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Sample records for metabolite networks affected

  1. The transcript and metabolite networks affected by the two clades of Arabidopsis glucosinolate biosynthesis regulators.

    Science.gov (United States)

    Malitsky, Sergey; Blum, Eyal; Less, Hadar; Venger, Ilya; Elbaz, Moshe; Morin, Shai; Eshed, Yuval; Aharoni, Asaph

    2008-12-01

    In this study, transcriptomics and metabolomics data were integrated in order to examine the regulation of glucosinolate (GS) biosynthesis in Arabidopsis (Arabidopsis thaliana) and its interface with pathways of primary metabolism. Our genetic material for analyses were transgenic plants overexpressing members of two clades of genes (ALTERED TRYPTOPHAN REGULATION1 [ATR1]-like and MYB28-like) that regulate the aliphatic and indole GS biosynthetic pathways (AGs and IGs, respectively). We show that activity of these regulators is not restricted to the metabolic space surrounding GS biosynthesis but is tightly linked to more distal metabolic networks of primary metabolism. This suggests that with similarity to the regulators we have investigated here, other factors controlling pathways of secondary metabolism might also control core pathways of central metabolism. The relatively broad view of transcripts and metabolites altered in transgenic plants overexpressing the different factors underlined novel links of GS metabolism to additional metabolic pathways, including those of jasmonic acid, folate, benzoic acid, and various phenylpropanoids. It also revealed transcriptional and metabolic hubs in the "distal" network of metabolic pathways supplying precursors to GS biosynthesis and that overexpression of the ATR1-like clade genes has a much broader effect on the metabolism of indolic compounds than described previously. While the reciprocal, negative cross talk between the methionine and tryptophan pathways that generate GSs in Arabidopsis has been suggested previously, we now show that it is not restricted to AGs and IGs but includes additional metabolites, such as the phytoalexin camalexin. Combining the profiling data of transgenic lines with gene expression correlation analysis allowed us to propose a model of how the balance in the metabolic network is maintained by the GS biosynthesis regulators. It appears that ATR1/MYB34 is an important mediator between the gene

  2. The Transcript and Metabolite Networks Affected by the Two Clades of Arabidopsis Glucosinolate Biosynthesis Regulators1[W

    Science.gov (United States)

    Malitsky, Sergey; Blum, Eyal; Less, Hadar; Venger, Ilya; Elbaz, Moshe; Morin, Shai; Eshed, Yuval; Aharoni, Asaph

    2008-01-01

    In this study, transcriptomics and metabolomics data were integrated in order to examine the regulation of glucosinolate (GS) biosynthesis in Arabidopsis (Arabidopsis thaliana) and its interface with pathways of primary metabolism. Our genetic material for analyses were transgenic plants overexpressing members of two clades of genes (ALTERED TRYPTOPHAN REGULATION1 [ATR1]-like and MYB28-like) that regulate the aliphatic and indole GS biosynthetic pathways (AGs and IGs, respectively). We show that activity of these regulators is not restricted to the metabolic space surrounding GS biosynthesis but is tightly linked to more distal metabolic networks of primary metabolism. This suggests that with similarity to the regulators we have investigated here, other factors controlling pathways of secondary metabolism might also control core pathways of central metabolism. The relatively broad view of transcripts and metabolites altered in transgenic plants overexpressing the different factors underlined novel links of GS metabolism to additional metabolic pathways, including those of jasmonic acid, folate, benzoic acid, and various phenylpropanoids. It also revealed transcriptional and metabolic hubs in the “distal” network of metabolic pathways supplying precursors to GS biosynthesis and that overexpression of the ATR1-like clade genes has a much broader effect on the metabolism of indolic compounds than described previously. While the reciprocal, negative cross talk between the methionine and tryptophan pathways that generate GSs in Arabidopsis has been suggested previously, we now show that it is not restricted to AGs and IGs but includes additional metabolites, such as the phytoalexin camalexin. Combining the profiling data of transgenic lines with gene expression correlation analysis allowed us to propose a model of how the balance in the metabolic network is maintained by the GS biosynthesis regulators. It appears that ATR1/MYB34 is an important mediator between the

  3. Metabolite Depletion Affects Flux Profiling of Cell Lines

    DEFF Research Database (Denmark)

    Nilsson, A.; Haanstra, J. R.; Teusink, B.

    2018-01-01

    Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation.......Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation....

  4. 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.

  5. Global Prioritization of Disease Candidate Metabolites Based on a Multi-omics Composite Network

    Science.gov (United States)

    Yao, Qianlan; Xu, Yanjun; Yang, Haixiu; Shang, Desi; Zhang, Chunlong; Zhang, Yunpeng; Sun, Zeguo; Shi, Xinrui; Feng, Li; Han, Junwei; Su, Fei; Li, Chunquan; Li, Xia

    2015-01-01

    The identification of disease-related metabolites is important for a better understanding of metabolite pathological processes in order to improve human medicine. Metabolites, which are the terminal products of cellular regulatory process, can be affected by multi-omic processes. In this work, we propose a powerful method, MetPriCNet, to predict and prioritize disease candidate metabolites based on integrated multi-omics information. MetPriCNet prioritized candidate metabolites based on their global distance similarity with seed nodes in a composite network, which integrated multi-omics information from the genome, phenome, metabolome and interactome. After performing cross-validation on 87 phenotypes with a total of 602 metabolites, MetPriCNet achieved a high AUC value of up to 0.918. We also assessed the performance of MetPriCNet on 18 disease classes and found that 4 disease classes achieved an AUC value over 0.95. Notably, MetPriCNet can also predict disease metabolites without known disease metabolite knowledge. Some new high-risk metabolites of breast cancer were predicted, although there is a lack of known disease metabolite information. A predicted disease metabolic landscape was constructed and analyzed based on the results of MetPriCNet for 87 phenotypes to help us understand the genetic and metabolic mechanism of disease from a global view. PMID:26598063

  6. 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.

    2016-01-01

    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. PMID:26761036

  7. (1) H-MRS processing parameters affect metabolite quantification

    DEFF Research Database (Denmark)

    Bhogal, Alex A; Schür, Remmelt R; Houtepen, Lotte C

    2017-01-01

    Proton magnetic resonance spectroscopy ((1) H-MRS) can be used to quantify in vivo metabolite levels, such as lactate, γ-aminobutyric acid (GABA) and glutamate (Glu). However, there are considerable analysis choices which can alter the accuracy or precision of (1) H-MRS metabolite quantification....... reinforce the notion that standard practices should be established to regularize outcomes of (1) H-MRS studies, and that basis sets used for processing should be made available to the scientific community....... individualized and optimal parameter settings using LCModel software. Data were processed a second time in one group using an independent software package (NMRWizard) for an additional comparison with a different post-processing platform. Correlations across research groups of the ratio between the highest and...... + NAAG/Cr + PCr and Glu/Cr + PCr, respectively. Metabolite quantification using identical (1) H-MRS data was influenced by processing parameters, basis sets and software choice. Locally preferred processing choices affected metabolite quantification, even when using identical software. Our results...

  8. 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. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier

  9. Bacterial metabolism in immediate response to nutritional perturbation with temporal and network view of metabolites.

    Science.gov (United States)

    Yukihira, Daichi; Fujimura, Yoshinori; Wariishi, Hiroyuki; Miura, Daisuke

    2015-09-01

    In this study, the initial propagation of metabolic perturbation in Escherichia coli was visualized to understand the dynamic characteristics of the metabolic pathways without the association of transcription alterations. E. coli cells were exposed to the sudden relief of glucose starvation, and time-dependent variances in metabolite balances were traced in the second scale. The acquired time-course data were represented by structural variations of the metabolite-metabolite correlation network. The initial correlation structure was altered immediately by the glucose pulse, followed by further structural variations within a few minutes. It was demonstrated that one metabolite temporally correlated with distinct metabolites with different timings, and such a behavior could imply a regulatory role for the metabolite in the metabolic network. Centrality analysis of the networks and partial correlation analysis indicated that preparation for growth and oxidative stress could be coupled as a structural property of the metabolic pathways.

  10. Metabolite diversity in the plant pathogen Alternaria brassicicola: factors affecting production of brassicicolin A, depudecin, phomapyrone A and other metabolites.

    Science.gov (United States)

    Pedras, M Soledade C; Park, Myung Ryeol

    2015-01-01

    A systematic investigation of the metabolites of Alternaria brassicicola produced under various culture conditions is reported. The phytotoxin brassicicolin A is produced in significantly larger amounts in potato dextrose broth than in minimal medium cultures. In general an increase in the incubation temperature of cultures 23-30 C increases the production of brassicicolin A but decreases depudecin production. Reducing or eliminating nitrate from culture media or adding ammonium chloride increases the production of brassicicolin A at 30 C, depudecin at 23 C and α-acetylorcinol at either temperature, suggesting that nitrogen represses their biosynthesis. Siderophores are detected in cultures of A. brassicicola containing low and high ferric ion concentrations. The metabolites α-acetylorcinol and tyrosol are isolated for the first time from cultures of A. brassicicola, and α-acetylorcinol is synthesized in four steps and 36% overall yield. Only brassicicolin A and no other isolated metabolites, including depudecin and phomapyrone A, display phytotoxicity on leaves of Brassica species (up to 5.0 mM). Epigenetic modifiers, 5-azacitidin (5-AZA), suberoylanilide hydroxamic acid (SAHA) and suberoyl bis-hydroxamic acid (SBHA) do not affect the metabolite profiles of liquid cultures of this fungal pathogen. © 2015 by The Mycological Society of America.

  11. Blood sampling and hemolysis affect concentration of plasma metabolites

    DEFF Research Database (Denmark)

    Theil, Peter Kappel; Pedersen, Lene Juul; Jensen, Margit Bak

    2012-01-01

    design and blood was collected after restraint via vein puncture 1, 4, 11, and 23 h after morning feeding. Plasma samples were categorized as without or with minor or major hemolysis [clear (n = 218), yellow (n = 97), or red (n = 37)] upon centrifugation. Plasma NEFA (P ...Two experiments were carried out to reveal and quantify plasma metabolites that are sensitive to hemolysis and animal stress due to the blood sampling procedure (vein puncture vs. catheter). In Exp. 1, 48 sows were fed 4 diets either once (0800 h) or twice daily (0800 h and 1500 h) in a crossover......, a subset of samples from 24 sows fed twice daily in Exp. 1 was combined with data obtained from 30 sows sampled using jugular vein catheters. All sows in Exp. 2 were fed twice daily (0800 h and 1500 h) and blood samples collected repeatedly 1, 4, 11, and 23 h after morning feeding (other conditions were...

  12. MSD-MAP: A Network-Based Systems Biology Platform for Predicting Disease-Metabolite Links.

    Science.gov (United States)

    Wathieu, Henri; Issa, Naiem T; Mohandoss, Manisha; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2017-01-01

    Cancer-associated metabolites result from cell-wide mechanisms of dysregulation. The field of metabolomics has sought to identify these aberrant metabolites as disease biomarkers, clues to understanding disease mechanisms, or even as therapeutic agents. This study was undertaken to reliably predict metabolites associated with colorectal, esophageal, and prostate cancers. Metabolite and disease biological action networks were compared in a computational platform called MSD-MAP (Multi Scale Disease-Metabolite Association Platform). Using differential gene expression analysis with patient-based RNAseq data from The Cancer Genome Atlas, genes up- or down-regulated in cancer compared to normal tissue were identified. Relational databases were used to map biological entities including pathways, functions, and interacting proteins, to those differential disease genes. Similar relational maps were built for metabolites, stemming from known and in silico predicted metabolite-protein associations. The hypergeometric test was used to find statistically significant relationships between disease and metabolite biological signatures at each tier, and metabolites were assessed for multi-scale association with each cancer. Metabolite networks were also directly associated with various other diseases using a disease functional perturbation database. Our platform recapitulated metabolite-disease links that have been empirically verified in the scientific literature, with network-based mapping of jointly-associated biological activity also matching known disease mechanisms. This was true for colorectal, esophageal, and prostate cancers, using metabolite action networks stemming from both predicted and known functional protein associations. By employing systems biology concepts, MSD-MAP reliably predicted known cancermetabolite links, and may serve as a predictive tool to streamline conventional metabolomic profiling methodologies. Copyright© Bentham Science Publishers; For any

  13. Factors affecting farmers networking decisions

    NARCIS (Netherlands)

    Pascucci, S.

    2011-01-01

    This paper analyses farmers' decisions to carry out transactions by using three different types of networks: input supply cooperatives, processing and/or marketing cooperatives, and producers associations. We use arguments from economic sociology and new institutional economics to define the main

  14. An interaction map of circulating metabolites, immune gene networks, and their genetic regulation.

    Science.gov (United States)

    Nath, Artika P; Ritchie, Scott C; Byars, Sean G; Fearnley, Liam G; Havulinna, Aki S; Joensuu, Anni; Kangas, Antti J; Soininen, Pasi; Wennerström, Annika; Milani, Lili; Metspalu, Andres; Männistö, Satu; Würtz, Peter; Kettunen, Johannes; Raitoharju, Emma; Kähönen, Mika; Juonala, Markus; Palotie, Aarno; Ala-Korpela, Mika; Ripatti, Samuli; Lehtimäki, Terho; Abraham, Gad; Raitakari, Olli; Salomaa, Veikko; Perola, Markus; Inouye, Michael

    2017-08-01

    Immunometabolism plays a central role in many cardiometabolic diseases. However, a robust map of immune-related gene networks in circulating human cells, their interactions with metabolites, and their genetic control is still lacking. Here, we integrate blood transcriptomic, metabolomic, and genomic profiles from two population-based cohorts (total N = 2168), including a subset of individuals with matched multi-omic data at 7-year follow-up. We identify topologically replicable gene networks enriched for diverse immune functions including cytotoxicity, viral response, B cell, platelet, neutrophil, and mast cell/basophil activity. These immune gene modules show complex patterns of association with 158 circulating metabolites, including lipoprotein subclasses, lipids, fatty acids, amino acids, small molecules, and CRP. Genome-wide scans for module expression quantitative trait loci (mQTLs) reveal five modules with mQTLs that have both cis and trans effects. The strongest mQTL is in ARHGEF3 (rs1354034) and affects a module enriched for platelet function, independent of platelet counts. Modules of mast cell/basophil and neutrophil function show temporally stable metabolite associations over 7-year follow-up, providing evidence that these modules and their constituent gene products may play central roles in metabolic inflammation. Furthermore, the strongest mQTL in ARHGEF3 also displays clear temporal stability, supporting widespread trans effects at this locus. This study provides a detailed map of natural variation at the blood immunometabolic interface and its genetic basis, and may facilitate subsequent studies to explain inter-individual variation in cardiometabolic disease.

  15. Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

    Science.gov (United States)

    2014-01-01

    Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

  16. Dead end metabolites--defining the known unknowns of the E. coli metabolic network.

    Directory of Open Access Journals (Sweden)

    Amanda Mackie

    Full Text Available The EcoCyc database is an online scientific database which provides an integrated view of the metabolic and regulatory network of the bacterium Escherichia coli K-12 and facilitates computational exploration of this important model organism. We have analysed the occurrence of dead end metabolites within the database--these are metabolites which lack the requisite reactions (either metabolic or transport that would account for their production or consumption within the metabolic network. 127 dead end metabolites were identified from the 995 compounds that are contained within the EcoCyc metabolic network. Their presence reflects either a deficit in our representation of the network or in our knowledge of E. coli metabolism. Extensive literature searches resulted in the addition of 38 transport reactions and 3 metabolic reactions to the database and led to an improved representation of the pathway for Vitamin B12 salvage. 39 dead end metabolites were identified as components of reactions that are not physiologically relevant to E. coli K-12--these reactions are properties of purified enzymes in vitro that would not be expected to occur in vivo. Our analysis led to improvements in the software that underpins the database and to the program that finds dead end metabolites within EcoCyc. The remaining dead end metabolites in the EcoCyc database likely represent deficiencies in our knowledge of E. coli metabolism.

  17. Flow rate of transport network controls uniform metabolite supply to tissue.

    Science.gov (United States)

    Meigel, Felix J; Alim, Karen

    2018-05-01

    Life and functioning of higher organisms depends on the continuous supply of metabolites to tissues and organs. What are the requirements on the transport network pervading a tissue to provide a uniform supply of nutrients, minerals or hormones? To theoretically answer this question, we present an analytical scaling argument and numerical simulations on how flow dynamics and network architecture control active spread and uniform supply of metabolites by studying the example of xylem vessels in plants. We identify the fluid inflow rate as the key factor for uniform supply. While at low inflow rates metabolites are already exhausted close to flow inlets, too high inflow flushes metabolites through the network and deprives tissue close to inlets of supply. In between these two regimes, there exists an optimal inflow rate that yields a uniform supply of metabolites. We determine this optimal inflow analytically in quantitative agreement with numerical results. Optimizing network architecture by reducing the supply variance over all network tubes, we identify patterns of tube dilation or contraction that compensate sub-optimal supply for the case of too low or too high inflow rate. © 2018 The Authors.

  18. Fruit metabolite networks in engineered and non-engineered tomato genotypes reveal fluidity in a hormone and agroecosystem specific manner.

    Science.gov (United States)

    Fatima, Tahira; Sobolev, Anatoly P; Teasdale, John R; Kramer, Matthew; Bunce, Jim; Handa, Avtar K; Mattoo, Autar K

    the pattern of changes in correlation between metabolites. Changes in primary metabolites of genotypes mutated for the deficiency of ethylene or methyl jasmonate were unique under all growth conditions and opposite of high polyamine genotype results. The high polyamine trait was found to dominate the low ethylene and low jasmonate mutations under field conditions. For several metabolites low ethylene and low methyl jasmonate genotypes had an inverse relationship. Collectively, these results affirm that interactions between metabolite pathways and growth environments are affected by genotype, and influence the metabolite quality of a crop. This study portrays how metabolite relationships change, both in mean and in correlation, under different genotypic and environmental conditions. Although these networks are surprisingly dynamic, we also find examples of selectively conserved associations.

  19. Metabolic Networks and Metabolites Underlie Associations Between Maternal Glucose During Pregnancy and Newborn Size at Birth.

    Science.gov (United States)

    Scholtens, Denise M; Bain, James R; Reisetter, Anna C; Muehlbauer, Michael J; Nodzenski, Michael; Stevens, Robert D; Ilkayeva, Olga; Lowe, Lynn P; Metzger, Boyd E; Newgard, Christopher B; Lowe, William L

    2016-07-01

    Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and nontargeted gas chromatography/mass spectrometry metabolomics on maternal serum collected at fasting and 1 h following glucose beverage consumption during an oral glucose tolerance test (OGTT) for 400 northern European mothers at ∼28 weeks' gestation in the Hyperglycemia and Adverse Pregnancy Outcome Study. Amino acids, fatty acids, acylcarnitines, and products of lipid metabolism decreased and triglycerides increased during the OGTT. Analyses of individual metabolites indicated limited maternal glucose associations at fasting, but broader associations, including amino acids, fatty acids, carbohydrates, and lipids, were found at 1 h. Network analyses modeling metabolite correlations provided context for individual metabolite associations and elucidated collective associations of multiple classes of metabolic fuels with newborn size and adiposity, including acylcarnitines, fatty acids, carbohydrates, and organic acids. Random forest analyses indicated an improved ability to predict newborn size outcomes by using maternal metabolomics data beyond traditional risk factors, including maternal glucose. Broad-scale association of fuel metabolites with maternal glucose is evident during pregnancy, with unique maternal metabolites potentially contributing specifically to newborn birth weight and adiposity. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. Contribution of Network Connectivity in Determining the Relationship between Gene Expression and Metabolite Concentration Changes

    DEFF Research Database (Denmark)

    Zelezniak, Aleksej; Sheridan, Steven; Patil, Kiran Raosaheb

    2014-01-01

    biological perturbations, namely gene knockout, nutrient shock and nutrient change. While the kinetic constraints applied at the level of individual reactions were found to be poor descriptors of the mRNA-metabolite relationship, their use in the context of the network enabled us to correlate changes...

  1. Plasma and Serum Metabolite Association Networks: Comparability within and between Studies Using NMR and MS Profiling.

    Science.gov (United States)

    Suarez-Diez, Maria; Adam, Jonathan; Adamski, Jerzy; Chasapi, Styliani A; Luchinat, Claudio; Peters, Annette; Prehn, Cornelia; Santucci, Claudio; Spyridonidis, Alexandros; Spyroulias, Georgios A; Tenori, Leonardo; Wang-Sattler, Rui; Saccenti, Edoardo

    2017-07-07

    Blood is one of the most used biofluids in metabolomics studies, and the serum and plasma fractions are routinely used as a proxy for blood itself. Here we investigated the association networks of an array of 29 metabolites identified and quantified via NMR in the plasma and serum samples of two cohorts of ∼1000 healthy blood donors each. A second study of 377 individuals was used to extract plasma and serum samples from the same individual on which a set of 122 metabolites were detected and quantified using FIA-MS/MS. Four different inference algorithms (ARANCE, CLR, CORR, and PCLRC) were used to obtain consensus networks. The plasma and serum networks obtained from different studies showed different topological properties with the serum network being more connected than the plasma network. On a global level, metabolite association networks from plasma and serum fractions obtained from the same blood sample of healthy people show similar topologies, and at a local level, some differences arise like in the case of amino acids.

  2. 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. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. A Computational Solution to Automatically Map Metabolite Libraries in the Context of Genome Scale Metabolic Networks.

    Science.gov (United States)

    Merlet, Benjamin; Paulhe, Nils; Vinson, Florence; Frainay, Clément; Chazalviel, Maxime; Poupin, Nathalie; Gloaguen, Yoann; Giacomoni, Franck; Jourdan, Fabien

    2016-01-01

    This article describes a generic programmatic method for mapping chemical compound libraries on organism-specific metabolic networks from various databases (KEGG, BioCyc) and flat file formats (SBML and Matlab files). We show how this pipeline was successfully applied to decipher the coverage of chemical libraries set up by two metabolomics facilities MetaboHub (French National infrastructure for metabolomics and fluxomics) and Glasgow Polyomics (GP) on the metabolic networks available in the MetExplore web server. The present generic protocol is designed to formalize and reduce the volume of information transfer between the library and the network database. Matching of metabolites between libraries and metabolic networks is based on InChIs or InChIKeys and therefore requires that these identifiers are specified in both libraries and networks. In addition to providing covering statistics, this pipeline also allows the visualization of mapping results in the context of metabolic networks. In order to achieve this goal, we tackled issues on programmatic interaction between two servers, improvement of metabolite annotation in metabolic networks and automatic loading of a mapping in genome scale metabolic network analysis tool MetExplore. It is important to note that this mapping can also be performed on a single or a selection of organisms of interest and is thus not limited to large facilities.

  4. Computational solution to automatically map metabolite libraries in the context of genome scale metabolic networks

    Directory of Open Access Journals (Sweden)

    Benjamin eMerlet

    2016-02-01

    Full Text Available This article describes a generic programmatic method for mapping chemical compound libraries on organism-specific metabolic networks from various databases (KEGG, BioCyc and flat file formats (SBML and Matlab files. We show how this pipeline was successfully applied to decipher the coverage of chemical libraries set up by two metabolomics facilities MetaboHub (French National infrastructure for metabolomics and fluxomics and Glasgow Polyomics on the metabolic networks available in the MetExplore web server. The present generic protocol is designed to formalize and reduce the volume of information transfer between the library and the network database. Matching of metabolites between libraries and metabolic networks is based on InChIs or InChIKeys and therefore requires that these identifiers are specified in both libraries and networks.In addition to providing covering statistics, this pipeline also allows the visualization of mapping results in the context of metabolic networks.In order to achieve this goal we tackled issues on programmatic interaction between two servers, improvement of metabolite annotation in metabolic networks and automatic loading of a mapping in genome scale metabolic network analysis tool MetExplore. It is important to note that this mapping can also be performed on a single or a selection of organisms of interest and is thus not limited to large facilities.

  5. Toxic Diatom Aldehydes Affect Defence Gene Networks in Sea Urchins.

    Science.gov (United States)

    Varrella, Stefano; Romano, Giovanna; Costantini, Susan; Ruocco, Nadia; Ianora, Adrianna; Bentley, Matt G; Costantini, Maria

    2016-01-01

    Marine organisms possess a series of cellular strategies to counteract the negative effects of toxic compounds, including the massive reorganization of gene expression networks. Here we report the modulated dose-dependent response of activated genes by diatom polyunsaturated aldehydes (PUAs) in the sea urchin Paracentrotus lividus. PUAs are secondary metabolites deriving from the oxidation of fatty acids, inducing deleterious effects on the reproduction and development of planktonic and benthic organisms that feed on these unicellular algae and with anti-cancer activity. Our previous results showed that PUAs target several genes, implicated in different functional processes in this sea urchin. Using interactomic Ingenuity Pathway Analysis we now show that the genes targeted by PUAs are correlated with four HUB genes, NF-κB, p53, δ-2-catenin and HIF1A, which have not been previously reported for P. lividus. We propose a working model describing hypothetical pathways potentially involved in toxic aldehyde stress response in sea urchins. This represents the first report on gene networks affected by PUAs, opening new perspectives in understanding the cellular mechanisms underlying the response of benthic organisms to diatom exposure.

  6. Toxic Diatom Aldehydes Affect Defence Gene Networks in Sea Urchins.

    Directory of Open Access Journals (Sweden)

    Stefano Varrella

    Full Text Available Marine organisms possess a series of cellular strategies to counteract the negative effects of toxic compounds, including the massive reorganization of gene expression networks. Here we report the modulated dose-dependent response of activated genes by diatom polyunsaturated aldehydes (PUAs in the sea urchin Paracentrotus lividus. PUAs are secondary metabolites deriving from the oxidation of fatty acids, inducing deleterious effects on the reproduction and development of planktonic and benthic organisms that feed on these unicellular algae and with anti-cancer activity. Our previous results showed that PUAs target several genes, implicated in different functional processes in this sea urchin. Using interactomic Ingenuity Pathway Analysis we now show that the genes targeted by PUAs are correlated with four HUB genes, NF-κB, p53, δ-2-catenin and HIF1A, which have not been previously reported for P. lividus. We propose a working model describing hypothetical pathways potentially involved in toxic aldehyde stress response in sea urchins. This represents the first report on gene networks affected by PUAs, opening new perspectives in understanding the cellular mechanisms underlying the response of benthic organisms to diatom exposure.

  7. Metabolic Networks and Metabolites Underlie Associations Between Maternal Glucose During Pregnancy and Newborn Size at Birth

    OpenAIRE

    Scholtens, Denise M.; Bain, James R.; Reisetter, Anna C.; Muehlbauer, Michael J.; Nodzenski, Michael; Stevens, Robert D.; Ilkayeva, Olga; Lowe, Lynn P.; Metzger, Boyd E.; Newgard, Christopher B.; Lowe, William L.

    2016-01-01

    Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and nontargeted gas chromatography/mass spectrometry metabolomics on maternal serum collected at fasting and 1 h following glucose beverage consumption during an oral glucose tolerance test (OGTT) for 400 northern European mothers at ?28 weeks' gestation in the Hyperglycemia and Adverse Pregna...

  8. Gene-metabolite network analysis in different nonalcoholic fatty liver disease phenotypes.

    Science.gov (United States)

    Liu, Xiao-Lin; Ming, Ya-Nan; Zhang, Jing-Yi; Chen, Xiao-Yu; Zeng, Min-De; Mao, Yi-Min

    2017-01-13

    We sought to identify common key regulators and build a gene-metabolite network in different nonalcoholic fatty liver disease (NAFLD) phenotypes. We used a high-fat diet (HFD), a methionine-choline-deficient diet (MCDD) and streptozocin (STZ) to establish nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH) and NAFL+type 2 diabetes mellitus (T2DM) in rat models, respectively. Transcriptomics and metabolomics analyses were performed in rat livers and serum. A functional network-based regulation model was constructed using Cytoscape with information derived from transcriptomics and metabolomics. The results revealed that 96 genes, 17 liver metabolites and 4 serum metabolites consistently changed in different NAFLD phenotypes (>2-fold, Pmetabolism in HFD models, the inflammatory and immune response in MCDD models, and the AMPK signaling pathway and response to insulin in HFD+STZ models. Our study identified networks showing the general and specific characteristics in different NAFLD phenotypes, complementing the genetic and metabolic features in NAFLD with hepatic and extra-hepatic manifestations.

  9. Cultivar and Year Rather than Agricultural Practices Affect Primary and Secondary Metabolites in Apple Fruit.

    Directory of Open Access Journals (Sweden)

    Carine Le Bourvellec

    Full Text Available Many biotic and abiotic parameters affect the metabolites involved in the organoleptic and health value of fruits. It is therefore important to understand how the growers' decisions for cultivar and orchard management can affect the fruit composition. Practices, cultivars and/or year all might participate to determine fruit composition. To hierarchize these factors, fruit weight, dry matter, soluble solids contents, titratable acidity, individual sugars and organics acids, and phenolics were measured in three apple cultivars ('Ariane', 'Melrose' and 'Smoothee' managed under organic, low-input and conventional management. Apples were harvested at commercial maturity in the orchards of the cropping system experiment BioREco at INRA Gotheron (Drôme, 26 over the course of three years (2011, 2012 and 2013. The main factors affecting primary and secondary metabolites, in both apple skin and flesh, were by far the cultivar and the yearly conditions, while the management system had a very limited effect. When considering the three cultivars and the year 2011 to investigate the effect of the management system per se, only few compounds differed significantly between the three systems and in particular the total phenolic content did not differ significantly between systems. Finally, when considering orchards grown in the same pedoclimatic conditions and of the same age, instead of the usual organic vs. conventional comparison, the effect of the management system on the apple fruit quality (Fruit weight, dry matter, soluble solids content, titratable acidity, individual sugars, organic acids, and phenolics was very limited to non-significant. The main factors of variation were the cultivar and the year of cropping rather than the cropping system. More generally, as each management system (e.g. conventional, organic… encompasses a great variability of practices, this highlights the importance of accurately documenting orchard practices and design beside

  10. Cultivar and Year Rather than Agricultural Practices Affect Primary and Secondary Metabolites in Apple Fruit.

    Science.gov (United States)

    Le Bourvellec, Carine; Bureau, Sylvie; Renard, Catherine M G C; Plenet, Daniel; Gautier, Hélène; Touloumet, Line; Girard, Thierry; Simon, Sylvaine

    2015-01-01

    Many biotic and abiotic parameters affect the metabolites involved in the organoleptic and health value of fruits. It is therefore important to understand how the growers' decisions for cultivar and orchard management can affect the fruit composition. Practices, cultivars and/or year all might participate to determine fruit composition. To hierarchize these factors, fruit weight, dry matter, soluble solids contents, titratable acidity, individual sugars and organics acids, and phenolics were measured in three apple cultivars ('Ariane', 'Melrose' and 'Smoothee') managed under organic, low-input and conventional management. Apples were harvested at commercial maturity in the orchards of the cropping system experiment BioREco at INRA Gotheron (Drôme, 26) over the course of three years (2011, 2012 and 2013). The main factors affecting primary and secondary metabolites, in both apple skin and flesh, were by far the cultivar and the yearly conditions, while the management system had a very limited effect. When considering the three cultivars and the year 2011 to investigate the effect of the management system per se, only few compounds differed significantly between the three systems and in particular the total phenolic content did not differ significantly between systems. Finally, when considering orchards grown in the same pedoclimatic conditions and of the same age, instead of the usual organic vs. conventional comparison, the effect of the management system on the apple fruit quality (Fruit weight, dry matter, soluble solids content, titratable acidity, individual sugars, organic acids, and phenolics) was very limited to non-significant. The main factors of variation were the cultivar and the year of cropping rather than the cropping system. More generally, as each management system (e.g. conventional, organic…) encompasses a great variability of practices, this highlights the importance of accurately documenting orchard practices and design beside the generic

  11. How does P affect photosynthesis and metabolite profiles of Eucalyptus globulus?

    Science.gov (United States)

    Warren, Charles R

    2011-07-01

    Phosphorus (P) has multiple effects on plant metabolism, but there are many unresolved questions especially for evergreen trees. For example, we do not know the general effects of P on metabolism, or if P affects photosynthesis via the internal conductance to CO(2) transfer from sub-stomatal cavities to chloroplast or amounts of Rubisco. This study investigates how P deficiency affects seedlings of the evergreen tree Eucalyptus globulus grown for 2.5 months with four nutrient solutions differing in P concentration. To determine why photosynthesis was affected by P supply, Rubisco was quantified by capillary electrophoresis, internal conductance was quantified from gas exchange and carbon isotope discrimination, and biochemical parameters of photosynthesis were estimated from A/C(c) responses. Additional insights into the effect of P on metabolism were provided by gas chromatography-mass spectrometry (GC-MS) metabolite profiling. Larger concentrations of P in the nutrient solution led to significantly faster rates of photosynthesis. There was no evidence that stomatal or internal conductances contributed to the effect of P supply on photosynthesis. The increase in photosynthesis with P supply was correlated with V(cmax), and amounts of P, phosphate and fructose 6-phosphate (6-P). Phosphorous supply affected approximately one-third of the 90 aqueous metabolites quantified by GC-MS, but the effect size was generally smaller than reported for experiments on herbaceous species. Phosphorus deficiency decreased concentrations of phosphate, glucose 6-P and fructose 6-P more than it decreased photosynthesis, suggesting faster turnover of smaller pools of phosphate and phosphorylated intermediates. The effect of P supply on most amino acids was small, with the exception of arginine and glutamine, which increased dramatically under P deficiency. P deficiency had small or non-significant effects on carbohydrates and organic acids of the tricarboxylic acid (TCA) cycle. The

  12. Inferring the metabolism of human orphan metabolites from their metabolic network context affirms human gluconokinase activity.

    Science.gov (United States)

    Rolfsson, Óttar; Paglia, Giuseppe; Magnusdóttir, Manuela; Palsson, Bernhard Ø; Thiele, Ines

    2013-01-15

    Metabolic network reconstructions define metabolic information within a target organism and can therefore be used to address incomplete metabolic information. In the present study we used a computational approach to identify human metabolites whose metabolism is incomplete on the basis of their detection in humans but exclusion from the human metabolic network reconstruction RECON 1. Candidate solutions, composed of metabolic reactions capable of explaining the metabolism of these compounds, were then identified computationally from a global biochemical reaction database. Solutions were characterized with respect to how metabolites were incorporated into RECON 1 and their biological relevance. Through detailed case studies we show that biologically plausible non-intuitive hypotheses regarding the metabolism of these compounds can be proposed in a semi-automated manner, in an approach that is similar to de novo network reconstruction. We subsequently experimentally validated one of the proposed hypotheses and report that C9orf103, previously identified as a candidate tumour suppressor gene, encodes a functional human gluconokinase. The results of the present study demonstrate how semi-automatic gap filling can be used to refine and extend metabolic reconstructions, thereby increasing their biological scope. Furthermore, we illustrate how incomplete human metabolic knowledge can be coupled with gene annotation in order to prioritize and confirm gene functions.

  13. Interactions between Plant Metabolites Affect Herbivores: A Study with Pyrrolizidine Alkaloids and Chlorogenic Acid

    Science.gov (United States)

    Liu, Xiaojie; Vrieling, Klaas; Klinkhamer, Peter G.L.

    2017-01-01

    The high structural diversity of plant metabolites suggests that interactions among them should be common. We investigated the effects of single metabolites and combinations of plant metabolites on insect herbivores. In particular we studied the interacting effects of pyrrolizidine alkaloid (PAs), and chlorogenic acid (CGA), on a generalist herbivore, Frankliniella occidentalis. We studied both the predominantly occurring PA N-oxides and the less frequent PA free bases. We found antagonistic effects between CGA and PA free bases on thrips mortality. In contrast PA N-oxides showed synergistic interactions with CGA. PA free bases caused a higher thrips mortality than PA N-oxides while the reverse was through for PAs in combination with CGA. Our results provide an explanation for the predominate storage of PA N-oxides in plants. We propose that antagonistic interactions represent a constraint on the accumulation of plant metabolites, as we found here for Jacobaea vulgaris. The results show that the bioactivity of a given metabolite is not merely dependent upon the amount and chemical structure of that metabolite, but also on the co-occurrence metabolites in, e.g., plant cells, tissues and organs. The significance of this study is beyond the concerns of the two specific groups tested here. The current study is one of the few studies so far that experimentally support the general conception that the interactions among plant metabolites are of great importance to plant-environment interactions. PMID:28611815

  14. Interactions between Plant Metabolites Affect Herbivores: A Study with Pyrrolizidine Alkaloids and Chlorogenic Acid

    Directory of Open Access Journals (Sweden)

    Xiaojie Liu

    2017-05-01

    Full Text Available The high structural diversity of plant metabolites suggests that interactions among them should be common. We investigated the effects of single metabolites and combinations of plant metabolites on insect herbivores. In particular we studied the interacting effects of pyrrolizidine alkaloid (PAs, and chlorogenic acid (CGA, on a generalist herbivore, Frankliniella occidentalis. We studied both the predominantly occurring PA N-oxides and the less frequent PA free bases. We found antagonistic effects between CGA and PA free bases on thrips mortality. In contrast PA N-oxides showed synergistic interactions with CGA. PA free bases caused a higher thrips mortality than PA N-oxides while the reverse was through for PAs in combination with CGA. Our results provide an explanation for the predominate storage of PA N-oxides in plants. We propose that antagonistic interactions represent a constraint on the accumulation of plant metabolites, as we found here for Jacobaea vulgaris. The results show that the bioactivity of a given metabolite is not merely dependent upon the amount and chemical structure of that metabolite, but also on the co-occurrence metabolites in, e.g., plant cells, tissues and organs. The significance of this study is beyond the concerns of the two specific groups tested here. The current study is one of the few studies so far that experimentally support the general conception that the interactions among plant metabolites are of great importance to plant-environment interactions.

  15. Reconstruction of biological pathways and metabolic networks from in silico labeled metabolites.

    Science.gov (United States)

    Hadadi, Noushin; Hafner, Jasmin; Soh, Keng Cher; Hatzimanikatis, Vassily

    2017-01-01

    Reaction atom mappings track the positional changes of all of the atoms between the substrates and the products as they undergo the biochemical transformation. However, information on atom transitions in the context of metabolic pathways is not widely available in the literature. The understanding of metabolic pathways at the atomic level is of great importance as it can deconvolute the overlapping catabolic/anabolic pathways resulting in the observed metabolic phenotype. The automated identification of atom transitions within a metabolic network is a very challenging task since the degree of complexity of metabolic networks dramatically increases when we transit from metabolite-level studies to atom-level studies. Despite being studied extensively in various approaches, the field of atom mapping of metabolic networks is lacking an automated approach, which (i) accounts for the information of reaction mechanism for atom mapping and (ii) is extendable from individual atom-mapped reactions to atom-mapped reaction networks. Hereby, we introduce a computational framework, iAM.NICE (in silico Atom Mapped Network Integrated Computational Explorer), for the systematic atom-level reconstruction of metabolic networks from in silico labelled substrates. iAM.NICE is to our knowledge the first automated atom-mapping algorithm that is based on the underlying enzymatic biotransformation mechanisms, and its application goes beyond individual reactions and it can be used for the reconstruction of atom-mapped metabolic networks. We illustrate the applicability of our method through the reconstruction of atom-mapped reactions of the KEGG database and we provide an example of an atom-level representation of the core metabolic network of E. coli. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Brain Networks Implicated in Seasonal Affective Disorder

    DEFF Research Database (Denmark)

    Nørgaard, Martin; Ganz, Melanie; Svarer, Claus

    2017-01-01

    , patients with SAD fail to globally downregulate their cerebral serotonin transporter (5-HTT) in winter, and that this effect seemed to be particularly pronounced in female S-carriers of the 5-HTTLPR genotype. The purpose of this study was to identify a 5-HTT brain network that accounts for the adaption...... to the environmental stressor of winter in females with the short 5-HTTLPR genotype, a specific subgroup previously reported to be at increased risk for developing SAD. Methods: Nineteen females, either S' carriers (LG- and S-carriers) without SAD (N = 13, mean age 23.6 ± 3.2 year, range 19-28) or S' carriers with SAD...... (N = 6, mean age 23.7 ± 2.4, range 21-26) were PET-scanned with [11C]DASB during both summer and winter seasons (asymptomatic and symptomatic phase, 38 scans in total) in randomized order, defined as a 12-week interval centered on summer or winter solstice. We used a multivariate Partial Least...

  17. Drugs with antidepressant properties affect tryptophan metabolites differently in rodent models with depression-like behavior.

    Science.gov (United States)

    Eskelund, Amanda; Li, Yan; Budac, David P; Müller, Heidi K; Gulinello, Maria; Sanchez, Connie; Wegener, Gregers

    2017-07-01

    The metabolism of tryptophan through kynurenine and serotonin pathways is linked to depression. Here, effects of different drugs with antidepressant properties (vortioxetine, fluoxetine, and ketamine) on various tryptophan metabolites in different brain regions and plasma were examined using tandem mass spectrometry (LC-MS/MS), in Flinders Sensitive Line rats, a genetic rat model of depression, and its controls: Flinders Sensitive Line and Sprague-Dawley rats. Protein levels of kynurenine pathway enzymes were measured in the brains and livers of these rat strains. Furthermore, effects of vortioxetine on tryptophan metabolites were assessed in the cortical regions of lupus mice (MRL/MpJ-Fas Ipr ), a murine model of increased depression-like behavior associated with inflammation. Sustained vortioxetine or fluoxetine (at doses aimed to fully occupy serotonin transporter via food or drinking water for at least 14 days) reduced levels of the excitotoxin quinolinic acid (QUIN) in various brain regions in all rats. Furthermore, chronic vortioxetine reduced levels of QUIN in MRL/MpJ-Fas Ipr mice. Acute i.p. administration of fluoxetine (10 mg/kg) or vortioxetine (10 mg/kg) led to reduced brain 5-hydroxyindoleacetic acid in Sprague-Dawley rats (2, 4, 6, and 8 h) and a similar trend was evident in Flinders Sensitive Line and Flinders Sensitive Line rats after 4 h. In contrast, single or repeated administration of ketamine (15 mg/kg i.p.) did not induce significant changes in metabolite levels. In conclusion, sustained vortioxetine and fluoxetine administration decreased QUIN independent of species, while ketamine was ineffective. These results support the hypothesis that modulating tryptophan metabolism may be part of the mechanism of action for some antidepressants. © 2017 International Society for Neurochemistry.

  18. Heat and light stresses affect metabolite production in the fruit body of the medicinal mushroom Cordyceps militaris.

    Science.gov (United States)

    Jiaojiao, Zhang; Fen, Wang; Kuanbo, Liu; Qing, Liu; Ying, Yang; Caihong, Dong

    2018-03-29

    Cordyceps militaris is a highly valued edible and medicinal fungus due to its production of various metabolites, including adenosine, cordycepin, N 6 -(2-hydroxyethyl)-adenosine, and carotenoids. The contents of these metabolites are indicative of the quality of commercially available fruit body of this fungus. In this work, the effects of environmental abiotic factors, including heat and light stresses, on the fruit body growth and metabolite production in C. militaris were evaluated during the late growth stage. The optimal growth temperature of C. militaris was 20 °C. It was found that a heat stress of 25 °C for 5-20 days during the late growth stage significantly promoted cordycepin and carotenoid production without affecting the biological efficiency. Light stress at 6000 lx for 5-20 days during the late growth stage significantly promoted cordycepin production but decreased the carotenoid content. Both heat and light stresses promoted N 6 -(2-hydroxyethyl)-adenosine production. In addition, gene expression analysis showed that there were simultaneous increases in the expression of genes encoding a metal-dependent phosphohydrolase (CCM_04437) and ATP phosphoribosyltransferase (CCM_04438) that are involved in the cordycepin biosynthesis pathway, which was consistent with the accumulation of cordycepin during heat stress for 5-20 days. A positive weak correlation between the cordycepin and adenosine contents was observed with a Pearson correlation coefficient of 0.338 (P < 0.05). The results presented herein provide a new strategy for the production of a superior quality fruit body of C. militaris and contribute to further elucidation of the effects of abiotic stress on metabolite accumulation in fungi.

  19. Production performance and plasma metabolites of dairy ewes in early lactation as affected by chitosan

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Rodriguez, A.; Arranz, J.; Mandaluniz, N.; Beltrán-de-Heredia, I.; Ruiz, R.; Goiri, I.

    2015-07-01

    The objective of this study was to evaluate the effects of chitosan (CHI) supplementation on production performance and blood parameters in dairy ewes. Twenty-four multiparous Latxa dairy ewes at d 16 of lactation were divided into two groups of 12 ewes each. Ewes were fed one of two experimental concentrates (0.840 kg dry matter/d), control or supplemented with 1.2% CHI, on a dry matter basis. Ewes also had free access to tall fescue hay, water, and mineral salts. The experimental period lasted for 25 d, of which the first 14 d were for treatment adaptation and the last 11 d for measurements and samplings. Supplementation with CHI decreased total (p=0.043) and fescue (p=0.035) dry matter intake (DMI), but did not affect concentrate DMI. Supplementation with CHI, moreover, increased plasma glucose (p=0.013) and BUN concentrations (p=0.035), but did not affect those of non-esterified fatty acids. Dietary supplementation with CHI, however, did not affect milk yield, 6.5% FCM, milk composition, or BW, but it improved dietary apparent efficiency by increasing the milk yield-to-DMI (p=0.055) and 6.5% FCM-to-DMI (p=0.045) ratios. In conclusion, dietary supplementation of chitosan maintained ewe performance while reducing feed intake and improving dietary apparent efficiency. (Author)

  20. Factors Affecting Green Residential Building Development: Social Network Analysis

    Directory of Open Access Journals (Sweden)

    Xiaodong Yang

    2018-05-01

    Full Text Available Green residential buildings (GRBs are one of the effective practices of energy saving and emission reduction in the construction industry. However, many real estate developers in China are less willing to develop GRBs, because of the factors affecting green residential building development (GRBD. In order to promote the sustainable development of GRBs in China, this paper, based on the perspective of real estate developers, identifies the influential and critical factors affecting GRBD, using the method of social network analysis (SNA. Firstly, 14 factors affecting GRBD are determined from 64 preliminary factors of three main elements, and the framework is established. Secondly, the relationships between the 14 factors are analyzed by SNA. Finally, four critical factors for GRBD, which are on the local economy development level, development strategy and innovation orientation, developer’s acknowledgement and positioning for GRBD, and experience and ability for GRBD, are identified by the social network centrality test. The findings illustrate the key issues that affect the development of GRBs, and provide references for policy making by the government and strategy formulation by real estate developers.

  1. Drought stress affects plant metabolites and herbivore preference but not host location by its parasitoids.

    Science.gov (United States)

    Weldegergis, Berhane T; Zhu, Feng; Poelman, Erik H; Dicke, Marcel

    2015-03-01

    One of the main abiotic stresses that strongly affects plant survival and the primary cause of crop loss around the world is drought. Drought stress leads to sequential morphological, physiological, biochemical and molecular changes that can have severe effects on plant growth, development and productivity. As a consequence of these changes, the interaction between plants and insects can be altered. Using cultivated Brassica oleracea plants, the parasitoid Microplitis mediator and its herbivorous host Mamestra brassicae, we studied the effect of drought stress on (1) the emission of plant volatile organic compounds (VOCs), (2) plant hormone titres, (3) preference and performance of the herbivore, and (4) preference of the parasitoid. Higher levels of jasmonic acid (JA) and abscisic acid (ABA) were recorded in response to herbivory, but no significant differences were observed for salicylic acid (SA) and indole-3-acetic acid (IAA). Drought significantly impacted SA level and showed a significant interactive effect with herbivory for IAA levels. A total of 55 VOCs were recorded and the difference among the treatments was influenced largely by herbivory, where the emission rate of fatty acid-derived volatiles, nitriles and (E)-4,8-dimethylnona-1,3,7-triene [(E)-DMNT] was enhanced. Mamestra brassicae moths preferred to lay eggs on drought-stressed over control plants; their offspring performed similarly on plants of both treatments. VOCs due to drought did not affect the choice of M. mediator parasitoids. Overall, our study reveals an influence of drought on plant chemistry and insect-plant interactions.

  2. Affective network and default mode network in depressive adolescents with disruptive behaviors.

    Science.gov (United States)

    Kim, Sun Mi; Park, Sung Yong; Kim, Young In; Son, Young Don; Chung, Un-Sun; Min, Kyung Joon; Han, Doug Hyun

    2016-01-01

    Disruptive behaviors are thought to affect the progress of major depressive disorder (MDD) in adolescents. In resting-state functional connectivity (RSFC) studies of MDD, the affective network (limbic network) and the default mode network (DMN) have garnered a great deal of interest. We aimed to investigate RSFC in a sample of treatment-naïve adolescents with MDD and disruptive behaviors. Twenty-two adolescents with MDD and disruptive behaviors (disrup-MDD) and 20 age- and sex-matched healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). We used a seed-based correlation approach concerning two brain circuits including the affective network and the DMN, with two seed regions including the bilateral amygdala for the limbic network and the bilateral posterior cingulate cortex (PCC) for the DMN. We also observed a correlation between RSFC and severity of depressive symptoms and disruptive behaviors. The disrup-MDD participants showed lower RSFC from the amygdala to the orbitofrontal cortex and parahippocampal gyrus compared to HC participants. Depression scores in disrup-MDD participants were negatively correlated with RSFC from the amygdala to the right orbitofrontal cortex. The disrup-MDD participants had higher PCC RSFC compared to HC participants in a cluster that included the left precentral gyrus, left insula, and left parietal lobe. Disruptive behavior scores in disrup-MDD patients were positively correlated with RSFC from the PCC to the left insular cortex. Depressive mood might be correlated with the affective network, and disruptive behavior might be correlated with the DMN in adolescent depression.

  3. Tripartite purinergic modulation of central respiratory networks during perinatal development: the influence of ATP, ectonucleotidases, and ATP metabolites.

    Science.gov (United States)

    Huxtable, Adrianne G; Zwicker, Jennifer D; Poon, Betty Y; Pagliardini, Silvia; Vrouwe, Sebastian Q; Greer, John J; Funk, Gregory D

    2009-11-25

    ATP released during hypoxia from the ventrolateral medulla activates purinergic receptors (P2Rs) to attenuate the secondary hypoxic depression of breathing by a mechanism that likely involves a P2Y(1)R-mediated excitation of preBötzinger complex (preBötC) inspiratory rhythm-generating networks. In this study, we used rhythmically active in vitro preparations from embryonic and postnatal rats and ATP microinjection into the rostral ventral respiratory group (rVRG)/preBötC to reveal that these networks are sensitive to ATP when rhythm emerges at embryonic day 17 (E17). The peak frequency elicited by ATP at E19 and postnatally was the same ( approximately 45 bursts/min), but relative sensitivity was threefold greater at E19, reflecting a lower baseline frequency (5.6 +/- 0.9 vs 19.0 +/- 1.3 bursts/min). Combining microinjection techniques with ATP biosensors revealed that ATP concentration in the rVRG/preBötC falls rapidly as a result of active processes and closely correlates with inspiratory frequency. A phosphate assay established that preBötC-containing tissue punches degrade ATP at rates that increase perinatally. Thus, the agonist profile [ATP/ADP/adenosine (ADO)] produced after ATP release in the rVRG/preBötC will change perinatally. Electrophysiology further established that the ATP metabolite ADP is excitatory and that, in fetal but not postnatal animals, ADO at A(1) receptors exerts a tonic depressive action on rhythm, whereas A(1) antagonists extend the excitatory action of ATP on inspiratory rhythm. These data demonstrate that ATP is a potent excitatory modulator of the rVRG/preBötC inspiratory network from the time it becomes active and that ATP actions are determined by a dynamic interaction between the actions of ATP at P2 receptors, ectonucleotidases that degrade ATP, and ATP metabolites on P2Y and P1 receptors.

  4. Probabilistic networks of blood metabolites in healthy subjects as indicators of latent cardiovascular risk

    NARCIS (Netherlands)

    Saccenti, E.; Suarez Diez, M.; Luchinat, C.; Santucci, C.; Tenori, L.

    2015-01-01

    The complex nature of the mechanisms behind cardiovascular diseases prevents the detection of latent early risk conditions. Network representations are ideally suited to investigate the complex interconnections between the individual components of a biological system underlying complex diseases.

  5. Pyrethroid Pesticide Metabolite in Urine and Microelements in Hair of Children Affected by Autism Spectrum Disorders: A Preliminary Investigation

    Directory of Open Access Journals (Sweden)

    Valentina F. Domingues

    2016-03-01

    Full Text Available The number of children affected by Autism Spectrum Disorders (ASD is dramatically increasing as well as the studies aimed at understanding the risk factors associated with the development of ASD. Since the etiology of ASD is partly genetic and partly environmental, factors (i.e., heavy metals, pesticides as well as lifestyle seem to have a key role in the development of the disease. ASD and Control (CTR children, aged 5–12 years, were compared. Gas chromatography coupled with trap mass detector was used to measure the level of 3-PBA, the main pyrethroid metabolite in urine in a group of ASD patients, while optical emission spectrometry analysis was employed to estimate the level of metals and microelements in hair in a different group of ASD children. The presence of 3-PBA in urine seems to be independent of age in ASD children, while a positive correlation between 3-PBA and age was observed in the control group of the same age range. Urine concentration of 3-BPA in ASD children had higher values than in the control group, which were marginally significant (p = 0.054. Mg results were significantly decreased in ASD with respect to controls, while V, S, Zn, and Ca/Mg were marginally increased, without reaching statistical significance. Results of Principal Component (PC analysis of metals and microelements in hair were not associated with either age or health status. In conclusion, 3-PBA in urine and Mg in hair were changed in ASD children relative to control ones.

  6. Solanum tuberosum and Lycopersicon esculentum Leaf Extracts and Single Metabolites Affect Development and Reproduction of Drosophila melanogaster.

    Science.gov (United States)

    Ventrella, Emanuela; Adamski, Zbigniew; Chudzińska, Ewa; Miądowicz-Kobielska, Mariola; Marciniak, Paweł; Büyükgüzel, Ender; Büyükgüzel, Kemal; Erdem, Meltem; Falabella, Patrizia; Scrano, Laura; Bufo, Sabino Aurelio

    2016-01-01

    Glycoalkaloids are secondary metabolites commonly found in Solanaceae plants. They have anti-bacterial, anti-fungal and insecticidal activities. In the present study we examine the effects of potato and tomato leaf extracts and their main components, the glycoalkaloids α-solanine, α-chaconine and α-tomatine, on development and reproduction of Drosophila melanogaster wild-type flies at different stages. Parental generation was exposed to five different concentrations of tested substances. The effects were examined also on the next, non-exposed generation. In the first (exposed) generation, addition of each extract reduced the number of organisms reaching the pupal and imaginal stages. Parent insects exposed to extracts and metabolites individually applied showed faster development. However, the effect was weaker in case of single metabolites than in case of exposure to extracts. An increase of developmental rate was also observed in the next, non-exposed generation. The imagoes of both generations exposed to extracts and pure metabolites showed some anomalies in body size and malformations, such as deformed wings and abdomens, smaller black abdominal zone. Our results further support the current idea that Solanaceae can be an impressive source of molecules, which could efficaciously be used in crop protection, as natural extract or in formulation of single pure metabolites in sustainable agriculture.

  7. Solanum tuberosum and Lycopersicon esculentum Leaf Extracts and Single Metabolites Affect Development and Reproduction of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Emanuela Ventrella

    Full Text Available Glycoalkaloids are secondary metabolites commonly found in Solanaceae plants. They have anti-bacterial, anti-fungal and insecticidal activities. In the present study we examine the effects of potato and tomato leaf extracts and their main components, the glycoalkaloids α-solanine, α-chaconine and α-tomatine, on development and reproduction of Drosophila melanogaster wild-type flies at different stages. Parental generation was exposed to five different concentrations of tested substances. The effects were examined also on the next, non-exposed generation. In the first (exposed generation, addition of each extract reduced the number of organisms reaching the pupal and imaginal stages. Parent insects exposed to extracts and metabolites individually applied showed faster development. However, the effect was weaker in case of single metabolites than in case of exposure to extracts. An increase of developmental rate was also observed in the next, non-exposed generation. The imagoes of both generations exposed to extracts and pure metabolites showed some anomalies in body size and malformations, such as deformed wings and abdomens, smaller black abdominal zone. Our results further support the current idea that Solanaceae can be an impressive source of molecules, which could efficaciously be used in crop protection, as natural extract or in formulation of single pure metabolites in sustainable agriculture.

  8. Solanum tuberosum and Lycopersicon esculentum Leaf Extracts and Single Metabolites Affect Development and Reproduction of Drosophila melanogaster

    Science.gov (United States)

    Ventrella, Emanuela; Adamski, Zbigniew; Chudzińska, Ewa; Miądowicz-Kobielska, Mariola; Marciniak, Paweł; Büyükgüzel, Ender; Büyükgüzel, Kemal; Erdem, Meltem; Falabella, Patrizia; Scrano, Laura; Bufo, Sabino Aurelio

    2016-01-01

    Glycoalkaloids are secondary metabolites commonly found in Solanaceae plants. They have anti-bacterial, anti-fungal and insecticidal activities. In the present study we examine the effects of potato and tomato leaf extracts and their main components, the glycoalkaloids α-solanine, α-chaconine and α-tomatine, on development and reproduction of Drosophila melanogaster wild-type flies at different stages. Parental generation was exposed to five different concentrations of tested substances. The effects were examined also on the next, non-exposed generation. In the first (exposed) generation, addition of each extract reduced the number of organisms reaching the pupal and imaginal stages. Parent insects exposed to extracts and metabolites individually applied showed faster development. However, the effect was weaker in case of single metabolites than in case of exposure to extracts. An increase of developmental rate was also observed in the next, non-exposed generation. The imagoes of both generations exposed to extracts and pure metabolites showed some anomalies in body size and malformations, such as deformed wings and abdomens, smaller black abdominal zone. Our results further support the current idea that Solanaceae can be an impressive source of molecules, which could efficaciously be used in crop protection, as natural extract or in formulation of single pure metabolites in sustainable agriculture. PMID:27213896

  9. Developmental, genetic and environmental factors affect the expression of flavonoid genes, enzymes and metabolites in strawberry fruits

    NARCIS (Netherlands)

    Carbone, F.; Preuss, A.; Vos, de C.H.; Amico, d' E.; Perrotta, G.; Bovy, A.G.; Martens, S.; Rosati, C.

    2009-01-01

    The influence of internal (genetic and developmental) and external (environmental) factors on levels of flavonoid gene transcripts, enzyme activity and metabolites was studied in fruit of six cultivated strawberry (Fragaria × ananassa Duch.) genotypes grown at two Italian locations. Gene expression

  10. GC-MS metabolic profiling of Cabernet Sauvignon and Merlot cultivars during grapevine berry development and network analysis reveals a stage- and cultivar-dependent connectivity of primary metabolites.

    Science.gov (United States)

    Cuadros-Inostroza, Alvaro; Ruíz-Lara, Simón; González, Enrique; Eckardt, Aenne; Willmitzer, Lothar; Peña-Cortés, Hugo

    Information about the total chemical composition of primary metabolites during grape berry development is scarce, as are comparative studies trying to understand to what extent metabolite modifications differ between cultivars during ripening. Thus, correlating the metabolic profiles with the changes occurring in berry development and ripening processes is essential to progress in their comprehension as well in the development of new approaches to improve fruit attributes. Here, the developmental metabolic profiling analysis across six stages from flowering to fully mature berries of two cultivars, Cabernet Sauvignon and Merlot, is reported at metabolite level. Based on a gas chromatography-mass spectrometry untargeted approach, 115 metabolites were identified and relative quantified in both cultivars. Sugars and amino acids levels show an opposite behaviour in both cultivars undergoing a highly coordinated shift of metabolite associated to primary metabolism during the stages involved in growth, development and ripening of berries. The changes are characteristic for each stage, the most pronounced ones occuring at fruit setting and pre-Veraison. They are associated to a reduction of the levels of metabolites present in the earlier corresponding stage, revealing a required catabolic activity of primary metabolites for grape berry developmental process. Network analysis revealed that the network connectivity of primary metabolites is stage- and cultivar-dependent, suggesting differences in metabolism regulation between both cultivars as the maturity process progresses. Furthermore, network analysis may represent an appropriate method to display the association between primary metabolites during berry developmental processes among different grapevine cultivars and for identifying potential biologically relevant metabolites.

  11. Gene and metabolite regulatory network analysis of early developing fruit tissues highlights new candidate genes for the control of tomato fruit composition and development.

    Science.gov (United States)

    Mounet, Fabien; Moing, Annick; Garcia, Virginie; Petit, Johann; Maucourt, Michael; Deborde, Catherine; Bernillon, Stéphane; Le Gall, Gwénaëlle; Colquhoun, Ian; Defernez, Marianne; Giraudel, Jean-Luc; Rolin, Dominique; Rothan, Christophe; Lemaire-Chamley, Martine

    2009-03-01

    Variations in early fruit development and composition may have major impacts on the taste and the overall quality of ripe tomato (Solanum lycopersicum) fruit. To get insights into the networks involved in these coordinated processes and to identify key regulatory genes, we explored the transcriptional and metabolic changes in expanding tomato fruit tissues using multivariate analysis and gene-metabolite correlation networks. To this end, we demonstrated and took advantage of the existence of clear structural and compositional differences between expanding mesocarp and locular tissue during fruit development (12-35 d postanthesis). Transcriptome and metabolome analyses were carried out with tomato microarrays and analytical methods including proton nuclear magnetic resonance and liquid chromatography-mass spectrometry, respectively. Pairwise comparisons of metabolite contents and gene expression profiles detected up to 37 direct gene-metabolite correlations involving regulatory genes (e.g. the correlations between glutamine, bZIP, and MYB transcription factors). Correlation network analyses revealed the existence of major hub genes correlated with 10 or more regulatory transcripts and embedded in a large regulatory network. This approach proved to be a valuable strategy for identifying specific subsets of genes implicated in key processes of fruit development and metabolism, which are therefore potential targets for genetic improvement of tomato fruit quality.

  12. Affective state-dependent changes in the brain functional network in major depressive disorder.

    Science.gov (United States)

    Park, Chang-hyun; Wang, Sheng-Min; Lee, Hae-Kook; Kweon, Yong-Sil; Lee, Chung Tai; Kim, Ki-Tae; Kim, Young-Joo; Lee, Kyoung-Uk

    2014-09-01

    In major depressive disorder (MDD), as a network-level disease, the pathophysiology would be displayed to a wide extent over the brain. Moreover, the network-wide changes could be dependent on the context of affective processing. In this study, we sought affective state-dependent changes of the brain functional network by applying a graph-theoretical approach to functional magnetic resonance imaging data acquired in 13 patients with MDD and 12 healthy controls who were exposed to video clips inducing the negative, neutral or positive affective state. For each affective condition, a group-wise brain functional network was constructed based on partial correlation of mean activity across subjects between brain areas. Network parameters, global and local efficiencies, were measured from the brain functional network. Compared with controls', patients' brain functional network shifted to the regular network in the topological architecture, showing decreased global efficiency and increased local efficiency, during negative and neutral affective processing. Further, the shift to the regular network in patients was most evident during negative affective processing. MDD is proposed to provoke widespread changes across the whole brain in an affective state-dependent manner, specifically in the negative affective state. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Family and Personal Networks : How a Partner and Children Affect Social Relationships

    NARCIS (Netherlands)

    Rözer, J.J.

    2016-01-01

    This books describes and explains how a romantic partner and child(-ren) affect social relationships. Whereas many scholars have studied the importance of personal networks as a resource for the individual, comparatively little is known about how social networks emerge and how network composition

  14. Ultraperformance liquid chromatography-mass spectrometry based comprehensive metabolomics combined with pattern recognition and network analysis methods for characterization of metabolites and metabolic pathways from biological data sets.

    Science.gov (United States)

    Zhang, Ai-hua; Sun, Hui; Han, Ying; Yan, Guang-li; Yuan, Ye; Song, Gao-chen; Yuan, Xiao-xia; Xie, Ning; Wang, Xi-jun

    2013-08-06

    Metabolomics is the study of metabolic changes in biological systems and provides the small molecule fingerprints related to the disease. Extracting biomedical information from large metabolomics data sets by multivariate data analysis is of considerable complexity. Therefore, more efficient and optimizing metabolomics data processing technologies are needed to improve mass spectrometry applications in biomarker discovery. Here, we report the findings of urine metabolomic investigation of hepatitis C virus (HCV) patients by high-throughput ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) coupled with pattern recognition methods (principal component analysis, partial least-squares, and OPLS-DA) and network pharmacology. A total of 20 urinary differential metabolites (13 upregulated and 7 downregulated) were identified and contributed to HCV progress, involve several key metabolic pathways such as taurine and hypotaurine metabolism, glycine, serine and threonine metabolism, histidine metabolism, arginine and proline metabolism, and so forth. Metabolites identified through metabolic profiling may facilitate the development of more accurate marker algorithms to better monitor disease progression. Network analysis validated close contact between these metabolites and implied the importance of the metabolic pathways. Mapping altered metabolites to KEGG pathways identified alterations in a variety of biological processes mediated through complex networks. These findings may be promising to yield a valuable and noninvasive tool that insights into the pathophysiology of HCV and to advance the early diagnosis and monitor the progression of disease. Overall, this investigation illustrates the power of the UPLC-MS platform combined with the pattern recognition and network analysis methods that can engender new insights into HCV pathobiology.

  15. Mild hypoxia affects synaptic connectivity in cultured neuronal networks.

    Science.gov (United States)

    Hofmeijer, Jeannette; Mulder, Alex T B; Farinha, Ana C; van Putten, Michel J A M; le Feber, Joost

    2014-04-04

    Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting from chronic heart failure or pulmonary disease have cognitive impairment. Overt structural neuronal damage is lacking and the precise cause of neuronal damage is unclear. As almost half of the cerebral energy consumption is used for synaptic transmission, and synaptic failure is the first abrupt consequence of acute complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic functioning in patients is problematic, we use cultured networks of cortical neurons from new born rats, grown over a multi-electrode array, as a model system. These were exposed to partial hypoxia (partial oxygen pressure of 150Torr lowered to 40-50Torr) during 3 (n=14) or 6 (n=8) hours. Synaptic functioning was assessed before, during, and after hypoxia by assessment of spontaneous network activity, functional connectivity, and synaptically driven network responses to electrical stimulation. Action potential heights and shapes and non-synaptic stimulus responses were used as measures of individual neuronal integrity. During hypoxia of 3 and 6h, there was a statistically significant decrease of spontaneous network activity, functional connectivity, and synaptically driven network responses, whereas direct responses and action potentials remained unchanged. These changes were largely reversible. Our results indicate that in cultured neuronal networks, partial hypoxia during 3 or 6h causes isolated disturbances of synaptic connectivity. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. The concentration of plasma metabolites varies throughout reproduction and affects offspring number in wild brown trout (Salmo trutta).

    Science.gov (United States)

    Gauthey, Zoé; Freychet, Marine; Manicki, Aurélie; Herman, Alexandre; Lepais, Olivier; Panserat, Stéphane; Elosegi, Arturo; Tentelier, Cédric; Labonne, Jacques

    2015-06-01

    In wild populations, measuring energy invested in the reproduction and disentangling investment in gametes versus investment in reproductive behavior (such as intrasexual competition or intersexual preference) remain challenging. In this study, we investigated the energy expenditure in brown trout reproductive behavior by using two proxies: variation in weight and variation of plasma metabolites involved in energy production, over the course of reproductive season in a semi natural experimental river. We estimated overall reproductive success using genetic assignment at the end of the reproductive season. Results show that triglycerides and free fatty acid concentrations vary negatively during reproduction, while amino-acids and glucose concentrations remain stable. Decrease in triglyceride and free fatty acid concentrations during reproduction is not related to initial concentration levels or to weight variation. Both metabolite concentration variations and weight variations are correlated to the number of offspring produced, which could indicate that gametic and behavioral reproductive investments substantially contribute to reproductive success in wild brown trout. This study opens a path to further investigate variations in reproductive investment in wild populations. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Metal contamination in urban street sediment in Pisa (Italy) can affect the production of antioxidant metabolites in Taraxacum officinale Weber.

    Science.gov (United States)

    Bretzel, Francesca; Benvenuti, Stefano; Pistelli, Laura

    2014-02-01

    Taraxacum officinale Weber (dandelion) is a very ubiquitous species, and it can grow in urban environments on metal-polluted sediments deposited in the gutters. This study represents a preliminary step to verify the presence of metals in sediments collected in urban streets in Pisa and to assess the alteration in dandelion metabolites in order to understand its adaptation to polluted environments. The soil and sediments were collected at three urban streets and analyzed for total and extractable Cr, Pb, Cu, Ni, and Zn. The total values of Pb and Zn in street sediments exceeded the limits for residential areas of soils. Zn was the most mobile of the metals analyzed. Floating cultivations trials were set up with dandelion seedlings and street sediments. The metals were analyzed in roots and leaves. Antioxidant power, anthocyanins, polyphenols, non-protein thiols (NP-TH) and chlorophylls were measured in dandelion leaves. The first two parameters (anthocyanins and antioxidant power) were higher in the polluted samples compared to the control; chlorophyll content was lower in the treated samples, whereas NP-TH showed no differences. NP-TH groups determined in roots were associated with the root content of Zn and Pb. These results indicate that dandelion can tolerate plant stress by altering its metabolite content.

  18. Chemometric analysis of the secondary metabolite profile of Yarrow (Achillea collina Becker ex Rchb. affected by phloem feeding Myzus persicae Sulzer aphids

    Directory of Open Access Journals (Sweden)

    Annamaria Giorgi

    2010-07-01

    Full Text Available Yarrow (Achillea collina Becker ex Rchb. has a high content of secondary metabolites including phenolic acids. Among them, hydroxycinnamic acid such as chlorogenic acid and its derivatives were found to be the most abundant ones. The phloem feeding Myzus persicae Sulzer was hypothesized to affect the contents of secondary metabolites and change the metabolite profile. A high-performance liquid chromatography technique (HPLC was used to evaluate whether there is a difference in the phenolic profile between aphid infested and non-infested yarrow leaves. M. persicae colonies composed of between 20 and 30 individuals were allowed to feed for 10 and 20 days. Preprocessing was carried out to standardize the procedures in order to obtain optimal separation of analytes, good chromatographic peak shape and robustness of the results. The methanol extracts of leaves were analyzed by means of HPLC, and the time series of peak areas obtained from each extract were evaluated through chemometric analyses. Results of the phenolic fingerprints showed a specific chromatographic profile with 58 peaks. An autoregression analysis demonstrated the absence of correlation. The discriminant analysis carried out with the data satisfying the assumption of the absence of collinearity showed a significant effect of phloem feeding on soluble phenolic compounds and identified two peaks that separate aphid infested from non-infested plants. The hydroxycinnamic acids widely found in A. collina leaves were not affected by M. persicae feeding. The results are the basis for the current studies aiming at the identification of chemical compounds that correspond to the peaks.

  19. Network Diversity and Affect Dynamics: The Role of Personality Traits.

    Science.gov (United States)

    Alshamsi, Aamena; Pianesi, Fabio; Lepri, Bruno; Pentland, Alex; Rahwan, Iyad

    2016-01-01

    People divide their time unequally among their social contacts due to time constraints and varying strength of relationships. It was found that high diversity of social communication, dividing time more evenly among social contacts, is correlated with economic well-being both at macro and micro levels. Besides economic well-being, it is not clear how the diversity of social communication is also associated with the two components of individuals' subjective well-being, positive and negative affect. Specifically, positive affect and negative affect are two independent dimensions representing the experience (feeling) of emotions. In this paper, we investigate the relationship between the daily diversity of social communication and dynamic affect states that people experience in their daily lives. We collected two high-resolution datasets that capture affect scores via daily experience sampling surveys and social interaction through wearable sensing technologies: sociometric badges for face-to-face interaction and smart phones for mobile phone calls. We found that communication diversity correlates with desirable affect states--e.g. an increase in the positive affect state or a decrease in the negative affect state--for some personality types, but correlates with undesirable affect states for others. For example, diversity in phone calls is experienced as good by introverts, but bad by extroverts; diversity in face-to-face interaction is experienced as good by people who tend to be positive by nature (trait) but bad for people who tend to be not positive by nature. More broadly, the moderating effect of personality type on the relationship between diversity and affect was detected without any knowledge of the type of social tie or the content of communication. This provides further support for the power of unobtrusive sensing in understanding social dynamics, and in measuring the effect of potential interventions designed to improve well-being.

  20. Network Diversity and Affect Dynamics: The Role of Personality Traits.

    Directory of Open Access Journals (Sweden)

    Aamena Alshamsi

    Full Text Available People divide their time unequally among their social contacts due to time constraints and varying strength of relationships. It was found that high diversity of social communication, dividing time more evenly among social contacts, is correlated with economic well-being both at macro and micro levels. Besides economic well-being, it is not clear how the diversity of social communication is also associated with the two components of individuals' subjective well-being, positive and negative affect. Specifically, positive affect and negative affect are two independent dimensions representing the experience (feeling of emotions. In this paper, we investigate the relationship between the daily diversity of social communication and dynamic affect states that people experience in their daily lives. We collected two high-resolution datasets that capture affect scores via daily experience sampling surveys and social interaction through wearable sensing technologies: sociometric badges for face-to-face interaction and smart phones for mobile phone calls. We found that communication diversity correlates with desirable affect states--e.g. an increase in the positive affect state or a decrease in the negative affect state--for some personality types, but correlates with undesirable affect states for others. For example, diversity in phone calls is experienced as good by introverts, but bad by extroverts; diversity in face-to-face interaction is experienced as good by people who tend to be positive by nature (trait but bad for people who tend to be not positive by nature. More broadly, the moderating effect of personality type on the relationship between diversity and affect was detected without any knowledge of the type of social tie or the content of communication. This provides further support for the power of unobtrusive sensing in understanding social dynamics, and in measuring the effect of potential interventions designed to improve well-being.

  1. Network Diversity and Affect Dynamics: The Role of Personality Traits

    Science.gov (United States)

    Alshamsi, Aamena; Pianesi, Fabio; Lepri, Bruno; Pentland, Alex; Rahwan, Iyad

    2016-01-01

    People divide their time unequally among their social contacts due to time constraints and varying strength of relationships. It was found that high diversity of social communication, dividing time more evenly among social contacts, is correlated with economic well-being both at macro and micro levels. Besides economic well-being, it is not clear how the diversity of social communication is also associated with the two components of individuals’ subjective well-being, positive and negative affect. Specifically, positive affect and negative affect are two independent dimensions representing the experience (feeling) of emotions. In this paper, we investigate the relationship between the daily diversity of social communication and dynamic affect states that people experience in their daily lives. We collected two high-resolution datasets that capture affect scores via daily experience sampling surveys and social interaction through wearable sensing technologies: sociometric badges for face-to-face interaction and smart phones for mobile phone calls. We found that communication diversity correlates with desirable affect states–e.g. an increase in the positive affect state or a decrease in the negative affect state–for some personality types, but correlates with undesirable affect states for others. For example, diversity in phone calls is experienced as good by introverts, but bad by extroverts; diversity in face-to-face interaction is experienced as good by people who tend to be positive by nature (trait) but bad for people who tend to be not positive by nature. More broadly, the moderating effect of personality type on the relationship between diversity and affect was detected without any knowledge of the type of social tie or the content of communication. This provides further support for the power of unobtrusive sensing in understanding social dynamics, and in measuring the effect of potential interventions designed to improve well-being. PMID:27035904

  2. Altered default mode and affective network connectivity in stroke patients with and without dysphagia.

    Science.gov (United States)

    Li, Shasha; Zhou, Muke; Yu, Bo; Ma, Zhenxing; Chen, Sihan; Gong, Qiyong; He, Li; Huang, Xiaoqi; Lui, Su; Wang, Xiaotong; Zhou, Dong; He, Chengqi

    2014-02-01

    Neuroimaging studies in stroke patients provide substantial evidence for the involvement of widespread cortical and subcortical regions in the control of swallowing. Although the affective network and the default mode network are functionally related to "autonomic" and "volitional" swallowing, little is known about their functional changes in dysphagic stroke patients. Unbiased seeds functional connectivity analysis was used to study the connectivity patterns of these resting-state networks. Resting-state functional magnetic resonance imaging was performed in stroke patients with (n = 12) and without dysphagia (n = 12). Compared with healthy controls, stroke patients with and without dysphagia had decreased functional connectivity in the default mode network and the affective network. Moreover, stroke patients with dysphagia also had decreased functional connectivity in both the default mode network and the affective network relative to patients without dysphagia. The difference in the extent of impairment in the default mode network and affective network of stroke patients with and without dysphagia may lead to improved understanding of the neuropathophysiological mechanism and rehabilitation of dysphagia.

  3. Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial.

    Science.gov (United States)

    Brown, Dustin G; Borresen, Erica C; Brown, Regina J; Ryan, Elizabeth P

    2017-05-01

    Rice bran (RB) consumption has been shown to reduce colorectal cancer (CRC) growth in mice and modify the human stool microbiome. Changes in host and microbial metabolism induced by RB consumption was hypothesised to modulate the stool metabolite profile in favour of promoting gut health and inhibiting CRC growth. The objective was to integrate gut microbial metabolite profiles and identify metabolic pathway networks for CRC chemoprevention using non-targeted metabolomics. In all, nineteen CRC survivors participated in a parallel randomised controlled dietary intervention trial that included daily consumption of study-provided foods with heat-stabilised RB (30 g/d) or no additional ingredient (control). Stool samples were collected at baseline and 4 weeks and analysed using GC-MS and ultra-performance liquid chromatography-MS. Stool metabolomics revealed 93 significantly different metabolites in individuals consuming RB. A 264-fold increase in β-hydroxyisovaleroylcarnitine and 18-fold increase in β-hydroxyisovalerate exemplified changes in leucine, isoleucine and valine metabolism in the RB group. A total of thirty-nine stool metabolites were significantly different between RB and control groups, including increased hesperidin (28-fold) and narirutin (14-fold). Metabolic pathways impacted in the RB group over time included advanced glycation end products, steroids and bile acids. Fatty acid, leucine/valine and vitamin B6 metabolic pathways were increased in RB compared with control. There were 453 metabolites identified in the RB food metabolome, thirty-nine of which were identified in stool from RB consumers. RB consumption favourably modulated the stool metabolome of CRC survivors and these findings suggest the need for continued dietary CRC chemoprevention efforts.

  4. Does human migration affect international trade? A complex-network perspective.

    Directory of Open Access Journals (Sweden)

    Giorgio Fagiolo

    Full Text Available This paper explores the relationships between international human migration and merchandise trade, using a complex-network approach. We firstly compare the topological structure of worldwide networks of human migration and bilateral trade over the period 1960-2000. Next, we ask whether the position of any pair of countries in the migration network affects their bilateral trade flows. We show that: (i both weighted and binary versions of the networks of international migration and trade are strongly correlated; (ii such correlations can be mostly explained by country economic/demographic size and geographical distance; and (iii pairs of countries that are more central in the international-migration network trade more. Our findings suggest that bilateral trade between any two countries is not only affected by the presence of migrants from either countries but also by their relative embeddedness in the complex web of corridors making up the network of international human migration.

  5. Social adaptation in multi-agent model of linguistic categorization is affected by network information flow.

    Science.gov (United States)

    Zubek, Julian; Denkiewicz, Michał; Barański, Juliusz; Wróblewski, Przemysław; Rączaszek-Leonardi, Joanna; Plewczynski, Dariusz

    2017-01-01

    This paper explores how information flow properties of a network affect the formation of categories shared between individuals, who are communicating through that network. Our work is based on the established multi-agent model of the emergence of linguistic categories grounded in external environment. We study how network information propagation efficiency and the direction of information flow affect categorization by performing simulations with idealized network topologies optimizing certain network centrality measures. We measure dynamic social adaptation when either network topology or environment is subject to change during the experiment, and the system has to adapt to new conditions. We find that both decentralized network topology efficient in information propagation and the presence of central authority (information flow from the center to peripheries) are beneficial for the formation of global agreement between agents. Systems with central authority cope well with network topology change, but are less robust in the case of environment change. These findings help to understand which network properties affect processes of social adaptation. They are important to inform the debate on the advantages and disadvantages of centralized systems.

  6. Social adaptation in multi-agent model of linguistic categorization is affected by network information flow.

    Directory of Open Access Journals (Sweden)

    Julian Zubek

    Full Text Available This paper explores how information flow properties of a network affect the formation of categories shared between individuals, who are communicating through that network. Our work is based on the established multi-agent model of the emergence of linguistic categories grounded in external environment. We study how network information propagation efficiency and the direction of information flow affect categorization by performing simulations with idealized network topologies optimizing certain network centrality measures. We measure dynamic social adaptation when either network topology or environment is subject to change during the experiment, and the system has to adapt to new conditions. We find that both decentralized network topology efficient in information propagation and the presence of central authority (information flow from the center to peripheries are beneficial for the formation of global agreement between agents. Systems with central authority cope well with network topology change, but are less robust in the case of environment change. These findings help to understand which network properties affect processes of social adaptation. They are important to inform the debate on the advantages and disadvantages of centralized systems.

  7. Oxytocin Intranasal Administration Affects Neural Networks Upstream of GNRH Neurons.

    Science.gov (United States)

    Salehi, Mohammad Saied; Khazali, Homayoun; Mahmoudi, Fariba; Janahmadi, Mahyar

    2017-08-01

    The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus. In addition, we assessed expression of two excitatory (kisspeptin and neurokinin B) and two inhibitory (dynorphin and RFamide-related peptide-3) neuropeptides upstream of GNRH neurons as a possible route to relay oxytocin information. Here, adult male rats received 20, 40, or 80 μg oxytocin intranasally once a day for 10 consecutive days, and then, the posterior (PH) and anterior hypothalamus (AH) dissected for evaluation of target genes. Using qRT-PCR, we found that oxytocin treatment increased Gnrh mRNA levels in both the PH and AH. In addition, oxytocin at its highest dose increased kisspeptin expression in the AH by around 400%, whereas treatments, dose dependently decreased kisspeptin mRNA in the PH. The expression of neurokinin B was increased from the basal levels following the intervention. Furthermore, although intranasal-applied oxytocin decreased hypothalamic RFamide-related peptide-3 mRNA level, the dynorphin mRNA was not affected. These observations are consistent with the hypothesis that applications of intranasal oxytocin can affect the GNRH system.

  8. FACTORS AFFECTING WATER QUALITY IN A WATER SUPPLY NETWORK

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    Artur Jachimowski

    2017-07-01

    Full Text Available An effect of factors determining water quality in the water supply network in Kraków is assessed. Data collected over a four-year research period included quality parameters of water taken from the water distribution system in the period between 1 January 2011 and 31 December 2014. In analysis the supply zones of four municipal water treatment plants in Krakow were considered. The selection of 29 water sampling points within the supply area allowed water quality to to be compared with respect to operational and technological aspects. Factor analysis enabled 4 components explaining correlations between tap water quality variables to be distinguished. It follows from the research performed that the obtained factors applied to 77% of overall water variability. The highest share was assigned to factor 1 that explained in 32% the chemical composition of water under consideration and was correlated with calcium, conductance, nitrates (V, magnesium and to a moderate extent with ∑ THM (with negative sign.

  9. Integration Strategy Is a Key Step in Network-Based Analysis and Dramatically Affects Network Topological Properties and Inferring Outcomes

    Directory of Open Access Journals (Sweden)

    Nana Jin

    2014-01-01

    Full Text Available An increasing number of experiments have been designed to detect intracellular and intercellular molecular interactions. Based on these molecular interactions (especially protein interactions, molecular networks have been built for using in several typical applications, such as the discovery of new disease genes and the identification of drug targets and molecular complexes. Because the data are incomplete and a considerable number of false-positive interactions exist, protein interactions from different sources are commonly integrated in network analyses to build a stable molecular network. Although various types of integration strategies are being applied in current studies, the topological properties of the networks from these different integration strategies, especially typical applications based on these network integration strategies, have not been rigorously evaluated. In this paper, systematic analyses were performed to evaluate 11 frequently used methods using two types of integration strategies: empirical and machine learning methods. The topological properties of the networks of these different integration strategies were found to significantly differ. Moreover, these networks were found to dramatically affect the outcomes of typical applications, such as disease gene predictions, drug target detections, and molecular complex identifications. The analysis presented in this paper could provide an important basis for future network-based biological researches.

  10. Definition and characterization of an extended social-affective default network

    Science.gov (United States)

    Amft, Maren; Bzdok, Danilo; Laird, Angela R.; Fox, Peter T.; Schilbach, Leonhard; Eickhoff, Simon B.

    2014-01-01

    Recent evidence suggests considerable overlap between the default mode network (DMN) and regions involved in social, affective and introspective processes. We considered these overlapping regions as the social-affective part of the default mode network. In this study we established a robust mapping of the underlying brain network formed by these regions and those strongly connected to them (the extended social-affective default network: eSAD). We first seeded meta-analytic connectivity modeling and resting state analyses in the meta-analytically defined DMN regions that showed statistical overlap with regions associated with social and affective processing. Consensus connectivity of each seed was subsequently delineated by a conjunction across both connectivity analyses. We then functionally characterized the ensuing regions and performed several cluster analyses. Among the identified regions the amygdala/hippocampus formed a cluster associated with emotional processes and memory functions. The ventral striatum, anterior cingulum, subgenual cingulum and ventromedial prefrontal cortex formed a heterogeneous subgroup associated with motivation, reward and cognitive modulation of affect. Posterior cingulum/precuneus and dorsomedial prefrontal cortex were associated with mentalizing, self-reference and autobiographic information. The cluster formed by the temporo-parietal junction and anterior middle temporal sulcus/gyrus was associated with language and social cognition. Taken together, the current work highlights a robustly interconnected network that may be central to interospective, socio-affective, that is, self- and other-related mental processes. PMID:24399179

  11. The sound of emotions-Towards a unifying neural network perspective of affective sound processing.

    Science.gov (United States)

    Frühholz, Sascha; Trost, Wiebke; Kotz, Sonja A

    2016-09-01

    Affective sounds are an integral part of the natural and social environment that shape and influence behavior across a multitude of species. In human primates, these affective sounds span a repertoire of environmental and human sounds when we vocalize or produce music. In terms of neural processing, cortical and subcortical brain areas constitute a distributed network that supports our listening experience to these affective sounds. Taking an exhaustive cross-domain view, we accordingly suggest a common neural network that facilitates the decoding of the emotional meaning from a wide source of sounds rather than a traditional view that postulates distinct neural systems for specific affective sound types. This new integrative neural network view unifies the decoding of affective valence in sounds, and ascribes differential as well as complementary functional roles to specific nodes within a common neural network. It also highlights the importance of an extended brain network beyond the central limbic and auditory brain systems engaged in the processing of affective sounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Affective and executive network processing associated with persuasive antidrug messages.

    Science.gov (United States)

    Ramsay, Ian S; Yzer, Marco C; Luciana, Monica; Vohs, Kathleen D; MacDonald, Angus W

    2013-07-01

    Previous research has highlighted brain regions associated with socioemotional processes in persuasive message encoding, whereas cognitive models of persuasion suggest that executive brain areas may also be important. The current study aimed to identify lateral prefrontal brain areas associated with persuasive message viewing and understand how activity in these executive regions might interact with activity in the amygdala and medial pFC. Seventy adolescents were scanned using fMRI while they watched 10 strongly convincing antidrug public service announcements (PSAs), 10 weakly convincing antidrug PSAs, and 10 advertisements (ads) unrelated to drugs. Antidrug PSAs compared with nondrug ads more strongly elicited arousal-related activity in the amygdala and medial pFC. Within antidrug PSAs, those that were prerated as strongly persuasive versus weakly persuasive showed significant differences in arousal-related activity in executive processing areas of the lateral pFC. In support of the notion that persuasiveness involves both affective and executive processes, functional connectivity analyses showed greater coactivation between the lateral pFC and amygdala during PSAs known to be strongly (vs. weakly) convincing. These findings demonstrate that persuasive messages elicit activation in brain regions responsible for both emotional arousal and executive control and represent a crucial step toward a better understanding of the neural processes responsible for persuasion and subsequent behavior change.

  13. Factors Affecting Social Network Use by Students in Indonesia

    Directory of Open Access Journals (Sweden)

    Budhi Kristianto

    2017-03-01

    Full Text Available Background: Although Indonesia is one of the world’s most populated countries with a high penetration of internet usage there has been little research on SNS usage in Indonesia, especially involving children. Instead, SNS research in Indonesia has focused on university students and political, marketing, and disaster mitigation issues. Aim/Purpose: In order to address this gap a theoretical model is formulated from a review of previous studies incorporating basic constructs found in the Technology Acceptance Model (Perceived Usefulness, Perceived Ease of Use, and Attitude as well as other influences, motivations, and individual characteristics that affect a child’s attitude toward the use of SNS. Methodology\t: The model is evaluated and developed using data collected from 460 children in primary school grades 4, 5, and 6 in five cities in Indonesia. The statistical techniques implemented with SPSS and Amos computer software (t-tests, correlation coefficients, principal component factor analysis, Cronbach alpha coefficients, and structural equation modeling (SEM analysis. Findings: The results confirm many of the effects on a child’s attitude toward SNS reported in previous studies due to: the usefulness and ease of use of SNS; parental influence; feelings of flow experience and risk; and the child’s level of access, technical expertise, and experience with SNS. New findings include significant correlations and causal effects involving: the influences of peers and parents; the child’s level of technical expertise; and feelings of flow experience. Contribution: Despite limitations related to sampling and the administration of a questionnaire among young children, the findings contribute to theory as well as practice and provide guidance on effective ways to improve children’s attitudes towards the use of SNS.

  14. Altered affective, executive and sensorimotor resting state networks in patients with pediatric mania

    Science.gov (United States)

    Wu, Minjie; Lu, Lisa H.; Passarotti, Alessandra M.; Wegbreit, Ezra; Fitzgerald, Jacklynn; Pavuluri, Mani N.

    2013-01-01

    Background The aim of the present study was to map the pathophysiology of resting state functional connectivity accompanying structural and functional abnormalities in children with bipolar disorder. Methods Children with bipolar disorder and demographically matched healthy controls underwent resting-state functional magnetic resonance imaging. A model-free independent component analysis was performed to identify intrinsically interconnected networks. Results We included 34 children with bipolar disorder and 40 controls in our analysis. Three distinct resting state networks corresponding to affective, executive and sensorimotor functions emerged as being significantly different between the pediatric bipolar disorder (PBD) and control groups. All 3 networks showed hyperconnectivity in the PBD relative to the control group. Specifically, the connectivity of the dorsal anterior cingulate cortex (ACC) differentiated the PBD from the control group in both the affective and the executive networks. Exploratory analysis suggests that greater connectivity of the right amygdala within the affective network is associated with better executive function in children with bipolar disorder, but not in controls. Limitations Unique clinical characteristics of the study sample allowed us to evaluate the pathophysiology of resting state connectivity at an early state of PBD, which led to the lack of generalizability in terms of comorbid disorders existing in a typical PBD population. Conclusion Abnormally engaged resting state affective, executive and sensorimotor networks observed in children with bipolar disorder may reflect a biological context in which abnormal task-based brain activity can occur. Dual engagement of the dorsal ACC in affective and executive networks supports the neuroanatomical interface of these networks, and the amygdala’s engagement in moderating executive function illustrates the intricate interplay of these neural operations at rest. PMID:23735583

  15. Energy intake in late gestation affects blood metabolites in early lactation independently of milk production in dairy cows

    DEFF Research Database (Denmark)

    Nielsen, Nicolaj Ingemann; Hameleers, A; Young, F J

    2010-01-01

    calving; the H TMR was fed ad libitum whereas the L TMR was restricted to 10 kg dry matter/day during late lactation, and to approximately 75% of energy requirements from drying off until calving. Both diets were offered ad libitum post-calving. Feeding diet H compared to L pre-calving led to higher BCS...... at calving (2.68 v. 2.34, P intake post-calving were not affected by pre-calving diets. Changes in BCS and blood concentrations of non-esterified fatty acids, beta-hydroxybutyrate and glucose in early lactation showed that cows offered diet H pre-calving...... allocated to one of four treatments in a 2 × 2 factorial design, where the factors were H- or L-energy density in a total mixed ration (TMR) both pre- and post-calving. Consequently, there were four treatment groups: HH, HL, LL and LH. The pre-calving treatment was initiated 100 days prior to expected...

  16. Attention Network Test in adults with ADHD - the impact of affective fluctuations

    DEFF Research Database (Denmark)

    Lundervold, Astri J; Adolfsdottir, Steinunn; Halleland, Helene

    2011-01-01

    ABSTRACT: BACKGROUND: The Attention Network Test (ANT) generates measures of different aspects of attention/executive function. In the present study we investigated whether adults with ADHD performed different from controls on measures of accuracy, variability and vigilance as well as the control...... network. Secondly, we studied subgroups of adults with ADHD, expecting impairment on measures of the alerting and control networks in a subgroup with additional symptoms of affective fluctuations. METHODS: A group of 114 adults (ADHD n=58; controls n=56) performed the ANT and completed the Adult ADHD....... The significance was retained for the alerting network (p=.011), but not on the conflict network (p=.061) when we controlled for the total ASRS and IQ scores. DISCUSSION: Adults with ADHD were characterized by impairment on accuracy and variability measures calculated from the ANT. Within the ADHD group, adults...

  17. Growth and Accumulation of Secondary Metabolites in Perilla as Affected by Photosynthetic Photon Flux Density and Electrical Conductivity of the Nutrient Solution

    Directory of Open Access Journals (Sweden)

    Na Lu

    2017-05-01

    Full Text Available The global demand for medicinal plants is increasing. The quality of plants grown outdoors, however, is difficult to control. Myriad environmental factors influence plant growth and directly impact biosynthetic pathways, thus affecting the secondary metabolism of bioactive compounds. Plant factories use artificial lighting to increase the quality of medicinal plants and stabilize production. Photosynthetic photon flux density (PPFD and electrical conductivity (EC of nutrient solutions are two important factors that substantially influence perilla (Perilla frutescens, Labiatae plant growth and quality. To identify suitable levels of PPFD and EC for perilla plants grown in a plant factory, the growth, photosynthesis, and accumulation of secondary metabolites in red and green perilla plants were measured at PPFD values of 100, 200, and 300 μmol m-2 s-1 in nutrient solutions with EC values of 1.0, 2.0, and 3.0 dS m-1. The results showed significant interactive effects between PPFD and EC for both the fresh and dry weights of green perilla, but not for red perilla. The fresh and dry weights of shoots and leafy areas were affected more by EC than by PPFD in green perilla, whereas they were affected more by PPFD than by EC in red perilla. Leaf net photosynthetic rates were increased as PPFD increased in both perilla varieties, regardless of EC. The perillaldehyde concentration (mg g-1 in red perilla was unaffected by the treatments, but accumulation in plants (mg per plant was significantly enhanced as the weight of dry leaves increased. Perillaldehyde concentrations in green perilla showed significant differences between combinations of the highest PPFD with the highest EC and the lowest PPFD with the lowest EC. Rosmarinic acid concentration (mg g-1 was increased in a combination of low EC and high PPFD conditions. Optimal cultivation conditions of red and green perilla in plant factory will be discussed in terms of plant growth and contents of

  18. Attention network hypoconnectivity with default and affective network hyperconnectivity in adults diagnosed with attention-deficit/hyperactivity disorder in childhood.

    Science.gov (United States)

    McCarthy, Hazel; Skokauskas, Norbert; Mulligan, Aisling; Donohoe, Gary; Mullins, Diane; Kelly, John; Johnson, Katherine; Fagan, Andrew; Gill, Michael; Meaney, James; Frodl, Thomas

    2013-12-01

    The neurobiological underpinnings of attention-deficit/hyperactivity disorder (ADHD) and particularly those associated with the persistence of ADHD into adulthood are not yet well understood. The correlation patterns in spontaneous neural fluctuations at rest are known as resting-state functional connectivity (RSFC) and could characterize ADHD-specific connectivity changes. To determine the specific location of possible ADHD-related differences in RSFC between adults diagnosed as having ADHD in childhood and control subjects. DESIGN Using resting-state functional magnetic resonance imaging, we calculated and compared functional connectivity from attention, affective, default, and cognitive control networks involved in the psychopathology of ADHD between the ADHD and control groups. SETTING University psychiatric service and magnetic resonance imaging research center. Sixteen drug-free adults (5 women and 11 men; mean age, 24.5 years) diagnosed with combined-type ADHD in childhood and 16 healthy controls matched for age (mean age, 24.4 years), sex, handedness, and educational level recruited from the community. Functional magnetic resonance imaging. Connectivity data from ventral and dorsal attention, affective, default, and cognitive control networks and ADHD symptoms derived from ADHD-specific rating instruments. Adults with ADHD showed significantly decreased RSFC within the attention networks and increased RSFC within the affective and default mode and the right lateralized cognitive control networks compared with healthy controls (P < .01, familywise error for whole-brain cluster correction). Lower RSFC in the ventral and dorsal attention network was significantly correlated with higher levels of ADHD symptoms (P < .001). These RSFC findings might underpin a biological basis for adult ADHD and are functionally related to persistent inattention, disturbance in cognitive control, and emotional dysregulation in adults with ADHD. These findings need to be

  19. 47 CFR 73.4157 - Network signals which adversely affect affiliate broadcast service.

    Science.gov (United States)

    2010-10-01

    ... affiliate broadcast service. 73.4157 Section 73.4157 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.4157 Network signals which adversely affect affiliate broadcast service. See Public Notice, FCC 79-387...

  20. A Comprehensive Risk Analysis of Transportation Networks Affected by Rainfall-Induced Multihazards.

    Science.gov (United States)

    Liu, Kai; Wang, Ming; Cao, Yinxue; Zhu, Weihua; Wu, Jinshan; Yan, Xiaoyong

    2018-01-26

    Climate change and its projected natural hazards have an adverse impact on the functionality and operation of transportation infrastructure systems. This study presents a comprehensive framework to analyze the risk to transportation infrastructure networks that are affected by natural hazards. The proposed risk analysis method considers both the failure probability of infrastructure components and the expected infrastructure network efficiency and capacity loss due to component failure. This comprehensive approach facilitates the identification of high-risk network links in terms of not only their susceptibility to natural hazards but also their overall impact on the network. The Chinese national rail system and its exposure to rainfall-related multihazards are used as a case study. The importance of various links is comprehensively assessed from the perspectives of topological, efficiency, and capacity criticality. Risk maps of the national railway system are generated, which can guide decisive action regarding investments in preventative and adaptive measures to reduce risk. © 2018 Society for Risk Analysis.

  1. Relationships between brain metabolite levels, functional connectivity, and negative mood in urologic chronic pelvic pain syndrome patients compared to controls: A MAPP research network study

    Directory of Open Access Journals (Sweden)

    Daniel E. Harper

    2018-01-01

    Full Text Available Until recently, the predominant pathology of chronic pelvic pain conditions was thought to reside in the peripheral tissues. However, mounting evidence from neuroimaging studies suggests an important role of the central nervous system in the pathogenesis of these conditions. In the present cross-sectional study, proton magnetic resonance spectroscopy (1H-MRS of the brain was conducted in female patients with urologic chronic pelvic pain syndrome (UCPPS to determine if they exhibit abnormal concentrations of brain metabolites (e.g. those indicative of heightened excitatory tone in regions involved in the processing and modulation of pain, including the anterior cingulate cortex (ACC and the anterior and posterior insular cortices. Compared to a group of age-matched healthy subjects, there were significantly higher levels of choline (p = 0.006, uncorrected in the ACC of UCPPS patients. ACC choline levels were therefore compared with the region's resting functional connectivity to the rest of the brain. Higher choline was associated with greater ACC-to-limbic system connectivity in UCPPS patients, contrasted with lower connectivity in controls (i.e. an interaction. In patients, ACC choline levels were also positively correlated with negative mood. ACC γ-aminobutyric acid (GABA levels were lower in UCPPS patients compared with controls (p = 0.02, uncorrected, but this did not meet statistical correction for the 4 separate regional comparisons of metabolites. These results are the first to uncover abnormal GABA and choline levels in the brain of UCPPS patients compared to controls. Low GABA levels have been identified in other pain syndromes and might contribute to CNS hyper-excitability in these conditions. The relationships between increased ACC choline levels, ACC-to-limbic connectivity, and negative mood in UCPPS patients suggest that this metabolite could be related to the affective symptomatology of this syndrome.

  2. Identification of Loci Affecting Accumulation of Secondary Metabolites in Tomato Fruit of a Solanum lycopersicum × Solanum chmielewskii Introgression Line Population.

    Science.gov (United States)

    Ballester, Ana-Rosa; Tikunov, Yury; Molthoff, Jos; Grandillo, Silvana; Viquez-Zamora, Marcela; de Vos, Ric; de Maagd, Ruud A; van Heusden, Sjaak; Bovy, Arnaud G

    2016-01-01

    Semi-polar metabolites such as flavonoids, phenolic acids, and alkaloids are very important health-related compounds in tomato. As a first step to identify genes responsible for the synthesis of semi-polar metabolites, quantitative trait loci (QTLs) that influence the semi-polar metabolite content in red-ripe tomato fruit were identified, by characterizing fruits of a population of introgression lines (ILs) derived from a cross between the cultivated tomato Solanum lycopersicum and the wild species Solanum chmielewskii . By analyzing fruits of plants grown at two different locations, we were able to identify robust metabolite QTLs for changes in phenylpropanoid glycoconjugation on chromosome 9, for accumulation of flavonol glycosides on chromosome 5, and for alkaloids on chromosome 7. To further characterize the QTLs we used a combination of genome sequencing, transcriptomics and targeted metabolomics to identify candidate key genes underlying the observed metabolic variation.

  3. Mutagenic azide metabolite is azidoalanine

    International Nuclear Information System (INIS)

    Owais, W.M.; Rosichan, J.L.; Ronald, R.C.; Kleinhofs, A.; Nilan, R.A.

    1981-01-01

    Sodium axide produces high mutation rates in a number of species. Azide mutagenicity is mediated through a metabolite in barley and bacteria. Many studies showed that azide affects the L-cysteine biosynthesis pathway. Cell-free extracts of Salmonella typhimurium convert azide and O-acetylserine to the mutagenic metabolite. O-acetylserine sulfhydrylase was identified as the enzyme responsible for the metabolite biosynthesis. To confirm the conclusion that the azide metabolite is formed through the β-substitution pathway of L-cysteine, we radioactively labeled the azide metabolite using 14 C-labeled precursors. Moreover, the mutagenic azide metabolite was purified and identified as azidoalanine based on mass spectroscopy and elemental analysis. 26 refs., 3 figs., 1 tab

  4. Attention Network Test in adults with ADHD--the impact of affective fluctuations.

    Science.gov (United States)

    Lundervold, Astri J; Adolfsdottir, Steinunn; Halleland, Helene; Halmøy, Anne; Plessen, Kerstin; Haavik, Jan

    2011-07-27

    The Attention Network Test (ANT) generates measures of different aspects of attention/executive function. In the present study we investigated whether adults with ADHD performed different from controls on measures of accuracy, variability and vigilance as well as the control network. Secondly, we studied subgroups of adults with ADHD, expecting impairment on measures of the alerting and control networks in a subgroup with additional symptoms of affective fluctuations. A group of 114 adults (ADHD n = 58; controls n = 56) performed the ANT and completed the Adult ADHD Rating Scale (ASRS) and the Mood Disorder Questionnaire (MDQ). The latter was used to define affective fluctuations. The sex distribution was similar in the two groups, but the ADHD group was significantly older (p = .005) and their score on a test of intellectual function (WASI) significantly lower than in the control group (p = .007). The two groups were not significantly different on measures of the three attention networks, but the ADHD group was generally less accurate (p = .001) and showed a higher variability through the task (p = .033).The significance was only retained for the accuracy measure when age and IQ scores were controlled for. Within the ADHD group, individuals reporting affective fluctuations (n = 22) were slower (p = .015) and obtained a lower score on the alerting network (p = .018) and a higher score on the conflict network (p = .023) than those without these symptoms. The significance was retained for the alerting network (p = .011), but not the conflict network (p = .061) when we controlled for the total ASRS and IQ scores. Adults with ADHD were characterized by impairment on accuracy and variability measures calculated from the ANT. Within the ADHD group, adults reporting affective fluctuations seemed to be more alert (i.e., less impacted by alerting cues), but slower and more distracted by conflicting stimuli than the subgroup without such fluctuations. The results suggest

  5. Attention Network Test in adults with ADHD - the impact of affective fluctuations

    Directory of Open Access Journals (Sweden)

    Lundervold Astri J

    2011-07-01

    Full Text Available Abstract Background The Attention Network Test (ANT generates measures of different aspects of attention/executive function. In the present study we investigated whether adults with ADHD performed different from controls on measures of accuracy, variability and vigilance as well as the control network. Secondly, we studied subgroups of adults with ADHD, expecting impairment on measures of the alerting and control networks in a subgroup with additional symptoms of affective fluctuations. Methods A group of 114 adults (ADHD n = 58; controls n = 56 performed the ANT and completed the Adult ADHD Rating Scale (ASRS and the Mood Disorder Questionnaire (MDQ. The latter was used to define affective fluctuations. Results The sex distribution was similar in the two groups, but the ADHD group was significantly older (p = .005 and their score on a test of intellectual function (WASI significantly lower than in the control group (p = .007. The two groups were not significantly different on measures of the three attention networks, but the ADHD group was generally less accurate (p = .001 and showed a higher variability through the task (p = .033. The significance was only retained for the accuracy measure when age and IQ scores were controlled for. Within the ADHD group, individuals reporting affective fluctuations (n = 22 were slower (p = .015 and obtained a lower score on the alerting network (p = .018 and a higher score on the conflict network (p = .023 than those without these symptoms. The significance was retained for the alerting network (p = .011, but not the conflict network (p = .061 when we controlled for the total ASRS and IQ scores. Discussion Adults with ADHD were characterized by impairment on accuracy and variability measures calculated from the ANT. Within the ADHD group, adults reporting affective fluctuations seemed to be more alert (i.e., less impacted by alerting cues, but slower and more distracted by conflicting stimuli than the

  6. Online social networking addiction among college students in Singapore: Comorbidity with behavioral addiction and affective disorder.

    Science.gov (United States)

    Tang, Catherine So-Kum; Koh, Yvaine Yee Woen

    2017-02-01

    This study aimed to determine the prevalence of addiction to social networking sites/platforms (SNS) and its comorbidity with other behavioral addiction and affective disorder among college students in Singapore. 1110 college students (age: M=21.46, SD=1.80) in Singapore completed measures assessing online social networking, unhealthy food intake and shopping addiction as well as depression, anxiety and mania. Descriptive analyses were conducted to investigate the prevalence and comorbidity of behavioral addiction and affective disorder. Chi-square tests were used to examine gender differences. The prevalence rates of SNS, food and shopping addiction were 29.5%, 4.7% and 9.3% respectively for the total sample. SNS addiction was found to co-occur with food addiction (3%), shopping addiction (5%), and both food and shopping addiction (1%). The comorbidity rates of SNS addiction and affective disorder were 21% for depression, 27.7% for anxiety, and 26.1% for mania. Compared with the total sample, students with SNS addiction reported higher comorbidity rates with other behavioral addiction and affective disorder. In general, females as compared to males reported higher comorbidity rates of SNS addiction and affective disorder. SNS addiction has a high prevalence rate among college students in Singapore. Students with SNS addiction were vulnerable to experience other behavior addiction as well as affective disorder, especially among females. Copyright © 2016. Published by Elsevier B.V.

  7. 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...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...

  8. An Empirical Examination of Factors Affecting Continuance Intention Towards Social Networking Sites

    OpenAIRE

    Abed, Salma,

    2016-01-01

    Part 3: Adoption and Diffusion; International audience; This study examines the factors that affect consumer continuance intention to use social networking sites as a business tool. Using the Technology Acceptance Model (TAM) as the theoretical framework, the researcher tested the research model and related hypotheses using structural equation modelling. The results from a survey of 304 Facebook users in Saudi Arabia indicate that trust, perceived usefulness, and perceived enjoyment had signi...

  9. The centrality of affective instability and identity in Borderline Personality Disorder: Evidence from network analysis.

    Science.gov (United States)

    Richetin, Juliette; Preti, Emanuele; Costantini, Giulio; De Panfilis, Chiara

    2017-01-01

    We argue that the series of traits characterizing Borderline Personality Disorder samples do not weigh equally. In this regard, we believe that network approaches employed recently in Personality and Psychopathology research to provide information about the differential relationships among symptoms would be useful to test our claim. To our knowledge, this approach has never been applied to personality disorders. We applied network analysis to the nine Borderline Personality Disorder traits to explore their relationships in two samples drawn from university students and clinical populations (N = 1317 and N = 96, respectively). We used the Fused Graphical Lasso, a technique that allows estimating networks from different populations separately while considering their similarities and differences. Moreover, we examined centrality indices to determine the relative importance of each symptom in each network. The general structure of the two networks was very similar in the two samples, although some differences were detected. Results indicate the centrality of mainly affective instability, identity, and effort to avoid abandonment aspects in Borderline Personality Disorder. Results are consistent with the new DSM Alternative Model for Personality Disorders. We discuss them in terms of implications for therapy.

  10. The centrality of affective instability and identity in Borderline Personality Disorder: Evidence from network analysis.

    Directory of Open Access Journals (Sweden)

    Juliette Richetin

    Full Text Available We argue that the series of traits characterizing Borderline Personality Disorder samples do not weigh equally. In this regard, we believe that network approaches employed recently in Personality and Psychopathology research to provide information about the differential relationships among symptoms would be useful to test our claim. To our knowledge, this approach has never been applied to personality disorders. We applied network analysis to the nine Borderline Personality Disorder traits to explore their relationships in two samples drawn from university students and clinical populations (N = 1317 and N = 96, respectively. We used the Fused Graphical Lasso, a technique that allows estimating networks from different populations separately while considering their similarities and differences. Moreover, we examined centrality indices to determine the relative importance of each symptom in each network. The general structure of the two networks was very similar in the two samples, although some differences were detected. Results indicate the centrality of mainly affective instability, identity, and effort to avoid abandonment aspects in Borderline Personality Disorder. Results are consistent with the new DSM Alternative Model for Personality Disorders. We discuss them in terms of implications for therapy.

  11. Antecedent acute cycling exercise affects attention control: an ERP study using attention network test

    Directory of Open Access Journals (Sweden)

    Yu-Kai eChang

    2015-04-01

    Full Text Available The purpose of this study was to investigate the after-effects of an acute bout of moderate-intensity aerobic cycling exercise on neuroelectric and behavioral indices of efficiency of three attentional networks: alerting, orienting, and executive (conflict control. Thirty young, highly fit amateur basketball players performed a multifunctional attentional reaction time task, the attention network test (ANT, with a two-group randomized experimental design after an acute bout of moderate-intensity spinning wheel exercise or without antecedent exercise. The ANT combined warning signals prior to targets, spatial cueing of potential target locations and target stimuli surrounded by congruent or incongruent flankers, which were provided to assess three attentional networks. Event-related brain potentials and task performance were measured during the ANT. Exercise resulted in a larger P3 amplitude in the alerting and executive control subtasks across frontal, central and parietal midline sites that was paralleled by an enhanced reaction speed only on trials with incongruent flankers of the executive control network. The P3 latency and response accuracy were not affected by exercise. These findings suggest that after spinning, more resources are allocated to task-relevant stimuli in tasks that rely on the alerting and executive control networks. However, the improvement in performance was observed in only the executively challenging conflict condition, suggesting that whether the brain resources that are rendered available immediately after acute exercise translate into better attention performance depends on the cognitive task complexity.

  12. The centrality of affective instability and identity in Borderline Personality Disorder: Evidence from network analysis

    Science.gov (United States)

    Costantini, Giulio; De Panfilis, Chiara

    2017-01-01

    We argue that the series of traits characterizing Borderline Personality Disorder samples do not weigh equally. In this regard, we believe that network approaches employed recently in Personality and Psychopathology research to provide information about the differential relationships among symptoms would be useful to test our claim. To our knowledge, this approach has never been applied to personality disorders. We applied network analysis to the nine Borderline Personality Disorder traits to explore their relationships in two samples drawn from university students and clinical populations (N = 1317 and N = 96, respectively). We used the Fused Graphical Lasso, a technique that allows estimating networks from different populations separately while considering their similarities and differences. Moreover, we examined centrality indices to determine the relative importance of each symptom in each network. The general structure of the two networks was very similar in the two samples, although some differences were detected. Results indicate the centrality of mainly affective instability, identity, and effort to avoid abandonment aspects in Borderline Personality Disorder. Results are consistent with the new DSM Alternative Model for Personality Disorders. We discuss them in terms of implications for therapy. PMID:29040324

  13. The major glucagon-like peptide-1 metabolite, GLP-1-(9-36)-amide, does not affect glucose or insulin levels in mice

    DEFF Research Database (Denmark)

    Rolin, Bidda; Deacon, Carolyn F; Carr, Richard D

    2004-01-01

    Glucagon-like peptide-1 (GLP-1), a future treatment for type 2 diabetes, is efficiently degraded by the enzyme dipeptidyl peptidase IV (DPP IV), yielding the major metabolite GLP-1-(9-36)-amide. In this study, we examined the potential glucose lowering effect of GLP-1-(9-36)-amide in mice and fou...

  14. Brain network analysis reveals affected connectome structure in bipolar I disorder.

    Science.gov (United States)

    Collin, Guusje; van den Heuvel, Martijn P; Abramovic, Lucija; Vreeker, Annabel; de Reus, Marcel A; van Haren, Neeltje E M; Boks, Marco P M; Ophoff, Roel A; Kahn, René S

    2016-01-01

    The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections--i.e., the connectome--suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs, and affected "rich club" organization. Whether similar deficits are present in bipolar disorder is currently unknown. This study examines structural connectome topology in 216 bipolar I disorder patients as compared to 144 healthy controls, focusing in particular on central regions (i.e., brain hubs) and connections (i.e., rich club connections, interhemispheric connections) of the brain's network. We find that bipolar I disorder patients exhibit reduced global efficiency (-4.4%, P =0.002) and that this deficit relates (r = 0.56, P 0.1). These findings highlight a role for aberrant brain network architecture in bipolar I disorder with reduced global efficiency in association with disruptions in interhemispheric connectivity, while the central "rich club" system appears not to be particularly affected. © 2015 Wiley Periodicals, Inc.

  15. Compassion-based emotion regulation up-regulates experienced positive affect and associated neural networks

    Science.gov (United States)

    Singer, Tania

    2015-01-01

    Emotion regulation research has primarily focused on techniques that attenuate or modulate the impact of emotional stimuli. Recent evidence suggests that this mode regulation can be problematic in the context of regulation of emotion elicited by the suffering of others, resulting in reduced emotional connectedness. Here, we investigated the effects of an alternative emotion regulation technique based on the up-regulation of positive affect via Compassion-meditation on experiential and neural affective responses to depictions of individuals in distress, and compared these with the established emotion regulation strategy of Reappraisal. Using fMRI, we scanned 15 expert practitioners of Compassion-meditation either passively viewing, or using Compassion-meditation or Reappraisal to modulate their emotional reactions to film clips depicting people in distress. Both strategies effectively, but differentially regulated experienced affect, with Compassion primarily increasing positive and Reappraisal primarily decreasing negative affect. Imaging results showed that Compassion, relative to both passive-viewing and Reappraisal increased activation in regions involved in affiliation, positive affect and reward processing including ventral striatum and medial orbitfrontal cortex. This network was shown to be active prior to stimulus presentation, suggesting that the regulatory mechanism of Compassion is the stimulus-independent endogenous generation of positive affect. PMID:25698699

  16. Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.

    Science.gov (United States)

    Fazeli, Walid; Zappettini, Stefania; Marguet, Stephan Lawrence; Grendel, Jasper; Esclapez, Monique; Bernard, Christophe; Isbrandt, Dirk

    2017-09-01

    The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy in humans, caffeine was added to the drinking water of female mice and their offspring were compared to control offspring. Caffeine altered the construction of GABAergic neuronal networks in V1, as reflected by a reduced number of somatostatin-containing GABA neurons at postnatal days 6-7, with the remaining ones showing poorly developed dendritic arbors. These findings were accompanied by increased synaptic activity in vitro and elevated network activity in vivo in V1. Similarly, in vivo hippocampal network activity was altered from the neonatal period until adulthood. Finally, caffeine-exposed offspring showed increased seizure susceptibility in a hyperthermia-induced seizure model. In summary, our results indicate detrimental effects of developmental caffeine exposure on mouse brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Unilateral deafness in children affects development of multi-modal modulation and default mode networks.

    Science.gov (United States)

    Schmithorst, Vincent J; Plante, Elena; Holland, Scott

    2014-01-01

    Monaural auditory input due to congenital or acquired unilateral hearing loss (UHL) may have neurobiological effects on the developing brain. Using functional magnetic resonance imaging (fMRI), we investigated the effect of UHL on the development of functional brain networks used for cross-modal processing. Children ages 7-12 with moderate or greater unilateral hearing loss of sensorineural origin (UHL-SN; N = 21) and normal-hearing controls (N = 23) performed an fMRI-compatible adaptation of the Token Test involving listening to a sentence such as "touched the small green circle and the large blue square" and simultaneously viewing an arrow touching colored shapes on a video. Children with right or severe-to-profound UHL-SN displayed smaller activation in a region encompassing the right inferior temporal, middle temporal, and middle occipital gyrus (BA 19/37/39), evidencing differences due to monaural hearing in cross-modal modulation of the visual processing pathway. Children with UHL-SN displayed increased activation in the left posterior superior temporal gyrus, likely the result either of more effortful low-level processing of auditory stimuli or differences in cross-modal modulation of the auditory processing pathway. Additionally, children with UHL-SN displayed reduced deactivation of anterior and posterior regions of the default mode network. Results suggest that monaural hearing affects the development of brain networks related to cross-modal sensory processing and the regulation of the default network during processing of spoken language.

  18. Unilateral deafness in children affects development of multi-modal modulation and default mode networks

    Directory of Open Access Journals (Sweden)

    Vincent eSchmithorst

    2014-03-01

    Full Text Available Monaural auditory input due to congenital or acquired unilateral hearing loss (UHL may have neurobiological effects on the developing brain. Using fMRI, we investigated the effect of UHL on the development of functional brain networks used for cross-modal processing. Children ages 7-12 with moderate or greater unilateral hearing loss of sensorineural origin (UHL-SN; N = 21 and normal-hearing controls (N = 23 performed an fMRI-compatible adaptation of the Token Test involving listening to a sentence such as touched the small green circle and the large blue square and simultaneously viewing an arrow touching colored shapes on a video. Children with right or severe-to-profound UHL-SN displayed smaller activation in a region encompassing the right inferior temporal, middle temporal, and middle occipital gyrus (BA 19/37/39, evidencing differences due to monaural hearing in cross-modal modulation of the visual processing pathway. Children with UHL-SN displayed increased activation in the left posterior superior temporal gyrus, likely the result either of more effortful low-level processing of auditory stimuli or differences in cross-modal modulation of the auditory processing pathway. Additionally, children with UHL-SN displayed reduced deactivation of anterior and posterior regions of the default mode network. Results suggest that monaural hearing affects the development of brain networks related to cross-modal sensory processing and the regulation of the default network during processing of spoken language.

  19. Network Regulation and Support Schemes - How Policy Interactions Affect the Integration of Distributed Generation

    DEFF Research Database (Denmark)

    Ropenus, Stephanie; Jacobsen, Henrik; Schröder, Sascha Thorsten

    2011-01-01

    This article seeks to investigate the interactions between the policy dimensions of support schemes and network regulation and how they affect distributed generation. Firstly, the incentives of distributed generators and distribution system operators are examined. Frequently there exists a trade......-off between the incentives for these two market agents to facilitate the integration of distributed generation. Secondly, the interaction of these policy dimensions is analyzed, including case studies based on five EU Member States. Aspects of operational nature and investments in grid and distributed...

  20. Factors Affecting Intention to Use in Social Networking Sites: An Empirical Study on Thai Society

    Science.gov (United States)

    Jairak, Rath; Sahakhunchai, Napath; Jairak, Kallaya; Praneetpolgrang, Prasong

    This research aims to explore the factors that affect the intention to use in Social Networking Sites (SNS). We apply the theory of Technology Acceptance Model (TAM), intrinsic motivation, and trust properties to develop the theoretical framework for SNS users' intention. The results show that the important factors influencing SNS users' intention for general purpose and collaborative learning are task-oriented, pleasure-oriented, and familiarity-based trust. In marketing usage, dispositional trust and pleasure-oriented are two main factors that reflect intention to use in SNS.

  1. Meta-analytically informed network analysis of resting state FMRI reveals hyperconnectivity in an introspective socio-affective network in depression.

    Science.gov (United States)

    Schilbach, Leonhard; Müller, Veronika I; Hoffstaedter, Felix; Clos, Mareike; Goya-Maldonado, Roberto; Gruber, Oliver; Eickhoff, Simon B

    2014-01-01

    Alterations of social cognition and dysfunctional interpersonal expectations are thought to play an important role in the etiology of depression and have, thus, become a key target of psychotherapeutic interventions. The underlying neurobiology, however, remains elusive. Based upon the idea of a close link between affective and introspective processes relevant for social interactions and alterations thereof in states of depression, we used a meta-analytically informed network analysis to investigate resting-state functional connectivity in an introspective socio-affective (ISA) network in individuals with and without depression. Results of our analysis demonstrate significant differences between the groups with depressed individuals showing hyperconnectivity of the ISA network. These findings demonstrate that neurofunctional alterations exist in individuals with depression in a neural network relevant for introspection and socio-affective processing, which may contribute to the interpersonal difficulties that are linked to depressive symptomatology.

  2. Meta-analytically informed network analysis of resting state FMRI reveals hyperconnectivity in an introspective socio-affective network in depression.

    Directory of Open Access Journals (Sweden)

    Leonhard Schilbach

    Full Text Available Alterations of social cognition and dysfunctional interpersonal expectations are thought to play an important role in the etiology of depression and have, thus, become a key target of psychotherapeutic interventions. The underlying neurobiology, however, remains elusive. Based upon the idea of a close link between affective and introspective processes relevant for social interactions and alterations thereof in states of depression, we used a meta-analytically informed network analysis to investigate resting-state functional connectivity in an introspective socio-affective (ISA network in individuals with and without depression. Results of our analysis demonstrate significant differences between the groups with depressed individuals showing hyperconnectivity of the ISA network. These findings demonstrate that neurofunctional alterations exist in individuals with depression in a neural network relevant for introspection and socio-affective processing, which may contribute to the interpersonal difficulties that are linked to depressive symptomatology.

  3. Mycorrhizal networks affect ectomycorrhizal fungal community similarity between conspecific trees and seedlings.

    Science.gov (United States)

    Bingham, Marcus A; Simard, Suzanne W

    2012-05-01

    Ectomycorrhizal (EM) networks (MN) are thought to be an important mode of EM fungal colonization of coniferous seedlings. How MNs affect EM communities on seedlings, and how this varies with biotic and abiotic factors, is integral to understanding their importance in seedling establishment. We examined EM fungal community similarity between mature trees and conspecific interior Douglas-fir (Pseudotsuga menziesii var. glauca) seedlings in two experiments where seed and nursery-grown seedlings originating from different locations were planted at various distances from trees along a climatic gradient. At harvest, trees shared 60% of their fungal taxa in common with outplanted seedlings and 77% with germinants, indicating potential for seedlings to join the network of residual trees. In both experiments, community similarity between trees and seedlings increased with drought. However, community similarity was lower among nursery seedlings growing at 2.5 m from trees when they were able to form an MN, suggesting MNs reduced seedling EM fungal richness. For field germinants, MNs resulted in lower community similarity in the driest climates. Distance from trees affected community similarity of nursery seedlings to trees, but there was no interaction of provenance with MNs in their effect on similarity in either nursery seedlings or field germinants as hypothesized. We conclude that MNs of trees influence EM colonization patterns of seedlings, and the strength of these effects increases with climatic drought. © Springer-Verlag 2012

  4. Five years database of landslides and floods affecting Swiss transportation networks

    Science.gov (United States)

    Voumard, Jérémie; Derron, Marc-Henri; Jaboyedoff, Michel

    2017-04-01

    Switzerland is a country threatened by a lot of natural hazards. Many events occur in built environment, affecting infrastructures, buildings or transportation networks and producing occasionally expensive damages. This is the reason why large landslides are generally well studied and monitored in Switzerland to reduce the financial and human risks. However, we have noticed a lack of data on small events which have impacted roads and railways these last years. This is why we have collect all the reported natural hazard events which have affected the Swiss transportation networks since 2012 in a database. More than 800 roads and railways closures have been recorded in five years from 2012 to 2016. These event are classified into six classes: earth flow, debris flow, rockfall, flood, avalanche and others. Data come from Swiss online press articles sorted by Google Alerts. The search is based on more than thirty keywords, in three languages (Italian, French, German). After verifying that the article relates indeed an event which has affected a road or a railways track, it is studied in details. We get finally information on about sixty attributes by event about event date, event type, event localisation, meteorological conditions as well as impacts and damages on the track and human damages. From this database, many trends over the five years of data collection can be outlined: in particular, the spatial and temporal distributions of the events, as well as their consequences in term of traffic (closure duration, deviation, etc.). Even if the database is imperfect (by the way it was built and because of the short time period considered), it highlights the not negligible impact of small natural hazard events on roads and railways in Switzerland at a national level. This database helps to better understand and quantify this events, to better integrate them in risk assessment.

  5. Network-oriented modeling addressing complexity of cognitive, affective and social interactions

    CERN Document Server

    Treur, Jan

    2016-01-01

    This book presents a new approach that can be applied to complex, integrated individual and social human processes. It provides an alternative means of addressing complexity, better suited for its purpose than and effectively complementing traditional strategies involving isolation and separation assumptions. Network-oriented modeling allows high-level cognitive, affective and social models in the form of (cyclic) graphs to be constructed, which can be automatically transformed into executable simulation models. The modeling format used makes it easy to take into account theories and findings about complex cognitive and social processes, which often involve dynamics based on interrelating cycles. Accordingly, it makes it possible to address complex phenomena such as the integration of emotions within cognitive processes of all kinds, of internal simulations of the mental processes of others, and of social phenomena such as shared understandings and collective actions. A variety of sample models – including ...

  6. Building a Global Network of Hydro-climatology Sites in Cloud-affected Tropical Montane Forests

    Science.gov (United States)

    Moore, G. W.; Asbjornsen, H.; Bruijnzeel, S., Sr.; Berry, Z. C.; Giambelluca, T. W.; Martin, P.; Mulligan, M.

    2015-12-01

    Tropical montane forests are characteristically wet environments with low evapotranspiration and sometimes significant contributions from fog interception. They are often located at headwater catchments critical for water supplies, but ecohydroclimate data in these regions are sparse. Such evidence may be crucial for assessing climate alterations in these sensitive ecosystems. As part of a global effort led by the Tropical Montane Cloud Forest Research Coordination Network (Cloudnet - http://cloudnet.agsci.colostate.edu), we aim to extend the network of tropical montane forest sites and establish robust protocols for measuring key ecohydroclimatic parameters, including fog interception, windblown rain, throughfall, leaf wetness, and micrometeorological conditions. Specific recommendations for standardized protocols include (1) rain and fog collectors uniquely designed to separately quantify fog interception from direct rain inputs, even in windy conditions, (2) trough-style throughfall gages that collect 40 times the area of a typical tipping bucket gage with added features to reduce splash-out, (3) clusters of leaf wetness sensors to differentiate frequency and duration of wetness caused by rain and fog on windward and leeward exposures, and (4) basic micrometeorological sensors for solar radiation, temperature, humidity, and wind. At sites where resources allow for additional measurements, we developed protocols for quantifying soil moisture, soil saturation, and plant water uptake from both roots and leaves (i.e. foliar absorption), since these are also important drivers in these systems. Participating sites will be invited to contribute to a global meta-analysis that will provide new insights into the ecohydrology of cloud-affected tropical montane forests.

  7. Pharmacological treatments in asthma-affected horses: A pair-wise and network meta-analysis.

    Science.gov (United States)

    Calzetta, L; Roncada, P; di Cave, D; Bonizzi, L; Urbani, A; Pistocchini, E; Rogliani, P; Matera, M G

    2017-11-01

    Equine asthma is a disease characterised by reversible airflow obstruction, bronchial hyper-responsiveness and airway inflammation following exposure of susceptible horses to specific airborne agents. Although clinical remission can be achieved in a low-airborne dust environment, repeated exacerbations may lead to irreversible airway remodelling. The available data on the pharmacotherapy of equine asthma result from several small studies, and no head-to-head clinical trials have been conducted among the available medications. To assess the impact of the pharmacological interventions in equine asthma and compare the effect of different classes of drugs on lung function. Pair-wise and network meta-analysis. Literature searches for clinical trials on the pharmacotherapy of equine asthma were performed. The risk of publication bias was assessed by funnel plots and Egger's test. Changes in maximum transpulmonary or pleural pressure, pulmonary resistance and dynamic lung compliance vs. control were analysed via random-effects models and Bayesian networks. The results obtained from 319 equine asthma-affected horses were extracted from 32 studies. Bronchodilators, corticosteroids and chromones improved maximum transpulmonary or pleural pressure (range: -8.0 to -21.4 cmH 2 O; Ptherapies. Long-term treatments were more effective than short-term treatments. Weak publication bias was detected. This study demonstrates that long-term treatments with inhaled corticosteroids and long-acting β 2 -AR agonists may represent the first choice for treating equine asthma. Further high quality clinical trials are needed to clarify whether inhaled bronchodilators should be preferred to inhaled corticosteroids or vice versa, and to investigate the potential superiority of combination therapy in equine asthma. © 2017 EVJ Ltd.

  8. Identifying diseases-related metabolites using random walk.

    Science.gov (United States)

    Hu, Yang; Zhao, Tianyi; Zhang, Ningyi; Zang, Tianyi; Zhang, Jun; Cheng, Liang

    2018-04-11

    Metabolites disrupted by abnormal state of human body are deemed as the effect of diseases. In comparison with the cause of diseases like genes, these markers are easier to be captured for the prevention and diagnosis of metabolic diseases. Currently, a large number of metabolic markers of diseases need to be explored, which drive us to do this work. The existing metabolite-disease associations were extracted from Human Metabolome Database (HMDB) using a text mining tool NCBO annotator as priori knowledge. Next we calculated the similarity of a pair-wise metabolites based on the similarity of disease sets of them. Then, all the similarities of metabolite pairs were utilized for constructing a weighted metabolite association network (WMAN). Subsequently, the network was utilized for predicting novel metabolic markers of diseases using random walk. Totally, 604 metabolites and 228 diseases were extracted from HMDB. From 604 metabolites, 453 metabolites are selected to construct the WMAN, where each metabolite is deemed as a node, and the similarity of two metabolites as the weight of the edge linking them. The performance of the network is validated using the leave one out method. As a result, the high area under the receiver operating characteristic curve (AUC) (0.7048) is achieved. The further case studies for identifying novel metabolites of diabetes mellitus were validated in the recent studies. In this paper, we presented a novel method for prioritizing metabolite-disease pairs. The superior performance validates its reliability for exploring novel metabolic markers of diseases.

  9. Biochemical and secondary metabolites changes under moisture ...

    African Journals Online (AJOL)

    The study showed the importance of carbohydrate and nitrogen cycle related metabolites in mediating tolerance in cassava by affecting their phenotypic expression in the plant. Keywords: Hydrothermal stress, bio-chemicals, pigments, secondary metabolites, cassava. African Journal of Biotechnology, Vol 13(31) 3173-3186 ...

  10. Inertial forces affect fluid front displacement dynamics in a pore-throat network model.

    Science.gov (United States)

    Moebius, Franziska; Or, Dani

    2014-08-01

    The seemingly regular and continuous motion of fluid displacement fronts in porous media at the macroscopic scale is propelled by numerous (largely invisible) pore-scale abrupt interfacial jumps and pressure bursts. Fluid fronts in porous media are characterized by sharp phase discontinuities and by rapid pore-scale dynamics that underlie their motion; both attributes challenge standard continuum theories of these flow processes. Moreover, details of pore-scale dynamics affect front morphology and subsequent phase entrapment behind a front and thereby shape key macroscopic transport properties of the unsaturated zone. The study presents a pore-throat network model that focuses on quantifying interfacial dynamics and interactions along fluid displacement fronts. The porous medium is represented by a lattice of connected pore throats capable of detaining menisci and giving rise to fluid-fluid interfacial jumps (the study focuses on flow rate controlled drainage). For each meniscus along the displacement front we formulate a local inertial, capillary, viscous, and hydrostatic force balance that is then solved simultaneously for the entire front. The model enables systematic evaluation of the role of inertia and boundary conditions. Results show that while displacement patterns are affected by inertial forces mainly by invasion of throats with higher capillary resistance, phase entrapment (residual saturation) is largely unaffected by inertia, limiting inertial effects on hydrological properties behind a front. Interfacial jump velocities are often an order of magnitude larger than mean front velocity, are strongly dependent on geometrical throat dimensions, and become less predictable (more scattered) when inertia is considered. Model simulations of the distributions of capillary pressure fluctuations and waiting times between invasion events follow an exponential distribution and are in good agreement with experimental results. The modeling approach provides insights

  11. What is Impulse Buying? An analytical network processing framework for prioritizing factors affecting impulse buying

    Directory of Open Access Journals (Sweden)

    Javad Siahkali Moradi

    2012-08-01

    Full Text Available One of the most important issues affecting profitability is to determine the impact of different factors influencing purchasing activities. In this paper, we perform an extensive literature survey to detect different purchasing factors influencing customers' behavior. The factors are categorized in three different groups and they are ranked using analytical network process. The results of our survey indicate that three factors of personal, product and situational play important roles in purchasing impulse. The personal item includes different factors where demographic characteristic factors receive the highest ranking (35% followed by other factors are feelings, excitement and fun, self identify, education and novelty. There are also three sub-factors associated with demographic characteristics including gender, age and race and the weights are 0.46748, 0.42668 and 0.10584, respectively, which means gender is the most important factor followed by age and race. Finally, the other factor is associated with situational factors' group, which includes presence of others, culture, design of store, time available, local market condition, sales staff and self service with the relative importance of 0.04296, 0.08733, 0.12130, 0.22217, 0.05643, 0.15346 and 0.31635, respectively.

  12. Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder.

    Science.gov (United States)

    Hamilton, J Paul; Glover, Gary H; Bagarinao, Epifanio; Chang, Catie; Mackey, Sean; Sacchet, Matthew D; Gotlib, Ian H

    2016-03-30

    Neural models of major depressive disorder (MDD) posit that over-response of components of the brain's salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the real-neurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. DETERMINATION OF AGE AND GENDER DIFFERENCES IN BIOCHEMICAL PROCESSES AFFECTING THE DISPOSITION OF 2-BUTOXYETHANOL AND ITS METABOLITES IN MICE AND RATS TO IMPROVE PBPK MODELING

    Energy Technology Data Exchange (ETDEWEB)

    Corley, Rick A.; Grant, Donna M.; Farris, Elizabeth; Weitz, Karl K.; Soelberg, Jolen J.; Thrall, K D.; Poet, Torka S.

    2005-03-28

    2-Butoxyethanol (BE) is the most widely used glycol ether solvent. BE's major metabolite, butoxyacetic acid (BAA), causes hemolysis with significant species differences in sensitivity. Several PBPK models have been developed over the past two decades to describe the disposition of BE and BAA in male rats and humans to refine health risk assessments. More recent efforts by Lee et al. (1998) to describe the kinetics of BE and BAA in the National Toxicology Program (NTP) chronic inhalation studies required the use of several assumptions to extrapolate model parameters from earlier PBPK models developed for young male rats to include female F344 and both sexes of B6C3F1 mice and the effects of aging. To replace these assumptions, studies were conducted to determine the impact of age, gender and species on the metabolism of BE, and the tissue partitioning, renal acid transport and plasma protein binding of BAA. In the current study, the Lee et al. PBPK model was updated and expanded to include the further metabolism of BAA and the salivary excretion of BE and BAA which may contribute to the forestomach irritation observed in mice in the NTP study. The revised model predicted that peak blood concentrations of BAA achieved following 6-hr inhalation exposures are greatest in young adult female rats at concentrations up to 300 ppm. This is not the case predicted for old (>18 months) animals, where peak blood concentrations of BAA in male and female mice were similar to or greater than female rats. The revised model serves as a quantitative tool for integrating an extensive pharmacokinetic and mechanistic database into a format that can readily be used to compare internal dosimetry across dose, route of exposure and species.

  14. Hyper-modulation of brain networks by the amygdala among women with Borderline Personality Disorder: Network signatures of affective interference during cognitive processing.

    Science.gov (United States)

    Soloff, Paul H; Abraham, Kristy; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A

    2017-05-01

    Emotion dysregulation is a core characteristic of patients with Borderline Personality Disorder (BPD), and is often attributed to an imbalance in fronto-limbic network function. Hyperarousal of amygdala, especially in response to negative affective stimuli, results in affective interference with cognitive processing of executive functions. Clinical consequences include the impulsive-aggression, suicidal and self-injurious behaviors which characterize BPD. Dysfunctional interactions between amygdala and its network targets have not been well characterized during cognitive task performance. Using psychophysiological interaction analysis (PPI), we mapped network profiles of amygdala interaction with key regulatory regions during a Go No-Go task, modified to use negative, positive and neutral Ekman faces as targets. Fifty-six female subjects, 31 BPD and 25 healthy controls (HC), completed the affectively valenced Go No-Go task during fMRI scanning. In the negative affective condition, the amygdala exerted greater modulation of its targets in BPD compared to HC subjects in Rt. OFC, Rt. dACC, Rt. Parietal cortex, Rt. Basal Ganglia, and Rt. dlPFC. Across the spectrum of affective contrasts, hypermodulation in BPD subjects observed the following ordering: Negative > Neutral > Positive contrast. The amygdala seed exerted modulatory effects on specific target regions important in processing response inhibition and motor impulsiveness. The vulnerability of BPD subjects to affective interference with impulse control may be due to specific network dysfunction related to amygdala hyper-arousal and its effects on prefrontal regulatory regions such as the OFC and dACC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Parameters affecting the resilience of scale-free networks to random failures.

    Energy Technology Data Exchange (ETDEWEB)

    Link, Hamilton E.; LaViolette, Randall A.; Lane, Terran (University of New Mexico, Albuquerque, NM); Saia, Jared (University of New Mexico, Albuquerque, NM)

    2005-09-01

    It is commonly believed that scale-free networks are robust to massive numbers of random node deletions. For example, Cohen et al. in (1) study scale-free networks including some which approximate the measured degree distribution of the Internet. Their results suggest that if each node in this network failed independently with probability 0.99, most of the remaining nodes would still be connected in a giant component. In this paper, we show that a large and important subclass of scale-free networks are not robust to massive numbers of random node deletions. In particular, we study scale-free networks which have minimum node degree of 1 and a power-law degree distribution beginning with nodes of degree 1 (power-law networks). We show that, in a power-law network approximating the Internet's reported distribution, when the probability of deletion of each node is 0.5 only about 25% of the surviving nodes in the network remain connected in a giant component, and the giant component does not persist beyond a critical failure rate of 0.9. The new result is partially due to improved analytical accommodation of the large number of degree-0 nodes that result after node deletions. Our results apply to power-law networks with a wide range of power-law exponents, including Internet-like networks. We give both analytical and empirical evidence that such networks are not generally robust to massive random node deletions.

  16. Multi-Omics and Integrated Network Analyses Reveal New Insights into the Systems Relationships between Metabolites, Structural Genes, and Transcriptional Regulators in Developing Grape Berries (Vitis vinifera L. Exposed to Water Deficit

    Directory of Open Access Journals (Sweden)

    Stefania Savoi

    2017-07-01

    Full Text Available Grapes are one of the major fruit crops and they are cultivated in many dry environments. This study comprehensively characterizes the metabolic response of grape berries exposed to water deficit at different developmental stages. Increases of proline, branched-chain amino acids, phenylpropanoids, anthocyanins, and free volatile organic compounds have been previously observed in grape berries exposed to water deficit. Integrating RNA-sequencing analysis of the transcriptome with large-scale analysis of central and specialized metabolites, we reveal that these increases occur via a coordinated regulation of key structural pathway genes. Water deficit-induced up-regulation of flavonoid genes is also coordinated with the down-regulation of many stilbene synthases and a consistent decrease in stilbenoid concentration. Water deficit activated both ABA-dependent and ABA-independent signal transduction pathways by modulating the expression of several transcription factors. Gene-gene and gene-metabolite network analyses showed that water deficit-responsive transcription factors such as bZIPs, AP2/ERFs, MYBs, and NACs are implicated in the regulation of stress-responsive metabolites. Enrichment of known and novel cis-regulatory elements in the promoters of several ripening-specific/water deficit-induced modules further affirms the involvement of a transcription factor cross-talk in the berry response to water deficit. Together, our integrated approaches show that water deficit-regulated gene modules are strongly linked to key fruit-quality metabolites and multiple signal transduction pathways may be critical to achieve a balance between the regulation of the stress-response and the berry ripening program. This study constitutes an invaluable resource for future discoveries and comparative studies, in grapes and other fruits, centered on reproductive tissue metabolism under abiotic stress.

  17. Multi-Omics and Integrated Network Analyses Reveal New Insights into the Systems Relationships between Metabolites, Structural Genes, and Transcriptional Regulators in Developing Grape Berries (Vitis viniferaL.) Exposed to Water Deficit.

    Science.gov (United States)

    Savoi, Stefania; Wong, Darren C J; Degu, Asfaw; Herrera, Jose C; Bucchetti, Barbara; Peterlunger, Enrico; Fait, Aaron; Mattivi, Fulvio; Castellarin, Simone D

    2017-01-01

    Grapes are one of the major fruit crops and they are cultivated in many dry environments. This study comprehensively characterizes the metabolic response of grape berries exposed to water deficit at different developmental stages. Increases of proline, branched-chain amino acids, phenylpropanoids, anthocyanins, and free volatile organic compounds have been previously observed in grape berries exposed to water deficit. Integrating RNA-sequencing analysis of the transcriptome with large-scale analysis of central and specialized metabolites, we reveal that these increases occur via a coordinated regulation of key structural pathway genes. Water deficit-induced up-regulation of flavonoid genes is also coordinated with the down-regulation of many stilbene synthases and a consistent decrease in stilbenoid concentration. Water deficit activated both ABA-dependent and ABA-independent signal transduction pathways by modulating the expression of several transcription factors. Gene-gene and gene-metabolite network analyses showed that water deficit-responsive transcription factors such as bZIPs, AP2/ERFs, MYBs, and NACs are implicated in the regulation of stress-responsive metabolites. Enrichment of known and novel cis -regulatory elements in the promoters of several ripening-specific/water deficit-induced modules further affirms the involvement of a transcription factor cross-talk in the berry response to water deficit. Together, our integrated approaches show that water deficit-regulated gene modules are strongly linked to key fruit-quality metabolites and multiple signal transduction pathways may be critical to achieve a balance between the regulation of the stress-response and the berry ripening program. This study constitutes an invaluable resource for future discoveries and comparative studies, in grapes and other fruits, centered on reproductive tissue metabolism under abiotic stress.

  18. Stress affects theta activity in limbic networks and impairs novelty-induced exploration and familiarization

    Directory of Open Access Journals (Sweden)

    Luis eJacinto

    2013-10-01

    Full Text Available Exposure to a novel environment triggers the response of several brain areas that regulate emotional behaviors. Here, we studied theta oscillations within the hippocampus (HPC-amygdala (AMY-medial prefrontal cortex (mPFC network in exploration of a novel environment and subsequent familiarization through repeated exposures to that same environment; in addition, we assessed how concomitant stress exposure could disrupt this activity and impair both behavioral processes. Local field potentials were simultaneously recorded from dorsal and ventral hippocampus (dHPC and vHPC respectively, basolateral amygdala (BLA and mPFC in freely behaving rats while they were exposed to a novel environment, then repeatedly re-exposed over the course of 3 weeks to that same environment and, finally, on re-exposure to a novel unfamiliar environment. A longitudinal analysis of theta activity within this circuit revealed a reduction of vHPC and BLA theta power and vHPC-BLA theta coherence through familiarization which was correlated with a return to normal exploratory behavior in control rats. In contrast, a persistent over-activation of the same brain regions was observed in stressed rats that displayed impairments in novel exploration and familiarization processes. Importantly, we show that stress also affected intra-hippocampal synchrony and heightened the coherence between vHPC and BLA. In summary, we demonstrate that modulatory theta activity in the aforementioned circuit, namely in the vHPC and BLA, is correlated with the expression of anxiety in novelty-induced exploration and familiarization in both normal and pathological conditions.

  19. An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    František Váša

    2016-01-01

    Full Text Available Chromosome 22q11.2 deletion syndrome (22q11DS is a genetic disease known to lead to cerebral structural alterations, which we study using the framework of the macroscopic white-matter connectome. We create weighted connectomes of 44 patients with 22q11DS and 44 healthy controls using diffusion tensor magnetic resonance imaging, and perform a weighted graph theoretical analysis. After confirming global network integration deficits in 22q11DS (previously identified using binary connectomes, we identify the spatial distribution of regions responsible for global deficits. Next, we further characterize the dysconnectivity of the deficient regions in terms of sub-network properties, and investigate their relevance with respect to clinical profiles. We define the subset of regions with decreased nodal integration (evaluated using the closeness centrality measure as the affected core (A-core of the 22q11DS structural connectome. A-core regions are broadly bilaterally symmetric and consist of numerous network hubs — chiefly parietal and frontal cortical, as well as subcortical regions. Using a simulated lesion approach, we demonstrate that these core regions and their connections are particularly important to efficient network communication. Moreover, these regions are generally densely connected, but less so in 22q11DS. These specific disturbances are associated to a rerouting of shortest network paths that circumvent the A-core in 22q11DS, “de-centralizing” the network. Finally, the efficiency and mean connectivity strength of an orbito-frontal/cingulate circuit, included in the affected regions, correlate negatively with the extent of negative symptoms in 22q11DS patients, revealing the clinical relevance of present findings. The identified A-core overlaps numerous regions previously identified as affected in 22q11DS as well as in schizophrenia, which approximately 30–40% of 22q11DS patients develop.

  20. Meta-Analytically Informed Network Analysis of Resting State fMRI Reveals Hyperconnectivity in an Introspective Socio-Affective Network in Depression

    OpenAIRE

    Schilbach, Leonhard; Müller, Veronika I.; Hoffstaedter, Felix; Clos, Mareike; Goya-Maldonado, Roberto; Gruber, Oliver; Eickhoff, Simon B.

    2014-01-01

    Alterations of social cognition and dysfunctional interpersonal expectations are thought to play an important role in the etiology of depression and have, thus, become a key target of psychotherapeutic interventions. The underlying neurobiology, however, remains elusive. Based upon the idea of a close link between affective and introspective processes relevant for social interactions and alterations thereof in states of depression, we used a meta-analytically informed network analysis to inve...

  1. Large-scale brain networks in affective and social neuroscience: Towards an integrative functional architecture of the brain

    Science.gov (United States)

    Barrett, Lisa Feldman; Satpute, Ajay

    2013-01-01

    Understanding how a human brain creates a human mind ultimately depends on mapping psychological categories and concepts to physical measurements of neural response. Although it has long been assumed that emotional, social, and cognitive phenomena are realized in the operations of separate brain regions or brain networks, we demonstrate that it is possible to understand the body of neuroimaging evidence using a framework that relies on domain general, distributed structure-function mappings. We review current research in affective and social neuroscience and argue that the emerging science of large-scale intrinsic brain networks provides a coherent framework for a domain-general functional architecture of the human brain. PMID:23352202

  2. Real-time Monitoring Network to Characterize Anthropogenic and Natural Events Affecting the Hudson River, NY

    Science.gov (United States)

    Islam, M. S.; Bonner, J. S.; Fuller, C.; Kirkey, W.; Ojo, T.

    2011-12-01

    The Hudson River watershed spans 34,700 km2 predominantly in New York State, including agricultural, wilderness, and urban areas. The Hudson River supports many activities including shipping, supplies water for municipal, commercial, and agricultural uses, and is an important recreational resource. As the population increases within this watershed, so does the anthropogenic impact on this natural system. To address the impacts of anthropogenic and natural activities on this ecosystem, the River and Estuary Observatory Network (REON) is being developed through a joint venture between the Beacon Institute, Clarkson University, General Electric Inc. and IBM Inc. to monitor New York's Hudson and Mohawk Rivers in real-time. REON uses four sensor platform types with multiple nodes within the network to capture environmentally relevant episodic events. Sensor platform types include: 1) fixed robotic vertical profiler (FRVP); 2) mobile robotic undulating platform (MRUP); 3) fixed acoustic Doppler current profiler (FADCP) and 4) Autonomous Underwater Vehicle (AUV). The FRVP periodically generates a vertical profile with respect to water temperature, salinity, dissolved oxygen, particle concentration and size distribution, and fluorescence. The MRUP utilizes an undulating tow-body tethered behind a research vessel to measure the same set of water parameters as the FRVP, but does so 'synchronically' over a highly-resolved spatial regime. The fixed ADCP provides continuous water current profiles. The AUV maps four-dimensional (time, latitude, longitude, depth) variation of water quality, water currents and bathymetry along a pre-determined transect route. REON data can be used to identify episodic events, both anthropogenic and natural, that impact the Hudson River. For example, a strong heat signature associated with cooling water discharge from the Indian Point nuclear power plant was detected with the MRUP. The FRVP monitoring platform at Beacon, NY, located in the

  3. Customer social network affects marketing strategy: A simulation analysis based on competitive diffusion model

    Science.gov (United States)

    Hou, Rui; Wu, Jiawen; Du, Helen S.

    2017-03-01

    To explain the competition phenomenon and results between QQ and MSN (China) in the Chinese instant messaging software market, this paper developed a new population competition model based on customer social network. The simulation results show that the firm whose product with greater network externality effect will gain more market share than its rival when the same marketing strategy is used. The firm with the advantage of time, derived from the initial scale effect will become more competitive than its rival when facing a group of common penguin customers within a social network, verifying the winner-take-all phenomenon in this case.

  4. Dietary strawberry seed oil affects metabolite formation in the distal intestine and ameliorates lipid metabolism in rats fed an obesogenic diet

    Directory of Open Access Journals (Sweden)

    Adam Jurgoński

    2015-01-01

    Full Text Available Objective: To answer the question whether dietary strawberry seed oil rich in α-linolenic acid and linoleic acid (29.3 and 47.2% of total fatty acids, respectively can beneficially affect disorders induced by the consumption of an obesogenic diet. Design: Thirty-two male Wistar rats were randomly assigned to four groups of eight animals each and fed with a basal or obesogenic (high in fat and low in fiber diet that contained either strawberry seed oil or an edible rapeseed oil. A two-way analysis of variance was then applied to assess the effects of diet and oil and the interaction between them. Results: After 8 weeks of feeding, the obesogenic diet increased the body weight and the liver mass and fat content, whereas decreased the cecal acetate and butyrate concentration. This diet also altered the plasma lipid profile and decreased the liver sterol regulatory element-binding protein 1c (SREBP-1c content. However, the lowest liver SREBP-1c content was observed in rats fed an obesogenic diet containing strawberry seed oil. Moreover, dietary strawberry seed oil decreased the cecal short-chain fatty acid concentrations (acetate, propionate, and butyrate regardless of the diet type, whereas the cecal β-glucuronidase activity was considerably increased only in rats fed an obesogenic diet containing strawberry seed oil. Dietary strawberry seed oil also lowered the liver fat content, the plasma triglyceride level and the atherogenic index of plasma. Conclusions: Strawberry seed oil has a potent lipid-lowering activity but can unfavorably affect microbial metabolism in the distal intestine. The observed effects are partly due to the synergistic action of the oil and the obesogenic diet.

  5. Comparing social factors affecting recommender decisions in online and educational social network

    Science.gov (United States)

    MartÍn, Estefanía; Hernán-Losada, Isidoro; Haya, Pablo A.

    2016-01-01

    In the educational context, there is an increasing interest in learning networks. Recommender systems (RSs) can play an important role in achieving educational objectives. Although we can find many papers focused on recommendation techniques and algorithms, in general, less attention has been dedicated to social factors that influence the recommendation process. This process could be improved if we had a deeper understanding of the social factors that influence the quality or validity of a suggestion made by the RS. This work elucidates and analyses the social factors that influence the design and decision-making process of RSs. We conducted a survey in which 126 undergraduate students were asked to extract which are the main factors for improving suggestions when they are interacting with an Online Social Network (OSN) or in an Educational Social Network (ESN). The results show that different factors have to be considered depending on the type of network.

  6. Ethanol affects network activity in cultured rat hippocampus: mediation by potassium channels.

    Directory of Open Access Journals (Sweden)

    Eduard Korkotian

    Full Text Available The effects of ethanol on neuronal network activity were studied in dissociated cultures of rat hippocampus. Exposure to low (0.25-0.5% ethanol concentrations caused an increase in synchronized network spikes, and a decrease in the duration of individual spikes. Ethanol also caused an increase in rate of miniature spontaneous excitatory postsynaptic currents. Higher concentrations of ethanol eliminated network spikes. These effects were reversible upon wash. The effects of the high, but not the low ethanol were blocked by the GABA antagonist bicuculline. The enhancing action of low ethanol was blocked by apamin, an SK potassium channel antagonist, and mimicked by 1-EBIO, an SK channel opener. It is proposed that in cultured hippocampal networks low concentration of ethanol is associated with SK channel activity, rather than the GABAergic receptor.

  7. Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter

    Directory of Open Access Journals (Sweden)

    Martin Nørgaard

    2017-11-01

    Full Text Available Background: Seasonal Affective Disorder (SAD is a subtype of Major Depressive Disorder characterized by seasonally occurring depression that often presents with atypical vegetative symptoms such as hypersomnia and carbohydrate craving. It has recently been shown that unlike healthy people, patients with SAD fail to globally downregulate their cerebral serotonin transporter (5-HTT in winter, and that this effect seemed to be particularly pronounced in female S-carriers of the 5-HTTLPR genotype. The purpose of this study was to identify a 5-HTT brain network that accounts for the adaption to the environmental stressor of winter in females with the short 5-HTTLPR genotype, a specific subgroup previously reported to be at increased risk for developing SAD.Methods: Nineteen females, either S' carriers (LG- and S-carriers without SAD (N = 13, mean age 23.6 ± 3.2 year, range 19–28 or S' carriers with SAD (N = 6, mean age 23.7 ± 2.4, range 21–26 were PET-scanned with [11C]DASB during both summer and winter seasons (asymptomatic and symptomatic phase, 38 scans in total in randomized order, defined as a 12-week interval centered on summer or winter solstice. We used a multivariate Partial Least Squares (PLS approach with NPAIRS split-half cross-validation, to identify and map a whole-brain pattern of 5-HTT levels that distinguished the brains of females without SAD from females suffering from SAD.Results: We identified a pattern of 5-HTT levels, distinguishing females with SAD from those without SAD; it included the right superior frontal gyrus, brainstem, globus pallidus (bilaterally and the left hippocampus. Across seasons, female S' carriers without SAD showed nominally higher 5-HTT levels in these regions compared to female S' carriers with SAD, but the group difference was only significant in the winter. Female S' carriers with SAD, in turn, displayed robustly increased 5-HTT levels in the ventral striatum (bilaterally, right orbitofrontal

  8. Dysfunction of Affective Network in Post Ischemic Stroke Depression: A Resting-State Functional Magnetic Resonance Imaging Study

    OpenAIRE

    Peiyao Zhang; Qin Xu; Jianping Dai; Jun Wang; Ning Zhang; Yuejia Luo

    2014-01-01

    Objective. Previous studies have demonstrated that stroke characteristics and social and psychological factors jointly contribute to the development of poststroke depression (PSD). The purpose of this study was to identify altered functional connectivity (FC) of the affective network (AN) in patients with PSD and to explore the correlation between FC and the severity of PSD. Materials and Methods. 26 PSD patients, 24 stroke patients without depression, and 24 age-matched normal controls under...

  9. Ecologically relevant UV-B dose combined with high PAR intensity distinctly affect plant growth and accumulation of secondary metabolites in leaves of Centella asiatica L. Urban.

    Science.gov (United States)

    Müller, Viola; Albert, Andreas; Barbro Winkler, J; Lankes, Christa; Noga, Georg; Hunsche, Mauricio

    2013-10-05

    We investigated the effects of environmentally relevant dose of ultraviolet (UV)-B and photosynthetic active radiation (PAR) on saponin accumulation in leaves on the example of Centella asiatica L. Urban. For this purpose, plants were exposed to one of four light regimes i.e., two PAR intensities with or without UV-B radiation. The experiment was conducted in technically complex sun simulators under almost natural irradiance and climatic conditions. As observed, UV-B radiation increased herb and leaf production as well as the content of epidermal flavonols, which was monitored by non-destructive fluorescence measurements. Specific fluorescence indices also indicate an increase in the content of anthocyanins under high PAR; this increase was likewise observed for the saponin concentrations. In contrast, UV-B radiation had no distinct effects on saponin and sapogenin concentrations. Our findings suggest that besides flavonoids, also saponins were accumulated under high PAR protecting the plant from oxidative damage. Furthermore, glycosylation of sapogenins seems to be important either for the protective function and/or for compartmentalization of the compounds. Moreover, our study revealed that younger leaves contain higher amounts of saponins, while in older leaves the sapogenins were the most abundant constituents. Concluding, our results proof that ambient dose of UV-B and high PAR intensity distinctly affect the accumulation of flavonoids and saponins, enabling the plant tissue to adapt to the light conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. The BDNF Val66Met Polymorphism Affects the Vulnerability of the Brain Structural Network

    Directory of Open Access Journals (Sweden)

    Chang-hyun Park

    2017-08-01

    Full Text Available Val66Met, a naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF gene resulting in a valine (Val to methionine (Met substitution at codon 66, plays an important role in neuroplasticity. While the effect of the BDNF Val66Met polymorphism on local brain structures has previously been examined, its impact on the configuration of the graph-based white matter structural networks is yet to be investigated. In the current study, we assessed the effect of the BDNF polymorphism on the network properties and robustness of the graph-based white matter structural networks. Graph theory was employed to investigate the structural connectivity derived from white matter tractography in two groups, Val homozygotes (n = 18 and Met-allele carriers (n = 55. Although there were no differences in the global network measures including global efficiency, local efficiency, and modularity between the two genotype groups, we found the effect of the BDNF Val66Met polymorphism on the robustness properties of the white matter structural networks. Specifically, the white matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygote group. These findings suggest that the central role of the BDNF Val66Met polymorphism in regards to neuroplasticity may be associated with inherent differences in the robustness of the white matter structural network according to the genetic variants. Furthermore, greater susceptibility to brain disorders in Met-allele carriers may be understood as being due to their limited stability in white matter structural connectivity.

  11. Coupling between feedback loops in autoregulatory networks affects bistability range, open-loop gain and switching times

    International Nuclear Information System (INIS)

    Tiwari, Abhinav; Igoshin, Oleg A

    2012-01-01

    Biochemical regulatory networks governing diverse cellular processes such as stress-response, differentiation and cell cycle often contain coupled feedback loops. We aim at understanding how features of feedback architecture, such as the number of loops, the sign of the loops and the type of their coupling, affect network dynamical performance. Specifically, we investigate how bistability range, maximum open-loop gain and switching times of a network with transcriptional positive feedback are affected by additive or multiplicative coupling with another positive- or negative-feedback loop. We show that a network's bistability range is positively correlated with its maximum open-loop gain and that both quantities depend on the sign of the feedback loops and the type of feedback coupling. Moreover, we find that the addition of positive feedback could decrease the bistability range if we control the basal level in the signal-response curves of the two systems. Furthermore, the addition of negative feedback has the capacity to increase the bistability range if its dissociation constant is much lower than that of the positive feedback. We also find that the addition of a positive feedback to a bistable network increases the robustness of its bistability range, whereas the addition of a negative feedback decreases it. Finally, we show that the switching time for a transition from a high to a low steady state increases with the effective fold change in gene regulation. In summary, we show that the effect of coupled feedback loops on the bistability range and switching times depends on the underlying mechanistic details. (paper)

  12. Concurrent information affects response inhibition processes via the modulation of theta oscillations in cognitive control networks.

    Science.gov (United States)

    Chmielewski, Witold X; Mückschel, Moritz; Dippel, Gabriel; Beste, Christian

    2016-11-01

    Inhibiting responses is a challenge, where the outcome (partly) depends on the situational context. In everyday situations, response inhibition performance might be altered when irrelevant input is presented simultaneously with the information relevant for response inhibition. More specifically, irrelevant concurrent information may either brace or interfere with response-relevant information, depending on whether these inputs are redundant or conflicting. The aim of this study is to investigate neurophysiological mechanisms and the network underlying such modulations using EEG beamforming as method. The results show that in comparison to a baseline condition without concurrent information, response inhibition performance can be aggravated or facilitated by manipulating the extent of conflict via concurrent input. This depends on whether the requirement for cognitive control is high, as in conflicting trials, or whether it is low, as in redundant trials. In line with this, the total theta frequency power decreases in a right hemispheric orbitofrontal response inhibition network including the SFG, MFG, and SMA, when concurrent redundant information facilitates response inhibition processes. Vice versa, theta activity in a left-hemispheric response inhibition network (i.e., SFG, MFG, and IFG) increases, when conflicting concurrent information compromises response inhibition processes. We conclude that concurrent information bi-directionally shifts response inhibition performance and modulates the network architecture underlying theta oscillations which are signaling different levels of the need for cognitive control.

  13. Brain network analysis reveals affected connectome structure in bipolar I disorder

    NARCIS (Netherlands)

    Collin, Guusje; van den Heuvel, Martijn P.; Abramovic, Lucija; Vreeker, Annabel; de Reus, Marcel A.; van Haren, Neeltje E M; Boks, Marco P M; Ophoff, Roel A.; Kahn, René S.

    The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections-i.e., the connectome-suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in

  14. Network Analysis Reveals Putative Genes Affecting Meat Quality in Angus Cattle

    Directory of Open Access Journals (Sweden)

    Raluca G. Mateescu

    2017-11-01

    Full Text Available Improvements in eating satisfaction will benefit consumers and should increase beef demand which is of interest to the beef industry. Tenderness, juiciness, and flavor are major determinants of the palatability of beef and are often used to reflect eating satisfaction. Carcass qualities are used as indicator traits for meat quality, with higher quality grade carcasses expected to relate to more tender and palatable meat. However, meat quality is a complex concept determined by many component traits making interpretation of genome-wide association studies (GWAS on any one component challenging to interpret. Recent approaches combining traditional GWAS with gene network interactions theory could be more efficient in dissecting the genetic architecture of complex traits. Phenotypic measures of 23 traits reflecting carcass characteristics, components of meat quality, along with mineral and peptide concentrations were used along with Illumina 54k bovine SNP genotypes to derive an annotated gene network associated with meat quality in 2,110 Angus beef cattle. The efficient mixed model association (EMMAX approach in combination with a genomic relationship matrix was used to directly estimate the associations between 54k SNP genotypes and each of the 23 component traits. Genomic correlated regions were identified by partial correlations which were further used along with an information theory algorithm to derive gene network clusters. Correlated SNP across 23 component traits were subjected to network scoring and visualization software to identify significant SNP. Significant pathways implicated in the meat quality complex through GO term enrichment analysis included angiogenesis, inflammation, transmembrane transporter activity, and receptor activity. These results suggest that network analysis using partial correlations and annotation of significant SNP can reveal the genetic architecture of complex traits and provide novel information regarding

  15. Metabolic pathway of non-alcoholic fatty liver disease: Network properties and robustness

    Directory of Open Access Journals (Sweden)

    WenJun Zhang

    2017-03-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a systematic and complex disease involving various cytokines/metabolites. In present article, we use methodology of network biology to analyze network properties of NAFLD metabolic pathway. It is found that the metabolic pathway of NAFLD is not a typical complex network with power-law degree distribution, p(x=x^(-4.4275, x>=5. There is only one connected component in the metabolic pathway. The calculated cut cytokines/metabolites of the metabolic pathway are SREBP-1c, ChREBP, ObR, AMPK, IRE1alpha, ROS, PERK, elF2alpha, ATF4, CHOP, Bim, CASP8, Bid, CxII, Lipogenic enzymes, XBP1, and FFAs. The most important cytokine/metabolite for possible network robustness is FFAs, seconded by TNF-alpha. It is concluded that FFAs is the most important cytokine/metabolite in the metabolic pathway, seconded by ROS. FFAs, LEP, ACDC, CYP2E1, and Glucose are the only cytokines/metabolites that affect others without influences from other cytokines/metabolites. Finally, the IDs matrix for identifying possible sub-networks/modules is given. However, jointly combining the results of connectedness analysis and sub-networks/modules identification, we hold that there are not significant sub-networks/modules in the pathway.

  16. Functions of secondary metabolites of lichens

    OpenAIRE

    Zvěřinová, Gabriela

    2014-01-01

    This bachelor thesis is a review of available literature about lichen secondary metabolites and their functions. Lichens produce a great variety of these compounds; most of them are unique to the lichen symbiosis and are not found in higher plants. Besides the role of these compounds in chemotaxonomy and systematics, lichen secondary metabolites exhibit various biological functions and can affect biotic and abiotic interactions of lichens with their environment. Well-known and often described...

  17. Factors affecting Malaysian university students’ purchase intention in social networking sites

    Directory of Open Access Journals (Sweden)

    Saeideh Sharifi fard

    2016-12-01

    Full Text Available This study applied the unified theory of acceptance and use of technology 2 to examine acceptance and use of social networking sites in a marketing setting. This study uses 370 regular higher education students in Malaysia as respondents. Quantitative method is used. The findings revealed that performance expectancy (PE and hedonic motivation were the main factors that influence users’ online purchase intention (PI through social networking sites (SNSs in Malaysia. As for moderating influences of gender and age, the results showed that gender significantly moderated purposed association between these four elements and the online PI, while the moderating effect of age was only recognized in PE. Findings of this research offer practitioners with better insights that would aid them in developing effective online marketing strategies to attract online purchasing users through SNSs.

  18. Alcohol affects the brain's resting-state network in social drinkers.

    Directory of Open Access Journals (Sweden)

    Chrysa Lithari

    Full Text Available Acute alcohol intake is known to enhance inhibition through facilitation of GABA(A receptors, which are present in 40% of the synapses all over the brain. Evidence suggests that enhanced GABAergic transmission leads to increased large-scale brain connectivity. Our hypothesis is that acute alcohol intake would increase the functional connectivity of the human brain resting-state network (RSN. To test our hypothesis, electroencephalographic (EEG measurements were recorded from healthy social drinkers at rest, during eyes-open and eyes-closed sessions, after administering to them an alcoholic beverage or placebo respectively. Salivary alcohol and cortisol served to measure the inebriation and stress levels. By calculating Magnitude Square Coherence (MSC on standardized Low Resolution Electromagnetic Tomography (sLORETA solutions, we formed cortical networks over several frequency bands, which were then analyzed in the context of functional connectivity and graph theory. MSC was increased (p<0.05, corrected with False Discovery Rate, FDR corrected in alpha, beta (eyes-open and theta bands (eyes-closed following acute alcohol intake. Graph parameters were accordingly altered in these bands quantifying the effect of alcohol on the structure of brain networks; global efficiency and density were higher and path length was lower during alcohol (vs. placebo, p<0.05. Salivary alcohol concentration was positively correlated with the density of the network in beta band. The degree of specific nodes was elevated following alcohol (vs. placebo. Our findings support the hypothesis that short-term inebriation considerably increases large-scale connectivity in the RSN. The increased baseline functional connectivity can -at least partially- be attributed to the alcohol-induced disruption of the delicate balance between inhibitory and excitatory neurotransmission in favor of inhibitory influences. Thus, it is suggested that short-term inebriation is associated, as

  19. Alcohol affects the brain's resting-state network in social drinkers.

    Science.gov (United States)

    Lithari, Chrysa; Klados, Manousos A; Pappas, Costas; Albani, Maria; Kapoukranidou, Dorothea; Kovatsi, Leda; Bamidis, Panagiotis D; Papadelis, Christos L

    2012-01-01

    Acute alcohol intake is known to enhance inhibition through facilitation of GABA(A) receptors, which are present in 40% of the synapses all over the brain. Evidence suggests that enhanced GABAergic transmission leads to increased large-scale brain connectivity. Our hypothesis is that acute alcohol intake would increase the functional connectivity of the human brain resting-state network (RSN). To test our hypothesis, electroencephalographic (EEG) measurements were recorded from healthy social drinkers at rest, during eyes-open and eyes-closed sessions, after administering to them an alcoholic beverage or placebo respectively. Salivary alcohol and cortisol served to measure the inebriation and stress levels. By calculating Magnitude Square Coherence (MSC) on standardized Low Resolution Electromagnetic Tomography (sLORETA) solutions, we formed cortical networks over several frequency bands, which were then analyzed in the context of functional connectivity and graph theory. MSC was increased (p<0.05, corrected with False Discovery Rate, FDR corrected) in alpha, beta (eyes-open) and theta bands (eyes-closed) following acute alcohol intake. Graph parameters were accordingly altered in these bands quantifying the effect of alcohol on the structure of brain networks; global efficiency and density were higher and path length was lower during alcohol (vs. placebo, p<0.05). Salivary alcohol concentration was positively correlated with the density of the network in beta band. The degree of specific nodes was elevated following alcohol (vs. placebo). Our findings support the hypothesis that short-term inebriation considerably increases large-scale connectivity in the RSN. The increased baseline functional connectivity can -at least partially- be attributed to the alcohol-induced disruption of the delicate balance between inhibitory and excitatory neurotransmission in favor of inhibitory influences. Thus, it is suggested that short-term inebriation is associated, as expected

  20. Coated or doped carbon nanotube network sensors as affected by environmental parameters

    Science.gov (United States)

    Li, Jing (Inventor)

    2011-01-01

    Methods for using modified single wall carbon nanotubes ("SWCNTs") to detect presence and/or concentration of a gas component, such as a halogen (e.g., Cl.sub.2), hydrogen halides (e.g., HCl), a hydrocarbon (e.g., C.sub.nH.sub.2n+2), an alcohol, an aldehyde or a ketone, to which an unmodified SWCNT is substantially non-reactive. In a first embodiment, a connected network of SWCNTs is coated with a selected polymer, such as chlorosulfonated polyethylene, hydroxypropyl cellulose, polystyrene and/or polyvinylalcohol, and change in an electrical parameter or response value (e.g., conductance, current, voltage difference or resistance) of the coated versus uncoated SWCNT networks is analyzed. In a second embodiment, the network is doped with a transition element, such as Pd, Pt, Rh, Ir, Ru, Os and/or Au, and change in an electrical parameter value is again analyzed. The parameter change value depends monotonically, not necessarily linearly, upon concentration of the gas component. Two general algorithms are presented for estimating concentration value(s), or upper or lower concentration bounds on such values, from measured differences of response values.

  1. Factors affecting patient enrollment in radiology clinical trials: a case study of the American College of Radiology Imaging Network.

    Science.gov (United States)

    Seltzer, Steven E; Sullivan, Daniel C; Hillman, Bruce J; Staab, Edward V

    2002-07-01

    This study was designed to identify factors that affect the enrollment of patients into American College of Radiology Imaging Network clinical trials. A quality improvement study was performed. Brainstorming produced an exhaustive list of factors that could affect the interest of sites in participating in American College of Radiology Imaging Network trials, as well as factors that could influence patient recruitment. Surveys, structured interviews, and benchmarking were used to validate and rank the importance of these factors. Site participation was influenced mainly by the support of the department chair and the interest of the investigator. Patient recruitment was affected primarily by the ease of identifying candidates and the perceived experience level and skill of the support staff. Because radiologists do not control patient referrals for imaging tests, a premium must be placed on developing systems to maximize the identification and enrollment of candidates for clinical trials. Other factors considered critical to success in patient enrollment include the supportiveness of the departmental leadership, the experience and skill level of study personnel, and the availability of site-specific infrastructure to support the study.

  2. A Simple Network to Remove Interference in Surface EMG Signal from Single Gene Affected Phenylketonuria Patients for Proper Diagnosis

    Science.gov (United States)

    Mohanty, Madhusmita; Basu, Mousumi; Pattanayak, Deba Narayan; Mohapatra, Sumant Kumar

    2018-04-01

    Recently Autosomal Recessive Single Gene (ARSG) diseases are highly effective to the children within the age of 5-10 years. One of the most ARSG disease is a Phenylketonuria (PKU). This single gene disease is associated with mutations in the gene that encodes the enzyme phenylalanine hydroxylase (PAH, Gene 612349). Through this mutation process, PAH of the gene affected patient can not properly manufacture PAH as a result the patients suffer from decreased muscle tone which shows abnormality in EMG signal. Here the extraction of the quality of the PKU affected EMG (PKU-EMG) signal is a keen interest, so it is highly necessary to remove the added ECG signal as well as the biological and instrumental noises. In the Present paper we proposed a method for detection and classification of the PKU affected EMG signal. Here Discrete Wavelet Transformation is implemented for extraction of the features of the PKU affected EMG signal. Adaptive Neuro-Fuzzy Inference System (ANFIS) network is used for the classification of the signal. Modified Particle Swarm Optimization (MPSO) and Modified Genetic Algorithm (MGA) are used to train the ANFIS network. Simulation result shows that the proposed method gives better performance as compared to existing approaches. Also it gives better accuracy of 98.02% for the detection of PKU-EMG signal. The advantages of the proposed model is to use MGA and MPSO to train the parameters of ANFIS network for classification of ECG and EMG signal of PKU affected patients. The proposed method obtained the high SNR (18.13 ± 0.36 dB), SNR (0.52 ± 1.62 dB), RE (0.02 ± 0.32), MSE (0.64 ± 2.01), CC (0.99 ± 0.02), RMSE (0.75 ± 0.35) and MFRE (0.01 ± 0.02), RMSE (0.75 ± 0.35) and MFRE (0.01 ± 0.02). From authors knowledge, this is the first time a composite method is used for diagnosis of PKU affected patients. The accuracy (98.02%), sensitivity (100%) and specificity (98.59%) helps for proper clinical treatment. It can help for readers

  3. A Simple Network to Remove Interference in Surface EMG Signal from Single Gene Affected Phenylketonuria Patients for Proper Diagnosis

    Science.gov (United States)

    Mohanty, Madhusmita; Basu, Mousumi; Pattanayak, Deba Narayan; Mohapatra, Sumant Kumar

    2018-01-01

    Recently Autosomal Recessive Single Gene (ARSG) diseases are highly effective to the children within the age of 5-10 years. One of the most ARSG disease is a Phenylketonuria (PKU). This single gene disease is associated with mutations in the gene that encodes the enzyme phenylalanine hydroxylase (PAH, Gene 612349). Through this mutation process, PAH of the gene affected patient can not properly manufacture PAH as a result the patients suffer from decreased muscle tone which shows abnormality in EMG signal. Here the extraction of the quality of the PKU affected EMG (PKU-EMG) signal is a keen interest, so it is highly necessary to remove the added ECG signal as well as the biological and instrumental noises. In the Present paper we proposed a method for detection and classification of the PKU affected EMG signal. Here Discrete Wavelet Transformation is implemented for extraction of the features of the PKU affected EMG signal. Adaptive Neuro-Fuzzy Inference System (ANFIS) network is used for the classification of the signal. Modified Particle Swarm Optimization (MPSO) and Modified Genetic Algorithm (MGA) are used to train the ANFIS network. Simulation result shows that the proposed method gives better performance as compared to existing approaches. Also it gives better accuracy of 98.02% for the detection of PKU-EMG signal. The advantages of the proposed model is to use MGA and MPSO to train the parameters of ANFIS network for classification of ECG and EMG signal of PKU affected patients. The proposed method obtained the high SNR (18.13 ± 0.36 dB), SNR (0.52 ± 1.62 dB), RE (0.02 ± 0.32), MSE (0.64 ± 2.01), CC (0.99 ± 0.02), RMSE (0.75 ± 0.35) and MFRE (0.01 ± 0.02), RMSE (0.75 ± 0.35) and MFRE (0.01 ± 0.02). From authors knowledge, this is the first time a composite method is used for diagnosis of PKU affected patients. The accuracy (98.02%), sensitivity (100%) and specificity (98.59%) helps for proper clinical treatment. It can help for readers

  4. Thinking Big or Small: Does Mental Abstraction Affect Social Network Organization?

    Science.gov (United States)

    Bacev-Giles, Chantal; Peetz, Johanna

    2016-01-01

    Four studies examined how mental abstraction affects how people perceive their relationships with other people, specifically, how these relationships may be categorized in social groups. We expected that individuals induced to think abstractly would report fewer more global social groups, compared to those induced to think concretely, who would report more specific groups. However, induced abstract mindset did not affect how people structured their social groups (Study 2–4), despite evidence that the mindset manipulation changed the level of abstraction in their thoughts (Study 3) and evidence that it changed how people structured groups for a control condition (household objects, Study 4). Together, these studies suggest that while the way people organize their relationships into groups is malleable; cognitive abstraction does not seem to affect how people categorize their relationships into social groups. PMID:26808086

  5. How the amygdala affects emotional memory by altering brain network properties.

    Science.gov (United States)

    Hermans, Erno J; Battaglia, Francesco P; Atsak, Piray; de Voogd, Lycia D; Fernández, Guillén; Roozendaal, Benno

    2014-07-01

    The amygdala has long been known to play a key role in supporting memory for emotionally arousing experiences. For example, classical fear conditioning depends on neural plasticity within this anterior medial temporal lobe region. Beneficial effects of emotional arousal on memory, however, are not restricted to simple associative learning. Our recollection of emotional experiences often includes rich representations of, e.g., spatiotemporal context, visceral states, and stimulus-response associations. Critically, such memory features are known to bear heavily on regions elsewhere in the brain. These observations led to the modulation account of amygdala function, which postulates that amygdala activation enhances memory consolidation by facilitating neural plasticity and information storage processes in its target regions. Rodent work in past decades has identified the most important brain regions and neurochemical processes involved in these modulatory actions, and neuropsychological and neuroimaging work in humans has produced a large body of convergent data. Importantly, recent methodological developments make it increasingly realistic to monitor neural interactions underlying such modulatory effects as they unfold. For instance, functional connectivity network modeling in humans has demonstrated how information exchanges between the amygdala and specific target regions occur within the context of large-scale neural network interactions. Furthermore, electrophysiological and optogenetic techniques in rodents are beginning to make it possible to quantify and even manipulate such interactions with millisecond precision. In this paper we will discuss that these developments will likely lead to an updated view of the amygdala as a critical nexus within large-scale networks supporting different aspects of memory processing for emotionally arousing experiences. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. How wind turbines affect the performance of seismic monitoring stations and networks

    Science.gov (United States)

    Neuffer, Tobias; Kremers, Simon

    2017-12-01

    In recent years, several minor seismic events were observed in the apparently aseismic region of the natural gas fields in Northern Germany. A seismic network was installed in the region consisting of borehole stations with sensor depths up to 200 m and surface stations to monitor induced seismicity. After installation of the network in 2012, an increasing number of wind turbines was established in proximity (<5 km) to several stations, thereby influencing the local noise conditions. This study demonstrates the impact of wind turbines on seismic noise level in a frequency range of 1-10 Hz at the monitoring sites with correlation to wind speed, based on the calculation of power spectral density functions and I95 values of waveforms over a time period of 4 yr. It could be shown that higher wind speeds increase the power spectral density amplitudes at distinct frequencies in the considered frequency band, depending on height as well as number and type of influencing wind turbines. The azimuthal direction of incoming Rayleigh waves at a surface station was determined to identify the noise sources. The analysis of the perturbed wave field showed that Rayleigh waves with backazimuths pointing to wind turbines in operation are dominating the wave field in a frequency band of 3-4 Hz. Additional peaks in a frequency range of 1-4 Hz could be attributed to turbine tower eigenfrequencies of various turbine manufactures with the hub height as defining parameter. Moreover, the influence of varying noise levels at a station on the ability to automatically detect seismic events was investigated. The increased noise level in correlation to higher wind speeds at the monitoring sites deteriorates the station's recording quality inhibiting the automatic detection of small seismic events. As a result, functionality and task fulfilment of the seismic monitoring network is more and more limited by the increasing number of nearby wind turbines.

  7. Networks of neuronal genes affected by common and rare variants in autism spectrum disorders.

    Directory of Open Access Journals (Sweden)

    Eyal Ben-David

    Full Text Available Autism spectrum disorders (ASD are neurodevelopmental disorders with phenotypic and genetic heterogeneity. Recent studies have reported rare and de novo mutations in ASD, but the allelic architecture of ASD remains unclear. To assess the role of common and rare variations in ASD, we constructed a gene co-expression network based on a widespread survey of gene expression in the human brain. We identified modules associated with specific cell types and processes. By integrating known rare mutations and the results of an ASD genome-wide association study (GWAS, we identified two neuronal modules that are perturbed by both rare and common variations. These modules contain highly connected genes that are involved in synaptic and neuronal plasticity and that are expressed in areas associated with learning and memory and sensory perception. The enrichment of common risk variants was replicated in two additional samples which include both simplex and multiplex families. An analysis of the combined contribution of common variants in the neuronal modules revealed a polygenic component to the risk of ASD. The results of this study point toward contribution of minor and major perturbations in the two sub-networks of neuronal genes to ASD risk.

  8. Centrality and Charisma: Comparing How Leader Networks "and" Attributions Affect Team Performance

    Science.gov (United States)

    Balkundi, Prasad; Kilduff, Martin; Harrison, David A.

    2011-01-01

    When leaders interact in teams with their subordinates, they build social capital that can have positive effects on team performance. Does this social capital affect team performance because subordinates come to see the leader as charismatic? We answered this question by examining 2 models. First, we tested the charisma-to-centrality model…

  9. Analysis of Factors Affecting Rural People's Participation in Management and Exploitation of Irrigation and Drainage Networks of Lishter Plain

    Directory of Open Access Journals (Sweden)

    Mehdi Nooripoor

    2016-05-01

    Full Text Available The importance of water as a life source and a requisite for survival of rural areas as well as main driver of agricultural development made it necessary to manage its usage efficiently. Thus, it is really necessary that water users have a responsible and active participation in the management of water systems. The purpose of this survey research was to identify the factors affecting rural people's participation in the management and exploitation of irrigation and drainage networks in the Lishter Plain of Gachsaran County. Data was collected from a sample of 163 villagers which was selected based on stratified random sampling procedure. In the survey, data gathering tool was a close ended questionnaire. Its validity was verified using the face validity procedure. Its reliability was also calculated using Cronbach's alpha reliability from 0.633 to 0.923 based on a pilot study scores. The results showed that social capital, attitude towards participation, farming experience and prior participation experience have a positive and statistically significant effects on management and exploitation of irrigation systems, while other variables such as economic concerns, attitude towards official staff, the period of residency in village, educational level, planting area, number of farms and irrigation network coverage had no significant effects. The results of multiple linear regression indicated that structural factors and farming experience can explain about 0.439 of the variance of dependent variable that is participation in the management and exploitation of irrigation networks of the study area.

  10. How the government's punishment and individual's sensitivity affect the rumor spreading in online social networks

    Science.gov (United States)

    Li, Dandan; Ma, Jing

    2017-03-01

    We explore the impact of punishment of governments and sensitivity of individuals on the rumor spreading in this paper. Considering the facts that some rumors that relate to the hot events could be disseminated repeatedly, however, some other rumors will never be disseminated after they have been popular for some time. Therefore, we investigate two types (SIS and SIR) of rumor spreading models in which the punishment of government and sensitivity of individuals are considered. Based on the mean-field method, we have calculated the spreading threshold of SIS and SIR model, respectively. Furthermore, we perform the rumor spreading process in the Facebook and POK social networks, and achieve that there is an excellent agreement between the theoretical and numerical results of spreading threshold. The results indicate that improving the punishment of government and increasing the sensitivity of individuals could control the spreading of rumor effectively.

  11. Writing affects the brain network of reading in Chinese: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Cao, Fan; Vu, Marianne; Chan, Derek Ho Lung; Lawrence, Jason M; Harris, Lindsay N; Guan, Qun; Xu, Yi; Perfetti, Charles A

    2013-07-01

    We examined the hypothesis that learning to write Chinese characters influences the brain's reading network for characters. Students from a college Chinese class learned 30 characters in a character-writing condition and 30 characters in a pinyin-writing condition. After learning, functional magnetic resonance imaging collected during passive viewing showed different networks for reading Chinese characters and English words, suggesting accommodation to the demands of the new writing system through short-term learning. Beyond these expected differences, we found specific effects of character writing in greater activation (relative to pinyin writing) in bilateral superior parietal lobules and bilateral lingual gyri in both a lexical decision and an implicit writing task. These findings suggest that character writing establishes a higher quality representation of the visual-spatial structure of the character and its orthography. We found a greater involvement of bilateral sensori-motor cortex (SMC) for character-writing trained characters than pinyin-writing trained characters in the lexical decision task, suggesting that learning by doing invokes greater interaction with sensori-motor information during character recognition. Furthermore, we found a correlation of recognition accuracy with activation in right superior parietal lobule, right lingual gyrus, and left SMC, suggesting that these areas support the facilitative effect character writing has on reading. Finally, consistent with previous behavioral studies, we found character-writing training facilitates connections with semantics by producing greater activation in bilateral middle temporal gyri, whereas pinyin-writing training facilitates connections with phonology by producing greater activation in right inferior frontal gyrus. Copyright © 2012 Wiley Periodicals, Inc.

  12. Dysfunction of Affective Network in Post Ischemic Stroke Depression: A Resting-State Functional Magnetic Resonance Imaging Study

    Directory of Open Access Journals (Sweden)

    Peiyao Zhang

    2014-01-01

    Full Text Available Objective. Previous studies have demonstrated that stroke characteristics and social and psychological factors jointly contribute to the development of poststroke depression (PSD. The purpose of this study was to identify altered functional connectivity (FC of the affective network (AN in patients with PSD and to explore the correlation between FC and the severity of PSD. Materials and Methods. 26 PSD patients, 24 stroke patients without depression, and 24 age-matched normal controls underwent the resting-state functional MRI (fMRI scanning. The bilateral anterior cingulated cortices (ACCs were selected as regions of interest (ROIs. FC was calculated and compared among the three groups. The association between FC and Hamilton Depression Rate Scale (HDRS scores of PSD group was investigated. Results. The FC of the AN was disrupted in PSD patients compared to stroke patients without depression and normal controls. Moreover, the left orbital part of inferior frontal gyrus which indicated altered FC was significantly correlated with HDRS scores in PSD patients. Conclusions. Dysfunction of the affective network may be one of the reasons of the development of PSD.

  13. Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols.

    Science.gov (United States)

    Pinu, Farhana R; Villas-Boas, Silas G; Aggio, Raphael

    2017-10-23

    Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

  14. Dynamic Metabolite Profiling in an Archaeon Connects Transcriptional Regulation to Metabolic Consequences.

    Directory of Open Access Journals (Sweden)

    Horia Todor

    Full Text Available Previous work demonstrated that the TrmB transcription factor is responsible for regulating the expression of many enzyme-coding genes in the hypersaline-adapted archaeon Halobacterium salinarum via a direct interaction with a cis-regulatory sequence in their promoters. This interaction is abolished in the presence of glucose. Although much is known about the effects of TrmB at the transcriptional level, it remains unclear whether and to what extent changes in mRNA levels directly affect metabolite levels. In order to address this question, here we performed a high-resolution metabolite profiling time course during a change in nutrients using a combination of targeted and untargeted methods in wild-type and ΔtrmB strain backgrounds. We found that TrmB-mediated transcriptional changes resulted in widespread and significant changes to metabolite levels across the metabolic network. Additionally, the pattern of growth complementation using various purines suggests that the mis-regulation of gluconeogenesis in the ΔtrmB mutant strain in the absence of glucose results in low phosphoribosylpyrophosphate (PRPP levels. We confirmed these low PRPP levels using a quantitative mass spectrometric technique and found that they are associated with a metabolic block in de novo purine synthesis, which is partially responsible for the growth defect of the ΔtrmB mutant strain in the absence of glucose. In conclusion, we show how transcriptional regulation of metabolism affects metabolite levels and ultimately, phenotypes.

  15. Hydrophobicity and charge shape cellular metabolite concentrations.

    Directory of Open Access Journals (Sweden)

    Arren Bar-Even

    2011-10-01

    Full Text Available What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108 of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ~100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findings can be explained by evolutionary constraints imposed on metabolite concentrations and discuss possible selective pressures that can account for them. These include the reduction of solute leakage through the lipid membrane, avoidance of deleterious aggregates and reduction of non-specific hydrophobic binding. By highlighting the global constraints imposed on metabolic pathways, future research could shed light onto aspects of biochemical evolution and the chemical constraints that bound metabolic engineering efforts.

  16. APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults: A STROBE Article.

    Science.gov (United States)

    Su, Yun Yan; Liang, Xue; Schoepf, U Joseph; Varga-Szemes, Akos; West, Henry C; Qi, Rongfeng; Kong, Xiang; Chen, Hui Juan; Lu, Guang Ming; Zhang, Long Jiang

    2015-12-01

    To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging.Seventy-six healthy adults (34 men, 23.7 ± 2.8 y; 31 APOE ε4/ε3 carriers, 31 ε3/ε3 carriers, and 14 ε2/ε3 carriers) were included. For resting-state functional MRI data, default mode network (DMN) and amplitude of low-frequency fluctuation maps were extracted and analyzed. Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests.There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the ε4/ε3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the ε3/ε3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the ε2/ε3 group (P brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect.

  17. Green Power Grids: How Energy from Renewable Sources Affects Networks and Markets.

    Science.gov (United States)

    Mureddu, Mario; Caldarelli, Guido; Chessa, Alessandro; Scala, Antonio; Damiano, Alfonso

    2015-01-01

    The increasing attention to environmental issues is forcing the implementation of novel energy models based on renewable sources. This is fundamentally changing the configuration of energy management and is introducing new problems that are only partly understood. In particular, renewable energies introduce fluctuations which cause an increased request for conventional energy sources to balance energy requests at short notice. In order to develop an effective usage of low-carbon sources, such fluctuations must be understood and tamed. In this paper we present a microscopic model for the description and for the forecast of short time fluctuations related to renewable sources in order to estimate their effects on the electricity market. To account for the inter-dependencies in the energy market and the physical power dispatch network, we use a statistical mechanics approach to sample stochastic perturbations in the power system and an agent based approach for the prediction of the market players' behavior. Our model is data-driven; it builds on one-day-ahead real market transactions in order to train agents' behaviour and allows us to deduce the market share of different energy sources. We benchmarked our approach on the Italian market, finding a good accordance with real data.

  18. Metabolites in vertebrate Hedgehog signaling.

    Science.gov (United States)

    Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

    2014-04-11

    The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Proteomics identifies molecular networks affected by tetradecylthioacetic acid and fish oil supplemented diets

    DEFF Research Database (Denmark)

    Wrzesinski, Krzysztof; León, Ileana R.; Kulej, Katarzyna

    2013-01-01

    of the symptoms of the metabolic syndrome. To date very little is known about the molecular mechanisms behind these beneficial effects and the potential pitfalls of the consumption of those two compounds. Only studies of each compound separately and using only small scale molecular biology approaches have been......Fish oil (FO) and tetradecylthioacetic acid (TTA) - a synthetic modified fatty acid have beneficial effects in regulating lipid metabolism. In order to dissect the mechanisms underlying the molecular action of those two fatty acids we have investigated the changes in mitochondrial protein...... modulate mitochondrial metabolism in a synergistic manner yet the effects of TTA are much more dramatic. We demonstrate in a large scale that fatty acid metabolism and lipid oxidation are affected by fish oil and TTA, a phenomenon already known from more directed molecular biology studies. Our approach...

  20. Change in Allosteric Network Affects Binding Affinities of PDZ Domains: Analysis through Perturbation Response Scanning

    Science.gov (United States)

    Gerek, Z. Nevin; Ozkan, S. Banu

    2011-01-01

    The allosteric mechanism plays a key role in cellular functions of several PDZ domain proteins (PDZs) and is directly linked to pharmaceutical applications; however, it is a challenge to elaborate the nature and extent of these allosteric interactions. One solution to this problem is to explore the dynamics of PDZs, which may provide insights about how intramolecular communication occurs within a single domain. Here, we develop an advancement of perturbation response scanning (PRS) that couples elastic network models with linear response theory (LRT) to predict key residues in allosteric transitions of the two most studied PDZs (PSD-95 PDZ3 domain and hPTP1E PDZ2 domain). With PRS, we first identify the residues that give the highest mean square fluctuation response upon perturbing the binding sites. Strikingly, we observe that the residues with the highest mean square fluctuation response agree with experimentally determined residues involved in allosteric transitions. Second, we construct the allosteric pathways by linking the residues giving the same directional response upon perturbation of the binding sites. The predicted intramolecular communication pathways reveal that PSD-95 and hPTP1E have different pathways through the dynamic coupling of different residue pairs. Moreover, our analysis provides a molecular understanding of experimentally observed hidden allostery of PSD-95. We show that removing the distal third alpha helix from the binding site alters the allosteric pathway and decreases the binding affinity. Overall, these results indicate that (i) dynamics plays a key role in allosteric regulations of PDZs, (ii) the local changes in the residue interactions can lead to significant changes in the dynamics of allosteric regulations, and (iii) this might be the mechanism that each PDZ uses to tailor their binding specificities regulation. PMID:21998559

  1. Mood-dependent integration in discourse comprehension: happy and sad moods affect consistency processing via different brain networks.

    Science.gov (United States)

    Egidi, Giovanna; Caramazza, Alfonso

    2014-12-01

    According to recent research on language comprehension, the semantic features of a text are not the only determinants of whether incoming information is understood as consistent. Listeners' pre-existing affective states play a crucial role as well. The current fMRI experiment examines the effects of happy and sad moods during comprehension of consistent and inconsistent story endings, focusing on brain regions previously linked to two integration processes: inconsistency detection, evident in stronger responses to inconsistent endings, and fluent processing (accumulation), evident in stronger responses to consistent endings. The analysis evaluated whether differences in the BOLD response for consistent and inconsistent story endings correlated with self-reported mood scores after a mood induction procedure. Mood strongly affected regions previously associated with inconsistency detection. Happy mood increased sensitivity to inconsistency in regions specific for inconsistency detection (e.g., left IFG, left STS), whereas sad mood increased sensitivity to inconsistency in regions less specific for language processing (e.g., right med FG, right SFG). Mood affected more weakly regions involved in accumulation of information. These results show that mood can influence activity in areas mediating well-defined language processes, and highlight that integration is the result of context-dependent mechanisms. The finding that language comprehension can involve different networks depending on people's mood highlights the brain's ability to reorganize its functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Purine metabolites in fibromyalgia syndrome.

    Science.gov (United States)

    Fais, A; Cacace, E; Corda, M; Era, B; Peri, M; Utzeri, S; Ruggiero, V

    2013-01-01

    To evaluate serum purine metabolite concentrations in patients affected by fibromyalgia syndrome (FMS) and the relationships between their levels and FM clinical parameters. Serum purine levels were quantified using LC/UV-vis in 22 fibromyalgic females (according to the American College of Rheumatology classification criteria) and 22 healthy females. Significantly higher serum inosine, hypoxanthine and xanthine levels (pFibromyalgia Impact Questionnaire (FIQ). Study results suggest that purines, in particular adenosine and inosine, may be involved in pain transmission in fibromyalgia. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  3. Motivation by potential gains and losses affects control processes via different mechanisms in the attentional network.

    Science.gov (United States)

    Paschke, Lena M; Walter, Henrik; Steimke, Rosa; Ludwig, Vera U; Gaschler, Robert; Schubert, Torsten; Stelzel, Christine

    2015-05-01

    Attentional control in demanding cognitive tasks can be improved by manipulating the motivational state. Motivation to obtain gains and motivation to avoid losses both usually result in faster reaction times and stronger activation in relevant brain areas such as the prefrontal cortex, but little is known about differences in the underlying neurocognitive mechanisms of these types of motivation in an attentional control context. In the present functional magnetic resonance imaging (fMRI) study, we tested whether potential gain and loss as motivating incentives lead to overlapping or distinct neural effects in the attentional network, and whether one of these conditions is more effective than the other. A Flanker task with word stimuli as targets and distracters was performed by 115 healthy participants. Using a mixed blocked and event-related design allowed us to investigate transient and sustained motivation-related effects. Participants could either gain money (potential gain) or avoid losing money (potential loss) in different task blocks. Participants showed a congruency effect with increased reaction times for incongruent compared to congruent trials. Potential gain led to generally faster responses compared to the neutral condition and to stronger improvements than potential loss. Potential loss also led to shorter response times compared to the neutral condition, but participants improved mainly during incongruent and not during congruent trials. The event-related fMRI data revealed a main effect of congruency with increased activity in the left inferior frontal gyrus (IFG) and inferior frontal junction area (IFJ), the pre-supplementary motor area (pre-SMA), bilateral insula, intraparietal sulcus (IPS) and visual word form area (VWFA). While potential gain led to increased activity in a cluster of the IFJ and the VWFA only during incongruent trials, potential loss was linked to activity increases in these regions during incongruent and congruent trials. The

  4. 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.

  5. Domains I and IV of annexin A2 affect the formation and integrity of in vitro capillary-like networks.

    Science.gov (United States)

    Raddum, Aase M; Evensen, Lasse; Hollås, Hanne; Grindheim, Ann Kari; Lorens, James B; Vedeler, Anni

    2013-01-01

    Annexin A2 (AnxA2) is a widely expressed multifunctional protein found in different cellular compartments. In spite of lacking a hydrophobic signal peptide, AnxA2 is found at the cell surface of endothelial cells, indicative of a role in angiogenesis. Increased extracellular levels of AnxA2 in tumours correlate with neoangiogenesis, metastasis and poor prognosis. We hypothesised that extracellular AnxA2 may contribute to angiogenesis by affecting endothelial cell-cell interactions and motility. To address this question, we studied the effect of heterotetrameric and monomeric forms of AnxA2, as well as its two soluble domains on the formation and maintenance of capillary-like structures by using an in vitro co-culture system consisting of endothelial and smooth muscle cells. In particular, addition of purified domains I and IV of AnxA2 potently inhibited the vascular endothelial growth factor (VEGF)-dependent formation of the capillary-like networks in a dose-dependent manner. In addition, these AnxA2 domains disrupted endothelial cell-cell contacts in preformed capillary-like networks, resulting in the internalisation of vascular endothelial (VE)-cadherin and the formation of VE-cadherin-containing filopodia-like structures between the endothelial cells, suggesting increased cell motility. Addition of monoclonal AnxA2 antibodies, in particular against Tyr23 phosphorylated AnxA2, also strongly inhibited network formation in the co-culture system. These results suggest that extracellular AnxA2, most likely in its Tyr phosphorylated form, plays a pivotal role in angiogenesis. The exogenously added AnxA2 domains most likely mediate their effects by competing with endogenous AnxA2 for extracellular factors necessary for the initiation and maintenance of angiogenesis, such as those involved in the formation/integrity of cell-cell contacts.

  6. Domains I and IV of annexin A2 affect the formation and integrity of in vitro capillary-like networks.

    Directory of Open Access Journals (Sweden)

    Aase M Raddum

    Full Text Available Annexin A2 (AnxA2 is a widely expressed multifunctional protein found in different cellular compartments. In spite of lacking a hydrophobic signal peptide, AnxA2 is found at the cell surface of endothelial cells, indicative of a role in angiogenesis. Increased extracellular levels of AnxA2 in tumours correlate with neoangiogenesis, metastasis and poor prognosis. We hypothesised that extracellular AnxA2 may contribute to angiogenesis by affecting endothelial cell-cell interactions and motility. To address this question, we studied the effect of heterotetrameric and monomeric forms of AnxA2, as well as its two soluble domains on the formation and maintenance of capillary-like structures by using an in vitro co-culture system consisting of endothelial and smooth muscle cells. In particular, addition of purified domains I and IV of AnxA2 potently inhibited the vascular endothelial growth factor (VEGF-dependent formation of the capillary-like networks in a dose-dependent manner. In addition, these AnxA2 domains disrupted endothelial cell-cell contacts in preformed capillary-like networks, resulting in the internalisation of vascular endothelial (VE-cadherin and the formation of VE-cadherin-containing filopodia-like structures between the endothelial cells, suggesting increased cell motility. Addition of monoclonal AnxA2 antibodies, in particular against Tyr23 phosphorylated AnxA2, also strongly inhibited network formation in the co-culture system. These results suggest that extracellular AnxA2, most likely in its Tyr phosphorylated form, plays a pivotal role in angiogenesis. The exogenously added AnxA2 domains most likely mediate their effects by competing with endogenous AnxA2 for extracellular factors necessary for the initiation and maintenance of angiogenesis, such as those involved in the formation/integrity of cell-cell contacts.

  7. Social grooming network in captive chimpanzees: does the wild or captive origin of group members affect sociality?

    Science.gov (United States)

    Levé, Marine; Sueur, Cédric; Petit, Odile; Matsuzawa, Tetsuro; Hirata, Satoshi

    2016-01-01

    Many chimpanzees throughout the world are housed in captivity, and there is an increasing effort to recreate social groups by mixing individuals with captive origins with those with wild origins. Captive origins may entail restricted rearing conditions during early infant life, including, for example, no maternal rearing and a limited social life. Early rearing conditions have been linked with differences in tool-use behavior between captive- and wild-born chimpanzees. If physical cognition can be impaired by non-natural rearing, what might be the consequences for social capacities? This study describes the results of network analysis based on grooming interactions in chimpanzees with wild and captive origins living in the Kumamoto Sanctuary in Kumamoto, Japan. Grooming is a complex social activity occupying up to 25% of chimpanzees' waking hours and plays a role in the emergence and maintenance of social relationships. We assessed whether the social centralities and roles of chimpanzees might be affected by their origin (captive vs wild). We found that captive- and wild-origin chimpanzees did not differ in their grooming behavior, but that theoretical removal of individuals from the network had differing impacts depending on the origin of the individual. Contrary to findings that non-natural early rearing has long-term effects on physical cognition, living in social groups seems to compensate for the negative effects of non-natural early rearing. Social network analysis (SNA) and, in particular, theoretical removal analysis, were able to highlight differences between individuals that would have been impossible to show using classical methods. The social environment of captive animals is important to their well-being, and we are only beginning to understand how SNA might help to enhance animal welfare.

  8. Entrepreneurs’ gender, age and education affecting their networks in private and public spheres: Denmark, Middle East and North Africa

    DEFF Research Database (Denmark)

    Ashourizadeh, Shayegheh; Schøtt, Thomas

    2013-01-01

    The purpose is to account for entrepreneurs’ networking in private and public spheres, as influenced by gender, age and education in the context of culture. The Global Entrepreneurship Monitor has surveyed 17,742 entrepreneurs’ networking for advice in Denmark and 14 countries representative...... broader than female entrepreneurs, especially in the public sphere and especially in traditional culture, whereas women network more intensely in the private sphere. Age influences networking in the way that networking in the private sphere is more extensive among young than among older entrepreneurs....... Education influences networking in the way that networking in the public sphere is especially extensive among educated entrepreneurs....

  9. Orange juice-derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: a randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease.

    Science.gov (United States)

    Schär, Manuel Y; Curtis, Peter J; Hazim, Sara; Ostertag, Luisa M; Kay, Colin D; Potter, John F; Cassidy, Aedín

    2015-05-01

    Epidemiologic data suggest inverse associations between citrus flavanone intake and cardiovascular disease (CVD) risk. However, insufficient randomized controlled trial data limit our understanding of the mechanisms by which flavanones and their metabolites potentially reduce cardiovascular risk factors. We examined the effects of orange juice or a dose-matched hesperidin supplement on plasma concentrations of established and novel flavanone metabolites and their effects on cardiovascular risk biomarkers in men at moderate CVD risk. In an acute, randomized, placebo-controlled crossover trial, 16 fasted participants (aged 51-69 y) received orange juice or a hesperidin supplement (both providing 320 mg hesperidin) or control (all matched for sugar and vitamin C content). At baseline and 5 h postintake, endothelial function (primary outcome), blood pressure, arterial stiffness, cardiac autonomic function, platelet activation, and NADPH oxidase gene expression and plasma flavanone metabolites were assessed. Before each intervention, a diet low in flavonoids, nitrate/nitrite, alcohol, and caffeine was followed, and a standardized low-flavonoid evening meal was consumed. Orange juice intake significantly elevated mean ± SEM plasma concentrations of 8 flavanone (1.75 ± 0.35 μmol/L, P orange juice matrix. After single-dose flavanone intake within orange juice, circulating flavanone and phenolic metabolites collectively reached a concentration of 15.20 ± 2.15 μmol/L, but no effects were observed on cardiovascular risk biomarkers. Longer-duration randomized controlled trials are required to examine previous associations between higher flavanone intakes and improved cardiovascular health and to ascertain the relative importance of food matrix and flavanone-derived phenolic metabolites. This trial was registered at clinicaltrials.gov as NCT01530893.

  10. Metabolite damage and repair in metabolic engineering design

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.; Bruner, Steven D.; Hanson, Andrew D.

    2017-11-01

    The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.

  11. Entrepreneurs’ gender, age and education affecting their networks in private and public spheres: Denmark, Middle East and North Africa

    DEFF Research Database (Denmark)

    Ashourizadeh, Shayegheh; Schøtt, Thomas

    2013-01-01

    The purpose is to account for entrepreneurs’ networking in private and public spheres, as influenced by gender, age and education in the context of culture. The Global Entrepreneurship Monitor has surveyed 17,742 entrepreneurs’ networking for advice in Denmark and 14 countries representative...... of the Middle East and North Africa. Analyses show that entrepreneurs are networking in the private sphere of family and friends, especially in traditional culture in Middle East and North Africa, and are networking in public spheres, especially in secular-rational culture in Denmark. Male entrepreneurs network...... broader than female entrepreneurs, especially in the public sphere and especially in traditional culture, whereas women network more intensely in the private sphere. Age influences networking in the way that networking in the private sphere is more extensive among young than among older entrepreneurs...

  12. Mutations in RNA Polymerase Bridge Helix and Switch Regions Affect Active-Site Networks and Transcript-Assisted Hydrolysis.

    Science.gov (United States)

    Zhang, Nan; Schäfer, Jorrit; Sharma, Amit; Rayner, Lucy; Zhang, Xiaodong; Tuma, Roman; Stockley, Peter; Buck, Martin

    2015-11-06

    In bacterial RNA polymerase (RNAP), the bridge helix and switch regions form an intricate network with the catalytic active centre and the main channel. These interactions are important for catalysis, hydrolysis and clamp domain movement. By targeting conserved residues in Escherichia coli RNAP, we are able to show that functions of these regions are differentially required during σ(70)-dependent and the contrasting σ(54)-dependent transcription activations and thus potentially underlie the key mechanistic differences between the two transcription paradigms. We further demonstrate that the transcription factor DksA directly regulates σ(54)-dependent activation both positively and negatively. This finding is consistent with the observed impacts of DksA on σ(70)-dependent promoters. DksA does not seem to significantly affect RNAP binding to a pre-melted promoter DNA but affects extensively activity at the stage of initial RNA synthesis on σ(54)-regulated promoters. Strikingly, removal of the σ(54) Region I is sufficient to invert the action of DksA (from stimulation to inhibition or vice versa) at two test promoters. The RNAP mutants we generated also show a strong propensity to backtrack. These mutants increase the rate of transcript-hydrolysis cleavage to a level comparable to that seen in the Thermus aquaticus RNAP even in the absence of a non-complementary nucleotide. These novel phenotypes imply an important function of the bridge helix and switch regions as an anti-backtracking ratchet and an RNA hydrolysis regulator. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Getting by with a little help from friends and colleagues: Testing how residents' social support networks affect loneliness and burnout.

    Science.gov (United States)

    Rogers, Eamonn; Polonijo, Andrea N; Carpiano, Richard M

    2016-11-01

    To determine how residents' relationships with their sources of social support (ie, family, friends, and colleagues) affect levels of burnout and loneliness. Cross-sectional survey. Faculty of Medicine at the University of British Columbia in Vancouver. A total of 198 physician-trainees in the university's postgraduate medical education program. Residents' personal and work-related burnout scores (measured using items from the Copenhagen Burnout Inventory); loneliness (measured using a 3-item loneliness scale); and social support (assessed with the Lubben Social Network Scale, version 6). Of the 234 respondents who completed the Internet-based survey (a 22% response rate), 198 provided complete information on all study variables and thus constituted the analytic sample. Seemingly unrelated regression analyses indicated that loneliness was significantly ( P social support were both indirectly associated with lower personal and work-related burnout scores through their negative associations with loneliness. Social relationships might help residents mitigate the deleterious effects of burnout. By promoting interventions that stabilize and nurture social relationships, hospitals and universities can potentially help promote resident resilience and well-being and, in turn, improve patient care. Copyright© the College of Family Physicians of Canada.

  14. The minor wall-networks between monolignols and interlinked-phenolics predominantly affect biomass enzymatic digestibility in Miscanthus.

    Directory of Open Access Journals (Sweden)

    Zhengru Li

    Full Text Available Plant lignin is one of the major wall components that greatly contribute to biomass recalcitrance for biofuel production. In this study, total 79 representative Miscanthus germplasms were determined with wide biomass digestibility and diverse monolignol composition. Integrative analyses indicated that three major monolignols (S, G, H and S/G ratio could account for lignin negative influence on biomass digestibility upon NaOH and H2SO4 pretreatments. Notably, the biomass enzymatic digestions were predominately affected by the non-KOH-extractable lignin and interlinked-phenolics, other than the KOH-extractable ones that cover 80% of total lignin. Furthermore, a positive correlation was found between the monolignols and phenolics at p<0.05 level in the non-KOH-extractable only, suggesting their tight association to form the minor wall-networks against cellulases accessibility. The results indicated that the non-KOH-extractable lignin-complex should be the target either for cost-effective biomass pretreatments or for relatively simply genetic modification of plant cell walls in Miscanthus.

  15. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

    Science.gov (United States)

    Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

    2014-01-01

    Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

  17. Networking

    OpenAIRE

    Rauno Lindholm, Daniel; Boisen Devantier, Lykke; Nyborg, Karoline Lykke; Høgsbro, Andreas; Fries, de; Skovlund, Louise

    2016-01-01

    The purpose of this project was to examine what influencing factor that has had an impact on the presumed increasement of the use of networking among academics on the labour market and how it is expressed. On the basis of the influence from globalization on the labour market it can be concluded that the globalization has transformed the labour market into a market based on the organization of networks. In this new organization there is a greater emphasis on employees having social qualificati...

  18. Metabolite Damage and Metabolite Damage Control in Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, Andrew D. [Horticultural Sciences Department and; Henry, Christopher S. [Mathematics and Computer Science Division, Argonne National Laboratory, Argonne, Illinois 60439, email:; Computation Institute, University of Chicago, Chicago, Illinois 60637; Fiehn, Oliver [Genome Center, University of California, Davis, California 95616, email:; de Crécy-Lagard, Valérie [Microbiology and Cell Science Department, University of Florida, Gainesville, Florida 32611, email: ,

    2016-04-29

    It is increasingly clear that (a) many metabolites undergo spontaneous or enzyme-catalyzed side reactions in vivo, (b) the damaged metabolites formed by these reactions can be harmful, and (c) organisms have biochemical systems that limit the buildup of damaged metabolites. These damage-control systems either return a damaged molecule to its pristine state (metabolite repair) or convert harmful molecules to harmless ones (damage preemption). Because all organisms share a core set of metabolites that suffer the same chemical and enzymatic damage reactions, certain damage-control systems are widely conserved across the kingdoms of life. Relatively few damage reactions and damage-control systems are well known. Uncovering new damage reactions and identifying the corresponding damaged metabolites, damage-control genes, and enzymes demands a coordinated mix of chemistry, metabolomics, cheminformatics, biochemistry, and comparative genomics. This review illustrates the above points using examples from plants, which are at least as prone to metabolite damage as other organisms.

  19. Network analysis of metabolite GWAS hits

    DEFF Research Database (Denmark)

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

    2016-01-01

    AND RESULTS: A genome wide association study identified SNPs associated with plasma glycine levels within the CPS1 (Carbamoyl-Phosphate Synthase 1) gene (rs10206976, p-value = 4.709e-11 and rs12613336, p-value = 1.368e-08). Furthermore, gene expression in the adipose tissue showed that CPS1 expression levels...

  20. Metabolite Profiling of Peppers of Various Colors Reveals Relationships Between Tocopherol, Carotenoid, and Phytosterol Content.

    Science.gov (United States)

    Kim, Tae Jin; Choi, Jaehyuk; Kim, Kil Won; Ahn, Soon Kil; Ha, Sun-Hwa; Choi, Yongsoo; Park, Nam Il; Kim, Jae Kwang

    2017-12-01

    Peppers are widely consumed in Korea; the varietal development of peppers with increased content of beneficial plant metabolites is, therefore, of considerable interest. This requires a comprehensive understanding of the metabolic profile of pepper plants and the factors affecting this profile. To this end, we determined the content of various metabolites, such as hydrophilic and lipophilic compounds, phenolic acids, carotenoids, and capsaicinoids in peppers of various colors (green, red, pale green, and violet peppers) and in a high-pungency (green) pepper. We also performed principal component analysis (PCA), Pearson's correlation analysis, and hierarchical clustering analysis (HCA) to determine the relationships among these metabolites in peppers. PCA results indicated no significant variances among the 3 sample replicates. The HCA showed correlations between the metabolites resulting from common or closely linked biosynthesis pathways. Our results showed that carotenoids correlated positively with tocopherols and negatively with phytosterols; our findings also indicated a close relationship between the methylerythritol 4-phosphate and mevalonic acid biosynthesis pathways, providing evidence in favor of an earlier hypothesis regarding crosstalk across the chloroplast membrane. We, thus, demonstrate that metabolic profiling combined with multivariate analysis is a useful tool for analyzing metabolic networks. A total of 71 metabolites were measured in 5 peppers of different colors. The metabolic profiling with multivariate analysis revealed that tocopherol content had a positive correlation with the carotenoid content and a negative correlation with the phytosterol content. The results of this study may help in breeding programs to produce new germplasm with enhanced nutritional quality. © 2017 Institute of Food Technologists®.

  1. 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

  2. Hormonal Cycle and Contraceptive Effects on Amygdala and Salience Resting-State Networks in Women with Previous Affective Side Effects on the Pill.

    Science.gov (United States)

    Engman, Jonas; Sundström Poromaa, Inger; Moby, Lena; Wikström, Johan; Fredrikson, Mats; Gingnell, Malin

    2018-02-01

    The mechanisms linking ovarian hormones to negative affect are poorly characterized, but important clues may come from the examination of the brain's intrinsic organization. Here, we studied the effects of both the menstrual cycle and oral contraceptives (OCs) on amygdala and salience network resting-state functional connectivity using a double-blind, randomized, and placebo-controlled design. Hormone levels, depressive symptoms, and resting-state functional connectivity were measured in 35 healthy women (24.9±4.2 years) who had previously experienced OC-related negative affect. All participants were examined in the follicular phase of a baseline cycle and in the third week of the subsequent cycle during treatment with either a combined OC (30 μg ethinyl estradiol/0.15 mg levonorgestrel) or placebo. The latter time point targeted the midluteal phase in placebo users and steady-state ethinyl estradiol and levonorgestrel concentrations in OC users. Amygdala and salience network connectivity generally increased with both higher endogenous and synthetic hormone levels, although amygdala-parietal cortical connectivity decreased in OC users. When in the luteal phase, the naturally cycling placebo users demonstrated higher connectivity in both networks compared with the women receiving OCs. Our results support a causal link between the exogenous administration of synthetic hormones and amygdala and salience network connectivity. Furthermore, they suggest a similar, potentially stronger, association between the natural hormonal variations across the menstrual cycle and intrinsic network connectivity.

  3. Investigation of Time Dependent Development of Soil Structure and Formation of Macropore Networks as Affected by Various Precrop Species

    OpenAIRE

    Pagenkemper, Sebastian K.; Puschmann, Daniel Uteau; Peth, Stephan; Horn, Rainer

    2014-01-01

    A well developed macropore network is advantageous in terms of transport processes regarding gas and water, as well as nutrient acquisition and root growth of crops. X-ray computed tomography provides a non-destructive method to visualize and quantify three-dimensional pore networks. Geometrical and morphological parameters of the complex pore system such as connectivity, tortuosity, porosity and pore surface area would be very useful for modeling and simulation of transport and exchange proc...

  4. 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...

  5. Altered Behavioral and Autonomic Pain Responses in Alzheimer’s Disease Are Associated with Dysfunctional Affective, Self-Reflective and Salience Network Resting-State Connectivity

    Directory of Open Access Journals (Sweden)

    Paul A. Beach

    2017-09-01

    Full Text Available While pain behaviors are increased in Alzheimer’s disease (AD patients compared to healthy seniors (HS across multiple disease stages, autonomic responses are reduced with advancing AD. To better understand the neural mechanisms underlying these phenomena, we undertook a controlled cross-sectional study examining behavioral (Pain Assessment in Advanced Dementia, PAINAD scores and autonomic (heart rate, HR pain responses in 24 HS and 20 AD subjects using acute pressure stimuli. Resting-state fMRI was utilized to investigate how group connectivity differences were related to altered pain responses. Pain behaviors (slope of PAINAD score change and mean PAINAD score were increased in patients vs. controls. Autonomic measures (HR change intercept and mean HR change were reduced in severe vs. mildly affected AD patients. Group functional connectivity differences associated with greater pain behavior reactivity in patients included: connectivity within a temporal limbic network (TLN and between the TLN and ventromedial prefrontal cortex (vmPFC; between default mode network (DMN subcomponents; between the DMN and ventral salience network (vSN. Reduced HR responses within the AD group were associated with connectivity changes within the DMN and vSN—specifically the precuneus and vmPFC. Discriminant classification indicated HR-related connectivity within the vSN to the vmPFC best distinguished AD severity. Thus, altered behavioral and autonomic pain responses in AD reflects dysfunction of networks and structures subserving affective, self-reflective, salience and autonomic regulation.

  6. [Antiviral properties of basidiomycetes metabolites].

    Science.gov (United States)

    Avtonomova, A V; Krasnopolskaya, L M

    2014-01-01

    The data on the antiviral action of the Ganoderma lucidum, Lentinus edodes, Grifola frondosa, Agaricus brasiliensis and other basidiomycetes metabolites are summurized. The metabolites of these species of basidiomycetes exhibit a direct antiviral effect on herpes simplex virus types I and II, human immunodeficiency virus (HIV), hepatitis B virus, vesicular stomatitis virus, influenza virus, Epstein-Barr virus, and others. Moreover, metabolites of basidiomycetes increased antiviral immunity.

  7. How Do Social Networks and Faculty Development Courses Affect Clinical Supervisors' Adoption of a Medical Education Innovation? An Exploratory Study

    NARCIS (Netherlands)

    Jippes, Erik; Steinert, Yvonne; Pols, Jan; Achterkamp, Marjolein C.; van Engelen, Jo M. L.; Brand, Paul L. P.

    Purpose To examine the impact of social networks and a two-day faculty development course on clinical supervisors' adoption of an educational innovation. Method During 2007-2010, 571 residents and 613 clinical supervisors in four specialties in the Netherlands were invited to complete a Web-based

  8. Secondary metabolites from bromeliaceae family

    OpenAIRE

    Manetti, Liliana Maria; Delaporte, Rosemeres Horwat; Laverde Jr., Antonio

    2009-01-01

    This review describes aspects of the Bromeliaceae family dealing the traditional applications, biological activities and distribution of secondary metabolites in distinct subfamilies. Some species are used with medicinal purposed in the treatment of respiratory, diabetes or inflammation diseases, and gastrointestinal disorders. Special emphasis on cycloartane triterpenoids and flavonoids, typical metabolites of this family, are presented. Bromeliaceae is unique amongst the monocotyledons in t...

  9. Immune regulation by microbiome metabolites.

    Science.gov (United States)

    Kim, Chang H

    2018-03-22

    Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

  10. Using Coexpression Protein Interaction Network Analysis to Identify Mechanisms of Danshensu Affecting Patients with Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Mengqi Huo

    2017-06-01

    Full Text Available Salvia miltiorrhiza, known as Danshen, has attracted worldwide interest for its substantial effects on coronary heart disease (CHD. Danshensu (DSS is one of the main active ingredients of Danshen on CHD. Although it has been proven to have a good clinical effect on CHD, the action mechanisms remain elusive. In the current study, a coexpression network-based approach was used to illustrate the beneficial properties of DSS in the context of CHD. By integrating the gene expression profile data and protein-protein interactions (PPIs data, two coexpression protein interaction networks (CePIN in a CHD state (CHD CePIN and a non-CHD state (non-CHD CePIN were generated. Then, shared nodes and unique nodes in CHD CePIN were attained by conducting a comparison between CHD CePIN and non-CHD CePIN. By calculating the topological parameters of each shared node and unique node in the networks, and comparing the differentially expressed genes, target proteins involved in disease regulation were attained. Then, Gene Ontology (GO enrichment was utilized to identify biological processes associated to target proteins. Consequently, it turned out that the treatment of CHD with DSS may be partly attributed to the regulation of immunization and blood circulation. Also, it indicated that sodium/hydrogen exchanger 3 (SLC9A3, Prostaglandin G/H synthase 2 (PTGS2, Oxidized low-density lipoprotein receptor 1 (OLR1, and fibrinogen gamma chain (FGG may be potential therapeutic targets for CHD. In summary, this study provided a novel coexpression protein interaction network approach to provide an explanation of the mechanisms of DSS on CHD and identify key proteins which maybe the potential therapeutic targets for CHD.

  11. How do social networks and faculty development courses affect clinical supervisors' adoption of a medical education innovation? An exploratory study.

    Science.gov (United States)

    Jippes, Erik; Steinert, Yvonne; Pols, Jan; Achterkamp, Marjolein C; van Engelen, Jo M L; Brand, Paul L P

    2013-03-01

    To examine the impact of social networks and a two-day faculty development course on clinical supervisors' adoption of an educational innovation. During 2007-2010, 571 residents and 613 clinical supervisors in four specialties in the Netherlands were invited to complete a Web-based questionnaire. Residents rated their clinical supervisors' adoption of an educational innovation, the use of structured and constructive (S&C) feedback. Clinical supervisors self-assessed their adoption of this innovation and rated their communication intensity with other clinical supervisors in their department. For each supervisor, a centrality score was calculated, representing the extent to which the supervisor was connected to departmental colleagues. The authors analyzed the effects of supervisor centrality and participation in a two-day Teach-the-Teacher course on the degree of innovation adoption using hierarchical linear modeling, adjusting for age, gender, and attitude toward the S&C feedback innovation. Respondents included 370 (60%) supervisors and 357 (63%) residents. Although Teach-the-Teacher course participation (n=172; 46.5%) was significantly related to supervisors' self-assessments of adoption (P=.001), it had no effect on residents' assessments of supervisors' adoption (P=.371). Supervisor centrality was significantly related to innovation adoption in both residents' assessments (P=.023) and supervisors' self-assessments (P=.024). A clinical supervisor's social network may be as important as faculty development course participation in determining whether the supervisor adopts an educational innovation. Faculty development initiatives should use faculty members' social networks to improve the adoption of educational innovations and help build and maintain communities of practice.

  12. How do parcellation size and short-range connectivity affect dynamics in large-scale brain network models?

    Science.gov (United States)

    Proix, Timothée; Spiegler, Andreas; Schirner, Michael; Rothmeier, Simon; Ritter, Petra; Jirsa, Viktor K

    2016-11-15

    Recent efforts to model human brain activity on the scale of the whole brain rest on connectivity estimates of large-scale networks derived from diffusion magnetic resonance imaging (dMRI). This type of connectivity describes white matter fiber tracts. The number of short-range cortico-cortical white-matter connections is, however, underrepresented in such large-scale brain models. It is still unclear on the one hand, which scale of representation of white matter fibers is optimal to describe brain activity on a large-scale such as recorded with magneto- or electroencephalography (M/EEG) or functional magnetic resonance imaging (fMRI), and on the other hand, to which extent short-range connections that are typically local should be taken into account. In this article we quantified the effect of connectivity upon large-scale brain network dynamics by (i) systematically varying the number of brain regions before computing the connectivity matrix, and by (ii) adding generic short-range connections. We used dMRI data from the Human Connectome Project. We developed a suite of preprocessing modules called SCRIPTS to prepare these imaging data for The Virtual Brain, a neuroinformatics platform for large-scale brain modeling and simulations. We performed simulations under different connectivity conditions and quantified the spatiotemporal dynamics in terms of Shannon Entropy, dwell time and Principal Component Analysis. For the reconstructed connectivity, our results show that the major white matter fiber bundles play an important role in shaping slow dynamics in large-scale brain networks (e.g. in fMRI). Faster dynamics such as gamma oscillations (around 40 Hz) are sensitive to the short-range connectivity if transmission delays are considered. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Bignoniaceae Metabolites as Semiochemicals

    Directory of Open Access Journals (Sweden)

    Lucía Castillo

    2010-10-01

    Full Text Available Members of the family Bignoniaceae are mostly found in tropical and neo-tropical regions in America, Asia and Africa, although some of them are cultivated in other regions as ornamentals. Species belonging to this family have been extensively studied in regard to their pharmacological properties (as extracts and isolated compounds. The aim of this review is to summarize the reported scientific evidence about the chemical properties as well as that of the extracts and isolated compounds from species of this family, focusing mainly in insect-plant interactions. As it is known, this family is recognized for the presence of iridoids which are markers of oviposition and feeding preference to species which have became specialist feeders. Some herbivore species have also evolved to the point of been able to sequester iridoids and use them as defenses against their predators. However, iridoids also exhibit anti-insect properties, and therefore they may be good lead molecules to develop botanical pesticides. Other secondary metabolites, such as quinones, and whole extracts have also shown potential as anti-insect agents.

  14. Case Study: Does training of private networks of Family Planning clinicians in urban Pakistan affect service utilization?

    Science.gov (United States)

    Qureshi, Asma M

    2010-11-09

    To determine whether training of providers participating in franchise clinic networks is associated with increased Family Planning service use among low-income urban families in Pakistan. The study uses 2001 survey data consisting of interviews with 1113 clinical and non-clinical providers working in public and private hospitals/clinics. Data analysis excludes non-clinical providers reducing sample size to 822. Variables for the analysis are divided into client volume, and training in family planning. Regression models are used to compute the association between training and service use in franchise versus private non-franchise clinics. In franchise clinic networks, staff are 6.5 times more likely to receive family planning training (P = 0.00) relative to private non-franchises. Service use was significantly associated with training (P = 0.00), franchise affiliation (P = 0.01), providers' years of family planning experience (P = 0.02) and the number of trained staff working at government owned clinics (P = 0.00). In this setting, nurses are significantly less likely to receive training compared to doctors (P = 0.00). These findings suggest that franchises recruit and train various cadres of health workers and training maybe associated with increased service use through improvement in quality of services.

  15. Case Study: Does training of private networks of Family Planning clinicians in urban Pakistan affect service utilization?

    Directory of Open Access Journals (Sweden)

    Qureshi Asma M

    2010-11-01

    Full Text Available Abstract Background To determine whether training of providers participating in franchise clinic networks is associated with increased Family Planning service use among low-income urban families in Pakistan. Methods The study uses 2001 survey data consisting of interviews with 1113 clinical and non-clinical providers working in public and private hospitals/clinics. Data analysis excludes non-clinical providers reducing sample size to 822. Variables for the analysis are divided into client volume, and training in family planning. Regression models are used to compute the association between training and service use in franchise versus private non-franchise clinics. Results In franchise clinic networks, staff are 6.5 times more likely to receive family planning training (P = 0.00 relative to private non-franchises. Service use was significantly associated with training (P = 0.00, franchise affiliation (P = 0.01, providers' years of family planning experience (P = 0.02 and the number of trained staff working at government owned clinics (P = 0.00. In this setting, nurses are significantly less likely to receive training compared to doctors (P = 0.00. Conclusions These findings suggest that franchises recruit and train various cadres of health workers and training maybe associated with increased service use through improvement in quality of services.

  16. Genome-wide association study and annotating candidate gene networks affecting age at first calving in Nellore cattle.

    Science.gov (United States)

    Mota, R R; Guimarães, S E F; Fortes, M R S; Hayes, B; Silva, F F; Verardo, L L; Kelly, M J; de Campos, C F; Guimarães, J D; Wenceslau, R R; Penitente-Filho, J M; Garcia, J F; Moore, S

    2017-12-01

    We performed a genome-wide mapping for the age at first calving (AFC) with the goal of annotating candidate genes that regulate fertility in Nellore cattle. Phenotypic data from 762 cows and 777k SNP genotypes from 2,992 bulls and cows were used. Single nucleotide polymorphism (SNP) effects based on the single-step GBLUP methodology were blocked into adjacent windows of 1 Megabase (Mb) to explain the genetic variance. SNP windows explaining more than 0.40% of the AFC genetic variance were identified on chromosomes 2, 8, 9, 14, 16 and 17. From these windows, we identified 123 coding protein genes that were used to build gene networks. From the association study and derived gene networks, putative candidate genes (e.g., PAPPA, PREP, FER1L6, TPR, NMNAT1, ACAD10, PCMTD1, CRH, OPKR1, NPBWR1 and NCOA2) and transcription factors (TF) (STAT1, STAT3, RELA, E2F1 and EGR1) were strongly associated with female fertility (e.g., negative regulation of luteinizing hormone secretion, folliculogenesis and establishment of uterine receptivity). Evidence suggests that AFC inheritance is complex and controlled by multiple loci across the genome. As several windows explaining higher proportion of the genetic variance were identified on chromosome 14, further studies investigating the interaction across haplotypes to better understand the molecular architecture behind AFC in Nellore cattle should be undertaken. © 2017 Blackwell Verlag GmbH.

  17. The Application of Ultra-High-Performance Liquid Chromatography Coupled with a LTQ-Orbitrap Mass Technique to Reveal the Dynamic Accumulation of Secondary Metabolites in Licorice under ABA Stress

    Directory of Open Access Journals (Sweden)

    Da Li

    2017-10-01

    Full Text Available The traditional medicine licorice is the most widely consumed herbal product in the world. Although much research work on studying the changes in the active compounds of licorice has been reported, there are still many areas, such as the dynamic accumulation of secondary metabolites in licorice, that need to be further studied. In this study, the secondary metabolites from licorice under two different methods of stress were investigated by ultra-high-performance liquid chromatography coupled with hybrid linear ion trap–Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS. A complex continuous coordination of flavonoids and triterpenoids in a network was modulated by different methods of stress during growth. The results showed that a total of 51 secondary metabolites were identified in licorice under ABA stress. The partial least squares–discriminate analysis (PLS-DA revealed the distinction of obvious compounds among stress-specific districts relative to ABA stress. The targeted results showed that there were significant differences in the accumulation patterns of the deeply targeted 41 flavonoids and 10 triterpenoids compounds by PCA and PLS-DA analyses. To survey the effects of flavonoid and triterpenoid metabolism under ABA stress, we inspected the stress-specific metabolic changes. Our study testified that the majority of flavonoids and triterpenoids were elevated in licorice under ABA stress, while the signature metabolite affecting the dynamic accumulation of secondary metabolites was detected. Taken together, our results suggest that ABA-specific metabolite profiling dynamically changed in terms of the biosynthesis of flavonoids and triterpenoids, which may offer new trains of thought on the regular pattern of dynamic accumulation of secondary metabolites in licorice at the metabolite level. Our results also provide a reference for clinical applications and directional planting and licorice breeding.

  18. The Clostridium small RNome that responds to stress: the paradigm and importance of toxic metabolite stress in C. acetobutylicum.

    Science.gov (United States)

    Venkataramanan, Keerthi P; Jones, Shawn W; McCormick, Kevin P; Kunjeti, Sridhara G; Ralston, Matthew T; Meyers, Blake C; Papoutsakis, Eleftherios T

    2013-12-04

    Small non-coding RNAs (sRNA) are emerging as major components of the cell's regulatory network, several possessing their own regulons. A few sRNAs have been reported as being involved in general or toxic-metabolite stress, mostly in Gram- prokaryotes, but hardly any in Gram+ prokaryotes. Significantly, the role of sRNAs in the stress response remains poorly understood at the genome-scale level. It was previously shown that toxic-metabolite stress is one of the most comprehensive and encompassing stress responses in the cell, engaging both the general stress (or heat-shock protein, HSP) response as well as specialized metabolic programs. Using RNA deep sequencing (RNA-seq) we examined the sRNome of C. acetobutylicum in response to the native but toxic metabolites, butanol and butyrate. 7.5% of the RNA-seq reads mapped to genome outside annotated ORFs, thus demonstrating the richness and importance of the small RNome. We used comparative expression analysis of 113 sRNAs we had previously computationally predicted, and of annotated mRNAs to set metrics for reliably identifying sRNAs from RNA-seq data, thus discovering 46 additional sRNAs. Under metabolite stress, these 159 sRNAs displayed distinct expression patterns, a select number of which was verified by Northern analysis. We identified stress-related expression of sRNAs affecting transcriptional (6S, S-box &solB) and translational (tmRNA & SRP-RNA) processes, and 65 likely targets of the RNA chaperone Hfq. Our results support an important role for sRNAs for understanding the complexity of the regulatory network that underlies the stress response in Clostridium organisms, whether related to normophysiology, pathogenesis or biotechnological applications.

  19. Domains I and IV of Annexin A2 Affect the Formation and Integrity of In Vitro Capillary-Like Networks

    OpenAIRE

    Raddum, Aase M.; Evensen, Lasse; Holl?s, Hanne; Grindheim, Ann Kari; Lorens, James B.; Vedeler, Anni

    2013-01-01

    Annexin A2 (AnxA2) is a widely expressed multifunctional protein found in different cellular compartments. In spite of lacking a hydrophobic signal peptide, AnxA2 is found at the cell surface of endothelial cells, indicative of a role in angiogenesis. Increased extracellular levels of AnxA2 in tumours correlate with neoangiogenesis, metastasis and poor prognosis. We hypothesised that extracellular AnxA2 may contribute to angiogenesis by affecting endothelial cell-cell interactions and motilit...

  20. 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.

  1. In vivo MRS metabolite quantification using genetic optimization

    Science.gov (United States)

    Papakostas, G. A.; Karras, D. A.; Mertzios, B. G.; van Ormondt, D.; Graveron-Demilly, D.

    2011-11-01

    The in vivo quantification of metabolites' concentrations, revealed in magnetic resonance spectroscopy (MRS) spectra, constitutes the main subject under investigation in this work. Significant contributions based on artificial intelligence tools, such as neural networks (NNs), with good results have been presented lately but have shown several drawbacks, regarding their quantification accuracy under difficult conditions. A general framework that encounters the quantification procedure as an optimization problem, which is solved using a genetic algorithm (GA), is proposed in this paper. Two different lineshape models are examined, while two GA configurations are applied on artificial data. Moreover, the introduced quantification technique deals with metabolite peaks' overlapping, a considerably difficult situation occurring under real conditions. Appropriate experiments have proved the efficiency of the introduced methodology, in artificial MRS data, by establishing it as a generic metabolite quantification procedure.

  2. In vivo MRS metabolite quantification using genetic optimization

    International Nuclear Information System (INIS)

    Papakostas, G A; Mertzios, B G; Karras, D A; Van Ormondt, D; Graveron-Demilly, D

    2011-01-01

    The in vivo quantification of metabolites' concentrations, revealed in magnetic resonance spectroscopy (MRS) spectra, constitutes the main subject under investigation in this work. Significant contributions based on artificial intelligence tools, such as neural networks (NNs), with good results have been presented lately but have shown several drawbacks, regarding their quantification accuracy under difficult conditions. A general framework that encounters the quantification procedure as an optimization problem, which is solved using a genetic algorithm (GA), is proposed in this paper. Two different lineshape models are examined, while two GA configurations are applied on artificial data. Moreover, the introduced quantification technique deals with metabolite peaks' overlapping, a considerably difficult situation occurring under real conditions. Appropriate experiments have proved the efficiency of the introduced methodology, in artificial MRS data, by establishing it as a generic metabolite quantification procedure

  3. Automated pathway and reaction prediction facilitates in silico identification of unknown metabolites in human cohort studies.

    Science.gov (United States)

    Quell, Jan D; Römisch-Margl, Werner; Colombo, Marco; Krumsiek, Jan; Evans, Anne M; Mohney, Robert; Salomaa, Veikko; de Faire, Ulf; Groop, Leif C; Agakov, Felix; Looker, Helen C; McKeigue, Paul; Colhoun, Helen M; Kastenmüller, Gabi

    2017-12-15

    Identification of metabolites in non-targeted metabolomics continues to be a bottleneck in metabolomics studies in large human cohorts. Unidentified metabolites frequently emerge in the results of association studies linking metabolite levels to, for example, clinical phenotypes. For further analyses these unknown metabolites must be identified. Current approaches utilize chemical information, such as spectral details and fragmentation characteristics to determine components of unknown metabolites. Here, we propose a systems biology model exploiting the internal correlation structure of metabolite levels in combination with existing biochemical and genetic information to characterize properties of unknown molecules. Levels of 758 metabolites (439 known, 319 unknown) in human blood samples of 2279 subjects were measured using a non-targeted metabolomics platform (LC-MS and GC-MS). We reconstructed the structure of biochemical pathways that are imprinted in these metabolomics data by building an empirical network model based on 1040 significant partial correlations between metabolites. We further added associations of these metabolites to 134 genes from genome-wide association studies as well as reactions and functional relations to genes from the public database Recon 2 to the network model. From the local neighborhood in the network, we were able to predict the pathway annotation of 180 unknown metabolites. Furthermore, we classified 100 pairs of known and unknown and 45 pairs of unknown metabolites to 21 types of reactions based on their mass differences. As a proof of concept, we then looked further into the special case of predicted dehydrogenation reactions leading us to the selection of 39 candidate molecules for 5 unknown metabolites. Finally, we could verify 2 of those candidates by applying LC-MS analyses of commercially available candidate substances. The formerly unknown metabolites X-13891 and X-13069 were shown to be 2-dodecendioic acid and 9

  4. Factors affecting growth in infants with single ventricle physiology: a report from the Pediatric Heart Network Infant Single Ventricle Trial.

    Science.gov (United States)

    Williams, Richard V; Zak, Victor; Ravishankar, Chitra; Altmann, Karen; Anderson, Jeffrey; Atz, Andrew M; Dunbar-Masterson, Carolyn; Ghanayem, Nancy; Lambert, Linda; Lurito, Karen; Medoff-Cooper, Barbara; Margossian, Renee; Pemberton, Victoria L; Russell, Jennifer; Stylianou, Mario; Hsu, Daphne

    2011-12-01

    To describe growth patterns in infants with single ventricle physiology and determine factors influencing growth. Data from 230 subjects enrolled in the Pediatric Heart Network Infant Single Ventricle Enalapril Trial were used to assess factors influencing change in weight-for-age z-score (z) from study enrollment (0.7 ± 0.4 months) to pre-superior cavopulmonary connection (SCPC; 5.1 ± 1.8 months, period 1) and pre-SCPC to final study visit (14.1 ± 0.9 months, period 2). Predictor variables included patient characteristics, feeding regimen, clinical center, and medical factors during neonatal (period 1) and SCPC hospitalizations (period 2). Univariate regression analysis was performed, followed by backward stepwise regression and bootstrapping reliability to inform a final multivariable model. Weights were available for 197 of 230 subjects for period 1 and 173 of 197 subjects for period 2. For period 1, greater gestational age, younger age at study enrollment, tube feeding at neonatal hospitalization discharge, and clinical center were associated with a greater negative z (poorer growth) in multivariable modeling (adjusted R(2) = 0.39, P SCPC and greater daily caloric intake were associated with greater positive z (better growth; R(2) = 0.10, P = .002). Aggressive nutritional support and earlier SCPC are modifiable factors associated with a favorable change in weight-for-age z-score. Copyright © 2011 Mosby, Inc. All rights reserved.

  5. The left middle temporal gyrus in the middle of an impaired social-affective communication network in social anxiety disorder.

    Science.gov (United States)

    Yun, Je-Yeon; Kim, Jae-Chang; Ku, Jeonghun; Shin, Jung-Eun; Kim, Jae-Jin; Choi, Soo-Hee

    2017-05-01

    Previous studies on patients diagnosed with social anxiety disorder (SAD) reported changed patterns of the resting-state functional connectivity network (rs-FCN) between the prefrontal cortices and other prefrontal, amygdalar or striatal regions. Using a graph theory approach, this study explored the modularity-based community profile and patterns of inter-/intra-modular communication for the rs-FCN in SAD. In total, for 28 SAD patients and 27 healthy controls (HC), functional magnetic resonance imaging (fMRI) data were acquired in resting-state and subjected to a graph theory analysis. The within-module degree z-score for a hub region [out of a total of 10 hub regions ranked using the participation coefficient] named left middle temporal gyrus was impaired in SAD compared to HC, proportional to the severity of clinician-scored and patient-reported functional impairment in SAD. Most of participants included in this study were undergraduate students in their early-to-mid 20's. This study showed the importance of functional communication from the left middle temporal gyrus with other opercular-insular-subcortical regions for better objective functioning and lesser subjective disability in SAD. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. It's not what you say, but how you say it: a reciprocal temporo-frontal network for affective prosody

    Directory of Open Access Journals (Sweden)

    David I Leitman

    2010-02-01

    Full Text Available Humans communicate emotion vocally by modulating acoustic cues such as pitch, intensity and voice quality. Research has documented how the relative presence or absence of such cues alters the likelihood of perceiving an emotion, but the neural underpinnings of acoustic cue-dependent emotion perception remain obscure. Using functional magnetic resonance imaging in 20 subjects we examined a reciprocal circuit consisting of superior temporal cortex, amygdala and inferior frontal gyrus that may underlie affective prosodic comprehension. Results showed that increased saliency of emotion-specific acoustic cues was associated with increased activation in superior temporal cortex (planum temporale (PT, posterior superior temporal gyrus (pSTG, and posterior superior middle gyrus (pMTG and amygdala, whereas decreased saliency of acoustic cues was associated with increased inferior frontal activity and temporo-frontal connectivity. These results suggest that sensory-integrative processing is facilitated when the acoustic signal is rich in affective information, yielding increased activation in temporal cortex and amygdala. Conversely, when the acoustic signal is ambiguous, greater evaluative processes are recruited, increasing activation in inferior frontal gyrus (IFG and IFG STG connectivity. Auditory regions may thus integrate acoustic information with amygdala input to form emotion-specific representations, which are evaluated within inferior frontal regions.

  7. Does IQ affect the functional brain network involved in pseudoword reading in students with reading disability? A magnetoencephalography study.

    Science.gov (United States)

    Simos, Panagiotis G; Rezaie, Roozbeh; Papanicolaou, Andrew C; Fletcher, Jack M

    2014-01-01

    The study examined whether individual differences in performance and verbal IQ affect the profiles of reading-related regional brain activation in 127 students experiencing reading difficulties and typical readers. Using magnetoencephalography in a pseudoword read-aloud task, we compared brain activation profiles of students experiencing word-level reading difficulties who did (n = 29) or did not (n = 36) meet the IQ-reading achievement discrepancy criterion. Typical readers assigned to a lower-IQ (n = 18) or a higher IQ (n = 44) subgroup served as controls. Minimum norm estimates of regional cortical activity revealed that the degree of hypoactivation in the left superior temporal and supramarginal gyri in both RD subgroups was not affected by IQ. Moreover, IQ did not moderate the positive association between degree of activation in the left fusiform gyrus and phonological decoding ability. We did find, however, that the hypoactivation of the left pars opercularis in RD was restricted to lower-IQ participants. In accordance with previous morphometric and fMRI studies, degree of activity in inferior frontal, and inferior parietal regions correlated with IQ across reading ability subgroups. Results are consistent with current views questioning the relevance of IQ-discrepancy criteria in the diagnosis of dyslexia.

  8. 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.

  9. Fetal Serum Metabolites Are Independently Associated with Gestational Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Yong-Ping Lu

    2018-01-01

    Full Text Available Background/Aims: Gestational diabetes (GDM might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32: 1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM.

  10. The minor wall-networks between monolignols and interlinked-phenolics predominantly affect biomass enzymatic digestibility in Miscanthus.

    Science.gov (United States)

    Li, Zhengru; Zhao, Chunqiao; Zha, Yi; Wan, Can; Si, Shengli; Liu, Fei; Zhang, Rui; Li, Fengcheng; Yu, Bin; Yi, Zili; Xu, Ning; Peng, Liangcai; Li, Qing

    2014-01-01

    Plant lignin is one of the major wall components that greatly contribute to biomass recalcitrance for biofuel production. In this study, total 79 representative Miscanthus germplasms were determined with wide biomass digestibility and diverse monolignol composition. Integrative analyses indicated that three major monolignols (S, G, H) and S/G ratio could account for lignin negative influence on biomass digestibility upon NaOH and H2SO4 pretreatments. Notably, the biomass enzymatic digestions were predominately affected by the non-KOH-extractable lignin and interlinked-phenolics, other than the KOH-extractable ones that cover 80% of total lignin. Furthermore, a positive correlation was found between the monolignols and phenolics at pnetworks against cellulases accessibility. The results indicated that the non-KOH-extractable lignin-complex should be the target either for cost-effective biomass pretreatments or for relatively simply genetic modification of plant cell walls in Miscanthus.

  11. Novel Approach to Classify Plants Based on Metabolite-Content Similarity

    Directory of Open Access Journals (Sweden)

    Kang Liu

    2017-01-01

    Full Text Available Secondary metabolites are bioactive substances with diverse chemical structures. Depending on the ecological environment within which they are living, higher plants use different combinations of secondary metabolites for adaptation (e.g., defense against attacks by herbivores or pathogenic microbes. This suggests that the similarity in metabolite content is applicable to assess phylogenic similarity of higher plants. However, such a chemical taxonomic approach has limitations of incomplete metabolomics data. We propose an approach for successfully classifying 216 plants based on their known incomplete metabolite content. Structurally similar metabolites have been clustered using the network clustering algorithm DPClus. Plants have been represented as binary vectors, implying relations with structurally similar metabolite groups, and classified using Ward’s method of hierarchical clustering. Despite incomplete data, the resulting plant clusters are consistent with the known evolutional relations of plants. This finding reveals the significance of metabolite content as a taxonomic marker. We also discuss the predictive power of metabolite content in exploring nutritional and medicinal properties in plants. As a byproduct of our analysis, we could predict some currently unknown species-metabolite relations.

  12. Effect of fertilisation and harvest period on polar metabolites of Calendula oficcinalis

    Directory of Open Access Journals (Sweden)

    Eduardo Felipe Alves Fernandes

    Full Text Available The present study evaluated the chemical profile of polar extracts of Calendula officinalis L., Asteraceae, that were grown under different cultivation conditions: chemical fertilisation, organic fertilisation and mulching. Furthermore, we investigated metabolite variations during plant development by comparing the metabolites from harvested plants at 60 and 120 days after planting. We used HPLC-DAD-MS/MS to tentatively identify metabolites. In total, we identified seven known compounds: five flavonoid glycosides and two caffeoylquinic acids derivatives. There were no statistically significant differences in the expression of metabolites from plants grown under the examined soil treatments. However, five substances varied according to harvest time, suggesting that the biosynthesis of polar metabolites of Calendula officinalis is not affected by changes in soil composition. Therefore, this plant could represent a source for phytomedicines with a constant content of polar metabolites.

  13. Developmental exposure to ethinylestradiol affects reproductive physiology, the GnRH neuroendocrine network and behaviors in female mouse

    Directory of Open Access Journals (Sweden)

    Lyes eDerouiche

    2015-12-01

    Full Text Available During development, environmental estrogens are able to induce an estrogen mimetic action that may interfere with endocrine and neuroendocrine systems. The present study investigated the effects on the reproductive function in female mice following developmental exposure to pharmaceutical ethinylestradiol (EE2, the most widespread and potent synthetic steroid present in aquatic environments. EE2 was administrated in drinking water at environmentally relevant (ENVIR or pharmacological (PHARMACO doses (0.1 and 1 µg/kg (body weight/day respectively, from embryonic day 10 until postnatal day 40. Our results show that both groups of EE2-exposed females had advanced vaginal opening and shorter estrus cycles, but a normal fertility rate compared to CONTROL females. The hypothalamic population of GnRH neurons was affected by EE2 exposure with a significant increase in the number of perikarya in the preoptic area of the PHARMACO group and a modification in their distribution in the ENVIR group, both associated with a marked decrease in GnRH fibers immunoreactivity in the median eminence. In EE2-exposed females, behavioral tests highlighted a disturbed maternal behavior, a higher lordosis response, a lack of discrimination between gonad-intact and castrated males in sexually experienced females, and an increased anxiety-related behavior. Altogether, these results put emphasis on the high sensitivity of sexually dimorphic behaviors and neuroendocrine circuits to disruptive effects of EDCs.

  14. Secondary metabolites from Eremostachys laciniata

    DEFF Research Database (Denmark)

    Calis, Ihsan; Güvenc, Aysegül; Armagan, Metin

    2008-01-01

    ), 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...... 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....

  15. Microbial production of primary metabolites

    Science.gov (United States)

    Demain, Arnold L.

    1980-12-01

    Microbial production of primary metabolites contributes significantly to the quality of life. Through fermentation, microorganisms growing on inexpensive carbon sources can produce valuable products such as amino acids, nucleotides, organic acids, and vitamins which can be added to food to enhance its flavor or increase its nutritive value. The contribution of microorganisms will go well beyond the food industry with the renewed interest in solvent fermentations. Microorganisms have the potential to provide many petroleum-derived products as well as the ethanol necessary for liquid fuel. The role of primary metabolites and the microbes which produce them will certainly increase in importance.

  16. Network maintenance

    CERN Multimedia

    GS Department

    2009-01-01

    A site-wide network maintenance operation has been scheduled for Saturday 28 February. Most of the network devices of the general purpose network will be upgraded to a newer software version, in order to improve our network monitoring capabilities. This will result in a series of short (2-5 minutes) random interruptions everywhere on the CERN sites throughout the day. This upgrade will not affect the Computer Centre itself, Building 613, the Technical Network and the LHC experiments, dedicated networks at the pits. For further details of this intervention, please contact Netops by phone 74927 or e-mail mailto:Netops@cern.ch. IT/CS Group

  17. Network maintenance

    CERN Multimedia

    IT Department

    2009-01-01

    A site wide network maintenance has been scheduled for Saturday 28 February. Most of the network devices of the General Purpose network will be upgraded to a newer software version, in order to improve our network monitoring capabilities. This will result in a series of short (2-5 minutes) random interruptions everywhere on the CERN sites along this day. This upgrade will not affect: the Computer centre itself, building 613, the Technical Network and the LHC experiments dedicated networks at the pits. Should you need more details on this intervention, please contact Netops by phone 74927 or email mailto:Netops@cern.ch. IT/CS Group

  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. [Systems biology applications to explore secondary metabolites in medicinal plants].

    Science.gov (United States)

    Huang, Luqi; Gao, Wei; Zhou, Jie; Wang, Ruiting

    2010-01-01

    Secondary metabolites are produced during the growth and development of plants along with the adaptation of outer environment, as a rule they are the main active ingredients in medicinal plants and ensure the quality of crude drugs. Since biogenesis is quite complex, the production and accumulation of secondary metabolites are influenced by various biotic and abiotic factors either from gene or environments, the complexity may affect quality control of crude drugs and utilization of the active ingredients. The thought and approach adopted in systems biology is a powerful tool to explore biology fully, along with the development of modern molecular biology and information biology, omics integration like genomics, transcriptomics, proteomics, and metabolomics will bring new opportunities for the study of secondary metabolites of medicinal plant. It has great significance to apply this holistic and systematic method in researches on biosynthetic pathway, signal transduction, ecological environment and metabolic engineering of the formation of the secondary metabolites of medicinal plants, and in building secondary metabolite biosynthesis gene expression and regulation system model, in order to explain the origin of the active ingredients of medicinal plants, formation mechanism of the Chinese herbs, metabolic engineering effecting active ingredients of medicinal plants, and the rational exploitation and utilization of resources of medicinal plants systematically.

  20. Some Metabolites Act as Second Messengers in Yeast Chronological Aging

    Directory of Open Access Journals (Sweden)

    Karamat Mohammad

    2018-03-01

    Full Text Available The concentrations of some key metabolic intermediates play essential roles in regulating the longevity of the chronologically aging yeast Saccharomyces cerevisiae. These key metabolites are detected by certain ligand-specific protein sensors that respond to concentration changes of the key metabolites by altering the efficiencies of longevity-defining cellular processes. The concentrations of the key metabolites that affect yeast chronological aging are controlled spatially and temporally. Here, we analyze mechanisms through which the spatiotemporal dynamics of changes in the concentrations of the key metabolites influence yeast chronological lifespan. Our analysis indicates that a distinct set of metabolites can act as second messengers that define the pace of yeast chronological aging. Molecules that can operate both as intermediates of yeast metabolism and as second messengers of yeast chronological aging include reduced nicotinamide adenine dinucleotide phosphate (NADPH, glycerol, trehalose, hydrogen peroxide, amino acids, sphingolipids, spermidine, hydrogen sulfide, acetic acid, ethanol, free fatty acids, and diacylglycerol. We discuss several properties that these second messengers of yeast chronological aging have in common with second messengers of signal transduction. We outline how these second messengers of yeast chronological aging elicit changes in cell functionality and viability in response to changes in the nutrient, energy, stress, and proliferation status of the cell.

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

    Science.gov (United States)

    Jančič, Sašo; Frisvad, Jens C; Kocev, Dragi; Gostinčar, Cene; 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.

  2. Determination of the Most Important Soil Parameters Affecting the Availability of Phosphorus in Sistan Plain, Using Connection Weight Method in Neural Networks

    Directory of Open Access Journals (Sweden)

    H. Mir

    2016-09-01

    Full Text Available Introduction: Phosphorus is important as an essential element in the production of agricultural products. On the other hand, its ability to induce essential micronutrient deficiency and its negative effects on the environment, have attracted more attention to this element. The knowledge of phosphorus availability conditions in the soil and consequently the accurate management of fertilizer consumption has a key role in the environmental protection. The degree of phosphorus absorption in the soil depends on the environmental factors, soil characteristics and compositions, and phosphorus fertilizer which have been used. The amount of available phosphorus in the soil has relationship with some of the physical and chemical properties of the soil. Since, the soil characteristics are important factors in the reaction of phosphorus in the soil, the present study aimed to investigate and determine the most important soil characteristics affecting the availability of phosphorus using regression and artificial neural network techniques, in the soils of Sistan plain. Materials and Methods: Soil sampling was done in 1.5×1.5 km intervals, from 0-30 cm depth, and 200 soil samples were taken. The amounts of available phosphorus and the soil properties including the percentages of clay , organic matter, calcium carbonate and the amount of pH were measured. Then, stepwise multivariate linear regression analysis was performed to determine linear relation between available phosphorus and the soil properties. In order to model and validate the regression model, respectively 80 and 20% of data were selected and entered into SPSS software. To train the neural network, multilayer perceptron (MLP network was used by MATLAB 7.6 package. In this type of network, 70% of data is selected for training, 15% for validation and 15% for testing the model. Levenberg-Marquardt algorithm and hyperbolic tangent (as a transfer function were used to train the network. The numbers of

  3. Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

    Directory of Open Access Journals (Sweden)

    Jaroslaw Suchanski

    Full Text Available In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first

  4. Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

    Science.gov (United States)

    Suchanski, Jaroslaw; Tejchman, Anna; Zacharski, Maciej; Piotrowska, Aleksandra; Grzegrzolka, Jedrzej; Chodaczek, Grzegorz; Nowinska, Katarzyna; Rys, Janusz; Dziegiel, Piotr; Kieda, Claudine; Ugorski, Maciej

    2017-01-01

    In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such

  5. 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...

  6. Robustness of metabolic networks

    Science.gov (United States)

    Jeong, Hawoong

    2009-03-01

    We investigated the robustness of cellular metabolism by simulating the system-level computational models, and also performed the corresponding experiments to validate our predictions. We address the cellular robustness from the ``metabolite''-framework by using the novel concept of ``flux-sum,'' which is the sum of all incoming or outgoing fluxes (they are the same under the pseudo-steady state assumption). By estimating the changes of the flux-sum under various genetic and environmental perturbations, we were able to clearly decipher the metabolic robustness; the flux-sum around an essential metabolite does not change much under various perturbations. We also identified the list of the metabolites essential to cell survival, and then ``acclimator'' metabolites that can control the cell growth were discovered. Furthermore, this concept of ``metabolite essentiality'' should be useful in developing new metabolic engineering strategies for improved production of various bioproducts and designing new drugs that can fight against multi-antibiotic resistant superbacteria by knocking-down the enzyme activities around an essential metabolite. Finally, we combined a regulatory network with the metabolic network to investigate its effect on dynamic properties of cellular metabolism.

  7. Abnormal Metabolite in Alcoholic Subjects,

    Science.gov (United States)

    1982-01-01

    0.01 0.12 81 A.A. 51 M 0 ɘ.01 0.09 Schizophrenia 85a W.G. 67 M 0 ɘ.01 0.21 Proteins & Ketones in Urine b 0 ɘ.01 0.11 86a W.H. 67 M 0 ɘ.01 0.15 b 0...AD-AS 90 TOTTS GAP MEDICAL RESEARCH LABS INC BANGOR PA F/G 6/5 ABNORMAL METABOLITE IN ALCOHOLIC SUBJECTS, U) 1982 R L BEECH, M E FELVER, M R...LAKSCHMANAN NOOBIN 70 C 0233 UNJCLASSIFIED NL I ,I/ ABNORMAL METABOLITE IN ALCOHOLIC SUBJECTS Richard L . Veech, Michael E. Felver, M.R. Lakschmanan, Stewart

  8. Chromatographic analysis of tryptophan metabolites.

    Science.gov (United States)

    Sadok, Ilona; Gamian, Andrzej; Staniszewska, Magdalena Maria

    2017-08-01

    The kynurenine pathway generates multiple tryptophan metabolites called collectively kynurenines and leads to formation of the enzyme cofactor nicotinamide adenine dinucleotide. The first step in this pathway is tryptophan degradation, initiated by the rate-limiting enzymes indoleamine 2,3-dioxygenase, or tryptophan 2,3-dioxygenase, depending on the tissue. The balanced kynurenine metabolism, which has been a subject of multiple studies in last decades, plays an important role in several physiological and pathological conditions such as infections, autoimmunity, neurological disorders, cancer, cataracts, as well as pregnancy. Understanding the regulation of tryptophan depletion provide novel diagnostic and treatment opportunities, however it requires reliable methods for quantification of kynurenines in biological samples with complex composition (body fluids, tissues, or cells). Trace concentrations, interference of sample components, and instability of some tryptophan metabolites need to be addressed using analytical methods. The novel separation approaches and optimized extraction protocols help to overcome difficulties in analyzing kynurenines within the complex tissue material. Recent developments in chromatography coupled with mass spectrometry provide new opportunity for quantification of tryptophan and its degradation products in various biological samples. In this review, we present current accomplishments in the chromatographic methodologies proposed for detection of tryptophan metabolites and provide a guide for choosing the optimal approach. © 2017 The Authors. Journal of Separation Science published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Quantification of stable isotope label in metabolites via mass spectrometry.

    Science.gov (United States)

    Huege, Jan; Goetze, Jan; Dethloff, Frederik; Junker, Bjoern; Kopka, Joachim

    2014-01-01

    Isotope labelling experiments with stable or radioactive isotopes have long been an integral part of biological and medical research. Labelling experiments led to the discovery of new metabolic pathways and made it possible to calculate the fluxes responsible for a metabolic phenotype, i.e., the qualitative and quantitative composition of metabolites in a biological system. Prerequisite for efficient isotope labelling experiments is a reliable and precise method to analyze the redistribution of isotope label in a metabolic network. Here we describe the use of the CORRECTOR program, which utilizes matrix calculations to correct mass spectral data from stable isotope labelling experiments for the distorting effect of naturally occurring stable isotopes (NOIs). CORRECTOR facilitates and speeds up the routine quantification of experimentally introduced isotope label from multiple mass spectral readouts, which are generated by routine metabolite profiling when combined with stable isotope labelling experiments.

  10. 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: ...

  11. Engineering Microbial Metabolite Dynamics and Heterogeneity.

    Science.gov (United States)

    Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

    2017-10-01

    As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. 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.

  13. 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.

  14. 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

  15. 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......://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....

  16. 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

  17. Precursors and metabolites of 5-hydroxytryptamine and dopamine in the ventricular cerebrospinal fluid of psychiatric patients.

    Science.gov (United States)

    Bridges, P K; Bartlett, J R; Sepping, P; Kantamaneni, B D; Curzon, G

    1976-08-01

    Tryptophan and 5-hydroxyindoleacetic acid (precursor and metabolite respectively of 5-hydroxytryptamine) were determined in ventricular CSF of psychiatric patients undergoing stereotactic subcaudate tractotomy. Tyrosine and homovanillic acid (precursor and metabolite respectively of dopamine) were also determined. Results suggest an association between affective state and the above precursor amino acids with lower concentrations in primary depression and higher ones when anxiety or agitation predominate. This leads to lower 5-hydroxyindoleacetic acid concentrations in depression and higher concentrations in anxiety and agitation.

  18. of Several Organophosphorus Insecticide Metabolites

    Directory of Open Access Journals (Sweden)

    Russell L. Carr

    2015-01-01

    Full Text Available Paraoxonase (PON1 is a calcium dependent enzyme that is capable of hydrolyzing organophosphate anticholinesterases. PON1 activity is present in most mammals and previous research established that PON1 activity differs depending on the species. These studies mainly used the organophosphate substrate paraoxon, the active metabolite of the insecticide parathion. Using serum PON1 from different mammalian species, we compared the hydrolysis of paraoxon with the hydrolysis of the active metabolites (oxons of two additional organophosphorus insecticides, methyl parathion and chlorpyrifos. Paraoxon hydrolysis was greater than that of methyl paraoxon, but the level of activity between species displayed a similar pattern. Regardless of the species tested, the hydrolysis of chlorpyrifos-oxon was significantly greater than that of paraoxon or methyl paraoxon. These data indicate that chlorpyrifos-oxon is a better substrate for PON1 regardless of the species. The pattern of species differences in PON1 activity varied with the change in substrate to chlorpyrifos-oxon from paraoxon or methyl paraoxon. For example, the sex difference observed here and reported elsewhere in the literature for rat PON1 hydrolysis of paraoxon was not present when chlorpyrifos-oxon was the substrate.

  19. Vulnerability of network of networks

    Science.gov (United States)

    Havlin, S.; Kenett, D. Y.; Bashan, A.; Gao, J.; Stanley, H. E.

    2014-10-01

    Our dependence on networks - be they infrastructure, economic, social or others - leaves us prone to crises caused by the vulnerabilities of these networks. There is a great need to develop new methods to protect infrastructure networks and prevent cascade of failures (especially in cases of coupled networks). Terrorist attacks on transportation networks have traumatized modern societies. With a single blast, it has become possible to paralyze airline traffic, electric power supply, ground transportation or Internet communication. How, and at which cost can one restructure the network such that it will become more robust against malicious attacks? The gradual increase in attacks on the networks society depends on - Internet, mobile phone, transportation, air travel, banking, etc. - emphasize the need to develop new strategies to protect and defend these crucial networks of communication and infrastructure networks. One example is the threat of liquid explosives a few years ago, which completely shut down air travel for days, and has created extreme changes in regulations. Such threats and dangers warrant the need for new tools and strategies to defend critical infrastructure. In this paper we review recent advances in the theoretical understanding of the vulnerabilities of interdependent networks with and without spatial embedding, attack strategies and their affect on such networks of networks as well as recently developed strategies to optimize and repair failures caused by such attacks.

  20. 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.

  1. MET-XAlign: a metabolite cross-alignment tool for LC/MS-based comparative metabolomics.

    Science.gov (United States)

    Zhang, Wenchao; Lei, Zhentian; Huhman, David; Sumner, Lloyd W; Zhao, Patrick X

    2015-09-15

    Liquid chromatography/mass spectrometry (LC/MS) metabolite profiling has been widely used in comparative metabolomics studies; however, LC/MS-based comparative metabolomics currently faces several critical challenges. One of the greatest challenges is how to effectively align metabolites across different LC/MS profiles; a single metabolite can give rise to multiple peak features, and the grouped peak features that can be used to construct a spectrum pattern of single metabolite can vary greatly between biochemical experiments and even between instrument runs. Another major challenge is that the observed retention time for a single metabolite can also be significantly affected by experimental conditions. To overcome these two key challenges, we present a novel metabolite-based alignment approach entitled MET-XAlign to align metabolites across LC/MS metabolomics profiles. MET-XAlign takes the deduced molecular mass and estimated compound retention time information that can be extracted by our previously published tool, MET-COFEA, and aligns metabolites based on this information. We demonstrate that MET-XAlign is able to cross-align metabolite compounds, either known or unknown, in LC/MS profiles not only across different samples but also across different biological experiments and different electrospray ionization modes. Therefore, our proposed metabolite-based cross-alignment approach is a great step forward and its implementation, MET-XAlign, is a very useful tool in LC/MS-based comparative metabolomics. MET-XAlign has been successfully implemented with core algorithm coding in C++, making it very efficient, and visualization interface coding in the Microsoft.NET Framework. The MET-XAlign software along with demonstrative data is freely available at http://bioinfo.noble.org/manuscript-support/met-xalign/ .

  2. Managing business networks and buyer-supplier relationships. How information obtained from the business network affects trust, transaction specific investments, collaboration and performance in the Dutch Potted Plant and Flower Industry

    NARCIS (Netherlands)

    Claro, D.P.

    2004-01-01

    Managing networks and buyer-supplier relationships " attempt to provide scientific sound discussion for problems faced in business linkages. Business networks, supply chains and buyer-supplier relationships all refer to business linkages, from a web of connected relationships to a dyadic

  3. The Networks of Genes Encoding Palmitoylated Proteins in Axonal and Synaptic Compartments Are Affected in PPT1 Overexpressing Neuronal-Like Cells

    Directory of Open Access Journals (Sweden)

    Francesco Pezzini

    2017-08-01

    Full Text Available CLN1 disease (OMIM #256730 is an early childhood ceroid-lipofuscinosis associated with mutated CLN1, whose product Palmitoyl-Protein Thioesterase 1 (PPT1 is a lysosomal enzyme involved in the removal of palmitate residues from S-acylated proteins. In neurons, PPT1 expression is also linked to synaptic compartments. The aim of this study was to unravel molecular signatures connected to CLN1. We utilized SH-SY5Y neuroblastoma cells overexpressing wild type CLN1 (SH-p.wtCLN1 and five selected CLN1 patients’ mutations. The cellular distribution of wtPPT1 was consistent with regular processing of endogenous protein, partially detected inside Lysosomal Associated Membrane Protein 2 (LAMP2 positive vesicles, while the mutants displayed more diffuse cytoplasmic pattern. Transcriptomic profiling revealed 802 differentially expressed genes (DEGs in SH-p.wtCLN1 (as compared to empty-vector transfected cells, whereas the number of DEGs detected in the two mutants (p.L222P and p.M57Nfs*45 was significantly lower. Bioinformatic scrutiny linked DEGs with neurite formation and neuronal transmission. Specifically, neuritogenesis and proliferation of neuronal processes were predicted to be hampered in the wtCLN1 overexpressing cell line, and these findings were corroborated by morphological investigations. Palmitoylation survey identified 113 palmitoylated protein-encoding genes in SH-p.wtCLN1, including 25 ones simultaneously assigned to axonal growth and synaptic compartments. A remarkable decrease in the expression of palmitoylated proteins, functionally related to axonal elongation (GAP43, CRMP1 and NEFM and of the synaptic marker SNAP25, specifically in SH-p.wtCLN1 cells was confirmed by immunoblotting. Subsequent, bioinformatic network survey of DEGs assigned to the synaptic annotations linked 81 DEGs, including 23 ones encoding for palmitoylated proteins. Results obtained in this experimental setting outlined two affected functional modules (connected to

  4. Does recipient work status pre-transplant affect post-heart transplant survival? A United Network for Organ Sharing database review.

    Science.gov (United States)

    Ravi, Yazhini; Lella, Srihari K; Copeland, Laurel A; Zolfaghari, Kiumars; Grady, Kathleen; Emani, Sitaramesh; Sai-Sudhakar, Chittoor B

    2018-01-31

    Recipient-related factors, such as education level and type of health insurance, are known to affect heart transplantation outcomes. Pre-operative employment status has shown an association with survival in abdominal organ transplant patients. We sought to evaluate the effect of work status of heart transplant (HTx) recipients at the time of listing and at the time of transplantation on short- and long-term survival. We evaluated the United Network for Organ Sharing (UNOS) registry for all adult HTx recipients from 2001 to 2014. Recipients were grouped based on their work status at listing and at heart transplantation. Kaplan-Meier estimates illustrated 30-day, 1-year, 5-year, and 10-year survival comparing working with non-working groups. The Cox proportional hazards regression model was applied to adjust for covariates that could potentially confound the post-transplantation survival analysis. Working at listing for HTx was not significantly associated with 30-day and 1-year survival. However, 5- and 10-year mortality were 14.5% working vs 19.8% not working (p transplantation. The Cox proportional hazards regression model showed that working at listing and working at transplantation were each associated with decreased mortality (hazard ratio [HR] = 0.8, 95% confidence interval [CI] 0.71 to 0.91; and HR = 0.76, 95% CI 0.65 to 0.89, respectively). This study is the first analysis of UNOS STAR data on recipient work status pre-HTx demonstrating: (1) an improvement in post-transplant survival for working HTx candidates; and (2) an association between working pre-HTx and longer post-HTx survival. Given that work status before HTx may be a modifiable risk factor for better outcomes after HTx, we strongly recommend that UNOS consider these important findings for moving forward this patient-centered research on work status. Working at listing and working at HTx are associated with long-term survival benefits. The association may be reciprocal, where working

  5. Evidence for biological denitrification inhibition (BDI) by plant secondary metabolites.

    Science.gov (United States)

    Bardon, Clément; Piola, Florence; Bellvert, Floriant; Haichar, Feth el Zahar; Comte, Gilles; Meiffren, Guillaume; Pommier, Thomas; Puijalon, Sara; Tsafack, Noelline; Poly, Franck

    2014-11-01

    Previous studies on the effect of secondary metabolites on the functioning of rhizosphere microbial communities have often focused on aspects of the nitrogen (N) cycle but have overlooked biological denitrification inhibition (BDI), which can affect plant N-nutrition. Here, we investigated the BDI by the compounds of Fallopia spp., an invasive weed shown to be associated with a low potential denitrification of the soil. Fallopia spp. extracts were characterized by chromatographic analysis and were used to test the BDI effects on the metabolic and respiratory activities of denitrifying bacteria, under aerobic and anaerobic (denitrification) conditions. The BDI of Fallopia spp. extracts was tested on a complex soil community by measuring denitrification enzyme activity (DEA), substrate induced respiration (SIR), as well as abundances of denitrifiers and total bacteria. In 15 strains of denitrifying bacteria, extracts led to a greater BDI (92%) than respiration inhibition (50%). Anaerobic metabolic activity reduction was correlated with catechin concentrations and the BDI was dose dependent. In soil, extracts reduced the DEA/SIR ratio without affecting the denitrifiers: total bacteria ratio. We show that secondary metabolite(s) from Fallopia spp. inhibit denitrification. This provides new insight into plant-soil interactions and improves our understanding of a plant's ability to shape microbial soil functioning. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

  6. Ecological role of a seaweed secondary metabolite for a colonizing bacterial community.

    Science.gov (United States)

    Persson, Frank; Svensson, Robin; Nylund, Goran M; Fredriksson, N Johan; Pavia, Henrik; Hermansson, Malte

    2011-07-01

    Bacteria associated with seaweeds can both harm and benefit their hosts. Many seaweed species are known to produce compounds that inhibit growth of bacterial isolates, but the ecological role of seaweed metabolites for the associated bacterial community structure is not well understood. In this study the response of a colonizing bacterial community to the secondary metabolite (1,1,3,3-tetrabromo-2-heptanone) from the red alga Bonnemaisonia hamifera was investigated by using field panels coated with the metabolite at a range of concentrations covering those measured at the algal surface. The seaweed metabolite has previously been shown to have antibacterial effects. The metabolite significantly affected the natural fouling community by (i) altering the composition, (ii) altering the diversity by increasing the evenness and (iii) decreasing the density, as measured by terminal restriction fragment length polymorphism in conjunction with clone libraries of the 16S rRNA genes and by bacterial enumeration. No single major bacterial taxon (phylum, class) was particularly affected by the metabolite. Instead changes in community composition were observed at a more detailed phylogenetic level. This indicates a broad specificity of the seaweed metabolite against bacterial colonization, which is supported by the observation that the bacterial density was significantly affected at a lower concentration (0.02 μg cm⁻²) than the composition (1-2.5 μg cm⁻²) and the evenness (5 μg cm⁻²) of the bacterial communities. Altogether, the results emphasize the role of secondary metabolites for control of the density and structure of seaweed-associated bacterial communities.

  7. Antimycobacterial Metabolites from Marine Invertebrates.

    Science.gov (United States)

    Daletos, Georgios; Ancheeva, Elena; Chaidir, Chaidir; Kalscheuer, Rainer; Proksch, Peter

    2016-10-01

    Marine organisms play an important role in natural product-based drug research due to accumulation of structurally unique and bioactive metabolites. The exploration of marine-derived compounds may significantly extend the scientific knowledge of potential scaffolds for antibiotic drug discovery. Development of novel antitubercular agents is especially significant as the emergence of drug-resistant Mycobacterium tuberculosis strains remains threateningly high. Marine invertebrates (i.e., sponges, corals, gorgonians) as a source of new chemical entities are the center of research for several scientific groups, and the wide spectrum of biological activities of marine-derived compounds encourages scientists to carry out investigations in the field of antibiotic research, including tuberculosis treatment. The present review covers published data on antitubercular natural products from marine invertebrates grouped according to their biogenetic origin. Studies on the structure-activity relationships of these important leads are highlighted as well. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Ecotoxicological effects of selected cyanobacterial secondary metabolites a short review

    International Nuclear Information System (INIS)

    Wiegand, C.; Pflugmacher, S.

    2005-01-01

    Cyanobacteria are one of the most diverse groups of gram-negative photosynthetic prokaryotes. Many of them are able to produce a wide range of toxic secondary metabolites. These cyanobacterial toxins can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). Cyanobacterial blooms are hazardous due to this production of secondary metabolites and endotoxins, which could be toxic to animals and plants. Many of the freshwater cyanobacterial blooms include species of the toxigenic genera Microcystis, Anabaena, or Plankthotrix. These compounds differ in mechanisms of uptake, affected organs, and molecular mode of action. In this review, the main focus is the aquatic environment and the effects of these toxins to the organisms living there. Some basic toxic mechanisms will be discussed in comparison to the mammalian system

  9. 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

  10. Determination of flutamide and two major metabolites using HPLC-DAD and HPTLC methods.

    Science.gov (United States)

    Abdelwahab, Nada S; Elshemy, Heba A H; Farid, Nehal F

    2018-01-25

    Flutamide is a potential antineoplastic drug classified as an anti-androgen. It is a therapy for men with advanced prostate cancer, administered orally after which it undergoes extensively first pass metabolism in the liver with the production of several metabolites. These metabolites are predominantly excreted in urine. One of the important metabolites in plasma is 4-nitro-3-(trifluoromethyl)phenylamine (Flu-1), while the main metabolite in urine is 2-amino-5-nitro-4-(trifluoromethyl)phenol (Flu-3). In this work the two metabolites, Flu-1 and Flu-3, have been synthesized, and then structural confirmation has been carried out by HNMR analysis. Efforts were exerted to develop chromatographic methods for resolving Flutamide and its metabolites with the use of acceptable solvents without affecting the efficiency of the methods. The drug along with its metabolites were quantitatively analyzed in pure form, human urine, and plasma samples using two chromatographic methods, HPTLC and HPLC-DAD methods. FDA guidelines for bio-analytical method validation were followed and USP recommendations were used for analytical method validation. Interference from excipients has been tested by application of the methods to pharmaceutical tablets. No significant difference was found between the proposed methods and the official one when they were statistically compared at p value of 0.05%.

  11. Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing.

    Science.gov (United States)

    Sankarasubramanian, Vishwanath; Cunningham, David A; Potter-Baker, Kelsey A; Beall, Erik B; Roelle, Sarah M; Varnerin, Nicole M; Machado, Andre G; Jones, Stephen E; Lowe, Mark J; Plow, Ela B

    2017-04-01

    The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks

  12. GPCR-Mediated Signaling of Metabolites

    DEFF Research Database (Denmark)

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

    2017-01-01

    In addition to their bioenergetic intracellular function, several classical metabolites act as extracellular signaling molecules activating cell-surface G-protein-coupled receptors (GPCRs), similar to hormones and neurotransmitters. "Signaling metabolites" generated from nutrients or by gut...... microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals...... 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...

  13. Spectroscopic methods to analyze drug metabolites.

    Science.gov (United States)

    Yi, Jong-Jae; Park, Kyeongsoon; Kim, Won-Je; Rhee, Jin-Kyu; Son, Woo Sung

    2018-03-09

    Drug metabolites have been monitored with various types of newly developed techniques and/or combination of common analytical methods, which could provide a great deal of information on metabolite profiling. Because it is not easy to analyze whole drug metabolites qualitatively and quantitatively, a single solution of analytical techniques is combined in a multilateral manner to cover the widest range of drug metabolites. Mass-based spectroscopic analysis of drug metabolites has been expanded with the help of other parameter-based methods. The current development of metabolism studies through contemporary pharmaceutical research are reviewed with an overview on conventionally used spectroscopic methods. Several technical approaches for conducting drug metabolic profiling through spectroscopic methods are discussed in depth.

  14. Network effects in railways

    DEFF Research Database (Denmark)

    Landex, Alex

    2012-01-01

    . Therefore, sections 3 and 4 describe the network effects for passengers and how they can be measured using passenger delay models. Before the concluding remarks in section 6, section 5 discusses how the operation can be improved by examining network effects in the planning process. © 2012 WIT Press....... each other everywhere in the network. First this paper describes network effects in general (section 1). In section 2 the network effects for trains and how they can be measured by scheduled waiting time is described. When the trains are affected by network effects the passengers are also affected......Railway operation is often affected by network effects as a change in one part of the network can influence other parts of the network. Network effects occur because the train runs may be quite long and since the railway system has a high degree of interdependencies as trains cannot cross/overtake...

  15. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    International Nuclear Information System (INIS)

    Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

    2006-01-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

  16. Complicating factors in safety testing of drug metabolites: kinetic differences between generated and preformed metabolites.

    Science.gov (United States)

    Prueksaritanont, Thomayant; Lin, Jiunn H; Baillie, Thomas A

    2006-12-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models.

  17. How Do Vegetation Density and Transportation Network Density Affect Crime across an Urban Central-Peripheral Gradient? A Case Study in Kitchener—Waterloo, Ontario

    Directory of Open Access Journals (Sweden)

    Yikang Du

    2016-07-01

    Full Text Available The relationship between vegetation, transportation networks, and crime has been under debate. Vegetation has been positively correlated with fear of crime; however, the actual correlation between vegetation and occurrences of crime is uncertain. Transportation networks have also been connected with crime occurrence but their impact on crime tends to vary over different circumstances. By conducting spatial analyses, this study explores the associations between crime and vegetation as well as transportation networks in Kitchener-Waterloo. Further, geographically weighted regression modeling and a dummy urban variable representing the urban center/other urban areas were employed to explore the associations across an urban central-peripheral gradient. Associations were analyzed for crimes against persons and crimes against property for four specific crime types (assaults, vehicle theft, sex offences, and drugs. Results suggest that vegetation has a reverse association with crimes against persons and crimes against property while transportation networks have a positive relationship with these two types of crime. Additionally, vegetation can be a deterrent to vehicle theft crime and drugs, while transportation networks can be a facilitator of drug-related crimes. Besides, these two associations appear stronger in the urban center compared to the urban periphery.

  18. The Ecological Role of Volatile and Soluble Secondary Metabolites Produced by Soil Bacteria.

    Science.gov (United States)

    Tyc, Olaf; Song, Chunxu; Dickschat, Jeroen S; Vos, Michiel; Garbeva, Paolina

    2017-04-01

    The rich diversity of secondary metabolites produced by soil bacteria has been appreciated for over a century, and advances in chemical analysis and genome sequencing continue to greatly advance our understanding of this biochemical complexity. However, we are just at the beginning of understanding the physicochemical properties of bacterial metabolites, the factors that govern their production and ecological roles. Interspecific interactions and competitor sensing are among the main biotic factors affecting the production of bacterial secondary metabolites. Many soil bacteria produce both volatile and soluble compounds. In contrast to soluble compounds, volatile organic compounds can diffuse easily through air- and gas-filled pores in the soil and likely play an important role in long-distance microbial interactions. In this review we provide an overview of the most important soluble and volatile classes of secondary metabolites produced by soil bacteria, their ecological roles, and their possible synergistic effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Can videoconferencing affect older people's engagement and perception of their social support in long-term conditions management: a social network analysis from the Telehealth Literacy Project.

    Science.gov (United States)

    Banbury, Annie; Chamberlain, Daniel; Nancarrow, Susan; Dart, Jared; Gray, Len; Parkinson, Lynne

    2017-05-01

    Social support is a key component in managing long-term conditions. As people age in their homes, there is a greater risk of social isolation, which can be ameliorated by informal support networks. This study examined the relationship between changes in social support networks for older people living in a regional area following weekly videoconference groups delivered to the home. Between February and June 2014, we delivered 44 weekly group meetings via videoconference to participants in a regional town in Australia. The meetings provided participants with education and an opportunity to discuss health issues and connect with others in similar circumstances. An uncontrolled, pre-post-test methodology was employed. A social network tool was completed by 45 (87%) participants either pre- or post-intervention, of which 24 (46%) participants completed the tool pre- and post-intervention. In addition, 14 semi-structured interviews and 4 focus groups were conducted. Following the intervention, participants identified increased membership of their social networks, although they did not identify individuals from the weekly videoconference groups. The most important social support networks remained the same pre- and post-intervention namely, health professionals, close family and partners. However, post-intervention participants identified friends and wider family as more important to managing their chronic condition compared to pre-intervention. Participants derived social support, in particular, companionship, emotional and informational support as well as feeling more engaged with life, from the weekly videoconference meetings. Videoconference education groups delivered into the home can provide social support and enhance self-management for older people with chronic conditions. They provide the opportunity to develop a virtual social support network containing new and diverse social connections. © 2016 John Wiley & Sons Ltd.

  20. Differential responses of human dendritic cells to metabolites from the oral/airway microbiome.

    Science.gov (United States)

    Whiteson, K; Agrawal, S; Agrawal, A

    2017-06-01

    Small molecule metabolites that are produced or altered by host-associated microbial communities are emerging as significant immune response modifiers. However, there is a key gap in our knowledge of how oral microbial metabolites affect the immune response. Here, we examined the effects of metabolites from five bacterial strains found commonly in the oral/airway microbial communities of humans. The five strains, each isolated from cystic fibrosis patient sputum, were Pseudomonas aeruginosa FLR01 non-mucoid (P1) and FLR02 mucoid (P2) forms, Streptococcus pneumoniae (Sp), S. salivarius (Ss) and Rothia mucilaginosa (Rm). The effect of bacterial metabolites on dendritic cell (DC) activation, T cell priming and cytokine secretion was determined by exposing DCs to bacterial supernatants and individual metabolites of interest. Supernatants from P1 and P2 induced high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-12 and IL-6 from DCs and primed T cells to secrete interferon (IFN)-γ, IL-22 compared to supernatants from Sp, Ss and Rm. Investigations into the composition of supernatants using gas chromatography-mass spectroscopy (GC-MS) revealed signature metabolites for each of the strains. Supernatants from P1 and P2 contained high levels of putrescine and glucose, while Sp and Ss contained high levels of 2,3-butanediol. The individual metabolites replicated the results of whole supernatants, although the magnitudes of their effects were reduced significantly. Altogether, our data demonstrate for the first time that the signature metabolites produced by different bacteria have different effects on DC functions. The identification of signature metabolites and their effects on the host immune system can provide mechanistic insights into diseases and may also be developed as biomarkers. © 2017 British Society for Immunology.

  1. Characterization of the radiolabeled metabolite of tau PET tracer {sup 18}F-THK5351

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Ryuichi [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Furumoto, Shozo; Tago, Tetsuro; Iwata, Ren; Tashiro, Manabu [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Katsutoshi, Furukawa; Ishiki, Aiko; Tomita, Naoki; Arai, Hiroyuki [Tohoku University, Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Sendai (Japan); Yanai, Kazuhiko [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Okamura, Nobuyuki [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku Medical and Pharmaceutical University, Division of Pharmacology, Faculty of Medicine, Sendai (Japan)

    2016-11-15

    {sup 18}F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of {sup 18}F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties. Venous blood samples were collected from three human subjects after injection of {sup 18}F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples. About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of {sup 18}F-THK5351. The isolated radiometabolite of {sup 18}F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples. These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images. (orig.)

  2. Temperament type specific metabolite profiles of the prefrontal cortex and serum in cattle.

    Directory of Open Access Journals (Sweden)

    Bodo Brand

    Full Text Available In the past decade the number of studies investigating temperament in farm animals has increased greatly because temperament has been shown not only to affect handling but also reproduction, health and economically important production traits. However, molecular pathways underlying temperament and molecular pathways linking temperament to production traits, health and reproduction have yet to be studied in full detail. Here we report the results of metabolite profiling of the prefrontal cortex and serum of cattle with distinct temperament types that were performed to further explore their molecular divergence in the response to the slaughter procedure and to identify new targets for further research of cattle temperament. By performing an untargeted comprehensive metabolite profiling, 627 and 1097 metabolite features comprising 235 and 328 metabolites could be detected in the prefrontal cortex and serum, respectively. In total, 54 prefrontal cortex and 51 serum metabolite features were indicated to have a high relevance in the classification of temperament types by a sparse partial least square discriminant analysis. A clear discrimination between fearful/neophobic-alert, interested-stressed, subdued/uninterested-calm and outgoing/neophilic-alert temperament types could be observed based on the abundance of the identified relevant prefrontal cortex and serum metabolites. Metabolites with high relevance in the classification of temperament types revealed that the main differences between temperament types in the response to the slaughter procedure were related to the abundance of glycerophospholipids, fatty acyls and sterol lipids. Differences in the abundance of metabolites related to C21 steroid metabolism and oxidative stress indicated that the differences in the metabolite profiles of the four extreme temperament types could be the result of a temperament type specific regulation of molecular pathways that are known to be involved in the

  3. Modules of co-regulated metabolites in turmeric (Curcuma longa) rhizome suggest the existence of biosynthetic modules in plant specialized metabolism.

    Science.gov (United States)

    Xie, Zhengzhi; Ma, Xiaoqiang; Gang, David R

    2009-01-01

    Turmeric is an excellent example of a plant that produces large numbers of metabolites from diverse metabolic pathways or networks. It is hypothesized that these metabolic pathways or networks contain biosynthetic modules, which lead to the formation of metabolite modules-groups of metabolites whose production is co-regulated and biosynthetically linked. To test whether such co-regulated metabolite modules do exist in this plant, metabolic profiling analysis was performed on turmeric rhizome samples that were collected from 16 different growth and development treatments, which had significant impacts on the levels of 249 volatile and non-volatile metabolites that were detected. Importantly, one of the many co-regulated metabolite modules that were indeed readily detected in this analysis contained the three major curcuminoids, whereas many other structurally related diarylheptanoids belonged to separate metabolite modules, as did groups of terpenoids. The existence of these co-regulated metabolite modules supported the hypothesis that the 3-methoxyl groups on the aromatic rings of the curcuminoids are formed before the formation of the heptanoid backbone during the biosynthesis of curcumin and also suggested the involvement of multiple polyketide synthases with different substrate selectivities in the formation of the array of diarylheptanoids detected in turmeric. Similar conclusions about terpenoid biosynthesis could also be made. Thus, discovery and analysis of metabolite modules can be a powerful predictive tool in efforts to understand metabolism in plants.

  4. Association between plasma metabolites and gene expression profiles in five porcine endocrine tissues

    Directory of Open Access Journals (Sweden)

    Bassols Anna

    2011-07-01

    Full Text Available Abstract Background Endocrine tissues play a fundamental role in maintaining homeostasis of plasma metabolites such as non-esterified fatty acids and glucose, the levels of which reflect the energy balance or the health status of animals. However, the relationship between the transcriptome of endocrine tissues and plasma metabolites has been poorly studied. Methods We determined the blood levels of 12 plasma metabolites in 27 pigs belonging to five breeds, each breed consisting of both females and males. The transcriptome of five endocrine tissues i.e. hypothalamus, adenohypophysis, thyroid gland, gonads and backfat tissues from 16 out of the 27 pigs was also determined. Sex and breed effects on the 12 plasma metabolites were investigated and associations between genes expressed in the five endocrine tissues and the 12 plasma metabolites measured were analyzed. A probeset was defined as a quantitative trait transcript (QTT when its association with a particular metabolic trait achieved a nominal P value Results A larger than expected number of QTT was found for non-esterified fatty acids and alanine aminotransferase in at least two tissues. The associations were highly tissue-specific. The QTT within the tissues were divided into co-expression network modules enriched for genes in Kyoto Encyclopedia of Genes and Genomes or gene ontology categories that are related to the physiological functions of the corresponding tissues. We also explored a multi-tissue co-expression network using QTT for non-esterified fatty acids from the five tissues and found that a module, enriched in hypothalamus QTT, was positioned at the centre of the entire multi-tissue network. Conclusions These results emphasize the relationships between endocrine tissues and plasma metabolites in terms of gene expression. Highly tissue-specific association patterns suggest that candidate genes or gene pathways should be investigated in the context of specific tissues.

  5. Green tea catechins and their metabolites in human skin before and after exposure to ultraviolet radiation.

    Science.gov (United States)

    Clarke, Kayleigh A; Dew, Tristan P; Watson, Rachel E B; Farrar, Mark D; Osman, Joanne E; Nicolaou, Anna; Rhodes, Lesley E; Williamson, Gary

    2016-01-01

    Dietary flavonoids may protect against sunburn inflammation in skin. Preliminary reports using less complete analysis suggest that certain catechins and their metabolites are found in skin biopsies and blister fluid after consumption of green tea; however, it is not known if they are affected by solar-simulated ultraviolet radiation (UVR) or whether conjugated forms, with consequently altered bioactivity, are present. The present study tested the hypothesis that UVR affects the catechin levels in the skin of healthy volunteers after consumption of green tea and how catechins in the plasma are related to their presence in skin tissue samples. In an open oral intervention study, 11 subjects consumed green tea and vitamin C supplements daily for 3months. Presupplementation and postsupplementation plasma samples, suction blister fluid and skin biopsies were collected; the latter two samples were collected both before and after UVR. A sensitive high-performance liquid chromatography/mass spectrometric assay was used to measure the intact catechin metabolites, conjugates and free forms. Seven green tea catechins and their corresponding metabolites were identified postsupplementation in skin biopsies, 20 in blister fluid and 26 in plasma, with 15 green tea catechin metabolites present in both blister fluid and plasma. The valerolactone, O-methyl-M4-O-sulfate, a gut microbiota metabolite of catechins, was significantly increased 1.6-fold by UVR in blister fluid samples. In conclusion, there were some common catechin metabolites in the plasma and blister fluid, and the concentration was always higher in plasma. The results suggest that green tea catechins and metabolites are bioavailable in skin and provide a novel link between catechin metabolites derived from the skin and gut microbiota. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. LC-MS metabolomic analysis of environmental stressor impacts on the metabolite diversity in Nephthea spp.

    Directory of Open Access Journals (Sweden)

    Hedi Indra Januar

    2012-01-01

    Full Text Available Context: The soft coral Nephthea spp. is a source of terpenoid class that potentially has pharmaceutical properties. However, metabolite diversity and cytotoxic activity of this species are varied among coral reefs from various sites. Aim: To analyze the water quality in Nephthea spp. environment as a possible factor causing a difference in its metabolite diversity. Settings and Design: Nephthea spp. from seven sites were taken in October 2010 at the Alor District of Marine Protected Area, Indonesia. Materials and Methods: Water quality assessment was analyzed in situ and indexed by Canadian Council of Ministry Environment-Water Quality Index (CCME-WQI method. Meanwhile, metabolite diversity was analyzed by a LC-MS metabolomic method, using C18 reversed phase and gradient water-acetonitrile system. Statistical Analysis Used: Spearman′s rho and regression analysis were applied to correlate the water quality index to ecological index (richness, diversity, and evenness from LC-MS results. Results: The water quality index had a significant positive correlation and strong linear regression determinant to the total metabolite (R 2 = 0.704, particularly to semipolar metabolite richness (R 2 = 0.809, the area of terpenoid class in the organism. Conclusion: It can be concluded that water quality may serve as a major factor that affects the amount of richness in Nephthea spp. metabolites. When the water quality is lower, as environment stresses increases, it may affect the metabolite richness within direct disrupt of metabolite biosynthesis or indirect ecological means. Terpenoids are known as a soft coral antipredator (coral fishes, the amount of which depends on the water quality.

  7. Biosynthesis of human diazepam and clonazepam metabolites.

    Science.gov (United States)

    de Paula, Núbia C; Araujo Cordeiro, Kelly C F; de Melo Souza, Paula L; Nogueira, Diogo F; da Silva e Sousa, Diego B; Costa, Maísa B; Noël, François; de Oliveira, Valéria

    2015-03-01

    A screening of fungal and microbial strains allowed to select the best microorganisms to produce in high yields some of the human metabolites of two benzodiazepine drugs, diazepam and clonazepam, in order to study new pharmacological activities and for chemical standard proposes. Among the microorganisms tested, Cunninghamella echinulata ATCC 9244 and Rhizopus arrhizus ATCC 11145 strains, were the most active producers of the mains metabolites of diazepam which included demethylated, hydroxylated derivatives. Beauveria bassiana ATCC 7159 and Chaetomium indicum LCP 984200 produced the 7 amino-clonazepam metabolite and a product of acid hydrolysis of this benzodiazepine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Plant products and secondary metabolites with acaricide activity against ticks.

    Science.gov (United States)

    Rosado-Aguilar, J A; Arjona-Cambranes, K; Torres-Acosta, J F J; Rodríguez-Vivas, R I; Bolio-González, M E; Ortega-Pacheco, A; Alzina-López, A; Gutiérrez-Ruiz, E J; Gutiérrez-Blanco, E; Aguilar-Caballero, A J

    2017-04-30

    The present review documents the results of studies evaluating the acaricidal activity of different plant products and secondary metabolites against ticks that are resistant and susceptible to conventional acaricides. Studies published from 1998 to 2016 were included. The acaricidal activity of plant extracts, essential oils and secondary compounds from plants have been evaluated using bioassays with ticks in the larval and adult stages. There is variable effectiveness according to the species of plant and the concentrations used, with observed mortalities ranging from 5 to 100% against the Rhipicephalus (Boophilus), Amblyomma, Dermacentor, Hyalomma, and Argas genera. A number of plants have been reported to cause high mortalities and/or affect the reproductive capacity of ticks in the adult phase. In the majority of these trials, the main species of plants evaluated correspond to the families Lamiaceae, Fabaceae, Asteraceae, Piperaceae, Verbenaceae, and Poaceae. Different secondary metabolites such as thymol, carvacrol, 1,8-cineol and n-hexanal, have been found to be primarily responsible for the acaricidal activity of different essential oils against different species of ticks, while nicotine, dibenzyldisulfide and dibenzyltrisulfide have been evaluated for plant extracts. Only thymol, carvacrol and 1,8-cineol have been evaluated for acaricidal activity under in vivo conditions. The information in the present review allows the conclusion that the secondary metabolites contained in plant products could be used as an alternative for the control of ticks that are susceptible or resistant to commercial acaricides. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The radioimmunological determination of glibenclamide and its metabolites in serum

    International Nuclear Information System (INIS)

    Glogner, P.; Heni, N.; Nissen, L.

    1977-01-01

    This report describes a sensitive and specific radio-immunological method for determining serum levels of the 1-(p-[2- (5-chloro-2-methoxybenzamido) -ethyl]-benzenesulfonyl) -3-cyclohexylurea (clibenclamide) and its metabolites. The antigen was prepared by coupling a metabolite to bovine serum albumin. Antibodies could be demonstrated in serum after immunisation of rabbits. The separation of free and antibody-bound glibenclamide was achieved by a dextran-charcoal suspension. Presence of serum did not influence the binding characteristics. The limit of detection was 20 ng/ml. The affinity of the metabolites differed only slightly from that of glibenclamide. The presence of related drugs from the sulfonylurea series such as tolbutamide, glibornuride and the sulfonamide sulfamethoxazol did not affect the determination. Only closely related substances showed a variable degree of affinity towards antibodies. As an example of the possible application of this method, the serum concentration of glibenclamide was determined over a period of 8 h after single i.v. injection to a volunteer. The data are in close accordance with the results of authors using radioactive glibenclamide. (orig.) [de

  10. Metabolomics in epidemiology: from metabolite concentrations to integrative reaction networks.

    Science.gov (United States)

    Fearnley, Liam G; Inouye, Michael

    2016-10-01

    Metabolomics is becoming feasible for population-scale studies of human disease. In this review, we survey epidemiological studies that leverage metabolomics and multi-omics to gain insight into disease mechanisms. We outline key practical, technological and analytical limitations while also highlighting recent successes in integrating these data. The use of multi-omics to infer reaction rates is discussed as a potential future direction for metabolomics research, as a means of identifying biomarkers as well as inferring causality. Furthermore, we highlight established analysis approaches as well as simulation-based methods currently used in single- and multi-cell levels in systems biology. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

  11. Networks of networks – An introduction

    International Nuclear Information System (INIS)

    Kenett, Dror Y.; Perc, Matjaž; Boccaletti, Stefano

    2015-01-01

    Graphical abstract: Interdependent network reciprocity. Only those blue cooperative domains that are initially present on both networks survive. Abstract: This is an introduction to the special issue titled “Networks of networks” that is in the making at Chaos, Solitons & Fractals. Recent research and reviews attest to the fact that networks of networks are the next frontier in network science [1–7]. Not only are interactions limited and thus inadequately described by well-mixed models, it is also a fact that the networks that should be an integral part of such models are often interconnected, thus making the processes that are unfolding on them interdependent. From the World economy and transportation systems to social media, it is clear that processes taking place in one network might significantly affect what is happening in many other networks. Within an interdependent system, each type of interaction has a certain relevance and meaning, so that treating all the links identically inevitably leads to information loss. Networks of networks, interdependent networks, or multilayer networks are therefore a much better and realistic description of such systems, and this Special Issue is devoted to their structure, dynamics and evolution, as well as to the study of emergent properties in multi-layered systems in general. Topics of interest include but are not limited to the spread of epidemics and information, percolation, diffusion, synchronization, collective behavior, and evolutionary games on networks of networks. Interdisciplinary work on all aspects of networks of networks, regardless of background and motivation, is very welcome.

  12. Coping with shrub secondary metabolites by ruminants

    Science.gov (United States)

    Rangelands throughout the world contain varying but often substantial proportions of shrubs. Shrubs are generally heavily chemically defended, and herbivores must either contend with their plant secondary metabolites (PSM) or avoid a significant component of the available forage. Browsing ruminants ...

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

    African Journals Online (AJOL)

    SERVER

    2007-05-16

    May 16, 2007 ... immobilise microbial cells or enzymes, depending on the bioreactor's application. Operational ... perspective. Key words: Membrane bioreactor, gradostat reactor, secondary metabolite production, biofilm, wastewater treatment. INTRODUCTION ... suitable to immobilize P. chrysosporium biofilms in MGR.

  14. Metabolite production by species of Stemphylium.

    Science.gov (United States)

    Olsen, Kresten Jon Kromphardt; Rossman, Amy; Andersen, Birgitte

    Morphology and phylogeny have been used to distinguish members of the plant pathogenic fungal genus Stemphylium. A third method for distinguishing species of fungi is by chemotaxonomy. The main goal of the present study was to investigate the chemical potential of Stemphylium via HPLC-UV-MS analysis, while also exploring the potential of chemotaxonomy as a robust identification method for Stemphylium. Several species were found to have species-specific metabolites, while other species were distinguishable by a broader metabolic profile rather than specific metabolites. Many previously described metabolites were found to be important for distinguishing species, while some unknown metabolites were also determined to have important roles in distinguishing species of Stemphylium. This study is the first of its kind to investigate the chemical potential of Stemphylium across the whole genus. Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  15. How does language distance between L1 and L2 affect the L2 brain network? An fMRI study of Korean-Chinese-English trilinguals.

    Science.gov (United States)

    Kim, Say Young; Qi, Ting; Feng, Xiaoxia; Ding, Guosheng; Liu, Li; Cao, Fan

    2016-04-01

    The present study tested the hypothesis that language distance between first language (L1) and second language (L2) influences the assimilation and accommodation pattern in Korean-Chinese-English trilinguals. The distance between English and Korean is smaller than that between Chinese and Korean in terms of orthographic transparency, because both English and Korean are alphabetic, whereas Chinese is logographic. During fMRI, Korean trilingual participants performed a visual rhyming judgment task in three languages (Korean: KK, Chinese: KC, English: KE). Two L1 control groups were native Chinese and English speakers performing the task in their native languages (CC and EE, respectively). The general pattern of brain activation of KC was more similar to that of CC than KK, suggesting accommodation. Higher accuracy in KC was associated with decreased activation in regions of the KK network, suggesting reduced assimilation. In contrast, the brain activation of KE was more similar to that of KK than EE, suggesting assimilation. Higher accuracy in KE was associated with decreased activation in regions of the EE network, suggesting reduced accommodation. Finally, an ROI analysis on the left middle frontal gyrus revealed greater activation for KC than for KE, suggesting its selective involvement in the L2 with more arbitrary mapping between orthography and phonology (i.e., Chinese). Taken together, the brain network involved in L2 reading is similar to the L1 network when L2 and L1 are similar in orthographic transparency, while significant accommodation is expected when L2 is more opaque than L1. Copyright © 2015. Published by Elsevier Inc.

  16. Biologically Active Secondary Metabolites from the Fungi.

    Science.gov (United States)

    Bills, Gerald F; Gloer, James B

    2016-11-01

    Many Fungi have a well-developed secondary metabolism. The diversity of fungal species and the diversification of biosynthetic gene clusters underscores a nearly limitless potential for metabolic variation and an untapped resource for drug discovery and synthetic biology. Much of the ecological success of the filamentous fungi in colonizing the planet is owed to their ability to deploy their secondary metabolites in concert with their penetrative and absorptive mode of life. Fungal secondary metabolites exhibit biological activities that have been developed into life-saving medicines and agrochemicals. Toxic metabolites, known as mycotoxins, contaminate human and livestock food and indoor environments. Secondary metabolites are determinants of fungal diseases of humans, animals, and plants. Secondary metabolites exhibit a staggering variation in chemical structures and biological activities, yet their biosynthetic pathways share a number of key characteristics. The genes encoding cooperative steps of a biosynthetic pathway tend to be located contiguously on the chromosome in coregulated gene clusters. Advances in genome sequencing, computational tools, and analytical chemistry are enabling the rapid connection of gene clusters with their metabolic products. At least three fungal drug precursors, penicillin K and V, mycophenolic acid, and pleuromutilin, have been produced by synthetic reconstruction and expression of respective gene clusters in heterologous hosts. This review summarizes general aspects of fungal secondary metabolism and recent developments in our understanding of how and why fungi make secondary metabolites, how these molecules are produced, and how their biosynthetic genes are distributed across the Fungi. The breadth of fungal secondary metabolite diversity is highlighted by recent information on the biosynthesis of important fungus-derived metabolites that have contributed to human health and agriculture and that have negatively impacted crops

  17. 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.

  18. New metabolites of hongdenafil, homosildenafil and hydroxyhomosildenafil.

    Science.gov (United States)

    Yeo, Miseon; Park, Yujin; Lee, Heesang; Choe, Sanggil; Baek, Seung-Hoon; Kim, Hye Kyung; Pyo, Jae Sung

    2018-02-05

    Recently, illegal sildenafil analogues have emerged, causing serious social issues. In spite of the importance of sildenafil analogues, their metabolic profiles or clinical effects have not been reported yet. In this study, new metabolites of illegal sildenafil analogues such as hongdenafil, homosildenafil, and hydroxyhomosildenafil were determined using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS) and tandem mass spectrometry (LC-Q-TOF-MS/MS). To prepare metabolic samples, in vitro and in vivo studies were performed. For in vivo metabolites analysis, urine and feces samples of rats treated with sildenafil analogues were analyzed. For in vitro metabolites analysis, human liver microsomes incubated with sildenafil analogues were extracted and analyzed. All metabolites were characterized by LC-Q-TOF-MS and LC-Q-TOF-MS/MS. As a result, five, six, and seven metabolites were determined in hongdenafil, homosildenafil, and hydroxyhomosildenafil treated samples, respectively. These results could be applied to forensic science and other analytical fields. Moreover, these newly identified metabolites could be used as fundamental data to determine the side effect and toxicity of illegal sildenafil analogues. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Metabolites of cannabidiol identified in human urine.

    Science.gov (United States)

    Harvey, D J; Mechoulam, R

    1990-03-01

    1. Urine from a dystonic patient treated with cannabidiol (CBD) was examined by g.l.c.-mass spectrometry for CBD metabolites. Metabolites were identified as their trimethylsilyl (TMS), [2H9]TMS, and methyl ester/TMS derivatives and as the TMS derivatives of the product of lithium aluminium deuteride reduction. 2. Thirty-three metabolites were identified in addition to unmetabolized CBD, and a further four metabolites were partially characterized. 3. The major metabolic route was hydroxylation and oxidation at C-7 followed by further hydroxylation in the pentyl and propenyl groups to give 1"-, 2"-, 3"-, 4"- and 10-hydroxy derivatives of CBD-7-oic acid. Other metabolites, mainly acids, were formed by beta-oxidation and related biotransformations from the pentyl side-chain and these were also hydroxylated at C-6 or C-7. The major oxidized metabolite was CBD-7-oic acid containing a hydroxyethyl side-chain. 4. Two 8,9-dihydroxy compounds, presumably derived from the corresponding epoxide were identified. 5. Also present were several cyclized cannabinoids including delta-6- and delta-1-tetrahydrocannabinol and cannabinol. 6. This is the first metabolic study of CBD in humans; most observed metabolic routes were typical of those found for CBD and related cannabinoids in other species.

  20. Development and In silico Evaluation of Large-Scale Metabolite Identification Methods using Functional Group Detection for Metabolomics

    Directory of Open Access Journals (Sweden)

    Joshua M Mitchell

    2014-07-01

    Full Text Available Large-scale identification of metabolites is key to elucidating and modeling metabolism at the systems level. Advances in metabolomics technologies, particularly ultra-high resolution mass spectrometry enable comprehensive and rapid analysis of metabolites. However, a significant barrier to meaningful data interpretation is the identification of a wide range of metabolites including unknowns and the determination of their role(s in various metabolic networks. Chemoselective (CS probes to tag metabolite functional groups combined with high mass accuracy provide additional structural constraints for metabolite identification and quantification. We have developed a novel algorithm, Chemically Aware Substructure Search (CASS that efficiently detects functional groups within existing metabolite databases, allowing for combined molecular formula and functional group (from CS tagging queries to aid in metabolite identification without a priori knowledge. Analysis of the isomeric compounds in both Human Metabolome Database (HMDB and KEGG Ligand demonstrated a high percentage of isomeric molecular formulae (43% and 28% respectively, indicating the necessity for techniques such as CS-tagging. Furthermore, these two databases have only moderate overlap in molecular formulae. Thus, it is prudent to use multiple databases in metabolite assignment, since each major metabolite database represents different portions of metabolism within the biosphere. In silico analysis of various CS-tagging strategies under different conditions for adduct formation demonstrate that combined FT-MS derived molecular formulae and CS-tagging can uniquely identify up to 71% of KEGG and 37% of the combined KEGG/HMDB database versus 41% and 17% respectively without adduct formation. This difference between database isomer disambiguation highlights the strength of CS-tagging for non-lipid metabolite identification. However, unique identification of complex lipids still needs

  1. Cyproheptadine metabolites inhibit proinsulin and insulin biosynthesis and insulin release in isolated rat pancreatic islets

    International Nuclear Information System (INIS)

    Chow, S.A.; Falany, J.L.; Fischer, L.J.

    1989-01-01

    The contribution of drug metabolites to cyproheptadine (CPH)-induced alterations in endocrine pancreatic beta-cells was investigated by examining the inhibitory activity of CPH and its biotransformation products, desmethylcyproheptadine (DMCPH), CPH-epoxide and DMCPH-epoxide, on hormone biosynthesis and secretion in pancreatic islets isolated from 50-day-old rats. Measurement of (pro)insulin (proinsulin and insulin) synthesis using incorporation of 3H-leucine showed that DMCPH-epoxide, DMCPH and CPH-epoxide were 22, 10 and 4 times, respectively, more potent than CPH in inhibiting hormone synthesis. The biosynthesis of (pro)insulin was also inhibited by CPH and DMCPH-epoxide in islets isolated from 21-day-old rat fetuses. The inhibitory action of CPH and its metabolites was apparently specific for (pro)insulin, and the synthesis of other islet proteins was not affected. Other experiments showed the metabolites of CPH were active in inhibiting glucose-stimulated insulin secretion but were less potent than the parent drug in producing this effect. CPH and its structurally related metabolites, therefore, have differential inhibitory activities on insulin synthesis and release. The observation that CPH metabolites have higher potency than CPH to inhibit (pro)insulin synthesis, when considered with published reports on the disposition of the drug in rats, indicate that CPH metabolites, particularly DMCPH-epoxide, are primarily responsible for the insulin depletion observed when the parent compound is given to fetal and adult animals

  2. 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.

  3. 40 CFR 159.179 - Metabolites, degradates, contaminants, and impurities.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Metabolites, degradates, contaminants.../Benefit Information § 159.179 Metabolites, degradates, contaminants, and impurities. (a) Metabolites and degradates. Information which shows the existence of any metabolite or degradate of a pesticide product must...

  4. Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes.

    Science.gov (United States)

    Isherwood, Cheryl M; Van der Veen, Daan R; Johnston, Jonathan D; Skene, Debra J

    2017-12-01

    Metabolic profiling of individuals with type 2 diabetes mellitus (T2DM) has previously been limited to single-time-point samples, ignoring time-of-day variation. Here, we tested our hypothesis that body mass and T2DM affect daily rhythmicity and concentrations of circulating metabolites across a 24-h day in 3 age-matched, male groups-lean, overweight/obese (OW/OB), and OW/OB with T2DM-in controlled laboratory conditions, which were not confounded by large meals. By using targeted liquid chromatography/mass spectrometry metabolomics, we quantified 130 plasma metabolites every 2 h over 24 h, and we show that average metabolite concentrations were significantly altered by increased body mass (90 of 130) and T2DM (56 of 130). Thirty-eight percent of metabolites exhibited daily rhythms in at least 1 study group, and where a metabolite was rhythmic in >1 group, its peak time was comparable. The optimal time of day was assessed to provide discriminating biomarkers. This differed between metabolite classes and study groups-for example, phospholipids showed maximal difference at 5:00 AM (lean vs. OW/OB) and at 5:00 PM (OW/OB vs. T2DM). Metabolites that were identified with both robust 24-h rhythms and significant concentration differences between study groups emphasize the importance of controlling the time of day for diagnosis and biomarker discovery, offering a significant improvement over current single sampling.-Isherwood, C. M., Van der Veen, D. R., Johnston, J. D., Skene, D. J. Twenty-four-hour rhythmicity of circulating metabolites: effect of body mass and type 2 diabetes. © The Author(s).

  5. Analysis of the Factors Affecting Men's Attitudes Toward Cosmetic Surgery: Body Image, Media Exposure, Social Network Use, Masculine Gender Role Stress and Religious Attitudes.

    Science.gov (United States)

    Abbas, Ozan Luay; Karadavut, Ufuk

    2017-12-01

    Cosmetic surgery is no longer just for females. More men are opting for cosmetic procedures, with marked increases seen in both minimally invasive and surgical options over the last decade. Compared to females, relatively little work has specifically focused on factors predicting males' attitudes toward cosmetic surgery. Therefore, we evaluated a number of variables that may predict some facet of men's attitudes toward cosmetic surgery according to evidence reported in the literature METHODS: A total of 151 male patients who applied for a surgical or minimally invasive cosmetic surgery procedure (patient group) and 151 healthy male volunteers who do not desire any type of cosmetic procedure (control group) were asked to fill out questionnaires about measures of body image, media exposure (television and magazine), social network site use, masculine gender role stress and religious attitudes. Our findings showed that lower ratings of body image satisfaction, increased time spent watching television, more frequent social network site use and higher degrees of masculine gender role stress were all significant predictors of attitudes toward cosmetic surgery among males. The current study confirmed the importance of body image dissatisfaction as a predictor of the choice to undergo cosmetic procedure. More importantly, a new predictor of cosmetic procedure attitudes was identified, namely masculine gender role stress. Finally, we demonstrated the effects television exposure and social network site use in promoting acceptance of surgical and nonsurgical routes to appearance enhancement. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  6. Correlated measurement error hampers association network inference

    NARCIS (Netherlands)

    Kaduk, M.; Hoefsloot, H.C.J.; Vis, D.J.; Reijmers, T.; Greef, J. van der; Smilde, A.K.; Hendriks, M.M.W.B.

    2014-01-01

    Modern chromatography-based metabolomics measurements generate large amounts of data in the form of abundances of metabolites. An increasingly popular way of representing and analyzing such data is by means of association networks. Ideally, such a network can be interpreted in terms of the

  7. Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling.

    Science.gov (United States)

    Vijayendran, Chandran; Barsch, Aiko; Friehs, Karl; Niehaus, Karsten; Becker, Anke; Flaschel, Erwin

    2008-04-10

    Evolutionary changes that are due to different environmental conditions can be examined based on the various molecular aspects that constitute a cell, namely transcript, protein, or metabolite abundance. We analyzed changes in transcript and metabolite abundance in evolved and ancestor strains in three different evolutionary conditions - excess nutrient adaptation, prolonged stationary phase adaptation, and adaptation because of environmental shift - in two different strains of bacterium Escherichia coli K-12 (MG1655 and DH10B). Metabolite profiling of 84 identified metabolites revealed that most of the metabolites involved in the tricarboxylic acid cycle and nucleotide metabolism were altered in both of the excess nutrient evolved lines. Gene expression profiling using whole genome microarray with 4,288 open reading frames revealed over-representation of the transport functional category in all evolved lines. Excess nutrient adapted lines were found to exhibit greater degrees of positive correlation, indicating parallelism between ancestor and evolved lines, when compared with prolonged stationary phase adapted lines. Gene-metabolite correlation network analysis revealed over-representation of membrane-associated functional categories. Proteome analysis revealed the major role played by outer membrane proteins in adaptive evolution. GltB, LamB and YaeT proteins in excess nutrient lines, and FepA, CirA, OmpC and OmpA in prolonged stationary phase lines were found to be differentially over-expressed. In summary, we report the vital involvement of energy metabolism and membrane-associated functional categories in all of the evolutionary conditions examined in this study within the context of transcript, outer membrane protein, and metabolite levels. These initial data obtained may help to enhance our understanding of the evolutionary process from a systems biology perspective.

  8. BIOACTIVE METABOLITES FROM TRICHODERMA HARZIANUM ...

    African Journals Online (AJOL)

    a

    ABSTRACT. The tea plant, Camellia sinensis (L.) O. Kuntze is an important crop in the agriculturally based economy of Kenya. Many diseases affect the tea plant but the most prevalent is armillaria root rot caused by the fungus Armillaria mellea. Compounds from the fermentation of. Trichoderma species in different media ...

  9. Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats.

    Science.gov (United States)

    van der Vegt, Bea J; Lieuwes, Natasja; Cremers, Thomas I F H; de Boer, Sietse F; Koolhaas, Jaap M

    2003-09-01

    In humans and other primates low cerebrospinal fluid (CSF) levels of the major serotonin (5-HT) metabolite 5-hydroxyindoleacetic acid (5-HIAA) have been correlated to high aggressiveness. This finding forms the basis of the 5-HT deficiency hypothesis of aggression. Surprisingly, this correlation has not been confirmed in rodents so far, while manipulation studies aimed to investigate the link between 5-HT and aggressive behaviour are mostly carried out in rodents. In this study the relation between aggression and CSF monoamine and metabolite concentrations was investigated in male Wildtype Groningen rats. In sharp contrast to the hypothesis and our expectation, a clear positive correlation was found between the individual level of trait-like aggressiveness and CSF concentrations of 5-HT, 5-HIAA, norepinephrine (NE), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC). Shortly after the acute display of aggressive behaviour (as a state-like phenomenon), decreased 5-HT levels and an increase in 5-HIAA/5-HT ratio and NE concentrations were found. Surprisingly, pharmacological challenges known to influence 5-HT transmission and aggressive behaviour did not affect CSF 5-HT and 5-HIAA concentrations, only the NE level was increased. Lesioning 5-HT terminals by 5,7-dihydroxytryptamine (5,7-DHT) administration caused a decrease in CSF 5-HT and 5-HIAA, but without affecting aggressive behaviour. The observed positive correlation between CSF 5-HIAA and trait aggressiveness makes it questionable whether a direct extrapolation of neurobiological mechanisms of aggression between species is justified. Interpretation of CSF metabolite levels in terms of activity of neural substrates requires a far more detailed knowledge of the dynamics and kinetics of a neurotransmitter after its release.

  10. Physiological and biochemical effect of neem and other Meliaceae plants secondary metabolites against Lepidopteran insects

    Directory of Open Access Journals (Sweden)

    Senthil-Nathan eSengottayan

    2013-12-01

    Full Text Available This review described the physiological and biochemical effects of various secondary metabolites from Meliaceae against major Lepidopteran insect pest including, Noctuidae and Pyralidae. The biochemical effect of major Meliaceae secondary metabolites were discussed more in this review. Several enzymes based on food materials have critical roles in nutritional indices (food utilization of the insect pest population. Several research work has been referred and the effect of Meliaceae secondary metabolites on feeding parameters of insects by demonstrating food consumption, approximate digestibility of consumed food, efficiency of converting the ingested food to body substance, efficiency of converting digested food to body substance and consumption index was reviewed in detail. Further how the digestive enzymes including a-Amylases, α and β- glucosidases (EC 3.2.1.1, lipases (EC 3.1.1 Proteases, serine, cysteine, and aspartic proteinases affected by the Meliaceae secondary metabolites was reviewed. Further effect of Meliaceae secondary metabolites on detoxifying enzymes have been found to react against botanical insecticides including general esterases (EST, glutathione S-transferase (GST and phosphatases was reviewed. Alkaline phosphatase (ALP, E.C.3.1.3.1 and acid phosphatase (ACP, E.C.3.1.3.2 are hydrolytic enzymes, which hydrolyze phosphomonoesters under alkaline or acid conditions, respectively. These enzymes were affected by the secondary metabolites treatment. The detailed mechanism of action was further explained in this review. Acethylcholine esterase (AChE is a key enzyme that terminates nerve impulses by catalyzing the hydrolysis of neurotransmitter, acetylcholine, in the nervous system of various organisms. How the AChE activity was altered by the Meliaceae secondary metabolites reviewed in detail.

  11. Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort.

    Science.gov (United States)

    Org, Elin; Blum, Yuna; Kasela, Silva; Mehrabian, Margarete; Kuusisto, Johanna; Kangas, Antti J; Soininen, Pasi; Wang, Zeneng; Ala-Korpela, Mika; Hazen, Stanley L; Laakso, Markku; Lusis, Aldons J

    2017-04-13

    The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study. We investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite associated with coronary artery disease and stroke. We further investigate the gut microbiota composition and microbiota-metabolite relationships in subjects with different body mass index and individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state. Our study identifies novel relationships between the composition of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host-gut microbiota relationships.

  12. Identity and Professional Networking.

    Science.gov (United States)

    Raj, Medha; Fast, Nathanael J; Fisher, Oliver

    2017-06-01

    Despite evidence that large professional networks afford a host of financial and professional benefits, people vary in how motivated they are to build such networks. To help explain this variance, the present article moves beyond a rational self-interest account to examine the possibility that identity shapes individuals' intentions to network. Study 1 established a positive association between viewing professional networking as identity-congruent and the tendency to prioritize strengthening and expanding one's professional network. Study 2 revealed that manipulating the salience of the self affects networking intentions, but only among those high in networking identity-congruence. Study 3 further established causality by experimentally manipulating identity-congruence to increase networking intentions. Study 4 examined whether identity or self-interest is a better predictor of networking intentions, providing support for the former. These findings indicate that identity influences the networks people develop. Implications for research on the self, identity-based motivation, and professional networking are discussed.

  13. The effects of GA and ABA treatments on metabolite profile of germinating barley.

    Science.gov (United States)

    Huang, Yuqing; Cai, Shengguan; Ye, Lingzhen; Hu, Hongliang; Li, Chengdao; Zhang, Guoping

    2016-02-01

    Sugar degradation during grain germination is important for malt quality. In malting industry, gibberellin (GA) is frequently used for improvement of malting quality. In this study, the changes of metabolite profiles and starch-degrading enzymes during grain germination, and as affected by GA and abscisic acid (ABA) were investigated using two wild barley accessions XZ72 and XZ95. Totally fifty-two metabolites with known structures were detected and the change of metabolite during germination was time- and genotype dependent. Sugars and amino acids were the most dramatically changed compounds. Addition of GA enhanced the activities of starch-degrading enzymes, and increased most metabolites, especially sugars and amino acids, whereas ABA had the opposite effect. The effect varied with the barley accessions. The current study is the first attempt in investigating the effect of hormones on metabolite profiles in germinating barley grain, being helpful for identifying the factors affecting barley germination or malt quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. An in silico platform for the design of heterologous pathways in nonnative metabolite production

    Directory of Open Access Journals (Sweden)

    Chatsurachai Sunisa

    2012-05-01

    Full Text Available Abstract Background Microorganisms are used as cell factories to produce valuable compounds in pharmaceuticals, biofuels, and other industrial processes. Incorporating heterologous metabolic pathways into well-characterized hosts is a major strategy for obtaining these target metabolites and improving productivity. However, selecting appropriate heterologous metabolic pathways for a host microorganism remains difficult owing to the complexity of metabolic networks. Hence, metabolic network design could benefit greatly from the availability of an in silico platform for heterologous pathway searching. Results We developed an algorithm for finding feasible heterologous pathways by which nonnative target metabolites are produced by host microorganisms, using Escherichia coli, Corynebacterium glutamicum, and Saccharomyces cerevisiae as templates. Using this algorithm, we screened heterologous pathways for the production of all possible nonnative target metabolites contained within databases. We then assessed the feasibility of the target productions using flux balance analysis, by which we could identify target metabolites associated with maximum cellular growth rate. Conclusions This in silico platform, designed for targeted searching of heterologous metabolic reactions, provides essential information for cell factory improvement.

  15. The transporter-mediated cellular uptake of pharmaceutical drugs is based on their metabolite-likeness and not on their bulk biophysical properties: Towards a systems pharmacology

    Directory of Open Access Journals (Sweden)

    Douglas B. Kell

    2015-12-01

    Full Text Available Several recent developments are brought together: (i the new availability of a consensus, curated human metabolic network reconstruction (Recon2, approximately a third of whose steps are represented by transporters, (ii the recognition that most successful (marketed drugs, as well as natural products, bear significant similarities to the metabolites in Recon2, (iii the recognition that to get into and out of cells such drugs hitchhike on the transporters that are part of normal intermediary metabolism, and the consequent recognition that for intact biomembrane Phospholipid Bilayer diffusion Is Negligible (PBIN, and (iv the consequent recognition that we need to exploit this and to use more phenotypic assays to understand how drugs affect cells and organisms. I show in particular that lipophilicity is a very poor predictor of drug permeability, and that we need to (and can bring together our knowledge of both pharmacology and systems biology modelling into a new systems pharmacology.

  16. Interplay between gut microbiota, its metabolites and human metabolism: Dissecting cause from consequence

    NARCIS (Netherlands)

    Hartstra, A. V.; Nieuwdorp, M.; Herrema, H.

    2016-01-01

    Background: Alterations in gut microbiota composition and bacterial metabolites have been increasingly recognized to affect host metabolism and are at the basis of metabolic diseases such as obesity and type 2 diabetes (DM2). Intestinal enteroendocrine cells (EEC's) sense gut luminal content and

  17. Metabolite profiling of microfluidic cell culture conditions for droplet based screening

    DEFF Research Database (Denmark)

    Björk, Sara M.; Sjoström, Staffan L.; Svahn, Helene Andersson

    2015-01-01

    , such as directed evolution of yeast, as cell metabolic state directly affects production yields from cell factories. Here, we analyze glucose, pyruvate, ethanol, and glycerol, central metabolites in yeast glucose dissimilation to establish culture formats for screening of respiring as well as fermenting yeast...

  18. Plant metabolites and nutritional quality of vegetables.

    Science.gov (United States)

    Hounsome, N; Hounsome, B; Tomos, D; Edwards-Jones, G

    2008-05-01

    Vegetables are an important part of the human diet and a major source of biologically active substances such as vitamins, dietary fiber, antioxidants, and cholesterol-lowering compounds. Despite a large amount of information on this topic, the nutritional quality of vegetables has not been defined. Historically, the value of many plant nutrients and health-promoting compounds was discovered by trial and error. By the turn of the century, the application of chromatography, mass spectrometry, infrared spectrometry, and nuclear magnetic resonance allowed quantitative and qualitative measurements of a large number of plant metabolites. Approximately 50000 metabolites have been elucidated in plants, and it is predicted that the final number will exceed 200000. Most of them have unknown function. Metabolites such as carbohydrates, organic and amino acids, vitamins, hormones, flavonoids, phenolics, and glucosinolates are essential for plant growth, development, stress adaptation, and defense. Besides the importance for the plant itself, such metabolites determine the nutritional quality of food, color, taste, smell, antioxidative, anticarcinogenic, antihypertension, anti-inflammatory, antimicrobial, immunostimulating, and cholesterol-lowering properties. This review is focused on major plant metabolites that characterize the nutritional quality of vegetables, and methods of their analysis.

  19. Detecting Beer Intake by Unique Metabolite Patterns.

    Science.gov (United States)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian; Bech, Lene; Lund, Erik; Dragsted, Lars Ove

    2016-12-02

    Evaluation of the 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 nonalcoholic 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 of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

  20. Secondary metabolites in fungus-plant interactions

    Science.gov (United States)

    Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István

    2015-01-01

    Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed. PMID:26300892

  1. Simvastatin (SV) metabolites in mouse tissues

    International Nuclear Information System (INIS)

    Duncan, C.A.; Vickers, S.

    1990-01-01

    SV, a semisynthetic analog of lovastatin, is hydrolyzed in vivo to its hydroxy acid (SVA), a potent inhibitor of HMG CoA reductase (HR). Thus SV lowers plasma cholesterol. SV is a substrate for mixed function oxidases whereas SVA undergoes lactonization and β-oxidation. Male CD-1 mice were dosed orally with a combination of ( 14 C)SV and ( 3 H)SVA at 25 mg/kg of each, bled and killed at 0.5, 2 and 4 hours. Labeled SV, SVA, 6'exomethylene SV (I), 6'CH 2 OH-SV (II), 6'COOH-SV (III) and a β-oxidized metabolite (IV) were assayed in liver, bile, kidneys, testes and plasma by RIDA. Levels of potential and active HR inhibitors in liver were 10 to 40 fold higher than in other tissues. II and III, in which the configuration at 6' is inverted, may be 2 metabolites of I. Metabolites I-III are inhibitors of HR in their hydroxy acid forms. Qualitatively ( 14 C)SV and ( 3 H)SVA were metabolized similarly (consistent with their proposed interconversion). However 3 H-SVA, I-III (including hydroxy acid forms) achieved higher concentrations than corresponding 14 C compounds (except in gall bladder bile). Major radioactive metabolites in liver were II-IV (including hydroxy acid forms). These metabolites have also been reported in rat tissues. In bile a large fraction of either label was unidentified polar metabolites. The presence of IV indicated that mice (like rats) are not good models for SV metabolism in man

  2. 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 compounds...... of proguanil and cycloguanil appeared after seven hours. Trough concentrations (pre-dose in the morning) of proguanil and cycloguanil were about 200 and 100 nmol/l, respectively. Mean half-life of proguanil was estimated to approximately 20 h. The active metabolite cycloguanil constituted 30% of the total...

  3. Animal bioavailability of defined xenobiotic lignin metabolites

    International Nuclear Information System (INIS)

    Sandermann, H. Jr.; Arjmand, M.; Gennity, I.; Winkler, R.; Struble, C.B.; Aschbacher, P.W.

    1990-01-01

    Lignin has been recognized as a major component of bound pesticide residues in plants and is thought to be undigestible in animals. Two defined ring-U- 14 C-labeled chloroaniline/lignin metabolites have now been fed to rats, where a release of ∼66% of the bound xenobiotic occurred in the form of simple chloroaniline derivatives. The observed high degree of bioavailability indicates that bound pesticidal residues may possess ecotoxicological significance. In parallel studies, the white-rot fungus Phanerochaete chrysosporium was more efficient, and a soil system was much less efficient, in the degradation of the [ring-U- 14 C]chloroaniline/lignin metabolites

  4. Detecting beer intake by unique metabolite patterns

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  5. METABOLITE CHARACTERIZATION IN SERUM SAMPLES FROM ...

    African Journals Online (AJOL)

    Preferred Customer

    and 13C chemical shifts is given in Table 1. Table 1. Resonance assignments of most significant metabolites of serum control healthy samples. S. No Metabolite. Group. 1H shift 13C shift Multiplicities. 1 Fatty acids. CH3. 0.90. 19.7 t. 2 Isoleucine. δCH3. 0.94. 13.8 t. 3 Leucine. δCH3. 0.95. 23.5 d. 4 Leucine. δCH3. 0.96. 24.7.

  6. Metabolite production by species of Stemphylium

    DEFF Research Database (Denmark)

    Olsen, Kresten Jon Kromphardt; Rossman, Amy; Andersen, Birgitte

    2018-01-01

    Morphology and phylogeny has been used to distinguish members of the plant pathogenic fungal genus Stemphylium. A third method for distinguishing species is by chemotaxonomy. The main goal of the present study was to investigate the chemical potential of Stemphylium via HPLC-UV-MS analysis, while...... also exploring the potential of chemotaxonomy as a robust identification method for Stemphylium. Several species were found to have species-specific metabolites, while other species were distinguishable by a broader metabolic profile rather than specific metabolites. Many previously described...

  7. compMS2Miner: An Automatable Metabolite Identification, Visualization, and Data-Sharing R Package for High-Resolution LC-MS Data Sets.

    Science.gov (United States)

    Edmands, William M B; Petrick, Lauren; Barupal, Dinesh K; Scalbert, Augustin; Wilson, Mark J; Wickliffe, Jeffrey K; Rappaport, Stephen M

    2017-04-04

    A long-standing challenge of untargeted metabolomic profiling by ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) is efficient transition from unknown mass spectral features to confident metabolite annotations. The compMS 2 Miner (Comprehensive MS 2 Miner) package was developed in the R language to facilitate rapid, comprehensive feature annotation using a peak-picker-output and MS 2 data files as inputs. The number of MS 2 spectra that can be collected during a metabolomic profiling experiment far outweigh the amount of time required for pain-staking manual interpretation; therefore, a degree of software workflow autonomy is required for broad-scale metabolite annotation. CompMS 2 Miner integrates many useful tools in a single workflow for metabolite annotation and also provides a means to overview the MS 2 data with a Web application GUI compMS 2 Explorer (Comprehensive MS 2 Explorer) that also facilitates data-sharing and transparency. The automatable compMS 2 Miner workflow consists of the following steps: (i) matching unknown MS 1 features to precursor MS 2 scans, (ii) filtration of spectral noise (dynamic noise filter), (iii) generation of composite mass spectra by multiple similar spectrum signal summation and redundant/contaminant spectra removal, (iv) interpretation of possible fragment ion substructure using an internal database, (v) annotation of unknowns with chemical and spectral databases with prediction of mammalian biotransformation metabolites, wrapper functions for in silico fragmentation software, nearest neighbor chemical similarity scoring, random forest based retention time prediction, text-mining based false positive removal/true positive ranking, chemical taxonomic prediction and differential evolution based global annotation score optimization, and (vi) network graph visualizations, data curation, and sharing are made possible via the compMS 2 Explorer application. Metabolite identities and comments

  8. Novel urinary metabolite signature for diagnosing postpartum depression

    Directory of Open Access Journals (Sweden)

    Lin L

    2017-05-01

    Full Text Available Lin Lin, Xiao-mei Chen, Rong-hua Liu Department of Obstetrics and Gynecology, Linyi People’s Hospital, Shandong, People’s Republic of China Background: Postpartum depression (PPD could affect ~10% of women and impair the quality of mother–infant interactions. Currently, there are no objective methods to diagnose PPD. Therefore, this study was conducted to identify potential biomarkers for diagnosing PPD.Materials and methods: Morning urine samples of PPD subjects, postpartum women without depression (PPWD and healthy controls (HCs were collected. The gas chromatography-mass spectroscopy (GC-MS-based urinary metabolomic approach was performed to characterize the urinary metabolic profiling. The orthogonal partial least-squares-discriminant analysis (OPLS-DA was used to identify the differential metabolites. The logistic regression analysis and Bayesian information criterion rule were further used to identify the potential biomarker panel. The receiver operating characteristic curve analysis was conducted to evaluate the diagnostic performance of the identified potential biomarker panel.Results: Totally, 73 PPD subjects, 73 PPWD and 74 HCs were included, and 68 metabolites were identified using GC-MS. The OPLS-DA model showed that there were 22 differential metabolites (14 upregulated and 8 downregulated responsible for separating PPD subjects from HCs and PPWD. Meanwhile, a panel of five potential biomarkers – formate, succinate, 1-methylhistidine, a-glucose and dimethylamine – was identified. This panel could effectively distinguish PPD subjects from HCs and PPWD with an area under the curve (AUC curve of 0.948 in the training set and 0.944 in the testing set.Conclusion: These results demonstrated that the potential biomarker panel could aid in the future development of an objective diagnostic method for PPD. Keywords: postpartum depression, gas chromatography-mass spectroscopy, biomarker, metabolomics

  9. Can Diet Influence Our Health by Altering Intestinal Microbiota-Derived Fecal Metabolites?

    Science.gov (United States)

    Lyu, Qiang

    2018-01-01

    ABSTRACT The human gastrointestinal tract harbors a diverse, highly mutualistic microbial flora which could produce a myriad of specialized metabolites. These specialized metabolites are the chemical cellphones that gut microflora use to communicate with their human host and could potentially be used to cure diseases. Chemical compounds in diet also shape the gut flora. In order to understand which and how the gut microbe-derived specialized metabolites affect human health, the “gut microbiome-metabolomic-human health axis” is thus proposed. In our laboratory, a strategy combining genomic, chemical, phenotypical analyses has been implemented to mine the treasures of bioactive molecules found in our gut and stool. We believe that the cutting edge metabolomics will bridge microbiology and human health.

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

    African Journals Online (AJOL)

    Aghomotsegin

    2015-10-28

    Oct 28, 2015 ... The aims of this study were the analysis of the secondary metabolites and evaluation of the antibacterial and antifungal activity of Alternaria alternata. Twenty six bioactive compounds were identified in methanolic extract of Alternaria alternata. The identification of bioactive chemical compounds is based on ...

  11. Anticancer and antibacterial secondary metabolites from the ...

    African Journals Online (AJOL)

    Background: The emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents. Objectives: This study aims to evaluate the anticancer and antibacterial activities of secondary metabolites from Penicillium sp., ...

  12. Chemical composition, secondary metabolites, in vitro gas ...

    African Journals Online (AJOL)

    Chemical composition, secondary metabolites, in vitro gas production characteristics and acceptability study of some forage for ruminant feeding in South-Western Nigeria. ... Chemical composition and qualitative analysis of saponins, phenol and steroids of the plants were determined. In vitro gas production (IVGP) was ...

  13. Homeorhetic hormones, metabolites and accelerated growth

    African Journals Online (AJOL)

    Homeorhetic hormones, metabolites and accelerated growth. A.L. Marais and J.G. van der Walt. Rumen Biochemistry, Animal and Dairy Science Research Institute,. Irene 1675, Republic of South Africa. Six newly weaned karakul ewes, three with fat tails and three without tails, were used to investigate the metabolic and hor ...

  14. Organic metabolites produced by Vibrio parahaemolyticus strain ...

    African Journals Online (AJOL)

    Identification and action of several antibacterial metabolites produced by a fish pathogen Vibrio parahaemolyticus strain An3 from marine ecosystem of Goa has been demonstrated. Antibacterial activity of the crude cell extract of the test bacterium has been evaluated against indicator pathogenic bacterial strains such as ...

  15. Secondary metabolites from Scorzonera latifolia roots

    Czech Academy of Sciences Publication Activity Database

    Acikara, O. B.; Šmejkal, K.; Cvačka, Josef; Buděšínský, Miloš; Dračínský, Martin; Saltan, G.

    2015-01-01

    Roč. 81, č. 16 (2015), PM167 ISSN 0032-0943. [GA 2015. International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research /63./. 23.08.2015-27.08.2015, Budapest] Institutional support: RVO:61388963 Keywords : medical plant * metabolites * Asteraceae Subject RIV: CB - Analytical Chemistry, Separation

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

    African Journals Online (AJOL)

    The aims of this study were the analysis of the secondary metabolites and evaluation of the antibacterial and antifungal activity of Alternaria alternata. Twenty six bioactive compounds were identified in methanolic extract of Alternaria alternata. The identification of bioactive chemical compounds is based on the peak area, ...

  17. Blood metabolite concentrations and postpartum resumption of ...

    African Journals Online (AJOL)

    Fred

    2014-01-29

    Jan 29, 2014 ... Abstract. An experiment was conducted to investigate the effect of concentrations of certain blood nutrient- sensitive metabolites and the resumption of postpartum ovarian cyclicity in 16 Sanga cows (mean BCS 5). Blood samples were taken from cows from weeks 1 to 13 (90 days) postpartum, processed ...

  18. Diuron metabolites act as endocrine disruptors and alter aggressive behavior in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Boscolo, Camila Nomura Pereira; Pereira, Thiago Scremin Boscolo; Batalhão, Isabela Gertrudes; Dourado, Priscila Leocadia Rosa; Schlenk, Daniel; de Almeida, Eduardo Alves

    2018-01-01

    Diuron and its biodegradation metabolites were recently reported to cause alterations in plasma steroid hormone concentrations with subsequent impacts on reproductive development in fish. Since steroid hormone biosynthesis is regulated through neurotransmission of the central nervous system (CNS), studies were conducted to determine whether neurotransmitters that control hormone biosynthesis could be affected after diuron and diuron metabolites treatment. As the same neurotransmitters and steroid hormones regulate behavioral outcomes, aggression was also evaluated in male Nile tilapia (Oreochromis niloticus). Male tilapias were exposed for 10 days to waterborne diuron and the metabolites 3,4-dichloroaniline (DCA), 3,4-dichlorophenyl-N-methylurea (DCPMU), at nominal concentrations of 100 ng L -1 . In contrast to Diuron, DCA and DCPMU significantly diminished plasma testosterone concentrations (39.4% and 36.8%, respectively) and reduced dopamine levels in the brain (47.1% and 44.2%, respectively). In addition, concentrations of the stress steroid, cortisol were increased after DCA (71.0%) and DCPMU (57.8-%) exposure. A significant decrease in aggressive behavior was also observed in animals treated with the metabolites DCA (50.9%) and DCPMU (68.8%). These results indicate that biotransformation of diuron to active metabolites alter signaling pathways of the CNS which may impact androgen and the stress response as well as behavior necessary for social dominance, growth, and reproduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Induction of phenolic metabolites and physiological changes in chamomile plants in relation to nitrogen nutrition.

    Science.gov (United States)

    Kováčik, Jozef; Klejdus, Bořivoj

    2014-01-01

    Alternative tools, such as the manipulation of mineral nutrition, may affect secondary metabolite production and thus the nutritional value of food/medicinal plants. We studied the impact of nitrogen (N) nutrition (nitrate/NO3(-) or ammonium/NH4(+) nitrogen) and subsequent nitrogen deficit on phenolic metabolites and physiology in Matricaria chamomilla plants. NH4(+)-fed plants revealed a strong induction of selected phenolic metabolites but, at the same time, growth, Fv/Fm, tissue water content and soluble protein depletion occurred in comparison with NO3(-)-fed ones. On the other hand, NO3(-)-deficient plants also revealed an increase in phenolic metabolites but growth depression was not observed after the given exposure period. Free amino acids were more accumulated in NH4(+)-fed shoots (strong increase in arginine and proline mainly), while the pattern of roots' accumulation was independent of N form. Among phenolic acids, NH4(+) strongly elevated mainly the accumulation of chlorogenic acid. Within flavonoids, flavonols decreased while flavones strongly increased in response to N deficiency. Coumarin-related metabolites revealed a similar increase in herniarin glucosidic precursor in response to N deficiency, while herniarin was more accumulated in NO3(-)- and umbelliferone in NH4(+)-cultured plants. These data indicate a negative impact of NH4(+) as the only source of N on physiology, but also a higher stimulation of some valuable phenols. Nitrogen-induced changes in comparison with other food/crop plants are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. A sex-specific metabolite identified in a marine invertebrate utilizing phosphorus-31 nuclear magnetic resonance.

    Directory of Open Access Journals (Sweden)

    Robert A Kleps

    Full Text Available Hormone level differences are generally accepted as the primary cause for sexual dimorphism in animal and human development. Levels of low molecular weight metabolites also differ between men and women in circulating amino acids, lipids and carbohydrates and within brain tissue. While investigating the metabolism of blue crab tissues using Phosphorus-31 Nuclear Magnetic Resonance, we discovered that only the male blue crab (Callinectes sapidus contained a phosphorus compound with a chemical shift well separated from the expected phosphate compounds. Spectra obtained from male gills were readily differentiated from female gill spectra. Analysis from six years of data from male and female crabs documented that the sex-specificity of this metabolite was normal for this species. Microscopic analysis of male and female gills found no differences in their gill anatomy or the presence of parasites or bacteria that might produce this phosphorus compound. Analysis of a rare gynandromorph blue crab (laterally, half male and half female proved that this sex-specificity was an intrinsic biochemical process and was not caused by any variations in the diet or habitat of male versus female crabs. The existence of a sex-specific metabolite is a previously unrecognized, but potentially significant biochemical phenomenon. An entire enzyme system has been synthesized and activated only in one sex. Unless blue crabs are a unique species, sex-specific metabolites are likely to be present in other animals. Would the presence or absence of a sex-specific metabolite affect an animal's development, anatomy and biochemistry?

  1. HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation.

    Directory of Open Access Journals (Sweden)

    Jeffrey B Carroll

    Full Text Available The HTT CAG expansion mutation causes Huntington's Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue, using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219 in the striatum to 12% (25/212 in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219 of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224 in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and

  2. Medicinal plants: a source of anti-parasitic secondary metabolites.

    Science.gov (United States)

    Wink, Michael

    2012-10-31

    This review summarizes human infections caused by endoparasites, including protozoa, nematodes, trematodes, and cestodes, which affect more than 30% of the human population, and medicinal plants of potential use in their treatment. Because vaccinations do not work in most instances and the parasites have sometimes become resistant to the available synthetic therapeutics, it is important to search for alternative sources of anti-parasitic drugs. Plants produce a high diversity of secondary metabolites with interesting biological activities, such as cytotoxic, anti-parasitic and anti-microbial properties. These drugs often interfere with central targets in parasites, such as DNA (intercalation, alkylation), membrane integrity, microtubules and neuronal signal transduction. Plant extracts and isolated secondary metabolites which can inhibit protozoan parasites, such as Plasmodium, Trypanosoma, Leishmania, Trichomonas and intestinal worms are discussed. The identified plants and compounds offer a chance to develop new drugs against parasitic diseases. Most of them need to be tested in more detail, especially in animal models and if successful, in clinical trials.

  3. An update on organohalogen metabolites produced by basidiomycetes

    NARCIS (Netherlands)

    Field, J.A.; Wijnberg, J.B.P.A.

    2003-01-01

    Basidiomycetes are an ecologically important group of higher fungi known for their widespread capacity to produce organohalogen metabolites. To date, 100 different organohalogen metabolites (mostly chlorinated) have been identified from strains in 70 genera of Basidiomycetes. This manuscript

  4. 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.

  5. Rationalization and prediction of in vivo metabolite exposures: The role of metabolite kinetics, clearance predictions and in vitro parameters

    Science.gov (United States)

    Lutz, Justin D.; Fujioka, Yasushi; Isoherranen, Nina

    2010-01-01

    Importance of the field Due to growing concerns over toxic or active metabolites, significant efforts have been focused on qualitative identification of potential in vivo metabolites from in vitro data. However, limited tools are available to quantitatively predict their human exposures. Areas covered in this review Theory of clearance predictions and metabolite kinetics is reviewed together with supporting experimental data. In vitro and in vivo data of known circulating metabolites and their parent drugs was collected and the predictions of in vivo exposures of the metabolites were evaluated. What the reader will gain The theory and data reviewed will be useful in early identification of human metabolites that will circulate at significant levels in vivo and help in designing in vivo studies that focus on characterization of metabolites. It will also assist in rationalization of metabolite-to-parent ratios used as markers of specific enzyme activity. Take home message The relative importance of a metabolite in comparison to the parent compound as well as other metabolites in vivo can only be predicted using the metabolites in vitro formation and elimination clearances, and the in vivo disposition of a metabolite can only be rationalized when the elimination pathways of that metabolite are known. PMID:20557268

  6. Epidemic Network Failures in Optical Transport Networks

    DEFF Research Database (Denmark)

    Ruepp, Sarah Renée; Katsikas, Dimitrios; Fagertun, Anna Manolova

    2013-01-01

    This paper presents a failure propagation model for transport networks which are affected by epidemic failures. The network is controlled using the GMPLS protocol suite. The Susceptible Infected Disabled (SID) epidemic model is investigated and new signaling functionality of GMPLS to support...

  7. Affective monitoring: A generic mechanism for affect elicitation

    Directory of Open Access Journals (Sweden)

    Hans ePhaf

    2012-03-01

    Full Text Available In this paper we sketch a new framework for affect elicitation, which is based on previous evolutionary and connectionist modeling and experimental work from our group. Affective monitoring is considered a local match-mismatch process within a module of the neural network. Negative affect is raised instantly by mismatches, incongruency, disfluency, novelty, incoherence, and dissonance, whereas positive affect follows from matches, congruency, fluency, familiarity, coherence, and resonance, at least when an initial mismatch can be solved quickly. Affective monitoring is considered an evolutionary-early conflict and change detection process operating at the same level as, for instance, attentional selection. It runs in parallel and imparts affective flavour to emotional behavior systems, which involve evolutionary-prepared stimuli and action tendencies related to for instance defensive, exploratory, attachment, or appetitive behavior. Positive affect is represented in the networks by high-frequency oscillations, presumably in the gamma band. Negative affect corresponds to more incoherent lower-frequency oscillations, presumably in the theta band. For affect to become conscious, large-scale synchronization of the oscillations over the network and the construction of emotional experiences are required. These constructions involve perceptions of bodily states and action tendencies, but also appraisals as well as efforts to regulate the emotion. Importantly, affective monitoring accompanies every kind of information processing, but conscious emotions, which result from the later integration of affect in a cognitive context, are much rarer events.

  8. Complex networks: Dynamics and security

    Indian Academy of Sciences (India)

    cusing on how dynamics may affect network security under attacks. In particular, we review two related ... portation network etc., are an essential part of a modern society. The security of such a network under ... communication (or information flow) within the network, is changed under random or intentional attacks [7–10].

  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

  10. Antibacterial secondary metabolites from the cave sponge Xestospongia sp.

    Science.gov (United States)

    Ankisetty, Sridevi; Slattery, Marc

    2012-05-01

    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.

  11. Antibacterial Secondary Metabolites from the Cave Sponge Xestospongia sp

    OpenAIRE

    Ankisetty, Sridevi; Slattery, Marc

    2012-01-01

    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.

  12. Production of fungal and bacterial growth modulating secondary metabolites is widespread among mycorrhiza-associated streptomycetes

    Directory of Open Access Journals (Sweden)

    Schrey Silvia D

    2012-08-01

    Full Text Available Abstract Background Studies on mycorrhiza associated bacteria suggest that bacterial-fungal interactions play important roles during mycorrhiza formation and affect plant health. We surveyed Streptomyces Actinobacteria, known as antibiotic producers and antagonists of fungi, from Norway spruce mycorrhizas with predominantly Piloderma species as the fungal partner. Results Fifteen Streptomyces isolates exhibited substantial variation in inhibition of tested mycorrhizal and plant pathogenic fungi (Amanita muscaria, Fusarium oxysporum, Hebeloma cylindrosporum, Heterobasidion abietinum, Heterobasidion annosum, Laccaria bicolor, Piloderma croceum. The growth of the mycorrhiza-forming fungus Laccaria bicolor was stimulated by some of the streptomycetes, and Piloderma croceum was only moderately affected. Bacteria responded to the streptomycetes differently than the fungi. For instance the strain Streptomyces sp. AcM11, which inhibited most tested fungi, was less inhibitory to bacteria than other tested streptomycetes. The determined patterns of Streptomyces-microbe interactions were associated with distinct patterns of secondary metabolite production. Notably, potentially novel metabolites were produced by strains that were less antagonistic to fungi. Most of the identified metabolites were antibiotics (e.g. cycloheximide, actiphenol and siderophores (e.g. ferulic acid, desferroxiamines. Plant disease resistance was activated by a single streptomycete strain only. Conclusions Mycorrhiza associated streptomycetes appear to have an important role in inhibiting the growth of fungi and bacteria. Additionally, our study indicates that the Streptomyces strains, which are not general antagonists of fungi, may produce still un-described metabolites.

  13. Factors affecting growth and pigmentation of Penicillium caseifulvum

    DEFF Research Database (Denmark)

    Suhr, Karin Isabel; Haasum, I.; Steenstrup, L.D.

    2002-01-01

    and the trace metals Fe, Cu, Zn, Mn on yellow color formation, metabolite production and mold growth. Multivariate statistical analysis showed that the most important factor affecting yellow color formation was pH. The most pronounced formation of yellow color, supported by highest amount of colored metabolites......, appeared at low pH (pH 4). Mold growth was not correlated to the yellow color formation. Salt concentration was the most important factor affecting mold growth and length of lag phase. Production of secondary metabolites was strongly influenced by both pH and salt concentration. The screening results were......Color formation, metabolite production and growth of Penicillium caseifulvum were studied in order to elucidate factors contributing to. yellow discoloration of Blue Cheese caused by the mold. A screening experiment was set up to study the effect of pH, concentration of salt (NaCl), P, K, N, S, Mg...

  14. Factors affecting growth and pigmentation of Penicillium caseifulvum

    DEFF Research Database (Denmark)

    Suhr, Karin Isabel; Haasum, I.; Steenstrup, L.D.

    2002-01-01

    Color formation, metabolite production and growth of Penicillium caseifulvum were studied in order to elucidate factors contributing to. yellow discoloration of Blue Cheese caused by the mold. A screening experiment was set up to study the effect of pH, concentration of salt (NaCl), P, K, N, S, Mg...... and the trace metals Fe, Cu, Zn, Mn on yellow color formation, metabolite production and mold growth. Multivariate statistical analysis showed that the most important factor affecting yellow color formation was pH. The most pronounced formation of yellow color, supported by highest amount of colored metabolites......, appeared at low pH (pH 4). Mold growth was not correlated to the yellow color formation. Salt concentration was the most important factor affecting mold growth and length of lag phase. Production of secondary metabolites was strongly influenced by both pH and salt concentration. The screening results were...

  15. Molluscicidal metabolites from an assemblage of Palmyra Atoll cyanobacteria.

    Science.gov (United States)

    Pereira, Alban R; Etzbach, Lena; Engene, Niclas; Müller, Rolf; Gerwick, William H

    2011-05-27

    Molluscicides can play an important role in the control of schistosomiasis because snails of the genus Biomphalaria act as intermediate hosts for the parasite. Schistosomiasis is one of 13 neglected tropical diseases with high morbidity and mortality that collectively affect one billion of the world's poorest population, mainly in developing countries. Thiopalmyrone (1) and palmyrrolinone (2), metabolites isolated from extracts of a Palmyra Atoll environmental assemblage of two cyanobacteria, cf. Oscillatoria and Hormoscilla spp., represent new and potent molluscicidal chemotypes against Biomphalaria glabrata (LC50=8.3 and 6.0 μM, respectively). A slight enhancement in molluscicidal effect (LC50=5.0 μM) was observed when these two natural products were utilized as an equimolar binary mixture.

  16. Identification of drug metabolites in human plasma or serum integrating metabolite prediction, LC-HRMS and untargeted data processing

    NARCIS (Netherlands)

    Jacobs, P.L.; Ridder, L.; Ruijken, M.; Rosing, H.; Jager, N.G.L.; Beijnen, J.H.; Bas, R.R.; Dongen, W.D. van

    2013-01-01

    Background: Comprehensive identification of human drug metabolites in first-in-man studies is crucial to avoid delays in later stages of drug development. We developed an efficient workflow for systematic identification of human metabolites in plasma or serum that combines metabolite prediction,

  17. 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.

  18. 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.

  19. 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...... 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...... to Ulocladium atrum, while most species produced infectopyrones and derivatives of altertoxin I. None of the 52 Ulocladium strains produced alternariols, tenuazonic acid, altersolanols or macrosporin, which are common in species of Alternaria. (c) 2008 Elsevier B.V. All rights reserved...

  20. Vitamin D metabolites in human milk

    International Nuclear Information System (INIS)

    Weisman, Y.; Bawnik, J.C.; Eisenberg, Z.; Spirer, Z.

    1982-01-01

    The concentrations of unconjugated 25-OHD, 24, 25(OH)2D, and 1,25(OH)2D were measured in human milk by competitive protein-binding radioassays following successive preparative Sephadex LH-20 chromatography and HPLC. The mean (+/- SE) concentration of 25-OHD was 0.37 +/- 0.03 ng/ml, of 24,25(OH)2D was 24.8 +/- 1.9 pg/ml, and of 1,25(OH)2D was 2.2 +/-0.1 pg/ml. The concentration of 25-OHD3 in milk as determined by HPLC and UV detection at 254 nm was 0.27 +/- 0.08 ng/ml. The milk concentrations of vitamin D metabolites did not correlate with the maternal serum 25-OHD levels. The total amounts of unconjugated vitamin D metabolites correspond to the known low bioassayable vitamin D antirachitic activity in human milk

  1. 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.

  2. Biologically Active Metabolites Synthesized by Microalgae

    Science.gov (United States)

    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

  3. Role of metabolites of cyclophosphamide in cardiotoxicity

    OpenAIRE

    Kurauchi, Koichiro; Nishikawa, Takuro; Miyahara, Emiko; Okamoto, Yasuhiro; Kawano, Yoshifumi

    2017-01-01

    Background The dose-limiting toxic effect of cyclophosphamide (CY) is cardiotoxicity. The pathogenesis of myocardial damage is poorly understood, and there is no established means of prevention. In previous studies, we suggested that for CY-induced cardiotoxicity, whereas acrolein is the key toxic metabolite, carboxyethylphosphoramide mustard (CEPM) is protective. We sought to verify that acrolein is the main cause of cardiotoxicity and to investigate whether aldehyde dehydrogenase (ALDH), wh...

  4. Research for the lichen Usnea barbata metabolites.

    Science.gov (United States)

    Bazarnova, Yulia; Politaeva, Natalia; Lyskova, Nadegda

    2018-03-29

    This work presents investigations of biologically active metabolites of Usnea barbata lichen. Extraction conditions for usnic acid and other biologically active phytocomponents using various solvent systems were chosen. Modern analytical techniques were used to study composition of the obtained extracts; usnic acid and phenolic compound contents were estimated. Antioxidant activity and antimicrobial properties of lichen dry extract against bacteria Bacillus subtilis and Pseudomonas fluorescens were studied.

  5. A compendium of inborn errors of metabolism mapped onto the human metabolic network.

    Science.gov (United States)

    Sahoo, Swagatika; Franzson, Leifur; Jonsson, Jon J; Thiele, Ines

    2012-10-01

    Inborn errors of metabolism (IEMs) are hereditary metabolic defects, which are encountered in almost all major metabolic pathways occurring in man. Many IEMs are screened for in neonates through metabolomic analysis of dried blood spot samples. To enable the mapping of these metabolomic data onto the published human metabolic reconstruction, we added missing reactions and pathways involved in acylcarnitine (AC) and fatty acid oxidation (FAO) metabolism. Using literary data, we reconstructed an AC/FAO module consisting of 352 reactions and 139 metabolites. When this module was combined with the human metabolic reconstruction, the synthesis of 39 acylcarnitines and 22 amino acids, which are routinely measured, was captured and 235 distinct IEMs could be mapped. We collected phenotypic and clinical features for each IEM enabling comprehensive classification. We found that carbohydrate, amino acid, and lipid metabolism were most affected by the IEMs, while the brain was the most commonly affected organ. Furthermore, we analyzed the IEMs in the context of metabolic network topology to gain insight into common features between metabolically connected IEMs. While many known examples were identified, we discovered some surprising IEM pairs that shared reactions as well as clinical features but not necessarily causal genes. Moreover, we could also re-confirm that acetyl-CoA acts as a central metabolite. This network based analysis leads to further insight of hot spots in human metabolism with respect to IEMs. The presented comprehensive knowledge base of IEMs will provide a valuable tool in studying metabolic changes involved in inherited metabolic diseases.

  6. Transfer of metabolites across the peroxisomal membrane.

    Science.gov (United States)

    Antonenkov, Vasily D; Hiltunen, J Kalervo

    2012-09-01

    Peroxisomes perform a large variety of metabolic functions that require a constant flow of metabolites across the membranes of these organelles. Over the last few years it has become clear that the transport machinery of the peroxisomal membrane is a unique biological entity since it includes nonselective channels conducting small solutes side by side with transporters for 'bulky' solutes such as ATP. Electrophysiological experiments revealed several channel-forming activities in preparations of plant, mammalian, and yeast peroxisomes and in glycosomes of Trypanosoma brucei. The properties of the first discovered peroxisomal membrane channel - mammalian Pxmp2 protein - have also been characterized. The channels are apparently involved in the formation of peroxisomal shuttle systems and in the transmembrane transfer of various water-soluble metabolites including products of peroxisomal β-oxidation. These products are processed by a large set of peroxisomal enzymes including carnitine acyltransferases, enzymes involved in the synthesis of ketone bodies, thioesterases, and others. This review discusses recent data pertaining to solute permeability and metabolite transport systems in peroxisomal membranes and also addresses mechanisms responsible for the transfer of ATP and cofactors such as an ATP transporter and nudix hydrolases. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. 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.

  8. Nontargeted Identification of Reactive Metabolite Protein Adducts.

    Science.gov (United States)

    Leeming, Michael G; Donald, William A; O'Hair, Richard A J

    2017-06-06

    Metabolic bioactivation of many different chemicals results in the formation of highly reactive compounds (chemically reactive metabolites, CRMs) that can lead to toxicity via binding to macromolecular targets (e.g., proteins or DNA). There is a need to develop robust, rapid, and nontargeted analytical techniques to determine the identity of the protein targets of CRMs and their sites of modification. Here, we introduce a nontargeted methodology capable of determining both the identity of a CRM formed from an administered compound as well as the protein targets modified by the reactive metabolite in a single experiment without prior information. Acetaminophen (N-acetyl-p-aminophenol, APAP) and 13 C 6 -APAP were incubated with rat liver microsomes, which are known to bioactivate APAP to the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI). Global tryptic digestion followed by liquid chromatographic/mass spectrometric (LC/MS) analysis was used to locate "twin" ion peaks of peptides adducted by NAPQI and for shotgun proteomics via tandem mass spectrometry (MS/MS). By the development of blended data analytics software called Xenophile, the identity of the amino acid residue that was adducted can be established, which eliminates the need for specific parametrization of protein database search algorithms. This combination of experimental design and data analysis software allows the identity of a CRM, the protein target, and the amino acid residues that are modified to be rapidly established directly from experimental data. Xenophile is freely available from https://github.com/mgleeming/Xenophile .

  9. The WEIZMASS spectral library for high-confidence metabolite identification.

    Science.gov (United States)

    Shahaf, Nir; Rogachev, Ilana; Heinig, Uwe; Meir, Sagit; Malitsky, Sergey; Battat, Maor; Wyner, Hilary; Zheng, Shuning; Wehrens, Ron; Aharoni, Asaph

    2016-08-30

    Annotation of metabolites is an essential, yet problematic, aspect of mass spectrometry (MS)-based metabolomics assays. The current repertoire of definitive annotations of metabolite spectra in public MS databases is limited and suffers from lack of chemical and taxonomic diversity. Furthermore, the heterogeneity of the data prevents the development of universally applicable metabolite annotation tools. Here we present a combined experimental and computational platform to advance this key issue in metabolomics. WEIZMASS is a unique reference metabolite spectral library developed from high-resolution MS data acquired from a structurally diverse set of 3,540 plant metabolites. We also present MatchWeiz, a multi-module strategy using a probabilistic approach to match library and experimental data. This strategy allows efficient and high-confidence identification of dozens of metabolites in model and exotic plants, including metabolites not previously reported in plants or found in few plant species to date.

  10. Learning Networks, Networked Learning

    NARCIS (Netherlands)

    Sloep, Peter; Berlanga, Adriana

    2010-01-01

    Sloep, P. B., & Berlanga, A. J. (2011). Learning Networks, Networked Learning [Redes de Aprendizaje, Aprendizaje en Red]. Comunicar, XIX(37), 55-63. Retrieved from http://dx.doi.org/10.3916/C37-2011-02-05

  11. Wireless mesh networks

    CERN Document Server

    Held, Gilbert

    2005-01-01

    Wireless mesh networking is a new technology that has the potential to revolutionize how we access the Internet and communicate with co-workers and friends. Wireless Mesh Networks examines the concept and explores its advantages over existing technologies. This book explores existing and future applications, and examines how some of the networking protocols operate.The text offers a detailed analysis of the significant problems affecting wireless mesh networking, including network scale issues, security, and radio frequency interference, and suggests actual and potential solutions for each pro

  12. Network Characterization Service (NCS)

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Guojun [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Yang, George [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Crowley, Brian [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Agarwal, Deborah [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2001-06-06

    Distributed applications require information to effectively utilize the network. Some of the information they require is the current and maximum bandwidth, current and minimum latency, bottlenecks, burst frequency, and congestion extent. This type of information allows applications to determine parameters like optimal TCP buffer size. In this paper, we present a cooperative information-gathering tool called the network characterization service (NCS). NCS runs in user space and is used to acquire network information. Its protocol is designed for scalable and distributed deployment, similar to DNS. Its algorithms provide efficient, speedy and accurate detection of bottlenecks, especially dynamic bottlenecks. On current and future networks, dynamic bottlenecks do and will affect network performance dramatically.

  13. Grapevine Plasticity in Response to an Altered Microclimate: Sauvignon Blanc Modulates Specific Metabolites in Response to Increased Berry Exposure.

    Science.gov (United States)

    Young, Philip R; Eyeghe-Bickong, Hans A; du Plessis, Kari; Alexandersson, Erik; Jacobson, Dan A; Coetzee, Zelmari; Deloire, Alain; Vivier, Melané A

    2016-03-01

    In this study, the metabolic and physiological impacts of an altered microclimate on quality-associated primary and secondary metabolites in grape (Vitis vinifera) 'Sauvignon Blanc' berries was determined in a high-altitude vineyard. The leaf and lateral shoot removal in the bunch zones altered the microclimate by increasing the exposure of the berries. The physical parameters (berry diameter and weight), primary metabolites (sugars and organic acids), as well as bunch temperature and leaf water potential were predominantly not affected by the treatment. The increased exposure led to higher levels of specific carotenoids and volatile terpenoids in the exposed berries, with earlier berry stages reacting distinctly from the later developmental stages. Plastic/nonplastic metabolite responses could be further classified to identify metabolites that were developmentally controlled and/or responded to the treatment in a predictable fashion (assessed over two consecutive vintages). The study demonstrates that grapevine berries exhibit a degree of plasticity within their secondary metabolites and respond physiologically to the increased exposure by increasing metabolites with potential antioxidant activity. Taken together, the data provide evidence that the underlying physiological responses relate to the maintenance of stress pathways by modulating antioxidant molecules in the berries. © 2016 American Society of Plant Biologists. All Rights Reserved.

  14. Grapevine Plasticity in Response to an Altered Microclimate: Sauvignon Blanc Modulates Specific Metabolites in Response to Increased Berry Exposure1

    Science.gov (United States)

    du Plessis, Kari; Jacobson, Dan A.

    2016-01-01

    In this study, the metabolic and physiological impacts of an altered microclimate on quality-associated primary and secondary metabolites in grape (Vitis vinifera) ‘Sauvignon Blanc’ berries was determined in a high-altitude vineyard. The leaf and lateral shoot removal in the bunch zones altered the microclimate by increasing the exposure of the berries. The physical parameters (berry diameter and weight), primary metabolites (sugars and organic acids), as well as bunch temperature and leaf water potential were predominantly not affected by the treatment. The increased exposure led to higher levels of specific carotenoids and volatile terpenoids in the exposed berries, with earlier berry stages reacting distinctly from the later developmental stages. Plastic/nonplastic metabolite responses could be further classified to identify metabolites that were developmentally controlled and/or responded to the treatment in a predictable fashion (assessed over two consecutive vintages). The study demonstrates that grapevine berries exhibit a degree of plasticity within their secondary metabolites and respond physiologically to the increased exposure by increasing metabolites with potential antioxidant activity. Taken together, the data provide evidence that the underlying physiological responses relate to the maintenance of stress pathways by modulating antioxidant molecules in the berries. PMID:26628747

  15. Influence of the RelA Activity on E. coli Metabolism by Metabolite Profiling of Glucose-Limited Chemostat Cultures

    Directory of Open Access Journals (Sweden)

    Sónia Carneiro

    2012-10-01

    Full Text Available Metabolite profiling of E. coli W3110 and the isogenic DrelA mutant cells was used to characterize the RelA-dependent stringent control of metabolism under different growth conditions. Metabolic profiles were obtained by gas chromatography–mass spectrometry (GC-MS analysis and revealed significant differences between E. coli strains grown at different conditions. Major differences between the two strains were assessed in the levels of amino acids and fatty acids and their precursor metabolites, especially when growing at the lower dilution rates, demonstrating differences in their metabolic behavior. Despite the fatty acid biosynthesis being the most affected due to the lack of the RelA activity, other metabolic pathways involving succinate, lactate and threonine were also affected. Overall, metabolite profiles indicate that under nutrient-limiting conditions the RelA-dependent stringent response may be elicited and promotes key changes in the E. coli metabolism.

  16. A network of networks.

    Science.gov (United States)

    Iedema, Rick; Verma, Raj; Wutzke, Sonia; Lyons, Nigel; McCaughan, Brian

    2017-04-10

    Purpose To further our insight into the role of networks in health system reform, the purpose of this paper is to investigate how one agency, the NSW Agency for Clinical Innovation (ACI), and the multiple networks and enabling resources that it encompasses, govern, manage and extend the potential of networks for healthcare practice improvement. Design/methodology/approach This is a case study investigation which took place over ten months through the first author's participation in network activities and discussions with the agency's staff about their main objectives, challenges and achievements, and with selected services around the state of New South Wales to understand the agency's implementation and large system transformation activities. Findings The paper demonstrates that ACI accommodates multiple networks whose oversight structures, self-organisation and systems change approaches combined in dynamic ways, effectively yield a diversity of network governances. Further, ACI bears out a paradox of "centralised decentralisation", co-locating agents of innovation with networks of implementation and evaluation expertise. This arrangement strengthens and legitimates the role of the strategic hybrid - the healthcare professional in pursuit of change and improvement, and enhances their influence and impact on the wider system. Research limitations/implications While focussing the case study on one agency only, this study is unique as it highlights inter-network connections. Contributing to the literature on network governance, this paper identifies ACI as a "network of networks" through which resources, expectations and stakeholder dynamics are dynamically and flexibly mediated and enhanced. Practical implications The co-location of and dynamic interaction among clinical networks may create synergies among networks, nurture "strategic hybrids", and enhance the impact of network activities on health system reform. Social implications Network governance requires more

  17. Urinary polycyclic aromatic hydrocarbon metabolites among 3-year-old children from Krakow, Poland.

    Science.gov (United States)

    Sochacka-Tatara, Elżbieta; Majewska, Renata; Perera, Frederica P; Camann, David; Spengler, John; Wheelock, Kylie; Sowa, Agata; Jacek, Ryszard; Mróz, Elżbieta; Pac, Agnieszka

    2018-07-01

    Polycyclic aromatic hydrocarbons (PAHs) are widespread in the environment and can adversely affect human health. The aim of the present study is to describe the level of PAHs exposure in children living in Kraków, one of the most polluted cities in Poland, and to determine the relationship of urinary biomarkers with environmental PAHsexposure. Urinary monohydroxy metabolites (OH-PAHs) of 20 PAHs were assessed in 218 three-year old children, of which only 10 were present in nearly all the samples: monohydroxy metabolites of naphthalene, fluorene, phenantrene and pyrene. Of the metabolites analyzed, hydroxynaphthalenes were predominant and constituted almost 73% of total excreted OH-PAHs, while 1-OH-PYRene was the least abundant (2.3% of total OH-PAHs). All measured urinary OH-PAHs were statistically significantly correlated with each other (R = 0.165-0.880) but the highest correlation coefficients with other individual OH-PAHs and with total OH-PAHs were observed for 2-OH-FLUOR. Children exposed at home to environmental tobacco smoke (ETS) had higher concentrations of fluorene and pyrene urinary metabolites compared to those without ETS exposure; and those exposed to gas-based appliances used for cooking or heating water had higher levels of fluorene and phenanthrene metabolites than children not exposed. The use of coal, wood or oil for heating was associated with elevated levels of 1-OH-PYRene. Urinary PAHs metabolites only modestly reflect high molecular weight carcinogenic PAHs exposures such as those monitored in air in the present study. None of the measured PAHs metabolites was correlated with airborne PM 2.5 and only two were slightly correlated with measured higher molecular mass airborne PAHs. The average concentrations of these specific metabolites in Polish children were much higher than observed in other pediatric populations living in developed countries. Our findings suggest that to capture various sources of PAHs, in addition to 1-OH

  18. The drug transporter OAT3 (SLC22A8) and endogenous metabolite communication via the gut-liver-kidney axis.

    Science.gov (United States)

    Bush, Kevin T; Wu, Wei; Lun, Christina; Nigam, Sanjay K

    2017-09-22

    The organic anion transporters OAT1 (SLC22A6) and OAT3 (SLC22A8) have similar substrate specificity for drugs, but it is far from clear whether this holds for endogenous substrates. By analysis of more than 600 metabolites in the Oat3KO (Oat3 knockout) by LC/MS, we demonstrate OAT3 involvement in the movement of gut microbiome products, key metabolites, and signaling molecules, including those flowing through the gut-liver-kidney axis. Major pathways affected included those involved in metabolism of bile acids, flavonoids, nutrients, amino acids (including tryptophan-derivatives that are uremic toxins), and lipids. OAT3 is also critical in elimination of liver-derived phase II metabolites, particularly those undergoing glucuronidation. Analysis of physicochemical features revealed nine distinct metabolite groups; at least one member of most clusters has been previously validated in transport assays. In contrast to drugs interacting with the OATs, endogenous metabolites accumulating in the Oat1KO (Oat1 knockout) versus Oat3KO have distinct differences in their physicochemical properties; they are very different in size, number of rings, hydrophobicity, and molecular complexity. Consistent with the Remote Sensing and Signaling Hypothesis, the data support the importance of the OAT transporters in inter-organ and inter-organismal remote communication via transporter-mediated movement of key metabolites and signaling molecules ( e.g. gut microbiome-to-intestine-to-blood-to-liver-to-kidney-to-urine). We discuss the possibility of an intimate connection between OATs and metabolite sensing and signaling pathways ( e.g. bile acids). Furthermore, the metabolomics and pathway analysis support the view that OAT1 plays a greater role in kidney proximal tubule metabolism and OAT3 appears relatively more important in systemic metabolism, modulating levels of metabolites flowing through intestine, liver, and kidney. © 2017 by The American Society for Biochemistry and Molecular

  19. Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites on cardiovascular function in conscious rats.

    Science.gov (United States)

    Schindler, Charles W; Thorndike, Eric B; Blough, Bruce E; Tella, Srihari R; Goldberg, Steven R; Baumann, Michael H

    2014-01-01

    The cardiovascular effects produced by 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') contribute to its acute toxicity, but the potential role of its metabolites in these cardiovascular effects is not known. Here we examined the effects of MDMA metabolites on cardiovascular function in rats. Radiotelemetry was employed to evaluate the effects of s.c. administration of racemic MDMA and its phase I metabolites on BP, heart rate (HR) and locomotor activity in conscious male rats. MDMA (1-20 mg·kg(-1)) produced dose-related increases in BP, HR and activity. The peak effects on HR occurred at a lower dose than peak effects on BP or activity. The N-demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), produced effects that mimicked those of MDMA. The metabolite 3,4-dihydroxymethamphetamine (HHMA; 1-10 mg·kg(-1)) increased HR more potently and to a greater extent than MDMA, whereas 3,4-dihydroxyamphetamine (HHA) increased HR, but to a lesser extent than HHMA. Neither dihydroxy metabolite altered motor activity. The metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA) and 4-hydroxy-3-methoxyamphetamine (HMA) did not affect any of the parameters measured. The tachycardia produced by MDMA and HHMA was blocked by the β-adrenoceptor antagonist propranolol. Our results demonstrate that HHMA may contribute significantly to the cardiovascular effects of MDMA in vivo. As such, determining the molecular mechanism of action of HHMA and the other hydroxyl metabolites of MDMA warrants further study. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  20. In vivo brain macromolecule signals in healthy and glioblastoma mouse models: 1H magnetic resonance spectroscopy, post-processing and metabolite quantification at 14.1 T.

    Science.gov (United States)

    Craveiro, Mélanie; Clément-Schatlo, Virginie; Marino, Denis; Gruetter, Rolf; Cudalbu, Cristina

    2014-06-01

    In (1)H magnetic resonance spectroscopy, macromolecule signals underlay metabolite signals, and knowing their contribution is necessary for reliable metabolite quantification. When macromolecule signals are measured using an inversion-recovery pulse sequence, special care needs to be taken to correctly remove residual metabolite signals to obtain a pure macromolecule spectrum. Furthermore, since a single spectrum is commonly used for quantification in multiple experiments, the impact of potential macromolecule signal variability, because of regional differences or pathologies, on metabolite quantification has to be assessed. In this study, we introduced a novel method to post-process measured macromolecule signals that offers a flexible and robust way of removing residual metabolite signals. This method was applied to investigate regional differences in the mouse brain macromolecule signals that may affect metabolite quantification when not taken into account. However, since no significant differences in metabolite quantification were detected, it was concluded that a single macromolecule spectrum can be generally used for the quantification of healthy mouse brain spectra. Alternatively, the study of a mouse model of human glioma showed several alterations of the macromolecule spectrum, including, but not limited to, increased mobile lipid signals, which had to be taken into account to avoid significant metabolite quantification errors. © 2014 International Society for Neurochemistry.

  1. Structure and Function in Fluvials Biofilms. Implications in River DOC Dynamics and Nuisance Metabolite Production

    OpenAIRE

    Vilalta Baliellas, Elisabet

    2004-01-01

    The role of natural biofilms affecting the water quality in rivers has been the main theme in this study. Firstly, the study developed the capacity of biofilms in retention and/or production of DOC. Secondly, the study also approached the production of the geosmin metabolite by benthic cyanobacterial mats. In the two developed aspects, the structure and function of the biofilms showed their relevance in evaluating the capacity of biofilms on the amelioration of the water quality. The importan...

  2. An Invasive Plant Promotes Its Arbuscular Mycorrhizal Symbioses and Competitiveness through Its Secondary Metabolites: Indirect Evidence from Activated Carbon

    Science.gov (United States)

    Yuan, Yongge; Tang, Jianjun; Leng, Dong; Hu, Shuijin; Yong, Jean W. H.; Chen, Xin

    2014-01-01

    Secondary metabolites released by invasive plants can increase their competitive ability by affecting native plants, herbivores, and pathogens at the invaded land. Whether these secondary metabolites affect the invasive plant itself, directly or indirectly through microorganisms, however, has not been well documented. Here we tested whether activated carbon (AC), a well-known absorbent for secondary metabolites, affect arbuscular mycorrhizal (AM) symbioses and competitive ability in an invasive plant. We conducted three experiments (experiments 1–3) with the invasive forb Solidago canadensis and the native Kummerowia striata. Experiment 1 determined whether AC altered soil properties, levels of the main secondary metabolites in the soil, plant growth, and AMF communities associated with S. canadensis and K. striata. Experiment 2 determined whether AC affected colonization of S. canadensis by five AMF, which were added to sterilized soil. Experiment 3 determined the competitive ability of S. canadensis in the presence and absence of AMF and AC. In experiment 1, AC greatly decreased the concentrations of the main secondary metabolites in soil, and the changes in concentrations were closely related with the changes of AMF in S. canadensis roots. In experiment 2, AC inhibited the AMF Glomus versiforme and G. geosporum but promoted G. mosseae and G. diaphanum in the soil and also in S. canadensis roots. In experiment 3, AC reduced S. canadensis competitive ability in the presence but not in the absence of AMF. Our results provided indirect evidence that the secondary metabolites (which can be absorbed by AC) of the invasive plant S. canadensis may promote S. canadensis competitiveness by enhancing its own AMF symbionts. PMID:24817325

  3. An invasive plant promotes its arbuscular mycorrhizal symbioses and competitiveness through its secondary metabolites: indirect evidence from activated carbon.

    Directory of Open Access Journals (Sweden)

    Yongge Yuan

    Full Text Available Secondary metabolites released by invasive plants can increase their competitive ability by affecting native plants, herbivores, and pathogens at the invaded land. Whether these secondary metabolites affect the invasive plant itself, directly or indirectly through microorganisms, however, has not been well documented. Here we tested whether activated carbon (AC, a well-known absorbent for secondary metabolites, affect arbuscular mycorrhizal (AM symbioses and competitive ability in an invasive plant. We conducted three experiments (experiments 1-3 with the invasive forb Solidago canadensis and the native Kummerowia striata. Experiment 1 determined whether AC altered soil properties, levels of the main secondary metabolites in the soil, plant growth, and AMF communities associated with S. canadensis and K. striata. Experiment 2 determined whether AC affected colonization of S. canadensis by five AMF, which were added to sterilized soil. Experiment 3 determined the competitive ability of S. canadensis in the presence and absence of AMF and AC. In experiment 1, AC greatly decreased the concentrations of the main secondary metabolites in soil, and the changes in concentrations were closely related with the changes of AMF in S. canadensis roots. In experiment 2, AC inhibited the AMF Glomus versiforme and G. geosporum but promoted G. mosseae and G. diaphanum in the soil and also in S. canadensis roots. In experiment 3, AC reduced S. canadensis competitive ability in the presence but not in the absence of AMF. Our results provided indirect evidence that the secondary metabolites (which can be absorbed by AC of the invasive plant S. canadensis may promote S. canadensis competitiveness by enhancing its own AMF symbionts.

  4. An invasive plant promotes its arbuscular mycorrhizal symbioses and competitiveness through its secondary metabolites: indirect evidence from activated carbon.

    Science.gov (United States)

    Yuan, Yongge; Tang, Jianjun; Leng, Dong; Hu, Shuijin; Yong, Jean W H; Chen, Xin

    2014-01-01

    Secondary metabolites released by invasive plants can increase their competitive ability by affecting native plants, herbivores, and pathogens at the invaded land. Whether these secondary metabolites affect the invasive plant itself, directly or indirectly through microorganisms, however, has not been well documented. Here we tested whether activated carbon (AC), a well-known absorbent for secondary metabolites, affect arbuscular mycorrhizal (AM) symbioses and competitive ability in an invasive plant. We conducted three experiments (experiments 1-3) with the invasive forb Solidago canadensis and the native Kummerowia striata. Experiment 1 determined whether AC altered soil properties, levels of the main secondary metabolites in the soil, plant growth, and AMF communities associated with S. canadensis and K. striata. Experiment 2 determined whether AC affected colonization of S. canadensis by five AMF, which were added to sterilized soil. Experiment 3 determined the competitive ability of S. canadensis in the presence and absence of AMF and AC. In experiment 1, AC greatly decreased the concentrations of the main secondary metabolites in soil, and the changes in concentrations were closely related with the changes of AMF in S. canadensis roots. In experiment 2, AC inhibited the AMF Glomus versiforme and G. geosporum but promoted G. mosseae and G. diaphanum in the soil and also in S. canadensis roots. In experiment 3, AC reduced S. canadensis competitive ability in the presence but not in the absence of AMF. Our results provided indirect evidence that the secondary metabolites (which can be absorbed by AC) of the invasive plant S. canadensis may promote S. canadensis competitiveness by enhancing its own AMF symbionts.

  5. Trophic transfer of pyrene metabolites between aquatic invertebrates

    International Nuclear Information System (INIS)

    Carrasco Navarro, V.; Leppänen, M.T.; Kukkonen, J.V.K.; Godoy Olmos, S.

    2013-01-01

    The trophic transfer of pyrene metabolites was studied using Gammarus setosus as a predator and the invertebrates Lumbriculus variegatus and Chironomus riparius as prey. The results obtained by liquid scintillation counting confirmed that the pyrene metabolites produced by the aquatic invertebrates L. variegatus and C. riparius were transferred to G. setosus through the diet. More detailed analyses by liquid chromatography discovered that two of the metabolites produced by C. riparius appeared in the chromatograms of G. setosus tissue extracts, proving their trophic transfer. These metabolites were not present in chromatograms of G. setosus exclusively exposed to pyrene. The present study supports the trophic transfer of PAH metabolites between benthic macroinvertebrates and common species of an arctic amphipod. As some PAH metabolites are more toxic than the parent compounds, the present study raises concerns about the consequences of their trophic transfer and the fate and effects of PAHs in natural environments. - Highlights: ► The trophic transfer of pyrene metabolites between invertebrates was evaluated. ► Biotransformation of pyrene by L. variegatus and C. riparius is different. ► Metabolites produced by L. variegatus and C. riparius are transferred to G. setosus. ► Specifically, two metabolites produced by C. riparius were transferred. - Some of the pyrene metabolites produced by the model invertebrates L. variegatus and C. riparius are transferred to G. setosus through the diet, proving their trophic transfer.

  6. Antifeedant Activity of Ginkgo biloba Secondary Metabolites against Hyphantria cunea Larvae: Mechanisms and Applications.

    Science.gov (United States)

    Pan, Long; Ren, Lili; Chen, Fang; Feng, Yuqian; Luo, Youqing

    2016-01-01

    Ginkgo biloba is a typical relic plant that rarely suffers from pest hazards. This study analyzed the pattern of G. biloba pest hazards in Beijing; tested the antifeedant activity of G. biloba extracts, including ginkgo flavonoids, ginkgolide, and bilobalide, against Hyphantria cunea larvae; determined the activities of glutathione transferase (GSTs), acetylcholinesterase (AChE), carboxylesterase (CarE) and mixed-functional oxidase (MFO), in larvae after feeding on these G. biloba secondary metabolites; and screened for effective botanical antifeedants in the field. In this study, no indicators of insect infestation were found for any of the examined leaves of G. biloba; all tested secondary metabolites showed significant antifeedant activity and affected the activity of the four larval detoxifying enzymes. Ginkgolide had the highest antifeedant activity and the most significant effect on the detoxifying enzymes (Pbiloba extracts or ginkgolide both significantly repelled H. cunea larvae in the field (Pbiloba secondary metabolites against H. cunea larvae, and the results provide new insights into the mechanism of G. biloba pest resistance. This study also developed new applications of G. biloba secondary metabolites for effective pest control.

  7. Urine nicotine metabolites and smoking behavior in a multiracial/multiethnic national sample of young adults.

    Science.gov (United States)

    Kandel, Denise B; Hu, Mei-Chen; Schaffran, Christine; Udry, J Richard; Benowitz, Neal L

    2007-04-15

    Nicotine metabolism has been hypothesized to affect patterns of smoking. The recent development of a noninvasive measure of nicotine metabolism, the nicotine metabolite ratio (trans-3'-hydroxycotinine/cotinine), makes it possible to examine the association between rate of nicotine metabolism and smoking behavior in the general population. This US study examined group differences in the ratio measured in urine and the association between the ratio and multiple measures of smoking behavior and nicotine dependence in a large, national representative sample of young adults. The sample included 900 daily smokers aged 18-26 years from wave III (2001-2002) of the National Longitudinal Survey of Adolescent Health. Nicotine dependence was measured by using the Fagerström Test for Nicotine Dependence. Females had higher nicotine metabolite ratios than males; Whites and Hispanics had higher nicotine metabolite ratios than African Americans or Asians. This finding is consistent with those from laboratory studies of older smokers based on intravenous infusion of nicotine. No significant association was found between the nicotine metabolite ratio and number of cigarettes smoked per day or nicotine dependence. The availability of a noninvasive measure makes possible systematic testing of causal hypotheses generated by laboratory studies in the general population.

  8. Levels of compounds and metabolites in wheat ears and grains in organic and conventional agriculture.

    Science.gov (United States)

    Zörb, Christian; Niehaus, Karsten; Barsch, Aiko; Betsche, Thomas; Langenkämper, Georg

    2009-10-28

    In this work, wheat from two farming systems, organic and conventional, was analyzed. Organic agriculture is one of the fastest growing sectors in the food industry of Europe and the United States. It is an open question, whether organic or conventional agricultural management influences variables such as metabolism, nutrient supply, seed loading and metabolite composition of wheat. Our aim was to detect if organic or conventional farming systems would affect concentrations of metabolites and substances in developing ears and in corresponding matured grain. Therefore, broadband metabolite profiles together with lipids, cations, starch and protein concentrations of wheat ears in the last phase of grain development and of matured grain from organic and conventional agriculture of a rigorously controlled field trial with two organic and two conventional systems were examined. It appears that seed metabolism and supply of developing ears differ in organic and conventional agriculture. However, the differences in 62 metabolite concentrations become marginal or disappear in the matured grains, indicating an adjustment of nutrients in the matured grain from organic agriculture. This result suggests a high degree of homeostasis in the final seed set independent of the growing regime.

  9. Levels of caffeine and its metabolites among U.S. smokers and nonsmokers.

    Science.gov (United States)

    Jain, Ram B

    2015-03-01

    Data from National Health and Nutrition Examination Survey for the years 2009-2010 were used to estimate the levels of caffeine and 14 of its metabolite among U.S. smokers and nonsmokers after adjustments were made for other factors that affect observed caffeine levels. In this study, when adjusted for daily caffeine intake, adjusted levels (AGM) of caffeine and its metabolites were not found to be statistically significantly different between smokers and nonsmokers. AGMs for caffeine and all of its metabolites were found to be statistically significantly higher (p whites > Hispanics > non-Hispanic blacks and most of the differences were statistically significant, at least between non-Hispanic whites and non-Hispanic blacks (p < 0.01). In general, there was a statistically significant positive association between the levels of caffeine and its metabolites and body mass index as well as daily caffeine intake. However, the levels of 7-methylxanthine were negatively associated with body mass index. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. 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.

  11. Reward and Toxicity of Cocaine Metabolites Generated by Cocaine Hydrolase.

    Science.gov (United States)

    Murthy, Vishakantha; Geng, Liyi; Gao, Yang; Zhang, Bin; Miller, Jordan D; Reyes, Santiago; Brimijoin, Stephen

    2015-08-01

    Butyrylcholinesterase (BChE) gene therapy is emerging as a promising concept for treatment of cocaine addiction. BChE levels after gene transfer can rise 1000-fold above those in untreated mice, making this enzyme the second most abundant plasma protein. For months or years, gene transfer of a BChE mutated into a cocaine hydrolase (CocH) can maintain enzyme levels that destroy cocaine within seconds after appearance in the blood stream, allowing little to reach the brain. Rapid enzyme action causes a sharp rise in plasma levels of two cocaine metabolites, benzoic acid (BA) and ecgonine methyl ester (EME), a smooth muscle relaxant that is mildly hypotensive and, at best, only weakly rewarding. The present study, utilizing Balb/c mice, tested reward effects and cardiovascular effects of administering EME and BA together at molar levels equivalent to those generated by a given dose of cocaine. Reward was evaluated by conditioned place preference. In this paradigm, cocaine (20 mg/kg) induced a robust positive response but the equivalent combined dose of EME + BA failed to induce either place preference or aversion. Likewise, mice that had undergone gene transfer with mouse CocH (mCocH) showed no place preference or aversion after repeated treatments with a near-lethal 80 mg/kg cocaine dose. Furthermore, a single administration of that same high cocaine dose failed to affect blood pressure as measured using the noninvasive tail-cuff method. These observations confirm that the drug metabolites generated after CocH gene transfer therapy are safe even after a dose of cocaine that would ordinarily be lethal.

  12. Cytotoxicity of lapachol metabolites produced by probiotics.

    Science.gov (United States)

    Oliveira Silva, E; Cruz de Carvalho, T; Parshikov, I A; Alves dos Santos, R; Silva Emery, F; Jacometti Cardoso Furtado, N A

    2014-07-01

    Probiotics are currently added to a variety of functional foods to provide health benefits to the host and are commonly used by patients with gastrointestinal complaints or diseases. The therapeutic effects of lapachol continue to inspire studies to obtain derivatives with improved bioactivity and lower unwanted effects. Therefore, the general goal of this study was to show that probiotics are able to convert lapachol and are important to assess the effects of bacterial metabolism on drug performance and toxicity. The microbial transformations of lapachol were carried out by Bifidobacterium sp. and Lactobacillus acidophilus and different metabolites were produced in mixed and isolated cultures. The cytotoxic activities against breast cancer and normal fibroblast cell lines of the isolated metabolites (4α-hydroxy-2,2-dimethyl-5-oxo-2,3,4,4α,5,9β-hexahydroindeno[1,2-β]pyran-9β-carboxilic acid, a new metabolite produced by mixed culture and dehydro-α-lapachone produced by isolated cultures) were assessed and compared with those of lapachol. The new metabolite displayed a lower activity against a breast cancer cell line (IC50 = 532.7 μmol l(-1) ) than lapachol (IC50 = 72.3 μmol l(-1) ), while dehydro-α-lapachone (IC50 = 10.4 μmol l(-1) ) displayed a higher activity than lapachol. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. Probiotics have been used in dairy products to promote human health and have the ability to metabolize drugs and other xenobiotics. Naphthoquinones, such as lapachol, are considered privileged scaffolds due to their high propensity to interact with biological targets. The present study is the first to demonstrate that probiotics are capable of converting lapachol into the most effective cytotoxic compound against a breast cancer cell line. The developed approach highlights the importance of probiotics to assess

  13. Maximum entropy networks are more controllable than preferential attachment networks

    International Nuclear Information System (INIS)

    Hou, Lvlin; Small, Michael; Lao, Songyang

    2014-01-01

    A maximum entropy (ME) method to generate typical scale-free networks has been recently introduced. We investigate the controllability of ME networks and Barabási–Albert preferential attachment networks. Our experimental results show that ME networks are significantly more easily controlled than BA networks of the same size and the same degree distribution. Moreover, the control profiles are used to provide insight into control properties of both classes of network. We identify and classify the driver nodes and analyze the connectivity of their neighbors. We find that driver nodes in ME networks have fewer mutual neighbors and that their neighbors have lower average degree. We conclude that the properties of the neighbors of driver node sensitively affect the network controllability. Hence, subtle and important structural differences exist between BA networks and typical scale-free networks of the same degree distribution. - Highlights: • The controllability of maximum entropy (ME) and Barabási–Albert (BA) networks is investigated. • ME networks are significantly more easily controlled than BA networks of the same degree distribution. • The properties of the neighbors of driver node sensitively affect the network controllability. • Subtle and important structural differences exist between BA networks and typical scale-free networks

  14. Observability of plant metabolic networks is reflected in the correlation of metabolic profiles

    DEFF Research Database (Denmark)

    Schwahn, Kevin; Küken, Anika; Kliebenstein, Daniel James

    2016-01-01

    -of-the-art genome-scale metabolic networks. By using metabolic data profiles from a set of seven environmental perturbations as well as from natural variability, we demonstrate that the data profiles of sensor metabolites are more correlated than those of nonsensor metabolites. This pattern was confirmed...

  15. [Identification of saponins from Panax notoginseng in metabolites of rats].

    Science.gov (United States)

    Shen, Wen-Wen; Zhang, Yin; Qiu, Shou-Bei; Zhu, Fen-Xia; Jia, Xiao-Bin; Tang, Dao-Quan; Chen, Bin

    2017-10-01

    UPLC-QTOF-MS/MS was used to identify metabolites in rat blood, urine and feces after the administration of n-butanol extract derived from steamed notoginseng. The metabolic process of saponins came from steamed notoginseng was analyzed. The metabolites were processed by PeakView software, and identified according to the structural characteristics of prototype compounds and the accurate qualitative and quantitative changes of common metabolic pathways. Four saponins metabolites were identified based on MS/MS information of metabolites, namely ginsenoside Rh₄, Rk₃, Rk₁, Rg₅,and their 15 metabolites were verified. The metabolic pathways of the four ginsenosides in n-butanol extract included glucuronidation, desugar, sulfation, dehydromethylation, and branch loss. The metabolites of main active saponin components derived from steamed Panax notoginseng were analyzed from the perspective of qualitative analysis. And the material basis for the efficacy of steamed notoginseng was further clarified. Copyright© by the Chinese Pharmaceutical Association.

  16. Increased plasma concentrations of vitamin D metabolites and vitamin D binding protein in women using hormonal contraceptives

    DEFF Research Database (Denmark)

    Møller, Ulla K; Streym, Susanna við; Jensen, Lars T

    2013-01-01

    UNLABELLED: Use of hormonal contraceptives (HC) may influence total plasma concentrations of vitamin D metabolites. A likely cause is an increased synthesis of vitamin D binding protein (VDBP). Discrepant results are reported on whether the use of HC affects free concentrations of vitamin D...

  17. Protozoan growth rates on secondary-metabolite-producing Pseudomonas spp. correlate with high-level protozoan taxonomy

    DEFF Research Database (Denmark)

    Pedersen, Annette L.; Winding, Anne; Altenburger, Andreas

    2011-01-01

    Different features can protect bacteria against protozoan grazing, for example large size, rapid movement, and production of secondary metabolites. Most papers dealing with these matters focus on bacteria. Here, we describe protozoan features that affect their ability to grow on secondary-metabol...

  18. Affective Urbanism

    DEFF Research Database (Denmark)

    Samson, Kristine

    Urban design and architecture are increasingly used as material and affective strategies for setting the scene, for manipulation and the production of urban life: The orchestration of atmospheres, the framing and staging of urban actions, the programming for contemplation, involvement, play......, experience and consumption are all strategic design tools applied by planners and architects. Whereas urban design in former modernist planning served merely functional or political means, urban design has increasingly become an aesthetical mediator of ideologies embedded in the urban field of life forces....... Under these circumstances affective aesthetics operate strategically within the urban field of interests, capital flows and desires of the social. This ‘affective urbanism’ (Anderson & Holden 2008) is linked to a society influenced by new kinds of information flows, where culture is mediated and enacted...

  19. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    . In particular, mapping environmental damage, endangered species, and human made disasters has become one of the focal point of affective knowledge production. These ‘more-than-humangeographies’ practices include notions of species, space and territory, and movement towards a new political ecology. This type...... of digital cartographies has been highlighted as the ‘processual turn’ in critical cartography, whereas in related computational journalism it can be seen as an interactive and iterative process of mapping complex and fragile ecological developments. This paper looks at computer-assisted cartography as part...... of environmental knowledge production. It uses InfoAmazonia, the databased platform on Amazon rainforests, as an example of affective geo-visualization within information mapping that enhances embodiment in the experience of the information. Amazonia is defined as a digitally created affective (map)space within...

  20. Catalyzed Synthesis of Zinc Clays by Prebiotic Central Metabolites.

    Science.gov (United States)

    Zhou, Ruixin; Basu, Kaustuv; Hartman, Hyman; Matocha, Christopher J; Sears, S Kelly; Vali, Hojatollah; Guzman, Marcelo I

    2017-04-03

    How primordial metabolic networks such as the reverse tricarboxylic acid (rTCA) cycle and clay mineral catalysts coevolved remains a mystery in the puzzle to understand the origin of life. While prebiotic reactions from the rTCA cycle were accomplished via photochemistry on semiconductor minerals, the synthesis of clays was demonstrated at low temperature and ambient pressure catalyzed by oxalate. Herein, the crystallization of clay minerals is catalyzed by succinate, an example of a photoproduced intermediate from central metabolism. The experiments connect the synthesis of sauconite, a model for clay minerals, to prebiotic photochemistry. We report the temperature, pH, and concentration dependence on succinate for the synthesis of sauconite identifying new mechanisms of clay formation in surface environments of rocky planets. The work demonstrates that seeding induces nucleation at low temperatures accelerating the crystallization process. Cryogenic and conventional transmission electron microscopies, X-ray diffraction, diffuse reflectance Fourier transformed infrared spectroscopy, and measurements of total surface area are used to build a three-dimensional representation of the clay. These results suggest the coevolution of clay minerals and early metabolites in our planet could have been facilitated by sunlight photochemistry, which played a significant role in the complex interplay between rocks and life over geological time.

  1. Biopotential of secondary metabolites isolated from marine sponge Dendrilla nigra

    OpenAIRE

    Valentin Bhimba B; V Vinod; M Cindhu Beulah

    2011-01-01

    Objective: To evaluate the biopotential activity of secondary metabolites from marine sponge Dendrilla nigra (D. nigra) collected from the Gulf of Mannar. Objective: Soxhlet extraction method was used to extract the secondary metabolites and various assays were carried out. Results: D. nigra showed potent antibacterial, antioxidant, anti-inflammatory and anticancer activities and it was also subjected for brine shrimp lethality and cytotoxicity assays. The secondary metabolites...

  2. 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

  3. 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....

  4. Secondary metabolites in grasses: characterization and biological activity

    OpenAIRE

    Aldo Tava

    2007-01-01

    In a series of studies dealing on the nutritional value of forage species, more attention was focussed on several compounds, named secondary metabolites, that are important in determining nutritional characteristics. Secondary metabolites are compounds detected in the green materials in low concentration compared to primary metabolites (proteins, sugars, lipids, fibers), but of fundamental importance for the plant physiology. The possess several biological activities and this contribute to th...

  5. 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...

  6. Cyanobacteria as Cell Factories to Produce Plant Secondary Metabolites

    OpenAIRE

    Xue, Yong; He, Qingfang

    2015-01-01

    Cyanobacteria represent a promising platform for the production of plant secondary metabolites. Their capacity to express plant P450 proteins, which have essential functions in the biosynthesis of many plant secondary metabolites, makes cyanobacteria ideal for this purpose, and their photosynthetic capability allows cyanobacteria to grow with simple nutrient inputs. This review summarizes the advantages of using cyanobacteria to transgenically produce plant secondary metabolites. Some techniq...

  7. 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...

  8. Exometabolomic Analysis of Cross-Feeding Metabolites.

    Science.gov (United States)

    Lubbe, Andrea; Bowen, Benjamin P; Northen, Trent

    2017-10-04

    Microbial consortia have the potential to perform complex, industrially important tasks. The design of microbial consortia requires knowledge of the substrate preferences and metabolic outputs of each member, to allow understanding of potential interactions such as competition and beneficial metabolic exchange. Here, we used exometabolite profiling to follow the resource processing by a microbial co-culture of two biotechnologically relevant microbes, the bacterial cellulose degrader Cellulomonas fimi, and the oleaginous yeast Yarrowia lipolytica. We characterized the substrate preferences of the two strains on compounds typically found in lignocellulose hydrolysates. This allowed prediction that specific sugars resulting from hemicellulose polysaccharide degradation by C. fimi may serve as a cross-feeding metabolites to Y. lipolytica in co-culture. We also showed that products of ionic liquid-treated switchgrass lignocellulose degradation by C. fimi were channeled to Y. lipolytica in a co-culture. Additionally, we observed metabolites, such as shikimic acid accumulating in the co-culture supernatants, suggesting the potential for producing interesting co-products. Insights gained from characterizing the exometabolite profiles of individual and co-cultures of the two strains can help to refine this interaction, and guide strategies for making this an industrially viable co-culture to produce valuable products from lignocellulose material.

  9. Exometabolomic Analysis of Cross-Feeding Metabolites

    Directory of Open Access Journals (Sweden)

    Andrea Lubbe

    2017-10-01

    Full Text Available Microbial consortia have the potential to perform complex, industrially important tasks. The design of microbial consortia requires knowledge of the substrate preferences and metabolic outputs of each member, to allow understanding of potential interactions such as competition and beneficial metabolic exchange. Here, we used exometabolite profiling to follow the resource processing by a microbial co-culture of two biotechnologically relevant microbes, the bacterial cellulose degrader Cellulomonas fimi, and the oleaginous yeast Yarrowia lipolytica. We characterized the substrate preferences of the two strains on compounds typically found in lignocellulose hydrolysates. This allowed prediction that specific sugars resulting from hemicellulose polysaccharide degradation by C. fimi may serve as a cross-feeding metabolites to Y. lipolytica in co-culture. We also showed that products of ionic liquid-treated switchgrass lignocellulose degradation by C. fimi were channeled to Y. lipolytica in a co-culture. Additionally, we observed metabolites, such as shikimic acid accumulating in the co-culture supernatants, suggesting the potential for producing interesting co-products. Insights gained from characterizing the exometabolite profiles of individual and co-cultures of the two strains can help to refine this interaction, and guide strategies for making this an industrially viable co-culture to produce valuable products from lignocellulose material.

  10. Bacterial Unculturability and the Formation of Intercellular Metabolic Networks.

    Science.gov (United States)

    Pande, Samay; Kost, Christian

    2017-05-01

    The majority of known bacterial species cannot be cultivated under laboratory conditions. Here we argue that the adaptive emergence of obligate metabolic interactions in natural bacterial communities can explain this pattern. Bacteria commonly release metabolites into the external environment. Accumulating pools of extracellular metabolites create an ecological niche that benefits auxotrophic mutants, which have lost the ability to autonomously produce the corresponding metabolites. In addition to a diffusion-based metabolite transfer, auxotrophic cells can use contact-dependent means to obtain nutrients from other co-occurring cells. Spatial colocalisation and a continuous coevolution further increase the nutritional dependency and optimise fluxes through combined metabolic networks. Thus, bacteria likely function as networks of interacting cells that reciprocally exchange nutrients and biochemical functions rather than as physiologically autonomous units. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Prospective study of blood metabolites associated with colorectal cancer risk.

    Science.gov (United States)

    Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei

    2018-02-26

    Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.

  12. Possible endocrine disrupting effects of parabens and their metabolites

    DEFF Research Database (Denmark)

    Boberg, Julie; Taxvig, Camilla; Christiansen, Sofie

    2010-01-01

    and provides an overview of studies on toxicokinetics. After dermal uptake, parabens are hydrolyzed and conjugated and excreted in urine. Despite high total dermal uptake of paraben and metabolites,little intact paraben can be recovered in blood and urine. Paraben metabolites may play a role in the endocrine...... disruption seen in experimental animals and studies are needed to determine human levels of parabens and metabolites. Overall, the estrogenic burden of parabens and their metabolites in blood may exceed the action of endogenous estradiol in childhood and the safety margin for propylparaben is very low when...

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

    DEFF Research Database (Denmark)

    Petersen, Lene Maj; Frisvad, Jens Christian; Knudsen, Peter Boldsen

    2015-01-01

    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...... 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....

  14. Secondary metabolites in grasses: characterization and biological activity

    Directory of Open Access Journals (Sweden)

    Aldo Tava

    2007-12-01

    Full Text Available In a series of studies dealing on the nutritional value of forage species, more attention was focussed on several compounds, named secondary metabolites, that are important in determining nutritional characteristics. Secondary metabolites are compounds detected in the green materials in low concentration compared to primary metabolites (proteins, sugars, lipids, fibers, but of fundamental importance for the plant physiology. The possess several biological activities and this contribute to their possible pharmacological use. In the present paper studies on secondary metabolites from herbaceous plants are reviewed. Indications of the chemical methods used for their analyses, their presence in the green material and their biological activity are also reported.

  15. Secondary metabolites in grasses: characterization and biological activity

    Directory of Open Access Journals (Sweden)

    Aldo Tava

    2011-02-01

    Full Text Available In a series of studies dealing on the nutritional value of forage species, more attention was focussed on several compounds, named secondary metabolites, that are important in determining nutritional characteristics. Secondary metabolites are compounds detected in the green materials in low concentration compared to primary metabolites (proteins, sugars, lipids, fibers, but of fundamental importance for the plant physiology. The possess several biological activities and this contribute to their possible pharmacological use. In the present paper studies on secondary metabolites from herbaceous plants are reviewed. Indications of the chemical methods used for their analyses, their presence in the green material and their biological activity are also reported.

  16. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

    Science.gov (United States)

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies.

  17. Affect Regulation

    DEFF Research Database (Denmark)

    Pedersen, Signe Holm; Poulsen, Stig Bernt; Lunn, Susanne

    2014-01-01

    Gergely and colleagues’ state that their Social Biofeedback Theory of Parental Affect Mirroring” can be seen as a kind of operationalization of the classical psychoanalytic concepts of holding, containing and mirroring. This article examines to what extent the social biofeedback theory of parenta...

  18. Selfish cellular networks and the evolution of complex organisms.

    Science.gov (United States)

    Kourilsky, Philippe

    2012-03-01

    Human gametogenesis takes years and involves many cellular divisions, particularly in males. Consequently, gametogenesis provides the opportunity to acquire multiple de novo mutations. A significant portion of these is likely to impact the cellular networks linking genes, proteins, RNA and metabolites, which constitute the functional units of cells. A wealth of literature shows that these individual cellular networks are complex, robust and evolvable. To some extent, they are able to monitor their own performance, and display sufficient autonomy to be termed "selfish". Their robustness is linked to quality control mechanisms which are embedded in and act upon the individual networks, thereby providing a basis for selection during gametogenesis. These selective processes are equally likely to affect cellular functions that are not gamete-specific, and the evolution of the most complex organisms, including man, is therefore likely to occur via two pathways: essential housekeeping functions would be regulated and evolve during gametogenesis within the parents before being transmitted to their progeny, while classical selection would operate on other traits of the organisms that shape their fitness with respect to the environment. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  19. The environmental occurrence and effect of alkylphenol polyethoxylates and their metabolites in Taiwan

    Science.gov (United States)

    Ding, W.

    2009-12-01

    Alkylphenol polyethoxylates (APEOs) are widely used nonionic surfactants in domestic, agricultural and household applications, which have been commonly found in wastewater discharges and in sewage treatment plant effluents. Degradation of APEOs in wastewater or in the environment generates more persistent pollutants, including alkylphenols (APs, such as 4-nonylphenol isomers (4-NPs) and 4-t-octylphenol (4-t-OP)) and shortened ethoxy chain APEO residues (such as AP1~3EO). These metabolites of APEOs are of interest in the field of environmental monitoring because of the volume of these substances used and their activity as either endocrine disruptors or as persistent pollutants. APEOs are mass-produced and used widely in Taiwan. Large quantities of these metabolites in wastewater are discharged into the rivers directly because Taiwan’s municipal and industrial wastewater treatment facilities are deficient. However, the occurrence and fate of these metabolites are unclear and can potentially affect the aquatic environment and public health in Taiwan. Determination of APEOs and their metabolites have been performed for household detergents, various surface water, soil, sediments, biota, foodstuffs and even in breast milk. APEOs and their metabolites were detected in all media analyzed and in all environmental samples. The relatively high concentrations detected in oysters and snails provide evidence for bioaccumulation of APs. The presence of APs in breast milk implies that APs enter the food chain in local biota after long chain APEOs were biodegraded. There are also some indications that the plastic wrappings and containers for foodstuffs sold in Taiwan may contain NP or tris(nonylphenol) phosphate (TNPP) used as plasticizers or antioxidants. In addition, possible sources of APs may come from the extensive use of pesticides containing APEO as emulsifiers in agriculture.

  20. Oxidative defense metabolites induced by salinity stress in roots of Salicornia herbacea.

    Science.gov (United States)

    Lee, Seung Jae; Jeong, Eun-Mi; Ki, Ah Young; Oh, Kyung-Seo; Kwon, Joseph; Jeong, Jae-Hyuk; Chung, Nam-Jin

    2016-11-01

    High salinity is a major abiotic stress that affects the growth and development of plants. This type of stress can influence flowering, the production of crops, defense mechanisms and other physiological processes. Previous studies have attempted to elucidate salt-tolerance mechanisms to improve plant growth and productivity in the presence of sodium chloride. One such plant that has been studied in detail is Salicornia, a well-known halophyte, which has adapted to grow in the presence of high salt. To further the understanding of how Salicornia grows and develops under high saline conditions, Salicornia herbacea (S. herbacea) was grown under varying saline concentrations (0, 50, 100, 200, 300, and 400mM), and the resulting phenotype, ion levels, and metabolites were investigated. The optimal condition for the growth of S. herbacea was determined to be 100mM NaCl, and increased salt concentrations directly decreased the internal concentrations of other inorganic ions including Ca 2+ , K + , and Mg 2+ . Metabolomics were performed on the roots of the plant as a systematic metabolomics study has not yet been reported for Salicornia roots. Using ethylacetate and methanol extraction followed by high resolution ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS), 1793 metabolites were identified at different NaCl levels. Structural and functional analyses demonstrated that the concentration of 53 metabolites increased as the concentration of NaCl increased. These metabolites have been linked to stress responses, primarily oxidative stress responses, which increase under saline stress. Most metabolites can be classified as polyols, alkaloids, and steroids. Functional studies of these metabolites show that shikimic acid, vitamin K1, and indole-3-carboxylic acid are generated as a result of defense mechanisms, including the shikimate pathway, to protect against reactive oxygen species (ROS) generated by salt stress. This metabolite profiling

  1. Communication in Animal Social Networks

    NARCIS (Netherlands)

    Snijders, Lysanne; Naguib, Marc

    2017-01-01

    Animal social networks and animal communication networks are key disciplines for understanding animal social behavior, yet these disciplines remain poorly integrated. In this review, we show how communication and social networks are inherently linked, with social signals reflecting and affecting

  2. Graphene nano-ink biosensor arrays on a microfluidic paper for multiplexed detection of metabolites.

    Science.gov (United States)

    Labroo, Pratima; Cui, Yue

    2014-02-27

    The development of a miniaturized and low-cost platform for the highly sensitive, selective and rapid detection of multiplexed metabolites is of great interest for healthcare, pharmaceuticals, food science, and environmental monitoring. Graphene is a delicate single-layer, two-dimensional network of carbon atoms with extraordinary electrical sensing capability. Microfluidic paper with printing technique is a low cost matrix. Here, we demonstrated the development of graphene-ink based biosensor arrays on a microfluidic paper for the multiplexed detection of different metabolites, such as glucose, lactate, xanthine and cholesterol. Our results show that the graphene biosensor arrays can detect multiple metabolites on a microfluidic paper sensitively, rapidly and simultaneously. The device exhibits a fast measuring time of less than 2 min, a low detection limit of 0.3 μM, and a dynamic detection range of 0.3-15 μM. The process is simple and inexpensive to operate and requires a low consumption of sample volume. We anticipate that these results could open exciting opportunities for a variety of applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Solid-Phase Extraction of Sulfur Mustard Metabolites Using an Activated Carbon Fiber Sorbent.

    Science.gov (United States)

    Lee, Jin Young; Lee, Yong Han

    2016-01-01

    A novel solid-phase extraction method using activated carbon fiber (ACF) was developed and validated. ACF has a vast network of pores of varying sizes and microporous structures that result in rapid adsorption and selective extraction of sulfur mustard metabolites according to the pH of eluting solvents. ACF could not only selectively extract thiodiglycol and 1-methylsulfinyl-2-[2-(methylthio)-ethylsulfonyl]ethane eluting a 9:1 ratio of dichloromethane to acetone, and 1,1'-sulfonylbis[2-(methylsulfinyl)ethane] and 1,1'-sulfonylbis- [2-S-(N-acetylcysteinyl)ethane] eluting 3% hydrogen chloride in methanol, but could also eliminate most interference without loss of analytes during the loading and washing steps. A sample preparation method has been optimized for the extraction of sulfur mustard metabolites from human urine using an ACF sorbent. The newly developed extraction method was applied to the trace analysis of metabolites of sulfur mustard in human urine matrices in a confidence-building exercise for the analysis of biomedical samples provided by the Organisation for the Prohibition of Chemical Weapons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Water and salinity stress in grapevines: early and late changes in transcript and metabolite profiles.

    Science.gov (United States)

    Cramer, Grant R; Ergül, Ali; Grimplet, Jerome; Tillett, Richard L; Tattersall, Elizabeth A R; Bohlman, Marlene C; Vincent, Delphine; Sonderegger, Justin; Evans, Jason; Osborne, Craig; Quilici, David; Schlauch, Karen A; Schooley, David A; Cushman, John C

    2007-04-01

    Grapes are grown in semiarid environments, where drought and salinity are common problems. Microarray transcript profiling, quantitative reverse transcription-PCR, and metabolite profiling were used to define genes and metabolic pathways in Vitis vinifera cv. Cabernet Sauvignon with shared and divergent responses to a gradually applied and long-term (16 days) water-deficit stress and equivalent salinity stress. In this first-of-a-kind study, distinct differences between water deficit and salinity were revealed. Water deficit caused more rapid and greater inhibition of shoot growth than did salinity at equivalent stem water potentials. One of the earliest responses to water deficit was an increase in the transcript abundance of RuBisCo activase (day 4), but this increase occurred much later in salt-stressed plants (day 12). As water deficit progressed, a greater number of affected transcripts were involved in metabolism, transport, and the biogenesis of cellular components than did salinity. Salinity affected a higher percentage of transcripts involved in transcription, protein synthesis, and protein fate than did water deficit. Metabolite profiling revealed that there were higher concentrations of glucose, malate, and proline in water-deficit-treated plants as compared to salinized plants. The metabolite differences were linked to differences in transcript abundance of many genes involved in energy metabolism and nitrogen assimilation, particularly photosynthesis, gluconeogenesis, and photorespiration. Water-deficit-treated plants appear to have a higher demand than salinized plants to adjust osmotically, detoxify free radicals (reactive oxygen species), and cope with photoinhibition.

  5. High-Temperature Induced Changes of Extracellular Metabolites in Pleurotus ostreatus and Their Positive Effects on the Growth of Trichoderma asperellum

    Directory of Open Access Journals (Sweden)

    Zhiheng Qiu

    2018-01-01

    Full Text Available Pleurotus ostreatus is a widely cultivated edible fungus in China. Green mold disease of P. ostreatus which can seriously affect yield is a common disease during cultivation. It occurs mostly after P. ostreatus mycelia have been subjected to high temperatures. However, little information is available on the relationship between high temperature and green mold disease. The aim of this study is to prove that extracellular metabolites of P. ostreatus affected by high temperature can promote the growth of Trichoderma asperellum. After P. ostreatus mycelia was subjected to high temperature, the extracellular fluid of P. ostreatus showed a higher promoting effect on mycelial growth and conidial germination of T. asperellum. The thiobarbituric acid reactive substance (TBARS content reached the maximum after 48 h at 36°C. A comprehensive metabolite profiling strategy involving gas chromatography-mass spectrometry (GC/MS combined with liquid chromatography-mass spectrometry (LC/MS was used to analyze the changes of extracellular metabolites in response to high temperature. A total of 141 differential metabolites were identified, including 84.4% up-regulated and 15.6% down-regulated. Exogenous metabolites whose concentrations were increased after high temperature were randomly selected, and nearly all of them were able to promote the mycelial growth and conidial germination of T. asperellum. The combination of all selected exogenous metabolites also has the promotion effects on the mycelial growth and conidial germination of T. asperellum in a given concentration range in vitro. Overall, these results provide a first view that high temperature affects the extracellular metabolites of P. ostreatus, and the extensive change in metabolites promotes T. asperellum growth.

  6. High-Temperature Induced Changes of Extracellular Metabolites in Pleurotus ostreatus and Their Positive Effects on the Growth of Trichoderma asperellum.

    Science.gov (United States)

    Qiu, Zhiheng; Wu, Xiangli; Zhang, Jinxia; Huang, Chenyang

    2018-01-01

    Pleurotus ostreatus is a widely cultivated edible fungus in China. Green mold disease of P. ostreatus which can seriously affect yield is a common disease during cultivation. It occurs mostly after P. ostreatus mycelia have been subjected to high temperatures. However, little information is available on the relationship between high temperature and green mold disease. The aim of this study is to prove that extracellular metabolites of P. ostreatus affected by high temperature can promote the growth of Trichoderma asperellum . After P. ostreatus mycelia was subjected to high temperature, the extracellular fluid of P. ostreatus showed a higher promoting effect on mycelial growth and conidial germination of T. asperellum . The thiobarbituric acid reactive substance (TBARS) content reached the maximum after 48 h at 36°C. A comprehensive metabolite profiling strategy involving gas chromatography-mass spectrometry (GC/MS) combined with liquid chromatography-mass spectrometry (LC/MS) was used to analyze the changes of extracellular metabolites in response to high temperature. A total of 141 differential metabolites were identified, including 84.4% up-regulated and 15.6% down-regulated. Exogenous metabolites whose concentrations were increased after high temperature were randomly selected, and nearly all of them were able to promote the mycelial growth and conidial germination of T. asperellum . The combination of all selected exogenous metabolites also has the promotion effects on the mycelial growth and conidial germination of T. asperellum in a given concentration range in vitro . Overall, these results provide a first view that high temperature affects the extracellular metabolites of P. ostreatus , and the extensive change in metabolites promotes T. asperellum growth.

  7. 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.

  8. Formation of reactive metabolites from benzene

    International Nuclear Information System (INIS)

    Snyder, R.; Jowa, L.; Witz, G.; Kalf, G.; Rushmore, T.

    1986-01-01

    Rat liver mitoplasts were incubated first with [ 3 H]dGTP, to form DNA labeled in G, and then with [ 14 C]benzene. The DNA was isolated and upon isopycnic density gradient centrifugation in CsCl yielded a single fraction of DNA labeled with both [ 3 H] and [ 14 C]. These data are consistent with the covalent binding of one or more metabolites of benzene to DNA. The DNA was enzymatically hydrolyzed to deoxynucleosides and chromatographed to reveal at least seven deoxyguanosine adducts. Further studies with labeled deoxyadenine revealed one adduct on deoxyadenine. [ 3 H]Deoxyguanosine was reacted with [ 14 C]hydroquinone or benzoquinone. The product was characterized using uv, fluorescence, mass and NMR spectroscopy. A proposed structure is described. (orig.)

  9. 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.

  10. Atranorin - An Interesting Lichen Secondary Metabolite.

    Science.gov (United States)

    Studzinska-Sroka, Elzbieta; Galanty, Agnieszka; Bylka, Wieslawa

    2017-01-01

    Atranorin, a compound with the depside structure, is one of the most common lichen secondary metabolites, characteristic for numerous lichen families but rarely found in some mosses and higher plants. Over the years various biological properties of atranorin were examined. This review summarizes the studies on atranorin, focusing on a number of biological activities in different fields. The literature describes anti-inflammatory, analgesic, as well as wound healing, antibacterial, antifungal, cytotoxic, antioxidant, antiviral, and immunomodulatory activities of the depside. Furthermore, lack of toxicity of atranorin was confirmed in the animals' in vivo assays. In conclusion, atranorin seems to be an interesting lichen substance, which needs to be investigated in more detail in order to allow further applications, e.g. in pharmacy, medicine or cosmetology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Effects of Different Salt Treatments on the Fermentation Metabolites and Bacterial Profiles of Kimchi.

    Science.gov (United States)

    Kim, Dong Wook; Kim, Bo-Min; Lee, Hyeon-Jeong; Jang, Gwang-Ju; Song, Seong Hwa; Lee, Jae-In; Lee, Sang Bong; Shim, Jae Min; Lee, Kang Wook; Kim, Jeong Hwan; Ham, Kyung-Sik; Chen, Feng; Kim, Hyun-Jin

    2017-05-01

    The effects of purified salt (PS) and mineral-rich sea salt (MRS), both with different mineral profiles, on kimchi fermentation were studied using a culture-dependent 16S rRNA sequencing technique and mass-based metabolomic analysis. The different mineral profiles in the fermentation medium caused changes in the bacterial profiles of the 2 kimchi products. An increase of Leuconostoc species in MRS-kimchi decreased the Lactobacillus/Leuconostoc ratio, which led to changes in metabolites (including sugars, amino acids, organic acids, lipids, sulfur compounds, and terpenoids) associated with kimchi quality. Although further studies on the relationship between these salt types and kimchi fermentation are needed, these results suggested that the MRS treatment had positively affected the changes of the kimchi mineral contents, bacterial growth, and metabolite profiles, which are linked to kimchi quality. © 2017 Institute of Food Technologists®.

  12. Formation and Change of Chloroplast-Located Plant Metabolites in Response to Light Conditions

    Directory of Open Access Journals (Sweden)

    Yiyong Chen

    2018-02-01

    Full Text Available Photosynthesis is the central energy conversion process for plant metabolism and occurs within mature chloroplasts. Chloroplasts are also the site of various metabolic reactions involving amino acids, lipids, starch, and sulfur, as well as where the production of some hormones takes place. Light is one of the most important environmental factors, acting as an essential energy source for plants, but also as an external signal influencing their growth and development. Plants experience large fluctuations in the intensity and spectral quality of light, and many attempts have been made to improve or modify plant metabolites by treating them with different light qualities (artificial lighting or intensities. In this review, we discuss how changes in light intensity and wavelength affect the formation of chloroplast-located metabolites in plants.

  13. Lichen secondary metabolite evernic acid as potential quorum sensing inhibitor against Pseudomonas aeruginosa.

    Science.gov (United States)

    Gökalsın, Barış; Sesal, Nüzhet Cenk

    2016-09-01

    Cystic Fibrosis is a genetic disease and it affects the respiratory and digestive systems. Pseudomonas aeruginosa infections in Cystic Fibrosis are presented as the main cause for high mortality and morbidity rates. Pseudomonas aeruginosa populations can regulate their virulence gene expressions via the bacterial communication system: quorum sensing. Inhibition of quorum sensing by employing quorum sensing inhibitors can leave the bacteria vulnerable. Therefore, determining natural sources to obtain potential quorum sensing inhibitors is essential. Lichens have ethnobotanical value for their medicinal properties and it is possible that their secondary metabolites have quorum sensing inhibitor properties. This study aims to investigate an alternative treatment approach by utilizing lichen secondary metabolite evernic acid to reduce the expressions of Pseudomonas aeruginosa virulence factors by inhibiting quorum sensing. For this purpose, fluorescent monitor strains were utilized for quorum sensing inhibitor screens and quantitative reverse-transcriptase PCR analyses were conducted for comparison. Results indicate that evernic acid is capable of inhibiting Pseudomonas aeruginosa quorum sensing systems.

  14. Methionine Metabolites in Patients With Sepsis.

    Science.gov (United States)

    Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

    2018-01-01

    Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

  15. 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...

  16. Towards systems metabolic engineering of streptomycetes for secondary metabolites production

    DEFF Research Database (Denmark)

    Robertsen, Helene Lunde; Weber, Tilmann; Kim, Hyun Uk

    2017-01-01

    Streptomycetes are known for their inherent ability to produce pharmaceutically relevant secondary metabolites. Discovery of medically useful, yet novel compounds has become a great challenge due to frequent rediscovery of known compounds and a consequent decline in the number of relevant clinical...... of streptomycetes for uncovering their hidden potential to produce novel compounds and for the improved production of secondary metabolites....

  17. Pharmacokinetics of ifosfamide and some metabolites in children

    NARCIS (Netherlands)

    Kaijser, G. P.; de Kraker, J.; Bult, A.; Underberg, W. J.; Beijnen, J. H.

    1998-01-01

    The pharmacokinetics of ifosfamide and some metabolites in children was investigated. The patients received various doses of ifosfamide, mostly by continuous infusion, over several days. The penetration of ifosfamide and its metabolites into the cerebrospinal fluid was also studied in four cases.

  18. Aspergillus flavus secondary metabolites: more than just aflatoxins

    Science.gov (United States)

    Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of t...

  19. Effect of metabolites produced by Trichoderma species against ...

    African Journals Online (AJOL)

    Metabolites released from Trichoderma viride, T. polysporum, T. hamatum and T. aureoviride were tested in culture medium against Ceratocystis paradoxa, which causes black seed rot in oil palm sprouted seeds. The Trichoderma metabolites had similar fungistatic effects on the growth of C. paradoxa except those from T.

  20. 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...

  1. Automated de novo metabolite identification with mass spectrometry and cheminformatics

    NARCIS (Netherlands)

    Peironcely Miguel, Julio Eduardo

    2014-01-01

    In this thesis new algorithms and methods that enable the de novo identification of metabolites have been developed. The aim was to find methods to propose candidate structures for unknown metabolites using MSn data as starting point. These methods have been integrated into a semi-automated pipeline

  2. Fatty acid metabolites in rapidly proliferating breast cancer.

    Directory of Open Access Journals (Sweden)

    Joseph T O'Flaherty

    Full Text Available 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.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.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.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.

  3. Influence of abiotic stress signals on secondary metabolites in plants

    Science.gov (United States)

    Ramakrishna, Akula; Ravishankar, Gokare Aswathanarayana

    2011-01-01

    Plant secondary metabolites are unique sources for pharmaceuticals, food additives, flavors, and industrially important biochemicals. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Secondary metabolites play a major role in the adaptation of plants to the environment and in overcoming stress conditions. Environmental factors viz. temperature, humidity, light intensity, the supply of water, minerals, and CO2 influence the growth of a plant and secondary metabolite production. Drought, high salinity, and freezing temperatures are environmental conditions that cause adverse effects on the growth of plants and the productivity of crops. Plant cell culture technologies have been effective tools for both studying and producing plant secondary metabolites under in vitro conditions and for plant improvement. This brief review summarizes the influence of different abiotic factors include salt, drought, light, heavy metals, frost etc. on secondary metabolites in plants. The focus of the present review is the influence of abiotic factors on secondary metabolite production and some of important plant pharmaceuticals. Also, we describe the results of in vitro cultures and production of some important secondary metabolites obtained in our laboratory. PMID:22041989

  4. Profiling and Identification of the Metabolites of Evodiamine in Rats ...

    African Journals Online (AJOL)

    linear ion trap Orbitrap mass spectrometer (UPLC-LTQ-Orbitrap) method to profile and identify the metabolites of evodiamine in ... Keywords: Evodiamine, Ultra–performance liquid chromatography with linear ion trap-Orbitrap,. Hydroxyevodiamine ..... janthinellum and its application for metabolite identification in rat urine.

  5. Prototype of an intertwined secondary-metabolite supercluster

    Science.gov (United States)

    Phillipp Wiemann; Chun-Jun. Guo; Jonathan M. Palmer; Relebohile Sekonyela; Clay C.C. Wang; Nancy P. Keller

    2013-01-01

    The hallmark trait of fungal secondary-metabolite gene clusters is well established, consisting of contiguous enzymatic and often regulatory gene(s) devoted to the production of a metabolite of a specific chemical class. Unexpectedly, we have found a deviation from this motif in a subtelomeric region of Aspergillus fumigatus. This region, under the...

  6. Isolation and identification of two galangin metabolites from rat urine ...

    African Journals Online (AJOL)

    treatment of obesity and diabetes [3-4]. Natural products such as ... rat urine. In addition, the effects of these two metabolites on lipid ..... its five metabolites using ultra-fast liquid chromatography electrospray ionization tandem mass spectrometry to investigate influence of multiple-dose and food. J Chromatogr A 2014; 1358: ...

  7. 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,…

  8. 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

  9. Mycelial growth and antibacterial metabolite production by wild ...

    African Journals Online (AJOL)

    Russula sp. and Pycnoporus cinnabarinus (wild mushrooms) were subjected to laboratory cultivation by spore germination and tissue culturing on Sabouraud dextrose agar plates. Subsequently, the growth and production of metabolite(s) were monitored in submerged fermentation for 7days using agar diffusion method.

  10. The WEIZMASS spectral library for high-confidence metabolite identification

    NARCIS (Netherlands)

    Shahaf, Nir; Rogachev, Ilana; Heinig, Uwe; Meir, Sagit; Malitsky, Sergey; Battat, Maor; Wyner, Hilary; Zheng, Shuning; Wehrens, Ron; Aharoni, Asaph

    2016-01-01

    Annotation of metabolites is an essential, yet problematic, aspect of mass spectrometry (MS)-based metabolomics assays. The current repertoire of definitive annotations of metabolite spectra in public MS databases is limited and suffers from lack of chemical and taxonomic diversity. Furthermore,

  11. Social networking and inequality: the role of clustered networks

    OpenAIRE

    Emanuela D'Angelo; Marco Lilla

    2010-01-01

    The paper aims to analyse how income inequality affects social networking in 14 European countries. By using the European Community Household Panel, we introduce new evidence to test the network-inequality nexus and construct inequality indexes directly from the microdata as well their decomposition. We explore how total income inequality is related to three specific levels of social networking; then, we introduce the 'clustered network' definition, decomposing total income inequality based o...

  12. Affective Maps

    DEFF Research Database (Denmark)

    Salovaara-Moring, Inka

    . In particular, mapping environmental damage, endangered species, and human made disasters has become one of the focal point of affective knowledge production. These ‘more-than-humangeographies’ practices include notions of species, space and territory, and movement towards a new political ecology. This type...... of digital cartographies has been highlighted as the ‘processual turn’ in critical cartography, whereas in related computational journalism it can be seen as an interactive and iterative process of mapping complex and fragile ecological developments. This paper looks at computer-assisted cartography as part...

  13. Borna disease virus infection perturbs energy metabolites and amino acids in cultured human oligodendroglia cells.

    Directory of Open Access Journals (Sweden)

    Rongzhong Huang

    Full Text Available BACKGROUND: Borna disease virus is a neurotropic, non-cytolytic virus that has been widely employed in neuroscientific research. Previous studies have revealed that metabolic perturbations are associated with Borna disease viral infection. However, the pathophysiological mechanism underlying its mode of action remains unclear. METHODOLOGY: Human oligodendroglia cells infected with the human strain Borna disease virus Hu-H1 and non-infected matched control cells were cultured in vitro. At day 14 post-infection, a proton nuclear magnetic resonance-based metabonomic approach was used to differentiate the metabonomic profiles of 28 independent intracellular samples from Borna disease virus-infected cells (n = 14 and matched control cells (n = 14. Partial least squares discriminant analysis was performed to demonstrate that the whole metabonomic patterns enabled discrimination between the two groups, and further statistical testing was applied to determine which individual metabolites displayed significant differences between the two groups. FINDINGS: Metabonomic profiling revealed perturbations in 23 metabolites, 19 of which were deemed individually significant: nine energy metabolites (α-glucose, acetate, choline, creatine, formate, myo-inositol, nicotinamide adenine dinucleotide, pyruvate, succinate and ten amino acids (aspartate, glutamate, glutamine, glycine, histidine, isoleucine, phenylalanine, threonine, tyrosine, valine. Partial least squares discriminant analysis demonstrated that the whole metabolic patterns enabled statistical discrimination between the two groups. CONCLUSION: Borna disease viral infection perturbs the metabonomic profiles of several metabolites in human oligodendroglia cells cultured in vitro. The findings suggest that Borna disease virus manipulates the host cell's metabolic network to support viral replication and proliferation.

  14. Influence of colour type and previous cultivation on secondary metabolites in hypocotyls and leaves of maca (Lepidium meyenii Walpers).

    Science.gov (United States)

    Clément, Céline; Diaz Grados, Diego A; Avula, Bharathi; Khan, Ihklas A; Mayer, Andrea C; Ponce Aguirre, Dante D; Manrique, Ivan; Kreuzer, Michael

    2010-04-15

    Maca is an Andean crop of the Brassicaceae family which is mainly known for its fertility-enhancing properties following consumption. The hypocotyls display various colours ranging from white to black. Each colour has different biological effects. The aim of this study was to analyse the concentrations of major secondary metabolites in hypocotyls and leaves of maca in a controlled planting experiment in the Peruvian Andes at 4130 m above sea level. The effects of colour type and of previous cultivation of the field were examined. In the hypocotyls, the colour type effect was significant for most secondary metabolites; exceptions were beta-sitosterol and campesterol. The lead-coloured, yellow and violet maca hypocotyls were rich in glucosinolates, macaene and macamides, respectively. Previous cultivation affected macaene, campesterol and indole glucosinolate concentrations. Effects on metabolite concentrations in the leaves were minor. Hypocotyls were richer in macaene, macamides and glucosinolates than were leaves, and were poorer in beta-sitosterol and total phenols. Colour type has to be considered in maca production, as colour associates with variations in concentrations of distinct bioactive metabolites. Leaves may be interesting for animal nutrition purposes as they contain essentially the same secondary metabolites as the hypocotyls but in clearly lower concentrations. (c) 2010 Society of Chemical Industry.

  15. Biological treatment options for cyanobacteria metabolite removal--a review.

    Science.gov (United States)

    Ho, Lionel; Sawade, Emma; Newcombe, Gayle

    2012-04-01

    The treatment of cyanobacterial metabolites can consume many resources for water authorities which can be problematic especially with the recent shift away from chemical- and energy-intensive processes towards carbon and climate neutrality. In recent times, there has been a renaissance in biological treatment, in particular, biological filtration processes, for cyanobacteria metabolite removal. This in part, is due to the advances in molecular microbiology which has assisted in further understanding the biodegradation processes of specific cyanobacteria metabolites. However, there is currently no concise portfolio which captures all the pertinent information for the biological treatment of a range of cyanobacterial metabolites. This review encapsulates all the relevant information to date in one document and provides insights into how biological treatment options can be implemented in treatment plants for optimum cyanobacterial metabolite removal. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. 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....... Analysis of the fermentation medium extract was performed using an HPLC-PDA-MS-SPE-NMR hyphenated system, which led to the identification of a total of eight metabolites (1-8), six of which are new. Most of the metabolites are structurally related and are derivatives of benzo[c]oxepin, rare among natural...... supported by time-dependent density-functional theory calculations (B3LYP/TZVP level). This work demonstrates that a largely complete structure elucidation of numerous metabolites present in a raw fermentation medium extract can be performed by the HPLC-SPE-NMR technique using only a small amount...

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... 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...

  18. RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites.

    Science.gov (United States)

    Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K; Mathé, Ewy A

    2018-02-22

    The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be

  19. Decrease of intracellular pH as possible mechanism of embryotoxicity of glycol ether alkoxyacetic acid metabolites

    International Nuclear Information System (INIS)

    Louisse, Jochem; Bai Yanqing; Verwei, Miriam; Sandt, Johannes J.M. van de; Blaauboer, Bas J.; Rietjens, Ivonne M.C.M.

    2010-01-01

    Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabolites using the methoxyacetic acid (MAA) metabolite of ethylene glycol monomethyl ether as the model compound. The results obtained demonstrate an MAA-induced decrease of the intracellular pH (pH i ) of embryonic BALB/c-3T3 cells as well as of embryonic stem (ES)-D3 cells, at concentrations that affect ES-D3 cell differentiation. These results suggest a mechanism for MAA-mediated embryotoxicity similar to the mechanism of embryotoxicity of the drugs valproic acid and acetazolamide (ACZ), known to decrease the pH i in vivo, and therefore used as positive controls. The embryotoxic alkoxyacetic acid metabolites ethoxyacetic acid, butoxyacetic acid and phenoxyacetic acid also caused an intracellular acidification of BALB/c-3T3 cells at concentrations that are known to inhibit ES-D3 cell differentiation. Two other embryotoxic compounds, all-trans-retinoic acid and 5-fluorouracil, did not decrease the pH i of embryonic cells at concentrations that affect ES-D3 cell differentiation, pointing at a different mechanism of embryotoxicity of these compounds. MAA and ACZ induced a concentration-dependent inhibition of ES-D3 cell differentiation, which was enhanced by amiloride, an inhibitor of the Na + /H + -antiporter, corroborating an important role of the pH i in the embryotoxic mechanism of both compounds. Together, the results presented indicate that a decrease of the pH i may be the mechanism of embryotoxicity of the alkoxyacetic acid metabolites of the glycol ethers.

  20. Macroecology of pollination networks

    DEFF Research Database (Denmark)

    Nielsen, Kristian Trøjelsgaard; Olesen, Jens Mogens

    2013-01-01

    towards the tropics, and that network topology would be affected by current climate. Location Global. Methods Each network was organized as a presence/absence matrix, consisting of P plant species, A pollinator species and their links. From these matrices, network parameters were estimated. Additionally...... peaked at mid-latitude whereas modularity decreased linearly. Both patterns are suggestive of a more specialized interaction structure towards the tropics. In particular, mean annual precipitation appeared influential on network topology as both nestedness and modularity varied significantly. Importantly......Aim Interacting communities of species are organized into complex networks, and network analysis is reckoned to be a strong tool for describing their architecture. Many species assemblies show strong macroecological patterns, e.g. increasing species richness with decreasing latitude, but whether...

  1. Gluconeogenic supplements do not affect production, reproductive traits and blood metabolite of holstein cows during the transition period Produtos gliconeogênicos não afetam respostas produtivas, reprodutivas e sangüínea de vacas holandesas em transição

    Directory of Open Access Journals (Sweden)

    Paulo Garcez de Oliveira

    2004-01-01

    Full Text Available The use of gluconeogenic supplements for dairy cows during the transition period has produced contradictory responses in the literature, making it difficult to recommend them. The objective of this trial was to evaluate supplementation with propylene glycol (PG, calcium propionate (CP, and "Dairy Power Drench®" (DR on the transitional period of Holstein cows. Parameters studied were variation of body condition score (BCS, body weight (BW, milk production (MP, reproductive efficiency and nonesterified fatty acid concentration (NEFA. One hundred and sixty five animals from two commercial herds were used. Treatments consisted of: C- Control; DR- administration of "Dairy Power Drench®" (3 applications during postpartum; CP- daily administration of calcium propionate (500 g; PG- daily administration of propylene glycol (500 mL. Variation sources studied were the effect of treatments and blocks as function of farm and parity. No interaction between time (weeks and treatments, or treatment effects, were found for BCS. However, there was a quadratic effect of time. Body weight and its variation were not affected by treatment nor by the time × treatment interaction. However, a quadratic effect of time was observed. An interaction time × treatment was observed on MP, but possible differences within each week were not detected. Treatments also did not affect reproductive efficiency parameters. On average, the number of days to first detected postpartum estrus was 69.5, with 2.23 services per conception and 172.6 days open. The mean concentration of nonesterified fatty acids was 376.6 mmol L-1 and no effect of the interaction time × treatment, or of treatment, was observed. However, a linear effect was observed with time, with a decrease of 48.2 mmol L-1 per week.O uso de produtos gliconeogênicos para vacas leiteiras no período de transição tem gerado respostas contraditórias na literatura, dificultando a sua recomendação. O objetivo deste

  2. Plasma Metabolite Profiles in Response to Chronic Exercise.

    Science.gov (United States)

    Brennan, Andrea M; Benson, Mark; Morningstar, Jordan; Herzig, Matthew; Robbins, Jeremy; Gerszten, Robert E; Ross, Robert

    2018-03-05

    High throughput profiling of metabolic status (metabolomics) allows for the assessment of small-molecule metabolites that may participate in exercise-induced biochemical pathways and corresponding cardiometabolic risk modification. We sought to describe the changes in a diverse set of plasma metabolite profiles in patients undergoing chronic exercise training and assess the relationship between metabolites and cardiometabolic response to exercise. A secondary analysis was performed in 216 middle-aged abdominally obese men and women ([mean (SD)], 52.4 (8.0) years) randomized into one of four groups varying in exercise amount and intensity for 6 months duration: high amount high intensity, high amount low intensity, low amount low intensity, and control. 147 metabolites were profiled by liquid chromatography-tandem mass spectrometry. No significant differences in metabolite changes between specific exercise groups were observed; therefore, subsequent analyses were collapsed across exercise groups. There were no significant differences in metabolite changes between the exercise and control groups after 24 weeks at a Bonferroni-adjusted statistical significance (p < 3.0 x 10). Seven metabolites changed in the exercise group compared to the control group at p < 0.05. Changes in several metabolites from distinct metabolic pathways were associated with change in cardiometabolic risk traits, and three baseline metabolite levels predicted changes in cardiometabolic risk traits. Metabolomic profiling revealed no significant plasma metabolite changes between exercise compared to control after 24-weeks at Bonferroni significance. However, we identified circulating biomarkers that were predictive or reflective of improvements in cardiometabolic traits in the exercise group.

  3. Topological Fidelity in Sensor Networks

    OpenAIRE

    Chintakunta, Harish; Krim, Hamid

    2011-01-01

    Sensor Networks are inherently complex networks, and many of their associated problems require analysis of some of their global characteristics. These are primarily affected by the topology of the network. We present in this paper, a general framework for a topological analysis of a network, and develop distributed algorithms in a generalized combinatorial setting in order to solve two seemingly unrelated problems, 1) Coverage hole detection and Localization and 2) Worm hole attack detection ...

  4. Declarative Networking

    CERN Document Server

    Loo, Boon Thau

    2012-01-01

    Declarative Networking is a programming methodology that enables developers to concisely specify network protocols and services, which are directly compiled to a dataflow framework that executes the specifications. Declarative networking proposes the use of a declarative query language for specifying and implementing network protocols, and employs a dataflow framework at runtime for communication and maintenance of network state. The primary goal of declarative networking is to greatly simplify the process of specifying, implementing, deploying and evolving a network design. In addition, decla

  5. Urinary excretion of androgen metabolites, comparison with excretion of radioactive metabolites after injection of [4-14C]testosterone

    International Nuclear Information System (INIS)

    Deslypere, J.P.; Sayed, A.; Vermeulen, A.; Wiers, P.W.

    1981-01-01

    The influence of age on the metabolic pattern of [4- 14 C]testosterone was studied in 20 young and 8 elderly males and compared to the metabolic pattern of endogenous androgens; the latter was also studied in 16 young and 8 elderly women. In both young and elderly males, androsterone and aetiocholanolone glucuronide represent 65% of [4- 14 C]testosterone metabolites: together with their suephoconjugates as well as with 5α- and 5β-androstane-3α, 17β-diol they represent even more than 75% of total urinary metabolites. The 5α/5β ratio of metabolites of [4- 14 C]testosterone was significantly (P 14 C]testosterone metabolites was generally higher than the ratio of metabolites of endogenous androgens, suggesting that the transformation of T to ring A saturated metabolites occurs at least partially in another compartment than the transformation of DHEA to these metabolites. For both [4- 14 C]testosterone and endogenous androgen metabolites we observed a statistically significant reduction of the 5α/5β ratio with age, a general phenomenon in both males and females. This reduction concern also 11-OH-androst-4-ene-3.17-dione metabolism. Neither sex hormone levels, nor specific binding seems to determine this age dependent shift; neither is there convincing evidence for latent hypothyroisism or liver dysfunction in the elderly. An age associated primary decrease of the 5α-reductase activity seems the most likely explanation. (author)

  6. The significance of estradiol metabolites in human corpus luteum physiology.

    Science.gov (United States)

    Devoto, Luigi; Henríquez, Soledad; Kohen, Paulina; Strauss, Jerome F

    2017-07-01

    The human corpus luteum (CL) is a temporary endocrine gland derived from the ovulated follicle. Its formation and limited lifespan is critical for steroid hormone production required to support menstrual cyclicity, endometrial receptivity for successful implantation, and the maintenance of early pregnancy. Endocrine and paracrine-autocrine molecular mechanisms associated with progesterone production throughout the luteal phase are critical for the development, maintenance, regression, and rescue by hCG which sustains CL function into early pregnancy. However, the signaling systems driving the regression of the primate corpus luteum in non-conception cycles are not well understood. Recently, there has been interest in the functional roles of estradiol metabolites (EMs), mostly in estrogen-producing tissues. The human CL produces a number of EMs, and it has been postulated that the EMs acting via paracrine-autocrine pathways affect angiogenesis or LH-mediated events. The present review describes advances in understanding the role of EMs in the functional lifespan and regression of the human CL in non-conception cycles. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Bioactive metabolites from Trichoderma harzianum and Trichoderma longibrachiatum

    Directory of Open Access Journals (Sweden)

    S.C. Chhabra

    2003-12-01

    Full Text Available The tea plant, Camellia sinensis (L. O. Kuntze is an important crop in the agriculturally based economy of Kenya. Many diseases affect the tea plant but the most prevalent is armillaria root rot caused by the fungus Armillaria mellea. Compounds from the fermentation of Trichoderma species in different media were bioassayed against some selected gram-positive and gram-negative bacteria, fungi including Armillaria mellea, a yeast and a Mucor. Compounds obtained from T. harzianum, and T. longibrachiatum when cultured in various media were investigated individually for in-vitro antifungal and antibacterial activities by agar diffusion technique. Some of the compounds produced definite antifungal and antibacterial activities. 2-Phenylethanol (1 and tyrosol (2 obtained from T. harzianum are reported for the first time from Trichoderma species. The most active metabolite isolated from these strains was 6-n-pentyl-α-pyrone (3, which showed the highest antifungal and antibacterial activity and completely inhibited the growth of Armillaria mellea fungus at a concentration of 200 ppm. Compound 4 (sorbicillin exhibited moderate activity against the fungal test organisms.

  8. Zooplankton excretion metabolites stimulate Southern Ocean phytoplankton growth

    KAUST Repository

    Coello-Camba, A.

    2017-04-24

    Warming over Antarctica is leading to changes in the zooplankton communities inhabiting the Southern Ocean. It has been observed that zooplankton not only regulates phytoplankton through grazing, but also through the recycling of nutrients that are essential for phytoplankton growth. In this way, the effects of warming on zooplankton populations will change the amount or proportion at which recycled nutrients are restored. To estimate how the recycled nutrients released by zooplankton populations, dominated by krill (Euphausia superba), amphipods or copepods, affect the phytoplankton uptake and communities, we performed four incubation experiments: two close to the Antarctic Peninsula and two at the Southern Atlantic Ocean. Our results showed a stimulating effect of the addition of metabolites on ammonia removal rates and on the net growth of phytoplankton communities, with different responses amongst the different phytoplankton groups. According to our results, phytoplankton net growth and community composition may be altered if this relevant source of nutrients is lost due to projected changes in the abundance or distribution of these zooplankton populations.

  9. Urban Interaction and Affective Experience

    DEFF Research Database (Denmark)

    Fritsch, Jonas; Brynskov, Martin

    2008-01-01

    in favor of three points in that direction: First we argue that interaction – and the definition of interaction – is central to unfold the potential of digital urban media, from big, shared screens and media facades to small pri-vate, networked mobile and embedded platforms. Then we argue that an affective...

  10. Concurrent conditional clustering of multiple networks: COCONETS.

    Directory of Open Access Journals (Sweden)

    Sabrina Kleessen

    Full Text Available The accumulation of high-throughput data from different experiments has facilitated the extraction of condition-specific networks over the same set of biological entities. Comparing and contrasting of such multiple biological networks is in the center of differential network biology, aiming at determining general and condition-specific responses captured in the network structure (i.e., included associations between the network components. We provide a novel way for comparison of multiple networks based on determining network clustering (i.e., partition into communities which is optimal across the set of networks with respect to a given cluster quality measure. To this end, we formulate the optimization-based problem of concurrent conditional clustering of multiple networks, termed COCONETS, based on the modularity. The solution to this problem is a clustering which depends on all considered networks and pinpoints their preserved substructures. We present theoretical results for special classes of networks to demonstrate the implications of conditionality captured by the COCONETS formulation. As the problem can be shown to be intractable, we extend an existing efficient greedy heuristic and applied it to determine concurrent conditional clusters on coexpression networks extracted from publically available time-resolved transcriptomics data of Escherichia coli under five stresses as well as on metabolite correlation networks from metabolomics data set from Arabidopsis thaliana exposed to eight environmental conditions. We demonstrate that the investigation of the differences between the clustering based on all networks with that obtained from a subset of networks can be used to quantify the specificity of biological responses. While a comparison of the Escherichia coli coexpression networks based on seminal properties does not pinpoint biologically relevant differences, the common network substructures extracted by COCONETS are supported by

  11. [Affective dependency].

    Science.gov (United States)

    Scantamburlo, G; Pitchot, W; Ansseau, M

    2013-01-01

    Affective dependency is characterized by emotional distress (insecure attachment) and dependency to another person with a low self-esteem and reassurance need. The paper proposes a reflection on the definition of emotional dependency and the confusion caused by various denominations. Overprotective and authoritarian parenting, cultural and socio-environmental factors may contribute to the development of dependent personality. Psychological epigenetic factors, such as early socio-emotional trauma could on neuronal circuits in prefronto-limbic regions that are essential for emotional behaviour.We also focus on the interrelations between dependent personality, domestic violence and addictions. The objective for the clinician is to propose a restoration of self-esteem and therapeutic strategies focused on autonomy.

  12. 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

    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...

  13. Biologically driven neural platform invoking parallel electrophoretic separation and urinary metabolite screening.

    Science.gov (United States)

    Page, Tessa; Nguyen, Huong Thi Huynh; Hilts, Lindsey; Ramos, Lorena; Hanrahan, Grady

    2012-06-01

    This work reveals a computational framework for parallel electrophoretic separation of complex biological macromolecules and model urinary metabolites. More specifically, the implementation of a particle swarm optimization (PSO) algorithm on a neural network platform for multiparameter optimization of multiplexed 24-capillary electrophoresis technology with UV detection is highlighted. Two experimental systems were examined: (1) separation of purified rabbit metallothioneins and (2) separation of model toluene urinary metabolites and selected organic acids. Results proved superior to the use of neural networks employing standard back propagation when examining training error, fitting response, and predictive abilities. Simulation runs were obtained as a result of metaheuristic examination of the global search space with experimental responses in good agreement with predicted values. Full separation of selected analytes was realized after employing optimal model conditions. This framework provides guidance for the application of metaheuristic computational tools to aid in future studies involving parallel chemical separation and screening. Adaptable pseudo-code is provided to enable users of varied software packages and modeling framework to implement the PSO algorithm for their desired use.

  14. The urinary metabolites of DINCH® have an impact on the activities of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ.

    Science.gov (United States)

    Engel, Anika; Buhrke, Thorsten; Kasper, Stefanie; Behr, Anne-Cathrin; Braeuning, Albert; Jessel, Sönke; Seidel, Albrecht; Völkel, Wolfgang; Lampen, Alfonso

    2018-05-01

    DINCH ® (di-isononyl cyclohexane-1,2-dicarboxylate) is a non-phthalate plasticizer that has been developed to replace phthalate plasticizers such as DEHP (di-2-ethylhexyl phthalate) or DINP (di-isononyl phthalate). DINCH ® is metabolized to its corresponding monoester and subsequently to oxidized monoester derivatives. These are conjugated to glucuronic acid and subject to urinary excretion. In contrast to DINCH ® , there are almost no toxicological data available regarding its primary and secondary metabolites. The present study aimed at the characterization of potential endocrine properties of DINCH ® and five DINCH ® metabolites by using reporter gene assays to monitor the activity of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ in vitro. DINCH ® itself did not have any effect on the activity of these receptors whereas DINCH ® metabolites were shown to activate all these receptors. In the case of AR, DINCH ® metabolites predominantly enhanced dihydrotestosterone-stimulated AR activity. In the H295R steroidogenesis assay, neither DINCH ® nor any of its metabolites affected estradiol or testosterone synthesis. In conclusion, primary and secondary DINCH ® metabolites exert different effects at the molecular level compared to DINCH ® itself. All these in vitro effects of DINCH ® metabolites, however, were only observed at high concentrations such as 10 μM or above which is about three orders of magnitude above reported DINCH ® metabolite concentrations in human urine. Thus, the in vitro data do not support the notion that DINCH ® or any of the investigated metabolites may exert considerable endocrine effects in vivo at relevant human exposure levels. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Urinary composition and postprandial blood changes in H-secoisolariciresinol diglycoside (SDG) metabolites in rats do not differ between acute and chronic SDG treatments.

    Science.gov (United States)

    Rickard, S E; Thompson, L U

    2000-09-01

    Although chronic exposure to secoisolariciresinol diglycoside (SDG) was shown to alter (3)H-SDG metabolite disposition in rats, the proportion of measured radioactivity attributed to known or unknown SDG metabolites was not determined. Using HPLC and GC-MS, two experiments were conducted to determine the effect of acute (1 d) vs. chronic (10 d) SDG treatment on major urinary metabolites of (3)H-SDG in female, Sprague-Dawley rats (70-72-d-old) over a 48-h period and if new urinary metabolites were detectable in rats fed nonradioactive flaxseed or SDG. A third experiment was conducted to determine changes in postprandial blood levels of (3)H-SDG metabolites over a 24-h period with acute or chronic SDG treatment. Regardless of treatment, enterodiol, enterolactone and secoisolariciresinol accounted for 75-80% of urine radioactivity. Four potential new lignan metabolites, two of which were detected in the urine of rats fed nonradioactive flaxseed or SDG, were found. Type of treatment had no effect on levels of individual urinary metabolites of (3)H-SDG. As observed for plasma lignans in women fed flaxseed, blood radioactivity peaked at 9 h and remained high until 24 h in both treatment groups, suggesting that blood lignan kinetics might be similar with flaxseed or SDG consumption and that they were comparable between humans and rats. In conclusion, the main urinary lignan metabolites were enterodiol, enterolactone and secoisolariciresinol. Urinary composition or blood levels of radioactive lignans were not affected by the duration of SDG exposure. Thus, while chronic SDG exposure alters lignan disposition in rats, it does not change the metabolite profile.

  16. Differential Retention of Gene Functions in a Secondary Metabolite Cluster.

    Science.gov (United States)

    Reynolds, Hannah T; Slot, Jason C; Divon, Hege H; Lysøe, Erik; Proctor, Robert H; Brown, Daren W

    2017-08-01

    In fungi, distribution of secondary metabolite (SM) gene clusters is often associated with host- or environment-specific benefits provided by SMs. In the plant pathogen Alternaria brassicicola (Dothideomycetes), the DEP cluster confers an ability to synthesize the SM depudecin, a histone deacetylase inhibitor that contributes weakly to virulence. The DEP cluster includes genes encoding enzymes, a transporter, and a transcription regulator. We investigated the distribution and evolution of the DEP cluster in 585 fungal genomes and found a wide but sporadic distribution among Dothideomycetes, Sordariomycetes, and Eurotiomycetes. We confirmed DEP gene expression and depudecin production in one fungus, Fusarium langsethiae. Phylogenetic analyses suggested 6-10 horizontal gene transfers (HGTs) of the cluster, including a transfer that led to the presence of closely related cluster homologs in Alternaria and Fusarium. The analyses also indicated that HGTs were frequently followed by loss/pseudogenization of one or more DEP genes. Independent cluster inactivation was inferred in at least four fungal classes. Analyses of transitions among functional, pseudogenized, and absent states of DEP genes among Fusarium species suggest enzyme-encoding genes are lost at higher rates than the transporter (DEP3) and regulatory (DEP6) genes. The phenotype of an experimentally-induced DEP3 mutant of Fusarium did not support the hypothesis that selective retention of DEP3 and DEP6 protects fungi from exogenous depudecin. Together, the results suggest that HGT and gene loss have contributed significantly to DEP cluster distribution, and that some DEP genes provide a greater fitness benefit possibly due to a differential tendency to form network connections. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution 2017. This work is written by US Government employees and is in the public domain in the US.

  17. Social network visualization in epidemiology

    Directory of Open Access Journals (Sweden)

    Nicholas A. Christakis

    2009-09-01

    Full Text Available Epidemiological investigations and interventions are increasingly focusing on social networks. Two aspects of social networks are relevant in this regard: the structure of networks and the function of networks. A better understanding of the processes that determine how networks form and how they operate with respect to the spread of behavior holds promise for improving public health. Visualizing social networks is a key to both research and interventions. Network images supplement statistical analyses and allow the identification of groups of people for targeting, the identification of central and peripheral individuals, and the clarification of the macro-structure of the network in a way that should affect public health interventions. People are inter-connected and so their health is inter-connected. Inter-personal health effects in social networks provide a new foundation for public health

  18. 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.

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

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava; Rajagopalan, NandhaKishore; Tulpan, Dan; Loewen, Michele C

    2016-09-30

    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.

  20. 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.

  1. 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.

  2. 2,2',3,3',6,6'-Hexachlorobiphenyl (PCB 136) is Enantioselectively Oxidized to Hydroxylated Metabolites by Rat Liver Microsomes

    Science.gov (United States)

    Wu, Xianai; Pramanik, Ananya; Duffel, Michael W.; Hrycay, Eugene G.; Bandiera, Stelvio M.; Lehmler, Hans-Joachim; Kania-Korwel, Izabela

    2011-01-01

    Developmental exposure to multiple-ortho substituted polychlorinated biphenyls (PCBs) causes adverse neurodevelopmental outcomes in laboratory animals and humans by mechanisms involving the sensitization of Ryanodine receptors (RyRs). In the case of PCB 136, the sensitization of RyR is enantiospecific, with only (-)-PCB 136 being active. However, the role of enantioselective metabolism in the developmental neurotoxicity of PCB 136 is poorly understood. The present study employed hepatic microsomes from phenobarbital (PB-), dexamethasone (DEX-) and corn oil (VEH-)treated male Sprague-Dawley rats to investigate the hypothesis that PCB 136 atropisomers are enantioselectively metabolized by P450 enzymes to potentially neurotoxic, hydroxylated PCB 136 metabolites. The results demonstrated the time- and isoform-dependent formation of three metabolites, with 5-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-5-ol) being the major metabolite. The formation of 5-OH-PCB 136 increased with the activity of P450 2B enzymes in the microsomal preparation, which is consistent with PCB 136 metabolism by rat P450 2B1. The minor metabolite 4-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-4-ol) was produced by a currently unidentified P450 enzymes. An enantiomeric enrichment of (-)-PCB 136 was observed in microsomal incubations due to the preferential metabolism of (+)-PCB 136 to the corresponding 5-OH-PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl-5-ol) atropisomer. 4-OH-PCB 136 displayed an enrichment of the atropisomer formed from (-)-PCB 136; however, the enrichment of this metabolite atropisomer didn't affect the enantiomeric enrichment of the parent PCB because 4-OH-PCB 136 is only a minor metabolite. Although the formation of 5- and 4-OH-PCB 136 atropisomers increased with time, the enantioselective formation of the OH-PCB metabolites resulted in constant enantiomeric enrichment, especially at later incubation times. These observations not only demonstrate that the chiral signatures of

  3. Direct detection of glucuronide metabolites of lidocaine in sheep urine.

    Science.gov (United States)

    Doran, Gregory S; Smith, Alistair K; Rothwell, Jim T; Edwards, Scott H

    2018-02-15

    The anaesthetic lidocaine is metabolised quickly to produce a series of metabolites, including several hydroxylated metabolites, which are further metabolised by addition of a glucuronic acid moiety. Analysis of these glucuronide metabolites in urine is performed indirectly by cleaving the glucuronic acid group using β-glucuronidase. However, direct analysis of intact glucuronide conjugates is a more straightforward approach as it negates the need for long hydrolysis incubations, and minimises the oxidation of sensitive hydrolysis products, while also distinguishing between the two forms of hydroxylated metabolites. A method was developed to identify three intact glucuronides of lidocaine in sheep urine using LC-MS/MS, which was further confirmed by the synthesis of glucuronide derivatives of 3OH-MEGX and 4OH-LIDO. Direct analysis of urine allowed the detection of the glucuronide metabolites of hydroxylidocaine (OH-LIDO), hydroxyl-monoethylglycinexylidide (OH-MEGX), and hydroxy-2,6-xylidine (OH-XYL). Analysis of urine before and after β-glucuronidase digestion showed that the efficiency of hydrolysis of these glucuronide metabolites may be underestimated in some studies. Analysis of urine in the current study from three different sheep with similar glucuronide metabolite concentrations resulted in different hydrolysis efficiencies, which may have been a result of different levels of substrate binding by matrix components, preventing enzyme cleavage. The use of direct analysis of intact glucuronides has the benefit of being less influenced by these matrix effects, while also allowing analysis of unstable metabolites like 4OH-XYL, which rapidly oxidises after hydrolysis. Additionally, direct analysis is less expensive and less time consuming, while providing more information about the status of hydroxylated metabolites in urine. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  4. Working night shifts affects surgeons' biological rhythm

    DEFF Research Database (Denmark)

    Amirian, Ilda; Andersen, Lærke T; Rosenberg, Jacob

    2015-01-01

    BACKGROUND: Chronic sleep deprivation combined with work during the night is known to affect performance and compromise residents' own safety. The aim of this study was to examine markers of circadian rhythm and the sleep-wake cycle in surgeons working night shifts. METHODS: Surgeons were monitored...... prospectively for 4 days: pre call, on call, post call day 1 (PC1), and post call day 2 (PC2). The urinary metabolite of melatonin and cortisol in saliva were measured to assess the circadian rhythm. Sleep and activity were measured by actigraphy. Subjective measures were assessed by the Karolinska Sleepiness...... Scale and Visual Analog Scale of fatigue, general well-being, and sleep quality. RESULTS: For both metabolite of melatonin and cortisol, a significant difference (P sleep time during the day on call...

  5. 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.

  6. 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.

  7. 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.

  8. Biopotential of secondary metabolites isolated from marine sponge Dendrilla nigra

    Directory of Open Access Journals (Sweden)

    Valentin Bhimba B

    2011-12-01

    Full Text Available Objective: To evaluate the biopotential activity of secondary metabolites from marine sponge Dendrilla nigra (D. nigra collected from the Gulf of Mannar. Objective: Soxhlet extraction method was used to extract the secondary metabolites and various assays were carried out. Results: D. nigra showed potent antibacterial, antioxidant, anti-inflammatory and anticancer activities and it was also subjected for brine shrimp lethality and cytotoxicity assays. The secondary metabolites were characterized by gas chromatography-mass spectrometry (GC-MS analysis. Conclusions: Based on the present study, it can be inferred that the bioassay guided fractionation and purification of D. nigra may come up with potent bioactive drug.

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...

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

    DEFF Research Database (Denmark)

    Andersen, B.; Frisvad, Jens Christian

    2004-01-01

    Fresh tomatoes, homegrown and from supermarkets, with developing fungal lesions were collected. Each lesion was sampled, and the resulting fungal cultures were identified morphologically, and extracted for analyzes of secondary metabolites. The tomatoes were incubated at 25 degreesC for a week....... 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...

  11. Probing of Metabolites in Finely Powdered Plant Material by Direct Laser Desorption Ionization Mass Spectrometry

    Science.gov (United States)

    Musharraf, Syed Ghulam; Ali, Arslan; Choudhary, M. Iqbal; Atta-ur-Rahman

    2014-04-01

    Natural products continue to serve as an important source of novel drugs since the beginning of human history. High-throughput techniques, such as MALDI-MS, can be techniques of choice for the rapid screening of natural products in plant materials. We present here a fast and reproducible matrix-free approach for the direct detection of UV active metabolites in plant materials without any prior sample preparation. The plant material is mechanically ground to a fine powder and then sieved through different mesh sizes. The collected plant material is dispersed using 1 μL solvent on a target plate is directly exposed to Nd:YAG 335 nm laser. The strategy was optimized for the analysis of plant metabolites after study of the different factors affecting the reproducibility and effectiveness of the analysis, including particle sizes effects, types of solvents used to disperse the sample, and the part of the plant analyzed. Moreover, several plant species, known for different classes of metabolites, were screened to establish the generality of the approach. The developed approach was validated by the characterization of withaferin A and nicotine in the leaves of Withania somnifera and Nicotiana tabacum, respectively, through comparison of its MS/MS data with the standard compound. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques were used for the tissue imaging purposes. This approach can be used to directly probe small molecules in plant materials as well as in herbal and pharmaceutical formulations for fingerprinting development.

  12. Grains colonised by moulds: fungal identification and headspace analysis of produced volatile metabolites

    Directory of Open Access Journals (Sweden)

    Maria Paola Tampieri

    2010-01-01

    Full Text Available The aim of this work was to verify if the headspace analysis of fungal volatile compounds produced by some species of Fusarium can be used as a marker of mould presence on maize. Eight samples of maize (four yellow maize from North Italy and four white maize from Hungary, naturally contaminated by Fusarium and positive for the presence of fumonisins, were analyzed to detect moisture content, Aw, volatile metabolites and an enumeration of viable moulds was performed by means of a colony count technique. Headspace samples were analysed using a gas-chromatograph equipped with a capillary column TR-WAX to detect volatile metabolites of moulds. Furthermore macro and microscopic examination of the colonies was performed in order to distinguish, according to their morphology, the genera of the prevalent present moulds. Prevalent mould of eight samples was Fusarium, but other fungi, like Aspergillus, Penicillum and Mucoraceae, were observed. The metabolites produced by F.graminearum and F. moniliforme were Isobutyl-acetate, 3-Methyl-1-butanol and, only at 8 days, 3-Octanone. The incubation time can affect off flavour production in consequence of the presence of other moulds. Further studies on maize samples under different conditions are needed in order to establish the presence of moulds using the count technique and through the identification of volatile compounds.

  13. Differential urinary metabolites related with the severity of major depressive disorder.

    Science.gov (United States)

    Chen, Jian-Jun; Zhou, Chan-Juan; Zheng, Peng; Cheng, Ke; Wang, Hai-Yang; Li, Juan; Zeng, Li; Xie, Peng

    2017-08-14

    Major depressive disorder (MDD) is a common mental disorder that affects a person's general health. However, there is still no objective laboratory test for diagnosing MDD. Here, an integrated analysis of data from our previous studies was performed to identify the differential metabolites in the urine of moderate and severe MDD patients. A dual platform approach (NMR spectroscopy and GC-MS) was used. Consequently, 14 and 22 differential metabolites responsible for separating moderate and severe MDD patients, respectively, from their respective healthy controls (HCs) were identified. Meanwhile, the moderate MDD-specific panel (N-Methylnicotinamide, Acetone, Choline, Citrate, vanillic acid and azelaic acid) and severe MDD-specific panel (indoxyl sulphate, Taurine, Citrate, 3-hydroxyphenylacetic acid, palmitic acid and Lactate) could discriminate moderate and severe MDD patients, respectively, from their respective HCs with high accuracy. Moreover, the differential metabolites in severe MDD were significantly involved in three metabolic pathways and some biofunctions. These results showed that there were divergent urinary metabolic phenotypes in moderate and severe MDD patients, and the identified potential urinary biomarkers might be useful for future developing objective diagnostic tests for MDD diagnosis. Our results could also be helpful for researchers to study the pathogenesis of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Metabolite adjustments in drought tolerant and sensitive soybean genotypes in response to water stress.

    Directory of Open Access Journals (Sweden)

    Sonia Silvente

    Full Text Available Soybean (Glycine max L. is an important source of protein for human and animal nutrition, as well as a major source of vegetable oil. The soybean crop requires adequate water all through its growth period to attain its yield potential, and the lack of soil moisture at critical stages of growth profoundly impacts the productivity. In this study, utilizing (1H NMR-based metabolite analysis combined with the physiological studies we assessed the effects of short-term water stress on overall growth, nitrogen fixation, ureide and proline dynamics, as well as metabolic changes in drought tolerant (NA5009RG and sensitive (DM50048 genotypes of soybean in order to elucidate metabolite adjustments in relation to the physiological responses in the nitrogen-fixing plants towards water limitation. The results of our analysis demonstrated critical differences in physiological responses between these two genotypes, and identified the metabolic pathways that are affected by short-term water limitation in soybean plants. Metabolic changes in response to drought conditions highlighted pools of metabolites that play a role in the adjustment of metabolism and physiology of the soybean varieties to meet drought effects.

  15. Volatile metabolites from microorganisms grown on humid building materials and synthetic media.

    Science.gov (United States)

    Claeson, Anna-Sara; Levin, Jan-Olof; Blomquist, Göran; Sunesson, Anna-Lena

    2002-10-01

    Growth of different microorganisms is often related to dampness in buildings. Both fungi and bacteria produce complicated mixtures of volatile organic compounds that include hydrocarbons, alcohols, ketones, sulfur- and nitrogen-containing compounds etc. Microbially produced substances are one possible explanation of odour problems and negative health effects in buildings affected by microbial growth. A mixture of five fungi, Aspergillus versicolor, Fusarium culmorum, Penicillium chrysogenum, Ulocladium botrytis and Wallemia sebi were grown on three different humid building materials (pinewood, particle board and gypsum board) and on one synthetic medium. Six different sampling methods were used, to be able to collect both non-reactive volatile organic compounds and reactive compounds such as volatile amines, aldehydes and carboxylic acids. Analysis was performed using gas chromatography, high-performance liquid chromatography and ion chromatography, mass spectrometry was used for identification of compounds. The main microbially produced metabolites found on pinewood were ketones (e.g. 2-heptanone) and alcohols (e.g. 2-methyl-1-propanol). Some of these compounds were also found on particle board, gypsum board and the synthetic medium, but there were more differences than similarities between the materials. For example, dimethoxymethane and 1,3,5-trioxepane and some nitrogen containing compounds were found only on particle board. The metabolite production on gypsum board was very low, although some terpenes (e.g. 3-carene) could be identified as fungal metabolites. On all materials, except gypsum board, the emission of aldehydes decreased during microbial growth. No low molecular weight carboxylic acids were identified.

  16. Urinary Metabolite Profiles in Premature Infants Show Early Postnatal Metabolic Adaptation and Maturation

    Directory of Open Access Journals (Sweden)

    Sissel J. Moltu

    2014-05-01

    Full Text Available Objectives: Early nutrition influences metabolic programming and long-term health. We explored the urinary metabolite profiles of 48 premature infants (birth weight < 1500 g randomized to an enhanced or a standard diet during neonatal hospitalization. Methods: Metabolomics using nuclear magnetic resonance spectroscopy (NMR was conducted on urine samples obtained during the first week of life and thereafter fortnightly. Results: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group. Enhanced nutrition did not appear to affect the urine profiles to an extent exceeding individual variation. However, in all infants the glucogenic amino acids glycine, threonine, hydroxyproline and tyrosine increased substantially during the early postnatal period, along with metabolites of the tricarboxylic acid cycle (succinate, oxoglutarate, fumarate and citrate. The metabolite changes correlated with postmenstrual age. Moreover, we observed elevated threonine and glycine levels in first-week urine samples of the small for gestational age (SGA; birth weight < 10th percentile for gestational age as compared to the appropriate for gestational age infants. Conclusion: This first nutri-metabolomics study in premature infants demonstrates that the physiological adaptation during the fetal-postnatal transition as well as maturation influences metabolism during the breastfeeding period. Elevated glycine and threonine levels were found in the first week urine samples of the SGA infants and emerged as potential biomarkers of an altered metabolic phenotype.

  17. Anti-Biofilm and Antivirulence Activities of Metabolites from Plectosphaerella cucumerina against Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Jinwei Zhou

    2017-05-01

    Full Text Available This study reported the efficacy of the metabolites of Plectosphaerella cucumerina, one phyllosphere fungus from Orychophragmus violaceus, against Pseudomonas aeruginosa quorum sensing (QS and QS-regulated biofilms. The minimum inhibitory concentration (MIC of the ethyl acetate (EtOAc extract from P. cucumerina against P. aeruginosa PAO1 was 1.25 mg mL−1. At sub-MIC concentrations, P. cucumerina extract (0.25–1 mg mL−1 not only inhibited biofilm formation but also disrupted preformed biofilms of P. aeruginosa PAO1 without affecting its growth. Fluorescence and scanning electron microscope (SEM showed architectural disruption of the biofilms when treated with P. cucumerina metabolites. Further investigation demonstrated that metabolites in P. cucumerina attenuated the QS-dependent virulence factors. LC-MS/MS spectra coupled with experimentally standard samples suggested that patulin and emodin might act as the principal components possessing anti-biofilm and antivirulence activities. This is the first report of (1 the isolation of P. cucumerina from the phyllosphere of O. violaceus and (2 anti-biofilm, antivirulence, and biofilm disruption activities of this fungus. Thus, this study provides fascinating new pathways for screening antipathogenic agents.

  18. Network cohesion

    OpenAIRE

    Cavalcanti, Tiago Vanderlei; Giannitsarou, Chrysi; Johnson, CR

    2017-01-01

    We define a measure of network cohesion and show how it arises naturally in a broad class of dynamic models of endogenous perpetual growth with network externalities. Via a standard growth model, we show why network cohesion is crucial for conditional convergence and explain that as cohesion increases, convergence is faster. We prove properties of network cohesion and define a network aggregator that preserves network cohesion.

  19. Drug and chemical metabolites in clinical toxicology investigations: the importance of ethylene glycol, methanol and cannabinoid metabolite analyses.

    Science.gov (United States)

    Fraser, Albert D; Coffin, Lawrence; Worth, David

    2002-10-01

    Metabolic pathways in humans have been elucidated for most therapeutic drugs, drugs of abuse, and various chemical/solvents. In most drug overdose cases and chemical exposures, laboratory analysis is directed toward identification and quantitation of the unchanged drug or chemical in a biologic fluid such as serum or whole blood. Specifically, most clinical laboratories routinely screen and quantitate unchanged methanol and/or ethylene glycol in suspected poisonings without toxic metabolite analysis. Martin-Amat established in 1978 that methanol associated toxicity to the optic nerve in human poisonings was due to the toxic metabolite formic acid found in methanol poisonings and not due to the direct action by unchanged methanol. Jacobsen reported in 1981 that ethylene glycol central nervous system and renal toxicity were primarily due to one acidic metabolite (glycolic acid) and not due to unchanged ethylene glycol. The first objective of this review is to describe clinical experience with formic acid and glycolic acid analysis in methanol and ethylene glycol human poisonings. Drug metabolite analysis also provides useful information in the assessment and monitoring of drug use in psychiatry and substance abusing populations. Drug analysis in substance abuse monitoring is focused on urine analysis of one or more major metabolites, and less frequently on the unchanged drug(s). Serial monitoring of the major urinary cannabinoid metabolite (delta(9)-THC-COOH) to creatinine ratios in paired urine specimens (collected at least 24 h apart) could differentiate new marijuana or hashish use from residual cannabinoid metabolite excretion in urine after drug use according to Huestis. The second objective is to demonstrate that creatinine corrected urine specimens positive for cannabinoids may help differentiate new marijuana use from the excretion of residual delta(9) -THC-COOH in chronic users of marijuana or hashish. Analysis of toxic chemical metabolites are helpful in

  20. Impact of nutrient excess and endothelial nitric oxide synthase on the plasma metabolite profile in mice

    Directory of Open Access Journals (Sweden)

    Brian E Sansbury

    2014-11-01

    Full Text Available An increase in calorie consumption is associated with the recent rise in obesity prevalence. However, our current understanding of the effects of nutrient excess on major metabolic pathways appears insufficient to develop safe and effective metabolic interventions to prevent obesity. Hence, we sought to identify systemic metabolic changes caused by nutrient excess and to determine how endothelial nitric oxide synthase (eNOS—which has anti-obesogenic properties—affects systemic metabolism by measuring plasma metabolites. Wild-type (WT and eNOS transgenic (eNOS-TG mice were placed on low fat or high fat diets for six weeks, and plasma metabolites were measured using an unbiased metabolomic approach. High fat feeding in WT mice led to significant increases in fat mass, which was associated with significantly lower plasma levels of 1,5-anhydroglucitol, lysophospholipids, 3-dehydrocarnitine, and bile acids, as well as branched chain amino acids (BCAAs and their metabolites. Plasma levels of several lipids including sphingomyelins, stearoylcarnitine, dihomo-linoleate and metabolites associated with oxidative stress were increased by high fat diet. In comparison with low fat-fed WT mice, eNOS-TG mice showed lower levels of several free fatty acids, but in contrast, the levels of bile acids, amino acids, and BCAA catabolites were increased. When placed on a high fat diet, eNOS overexpressing mice showed remarkably higher levels of plasma bile acids and elevated levels of plasma BCAAs and their catabolites compared with WT mice. Treatment with GW4064, an inhibitor of bile acid synthesis, decreased plasma bile acid levels but was not sufficient to reverse the anti-obesogenic effects of eNOS overexpression. These findings reveal unique metabolic changes in response to high fat diet and eNOS overexpression and suggest that the anti-obesity effects of eNOS are likely independent of changes in the bile acid pool.

  1. Bisphenol A Is More Potent than Phthalate Metabolites in Reducing Pancreatic β-Cell Function

    Directory of Open Access Journals (Sweden)

    Nina Mickelson Weldingh

    2017-01-01

    Full Text Available Bisphenol A (BPA and phthalates are common environmental contaminants that have been proposed to influence incidence and development of types 1 and 2 diabetes. Thus, effects of BPA and three phthalate metabolites (monoisobutyl phthalate (MiBP, mono-n-butyl phthalate (MnBP, and mono-(2-ethylhexyl phthalate (MEHP were studied in the pancreatic β-cell line INS-1E, after 2–72 h of exposure to 5–500 μM. Three endpoints relevant to accelerated development of types 1 or 2 diabetes were investigated: β-cell viability, glucose-induced insulin secretion, and β-cell susceptibility to cytokine-induced cell death. BPA and the phthalate metabolites reduced cellular viability after 72 h of exposure, with BPA as the most potent chemical. Moreover, BPA, MEHP, and MnBP increased insulin secretion after 2 h of simultaneous exposure to chemicals and glucose, with potency BPA > MEHP > MnBP. Longer chemical exposures (24–72 h showed no consistent effects on glucose-induced insulin secretion, and none of the environmental chemicals affected susceptibility to cytokine-induced cell death. Overall, BPA was more potent than the investigated phthalate metabolites in affecting insulin secretion and viability in the INS-1E pancreatic β-cells. In contrast to recent literature, concentrations with relevance to human exposures (1–500 nM did not affect the investigated endpoints, suggesting that this experimental model displayed relatively low sensitivity to environmental chemical exposure.

  2. Changes of primary and secondary metabolites in barley plants exposed to CdO nanoparticles.

    Science.gov (United States)

    Večeřová, Kristýna; Večeřa, Zbyněk; Dočekal, Bohumil; Oravec, Michal; Pompeiano, Antonio; Tříska, Jan; Urban, Otmar

    2016-11-01

    The environmental fate of airborne nanoparticles and their toxicity to plants is not yet fully understood. Pot-grown barley plants with second leaves developed were therefore exposed to CdO nanoparticles (CdONPs) of ecologically relevant size (7-60 nm) and concentration (2.03 ± 0.45 × 10 5  particles cm -3 ) in air for 3 weeks. An experiment was designed to test the effects of different treatments when only leaves (T1); leaves and soil substrate (T2); and leaves, soil, and water supply were exposed to nanoparticles (T3). A fourth, control group of plants was left without treatment (T0). Although CdONPs were directly absorbed by leaves from the air, a part of leaf-allocated Cd was also transported from roots by transpiration flow. Chromatographic assays revealed that CdONPs had a significant effect on total content of primary metabolites (amino acids and saccharides) but no significant effect on total content of secondary metabolites (phenolic compounds, Krebs cycle acids, and fatty acids). In addition, the compositions of individual metabolite classes were affected by CdONP treatment. For example, tryptophan and phenylalanine were the most affected amino acids in both analysed organs, while ferulic acid and isovitexin constituted the polyphenols most affected in leaves. Even though CdONP treatment had no effect on total fatty acids content, there were significant changes in the composition of saturated and unsaturated fatty acids in both the roots and leaves of treated plants. Although the results indicate the most pronounced effect in T3 plants as compared to T1 and T2 plants, even just leaf exposure to CdONPs has the potential to induce changes in plant metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Winery vermicomposts to control the leaching of diuron, imidacloprid and their metabolites: role of dissolved organic carbon content.

    Science.gov (United States)

    Fernández-Bayo, Jesús D; Nogales, Rogelio; Romero, Esperanza

    2015-01-01

    Soil organic amendment addition is an effective practice in Mediterranean areas due to its associated high agricultural benefits and its potential to reduce the pesticide impact on water resources. However, their metabolites have received scarce attention, even when they may pose more risk than their parent compounds. Two winery vermicomposts obtained from spent grape marc (V1) and the mixture vine shoot-biosolid vinasses (V2) have been investigated as low cost organic amendments to minimize the leaching of diuron, imidacloprid and their metabolites in columns packed with a sandy loam (S1) and a silty-clay loam soil (S2) under steady state flow conditions. In the unamended soil columns, leached amounts of diuron were 75% and 53% in S1 and S2, respectively. Its metabolites (3-(3,4-dichlorophenyl)-1-methylurea, DPMU; and 3,4-dichlorophenylurea, DPU) percolated less than 35% of the total applied amount. The amount of the metabolite 3,4-dichloroaniline (DCA) was 2% and 30% for S1 and S2, respectively. Leaching of imidacloprid was 79% and 96% for S1 and S2, respectively, while its metabolite 6-chloronicotinic acid (CNA) was entirely leached. In the vermicompost-amended columns, the leaching of diuron was reduced 2 to 3-fold. DPMU and DPU were also significantly reduced (more than 6-fold). DCA did not appear in any of the leachates of the amended soil columns. Imidacloprid leaching was reduced 1 to 2-folds in the amended columns. The amendments did not affect the transport of CNA. The dissolved organic carbon (DOC) from the vermicomposts did not enhance pesticide transport throughout the soil in any case. This qualitative study presents these vermicomposts as an effective potential low-cost tool in reducing pesticide and metabolite leaching. The next step would be to test them under more realistic conditions.

  4. Genome-scale reconstruction of the Streptococcus pyogenes M49 metabolic network reveals growth requirements and indicates potential drug targets

    NARCIS (Netherlands)

    Levering, J.; Fiedler, T.; Sieg, A.; van Grinsven, K.W.A.; Hering, S.; Veith, N.; Olivier, B.G.; Klett, L.; Hugenholtz, J.; Teusink, B.; Kreikemeyer, B.; Kummer, U.

    2016-01-01

    Genome-scale metabolic models comprise stoichiometric relations between metabolites, as well as associations between genes and metabolic reactions and facilitate the analysis of metabolism. We computationally reconstructed the metabolic network of the lactic acid bacterium Streptococcus pyogenes

  5. Network planning under uncertainties

    Science.gov (United States)

    Ho, Kwok Shing; Cheung, Kwok Wai

    2008-11-01

    One of the main focuses for network planning is on the optimization of network resources required to build a network under certain traffic demand projection. Traditionally, the inputs to this type of network planning problems are treated as deterministic. In reality, the varying traffic requirements and fluctuations in network resources can cause uncertainties in the decision models. The failure to include the uncertainties in the network design process can severely affect the feasibility and economics of the network. Therefore, it is essential to find a solution that can be insensitive to the uncertain conditions during the network planning process. As early as in the 1960's, a network planning problem with varying traffic requirements over time had been studied. Up to now, this kind of network planning problems is still being active researched, especially for the VPN network design. Another kind of network planning problems under uncertainties that has been studied actively in the past decade addresses the fluctuations in network resources. One such hotly pursued research topic is survivable network planning. It considers the design of a network under uncertainties brought by the fluctuations in topology to meet the requirement that the network remains intact up to a certain number of faults occurring anywhere in the network. Recently, the authors proposed a new planning methodology called Generalized Survivable Network that tackles the network design problem under both varying traffic requirements and fluctuations of topology. Although all the above network planning problems handle various kinds of uncertainties, it is hard to find a generic framework under more general uncertainty conditions that allows a more systematic way to solve the problems. With a unified framework, the seemingly diverse models and algorithms can be intimately related and possibly more insights and improvements can be brought out for solving the problem. This motivates us to seek a

  6. Active Traffic Capture for Network Forensics

    Science.gov (United States)

    Slaviero, Marco; Granova, Anna;