supported film of hybrid PMMA (poly[methyl-methacrylate])-TiO2 superlattice (SL). In the direction normal to the layers, this one-dimensional periodic structure opens propagation band gaps for both hypersonic (GHz) phonons and near-UV photons. The high mismatch of elastic and optical impedance results in a large dual phoxonic band gap. The presence of defects inherent to the spin-coating fabrication technique is sensitively manifested in the band gap region. Utilizing Brillouin light scattering, phonon propagation along the layers was observed to be distinctly different from propagation normal to them and can, under certain conditions (SL thickness and substrate elasticity), reveal the nanomechanical properties of the constituent layers. Besides the first realization of unidirectional phoxonic behavior, hybrid (soft-hard) periodic materials are a promising simple platform for opto-acoustic interactions and applications such as filters and Bragg mirrors.

  13. The Power of Hybridization

    CERN Document Server

    CERN. Geneva

    2011-01-01

    Programming languages always seem to do some things well but not others: Python punts when it comes to user interfaces, Java’s artificial complexity prevents rapid development and produces tangles, and it will be awhile before we see benefits from C++ concurrency work. The cognitive load of languages and their blind spots increases the cost of experimentation, impeding your ability to fail fast and iterate. If you use a single language to solve your problem, you are binding yourself to the worldview limitations and the mistakes made by the creator of that language. Consider increasing your wiggle room by crossing language boundaries, complementing a language that is powerful in one area with a different language powerful in another. Language hybridization can speed development to quickly discover your real problems, giving you more time to fix them. After making a case for hybridizing your thinking in general, I will present a number of simple examples; first showing the benefits of using other languages...

  14. A Pseudoscalar Hybrid Meson?

    CERN Document Server

    Page, P R

    1996-01-01

    New experimental information on the non--exotic J^{PC} = 0^{-+} isovector seen at 1.8 GeV by VES yields convincing evidence of its excited gluonic (hybrid) nature when a critical study of alternative quarkonium assignments is made in the context of ^3 P_0 decay by flux--tube breaking. Production of this gluonic excitation via meson exchange is promising, although its two photon production vanishes.

  15. Military Hybrid Vehicle Survey

    Science.gov (United States)

    2011-08-03

    Furthermore, a standard duty cycle that is accepted for measuring fuel economy does not exist nor does a focus towards a particular technology. This...expanded into mild hybrid with the addition of a clutch connecting the generator to the transmission and additional energy storage [16-17...speed control and one for engine/generator torque [35]. Urban, Highway, Composite 33%, 27.9%, 49% General vehicle simulation [30]. Urban 19.0

  16. Fibonacci-Pell Hybridities

    Science.gov (United States)

    Koshy, Thomas; Gao, Zhenguang

    2012-01-01

    We develop a recurrence satisfied by the Fibonacci and Pell families. We then use it to find explicit formulae and generating functions for the hybrids "F[subscript n]P[subscript n]", "L[subscript n]P[subscript n]", "F[subscript n]Q[subscript n]" and "L[subscript n]Q[subscript n]", where "F[subscript n]", "L[subscript n]", "P[subscript n]" and…

  17. Hybrid electroluminescent devices

    Science.gov (United States)

    Shiang, Joseph John; Duggal, Anil Raj; Michael, Joseph Darryl

    2010-08-03

    A hybrid electroluminescent (EL) device comprises at least one inorganic diode element and at least one organic EL element that are electrically connected in series. The absolute value of the breakdown voltage of the inorganic diode element is greater than the absolute value of the maximum reverse bias voltage across the series. The inorganic diode element can be a power diode, a Schottky barrier diode, or a light-emitting diode.

  18. Hybrid undulator numerical optimization

    Energy Technology Data Exchange (ETDEWEB)

    Hairetdinov, A.H. [Kurchatov Institute, Moscow (Russian Federation); Zukov, A.A. [Solid State Physics Institute, Chernogolovka (Russian Federation)

    1995-12-31

    3D properties of the hybrid undulator scheme arc studied numerically using PANDIRA code. It is shown that there exist two well defined sets of undulator parameters which provide either maximum on-axis field amplitude or minimal higher harmonics amplitude of the basic undulator field. Thus the alternative between higher field amplitude or pure sinusoidal field exists. The behavior of the undulator field amplitude and harmonics structure for a large set of (undulator gap)/(undulator wavelength) values is demonstrated.

  19. Asymmetric Hybrid Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Chumanov, George [Clemson Univ., SC (United States)

    2015-11-05

    Hybrid Nanoparticles (AHNs) are rationally-designed multifunctional nanostructures and novel building blocks for the next generation of advanced materials and devices. Nanoscale materials attract considerable interest because of their unusual properties and potential for practical applications. Most of the activity in this field is focused on the synthesis of homogeneous nanoparticles from metals, metal oxides, semiconductors, and polymers. It is well recognized that properties of nanoparticles can be further enhanced if they are made as hybrid structures. This program is concerned with the synthesis, characterization, and application of such hybrid structures termed AHNs. AHNs are composed of a homogeneous core and several caps of different materials deposited on its surface (Fig. 1). Combined properties of the core and the caps as well as new properties that arise from core-cap and cap-cap interactions render AHNs multifunctional. In addition, specific chemical reactivity of the caps enables directional self-assembly of AHNs into complex architectures that are not possible with only spherical nanoparticles.

  20. Hybrid Keyword Search Auctions

    CERN Document Server

    Goel, Ashish

    2008-01-01

    Search auctions have become a dominant source of revenue generation on the Internet. Such auctions have typically used per-click bidding and pricing. We propose the use of hybrid auctions where an advertiser can make a per-impression as well as a per-click bid, and the auctioneer then chooses one of the two as the pricing mechanism. We assume that the advertiser and the auctioneer both have separate beliefs (called priors) on the click-probability of an advertisement. We first prove that the hybrid auction is truthful, assuming that the advertisers are risk-neutral. We then show that this auction is superior to the existing per-click auction in multiple ways: 1) It takes into account the risk characteristics of the advertisers. 2) For obscure keywords, the auctioneer is unlikely to have a very sharp prior on the click-probabilities. In such situations, the hybrid auction can result in significantly higher revenue. 3) An advertiser who believes that its click-probability is much higher than the auctioneer's es...

  1. Printed hybrid systems

    Science.gov (United States)

    Karioja, Pentti; Mäkinen, Jukka-Tapani; Keränen, Kimmo; Aikio, Janne; Alajoki, Teemu; Jaakola, Tuomo; Koponen, Matti; Keränen, Antti; Heikkinen, Mikko; Tuomikoski, Markus; Suhonen, Riikka; Hakalahti, Leena; Kopola, Pälvi; Hast, Jukka; Liedert, Ralf; Hiltunen, Jussi; Masuda, Noriyuki; Kemppainen, Antti; Rönkä, Kari; Korhonen, Raimo

    2012-04-01

    This paper presents research activities carried out at VTT Technical Research Centre of Finland in the field of hybrid integration of optics, electronics and mechanics. Main focus area in our research is the manufacturing of electronic modules and product structures with printed electronics, film-over-molding and polymer sheet lamination technologies and the goal is in the next generation of smart systems utilizing monolithic polymer packages. The combination of manufacturing technologies such as roll-to-roll -printing, injection molding and traditional component assembly is called Printed Hybrid Systems (PHS). Several demonstrator structures have been made, which show the potential of polymer packaging technology. One demonstrator example is a laminated structure with embedded LED chips. Element thickness is only 0.3mm and the flexible stack of foils can be bent in two directions after assembly process and was shaped curved using heat and pressure. The combination of printed flexible circuit boards and injection molding has also been demonstrated with several functional modules. The demonstrators illustrate the potential of origami electronics, which can be cut and folded to 3D shapes. It shows that several manufacturing process steps can be eliminated by Printed Hybrid Systems technology. The main benefits of this combination are small size, ruggedness and conformality. The devices are ideally suited for medical applications as the sensitive electronic components are well protected inside the plastic and the structures can be cleaned easily due to the fact that they have no joints or seams that can accumulate dirt or bacteria.

  2. Identification and characterization of oxidative metabolites of 1-chloropyrene.

    Science.gov (United States)

    Kakimoto, Kensaku; Nagayoshi, Haruna; Inazumi, Naoya; Tani, Atsushi; Konishi, Yoshimasa; Kajimura, Keiji; Ohura, Takeshi; Nakano, Takeshi; Tang, Ning; Hayakawa, Kazuichi; Toriba, Akira

    2015-09-21

    Polycyclic aromatic hydrocarbons (PAHs) and chlorinated PAHs (ClPAHs) are ubiquitous contaminants that bind to the aryl hydrocarbon receptor (AhR) and exhibit mutagenic potential. It is difficult to monitor human exposure levels to ClPAHs because the exposure routes are complicated, and environmental concentrations are not always correlated with the levels of PAHs. Urinary PAH metabolites are useful biomarkers for evaluating PAH exposure, and ClPAH metabolites may therefore contribute to the estimation of ClPAH exposure. One of the most abundant ClPAHs present in the environment is 1-chloropyrene (ClPyr), and urinary ClPyr metabolites have the potential to be good biomarkers to evaluate the level of exposure to ClPAHs. Since the metabolic pathways involving ClPAHs are still undetermined, we investigated the effect of human cytochrome P450 enzymes on ClPyr and identified three oxidative metabolites by liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance. We found that ClPyr was metabolized most efficiently by the P450 1A1 enzyme, followed by the 1B1 and 1A2 enzymes. Similar to ClPyr, these metabolites were shown to have agonist activity for the human AhR. We detected these metabolites when ClPyr reacted with a pooled human liver S9 fraction as well as in human urine samples. These results suggest that the metabolites may be used as biomarkers to evaluate the extent of exposure to ClPAHs.

  3. Urine Metabolite Profiles Predictive of Human Kidney Allograft Status.

    Science.gov (United States)

    Suhre, Karsten; Schwartz, Joseph E; Sharma, Vijay K; Chen, Qiuying; Lee, John R; Muthukumar, Thangamani; Dadhania, Darshana M; Ding, Ruchuang; Ikle, David N; Bridges, Nancy D; Williams, Nikki M; Kastenmüller, Gabi; Karoly, Edward D; Mohney, Robert P; Abecassis, Michael; Friedewald, John; Knechtle, Stuart J; Becker, Yolanda T; Samstein, Benjamin; Shaked, Abraham; Gross, Steven S; Suthanthiran, Manikkam

    2016-02-01

    Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite-mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.

  4. The metabolite profiling of coastal coccolithophorid species Pleurochrysis carterae (Haptophyta)

    Science.gov (United States)

    Zhou, Chengxu; Luo, Jie; Ye, Yangfang; Yan, Xiaojun; Liu, Baoning; Wen, Xin

    2016-07-01

    Pleurochrysis carterae is a calcified coccolithophorid species that usually blooms in the coastal area and causes aquaculture losses. The cellular calcification, blooming and many other critical species specific eco-physiological processes are closely related to various metabolic pathways. The purpose of this study is to apply the unbiased and non-destructive method of nuclear magnetic resonance (NMR) to detect the unknown holistic metabolite of P. carterae. The results show that NMR spectroscopic method is practical in the analysis of metabolites of phytoplankton. The metabolome of P. carterae was dominated by 26 metabolites involved in a number of different primary and secondary metabolic pathways. Organic acids and their derivatives, amino acids, sugars, nucleic aides were mainly detected. The abundant metabolites are that closely related to the process of cellular osmotic adjustment, which possibly reflect the active ability of P. carterae to adapt to the versatile coastal niche. DMSP (dimethylsulphoniopropionate) was the most dominant metabolite in P. carterae, up to 2.065±0.278 mg/g lyophilized cells, followed by glutamate and lactose, the contents were 0.349±0.035 and 0.301±0.073 mg/g lyophilized cells respectively. Other metabolites that had the content ranged between 0.1-0.2 mg/g lyophilized cells were alanine, isethionate and arabinose. Amino acid (valine, phenylalanine, isoleucine, tyrosine), organic acid salts (lactate, succinate), scyllitol and uracil had content ranged from 0.01 to below 0.1 mg/g lyophilized cells. Trigonelline, fumarate and formate were detected in very low content (only thousandths of 1 mg per gram of lyophilized cells or below). Our results of the holistic metabolites of P. carterae are the basic references for the further studies when multiple problems will be addressed to this notorious blooming calcifying species.

  5. Hybrid2 - The hybrid power system simulation model

    Energy Technology Data Exchange (ETDEWEB)

    Baring-Gould, E.I.; Green, H.J.; Dijk, V.A.P. van [National Renewable Energy Lab., Golden, CO (United States); Manwell, J.F. [Univ. of Massachusetts, Amherst, MA (United States)

    1996-12-31

    There is a large-scale need and desire for energy in remote communities, especially in the developing world; however the lack of a user friendly, flexible performance prediction model for hybrid power systems incorporating renewables hindered the analysis of hybrids as options to conventional solutions. A user friendly model was needed with the versatility to simulate the many system locations, widely varying hardware configurations, and differing control options for potential hybrid power systems. To meet these ends, researchers from the National Renewable Energy Laboratory (NREL) and the University of Massachusetts (UMass) developed the Hybrid2 software. This paper provides an overview of the capabilities, features, and functionality of the Hybrid2 code, discusses its validation and future plans. Model availability and technical support provided to Hybrid2 users are also discussed. 12 refs., 3 figs., 4 tabs.

  6. NMR identification of endogenous metabolites interacting with fatted and non-fatted human serum albumin in blood plasma: Fatty acids influence the HSA-metabolite interaction

    Science.gov (United States)

    Jupin, Marc; Michiels, Paul J.; Girard, Frederic C.; Spraul, Manfred; Wijmenga, Sybren S.

    2013-03-01

    Metabolites and their concentrations are direct reporters on body biochemistry. Thanks to technical developments metabolic profiling of body fluids, such as blood plasma, by for instance NMR has in the past decade become increasingly accurate enabling successful clinical diagnostics. Human Serum Albumin (HSA) is the main plasma protein (∼60% of all plasma protein) and responsible for the transport of endogenous (e.g. fatty acids) and exogenous metabolites, which it achieves thanks to its multiple binding sites and its flexibility. HSA has been extensively studied with regard to its binding of drugs (exogenous metabolites), but only to a lesser extent with regard to its binding of endogenous (non-fatty acid) metabolites. To obtain correct NMR measured metabolic profiles of blood plasma and/or potentially extract information on HSA and fatty acids content, it is necessary to characterize these endogenous metabolite/plasma protein interactions. Here, we investigate these metabolite-HSA interactions in blood plasma and blood plasma mimics. The latter contain the roughly twenty metabolites routinely detected by NMR (also most abundant) in normal relative concentrations with fatted or non-fatted HSA added or not. First, we find that chemical shift changes are small and seen only for a few of the metabolites. In contrast, a significant number of the metabolites display reduced resonance integrals and reduced free concentrations in the presence of HSA or fatted HSA. For slow-exchange (or strong) interactions, NMR resonance integrals report the free metabolite concentration, while for fast exchange (weak binding) the chemical shift reports on the binding. Hence, these metabolites bind strongly to HSA and/or fatted HSA, but to a limited degree because for most metabolites their concentration is smaller than the HSA concentration. Most interestingly, fatty acids decrease the metabolite-HSA binding quite significantly for most of the interacting metabolites. We further find

  7. Study of Blood Metabolites Changes of Purebred Ghezel and Crossbred Arkhar Merinos × Ghezel Ewes during Late Pregnancy

    Directory of Open Access Journals (Sweden)

    Leila Ahmadzadeh

    2016-11-01

    analysis of metabolites. Measurement of blood metabolites, including total protein, calcium, glucose, cholesterol, blood urea nitrogen and albumin was done by spectrophotometer set. SAS software (2003 was used for statistical analysis. Mixed procedure of SAS software was used for statistical analysis and Tukey- Kramer test was applied for comparison of means. T-test was used for comparison of blood metabolites between ewes with single and twin lambs. Results and Discussion The results showed that the blood glucose, total protein, albumin and calcium on days 90, 120 and 140 of pregnancy were less than 15 days prior to mating but blood urea nitrogen and cholesterol levels were increased. These variations could originate from fetus metabolism since fetus requirements for tissue growth, muscles and bones increases during pregnancy, which should be supplied from maternal body reserves. The comparison of blood metabolites on the both crossbred and purebred pregnant ewes showed that in the late pregnancy, twin pregnant ewes had less glucose, total protein and calcium and more blood urea nitrogen and cholesterol compared with single pregnant ewes because there is a higher fetus requirement for twin fetuses during gestation. Our results also showed that glucose, total protein, albumin and blood urea nitrogen ‏levels of crossbred ewes were higher than purebred Ghezel ewes on 15 days prior to mating period. This may be due to different genetic potential of these breeds. During the gestation period, levels of mentioned metabolites except for blood urea nitrogen‏ were higher in both single and twin crossbred pregnant ewes than purebred Ghezel ewes significantly. It is seemed that these differences may be related to variation in the genetic potential of studying animals. Conclusion The results of present study showed that there were no signs of pregnancy toxemia in the two experimental groups; however some differences among blood metabolites of purebred and hybrid ewes were found

  8. Convulsive liability of bupropion hydrochloride metabolites in Swiss albino mice

    Directory of Open Access Journals (Sweden)

    McMahon Louis

    2008-10-01

    Full Text Available Abstract Background It is known that following chronic dosing with bupropion HCl active metabolites are present in plasma at levels that are several times higher than that of the parent drug, but the possible convulsive effects of the major metabolites are not known. Methods We investigated the convulsive liability and dose-response of the three major bupropion metabolites following intraperitoneal administration of single doses in female Swiss albino mice, namely erythrohydrobupropion HCl, threohydrobupropion HCl, and hydroxybupropion HCl. We compared these to bupropion HCl. The actual doses of the metabolites administered to mice (n = 120; 10 per dose group were equimolar equivalents of bupropion HCl 25, 50 and 75 mg/kg. Post treatment, all animals were observed continuously for 2 h during which the number, time of onset, duration and intensity of convulsions were recorded. The primary outcome variable was the percentage of mice in each group who had a convulsion at each dose. Other outcome measures were the time to onset of convulsions, mean convulsions per mouse, and the duration and intensity of convulsions. Results All metabolites were associated with a greater percentage of seizures compared to bupropion, but the percentage of convulsions differed between metabolites. Hydroxybupropion HCl treatment induced the largest percentage of convulsing mice (100% at both 50 and 75 mg/kg followed by threohydrobupropion HCl (50% and 100%, and then erythrohydrobupropion HCl (10% and 90%, compared to bupropion HCl (0% and 10%. Probit analysis also revealed the dose-response curves were significantly different (p 50 values of 35, 50, 61 and 82 mg/kg, respectively for the four different treatments. Cox proportional hazards model results showed that bupropion HCl, erythrohydrobupropion HCl, and threohydrobupropion HCl were significantly less likely to induce convulsions within the 2-h post treatment observation period compared to hydroxybupropion HCl. The

  9. Pyrazolones metabolites are relevant for identifying selective anaphylaxis to metamizole

    Science.gov (United States)

    Ariza, Adriana; García-Martín, Elena; Salas, María; Montañez, María I.; Mayorga, Cristobalina; Blanca-Lopez, Natalia; Andreu, Inmaculada; Perkins, James; Blanca, Miguel; Agúndez, José A. G.; Torres, María J.

    2016-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of hypersensitivity reactions, with pyrazolones the most frequent drugs inducing selective reactions. Immediate selective hypersensitivity to pyrazolones is thought to be mediated by specific-IgE. Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved. Here we investigated whether main metabolites of metamizole (dipyrone) in human could be involved in the immune response using the basophil activation test (BAT). We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug. Our findings indicate that pyrazolone metabolites are useful for improving the in vitro diagnosis of allergic reactions to metamizole. PMID:27030298

  10. Secondary metabolites from three Florida sponges with antidepressant activity.

    Science.gov (United States)

    Kochanowska, Anna J; Rao, Karumanchi V; Childress, Suzanne; El-Alfy, Abir; Matsumoto, Rae R; Kelly, Michelle; Stewart, Gina S; Sufka, Kenneth J; Hamann, Mark T

    2008-02-01

    Brominated indole alkaloids are a common class of metabolites reported from sponges of the order Verongida. Herein we report the isolation, structure determination, and activity of metabolites from three Florida sponges, namely, Verongula rigida (order Verongida, family Aplysinidae), Smenospongia aurea, and S. cerebriformis (order Dictyoceratida, family Thorectidae). All three species were investigated chemically, revealing similarities in secondary metabolites. Brominated compounds, as well as sesquiterpene quinones and hydroquinones, were identified from both V. rigida and S. aurea despite their apparent taxonomic differences at the ordinal level. Similar metabolites found in these distinct sponge species of two different genera provide evidence for a microbial origin of the metabolites. Isolated compounds were evaluated in the Porsolt forced swim test (FST) and the chick anxiety-depression continuum model. Among the isolated compounds, 5,6-dibromo- N,N-dimethyltryptamine ( 1) exhibited significant antidepressant-like action in the rodent FST model, while 5-bromo- N,N-dimethyltryptamine ( 2) caused significant reduction of locomotor activity indicative of a potential sedative action. The current study provides ample evidence that marine natural products with the diversity of brominated marine alkaloids will provide potential leads for antidepressant and anxiolytic drugs.

  11. Biodegradation of clofibric acid and identification of its metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Salgado, R. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); ESTS-IPS, Escola Superior de Tecnologia de Setubal do Instituto Politecnico de Setubal, Rua Vale de Chaves, Campus do IPS, Estefanilha, 2910-761 Setubal (Portugal); Oehmen, A. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Carvalho, G. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Instituto de Biologia Experimental e Tecnologica (IBET), Av. da Republica (EAN), 2784-505 Oeiras (Portugal); Noronha, J.P. [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Reis, M.A.M., E-mail: amr@fct.unl.pt [REQUIMTE/CQFB, Chemistry Department, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)

    2012-11-30

    Graphical abstract: Metabolites produced during clofibric acid biodegradation. Highlights: Black-Right-Pointing-Pointer Clofibric acid is biodegradable. Black-Right-Pointing-Pointer Mainly heterotrophic bacteria degraded the clofibric acid. Black-Right-Pointing-Pointer Metabolites of clofibric acid biodegradation were identified. Black-Right-Pointing-Pointer The metabolic pathway of clofibric acid biodegradation is proposed. - Abstract: Clofibric acid (CLF) is the pharmaceutically active metabolite of lipid regulators clofibrate, etofibrate and etofyllinclofibrate, and it is considered both environmentally persistent and refractory. This work studied the biotransformation of CLF in aerobic sequencing batch reactors (SBRs) with mixed microbial cultures, monitoring the efficiency of biotransformation of CLF and the production of metabolites. The maximum removal achieved was 51% biodegradation (initial CLF concentration = 2 mg L{sup -1}), where adsorption and abiotic removal mechanisms were shown to be negligible, showing that CLF is indeed biodegradable. Tests showed that the observed CLF biodegradation was mainly carried out by heterotrophic bacteria. Three main metabolites were identified, including {alpha}-hydroxyisobutyric acid, lactic acid and 4-chlorophenol. The latter is known to exhibit higher toxicity than the parent compound, but it did not accumulate in the SBRs. {alpha}-Hydroxyisobutyric acid and lactic acid accumulated for a period, where nitrite accumulation may have been responsible for inhibiting their degradation. A metabolic pathway for the biodegradation of CLF is proposed in this study.

  12. Concurrent quantification of tryptophan and its major metabolites

    Science.gov (United States)

    Lesniak, Wojciech G.; Jyoti, Amar; Mishra, Manoj K.; Louissaint, Nicolette; Romero, Roberto; Chugani, Diane C.; Kannan, Sujatha; Kannan, Rangaramanujam M.

    2014-01-01

    An imbalance in tryptophan (TRP) metabolites is associated with several neurological and inflammatory disorders. Therefore, analytical methods allowing for simultaneous quantification of TRP and its major metabolites would be highly desirable, and may be valuable as potential biomarkers. We have developed a HPLC method for concurrent quantitative determination of tryptophan, serotonin, 5-hydroxyindoleacetic acid, kynurenine, and kynurenic acid in tissue and fluids. The method utilizes the intrinsic spectroscopic properties of TRP and its metabolites that enable UV absorbance and fluorescence detection by HPLC, without additional labeling. The origin of the peaks related to analytes of interest was confirmed by UV–Vis spectral patterns using a PDA detector and mass spectrometry. The developed methods were validated in rabbit fetal brain and amniotic fluid at gestational day 29. Results are in excellent agreement with those reported in the literature for the same regions. This method allows for rapid quantification of tryptophan and four of its major metabolites concurrently. A change in the relative ratios of these metabolites can provide important insights in predicting the presence and progression of neuroinflammation in disorders such as cerebral palsy, autism, multiple sclerosis, Alzheimer disease, and schizophrenia. PMID:24036037

  13. Control of endophytic Frankia sporulation by Alnus nodule metabolites.

    Science.gov (United States)

    Hay De-Bettignies, Anne-Emmanuelle; Boubakri, Hasna; Buonomo, Antoine; Rey, Marjolaine; Meiffren, Guillaume; Cotin-Galvan, Laetitia; Comte, Gilles; Herrera-Belaroussi, Aude

    2017-01-10

    A unique case of microbial symbiont capable of dormancy within its living host cells has been reported in actinorhizal symbioses: some Frankia strains, named Sp+, are able to sporulate inside plant cells, contrarily to Sp- strains. The presence of metabolically slowed down bacterial structures in host cells alters our understanding of symbiosis based on reciprocal benefits between both partners, and its impact on the symbiotic processes remains unknown. The present work reports a metabolomic study of Sp+ and Sp- nodules (from Alnus glutinosa), in order to highlight variabilities associated with in-planta sporulation. A total of 21 amino acids (AA), 44 sugars and organic acids (SOA), and 213 secondary metabolites (M) were detected using UV and mass spectrometric-based profiling. Little change was observed in primary metabolites, suggesting that in-planta sporulation would not strongly affect the primary functionalities of the symbiosis. One secondary metabolite (M27) was detected only in Sp+ nodules. It was identified as Gentisic acid 5-O-β-D-xylopyranoside, previously reported as involved in plant defenses against microbial pathogens. This metabolite significantly increased Frankia in-vitro sporulation, unlike another metabolite significantly more abundant in Sp- nodules (M168 = (5R)-1,7-bis-(3,4-) dihydroxyphenyl)-heptane-5-O-β-D-glucopyranoside). All these results suggest that the plant could play an important role in Frankia ability to sporulate in-planta, and allow us to discuss a possible sanction emitted by the host against less cooperative Sp+ symbionts.

  14. Detection of Volatile Metabolites of Garlic in Human Breast Milk.

    Science.gov (United States)

    Scheffler, Laura; Sauermann, Yvonne; Zeh, Gina; Hauf, Katharina; Heinlein, Anja; Sharapa, Constanze; Buettner, Andrea

    2016-06-06

    The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography-mass spectrometry/olfactometry (GC-MS/O), as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS), allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO₂). Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO₂ are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences.

  15. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

    Directory of Open Access Journals (Sweden)

    Chong-Zhi Wang

    2015-09-01

    Full Text Available Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc, and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management.

  16. Detection of Volatile Metabolites of Garlic in Human Breast Milk

    Directory of Open Access Journals (Sweden)

    Laura Scheffler

    2016-06-01

    Full Text Available The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography−mass spectrometry/olfactometry (GC-MS/O, as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS, allyl methyl sulfoxide (AMSO and allyl methyl sulfone (AMSO2. Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO2 are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences.

  17. Metabolite identification and molecular fingerprint prediction through machine learning.

    Science.gov (United States)

    Heinonen, Markus; Shen, Huibin; Zamboni, Nicola; Rousu, Juho

    2012-09-15

    Metabolite identification from tandem mass spectra is an important problem in metabolomics, underpinning subsequent metabolic modelling and network analysis. Yet, currently this task requires matching the observed spectrum against a database of reference spectra originating from similar equipment and closely matching operating parameters, a condition that is rarely satisfied in public repositories. Furthermore, the computational support for identification of molecules not present in reference databases is lacking. Recent efforts in assembling large public mass spectral databases such as MassBank have opened the door for the development of a new genre of metabolite identification methods. We introduce a novel framework for prediction of molecular characteristics and identification of metabolites from tandem mass spectra using machine learning with the support vector machine. Our approach is to first predict a large set of molecular properties of the unknown metabolite from salient tandem mass spectral signals, and in the second step to use the predicted properties for matching against large molecule databases, such as PubChem. We demonstrate that several molecular properties can be predicted to high accuracy and that they are useful in de novo metabolite identification, where the reference database does not contain any spectra of the same molecule. An Matlab/Python package of the FingerID tool is freely available on the web at http://www.sourceforge.net/p/fingerid. markus.heinonen@cs.helsinki.fi.

  18. Current approaches toward production of secondary plant metabolites

    Directory of Open Access Journals (Sweden)

    Md. Sarfaraj Hussain

    2012-01-01

    Full Text Available Plants are the tremendous source for the discovery of new products with medicinal importance in drug development. Today several distinct chemicals derived from plants are important drugs, which are currently used in one or more countries in the world. Secondary metabolites are economically important as drugs, flavor and fragrances, dye and pigments, pesticides, and food additives. Many of the drugs sold today are simple synthetic modifications or copies of the naturally obtained substances. The evolving commercial importance of secondary metabolites has in recent years resulted in a great interest in secondary metabolism, particularly in the possibility of altering the production of bioactive plant metabolites by means of tissue culture technology. Plant cell and tissue culture technologies can be established routinely under sterile conditions from explants, such as plant leaves, stems, roots, and meristems for both the ways for multiplication and extraction of secondary metabolites. In vitro production of secondary metabolite in plant cell suspension cultures has been reported from various medicinal plants, and bioreactors are the key step for their commercial production. Based on this lime light, the present review is aimed to cover phytotherapeutic application and recent advancement for the production of some important plant pharmaceuticals.

  19. Production of Secondary Metabolites in Extreme Environments: Food- and Airborne Wallemia spp. Produce Toxic Metabolites at Hypersaline Conditions

    Science.gov (United States)

    Frisvad, Jens C.; Kocev, Dragi; Džeroski, Sašo; Gunde-Cimerman, Nina

    2016-01-01

    The food- and airborne fungal genus Wallemia comprises seven xerophilic and halophilic species: W. sebi, W. mellicola, W. canadensis, W. tropicalis, W. muriae, W. hederae and W. ichthyophaga. All listed species are adapted to low water activity and can contaminate food preserved with high amounts of salt or sugar. In relation to food safety, the effect of high salt and sugar concentrations on the production of secondary metabolites by this toxigenic fungus was investigated. The secondary metabolite profiles of 30 strains of the listed species were examined using general growth media, known to support the production of secondary metabolites, supplemented with different concentrations of NaCl, glucose and MgCl2. In more than two hundred extracts approximately one hundred different compounds were detected using high-performance liquid chromatography-diode array detection (HPLC-DAD). Although the genome data analysis of W. mellicola (previously W. sebi sensu lato) and W. ichthyophaga revealed a low number of secondary metabolites clusters, a substantial number of secondary metabolites were detected at different conditions. Machine learning analysis of the obtained dataset showed that NaCl has higher influence on the production of secondary metabolites than other tested solutes. Mass spectrometric analysis of selected extracts revealed that NaCl in the medium affects the production of some compounds with substantial biological activities (wallimidione, walleminol, walleminone, UCA 1064-A and UCA 1064-B). In particular an increase in NaCl concentration from 5% to 15% in the growth media increased the production of the toxic metabolites wallimidione, walleminol and walleminone. PMID:28036382

  20. First-Order Hybrid Logic

    DEFF Research Database (Denmark)

    Braüner, Torben

    2011-01-01

    Hybrid logic is an extension of modal logic which allows us to refer explicitly to points of the model in the syntax of formulas. It is easy to justify interest in hybrid logic on applied grounds, with the usefulness of the additional expressive power. For example, when reasoning about time one...... often wants to build up a series of assertions about what happens at a particular instant, and standard modal formalisms do not allow this. What is less obvious is that the route hybrid logic takes to overcome this problem often actually improves the behaviour of the underlying modal formalism....... For example, it becomes far simpler to formulate proof-systems for hybrid logic, and completeness results can be proved of a generality that is simply not available in modal logic. That is, hybridization is a systematic way of remedying a number of known deficiencies of modal logic. First-order hybrid logic...

  1. Hybridization in geese: a review

    OpenAIRE

    Ottenburghs, Jente; Van Hooft, Pim; van Wieren, Sipke E.; Ydenberg, Ronald C; Herbert H. T. Prins

    2016-01-01

    The high incidence of hybridization in waterfowl (ducks, geese and swans) makes this bird group an excellent study system to answer questions related to the evolution and maintenance of species boundaries. However, knowledge on waterfowl hybridization is biased towards ducks, with a large knowledge gap in geese. In this review, we assemble the available information on hybrid geese by focusing on three main themes: (1) incidence and frequency, (2) behavioural mechanisms leading to hybridizatio...

  2. Carboxymefloquine, the major metabolite of the antimalarial drug mefloquine, induces drug-metabolizing enzyme and transporter expression by activation of pregnane X receptor.

    Science.gov (United States)

    Piedade, Rita; Traub, Stefanie; Bitter, Andreas; Nüssler, Andreas K; Gil, José P; Schwab, Matthias; Burk, Oliver

    2015-01-01

    Malaria patients are frequently coinfected with HIV and mycobacteria causing tuberculosis, which increases the use of coadministered drugs and thereby enhances the risk of pharmacokinetic drug-drug interactions. Activation of the pregnane X receptor (PXR) by xenobiotics, which include many drugs, induces drug metabolism and transport, thereby resulting in possible attenuation or loss of the therapeutic responses to the drugs being coadministered. While several artemisinin-type antimalarial drugs have been shown to activate PXR, data on nonartemisinin-type antimalarials are still missing. Therefore, this study aimed to elucidate the potential of nonartemisinin antimalarial drugs and drug metabolites to activate PXR. We screened 16 clinically used antimalarial drugs and six major drug metabolites for binding to PXR using the two-hybrid PXR ligand binding domain assembly assay; this identified carboxymefloquine, the major and pharmacologically inactive metabolite of the antimalarial drug mefloquine, as a potential PXR ligand. Two-hybrid PXR-coactivator and -corepressor interaction assays and PXR-dependent promoter reporter gene assays confirmed carboxymefloquine to be a novel PXR agonist which specifically activated the human receptor. In the PXR-expressing intestinal LS174T cells and in primary human hepatocytes, carboxymefloquine induced the expression of drug-metabolizing enzymes and transporters on the mRNA and protein levels. The crucial role of PXR for the carboxymefloquine-dependent induction of gene expression was confirmed by small interfering RNA (siRNA)-mediated knockdown of the receptor. Thus, the clinical use of mefloquine may result in pharmacokinetic drug-drug interactions by means of its metabolite carboxymefloquine. Whether these in vitro findings are of in vivo relevance has to be addressed in future clinical drug-drug interaction studies.

  3. Hybrid solar lighting distribution systems and components

    Science.gov (United States)

    Muhs, Jeffrey D.; Earl, Dennis D.; Beshears, David L.; Maxey, Lonnie C.; Jordan, John K.; Lind, Randall F.

    2011-07-05

    A hybrid solar lighting distribution system and components having at least one hybrid solar concentrator, at least one fiber receiver, at least one hybrid luminaire, and a light distribution system operably connected to each hybrid solar concentrator and each hybrid luminaire. A controller operates all components.

  4. Hybrid solar lighting systems and components

    Science.gov (United States)

    Muhs, Jeffrey D.; Earl, Dennis D.; Beshears, David L.; Maxey, Lonnie C.; Jordan, John K.; Lind, Randall F.

    2007-06-12

    A hybrid solar lighting system and components having at least one hybrid solar concentrator, at least one fiber receiver, at least one hybrid luminaire, and a light distribution system operably connected to each hybrid solar concentrator and each hybrid luminaire. A controller operates each component.

  5. The governance of hybrid organisations

    DEFF Research Database (Denmark)

    Spear, Roger; Cornforth, Chris

    2010-01-01

    The focus of this chapter is on the governance of third sector organizations (TSOs) and the challenges that are raised by hybridity. In particular it will focus on the question how does hybridity affect governance structures and processes and the challenges that governing bodies face?......The focus of this chapter is on the governance of third sector organizations (TSOs) and the challenges that are raised by hybridity. In particular it will focus on the question how does hybridity affect governance structures and processes and the challenges that governing bodies face?...

  6. Emerging New Strategies for Successful Metabolite Identification in Metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Bingol, Ahmet K.; Bruschweiler-Li, Lei; Li, Dawei; Zhang, Bo; Xie, Mouzhe; Bruschweiler, Rafael

    2016-02-26

    NMR is a very powerful tool for the identification of known and unknown (or unnamed) metabolites in complex mixtures as encountered in metabolomics. Known compounds can be reliably identified using 2D NMR methods, such as 13C-1H HSQC, for which powerful web servers with databases are available for semi-automated analysis. For the identification of unknown compounds, new combinations of NMR with MS have been developed recently that make synergistic use of the mutual strengths of the two techniques. The use of chemical additives to the NMR tube, such as reactive agents, paramagnetic ions, or charged silica nanoparticles, permit the identification of metabolites with specific physical chemical properties. In the following sections, we give an overview of some of the recent advances in metabolite identification and discuss remaining challenges.

  7. Secondary metabolites and insecticidal activity of Anemone pavonina.

    Science.gov (United States)

    Varitimidis, Christos; Petrakis, Panos V; Vagias, Constantinos; Roussis, Vassilios

    2006-01-01

    The insecticidal properties of the crude extracts of the leaves and flowers of Anemone pavonina were evaluated on Pheidole pallidula ants and showed significant levels of activity. Bioassay-guided fractionations led to the isolation of the butenolide ranunculin (1) as the active principle. Chemical investigations of the extracts showed them to contain as major components the sitosterol glycopyranoside lipids 2-5 and the glycerides 6-8. The structures of the metabolites were elucidated, following acetylation and hydrolysis of the natural products, by interpretation of their NMR and mass spectral data. The uncommon lipid metabolites 2-8 were isolated for the first time from the genus Anemone and this is the first report of insecticidal activity of the Anemone metabolite ranunculin against ants.

  8. Secondary metabolites from Penicillium corylophilum isolated from damp buildings.

    Science.gov (United States)

    McMullin, David R; Nsiama, Tienabe K; Miller, J David

    2014-01-01

    Indoor exposure to the spores and mycelial fragments of fungi that grow on damp building materials can result in increased non-atopic asthma and upper respiratory disease. The mechanism appears to involve exposure to low doses of fungal metabolites. Penicillium corylophilum is surprisingly common in damp buildings in USA, Canada and western Europe. We examined isolates of P. corylophilum geographically distributed across Canada in the first comprehensive study of secondary metabolites of this fungus. The sesquiterpene phomenone, the meroterpenoids citreohybridonol and andrastin A, koninginin A, E and G, three new alpha pyrones and four new isochromans were identified from extracts of culture filtrates. This is the first report of koninginins, meroterpenoids and alpha pyrones from P. corylophilum. These secondary metabolite data support the removal of P. corylophilum from Penicillium section Citrina and suggest that further taxonomic studies are required on this species.

  9. Plants and endophytes: equal partners in secondary metabolite production?

    Science.gov (United States)

    Ludwig-Müller, Jutta

    2015-07-01

    Well known plant production systems should be re-evaluated due to findings that the interesting metabolite might actually be produced by microbes intimately associated with the plant, so-called endophytes. Endophytes can be bacteria or fungi and they are characterized usually by the feature that they do not cause any harm to the host. Indeed, in some cases, such as mycorrhizal fungi or other growth promoting endophytes, they can be beneficial for the plant. Here some examples are reviewed where the host plant and/or endophyte metabolism can be induced by the other partner. Also, partial or complete biosynthesis pathways for plant secondary metabolites can be attributed to such endophytes. In other cases the host plant is able to metabolize substances from fungal origin. The question of the natural role of such metabolic changes for the endophyte will be briefly touched. Finally, the consequences for the use of plant cultures for secondary metabolite production is discussed.

  10. Understanding Boswellia papyrifera tree secondary metabolites through bark spectral analysis

    Science.gov (United States)

    Girma, Atkilt; Skidmore, Andrew K.; de Bie, C. A. J. M.; Bongers, Frans

    2015-07-01

    Decision makers are concerned whether to tap or rest Boswellia Papyrifera trees. Tapping for the production of frankincense is known to deplete carbon reserves from the tree leading to production of less viable seeds, tree carbon starvation and ultimately tree mortality. Decision makers use traditional experience without considering the amount of metabolites stored or depleted from the stem-bark of the tree. This research was designed to come up with a non-destructive B. papyrifera tree metabolite estimation technique relevant for management using spectroscopy. The concentration of biochemicals (metabolites) found in the tree bark was estimated through spectral analysis. Initially, a random sample of 33 trees was selected, the spectra of bark measured with an Analytical Spectral Device (ASD) spectrometer. Bark samples were air dried and ground. Then, 10 g of sample was soaked in Petroleum ether to extract crude metabolites. Further chemical analysis was conducted to quantify and isolate pure metabolite compounds such as incensole acetate and boswellic acid. The crude metabolites, which relate to frankincense produce, were compared to plant properties (such as diameter and crown area) and reflectance spectra of the bark. Moreover, the extract was compared to the ASD spectra using partial least square regression technique (PLSR) and continuum removed spectral analysis. The continuum removed spectral analysis were performed, on two wavelength regions (1275-1663 and 1836-2217) identified through PLSR, using absorption features such as band depth, area, position, asymmetry and the width to characterize and find relationship with the bark extracts. The results show that tree properties such as diameter at breast height (DBH) and the crown area of untapped and healthy trees were strongly correlated to the amount of stored crude metabolites. In addition, the PLSR technique applied to the first derivative transformation of the reflectance spectrum was found to estimate the

  11. Antitumor activity of two gelsemine metabolites in rat liver microsomes.

    Science.gov (United States)

    Zhao, Qing-Chun; Hua, Wei; Zhang, Lin; Guo, Tao; Zhao, Ming-Hong; Yan, Ming; Shi, Guo-Bing; Wu, Li-Jun

    2010-09-01

    Gelsemine is one of the major alkaloids from Gelsemium elegans Benth., which has been used as an antitumor remedy in clinic. In this paper, metabolism of gelsemine has been investigated in vitro in phenobarbital-treated rat liver microsomes. The metabolites of gelsemine were separated and evaluated using the flash silica gel column, preparative HPLC, using NMR and MS methods. According to the spectral data, two metabolites, M1 and M2, were identified as 4-N-demethylgelsemine and 21-oxogelsemine, respectively. By the MTT method in vitro, the antitumor activities between gelsemine and its metabolites were compared in the HepG2 and HeLa cell lines. Moreover, the main metabolic pathway was further proposed.

  12. Metabolome analysis - mass spectrometry and microbial primary metabolites

    DEFF Research Database (Denmark)

    Højer-Pedersen, Jesper Juul

    2008-01-01

    that are highly sensitive and specific, and to undertake this challenge mass spectrometry (MS) is among the best candidates. Along with analysis of the metabolome the research area of metabolomics has evolved. Metabolomics combines metabolite profiles, data mining and biochemistry and aims at understanding...... the interplay between metabolites. In this thesis, different topics have been addressed and discussed with the aim of advancing metabolomics to explore the concept in a physiological context. The metabolome comprises a wide variety of chemical compounds that act differently upon sample preparation...... glucose, galactose or ethanol, and metabolic footprinting by mass spectrometry was used to study the influence of carbon source on the extracellular metabolites. The results showed that footprints clustered according to the carbon source. Advances in technologies for analytical chemistry have mediated...

  13. Mass spectrometry imaging of plant metabolites--principles and possibilities.

    Science.gov (United States)

    Bjarnholt, Nanna; Li, Bin; D'Alvise, Janina; Janfelt, Christian

    2014-06-01

    Covering: up to the end of 2013 New mass spectrometry imaging (MSI) techniques are gaining importance in the analysis of plant metabolite distributions, and significant technological improvements have been introduced in the past decade. This review provides an introduction to the different MSI techniques and their applications in plant science. The most common methods for sample preparation are described, and the review also features a comprehensive table of published studies in MSI of plant material. A number of significant works are highlighted for their contributions to advance the understanding of plant biology through applications of plant metabolite imaging. Particular attention is given to the possibility for imaging of surface metabolites since this is highly dependent on the methods and techniques which are applied in imaging studies.

  14. Fragmentation trees for the structural characterisation of metabolites

    Science.gov (United States)

    Kasper, Piotr T; Rojas-Chertó, Miguel; Mistrik, Robert; Reijmers, Theo; Hankemeier, Thomas; Vreeken, Rob J

    2012-01-01

    Metabolite identification plays a crucial role in the interpretation of metabolomics research results. Due to its sensitivity and widespread implementation, a favourite analytical method used in metabolomics is electrospray mass spectrometry. In this paper, we demonstrate our results in attempting to incorporate the potentials of multistage mass spectrometry into the metabolite identification routine. New software tools were developed and implemented which facilitate the analysis of multistage mass spectra and allow for efficient removal of spectral artefacts. The pre-processed fragmentation patterns are saved as fragmentation trees. Fragmentation trees are characteristic of molecular structure. We demonstrate the reproducibility and robustness of the acquisition of such trees on a model compound. The specificity of fragmentation trees allows for distinguishing structural isomers, as shown on a pair of isomeric prostaglandins. This approach to the analysis of the multistage mass spectral characterisation of compounds is an important step towards formulating a generic metabolite identification method. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22956319

  15. Cryogenic Hybrid Magnetic Bearing

    Science.gov (United States)

    Meeks, Crawford R.; Dirusso, Eliseo; Brown, Gerald V.

    1994-01-01

    Cryogenic hybrid magnetic bearing is example of class of magnetic bearings in which permanent magnets and electromagnets used to suspend shafts. Electromagnets provide active control of position of shaft. Bearing operates at temperatures from -320 degrees F (-196 degrees C) to 650 degrees F (343 degrees C); designed for possible use in rocket-engine turbopumps, where effects of cryogenic environment and fluid severely limit lubrication of conventional ball bearings. This and similar bearings also suitable for terrestrial rotating machinery; for example, gas-turbine engines, high-vacuum pumps, canned pumps, precise gimbals that suspend sensors, and pumps that handle corrosive or gritty fluids.

  16. Hybrid power semiconductor

    Science.gov (United States)

    Chen, D. Y.

    1985-10-01

    The voltage rating of a bipolar transistor may be greatly extended while at the same time reducing its switching time by operating it in conjunction with FETs in a hybrid circuit. One FET is used to drive the bipolar transistor while the other FET is connected in series with the transistor and an inductive load. Both FETs are turned on or off by a single drive signal of load power, the second FET upon ceasing conductions, rendering one power electrode of the bipolar transistor open. Means are provided to dissipate currents which flow after the bipolar transistor is rendered nonconducting.

  17. Hybrid Random Fields

    CERN Document Server

    Freno, Antonino

    2011-01-01

    This book presents an exciting new synthesis of directed and undirected, discrete and continuous graphical models. Combining elements of Bayesian networks and Markov random fields, the newly introduced hybrid random fields are an interesting approach to get the best of both these worlds, with an added promise of modularity and scalability. The authors have written an enjoyable book---rigorous in the treatment of the mathematical background, but also enlivened by interesting and original historical and philosophical perspectives. -- Manfred Jaeger, Aalborg Universitet The book not only marks an

  18. Reflections on Intellectual Hybridity

    Directory of Open Access Journals (Sweden)

    Kimala Price

    2012-05-01

    Full Text Available Drawing from the growing literature on interdisciplinarity and my own experiences as an intellectual hybrid, I discuss the personal and institutional challenges inherent in crossing disciplinary boundaries in the academy. I argue that boundary crossing is a natural occurrence and that the issue of (interdisciplinarity is a matter of degree and of determining who gets to define the boundaries. Defining boundaries is not merely an intellectual enterprise, but also a political act that delineates what is, or is not, legitimate scholarship. This issue is especially salient to women's and gender studies during times of economic distress and educational budget cuts.

  19. Hybrid Keyword Search Auctions

    OpenAIRE

    Goel, Ashish; Munagala, Kamesh

    2008-01-01

    Search auctions have become a dominant source of revenue generation on the Internet. Such auctions have typically used per-click bidding and pricing. We propose the use of hybrid auctions where an advertiser can make a per-impression as well as a per-click bid, and the auctioneer then chooses one of the two as the pricing mechanism. We assume that the advertiser and the auctioneer both have separate beliefs (called priors) on the click-probability of an advertisement. We first prove that the ...

  20. Hybrid optofluidic biosensors

    Science.gov (United States)

    Parks, Joshua W.

    Optofluidics, born of the desire to create a system containing microfluidic environments with integrated optical elements, has seen dramatic increases in popularity over the last 10 years. In particular, the application of this technology towards chip based molecular sensors has undergone significant development. The most sensitive of these biosensors interface liquid- and solid-core antiresonant reflecting optical waveguides (ARROWs). These sensor chips are created using conventional silicon microfabrication. As such, ARROW technology has previously been unable to utilize state-of-the-art microfluidic developments because the technology used--soft polydimethyl siloxane (PDMS) micromolded chips--is unamenable to the silicon microfabrication workflows implemented in the creation of ARROW detection chips. The original goal of this thesis was to employ hybrid integration, or the connection of independently designed and fabricated optofluidic and microfluidic chips, to create enhanced biosensors with the capability of processing and detecting biological samples on a single hybrid system. After successful demonstration of this paradigm, this work expanded into a new direction--direct integration of sensing and detection technologies on a new platform with dynamic, multi-dimensional photonic re-configurability. This thesis reports a number of firsts, including: • 1,000 fold optical transmission enhancement of ARROW optofluidic detection chips through thermal annealing, • Detection of single nucleic acids on a silicon-based ARROW chip, • Hybrid optofluidic integration of ARROW detection chips and passive PDMS microfluidic chips, • Hybrid optofluidic integration of ARROW detection chips and actively controllable PDMS microfluidic chips with integrated microvalves, • On-chip concentration and detection of clinical Ebola nucleic acids, • Multimode interference (MMI) waveguide based wavelength division multiplexing for detection of single influenza virions,

  1. Quantitative Method for Simultaneous Analysis of Acetaminophen and 6 Metabolites.

    Science.gov (United States)

    Lammers, Laureen A; Achterbergh, Roos; Pistorius, Marcel C M; Romijn, Johannes A; Mathôt, Ron A A

    2017-04-01

    Hepatotoxicity after ingestion of high-dose acetaminophen [N-acetyl-para-aminophenol (APAP)] is caused by the metabolites of the drug. To gain more insight into factors influencing susceptibility to APAP hepatotoxicity, quantification of APAP and metabolites is important. A few methods have been developed to simultaneously quantify APAP and its most important metabolites. However, these methods require a comprehensive sample preparation and long run times. The aim of this study was to develop and validate a simplified, but sensitive method for the simultaneous quantification of acetaminophen, the main metabolites acetaminophen glucuronide and acetaminophen sulfate, and 4 Cytochrome P450-mediated metabolites by using liquid chromatography with mass spectrometric (LC-MS) detection. The method was developed and validated for the human plasma, and it entailed a single method for sample preparation, enabling quick processing of the samples followed by an LC-MS method with a chromatographic run time of 9 minutes. The method was validated for selectivity, linearity, accuracy, imprecision, dilution integrity, recovery, process efficiency, ionization efficiency, and carryover effect. The method showed good selectivity without matrix interferences. For all analytes, the mean process efficiency was >86%, and the mean ionization efficiency was >94%. Furthermore, the accuracy was between 90.3% and 112% for all analytes, and the within- and between-run imprecision were method presented here enables the simultaneous quantification of APAP and 6 of its metabolites. It is less time consuming than previously reported methods because it requires only a single and simple method for the sample preparation followed by an LC-MS method with a short run time. Therefore, this analytical method provides a useful method for both clinical and research purposes.

  2. Potential of small-molecule fungal metabolites in antiviral chemotherapy.

    Science.gov (United States)

    Roy, Biswajit G

    2017-08-01

    Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5-10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure-activity relationship of some common and important classes of fungal metabolites.

  3. Metabolite monitoring to guide thiopurine therapy in systemic autoimmune diseases.

    Science.gov (United States)

    Chapdelaine, Aurélie; Mansour, Anne-Marie; Troyanov, Yves; Williamson, David R; Doré, Maxime

    2017-01-27

    6-Thioguanine nucleotide (6-TGN) is the active metabolite of thiopurine drugs azathioprine and 6-mercaptopurine. 6-Methylmercaptopurine (6-MMP) is an inactive and potentially hepatotoxic metabolite. A subgroup of patients (shunters) preferentially produce 6-MMP instead of 6-TGN, therefore displaying thiopurine resistance and risk for hepatotoxicity. Outside inflammatory bowel disease literature, few data exist regarding individualized thiopurine therapy based on metabolite monitoring. This study sought to describe metabolite monitoring in patients receiving weight-based thiopurine for systemic autoimmune diseases. Patients were enrolled using a laboratory database, and data were retrospectively collected. The correlation between the highest thiopurine dose (mg/kg) and the 6-TGN concentration (pmol/8 × 10(8) erythrocytes) was estimated with Pearson's correlation coefficient. Seventy-one patients with various systemic autoimmune conditions were enrolled. The correlation between the thiopurine dose and the 6-TGN level was weak for the overall patient sample (r = 0.201, p = 0.092) and for the subgroup of non-shunters (r = 0.278, p = 0.053). Subjects with 6-MMP levels >5700 pmol/8 × 10(8) erythrocytes had more hepatic cytolysis compared to subjects with 6-MMP 5700. Eleven non-shunters had hepatotoxicity, one of which had 6-MMP >5700. Thiopurine metabolite monitoring shows wide variability in 6-TGN levels among patients treated with weight-based thiopurine for systemic autoimmune diseases. Thirty-one percent of the patients in our series fulfilled the shunter definition. Thiopurine metabolite monitoring and dose adjustment to improve maintenance of remission and avoid hepatotoxicity should be studied prospectively.

  4. Thermodynamics-based Metabolite Sensitivity Analysis in metabolic networks.

    Science.gov (United States)

    Kiparissides, A; Hatzimanikatis, V

    2017-01-01

    The increasing availability of large metabolomics datasets enhances the need for computational methodologies that can organize the data in a way that can lead to the inference of meaningful relationships. Knowledge of the metabolic state of a cell and how it responds to various stimuli and extracellular conditions can offer significant insight in the regulatory functions and how to manipulate them. Constraint based methods, such as Flux Balance Analysis (FBA) and Thermodynamics-based flux analysis (TFA), are commonly used to estimate the flow of metabolites through genome-wide metabolic networks, making it possible to identify the ranges of flux values that are consistent with the studied physiological and thermodynamic conditions. However, unless key intracellular fluxes and metabolite concentrations are known, constraint-based models lead to underdetermined problem formulations. This lack of information propagates as uncertainty in the estimation of fluxes and basic reaction properties such as the determination of reaction directionalities. Therefore, knowledge of which metabolites, if measured, would contribute the most to reducing this uncertainty can significantly improve our ability to define the internal state of the cell. In the present work we combine constraint based modeling, Design of Experiments (DoE) and Global Sensitivity Analysis (GSA) into the Thermodynamics-based Metabolite Sensitivity Analysis (TMSA) method. TMSA ranks metabolites comprising a metabolic network based on their ability to constrain the gamut of possible solutions to a limited, thermodynamically consistent set of internal states. TMSA is modular and can be applied to a single reaction, a metabolic pathway or an entire metabolic network. This is, to our knowledge, the first attempt to use metabolic modeling in order to provide a significance ranking of metabolites to guide experimental measurements.

  5. Mining Bacterial Genomes for Secondary Metabolite Gene Clusters.

    Science.gov (United States)

    Adamek, Martina; Spohn, Marius; Stegmann, Evi; Ziemert, Nadine

    2017-01-01

    With the emergence of bacterial resistance against frequently used antibiotics, novel antibacterial compounds are urgently needed. Traditional bioactivity-guided drug discovery strategies involve laborious screening efforts and display high rediscovery rates. With the progress in next generation sequencing methods and the knowledge that the majority of antibiotics in clinical use are produced as secondary metabolites by bacteria, mining bacterial genomes for secondary metabolites with antimicrobial activity is a promising approach, which can guide a more time and cost-effective identification of novel compounds. However, what sounds easy to accomplish, comes with several challenges. To date, several tools for the prediction of secondary metabolite gene clusters are available, some of which are based on the detection of signature genes, while others are searching for specific patterns in gene content or regulation.Apart from the mere identification of gene clusters, several other factors such as determining cluster boundaries and assessing the novelty of the detected cluster are important. For this purpose, comparison of the predicted secondary metabolite genes with different cluster and compound databases is necessary. Furthermore, it is advisable to classify detected clusters into gene cluster families. So far, there is no standardized procedure for genome mining; however, different approaches to overcome all of these challenges exist and are addressed in this chapter. We give practical guidance on the workflow for secondary metabolite gene cluster identification, which includes the determination of gene cluster boundaries, addresses problems occurring with the use of draft genomes, and gives an outlook on the different methods for gene cluster classification. Based on comprehensible examples a protocol is set, which should enable the readers to mine their own genome data for interesting secondary metabolites.

  6. Mechanistic Modeling to Predict Midazolam Metabolite Exposure from In Vitro Data.

    Science.gov (United States)

    Nguyen, Hoa Q; Kimoto, Emi; Callegari, Ernesto; Obach, R Scott

    2016-05-01

    Methods to predict the pharmacokinetics of drugs in humans from in vitro data have been established, but corresponding methods to predict exposure to circulating metabolites are unproven. The objective of this study was to use in vitro methods combined with static and dynamic physiologically based pharmacokinetic (PBPK) models to predict metabolite exposures, using midazolam and its major metabolites as a test system. Intrinsic clearances (CLint) of formation of individual metabolites were determined using human liver microsomes. Metabolic CLintof hydroxymidazolam metabolites via oxidation and glucuronidation were also determined. Passive diffusion intrinsic clearances of hydroxymidazolam metabolites were determined using sandwich cultured human hepatocytes and the combination of this term along with the metabolic CLint, and liver blood flow was used to estimate the fraction of the metabolite that can enter the systemic circulation after formation in the liver. The metabolite/parent drug area under the plasma concentration-time curve ratio (AUCm/AUCp) was predicted using a static model relating the fraction of midazolam clearance to each metabolite, the clearance rates of midazolam and hydroxymidazolam metabolites, and the availability of the metabolites. Additionally, the human disposition of midazolam metabolites was simulated using a SimCYP PBPK model. Both approaches yielded AUCm/AUCpratios that were in agreement with the in vivo ratios. This study shows that in vivo midazolam metabolite exposure can be predicted from in vitro data and PBPK modeling. This study emphasized the importance of metabolite systemic availability from its tissue of formation, which remains a challenge to quantitative prediction.

  7. Hybrid vehicle potential assessment. Volume 7. Hybrid vehicle review

    Energy Technology Data Exchange (ETDEWEB)

    Leschly, K.O.

    1979-09-30

    Review of hybrid vehicles (HVs) built during the past ten years or planned to be built in the near future is presented. An attempt is made to classify and analyze these vehicles to get an overall picture of their key characteristics. The review includes on-road hybrid passenger cars, trucks, vans, and buses.

  8. Hybrid vehicle potential assessment. Volume 7: Hybrid vehicle review

    Science.gov (United States)

    Leschly, K. O.

    1979-01-01

    Review of hybrid vehicles built during the past ten years or planned to be built in the near future is presented. An attempt is made to classify and analyze these vehicles to get an overall picture of their key characteristics. The review includes onroad hybrid passenger cars, trucks, vans, and buses.

  9. The Hybrid Advantage: Graduate Student Perspectives of Hybrid Education Courses

    Science.gov (United States)

    Hall, Sarah; Villareal, Donna

    2015-01-01

    Hybrid courses combine online and face-to-face learning environments. To organize and teach hybrid courses, instructors must understand the uses of multiple online learning tools and face-toface classroom activities to promote and monitor the progress of students. The purpose of this phenomenological study was to explore the perspectives of…

  10. Optical Properties of Drug Metabolites in Latent Fingermarks

    CERN Document Server

    Shen, Yao

    2015-01-01

    Drug metabolites usually have structures of split-ring resonators (SRRs), which might lead to negative permittivity and permeability in electromagnetic field. As a result, in the UV-vis region, the latent fingermarks images of drug addicts and non drug users are inverse. The optical properties of latent fingermarks are quite different between drug addicts and non-drug users. This is a technic superiority for crime scene investigation to distinguish them. In this paper, we calculate the permittivity and permeability of drug metabolites using tight-binding model. The latent fingermarks of smokers and non-smokers are given as an example.

  11. [Bioactive secondary metabolites produced by plants of the genus Physalis].

    Science.gov (United States)

    Agata, Karolina; Kusiak, Joanna; Stępień, Bartłomiej; Bergier, Katarzyna; Kuźniak, Elżbieta

    2010-12-30

    Plants from the genus Physalis L. (family Solanaceae), native to warm and subtropical regions of Central and South America, are particularly rich in secondary metabolites, e.g.: withanolides, physalins, calystegines, tropane and nortropane alkaloids. Due to the high biological activities of these compounds, in the tropics Physalis plants have been used for centuries as medicinal herbs in the treatment of urinary and skin diseases, gonorrhea, ulcers, sores and as a vermicidal drug. This review describes the main categories of secondary metabolites, their distribution, chemistry, biosynthesis as well as biological activities. Particular attention is given to their potent anticancer activities.

  12. The gut microbiota, bacterial metabolites and colorectal cancer.

    Science.gov (United States)

    Louis, Petra; Hold, Georgina L; Flint, Harry J

    2014-10-01

    Accumulating evidence suggests that the human intestinal microbiota contributes to the aetiology of colorectal cancer (CRC), not only via the pro-carcinogenic activities of specific pathogens but also via the influence of the wider microbial community, particularly its metabolome. Recent data have shown that the short-chain fatty acids acetate, propionate and butyrate function in the suppression of inflammation and cancer, whereas other microbial metabolites, such as secondary bile acids, promote carcinogenesis. In this Review, we discuss the relationship between diet, microbial metabolism and CRC and argue that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.

  13. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), variance...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  14. Media and growth conditions for induction of secondary metabolite production

    DEFF Research Database (Denmark)

    Frisvad, Jens Christian

    2012-01-01

    -defined media are suited for biochemical studies, but in order to get chemical diversity expressed in filamentous fungi, sources rich in amino acids, vitamins, and trace metals have to be added, such as yeast extract and oatmeal. A battery of solid agar media is recommended for exploration of chemical diversity......Growth media and incubation conditions have a very strong influence of secondary metabolite production. There is no consensus on which media are the optimal for metabolite production, but a series of useful and effective media and incubation conditions have been listed here. Chemically well...

  15. Metabolite variability in Caribbean sponges of the genus Aplysina

    Directory of Open Access Journals (Sweden)

    Monica Puyana

    2015-12-01

    Full Text Available Abstract Sponges of the genus Aplysina are among the most common benthic animals on reefs of the Caribbean, and display a wide diversity of morphologies and colors. Tissues of these sponges lack mineralized skeletal elements, but contain a dense spongin skeleton and an elaborate series of tyrosine-derived brominated alkaloid metabolites that function as chemical defenses against predatory fishes, but do not deter some molluscs. Among the earliest marine natural products to be isolated and identified, these metabolites remain the subject of intense interest for commercial applications because of their activities in various bioassays. In this study, crude organic extracts from 253 sponges from ten morphotypes among the species Aplysina archeri,Aplysina bathyphila,Aplysina cauliformis,Aplysina fistularis,Aplysina fulva,A. insularis, and Aplysina lacunosa were analyzed by liquid chromatography–mass spectrometry (LC–MS to characterize the pattern of intra- and interspecific variabilities of the twelve major secondary metabolites present therein. Patterns across Aplysina species ranged from the presence of mostly a single compound, fistularin-3, in A. cauliformis, to a mixture of metabolites present in the other species. These patterns did not support the biotransformation hypothesis for conversion of large molecular weight molecules to smaller ones for the purpose of enhanced defense. Discriminant analyses of the metabolite data revealed strong taxonomic patterns that support a close relationship between A. fistularis,A. fulva and A. insularis, while two morphotypes of A. cauliformis (lilac creeping vs. brown erect were very distinct. Two morphotypes of A. lacunosa, one with hard tissue consistency, the other soft and thought to belong to a separate genus (Suberea, had very similar chemical profiles. Of the twelve metabolites found among samples, variation in fistularin-3, dideoxyfistularin-3 and hydroxyaerothionin provided the most predictive

  16. Sulfate Metabolites of 4-Monochlorobiphenyl in Whole Poplar Plants

    OpenAIRE

    Zhai, Guangshu; Lehmler, Hans-Joachim; Schnoor, Jerald L.

    2012-01-01

    4-Monochlorobiphenyl (PCB3) has been proven to be transformed into hydroxylated metabolites of PCB3 (OH-PCB3s) in whole poplar plants in our previous work. However, hydroxylated metabolites of PCBs, including OH-PCB3s, as the substrates of sulfotransferases have not been studied in many organisms including plants in vivo. Poplar (Populus deltoides × nigra, DN34) was used to investigate the further metabolism from OH-PCB3s to PCB3 sulfates because it is a model plant and one that is frequently...

  17. Cocaine and metabolites by LC-MS/MS.

    Science.gov (United States)

    Snozek, Christine L H; Bjergum, Matthew W; Langman, Loralie J

    2012-01-01

    Abuse of the stimulant cocaine (COC) is a common problem in the United States and elsewhere. The drug can be used either as the powder or as the free base (crack COC), and causes feelings of alertness and euphoria; both forms of COC are powerfully addictive. The assay described here is designed to detect and quantitate parent COC, its major metabolite benzoylecgonine, and a selection of metabolites that can provide specific information about sample validity (m-hydroxybenzoylecgonine), potential toxicity (norcocaine), route of administration (anhydroecgonine methyl ester), and co-utilization with ethanol (cocaethylene).

  18. Specialized metabolites from the microbiome in health and disease.

    Science.gov (United States)

    Sharon, Gil; Garg, Neha; Debelius, Justine; Knight, Rob; Dorrestein, Pieter C; Mazmanian, Sarkis K

    2014-11-01

    The microbiota, and the genes that comprise its microbiome, play key roles in human health. Host-microbe interactions affect immunity, metabolism, development, and behavior, and dysbiosis of gut bacteria contributes to disease. Despite advances in correlating changes in the microbiota with various conditions, specific mechanisms of host-microbiota signaling remain largely elusive. We discuss the synthesis of microbial metabolites, their absorption, and potential physiological effects on the host. We propose that the effects of specialized metabolites may explain present knowledge gaps in linking the gut microbiota to biological host mechanisms during initial colonization, and in health and disease.

  19. Diversity of secondary metabolites from Genus Artocarpus (Moraceae

    Directory of Open Access Journals (Sweden)

    ALIEFMAN HAKIM

    2010-11-01

    Full Text Available Hakim A. 2010. The diversity of secondary metabolites from Genus Artocarpus (Moraceae. Nusantara Bioscience 2:146-156. Several species of the Artocarpus genus (Moraceae have been investigated their natural product. The secondary metabolites successfully being isolatad from Artocarpus genus consist of terpenoid, flavonoids, stilbenoid, arylbenzofuran, neolignan, and adduct Diels-Alder. Flavonoid group represent the compound which is the most found from Artocarpus plant. The flavonoids compound which are successfully isolated from Artocarpus plant consist of the varied frameworks like chalcone, flavanone, flavan-3-ol, simple flavone, prenylflavone, oxepinoflavone, pyranoflavone, dihydrobenzoxanthone, furanodihydrobenzoxanthone, pyranodihydrobenzoxanthone, quinonoxanthone, cyclopentenoxanthone, xanthonolide, dihydroxanthone.

  20. Biomarker Research in Parkinson's Disease Using Metabolite Profiling

    DEFF Research Database (Denmark)

    Havelund, Jesper F; Heegaard, Niels H H; Færgeman, Nils J K

    2017-01-01

    Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifa......Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered...

  1. Optical properties of drug metabolites in latent fingermarks

    Science.gov (United States)

    Shen, Yao; Ai, Qing

    2016-02-01

    Drug metabolites usually have structures of split-ring resonators (SRRs), which might lead to negative permittivity and permeability in electromagnetic field. As a result, in the UV-vis region, the latent fingermarks images of drug addicts and non drug users are inverse. The optical properties of latent fingermarks are quite different between drug addicts and non-drug users. This is a technic superiority for crime scene investigation to distinguish them. In this paper, we calculate the permittivity and permeability of drug metabolites using tight-binding model. The latent fingermarks of smokers and non-smokers are given as an example.

  2. Accurate prediction of secondary metabolite gene clusters in filamentous fungi

    DEFF Research Database (Denmark)

    Andersen, Mikael Rørdam; Nielsen, Jakob Blæsbjerg; Klitgaard, Andreas

    2013-01-01

    Biosynthetic pathways of secondary metabolites from fungi are currently subject to an intense effort to elucidate the genetic basis for these compounds due to their large potential within pharmaceutics and synthetic biochemistry. The preferred method is methodical gene deletions to identify suppo...... used A. nidulans for our method development and validation due to the wealth of available biochemical data, but the method can be applied to any fungus with a sequenced and assembled genome, thus supporting further secondary metabolite pathway elucidation in the fungal kingdom....

  3. Lichen secondary metabolites as DNA-interacting agents.

    Science.gov (United States)

    Plsíkova, J; Stepankova, J; Kasparkova, J; Brabec, V; Backor, M; Kozurkova, M

    2014-03-01

    A series of lichen secondary metabolites (parietin, atranorin, usnic and gyrophoric acid) and their interactions with calf thymus DNA were investigated using molecular biophysics and biochemical methods. The binding constants K were estimated to range from 4.3×10(5) to 2.4×10(7)M(-1) and the percentage of hypochromism was found to be 16-34% (from spectral titration). The results of spectral measurement indicate that the compounds act as effective DNA-interacting agents. Electrophoretic separation studies prove that from all the metabolites tested in this study, only gyrophoric acid exhibited an inhibitory effect on Topo I (25μM).

  4. Media and growth conditions for induction of secondary metabolite production

    DEFF Research Database (Denmark)

    Frisvad, Jens Christian

    2012-01-01

    Growth media and incubation conditions have a very strong influence of secondary metabolite production. There is no consensus on which media are the optimal for metabolite production, but a series of useful and effective media and incubation conditions have been listed here. Chemically well......-defined media are suited for biochemical studies, but in order to get chemical diversity expressed in filamentous fungi, sources rich in amino acids, vitamins, and trace metals have to be added, such as yeast extract and oatmeal. A battery of solid agar media is recommended for exploration of chemical diversity...

  5. Biosynthesis of secondary metabolites in sugarcane

    Directory of Open Access Journals (Sweden)

    S.C. França

    2001-12-01

    Full Text Available A set of genes related to secondary metabolism was extracted from the sugarcane expressed sequence tag (SUCEST database and was used to investigate both the gene expression pattern of key enzymes regulating the main biosynthetic secondary metabolism pathways and the major classes of metabolites involved in the response of sugarcane to environmental and developmental cues. The SUCEST database was constructed with tissues in different physiological conditions which had been collected under varied situation of environmental stress. This database allows researchers to identify and characterize the expressed genes of a wide range of putative enzymes able to catalyze steps in the phenylpropanoid, isoprenoid and other pathways of the special metabolic mechanisms involved in the response of sugarcane to environmental changes. Our results show that sugarcane cDNAs encoded putative ultra-violet induced sesquiterpene cyclases (SC; chalcone synthase (CHS, the first enzyme in the pathway branch for flavonoid biosynthesis; isoflavone synthase (IFS, involved in plant defense and root nodulation; isoflavone reductase (IFR, a key enzyme in phenylpropanoid phytoalexin biosynthesis; and caffeic acid-O-methyltransferase, a key enzyme in the biosynthesis of lignin cell wall precursors. High levels of CHS transcripts from plantlets infected with Herbaspirillum rubri or Gluconacetobacter diazotroficans suggests that agents of biotic stress can elicit flavonoid biosynthesis in sugarcane. From this data we have predicted the profile of isoprenoid and phenylpropanoid metabolism in sugarcane and pointed the branches of secondary metabolism activated during tissue-specific stages of development and the adaptive response of sugarcane to agents of biotic and abiotic stress, although our assignment of enzyme function should be confirmed by careful biochemical and genetic supporting evidence.Este trabalho foi realizado com os objetivos de gerar uma coleção de genes

  6. Analysis of hybrid viscous damper by real time hybrid simulations

    DEFF Research Database (Denmark)

    Brodersen, Mark Laier; Ou, Ge; Høgsberg, Jan Becker

    2016-01-01

    Results from real time hybrid simulations are compared to full numerical simulations for a hybrid viscous damper, composed of a viscous dashpot in series with an active actuator and a load cell. By controlling the actuator displacement via filtered integral force feedback the damping performance...... of the hybrid viscous damper is improved, while for pure integral force feedback the damper stroke is instead increased. In the real time hybrid simulations viscous damping is emulated by a bang-bang controlled Magneto-Rheological (MR) damper. The controller activates high-frequency modes and generates drift...... in the actuator displacement, and only a fraction of the measured damper force can therefore be used as input to the investigated integral force feedback in the real time hybrid simulations....

  7. Arabidopsis hybrid speciation processes.

    Science.gov (United States)

    Schmickl, Roswitha; Koch, Marcus A

    2011-08-23

    The genus Arabidopsis provides a unique opportunity to study fundamental biological questions in plant sciences using the diploid model species Arabidopsis thaliana and Arabidopsis lyrata. However, only a few studies have focused on introgression and hybrid speciation in Arabidopsis, although polyploidy is a common phenomenon within this genus. More recently, there is growing evidence of significant gene flow between the various Arabidopsis species. So far, we know Arabidopsis suecica and Arabidopsis kamchatica as fully stabilized allopolyploid species. Both species evolved during Pleistocene glaciation and deglaciation cycles in Fennoscandinavia and the amphi-Beringian region, respectively. These hybrid studies were conducted either on a phylogeographic scale or reconstructed experimentally in the laboratory. In our study we focus at a regional and population level. Our research area is located in the foothills of the eastern Austrian Alps, where two Arabidopsis species, Arabidopsis arenosa and A. lyrata ssp. petraea, are sympatrically distributed. Our hypothesis of genetic introgression, migration, and adaptation to the changing environment during the Pleistocene has been confirmed: We observed significant, mainly unidirectional gene flow between the two species, which has given rise to the tetraploid A. lyrata. This cytotype was able to escape from the narrow ecological niche occupied by diploid A. lyrata ssp. petraea on limestone outcrops by migrating northward into siliceous areas, leaving behind a trail of genetic differentiation.

  8. Suppression subtractive hybridization.

    Science.gov (United States)

    Ghorbel, Mohamed T; Murphy, David

    2011-01-01

    Comparing two RNA populations that differ from the effects of a single independent variable, such as a drug treatment or a specific genetic defect, can establish differences in the abundance of specific transcripts that vary in a population dependent manner. There are different methods for identifying differentially expressed genes. These methods include microarray, Serial Analysis of Gene Expression (SAGE), and quantitative Reverse-Transcriptase Polymerase Chain Reaction (qRT-PCR). Herein, the protocol describes an easy and cost-effective alternative that does not require prior knowledge of the transcriptomes under examination. It is specifically relevant when low levels of RNA starting material are available. This protocol describes the use of Switching Mechanism At RNA Termini Polymerase Chain Reaction (SMART-PCR) to amplify cDNA from small amounts of RNA. The amplified cDNA populations under comparison are then subjected to Suppression Subtractive Hybridization (SSH-PCR). SSH-PCR is a technique that couples subtractive hybridization with suppression PCR to selectively amplify fragments of differentially expressed genes. The resulting products are cDNA populations enriched for significantly overrepresented transcripts in either of the two input RNAs. These cDNA populations can then be cloned to generate subtracted cDNA library. Microarrays made with clones from the subtracted forward and reverse cDNA libraries are then screened for differentially expressed genes using targets generated from tester and driver total RNAs.

  9. Landmarks in Hybrid Planning

    Directory of Open Access Journals (Sweden)

    Mohamed Elkawkagy

    2013-11-01

    Full Text Available Although planning techniques achieved a significant progress during recent years, solving many planning problem still difficult even for modern planners. In this paper, we will adopt landmark concept to hybrid planning setting - a method that combines reasoning about procedural knowledge and causalities. Land-marks are a well-known concept in the realm of classical planning. Recently, they have been adapted to hierarchical approaches. Such landmarks can be extracted in a pre-processing step from a declarative hierarchical planning domain and problem description. It was shown how this technique allows for a considerable reduction of the search space by eliminating futile plan development options before the actual planning. Therefore, we will present a new approach to in¬tegrate landmark pre-processing technique in the context of hierarchical planning with landmark technique in the classical planning. This integration allows to incorporate the ability of using extracted landmark tasks from hierarchical domain knowledge in the form of HTN and using landmark literals from classical planning. To this end, we will construct a transformation technique to transform the hybrid planning domain into a classical domain model. The method¬ologies in this paper have been implemented successfully, and we will present some experimental results that give evidence for the consid-erable performance increase gained through planning system.

  10. Overview on hybrid propulsion

    Science.gov (United States)

    Calabro, M.

    2011-10-01

    Aside of research works, this historical survey shows propulsion units used by students for small satellites and for gas generation, or those for the Space Ship One, even if LOx/HTPB was studied and tested in large motors for its potential very low cost; however, this combination highlights a series of technical problems without any performance advantage over the existing LOx/Kerosene family and never been operational for ETO applications. The particularity of hybrid propulsion is to use the state-of-the-art of both liquids and solids; the only show stopper is the propellant itself. The past work focused on LOx/HTPB (selected for its low cost) appears to be a dead-end (combustion problems and global low performances resulting from a high level of residuals). The solution that appears through the past experience is the addition of hydrides to a binder (HTPB or other) or to a binder and a homogeneous fuel or a mixture of both, with or without others additives; within these solutions some will not present any manufacturing problem and some may have a low cost. Nevertheless, the studies of the following phases have to demonstrate the compatibility of the potential regression rate range with a high-performance global design of a hybrid Motor and the manufacturing at a reasonable cost of a hydride giving a high level of performances.

  11. Hybrid Turbine Electric Vehicle

    Science.gov (United States)

    Viterna, Larry A.

    1997-01-01

    Hybrid electric power trains may revolutionize today's ground passenger vehicles by significantly improving fuel economy and decreasing emissions. The NASA Lewis Research Center is working with industry, universities, and Government to develop and demonstrate a hybrid electric vehicle. Our partners include Bowling Green State University, the Cleveland Regional Transit Authority, Lincoln Electric Motor Division, the State of Ohio's Department of Development, and Teledyne Ryan Aeronautical. The vehicle will be a heavy class urban transit bus offering double the fuel economy of today's buses and emissions that are reduced to 1/10th of the Environmental Protection Agency's standards. At the heart of the vehicle's drive train is a natural-gas-fueled engine. Initially, a small automotive engine will be tested as a baseline. This will be followed by the introduction of an advanced gas turbine developed from an aircraft jet engine. The engine turns a high-speed generator, producing electricity. Power from both the generator and an onboard energy storage system is then provided to a variable-speed electric motor attached to the rear drive axle. An intelligent power-control system determines the most efficient operation of the engine and energy storage system.

  12. Hybrid internet access

    Science.gov (United States)

    Arora, Vivek; Baras, John S.; Dillon, Douglas; Falk, Aaron; Suphasindhu, Narin

    1995-01-01

    Access to the Internet is either too slow (dial-up SLIP) or too expensive (switched 56 kbps, frame relay) for the home user or small enterprise. The Center for Satellite and Hybrid Communication Networks and Hughes Network Systems have collaborated using systems integration principles to develop a prototype of a low-cost hybrid (dial-up and satellite) newtork terminal which can deliver data from the Internet to the user at rates up to 160 kbps. An asymmetric TCP/IP connection is used breaking the network link into two physical channels: a terrestrial dial-up for carrying data from the terminal into the Internet and a receive-only satellite link carrying IP packets from the Internet to the user. With a goal of supporting bandwidth hungry Internet applications such as Mosaic, Gopher, and FTP, this system has been designed to support any Intel 80386/486 PC, any commercial TCP/IP package, any unmodified host on the Internet, and any of the routers, etc., within the Internet. The design exploits the following three observations: 1) satellites are able to offer high bandwidth connections to a large geographical area, 2) a receive-only VSAT is cheap to manufacture and easier to install than one which can also transmit, and 3) most computer users, especially those in a home environment, will want to consume much more information than they generate. IP encapsulation, or tunneling, issued to manipulate the TCP/IP protocols to route packets asymmetrically.

  13. Production of Secondary Metabolites in Extreme Environments: Food- and Airborne Wallemia spp. Produce Toxic Metabolites at Hypersaline Conditions

    DEFF Research Database (Denmark)

    Jančič, Sašo; Frisvad, Jens Christian; Kocev, Dragi

    2016-01-01

    The food- and airborne fungal genus Wallemia comprises seven xerophilic and halophilic species: W. sebi, W. mellicola, W. canadensis, W. tropicalis, W. muriae, W. hederae and W. ichthyophaga. All listed species are adapted to low water activity and can contaminate food preserved with high amounts...... of salt or sugar. In relation to food safety, the effect of high salt and sugar concentrations on the production of secondary metabolites by this toxigenic fungus was investigated. The secondary metabolite profiles of 30 strains of the listed species were examined using general growth media, known...... higher influence on the production of secondary metabolites than other tested solutes. Mass spectrometric analysis of selected extracts revealed that NaCl in the medium affects the production of some compounds with substantial biological activities (wallimidione, walleminol, walleminone, UCA 1064-A...

  14. Characterization of in vitro metabolites of methylenedioxypyrovalerone (MDPV): An N-oxide metabolite formation mediated by flavin monooxygenase.

    Science.gov (United States)

    Kim, In Sook; Rehman, Shaheed Ur; Choi, Min Sun; Jang, Moonhee; Yang, Wonkyung; Kim, Eunmi; Yoo, Hye Hyun

    2016-11-30

    Methylenedioxypyrovalerone (MDPV) has emerged in recent years as a recreational substance with psychostimulant properties. In this study, in vitro metabolites of MDPV were characterized based on liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC/QTOF MS). MDPV was incubated with human liver microsomes, human recombinant cDNA-expressed cytochrome P450 enzymes and flavin monooxygenase (FMO). MDPV was metabolized to yield eight metabolites (M1-M8) with major metabolic reactions such as demethylenation and oxidation. Among them, M6 was assigned as an N-oxide metabolite. FMO was found to be a principal enzyme responsible for the formation of M6; FMO1 and FMO3 were the main enzymes involved in N-oxidation of MDPV. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Unified Hybrid Network Theoretical Model Trilogy

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The first of the unified hybrid network theoretical model trilogy (UHNTF) is the harmonious unification hybrid preferential model (HUHPM), seen in the inner loop of Fig. 1, the unified hybrid ratio is defined.

  16. A combined genetic and multi medium approach revels new secondary metabolites in Aspergillus nidulans

    DEFF Research Database (Denmark)

    Klejnstrup, Marie Louise; Nielsen, Morten Thrane; Frisvad, Jens Christian

    Secondary metabolites are a diverse group of metabolites which serve as important natural sources of drugs for treating diseases. The availability of full genome sequences of several filamentous fungi has revealed a large genetic potential for production of secondary metabolites that are not obse......Secondary metabolites are a diverse group of metabolites which serve as important natural sources of drugs for treating diseases. The availability of full genome sequences of several filamentous fungi has revealed a large genetic potential for production of secondary metabolites...

  17. The secondary metabolite bioinformatics portal: Computational tools to facilitate synthetic biology of secondary metabolite production

    Directory of Open Access Journals (Sweden)

    Tilmann Weber

    2016-06-01

    Full Text Available Natural products are among the most important sources of lead molecules for drug discovery. With the development of affordable whole-genome sequencing technologies and other ‘omics tools, the field of natural products research is currently undergoing a shift in paradigms. While, for decades, mainly analytical and chemical methods gave access to this group of compounds, nowadays genomics-based methods offer complementary approaches to find, identify and characterize such molecules. This paradigm shift also resulted in a high demand for computational tools to assist researchers in their daily work. In this context, this review gives a summary of tools and databases that currently are available to mine, identify and characterize natural product biosynthesis pathways and their producers based on ‘omics data. A web portal called Secondary Metabolite Bioinformatics Portal (SMBP at http://www.secondarymetabolites.org is introduced to provide a one-stop catalog and links to these bioinformatics resources. In addition, an outlook is presented how the existing tools and those to be developed will influence synthetic biology approaches in the natural products field.

  18. Metabolite Profiles of Maize Leaves in Drought, Heat, and Combined Stress Field Trials Reveal the Relationship between Metabolism and Grain Yield1[OPEN

    Science.gov (United States)

    Witt, Sandra; Lisec, Jan; Palacios-Rojas, Natalia; Yousfi, Salima; Araus, Jose Luis; Fernie, Alisdair R.

    2015-01-01

    The development of abiotic stress-resistant cultivars is of premium importance for the agriculture of developing countries. Further progress in maize (Zea mays) performance under stresses is expected by combining marker-assisted breeding with metabolite markers. In order to dissect metabolic responses and to identify promising metabolite marker candidates, metabolite profiles of maize leaves were analyzed and compared with grain yield in field trials. Plants were grown under well-watered conditions (control) or exposed to drought, heat, and both stresses simultaneously. Trials were conducted in 2010 and 2011 using 10 tropical hybrids selected to exhibit diverse abiotic stress tolerance. Drought stress evoked the accumulation of many amino acids, including isoleucine, valine, threonine, and 4-aminobutanoate, which has been commonly reported in both field and greenhouse experiments in many plant species. Two photorespiratory amino acids, glycine and serine, and myoinositol also accumulated under drought. The combination of drought and heat evoked relatively few specific responses, and most of the metabolic changes were predictable from the sum of the responses to individual stresses. Statistical analysis revealed significant correlation between levels of glycine and myoinositol and grain yield under drought. Levels of myoinositol in control conditions were also related to grain yield under drought. Furthermore, multiple linear regression models very well explained the variation of grain yield via the combination of several metabolites. These results indicate the importance of photorespiration and raffinose family oligosaccharide metabolism in grain yield under drought and suggest single or multiple metabolites as potential metabolic markers for the breeding of abiotic stress-tolerant maize. PMID:26424159

  19. Metabolite Profiles of Maize Leaves in Drought, Heat, and Combined Stress Field Trials Reveal the Relationship between Metabolism and Grain Yield.

    Science.gov (United States)

    Obata, Toshihiro; Witt, Sandra; Lisec, Jan; Palacios-Rojas, Natalia; Florez-Sarasa, Igor; Yousfi, Salima; Araus, Jose Luis; Cairns, Jill E; Fernie, Alisdair R

    2015-12-01

    The development of abiotic stress-resistant cultivars is of premium importance for the agriculture of developing countries. Further progress in maize (Zea mays) performance under stresses is expected by combining marker-assisted breeding with metabolite markers. In order to dissect metabolic responses and to identify promising metabolite marker candidates, metabolite profiles of maize leaves were analyzed and compared with grain yield in field trials. Plants were grown under well-watered conditions (control) or exposed to drought, heat, and both stresses simultaneously. Trials were conducted in 2010 and 2011 using 10 tropical hybrids selected to exhibit diverse abiotic stress tolerance. Drought stress evoked the accumulation of many amino acids, including isoleucine, valine, threonine, and 4-aminobutanoate, which has been commonly reported in both field and greenhouse experiments in many plant species. Two photorespiratory amino acids, glycine and serine, and myoinositol also accumulated under drought. The combination of drought and heat evoked relatively few specific responses, and most of the metabolic changes were predictable from the sum of the responses to individual stresses. Statistical analysis revealed significant correlation between levels of glycine and myoinositol and grain yield under drought. Levels of myoinositol in control conditions were also related to grain yield under drought. Furthermore, multiple linear regression models very well explained the variation of grain yield via the combination of several metabolites. These results indicate the importance of photorespiration and raffinose family oligosaccharide metabolism in grain yield under drought and suggest single or multiple metabolites as potential metabolic markers for the breeding of abiotic stress-tolerant maize.

  20. Chaotic Dynamics in Hybrid Systems

    NARCIS (Netherlands)

    P.J. Collins (Pieter)

    2008-01-01

    htmlabstractIn this paper we give an overview of some aspects of chaotic dynamics in hybrid systems, which comprise different types of behaviour. Hybrid systems may exhibit discontinuous dependence on initial conditions leading to new dynamical phenomena. We indicate how methods from topological

  1. Chaotic dynamics in hybrid systems

    NARCIS (Netherlands)

    P.J. Collins (Pieter)

    2008-01-01

    htmlabstractIn this paper we give an overview of some aspects of chaotic dynamics in hybrid systems, which comprise different types of behaviour. Hybrid systems may exhibit discontinuous dependence on initial conditions leading to new dynamical phenomena. We indicate how methods from topological

  2. The governance of hybrid organisations

    DEFF Research Database (Denmark)

    Spear, Roger; Cornforth, Chris

    2010-01-01

    The focus of this chapter is on the governance of third sector organizations (TSOs) and the challenges that are raised by hybridity. In particular it will focus on the question how does hybridity affect governance structures and processes and the challenges that governing bodies face?...

  3. Expanding Discourse Repertoires with Hybridity

    Science.gov (United States)

    Kelly, Gregory J.

    2012-01-01

    In "Hybrid discourse practice and science learning" Kamberelis and Wehunt present a theoretically rich argument about the potential of hybrid discourses for science learning. These discourses draw from different forms of "talk, social practice, and material practices" to create interactions that are "intertextually complex" and "interactionally…

  4. Design Principles for Hybrid Ventilation

    DEFF Research Database (Denmark)

    Heiselberg, Per

    For many years mechanical and natural ventilation systems have developed separately. Naturally, the next step in this development is the development of ventilation concepts that utilize and combine the best features from each system to create a new type of ventilation system -Hybrid Ventilation....... The hybrid ventilation concepts, design challenges and - principles are discussed and illustrated by four building examples....

  5. Hybridity in Embedded Computing Systems

    Institute of Scientific and Technical Information of China (English)

    虞慧群; 孙永强

    1996-01-01

    An embedded system is a system that computer is used as a component in a larger device.In this paper,we study hybridity in embedded systems and present an interval based temporal logic to express and reason about hybrid properties of such kind of systems.

  6. Electric/Hybrid Vehicle Simulation

    Science.gov (United States)

    Slusser, R. A.; Chapman, C. P.; Brennand, J. P.

    1985-01-01

    ELVEC computer program provides vehicle designer with simulation tool for detailed studies of electric and hybrid vehicle performance and cost. ELVEC simulates performance of user-specified electric or hybrid vehicle under user specified driving schedule profile or operating schedule. ELVEC performs vehicle design and life cycle cost analysis.

  7. Hybrid Charmonium from Lattice QCD

    CERN Document Server

    Luo, X Q

    2006-01-01

    We review our recent results on the JPC = 0¡¡ exotic hybrid charmonium mass and JPC = 0¡+, 1¡¡ and 1++ nonexotic hybrid charmonium spectrum from anisotropic improved lattice QCD and discuss the relevance to the recent discovery of the Y(4260) state and future experimental search for other states.

  8. Hybrid spread spectrum radio system

    Science.gov (United States)

    Smith, Stephen F [London, TN; Dress, William B [Camas, WA

    2010-02-09

    Systems and methods are described for hybrid spread spectrum radio systems. A method, includes receiving a hybrid spread spectrum signal including: fast frequency hopping demodulating and direct sequence demodulating a direct sequence spread spectrum signal, wherein multiple frequency hops occur within a single data-bit time and each bit is represented by chip transmissions at multiple frequencies.

  9. Hybrid laser-arc welding

    DEFF Research Database (Denmark)

    Hybrid laser-arc welding (HLAW) is a combination of laser welding with arc welding that overcomes many of the shortfalls of both processes. This important book gives a comprehensive account of hybrid laser-arc welding technology and applications. The first part of the book reviews...... the characteristics of the process, including the properties of joints produced by hybrid laser-arc welding and ways of assessing weld quality. Part II discusses applications of the process to such metals as magnesium alloys, aluminium and steel as well as the use of hybrid laser-arc welding in such sectors as ship...... building and the automotive industry. With its distinguished editor and international team of contributors, Hybrid laser-arc welding, will be a valuable source of reference for all those using this important welding technology. Professor Flemming Ove Olsen works in the Department of Manufacturing...

  10. Detecting hybridization using ancient DNA.

    Science.gov (United States)

    Schaefer, Nathan K; Shapiro, Beth; Green, Richard E

    2016-06-01

    It is well established that related species hybridize and that this can have varied but significant effects on speciation and environmental adaptation. It should therefore come as no surprise that hybridization is not limited to species that are alive today. In the last several decades, advances in technologies for recovering and sequencing DNA from fossil remains have enabled the assembly of high-coverage genome sequences for a growing diversity of organisms, including many that are extinct. Thanks to the development of new statistical approaches for detecting and quantifying admixture from genomic data, genomes from extinct populations have proven useful both in revealing previously unknown hybridization events and informing the study of hybridization between living organisms. Here, we review some of the key recent statistical innovations for detecting ancient hybridization using genomewide sequence data and discuss how these innovations have revised our understanding of human evolutionary history.

  11. A Novel Fungal Metabolite with Beneficial Properties for Agricultural Applications

    Directory of Open Access Journals (Sweden)

    Francesco Vinale

    2014-07-01

    Full Text Available Trichoderma are ubiquitous soil fungi that include species widely used as biocontrol agents in agriculture. Many isolates are known to secrete several secondary metabolites with different biological activities towards plants and other microbes. Harzianic acid (HA is a T. harzianum metabolite able to promote plant growth and strongly bind iron. In this work, we isolated from the culture filtrate of a T. harzianum strain a new metabolite, named isoharzianic acid (iso-HA, a stereoisomer of HA. The structure and absolute configuration of this compound has been determined by spectroscopic methods, including UV-Vis, MS, 1D and 2D NMR analyses. In vitro applications of iso-HA inhibited the mycelium radial growth of Sclerotinia sclerotiorum and Rhizoctonia solani. Moreover, iso HA improved the germination of tomato seeds and induced disease resistance. HPLC-DAD experiments showed that the production of HA and iso HA was affected by the presence of plant tissue in the liquid medium. In particular, tomato tissue elicited the production of HA but negatively modulated the biosynthesis of its analogue iso-HA, suggesting that different forms of the same Trichoderma secondary metabolite have specific roles in the molecular mechanism regulating the Trichoderma plant interaction.

  12. Secondary metabolites from polar fractions of Piper umbellatum.

    Science.gov (United States)

    Tabopda, Turibio Kuiate; Mitaine-Offer, Anne-Claire; Miyamoto, Tomofumi; Tanaka, Chiaki; Ngadjuic, Bonaventure Tchaleu; Lacaille-Dubois, Marie-Aleth

    2012-05-01

    Seven known secondary metabolites were isolated from the methanol extract of the branches of Piper umbellatum. The identification of these compounds was mainly achieved by 2D NMR spectroscopic techniques and FAB-MS. Among them, the known cepharadiones A and B can be considered aschemotaxonomic markers of the genus Piper.

  13. Quantification of benzoxazinoids and their metabolites in Nordic breads

    DEFF Research Database (Denmark)

    Dihm, Katharina; Vendelbo Lind, Mads; Sundén, Henrik

    2017-01-01

    Benzoxazinoids (Bx) and their metabolites are molecules with suggested health effects in humans, found in cereal grains and consequently in cereal foods. However, to date little is known about the amount of Bx in our diet. In this study, deuterated standards 2-hydroxy-1,4-benzoxazin-3-one (HBOA-d...

  14. Structural elucidation of low abundant metabolites in complex sample matrices

    NARCIS (Netherlands)

    Hooft, van der J.J.J.; Vos, de R.C.H.; Ridder, L.O.; Vervoort, J.; Bino, R.J.

    2013-01-01

    Identification of metabolites is a major challenge in biological studies and relies in principle on mass spectrometry (MS) and nuclear magnetic resonance (NMR) methods. The increased sensitivity and stability of both NMR and MS systems have made dereplication of complex biological samples feasible.

  15. Oxidative metabolites of lycopene and their biological functions

    Science.gov (United States)

    To gain a better understanding of the beneficial biological activities of lycopene on cancer prevention, a greater knowledge of the metabolism of lycopene is needed. In particular, the identification of lycopene metabolites and oxidation products in vivo; the importance of tissue specific lycopene c...

  16. Association between Metabolite Profiles, Metabolic Syndrome and Obesity Status.

    Science.gov (United States)

    Allam-Ndoul, Bénédicte; Guénard, Frédéric; Garneau, Véronique; Cormier, Hubert; Barbier, Olivier; Pérusse, Louis; Vohl, Marie-Claude

    2016-05-27

    Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW) and overweight/obese (Ov/Ob) individuals, with or without metabolic syndrome (MetS). Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1's (long chain glycerophospholipids) metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C) and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C) among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine) was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3's (medium chain acylcarnitines) metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.

  17. Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

    Science.gov (United States)

    Guo, Li; Tan, Guangguo; Liu, Ping; Li, Huijie; Tang, Lulu; Huang, Lan; Ren, Qian

    2015-10-01

    High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples.

  18. Raised dopamine metabolites in a case of malignant paraganglioma.

    OpenAIRE

    Florkowski, C M; Fairlamb, D. J.; Freeth, M G; Taylor, S.A.; A. Taylor; Weinkove, C.; Jacobs, A. G.

    1990-01-01

    This paper describes the case of a malignant retroperitoneal paraganglioma with extensive metastases. The patient presented with a supraclavicular mass and an absence of hypertension. Exclusively raised dopamine metabolites were detected which may be a marker of a malignant process and account for the lack of hypertension.

  19. Simple Method for Enhanced Production of Secondary Metabolites ...

    African Journals Online (AJOL)

    iict

    2013-04-10

    Apr 10, 2013 ... media supplemented with 1-naphthalene acetic acid (NAA) (9.0 µM) and benzyl amino purine .... and secondary metabolite content was obtained in MS .... Food. 28:45-53. Vanisree M, Lee CY, Lo SH, Nalawade SM, Lin CY, ...

  20. A New Glucuronidated Metabolite of Andrographolide in Human

    Institute of Scientific and Technical Information of China (English)

    Liang CUI; Feng QIU; Nai Li WANG; Xin Sheng YAO

    2005-01-01

    A new andrographolide metabolite 1 was isolated from human urine samples after oral administration. The structure was determined to be 3-carbonylandrographolide-19-O-β-D-glucuronide on the basis of chemical evidences and spectral analysis, especially by 2D-NMR techniques.

  1. Bioactive secondary metabolites with multiple activities from a fungal endophyte

    NARCIS (Netherlands)

    Bogner, C.W.; Kamdem, R.S.; Stichtermann, G.; Matthäus, C.; Hölscher, D.; Popp, J.; Proksch, P.; Grundler, F.M.; Schouten, A.

    2017-01-01

    In order to replace particularly biohazardous nematocides, there is a strong drive to finding natural product-based alternatives with the aim of containing nematode pests in agriculture. The metabolites produced by the fungal endophyte Fusarium oxysporum 162 when cultivated on rice media were isolat

  2. Coevolution can explain defensive secondary metabolite diversity in plants.

    Science.gov (United States)

    Speed, Michael P; Fenton, Andy; Jones, Meriel G; Ruxton, Graeme D; Brockhurst, Michael A

    2015-12-01

    Many plant species produce defensive compounds that are often highly diverse within and between populations. The genetic and cellular mechanisms by which metabolite diversity is produced are increasingly understood, but the evolutionary explanations for persistent diversification in plant secondary metabolites have received less attention. Here we consider the role of plant-herbivore coevolution in the maintenance and characteristics of diversity in plant secondary metabolites. We present a simple model in which plants can evolve to invest in a range of defensive toxins, and herbivores can evolve resistance to these toxins. We allow either single-species evolution or reciprocal coevolution. Our model shows that coevolution maintains toxin diversity within populations. Furthermore, there is a fundamental coevolutionary asymmetry between plants and their herbivores, because herbivores must resist all plant toxins, whereas plants need to challenge and nullify only one resistance trait. As a consequence, average plant fitness increases and insect fitness decreases as number of toxins increases. When costs apply, the model showed both arms race escalation and strong coevolutionary fluctuation in toxin concentrations across time. We discuss the results in the context of other evolutionary explanations for secondary metabolite diversification.

  3. Intestinal health functions of colonic microbial metabolites: A review

    NARCIS (Netherlands)

    Havenaar, R.

    2011-01-01

    This review tries to find a scientific answer on the following two questions: (1) to what extent do we understand the specific role of colonic microbial metabolites, especially short-chain fatty acids (SCFA), in maintaining the health status and prevention of diseases of the colon and the host; (2)

  4. Genomic Analysis of Secondary Metabolite Production by Pseudomonas fluorescens

    Science.gov (United States)

    Pseudomonas fluorescens is a diverse bacterial species known for its ubiquity in natural habitats and its production of secondary metabolites. The high degree of ecological and metabolic diversity represented in P. fluorescens is reflected in the genomic diversity displayed among strains. Certain st...

  5. Clinical pharmacokinetics and pharmacodynamics of ifosfamide and its metabolites

    NARCIS (Netherlands)

    Kerbusch, T; de Kraker, J; Keizer, HJ; van Putten, JWG; Groen, HJM; Jansen, RLH; Schellens, JHM; Beijnen, JH

    2001-01-01

    This review discusses several issues in the clinical pharmacology of the antitumour agent ifosfamide and its metabolites. Ifosfamide is effective in a large number of malignant diseases. Its use, however, can be accompanied by haematological toxicity, neurotoxicity and nephrotoxicity. Since its deve

  6. Metabolism of Dauricine and Identification of Its Main Metabolites

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the metabolism of dauricine in vivo and in vitro and identify the structure of its main metabolites, urine of rats after drug administration as the samples of dauricine metabolism in vivo was studied. Rat liver S9 fraction was prepared and the oxygenation metabolism system reconstituted to perform phase I reaction of dauricine in vitro. TLC, HPLC-DAD and MS were used to analyze and identify dauricine and its main phase I metabolites in the samples. The results showed that besides the untransformed dauricine, in the urine samples there was little product of X' which had the same features of TLC, HPLC-DAD and MS as those of N-desmethyl dauricine (N-ddau). Part of dauricine could be transformed to a main metabolite X after incubating with S9 fraction in appropriate conditions. The molecular ion peak of X was m/z 611. The full scan MS2 spectrum of m/z 611 peak from S9 sample were m/z 580, m/z 566, m/z 552, m/z 206, which were same as those of N-ddau. Liver is the major organ for dauricine metabolism and part of dauricine is biotransformed by liver. The major metabolite is considered to be N-ddau.

  7. Metabolite profiling identifies pathways associated with metabolic risk in humans.

    Science.gov (United States)

    Cheng, Susan; Rhee, Eugene P; Larson, Martin G; Lewis, Gregory D; McCabe, Elizabeth L; Shen, Dongxiao; Palma, Melinda J; Roberts, Lee D; Dejam, Andre; Souza, Amanda L; Deik, Amy A; Magnusson, Martin; Fox, Caroline S; O'Donnell, Christopher J; Vasan, Ramachandran S; Melander, Olle; Clish, Clary B; Gerszten, Robert E; Wang, Thomas J

    2012-05-08

    Although metabolic risk factors are known to cluster in individuals who are prone to developing diabetes mellitus and cardiovascular disease, the underlying biological mechanisms remain poorly understood. To identify pathways associated with cardiometabolic risk, we used liquid chromatography/mass spectrometry to determine the plasma concentrations of 45 distinct metabolites and to examine their relation to cardiometabolic risk in the Framingham Heart Study (FHS; n=1015) and the Malmö Diet and Cancer Study (MDC; n=746). We then interrogated significant findings in experimental models of cardiovascular and metabolic disease. We observed that metabolic risk factors (obesity, insulin resistance, high blood pressure, and dyslipidemia) were associated with multiple metabolites, including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites. We observed strong associations of insulin resistance traits with glutamine (standardized regression coefficients, -0.04 to -0.22 per 1-SD change in log-glutamine; Prisk of incident diabetes mellitus in FHS (odds ratio, 0.79; adjusted P=0.03) but not in MDC. In experimental models, administration of glutamine in mice led to both increased glucose tolerance (P=0.01) and decreased blood pressure (Pprofiling identified circulating metabolites not previously associated with metabolic traits. Experimentally interrogating one of these pathways demonstrated that excess glutamine relative to glutamate, resulting from exogenous administration, is associated with reduced metabolic risk in mice.

  8. Metabolite Profiles of Male and Female Humboldt Penguins

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Levengood

    2015-10-01

    Full Text Available We examined 185 metabolites in 30 adult Humboldt Penguins (Spheniscus humboldti nesting at the Punta San Juan Marine Protected Area, Peru, in order to examine gender differences in metabolome profiles, particularly those involved in metabolism and energetics. The majority of the compounds identified were fatty (26% of total identified compounds, organic (19%, and amino (16% acids. We were able to differentiate male and female penguins with 96.6% accuracy on the basis of 12 metabolites, most of which are involved in lipid and carbohydrate metabolism. These included 2-oxoglutarate, erythronic acid, GABA, mannitol, sedoheptulose 7-phosphate, and serine and six metabolites present in higher concentrations in females compared to males (2-aminoadipic acid, O-phosphorylethanolamine, glycerol 2-phosphate, glycerol 3-phosphate, pantothenic acid, and creatinine. Of these, 2-oxoglutarate and glycerol 3-phosphate were key metabolites distinguishing gender. Our results indicated that male and female Humboldt Penguins were characterized by differing metabolic states. Such differences could be important to individual and brood survival in times of environmental stress.

  9. Chemotyping the distribution of vitamin D metabolites in human serum

    Science.gov (United States)

    Müller, Miriam J.; Stokes, Caroline S.; Lammert, Frank; Volmer, Dietrich A.

    2016-02-01

    Most studies examining the relationships between vitamin D and disease or health focus on the main 25-hydroxyvitamin D3 (25(OH)D3) metabolite, thus potentially overlooking contributions and dynamic effects of other vitamin D metabolites, the crucial roles of several of which have been previously demonstrated. The ideal assay would determine all relevant high and low-abundant vitamin D species simultaneously. We describe a sensitive quantitative assay for determining the chemotypes of vitamin D metabolites from serum after derivatisation and ultra-high performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (UHPLC-ESI-MS/MS). We performed a validation according to the ‘FDA Guidance for Industry Bioanalytical Method Validation’. The proof-of-concept of the method was then demonstrated by following the metabolite concentrations in patients with chronic liver diseases (CLD) during the course of a vitamin D supplementation study. The new quantitative profiling assay provided highly sensitive, precise and accurate chemotypes of the vitamin D metabolic process rather than the usually determined 25(OH)D3 concentrations.

  10. Monitoring microbial metabolites using an inductively coupled resonance circuit

    NARCIS (Netherlands)

    Karnaushenko, Daniil; Baraban, Larysa; Ye, Dan; Uguz, Ilke; Mendes, Rafael G.; Rümmeli, Mark H.; Visser, de Arjan; Schmidt, Oliver G.; Cuniberti, Gianaurelio; Makarov, Denys

    2015-01-01

    We present a new approach to monitor microbial population dynamics in emulsion droplets via changes in metabolite composition, using an inductively coupled LC resonance circuit. The signal measured by such resonance detector provides information on the magnetic field interaction with the bacteria

  11. Secondary Metabolites from the Marine Sponge Genus Phyllospongia

    Science.gov (United States)

    Zhang, Huawei; Dong, Menglian; Wang, Hong; Crews, Phillip

    2017-01-01

    Phyllospongia, one of the most common marine sponges in tropical and subtropical oceans, has been shown to be a prolific producer of natural products with a broad spectrum of biological activities. This review for the first time provides a comprehensive overview of secondary metabolites produced by Phyllospongia spp. over the 37 years from 1980 to 2016. PMID:28067826

  12. Characterization of an Nmr homolog that modulates GATA factor-mediated nitrogen metabolite repression in Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    I Russel Lee

    Full Text Available Nitrogen source utilization plays a critical role in fungal development, secondary metabolite production and pathogenesis. In both the Ascomycota and Basidiomycota, GATA transcription factors globally activate the expression of catabolic enzyme-encoding genes required to degrade complex nitrogenous compounds. However, in the presence of preferred nitrogen sources such as ammonium, GATA factor activity is inhibited in some species through interaction with co-repressor Nmr proteins. This regulatory phenomenon, nitrogen metabolite repression, enables preferential utilization of readily assimilated nitrogen sources. In the basidiomycete pathogen Cryptococcus neoformans, the GATA factor Gat1/Are1 has been co-opted into regulating multiple key virulence traits in addition to nitrogen catabolism. Here, we further characterize Gat1/Are1 function and investigate the regulatory role of the predicted Nmr homolog Tar1. While GAT1/ARE1 expression is induced during nitrogen limitation, TAR1 transcription is unaffected by nitrogen availability. Deletion of TAR1 leads to inappropriate derepression of non-preferred nitrogen catabolic pathways in the simultaneous presence of favoured sources. In addition to exhibiting its evolutionary conserved role of inhibiting GATA factor activity under repressing conditions, Tar1 also positively regulates GAT1/ARE1 transcription under non-repressing conditions. The molecular mechanism by which Tar1 modulates nitrogen metabolite repression, however, remains open to speculation. Interaction between Tar1 and Gat1/Are1 was undetectable in a yeast two-hybrid assay, consistent with Tar1 and Gat1/Are1 each lacking the conserved C-terminus regions present in ascomycete Nmr proteins and GATA factors that are known to interact with each other. Importantly, both Tar1 and Gat1/Are1 are suppressors of C. neoformans virulence, reiterating and highlighting the paradigm of nitrogen regulation of pathogenesis.

  13. Importance of mycorrhization helper bacteria cell density and metabolite localization for the Pinus sylvestris-Lactarius rufus symbiosis.

    Science.gov (United States)

    Aspray, Thomas J; Eirian Jones, E; Whipps, John M; Bending, Gary D

    2006-04-01

    Mycorrhization helper bacteria, Paenibacillus sp. EJP73 and Burkholderia sp. EJP67, were used to study the importance of bacterial inoculum dose and bacterial derived soluble and volatile metabolites localization for enhancing mycorrhiza formation in the Pinus sylvestris-Lactarius rufus symbiosis, using a laboratory based microcosm. EJP73 and EJP67 produced different responses in relation to the inoculum dose; EJP73 significantly enhanced mycorrhiza formation to the same degree at all doses tested (10(5), 10(7), 10(9) and 10(10) CFU mL(-1)), whereas, EJP67 only stimulated mycorrhiza formation within a narrow range of inoculum densities (10(7) and 10(9) CFU mL(-1)). The importance of soluble bacterial metabolites was assessed by applying spent broth derived from exponential and stationary phase bacterial cultures to microcosms. No spent broth enhanced mycorrhiza formation over the control. As EJP73 produced the helper effect over a wide range of inoculum doses, this bacterium was chosen for further study. Physical separation of EJP73 from the fungal and plant symbiosis partners was carried out, in order to determine the contribution of constitutively produced bacterial volatile metabolites to the mycorrhization helper bacteria effect. When EJP73 was physically separated from the symbiosis, it had a significant negative effect on mycorrhiza formation. These results suggest that close proximity, or indeed cell contact, is required for the helper effect. Therefore, fluorescent in situ hybridization in conjunction with cryosectioning was used to determine the localization of EJP73 in mycorrhizal tissue. The cells were found to occur as rows or clusters ( approximately 10 cells) within the mycorrhizal mantle, both at the root tip and along the length of the mycorrhizal short roots.

  14. Molecular evidence for hybridization in Colias (Lepidoptera: Pieridae): are Colias hybrids really hybrids?

    Science.gov (United States)

    Dwyer, Heather E; Jasieniuk, Marie; Okada, Miki; Shapiro, Arthur M

    2015-01-01

    Gene flow and hybridization among species dramatically affect our understanding of the species as a biological unit, species relationships, and species adaptations. In North American Colias eurytheme and Colias eriphyle, there has been historical debate over the extent of hybridization occurring and the identity of phenotypically intermediate individuals as genetic hybrids. This study assesses the population structure of these two species to measure the extent of hybridization and the genetic identity of phenotypic intermediates as hybrids. Amplified fragment length polymorphism (AFLP) marker analysis was performed on 378 specimens collected from northern California and Nevada. Population structure was inferred using a Bayesian/Markov chain Monte Carlo method, which probabilistically assigns individuals to genetic clusters. Three genetic clusters provided the best fit for the data. C. eurytheme individuals were primarily assigned to two closely related clusters, and C. eriphyle individuals were mostly assigned to a third, more distantly related cluster. There appeared to be significant hybridization between the two species. Individuals of intermediate phenotype (putative hybrids) were found to be genetically indistinguishable from C. eriphyle, indicating that previous work based on the assumption that these intermediate forms are hybrids may warrant reconsideration. PMID:26306172

  15. Hybrid Natural Inflation

    Science.gov (United States)

    Ross, Graham G.; Germán, Gabriel; Vázquez, J. Alberto

    2016-05-01

    We construct two simple effective field theory versions of Hybrid Natural Inflation (HNI) that illustrate the range of its phenomenological implications. The resulting inflationary sector potential, V = Δ4(1 + acos( ϕ/f)), arises naturally, with the inflaton field a pseudo-Nambu-Goldstone boson. The end of inflation is triggered by a waterfall field and the conditions for this to happen are determined. Also of interest is the fact that the slow-roll parameter ɛ (and hence the tensor r) is a non-monotonic function of the field with a maximum where observables take universal values that determines the maximum possible tensor to scalar ratio r. In one of the models the inflationary scale can be as low as the electroweak scale. We explore in detail the associated HNI phenomenology, taking account of the constraints from Black Hole production, and perform a detailed fit to the Planck 2015 temperature and polarisation data.

  16. Auditing Hybrid IT Environments

    Directory of Open Access Journals (Sweden)

    Georgiana Mateescu

    2014-01-01

    Full Text Available This paper presents a personal approach of auditing the hybrid IT environments consisting in both on premise and on demand services and systems. The analysis is performed from both safety and profitability perspectives and it aims to offer to strategy, technical and business teams a representation of the value added by the cloud programme within the company’s portfolio. Starting from the importance of the IT Governance in the actual business environments, we presented in the first section the main principles that drive the technology strategy in order to maximize the value added by IT assets in the business products. Section two summarizes the frameworks leveraged by our approach in order to implement the safety and profitability computation algorithms described in the third section. The paper concludes with benefits of our personal frameworks and presents the future developments.

  17. Hybrid Noncoherent Network Coding

    CERN Document Server

    Skachek, Vitaly; Nedic, Angelia

    2011-01-01

    We describe a novel extension of subspace codes for noncoherent networks, suitable for use when the network is viewed as a communication system that introduces both dimension and symbol errors. We show that when symbol erasures occur in a significantly large number of different basis vectors transmitted through the network and when the min-cut of the networks is much smaller then the length of the transmitted codewords, the new family of codes outperforms their subspace code counterparts. For the proposed coding scheme, termed hybrid network coding, we derive two upper bounds on the size of the codes. These bounds represent a variation of the Singleton and of the sphere-packing bound. We show that a simple concatenated scheme that represents a combination of subspace codes and Reed-Solomon codes is asymptotically optimal with respect to the Singleton bound. Finally, we describe two efficient decoding algorithms for concatenated subspace codes that in certain cases have smaller complexity than subspace decoder...

  18. Nanoporous hybrid electrolytes

    KAUST Repository

    Schaefer, Jennifer L.

    2011-01-01

    Oligomer-suspended SiO2-polyethylene glycol nanoparticles are studied as porous media electrolytes. At SiO2 volume fractions, , bracketing a critical value y ≈ 0.29, the suspensions jam and their mechanical modulus increase by more than seven orders. For >y, the mean pore diameter is close to the anion size, yet the ionic conductivity remains surprisingly high and can be understood, at all , using a simple effective medium model proposed by Maxwell. SiO 2-polyethylene glycol hybrid electrolytes are also reported to manifest attractive electrochemical stability windows (0.3-6.3 V) and to reach a steady-state interfacial impedance when in contact with metallic lithium. © 2010 The Royal Society of Chemistry.

  19. Hybrid vehicle control

    Energy Technology Data Exchange (ETDEWEB)

    Shallvari, Iva; Velnati, Sashidhar; DeGroot, Kenneth P.

    2015-07-28

    A method and apparatus for heating a catalytic converter's catalyst to an efficient operating temperature in a hybrid electric vehicle when the vehicle is in a charge limited mode such as e.g., the charge depleting mode or when the vehicle's high voltage battery is otherwise charge limited. The method and apparatus determine whether a high voltage battery of the vehicle is incapable of accepting a first amount of charge associated with a first procedure to warm-up the catalyst. If it is determined that the high voltage battery is incapable of accepting the first amount of charge, a second procedure with an acceptable amount of charge is performed to warm-up the catalyst.

  20. Hybrid vehicle control

    Science.gov (United States)

    Shallvari, Iva; Velnati, Sashidhar; DeGroot, Kenneth P.

    2015-07-28

    A method and apparatus for heating a catalytic converter's catalyst to an efficient operating temperature in a hybrid electric vehicle when the vehicle is in a charge limited mode such as e.g., the charge depleting mode or when the vehicle's high voltage battery is otherwise charge limited. The method and apparatus determine whether a high voltage battery of the vehicle is incapable of accepting a first amount of charge associated with a first procedure to warm-up the catalyst. If it is determined that the high voltage battery is incapable of accepting the first amount of charge, a second procedure with an acceptable amount of charge is performed to warm-up the catalyst.

  1. Hybrid Batch Bayesian Optimization

    CERN Document Server

    Azimi, Javad; Fern, Xiaoli

    2012-01-01

    Bayesian Optimization aims at optimizing an unknown non-convex/concave function that is costly to evaluate. We are interested in application scenarios where concurrent function evaluations are possible. Under such a setting, BO could choose to either sequentially evaluate the function, one input at a time and wait for the output of the function before making the next selection, or evaluate the function at a batch of multiple inputs at once. These two different settings are commonly referred to as the sequential and batch settings of Bayesian Optimization. In general, the sequential setting leads to better optimization performance as each function evaluation is selected with more information, whereas the batch setting has an advantage in terms of the total experimental time (the number of iterations). In this work, our goal is to combine the strength of both settings. Specifically, we systematically analyze Bayesian optimization using Gaussian process as the posterior estimator and provide a hybrid algorithm t...

  2. Photochromic mesoporous hybrid coatings

    Science.gov (United States)

    Raboin, L.; Matheron, M.; Gacoin, T.; Boilot, J.-P.

    2008-09-01

    Spirooxazine (SO) photochromic molecules were trapped in sol-gel matrices. In order to increase the colourability and improve mechanical properties of sol-gel photochromic films, we present an original strategy in which SO photochromic molecules were dispersed in mesoporous organized films using the impregnation technique. Well-ordered organosilicate mesoporous coatings with the 3D-hexagonal symmetry were prepared by the sol-gel technique. These robust mesoporous films, which contain high amounts of hydrophobic methyl groups at the pore surface, offer optimized environments for photochromic dyes dispersed by impregnation technique. After impregnation by a spirooxazine solution, the photochromic response is only slightly slower when compared with mesostructured or soft sol-gel matrices, showing that mesoporous organized hybrid matrix are good host for photochromic dyes. Moreover, the molecular loading in films is easily adjustable in a large range using multi-impregnation procedure and increasing the film thickness leading to coatings for optical switching devices.

  3. Hybrid Heat Exchangers

    Science.gov (United States)

    Tu, Jianping Gene; Shih, Wei

    2010-01-01

    A hybrid light-weight heat exchanger concept has been developed that uses high-conductivity carbon-carbon (C-C) composites as the heat-transfer fins and uses conventional high-temperature metals, such as Inconel, nickel, and titanium as the parting sheets to meet leakage and structural requirements. In order to maximize thermal conductivity, the majority of carbon fiber is aligned in the fin direction resulting in 300 W/m.K or higher conductivity in the fin directions. As a result of this fiber orientation, the coefficient of thermal expansion (CTE) of the C-C composite in both non-fiber directions matches well with the CTE of various high-temperature metal alloys. This allows the joining of fins and parting sheets by using high-temperature braze alloys.

  4. Bioactive metabolite production by Streptomyces albolongus in favourable environment

    Directory of Open Access Journals (Sweden)

    Myn Uddin

    2013-06-01

    Full Text Available Objectives: Demand for new antibiotic is rising up due to continuous resistance risk against conventional antibiotic.This attempt was taken to find out a novel antimicrobial metabolite.Methods: Chili field antagonistic actinomycetes Streptomyces albolongus was isolated and tested for optimum antimicrobialmetabolite production. Primary screening was done by selective media and antibiotic assay was done by agarcup plate method. Fermented product was recovered by separating funnel using suitable solvent.Results: Maximum antimicrobial metabolite production was found at temperature 35°C and pH 9.0 and on 6th day ofincubation. The medium consisting of corn steep liquor (0.2%, glucose (1.0%, NaCl (0.5%, K2HPO4 (0.1% was screenedout as suitable medium for maximum antimicrobial production. Sucrose was found as the best carbon source amongfour sources. The antimicrobial metabolite was found to be stable at pH and temperature up to 11.0 and 100°C respectively.The active agent was best extracted with chloroform. The antimicrobial spectrum of the metabolite was wideand shows activity against Shigella dysenteriae (AE14612, Shigella sonnei (CRL, ICDDR, B, Salmonella typhi (AE14296,Vibrio cholerae (AE14748, Pseudomonas aeruginosa (CRL, ICDDR, B, Bacillus cereus (BTCC19, Staphylococcus aureus(ATCC6538, Bacillus subtilis (BTTC17 and Bacillus megaterium (BTTC18.Conclusions: The findings of antibacterial activity of S. albolongus against several species of human pathogens includingboth Gram-positive and Gram-negative bacteria indicated that our produced material might be an alternative antimicrobialsubstance to control human diseases. J Microbiol Infect Dis 2013; 3(2: 75-82Key words: Streptomyces albolongus, antimicrobial metabolite, optimum production, antimicrobial spectrum

  5. A breath fungal secondary metabolite signature to diagnose invasive aspergillosis.

    Science.gov (United States)

    Koo, Sophia; Thomas, Horatio R; Daniels, S David; Lynch, Robert C; Fortier, Sean M; Shea, Margaret M; Rearden, Preshious; Comolli, James C; Baden, Lindsey R; Marty, Francisco M

    2014-12-15

    Invasive aspergillosis (IA) remains a leading cause of mortality in immunocompromised patients, in part due to the difficulty of diagnosing this infection. Using thermal desorption-gas chromatography/mass spectrometry, we characterized the in vitro volatile metabolite profile of Aspergillus fumigatus, the most common cause of IA, and other pathogenic aspergilli. We prospectively collected breath samples from patients with suspected invasive fungal pneumonia from 2011 to 2013, and assessed whether we could discriminate patients with proven or probable IA from patients without aspergillosis, as determined by European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions, by direct detection of fungal volatile metabolites in these breath samples. The monoterpenes camphene, α- and β-pinene, and limonene, and the sesquiterpene compounds α- and β-trans-bergamotene were distinctive volatile metabolites of A. fumigatus in vitro, distinguishing it from other pathogenic aspergilli. Of 64 patients with suspected invasive fungal pneumonia based on host risk factors, clinical symptoms, and radiologic findings, 34 were diagnosed with IA, whereas 30 were ultimately diagnosed with other causes of pneumonia, including other invasive mycoses. Detection of α-trans-bergamotene, β-trans-bergamotene, a β-vatirenene-like sesquiterpene, or trans-geranylacetone identified IA patients with 94% sensitivity (95% confidence interval [CI], 81%-98%) and 93% specificity (95% CI, 79%-98%). In patients with suspected fungal pneumonia, an Aspergillus secondary metabolite signature in breath can identify individuals with IA. These results provide proof-of-concept that direct detection of exogenous fungal metabolites in breath can be used as a novel, noninvasive, pathogen-specific approach to identifying the precise microbial cause of pneumonia. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America

  6. From hybrid-media system to hybrid-media politicians

    DEFF Research Database (Denmark)

    Eberholst, Mads Kæmsgaard; Ørsten, Mark; Burkal, Rasmus

    2017-01-01

    An increasingly complex hybrid system of social- and traditional-news media surrounds Nordic election campaigns as politically experienced incumbents favour traditional news media, and younger, lesser-known candidates’ social media. Despite little evidence for hybrid-media politicians, politicians......’ media use is changing rapidly; 15%–16% of Danish candidates used Twitter in 2011 but 68% in 2015. In this large-sample content analysis, party leaders have high traditional-news-media and low Twitter presence, and younger candidates visa-versa, but some politicians have high presence in both. Hybrid...

  7. Profiling and Distribution of Metabolites of Procyanidin B2 in Mice by UPLC-DAD-ESI-IT-TOF-MSn Technique

    Directory of Open Access Journals (Sweden)

    Ying Xiao

    2017-05-01

    Full Text Available The metabolite profiles and distributions of procyanidin B2 were qualitatively described using UPLC-DAD-ESI-IT-TOF-MSn without help of reference standards, and a possible metabolic pathway was proposed in the present study. Summarily, 53 metabolites (24 new metabolites were detected as metabolites of procyanidin B2, and 45 of them were tentatively identified. Twenty seven metabolites were assigned as similar metabolites of (−-epicatechin by scission of the flavanol interflavanic bond C4–C8, including 16 aromatic metabolites, 5 conjugated metabolites, 3 ring-cleavage metabolites, and 2 phenylvalerolactone metabolites. Additionally, 14 metabolites were conjugates of free procyanidin B2, comprising 9 methylation metabolites, 8 sulfation metabolites, 5 hydration metabolites, 2 hydroxylation metabolites, 1 hydrogenation metabolites, and 1 glucuronidation metabolites. The results of metabolite distributions in organs indicated that the conjugated reaction of free procyanidin B2 mainly occurred in liver and diversified metabolites forms were observed in small intestine. The metabolic components of procyanidin B2 identified in mice provided useful information for further study of the bioactivity and mechanism of its action.

  8. Hybrid Filter Membrane

    Science.gov (United States)

    Laicer, Castro; Rasimick, Brian; Green, Zachary

    2012-01-01

    Cabin environmental control is an important issue for a successful Moon mission. Due to the unique environment of the Moon, lunar dust control is one of the main problems that significantly diminishes the air quality inside spacecraft cabins. Therefore, this innovation was motivated by NASA s need to minimize the negative health impact that air-suspended lunar dust particles have on astronauts in spacecraft cabins. It is based on fabrication of a hybrid filter comprising nanofiber nonwoven layers coated on porous polymer membranes with uniform cylindrical pores. This design results in a high-efficiency gas particulate filter with low pressure drop and the ability to be easily regenerated to restore filtration performance. A hybrid filter was developed consisting of a porous membrane with uniform, micron-sized, cylindrical pore channels coated with a thin nanofiber layer. Compared to conventional filter media such as a high-efficiency particulate air (HEPA) filter, this filter is designed to provide high particle efficiency, low pressure drop, and the ability to be regenerated. These membranes have well-defined micron-sized pores and can be used independently as air filters with discreet particle size cut-off, or coated with nanofiber layers for filtration of ultrafine nanoscale particles. The filter consists of a thin design intended to facilitate filter regeneration by localized air pulsing. The two main features of this invention are the concept of combining a micro-engineered straight-pore membrane with nanofibers. The micro-engineered straight pore membrane can be prepared with extremely high precision. Because the resulting membrane pores are straight and not tortuous like those found in conventional filters, the pressure drop across the filter is significantly reduced. The nanofiber layer is applied as a very thin coating to enhance filtration efficiency for fine nanoscale particles. Additionally, the thin nanofiber coating is designed to promote capture of

  9. Magnetic graphene oxide as adsorbent for the determination of polycyclic aromatic hydrocarbon metabolites in human urine.

    Science.gov (United States)

    Zhu, Linli; Xu, Hui

    2014-09-01

    Detection of monohydroxy polycyclic aromatic hydrocarbons metabolites in urine is an advisable and valid method to assess human environmental exposure to polycyclic aromatic hydrocarbons. In this work, novel Fe3O4/graphene oxide composites were prepared and their application in the magnetic solid-phase extraction of monohydroxy polycyclic aromatic hydrocarbons in urine was investigated by coupling with liquid chromatography and mass spectrometry. In the hybrid material, superparamagnetic Fe3O4 nanoparticles provide fast separation to simplify the analytical process and graphene oxide provides a large functional surface for the adsorption. The prepared magnetic nanocomposites were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and vibrating sample magnetometry. The experimental conditions were optimized systematically. Under the optimal conditions, the recoveries of these compounds were in the range of 98.3-125.2%, the relative standard deviations ranged between 6.8 and 15.5%, and the limits of detection were in the range of 0.01-0.15 ng/mL. The simple, quick, and affordable method was successfully used in the analysis of human urinary monohydroxy polycyclic aromatic hydrocarbons in two different cities. The results indicated that the monohydroxy polycyclic aromatic hydrocarbons level in human urine can provide useful information for environmental exposure to polycyclic aromatic hydrocarbons.

  10. Genes Linked to Production of Secondary Metabolites in Talaromyces atroroseus Revealed Using CRISPR-Cas9

    Science.gov (United States)

    Nielsen, Maria Lund; Isbrandt, Thomas; Rasmussen, Kasper Bøwig; Thrane, Ulf; Hoof, Jakob Blæsbjerg; Larsen, Thomas Ostenfeld; Mortensen, Uffe Hasbro

    2017-01-01

    The full potential of fungal secondary metabolism has until recently been impeded by the lack of universal genetic tools for most species. However, the emergence of several CRISPR-Cas9-based genome editing systems adapted for several genera of filamentous fungi have now opened the doors for future efforts in discovery of novel natural products and elucidation and engineering of their biosynthetic pathways in fungi where no genetic tools are in place. So far, most studies have focused on demonstrating the performance of CRISPR-Cas9 in various fungal model species, and recently we presented a versatile CRISPR-Cas9 system that can be successfully applied in several diverse Aspergillus species. Here we take it one step further and show that our system can be used also in a phylogenetically distinct and largely unexplored species from the genus of Talaromyces. Specifically, we exploit CRISPR-Cas9-based genome editing to identify a new gene in T. atroroseus responsible for production of polyketide-nonribosomal peptide hybrid products, hence, linking fungal secondary metabolites to their genetic origin in a species where no genetic engineering has previously been performed. PMID:28056079

  11. Genes Linked to Production of Secondary Metabolites in Talaromyces atroroseus Revealed Using CRISPR-Cas9.

    Science.gov (United States)

    Nielsen, Maria Lund; Isbrandt, Thomas; Rasmussen, Kasper Bøwig; Thrane, Ulf; Hoof, Jakob Blæsbjerg; Larsen, Thomas Ostenfeld; Mortensen, Uffe Hasbro

    2017-01-01

    The full potential of fungal secondary metabolism has until recently been impeded by the lack of universal genetic tools for most species. However, the emergence of several CRISPR-Cas9-based genome editing systems adapted for several genera of filamentous fungi have now opened the doors for future efforts in discovery of novel natural products and elucidation and engineering of their biosynthetic pathways in fungi where no genetic tools are in place. So far, most studies have focused on demonstrating the performance of CRISPR-Cas9 in various fungal model species, and recently we presented a versatile CRISPR-Cas9 system that can be successfully applied in several diverse Aspergillus species. Here we take it one step further and show that our system can be used also in a phylogenetically distinct and largely unexplored species from the genus of Talaromyces. Specifically, we exploit CRISPR-Cas9-based genome editing to identify a new gene in T. atroroseus responsible for production of polyketide-nonribosomal peptide hybrid products, hence, linking fungal secondary metabolites to their genetic origin in a species where no genetic engineering has previously been performed.

  12. Electrosynthesis methods and approaches for the preparative production of metabolites from parent drugs

    NARCIS (Netherlands)

    Gül, Turan; Bischoff, Rainer; Permentier, Hjalmar

    2015-01-01

    Identification of potentially toxic metabolites is important for drug discovery and development. Synthesis of drug metabolites is typically performed by organic synthesis or enzymatic methods, but is not always straightforward. Electrochemical (EC) methods are increasingly used to study drug oxidati

  13. Polar metabolites of polycyclic aromatic compounds from fungi are potential soil and groundwater contaminants

    DEFF Research Database (Denmark)

    Boll, Esther Sørensen; Johnsen, Anders R.; Christensen, Jan H.

    2015-01-01

    and either hydroxylated or oxidized to carboxylic acids at the methyl group. The metabolism of the sulfur-containing heterocyclic PAC resulted in sulfate conjugates. The sorption of the PAC metabolites to three soils was determined using a batch equilibrium method, and partition coefficients (Kd's) were......-methylphenanthrene, 1-methylpyrene), and one sulfur-containing heterocyclic PAC (dibenzothiophene). Fifty-eight metabolites were tentatively identified; metabolites from the un-substituted PACs were hydroxylated and sulfate conjugated, whereas metabolites from alkyl-substituted PACs were sulfate conjugated...... calculated for fourteen representative metabolites. Sulfate conjugated metabolites displayed Kd's below 70 whereas the metabolites with both a sulfate and a carboxylic acid group had Kd's below 2.8. The low Kd's of water-soluble PAC metabolites indicate high mobility in soil and a potential for leaching...

  14. Microsomal metabolism of trenbolone acetate metabolites: Transformation product formation and bioactivity.

    Science.gov (United States)

    Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbo...

  15. Secondary metabolite profiling of Alternaria dauci, A. porri, A. solani, and A. tomatophila

    DEFF Research Database (Denmark)

    Andersen, Birgitte; Dongo, Anita; Pryor, Barry M.

    2008-01-01

    Chemotaxonomy (secondary metabolite profiling) has been shown to be of great value in the classification and differentiation in Ascomycota. However, few studies have investigated the use of metabolite production for classification and identification purposes of plant pathogenic Alternaria species...

  16. Andrastin A and barceloneic acid metabolites, protein farnesyl transferase inhibitors from Penicillium alborcoremium: chemotaxonomic significance and pathological implications

    DEFF Research Database (Denmark)

    Overy, David Patrick; Larsen, Thomas Ostenfeld; Dalsgaard, P.W.

    2005-01-01

    A survey of Penicillium albocoremium was undertaken to identify potential taxonomic metabolite markers. One major and four minor metabolites were consistently produced by the 19 strains surveyed on three different media. Following purification and spectral studies, the metabolites were identified...

  17. Proanthocyanidin metabolites associated with dietary fibre from in vitro colonic fermentation and proanthocyanidin metabolites in human plasma.

    Science.gov (United States)

    Saura-Calixto, Fulgencio; Pérez-Jiménez, Jara; Touriño, Sonia; Serrano, José; Fuguet, Elisabet; Torres, Josep Lluis; Goñi, Isabel

    2010-07-01

    Proanthocyanidins (PAs) or condensed tannins, a major group of dietary polyphenols, are oligomers and polymers of flavan-3-ol and flavan-3, 4-diols widely distributed in plant foods. Most literature data on PAs' metabolic fate deal with PAs that can be extracted from the food matrix by aqueous-organic solvents ( extractable proanthocyanidins). However, there are no data on colonic fermentation of non-extractable proanthocyanidins (NEPAs), which arrive almost intact to the colon, mostly associated to dietary fibre (DF). The aim of the present work was to examine colonic fermentation of NEPAs associated with DF, using a model of in vitro small intestine digestion and colonic fermentation. Two NEPA-rich materials obtained from carob pod (Ceratonia siliqua L. proanthocyanidin) and red grapes (grape antioxidant dietary fibre) were used as test samples. The colonic fermentation of these two products released hydroxyphenylacetic acid, hydroxyphenylvaleric acid and two isomers of hydroxyphenylpropionic acid, detected by HPLC-ESI-MS/MS. Differences between the two products indicate that DF may enhance the yield of metabolites. In addition, the main NEPA metabolite in human plasma was 3,4-dihydroxyphenyl acetic acid. The presence in human plasma of the same metabolites as were detected after in vitro colonic fermentation of NEPAs suggests that dietary NEPAs would undergo colonic fermentation releasing absorbable metabolites with potential healthy effects.

  18. Metabolomics and bioanalysis of terpenoid derived secondary metabolites : Analysis of Cannabis sativa L. metabolite production and prenylases for cannabinoid production

    NARCIS (Netherlands)

    Muntendam, Remco

    2015-01-01

    Cannabinoid research has gained a renenewed interest by both the public and scientist. Focus is mainly directed to the medicinal activities, as reported for various cannabinoid structures. This thesis focusses on prenyl-derived secondary metabolites with main focus on cannabinoids. Firstly the produ

  19. Wankel engine for hybrid powertrain

    Energy Technology Data Exchange (ETDEWEB)

    Butti, A. [Univ. of Florence (Italy); Site, V.D.

    1995-12-31

    The Wankel engine is suited to be used to drive hybrid propulsion systems. The main disadvantage of hybrid propulsion systems is the complexity that causes a high weight and large dimensions. For these reason hybrid systems are more suitable for large size vehicle (buses, vans) rather than for small passenger cars. A considerable reduction of hybrid systems weight and dimensions can be obtained using a Wankel rotary engine instead of a conventional engine. The Wankel engine is light, compact, simple, and produces low noise and low vibrations. Therefore a Wankel engine powered hybrid system is suited to be used on small cars. In this paper a 1,000 kg parallel hybrid car with continuously variable transmission and a 6,000 kg series hybrid minibus both equipped with Wankel engines are considered. The Wankel engine works at steady state to minimize fuel consumption and exhaust emissions. The simulation of the behavior of these two vehicles during a ECE + EUDC test cycle is presented in order to evaluate the performances of the systems.

  20. Fabrication of Hybrid Petroelectric Vehicle

    Directory of Open Access Journals (Sweden)

    G. Adinarayana

    2014-10-01

    Full Text Available In automobile sector, the need for alternative fuel as a replacement of conventional fossil fuel, due to its depletion and amount of emission has given way for new technologies like Fuel cells vehicles, Electric vehicles. Still a lot of advancement has to take place in these technologies for commercialization. The gap between the current fossil fuel technology and zero emission vehicles can be bridged by hybrid technology. Hybrid vehicles are those which can run on two or more powering sources/fuels. Feasibility of this technology is been proved in four wheelers and automobile giants like Toyota, Honda, and Hyundai have launched successful vehicles like Toyota prius, Honda insight etc. This technology maximizes the advantages of the two fuels and minimizes the disadvantages of the same. The best preferred hybrid pair is electric and fossil fuel. This increases the mileage of the vehicle twice the existing and also reduces the emission to half. At present, we like to explore the hybrid technology in the two wheeler sector and its feasibility on road. This paper deals with an attempt to make a hybrid with electric start and petrol run. Further a design of basic hybrid elements like motor, battery, and engine. As on today, hybrid products are one of the best solutions for all pollution hazards at a fairly nominal price. An investment within the means of a common man that guarantees a better environment to live in.

  1. Assessment of polymorphic metabolite data in bioavailability/bioequivalence studies - considerations and challenges

    OpenAIRE

    Srinivas, Nuggehally R.

    2011-01-01

    Bioavailability (BA)/ bioequivalence (BE) studies are the cornerstone for the approval of generic drugs. While BA/BE assessment involving the pharmacokinetic data of the parent compound has been routinely performed, the introduction of the assessment of metabolite(s) data, alone or in addition to parent compound, has also emerged. In this context, the assessment of BA/BE of metabolite(s) may pose additional complexities and challenges, if the metabolic pathway is under the influence of a poly...

  2. Hybrid Vehicle Program. Final report

    Energy Technology Data Exchange (ETDEWEB)

    None

    1984-06-01

    This report summarizes the activities on the Hybrid Vehicle Program. The program objectives and the vehicle specifications are reviewed. The Hybrid Vehicle has been designed so that maximum use can be made of existing production components with a minimum compromise to program goals. The program status as of the February 9-10 Hardware Test Review is presented, and discussions of the vehicle subsystem, the hybrid propulsion subsystem, the battery subsystem, and the test mule programs are included. Other program aspects included are quality assurance and support equipment. 16 references, 132 figures, 47 tables.

  3. Pseudovector mesons, hybrids and glueballs

    CERN Document Server

    Burakovsky, L; Burakovsky, Leonid; Page, Philip R.

    2000-01-01

    We consider glueball- (hybrid) meson mixing for the low-lying four pseudovector states. The h_1'(1380) decays dominantly to K*K with some presence in rho pi and omega eta. The newly observed h_1(1600) has a D- to S-wave width ratio to omega eta which does not enable differentiation between a conventional and hybrid meson interpretation. We predict the decay pattern of the isopartner conventional or hybrid meson b_1(1650). A notably narrow s sbar partner h_1'(1810) is predicted.

  4. Completeness in Hybrid Type Theory

    DEFF Research Database (Denmark)

    Areces, Carlos; Blackburn, Patrick Rowan; Huertas, Antonia;

    2014-01-01

    We show that basic hybridization (adding nominals and @ operators) makes it possible to give straightforward Henkin-style completeness proofs even when the modal logic being hybridized is higher-order. The key ideas are to add nominals as expressions of type t, and to extend to arbitrary types...... the way we interpret @i in propositional and first-order hybrid logic. This means: interpret @iαa , where αa is an expression of any type a , as an expression of type a that rigidly returns the value that αa receives at the i-world. The axiomatization and completeness proofs are generalizations of those...

  5. Hybrid codes: Methods and applications

    Energy Technology Data Exchange (ETDEWEB)

    Winske, D. (Los Alamos National Lab., NM (USA)); Omidi, N. (California Univ., San Diego, La Jolla, CA (USA))

    1991-01-01

    In this chapter we discuss hybrid'' algorithms used in the study of low frequency electromagnetic phenomena, where one or more ion species are treated kinetically via standard PIC methods used in particle codes and the electrons are treated as a single charge neutralizing massless fluid. Other types of hybrid models are possible, as discussed in Winske and Quest, but hybrid codes with particle ions and massless fluid electrons have become the most common for simulating space plasma physics phenomena in the last decade, as we discuss in this paper.

  6. Hybrid laser-arc welding

    DEFF Research Database (Denmark)

    the characteristics of the process, including the properties of joints produced by hybrid laser-arc welding and ways of assessing weld quality. Part II discusses applications of the process to such metals as magnesium alloys, aluminium and steel as well as the use of hybrid laser-arc welding in such sectors as ship...... building and the automotive industry. With its distinguished editor and international team of contributors, Hybrid laser-arc welding, will be a valuable source of reference for all those using this important welding technology. Professor Flemming Ove Olsen works in the Department of Manufacturing...

  7. Antibacterial Secondary Metabolites from the Cave Sponge Xestospongia sp.

    Directory of Open Access Journals (Sweden)

    Sridevi Ankisetty

    2012-05-01

    Full Text Available Chemical investigation of the cave sponge Xestospongia sp. resulted in the isolation of three new polyacetylenic long chain compounds along with two known metabolites. The structures of the new metabolites were established by NMR and MS analyses. The antibacterial activity of the new metabolites was also evaluated.

  8. Suggesting a testing strategy for possible endocrine effects of drug metabolites.

    Science.gov (United States)

    Jacobsen, N W; Brooks, B W; Halling-Sørensen, B

    2012-04-01

    Most pharmaceuticals are extensively metabolized by organisms, which results in internal exposure to mixtures of parent compounds and various metabolites. Many of these metabolites are considered non-toxic, but some metabolites retain toxic properties of the parent compound or elicit other undesirable outcomes. Unfortunately, the effects of metabolites are often not considered when endocrine activities of chemicals are evaluated in vitro. In this study two approaches, an "effect-based" and a "compound-by-compound" testing design, were used to determine the effects of metabolites of the antidepressant sertraline on aromatase enzyme activity. In the "effect-based" approach, a mixture of sertraline metabolites, produced by liver microsomes, inhibited aromatase, but was less potent than sertraline. In the "compound-by-compound" testing design, three specific metabolites were evaluated individually and in mixtures. Though two N-desmethylated metabolites were more potent aromatase inhibitors than sertraline, hydroxyl ketone sertraline did not inhibit the enzyme and mixtures of these metabolites and sertraline were less potent than predicted from a concentration addition model. Our findings highlight the importance of considering aromatase inhibition, and potentially other biological activities, of pharmaceutical metabolites produced by liver microsome preparations and then comparing such observations to studies of specific metabolites available for testing in pure form. Subsequently, a five step integrated strategy for screening of the potential endocrine effects of drugs and their metabolites are proposed. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Incorporation of codeine and metabolites into hair. Role of pigmentation.

    Science.gov (United States)

    Gygi, S P; Joseph, R E; Cone, E J; Wilkins, D G; Rollins, D E

    1996-04-01

    Xenobiotics circulating in the blood may become incorporated into growing hair. Melanin has affinity for many pharmacologically unrelated drugs and is responsible for the pigmentation in hair. To assess the role of pigmentation in the incorporation of drugs into hair, the distribution of codeine and its metabolites was studied in Sprague-Dawley (SD; white nonpigmented hair), Dark Agouti (DA; brown pigmented hair), and hooded Long-Evans (LE; both black pigmented and white nonpigmented hair) rats. Codeine was administered at a dose of 40 mg/kg/day i.p. for 5 days. Fourteen days after beginning the dosing protocol, hair was collected and analyzed for codeine, and its metabolite, morphine, by positive-ion chemical ionization GC/ion-trap MS. The plasma pharmacokinetics for codeine and morphine were also determined after a single 40 mg/kg injection (equivalent to first dose in 5-day dosing protocol) in all three strains of rats. Hair and plasma codeine and morphine concentrations were also determined after acid hydrolysis to evaluate the presence of glucuronide metabolites. Codeine concentrations in the hair of SD, DA, and pigmented LE hair were 0.98 +/- 0.10, 5.99 +/- 1.24, and 111.93 +/- 18.69 ng/mg hair, respectively; morphine concentrations were 0.34 +/- 0.04, 0.51 +/- 0.11, and 14.46 +/- 1.81 ng/mg hair, respectively; morphine glucuronide concentrations were 0.67 +/- 0.08, 1.04 +/- 0.37, and 13.80 +/- 3.60 ng/mg hair, respectively. Studies examining the in vitro binding of [3H] codeine and [3H]morphine to hair demonstrated both specific and nonspecific binding sites for codeine and morphine. Pigmented hair from LE rats possessed the greatest number of binding sites, white hair from SD rats contained the least, and brown hair from DA rats was intermediate. A time course study of codeine and its metabolites showed pigment-mediated differences in incorporation of codeine and metabolites within a few hours of drug administration. These data indicate that pigmented hair

  10. HYBRIDIZATION AND CHAMELEONIC JOURNALISM

    Directory of Open Access Journals (Sweden)

    Adriana Schryver Kurtz

    2016-12-01

    Full Text Available O texto aborda a crescente hibridização entre o Jornalismo e demais formatos midiáticos como resultado natural de um processo que já está na própria raiz da comunicação enquanto atividade histórica. A lógica interna e as potencialidades estéticas e discursivas do fenômeno são analisadas a partir das convergências entre jornalismo e cinema. Para tanto, utiliza o falso documentário Zelig (1983, texto fílmico de Woody Allen, híbrido por natureza, postulado como um microcosmo rico em pistas e sugestões para refletir sobre a fusão entre conteúdos informativos e não informativos.   PALAVRAS-CHAVE: Hibridização; Jornalismo; Cinema; Zelig.       ABSTRACT The text discusses the growing hybridization between journalism and other media formats as a natural result of a process that is already in the very root of communication while historical activity. The internal logic and the aesthetic and discursive potential of the phenomenon are analyzed through the convergences between journalism and cinema. Therefore, uses the mockumentary Zelig (1983, filmic text of Woody Allen, hybrid by nature, postulated as a microcosm rich in clues and suggestions to reflect about the merger between informative and uninformative content.      KEYWORDS: Hybridization; Journalism; Cinema; Zelig.     RESUMEN El texto aborda la creciente hibridación entre el periodismo y otros formatos de medios como um resultado natural de un proceso que ya está en la raíz misma de la comunicación mientras actividad histórica. Se analizan la lógica interna y el potencial estético y discursivo del fenómeno a través de las convergencias entre el periodismo y el cine. Para ello, utiliza el falso documental Zelig (1983, texto fílmico de Woody Allen, híbrido en su naturaleza, postulado como un microcosmos rico en pistas y sugerencias para reflexionar sobre la fusión entre contenidos informativos y no informativos.      PALABRAS CLAVE: Hibridaci

  11. Advanced Hybrid Computer Systems. Software Technology.

    Science.gov (United States)

    This software technology final report evaluates advances made in Advanced Hybrid Computer System software technology . The report describes what...automatic patching software is available as well as which analog/hybrid programming languages would be most feasible for the Advanced Hybrid Computer...compiler software . The problem of how software would interface with the hybrid system is also presented.

  12. How common is homoploid hybrid speciation?

    Science.gov (United States)

    Schumer, Molly; Rosenthal, Gil G; Andolfatto, Peter

    2014-06-01

    Hybridization has long been considered a process that prevents divergence between species. In contrast to this historical view, an increasing number of empirical studies claim to show evidence for hybrid speciation without a ploidy change. However, the importance of hybridization as a route to speciation is poorly understood, and many claims have been made with insufficient evidence that hybridization played a role in the speciation process. We propose criteria to determine the strength of evidence for homoploid hybrid speciation. Based on an evaluation of the literature using this framework, we conclude that although hybridization appears to be common, evidence for an important role of hybridization in homoploid speciation is more circumscribed.

  13. A generic plant RNA isolation method suitable for RNA-Seq and suppression subtractive hybridization.

    Science.gov (United States)

    Zhu, Y Q; Wu, W J; Xiao, H W; Chen, H B; Zheng, Y; Zhang, Y J; Wang, H X; Huang, L Q

    2013-11-18

    A recently developed revolutionary approach to transcriptomics, RNA-Seq, and suppression subtractive hybridization are powerful tools for gene expression research. However, currently, the difficulty of isolating high-quality RNAs from plant tissues bearing abundant complex polysaccharides, polyphenolics, and secondary metabolites is a serious problem that not only limits the application of these technologies but also hinders studies dealing with RNA in general. We have developed a consistent protocol to prepare highly intact and pure RNAs from tissues of a variety of field-grown plant species, with high yields, in 2 to 3 h. Additionally, this method can be readily applied to mammalian, yeast, and bacterial cells.

  14. Real and Hybrid Atomic Orbitals.

    Science.gov (United States)

    Cook, D. B.; Fowler, P. W.

    1981-01-01

    Demonstrates that the Schrodinger equation for the hydrogenlike atom separates in both spheroconal and prolate spheroidal coordinates and that these separations provide a sound theoretical basis for the real and hybrid atomic orbitals. (Author/SK)

  15. Hybrid-Vehicle Transmission System

    Science.gov (United States)

    Lupo, G.; Dotti, G.

    1985-01-01

    Continuously-variable transmission system for hybrid vehicles couples internal-combustion engine and electric motor section, either individually or in parallel, to power vehicle wheels during steering and braking.

  16. Hybrid Fuel Cell Technology Overview

    Energy Technology Data Exchange (ETDEWEB)

    None available

    2001-05-31

    For the purpose of this STI product and unless otherwise stated, hybrid fuel cell systems are power generation systems in which a high temperature fuel cell is combined with another power generating technology. The resulting system exhibits a synergism in which the combination performs with an efficiency far greater than can be provided by either system alone. Hybrid fuel cell designs under development include fuel cell with gas turbine, fuel cell with reciprocating (piston) engine, and designs that combine different fuel cell technologies. Hybrid systems have been extensively analyzed and studied over the past five years by the Department of Energy (DOE), industry, and others. These efforts have revealed that this combination is capable of providing remarkably high efficiencies. This attribute, combined with an inherent low level of pollutant emission, suggests that hybrid systems are likely to serve as the next generation of advanced power generation systems.

  17. Hybrid models for complex fluids

    CERN Document Server

    Tronci, Cesare

    2010-01-01

    This paper formulates a new approach to complex fluid dynamics, which accounts for microscopic statistical effects in the micromotion. While the ordinary fluid variables (mass density and momentum) undergo usual dynamics, the order parameter field is replaced by a statistical distribution on the order parameter space. This distribution depends also on the point in physical space and its dynamics retains the usual fluid transport features while containing the statistical information on the order parameter space. This approach is based on a hybrid moment closure for Yang-Mills Vlasov plasmas, which replaces the usual cold-plasma assumption. After presenting the basic properties of the hybrid closure, such as momentum map features, singular solutions and Casimir invariants, the effect of Yang-Mills fields is considered and a direct application to ferromagnetic fluids is presented. Hybrid models are also formulated for complex fluids with symmetry breaking. For the special case of liquid crystals, a hybrid formul...

  18. Annular Hybrid Rocket Motor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Engineers at SpaceDev have conducted a preliminary design and analysis of a proprietary annular design concept for a hybrid motor. A U.S. Patent application has been...

  19. Design Procedure for Hybrid Ventilation

    DEFF Research Database (Denmark)

    Heiselberg, Per; Tjelflaat, Per Olaf

    Mechanical and natural ventilation systems have developed separately during many years. The natural next step in this development is development of ventilation concepts that utilises and combines the best features from each system into a new type of ventilation system - Hybrid Ventilation....... Buildings with hybrid ventilation often include other sustainable technologies and an energy optimisation requires an integrated approach in the design of the building and its mechanical systems. Therefore, the hybrid ventilation design procedure differs from the design procedure for conventional HVAC....... The first ideas on a design procedure for hybrid ventilation is presented and the different types of design methods, that is needed in different phases of the design process, is discussed....

  20. Towards Modelling of Hybrid Systems

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2006-01-01

    The article is an attempt to use methods of category theory and topology for analysis of hybrid systems. We use the notion of a directed topological space; it is a topological space together with a set of privileged paths. Dynamical systems are examples of directed topological spaces. A hybrid...... system consists of a number of dynamical systems that are glued together according to information encoded in the discrete part of the system. We develop a definition of a hybrid system as a functor from the category generated by a transition system to the category of directed topological spaces. Its...... directed homotopy colimit (geometric realization) is a single directed topological space. The behavior of hybrid systems can be then understood in terms of the behavior of dynamical systems through the directed homotopy colimit....

  1. Hybrid-Vehicle Transmission System

    Science.gov (United States)

    Lupo, G.; Dotti, G.

    1985-01-01

    Continuously-variable transmission system for hybrid vehicles couples internal-combustion engine and electric motor section, either individually or in parallel, to power vehicle wheels during steering and braking.

  2. Hybrid Platforms, Tools, and Resources

    Science.gov (United States)

    Linder, Kathryn E.; Bruenjes, Linda S.; Smith, Sarah A.

    2017-01-01

    This chapter discusses common tools and resources for building a hybrid course in a higher education setting and provides recommendations for best practices in Learning Management Systems and Open Educational Resources.

  3. A hybrid base isolation system

    Energy Technology Data Exchange (ETDEWEB)

    Hart, G.C. [Univ. of California, Los Angeles, CA (United States); Lobo, R.F.; Srinivasan, M. [Hart Consultant Group, Santa Monica, CA (United States); Asher, J.W. [kpff Engineers, Santa Monica, CA (United States)

    1995-12-01

    This paper proposes a new analysis procedure for hybrid base isolation buildings when considering the displacement response of a base isolated building to wind loads. The system is considered hybrid because of the presence of viscous dampers in the building above the isolator level. The proposed analysis approach incorporates a detailed site specific wind study combined with a dynamic nonlinear analysis of the building response.

  4. Ion-atom hybrid systems

    CERN Document Server

    Willitsch, Stefan

    2014-01-01

    The study of interactions between simultaneously trapped cold ions and atoms has emerged as a new research direction in recent years. The development of ion-atom hybrid experiments has paved the way for investigating elastic, inelastic and reactive collisions between these species at very low temperatures, for exploring new cooling mechanisms of ions by atoms and for implementing new hybrid quantum systems. The present lecture reviews experimental methods, recent results and upcoming developments in this emerging field.

  5. Information component of hybrid war

    OpenAIRE

    Bohdanov, Aleksander

    2015-01-01

    A hybrid warfare in the three-dimensional coordinate system «Matter-Information-measure» is considering. In particular, the information component is highlighted and analyzed. The factors of preparation of information operations is defined, which are disclosed as an example of experience of volunteer group information warfare of Institute of special communication and information security of NTUU «KPI».Keywords: coordinate system «Matter-Information-Measure» hybrid warfare, information componen...

  6. Formal Description of Hybrid Systems

    DEFF Research Database (Denmark)

    Zhou, Chaochen; Ji, Wang; Ravn, Anders P.

    1996-01-01

    A language to describe hybrid systems, i.e. networks of communicating discrete and continuous processes, is proposed. A semantics of the language is given in Extended Duration Calculus, a real-time interval logic with a proof system that allows reasoning in mathematical analysis about continuous ...... processes to be embedded into the logic. The semantics thus provides a secure link to hybrid system models based on a general theory of dynamical systems....

  7. Hybrid particles and associated methods

    Science.gov (United States)

    Fox, Robert V; Rodriguez, Rene; Pak, Joshua J; Sun, Chivin

    2015-02-10

    Hybrid particles that comprise a coating surrounding a chalcopyrite material, the coating comprising a metal, a semiconductive material, or a polymer; a core comprising a chalcopyrite material and a shell comprising a functionalized chalcopyrite material, the shell enveloping the core; or a reaction product of a chalcopyrite material and at least one of a reagent, heat, and radiation. Methods of forming the hybrid particles are also disclosed.

  8. DETERMINATION OF PRIMARY METABOLITES IN CEREAL MILLING FRACTIONS

    Directory of Open Access Journals (Sweden)

    Eva Ivanišová

    2013-10-01

    Full Text Available The aim of this study was to determine of primary metabolites (content of starch, total dietary fibre, reducing sugars, proteins and amino acids in four milling fractions of selected cereals (barley, wheat, oat, spelt, rye, triticale grew in the year 2009. It was found that flour fractions (break flour and reduction flour showed the lower content of primary metabolites than bran fractions (fine bran and coarse bran. The aim of this study was also to mention the potential use of bran parts of grain - substances from these parts can be isolated and after treatment, which causes their efficiently usable for human body, they can be used for fortification of wide range of food products.

  9. Identification of phenothiazine antihistamines and their metabolites in urine.

    Science.gov (United States)

    Maurer, H; Pfleger, K

    1988-01-01

    Identification of the phenothiazine antihistamines alimemazine, dimetotiazine, isothipendyl, mequitazine, oxomemazine, promethazine, thiethylperazine, triflupromazine and their metabolites in urine is described. After acid hydrolysis of the conjugates, extraction and acetylation the urine samples were analysed by computerized gas chromatography-mass spectrometry. Using ion chromatography with the selective ions m/z 58, 72, 100, 114, 124, 128, 141, and 199 the possible presence of phenothiazine antihistamines and/or their metabolites was indicated. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs.

  10. Analysis of human urine metabolites using SPE and NMR spectroscopy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Nuclear magnetic resonance (NMR) spectroscopic analysis of metabonome/metabolome has widespread applications in biomedical science researches. However, most of NMR resonances for urinary metabolites remain to be fully assigned. In the present study, human urine samples from two healthy volunteers were pre-treated with C18 solid-phase extraction and the resultant 5 sub-fractions were subjected to one- and two-dimensional NMR studies, including 1H J-Resolved, 1H-1H COSY, 1H-1H TOCSY, 1H-13C HSQC, and HMBC 2D NMR. More than 70 low molecular weight metabolites were identified, and complete assignments of 1H and 13C resonances including many complex coupled spin systems were obtained.

  11. Abiotic stresses as tools for metabolites in microalgae.

    Science.gov (United States)

    Paliwal, Chetan; Mitra, Madhusree; Bhayani, Khushbu; Bharadwaj, S V Vamsi; Ghosh, Tonmoy; Dubey, Sonam; Mishra, Sandhya

    2017-11-01

    Microalgae, due to various environmental stresses, constantly tune their cellular mechanisms to cope with them. The accumulation of the stress metabolites is closely related to the changes occurring in their metabolic pathways. The biosynthesis of metabolites can be triggered by a number of abiotic stresses like temperature, salinity, UV- radiation and nutrient deprivation. Although, microalgae have been considered as an alternative sustainable source for nutraceutical products like pigments and omega-3 polyunsaturated fatty acids (PUFAs) to cater the requirement of emerging human population but inadequate biomass generation makes the process economically impractical. The stress metabolism for carotenoid regulation in green algae is a 2-step metabolism. There are a few major stresses which can influence the formation of phycobiliprotein in cyanobacteria. This review would primarily focus on the cellular level changes under stress conditions and their corresponding effects on lipids (including omega-3 PUFAs), pigments and polymers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Cladobotryal: a Fungal Metabolite with a Novel Ring System

    DEFF Research Database (Denmark)

    Breinholt, Jens; Jensen, Helle C.; Kjær, Anders;

    1998-01-01

    In screening for antifungal metabolites a novel compound, cladobotryal, was isolated from the mycoparasitic fungus Cladobotryum varium. Its structure was established as (+)-(2R*,3R*)-2-[(Z)- 2-buten-2-yl]-3,7-dihydro-3-formyl-3-methyl-5-phenylfuro[2,3-b]pyr idin-4(2H)-one on the basis of spectros......In screening for antifungal metabolites a novel compound, cladobotryal, was isolated from the mycoparasitic fungus Cladobotryum varium. Its structure was established as (+)-(2R*,3R*)-2-[(Z)- 2-buten-2-yl]-3,7-dihydro-3-formyl-3-methyl-5-phenylfuro[2,3-b]pyr idin-4(2H)-one on the basis...

  13. Cladobotryal: a Fungal Metabolite with a Novel Ring System

    DEFF Research Database (Denmark)

    Breinholt, Jens; Jensen, Helle C.; Kjær, Anders

    1998-01-01

    In screening for antifungal metabolites a novel compound, cladobotryal, was isolated from the mycoparasitic fungus Cladobotryum varium. Its structure was established as (+)-(2R*,3R*)-2-[(Z)- 2-buten-2-yl]-3,7-dihydro-3-formyl-3-methyl-5-phenylfuro[2,3-b]pyr idin-4(2H)-one on the basis of spectros......In screening for antifungal metabolites a novel compound, cladobotryal, was isolated from the mycoparasitic fungus Cladobotryum varium. Its structure was established as (+)-(2R*,3R*)-2-[(Z)- 2-buten-2-yl]-3,7-dihydro-3-formyl-3-methyl-5-phenylfuro[2,3-b]pyr idin-4(2H)-one on the basis...

  14. Discriminative stimulus properties of mescaline: mescaline or metabolite?

    Science.gov (United States)

    Browne, R G; Ho, B T

    1975-01-01

    The purpose of this study was to investigate possible similarities in the interoceptive stimuli produced by mescaline and its metabolites. Rats were trained in a 2 lever operant chamber to discriminate between the drugged state (mescaline 25 mg/kg) and the nondrugged state (saline). Following acquisition of discriminative response control the rats were pretreated with either saline, aldehyde dehydrogenase inhibitors or amine oxidase inhibitors and tested stimulus generalization produced by i.p. injections of 3, 4, 5-trimethoxyphenylethanol (TMPE), 3, 4, 5-trimethoxyphenylacetaldehyde (TMPA), N-acetylmescaline, mescaline or saline. The results indicated that both aldehyde dehydrogenase and amine oxidase inhibitors enhanced the effects of mescaline, while TMPE, TMPA and N-acetylmescaline failed to exhibit generalization to the mescaline state, regardless of pretreatment. These findings do not indicate the role of a metabolite in the interoceptive cue produced by mescaline.

  15. Mutagenicity study of butachlor and its metabolites using Salmonella typhimurium.

    Science.gov (United States)

    Hsu, Kuei-Yao; Lin, Hwai-Jeng; Lin, Jen-Kun; Kuo, Wein-Shung; Ou, Yueh-Hsing

    2005-12-01

    Butachlor is the most commonly used herbicide in Taiwan and many other countries. It has been reported to be an indirect mutagen and carcinogen in various in vitro assay systems. Previous investigation has also demonstrated that butachlor stimulates cell proliferation, transforms normal embryonic cells, and induces stomach tumors in Spraque-Dawley rats. However, the mechanism of butachlor carcinogenicity is still not clear. In order to clarify the toxicologic and carcinogenic properties of butachlor, we proposed a metabolic pathway, and synthesized the authentic metabolites by chemical methods. In addition, we tested the mutagenicity of butachlor and these metabolites on Salmonella typhimurium. The results indicate that butachlor might manifest its carcinogenicity via the mutagenicity of its metabolic products. Although the molecular mechanism of butachlor-induced cellular toxicity is still not clear, it is likely that the cellular transformation ability of butachlor is partly associated with its mutagenicity.

  16. Secondary metabolites in plants: transport and self-tolerance mechanisms.

    Science.gov (United States)

    Shitan, Nobukazu

    2016-07-01

    Plants produce a host of secondary metabolites with a wide range of biological activities, including potential toxicity to eukaryotic cells. Plants generally manage these compounds by transport to the apoplast or specific organelles such as the vacuole, or other self-tolerance mechanisms. For efficient production of such bioactive compounds in plants or microbes, transport and self-tolerance mechanisms should function cooperatively with the corresponding biosynthetic enzymes. Intensive studies have identified and characterized the proteins responsible for transport and self-tolerance. In particular, many transporters have been isolated and their physiological functions have been proposed. This review describes recent progress in studies of transport and self-tolerance and provides an updated inventory of transporters according to their substrates. Application of such knowledge to synthetic biology might enable efficient production of valuable secondary metabolites in the future.

  17. In vivo nuclear magnetic resonance metabolite profiling in plant seeds.

    Science.gov (United States)

    Terskikh, Victor; Kermode, Allison R

    2011-01-01

    Nuclear magnetic resonance (NMR) spectroscopy has been successfully applied to profile a variety of primary and secondary metabolites in whole intact plant seeds in vivo. The nondestructive nature of NMR spectroscopy allows direct metabolic studies to be performed on the same seed throughout a given physio-logical process or key lifecycle transition, such as dormancy breakage, germination, and early postgerminative growth. Multinuclear NMR is capable of evaluating seed quality by assessing nondestructively nutrient reserves and seed protectants at seed maturity and to further monitor reserve mobilization following germination, which is critical for seedling emergence. In this chapter, we illustrate the use of several in vivo NMR techniques for metabolite profiling in seeds. Importantly, some of these methods have potential for the screening of single seeds or seed populations to identify seedlots with compromised viability either due to developmental problems or as a result of deterioration during prolonged storage.

  18. Estradiol Metabolites and their Possible Role in Gynaecological Cancer

    Directory of Open Access Journals (Sweden)

    Seeger H

    2010-01-01

    Full Text Available Evidence is growing that certain estradiol metabolites are biologically active, especially in the field of cancer. Currently research focuses on the anticancerogenic effects of 2-hydroxyestrone and particularly 2-methoxyestradiol, as well as the possible carcinogenic properties of 4-hydroxyestrogens and 16α-hydroxyestrone. The clinical relevance of these activities, demonstrated in in vitro and animal experiments, remains unclear – it is proven, however, that the metabolite production can be altered in certain malignancies such as endometrial-, breast- and cervical carcinoma. Clinical studies, including own investigations, demonstrated a negative correlation between the ratio of 2-hydroxyestrone to 16α-hydroxyestrone and breast cancer risk. However, the design and interpretation of such studies should consider factors influencing metabolic pattern such as diet, physical activity, smoking as well as internal diseases and certain drugs.

  19. Antioxidant properties of fungal metabolite nigerloxin in vitro.

    Science.gov (United States)

    Suresha, B S; Srinivasan, K

    2013-01-01

    We have recently reported the beneficial influence of the fungal metabolite nigerloxin, a new aldose reductase inhibitor and a lipoxygenase inhibitor on oxidative stress in streptozotocin induced diabetic rats. In the present study we have investigated the antioxidant potential of nigerloxin in vitro as compared to one of the well known natural antioxidant, curcumin. The fungal metabolite nigerloxin was found to be an effective antioxidant in different in vitro assays including the phosphomolybdenum, 2,2-diphenyl-1-picrylhydrazyl (DPPH.),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS.+) and ferric reducing antioxidant power (FRAP) methods. The antioxidant potency of nigerloxin may be attributed to its electron donating nature. The ferric reducing potency of nigerloxin as demonstrated by FRAP assay method was even found to be superior to that of the natural antioxidant curcumin.

  20. Metabolites of amygdalin under simulated human digestive fluids.

    Science.gov (United States)

    Shim, Soon-Mi; Kwon, Hoonjeong

    2010-12-01

    In the present study, degradation of amygdalin in the human digestive fluids and absorption of its metabolites by the human small intestine were evaluated by simulating a gastrointestinal digestion model combined with a human intestinal cell culture. Orally administered amygdalin was degraded into prunasin by digestive enzymes after passing through the salivary and gastrointestinal phases. Prunasin, the major metabolite of amygdalin in the digestive fluids, was incubated in a caco-2 cell culture system. Prunasin was degraded into the mandelonitrile by β-glucosidase and then hydroxylated across the small intestinal wall, producing hydroxymandelonitrile (149 Da). Results from this study suggest that risk assessment of amygdalin from food consumption can be done in a more accurate way by determining a pathway of amygdalin metabolism in the simulating human upper gastrointestinal tract.