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Sample records for adaptation metabolic profiling

  1. Urinary Metabolite Profiles in Premature Infants Show Early Postnatal Metabolic Adaptation and Maturation

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    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.

  2. Transcriptome profiles of the protoscoleces of Echinococcus granulosus reveal that excretory-secretory products are essential to metabolic adaptation.

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    Wei Pan

    2014-12-01

    Full Text Available Cystic hydatid disease (CHD is caused by the larval stages of the cestode and affects humans and domestic animals worldwide. Protoscoleces (PSCs are one component of the larval stages that can interact with both definitive and intermediate hosts. Previous genomic and transcriptomic data have provided an overall snapshot of the genomics of the growth and development of this parasite. However, our understanding of how PSCs subvert the immune response of hosts and maintains metabolic adaptation remains unclear. In this study, we used Roche 454 sequencing technology and in silico secretome analysis to explore the transcriptome profiles of the PSCs from E. granulosus and elucidate the potential functions of the excretory-secretory proteins (ESPs released by the parasite.A large number of nonredundant sequences as unigenes were generated (26,514, of which 22,910 (86.4% were mapped to the newly published E. granulosus genome and 17,705 (66.8% were distributed within the coding sequence (CDS regions. Of the 2,280 ESPs predicted from the transcriptome, 138 ESPs were inferred to be involved in the metabolism of carbohydrates, while 124 ESPs were inferred to be involved in the metabolism of protein. Eleven ESPs were identified as intracellular enzymes that regulate glycolysis/gluconeogenesis (GL/GN pathways, while a further 44 antigenic proteins, 25 molecular chaperones and four proteases were highly represented. Many proteins were also found to be significantly enriched in development-related signaling pathways, such as the TGF-β receptor pathways and insulin pathways.This study provides valuable information on the metabolic adaptation of parasites to their hosts that can be used to aid the development of novel intervention targets for hydatid treatment and control.

  3. Multi-omic profiling of EPO-producing Chinese hamster ovary cell panel reveals metabolic adaptation to heterologous protein production

    DEFF Research Database (Denmark)

    Ley, Daniel; Kazemi Seresht, Ali; Engmark, Mikael

    2015-01-01

    Chinese hamster ovary (CHO) cells are the preferred production host for many therapeutic proteins. The production of heterologous proteins in CHO cells imposes a burden on the host cell metabolism and impact cellular physiology on a global scale. In this work, a multi-omics approach was applied...... to 5 pg/cell/day. Time-course analysis of high- and low-producing clones in chemostat culture revealed rapid adaptation of transcription levels of amino acid catabolic genes in favor of EPO production within nine generations. Interestingly, the adaptation was followed by an increase in specific EPO...

  4. Profiling metabolic networks to study cancer metabolism.

    Science.gov (United States)

    Hiller, Karsten; Metallo, Christian M

    2013-02-01

    Cancer is a disease of unregulated cell growth and survival, and tumors reprogram biochemical pathways to aid these processes. New capabilities in the computational and bioanalytical characterization of metabolism have now emerged, facilitating the identification of unique metabolic dependencies that arise in specific cancers. By understanding the metabolic phenotype of cancers as a function of their oncogenic profiles, metabolic engineering may be applied to design synthetically lethal therapies for some tumors. This process begins with accurate measurement of metabolic fluxes. Here we review advanced methods of quantifying pathway activity and highlight specific examples where these approaches have uncovered potential opportunities for therapeutic intervention. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. C-source metabolic profilings of foodborne Shiga-toxin producing E. coli match serogroup differentiations and highlight functional adaptations.

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    Kerangart, Stéphane; Cournoyer, Benoit; Loukiadis, Estelle

    2018-02-02

    The tropism of pathogenic STEC for foodstuffs and cattle reservoir is related to functional specializations. An investigation of C-source utilization patterns among and between STEC serogroups was performed using omnilog phenotypic microarrays (OM). OM functional groupings were compared with STEC phylogroups, seropathotypes, EFSA's molecular risk assessment groups and serogroups. OM INT reduction activities of 37 STEC strains growing on 190 C-substrates were compared. Each strain had its own specific C-utilization profile but 23% of the substrates was used by all strains, 47% by none, and 30% was variably metabolized. Galactose, mannose, N-acetyl-glucosamine (GlcNAc), and N-acetyl neuraminic acid (Neu5Ac) found in the mucus layer of the bovine small intestine were metabolized by all strains. The 56 most informative substrates divided the C-utilization patterns (CP) into three clusters with: (A) harboring all O157 and O145 strains; (B) all O26 strains, and (C) strains of the other serogroups. Significant correlations between INT reduction values of pair of strains per CP group supported these differentiations. CP of group A and B strains were respectively defective in the use of galactonic acid-γ-lactone and rhamnose. Most CP group C strains grew with l-lyxose. Adjusted Wallace coefficients analyses of the datasets indicated high probabilities for the prediction of the use of glycolic acid, β-hydroxybutyric acid, l-lyxose and d-galactonic acid-γ-lactone and 5-keto-d-gluconic acid by a serogroup. The use of a C-substrate could be predicted from the classification of a strain into a phylogroup or seropathotype. Significantly lower numbers of C-substrates were used by seropathotype A strains like O157 ones. Improvements of STEC identification keys were proposed using the most discriminant C-substrates found in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Multi-omic profiling of EPO producing Chinese hamster ovary cell panel reveals metabolic adaptation to heterologous protein production

    DEFF Research Database (Denmark)

    Ley, Daniel; Kazemi Seresht, Ali; Engmark, Mikael

    Heterologous protein production in CHO cells imposes a burden on the host cell metabolism and impact cellular physiology on a global scale. In this work, a multi-omics approach was applied to characterize the physiological impact of erythropoietin production, and discover production bottlenecks...

  7. Adaptations in the energy metabolism of parasites

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    van Grinsven, K.W.A.|info:eu-repo/dai/nl/304833436

    2009-01-01

    For this thesis fundamental research was performed on the metabolic adaptations found in parasites. Studying the adaptations in parasite metabolisms leads to a better understanding of parasite bioenergetics and can also result in the identification of new anti-parasitic drug targets. We focussed on

  8. Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL: adapting the Partial Phylogenetic Profiling algorithm to scan sequences for signatures that predict protein function

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    Rusch Douglas B

    2010-01-01

    Full Text Available Abstract Background Comparative genomics methods such as phylogenetic profiling can mine powerful inferences from inherently noisy biological data sets. We introduce Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL, a method that applies the Partial Phylogenetic Profiling (PPP approach locally within a protein sequence to discover short sequence signatures associated with functional sites. The approach is based on the basic scoring mechanism employed by PPP, namely the use of binomial distribution statistics to optimize sequence similarity cutoffs during searches of partitioned training sets. Results Here we illustrate and validate the ability of the SIMBAL method to find functionally relevant short sequence signatures by application to two well-characterized protein families. In the first example, we partitioned a family of ABC permeases using a metabolic background property (urea utilization. Thus, the TRUE set for this family comprised members whose genome of origin encoded a urea utilization system. By moving a sliding window across the sequence of a permease, and searching each subsequence in turn against the full set of partitioned proteins, the method found which local sequence signatures best correlated with the urea utilization trait. Mapping of SIMBAL "hot spots" onto crystal structures of homologous permeases reveals that the significant sites are gating determinants on the cytosolic face rather than, say, docking sites for the substrate-binding protein on the extracellular face. In the second example, we partitioned a protein methyltransferase family using gene proximity as a criterion. In this case, the TRUE set comprised those methyltransferases encoded near the gene for the substrate RF-1. SIMBAL identifies sequence regions that map onto the substrate-binding interface while ignoring regions involved in the methyltransferase reaction mechanism in general. Neither method for training set construction requires any

  9. Adaptive User Profiles in Pervasive Advertising Environments

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    Alt, Florian; Balz, Moritz; Kristes, Stefanie; Shirazi, Alireza Sahami; Mennenöh, Julian; Schmidt, Albrecht; Schröder, Hendrik; Goedicke, Michael

    Nowadays modern advertising environments try to provide more efficient ads by targeting costumers based on their interests. Various approaches exist today as to how information about the users' interests can be gathered. Users can deliberately and explicitly provide this information or user's shopping behaviors can be analyzed implicitly. We implemented an advertising platform to simulate an advertising environment and present adaptive profiles, which let users setup profiles based on a self-assessment, and enhance those profiles with information about their real shopping behavior as well as about their activity intensity. Additionally, we explain how pervasive technologies such as Bluetooth can be used to create a profile anonymously and unobtrusively.

  10. Adaptive Evolution of Phosphorus Metabolism in Prochlorococcus

    DEFF Research Database (Denmark)

    Casey, John R; Mardinoglu, Adil; Nielsen, Jens

    2016-01-01

    Inorganic phosphorus is scarce in the eastern Mediterranean Sea, where the high-light-adapted ecotype HLI of the marine picocyanobacterium Prochlorococcus marinus thrives. Physiological and regulatory control of phosphorus acquisition and partitioning has been observed in HLI both in culture and ...... and an extremely high proportion of essential metabolic genes (47%; defined as the percentage of lethal in silico gene knockouts). These strategies are examples of nutrient-controlled adaptive evolution and confer a dramatic growth rate advantage to MED4 in phosphorus-limited regions. ...

  11. The evolution of metabolic profiling in parasitology.

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    Holmes, E

    2010-08-01

    The uses of metabolic profiling technologies such as mass spectrometry and nuclear magnetic resonance spectroscopy in parasitology have been multi-faceted. Traditional uses of spectroscopic platforms focused on determining the chemical composition of drugs or natural products used for treatment of parasitic infection. A natural progression of the use of these tools led to the generation of chemical profiles of the parasite in in vitro systems, monitoring the response of the parasite to chemotherapeutics, profiling metabolic consequences in the host organism and to deriving host-parasite interactions. With the dawn of the post-genomic era the paradigm in many research areas shifted towards Systems Biology and the integration of biomolecular interactions at the level of the gene, protein and metabolite. Although these technologies have yet to deliver their full potential, metabolic profiling has a key role to play in defining diagnostic or even prognostic metabolic signatures of parasitic infection and in deciphering the molecular mechanisms underpinning the development of parasite-induced pathologies. The strengths and weaknesses of the various spectroscopic technologies and analytical strategies are summarized here with respect to achieving these goals.

  12. Rural and urban differences in metabolic profiles in a Cameroonian ...

    African Journals Online (AJOL)

    Rural and urban differences in metabolic profiles in a Cameroonian population. ... to describe and compare the metabolic (fasting blood sugar and lipid profile) ... population, and study the association to anthropometric risk factors of obesity.

  13. MudPIT profiling reveals a link between anaerobic metabolism and the alkaline adaptive response of Listeria monocytogenes EGD-e.

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    Rolf E Nilsson

    Full Text Available Listeria monocytogenes is a foodborne human pathogen capable of causing life-threatening disease in susceptible populations. Previous proteomic analysis we performed demonstrated that different strains of L. monocytogenes initiate a stringent response when subjected to alkaline growth conditions. Here, using multidimensional protein identification technology (MudPIT, we show that in L. monocytogenes EGD-e this response involves an energy shift to anaerobic pathways in response to the extracellular pH environment. Importantly we show that this supports a reduction in relative lag time following an abrupt transition to low oxygen tension culture conditions. This has important implications for the packaging of fresh and ready-to-eat foods under reduced oxygen conditions in environments where potential exists for alkaline adaptation.

  14. Metabolic Profiling of Alpine and Ecuadorian Lichens

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    Verena K. Mittermeier

    2015-10-01

    Full Text Available Non-targeted 1H-NMR methods were used to determine metabolite profiles from crude extracts of Alpine and Ecuadorian lichens collected from their natural habitats. In control experiments, the robustness of metabolite detection and quantification was estimated using replicate measurements of Stereocaulon alpinum extracts. The deviations in the overall metabolite fingerprints were low when analyzing S. alpinum collections from different locations or during different annual and seasonal periods. In contrast, metabolite profiles observed from extracts of different Alpine and Ecuadorian lichens clearly revealed genus- and species-specific profiles. The discriminating functions determining cluster formation in principle component analysis (PCA were due to differences in the amounts of genus-specific compounds such as sticticin from the Sticta species, but also in the amounts of ubiquitous metabolites, such as sugar alcohols or trehalose. However, varying concentrations of these metabolites from the same lichen species e.g., due to different environmental conditions appeared of minor relevance for the overall cluster formation in PCA. The metabolic clusters matched phylogenetic analyses using nuclear ribosomal DNA (nrDNA internal transcribed spacer (ITS sequences of lichen mycobionts, as exemplified for the genus Sticta. It can be concluded that NMR-based non-targeted metabolic profiling is a useful tool in the chemo-taxonomy of lichens. The same approach could also facilitate the discovery of novel lichen metabolites on a rapid and systematical basis.

  15. Adaptive method for electron bunch profile prediction

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    Alexander Scheinker

    2015-10-01

    Full Text Available We report on an experiment performed at the Facility for Advanced Accelerator Experimental Tests (FACET at SLAC National Accelerator Laboratory, in which a new adaptive control algorithm, one with known, bounded update rates, despite operating on analytically unknown cost functions, was utilized in order to provide quasi-real-time bunch property estimates of the electron beam. Multiple parameters, such as arbitrary rf phase settings and other time-varying accelerator properties, were simultaneously tuned in order to match a simulated bunch energy spectrum with a measured energy spectrum. The simple adaptive scheme was digitally implemented using matlab and the experimental physics and industrial control system. The main result is a nonintrusive, nondestructive, real-time diagnostic scheme for prediction of bunch profiles, as well as other beam parameters, the precise control of which are important for the plasma wakefield acceleration experiments being explored at FACET.

  16. Metabolic profiling in disease diagnosis, toxicology and personalized healthcare.

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    Kamleh, M Anas; Spagou, Konstantina; Want, Elizabeth J

    2011-07-01

    Metabolic profiling employs a combination of sophisticated analytical tools to obtain global "untargeted" metabolic profiles from tissues, cells or biofluids. The resulting complex multivariate data are then modeled statistically to reveal differences between classes (e.g. dosed vs. control) and identify discriminatory metabolites. Metabolic profiling has a wide range of applications, encompassing nutrition, disease diagnosis, epidemiology and toxicology, providing insights into altered biological pathways and offering fresh mechanistic perspectives. Further, the untargeted nature of metabolic profiling can allow for new biomarkers of disease or toxic effect to be uncovered. In this review, key metabolic profiling technologies will be introduced and data analysis approaches described briefly. The role of metabolic profiling in disease diagnosis, toxicology and personalized healthcare will be discussed.

  17. Metabolic profiling of Alzheimer's disease brains

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    Inoue, Koichi; Tsutsui, Haruhito; Akatsu, Hiroyasu; Hashizume, Yoshio; Matsukawa, Noriyuki; Yamamoto, Takayuki; Toyo'Oka, Toshimasa

    2013-08-01

    Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.

  18. Global network reorganization during dynamic adaptations of Bacillus subtilis metabolism

    DEFF Research Database (Denmark)

    Buescher, Joerg Martin; Liebermeister, Wolfram; Jules, Matthieu

    2012-01-01

    Adaptation of cells to environmental changes requires dynamic interactions between metabolic and regulatory networks, but studies typically address only one or a few layers of regulation. For nutritional shifts between two preferred carbon sources of Bacillus subtilis, we combined statistical...

  19. 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...... with in silico generated metabolic profiles from a medium-size kinetic model of plant central carbon metabolism. Altogether, due to the small number of identified sensors, our study implies that targeted metabolite analyses may provide the vast majority of relevant information about plant metabolic systems....

  20. Possible stimuli for strength and power adaptation : acute metabolic responses.

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    Crewther, Blair; Cronin, John; Keogh, Justin

    2006-01-01

    The metabolic response to resistance exercise, in particular lactic acid or lactate, has a marked influence upon the muscular environment, which may enhance the training stimulus (e.g. motor unit activation, hormones or muscle damage) and thereby contribute to strength and power adaptation. Hypertrophy schemes have resulted in greater lactate responses (%) than neuronal and dynamic power schemes, suggesting possible metabolic-mediated changes in muscle growth. Factors such as age, sex, training experience and nutrition may also influence the lactate responses to resistance exercise and thereafter, muscular adaptation. Although the importance of the mechanical and hormonal stimulus to strength and power adaptation is well recognised, the contribution of the metabolic stimulus is largely unknown. Relatively few studies for example, have examined metabolic change across neuronal and dynamic power schemes, and not withstanding the fact that those mechanisms underpinning muscular adaptation, in relation to the metabolic stimulus, remain highly speculative. Inconsistent findings and methodological limitations within research (e.g. programme design, sampling period, number of samples) make interpretation further difficult. We contend that strength and power research needs to investigate those metabolic mechanisms likely to contribute to weight-training adaptation. Further research is also needed to examine the metabolic responses to different loading schemes, as well as interactions across age, sex and training status, so our understanding of how to optimise strength and power development is improved.

  1. Metabolic profile at first-time schizophrenia diagnosis

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    Horsdal, Henriette Thisted; Benros, Michael Eriksen; Köhler-Forsberg, Ole

    2017-01-01

    OBJECTIVE: Schizophrenia and/or antipsychotic drug use are associated with metabolic abnormalities; however, knowledge regarding metabolic status and physician's monitoring of metabolic status at first schizophrenia diagnosis is sparse. We assessed the prevalence of monitoring for metabolic blood...... abnormalities and characterized the metabolic profiles in people with a first-time schizophrenia diagnosis. METHODS: This is a population-based cross-sectional study including all adults born in Denmark after January 1, 1955, with their first schizophrenia diagnosis between 2000 and 2012 in the Central Denmark......-time schizophrenia diagnosis were identified, of whom 1,040 (42.4%) were monitored for metabolic abnormalities. Among those monitored, 58.4% had an abnormal lipid profile and 13.8% had an abnormal glucose profile. People who had previously filled prescription(s) for antipsychotic drugs were more likely to present...

  2. The metabolic profile of long-lived Drosophila melanogaster

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    Sarup, Pernille Merete; Pedersen, Simon Metz Mariendal; Nielsen, Niels Chr

    2012-01-01

    and among age groups. Contrary to results found in a previous study of the transcriptome of these lines the metabolic profile did not show a younger pattern in longevity-selected (LS) flies than in same aged control (C) flies. Rather, many of the metabolites affected by age had levels common to older......We investigated the age-related changes in the metabolic profile of male Drosophila melanogaster and compared the metabolic profile of flies selected for increased longevity to that of control flies of equal age. We found clear differences in metabolite composition between selection regimes...

  3. Metabolic Adaptations of Uropathogenic E. coli in the Urinary Tract

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    Riti Mann

    2017-06-01

    Full Text Available Escherichia coli ordinarily resides in the lower gastrointestinal tract in humans, but some strains, known as Uropathogenic E. coli (UPEC, are also adapted to the relatively harsh environment of the urinary tract. Infections of the urine, bladder and kidneys by UPEC may lead to potentially fatal bloodstream infections. To survive this range of conditions, UPEC strains must have broad and flexible metabolic capabilities and efficiently utilize scarce essential nutrients. Whole-organism (or “omics” methods have recently provided significant advances in our understanding of the importance of metabolic adaptation in the success of UPECs. Here we describe the nutritional and metabolic requirements for UPEC infection in these environments, and focus on particular metabolic responses and adaptations of UPEC that appear to be essential for survival in the urinary tract.

  4. Metabolic Adaptations of Uropathogenic E. coli in the Urinary Tract.

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    Mann, Riti; Mediati, Daniel G; Duggin, Iain G; Harry, Elizabeth J; Bottomley, Amy L

    2017-01-01

    Escherichia coli ordinarily resides in the lower gastrointestinal tract in humans, but some strains, known as Uropathogenic E. coli (UPEC), are also adapted to the relatively harsh environment of the urinary tract. Infections of the urine, bladder and kidneys by UPEC may lead to potentially fatal bloodstream infections. To survive this range of conditions, UPEC strains must have broad and flexible metabolic capabilities and efficiently utilize scarce essential nutrients. Whole-organism (or "omics") methods have recently provided significant advances in our understanding of the importance of metabolic adaptation in the success of UPECs. Here we describe the nutritional and metabolic requirements for UPEC infection in these environments, and focus on particular metabolic responses and adaptations of UPEC that appear to be essential for survival in the urinary tract.

  5. Metabolic Adaptations of Uropathogenic E. coli in the Urinary Tract

    Science.gov (United States)

    Mann, Riti; Mediati, Daniel G.; Duggin, Iain G.; Harry, Elizabeth J.; Bottomley, Amy L.

    2017-01-01

    Escherichia coli ordinarily resides in the lower gastrointestinal tract in humans, but some strains, known as Uropathogenic E. coli (UPEC), are also adapted to the relatively harsh environment of the urinary tract. Infections of the urine, bladder and kidneys by UPEC may lead to potentially fatal bloodstream infections. To survive this range of conditions, UPEC strains must have broad and flexible metabolic capabilities and efficiently utilize scarce essential nutrients. Whole-organism (or “omics”) methods have recently provided significant advances in our understanding of the importance of metabolic adaptation in the success of UPECs. Here we describe the nutritional and metabolic requirements for UPEC infection in these environments, and focus on particular metabolic responses and adaptations of UPEC that appear to be essential for survival in the urinary tract. PMID:28642845

  6. Cold climate specialization: adaptive covariation between metabolic rate and thermoregulation in pregnant vipers.

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    Lourdais, Olivier; Guillon, Michaël; Denardo, Dale; Blouin-Demers, Gabriel

    2013-07-02

    We compared thermoregulatory strategies during pregnancy in two congeneric viperid snakes (Vipera berus and Vipera aspis) with parapatric geographic ranges. V. berus is a boreal specialist with the largest known distribution among terrestrial snakes while V. aspis is a south-European species. Despite contrasted climatic affinities, the two species displayed identical thermal preferences (Tset) in a laboratory thermal gradient. Under identical natural conditions, however, V. berus was capable of maintaining Tset for longer periods, especially when the weather was constraining. Consistent with the metabolic cold adaptation hypothesis, V. berus displayed higher standard metabolic rate at all temperatures considered. We used the thermal dependence of metabolic rate to calculate daily metabolic profiles from body temperature under natural conditions. The boreal specialist experienced higher daily metabolic rate and minimized gestation duration chiefly because of differences in the metabolic reaction norms, but also superior thermoregulatory efficiency. Under cold climates, thermal constraints should make precise thermoregulation costly. However, a shift in the metabolic reaction norm may compensate for thermal constraints and modify the cost-benefit balance of thermoregulation. Covariation between metabolic rate and thermoregulation efficiency is likely an important adaptation to cold climates. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Metabolic profile at first-time schizophrenia diagnosis

    DEFF Research Database (Denmark)

    Horsdal, Henriette Thisted; Benros, Michael Eriksen; Köhler-Forsberg, Ole

    2017-01-01

    -time schizophrenia diagnosis were identified, of whom 1,040 (42.4%) were monitored for metabolic abnormalities. Among those monitored, 58.4% had an abnormal lipid profile and 13.8% had an abnormal glucose profile. People who had previously filled prescription(s) for antipsychotic drugs were more likely to present...... an abnormal lipid measure (65.7% vs 46.8%, Pprofile (16.4% vs 10.1%, P=0.01). CONCLUSION: Metabolic abnormalities are common at first schizophrenia diagnosis, particularly among those with previous antipsychotic prescription(s). Increased metabolic abnormalities already present...... abnormalities and characterized the metabolic profiles in people with a first-time schizophrenia diagnosis. METHODS: This is a population-based cross-sectional study including all adults born in Denmark after January 1, 1955, with their first schizophrenia diagnosis between 2000 and 2012 in the Central Denmark...

  8. Transcriptomic Analysis Reveals Selective Metabolic Adaptation of Streptococcus suis to Porcine Blood and Cerebrospinal Fluid

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    Anna Koczula

    2017-02-01

    Full Text Available Streptococcus suis is a zoonotic pathogen that can cause severe pathologies such as septicemia and meningitis in its natural porcine host as well as in humans. Establishment of disease requires not only virulence of the infecting strain but also an appropriate metabolic activity of the pathogen in its host environment. However, it is yet largely unknown how the streptococcal metabolism adapts to the different host niches encountered during infection. Our previous isotopologue profiling studies on S. suis grown in porcine blood and cerebrospinal fluid (CSF revealed conserved activities of central carbon metabolism in both body fluids. On the other hand, they suggested differences in the de novo amino acid biosynthesis. This prompted us to further dissect S. suis adaptation to porcine blood and CSF by RNA deep sequencing (RNA-seq. In blood, the majority of differentially expressed genes were associated with transport of alternative carbohydrate sources and the carbohydrate metabolism (pentose phosphate pathway, glycogen metabolism. In CSF, predominantly genes involved in the biosynthesis of branched-chain and aromatic amino acids were differentially expressed. Especially, isoleucine biosynthesis seems to be of major importance for S. suis in CSF because several related biosynthetic genes were more highly expressed. In conclusion, our data revealed niche-specific metabolic gene activity which emphasizes a selective adaptation of S. suis to host environments.

  9. Transcriptomic Analysis Reveals Selective Metabolic Adaptation of Streptococcus suis to Porcine Blood and Cerebrospinal Fluid.

    Science.gov (United States)

    Koczula, Anna; Jarek, Michael; Visscher, Christian; Valentin-Weigand, Peter; Goethe, Ralph; Willenborg, Jörg

    2017-02-15

    Streptococcus suis is a zoonotic pathogen that can cause severe pathologies such as septicemia and meningitis in its natural porcine host as well as in humans. Establishment of disease requires not only virulence of the infecting strain but also an appropriate metabolic activity of the pathogen in its host environment. However, it is yet largely unknown how the streptococcal metabolism adapts to the different host niches encountered during infection. Our previous isotopologue profiling studies on S. suis grown in porcine blood and cerebrospinal fluid (CSF) revealed conserved activities of central carbon metabolism in both body fluids. On the other hand, they suggested differences in the de novo amino acid biosynthesis. This prompted us to further dissect S. suis adaptation to porcine blood and CSF by RNA deep sequencing (RNA-seq). In blood, the majority of differentially expressed genes were associated with transport of alternative carbohydrate sources and the carbohydrate metabolism (pentose phosphate pathway, glycogen metabolism). In CSF, predominantly genes involved in the biosynthesis of branched-chain and aromatic amino acids were differentially expressed. Especially, isoleucine biosynthesis seems to be of major importance for S. suis in CSF because several related biosynthetic genes were more highly expressed. In conclusion, our data revealed niche-specific metabolic gene activity which emphasizes a selective adaptation of S. suis to host environments.

  10. Innate and Adaptive Immune Cell Metabolism in Tumor Microenvironment.

    Science.gov (United States)

    Wu, Duojiao

    2017-01-01

    During an immune response, leukocytes undergo major changes in growth and function that are tightly coupled to dynamic shifts in metabolic processes. Immunometabolism is an emerging field that investigates the interplay between immunological and metabolic processes. The immune system has a key role to play in controlling cancer initiation and progression. Increasing evidence indicates the immunosuppressive nature of the local environment in tumor. In tumor microenvironment, immune cells collectively adapt in a dynamic manner to the metabolic needs of cancer cells, thus prompting tumorigenesis and resistance to treatments. Here, we summarize the latest insights into the metabolic reprogramming of immune cells in tumor microenvironment and their potential roles in tumor progression and metastasis. Manipulating metabolic remodeling and immune responses may provide an exciting new option for cancer immunotherapy.

  11. Metabolic Profiles in Children During Fasting

    NARCIS (Netherlands)

    van Veen, Merel R.; van Hasselt, Peter M.; de Sain-van der Velden, Monique G. M.; Verhoeven, Nanda; Hofstede, Floris C.; de Koning, Tom J.; Visser, Gepke

    BACKGROUND: Hypoglycemia is one of the most common metabolic derangements in childhood. To establish the cause of hypoglycemia, fasting tolerance tests can be used. Currently available reference values for fasting tolerance tests have limitations in their use in daily practice. OBJECTIVE: The aim of

  12. AMPKα in Exercise-Induced Substrate Metabolism and Exercise Training-Induced Metabolic and Mitochondrial Adaptations

    DEFF Research Database (Denmark)

    Fentz, Joachim

    could also regulate muscle metabolism during exercise and long-term adaptations to exercise training. However, responses to exercise and exercise training are largely normal in AMPK KO/KD mice. At first hand this could mean that AMPK is not important to exercise/exercise training metabolic regulation......-regulated metabolism and exercise training-induced adaptations are abnormal. This could be due to a more complete ablation of AMPK function and perhaps related to the catalytic properires of the α-subunits. In study 1 we show that deletion of both AMPKα subunits in skeletal muscle of mice decreases exerciseinduced......-subunit. It is proposed to be involved in acute exercise-induced regulation of substrate metabolism as well as the adaptations in muscle protein expression that arise from repeated bouts of exercise, i.e. exercise training. Exercise regulates a plethora of signaling pathways in muscle which includes the activation...

  13. MetAssimulo: simulation of realistic NMR metabolic profiles.

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    Muncey, Harriet J; Jones, Rebecca; De Iorio, Maria; Ebbels, Timothy M D

    2010-10-06

    Probing the complex fusion of genetic and environmental interactions, metabolic profiling (or metabolomics/metabonomics), the study of small molecules involved in metabolic reactions, is a rapidly expanding 'omics' field. A major technique for capturing metabolite data is 1H-NMR spectroscopy and this yields highly complex profiles that require sophisticated statistical analysis methods. However, experimental data is difficult to control and expensive to obtain. Thus data simulation is a productive route to aid algorithm development. MetAssimulo is a MATLAB-based package that has been developed to simulate 1H-NMR spectra of complex mixtures such as metabolic profiles. Drawing data from a metabolite standard spectral database in conjunction with concentration information input by the user or constructed automatically from the Human Metabolome Database, MetAssimulo is able to create realistic metabolic profiles containing large numbers of metabolites with a range of user-defined properties. Current features include the simulation of two groups ('case' and 'control') specified by means and standard deviations of concentrations for each metabolite. The software enables addition of spectral noise with a realistic autocorrelation structure at user controllable levels. A crucial feature of the algorithm is its ability to simulate both intra- and inter-metabolite correlations, the analysis of which is fundamental to many techniques in the field. Further, MetAssimulo is able to simulate shifts in NMR peak positions that result from matrix effects such as pH differences which are often observed in metabolic NMR spectra and pose serious challenges for statistical algorithms. No other software is currently able to simulate NMR metabolic profiles with such complexity and flexibility. This paper describes the algorithm behind MetAssimulo and demonstrates how it can be used to simulate realistic NMR metabolic profiles with which to develop and test new data analysis techniques

  14. MetAssimulo:Simulation of Realistic NMR Metabolic Profiles

    Directory of Open Access Journals (Sweden)

    De Iorio Maria

    2010-10-01

    Full Text Available Abstract Background Probing the complex fusion of genetic and environmental interactions, metabolic profiling (or metabolomics/metabonomics, the study of small molecules involved in metabolic reactions, is a rapidly expanding 'omics' field. A major technique for capturing metabolite data is 1H-NMR spectroscopy and this yields highly complex profiles that require sophisticated statistical analysis methods. However, experimental data is difficult to control and expensive to obtain. Thus data simulation is a productive route to aid algorithm development. Results MetAssimulo is a MATLAB-based package that has been developed to simulate 1H-NMR spectra of complex mixtures such as metabolic profiles. Drawing data from a metabolite standard spectral database in conjunction with concentration information input by the user or constructed automatically from the Human Metabolome Database, MetAssimulo is able to create realistic metabolic profiles containing large numbers of metabolites with a range of user-defined properties. Current features include the simulation of two groups ('case' and 'control' specified by means and standard deviations of concentrations for each metabolite. The software enables addition of spectral noise with a realistic autocorrelation structure at user controllable levels. A crucial feature of the algorithm is its ability to simulate both intra- and inter-metabolite correlations, the analysis of which is fundamental to many techniques in the field. Further, MetAssimulo is able to simulate shifts in NMR peak positions that result from matrix effects such as pH differences which are often observed in metabolic NMR spectra and pose serious challenges for statistical algorithms. Conclusions No other software is currently able to simulate NMR metabolic profiles with such complexity and flexibility. This paper describes the algorithm behind MetAssimulo and demonstrates how it can be used to simulate realistic NMR metabolic profiles with

  15. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    Directory of Open Access Journals (Sweden)

    Samuel Rommelaere

    Full Text Available Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting.

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

    Directory of Open Access Journals (Sweden)

    Bénédicte Allam-Ndoul

    2016-05-01

    Full Text Available Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW and overweight/obese (Ov/Ob individuals, with or without metabolic syndrome (MetS. Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1’s (long chain glycerophospholipids metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3’s (medium chain acylcarnitines metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.

  17. Macropinocytosis: A Metabolic Adaptation to Nutrient Stress in Cancer

    Directory of Open Access Journals (Sweden)

    Maria Victoria Recouvreux

    2017-09-01

    Full Text Available Oncogenic mutations, such as Ras mutations, drive not only enhanced proliferation but also the metabolic adaptations that confer to cancer cells the ability to sustain cell growth in a harsh tumor microenvironment. These adaptations might represent metabolic vulnerabilities that can be exploited to develop novel and more efficient cancer therapies. Macropinocytosis is an evolutionarily conserved endocytic pathway that permits the internalization of extracellular fluid via large endocytic vesicles known as macropinosomes. Recently, macropinocytosis has been determined to function as a nutrient-scavenging pathway in Ras-driven cancer cells. Macropinocytic uptake of extracellular proteins, and their further degradation within endolysosomes, provides the much-needed amino acids that fuel cancer cell metabolism and tumor growth. Here, we review the molecular mechanisms that govern the process of macropinocytosis, as well as discuss recent work that provides evidence of the important role of macropinocytosis as a nutrient supply pathway in cancer cells.

  18. Macropinocytosis: A Metabolic Adaptation to Nutrient Stress in Cancer.

    Science.gov (United States)

    Recouvreux, Maria Victoria; Commisso, Cosimo

    2017-01-01

    Oncogenic mutations, such as Ras mutations, drive not only enhanced proliferation but also the metabolic adaptations that confer to cancer cells the ability to sustain cell growth in a harsh tumor microenvironment. These adaptations might represent metabolic vulnerabilities that can be exploited to develop novel and more efficient cancer therapies. Macropinocytosis is an evolutionarily conserved endocytic pathway that permits the internalization of extracellular fluid via large endocytic vesicles known as macropinosomes. Recently, macropinocytosis has been determined to function as a nutrient-scavenging pathway in Ras-driven cancer cells. Macropinocytic uptake of extracellular proteins, and their further degradation within endolysosomes, provides the much-needed amino acids that fuel cancer cell metabolism and tumor growth. Here, we review the molecular mechanisms that govern the process of macropinocytosis, as well as discuss recent work that provides evidence of the important role of macropinocytosis as a nutrient supply pathway in cancer cells.

  19. Ensemble Kinetic Modeling of Metabolic Networks from Dynamic Metabolic Profiles

    Directory of Open Access Journals (Sweden)

    Gengjie Jia

    2012-11-01

    Full Text Available Kinetic modeling of metabolic pathways has important applications in metabolic engineering, but significant challenges still remain. The difficulties faced vary from finding best-fit parameters in a highly multidimensional search space to incomplete parameter identifiability. To meet some of these challenges, an ensemble modeling method is developed for characterizing a subset of kinetic parameters that give statistically equivalent goodness-of-fit to time series concentration data. The method is based on the incremental identification approach, where the parameter estimation is done in a step-wise manner. Numerical efficacy is achieved by reducing the dimensionality of parameter space and using efficient random parameter exploration algorithms. The shift toward using model ensembles, instead of the traditional “best-fit” models, is necessary to directly account for model uncertainty during the application of such models. The performance of the ensemble modeling approach has been demonstrated in the modeling of a generic branched pathway and the trehalose pathway in Saccharomyces cerevisiae using generalized mass action (GMA kinetics.

  20. Mars entry guidance based on an adaptive reference drag profile

    Science.gov (United States)

    Liang, Zixuan; Duan, Guangfei; Ren, Zhang

    2017-08-01

    The conventional Mars entry tracks a fixed reference drag profile (FRDP). To improve the landing precision, a novel guidance approach that utilizes an adaptive reference drag profile (ARDP) is presented. The entry flight is divided into two phases. For each phase, a family of drag profiles corresponding to various trajectory lengths is planned. Two update windows are investigated for the reference drag profile. At each window, the ARDP is selected online from the profile database according to the actual range-to-go. The tracking law for the selected drag profile is designed based on the feedback linearization. Guidance approaches using the ARDP and the FRDP are then tested and compared. Simulation results demonstrate that the proposed ARDP approach achieves much higher guidance precision than the conventional FRDP approach.

  1. Determining the user profile for an adaptable training platform

    CSIR Research Space (South Africa)

    Helbig, M

    2010-10-01

    Full Text Available on their preferred learning style, learning preferences, literacy level and physical disabilities [13][16]. Human-computer interaction (HCI) systems must there- fore take into account this plethora of human factors that influence user interaction, as well..., literacy level and physical disabilities. Included in the profile is the causal relationship each one of these factors has on the adaptation of the user interaction by model- ing the impact on the system input and output modalities. This user profile...

  2. Metabolic profiles of three related Salvia species.

    Science.gov (United States)

    Yang, Dongfeng; Yang, Shushen; Zhang, Yuejin; Liu, Yonghong; Meng, Xianhai; Liang, Zongsuo

    2009-07-01

    Salvia miltiorrhiza Bunge is one of the most important and popular plant of the traditional Chinese medicine (TCM), but Salvia castanea Diels f. tomentosa Stib and Salvia miltiorrhiza Bunge f. alb have also been reported to have the same therapeutic effects as S. miltiorrhiza. To better distinguish between these species, the phytochemical profiles of three Salvia species were investigated by liquid chromatography. All the Salvia species were good sources of tanshinones, with the contents of phenolics being high in S. miltiorrhiza and S. miltiorrhiza f. alb, but not in S. castanea Diels f. tomentosa Stib. These results pave the way for a better phytotherapy exploitation of these plants.

  3. Metabolic Adaption of Ethanol-Tolerant Clostridium thermocellum

    Science.gov (United States)

    Zhu, Xinshu; Cui, Jiatao; Feng, Yingang; Fa, Yun; Zhang, Jingtao; Cui, Qiu

    2013-01-01

    Clostridium thermocellum is a major candidate for bioethanol production via consolidated bioprocessing. However, the low ethanol tolerance of the organism dramatically impedes its usage in industry. To explore the mechanism of ethanol tolerance in this microorganism, systematic metabolomics was adopted to analyse the metabolic phenotypes of a C. thermocellum wild-type (WT) strain and an ethanol-tolerant strain cultivated without (ET0) or with (ET3) 3% (v/v) exogenous ethanol. Metabolomics analysis elucidated that the levels of numerous metabolites in different pathways were changed for the metabolic adaption of ethanol-tolerant C. thermocellum. The most interesting phenomenon was that cellodextrin was significantly more accumulated in the ethanol-tolerant strain compared with the WT strain, although cellobiose was completely consumed in both the ethanol-tolerant and wild-type strains. These results suggest that the cellodextrin synthesis was active, which might be a potential mechanism for stress resistance. Moreover, the overflow of many intermediate metabolites, which indicates the metabolic imbalance, in the ET0 cultivation was more significant than in the WT and ET3 cultivations. This indicates that the metabolic balance of the ethanol-tolerant strain was adapted better to the condition of ethanol stress. This study provides additional insight into the mechanism of ethanol tolerance and is valuable for further metabolic engineering aimed at higher bioethanol production. PMID:23936233

  4. Metabolic profiles in children during fasting.

    Science.gov (United States)

    van Veen, Merel R; van Hasselt, Peter M; de Sain-van der Velden, Monique G M; Verhoeven, Nanda; Hofstede, Floris C; de Koning, Tom J; Visser, Gepke

    2011-04-01

    Hypoglycemia is one of the most common metabolic derangements in childhood. To establish the cause of hypoglycemia, fasting tolerance tests can be used. Currently available reference values for fasting tolerance tests have limitations in their use in daily practice. The aim of this study was to determine the reference values of metabolites involved in glucose homeostasis during fasting in healthy children. This study included a retrospective analysis of 488 fasting tests. All tests of patients (n = 321) with disorders, including metabolic and endocrine disorders, were excluded, as were tests performed in children who were over- or underweight. In 167 fasting tests performed in the study, hypoglycemia was reached in 52 (31%) tests. On the basis of the time until hypoglycemia was reached, 3 age groups could be defined: (1) children aged 0 to 24 months (median 15 months) (n = 49); (2) children aged 25 to 84 months (median 45 months) (n = 79); (3) and children aged 85 to 216 months (median 106 months) (n = 39). In all groups, a significant increase in ketone body levels and a significant decrease in glucose levels in plasma were observed during fasting. Younger children had a faster increase in ketone body levels and a faster decrease in glucose levels in plasma than older children. Reference values of the metabolites involved in glucose homeostasis during fasting in children were generated. Those values can be used to determine whether a child has a normal fasting response. For high-risk children, guidelines concerning maximum fasting time and dietary intervention during illness are of the utmost importance.

  5. Metabolic Risk Profile and Cancer in Korean Men and Women.

    Science.gov (United States)

    Ko, Seulki; Yoon, Seok-Jun; Kim, Dongwoo; Kim, A-Rim; Kim, Eun-Jung; Seo, Hye-Young

    2016-05-01

    Metabolic syndrome is a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease. Associations between metabolic syndrome and several types of cancer have recently been documented. We analyzed the sample cohort data from the Korean National Health Insurance Service from 2002, with a follow-up period extending to 2013. The cohort data included 99 565 individuals who participated in the health examination program and whose data were therefore present in the cohort database. The metabolic risk profile of each participant was assessed based on obesity, high serum glucose and total cholesterol levels, and high blood pressure. The occurrence of cancer was identified using Korean National Health Insurance claims data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for age group, smoking status, alcohol intake, and regular exercise. A total of 5937 cases of cancer occurred during a mean follow-up period of 10.4 years. In men with a high-risk metabolic profile, the risk of colon cancer was elevated (HR, 1.40; 95% CI, 1.14 to 1.71). In women, a high-risk metabolic profile was associated with a significantly increased risk of gallbladder and biliary tract cancer (HR, 2.05; 95% CI, 1.24 to 3.42). Non-significantly increased risks were observed in men for pharynx, larynx, rectum, and kidney cancer, and in women for colon, liver, breast, and ovarian cancer. The findings of this study support the previously suggested association between metabolic syndrome and the risk of several cancers. A high-risk metabolic profile may be an important risk factor for colon cancer in Korean men and gallbladder and biliary tract cancer in Korean women.

  6. Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes.

    Directory of Open Access Journals (Sweden)

    Suzan Wopereis

    Full Text Available BACKGROUND: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. METHODOLOGY: To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. CONCLUSIONS: Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men.

  7. HPLC-MS/MS targeted metabolic profiling reveals distinct metabolic profiles from Staphylococcus aureus small-colony variants.

    Science.gov (United States)

    Wang, Chen; Zhu, Jiangjiang

    2017-08-15

    Staphylococcus aureus is a world-wide health threat due to its prevalence and possible resistance to antibiotic treatment. A variety reasons can contribute to S. aureus antibiotic resistance and one group of phenotypes that may be discovered from S. aureus is named small-colony variants (SCVs). This study focused on applying a HPLC-MS/MS based targeted metabolic profiling approach to detect a set of metabolites that are dysregulated during S. aureus SCVs formation. Over one hundred and eighty metabolites were confidently detected and their difference between S. aureus SCVs and wild type control groups was compared via univariate and multivariate statistical analyses. Twenty metabolites, including 3',5'-cyclic AMP, tyrosine and adenine were identified as SCV specific metabolic features in comparison to the control group. Metabolic profile differences between individually isolated SCV were also observed and compared. Principal component analyses demonstrated clear metabolic profile differentiation between wild type control to SCVs. Metabolic pathway impact analysis also identified multiple metabolic pathways, including alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism, that were significantly impacted during SCV formation. To the best of our knowledge, our study is the very first report to detect a large set of altered metabolites induced by S. aureus SCV formation. We believe our method can be used in combination with genomic, transcriptomic and proteomic approaches to achieve a better understanding of the unique physiological and metabolic changes during S. aureus SCV formation, and to assist the potential future development of targeted treatment for S. aureus SCV infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Adaptive Sensing Based on Profiles for Sensor Systems

    Directory of Open Access Journals (Sweden)

    Yoshiteru Ishida

    2009-10-01

    Full Text Available This paper proposes a profile-based sensing framework for adaptive sensor systems based on models that relate possibly heterogeneous sensor data and profiles generated by the models to detect events. With these concepts, three phases for building the sensor systems are extracted from two examples: a combustion control sensor system for an automobile engine, and a sensor system for home security. The three phases are: modeling, profiling, and managing trade-offs. Designing and building a sensor system involves mapping the signals to a model to achieve a given mission.

  9. Haematological and metabolic profiles of smallholder dairy cows in ...

    African Journals Online (AJOL)

    Haematological and metabolic profiles of smallholder dairy cows in relation to weather patterns in southern highlands of Tanzania. ... and analysed for haemoglobin concentration (Hb), packed cell volume (PCV%), total protein (TP), glucose (Glu), calcium (Ca), inorganic phosphate (Pi) and zinc (Zn) using standard methods ...

  10. Indicators of dairy cow transition risks: Metabolic profiling revisited.

    Science.gov (United States)

    Van Saun, R J

    2016-01-01

    Periparturient disease conditions affecting transition dairy cows have been recognized as a critical contributor to impaired dairy performance and have become a focal point of herd diagnostic investigations. Over the past 40 years use of blood sampling in the form of metabolic profiling has been applied to herd diagnostics with mixed impressions of diagnostic robustness. Research has greatly increased our understanding of underpinning mechanisms related to cow biology, management, environment and their interactions responsible for peripartum diseases. Elevated β-hydroxybutyrate (BHB) concentration (> 1.2 mmol/l) within 7-10 days following calving identifies high risk cows for therapeutic intervention. Herd evaluations with 15-25% of first week fresh cows with elevated BHB indicates significant disease risk and productive losses. Elevated peripartal serum nonesterified fatty acids (NEFA) also indicate increased disease risk. This review discusses documented (BHB, NEFA) and other potential analytes using individual or pooled samples useful for disease risk assessment or nutritional status and their application in risk-based or herd screening methods of herd metabolic profiling diagnostics. A pooled sample approach modified from the original Compton Metabolic Profile allows for more economic assessment of multiple analytes, though interpretation and herd-size application may be limited. Pooled samples between 5 and 10 individuals accurately represent arithmetic means of individuals. Most importantly metabolic profiles must be used in concert with other diagnostic metrics of animal and facility evaluations, body condition scoring and ration evaluation to be fully useful in herd evaluations.

  11. A Personalised Profile-Based Intelligent and Adaptive Energy

    African Journals Online (AJOL)

    MoBateriE: A Personalised Profile-Based Intelligent and Adaptive. Energy Manager. Paper accepted on 11 May 2015. Abstract. Increasing electronic waste has forced the mobile phone industry to .... Turducken is a mobile device architecture which enables always-on availability .... an XML file which describes its structure.

  12. Expression profiling and comparative sequence derived insights into lipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Callow, Matthew J.; Rubin, Edward M.

    2001-12-19

    Expression profiling and genomic DNA sequence comparisons are increasingly being applied to the identification and analysis of the genes involved in lipid metabolism. Not only has genome-wide expression profiling aided in the identification of novel genes involved in important processes in lipid metabolism such as sterol efflux, but the utilization of information from these studies has added to our understanding of the regulation of pathways participating in the process. Coupled with these gene expression studies, cross species comparison, searching for sequences conserved through evolution, has proven to be a powerful tool to identify important non-coding regulatory sequences as well as the discovery of novel genes relevant to lipid biology. An example of the value of this approach was the recent chance discovery of a new apolipoprotein gene (apo AV) that has dramatic effects upon triglyceride metabolism in mice and humans.

  13. Metabolic profiling of triple-negative breast cancer cells reveals metabolic vulnerabilities.

    Science.gov (United States)

    Lanning, Nathan J; Castle, Joshua P; Singh, Simar J; Leon, Andre N; Tovar, Elizabeth A; Sanghera, Amandeep; MacKeigan, Jeffrey P; Filipp, Fabian V; Graveel, Carrie R

    2017-01-01

    Among breast cancers, the triple-negative breast cancer (TNBC) subtype has the worst prognosis with no approved targeted therapies and only standard chemotherapy as the backbone of systemic therapy. Unique metabolic changes in cancer progression provide innovative therapeutic opportunities. The receptor tyrosine kinases (RTKs) epidermal growth factor receptor (EGFR), and MET receptor are highly expressed in TNBC, making both promising therapeutic targets. RTK signaling profoundly alters cellular metabolism by increasing glucose consumption and subsequently diverting glucose carbon sources into metabolic pathways necessary to support the tumorigenesis. Therefore, detailed metabolic profiles of TNBC subtypes and their response to tyrosine kinase inhibitors may identify therapeutic sensitivities. We quantified the metabolic profiles of TNBC cell lines representing multiple TNBC subtypes using gas chromatography mass spectrometry. In addition, we subjected MDA-MB-231, MDA-MB-468, Hs578T, and HCC70 cell lines to metabolic flux analysis of basal and maximal glycolytic and mitochondrial oxidative rates. Metabolic pool size and flux measurements were performed in the presence and absence of the MET inhibitor, INC280/capmatinib, and the EGFR inhibitor, erlotinib. Further, the sensitivities of these cells to modulators of core metabolic pathways were determined. In addition, we annotated a rate-limiting metabolic enzymes library and performed a siRNA screen in combination with MET or EGFR inhibitors to validate synergistic effects. TNBC cell line models displayed significant metabolic heterogeneity with respect to basal and maximal metabolic rates and responses to RTK and metabolic pathway inhibitors. Comprehensive systems biology analysis of metabolic perturbations, combined siRNA and tyrosine kinase inhibitor screens identified a core set of TCA cycle and fatty acid pathways whose perturbation sensitizes TNBC cells to small molecule targeting of receptor tyrosine kinases

  14. Alterations in cancer cell metabolism: the Warburg effect and metabolic adaptation.

    Science.gov (United States)

    Asgari, Yazdan; Zabihinpour, Zahra; Salehzadeh-Yazdi, Ali; Schreiber, Falk; Masoudi-Nejad, Ali

    2015-05-01

    The Warburg effect means higher glucose uptake of cancer cells compared to normal tissues, whereas a smaller fraction of this glucose is employed for oxidative phosphorylation. With the advent of high throughput technologies and computational systems biology, cancer cell metabolism has been reinvestigated over the last decades toward identifying various events underlying "how" and "why" a cancer cell employs aerobic glycolysis. Significant progress has been shaped to revise the Warburg effect. In this study, we have integrated the gene expression of 13 different cancer cells with the genome-scale metabolic network of human (Recon1) based on the E-Flux method, and analyzed them based on constraint-based modeling. Results show that regardless of significant up- and down-regulated metabolic genes, the distribution of metabolic changes is similar in different cancer types. These findings support the theory that the Warburg effect is a consequence of metabolic adaptation in cancer cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Metabolic adaptation of Chlamydia trachomatis to mammalian host cells.

    Science.gov (United States)

    Mehlitz, Adrian; Eylert, Eva; Huber, Claudia; Lindner, Buko; Vollmuth, Nadine; Karunakaran, Karthika; Goebel, Werner; Eisenreich, Wolfgang; Rudel, Thomas

    2017-03-01

    Metabolic adaptation is a key feature for the virulence of pathogenic intracellular bacteria. Nevertheless, little is known about the pathways in adapting the bacterial metabolism to multiple carbon sources available from the host cell. To analyze the metabolic adaptation of the obligate intracellular human pathogen Chlamydia trachomatis, we labeled infected HeLa or Caco-2 cells with 13 C-marked glucose, glutamine, malate or a mix of amino acids as tracers. Comparative GC-MS-based isotopologue analysis of protein-derived amino acids from the host cell and the bacterial fraction showed that C. trachomatis efficiently imported amino acids from the host cell for protein biosynthesis. FT-ICR-MS analyses also demonstrated that label from exogenous 13 C-glucose was efficiently shuffled into chlamydial lipopolysaccharide probably via glucose 6-phosphate of the host cell. Minor fractions of bacterial Ala, Asp, and Glu were made de novo probably using dicarboxylates from the citrate cycle of the host cell. Indeed, exogenous 13 C-malate was efficiently taken up by C. trachomatis and metabolized into fumarate and succinate when the bacteria were kept in axenic medium containing the malate tracer. Together, the data indicate co-substrate usage of intracellular C. trachomatis in a stream-lined bipartite metabolism with host cell-supplied amino acids for protein biosynthesis, host cell-provided glucose 6-phosphate for cell wall biosynthesis, and, to some extent, one or more host cell-derived dicarboxylates, e.g. malate, feeding the partial TCA cycle of the bacterium. The latter flux could also support the biosynthesis of meso-2,6-diaminopimelate required for the formation of chlamydial peptidoglycan. © 2016 John Wiley & Sons Ltd.

  16. Circulating Metabolic Profile of High Producing Holstein Dairy Cows

    Directory of Open Access Journals (Sweden)

    Aliasghar CHALMEH

    2015-07-01

    Full Text Available Assessing the metabolic profile based on the concept that the laboratory measurement of certain circulating components is a tool to evaluate metabolic status of dairy cows. Veterinarian also can evaluate the energy input-output relationships by assessing the metabolic profile to prevent and control of negative energy balance, metabolic disorders and nutritional insufficiencies. In the present study, 25 multiparous Holstein dairy cows were divided to 5 equal groups containing early, mid and late lactation, and far-off and close-up dry. Blood samples were collected from all cows through jugular venipuncture and sera were evaluated for glucose, insulin, β-hydroxybutyric acid (BHBA, non-esterified fatty acid (NEFA, cholesterol, triglyceride (TG, high, low and very low density lipoproteins (HDL, LDL and VLDL. Insulin levels in mid lactation and close-up dry cows were significantly higher than other groups (P<0.05 and the lowest insulin concentration was detected in far-off dry group. Serum concentrations of NEFA and BHBA in early and mid-lactation and close-up dry cows were significantly higher than late lactation and far-off dry animals (P<0.05. Baseline levels of cholesterol in mid and late lactation were significantly higher than other groups. The level of LDL in mid lactation cows was higher than others significantly, and its value in far-off dry cows was significantly lower than other group (P<0.05. It may be concluded that the detected changes among different groups induce commonly by negative energy balance, lactogenesis and fetal growth in each state. The presented metabolic profile can be considered as a tool to assess the energy balance in dairy cows at different physiologic states. It can be used to evaluate the metabolic situations of herd and manage the metabolic and production disorders.

  17. Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population

    Directory of Open Access Journals (Sweden)

    Ellis James K

    2012-06-01

    Full Text Available Abstract Background The 'exposome' represents the accumulation of all environmental exposures across a lifetime. Top-down strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect human health. Metabolic profiling (metabonomics/metabolomics defines an individual's metabolic phenotype, which is influenced by genotype, diet, lifestyle, health and xenobiotic exposure, and could also reveal intermediate biomarkers for disease risk that reflect adaptive response to exposure. We investigated changes in metabolism in volunteers living near a point source of environmental pollution: a closed zinc smelter with associated elevated levels of environmental cadmium. Methods High-resolution 1H NMR spectroscopy (metabonomics was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with lifestyle or biological factors. Urinary levels of 8-oxo-deoxyguanosine were also measured, using mass spectrometry, as a marker of systemic oxidative stress. Results Six urinary metabolites, either associated with mitochondrial metabolism (citrate, 3-hydroxyisovalerate, 4-deoxy-erythronic acid or one-carbon metabolism (dimethylglycine, creatinine, creatine, were associated with cadmium exposure. In particular, citrate levels retained a significant correlation to urinary cadmium and smoking status after controlling for age and sex. Oxidative stress (as determined by urinary 8-oxo-deoxyguanosine levels was elevated in individuals with high cadmium exposure, supporting the hypothesis that heavy metal accumulation was causing mitochondrial dysfunction. Conclusions This study shows evidence that an NMR-based metabolic profiling study in an uncontrolled human population is capable of identifying intermediate biomarkers of response to toxicants at true environmental

  18. [Phase changes of energy metabolism during adaptation to immobilization stress].

    Science.gov (United States)

    Portnichenko, V I; Nosar, V I; Honchar, O O; Opanasenko, H V; Hlazyrin, I D; Man'kovs'ka, I M

    2014-01-01

    In stress, it was showed the organ and tissue changes associated with damage by lipid peroxides, and the disrupted barrier function. As a consequence, it was to lead to a syndrome of "stress-induced lung" and violation of oxygen delivery to the tissues and hypoxia. Purpose of the study was to investigate the dynamics of changes in gas exchange, blood glucose, body temperature, oxidant and antioxidant system activity, as well as mitochondrial respiration by Chance under the influence of chronic stress (6-hour immobilization daily for 3 weeks). It was identified 4 phase changes of energy metabolism in the dynamics of chronic stress. In the first phase, hypomethabolic, instability oxidative metabolism, decreased oxidation of NAD-dependent substrates, significant elevation of FAD-dependent substrates oxidation and low MRU were found. The activity of superoxide dismutase (MnSOD) was increased; it was occurred on a background low activity of glutathione peroxidase, and of misbalanced antioxidant system. After seven immobilizations, second phase-shift in energy metabolism, was observed, and then the third phase (hypermetabolic) started. It was characterized by gradual increase in oxidative metabolism, the restoration of oxidation of NAD-dependent substrates, MRU, as well as optimizing balance of oxidant and antioxidant systems. The fourth phase was started after 15 immobilizations, and characterized by the development of adaptive reactions expressed in increased tolerance of energy metabolism to the impact of immobilization. The results are correlated with changes in the dynamics of blood corticosterone. Thus, it was found the phase character of the energy metabolism rebuilding during the chronic stress.

  19. Expression profiling reveals metabolic and structural components of extraocular muscles.

    Science.gov (United States)

    Fischer, M Dominik; Gorospe, J Rafael; Felder, Edward; Bogdanovich, Sasha; Pedrosa-Domellöf, F; Ahima, Rexford S; Rubinstein, Neal A; Hoffman, Eric P; Khurana, Tejvir S

    2002-01-01

    The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne's muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.

  20. Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes

    NARCIS (Netherlands)

    Wopereis, S.; Rubingh, C.M.; van Erk, M.J.; Verheij, E.R.; van Vliet, T.; Cnubben, N.H.P.; Smilde, A.K.; van der Greef, J.; van Ommen, B.; Hendriks, H.F.J.

    2009-01-01

    Background: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one

  1. Quantifying environmental adaptation of metabolic pathways in metagenomics

    DEFF Research Database (Denmark)

    Gianoulis, Tara A; Raes, Jeroen; Patel, Prianka V

    2009-01-01

    of particular pathways and subnetworks reflects the adaptation of microbial communities across environments and habitats-i.e., how network dynamics relates to environmental features. Previous research has treated environments as discrete, somewhat simplified classes (e.g., terrestrial vs. marine), and searched...... for obvious metabolic differences among them (i.e., treating the analysis as a typical classification problem). However, environmental differences result from combinations of many factors, which often vary only slightly. Therefore, we introduce an approach that employs correlation and regression to relate...... multiple, continuously varying factors defining an environment to the extent of particular microbial pathways present in a geographic site. Moreover, rather than looking only at individual correlations (one-to-one), we adapted canonical correlation analysis and related techniques to define an ensemble...

  2. Forecasting societies' adaptive capacities through a demographic metabolism model

    Science.gov (United States)

    Lutz, Wolfgang; Muttarak, Raya

    2017-03-01

    In seeking to understand how future societies will be affected by climate change we cannot simply assume they will be identical to those of today, because climate and societies are both dynamic. Here we propose that the concept of demographic metabolism and the associated methods of multi-dimensional population projections provide an effective analytical toolbox to forecast important aspects of societal change that affect adaptive capacity. We present an example of how the changing educational composition of future populations can influence societies' adaptive capacity. Multi-dimensional population projections form the human core of the Shared Socioeconomic Pathways scenarios, and knowledge and analytical tools from demography have great value in assessing the likely implications of climate change on future human well-being.

  3. Intercultural Profiles and Adaptation Among Immigrant and Autochthonous Adolescents.

    Science.gov (United States)

    Inguglia, Cristiano; Musso, Pasquale

    2015-02-01

    Few studies examine relationships between intercultural strategies and adaptation among adolescents using a person-oriented approach. Framed from an intercultural psychology perspective, this study used such an approach in order to examine the influence of intercultural profiles, patterns of relationships among variables related to intercultural strategies, on the adaptation of adolescents of both non-dominant and dominant groups. Two hundred and fifty-six adolescents living in Italy and aged from 14 to 18 participated to the study: 127 immigrants from Tunisia (males = 49.61%) and 129 autochthonous (males = 44.19%). Data were collected through self-report questionnaires. Using cluster analytic methods to identify profiles, the results showed that immigrant adolescents were divided in two acculturation profiles, ethnic and integrated-national, with adolescents belonging to the latter showing higher self-esteem, life satisfaction and sociocultural competence than the former. Also among autochthonous adolescents two acculturation expectation profiles were identified, not-multicultural and multicultural, with adolescents belonging to the latter showing higher self-esteem and life satisfaction than the former. Findings highlight the importance of using multiple indicators in order to gain a more comprehensive understanding of the acculturation process as well as suggesting implications for the social policies in this field.

  4. Intercultural Profiles and Adaptation Among Immigrant and Autochthonous Adolescents

    Directory of Open Access Journals (Sweden)

    Cristiano Inguglia

    2015-02-01

    Full Text Available Few studies examine relationships between intercultural strategies and adaptation among adolescents using a person-oriented approach. Framed from an intercultural psychology perspective, this study used such an approach in order to examine the influence of intercultural profiles, patterns of relationships among variables related to intercultural strategies, on the adaptation of adolescents of both non-dominant and dominant groups. Two hundred and fifty-six adolescents living in Italy and aged from 14 to 18 participated to the study: 127 immigrants from Tunisia (males = 49.61% and 129 autochthonous (males = 44.19%. Data were collected through self-report questionnaires. Using cluster analytic methods to identify profiles, the results showed that immigrant adolescents were divided in two acculturation profiles, ethnic and integrated-national, with adolescents belonging to the latter showing higher self-esteem, life satisfaction and sociocultural competence than the former. Also among autochthonous adolescents two acculturation expectation profiles were identified, not-multicultural and multicultural, with adolescents belonging to the latter showing higher self-esteem and life satisfaction than the former. Findings highlight the importance of using multiple indicators in order to gain a more comprehensive understanding of the acculturation process as well as suggesting implications for the social policies in this field.

  5. Reconstruction of metabolic networks from high-throughput metabolite profiling data: in silico analysis of red blood cell metabolism

    OpenAIRE

    Nemenman, Ilya; Escola, G. Sean; Hlavacek, William S.; Unkefer, Pat J.; Unkefer, Clifford J.; Wall, Michael E.

    2007-01-01

    We investigate the ability of algorithms developed for reverse engineering of transcriptional regulatory networks to reconstruct metabolic networks from high-throughput metabolite profiling data. For this, we generate synthetic metabolic profiles for benchmarking purposes based on a well-established model for red blood cell metabolism. A variety of data sets is generated, accounting for different properties of real metabolic networks, such as experimental noise, metabolite correlations, and t...

  6. Magnetic resonance imaging of tumor oxygenation and metabolic profile

    DEFF Research Database (Denmark)

    Krishna, Murali C.; Matsumoto, Shingo; Saito, Keita

    2013-01-01

    which can characterize such features non-invasively and repeatedly will be of significant value in planning treatment as well as monitoring response to treatment. The three techniques based on magnetic resonance imaging (MRI) are reviewed here. Tumor pO2 can be measured by two MRI methods requiring...... an exogenous contrast agent: electron paramagnetic resonance imaging (EPRI) and Overhauser magnetic resonance imaging (OMRI). Tumor metabolic profile can be assessed by a third method, hyperpolarized metabolic MR, based on injection of hyperpolarized biological molecules labeled with 13C or 15N and MR......The tumor microenvironment is distinct from normal tissue as a result of abnormal vascular network characterized by hypoxia, low pH, high interstitial fluid pressure and elevated glycolytic activity. This poses a barrier to treatments including radiation therapy and chemotherapy. Imaging methods...

  7. Metabolic adaptation of Escherichia coli during temperature-induced recombinant protein production: 1. Readjustment of metabolic enzyme synthesis.

    Science.gov (United States)

    Hoffmann, Frank; Weber, Jan; Rinas, Ursula

    2002-11-05

    The metabolic burden and the stress load resulting from temperature-induced production of human basic fibroblast growth factor is connected to an increase in the respiratory activity of recombinant Escherichia coli, thereby reducing the biomass yield. To study the underlying changes in metabolic enzyme synthesis rates, the radiolabeled proteom was subjected to two-dimen- sional gel electrophoresis. After temperature-induction, the cAMP-CRP controlled dehydrogenases of the pyruvate dehydrogenase complex and the tricarboxylic acid cycle (LpdA and SdhA) were induced four times, reaching a maximum 1 h after the temperature upshift. The more abundant tricarboxylic acid cycle dehydrogenases (Icd and Mdh) were initially produced at reduced rates but regained preshift rates within 30 min. The adenylate energy charge dropped immediately after the temperature upshift but recovered within 1 h. Similar profiles in dehydrogenase synthesis rates and adenylate energy charge were found in a control cultivation of a strain carrying the "empty" parental expression vector. Although both strains exhibited significant differences in growth pattern and respiration rates after the temperature upshift, the adaptation of the energetic state of the cells and the synthesis of enzymes from the energy-generating catabolic pathway did not seem to be affected by the strong overproduction of the recombinant growth factor. In contrast, the synthesis rates of enzymes belonging to the biosynthetic machinery, e.g., translational elongation factors, decreased more strongly in the culture synthesizing the recombinant protein. In control and producing culture, synthesis rates of elongation factors paralleled the respective growth rate profiles. Thus, cells seem to readjust their metabolic activities according to their energetic requirements and, if necessary, at the cost of their biosynthetic capabilities. Copyright 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 313-319, 2002.

  8. Influence of the season on the metabolic profile in Chios sheep

    Directory of Open Access Journals (Sweden)

    Igor Dzadzovski

    2015-10-01

    Full Text Available Chios is a breed of sheep selected for milk production, with metabolic features typical for a dairy sheep breed. The energy requirements of pregnant sheep is increase in the last weeks of gestation. Metabolic imbalance in the late pregnancy in sheep, usually causea metabolic disorder known as pregnancy toxemia. Additionally, a pregnant sheep exposed to low environmental temperatures has increased energy demands, due to its adaptation to undesirable environmental conditions. The aim of this study was to compare the metabolic profile of Chios sheep exposed to different environmental conditions. Two groups of ewes were instigated. First group included 8 pregnant ewes with clinical signs of pregnancy toxemia exposed to cold stress during the winter season. The second group included 8 non-pregnant, clinically healthy ewes, that were examined during the non-breeding period, in the spring season. Blood samples were taken and serum concentrations of glucose, beta-hydroxybutirate (BHBA, total protein, albumin, urea, creatinine, triglyceride and cholesterol, as well as activity of AST and ALP were determined. Pregnant ewes exposed to cold stress had significantly lower levels of glucose and total protein, and significantly higher levels of BHBA, albumin and AST in the serum compared to non-pregnant ewes that were in optimal environmental conditions. There was no significant difference between the serum levels of urea, creatinine, cholesterol, triglycerides and ALP among the groups. In conclusion, low environmental temperature and poor feeding during the winter season caused metabolic distress in pregnant ewes during the early winter season.

  9. Gut microbiota composition modifies fecal metabolic profiles in mice.

    Science.gov (United States)

    Zhao, Ying; Wu, Junfang; Li, Jia V; Zhou, Ning-Yi; Tang, Huiru; Wang, Yulan

    2013-06-07

    The gut microbiome is known to be extensively involved in human health and disease. In order to reveal the metabolic relationship between host and microbiome, we monitored recovery of the gut microbiota composition and fecal profiles of mice after gentamicin and/or ceftriaxone treatments. This was performed by employing (1)H nuclear magnetic resonance (NMR)-based metabonomics and denaturing gradient gel electrophoresis (DGGE) fingerprint of gut microbiota. The common features of fecal metabolites postantibiotic treatment include decreased levels of short chain fatty acids (SCFAs), amino acids and primary bile acids and increased oligosaccharides, d-pinitol, choline and secondary bile acids (deoxycholic acid). This suggests suppressed bacterial fermentation, protein degradation and enhanced gut microbial modification of bile acids. Barnesiella, Prevotella, and Alistipes levels were shown to decrease as a result of the antibiotic treatment, whereas levels of Bacteroides, Enterococcus and Erysipelotrichaceae incertae sedis, and Mycoplasma increased after gentamicin and ceftriaxone treatment. In addition, there was a strong correlation between fecal profiles and levels of Bacteroides, Barnesiella, Alistipes and Prevotella. The integration of metabonomics and gut microbiota profiling provides important information on the changes of gut microbiota and their impact on fecal profiles during the recovery after antibiotic treatment. The correlation between gut microbiota and fecal metabolites provides important information on the function of bacteria, which in turn could be important in optimizing therapeutic strategies, and developing potential microbiota-based disease preventions and therapeutic interventions.

  10. Recurring adaptation effect on energy metabolism of atrophic shin muscles

    Directory of Open Access Journals (Sweden)

    Afanasyev М.А.

    2012-06-01

    Full Text Available The article is devoted to recurring adaptation effect on energy metabolism of atrophic shin muscles. The purpose: Investigation of markers of activity of muscular fibers of gravitation-dependent muscles in condition of early posthypoki-netic readaptation. Materials. Muscles-antagonists have been taken from the shin area of hind limbs of a rat. Methods. Immunohistochemical dyeing of myofibrils of different type (I and II on glycogen and triglycerides have been used. Results. We have revealed dynamic changes of the endocellular contents of researched energy substrata on different terms of the period of posthypokinetic restoration. Conclusion. Investigated substrata my serve as adequate functional markers of muscles in the conditions under the study

  11. Phthalate exposure changes the metabolic profile of cardiac muscle cells.

    Science.gov (United States)

    Posnack, Nikki Gillum; Swift, Luther M; Kay, Matthew W; Lee, Norman H; Sarvazyan, Narine

    2012-09-01

    Phthalates are common plasticizers present in medical-grade plastics and other everyday products. They can also act as endocrine-disrupting chemicals and have been linked to the rise in metabolic disorders. However, the effect of phthalates on cardiac metabolism remains largely unknown. We examined the effect of di(2-ethylhexyl)phthalate (DEHP) on the metabolic profile of cardiomyocytes because alterations in metabolic processes can lead to cell dysfunction. Neonatal rat cardiomyocytes were treated with DEHP at a concentration and duration comparable to clinical exposure (50-100 μg/mL, 72 hr). We assessed the effect of DEHP on gene expression using microarray analysis. Physiological responses were examined via fatty acid utilization, oxygen consumption, mitochondrial mass, and Western blot analysis. Exposure to DEHP led to up-regulation of genes associated with fatty acid transport, esterification, mitochondrial import, and β-oxidation. The functional outcome was an increase in myocyte fatty acid-substrate utilization, oxygen consumption, mitochondrial mass, PPARα (peroxisome proliferator-activated receptor α) protein expression, and extracellular acidosis. Treatment with a PPARα agonist (Wy-14643) only partially mimicked the effects observed in DEHP-treated cells. Data suggest that DEHP exposure results in metabolic remodeling of cardiomyocytes, whereby cardiac cells increase their dependence on fatty acids for energy production. This fuel switch may be regulated at both the gene expression and posttranscription levels. Our findings have important clinical implications because chronic dependence on fatty acids is associated with an accumulation in lipid intermediates, lactate, protons, and reactive oxygen species. This dependence can sensitize the heart to ischemic injury and ventricular dysfunction.

  12. Evaluation of different column chemistries for fast urinary metabolic profiling.

    Science.gov (United States)

    Kloos, Dick-Paul; Lingeman, Henk; Niessen, Wilfried M A; Deelder, André M; Giera, Martin; Mayboroda, Oleg A

    2013-05-15

    Fast analytical methodologies are mandatory for large scale metabolic profiling. Here, we present a thorough evaluation of different column chemistries in combination with different mobile phases for fast LC-MS urinary metabolic profiling. Three porous HILIC materials were investigated, next to core-shell C18-, XB-C18- and PFP-RPLC material. The performance of the selected column chemistries was tested in a non-targeted manner with pooled urine samples and in a targeted manner with a set of 54 common urinary metabolites. In order to evaluate the differential behaviour of the tested columns in a targeted manner, we applied a peak scoring algorithm. This algorithm takes into account several quality criteria such as retention time, dead time, peak height and peak shape. In general, HILIC columns generate more retention for polar metabolites. Our results show that the diol-HILIC column outperforms the RPLC columns. However, because of their opposite nature, comprehensive behaviour is observed as well, which was shown by investigating gender differences in a small urinary sample set. All applied column chemistries enabled sufficient peak capacity within a short gradient time. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Metabolic profiling of hypoxic cells revealed a catabolic signature required for cell survival.

    Directory of Open Access Journals (Sweden)

    Christian Frezza

    Full Text Available Hypoxia is one of the features of poorly vascularised areas of solid tumours but cancer cells can survive in these areas despite the low oxygen tension. The adaptation to hypoxia requires both biochemical and genetic responses that culminate in a metabolic rearrangement to counter-balance the decrease in energy supply from mitochondrial respiration. The understanding of metabolic adaptations under hypoxia could reveal novel pathways that, if targeted, would lead to specific death of hypoxic regions. In this study, we developed biochemical and metabolomic analyses to assess the effects of hypoxia on cellular metabolism of HCT116 cancer cell line. We utilized an oxygen fluorescent probe in anaerobic cuvettes to study oxygen consumption rates under hypoxic conditions without the need to re-oxygenate the cells and demonstrated that hypoxic cells can maintain active, though diminished, oxidative phosphorylation even at 1% oxygen. These results were further supported by in situ microscopy analysis of mitochondrial NADH oxidation under hypoxia. We then used metabolomic methodologies, utilizing liquid chromatography-mass spectrometry (LC-MS, to determine the metabolic profile of hypoxic cells. This approach revealed the importance of synchronized and regulated catabolism as a mechanism of adaptation to bioenergetic stress. We then confirmed the presence of autophagy under hypoxic conditions and demonstrated that the inhibition of this catabolic process dramatically reduced the ATP levels in hypoxic cells and stimulated hypoxia-induced cell death. These results suggest that under hypoxia, autophagy is required to support ATP production, in addition to glycolysis, and that the inhibition of autophagy might be used to selectively target hypoxic regions of tumours, the most notoriously resistant areas of solid tumours.

  14. Metabolic adaptation of Mycobacterium avium subsp. paratuberculosis to the gut environment.

    Science.gov (United States)

    Weigoldt, Mathias; Meens, Jochen; Bange, Franz-Christoph; Pich, Andreas; Gerlach, Gerald F; Goethe, Ralph

    2013-02-01

    Knowledge on the proteome level about the adaptation of pathogenic mycobacteria to the environment in their natural hosts is limited. Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease, a chronic and incurable granulomatous enteritis of ruminants, and has been suggested to be a putative aetiological agent of Crohn's disease in humans. Using a comprehensive LC-MS-MS and 2D difference gel electrophoresis (DIGE) approach, we compared the protein profiles of clinical strains of MAP prepared from the gastrointestinal tract of diseased cows with the protein profiles of the same strains after they were grown in vitro. LC-MS-MS analyses revealed that the principal enzymes for the central carbon metabolic pathways, including glycolysis, gluconeogenesis, the tricaboxylic acid cycle and the pentose phosphate pathway, were present under both conditions. Moreover, a broad spectrum of enzymes for β-oxidation of lipids, nine of which have been shown to be necessary for mycobacterial growth on cholesterol, were detected in vivo and in vitro. Using 2D-DIGE we found increased levels of several key enzymes that indicated adaptation of MAP to the host. Among these, FadE5, FadE25 and AdhB indicated that cholesterol is used as a carbon source in the bovine intestinal mucosa; the respiratory enzymes AtpA, NuoG and SdhA suggested increased respiration during infection. Furthermore higher levels of the pentose phosphate pathway enzymes Gnd2, Zwf and Tal as well as of KatG, SodA and GroEL indicated a vigorous stress response of MAP in vivo. In conclusion, our results provide novel insights into the metabolic adaptation of a pathogenic mycobacterium in its natural host.

  15. Noninvasive metabolic profiling using microfluidics for analysis of single preimplantation embryos.

    Science.gov (United States)

    Urbanski, John Paul; Johnson, Mark T; Craig, David D; Potter, David L; Gardner, David K; Thorsen, Todd

    2008-09-01

    Noninvasive analysis of metabolism at the single cell level will have many applications in evaluating cellular physiology. One clinically relevant application would be to determine the metabolic activities of embryos produced through assisted reproduction. There is increasing evidence that embryos with greater developmental capacity have distinct metabolic profiles. One of the standard techniques for evaluating embryonic metabolism has been to evaluate consumption and production of several key energetic substrates (glucose, pyruvate, and lactate) using microfluorometric enzymatic assays. These assays are performed manually using constriction pipets, which greatly limits the utility of this system. Through multilayer soft-lithography, we have designed a microfluidic device that can perform these assays in an automated fashion. Following manual loading of samples and enzyme cocktail reagents, this system performs sample and enzyme cocktail aliquotting, mixing of reagents, data acquisition, and data analysis without operator intervention. Optimization of design and operating regimens has resulted in the ability to perform serial measurements of glucose, pyruvate, and lactate in triplicate with submicroliter sample volumes within 5 min. The current architecture allows for automated analysis of 10 samples and intermittent calibration over a 3 h period. Standard curves generated for each metabolite have correlation coefficients that routinely exceed 0.99. With the use of a standard epifluorescent microscope and CCD camera, linearity is obtained with metabolite concentrations in the low micromolar range (low femtomoles of total analyte). This system is inherently flexible, being easily adapted for any NAD(P)H-based assay and scaled up in terms of sample ports. Open source JAVA-based software allows for simple alterations in routine algorithms. Furthermore, this device can be used as a standalone device in which media samples are loaded or be integrated into microfluidic

  16. Metabolic profiling of visceral adipose tissue from obese subjects with or without metabolic syndrome.

    Science.gov (United States)

    Candi, Eleonora; Tesauro, Manfredi; Cardillo, Carmine; Lena, Anna Maria; Schinzari, Francesca; Rodia, Giuseppe; Sica, Giuseppe; Gentileschi, Paolo; Rovella, Valentina; Annicchiarico-Petruzzelli, Margherita; Di Daniele, Nicola; Melino, Gerry

    2018-02-08

    Obesity represents one of the most complex public health challenges and has recently reached epidemic proportions.  Obesity is also considered to be primarily responsible for the rising prevalence of metabolic syndrome, defined as the coexistence in the same individual of several risk factors for atherosclerosis, including dyslipidaemia, hypertension and hyperglycaemia, as well as for cancer. Additionally, the presence of three of the five risk factors (abdominal obesity, low HDL cholesterol, high triglycerides, high fasting glucose and high blood pressure) characterizes metabolic syndrome, which has serious clinical consequences.  The current study was conducted in order to identify metabolic differences in visceral adipose tissue collected from obese (BMI 43-48) human subjects who were diagnosed with metabolic syndrome, obese individuals who were metabolically healthy and non-obese healthy controls. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analyses were used to obtain the untargeted visceral adipose tissue metabolomics profiles of 481 metabolites belonging to all biochemical pathways. Our results indicated consistent increases in oxidative stress markers from the pathologically obese samples in addition to subtle markers of elevated glucose levels that may be consistent with metabolic syndrome. In the tissue derived from the pathologically obese subjects, there were significantly elevated levels of plasmalogens, which may be increased in response to oxidative changes in addition to changes in glycerol-phosphorylcholine, glycerol-phosphorylethanolamine glycerol-phosphorylserine, ceramides and sphingolipids. These data could be potentially helpful for recognizing new pathways that underlie the metabolic-vascular complications of obesity and may lead to the development of innovative targeted therapies. ©2018 The Author(s).

  17. Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha

    Directory of Open Access Journals (Sweden)

    Guolin Li

    2018-01-01

    Conclusions: These findings indicate that PPARA activation prior to acute fasting cannot ameliorate fasting-induced hepatic steatosis, whereas EODF induced metabolic adaptations to protect against fasting-induced steatosis without altering PPARA signaling. Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis.

  18. Metabolic profiles of planktonic and biofilm cells of Candida orthopsilosis.

    Science.gov (United States)

    Pires, Regina Helena; Cataldi, Thaís Regiani; Franceschini, Livia Maria; Labate, Mônica Veneziano; Fusco-Almeida, Ana Marisa; Labate, Carlos Alberto; Palma, Mario Sérgio; Soares Mendes-Giannini, Maria José

    2016-10-01

    This study aims to understand which Candida orthopsilosis protein aids fungus adaptation upon its switching from planktonic growth to biofilm. Ion mobility separation within mass spectrometry analysis combination were used. Proteins mapped for different biosynthetic pathways showed that selective ribosome autophagy might occur in biofilms. Glucose, used as a carbon source in the glycolytic flux, changed to glycogen and trehalose. Candida orthopsilosis expresses proteins that combine a variety of mechanisms to provide yeasts with the means to adjust the catalytic properties of enzymes. Adjustment of the enzymes helps modulate the biosynthesis/degradation rates of the available nutrients, in order to control and coordinate the metabolic pathways that enable cells to express an adequate response to nutrient availability.

  19. The Contemporary Adaptive Model for the Expatriates’ Profile

    Directory of Open Access Journals (Sweden)

    Catalin Popa

    2016-12-01

    Full Text Available Considering the global realities and the technological evolution, within a knowledge-based economy, many organizations aim at the human capital development, setting up not just organizational standards but promoting environmentally HR’s adjustment criteria in order to provide sustainability for recruitment and selection processes. Therefore, developing an adapted employee profile for expatriates should be one of the major imperatives for International Human Resources Management (IHRM function. The work paper pleads for considering IHRM as an important organizational dimension, responsible for adjusting the international employee’s behaviour in accordance with the organizational and external domestic environment, in order to promote the overall value of foreign employees for national economy, culture and society.

  20. Metabolic profiling of umbilical cord blood in macrosomia.

    Science.gov (United States)

    Sun, H; Wang, Y; Wang, C; Xu, X; Wang, Y; Yan, H; Yang, X

    2017-11-21

    The term macrosomia is used to describe neonates with a birth weight of 4000 g or more. Macrosomia is a potential risk factor for obesity and metabolic syndromes in postnatal and adult life, yet little is known about its associations with metabolic difference in the early-age. We performed metabolic profiling of umbilical cord blood to discover differential metabolites of macrosomia. We conducted a case-control study of full-term singletons with normal maternal glucose tolerance [50 cases (macrosomia, birth weight ⩾4000 g); 50 controls (normal weight, birth weight 2500-3999 g)]. Metabolites in umbilical cord blood were detected using an untargeted metabolomic approach based on gas chromatography/mass spectrometry. We performed logistic regression to evaluate the associations between metabolites and macrosomia. We also performed pathway analysis based on KEGG and MBRole. Compared with controls, the macrosomia cases had a greater male proportion, gestational age, paternal BMI, and maternal pre-pregnancy BMI. Forty-two metabolites differed between the cases and controls. After multivariable adjustment, 2-methylfumarate [adjusted odds ratio (AOR)=1.232, 95% confidence interval (CI): 1.102-1.376], uracil (AOR=38.494, 95% CI: 5.635-262.951), elaidic acid (AOR=0.834, 95% CI: 0.761-0.915), ribose (AOR=0.089, 95% CI: 0.021-0.378), lactulose (AOR=0.815, 95% CI: 0.743-0.894), and 4-aminobutyric acid (AOR=0.835, 95% CI: 0.764-0.912) remained significantly associated with macrosomia. Pyrimidine metabolism and pentose and glucuronate interconversions were the two top-ranking pathways enriched with those metabolites (-log P-value=3.49 and 2.47, respectively). Levels of 2-methylfumarate, uracil, ribose, elaidic acid, lactulose, and 4-aminobutyric acid were associated with the incidence of macrosomia. The alteration of pathways involving those factors might be linked with the incidence of macrosomia and relevant metabolic syndromes later in life, and further studies are

  1. CSF metabolic and proteomic profiles in patients prodromal for psychosis.

    Directory of Open Access Journals (Sweden)

    Jeffrey T-J Huang

    Full Text Available BACKGROUND: The initial prodromal state of psychosis (IPS is defined as an early disease stage prior to the onset of overt psychosis characterized by sub-threshold or more unspecific psychiatric symptoms. Little is known regarding the biochemical changes during this period. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the metabolic/proteomic profiles of cerebrospinal fluid (CSF of first-onset drug naïve paranoid schizophrenia patients (n = 54 and individuals presenting with initial prodromal symptoms (n = 24, alongside healthy volunteers (n = 70 using proton nuclear magnetic resonance ((1H-NMR spectroscopy and surface enhanced laser desorption ionization (SELDI mass spectrometry, respectively. Partial least square discriminant analysis (PLS-DA showed that 36%/29% of IPS patients displayed proteomic/metabolic profiles characteristic of first-onset, drug naïve schizophrenia, i.e., changes in levels of glucose and lactate as well as changes in a VGF-derived peptide (VGF23-62 and transthyretin protein concentrations. However, only 29% (n = 7 of the investigated IPS patients (who to date have been followed up for up to three years have so far received a diagnosis of schizophrenia. The presence of biochemical alterations in the IPS group did not correlate with the risk to develop schizophrenia. CONCLUSIONS/SIGNIFICANCE: Our results imply that schizophrenia-related biochemical disease processes can be traced in CSF of prodromal patients. However, the biochemical disturbances identified in IPS patients, at least when measured at a single time point, may not be sufficient to predict clinical outcome.

  2. Olive phenolic compounds: metabolic and transcriptional profiling during fruit development

    Directory of Open Access Journals (Sweden)

    Alagna Fiammetta

    2012-09-01

    Full Text Available Abstract Background Olive (Olea europaea L. fruits contain numerous secondary metabolites, primarily phenolics, terpenes and sterols, some of which are particularly interesting for their nutraceutical properties. This study will attempt to provide further insight into the profile of olive phenolic compounds during fruit development and to identify the major genetic determinants of phenolic metabolism. Results The concentration of the major phenolic compounds, such as oleuropein, demethyloleuropein, 3–4 DHPEA-EDA, ligstroside, tyrosol, hydroxytyrosol, verbascoside and lignans, were measured in the developing fruits of 12 olive cultivars. The content of these compounds varied significantly among the cultivars and decreased during fruit development and maturation, with some compounds showing specificity for certain cultivars. Thirty-five olive transcripts homologous to genes involved in the pathways of the main secondary metabolites were identified from the massive sequencing data of the olive fruit transcriptome or from cDNA-AFLP analysis. Their mRNA levels were determined using RT-qPCR analysis on fruits of high- and low-phenolic varieties (Coratina and Dolce d’Andria, respectively during three different fruit developmental stages. A strong correlation was observed between phenolic compound concentrations and transcripts putatively involved in their biosynthesis, suggesting a transcriptional regulation of the corresponding pathways. OeDXS, OeGES, OeGE10H and OeADH, encoding putative 1-deoxy-D-xylulose-5-P synthase, geraniol synthase, geraniol 10-hydroxylase and arogenate dehydrogenase, respectively, were almost exclusively present at 45 days after flowering (DAF, suggesting that these compounds might play a key role in regulating secoiridoid accumulation during fruit development. Conclusions Metabolic and transcriptional profiling led to the identification of some major players putatively involved in biosynthesis of secondary compounds in the

  3. Polish Adaptation of the Death Attitude Profile-Revised.

    Science.gov (United States)

    Brudek, Paweł; Sękowski, Marcin; Steuden, Stanisława

    2018-01-01

    The article presents the results of work on the Polish adaptation of the Death Attitude Profile-Revised by Wong, Reker, and Gesser (1994). The psychometric properties of the Polish version of the tool have been described. The results are consistent with the original version of the questionnaire and confirm that the Polish version of Death Attitude Profile-Revised fulfils the psychometric requirements for psychological tests and, as a result, can be applied in scientific research. The final version of the questionnaire consists of 32 items (including 31 diagnostic ones) that make up five dimensions of attitudes toward death: (a) Fear of Death, (b) Death Avoidance, (c) Neutral Acceptance, (d) Escape Acceptance, and (e) Approach Acceptance. The questionnaire was tested on 1,285 subjects aged 13 to 90 years ( M = 47.27, SD = 18.21). Reliability values (Cronbach's α) for individual scales vary from α = .63 to α = .89. Confirmatory factor analysis was used to evaluate the validity of the questionnaire.

  4. Multidimensional Profiling Platforms Reveal Metabolic Dysregulation caused by Organophosphorus Pesticides

    Science.gov (United States)

    Medina-Cleghorn, Daniel; Heslin, Ann; Morris, Patrick J.; Mulvihill, Melinda M.; Nomura, Daniel K.

    2014-01-01

    We are environmentally exposed to countless synthetic chemicals on a daily basis with an increasing number of these chemical exposures linked to adverse health effects. However, our understanding of the (patho)physiological effects of these chemicals remains poorly understood, due in-part to a general lack of effort to systematically and comprehensively identify the direct interactions of environmental chemicals with biological macromolecules in mammalian systems in vivo. Here, we have used functional chemoproteomic and metabolomic platforms to broadly identify direct enzyme targets that are inhibited by widely used organophosphorus (OP) pesticides in vivo in mice and to determine metabolic alterations that are caused by these chemicals. We find that these pesticides directly inhibit over 20 serine hydrolases in vivo leading to widespread disruptions in lipid metabolism. Through identifying direct biological targets of OP pesticides, we show heretofore unrecognized modes of toxicity that may be associated with these agents and underscore the utility of utilizing multidimensional profiling approaches to obtain a more complete understanding of toxicities associated with environmental chemicals. PMID:24205821

  5. Reconstruction of metabolic networks from high-throughput metabolite profiling data: in silico analysis of red blood cell metabolism.

    Science.gov (United States)

    Nemenman, Ilya; Escola, G Sean; Hlavacek, William S; Unkefer, Pat J; Unkefer, Clifford J; Wall, Michael E

    2007-12-01

    We investigate the ability of algorithms developed for reverse engineering of transcriptional regulatory networks to reconstruct metabolic networks from high-throughput metabolite profiling data. For benchmarking purposes, we generate synthetic metabolic profiles based on a well-established model for red blood cell metabolism. A variety of data sets are generated, accounting for different properties of real metabolic networks, such as experimental noise, metabolite correlations, and temporal dynamics. These data sets are made available online. We use ARACNE, a mainstream algorithm for reverse engineering of transcriptional regulatory networks from gene expression data, to predict metabolic interactions from these data sets. We find that the performance of ARACNE on metabolic data is comparable to that on gene expression data.

  6. 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.

  7. Noninvasive metabolic profiling for painless diagnosis of human diseases and disorders.

    Science.gov (United States)

    Mal, Mainak

    2016-06-01

    Metabolic profiling provides a powerful diagnostic tool complementary to genomics and proteomics. The pain, discomfort and probable iatrogenic injury associated with invasive or minimally invasive diagnostic methods, render them unsuitable in terms of patient compliance and participation. Metabolic profiling of biomatrices like urine, breath, saliva, sweat and feces, which can be collected in a painless manner, could be used for noninvasive diagnosis. This review article covers the noninvasive metabolic profiling studies that have exhibited diagnostic potential for diseases and disorders. Their potential applications are evident in different forms of cancer, metabolic disorders, infectious diseases, neurodegenerative disorders, rheumatic diseases and pulmonary diseases. Large scale clinical validation of such diagnostic methods is necessary in future.

  8. The diagnosis of inherited metabolic diseases by microarray gene expression profiling

    OpenAIRE

    Arenas Hernandez, Monica; Schulz, Reiner; Chaplin, Tracy; Young, Bryan D; Perrett, David; Champion, Michael P; Taanman, Jan-Willem; Fensom, Anthony; Marinaki, Anthony M

    2010-01-01

    Abstract Background Inherited metabolic diseases (IMDs) comprise a diverse group of generally progressive genetic metabolic disorders of variable clinical presentations and severity. We have undertaken a study using microarray gene expression profiling of cultured fibroblasts to investigate 68 patients with a broad range of suspected metabolic disorders, including defects of lysosomal, mitochondrial, peroxisomal, fatty acid, carbohydrate, amino acid, molybdenum cofactor, and purine and pyrimi...

  9. Metabolic analysis of adaptation to short-term changes in culture conditions of the marine diatom Thalassiosira pseudonana.

    Directory of Open Access Journals (Sweden)

    Mariusz A Bromke

    Full Text Available This report describes the metabolic and lipidomic profiling of 97 low-molecular weight compounds from the primary metabolism and 124 lipid compounds of the diatom Thalassiosira pseudonana. The metabolic profiles were created for diatoms perturbed for 24 hours with four different treatments: (I removal of nitrogen, (II lower iron concentration, (III addition of sea salt, (IV addition of carbonate to their growth media. Our results show that as early as 24 hours after nitrogen depletion significant qualitative and quantitative change in lipid composition as well as in the primary metabolism of Thalassiosira pseudonana occurs. So we can observe the accumulation of several storage lipids, namely triacylglycerides, and TCA cycle intermediates, of which citric acid increases more than 10-fold. These changes are positively correlated with expression of TCA enzymes genes. Next to the TCA cycle intermediates and storage lipid changes, we have observed decrease in N-containing lipids and primary metabolites such as amino acids. As a measure of counteracting nitrogen starvation, we have observed elevated expression levels of nitrogen uptake and amino acid biosynthetic genes. This indicates that diatoms can fast and efficiently adapt to changing environment by altering the metabolic fluxes and metabolite abundances. Especially, the accumulation of proline and the decrease of dimethylsulfoniopropionate suggest that the proline is the main osmoprotectant for the diatom in nitrogen rich conditions.

  10. Metabolomic Profiling of 13 Diatom Cultures and Their Adaptation to Nitrate-Limited Growth Conditions

    Science.gov (United States)

    Bromke, Mariusz A.; Sabir, Jamal S.; Alfassi, Fahad A.; Hajarah, Nahid H.; Kabli, Saleh A.; Al-Malki, Abdulrahman L.; Ashworth, Matt P.; Méret, Michaël; Jansen, Robert K.; Willmitzer, Lothar

    2015-01-01

    Diatoms are very efficient in their use of available nutrients. Changes in nutrient availability influence the metabolism and the composition of the cell constituents. Since diatoms are valuable candidates to search for oil producing algae, measurements of diatom-produced compounds can be very useful for biotechnology. In order to explore the diversity of lipophilic compounds produced by diatoms, we describe the results from an analysis of 13 diatom strains. With the help of a lipidomics platform, which combines an UPLC separation with a high resolution/high mass accuracy mass spectrometer, we were able to measure and annotate 142 lipid species. Out of these, 32 were present in all 13 cultures. The annotated lipid features belong to six classes of glycerolipids. The data obtained from the measurements were used to create lipidomic profiles. The metabolomic overview of analysed cultures is amended by the measurement of 96 polar compounds. To further increase the lipid diversity and gain insight into metabolomic adaptation to nitrogen limitation, diatoms were cultured in media with high and low concentrations of nitrate. The growth in nitrogen-deplete or nitrogen-replete conditions affects metabolite accumulation but has no major influence on the species-specific metabolomic profile. Thus, the genetic component is stronger in determining metabolic patterns than nitrogen levels. Therefore, lipid profiling is powerful enough to be used as a molecular fingerprint for diatom cultures. Furthermore, an increase of triacylglycerol (TAG) accumulation was observed in low nitrogen samples, although this trend was not consistent across all 13 diatom strains. Overall, our results expand the current understanding of metabolomics diversity in diatoms and confirm their potential value for producing lipids for either bioenergy or as feed stock. PMID:26440112

  11. Metabolomic Profiling of 13 Diatom Cultures and Their Adaptation to Nitrate-Limited Growth Conditions.

    Directory of Open Access Journals (Sweden)

    Mariusz A Bromke

    Full Text Available Diatoms are very efficient in their use of available nutrients. Changes in nutrient availability influence the metabolism and the composition of the cell constituents. Since diatoms are valuable candidates to search for oil producing algae, measurements of diatom-produced compounds can be very useful for biotechnology. In order to explore the diversity of lipophilic compounds produced by diatoms, we describe the results from an analysis of 13 diatom strains. With the help of a lipidomics platform, which combines an UPLC separation with a high resolution/high mass accuracy mass spectrometer, we were able to measure and annotate 142 lipid species. Out of these, 32 were present in all 13 cultures. The annotated lipid features belong to six classes of glycerolipids. The data obtained from the measurements were used to create lipidomic profiles. The metabolomic overview of analysed cultures is amended by the measurement of 96 polar compounds. To further increase the lipid diversity and gain insight into metabolomic adaptation to nitrogen limitation, diatoms were cultured in media with high and low concentrations of nitrate. The growth in nitrogen-deplete or nitrogen-replete conditions affects metabolite accumulation but has no major influence on the species-specific metabolomic profile. Thus, the genetic component is stronger in determining metabolic patterns than nitrogen levels. Therefore, lipid profiling is powerful enough to be used as a molecular fingerprint for diatom cultures. Furthermore, an increase of triacylglycerol (TAG accumulation was observed in low nitrogen samples, although this trend was not consistent across all 13 diatom strains. Overall, our results expand the current understanding of metabolomics diversity in diatoms and confirm their potential value for producing lipids for either bioenergy or as feed stock.

  12. Genetic dissection of scent metabolic profiles in diploid rose populations.

    Science.gov (United States)

    Spiller, M; Berger, R G; Debener, Thomas

    2010-05-01

    The scent of flowers is a very important trait in ornamental roses in terms of both quantity and quality. In cut roses, scented varieties are a rare exception. Although metabolic profiling has identified more than 500 scent volatiles from rose flowers so far, nothing is known about the inheritance of scent in roses. Therefore, we analysed scent volatiles and molecular markers in diploid segregating populations. We resolved the patterns of inheritance of three volatiles (nerol, neryl acetate and geranyl acetate) into single Mendelian traits, and we mapped these as single or oligogenic traits in the rose genome. Three other volatiles (geraniol, beta-citronellol and 2-phenylethanol) displayed quantitative variation in the progeny, and we mapped a total of six QTLs influencing the amounts of these volatiles onto the rose marker map. Because we included known scent related genes and newly generated ESTs for scent volatiles as markers, we were able to link scent related QTLs with putative candidate genes. Our results serve as a starting point for both more detailed analyses of complex scent biosynthetic pathways and the development of markers for marker-assisted breeding of scented rose varieties.

  13. Metabolic and biological profile of autochthonous Vitis vinifera L. ecotypes.

    Science.gov (United States)

    Impei, Stefania; Gismondi, Angelo; Canuti, Lorena; Canini, Antonella

    2015-05-01

    Vitis vinifera L. is a plant species rich in phenolic compounds that are usually associated with the health benefits of wine and grape consumption in the diet. Anthocyanins, catechins, flavonol, phenolic acids and stilbenes are key molecular constituents of the Vitis berries, affecting the quality of grape products. The purpose of this work was to identify the metabolic profiles of 37 genetically certified V. vinifera Latial accessions. In particular, qualitative and quantitative analyses of specific secondary metabolites and total phenolic and tannin contents were performed by LC-MS and spectrophotometric analysis. In addition, since plant molecules are well-known for their free radical scavenging properties, the antioxidant effects of the sample extracts were evaluated through two different antiradical assays: DPPH and FRAP tests. Finally, a preliminary screening of the antiproliferative activity of each specimen on HCT-116 human colorectal cancer cells was conducted. All the results showed a great variety and amount of phenolic compounds in all accessions; moreover, we observed a significant correlation in the extracts between the metabolite concentration and bioactivity. Besides, some samples presented extraordinary biological effects, such as reduction of tumor cell growth not associated with cytotoxicity, supporting their use as possible future adjuvants for cancer therapy. In conclusion, the present research increased the scientific knowledge about Italian autochthonous vine ecotypes in order to valorize them and support their reintroduction in the local economic system.

  14. Metabolomic and proteomic profiles reveal the dynamics of primary metabolism during seed development of lotus (Nelumbo nucifera

    Directory of Open Access Journals (Sweden)

    Pingfang eYang

    2016-06-01

    Full Text Available Sacred lotus (Nelumbo nucifera belongs to Nelumbonaceae family. Its seeds are widely consumed in Asia countries as snacks or even medicine. Besides the market values, lotus seed also plays crucial roles in lotus life cycle. Consequently, it is essential to gain a comprehensive understanding of the development of lotus seed. During its development, lotus seed undergoes cell division, expansion, reserve accumulation, desiccation and maturation phases. We observed morphological and biochemical changes from 10 to 25 days after pollination (DAP which was corresponding to the reserve synthesis and accumulation phase. The volume of the seed expanded until 20 DAP with the color of the seed coat changing from yellow-green to dark green and gradually fading again. Starch and protein rapidly accumulated from 15 to 20 DAP. To further reveal the metabolism adaptation, primary metabolites and proteins profiles were obtained using mass spectrometry based platforms. Metabolites and enzymes involved in sugar metabolism, glycolysis, TCA cycle and amino acids metabolism showed sequential dynamics enabling the clear separation of the different metabolic states during lotus seed development. The integration of the data revealed a highly significant metabolic switch at 15 DAP going through a transition of metabolically highly active tissue to the preparation of storage tissue. The results provide reference data set for the evaluation of primary metabolism during lotus seed development.

  15. Vineland Adaptive Behavior Scales: II Profile of Young Children with Autism Spectrum Disorder

    Science.gov (United States)

    Yang, Sabrina; Paynter, Jessica M.; Gilmore, Linda

    2016-01-01

    Adaptive behaviour is a crucial area of assessment for individuals with Autism Spectrum Disorder (ASD). This study examined the adaptive behaviour profile of 77 young children with ASD using the Vineland-II, and analysed factors associated with adaptive functioning. Consistent with previous research with the original Vineland a distinct autism…

  16. Metabolic adaptations of white lupin roots and shoots under phosphorus deficiency

    Directory of Open Access Journals (Sweden)

    Julia eMüller

    2015-11-01

    Full Text Available White lupin (Lupinus albus L. is highly adapted to phosphorus-diminished soils. P-deficient white lupin plants modify their root architecture and physiology to acquire sparingly available soil phosphorus. We employed gas chromatography–mass spectrometry (GC MS for metabolic profiling of P-deficient white lupins, to investigate biochemical pathways involved in the P-acquiring strategy. After 14 days of P-deficiency, plants showed reduced levels of fructose, glucose and sucrose in shoots. Phosphorylated metabolites such as glucose-6-phosphate, fructose-6-phosphate, myo-inositol-phosphate and glycerol-3-phosphate were reduced in both shoots and roots. After 22 days of P-deficiency, no effect on shoot or root sugar metabolite levels was found, but the levels of phosphorylated metabolites were further reduced. Organic acids, amino acids and several shikimate pathway products showed enhanced levels in 22-day-old P-deficient roots and shoots. These results indicate that P-deficient white lupins adapt their carbohydrate partitioning between shoot and root in order to supply their growing root system as an early response to P-deficiency. Organic acids are released into the rhizosphere to mobilize phosphorus from soil particles. A longer period of P-deficiency leads to scavenging of Pi from P-containing metabolites and reduced protein anabolism, but enhanced formation of secondary metabolites. The latter can serve as stress protection molecules or actively acquire phosphorus from the soil.

  17. Metabolic Adaptations of White Lupin Roots and Shoots under Phosphorus Deficiency.

    Science.gov (United States)

    Müller, Julia; Gödde, Victoria; Niehaus, Karsten; Zörb, Christian

    2015-01-01

    White lupin (Lupinus albus L.) is highly adapted to phosphorus-diminished soils. P-deficient white lupin plants modify their root architecture and physiology to acquire sparingly available soil phosphorus. We employed gas chromatography-mass spectrometry (GC-MS) for metabolic profiling of P-deficient white lupins, to investigate biochemical pathways involved in the P-acquiring strategy. After 14 days of P-deficiency, plants showed reduced levels of fructose, glucose, and sucrose in shoots. Phosphorylated metabolites such as glucose-6-phosphate, fructose-6-phosphate, myo-inositol-phosphate and glycerol-3-phosphate were reduced in both shoots and roots. After 22 days of P-deficiency, no effect on shoot or root sugar metabolite levels was found, but the levels of phosphorylated metabolites were further reduced. Organic acids, amino acids and several shikimate pathway products showed enhanced levels in 22-day-old P-deficient roots and shoots. These results indicate that P-deficient white lupins adapt their carbohydrate partitioning between shoot and root in order to supply their growing root system as an early response to P-deficiency. Organic acids are released into the rhizosphere to mobilize phosphorus from soil particles. A longer period of P-deficiency leads to scavenging of Pi from P-containing metabolites and reduced protein anabolism, but enhanced formation of secondary metabolites. The latter can serve as stress protection molecules or actively acquire phosphorus from the soil.

  18. Adaptive Evolution and Functional Redesign of Core Metabolic Proteins in Snakes

    OpenAIRE

    Castoe, Todd A.; Jiang, Zhi J.; Wanjun Gu; Wang, Zhengyuan O.; Pollock, David D.

    2008-01-01

    BACKGROUND: Adaptive evolutionary episodes in core metabolic proteins are uncommon, and are even more rarely linked to major macroevolutionary shifts. METHODOLOGY/PRINCIPAL FINDINGS: We conducted extensive molecular evolutionary analyses on snake mitochondrial proteins and discovered multiple lines of evidence suggesting that the proteins at the core of aerobic metabolism in snakes have undergone remarkably large episodic bursts of adaptive change. We show that snake mitochondrial proteins ex...

  19. Metabolic and inflammatory profiles of biomarkers in obesity, metabolic syndrome, and diabetes in a Mediterranean population. DARIOS Inflammatory study.

    Science.gov (United States)

    Fernández-Bergés, Daniel; Consuegra-Sánchez, Luciano; Peñafiel, Judith; Cabrera de León, Antonio; Vila, Joan; Félix-Redondo, Francisco Javier; Segura-Fragoso, Antonio; Lapetra, José; Guembe, María Jesús; Vega, Tomás; Fitó, Montse; Elosua, Roberto; Díaz, Oscar; Marrugat, Jaume

    2014-08-01

    There is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus. We performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus. A total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated. There are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  20. Exercise training improves sleep pattern and metabolic profile in elderly people in a time-dependent manner.

    Science.gov (United States)

    Lira, Fábio S; Pimentel, Gustavo D; Santos, Ronaldo Vt; Oyama, Lila M; Damaso, Ana R; Oller do Nascimento, Cláudia M; Viana, Valter Ar; Boscolo, Rita A; Grassmann, Viviane; Santana, Marcos G; Esteves, Andrea M; Tufik, Sergio; de Mello, Marco T

    2011-07-06

    Aging and physical inactivity are two factors that favors the development of cardiovascular disease, metabolic syndrome, obesity, diabetes, and sleep dysfunction. In contrast, the adoption a habitual of moderate exercise may present a non-pharmacological treatment alternative for sleep and metabolic disorders. We aimed to assess the effects of moderate exercise training on sleep quality and on the metabolic profile of elderly people with a sedentary lifestyle. Fourteen male sedentary, healthy, elderly volunteers performed moderate training for 60 minutes/day, 3 days/week for 24 wk at a work rate equivalent to the ventilatory aerobic threshold. The environment was kept at a temperature of 23 ± 2 °C, with an air humidity 60 ± 5%. Blood and polysomnographs analysis were collected 3 times: at baseline (1 week before training began), 3 and 6 months (after 3 and 6 months of training). Training promoted increasing aerobic capacity (relative VO2, time and velocity to VO2max; p sleep parameters, awake time and REM sleep latency were decreased after 6 months exercise training (p exercise training protocol improves the sleep profile in older people, but the metabolism adaptation does not persist. Suggesting that this population requires training strategy modifications as to ensure consistent alterations regarding metabolism.

  1. Molecular and metabolic adaptations of Lactococcus lactis at near-zero growth rates

    NARCIS (Netherlands)

    Ercan, O.; Wels, M.; Smid, E.J.; Kleerebezem, M.

    2015-01-01

    This paper describes the molecular and metabolic adaptations of Lactococcus lactis during the transition from a growing to a near-zero growth state using carbon-limited retentostat cultivation. Transcriptomic analyses revealed that metabolic patterns shifted between lactic- and mixed-acid

  2. Molecular and metabolic adaptations of Lactococcus lactis at near-zero growth rates

    NARCIS (Netherlands)

    Ercan, O.; Wels, M.W.; Smid, E.J.; Kleerebezem, M

    2015-01-01

    This paper describes the molecular and metabolic adaptations of Lactococcus lactis during the transition from a growing to a near-zero growth state by using carbon-limited retentostat cultivation. Transcriptomic analyses revealed that metabolic patterns shifted between lactic- and mixed-acid

  3. Rumen-protected rice bran to induce the adaptation of calcium metabolism in dairy cows

    NARCIS (Netherlands)

    Martín-Tereso López, J.

    2010-01-01

    Dairy cows suffer from hypocalcaemia in the days around calving, which may result in a condition generally known as milk fever. Calcium metabolism sharply shifts at the start of lactation, because Ca needs suddenly become much greater than at the end of gestation. Calcium metabolism is able to adapt

  4. Molecular and Metabolic Adaptations of Lactococcus lactis at Near-Zero Growth Rates

    NARCIS (Netherlands)

    Ercan, O.; Wels, M.; Smid, E.J.; Kleerebezem, M.

    2015-01-01

    This paper describes the molecular and metabolic adaptations of Lactococcus lactis during the transition from a growing to a near-zero growth state by using carbon-limited retentostat cultivation. Transcriptomic analyses revealed that metabolic patterns shifted between lactic- and mixed-acid

  5. Metabolic profile of pancreatic acinar and islet tissue in culture.

    Science.gov (United States)

    Suszynski, T M; Mueller, K R; Gruessner, A C; Papas, K K

    2014-01-01

    The amount and condition of exocrine impurities may affect the quality of islet preparations, especially during culture. In this study, the objective was to determine the oxygen demand and viability of islet and acinar tissue post-isolation and whether they change disproportionately while in culture. We compared the oxygen consumption rate (OCR) normalized to DNA (OCR/DNA, a measure of fractional viability in units of nmol/min/mg DNA), and the percent change in OCR and DNA recoveries between adult porcine islet and acinar tissue from the same preparation (paired) over 6-9 days of standard culture. Paired comparisons were done to quantify differences in OCR/DNA between islet and acinar tissue from the same preparation, at specified time points during culture. The mean (±SE) OCR/DNA was 74.0 ± 11.7 units higher for acinar (vs islet) tissue on the day of isolation (n = 16, P culture. DNA and OCR recoveries decreased at different rates for acinar versus islet tissue over 6-9 days in culture (n = 6). DNA recovery decreased to 24 ± 7% for acinar and 75 ± 8% for islets (P = .002). Similarly, OCR recovery decreased to 16 ± 3% for acinar and remained virtually constant for islets (P = .005). Differences in the metabolic profile of acinar and islet tissue should be considered when culturing impure islet preparations. OCR-based measurements may help optimize pre-islet transplantation culture protocols. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Adaptation to different types of stress converge on mitochondrial metabolism

    DEFF Research Database (Denmark)

    Lahtvee, Petri-Jaan; Kumar, Rahul; Hallstrom, B. M.

    2016-01-01

    Yeast cell factories encounter physical and chemical stresses when used for industrial production of fuels and chemicals. These stresses reduce productivity and increase bioprocess costs. Understanding the mechanisms of the stress response is essential for improving cellular robustness in platform...... sufficient ATP, leading to onset of respirofermentative metabolism. Although stress-specific factors increase ATP demand for cellular growth under stressful conditions, increased ATP demand for cellular maintenance underpins a general stress response and is responsible for the onset of overflow metabolism....

  7. Fasting induces a biphasic adaptive metabolic response in murine small intestine

    Directory of Open Access Journals (Sweden)

    Evelo Chris TA

    2007-10-01

    Full Text Available Abstract Background The gut is a major energy consumer, but a comprehensive overview of the adaptive response to fasting is lacking. Gene-expression profiling, pathway analysis, and immunohistochemistry were therefore carried out on mouse small intestine after 0, 12, 24, and 72 hours of fasting. Results Intestinal weight declined to 50% of control, but this loss of tissue mass was distributed proportionally among the gut's structural components, so that the microarrays' tissue base remained unaffected. Unsupervised hierarchical clustering of the microarrays revealed that the successive time points separated into distinct branches. Pathway analysis depicted a pronounced, but transient early response that peaked at 12 hours, and a late response that became progressively more pronounced with continued fasting. Early changes in gene expression were compatible with a cellular deficiency in glutamine, and metabolic adaptations directed at glutamine conservation, inhibition of pyruvate oxidation, stimulation of glutamate catabolism via aspartate and phosphoenolpyruvate to lactate, and enhanced fatty-acid oxidation and ketone-body synthesis. In addition, the expression of key genes involved in cell cycling and apoptosis was suppressed. At 24 hours of fasting, many of the early adaptive changes abated. Major changes upon continued fasting implied the production of glucose rather than lactate from carbohydrate backbones, a downregulation of fatty-acid oxidation and a very strong downregulation of the electron-transport chain. Cell cycling and apoptosis remained suppressed. Conclusion The changes in gene expression indicate that the small intestine rapidly looses mass during fasting to generate lactate or glucose and ketone bodies. Meanwhile, intestinal architecture is maintained by downregulation of cell turnover.

  8. Improvement of metabolic risk profile under second-generation antipsychotics: a pilot intervention study.

    Science.gov (United States)

    Blouin, Mélissa; Binet, Mario; Bouchard, Roch-Hugo; Roy, Marc-André; Després, Jean-Pierre; Alméras, Natalie

    2009-04-01

    To assess the impact of a weight management program on metabolic health of second-generation antipsychotic (SGA)-treated patients. A prospective 12-week intervention program including individual exercise training and nutritional group sessions was performed as a pilot study. An intervention group of 6 SGA-treated patients (5 men and 1 woman; mean 15.0, SD 11.8 months) was compared with 10 reference patients under SGAs (8 men and 2 women; mean 14.0, SD 14.2 months), presenting similar age and baseline weekly levels of physical activity. For patients of both groups, anthropometric measurements and basic fasting lipid profile were assessed. For patients in the intervention group, an adapted Rockport Test was performed to evaluate their aerobic fitness and compliance to training sessions, and was recorded. After the 12-week period, reference patients significantly gained weight (P = 0.001), whereas intervention patients showed significant weight loss and decreased body mass index (P = 0.02); interaction between groups: P < 0.01. This weight loss was accompanied by a decreased cholesterol-high-density lipoprotein cholesterol ratio (P = 0.04). Overall, the intervention patients' adherence to exercise prescription was 95.1 %, and this adherence induced a significant improvement of their aerobic fitness (P = 0.05). This pilot study suggests that patients under SGAs may benefit from a weight management program and improve their metabolic health, as well as their aerobic fitness.

  9. Regulation of PGC-1α and exercise training-induced metabolic adaptations in skeletal muscle

    DEFF Research Database (Denmark)

    Brandt, Nina

    -induced improvements in skeletal muscle metabolic capacity, but may contribute to the exercise training-induced maintenance of skeletal muscle mass. In addition, the results indicate an exercise intensity dependent regulation of autophagy in skeletal muscle and suggest that PGC-1 α regulates both acute and exercise...... and intracellular signalling in human skeletal muscle depend on adrenaline levels or metabolic stress. 2) PGC-1α mediated exercise and exercise training-induced adaptive metabolic responses in mouse skeletal muscle depend on exercise intensity. 3) β-adrenergic signalling contributes to exercise training......-induced metabolic adaptations in mouse skeletal muscle through PGC-1α . Paper I demonstrated that di erences in plasma adrenaline and muscle metabolic stress during exercise do not reinforce exercise-induced PGC-1 α mRNA response in human skeletal muscle. In addition, di erences in exercise-induced AMPK and p38...

  10. Metabolic Profiles of Obesity in American Indians: The Strong Heart Family Study

    National Research Council Canada - National Science Library

    Zhao, Qi; Zhu, Yun; Best, Lyle G; Umans, Jason G; Uppal, Karan; Tran, ViLinh T; Jones, Dean P; Lee, Elisa T; Howard, Barbara V; Zhao, Jinying

    2016-01-01

    .... American Indians suffer disproportionately high rates of obesity and diabetes. The goal of this study is to identify metabolic profiles of obesity in 431 normoglycemic American Indians participating in the Strong Heart Family Study...

  11. Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children : The ABCD Study

    NARCIS (Netherlands)

    Vrijkotte, Tanja G M; van den Born, Bert-Jan H; Hoekstra, Christine M C A; Gademan, Maaike G J; van Eijsden, Manon; de Rooij, Susanne R; Twickler, Marcel T B

    2015-01-01

    BACKGROUND: In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system

  12. Adaptive Profiles in Autism and Other Neurodevelopmental Disorders

    Science.gov (United States)

    Mouga, Susana; Almeida, Joana; Café, Cátia; Duque, Frederico; Oliveira, Guiomar

    2015-01-01

    We investigated the influence of specific autism spectrum disorder (ASD) deficits in learning adaptive behaviour, besides intelligence quotient (IQ). Participated 217 school-aged: ASD (N = 115), and other neurodevelopmental disorders (OND) groups (N = 102) matched by Full-Scale IQ. We compared standard scores of Vineland Adaptive Behaviour Scale…

  13. Fagus sylvatica L. provenances maintain different leaf metabolic profiles and functional response

    Science.gov (United States)

    Aranda, Ismael; Sánchez-Gómez, David; de Miguel, Marina; Mancha, Jose Antonio; Guevara, María Angeles; Cadahía, Estrella; Fernández de Simón, María Brígida

    2017-07-01

    Most temperate forest tree species will suffer important environmental changes as result of the climate change. Adaptiveness to local conditions could change at different sites in the future. In this context, the study of intra-specific variability is important to clarify the singularity of different local populations. Phenotypic differentiation between three beech provenances covering a wide latitudinal range (Spain/ES, Germany/DE and Sweden/SE), was studied in a greenhouse experiment. Non-target leaf metabolite profiles and ecophysiological response was analyzed in well-watered and water stressed seedlings. There was a provenance-specific pattern in the relative concentrations of some leaf metabolites regardless watering treatment. The DE and SE from the center and north of the distribution area of the species showed a clear differentiation from the ES provenance in the relative concentration of some metabolites. Thus the ES provenance from the south maintained larger relative concentration of some organic and amino acids (e.g. fumaric and succinic acids or valine and isoleucine), and in some secondary metabolites (e.g. kaempferol, caffeic and ferulic acids). The ecophysiological response to mild water stress was similar among the three provenances as a consequence of the moderate water stress applied to seedlings, although leaf N isotope composition (δ15N) and leaf C:N ratio were higher and lower respectively in DE than in the other two provenances. This would suggest potential differences in the capacity to uptake and post-process nitrogen according to provenance. An important focus of the study was to address for the first time inter-provenance leaf metabolic diversity in beech from a non-targeted metabolic profiling approach that allowed differentiation of the three studied provenances.

  14. Inborn errors of metabolism revealed by organic acid profile analysis ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence and types of inborn errors of amino acid or organic acid metabolism in a group of high risk Egyptian children with clinical signs and symptoms suggestive of inherited metabolic diseases. Subjects and Methods: 117 (79 males ═ 67.5 % and 38 females ═ 32.5 %) high risk patients with ...

  15. Noninvasive metabolic profiling for painless diagnosis of human diseases and disorders

    OpenAIRE

    Mal, Mainak

    2016-01-01

    Metabolic profiling provides a powerful diagnostic tool complementary to genomics and proteomics. The pain, discomfort and probable iatrogenic injury associated with invasive or minimally invasive diagnostic methods, render them unsuitable in terms of patient compliance and participation. Metabolic profiling of biomatrices like urine, breath, saliva, sweat and feces, which can be collected in a painless manner, could be used for noninvasive diagnosis. This review article covers the noninvasiv...

  16. Metabolic profiling reveals metabolic shifts in Arabidopsis plants grown under different light conditions.

    Science.gov (United States)

    Jänkänpää, Hanna Johansson; Mishra, Yogesh; Schröder, Wolfgang P; Jansson, Stefan

    2012-10-01

    Plants have tremendous capacity to adjust their morphology, physiology and metabolism in response to changes in growing conditions. Thus, analysis solely of plants grown under constant conditions may give partial or misleading indications of their responses to the fluctuating natural conditions in which they evolved. To obtain data on growth condition-dependent differences in metabolite levels, we compared leaf metabolite profiles of Arabidopsis thaliana growing under three constant laboratory light conditions: 30 [low light (LL)], 300 [normal light (NL)] and 600 [high light (HL)]µmol photons m(-2) s(-1). We also shifted plants to the field and followed their metabolite composition for 3 d. Numerous compounds showed light intensity-dependent accumulation, including: many sugars and sugar derivatives (fructose, sucrose, glucose, galactose and raffinose); tricarboxylic acid (TCA) cycle intermediates; and amino acids (ca. 30% of which were more abundant under HL and 60% under LL). However, the patterns differed after shifting NL plants to field conditions. Levels of most identified metabolites (mainly amino acids, sugars and TCA cycle intermediates) rose after 2 h and peaked after 73 h, indicative of a 'biphasic response' and 'circadian' effects. The results provide new insight into metabolomic level mechanisms of plant acclimation, and highlight the role of known protectants under natural conditions. © 2012 Blackwell Publishing Ltd.

  17. Liver tissue metabolic profiling and pathways of non-alcoholic steatohepatitis in rats.

    Science.gov (United States)

    Qi, Suwen; Huang, Si; Chen, Xin; Huo, Qin; Xie, Ni; Xia, Jun

    2017-12-01

    The mechanisms of non-alcoholic steatohepatitis (NASH) in hepatocytes are unknown. Our aim is to study the tissue metabolic profiling and pathways of NASH. We built rat models for simple steatosis and NASH and analyzed the liver extract using a liquid chromatograph-mass spectrometer. The acquired data were processed by multivariate principal component analysis and partial least squares discriminant analysis (PLS-DA) to obtain metabolic profiling. Orthogonal projections to latent structures DA was used to obtain metabolites capable of distinguishing NASH and steatosis. The total differences in the metabolites between groups were analyzed to determine their metabolic pathways. Principal component analysis showed that the metabolic profiles of NASH and steatosis are different. The PLS-DA modeling revealed a clear separation between two groups with parameters R 2 Y and Q 2 Y all greater than 0.7. The orthogonal projections to latent structures DA model identified 171 metabolites capable of distinguishing NASH from steatosis. The identified metabolites are involved in fatty acid metabolism, tryptophan metabolism, the urea cycle, and the citric acid cycle in hepatocytes. These metabolic profiles and pathways in rat hepatocytes will offer useful information when studying metabolic disorders in patients with NASH. © 2017 The Japan Society of Hepatology.

  18. Preadipocyte factor-1 is associated with metabolic profile in severe obesity.

    LENUS (Irish Health Repository)

    O'Connell, J

    2011-04-01

    Dysfunctional adipose tissue has been proposed as a key pathological process linking obesity and metabolic disease. Preadipocyte factor-1 (Pref-1) has been shown to inhibit differentiation in adipocyte precursor cells and could thereby play a role in determining adipocyte size, adipose tissue functioning, and metabolic profile in obese individuals.

  19. The metabolic profiles of HIV-infected and non-infected women in ...

    African Journals Online (AJOL)

    Keywords: Black women; metabolism; ART-naive; glucose; lipids; proteins. The metabolic profiles of HIV-infected and non-infected women in Mangaung, South Africa. Introduction. Human Immunodeficiency Virus (HIV) infection has reached epidemic proportions in South Africa, where increasing numbers of people now die ...

  20. Adaptations to climate in candidate genes for common metabolic disorders.

    Directory of Open Access Journals (Sweden)

    Angela M Hancock

    2008-02-01

    Full Text Available Evolutionary pressures due to variation in climate play an important role in shaping phenotypic variation among and within species and have been shown to influence variation in phenotypes such as body shape and size among humans. Genes involved in energy metabolism are likely to be central to heat and cold tolerance. To test the hypothesis that climate shaped variation in metabolism genes in humans, we used a bioinformatics approach based on network theory to select 82 candidate genes for common metabolic disorders. We genotyped 873 tag SNPs in these genes in 54 worldwide populations (including the 52 in the Human Genome Diversity Project panel and found correlations with climate variables using rank correlation analysis and a newly developed method termed Bayesian geographic analysis. In addition, we genotyped 210 carefully matched control SNPs to provide an empirical null distribution for spatial patterns of allele frequency due to population history alone. For nearly all climate variables, we found an excess of genic SNPs in the tail of the distributions of the test statistics compared to the control SNPs, implying that metabolic genes as a group show signals of spatially varying selection. Among our strongest signals were several SNPs (e.g., LEPR R109K, FABP2 A54T that had previously been associated with phenotypes directly related to cold tolerance. Since variation in climate may be correlated with other aspects of environmental variation, it is possible that some of the signals that we detected reflect selective pressures other than climate. Nevertheless, our results are consistent with the idea that climate has been an important selective pressure acting on candidate genes for common metabolic disorders.

  1. Effect of probiotics on metabolic profiles in type 2 diabetes mellitus

    OpenAIRE

    Li, Caifeng; Li, Xin; Han, Hongqiu; Cui, Hailong; Peng, Min; Wang, Guolin; Wang, Zhiqiang

    2016-01-01

    Abstract Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease which is imposing heavy burden on global health and economy. Recent studies indicate gut microbiota play important role on the pathogenesis and metabolic disturbance of T2DM. As an effective mean of regulating gut microbiota, probiotics are live micro-organisms that are believed to provide a specific health benefit on the host. Whether probiotic supplementation could improve metabolic profiles by modifying gut microbiot...

  2. Adaptive evolution and functional redesign of core metabolic proteins in snakes.

    Science.gov (United States)

    Castoe, Todd A; Jiang, Zhi J; Gu, Wanjun; Wang, Zhengyuan O; Pollock, David D

    2008-05-21

    Adaptive evolutionary episodes in core metabolic proteins are uncommon, and are even more rarely linked to major macroevolutionary shifts. We conducted extensive molecular evolutionary analyses on snake mitochondrial proteins and discovered multiple lines of evidence suggesting that the proteins at the core of aerobic metabolism in snakes have undergone remarkably large episodic bursts of adaptive change. We show that snake mitochondrial proteins experienced unprecedented levels of positive selection, coevolution, convergence, and reversion at functionally critical residues. We examined Cytochrome C oxidase subunit I (COI) in detail, and show that it experienced extensive modification of normally conserved residues involved in proton transport and delivery of electrons and oxygen. Thus, adaptive changes likely altered the flow of protons and other aspects of function in CO, thereby influencing fundamental characteristics of aerobic metabolism. We refer to these processes as "evolutionary redesign" because of the magnitude of the episodic bursts and the degree to which they affected core functional residues. The evolutionary redesign of snake COI coincided with adaptive bursts in other mitochondrial proteins and substantial changes in mitochondrial genome structure. It also generally coincided with or preceded major shifts in ecological niche and the evolution of extensive physiological adaptations related to lung reduction, large prey consumption, and venom evolution. The parallel timing of these major evolutionary events suggests that evolutionary redesign of metabolic and mitochondrial function may be related to, or underlie, the extreme changes in physiological and metabolic efficiency, flexibility, and innovation observed in snake evolution.

  3. Adaptive evolution and functional redesign of core metabolic proteins in snakes.

    Directory of Open Access Journals (Sweden)

    Todd A Castoe

    Full Text Available BACKGROUND: Adaptive evolutionary episodes in core metabolic proteins are uncommon, and are even more rarely linked to major macroevolutionary shifts. METHODOLOGY/PRINCIPAL FINDINGS: We conducted extensive molecular evolutionary analyses on snake mitochondrial proteins and discovered multiple lines of evidence suggesting that the proteins at the core of aerobic metabolism in snakes have undergone remarkably large episodic bursts of adaptive change. We show that snake mitochondrial proteins experienced unprecedented levels of positive selection, coevolution, convergence, and reversion at functionally critical residues. We examined Cytochrome C oxidase subunit I (COI in detail, and show that it experienced extensive modification of normally conserved residues involved in proton transport and delivery of electrons and oxygen. Thus, adaptive changes likely altered the flow of protons and other aspects of function in CO, thereby influencing fundamental characteristics of aerobic metabolism. We refer to these processes as "evolutionary redesign" because of the magnitude of the episodic bursts and the degree to which they affected core functional residues. CONCLUSIONS/SIGNIFICANCE: The evolutionary redesign of snake COI coincided with adaptive bursts in other mitochondrial proteins and substantial changes in mitochondrial genome structure. It also generally coincided with or preceded major shifts in ecological niche and the evolution of extensive physiological adaptations related to lung reduction, large prey consumption, and venom evolution. The parallel timing of these major evolutionary events suggests that evolutionary redesign of metabolic and mitochondrial function may be related to, or underlie, the extreme changes in physiological and metabolic efficiency, flexibility, and innovation observed in snake evolution.

  4. Adaptive Evolution and Functional Redesign of Core Metabolic Proteins in Snakes

    Science.gov (United States)

    Gu, Wanjun; Wang, Zhengyuan O.; Pollock, David D.

    2008-01-01

    Background Adaptive evolutionary episodes in core metabolic proteins are uncommon, and are even more rarely linked to major macroevolutionary shifts. Methodology/Principal Findings We conducted extensive molecular evolutionary analyses on snake mitochondrial proteins and discovered multiple lines of evidence suggesting that the proteins at the core of aerobic metabolism in snakes have undergone remarkably large episodic bursts of adaptive change. We show that snake mitochondrial proteins experienced unprecedented levels of positive selection, coevolution, convergence, and reversion at functionally critical residues. We examined Cytochrome C oxidase subunit I (COI) in detail, and show that it experienced extensive modification of normally conserved residues involved in proton transport and delivery of electrons and oxygen. Thus, adaptive changes likely altered the flow of protons and other aspects of function in CO, thereby influencing fundamental characteristics of aerobic metabolism. We refer to these processes as “evolutionary redesign” because of the magnitude of the episodic bursts and the degree to which they affected core functional residues. Conclusions/Significance The evolutionary redesign of snake COI coincided with adaptive bursts in other mitochondrial proteins and substantial changes in mitochondrial genome structure. It also generally coincided with or preceded major shifts in ecological niche and the evolution of extensive physiological adaptations related to lung reduction, large prey consumption, and venom evolution. The parallel timing of these major evolutionary events suggests that evolutionary redesign of metabolic and mitochondrial function may be related to, or underlie, the extreme changes in physiological and metabolic efficiency, flexibility, and innovation observed in snake evolution. PMID:18493604

  5. Older adults learn less, but still reduce metabolic cost, during motor adaptation

    Science.gov (United States)

    Huang, Helen J.

    2013-01-01

    The ability to learn new movements and dynamics is important for maintaining independence with advancing age. Age-related sensorimotor changes and increased muscle coactivation likely alter the trial-and-error-based process of adapting to new movement demands (motor adaptation). Here, we asked, to what extent is motor adaptation to novel dynamics maintained in older adults (≥65 yr)? We hypothesized that older adults would adapt to the novel dynamics less well than young adults. Because older adults often use muscle coactivation, we expected older adults to use greater muscle coactivation during motor adaptation than young adults. Nevertheless, we predicted that older adults would reduce muscle activity and metabolic cost with motor adaptation, similar to young adults. Seated older (n = 11, 73.8 ± 5.6 yr) and young (n = 15, 23.8 ± 4.7 yr) adults made targeted reaching movements while grasping a robotic arm. We measured their metabolic rate continuously via expired gas analysis. A force field was used to add novel dynamics. Older adults had greater movement deviations and compensated for just 65% of the novel dynamics compared with 84% in young adults. As expected, older adults used greater muscle coactivation than young adults. Last, older adults reduced muscle activity with motor adaptation and had consistent reductions in metabolic cost later during motor adaptation, similar to young adults. These results suggest that despite increased muscle coactivation, older adults can adapt to the novel dynamics, albeit less accurately. These results also suggest that reductions in metabolic cost may be a fundamental feature of motor adaptation. PMID:24133222

  6. The effects of electrical stimulation on body composition and metabolic profile after spinal cord injury--Part II.

    Science.gov (United States)

    Gorgey, Ashraf S; Dolbow, David R; Dolbow, James D; Khalil, Refka K; Gater, David R

    2015-01-01

    Diet and exercise are cornerstones in the management of obesity and associated metabolic complications, including insulin resistance, type 2 diabetes, and disturbances in the lipid profile. However, the role of exercise in managing body composition adaptations and metabolic disorders after spinal cord injury (SCI) is not well established. The current review summarizes evidence about the efficacy of using neuromuscular electrical stimulation or functional electrical stimulation in exercising the paralytic lower extremities to improve body composition and metabolic profile after SCI. There are a number of trials that investigated the effects on muscle cross-sectional area, fat-free mass, and glucose/lipid metabolism. The duration of the intervention in these trials varied from 6 weeks to 24 months. Training frequency ranged from 2 to 5 days/week. Most studies documented significant increases in muscle size but no noticeable changes in adipose tissue. While increases in skeletal muscle size after twice weekly training were greater than those trials that used 3 or 5 days/week, other factors such as differences in the training mode, i.e. resistance versus cycling exercise and pattern of muscle activation may be responsible for this observation. Loading to evoke muscle hypertrophy is a key component in neuromuscular training after SCI. The overall effects on lean mass were modest and did not exceed 10% and the effects of training on trunk or pelvic muscles remain unestablished. Most studies reported improvement in glucose metabolism with the enhancement of insulin sensitivity being the major factor following training. The effect on lipid profile is unclear and warrants further investigation.

  7. The effects of electrical stimulation on body composition and metabolic profile after spinal cord injury – Part II

    Science.gov (United States)

    Gorgey, Ashraf S.; Dolbow, David R.; Dolbow, James D.; Khalil, Refka K.; Gater, David R.

    2015-01-01

    Diet and exercise are cornerstones in the management of obesity and associated metabolic complications, including insulin resistance, type 2 diabetes, and disturbances in the lipid profile. However, the role of exercise in managing body composition adaptations and metabolic disorders after spinal cord injury (SCI) is not well established. The current review summarizes evidence about the efficacy of using neuromuscular electrical stimulation or functional electrical stimulation in exercising the paralytic lower extremities to improve body composition and metabolic profile after SCI. There are a number of trials that investigated the effects on muscle cross-sectional area, fat-free mass, and glucose/lipid metabolism. The duration of the intervention in these trials varied from 6 weeks to 24 months. Training frequency ranged from 2 to 5 days/week. Most studies documented significant increases in muscle size but no noticeable changes in adipose tissue. While increases in skeletal muscle size after twice weekly training were greater than those trials that used 3 or 5 days/week, other factors such as differences in the training mode, i.e. resistance versus cycling exercise and pattern of muscle activation may be responsible for this observation. Loading to evoke muscle hypertrophy is a key component in neuromuscular training after SCI. The overall effects on lean mass were modest and did not exceed 10% and the effects of training on trunk or pelvic muscles remain unestablished. Most studies reported improvement in glucose metabolism with the enhancement of insulin sensitivity being the major factor following training. The effect on lipid profile is unclear and warrants further investigation. PMID:25001669

  8. An Adaptive Laboratory Evolution Method to Accelerate Autotrophic Metabolism

    DEFF Research Database (Denmark)

    Zhang, Tian; Tremblay, Pier-Luc

    2018-01-01

    Adaptive laboratory evolution (ALE) is an approach enabling the development of novel characteristics in microbial strains via the application of a constant selection pressure. This method is also an efficient tool to acquire insights on molecular mechanisms responsible for specific phenotypes. ALE...

  9. Adaptation to different types of stress converge on mitochondrial metabolism

    DEFF Research Database (Denmark)

    Lahtvee, Petri-Jaan; Kumar, Rahul; Hallstrom, B. M.

    2016-01-01

    Yeast cell factories encounter physical and chemical stresses when used for industrial production of fuels and chemicals. These stresses reduce productivity and increase bioprocess costs. Understanding the mechanisms of the stress response is essential for improving cellular robustness in platform......-level analysis, we found that most stress responses converge on mitochondrial processes. Our analysis revealed that stress-specific factors differ between applied stresses; however, they are underpinned by an increased ATP demand. We found that when ATP demand increases to high levels, respiration cannot provide...... sufficient ATP, leading to onset of respirofermentative metabolism. Although stress-specific factors increase ATP demand for cellular growth under stressful conditions, increased ATP demand for cellular maintenance underpins a general stress response and is responsible for the onset of overflow metabolism....

  10. Psychopathological Manifestations of Children with Intellectual Disabilities According to Their Cognitive and Adaptive Behavior Profile

    Science.gov (United States)

    Tremblay, Karine N.; Richer, Louis; Lachance, Lise; Cote, Alain

    2010-01-01

    Children with intellectual disabilities show deficits in cognitive abilities and adaptive behavior which increase the risk of psychopathological disorders. This exploratory study aims at delineating profiles of children based on their cognitive functioning and adaptive behaviors, and to compare them on psychopathological manifestations. A…

  11. Profiles and Development of Adaptive Behavior in Children with Down Syndrome.

    Science.gov (United States)

    Dykens, Elisabeth M.; And Others

    1993-01-01

    Examination of the profiles and developmental trajectories of adaptive behavior of 80 children with Down's syndrome indicated a significant weakness in communication skills (especially expressive language), relative to daily living and socialization skills. Children ages 1-6 showed significant age-related gains in adaptive functioning, but older…

  12. Longitudinal profiles of adaptive behavior in fragile X syndrome.

    Science.gov (United States)

    Klaiman, Cheryl; Quintin, Eve-Marie; Jo, Booil; Lightbody, Amy A; Hazlett, Heather Cody; Piven, Joseph; Hall, Scott S; Chromik, Lindsay C; Reiss, Allan L

    2014-08-01

    To examine longitudinally the adaptive behavior patterns in fragile X syndrome. Caregivers of 275 children and adolescents with fragile X syndrome and 225 typically developing children and adolescents (2-18 years) were interviewed with the Vineland Adaptive Behavior Scales every 2 to 4 years as part of a prospective longitudinal study. Standard scores of adaptive behavior in people with fragile X syndrome are marked by a significant decline over time in all domains for males and in communication for females. Socialization skills are a relative strength as compared with the other domains for males with fragile X syndrome. Females with fragile X syndrome did not show a discernible pattern of developmental strengths and weaknesses. This is the first large-scale longitudinal study to show that the acquisition of adaptive behavior slows as individuals with fragile X syndrome age. It is imperative to ensure that assessments of adaptive behavior skills are part of intervention programs focusing on childhood and adolescence in this condition. Copyright © 2014 by the American Academy of Pediatrics.

  13. Longitudinal Profiles of Adaptive Behavior in Fragile X Syndrome

    Science.gov (United States)

    Quintin, Eve-Marie; Jo, Booil; Lightbody, Amy A.; Hazlett, Heather Cody; Piven, Joseph; Hall, Scott S.; Reiss, Allan L.

    2014-01-01

    OBJECTIVE: To examine longitudinally the adaptive behavior patterns in fragile X syndrome. METHOD: Caregivers of 275 children and adolescents with fragile X syndrome and 225 typically developing children and adolescents (2–18 years) were interviewed with the Vineland Adaptive Behavior Scales every 2 to 4 years as part of a prospective longitudinal study. RESULTS: Standard scores of adaptive behavior in people with fragile X syndrome are marked by a significant decline over time in all domains for males and in communication for females. Socialization skills are a relative strength as compared with the other domains for males with fragile X syndrome. Females with fragile X syndrome did not show a discernible pattern of developmental strengths and weaknesses. CONCLUSIONS: This is the first large-scale longitudinal study to show that the acquisition of adaptive behavior slows as individuals with fragile X syndrome age. It is imperative to ensure that assessments of adaptive behavior skills are part of intervention programs focusing on childhood and adolescence in this condition. PMID:25070318

  14. [System analysis of metabolic profile of blood in patients with thermal trauma].

    Science.gov (United States)

    Solov'eva, A G; Martucevich, A K; Peretiagin, S P; Didenko, N V

    2014-01-01

    To make multiparametric analysis of blood metabolic profile in early period of burn disease. We tested blood samples of 15 healthy adults (control group) and 60 patients with thermal trauma (main group--II-4IIIA, B degree of burn, more then 15 bsp). Parameters of lipid metabolism, level of glucose, lactate, malonic dialdehyde and some enzymes in blood plasma and erythrocytes were estimated. In early period of burn disease we fixed the clear metabolic disorders, including tissues hypoxia, activation of plasma transaminases and oxidoreductases, inhibition of detoxication system, induction of oxidative stress. Connection of metabolic changes, associated with burn disease, was registered. It supported by numerous correlations between studied parameters, formed from first day after trauma. Our data expand the knowledge about mating metabolic changes of catalytic activity of blood enzymes, forming in early period of burn disease (system metabolic disadaptation), and diagnostic value of some blood biochemical parameters in estimation of burned patient metabolism.

  15. Metabolic adaptation of skeletal muscles to gravitational unloading

    Science.gov (United States)

    Ohira, Y.; Yasui, W.; Kariya, F.; Wakatsuki, T.; Nakamura, K.; Asakura, T.; Edgerton, V. R.

    Responses of high-energy phosphates and metabolic properties to hindlimb suspension were studied in adult rats. The relative content of phosphocreatine (PCr) in the calf muscles was significantly higher in rats suspended for 10 days than in age-matched cage controls. The Pi/PCr ratio, where Pi is inorganic phosphate, in suspended muscles was less than controls. The absolute weights of soleus and medial gastrocnemius (MG) were approximately 40% less than controls. Although the % fiber distribution in MG was unchanged, the % slow fibers decreased and the % fibers which were classified as both slow and fast was increased in soleus. The activities (per unit weight or protein) of succinate dehydrogenase and lactate dehydrogenase in soleus were unchanged but those of cytochrome oxidase, β-hydroxyacyl CoA dehydrogenase, and citrate synthase were decreased following unloading. None of these enzyme activities in MG changed. However, the total levels of all enzymes in whole muscles decreased by suspension. It is suggested that shift of slow muscle toward fast type by unloading is associated with a decrease in mitochondrial biogenesis. Further, gravitational unloading affected the levels of muscle proteins differently even in the same mitochondrial enzymes. Unloading-related atrophy is prominent in red muscle or slow-twitch fiber 1, 2. Such atrophy is accompanied by a shift of contractile properties toward fast-twitch type 2-9. Further, inhibition of mitochondrial metabolism in these muscles is also reported by some studies 10-14 suggesting a lowered mitochondrial biogenesis, although results from some studies do not necessarily agree 1, 7, 15. However, the precise mechanism responsible for such alterations of muscle properties in response to gravitational unloading is unclear. On the contrary, mitochondrial biogenesis, suggested by mitochondrial enzyme activities and/or mass, is stimulated in muscles with depleted high-energy phosphates by cold exposure 16 and/or by feeding

  16. Metabolic profiling as a tool for prioritizing antimicrobial compounds

    NARCIS (Netherlands)

    Wu, Changsheng; Choi, Young Hae; van Wezel, Gilles P.

    Metabolomics is an analytical technique that allows scientists to globally profile low molecular weight metabolites between samples in a medium- or high throughput environment. Different biological samples are statistically analyzed and correlated to a bioactivity of interest, highlighting

  17. Metabolic Model-Based Integration of Microbiome Taxonomic and Metabolomic Profiles Elucidates Mechanistic Links between Ecological and Metabolic Variation

    Energy Technology Data Exchange (ETDEWEB)

    Noecker, Cecilia; Eng, Alexander; Srinivasan, Sujatha; Theriot, Casey M.; Young, Vincent B.; Jansson, Janet K.; Fredricks, David N.; Borenstein, Elhanan; Sanchez, Laura M.

    2015-12-22

    ABSTRACT

    Multiple molecular assays now enable high-throughput profiling of the ecology, metabolic capacity, and activity of the human microbiome. However, to date, analyses of such multi-omic data typically focus on statistical associations, often ignoring extensive prior knowledge of the mechanisms linking these various facets of the microbiome. Here, we introduce a comprehensive framework to systematically link variation in metabolomic data with community composition by utilizing taxonomic, genomic, and metabolic information. Specifically, we integrate available and inferred genomic data, metabolic network modeling, and a method for predicting community-wide metabolite turnover to estimate the biosynthetic and degradation potential of a given community. Our framework then compares variation in predicted metabolic potential with variation in measured metabolites’ abundances to evaluate whether community composition can explain observed shifts in the community metabolome, and to identify key taxa and genes contributing to the shifts. Focusing on two independent vaginal microbiome data sets, each pairing 16S community profiling with large-scale metabolomics, we demonstrate that our framework successfully recapitulates observed variation in 37% of metabolites. Well-predicted metabolite variation tends to result from disease-associated metabolism. We further identify several disease-enriched species that contribute significantly to these predictions. Interestingly, our analysis also detects metabolites for which the predicted variation negatively correlates with the measured variation, suggesting environmental control points of community metabolism. Applying this framework to gut microbiome data sets reveals similar trends, including prediction of bile acid metabolite shifts. This framework is an important first step toward a system-level multi-omic integration and an improved mechanistic understanding of the microbiome activity and dynamics in

  18. Learner Profile Management for Collaborative Adaptive eLearning Application

    DEFF Research Database (Denmark)

    Alrifai, Mohammad; Dolog, Peter; Nejdl, Wolfgang

    2006-01-01

    Adaptive Learning Systems would perform better if they would be able to exchange as many relevant fragments of information about the learner as possible. The use of Web Services standards is recently gaining the attention of many researches as a promising solution for the problem of interfacing...

  19. Influence of physical and emotional activity on the metabolic profile of blood serum of race horses

    Directory of Open Access Journals (Sweden)

    T. I. Bayeva

    2016-09-01

    Full Text Available In the article data are presented on dynamics of the level of indicators of metabolic profile of blood serum of race horses of the Ukrainian riding breed in the conditions of physical and emotional loading. Clinically healthy race horses were the object of  research. Blood was taken from the jugular vein to obtain serum and for further biochemical research. For the research 12 race horses from a training group were chosen. From time to time the animals took part in competitions; they were not specially used in races and were mostly used for the training of junior riders and sportsmen of different levels. Blood was taken in conditions of relative rest after ordinary training and after emotional stress during the entertainment performances when a large number of people were present and loud music was played. In the blood serum the following biochemical indicators were defined: whole protein, urea, creatinine, uric acid, total bilirubin and its fractions, glucose, cholestererol, triacylglycerol, calcium, ferrum, lactate, pyruvate, activity of the AlAT, SGOT, GGTP, LDH, an alkaline phosphatase – which makes it possible to determine reasonably accurately the adaptation potential of a horse under various types of loading. We established that during training and psychoemotional loading of racing horses of the training group of the Ukrainian riding breed, multidirectional changes in the level of biochemical indicators of blood serum occurred, which is evidence of stress in the metabolic processes in the animals’ organisms. Concentration of a biomarker of an oxidative stress, uric acid, increased after physical loading by 8.6%, and after emotional loading by 55.1%, which demonstrates that emotional stress had the more negative effect, indicating insufficient adaptation by the horses before demonstration performances. After physical loading, reaction of transamination in the horses’ liver cells intensified, and after emotional loading its intensity

  20. Adaptation profiles comprising objective and subjective measures in fibromyalgia: the al-Ándalus project.

    Science.gov (United States)

    Estévez-López, Fernando; Segura-Jiménez, Víctor; Álvarez-Gallardo, Inmaculada C; Borges-Cosic, Milkana; Pulido-Martos, Manuel; Carbonell-Baeza, Ana; Aparicio, Virginia A; Geenen, Rinie; Delgado-Fernández, Manuel

    2017-11-01

    The aim of this study was to identify subgroups in terms of adaptation to FM and to test differences in FM severity between these subgroups. The al-Ándalus project made it possible to perform a comprehensive population-based cross-sectional study in 486 FM patients including multiple assessments of modifiable (could be targeted in therapy) resilience and vulnerability factors, measured by objective and subjective assessments, related to psychological and physical function. FM severity was assessed by means of FM impact (total score of the Revised Fibromyalgia Impact Questionnaire) and distress (Polysymptomatic Distress Scale of the modified 2011 preliminary criteria for FM). Exploratory factor analysis, cluster analysis and analysis of variance were conducted. Factor analysis yielded eight factors: three included objective measures (declarative memory, active lifestyle and objective physical fitness) and five included subjective measures (fatigue, psychological distress, catastrophizing, resilience and subjective physical fitness). Cluster analysis based on these eight factors identified five profiles: Adapted (16%), Fit (18%), Poor performer (20%), Positive (20%) and Maladapted (26%). Most profile comparisons revealed different levels of FM severity varying from Adapted (the most favourable profile) to Maladapted (the most unfavourable profile) with Fit, Poor performer and Positive obtaining intermediate positions. Heterogeneity of FM was shown by five clinically meaningful profiles of modifiable factors that were associated with FM severity. It is of clinical interest to examine whether these profiles are associated with FM prognosis and the effectiveness of interventions, which would enhance the development of customized interventions based on adaptation profiles in FM.

  1. Effects of culture media on metabolic profiling of the human gastric cancer cell line SGC7901.

    Science.gov (United States)

    Huang, Zicheng; Shao, Wei; Gu, Jinping; Hu, Xiaomin; Shi, Yuanzhi; Xu, Wenqi; Huang, Caihua; Lin, Donghai

    2015-07-01

    Cell culture metabolomics has demonstrated significant advantages in cancer research. However, its applications have been impeded by some influencing factors such as culture media, which could significantly affect cellular metabolic profiles and lead to inaccuracy and unreliability of comparative metabolomic analysis of cells. To evaluate the effects of different culture media on cellular metabolic profiling, we performed NMR-based metabolomic analysis of the human gastric cancer cell line SGC7901 cultured in both RPMI1640 and DMEM. We found that SGC7901 cultured in the two media exhibited distinct metabolic profiles with obviously different levels of discrepant metabolites, even though they showed almost the same cellular morphology and proliferation rates. When SGC7901 originally cultured in RPMI1640 was gradually acclimated in DMEM, both the metabolic profiles and most of the discrepant metabolite levels gradually converged toward those of the cells originally cultured in DMEM without significantly altered cell proliferation rates. However, several metabolite levels did not show the converging trends. Our results indicate that the effects of culture media on metabolic profiling must be carefully taken into account for comparative metabolomic analysis of cell lines. This work may be of benefit to the development of cell culture metabolomics.

  2. Obese Patients With a Binge Eating Disorder Have an Unfavorable Metabolic and Inflammatory Profile.

    Science.gov (United States)

    Succurro, Elena; Segura-Garcia, Cristina; Ruffo, Mariafrancesca; Caroleo, Mariarita; Rania, Marianna; Aloi, Matteo; De Fazio, Pasquale; Sesti, Giorgio; Arturi, Franco

    2015-12-01

    To evaluate whether obese patients with a binge eating disorder (BED) have an altered metabolic and inflammatory profile related to their eating behaviors compared with non-BED obese.A total of 115 White obese patients consecutively recruited underwent biochemical, anthropometrical evaluation, and a 75-g oral glucose tolerance test. Patients answered the Binge Eating Scale and were interviewed by a psychiatrist. The patients were subsequently divided into 2 groups according to diagnosis: non-BED obese (n = 85) and BED obese (n = 30). Structural equation modeling analysis was performed to elucidate the relation between eating behaviors and metabolic and inflammatory profile.BED obese exhibited significantly higher percentages of altered eating behaviors, body mass index (P Binge eating disorder obese also had a worse metabolic and inflammatory profile, exhibiting significantly lower high-density lipoprotein cholesterol levels (P eating behaviors of BED and the metabolic and inflammatory profile.Binge eating disorder obese exhibited an unfavorable metabolic and inflammatory profile, which is related to their characteristic eating habits.

  3. Metabolic profile in growing buffalo heifers fed diet with different energy content

    Directory of Open Access Journals (Sweden)

    B. Gasparrini

    2010-02-01

    Full Text Available Aim of this study was to verify the relation among the mediators and indicators of nutritional status like insulin, glucagon, urea, cholesterol, triglycerides and total proteins in growing buffalo heifers, fed diets with different energy density. 12 Murrah heifers were randomly allocated into two dietary treatments (High, Group H; Low, Group L that differed in energetic levels (Group H: 5.8 UFL/d; Group L: 3.6 UFL/d. Every 30 days, for a total of five times, blood samples were collected at 08.00 h, before feeding, from the jugular vein in vacutainer tubes and analysed to determine metabolic profile. Data on haematic constants were analysed by ANOVA for repeated measures with treatment as the main factor. Low energy availability and low NSC reduced the glucose and insulin and increased glucagone and urea blood levels. The increase of NSC in the diet of group H during the experiment may caused a reduction of the fibre digestibility after the period of adaptation of the rumen microflora and, as a paradox effect, suffered for an energetic lack with a subsequent activation of lipolysis and mobilization of their body reserves. Liver and muscular synthesis increase in group with a high energy availability.

  4. AntDAS: Automatic Data Analysis Strategy for UPLC-QTOF-Based Nontargeted Metabolic Profiling Analysis.

    Science.gov (United States)

    Fu, Hai-Yan; Guo, Xiao-Ming; Zhang, Yue-Ming; Song, Jing-Jing; Zheng, Qing-Xia; Liu, Ping-Ping; Lu, Peng; Chen, Qian-Si; Yu, Yong-Jie; She, Yuanbin

    2017-10-17

    High-quality data analysis methodology remains a bottleneck for metabolic profiling analysis based on ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. The present work aims to address this problem by proposing a novel data analysis strategy wherein (1) chromatographic peaks in the UPLC-QTOF data set are automatically extracted by using an advanced multiscale Gaussian smoothing-based peak extraction strategy; (2) a peak annotation stage is used to cluster fragment ions that belong to the same compound. With the aid of high-resolution mass spectrometer, (3) a time-shift correction across the samples is efficiently performed by a new peak alignment method; (4) components are registered by using a newly developed adaptive network searching algorithm; (5) statistical methods, such as analysis of variance and hierarchical cluster analysis, are then used to identify the underlying marker compounds; finally, (6) compound identification is performed by matching the extracted peak information, involving high-precision m/z and retention time, against our compound library containing more than 500 plant metabolites. A manually designed mixture of 18 compounds is used to evaluate the performance of the method, and all compounds are detected under various concentration levels. The developed method is comprehensively evaluated by an extremely complex plant data set containing more than 2000 components. Results indicate that the performance of the developed method is comparable with the XCMS. The MATLAB GUI code is available from http://software.tobaccodb.org/software/antdas .

  5. Locomotor Adaptation Improves Balance Control, Multitasking Ability and Reduces the Metabolic Cost of Postural Instability

    Science.gov (United States)

    Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. D.; Miller, C. A.; Ploutz-Snyder, R. J.; Guined, J. R.; Buxton, R. E.; Cohen, H. S.

    2011-01-01

    During exploration-class missions, sensorimotor disturbances may lead to disruption in the ability to ambulate and perform functional tasks during the initial introduction to a novel gravitational environment following a landing on a planetary surface. The overall goal of our current project is to develop a sensorimotor adaptability training program to facilitate rapid adaptation to these environments. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene. It provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. Greater metabolic cost incurred during balance instability means more physical work is required during adaptation to new environments possibly affecting crewmembers? ability to perform mission critical tasks during early surface operations on planetary expeditions. The goal of this study was to characterize adaptation to a discordant sensory challenge across a number of performance modalities including locomotor stability, multi-tasking ability and metabolic cost. METHODS: Subjects (n=15) walked (4.0 km/h) on a treadmill for an 8 -minute baseline walking period followed by 20-minutes of walking (4.0 km/h) with support surface motion (0.3 Hz, sinusoidal lateral motion, peak amplitude 25.4 cm) provided by the treadmill/motion-base system. Stride frequency and auditory reaction time were collected as measures of locomotor stability and multi-tasking ability, respectively. Metabolic data (VO2) were collected via a portable metabolic gas analysis system. RESULTS: At the onset of lateral support surface motion, subj ects walking on our treadmill showed an increase in stride frequency and auditory reaction time indicating initial balance and multi-tasking disturbances. During the 20-minute adaptation period, balance control and multi-tasking performance improved. Similarly, throughout the 20-minute adaptation period, VO2 gradually

  6. Metabolic Profiling of Human Benign and Malignant Pulmonary Nodules Using Mass Spectrometry-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Choon Nam Ong

    2013-07-01

    Full Text Available Solitary pulmonary nodule (SPN or coin lesion is a mass in the lung and can be commonly found in chest X-rays or computerized tomography (CT scans. However, despite the advancement of imaging technologies, it is still difficult to distinguish malignant cancer from benign SPNs. Here we investigated the metabolic profiling of patients with benign and malignant pulmonary nodules. A combination of gas chromatography/mass spectrometry (GC/MS and liquid chromatography/mass spectrometry (LC/MS was used to profile the plasma metabolites in 17 patients with malignant SPNs, 15 patients with benign SPNs and 20 healthy controls. The metabolic profiles were assayed using OPLS-DA, and further analyzed to identify marker metabolites related to diseases. Both GC/MS- and LC/MS-derived models showed clear discriminations in metabolic profiles among three groups. It was found that 63 metabolites (12 from GC/MS, 51 from LC/MS contributed to the differences. Of these, 48 metabolites showed same change trend in both malignant and benign SPNs as compared with healthy controls, indicating some common pathways including inflammation and oxidative injury shared by two diseases. In contrast, 14 metabolites constituted distinct profiles that differentiated malignant from benign SPNs, which might be a unique biochemical feature associated with lung cancer. Overall, our data suggested that integration of two highly sensitive and complementary metabolomics platforms could enable a comprehensive metabolic profiling and assist in discrimination malignant from benign SPNs.

  7. Profile-based adaptive anomaly detection for network security.

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Pengchu C. (Sandia National Laboratories, Albuquerque, NM); Durgin, Nancy Ann

    2005-11-01

    As information systems become increasingly complex and pervasive, they become inextricably intertwined with the critical infrastructure of national, public, and private organizations. The problem of recognizing and evaluating threats against these complex, heterogeneous networks of cyber and physical components is a difficult one, yet a solution is vital to ensuring security. In this paper we investigate profile-based anomaly detection techniques that can be used to address this problem. We focus primarily on the area of network anomaly detection, but the approach could be extended to other problem domains. We investigate using several data analysis techniques to create profiles of network hosts and perform anomaly detection using those profiles. The ''profiles'' reduce multi-dimensional vectors representing ''normal behavior'' into fewer dimensions, thus allowing pattern and cluster discovery. New events are compared against the profiles, producing a quantitative measure of how ''anomalous'' the event is. Most network intrusion detection systems (IDSs) detect malicious behavior by searching for known patterns in the network traffic. This approach suffers from several weaknesses, including a lack of generalizability, an inability to detect stealthy or novel attacks, and lack of flexibility regarding alarm thresholds. Our research focuses on enhancing current IDS capabilities by addressing some of these shortcomings. We identify and evaluate promising techniques for data mining and machine-learning. The algorithms are ''trained'' by providing them with a series of data-points from ''normal'' network traffic. A successful algorithm can be trained automatically and efficiently, will have a low error rate (low false alarm and miss rates), and will be able to identify anomalies in ''pseudo real-time'' (i.e., while the intrusion is still in progress

  8. Influence of common preanalytical variations on the metabolic profile of serum samples in biobanks

    Energy Technology Data Exchange (ETDEWEB)

    Fliniaux, Ophelie [University of Picardie Jules Verne, Laboratoire de Phytotechnologie EA 3900-BioPI (France); Gaillard, Gwenaelle [Biobanque de Picardie (France); Lion, Antoine [University of Picardie Jules Verne, Laboratoire de Phytotechnologie EA 3900-BioPI (France); Cailleu, Dominique [Batiment Serres-Transfert, rue de Mai/rue Dallery, Plateforme Analytique (France); Mesnard, Francois, E-mail: francois.mesnard@u-picardie.fr [University of Picardie Jules Verne, Laboratoire de Phytotechnologie EA 3900-BioPI (France); Betsou, Fotini [Integrated Biobank of Luxembourg (Luxembourg)

    2011-12-15

    A blood pre-centrifugation delay of 24 h at room temperature influenced the proton NMR spectroscopic profiles of human serum. A blood pre-centrifugation delay of 24 h at 4 Degree-Sign C did not influence the spectroscopic profile as compared with 4 h delays at either room temperature or 4 Degree-Sign C. Five or ten serum freeze-thaw cycles also influenced the proton NMR spectroscopic profiles. Certain common in vitro preanalytical variations occurring in biobanks may impact the metabolic profile of human serum.

  9. Gene expression profiles of auxin metabolism in maturing apple fruit

    Science.gov (United States)

    Variation exists among apple genotypes in fruit maturation and ripening patterns that influences at-harvest fruit firmness and postharvest storability. Based on the results from our previous large-scale transcriptome profiling on apple fruit maturation and well-documented auxin-ethylene crosstalk, t...

  10. Adaptive Super-Twisting Observer for Estimation of Random Road Excitation Profile in Automotive Suspension Systems

    Directory of Open Access Journals (Sweden)

    J. J. Rath

    2014-01-01

    Full Text Available The estimation of road excitation profile is important for evaluation of vehicle stability and vehicle suspension performance for autonomous vehicle control systems. In this work, the nonlinear dynamics of the active automotive system that is excited by the unknown road excitation profile are considered for modeling. To address the issue of estimation of road profile, we develop an adaptive supertwisting observer for state and unknown road profile estimation. Under Lipschitz conditions for the nonlinear functions, the convergence of the estimation error is proven. Simulation results with Ford Fiesta MK2 demonstrate the effectiveness of the proposed observer for state and unknown input estimation for nonlinear active suspension system.

  11. Alzheimer's disease and natural cognitive aging may represent adaptive metabolism reduction programs

    National Research Council Canada - National Science Library

    Reser, Jared Edward

    2009-01-01

    ... and Alzheimer's disease (AD), represent a metabolism reduction program. A number of such adaptive programs are known to accompany aging and are thought to have decreased energy requirements for ancestral hunter-gatherers in their 30s, 40s and 50s...

  12. Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery.

    Directory of Open Access Journals (Sweden)

    David M Mutch

    Full Text Available BACKGROUND: Roux-en-Y gastric bypass (RYGB surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data. METHODOLOGY AND PRINCIPAL FINDINGS: Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2+/-1.7. Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172 of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05, including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9 and obese/diabetic (n = 5 groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2, nervonic (C24:1 acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI and estimates for insulin resistance (HOMA-IR. Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = -0.55. CONCLUSIONS: Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.

  13. Metabolic Disorders in the Transition Period Indicate that the Dairy Cows’ Ability to Adapt is Overstressed

    Science.gov (United States)

    Sundrum, Albert

    2015-01-01

    Simple Summary Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. Problems derive from difficulties animals have to adapt to large variations and disturbances occurring both outside and inside the organism. A lack of success in solving these issues may be due to predominant approaches in farm management and agricultural science, dealing with such disorders as merely negative side effects. Instead, a successful adaptation of animals to their living conditions should be seen as an important end in itself. Both farm management and agricultural sciences should support animals in their ability to cope with nutritional and metabolic challenges by employing a functional and result-driven approach. Abstract Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. They mainly derive from difficulties the animals have in adapting to changes and disturbances occurring both outside and inside the organisms and due to varying gaps between nutrient supply and demand. Adaptation is a functional and target-oriented process involving the whole organism and thus cannot be narrowed down to single factors. Most problems which challenge the organisms can be solved in a number of different ways. To understand the mechanisms of adaptation, the interconnectedness of variables and the nutrient flow within a metabolic network need to be considered. Metabolic disorders indicate an overstressed ability to balance input, partitioning and output variables. Dairy cows will more easily succeed in adapting and in avoiding dysfunctional processes in the transition period when the gap between nutrient and energy demands and their supply is restricted. Dairy farms vary widely in relation to the living conditions of the animals. The complexity of nutritional and metabolic processes and their large variations on various scales

  14. Prediction of future risk of insulin resistance and metabolic syndrome based on Korean boy's metabolite profiling.

    Science.gov (United States)

    Lee, AeJin; Jang, Han Byul; Ra, Moonjin; Choi, Youngshim; Lee, Hye-Ja; Park, Ju Yeon; Kang, Jae Heon; Park, Kyung-Hee; Park, Sang Ick; Song, Jihyun

    2015-01-01

    Childhood obesity is strongly related to future insulin resistance and metabolic syndrome. Thus, identifying early biomarkers of obesity-related diseases based on metabolic profiling is useful to control future metabolic disorders. We compared metabolic profiles between obese and normal-weight children and investigated specific biomarkers of future insulin resistance and metabolic syndrome. In all, 186 plasma metabolites were analysed at baseline and after 2 years in 109 Korean boys (age 10.5±0.4 years) from the Korean Child Obesity Cohort Study using the AbsoluteIDQ™ p180 Kit. We observed that levels of 41 metabolites at baseline and 40 metabolites at follow-up were significantly altered in obese children (pObese children showed significantly higher levels of branched-chain amino acids (BCAAs) and several acylcarnitines and lower levels of acyl-alkyl phosphatidylcholines. Also, baseline BCAAs were significantly positively correlated with both homeostasis model assessment for insulin resistance (HOMA-IR) and continuous metabolic risk score at the 2-year follow-up. In logistic regression analyses with adjustments for degree of obesity at baseline, baseline BCAA concentration, greater than the median value, was identified as a predictor of future risk of insulin resistance and metabolic syndrome. High BCAA concentration could be "early" biomarkers for predicting future metabolic diseases. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  15. Association between urinary metabolic profile and the intestinal effects of cocoa in rats.

    Science.gov (United States)

    Massot-Cladera, Malen; Mayneris-Perxachs, Jordi; Costabile, Adele; Swann, Jonathan R; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

    2017-03-01

    The aim of this study was to elucidate the relationship between the urinary metabolic fingerprint and the effects of cocoa and cocoa fibre on body weight, hormone metabolism, intestinal immunity and microbiota composition. To this effect, Wistar rats were fed, for 3 weeks, a diet containing 10 % cocoa (C10) or two other diets with same the proportion of fibres: one based on cocoa fibre (CF) and another containing inulin as a reference (REF) diet. The rats' 24 h urine samples were analysed by an untargeted 1H NMR spectroscopy-based metabonomic approach. Concentrations of faecal IgA and plasma metabolic hormones were also quantified. The C10 diet decreased the intestinal IgA, plasma glucagon-like peptide-1 and glucagon concentrations and increased ghrelin levels compared with those in the REF group. Clear differences were observed between the metabolic profiles from the C10 group and those from the CF group. Urine metabolites derived from cocoa correlated with the cocoa effects on body weight, immunity and the gut microbiota. Overall, cocoa intake alters the host and bacterial metabolism concerning energy and amino acid pathways, leading to a metabolic signature that can be used as a marker for consumption. This metabolic profile correlates with body weight, metabolic hormones, intestinal immunity and microbiota composition.

  16. Elevated mitochondrial oxidative stress impairs metabolic adaptations to exercise in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Justin D Crane

    Full Text Available Mitochondrial oxidative stress is a complex phenomenon that is inherently tied to energy provision and is implicated in many metabolic disorders. Exercise training increases mitochondrial oxidative capacity in skeletal muscle yet it remains unclear if oxidative stress plays a role in regulating these adaptations. We demonstrate that the chronic elevation in mitochondrial oxidative stress present in Sod2 (+/- mice impairs the functional and biochemical mitochondrial adaptations to exercise. Following exercise training Sod2 (+/- mice fail to increase maximal work capacity, mitochondrial enzyme activity and mtDNA copy number, despite a normal augmentation of mitochondrial proteins. Additionally, exercised Sod2 (+/- mice cannot compensate for their higher amount of basal mitochondrial oxidative damage and exhibit poor electron transport chain complex assembly that accounts for their compromised adaptation. Overall, these results demonstrate that chronic skeletal muscle mitochondrial oxidative stress does not impact exercise induced mitochondrial biogenesis, but impairs the resulting mitochondrial protein function and can limit metabolic plasticity.

  17. Transition from metabolic adaptation to maladaptation of the heart in obesity: role of apelin.

    Science.gov (United States)

    Alfarano, C; Foussal, C; Lairez, O; Calise, D; Attané, C; Anesia, R; Daviaud, D; Wanecq, E; Parini, A; Valet, P; Kunduzova, O

    2015-02-01

    Impaired energy metabolism is the defining characteristic of obesity-related heart failure. The adipocyte-derived peptide apelin has a role in the regulation of cardiovascular and metabolic homeostasis and may contribute to the link between obesity, energy metabolism and cardiac function. Here we investigate the role of apelin in the transition from metabolic adaptation to maladaptation of the heart in obese state. Adult male C57BL/6J, apelin knock-out (KO) or wild-type mice were fed a high-fat diet (HFD) for 18 weeks. To induce heart failure, mice were subjected to pressure overload after 18 weeks of HFD. Long-term effects of apelin on fatty acid (FA) oxidation, glucose metabolism, cardiac function and mitochondrial changes were evaluated in HFD-fed mice after 4 weeks of pressure overload. Cardiomyocytes from HFD-fed mice were isolated for analysis of metabolic responses. In HFD-fed mice, pressure overload-induced transition from hypertrophy to heart failure is associated with reduced FA utilization (Pobesity-related decline in cardiac function is associated with defective myocardial energy metabolism and mitochondrial abnormalities. Furthermore, our work points for therapeutic potential of apelin to prevent myocardial metabolic abnormalities in heart failure paired with obesity.

  18. Acetobacter pasteurianus metabolic change induced by initial acetic acid to adapt to acetic acid fermentation conditions.

    Science.gov (United States)

    Zheng, Yu; Zhang, Renkuan; Yin, Haisong; Bai, Xiaolei; Chang, Yangang; Xia, Menglei; Wang, Min

    2017-09-01

    Initial acetic acid can improve the ethanol oxidation rate of acetic acid bacteria for acetic acid fermentation. In this work, Acetobacter pasteurianus was cultured in ethanol-free medium, and energy production was found to increase by 150% through glucose consumption induced by initial acetic acid. However, oxidation of ethanol, instead of glucose, became the main energy production pathway when upon culturing ethanol containing medium. Proteome assay was used to analyze the metabolism change induced by initial acetic acid, which provided insight into carbon metabolic and energy regulation of A. pasteurianus to adapt to acetic acid fermentation conditions. Results were further confirmed by quantitative real-time PCR. In summary, decreased intracellular ATP as a result of initial acetic acid inhibition improved the energy metabolism to produce more energy and thus adapt to the acetic acid fermentation conditions. A. pasteurianus upregulated the expression of enzymes related to TCA and ethanol oxidation to improve the energy metabolism pathway upon the addition of initial acetic acid. However, enzymes involved in the pentose phosphate pathway, the main pathway of glucose metabolism, were downregulated to induce a change in carbon metabolism. Additionally, the enhancement of alcohol dehydrogenase expression promoted ethanol oxidation and strengthened the acetification rate, thereby producing a strong proton motive force that was necessary for energy production and cell tolerance to acetic acid.

  19. Modeling phenotypic metabolic adaptations of Mycobacterium tuberculosis H37Rv under hypoxia.

    Directory of Open Access Journals (Sweden)

    Xin Fang

    Full Text Available The ability to adapt to different conditions is key for Mycobacterium tuberculosis, the causative agent of tuberculosis (TB, to successfully infect human hosts. Adaptations allow the organism to evade the host immune responses during acute infections and persist for an extended period of time during the latent infectious stage. In latently infected individuals, estimated to include one-third of the human population, the organism exists in a variety of metabolic states, which impedes the development of a simple strategy for controlling or eradicating this disease. Direct knowledge of the metabolic states of M. tuberculosis in patients would aid in the management of the disease as well as in forming the basis for developing new drugs and designing more efficacious drug cocktails. Here, we propose an in silico approach to create state-specific models based on readily available gene expression data. The coupling of differential gene expression data with a metabolic network model allowed us to characterize the metabolic adaptations of M. tuberculosis H37Rv to hypoxia. Given the microarray data for the alterations in gene expression, our model predicted reduced oxygen uptake, ATP production changes, and a global change from an oxidative to a reductive tricarboxylic acid (TCA program. Alterations in the biomass composition indicated an increase in the cell wall metabolites required for cell-wall growth, as well as heightened accumulation of triacylglycerol in preparation for a low-nutrient, low metabolic activity life style. In contrast, the gene expression program in the deletion mutant of dosR, which encodes the immediate hypoxic response regulator, failed to adapt to low-oxygen stress. Our predictions were compatible with recent experimental observations of M. tuberculosis activity under hypoxic and anaerobic conditions. Importantly, alterations in the flow and accumulation of a particular metabolite were not necessarily directly linked to

  20. Effect of alprazolam on rat serum metabolic profiles.

    Science.gov (United States)

    Li, Yan; Lin, Gaotong; Chen, Bingbao; Zhang, Jing; Wang, Lingtian; Li, Zixia; Cao, Yungang; Wen, Congcong; Yang, Xuezhi; Cao, Gaozhong; Wang, Xianqin; Cao, Guoquan

    2017-09-01

    We developed a serum metabolomic method by gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of alprazolam in rats. The GC-MS with HP-5MS (0.25 μm × 30 m × 0.25 mm) mass was conducted in electron impact ionization (EI) mode with electron energy of 70 eV, and full-scan mode with m/z 50-550. The rats were randomly divided to four groups, three alprazolam-treated groups and a control group. The alprazolam-treated rats were given 5, 10 or 20 mg/kg (low, medium, high) of alprazolam by intragastric administration each day for 14 days. The serum samples were corrected on the seventh and fourteenth days for metabolomic study. The blood was collected for biochemical tests. Then liver and brain were rapidly isolated and immersed for pathological study. Compared with the control group, on the seventh and fourteen days, the levels of d-glucose, 9,12-octadecadienoic acid, butanoic acid, l-proline, d-mannose and malic acid had changed, indicating that alprazolam induced energy metabolism, fatty acid metabolism and amino acid metabolism perturbations in rats. There was no significant difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea and uric acid between controls and alprazolam groups. According to the pathological results, alprazolam is not hepatotoxic. Metabolomics could distinguish different alprazolam doses in rats. Copyright © 2017 John Wiley & Sons, Ltd.

  1. AMPKα in Exercise-Induced Substrate Metabolism and Exercise Training-Induced Metabolic and Mitochondrial Adaptations

    DEFF Research Database (Denmark)

    Fentz, Joachim

    of AMPK. A highly specific activation of AMPK can be attained with the pharmacological compound AICAR. Similar to exercise, an acute dose of AICAR increases muscle glucose uptake and repeated stimulation with AICAR increases the metabolic capacity of rodent muscle. However, in genetically mutated mice...

  2. A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals

    Directory of Open Access Journals (Sweden)

    Dorian S Houser

    2013-11-01

    Full Text Available Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris, which fasts from food and water for periods of up to three months. During this time, ~90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM. All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures

  3. Assessing the metabolic effects of prednisolone in healthy volunteers using urine metabolic profiling

    NARCIS (Netherlands)

    Ellero-Simatos, S.; Szymańska, E.; Rullmann, T.; Dokter, W.H.A.; Ramaker, R.; Berger, R.; van Iersel, T.M.P.; Smilde, A.K.; Hankemeier, T.; Alkema, W.

    2012-01-01

    BACKGROUND Glucocorticoids, such as prednisolone, are widely used anti-inflammatory drugs, but therapy is hampered by a broad range of metabolic side effects including skeletal muscle wasting and insulin resistance. Therefore, development of improved synthetic glucocorticoids that display similar

  4. Metabolic Syndrome, Insulin Resistance and Cognitive Dysfunction: Does your metabolic profile affect your brain?

    DEFF Research Database (Denmark)

    Neergaard, Jesper S; Møller, Katrine Dragsbæk; Christiansen, Claus

    2017-01-01

    Dementia and type 2 diabetes are both characterized by long prodromal phases challenging the study of potential risk factors and their temporal relation. The progressive relation between metabolic syndrome, insulin resistance, and dementia has recently been questioned, wherefore the aim...

  5. Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.

    Science.gov (United States)

    Ammons, Mary Cloud B; Morrissey, Kathryn; Tripet, Brian P; Van Leuven, James T; Han, Anne; Lazarus, Gerald S; Zenilman, Jonathan M; Stewart, Philip S; James, Garth A; Copié, Valérie

    2015-01-01

    Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.

  6. Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.

    Directory of Open Access Journals (Sweden)

    Mary Cloud B Ammons

    Full Text Available Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.

  7. Plasma metabolic profiling of dairy cows affected with clinical ketosis using LC/MS technology.

    Science.gov (United States)

    Li, Y; Xu, C; Xia, C; Zhang, Hy; Sun, Lw; Gao, Y

    2014-01-01

    Ketosis in dairy cattle is an important metabolic disorder. Currently, the plasma metabolic profile of ketosis as determined using liquid chromatography-mass spectrometry (LC/MS) has not been reported. To investigate plasma metabolic profiles from cows with clinical ketosis in comparison to control cows. Twenty Holstein dairy cows were divided into two groups based on clinical signs and plasma β-hydroxybutyric acid and glucose concentrations 7-21 days postpartum: clinical ketosis and control cows. Plasma metabolic profiles were analyzed using LC/MS. Data were processed using principal component analysis and orthogonal partial least-squares discriminant analysis. Compared to control cows, the levels of valine, glycine, glycocholic, tetradecenoic acid, and palmitoleic acid increased significantly in clinical ketosis. On the other hand, the levels of arginine, aminobutyric acid, leucine/isoleucine, tryptophan, creatinine, lysine, norcotinine, and undecanoic acid decreased markedly. Our results showed that the metabolic changes in cows with clinical ketosis involve complex metabolic networks and signal transduction. These results are important for future studies elucidating the pathogenesis, diagnosis, and prevention of clinical ketosis in dairy cows.

  8. Staphylococcus aureus methicillin resistance detected by HPLC-MS/MS targeted metabolic profiling.

    Science.gov (United States)

    Schelli, Katie; Rutowski, Joshua; Roubidoux, Julia; Zhu, Jiangjiang

    2017-03-15

    Recently, novel bioanalytical methods, such as NMR and mass spectrometry based metabolomics approaches, have started to show promise in providing rapid, sensitive and reproducible detection of Staphylococcus aureus antibiotic resistance. Here we performed a proof-of-concept study focused on the application of HPLC-MS/MS based targeted metabolic profiling for detecting and monitoring the bacterial metabolic profile changes in response to sub-lethal levels of methicillin exposure. One hundred seventy-seven targeted metabolites from over 20 metabolic pathways were specifically screened and one hundred and thirty metabolites from in vitro bacterial tests were confidently detected from both methicillin susceptible and methicillin resistant Staphylococcus aureus (MSSA and MRSA, respectively). The metabolic profiles can be used to distinguish the isogenic pairs of MSSA strains from MRSA strains, without or with sub-lethal levels of methicillin exposure. In addition, better separation between MSSA and MRSA strains can be achieved in the latter case using principal component analysis (PCA). Metabolite data from isogenic pairs of MSSA and MRSA strains were further compared without and with sub-lethal levels of methicillin exposure, with metabolic pathway analyses additionally performed. Both analyses suggested that the metabolic activities of MSSA strains were more susceptible to the perturbation of the sub-lethal levels of methicillin exposure compared to the MRSA strains. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Radiation Changes the Metabolic Profiling of Melanoma Cell Line B16.

    Directory of Open Access Journals (Sweden)

    Lige Wu

    Full Text Available Radiation therapy can be an effective way to kill cancer cells using ionizing radiation, but some tumors are resistant to radiation therapy and the underlying mechanism still remains elusive. It is therefore necessary to establish an appropriate working model to study and monitor radiation-mediated cancer therapy. In response to cellular stress, the metabolome is the integrated profiling of changes in all metabolites in cells, which can be used to investigate radiation tolerance mechanisms and identify targets for cancer radiation sensibilization. In this study, using 1H nuclear magnetic resonance for untargeted metabolic profiling in radiation-tolerant mouse melanoma cell line B16, we comprehensively investigated changes in metabolites and metabolic network in B16 cells in response to radiation. Principal component analysis and partial least squares discriminant analysis indicated the difference in cellular metabolites between the untreated cells and X-ray radiated cells. In radiated cells, the content of alanine, glutamate, glycine and choline was increased, while the content of leucine, lactate, creatine and creatine phosphate was decreased. Enrichment analysis of metabolic pathway showed that the changes in metabolites were related to multiple metabolic pathways including the metabolism of glycine, arginine, taurine, glycolysis, and gluconeogenesis. Taken together, with cellular metabolome study followed by bioinformatic analysis to profile specific metabolic pathways in response to radiation, we deepened our understanding of radiation-resistant mechanisms and radiation sensibilization in cancer, which may further provide a theoretical and practical basis for personalized cancer therapy.

  10. Biochemical Association of Metabolic Profile and Microbiome in Chronic Pressure Ulcer Wounds

    Science.gov (United States)

    Ammons, Mary Cloud B.; Morrissey, Kathryn; Tripet, Brian P.; Van Leuven, James T.; Han, Anne; Lazarus, Gerald S.; Zenilman, Jonathan M.; Stewart, Philip S.; James, Garth A.; Copié, Valérie

    2015-01-01

    Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment. PMID:25978400

  11. FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function

    DEFF Research Database (Denmark)

    Jensen, Kim Steen; Binderup, Tina; Jensen, Klaus Thorleif

    2011-01-01

    Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful...... tumour tissue in vivo and that FoxO3A short-hairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia.......Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful...

  12. Prediction of glycated hemoglobin levels at 3 months after metabolic surgery based on the 7-day plasma metabolic profile.

    Directory of Open Access Journals (Sweden)

    Hyuk Nam Kwon

    Full Text Available Metabolic surgery has been shown to provide better glycemic control for type 2 diabetes than conventional therapies. Still, the outcomes of the surgery are variable, and prognostic markers reflecting the metabolic changes by the surgery are yet to be established. NMR-based plasma metabolomics followed by multivariate regression was used to test the correlation between the metabolomic profile at 7-days after surgery and glycated hemoglobin (HbA1c levels at 3-months (and up to 12 months with less patients, and to identify the relevant markers. Metabolomic profiles at 7-days could differentiate the patients according to the HbA1c improvement status at 3-months. The HbA1c values were predicted based on the metabolomics profile with partial least square regression, and found to be correlated with the observed values. Metabolite analysis suggested that 3-Hydroxybutyrate (3-HB and glucose contributes to this prediction, and the [3-HB]/[glucose] exhibited a modest to good correlation with the HbA1c level at 3-months. The prediction of 3-month HbA1c using 7-day metabolomic profile and the suggested new criterion [3-HB]/[glucose] could augment current prognostic modalities and help clinicians decide if drug therapy is necessary.

  13. Untargeted Metabolomics Analysis of ABCC6-Deficient Mice Discloses an Altered Metabolic Liver Profile

    DEFF Research Database (Denmark)

    Rasmussen, Mie Rostved; Nielsen, Kirstine Lykke; Christensen, Mia Benedicte Lykke Roest

    2016-01-01

    Loss-of-function mutations in the transmembrane ABCC6 transport protein cause pseudoxanthoma elasticum (PXE), an ectopic, metabolic mineralization disorder that affects the skin, eye, and vessels. ABCC6 is assumed to mediate efflux of one or several small molecule compounds from the liver cytosol...... in acetylation reactions, were accumulated in the liver. None of the identified metabolites seems to explain mineralization in extrahepatic tissues, but the present study now shows that abrogated ABCC6 function does cause alterations in the metabolic profile of the liver in accordance with PXE being a metabolic...

  14. Adaptation of manipulation skills in physical contact with the environment to reference force profiles

    DEFF Research Database (Denmark)

    Abu-Dakka, Fares J.; Nemec, Bojan; Jørgensen, Jimmy A.

    2015-01-01

    We propose a new methodology for learning and adaption of manipulation skills that involve physical contact with the environment. Pure position control is unsuitable for such tasks because even small errors in the desired trajectory can cause significant deviations from the desired forces...... and torques. The proposed algorithm takes a reference Cartesian trajectory and force/torque profile as input and adapts the movement so that the resulting forces and torques match the reference profiles. The learning algorithm is based on dynamic movement primitives and quaternion representation...

  15. Effect of tequila on homocysteine, insulin secretion, insulin sensitivity, and metabolic profile in healthy men.

    Science.gov (United States)

    González-Ortiz, Manuel; Pascoe-González, Sara; Kam-Ramos, Angélica M; Martínez-Abundis, Esperanza

    2005-01-01

    The purpose of this study is to identify the effect of a low dose of tequila on homocysteine, insulin secretion, insulin sensitivity, and metabolic profile in healthy young men. An open clinical trial was carried out in eight healthy nonobese, young male volunteers. The study was divided in two phases. The first one evaluated metabolic changes, including insulin secretion and sensitivity due to acute administration of 30 ml of straight tequila. The second phase of the study evaluated metabolic effects due to the daily administration of 30 ml of tequila during 30 days. There were no significant metabolic changes after the single oral administration of 30 ml of straight tequila. After the administration of tequila during 30 days, a significant increase in homocysteine levels and a tendency to increase the glucose concentration and to decrease the insulin sensitivity were found. Detrimental metabolic changes were observed with the daily administration of 30 ml of tequila during 30 days.

  16. Metabolic and inflammatory profile in obese patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Poulain, M; Doucet, M; Drapeau, V; Fournier, G; Tremblay, A; Poirier, P; Maltais, F

    2008-01-01

    Overweight and obesity have been associated with better survival in patients with chronic obstructive pulmonary disease (COPD). On the other hand, excess body weight is associated with abnormal metabolic and inflammatory profiles that define the metabolic syndrome and predispose to cardiovascular diseases. This study was undertaken to evaluate the impact of overweight and obesity on the prevalence of the metabolic syndrome and on the metabolic and inflammatory profiles in patients with COPD. Twenty-eight male patients with COPD were divided into an overweight/obese group [ n = 16, body mass index (BMI) = 33.5 +/- 4.2 kg/m(2)] and normal weight group (n = 12, BMI = 21.1 +/- 2.6 kg/m(2)). Anthropometry, pulmonary function and body composition were assessed. The metabolic syndrome was diagnosed according to waist circumference, circulating levels of triglyceride and high-density lipoprotein cholesterol levels, fasting glycemia and blood pressure. C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), leptin and adiponectin plasma levels were measured. Airflow obstruction was less severe in overweight/obese compared with normal weight patients (forced expiratory volume(1): 51 +/- 19% versus 31 +/- 12% predicted, respectively, P leptin were significantly higher in overweight/obese patients whereas the adiponectin levels were reduced in the presence of excess weight. The metabolic syndrome was frequent in overweight/obese patients with COPD. Obesity in COPD was associated with a spectrum of metabolic and inflammatory abnormalities.

  17. Metabolic Profiling in Association with Vascular Endothelial Cell Dysfunction Following Non-Toxic Cadmium Exposure

    Science.gov (United States)

    Li, Xiaofei; Nong, Qingjiao; Mao, Baoyu; Pan, Xue

    2017-01-01

    This study aimed to determine the metabolic profile of non-toxic cadmium (Cd)-induced dysfunctional endothelial cells using human umbilical vein endothelial cells (HUVECs). HUVECs (n = 6 per group) were treated with 0, 1, 5, or 10 μM cadmium chloride (CdCl2) for 48 h. Cell phenotypes, including nitric oxide (NO) production, the inflammatory response, and oxidative stress, were evaluated in Cd-exposed and control HUVECs. Cd-exposed and control HUVECs were analysed using gas chromatography time-of-flight/mass spectrometry. Compared to control HUVECs, Cd-exposed HUVECs were dysfunctional, exhibiting decreased NO production, a proinflammatory state, and non-significant oxidative stress. Further metabolic profiling revealed 24 significantly-altered metabolites in the dysfunctional endothelial cells. The significantly-altered metabolites were involved in the impaired tricarboxylic acid (TCA) cycle, activated pyruvate metabolism, up-regulated glucogenic amino acid metabolism, and increased pyrimidine metabolism. The current metabolic findings further suggest that the metabolic changes linked to TCA cycle dysfunction, glycosylation of the hexosamine biosynthesis pathway (HBP), and compensatory responses to genomic instability and energy deficiency may be generally associated with dysfunctional phenotypes, characterized by decreased NO production, a proinflammatory state, and non-significant oxidative stress, in endothelial cells following non-toxic Cd exposure. PMID:28872622

  18. The effect of combined inositol supplementation on maternal metabolic profile in pregnancies complicated by metabolic syndrome and obesity.

    Science.gov (United States)

    Ferrari, Francesca; Facchinetti, Fabio; Ontiveros, Alejandra E; Roberts, Robyn P; Saade, Mia M; Blackwell, Sean C; Sibai, Baha M; Refuerzo, Jerrie S; Longo, Monica

    2016-10-01

    Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype. The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model. Female heterozygous endothelial nitric oxide synthase(-/+) mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol-treated vs metabolic-like syndrome-nontreated mice and obese-myoinositol/D-chiroinositol-treated vs obese nontreated mice. Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo (P = .04), whereas there was no difference in systolic blood pressure between treated and placebo

  19. Metabolic engineering and profiling of rice with increased lysine.

    Science.gov (United States)

    Long, Xiaohang; Liu, Qiaoquan; Chan, Manling; Wang, Qing; Sun, Samuel S M

    2013-05-01

    Lysine (Lys) is the first limiting essential amino acid in rice, a stable food for half of the world population. Efforts, including genetic engineering, have not achieved a desirable level of Lys in rice. Here, we genetically engineered rice to increase Lys levels by expressing bacterial lysine feedback-insensitive aspartate kinase (AK) and dihydrodipicolinate synthase (DHPS) to enhance Lys biosynthesis; through RNA interference of rice lysine ketoglutaric acid reductase/saccharopine dehydropine dehydrogenase (LKR/SDH) to down-regulate its catabolism; and by combined expression of AK and DHPS and interference of LKR/SDH to achieve both metabolic effects. In these transgenic plants, free Lys levels increased up to ~12-fold in leaves and ~60-fold in seeds, substantially greater than the 2.5-fold increase in transgenic rice seeds reported by the only previous related study. To better understand the metabolic regulation of Lys accumulation in rice, metabolomic methods were employed to analyse the changes in metabolites of the Lys biosynthesis and catabolism pathways in leaves and seeds at different stages. Free Lys accumulation was mainly regulated by its biosynthesis in leaves and to a greater extent by catabolism in seeds. The transgenic plants did not show observable changes in plant growth and seed germination nor large changes in levels of asparagine (Asn) and glutamine (Gln) in leaves, which are the major amino acids transported into seeds. Although Lys was highly accumulated in leaves of certain transgenic lines, a corresponding higher Lys accumulation was not observed in seeds, suggesting that free Lys transport from leaves into seeds did not occur. © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  20. Metabolic profiling of Garcinia mangostana (mangosteen) based on ripening stages.

    Science.gov (United States)

    Parijadi, Anjaritha A R; Putri, Sastia P; Ridwani, Sobir; Dwivany, Fenny M; Fukusaki, Eiichiro

    2018-02-01

    Metabolomics is an emerging research field based on exhaustive metabolite profiling that have been proven useful to facilitate the study of postharvest fruit development and ripening. Specifically, tracking changes to the metabolome as fruit ripens should provide important clues for understanding ripening mechanisms and identify bio-markers to improve post-harvest technology of fruits. This study conducted a time-course metabolome analysis in mangosteen, an economically important tropical fruit valued for its flavor. Mangosteen is a climacteric fruit that requires an important plant hormone ethylene to regulate ripening processes and rate. We first categorized mangosteen samples in different ripening stages based on color changes, an established indicator of ripening. Using gas chromatography/mass spectrometry, small hydrophilic metabolites were profiled from non-ripened to fully ripened (ripening stages 0-6). These metabolites were then correlated with color changes to verify their involvement mangosteen ripening. Our results suggest that the increase of 2-aminoisobutyric acid, psicose, and several amino acids (phenylalanine, valine, isoleucine, serine, and tyrosine) showed a correlation with the progression of mangosteen ripening. This is the first report of the application of non-targeted metabolomics in mangosteen. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Transcript and metabolite profiling of the adaptive response to mild decreases in oxygen concentration in the roots of arabidopsis plants.

    Science.gov (United States)

    van Dongen, Joost T; Fröhlich, Anja; Ramírez-Aguilar, Santiago J; Schauer, Nicolas; Fernie, Alisdair R; Erban, Alexander; Kopka, Joachim; Clark, Jeremy; Langer, Anke; Geigenberger, Peter

    2009-01-01

    Oxygen can fall to low concentrations within plant tissues, either because of environmental factors that decrease the external oxygen concentration or because the movement of oxygen through the plant tissues cannot keep pace with the rate of oxygen consumption. Recent studies document that plants can decrease their oxygen consumption in response to relatively small changes in oxygen concentrations to avoid internal anoxia. The molecular mechanisms underlying this response have not been identified yet. The aim of this study was to use transcript and metabolite profiling to investigate the genomic response of arabidopsis roots to a mild decrease in oxygen concentrations. Arabidopsis seedlings were grown on vertical agar plates at 21, 8, 4 and 1 % (v/v) external oxygen for 0.5, 2 and 48 h. Roots were analysed for changes in transcript levels using Affymetrix whole genome DNA microarrays, and for changes in metabolite levels using routine GC-MS based metabolite profiling. Root extension rates were monitored in parallel to investigate adaptive changes in growth. The results show that root growth was inhibited and transcript and metabolite profiles were significantly altered in response to a moderate decrease in oxygen concentrations. Low oxygen leads to a preferential up-regulation of genes that might be important to trigger adaptive responses in the plant. A small but highly specific set of genes is induced very early in response to a moderate decrease in oxygen concentrations. Genes that were down-regulated mainly encoded proteins involved in energy-consuming processes. In line with this, root extension growth was significantly decreased which will ultimately save ATP and decrease oxygen consumption. This was accompanied by a differential regulation of metabolite levels at short- and long-term incubation at low oxygen. The results show that there are adaptive changes in root extension involving large-scale reprogramming of gene expression and metabolism when oxygen

  2. Defense Profiles in Adaptation Process to Sport Competition and Their Relationships with Coping, Stress and Control

    Directory of Open Access Journals (Sweden)

    Michel Nicolas

    2017-12-01

    Full Text Available The purpose of this study was to identify the potentially distinct defense profiles of athletes in order to provide insight into the complex associations that can exist between defenses and other important variables tied to performance in sports (e.g., coping, perceived stress and control and to further our understanding of the complexity of the adaptation process in sports. Two hundred and ninety-six (N = 296 athletes participated in a naturalistic study that involved a highly stressful situation: a sports competition. Participants were assessed before and after the competition. Hierarchical cluster analysis and a series of MANOVAs with post hoc comparisons indicated two stable defense profiles (high and low defense profiles of athletes both before and during sport competition. These profiles differed with regards to coping, stress and control. Athletes with high defense profiles reported higher levels of coping strategies, perceived stress and control than athletes with low defense profiles. This study confirmed that defenses are involved in the psychological adaptation process and that research and intervention should not be based only on coping, but rather must include defense mechanisms in order to improve our understanding of psychological adaptation in competitive sports.

  3. Relative Handgrip Strength Is Inversely Associated with Metabolic Profile and Metabolic Disease in the General Population in China

    Directory of Open Access Journals (Sweden)

    Dongxue Li

    2018-02-01

    Full Text Available Background: Absolute handgrip strength has been correlated with metabolic profile and metabolic disease. Whether relative handgrip strength is also associated with metabolic disease has not been assessed. This study aimed at assessing the association of relative handgrip strength with metabolic profile and metabolic disease in the general population in China.Methods: Data were derived from an ongoing cross-sectional survey of the 2013 National Physical and Health in Shanxi Province, which involved 5520 participants. Multiple linear regression or multiple logistic regression analysis were used to assess the association of absolute/relative handgrip strength with the metabolic profile, preclinical, and established stages of metabolic diseases.Results: This study revealed that relative handgrip strength, that is when normalized to BMI, was associated with: (1 in both genders for more favorable blood lipid levels of high-density lipoprotein cholesterol [males: b = 0.19 (0.15, 0.23; females: b = 0.22 (0.17, 0.28], low-density lipoprotein cholesterol [males: b = −0.14 (−0.23, −0.05; females: b = −0.19 (−0.31, −0.18], triglycerides [males: b = −0.58 (−0.74, −0.43; females: b = −0.55 (−0.74, −0.36] and total cholesterol [males: b = −0.20 (−0.31, −0.10; females: b = −0.19 (−0.32, −0.06]; and better serum glucose levels in males [b = −0.30 (−0.46, −0.15]. (2 lower risk of impaired fasting glucose in males {third quartile [OR = 0.66 (0.45–0.95] and fourth quartile [OR = 0.46 (0.30–0.71] vs. first quartile} and dyslipidemia in both genders {third quartile [males: OR = 0.65 (0.48–0.87; females: OR = 0.68 (0.53–0.86] and fourth quartile [males: OR = 0.47 (0.35–0.64; females: OR = 0.47(0.36–0.61] vs. first quartile}. (3 lower risk of hyperlipidemia in both genders third quartile [males: OR = 0.66 (0.50–0.87; females: OR = 0.57 (0.43–0.75] and fourth quartile [males: OR = 0.35 (0.26–0.47; females: OR

  4. Adaptation of the Biolog Phenotype MicroArrayTM Technology to Profile the Obligate Anaerobe Geobacter metallireducens

    Energy Technology Data Exchange (ETDEWEB)

    Joyner, Dominique; Fortney, Julian; Chakraborty, Romy; Hazen, Terry

    2010-05-17

    The Biolog OmniLog? Phenotype MicroArray (PM) plate technology was successfully adapted to generate a select phenotypic profile of the strict anaerobe Geobacter metallireducens (G.m.). The profile generated for G.m. provides insight into the chemical sensitivity of the organism as well as some of its metabolic capabilities when grown with a basal medium containing acetate and Fe(III). The PM technology was developed for aerobic organisms. The reduction of a tetrazolium dye by the test organism represents metabolic activity on the array which is detected and measured by the OmniLog(R) system. We have previously adapted the technology for the anaerobic sulfate reducing bacterium Desulfovibrio vulgaris. In this work, we have taken the technology a step further by adapting it for the iron reducing obligate anaerobe Geobacter metallireducens. In an osmotic stress microarray it was determined that the organism has higher sensitivity to impermeable solutes 3-6percent KCl and 2-5percent NaNO3 that result in osmotic stress by osmosis to the cell than to permeable non-ionic solutes represented by 5-20percent ethylene glycol and 2-3percent urea. The osmotic stress microarray also includes an array of osmoprotectants and precursor molecules that were screened to identify substrates that would provide osmotic protection to NaCl stress. None of the substrates tested conferred resistance to elevated concentrations of salt. Verification studies in which G.m. was grown in defined medium amended with 100mM NaCl (MIC) and the common osmoprotectants betaine, glycine and proline supported the PM findings. Further verification was done by analysis of transcriptomic profiles of G.m. grown under 100mM NaCl stress that revealed up-regulation of genes related to degradation rather than accumulation of the above-mentioned osmoprotectants. The phenotypic profile, supported by additional analysis indicates that the accumulation of these osmoprotectants as a response to salt stress does not

  5. Coregulation of host-adapted metabolism and virulence by pathogenic yersiniae

    Directory of Open Access Journals (Sweden)

    Ann Kathrin eHeroven

    2014-10-01

    Full Text Available Deciphering the principles how pathogenic bacteria adapt their metabolism to a specific host microenvironment is critical for understanding bacterial pathogenesis. The enteric pathogenic Yersinia species Y. pseudotuberculosis and Y. enterocolitica and the causative agent of plague, Y. pestis, are able to survive in a large variety of environmental reservoirs (e.g. soil, plants, insects as well as warm-blooded animals (e.g. rodents, pigs, humans with a particular preference for lymphatic tissues. In order to manage rapidly changing environmental conditions and inter-bacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly. In addition, nutrient availability has an impact on expression of virulence genes in response to C-sources, demonstrating a tight link between the pathogenicity of yersiniae and utilization of nutrients. Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp and the carbon storage regulator (Csr system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability. Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets.

  6. Integration of Posttranscriptional Gene Networks into Metabolic Adaptation and Biofilm Maturation in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Jiyoti Verma-Gaur

    2015-10-01

    Full Text Available The yeast Candida albicans is a human commensal and opportunistic pathogen. Although both commensalism and pathogenesis depend on metabolic adaptation, the regulatory pathways that mediate metabolic processes in C. albicans are incompletely defined. For example, metabolic change is a major feature that distinguishes community growth of C. albicans in biofilms compared to suspension cultures, but how metabolic adaptation is functionally interfaced with the structural and gene regulatory changes that drive biofilm maturation remains to be fully understood. We show here that the RNA binding protein Puf3 regulates a posttranscriptional mRNA network in C. albicans that impacts on mitochondrial biogenesis, and provide the first functional data suggesting evolutionary rewiring of posttranscriptional gene regulation between the model yeast Saccharomyces cerevisiae and C. albicans. A proportion of the Puf3 mRNA network is differentially expressed in biofilms, and by using a mutant in the mRNA deadenylase CCR4 (the enzyme recruited to mRNAs by Puf3 to control transcript stability we show that posttranscriptional regulation is important for mitochondrial regulation in biofilms. Inactivation of CCR4 or dis-regulation of mitochondrial activity led to altered biofilm structure and over-production of extracellular matrix material. The extracellular matrix is critical for antifungal resistance and immune evasion, and yet of all biofilm maturation pathways extracellular matrix biogenesis is the least understood. We propose a model in which the hypoxic biofilm environment is sensed by regulators such as Ccr4 to orchestrate metabolic adaptation, as well as the regulation of extracellular matrix production by impacting on the expression of matrix-related cell wall genes. Therefore metabolic changes in biofilms might be intimately linked to a key biofilm maturation mechanism that ultimately results in untreatable fungal disease.

  7. Earwax metabolomics: An innovative pilot metabolic profiling study for assessing metabolic changes in ewes during periparturition period.

    Directory of Open Access Journals (Sweden)

    Engy Shokry

    Full Text Available Important metabolic changes occur during transition period of late pregnancy and early lactation to meet increasing energy demands of the growing fetus and for milk production. The aim of this investigation is to present an innovative and non-invasive tool using ewe earwax sample analysis to assess the metabolic profile in ewes during late pregnancy and early lactation. In this work, earwax samples were collected from 28 healthy Brazilian Santa Inês ewes divided into 3 sub-groups: 9 non-pregnant ewes, 6 pregnant ewes in the last 30 days of gestation, and 13 lactating ewes ≤ 30 days postpartum. Then, a range of metabolites including volatile organic compounds (VOC, amino acids (AA, and minerals were profiled and quantified in the samples by applying headspace gas chromatography/mass spectrometry, high performance liquid chromatography/tandem mass spectrometry, and inductively coupled plasma-optical emission spectrometry, respectively. As evident in our results, significant changes were observed in the metabolite profile of earwax between the studied groups where a remarkable elevation was detected in the levels of non-esterified fatty acids, alcohols, ketones, and hydroxy urea in the VOC profile of samples obtained from pregnant and lactating ewes. Meanwhile, a significant decrease was detected in the levels of 9 minerals and 14 AA including essential AA (leucine, phenyl alanine, lysine, isoleucine, threonine, valine, conditionally essential AA (arginine, glycine, tyrosine, proline, serine, and a non-essential AA (alanine. Multivariate analysis using robust principal component analysis and hierarchical cluster analysis was successfully applied to discriminate the three study groups using the variations of metabolites in the two stress states (pregnancy and lactation from the healthy non-stress condition. The innovative developed method was successful in evaluating pre- and post-parturient metabolic changes using earwax and can in the future be

  8. African American parents' racial and emotion socialization profiles and young adults' emotional adaptation.

    Science.gov (United States)

    Dunbar, Angel S; Perry, Nicole B; Cavanaugh, Alyson M; Leerkes, Esther M

    2015-07-01

    The current study aimed to identify parents' profiles of racial and emotion socialization practices, to determine if these profiles vary as a function of family income and young adult child gender, and to examine their links with young adults' emotional adaptation. Participants included 192 African American young adults (70% women) who ranged in age from 18 to 24 years (M = 19.44 years). Four maternal profiles emerged: cultural-supportive (high cultural socialization and supportive responses to children's negative emotions), moderate bias preparation (moderate preparation for bias, promotion of mistrust, and nonsupportive responses to negative emotions), high bias preparation (high preparation for bias, promotion of mistrust, and nonsupportive responses), and low engaged (low across racial and socialization constructs). Three paternal profiles emerged: multifaceted (moderate across racial and emotion socialization constructs), high bias preparation, and low engaged. Men were more likely to have mothers in the high bias preparation and to have fathers in the multifaceted or high bias preparation profiles. Individuals with higher income were more likely to have mothers in the cultural-supportive profile and to have fathers in the multifaceted profile. Young adults whose mothers fit the cultural-supportive profile or the moderate bias preparation profile had lower levels of depressive symptoms than young adults whose mothers fit the high bias preparation profile. (c) 2015 APA, all rights reserved).

  9. Adolescent adaptive behavior profiles in Williams-Beuren syndrome, Down syndrome, and autism spectrum disorder.

    Science.gov (United States)

    Del Cole, Carolina Grego; Caetano, Sheila Cavalcante; Ribeiro, Wagner; Kümmer, Arthur Melo E E; Jackowski, Andrea Parolin

    2017-01-01

    Adaptive behavior can be impaired in different neurodevelopmental disorders and may be influenced by confounding factors, such as intelligence quotient (IQ) and socioeconomic classification. Our main objective was to verify whether adaptive behavior profiles differ in three conditions-Williams Beuren syndrome (WBS), Down syndrome (DS), and autism spectrum disorder (ASD), as compared with healthy controls (HC) and with each other. Although the literature points towards each disorder having a characteristic profile, no study has compared profiles to establish the specificity of each one. A secondary objective was to explore potential interactions between the conditions and socioeconomic status, and whether this had any effect on adaptive behavior profiles. One hundred and five adolescents were included in the study. All adolescents underwent the following evaluations: the Vineland Adaptive Behavior Scale (VABS), the Wechsler Intelligence Scale for Children (WISC), and the Brazilian Economic Classification Criteria. Our results demonstrated that the WBS group performed better than the DS group in the communication domain, β = -15.08, t(3.45), p = .005, and better than the ASD group in the socialization domain, β = 8.92, t(-2.08), p = .013. The DS group also performed better than the ASD group in socialization, β = 16.98, t(-2.32), p = .024. IQ was an important confounding factor, and socioeconomic status had an important effect on the adaptive behavior of all groups. There is a heterogeneity regarding adaptive behavior profiles in WBS, DS, and ASD. These data are important to better design specific strategies related to the health and social care of each particular group.

  10. Estimation of dynamic flux profiles from metabolic time series data

    Directory of Open Access Journals (Sweden)

    Chou I-Chun

    2012-07-01

    Full Text Available Abstract Background Advances in modern high-throughput techniques of molecular biology have enabled top-down approaches for the estimation of parameter values in metabolic systems, based on time series data. Special among them is the recent method of dynamic flux estimation (DFE, which uses such data not only for parameter estimation but also for the identification of functional forms of the processes governing a metabolic system. DFE furthermore provides diagnostic tools for the evaluation of model validity and of the quality of a model fit beyond residual errors. Unfortunately, DFE works only when the data are more or less complete and the system contains as many independent fluxes as metabolites. These drawbacks may be ameliorated with other types of estimation and information. However, such supplementations incur their own limitations. In particular, assumptions must be made regarding the functional forms of some processes and detailed kinetic information must be available, in addition to the time series data. Results The authors propose here a systematic approach that supplements DFE and overcomes some of its shortcomings. Like DFE, the approach is model-free and requires only minimal assumptions. If sufficient time series data are available, the approach allows the determination of a subset of fluxes that enables the subsequent applicability of DFE to the rest of the flux system. The authors demonstrate the procedure with three artificial pathway systems exhibiting distinct characteristics and with actual data of the trehalose pathway in Saccharomyces cerevisiae. Conclusions The results demonstrate that the proposed method successfully complements DFE under various situations and without a priori assumptions regarding the model representation. The proposed method also permits an examination of whether at all, to what degree, or within what range the available time series data can be validly represented in a particular functional format of

  11. Selection of metastatic breast cancer cells based on adaptability of their metabolic state.

    Directory of Open Access Journals (Sweden)

    Balraj Singh

    Full Text Available A small subpopulation of highly adaptable breast cancer cells within a vastly heterogeneous population drives cancer metastasis. Here we describe a function-based strategy for selecting rare cancer cells that are highly adaptable and drive malignancy. Although cancer cells are dependent on certain nutrients, e.g., glucose and glutamine, we hypothesized that the adaptable cancer cells that drive malignancy must possess an adaptable metabolic state and that such cells could be identified using a robust selection strategy. As expected, more than 99.99% of cells died upon glutamine withdrawal from the aggressive breast cancer cell line SUM149. The rare cells that survived and proliferated without glutamine were highly adaptable, as judged by additional robust adaptability assays involving prolonged cell culture without glucose or serum. We were successful in isolating rare metabolically plastic glutamine-independent (Gln-ind variants from several aggressive breast cancer cell lines that we tested. The Gln-ind cells overexpressed cyclooxygenase-2, an indicator of tumor aggressiveness, and they were able to adjust their glutaminase level to suit glutamine availability. The Gln-ind cells were anchorage-independent, resistant to chemotherapeutic drugs doxorubicin and paclitaxel, and resistant to a high concentration of a COX-2 inhibitor celecoxib. The number of cells being able to adapt to non-availability of glutamine increased upon prior selection of cells for resistance to chemotherapy drugs or resistance to celecoxib, further supporting a linkage between cellular adaptability and therapeutic resistance. Gln-ind cells showed indications of oxidative stress, and they produced cadherin11 and vimentin, indicators of mesenchymal phenotype. Gln-ind cells were more tumorigenic and more metastatic in nude mice than the parental cell line as judged by incidence and time of occurrence. As we decreased the number of cancer cells in xenografts, lung metastasis

  12. Metabolic profiling of strawberry (Fragaria x ananassa Duch.) during fruit development and maturation.

    Science.gov (United States)

    Zhang, Juanjuan; Wang, Xin; Yu, Oliver; Tang, Juanjuan; Gu, Xungang; Wan, Xiaochun; Fang, Congbing

    2011-01-01

    Strawberry (Fragaria × ananassa Duch), a fruit of economic and nutritional importance, is also a model species for fleshy fruits and genomics in Rosaceae. Strawberry fruit quality at different harvest stages is a function of the fruit's metabolite content, which results from physiological changes during fruit growth and ripening. In order to investigate strawberry fruit development, untargeted (GC-MS) and targeted (HPLC) metabolic profiling analyses were conducted. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were employed to explore the non-polar and polar metabolite profiles from fruit samples at seven developmental stages. Different cluster patterns and a broad range of metabolites that exerted influence on cluster formation of metabolite profiles were observed. Significant changes in metabolite levels were found in both fruits turning red and fruits over-ripening in comparison with red-ripening fruits. The levels of free amino acids decreased gradually before the red-ripening stage, but increased significantly in the over-ripening stage. Metabolite correlation and network analysis revealed the interdependencies of individual metabolites and metabolic pathways. Activities of several metabolic pathways, including ester biosynthesis, the tricarboxylic acid cycle, the shikimate pathway, and amino acid metabolism, shifted during fruit growth and ripening. These results not only confirmed published metabolic data but also revealed new insights into strawberry fruit composition and metabolite changes, thus demonstrating the value of metabolomics as a functional genomics tool in characterizing the mechanism of fruit quality formation, a key developmental stage in most economically important fruit crops.

  13. Blood-Based Bioenergetic Profiling Reflects Differences in Brain Bioenergetics and Metabolism

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    Daniel J. Tyrrell

    2017-01-01

    Full Text Available Blood-based bioenergetic profiling provides a minimally invasive assessment of mitochondrial health shown to be related to key features of aging. Previous studies show that blood cells recapitulate mitochondrial alterations in the central nervous system under pathological conditions, including the development of Alzheimer’s disease. In this study of nonhuman primates, we focus on mitochondrial function and bioenergetic capacity assessed by the respirometric profiling of monocytes, platelets, and frontal cortex mitochondria. Our data indicate that differences in the maximal respiratory capacity of brain mitochondria are reflected by CD14+ monocyte maximal respiratory capacity and platelet and monocyte bioenergetic health index. A subset of nonhuman primates also underwent [18F] fluorodeoxyglucose positron emission tomography (FDG-PET imaging to assess brain glucose metabolism. Our results indicate that platelet respiratory capacity positively correlates to measures of glucose metabolism in multiple brain regions. Altogether, the results of this study provide early evidence that blood-based bioenergetic profiling is related to brain mitochondrial metabolism. While these measures cannot substitute for direct measures of brain metabolism, provided by measures such as FDG-PET, they may have utility as a metabolic biomarker and screening tool to identify individuals exhibiting systemic bioenergetic decline who may therefore be at risk for the development of neurodegenerative diseases.

  14. Metabolomic profiles of lipid metabolism, arterial stiffness and hemodynamics in male coronary artery disease patients

    Directory of Open Access Journals (Sweden)

    Kaido Paapstel

    2016-06-01

    Conclusions: We demonstrated an independent association between the serum medium- and long-chain acylcarnitine profile and aortic stiffness for the CAD patients. In addition to the lipid-related classical CVD risk markers, the intermediates of lipid metabolism may serve as novel indicators for altered vascular function.

  15. Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs

    Science.gov (United States)

    New generation lipid emulsions comprised of fish oil or blends of soybean/fish/medium chain triglyceride/olive oil are emerging that result in favorable clinical metabolic outcomes in pediatric populations. Our aim was to characterize the lipidodomic, metabolomic, and transcriptomic profiles these ...

  16. Abdominal obesity has the highest impact on metabolic profile in an overweight African population

    DEFF Research Database (Denmark)

    Handlos, L. N.; Witte, D. R.; Mwaniki, D. L.

    2012-01-01

    Aim: The aim of this study was to determine the association between different anthropometric parameters and metabolic profile in an overweight, adult, black Kenyan population. Methods: An opportunity sample of 245 overweight adult Kenyans (body mass index (BMI) ≥ 25 kg/m2) was analysed. A score o...

  17. Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study

    DEFF Research Database (Denmark)

    Jørgenrud, Benedicte; Stene, Lars C; Tapia, German

    2017-01-01

    Aims: The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes. Method: Up to four longitudinal plasma samples from age 3 months from case...

  18. Effect of age and blood collection site on the metabolic profile of ...

    African Journals Online (AJOL)

    The serum metabolic profile of ostriches was studied in relation to the blood collection site (jugular vs. wing vein) and age (1 vs. 2 years) on 20 male birds. Blood was collected from the birds in the morning, after 12 h of fasting. Different collection site did not affect the examined parameters, but some statistically significant ...

  19. Vitamin C improves basal metabolic rate and lipid profile in alloxan ...

    Indian Academy of Sciences (India)

    Diabetes mellitus (DM) is a multi-factorial disease which is characterized by hyperglycaemia, lipoprotein abnormalities and oxidative stress. This study evaluated effect of oral vitamin C administration on basal metabolic rate and lipid profile of alloxan-induced diabetic rats. Vitamin C was administered at 200 mg/kg body wt.

  20. Association of altered cardiac autonomic function with psychopathology and metabolic profiles in schizophrenia.

    Science.gov (United States)

    Chung, Ming-Shun; Yang, Albert C; Lin, Yu-Chung; Lin, Chieh-Nan; Chang, Fang-Rong; Shen, Shu-hua; Ouyang, Wen-Chen; Loh, El-Wui; Chiu, Hsien-Jane

    2013-12-30

    Schizophrenia has been associated with autonomic dysregulation and increased cardiovascular co-morbidity. We hypothesised that autonomic dysregulation in patients with schizophrenia is associated with psychopathology and metabolic profiles. In this study, we aimed to evaluate psychopathology, comprehensive metabolic profiles and cardiac autonomic function using heart-rate variability (HRV) analysis in patients with schizophrenia. A total of 94 patients with schizophrenia and 51 healthy controls were recruited. Each patient underwent a physical examination, laboratory tests and rating scale evaluation, and all subjects underwent a 1-h electrocardiogram monitoring. Analysis of variance was used to compare demographic and HRV variables between control and patient groups. We applied multiple regression analysis with backward selection to examine the association between HRV indices and demographic, metabolic and psychopathology profiles. A decreased HRV was found in patient groups, compared to controls. Reduced vagal-related and complexity domain of HRV indices in patient groups were correlated with increased body mass indices, diastolic pressure, triglycerides, high- and low-density lipoprotein and severity of psychosis mainly in the negative symptom domain. This study provides evidence that altered autonomic function is associated with both psychopathology and metabolic profiles in patients with schizophrenia. These findings may warrant future research in using HRV as objective markers to monitor cardiovascular health and the severity of psychosis in patients with schizophrenia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. The metabolic syndrome in a memory clinic population: Relation with clinical profile and prognosis

    NARCIS (Netherlands)

    Exalto, L.G.; van der Flier, W.M.; van Boheemen, C.J.M.; Kappelle, L.J.; Vrenken, H.; Teunissen, C.; Koene, T.; Scheltens, P.; Biessels, G.J.

    2015-01-01

    Background The metabolic syndrome (MetS) refers to a cluster of cardiovascular risk factors that is associated with an increased risk of cognitive impairment and dementia. It is unclear however, if the presence of the MetS is associated with a particular clinical profile or a different prognosis in

  2. Metabolic profiling of body fluids and multivariate data analysis.

    Science.gov (United States)

    Trezzi, Jean-Pierre; Jäger, Christian; Galozzi, Sara; Barkovits, Katalin; Marcus, Katrin; Mollenhauer, Brit; Hiller, Karsten

    2017-01-01

    Metabolome analyses of body fluids are challenging due pre-analytical variations, such as pre-processing delay and temperature, and constant dynamical changes of biochemical processes within the samples. Therefore, proper sample handling starting from the time of collection up to the analysis is crucial to obtain high quality samples and reproducible results. A metabolomics analysis is divided into 4 main steps: 1) Sample collection, 2) Metabolite extraction, 3) Data acquisition and 4) Data analysis. Here, we describe a protocol for gas chromatography coupled to mass spectrometry (GC-MS) based metabolic analysis for biological matrices, especially body fluids. This protocol can be applied on blood serum/plasma, saliva and cerebrospinal fluid (CSF) samples of humans and other vertebrates. It covers sample collection, sample pre-processing, metabolite extraction, GC-MS measurement and guidelines for the subsequent data analysis. Advantages of this protocol include: •Robust and reproducible metabolomics results, taking into account pre-analytical variations that may occur during the sampling process•Small sample volume required•Rapid and cost-effective processing of biological samples•Logistic regression based determination of biomarker signatures for in-depth data analysis.

  3. (Im)Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis

    Science.gov (United States)

    2013-01-01

    Background Metabolic control analysis (MCA) and supply–demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply–demand theory has not yet considered gene-expression regulation explicitly whilst a variant of MCA, i.e. Hierarchical Control Analysis (HCA), has done so. Existing analyses based on control engineering approaches have not been very explicit about whether metabolic or gene-expression regulation would be involved, but designed different ways in which regulation could be organized, with the potential of causing adaptation to be perfect. Results This study integrates control engineering and classical MCA augmented with supply–demand theory and HCA. Because gene-expression regulation involves time integration, it is identified as a natural instantiation of the ‘integral control’ (or near integral control) known in control engineering. This study then focuses on robustness against and adaptation to perturbations of process activities in the network, which could result from environmental perturbations, mutations or slow noise. It is shown however that this type of ‘integral control’ should rarely be expected to lead to the ‘perfect adaptation’: although the gene-expression regulation increases the robustness of important metabolite concentrations, it rarely makes them infinitely robust. For perfect adaptation to occur, the protein degradation reactions should be zero order in the concentration of the protein, which may be rare biologically for cells growing steadily. Conclusions A proposed new framework integrating the methodologies of control engineering and metabolic and hierarchical control analysis, improves the understanding of biological systems that are regulated both metabolically and by gene expression. In particular, the new approach enables one to address the issue whether the intracellular biochemical networks that have been and

  4. Mass-spectra-based peak alignment for automatic nontargeted metabolic profiling analysis for biomarker screening in plant samples.

    Science.gov (United States)

    Fu, Hai-Yan; Hu, Ou; Zhang, Yue-Ming; Zhang, Li; Song, Jing-Jing; Lu, Peang; Zheng, Qing-Xia; Liu, Ping-Ping; Chen, Qian-Si; Wang, Bing; Wang, Xiao-Yu; Han, Lu; Yu, Yong-Jie

    2017-09-01

    Nontargeted metabolic profiling analysis is a difficult task in a routine investigation because hundreds of chromatographic peaks are eluted within a short time, and the time shift problem is severe across samples. To address these problems, the present work developed an automatic nontargeted metabolic profiling analysis (anTMPA) method. First, peaks from the total ion chromatogram were extracted using modified multiscale Gaussian smoothing method. Then, a novel peak alignment strategy was employed based on the mass spectra and retention times of the peaks in which the maximum mass spectral correlation coefficient path was extracted using a modified dynamic programming method. Moreover, an automatic landmark peak-searching strategy was employed for self-adapting time shift modification. Missing peaks across samples were grouped and registered into the aligned peak list table for final refinement. Finally, the aligned peaks across samples were analyzed using statistical methods to identify potential biomarkers. Mass spectral information on the screened biomarkers could be directly imported into the National Institute of Standards and Technology library to select the candidate compounds. The performance of the anTMPA method was evaluated using a complicated plant gas chromatography-mass spectrometry dataset with the aim of identifying biomarkers between the growth and maturation stages of the tested plant. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Metabolic Plasticity of Metastatic Breast Cancer Cells: Adaptation to Changes in the Microenvironment

    Directory of Open Access Journals (Sweden)

    Rui V. Simões

    2015-08-01

    Full Text Available Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer cells lines (highly metastatic 4T1; nonmetastatic 67NR to identify differences in their glucose and glutamine metabolism in response to metabolic and environmental stress. Dynamic magnetic resonance spectroscopy of 13C-isotopomers showed that 4T1 cells have higher glycolytic and tricarboxylic acid (TCA cycle flux than 67NR cells and readily switch between glycolysis and oxidative phosphorylation (OXPHOS in response to different extracellular environments. OXPHOS activity increased with metastatic potential in isogenic cell lines derived from the same primary breast cancer: 4T1 > 4T07 and 168FARN (local micrometastasis only > 67NR. We observed a restricted TCA cycle flux at the succinate dehydrogenase step in 67NR cells (but not in 4T1 cells, leading to succinate accumulation and hindering OXPHOS. In the four isogenic cell lines, environmental stresses modulated succinate dehydrogenase subunit A expression according to metastatic potential. Moreover, glucose-derived lactate production was more glutamine dependent in cell lines with higher metastatic potential. These studies show clear differences in TCA cycle metabolism between 4T1 and 67NR breast cancer cells. They indicate that metastases-forming 4T1 cells are more adept at adjusting their metabolism in response to environmental stress than isogenic, nonmetastatic 67NR cells. We suggest that the metabolic plasticity and adaptability are more important to the metastatic breast cancer phenotype than rapid cell proliferation alone, which could 1 provide a new biomarker for early detection of this phenotype, possibly at the time of diagnosis, and 2 lead to new treatment strategies of metastatic breast cancer by targeting mitochondrial metabolism.

  6. Barometer of type 2 diabetes in primary care. Metabolic control, styles of life and morbidity profile.

    Science.gov (United States)

    Pérez-Manchón, David; Rodríguez-Álvarez, María Lorena; Alcívar-Arteaga, Claudia; Redondo-Pico, Mercedes; Ramos-Quirós, Elena

    Knowing the profile of cardiovascular morbidity, degree of control and lifestyles in type 2 diabetes. Randomized multicenter cross-sectional study conducted in 2015 in primary care with 129 diabetics. It included sociodemographic variables, microvascular and macrovascular complications, organic damage, comorbidity and lifestyles of smoking, exercise and adherence to Mediterranean diet. Metabolic control was assessed with the latest annual glycosylated haemoglobin. 57% were men and 43% women. Metabolic control was acceptable (HbAc1%, 7.15%) without differences by town. 74.4% had cardiovascular comorbidity and the 99.2% risk factors. 23% were smokers and 41% sedentary with a 56% adherence to Mediterranean diet. The cardiometabolic profile of diabetes includes retinopathy, peripheral arterial disease, comorbidity of hypertension and cardiovascular risk factors. Individual or group health education in self-care and healthy lifestyles can improve metabolic control. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  7. Acculturation Profiles of Russian-Speaking Immigrants in Belgium and Their Socio-Economic Adaptation

    Science.gov (United States)

    Grigoryev, Dmitry; van de Vijver, Fons

    2017-01-01

    This article presents the results of a study on the relationship of acculturation profiles of Russian-speaking immigrants in Belgium, the duration of their stay, and their socio-economic adaptation. The data came from a socio-psychological survey of 132 Russian-speaking immigrants in Belgium (first generation) and were processed using latent…

  8. Acculturation profiles of Russian-speaking immigrants in Belgium and their socio-economic adaptation

    NARCIS (Netherlands)

    Grigoryev, Dmitry; van de Vijver, Fons

    2017-01-01

    This article presents the results of a study on the relationship of acculturation profiles of Russian-speaking immigrants in Belgium, the duration of their stay, and their socio-economic adaptation. The data came from a socio-psychological survey of 132 Russian-speaking immigrants in Belgium (first

  9. Change in Metabolic Profile after 1-Year Nutritional-Behavioral Intervention in Obese Children.

    Science.gov (United States)

    Verduci, Elvira; Lassandro, Carlotta; Giacchero, Roberta; Miniello, Vito Leonardo; Banderali, Giuseppe; Radaelli, Giovanni

    2015-12-03

    Research findings are inconsistent about improvement of specific cardio-metabolic variables after lifestyle intervention in obese children. The aim of this trial was to evaluate the effect of a 1-year intervention, based on normocaloric diet and physical activity, on body mass index (BMI), blood lipid profile, glucose metabolism and metabolic syndrome. Eighty-five obese children aged ≥6 years were analyzed. The BMI z-score was calculated. Fasting blood samples were analyzed for lipids, insulin and glucose. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated and insulin resistance was defined as HOMA-IR >3.16. HOMA-β%, quantitative insulin sensitivity check index and triglyceride glucose index were calculated. The metabolic syndrome was defined in accordance with the International Diabetes Federation criteria. At the end of intervention children showed a reduction (mean (95% CI)) in BMI z-score (-0.58 (-0.66; -0.50)), triglycerides (-0.35 (-0.45; -0.25) mmol/L) and triglyceride glucose index (-0.29 (-0.37; -0.21)), and an increase in HDL cholesterol (0.06 (0.01; 0.11) mmol/L). Prevalence of insulin resistance declined from 51.8% to 36.5% and prevalence of metabolic syndrome from 17.1% to 4.9%. Nutritional-behavioral interventions can improve the blood lipid profile and insulin sensitivity in obese children, and possibly provide benefits in terms of metabolic syndrome.

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

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

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

  11. Metabolic profiling of alternative NAD biosynthetic routes in mouse tissues.

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    Valerio Mori

    Full Text Available NAD plays essential redox and non-redox roles in cell biology. In mammals, its de novo and recycling biosynthetic pathways encompass two independent branches, the "amidated" and "deamidated" routes. Here we focused on the indispensable enzymes gating these two routes, i.e. nicotinamide mononucleotide adenylyltransferase (NMNAT, which in mammals comprises three distinct isozymes, and NAD synthetase (NADS. First, we measured the in vitro activity of the enzymes, and the levels of all their substrates and products in a number of tissues from the C57BL/6 mouse. Second, from these data, we derived in vivo estimates of enzymes'rates and quantitative contributions to NAD homeostasis. The NMNAT activity, mainly represented by nuclear NMNAT1, appears to be high and nonrate-limiting in all examined tissues, except in blood. The NADS activity, however, appears rate-limiting in lung and skeletal muscle, where its undetectable levels parallel a relative accumulation of the enzyme's substrate NaAD (nicotinic acid adenine dinucleotide. In all tissues, the amidated NAD route was predominant, displaying highest rates in liver and kidney, and lowest in blood. In contrast, the minor deamidated route showed higher relative proportions in blood and small intestine, and higher absolute values in liver and small intestine. Such results provide the first comprehensive picture of the balance of the two alternative NAD biosynthetic routes in different mammalian tissues under physiological conditions. This fills a gap in the current knowledge of NAD biosynthesis, and provides a crucial information for the study of NAD metabolism and its role in disease.

  12. Metabolic profiling of laser microdissected vascular bundles of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Fiehn Oliver

    2005-08-01

    Full Text Available Abstract Background Laser microdissection is a useful tool for collecting tissue-specific samples or even single cells from animal and plant tissue sections. This technique has been successfully employed to study cell type-specific expression at the RNA, and more recently also at the protein level. However, metabolites were not amenable to analysis after laser microdissection, due to the procedures routinely applied for sample preparation. Using standard tissue fixation and embedding protocols to prepare histological sections, metabolites are either efficiently extracted by dehydrating solvents, or washed out by embedding agents. Results In this study, we used cryosectioning as an alternative method that preserves sufficient cellular structure while minimizing metabolite loss by excluding any solute exchange steps. Using this pre-treatment procedure, Arabidopsis thaliana stem sections were prepared for laser microdissection of vascular bundles. Collected samples were subsequently analyzed by gas chromatography-time of flight mass spectrometry (GC-TOF MS to obtain metabolite profiles. From 100 collected vascular bundles (~5,000 cells, 68 metabolites could be identified. More than half of the identified metabolites could be shown to be enriched or depleted in vascular bundles as compared to the surrounding tissues. Conclusion This study uses the example of vascular bundles to demonstrate for the first time that it is possible to analyze a comprehensive set of metabolites from laser microdissected samples at a tissue-specific level, given that a suitable sample preparation procedure is used.

  13. A comprehensive metabolic profile of cultured astrocytes using isotopic transient metabolic flux analysis and 13C-labeled glucose

    Directory of Open Access Journals (Sweden)

    Ana I Amaral

    2011-09-01

    Full Text Available Metabolic models have been used to elucidate important aspects of brain metabolism in recent years. This work applies for the first time the concept of isotopic transient 13C metabolic flux analysis (MFA to estimate intracellular fluxes of cultured astrocytes. This methodology comprehensively explores the information provided by 13C labeling time-courses of intracellular metabolites after administration of a 13C labeled substrate. Cells were incubated with medium containing [1-13C]glucose for 24 h and samples of cell supernatant and extracts collected at different time-points were then analyzed by mass spectrometry and/or HPLC. Metabolic fluxes were estimated by fitting a carbon labeling network model to isotopomer profiles experimentally determined. Both the fast isotopic equilibrium of glycolytic metabolite pools and the slow labeling dynamics of TCA cycle intermediates are described well by the model. The large pools of glutamate and aspartate which are linked to the TCA cycle via reversible aminotransferase reactions are likely to be responsible for the observed delay in equilibration of TCA cycle intermediates. Furthermore, it was estimated that 11% of the glucose taken up by astrocytes was diverted to the pentose phosphate pathway. In addition, considerable fluxes through pyruvate carboxylase (PC (PC/pyruvate dehydrogenase (PDH ratio = 0.5, malic enzyme (5% of the total pyruvate production and catabolism of branched-chained amino acids (contributing with ~40% to total acetyl-CoA produced confirmed the significance of these pathways to astrocytic metabolism. Consistent with the need of maintaining cytosolic redox potential, the fluxes through the malate-aspartate shuttle and the PDH pathway were comparable. Finally, the estimated glutamate/α-ketoglutarate exchange rate (~0.7 µmol.mg prot-1.h-1 was similar to the TCA cycle flux. In conclusion, this work demonstrates the potential of isotopic transient MFA for a comprehensive analysis of

  14. Metabolic cold adaptation of polar fish based on measurements of aerobic oxygen consumption: fact or artefact? Artefact!

    DEFF Research Database (Denmark)

    Steffensen, John Fleng

    2002-01-01

    Whether metabolic cold adaptation in polar fish, based on measurements of aerobic standard metabolic rate, is a fact or an artefact has been a dispute since Holeton asked the question in 1974. So far polar fish had been considered to be metabolically cold adapted because they were reported to have...... a considerably elevated resting oxygen consumption, or standard metabolic rate, compared with oxygen consumption values of tropical or temperate fish extrapolated to similar low polar temperatures. Recent experiments on arctic and Antarctic fish, however, do not show elevated resting aerobic oxygen consumption...... values, or standard metabolic rate, and hence it is concluded that that metabolic cold adaptation in the traditional sense is an artefact....

  15. Gas chromatography-mass spectrometry-based metabolic profiling of cerebrospinal fluid from epileptic dogs.

    Science.gov (United States)

    Hasegawa, Tetsuya; Sumita, Maho; Horitani, Yusuke; Tamai, Reo; Tanaka, Katsuhiro; Komori, Masayuki; Takenaka, Shigeo

    2014-04-01

    Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinal fluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy.

  16. Monitoring and robust adaptive control of fed-batch cultures of microorganisms exhibiting overflow metabolism [abstract

    Directory of Open Access Journals (Sweden)

    Vande Wouwer, A.

    2010-01-01

    Full Text Available Overflow metabolism characterizes cells strains that are likely to produce inhibiting by-products resulting from an excess of substrate feeding and a saturated respiratory capacity. The critical substrate level separating the two different metabolic pathways is generally not well defined. Monitoring of this kind of cultures, going from model identification to state estimation, is first discussed. Then, a review of control techniques which all aim at maximizing the cell productivity of fed-batch fermentations is presented. Two main adaptive control strategies, one using an estimation of the critical substrate level as set-point and another regulating the by-product concentration, are proposed. Finally, experimental investigations of an adaptive RST control scheme using the observer polynomial for the regulation of the ethanol concentration in Saccharomyces cerevisiae fed-batch cultures ranging from laboratory to industrial scales, are also presented.

  17. The colitis-associated transcriptional profile of commensal Bacteroides thetaiotaomicron enhances adaptive immune responses to a bacterial antigen.

    Directory of Open Access Journals (Sweden)

    Jonathan J Hansen

    Full Text Available Inflammatory bowel diseases (IBD may be caused in part by aberrant immune responses to commensal intestinal microbes including the well-characterized anaerobic gut commensal Bacteroides thetaiotaomicron (B. theta. Healthy, germ-free HLA-B27 transgenic (Tg rats develop chronic colitis when colonized with complex gut commensal bacteria whereas non-transgenic (nTg rats remain disease-free. However, the role of B. theta in causing disease in Tg rats is unknown nor is much known about how gut microbes respond to host inflammation.Tg and nTg rats were monoassociated with a human isolate of B. theta. Colonic inflammation was assessed by histologic scoring and tissue pro-inflammatory cytokine measurement. Whole genome transcriptional profiling of B. theta recovered from ceca was performed using custom GeneChips and data analyzed using dChip, Significance Analysis of Microarrays, and Gene Set Enrichment Analysis (GSEA software. Western Blots were used to determine adaptive immune responses to a differentially expressed B. theta gene.B. theta monoassociated Tg rats, but not nTg or germ-free controls, developed chronic colitis. Transcriptional profiles of cecal B. theta were significantly different in Tg vs. nTg rats. GSEA revealed that genes in KEGG canonical pathways involved in bacterial growth and metabolism were downregulated in B. theta from Tg rats with colitis though luminal bacterial concentrations were unaffected. Bacterial genes in the Gene Ontology molecular function "receptor activity", most of which encode nutrient binding proteins, were significantly upregulated in B. theta from Tg rats and include a SusC homolog that induces adaptive immune responses in Tg rats.B. theta induces colitis in HLA-B27 Tg rats, which is associated with regulation of bacterial genes in metabolic and nutrient binding pathways that may affect host immune responses. These studies of the host-microbial dialogue may lead to the identification of novel microbial targets

  18. The colitis-associated transcriptional profile of commensal Bacteroides thetaiotaomicron enhances adaptive immune responses to a bacterial antigen.

    Science.gov (United States)

    Hansen, Jonathan J; Huang, Yong; Peterson, Daniel A; Goeser, Laura; Fan, Ting-Jia; Chang, Eugene B; Sartor, R Balfour

    2012-01-01

    Inflammatory bowel diseases (IBD) may be caused in part by aberrant immune responses to commensal intestinal microbes including the well-characterized anaerobic gut commensal Bacteroides thetaiotaomicron (B. theta). Healthy, germ-free HLA-B27 transgenic (Tg) rats develop chronic colitis when colonized with complex gut commensal bacteria whereas non-transgenic (nTg) rats remain disease-free. However, the role of B. theta in causing disease in Tg rats is unknown nor is much known about how gut microbes respond to host inflammation. Tg and nTg rats were monoassociated with a human isolate of B. theta. Colonic inflammation was assessed by histologic scoring and tissue pro-inflammatory cytokine measurement. Whole genome transcriptional profiling of B. theta recovered from ceca was performed using custom GeneChips and data analyzed using dChip, Significance Analysis of Microarrays, and Gene Set Enrichment Analysis (GSEA) software. Western Blots were used to determine adaptive immune responses to a differentially expressed B. theta gene. B. theta monoassociated Tg rats, but not nTg or germ-free controls, developed chronic colitis. Transcriptional profiles of cecal B. theta were significantly different in Tg vs. nTg rats. GSEA revealed that genes in KEGG canonical pathways involved in bacterial growth and metabolism were downregulated in B. theta from Tg rats with colitis though luminal bacterial concentrations were unaffected. Bacterial genes in the Gene Ontology molecular function "receptor activity", most of which encode nutrient binding proteins, were significantly upregulated in B. theta from Tg rats and include a SusC homolog that induces adaptive immune responses in Tg rats. B. theta induces colitis in HLA-B27 Tg rats, which is associated with regulation of bacterial genes in metabolic and nutrient binding pathways that may affect host immune responses. These studies of the host-microbial dialogue may lead to the identification of novel microbial targets for IBD

  19. Alzheimer's disease and natural cognitive aging may represent adaptive metabolism reduction programs

    OpenAIRE

    Reser Jared

    2009-01-01

    Abstract The present article examines several lines of converging evidence suggesting that the slow and insidious brain changes that accumulate over the lifespan, resulting in both natural cognitive aging and Alzheimer's disease (AD), represent a metabolism reduction program. A number of such adaptive programs are known to accompany aging and are thought to have decreased energy requirements for ancestral hunter-gatherers in their 30s, 40s and 50s. Foraging ability in modern hunter-gatherers ...

  20. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles

    Science.gov (United States)

    Hauschild, Anne-Christin; Frisch, Tobias; Baumbach, Jörg Ingo; Baumbach, Jan

    2015-01-01

    Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs) in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD). While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD) and bronchial

  1. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles

    Directory of Open Access Journals (Sweden)

    Anne-Christin Hauschild

    2015-06-01

    Full Text Available Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD. While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD

  2. Body weight regulation and obesity: dietary strategies to improve the metabolic profile.

    Science.gov (United States)

    Munsters, M J M; Saris, W H M

    2014-01-01

    This review discusses dietary strategies that may improve the metabolic profile and body weight regulation in obesity. Recent evidence demonstrated that long-term health effects seem to be more beneficial for low-glycemic index (GI) diets compared to high-protein diets. Still, these results need to be confirmed by other prospective cohort studies and long-term clinical trials, and the discrepancy between these study designs needs to be explored in more detail. Furthermore, the current literature is mixed with regard to the efficacy of increased meal frequency (or snacking) regimens in causing metabolic alterations, particularly in relation to body weight control. In conclusion, a growing body of evidence suggests that dietary strategies with the aim to reduce postprandial insulin response and increase fat oxidation, and that tend to restore metabolic flexibility, have a place in the prevention and treatment of obesity and associated metabolic disorders.

  3. Adverse Metabolic Risk Profiles in Greenlandic Inuit Children Compared to Danish Children

    DEFF Research Database (Denmark)

    Munch-Andersen, T.; Sorensen, K.; Andersen, L. B.

    2013-01-01

    Objective During recent decades, the prevalence of metabolic morbidity has increased rapidly in adult Greenlandic Inuit. To what extent this is also reflected in the juvenile Inuit population is unknown. The objective was, therefore, in the comparison with Danish children, to evaluate metabolic...... BMI, body fat %, HbA1c, and significantly lower aerobic fitness and ApoA1 levels than northern living Inuit children. Conclusions Greenlandic Inuit children had adverse metabolic health profile compared to the Danish children, the differences where more pronounced in Inuit children living in Nuuk....... The tendencies toward higher prevalence of diabetes and metabolic morbidity in the adult Greenlandic Inuit population may also be present in the Inuit children population....

  4. The glucagon receptor is required for the adaptive metabolic response to fasting.

    Science.gov (United States)

    Longuet, Christine; Sinclair, Elaine M; Maida, Adriano; Baggio, Laurie L; Maziarz, Marlena; Charron, Maureen J; Drucker, Daniel J

    2008-11-01

    Glucagon receptor (Gcgr) signaling maintains hepatic glucose production during the fasting state; however, the importance of the Gcgr for lipid metabolism is unclear. We show here that fasted Gcgr-/- mice exhibit a significant increase in hepatic triglyceride secretion and fasting increases fatty acid oxidation (FAO) in wild-type (WT) but not in Gcgr-/- mice. Moreover fasting upregulated the expression of FAO-related hepatic mRNA transcripts in Gcgr+/+ but not in Gcgr-/- mice. Exogenous glucagon administration reduced plasma triglycerides in WT mice, inhibited TG synthesis and secretion, and stimulated FA beta oxidation in Gcgr+/+ hepatocytes. The actions of glucagon on TG synthesis and FAO were abolished in PPARalpha-/- hepatocytes. These findings demonstrate that the Gcgr receptor is required for control of lipid metabolism during the adaptive metabolic response to fasting.

  5. Adaptive evolution of mitochondrial energy metabolism genes associated with increased energy demand in flying insects.

    Science.gov (United States)

    Yang, Yunxia; Xu, Shixia; Xu, Junxiao; Guo, Yan; Yang, Guang

    2014-01-01

    Insects are unique among invertebrates for their ability to fly, which raises intriguing questions about how energy metabolism in insects evolved and changed along with flight. Although physiological studies indicated that energy consumption differs between flying and non-flying insects, the evolution of molecular energy metabolism mechanisms in insects remains largely unexplored. Considering that about 95% of adenosine triphosphate (ATP) is supplied by mitochondria via oxidative phosphorylation, we examined 13 mitochondrial protein-encoding genes to test whether adaptive evolution of energy metabolism-related genes occurred in insects. The analyses demonstrated that mitochondrial DNA protein-encoding genes are subject to positive selection from the last common ancestor of Pterygota, which evolved primitive flight ability. Positive selection was also found in insects with flight ability, whereas no significant sign of selection was found in flightless insects where the wings had degenerated. In addition, significant positive selection was also identified in the last common ancestor of Neoptera, which changed its flight mode from direct to indirect. Interestingly, detection of more positively selected genes in indirect flight rather than direct flight insects suggested a stronger selective pressure in insects having higher energy consumption. In conclusion, mitochondrial protein-encoding genes involved in energy metabolism were targets of adaptive evolution in response to increased energy demands that arose during the evolution of flight ability in insects.

  6. Potential mechanisms for a role of metabolic stress in hypertrophic adaptations to resistance training.

    Science.gov (United States)

    Schoenfeld, Brad J

    2013-03-01

    It is well established that regimented resistance training can promote increases in muscle hypertrophy. The prevailing body of research indicates that mechanical stress is the primary impetus for this adaptive response and studies show that mechanical stress alone can initiate anabolic signalling. Given the dominant role of mechanical stress in muscle growth, the question arises as to whether other factors may enhance the post-exercise hypertrophic response. Several researchers have proposed that exercise-induced metabolic stress may in fact confer such an anabolic effect and some have even suggested that metabolite accumulation may be more important than high force development in optimizing muscle growth. Metabolic stress pursuant to traditional resistance training manifests as a result of exercise that relies on anaerobic glycolysis for adenosine triphosphate production. This, in turn, causes the subsequent accumulation of metabolites, particularly lactate and H(+). Acute muscle hypoxia associated with such training methods may further heighten metabolic buildup. Therefore, the purpose of this paper will be to review the emerging body of research suggesting a role for exercise-induced metabolic stress in maximizing muscle development and present insights as to the potential mechanisms by which these hypertrophic adaptations may occur. These mechanisms include increased fibre recruitment, elevated systemic hormonal production, alterations in local myokines, heightened production of reactive oxygen species and cell swelling. Recommendations are provided for potential areas of future research on the subject.

  7. Metabolic regulation rather than de novo enzyme synthesis dominates the osmo-adaptation of yeast.

    Science.gov (United States)

    Bouwman, Jildau; Kiewiet, José; Lindenbergh, Alexander; van Eunen, Karen; Siderius, Marco; Bakker, Barbara M

    2011-01-01

    Intracellular accumulation of glycerol is essential for yeast cells to survive hyperosmotic stress. Upon hyperosmotic stress the gene expression of enzymes in the glycerol pathway is strongly induced. Recently, however, it was shown that this gene-expression response is not essential for survival of an osmotic shock [Mettetal JT et al. (2008) Science 319: 482–484 and Westfall PJ et al. (2008) Proc Natl Acad Sci 105: 12212–12217]. Instead, pure metabolic adaptation can rescue the yeast. The existence of two alternative mechanisms urged the question which of these mechanisms dominates time-dependent adaptation of wild-type yeast to osmotic stress under physiological conditions. The regulation of the glycerol pathway was analysed in aerobic, glucose-limited cultures upon addition of 1 M of sorbitol, leading to a hyperosmotic shock. In agreement with earlier studies, the mRNA levels of the glycerol-producing enzymes as well as their catalytic capacities increased. Qualitatively this induction followed a similar time course to the increase of the glycerol flux. However, a quantitative regulation analysis of the data revealed an initial regulation by metabolism alone. After only a few minutes gene expression came into play, but even after an hour, 80% of the increase in the glycerol flux was explained by metabolic changes in the cell, and 20% by induction of gene expression. This demonstrates that the novel metabolic mechanism is not just a secondary rescue mechanism, but the most important mechanism to regulate the glycerol flux under physiological conditions.

  8. Metabolic Profiling of Human Peripheral Blood Mononuclear Cells: Influence of Vitamin D Status and Gender

    Directory of Open Access Journals (Sweden)

    Magdalena Stepien

    2014-04-01

    Full Text Available Metabolic profiling of peripheral blood mononuclear cells (PBMC could serve as a less invasive and more direct alternative to tissue biopsies or serum in metabolomic research. We conducted two exploratory independent studies in order to characterise PBMC’s metabolomic profile following short-term vitamin D3 supplementation and to determine gender effects. In the first study, eight healthy males and females aged 40–65 y were randomly selected for profiling of PBMCs after receiving either 15 µg of vitamin D3 or placebo for four weeks. In the second study, twenty younger healthy males and females were studied. Cell metabolites were extracted and deproteinised using methanol/chloroform/water method and analysed by GC-MS. Higher vitamin D status had no effect on the fatty acid profile of PBMCs, but inflammatory biomarkers and adipokines correlated positively with stearic acid levels. In the second study, no gender-specific metabolites were identified. Valine, leucine and aspartic acid were identified as potential BMI-sensitive amino acids. Larger studies are needed to confirm the influence of BMI on these parameters. This work clearly demonstrates the utility of metabolomics profiling of PBMCs and paves the way for future applications of metabolomics in identifying metabolic profiles of blood cells as a measure for dietary intakes or physiological status.

  9. Metabolic Engineering for Probiotics and their Genome-Wide Expression Profiling.

    Science.gov (United States)

    Yadav, Ruby; Singh, Puneet K; Shukla, Pratyoosh

    2018-01-01

    Probiotic supplements in food industry have attracted a lot of attention and shown a remarkable growth in this field. Metabolic engineering (ME) approaches enable understanding their mechanism of action and increases possibility of designing probiotic strains with desired functions. Probiotic microorganisms generally referred as industrially important lactic acid bacteria (LAB) which are involved in fermenting dairy products, food, beverages and produces lactic acid as final product. A number of illustrations of metabolic engineering approaches in industrial probiotic bacteria have been described in this review including transcriptomic studies of Lactobacillus reuteri and improvement in exopolysaccharide (EPS) biosynthesis yield in Lactobacillus casei LC2W. This review summaries various metabolic engineering approaches for exploring metabolic pathways. These approaches enable evaluation of cellular metabolic state and effective editing of microbial genome or introduction of novel enzymes to redirect the carbon fluxes. In addition, various system biology tools such as in silico design commonly used for improving strain performance is also discussed. Finally, we discuss the integration of metabolic engineering and genome profiling which offers a new way to explore metabolic interactions, fluxomics and probiogenomics using probiotic bacteria like Bifidobacterium spp and Lactobacillus spp. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Antipsychotic drugs: From receptor-binding profiles to metabolic side effects.

    Science.gov (United States)

    Siafis, Spyridon; Tzachanis, Dimitrios; Samara, Myrto; Papazisis, Georgios

    2017-06-30

    Antipsychotic-induced metabolic side effects are major concerns in psychopharmacology and clinical psychiatry. Their pathogenetic mechanisms are still not elucidated. Antipsychotic drugs seem to interfere with feeding behaviors and energy balance processes that control metabolic regulation. Reward and energy balance centers in central nervous system constitute the central level of metabolic regulation. The peripheral level consists of skeletal muscles, the liver, the pancreas, the adipose tissue and neuroendocrine connections. Neurotransmitter receptors have crucial roles in metabolic regulation and they are also targets of antipsychotic drugs. Interaction of antipsychotics with neurotransmitters could have both protective and harmful effects on metabolism. Emerging evidence suggests that antipsychotics have different liabilities to induce obesity, diabetes and dyslipidemia. However, this diversity cannot be explained merely by drugs' pharmacodynamic profiles, highlighting the need for further research. Herein, we review the impact of neurotransmitters on metabolic regulation, providing insights into antipsychotic-induced metabolic side effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Multi-Organ Contribution to the Metabolic Plasma Profile Using Hierarchical Modelling.

    Directory of Open Access Journals (Sweden)

    Frida Torell

    Full Text Available Hierarchical modelling was applied in order to identify the organs that contribute to the levels of metabolites in plasma. Plasma and organ samples from gut, kidney, liver, muscle and pancreas were obtained from mice. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC TOF-MS at the Swedish Metabolomics centre, Umeå University, Sweden. The multivariate analysis was performed by means of principal component analysis (PCA and orthogonal projections to latent structures (OPLS. The main goal of this study was to investigate how each organ contributes to the metabolic plasma profile. This was performed using hierarchical modelling. Each organ was found to have a unique metabolic profile. The hierarchical modelling showed that the gut, kidney and liver demonstrated the greatest contribution to the metabolic pattern of plasma. For example, we found that metabolites were absorbed in the gut and transported to the plasma. The kidneys excrete branched chain amino acids (BCAAs and fatty acids are transported in the plasma to the muscles and liver. Lactic acid was also found to be transported from the pancreas to plasma. The results indicated that hierarchical modelling can be utilized to identify the organ contribution of unknown metabolites to the metabolic profile of plasma.

  12. Metabolic adaptation of two in silico mutants of Mycobacterium tuberculosis during infection.

    Science.gov (United States)

    López-Agudelo, Víctor A; Baena, Andres; Ramirez-Malule, Howard; Ochoa, Silvia; Barrera, Luis F; Ríos-Estepa, Rigoberto

    2017-11-21

    Up to date, Mycobacterium tuberculosis (Mtb) remains as the worst intracellular killer pathogen. To establish infection, inside the granuloma, Mtb reprograms its metabolism to support both growth and survival, keeping a balance between catabolism, anabolism and energy supply. Mtb knockouts with the faculty of being essential on a wide range of nutritional conditions are deemed as target candidates for tuberculosis (TB) treatment. Constraint-based genome-scale modeling is considered as a promising tool for evaluating genetic and nutritional perturbations on Mtb metabolic reprogramming. Nonetheless, few in silico assessments of the effect of nutritional conditions on Mtb's vulnerability and metabolic adaptation have been carried out. A genome-scale model (GEM) of Mtb, modified from the H37Rv iOSDD890, was used to explore the metabolic reprogramming of two Mtb knockout mutants (pfkA- and icl-mutants), lacking key enzymes of central carbon metabolism, while exposed to changing nutritional conditions (oxygen, and carbon and nitrogen sources). A combination of shadow pricing, sensitivity analysis, and flux distributions patterns allowed us to identify metabolic behaviors that are in agreement with phenotypes reported in the literature. During hypoxia, at high glucose consumption, the Mtb pfkA-mutant showed a detrimental growth effect derived from the accumulation of toxic sugar phosphate intermediates (glucose-6-phosphate and fructose-6-phosphate) along with an increment of carbon fluxes towards the reductive direction of the tricarboxylic acid cycle (TCA). Furthermore, metabolic reprogramming of the icl-mutant (icl1&icl2) showed the importance of the methylmalonyl pathway for the detoxification of propionyl-CoA, during growth at high fatty acid consumption rates and aerobic conditions. At elevated levels of fatty acid uptake and hypoxia, we found a drop in TCA cycle intermediate accumulation that might create redox imbalance. Finally, findings regarding Mtb

  13. Alzheimer's disease and natural cognitive aging may represent adaptive metabolism reduction programs.

    Science.gov (United States)

    Reser, Jared Edward

    2009-02-28

    The present article examines several lines of converging evidence suggesting that the slow and insidious brain changes that accumulate over the lifespan, resulting in both natural cognitive aging and Alzheimer's disease (AD), represent a metabolism reduction program. A number of such adaptive programs are known to accompany aging and are thought to have decreased energy requirements for ancestral hunter-gatherers in their 30s, 40s and 50s. Foraging ability in modern hunter-gatherers declines rapidly, more than a decade before the average terminal age of 55 years. Given this, the human brain would have been a tremendous metabolic liability that must have been advantageously tempered by the early cellular and molecular changes of AD which begin to accumulate in all humans during early adulthood. Before the recent lengthening of life span, individuals in the ancestral environment died well before this metabolism reduction program resulted in clinical AD, thus there was never any selective pressure to keep adaptive changes from progressing to a maladaptive extent.Aging foragers may not have needed the same cognitive capacities as their younger counterparts because of the benefits of accumulated learning and life experience. It is known that during both childhood and adulthood metabolic rate in the brain decreases linearly with age. This trend is thought to reflect the fact that children have more to learn. AD "pathology" may be a natural continuation of this trend. It is characterized by decreasing cerebral metabolism, selective elimination of synapses and reliance on accumulating knowledge (especially implicit and procedural) over raw brain power (working memory). Over decades of subsistence, the behaviors of aging foragers became routinized, their motor movements automated and their expertise ingrained to a point where they no longer necessitated the first-rate working memory they possessed when younger and learning actively. Alzheimer changes selectively and

  14. Alzheimer's disease and natural cognitive aging may represent adaptive metabolism reduction programs

    Directory of Open Access Journals (Sweden)

    Reser Jared

    2009-02-01

    Full Text Available Abstract The present article examines several lines of converging evidence suggesting that the slow and insidious brain changes that accumulate over the lifespan, resulting in both natural cognitive aging and Alzheimer's disease (AD, represent a metabolism reduction program. A number of such adaptive programs are known to accompany aging and are thought to have decreased energy requirements for ancestral hunter-gatherers in their 30s, 40s and 50s. Foraging ability in modern hunter-gatherers declines rapidly, more than a decade before the average terminal age of 55 years. Given this, the human brain would have been a tremendous metabolic liability that must have been advantageously tempered by the early cellular and molecular changes of AD which begin to accumulate in all humans during early adulthood. Before the recent lengthening of life span, individuals in the ancestral environment died well before this metabolism reduction program resulted in clinical AD, thus there was never any selective pressure to keep adaptive changes from progressing to a maladaptive extent. Aging foragers may not have needed the same cognitive capacities as their younger counterparts because of the benefits of accumulated learning and life experience. It is known that during both childhood and adulthood metabolic rate in the brain decreases linearly with age. This trend is thought to reflect the fact that children have more to learn. AD "pathology" may be a natural continuation of this trend. It is characterized by decreasing cerebral metabolism, selective elimination of synapses and reliance on accumulating knowledge (especially implicit and procedural over raw brain power (working memory. Over decades of subsistence, the behaviors of aging foragers became routinized, their motor movements automated and their expertise ingrained to a point where they no longer necessitated the first-rate working memory they possessed when younger and learning actively. Alzheimer

  15. Dynamic metabolome profiling reveals significant metabolic changes during grain development of bread wheat (Triticum aestivum L.).

    Science.gov (United States)

    Zhen, Shoumin; Dong, Kun; Deng, Xiong; Zhou, Jiaxing; Xu, Xuexin; Han, Caixia; Zhang, Wenying; Xu, Yanhao; Wang, Zhimin; Yan, Yueming

    2016-08-01

    Metabolites in wheat grains greatly influence nutritional values. Wheat provides proteins, minerals, B-group vitamins and dietary fiber to humans. These metabolites are important to human health. However, the metabolome of the grain during the development of bread wheat has not been studied so far. In this work the first dynamic metabolome of the developing grain of the elite Chinese bread wheat cultivar Zhongmai 175 was analyzed, using non-targeted gas chromatography/mass spectrometry (GC/MS) for metabolite profiling. In total, 74 metabolites were identified over the grain developmental stages. Metabolite-metabolite correlation analysis revealed that the metabolism of amino acids, carbohydrates, organic acids, amines and lipids was interrelated. An integrated metabolic map revealed a distinct regulatory profile. The results provide information that can be used by metabolic engineers and molecular breeders to improve wheat grain quality. The present metabolome approach identified dynamic changes in metabolite levels, and correlations among such levels, in developing seeds. The comprehensive metabolic map may be useful when breeding programs seek to improve grain quality. The work highlights the utility of GC/MS-based metabolomics, in conjunction with univariate and multivariate data analysis, when it is sought to understand metabolic changes in developing seeds. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  16. Profile of Cardiovascular Risk Factors in Patients with Coronary Heart Disease, Normal and Impaired Carbohydrate Metabolism

    Directory of Open Access Journals (Sweden)

    І.V. Cherniavska

    2015-11-01

    Full Text Available The aim of research was to conduct the comparative analysis of the profile of cardiovascular risk factors in patients with coronary heart disease (CHD and normal either impaired carbohydrate metabolism. Materials and methods. One hundred and forty two patients were observed. In order to estimate the rate of different forms of CHD depending on the state of carbohydrate metabolism such groups were formed: the first group consisted of 83 patients with type 2 diabetes mellitus (DM, the second group involved 34 patients with impaired glucose tolerance (IGT, the third group consisted of 25 patients with normal carbohydrate metabolism. The ischemic changes of myocardium were detected by ambulatory ECG monitoring with the obligatory achievement of submaximal heart rate during the research. Results. Silent myocardial ischemia was educed in 19 (22.9 % patients with type 2 DM, in 3 (8.8 % persons with IGT and in 2 (8.0 % patients with normal carbohydrate metabolism. Smoking, burdened heredity, violation in the haemostatic system more often occurred in the group of patients with type 2 DM and silent myocardial ischemia in comparison with the patients with type 2 DM without CHD. The profile of general population cardiovascular risk factors in patients with CHD and type 2 DM belongs to the most unfavorable. At the same time for patients with early violations of carbohydrate metabolism and normal carbohydrate metabolism such profile statistically does not differentiate meaningfully. Conclusions. Patients with type 2 DM and silent myocardial ischemia as compared to patients with type 2 DM without CHD have more expressed violations of indexes of general population cardiovascular risk factors for certain.

  17. Association of glucocorticoid receptor polymorphisms with clinical and metabolic profiles in polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Gustavo A.Rosa Maciel

    2014-03-01

    Full Text Available OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1 polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment.

  18. Untargeted metabolite profiling of murine embryos to reveal metabolic perturbations associated with neural tube closure defects.

    Science.gov (United States)

    Hansler, Alex; Chen, Qiuying; Gray, Jason D; Ross, M Elizabeth; Finnell, Richard H; Gross, Steven S

    2014-08-01

    Neural tube closure defects (NTDs) are among the most common congenital malformation in human, typically presenting in liveborns as spina bifida. At least 240 gene mutations in mouse are known to increase the risk of NTD. There is a growing appreciation that environmental factors significantly contribute to NTD expression, and that NTDs likely arise from complex gene-environment interactions. Because maternal folic acid supplementation reduces human NTD risk in some populations by 60 to 70%, it is likely that NTD predisposition is often associated with a defect in folate-dependent one-carbon metabolism. A comprehensive, untargeted metabolic survey of NTD-associated changes in embryo metabolism would provide a valuable test of this assumption. We sought to establish a metabolic profiling platform that is capable of broadly assessing metabolic aberrations associated with NTD-promoting gene mutations in early-stage mouse embryos. A liquid chromatography/mass spectrometry-based untargeted metabolite profiling platform was used to broadly identify significant differences in small molecule levels (50-1000 Da) in NTD-affected embryonic day (E) 9.5 mouse embryos (Lrp6(-) (/) (-) ) versus unaffected (Lrp6(+/+) ) control embryos. Results provide proof-of-principal feasibility for the broad survey of the metabolome of individual E9.5 mouse embryos and identification of metabolic changes associated with NTDs and gene mutations. Levels of 30 different metabolites were altered in association with Lrp6 gene deletion. Some metabolites link to folate-dependent one-carbon transfer reactions, as anticipated, while others await structure elucidation and pathway integration. Whole-embryo metabolomics offers the potential to identify metabolic changes in genetically determined NTD-prone embryos. © 2014 Wiley Periodicals, Inc.

  19. Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children: The ABCD Study.

    Science.gov (United States)

    Vrijkotte, Tanja G M; van den Born, Bert-Jan H; Hoekstra, Christine M C A; Gademan, Maaike G J; van Eijsden, Manon; de Rooij, Susanne R; Twickler, Marcel T B

    2015-01-01

    In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5-6 years. Cross-sectional data from an apparently healthy population (within the ABCD study) were collected at age 5-6 years in 1540 children. Heart rate (HR), respiratory sinus arrhythmia (RSA; parasympathetic activity) and pre-ejection period (PEP; sympathetic activity) were assessed during rest. Metabolic components were waist-height ratio (WHtR), systolic blood pressure (SBP), fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed. In analysis adjusted for child's physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01), higher SBP (p<0.001) and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01). Lower PEP was only associated with higher SBP (p <0.05). Of all children, 5.6% had 3 or more (out of 5) adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001). This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5-6 years.

  20. Metabolic Profiling of Retrograde Pathway Transcription Factors Rtg1 and Rtg3 Knockout Yeast

    Directory of Open Access Journals (Sweden)

    Zanariah Hashim

    2014-07-01

    Full Text Available Rtg1 and Rtg3 are two basic helix-loop-helix (bHLH transcription factors found in yeast Saccharomyces cerevisiae that are involved in the regulation of the mitochondrial retrograde (RTG pathway. Under RTG response, anaplerotic synthesis of citrate is activated, consequently maintaining the supply of important precursors necessary for amino acid and nucleotide synthesis. Although the roles of Rtg1 and Rtg3 in TCA and glyoxylate cycles have been extensively reported, the investigation of other metabolic pathways has been lacking. Characteristic dimer formation in bHLH proteins, which allows for combinatorial gene expression, and the link between RTG and other regulatory pathways suggest more complex metabolic signaling involved in Rtg1/Rtg3 regulation. In this study, using a metabolomics approach, we examined metabolic alteration following RTG1 and RTG3 deletion. We found that apart from TCA and glyoxylate cycles, which have been previously reported, polyamine biosynthesis and other amino acid metabolism were significantly altered in RTG-deficient strains. We revealed that metabolic alterations occurred at various metabolic sites and that these changes relate to different growth phases, but the difference can be detected even at the mid-exponential phase, when mitochondrial function is repressed. Moreover, the effect of metabolic rearrangements can be seen through the chronological lifespan (CLS measurement, where we confirmed the role of the RTG pathway in extending the yeast lifespan. Through a comprehensive metabolic profiling, we were able to explore metabolic phenotypes previously unidentified by other means and illustrate the possible correlations of Rtg1 and Rtg3 in different pathways.

  1. Adaptation of maize source leaf metabolism to stress related disturbances in carbon, nitrogen and phosphorus balance.

    Science.gov (United States)

    Schlüter, Urte; Colmsee, Christian; Scholz, Uwe; Bräutigam, Andrea; Weber, Andreas P M; Zellerhoff, Nina; Bucher, Marcel; Fahnenstich, Holger; Sonnewald, Uwe

    2013-07-03

    Abiotic stress causes disturbances in the cellular homeostasis. Re-adjustment of balance in carbon, nitrogen and phosphorus metabolism therefore plays a central role in stress adaptation. However, it is currently unknown which parts of the primary cell metabolism follow common patterns under different stress conditions and which represent specific responses. To address these questions, changes in transcriptome, metabolome and ionome were analyzed in maize source leaves from plants suffering low temperature, low nitrogen (N) and low phosphorus (P) stress. The selection of maize as study object provided data directly from an important crop species and the so far underexplored C4 metabolism. Growth retardation was comparable under all tested stress conditions. The only primary metabolic pathway responding similar to all stresses was nitrate assimilation, which was down-regulated. The largest group of commonly regulated transcripts followed the expression pattern: down under low temperature and low N, but up under low P. Several members of this transcript cluster could be connected to P metabolism and correlated negatively to different phosphate concentration in the leaf tissue. Accumulation of starch under low temperature and low N stress, but decrease in starch levels under low P conditions indicated that only low P treated leaves suffered carbon starvation. Maize employs very different strategies to manage N and P metabolism under stress. While nitrate assimilation was regulated depending on demand by growth processes, phosphate concentrations changed depending on availability, thus building up reserves under excess conditions. Carbon and energy metabolism of the C4 maize leaves were particularly sensitive to P starvation.

  2. Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

    Science.gov (United States)

    Farney, Jaymelynn K.; Mamedova, Laman K.; Coetzee, Johann F.; KuKanich, Butch; Sordillo, Lorraine M.; Stoakes, Sara K.; Minton, J. Ernest; Hollis, Larry C.

    2013-01-01

    Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation. PMID:23678026

  3. The relationship between aerobic fitness level and metabolic profiles in healthy adults.

    Science.gov (United States)

    Morris, Ciara; Grada, Colm O; Ryan, Miriam; Roche, Helen M; De Vito, Giuseppe; Gibney, Michael J; Gibney, Eileen R; Brennan, Lorraine

    2013-07-01

    Application of metabolomics to nutrition and health research is increasing and while much effort has been invested in understanding factors that influence the metabolomic profile there is relatively little known about the impact of fitness level. This study aimed to examine the relationship between fitness level, substrate oxidation rates, and the metabolic profile. Two hundred and fourteen healthy adults (18-60 years) were recruited and 65 subjects were selected based on their estimated maximal oxygen consumption levels. Metabolomic analysis was performed. The subjects were split into fitness groups according to their maximal oxygen consumption levels (mL/kg/min) and analysis revealed significant differences in normalized fat and carbohydrate oxidation levels between the groups. Urinary metabolomic analysis revealed significantly different profiles in the groups with 15 amino acids significantly higher in the low fitness groups. Effects of fitness level in the plasma metabolic profiles were also demonstrated. This study demonstrates a relationship between fitness level and the amino acid profile. Moreover, the metabolite changes show that a reduced excretion of amino acids in adults is associated with increased fitness levels and an increased fat oxidation rate during exercise. Interestingly, higher levels of branched chain amino acids were associated with lower fitness levels and higher insulin resistance. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells.

    Science.gov (United States)

    Armitage, Emily G; Kotze, Helen L; Allwood, J William; Dunn, Warwick B; Goodacre, Royston; Williams, Kaye J

    2015-10-28

    Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

  5. Metabolic profiling by (1)H NMR of ground beef irradiated at different irradiation doses.

    Science.gov (United States)

    Zanardi, Emanuela; Caligiani, Augusta; Palla, Luigi; Mariani, Mario; Ghidini, Sergio; Di Ciccio, Pierluigi Aldo; Palla, Gerardo; Ianieri, Adriana

    2015-05-01

    This work describes a metabolic profiling study of non-irradiated and irradiated beef (at 2.5, 4.5 and 8 kGy) using (1)H NMR and chemometrics. The assignment of all major NMR signals of the aqueous/methanolic extracts was performed. A comprehensive multivariate data analysis proved the ability to distinguish between the irradiated and non-irradiated beef. Classification trees revealed that three metabolites (glycerol, lactic acid esters and tyramine or a p-substituted phenolic compound) are important biomarkers for classification of the irradiated and non-irradiated beef samples. Overall, the achieved metabolomic results show that the changes in the metabolic profile of meat provide a valuable insight to be used in detecting irradiated beef. The use of the NMR-based approach simplifies sample preparation and decrease the time required for analysis, compared to available official analytical procedures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Flavonoids: a metabolic network mediating plants adaptation to their real estate.

    Science.gov (United States)

    Mouradov, Aidyn; Spangenberg, German

    2014-01-01

    From an evolutionary perspective, the emergence of the sophisticated chemical scaffolds of flavonoid molecules represents a key step in the colonization of Earth's terrestrial environment by vascular plants nearly 500 million years ago. The subsequent evolution of flavonoids through recruitment and modification of ancestors involved in primary metabolism has allowed vascular plants to cope with pathogen invasion and damaging UV light. The functional properties of flavonoids as a unique combination of different classes of compounds vary significantly depending on the demands of their local real estate. Apart from geographical location, the composition of flavonoids is largely dependent on the plant species, their developmental stage, tissue type, subcellular localization, and key ecological influences of both biotic and abiotic origin. Molecular and metabolic cross-talk between flavonoid and other pathways as a result of the re-direction of intermediate molecules have been well investigated. This metabolic plasticity is a key factor in plant adaptive strength and is of paramount importance for early land plants adaptation to their local ecosystems. In human and animal health the biological and pharmacological activities of flavonoids have been investigated in great depth and have shown a wide range of anti-inflammatory, anti-oxidant, anti-microbial, and anti-cancer properties. In this paper we review the application of advanced gene technologies for targeted reprogramming of the flavonoid pathway in plants to understand its molecular functions and explore opportunities for major improvements in forage plants enhancing animal health and production.

  7. Flavonoids: A Metabolic Network Mediating Plants Adaptation to Their Real Estate

    Directory of Open Access Journals (Sweden)

    Aidyn eMouradov

    2014-11-01

    Full Text Available From an evolutionary perspective, the emergence of the sophisticated chemical scaffolds of flavonoid molecules represents a key step in the colonization of Earth’s terrestrial environment by vascular plants nearly 500 million years ago. The subsequent evolution of flavonoids through recruitment and modification of ancestors involved in primary metabolism has allowed vascular plants to cope with pathogen invasion and damaging UV light. The functional properties of flavonoids as a unique combination of different classes of compounds vary significantly depending on the demands of their local real estate. Apart from geographical location, the composition of flavonoids is largely dependent on the plant species, their developmental stage, tissue type, subcellular localization, and key ecological influences of both biotic and abiotic origin. Molecular and metabolic cross-talk between flavonoid and other pathways as a result of the re-direction of intermediate molecules have been well investigated. This metabolic plasticity is a key factor in plant adaptive strength and is of paramount importance for early land plants adaptation to their local ecosystems. In human and animal health the biological and pharmacological activities of flavonoids have been investigated in great depth and have shown a wide range of anti-inflammatory, anti-oxidant, anti-microbial and anti-cancer properties. In this paper we review the application of advanced gene technologies for targeted reprogramming of the flavonoid pathway in plants to understand its molecular functions and explore opportunities for major improvements in forage plants enhancing animal health and production.

  8. Molecular subtyping of metastatic melanoma based on cell ganglioside metabolism profiles.

    Science.gov (United States)

    Tringali, Cristina; Silvestri, Ilaria; Testa, Francesca; Baldassari, Paola; Anastasia, Luigi; Mortarini, Roberta; Anichini, Andrea; López-Requena, Alejandro; Tettamanti, Guido; Venerando, Bruno

    2014-08-01

    In addition to alterations concerning the expression of oncogenes and onco-suppressors, melanoma is characterized by the presence of distinctive gangliosides (sialic acid carrying glycosphingolipids). Gangliosides strongly control cell surface dynamics and signaling; therefore, it could be assumed that these alterations are linked to modifications of cell behavior acquired by the tumor. On these bases, this work investigated the correlations between melanoma cell ganglioside metabolism profiles and the biological features of the tumor and the survival of patients. Melanoma cell lines were established from surgical specimens of AJCC stage III and IV melanoma patients. Sphingolipid analysis was carried out on melanoma cell lines and melanocytes through cell metabolic labeling employing [3-3H]sphingosine and by FACS. N-glycolyl GM3 was identified employing the 14 F7 antibody. Gene expression was assayed by Real Time PCR. Cell invasiveness was assayed through a Matrigel invasion assay; cell proliferation was determined through the soft agar assay, MTT, and [3H] thymidine incorporation. Statistical analysis was performed using XLSTAT software for melanoma hierarchical clustering based on ganglioside profile, the Kaplan-Meier method, the log-rank (Mantel-Cox) test, and the Mantel-Haenszel test for survival analysis. Based on the ganglioside profiles, through a hierarchical clustering, we classified melanoma cells isolated from patients into three clusters: 1) cluster 1, characterized by high content of GM3, mainly in the form of N-glycolyl GM3, and GD3; 2) cluster 2, characterized by the appearance of complex gangliosides and by a low content of GM3; 3) cluster 3, which showed an intermediate phenotype between cluster 1 and cluster 3. Moreover, our data demonstrated that: a) a correlation could be traced between patients' survival and clusters based on ganglioside profiles, with cluster 1 showing the worst survival; b) the expression of several enzymes (sialidase NEU3

  9. Intraspecific variability in allelopathy of Heracleum mantegazzianum is linked to the metabolic profile of root exudates.

    Science.gov (United States)

    Jandová, Kateřina; Dostál, Petr; Cajthaml, Tomáš; Kameník, Zdeněk

    2015-04-01

    Allelopathy may drive invasions of some exotic plants, although empirical evidence for this theory remains largely inconclusive. This could be related to the large intraspecific variability of chemically mediated plant-plant interactions, which is poorly studied. This study addressed intraspecific variability in allelopathy of Heracleum mantegazzianum (giant hogweed), an invasive species with a considerable negative impact on native communities and ecosystems. Bioassays were carried out to test the alleopathic effects of H. mantegazzianum root exudates on germination of Arabidopsis thaliana and Plantago lanceolata. Populations of H. mantegazzianum from the Czech Republic were sampled and variation in the phytotoxic effects of the exudates was partitioned between areas, populations within areas, and maternal lines. The composition of the root exudates was determined by metabolic profiling using ultra-high-performance liquid chromatography with time-of-flight mass spectrometry, and the relationships between the metabolic profiles and the effects observed in the bioassays were tested using orthogonal partial least-squares analysis. Variance partitioning indicated that the highest variance in phytotoxic effects was within populations. The inhibition of germination observed in the bioassay for the co-occurring native species P. lanceolata could be predicted by the metabolic profiles of the root exudates of particular maternal lines. Fifteen compounds associated with this inhibition were tentatively identified. The results present strong evidence that intraspecific variability needs to be considered in research on allelopathy, and suggest that metabolic profiling provides an efficient tool for studying chemically mediated plant-plant interactions whenever unknown metabolites are involved. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis

    OpenAIRE

    Zhao, Yue; Fu, Li; Li, Rong; Wang, Li-Na; Yang, Yan; Liu, Na-Na; Zhang, Chun-Mei; Wang, Ying; Liu, Ping; Tu, Bin-Bin; Zhang, Xue; Qiao, Jie

    2012-01-01

    Background Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied with an increased risk of developing type 2 diabetes mellitus and cardiovascular disease; despite being a common condition, the pathogenesis of PCOS remains unclear. Our aim was to investigate the potential metabolic profiles for different phenotypes of PCOS, as well as for the early prognosis of complications. Methods A total of 217 women with PCOS and 48 healthy women as normal controls were studie...

  11. Metabolic profiling of human lung cancer blood plasma using 1H NMR spectroscopy

    Science.gov (United States)

    Kokova, Daria; Dementeva, Natalia; Kotelnikov, Oleg; Ponomaryova, Anastasia; Cherdyntseva, Nadezhda; Kzhyshkowska, Juliya

    2017-11-01

    Lung cancer (both small cell and non-small cell) is the second most common cancer in both men and women. The article represents results of evaluating of the plasma metabolic profiles of 100 lung cancer patients and 100 controls to investigate significant metabolites using 400 MHz 1H NMR spectrometer. The results of multivariate statistical analysis show that a medium-field NMR spectrometer can obtain the data which are already sufficient for clinical metabolomics.

  12. Metabolic profiling of an Echinostoma caproni infection in the mouse for biomarker discovery.

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    Jasmina Saric

    Full Text Available BACKGROUND: Metabolic profiling holds promise with regard to deepening our understanding of infection biology and disease states. The objectives of our study were to assess the global metabolic responses to an Echinostoma caproni infection in the mouse, and to compare the biomarkers extracted from different biofluids (plasma, stool, and urine in terms of characterizing acute and chronic stages of this intestinal fluke infection. METHODOLOGY/PRINCIPAL FINDINGS: Twelve female NMRI mice were infected with 30 E. caproni metacercariae each. Plasma, stool, and urine samples were collected at 7 time points up to day 33 post-infection. Samples were also obtained from non-infected control mice at the same time points and measured using (1H nuclear magnetic resonance (NMR spectroscopy. Spectral data were subjected to multivariate statistical analyses. In plasma and urine, an altered metabolic profile was already evident 1 day post-infection, characterized by reduced levels of plasma choline, acetate, formate, and lactate, coupled with increased levels of plasma glucose, and relatively lower concentrations of urinary creatine. The main changes in the urine metabolic profile started at day 8 post-infection, characterized by increased relative concentrations of trimethylamine and phenylacetylglycine and lower levels of 2-ketoisocaproate and showed differentiation over the course of the infection. CONCLUSION/SIGNIFICANCE: The current investigation is part of a broader NMR-based metabonomics profiling strategy and confirms the utility of this approach for biomarker discovery. In the case of E. caproni, a diagnosis based on all three biofluids would deliver the most comprehensive fingerprint of an infection. For practical purposes, however, future diagnosis might aim at a single biofluid, in which case urine would be chosen for further investigation, based on quantity of biomarkers, ease of sampling, and the degree of differentiation from the non

  13. Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life

    DEFF Research Database (Denmark)

    Pinola, Pekka; Puukka, Katri; Piltonen, Terhi

    2017-01-01

    OBJECTIVE: To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. DESIGN: Case-control study. SETTING: Not applicable. PATIENT(S): In all, 1,550 women with normoandrogenic (n......, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two- to fivefold higher in women with PCOS compared with control women, depending on age and phenotype......, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. CONCLUSION(S): When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from...

  14. Sleeve Gastrectomy Reduces Body Weight and Improves Metabolic Profile also in Obesity-Prone Rats.

    Science.gov (United States)

    Moncada, Rafael; Becerril, Sara; Rodríguez, Amaia; Méndez-Giménez, Leire; Ramírez, Beatriz; Catalán, Victoria; Gómez-Ambrosi, Javier; Gil, M Jesús; Fernández, Secundino; Cienfuegos, Javier A; Valentí, Víctor; Frühbeck, Gema

    2016-07-01

    Susceptibility to obesity is associated with a notable inter-individual variation. The aim of the present study was to compare the effectiveness of sleeve gastrectomy (SG) on weight loss and metabolic profile in obesity-prone (OP) rats vs animals that are non-susceptible to obesity (NSO). Young male Wistar rats (n = 101) were put in a diet-induced obesity (DIO) programme with ad libitum access to a high-fed diet (HFD) during 12 months. Body weight and food intake were regularly registered. Thereafter, rats were ranked by final body weight to identify the obesity-prone (OP) (n = 13) and non-susceptible to obesity (NSO) (n = 14) animals. OP and NSO rats were submitted to surgical interventions (sham operation, SG and pair-fed to the amount of food eaten by sleeve-gastrectomized rats). Body weight, food intake, energy expenditure, body temperature, fat pads weight, and metabolic profiling were analysed 4 weeks after surgical or dietary interventions. SG in both OP and NSO rats decreased body weight as compared to sham and pair-fed groups (P weight loss achieved in sleeve-gastrectomized OP and NSO rats was higher than that of pair-fed ones (P obesity-prone rats also benefit from surgery responding effectively to SG, as evidenced by the significant body weight reduction and the metabolic profile improvement.

  15. Metabolic profile of breast cancer in a population of women in southern Spain.

    Science.gov (United States)

    Lopez-Saez, Juan-Bosco; Martinez-Rubio, Jose Antonio; Alvarez, Maria Montes; Carrera, Carmen Gonzalez; Dominguez Villar, Margarita; de Lomas Mier, Antonio Garcia; Doménech, Charo; Senra-Varela, Avelino

    2008-01-18

    There are indications that mortality in breast cancer is related with dietary factors, but no study has been large enough to characterise reliably how, this risk is influenced. To establish a logistic regression equation that would predict breast cancer from factors in the endocrinological and metabolic profile, we studied endocrinological and metabolic risk factors that are modified by the diet, in a population of women with breast cancer in southern Spain. We carried out a simple a case-control study comparing 204 women with breast cancer (96 premenopausal and 108 postmenopausal women) and 250 healthy control subjects. The predictive variables were basal glycaemia, insulin, glycosylated haemoglobin (HbA1c), C-peptide, insulin-like growth factor-I (IGF-I), total cholesterol, triglycerides, high density lipoprotein-c (HDL-C), low density lipoprotein-c (LDL-C), selenium and Quetelet index (BMI). The metabolic profile differed between pre- and postmenopausal patients, and metabolic alterations were greater in postmenopausal than in premenopausal women. The differences between healthy subjects and breast cancer patients were clearly significant. Our findings have several potential practical applications in the early detection of breast cancer, especially in premenopausal women; in primary prevention; and in the development of a mathematical model of breast carcinogenesis.

  16. Feeding dairy cows with soybean by-products: effects on metabolic profile

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    Alves Marilia

    2004-01-01

    Full Text Available Soybean by-products are currently used in Rio Grande do Sul, Brazil, as a source of protein in dairy cows. However, the high protein breakdown of this feed source in the rumen causes loss of the intrinsic quality of the protein and increases plasma urea with deleterious consequences to animal metabolism. Thermal treatment of soybean can overcome this limitation. The aim of this study was to evaluate the metabolism of dairy cows fed with thermally treated soybean and raw soybean, through the analyses of the metabolic profile of plasma and milk. Twelve Holstein cows in mid-lactation period were studied using four treatments: commercial concentrated of protein, soybean meal, raw soybean and roasted soybean. Protein and urea levels in milk were measured in morning and afternoon samples. Data were arranged in a Latin square design (4 treatments and 3 animals in each square. There were no significant differences in glucose, beta-hydroxybutyrate, calcium, phosphorus and magnesium concentrations among treatments. Cows consuming raw and thermally treated soybean had higher levels of plasma cholesterol. Cows consuming roasted soybean had lower level of plasma and milk urea in the morning. Afternoon milk samples had higher levels of urea than morning samples. It is suggested that thermally treated soybean was effective in diminishing the breakdown of protein in the rumen. It is better to employ morning milk samples to evaluate metabolic profile than afternoon samples.

  17. Differential sensitivities of bladder cancer cell lines to resveratol are unrelated to its metabolic profile

    Science.gov (United States)

    Li, Hong; Wu, Moli; Ren, Changle; Zhen, Yuhong; Ma, Xiaochi; Diao, Yunpeng; Ma, Xiaodong; Deng, Sa; Liu, Jia

    2017-01-01

    Resveratrol (RV) is a natural polyphenol compound with a wide range of activities, including inhibition of human bladder cancer (HBC) cell growth. Because RV is rapidly metabolized and has poor bioavailability, it is unclear whether the antitumor activity is due to RV or its metabolites. We therefore used liquid chromatography-mass spectroscopy, qRT-PCR, immunocytochemistry and western blotting to evaluate the metabolic profile and biotransformation of RV in the T24 and EJ HBC cell lines. Both T24 and EJ cells generated the same RV metabolite, RV monosulfate (RVS), and both exhibited upregulation of the RV-associated metabolic enzyme SULT1A1 (sulfotransferase). Despite these similarities, T24 cells were more sensitive to RV than EJ cells, yet T24 cells exhibited no sensitivity to an RVS mixture (84.13% RVS). Primary rat bladder epithelial cells showed no adverse effects when exposed to a therapeutic dose (100 μM) of RV. The differences in RV sensitivity between the two HBC cell lines did not reflect differences in the RV metabolic profile or SULT1A1 expression. Because RV exhibited stronger antitumor activity and better safety than RVS, we conclude that RV has significant therapeutic potential for HBC treatment, provided individual differences are considered during clinical research and application. PMID:28178690

  18. Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose.

    Science.gov (United States)

    Zhou, Yue-Yue; Ji, Xiong-Fei; Fu, Jian-Ping; Zhu, Xiao-Juan; Li, Rong-Hua; Mu, Chang-Kao; Wang, Chun-Lin; Song, Wei-Wei

    2015-01-01

    D-galactose injection has been shown to induce many changes in mice that represent accelerated aging. This mouse model has been widely used for pharmacological studies of anti-aging agents. The underlying mechanism of D-galactose induced aging remains unclear, however, it appears to relate to glucose and 1ipid metabolic disorders. Currently, there has yet to be a study that focuses on investigating gene expression changes in D-galactose aging mice. In this study, integrated analysis of gas chromatography/mass spectrometry-based metabonomics and gene expression profiles was used to investigate the changes in transcriptional and metabolic profiles in mimetic aging mice injected with D-galactose. Our findings demonstrated that 48 mRNAs were differentially expressed between control and D-galactose mice, and 51 potential biomarkers were identified at the metabolic level. The effects of D-galactose on aging could be attributed to glucose and 1ipid metabolic disorders, oxidative damage, accumulation of advanced glycation end products (AGEs), reduction in abnormal substance elimination, cell apoptosis, and insulin resistance.

  19. Metagenomic and metabolic profiling of nonlithifying and lithifying stromatolitic mats of Highborne Cay, The Bahamas.

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    Christina L M Khodadad

    Full Text Available BACKGROUND: Stromatolites are laminated carbonate build-ups formed by the metabolic activity of microbial mats and represent one of the oldest known ecosystems on Earth. In this study, we examined a living stromatolite located within the Exuma Sound, The Bahamas and profiled the metagenome and metabolic potential underlying these complex microbial communities. METHODOLOGY/PRINCIPAL FINDINGS: The metagenomes of the two dominant stromatolitic mat types, a nonlithifying (Type 1 and lithifying (Type 3 microbial mat, were partially sequenced and compared. This deep-sequencing approach was complemented by profiling the substrate utilization patterns of the mats using metabolic microarrays. Taxonomic assessment of the protein-encoding genes confirmed previous SSU rRNA analyses that bacteria dominate the metagenome of both mat types. Eukaryotes comprised less than 13% of the metagenomes and were rich in sequences associated with nematodes and heterotrophic protists. Comparative genomic analyses of the functional genes revealed extensive similarities in most of the subsystems between the nonlithifying and lithifying mat types. The one exception was an increase in the relative abundance of certain genes associated with carbohydrate metabolism in the lithifying Type 3 mats. Specifically, genes associated with the degradation of carbohydrates commonly found in exopolymeric substances, such as hexoses, deoxy- and acidic sugars were found. The genetic differences in carbohydrate metabolisms between the two mat types were confirmed using metabolic microarrays. Lithifying mats had a significant increase in diversity and utilization of carbon, nitrogen, phosphorus and sulfur substrates. CONCLUSION/SIGNIFICANCE: The two stromatolitic mat types retained similar microbial communities, functional diversity and many genetic components within their metagenomes. However, there were major differences detected in the activity and genetic pathways of organic carbon

  20. Metagenomic and Metabolic Profiling of Nonlithifying and Lithifying Stromatolitic Mats of Highborne Cay, The Bahamas

    Science.gov (United States)

    Khodadad, Christina L. M.; Foster, Jamie S.

    2012-01-01

    Background Stromatolites are laminated carbonate build-ups formed by the metabolic activity of microbial mats and represent one of the oldest known ecosystems on Earth. In this study, we examined a living stromatolite located within the Exuma Sound, The Bahamas and profiled the metagenome and metabolic potential underlying these complex microbial communities. Methodology/Principal Findings The metagenomes of the two dominant stromatolitic mat types, a nonlithifying (Type 1) and lithifying (Type 3) microbial mat, were partially sequenced and compared. This deep-sequencing approach was complemented by profiling the substrate utilization patterns of the mats using metabolic microarrays. Taxonomic assessment of the protein-encoding genes confirmed previous SSU rRNA analyses that bacteria dominate the metagenome of both mat types. Eukaryotes comprised less than 13% of the metagenomes and were rich in sequences associated with nematodes and heterotrophic protists. Comparative genomic analyses of the functional genes revealed extensive similarities in most of the subsystems between the nonlithifying and lithifying mat types. The one exception was an increase in the relative abundance of certain genes associated with carbohydrate metabolism in the lithifying Type 3 mats. Specifically, genes associated with the degradation of carbohydrates commonly found in exopolymeric substances, such as hexoses, deoxy- and acidic sugars were found. The genetic differences in carbohydrate metabolisms between the two mat types were confirmed using metabolic microarrays. Lithifying mats had a significant increase in diversity and utilization of carbon, nitrogen, phosphorus and sulfur substrates. Conclusion/Significance The two stromatolitic mat types retained similar microbial communities, functional diversity and many genetic components within their metagenomes. However, there were major differences detected in the activity and genetic pathways of organic carbon utilization. These

  1. Change in Metabolic Profile after 1-Year Nutritional-Behavioral Intervention in Obese Children

    Directory of Open Access Journals (Sweden)

    Elvira Verduci

    2015-12-01

    Full Text Available Research findings are inconsistent about improvement of specific cardio-metabolic variables after lifestyle intervention in obese children. The aim of this trial was to evaluate the effect of a 1-year intervention, based on normocaloric diet and physical activity, on body mass index (BMI, blood lipid profile, glucose metabolism and metabolic syndrome. Eighty-five obese children aged ≥6 years were analyzed. The BMI z-score was calculated. Fasting blood samples were analyzed for lipids, insulin and glucose. The homeostatic model assessment of insulin resistance (HOMA-IR was calculated and insulin resistance was defined as HOMA-IR >3.16. HOMA-β%, quantitative insulin sensitivity check index and triglyceride glucose index were calculated. The metabolic syndrome was defined in accordance with the International Diabetes Federation criteria. At the end of intervention children showed a reduction (mean (95% CI in BMI z-score (−0.58 (−0.66; −0.50, triglycerides (−0.35 (−0.45; −0.25 mmol/L and triglyceride glucose index (−0.29 (−0.37; −0.21, and an increase in HDL cholesterol (0.06 (0.01; 0.11 mmol/L. Prevalence of insulin resistance declined from 51.8% to 36.5% and prevalence of metabolic syndrome from 17.1% to 4.9%. Nutritional-behavioral interventions can improve the blood lipid profile and insulin sensitivity in obese children, and possibly provide benefits in terms of metabolic syndrome.

  2. Effects of a cocaine hydrolase engineered from human butyrylcholinesterase on metabolic profile of cocaine in rats.

    Science.gov (United States)

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

    2016-11-25

    Accelerating cocaine metabolism through enzymatic hydrolysis at cocaine benzoyl ester is recognized as a promising therapeutic approach for cocaine abuse treatment. Our more recently designed A199S/F227A/S287G/A328W/Y332G mutant of human BChE, denoted as cocaine hydrolase-3 (CocH3), has a considerably improved catalytic efficiency against cocaine and has been proven active in blocking cocaine-induced toxicity and physiological effects. In the present study, we have further characterized the effects of CocH3 on the detailed metabolic profile of cocaine in rats administrated intravenously (IV) with 5 mg/kg cocaine, demonstrating that IV administration of 0.15 mg/kg CocH3 dramatically changed the metabolic profile of cocaine. Without CocH3 administration, the dominant cocaine-metabolizing pathway in rats was cocaine methyl ester hydrolysis to benzoylecgonine (BZE). With the CocH3 administration, the dominant cocaine-metabolizing pathway in rats became cocaine benzoyl ester hydrolysis to ecgonine methyl ester (EME), and the other two metabolic pathways (i.e. cocaine methyl ester hydrolysis to BZE and cocaine oxidation to norcocaine) became insignificant. The CocH3-catalyzed cocaine benzoyl ester hydrolysis to EME was so efficient such that the measured maximum blood cocaine concentration (∼38 ng/ml) was significantly lower than the threshold blood cocaine concentration (∼72 ng/ml) required to produce any measurable physiological effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions.

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    Vijayaraghava T S Rao

    Full Text Available Within the microenvironment of multiple sclerosis lesions, oligodendrocytes are subject to metabolic stress reflecting effects of focal ischemia and inflammation. Previous studies have shown that under optimal conditions in vitro, the respiratory activity of human adult brain-derived oligodendrocytes is lower and more predominantly glycolytic compared to oligodendrocytes differentiated in vitro from post natal rat brain oligodendrocyte progenitor cells. In response to sub-lethal metabolic stress, adult human oligodendrocytes reduce overall energy production rate impacting the capacity to maintain myelination. Here, we directly compare the metabolic profiles of oligodendrocytes derived from adult rat brain with oligodendrocytes newly differentiated in vitro from oligodendrocyte progenitor cells obtained from the post natal rat brain, under both optimal culture and metabolic stress (low/no glucose conditions. Oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. Our findings indicate that under optimal conditions, adult rat oligodendrocytes preferentially use glycolysis whereas newly differentiated post natal rat oligodendrocytes, and the oligodendrocyte progenitor cells from which they are derived, mainly utilize oxidative phosphorylation to produce ATP. Metabolic stress increases the rate of ATP production via oxidative phosphorylation and significantly reduces glycolysis in adult oligodendrocytes. The rate of ATP production was relatively unchanged in newly differentiated post natal oligodendrocytes under these stress conditions, while it was significantly reduced in oligodendrocyte progenitor cells. Our study indicates that both age and maturation influence the metabolic profile under optimal and stressed conditions, emphasizing the need to consider these variables for in vitro studies that aim to model adult human disease.

  4. Elucidation of xenobiotic metabolism pathways in human skin and human skin models by proteomic profiling.

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    Sven van Eijl

    Full Text Available BACKGROUND: Human skin has the capacity to metabolise foreign chemicals (xenobiotics, but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin. METHODOLOGY/PRINCIPAL FINDINGS: Label-free proteomic analysis of whole human skin (10 donors was applied and analysed using custom-built PROTSIFT software. The results showed the presence of enzymes with a capacity for the metabolism of alcohols through dehydrogenation, aldehydes through dehydrogenation and oxidation, amines through oxidation, carbonyls through reduction, epoxides and carboxylesters through hydrolysis and, of many compounds, by conjugation to glutathione. Whereas protein levels of these enzymes in skin were mostly just 4-10 fold lower than those in liver and sufficient to support metabolism, the levels of cytochrome P450 enzymes were at least 300-fold lower indicating they play no significant role. Four epidermal models of human skin had profiles very similar to one another and these overlapped substantially with that of whole skin. CONCLUSIONS/SIGNIFICANCE: The proteomics profiling approach was successful in producing a comprehensive analysis of the biotransformation characteristics of whole human skin and various in vitro skin models. The results show that skin contains a range of defined enzymes capable of metabolising different classes of chemicals. The degree of similarity of the profiles of the in vitro models indicates their suitability for epidermal toxicity testing. Overall, these

  5. Adaptive modulation of behavioural profiles by social stress during early phases of life and adolescence.

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    Sachser, Norbert; Hennessy, Michael B; Kaiser, Sylvia

    2011-06-01

    The development of individual behavioural profiles can be powerfully influenced by stressful social experiences. Using a comparative approach, we focus on the role of social stressors for the modulation of behavioural profile during early phases of life and adolescence. For gregarious species, the stability of the social environment in which the pregnant and lactating female lives is of major importance for foetal brain development and the behavioural profile of the offspring in later life. Social instability during these critical periods of development generally brings about a behavioural and neuroendocrine masculinisation in daughters and a less pronounced expression of male-typical traits in sons. Moreover, when mothers live in a socially threatening world during this time, anxiety-like behaviour of their offspring often is elevated in adulthood. These effects of the social environment are likely to be mediated by maternal hormones and/or maternal behaviour. In addition, they can be modulated significantly by offspring genotype. We favour the hypothesis that the behavioural effects of social stress during this phase of life are not necessarily "pathological" (nonadaptive) consequences or constraints of adverse social conditions. Rather, mothers could be adjusting the offspring to their environment in an adaptive way. Adolescence is another period in which behavioural development is particularly susceptible to social influences. There is some evidence that stressful social events experienced at this time alter and canalize behaviour in an adaptive fashion, so that earlier influences on behavioural profile development can be complemented and readjusted, if necessary, to meet current environmental conditions. In terms of underlying neuroendocrine mechanism, a central role for the interaction of testosterone and stress hormones is suggested. In summary, the modulation of behavioural profiles by social stress from the prenatal phase through adolescence appears to

  6. Plasma, urine and ligament tissue metabolite profiling reveals potential biomarkers of ankylosing spondylitis using NMR-based metabolic profiles.

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    Wang, Wei; Yang, Gen-Jin; Zhang, Ju; Chen, Chen; Jia, Zhen-Yu; Li, Jia; Xu, Wei-Dong

    2016-10-22

    Ankylosing spondylitis (AS) is an autoimmune rheumatic disease mostly affecting the axial skeleton. Currently, anti-tumour necrosis factor α (anti-TNF-α) represents an effective treatment for AS that may delay the progression of the disease and alleviate the symptoms if the diagnosis can be made early. Unfortunately, effective diagnostic biomarkers for AS are still lacking; therefore, most patients with AS do not receive timely and effective treatment. The intent of this study was to determine several key metabolites as potential biomarkers of AS using metabolomic methods to facilitate the early diagnosis of AS. First, we collected samples of plasma, urine, and ligament tissue around the hip joint from AS and control groups. The samples were examined by nuclear magnetic resonance spectrometry, and multivariate data analysis was performed to find metabolites that differed between the groups. Subsequently, according to the correlation coefficients, variable importance for the projection (VIP) and P values of the metabolites obtained in the multivariate data analysis, the most crucial metabolites were selected as potential biomarkers of AS. Finally, metabolic pathways involving the potential biomarkers were determined using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the metabolic pathway map was drawn. Forty-four patients with AS agreed to provide plasma and urine samples, and 30 provided ligament tissue samples. An equal number of volunteers were recruited for the control group. Multidimensional statistical analysis suggested significant differences between the patients with AS and control subjects, and the models exhibited good discrimination and predictive ability. A total of 20 different metabolites ultimately met the requirements for potential biomarkers. According to KEGG analysis, these marker metabolites were primarily related to fat metabolism, intestinal microbial metabolism, glucose metabolism and choline metabolism pathways, and

  7. Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia

    KAUST Repository

    Mojib, Nazia

    2014-06-01

    The tropical oligotrophic oceanic areas are characterized by high water transparency and annual solar radiation. Under these conditions, a large number of phylogenetically diverse mesozooplankton species living in the surface waters (neuston) are found to be blue pigmented. In the present study, we focused on understanding the metabolic and genetic basis of the observed blue phenotype functional equivalence between the blue-pigmented organisms from the phylum Arthropoda, subclass Copepoda (Acartia fossae) and the phylum Chordata, class Appendicularia (Oikopleura dioica) in the Red Sea. Previous studies have shown that carotenoid–protein complexes are responsible for blue coloration in crustaceans. Therefore, we performed carotenoid metabolic profiling using both targeted and nontargeted (high-resolution mass spectrometry) approaches in four different blue-pigmented genera of copepods and one blue-pigmented species of appendicularia. Astaxanthin was found to be the principal carotenoid in all the species. The pathway analysis showed that all the species can synthesize astaxanthin from β-carotene, ingested from dietary sources, via 3-hydroxyechinenone, canthaxanthin, zeaxanthin, adonirubin or adonixanthin. Further, using de novo assembled transcriptome of blue A. fossae (subclass Copepoda), we identified highly expressed homologous β-carotene hydroxylase enzymes and putative carotenoid-binding proteins responsible for astaxanthin formation and the blue phenotype. In blue O. dioica (class Appendicularia), corresponding putative genes were identified from the reference genome. Collectively, our data provide molecular evidences for the bioconversion and accumulation of blue astaxanthin–protein complexes underpinning the observed ecological functional equivalence and adaptive convergence among neustonic mesozooplankton.

  8. The associations between yogurt consumption, diet quality, and metabolic profiles in children in the USA.

    Science.gov (United States)

    Zhu, Yong; Wang, Huifen; Hollis, James H; Jacques, Paul F

    2015-06-01

    Recent studies have shown that yogurt consumption was associated with better diet quality and a healthier metabolic profile in adults. However, such associations have not been investigated in children. The present study examined the associations in children using data from a nationally representative survey. Data from 5,124 children aged 2-18 years, who participated in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2006 in the USA were analyzed. The frequency of yogurt consumption over 12 months was determined using a validated food frequency questionnaire. Diet quality was assessed by the Healthy Eating Index 2005 (HEI-2005) using one 24-HR dietary recall, and metabolic profiles were obtained from the NHANES laboratory data. It was found that only 33.1 % of children consumed yogurt at least once per week (frequent consumers). Adjusting for covariates, frequent consumers had better diet quality than infrequent consumers, as indicated by a higher HEI-2005 total score (P = 0.04). Frequent yogurt consumption was associated with a lower fasting insulin level (P yogurt consumption was not associated with body weight, fasting glucose, serum lipid profiles, C-reactive protein, and blood pressures (all P > 0.05). These results suggest that frequent yogurt consumption may contribute to improved diet quality and a healthier insulin profile in children. Future longitudinal studies and clinical trials in children are warranted to explore the health benefits of yogurt consumption.

  9. Determination of biodiversity of Coprinus comatus using genotyping and metabolic profiling tools.

    Science.gov (United States)

    Pawlik, Anna; Malinowska, Anna; Siwulski, Marek; Frąc, Magdalena; Rogalski, Jerzy; Janusz, Grzegorz

    2015-01-01

    Coprinus comatus strains (CCMs) originating from Poland were identified using ITS region sequencing. Based on the sequences obtained, the genetic relationship between the CCM strains was determined and a clear separation of all strains into two main clusters was obtained. The Coprinus strains were also genetically characterized for the first time by the AFLP technique. The analysis showed that the CCMs separated into four main clusters and a high complication of a UPGMA-based dendrogram was achieved. C. comatus strains included in the analysis displayed an AFLP profile similarity level in the range from 44 to 66%. The highest similarity coefficient, 0.490, was found between CCM12 and CCM13, and the lowest (0.202) between the CCM2 and CCM5 isolates. Biolog FF MicroPlates were applied to obtain data on utilization of 95 carbon sources and mycelial growth. The analysis allowed comparison of the functional diversity of the CCM strains and revealed a broad variability within the analyzed Coprinus species based on substrate utilization profiles. Significant differences (2-48) have been shown in the substrate richness values. The Biolog experiments proved to be a good profiling technology for studying the diversity in shaggy manes due to metabolic differences and demonstrated that all the strains might be considered individually. It is evident that the strain metabolic grouping does not correlate with the grouping based on the ITS sequences and AFLP profiles, however, some similarities may be observed.

  10. Metabolic adaptation to intermittent fasting is independent of peroxisome proliferator-activated receptor alpha.

    Science.gov (United States)

    Li, Guolin; Brocker, Chad N; Yan, Tingting; Xie, Cen; Krausz, Kristopher W; Xiang, Rong; Gonzalez, Frank J

    2018-01-01

    Peroxisome proliferator-activated receptor alpha (PPARA) is a major regulator of fatty acid oxidation and severe hepatic steatosis occurs during acute fasting in Ppara-null mice. Thus, PPARA is considered an important mediator of the fasting response; however, its role in other fasting regiments such as every-other-day fasting (EODF) has not been investigated. Mice were pre-conditioned using either a diet containing the potent PPARA agonist Wy-14643 or an EODF regimen prior to acute fasting. Ppara-null mice were used to assess the contribution of PPARA activation during the metabolic response to EODF. Livers were collected for histological, biochemical, qRT-PCR, and Western blot analysis. Acute fasting activated PPARA and led to steatosis, whereas EODF protected against fasting-induced hepatic steatosis without affecting PPARA signaling. In contrast, pretreatment with Wy-14,643 did activate PPARA signaling but did not ameliorate acute fasting-induced steatosis and unexpectedly promoted liver injury. Ppara ablation exacerbated acute fasting-induced hypoglycemia, hepatic steatosis, and liver injury in mice, whereas these detrimental effects were absent in response to EODF, which promoted PPARA-independent fatty acid metabolism and normalized serum lipids. These findings indicate that PPARA activation prior to acute fasting cannot ameliorate fasting-induced hepatic steatosis, whereas EODF induced metabolic adaptations to protect against fasting-induced steatosis without altering PPARA signaling. Therefore, PPARA activation does not mediate the metabolic adaptation to fasting, at least in preventing acute fasting-induced steatosis. Published by Elsevier GmbH.

  11. Effect of repeated forearm muscle cooling on the adaptation of skeletal muscle metabolism in humans

    Science.gov (United States)

    Wakabayashi, Hitoshi; Nishimura, Takayuki; Wijayanto, Titis; Watanuki, Shigeki; Tochihara, Yutaka

    2017-07-01

    This study aimed to investigate the effect of repeated cooling of forearm muscle on adaptation in skeletal muscle metabolism. It is hypothesized that repeated decreases of muscle temperature would increase the oxygen consumption in hypothermic skeletal muscle. Sixteen healthy males participated in this study. Their right forearm muscles were locally cooled to 25 °C by cooling pads attached to the skin. This local cooling was repeated eight times on separate days for eight participants (experimental group), whereas eight controls received no cold exposure. To evaluate adaptation in skeletal muscle metabolism, a local cooling test was conducted before and after the repeated cooling period. Change in oxy-hemoglobin content in the flexor digitorum at rest and during a 25-s isometric handgrip (10% maximal voluntary construction) was measured using near-infrared spectroscopy at every 2 °C reduction in forearm muscle temperature. The arterial blood flow was occluded for 15 s by upper arm cuff inflation at rest and during the isometric handgrip. The oxygen consumption in the flexor digitorum muscle was evaluated by a slope of the oxy-hemoglobin change during the arterial occlusion. In the experimental group, resting oxygen consumption in skeletal muscle did not show any difference between pre- and post-intervention, whereas muscle oxygen consumption during the isometric handgrip was significantly higher in post-intervention than in pre-test from thermoneutral baseline to 31 °C muscle temperature ( P < 0.05). This result indicated that repeated local muscle cooling might facilitate oxidative metabolism in the skeletal muscle. In summary, skeletal muscle metabolism during submaximal isometric handgrip was facilitated after repeated local muscle cooling.

  12. Plasma proteome profiles associated with diet-induced metabolic syndrome and the early onset of metabolic syndrome in a pig model.

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    Marinus F W te Pas

    Full Text Available Obesity and related diabetes are important health threatening multifactorial metabolic diseases and it has been suggested that 25% of all diabetic patients are unaware of their patho-physiological condition. Biomarkers for monitoring and control are available, but early stage predictive biomarkers enabling prevention of these diseases are still lacking. We used the pig as a model to study metabolic disease because humans and pigs share a multitude of metabolic similarities. Diabetes was chemically induced and control and diabetic pigs were either fed a high unsaturated fat (Mediterranean diet or a high saturated fat/cholesterol/sugar (cafeteria diet. Physiological parameters related to fat metabolism and diabetes were measured. Diabetic pigs' plasma proteome profiles differed more between the two diets than control pigs plasma proteome profiles. The expression levels of several proteins correlated well with (pathophysiological parameters related to the fat metabolism (cholesterol, VLDL, LDL, NEFA and diabetes (Glucose and to the diet fed to the animals. Studying only the control pigs as a model for metabolic syndrome when fed the two diets showed correlations to the same parameters but now more focused on insulin, glucose and abdominal fat depot parameters. We conclude that proteomic profiles can be used as a biomarker to identify pigs with developing metabolic syndrome (prediabetes and diabetes when fed a cafeteria diet. It could be developed into a potential biomarkers for the early recognition of metabolic diseases.

  13. Relative Quantitative Proteomic Analysis of Brucella abortus Reveals Metabolic Adaptation to Multiple Environmental Stresses

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    Xiaodong Zai

    2017-11-01

    Full Text Available Brucella spp. are facultative intracellular pathogens that cause chronic brucellosis in humans and animals. The virulence of Brucella primarily depends on its successful survival and replication in host cells. During invasion of the host tissue, Brucella is simultaneously subjected to a variety of harsh conditions, including nutrient limitation, low pH, antimicrobial defenses, and extreme levels of reactive oxygen species (ROS via the host immune response. This suggests that Brucella may be able to regulate its metabolic adaptation in response to the distinct stresses encountered during its intracellular infection of the host. An investigation into the differential proteome expression patterns of Brucella grown under the relevant stress conditions may contribute toward a better understanding of its pathogenesis and adaptive response. Here, we utilized a mass spectrometry-based label-free relative quantitative proteomics approach to investigate and compare global proteomic changes in B. abortus in response to eight different stress treatments. The 3 h short-term in vitro single-stress and multi-stress conditions mimicked the in vivo conditions of B. abortus under intracellular infection, with survival rates ranging from 3.17 to 73.17%. The proteomic analysis identified and quantified a total of 2,272 proteins and 74% of the theoretical proteome, thereby providing wide coverage of the B. abortus proteome. By including eight distinct growth conditions and comparing these with a control condition, we identified a total of 1,221 differentially expressed proteins (DEPs that were significantly changed under the stress treatments. Pathway analysis revealed that most of the proteins were involved in oxidative phosphorylation, ABC transporters, two-component systems, biosynthesis of secondary metabolites, the citrate cycle, thiamine metabolism, and nitrogen metabolism; constituting major response mechanisms toward the reconstruction of cellular

  14. Relative Quantitative Proteomic Analysis of Brucella abortus Reveals Metabolic Adaptation to Multiple Environmental Stresses.

    Science.gov (United States)

    Zai, Xiaodong; Yang, Qiaoling; Yin, Ying; Li, Ruihua; Qian, Mengying; Zhao, Taoran; Li, Yaohui; Zhang, Jun; Fu, Ling; Xu, Junjie; Chen, Wei

    2017-01-01

    Brucella spp. are facultative intracellular pathogens that cause chronic brucellosis in humans and animals. The virulence of Brucella primarily depends on its successful survival and replication in host cells. During invasion of the host tissue, Brucella is simultaneously subjected to a variety of harsh conditions, including nutrient limitation, low pH, antimicrobial defenses, and extreme levels of reactive oxygen species (ROS) via the host immune response. This suggests that Brucella may be able to regulate its metabolic adaptation in response to the distinct stresses encountered during its intracellular infection of the host. An investigation into the differential proteome expression patterns of Brucella grown under the relevant stress conditions may contribute toward a better understanding of its pathogenesis and adaptive response. Here, we utilized a mass spectrometry-based label-free relative quantitative proteomics approach to investigate and compare global proteomic changes in B. abortus in response to eight different stress treatments. The 3 h short-term in vitro single-stress and multi-stress conditions mimicked the in vivo conditions of B. abortus under intracellular infection, with survival rates ranging from 3.17 to 73.17%. The proteomic analysis identified and quantified a total of 2,272 proteins and 74% of the theoretical proteome, thereby providing wide coverage of the B. abortus proteome. By including eight distinct growth conditions and comparing these with a control condition, we identified a total of 1,221 differentially expressed proteins (DEPs) that were significantly changed under the stress treatments. Pathway analysis revealed that most of the proteins were involved in oxidative phosphorylation, ABC transporters, two-component systems, biosynthesis of secondary metabolites, the citrate cycle, thiamine metabolism, and nitrogen metabolism; constituting major response mechanisms toward the reconstruction of cellular homeostasis and metabolic

  15. In situ metabolic profiling of single cells by laser ablation electrospray ionization mass spectrometry.

    Science.gov (United States)

    Shrestha, Bindesh; Vertes, Akos

    2009-10-15

    Depending on age, phase in the cell cycle, nutrition, and environmental factors, individual cells exhibit large metabolic diversity. To explore metabolic variations in cell populations, laser ablation electrospray ionization (LAESI) mass spectrometry (MS) was used for the in situ analysis of individual cells at atmospheric pressure. Single cell ablation was achieved by delivering mid-IR laser pulses through the etched tip of a GeO(2)-based glass fiber. Metabolic analysis was performed from single cells and small cell populations of Allium cepa and Narcissus pseudonarcissus bulb epidermis, as well as single eggs of Lytechinus pictus. Of the 332 peaks detected for A. cepa, 35 were assigned to metabolites with the help of accurate ion masses and tandem MS. The metabolic profiles from single cells of the two plant species included a large variety of oligosaccharides including possibly fructans in A. cepa, and alkaloids, e.g., lycorine in N. pseudonarcissus. Analysis of adjacent individual cells with a difference in pigmentation showed that, in addition to essential metabolites found in both variants, the pigmented cells contained anthocyanidins, other flavonoids, and their glucosides. Analysis of single epidermal cells from different scale leaves in an A. cepa bulb showed metabolic differences corresponding to their age. Our results indicate the feasibility of using LAESI-MS for the in situ analysis of metabolites in single cells with potential applications in studying cell differentiation, changes due to disease states, and response to xenobiotics.

  16. Transcriptional profiling of rats subjected to gestational undernourishment: implications for the developmental variations in metabolic traits.

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    Tiffany J Morris

    Full Text Available A link has been established between prenatal nutrition and the development of metabolic and cardiovascular diseases later in life, a process referred to as developmental programming. It has been suggested that the trajectory of development is shifted by alterations in the maternal nutritional state leading to changes in developmental plasticity, in part underpinned by epigenetic changes in gene regulation. However, to date, only candidate gene approaches have been used to assess expression and molecular changes in the offspring of maternally undernourished animals. Furthermore, most work has focused on animals at an age where the programmed phenotype is already manifest and little is known about changes in gene expression in the offspring prior to development of obesity and related metabolic disorders. Gene expression profiles of liver, retroperitoneal white adipose fat, and biceps femoris skeletal muscle tissue from young adult male rats (55 days old in which nutritional status had been manipulated in utero by maternal undernutrition (UN were compared to the profiles of offspring of ad libitum fed mothers serving as the control group (AD (8 offspring/group. The expression profiles were determined using the Illumina RatRef-12 BeadChip. No significant changes in expression were identified for skeletal muscle or white adipose tissue. However, studies of liver tissue showed 249 differentially expressed genes (143 up regulated, 106 down regulated. Although the animals at day 55 have yet to develop obesity they already show biochemical abnormalities and by day 110 express a phenotype characterized by increased adiposity and altered insulin sensitivity. An analysis of pathways affected suggests that intrauterine programming of UN animals to favor fat as an energy source results in mitochondrial dysfunction which initially affects the postnatal hepatic function and subsequently, via the resultant metabolic changes in other organs leads to the evolution

  17. Impact of a synbiotic food on the gut microbial ecology and metabolic profiles

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    Candela Marco

    2010-01-01

    Full Text Available Abstract Background The human gut harbors a diverse community of microorganisms which serve numerous important functions for the host wellbeing. Functional foods are commonly used to modulate the composition of the gut microbiota contributing to the maintenance of the host health or prevention of disease. In the present study, we characterized the impact of one month intake of a synbiotic food, containing fructooligosaccharides and the probiotic strains Lactobacillus helveticus Bar13 and Bifidobacterium longum Bar33, on the gut microbiota composition and metabolic profiles of 20 healthy subjects. Results The synbiotic food did not modify the overall structure of the gut microbiome, as indicated by Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE. The ability of the probiotic L. helveticus and B. longum strains to pass through the gastrointestinal tract was hypothesized on the basis of real-time PCR data. In spite of a stable microbiota, the intake of the synbiotic food resulted in a shift of the fecal metabolic profiles, highlighted by the Gas Chromatography Mass Spectrometry Solid Phase Micro-Extraction (GC-MS/SPME analysis. The extent of short chain fatty acids (SCFA, ketones, carbon disulfide and methyl acetate was significantly affected by the synbiotic food consumption. Furthermore, the Canonical discriminant Analysis of Principal coordinates (CAP of GC-MS/SPME profiles allowed a separation of the stool samples recovered before and after the consumption of the functional food. Conclusion In this study we investigated the global impact of a dietary intervention on the gut ecology and metabolism in healthy humans. We demonstrated that the intake of a synbiotic food leads to a modulation of the gut metabolic activities with a maintenance of the gut biostructure. In particular, the significant increase of SCFA, ketones, carbon disulfide and methyl acetate following the feeding period suggests potential health

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

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    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.

  19. Characteristics and contributions of hyperandrogenism to insulin resistance and other metabolic profiles in polycystic ovary syndrome.

    Science.gov (United States)

    Huang, Rong; Zheng, Jun; Li, Shengxian; Tao, Tao; Ma, Jing; Liu, Wei

    2015-05-01

    To investigate the different characteristics in Chinese Han women with polycystic ovary syndrome, and to analyze the significance of hyperandrogenism in insulin resistance and other metabolic profiles. A cross-sectional study. Medical university hospital. A total of 229 women with polycystic ovary syndrome aged 18-45 years. Women with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided into four groups according to the quartile intervals of free androgen index levels. Comparisons between groups were performed using one-way analysis of variance. Stepwise logistic regression analysis was performed to investigate the association between homeostasis model assessment-insulin resistance and independent variables. Within the four phenotypes, women with phenotype 1 (hyperandrogenism, oligo/anovulation, and polycystic ovaries) exhibited higher total testosterone, free androgen index, androstenedione, low-density lipoprotein, and lower quantitative insulin sensitivity check index (p polycystic ovaries) showed lower total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance, but higher high-density lipoprotein (p < 0.05). The levels of triglycerides, total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance significantly increased, but high-density lipoprotein and quantitative insulin sensitivity check index decreased with the elevation of free androgen index intervals. After adjustment for lipid profiles, free androgen index was significantly associated with homeostasis model assessment-insulin resistance in both lean and overweight/obese women (odds ratio 1.302, p = 0.039 in lean vs. odds ratio 1.132, p = 0.036 in overweight/obese). Phenotypes 1 and 4 represent groups with the most and least severe metabolic profiles, respectively. Hyperandrogenism, particularly with elevated free androgen index, is likely a key contributing factor for insulin resistance and for the aggravation

  20. Physical activity: benefit or weakness in metabolic adaptations in a mouse model of chronic food restriction?

    Science.gov (United States)

    Méquinion, Mathieu; Caron, Emilie; Zgheib, Sara; Stievenard, Aliçia; Zizzari, Philippe; Tolle, Virginie; Cortet, Bernard; Lucas, Stéphanie; Prévot, Vincent; Chauveau, Christophe; Viltart, Odile

    2015-02-01

    In restrictive-type anorexia nervosa (AN) patients, physical activity is usually associated with food restriction, but its physiological consequences remain poorly characterized. In female mice, we evaluated the impact of voluntary physical activity with/without chronic food restriction on metabolic and endocrine parameters that might contribute to AN. In this protocol, FRW mice (i.e., food restriction with running wheel) reached a crucial point of body weight loss (especially fat mass) faster than FR mice (i.e., food restriction only). However, in contrast to FR mice, their body weight stabilized, demonstrating a protective effect of a moderate, regular physical activity. Exercise delayed meal initiation and duration. FRW mice displayed food anticipatory activity compared with FR mice, which was strongly diminished with the prolongation of the protocol. The long-term nature of the protocol enabled assessment of bone parameters similar to those observed in AN patients. Both restricted groups adapted their energy metabolism differentially in the short and long term, with less fat oxidation in FRW mice and a preferential use of glucose to compensate for the chronic energy imbalance. Finally, like restrictive AN patients, FRW mice exhibited low leptin levels, high plasma concentrations of corticosterone and ghrelin, and a disruption of the estrous cycle. In conclusion, our model suggests that physical activity has beneficial effects on the adaptation to the severe condition of food restriction despite the absence of any protective effect on lean and bone mass. Copyright © 2015 the American Physiological Society.

  1. TCA cycle rewiring fosters metabolic adaptation to oxygen restriction in skeletal muscle from rodents and humans.

    Science.gov (United States)

    Capitanio, Daniele; Fania, Chiara; Torretta, Enrica; Viganò, Agnese; Moriggi, Manuela; Bravatà, Valentina; Caretti, Anna; Levett, Denny Z H; Grocott, Michael P W; Samaja, Michele; Cerretelli, Paolo; Gelfi, Cecilia

    2017-08-29

    In mammals, hypoxic stress management is under the control of the Hypoxia Inducible Factors, whose activity depends on the stabilization of their labile α subunit. In particular, the skeletal muscle appears to be able to react to changes in substrates and O2 delivery by tuning its metabolism. The present study provides a comprehensive overview of skeletal muscle metabolic adaptation to hypoxia in mice and in human subjects exposed for 7/9 and 19 days to high altitude levels. The investigation was carried out combining proteomics, qRT-PCR mRNA transcripts analysis, and enzyme activities assessment in rodents, and protein detection by antigen antibody reactions in humans and rodents. Results indicate that the skeletal muscle react to a decreased O2 delivery by rewiring the TCA cycle. The first TCA rewiring occurs in mice in 2-day hypoxia and is mediated by cytosolic malate whereas in 10-day hypoxia the rewiring is mediated by Idh1 and Fasn, supported by glutamine and HIF-2α increments. The combination of these specific anaplerotic steps can support energy demand despite HIFs degradation. These results were confirmed in human subjects, demonstrating that the TCA double rewiring represents an essential factor for the maintenance of muscle homeostasis during adaptation to hypoxia.

  2. Metabolic homeostasis is maintained in myocardial hibernation by adaptive changes in the transcriptome and proteome.

    Science.gov (United States)

    Mayr, Manuel; May, Dalit; Gordon, Oren; Madhu, Basetti; Gilon, Dan; Yin, Xiaoke; Xing, Qiuru; Drozdov, Ignat; Ainali, Chrysanthi; Tsoka, Sophia; Xu, Qingbo; Griffiths, John; Horrevoets, Anton; Keshet, Eli

    2011-06-01

    A transgenic mouse model for conditional induction of long-term hibernation via myocardium-specific expression of a VEGF-sequestering soluble receptor allowed the dissection of the hibernation process into an initiation and a maintenance phase. The hypoxic initiation phase was characterized by peak levels of K(ATP) channel and glucose transporter 1 (GLUT1) expression. Glibenclamide, an inhibitor of K(ATP) channels, blocked GLUT1 induction. In the maintenance phase, tissue hypoxia and GLUT1 expression were reduced. Thus, we employed a combined "-omics" approach to resolve this cardioprotective adaptation process. Unguided bioinformatics analysis on the transcriptomic, proteomic and metabolomic datasets confirmed that anaerobic glycolysis was affected and that the observed enzymatic changes in cardiac metabolism were directly linked to hypoxia-inducible factor (HIF)-1 activation. Although metabolite concentrations were kept relatively constant, the combination of the proteomic and transcriptomic dataset improved the statistical confidence of the pathway analysis by 2 orders of magnitude. Importantly, proteomics revealed a reduced phosphorylation state of myosin light chain 2 and cardiac troponin I within the contractile apparatus of hibernating hearts in the absence of changes in protein abundance. Our study demonstrates how combining different "-omics" datasets aids in the identification of key biological pathways: chronic hypoxia resulted in a pronounced adaptive response at the transcript and the protein level to keep metabolite levels steady. This preservation of metabolic homeostasis is likely to contribute to the long-term survival of the hibernating myocardium. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Adaptive Evolution of Energy Metabolism-Related Genes in Hypoxia-Tolerant Mammals.

    Science.gov (United States)

    Tian, Ran; Yin, Daiqing; Liu, Yanzhi; Seim, Inge; Xu, Shixia; Yang, Guang

    2017-01-01

    Animals that are able to sustain life under hypoxic conditions have long captured the imagination of biologists and medical practitioners alike. Although the associated morphological modifications have been extensively described, the mechanisms underlying the evolution of hypoxia tolerance are not well understood. To provide such insights, we investigated genes in four major energy metabolism pathways, and provide evidence of distinct evolutionary paths to mammalian hypoxia-tolerance. Positive selection of genes in the oxidative phosphorylation pathway mainly occurred in terrestrial hypoxia-tolerant species; possible adaptations to chronically hypoxic environments. The strongest candidate for positive selection along cetacean lineages was the citrate cycle signaling pathway, suggestive of enhanced aerobic metabolism during and after a dive. Six genes with cetacean-specific amino acid changes are rate-limiting enzymes involved in the gluconeogenesis pathway, which would be expected to enhance the lactate removal after diving. Intriguingly, 38 parallel amino acid substitutions in 29 genes were observed between hypoxia-tolerant mammals. Of these, 76.3% were radical amino acid changes, suggesting that convergent molecular evolution drives the adaptation to hypoxic stress and similar phenotypic changes. This study provides further insights into life under low oxygen conditions and the evolutionary trajectories of hypoxia-tolerant species.

  4. Adaptive Evolution of Energy Metabolism-Related Genes in Hypoxia-Tolerant Mammals

    Directory of Open Access Journals (Sweden)

    Ran Tian

    2017-12-01

    Full Text Available Animals that are able to sustain life under hypoxic conditions have long captured the imagination of biologists and medical practitioners alike. Although the associated morphological modifications have been extensively described, the mechanisms underlying the evolution of hypoxia tolerance are not well understood. To provide such insights, we investigated genes in four major energy metabolism pathways, and provide evidence of distinct evolutionary paths to mammalian hypoxia-tolerance. Positive selection of genes in the oxidative phosphorylation pathway mainly occurred in terrestrial hypoxia-tolerant species; possible adaptations to chronically hypoxic environments. The strongest candidate for positive selection along cetacean lineages was the citrate cycle signaling pathway, suggestive of enhanced aerobic metabolism during and after a dive. Six genes with cetacean-specific amino acid changes are rate-limiting enzymes involved in the gluconeogenesis pathway, which would be expected to enhance the lactate removal after diving. Intriguingly, 38 parallel amino acid substitutions in 29 genes were observed between hypoxia-tolerant mammals. Of these, 76.3% were radical amino acid changes, suggesting that convergent molecular evolution drives the adaptation to hypoxic stress and similar phenotypic changes. This study provides further insights into life under low oxygen conditions and the evolutionary trajectories of hypoxia-tolerant species.

  5. Effects of cadmium exposure on growth and metabolic profile of bermudagrass [Cynodon dactylon (L. Pers].

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    Yan Xie

    Full Text Available Metabolic responses to cadmium (Cd may be associated with variations in Cd tolerance in plants. The objectives of this study were to examine changes in metabolic profiles in bermudagrass in response to Cd stress and to identify predominant metabolites associated with differential Cd tolerance using gas chromatography-mass spectrometry. Two genotypes of bermudagrass with contrasting Cd tolerance were exposed to 0 and 1.5 mM CdSO4 for 14 days in hydroponics. Physiological responses to Cd were evaluated by determining turf quality, growth rate, chlorophyll content and normalized relative transpiration. All these parameters exhibited higher tolerance in WB242 than in WB144. Cd treated WB144 transported more Cd to the shoot than in WB242. The metabolite analysis of leaf polar extracts revealed 39 Cd responsive metabolites in both genotypes, mainly consisting of amino acids, organic acids, sugars, fatty acids and others. A difference in the metabolic profiles was observed between the two bermudagrass genotypes exposed to Cd stress. Seven amino acids (norvaline, glycine, proline, serine, threonine, glutamic acid and gulonic acid, four organic acids (glyceric acid, oxoglutaric acid, citric acid and malic acid, and three sugars (xylulose, galactose and talose accumulated more in WB242 than WB144. However, compared to the control, WB144 accumulated higher quantities of sugars than WB242 in the Cd regime. The differential accumulation of these metabolites could be associated with the differential Cd tolerance in bermudagrass.

  6. Metabolic Profiles of Obesity in American Indians: The Strong Heart Family Study.

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    Qi Zhao

    Full Text Available Obesity is a typical metabolic disorder resulting from the imbalance between energy intake and expenditure. American Indians suffer disproportionately high rates of obesity and diabetes. The goal of this study is to identify metabolic profiles of obesity in 431 normoglycemic American Indians participating in the Strong Heart Family Study. Using an untargeted liquid chromatography-mass spectrometry, we detected 1,364 distinct m/z features matched to known compounds in the current metabolomics databases. We conducted multivariate analysis to identify metabolic profiles for obesity, adjusting for standard obesity indicators. After adjusting for covariates and multiple testing, five metabolites were associated with body mass index and seven were associated with waist circumference. Of them, three were associated with both. Majority of the obesity-related metabolites belongs to lipids, e.g., fatty amides, sphingolipids, prenol lipids, and steroid derivatives. Other identified metabolites are amino acids or peptides. Of the nine identified metabolites, five metabolites (oleoylethanolamide, mannosyl-diinositol-phosphorylceramide, pristanic acid, glutamate, and kynurenine have been previously implicated in obesity or its related pathways. Future studies are warranted to replicate these findings in larger populations or other ethnic groups.

  7. Metabolic Profiles of Obesity in American Indians: The Strong Heart Family Study.

    Science.gov (United States)

    Zhao, Qi; Zhu, Yun; Best, Lyle G; Umans, Jason G; Uppal, Karan; Tran, ViLinh T; Jones, Dean P; Lee, Elisa T; Howard, Barbara V; Zhao, Jinying

    2016-01-01

    Obesity is a typical metabolic disorder resulting from the imbalance between energy intake and expenditure. American Indians suffer disproportionately high rates of obesity and diabetes. The goal of this study is to identify metabolic profiles of obesity in 431 normoglycemic American Indians participating in the Strong Heart Family Study. Using an untargeted liquid chromatography-mass spectrometry, we detected 1,364 distinct m/z features matched to known compounds in the current metabolomics databases. We conducted multivariate analysis to identify metabolic profiles for obesity, adjusting for standard obesity indicators. After adjusting for covariates and multiple testing, five metabolites were associated with body mass index and seven were associated with waist circumference. Of them, three were associated with both. Majority of the obesity-related metabolites belongs to lipids, e.g., fatty amides, sphingolipids, prenol lipids, and steroid derivatives. Other identified metabolites are amino acids or peptides. Of the nine identified metabolites, five metabolites (oleoylethanolamide, mannosyl-diinositol-phosphorylceramide, pristanic acid, glutamate, and kynurenine) have been previously implicated in obesity or its related pathways. Future studies are warranted to replicate these findings in larger populations or other ethnic groups.

  8. Metabolic profiles and free radical scavenging activity of Cordyceps bassiana fruiting bodies according to developmental stage.

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    Sun-Hee Hyun

    Full Text Available The metabolic profiles of Cordyceps bassiana according to fruiting body developmental stage were investigated using gas chromatography-mass spectrometry. We were able to detect 62 metabolites, including 48 metabolites from 70% methanol extracts and 14 metabolites from 100% n-hexane extracts. These metabolites were classified as alcohols, amino acids, organic acids, phosphoric acids, purine nucleosides and bases, sugars, saturated fatty acids, unsaturated fatty acids, or fatty amides. Significant changes in metabolite levels were found according to developmental stage. Relative levels of amino acids, purine nucleosides, and sugars were higher in development stage 3 than in the other stages. Among the amino acids, valine, isoleucine, lysine, histidine, glutamine, and aspartic acid, which are associated with ABC transporters and aminoacyl-tRNA biosynthesis, also showed higher levels in stage 3 samples. The free radical scavenging activities, which were significantly higher in stage 3 than in the other stages, showed a positive correlation with purine nucleoside metabolites such as adenosine, guanosine, and inosine. These results not only show metabolic profiles, but also suggest the metabolic pathways associated with fruiting body development stages in cultivated C. bassiana.

  9. Adenovirus-36 Seropositivity and Its Relation with Obesity and Metabolic Profile in Children

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    Isela Parra-Rojas

    2013-01-01

    Full Text Available The human adenovirus 36 (Ad-36 is causally and correlatively associated in animals and humans, respectively, with increased adiposity and altered metabolic profile. In previous studies, the relationship between Ad-36 seropositivity with obesity was established in adults and children. We evaluated the association of positive antibodies to Ad-36 with obesity and metabolic profile in Mexican children. Seventy-five children with normal-weight and 82 with obesity were studied in this research. All children had a clinic assessment which included weight, height, body circumferences, and skinfold thickness. Laboratory analyzes included triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, and glucose and insulin levels. An enzyme-linked immunosorbent assay (ELISA was used to determine the antibodies to Ad-36 in the serum samples. The overall Ad-36 seroprevalence was 73.9%. Ad-36 seropositivity had a higher prevalence in obese children than in normal weight group (58.6 versus 41.4%, P=0.007. Ad-36 seropositivity was associated with obesity (OR=2.66, P=0.01 and high-density lipoprotein <40 mg/dL (OR=2.85, P=0.03. The Ad-36 seropositive group had greater risk of 4 metabolic abnormalities compared with those children without none alteration. In summary, Ad-36 seropositivity was associated with obesity and low HDL-c levels in the sample of children studied.

  10. Adenovirus-36 Seropositivity and Its Relation with Obesity and Metabolic Profile in Children

    Science.gov (United States)

    Del Moral-Hernández, Oscar; Salgado-Bernabé, Aralia B.; Guzmán-Guzmán, Iris P.; Salgado-Goytia, Lorenzo; Muñoz-Valle, José F.

    2013-01-01

    The human adenovirus 36 (Ad-36) is causally and correlatively associated in animals and humans, respectively, with increased adiposity and altered metabolic profile. In previous studies, the relationship between Ad-36 seropositivity with obesity was established in adults and children. We evaluated the association of positive antibodies to Ad-36 with obesity and metabolic profile in Mexican children. Seventy-five children with normal-weight and 82 with obesity were studied in this research. All children had a clinic assessment which included weight, height, body circumferences, and skinfold thickness. Laboratory analyzes included triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, and glucose and insulin levels. An enzyme-linked immunosorbent assay (ELISA) was used to determine the antibodies to Ad-36 in the serum samples. The overall Ad-36 seroprevalence was 73.9%. Ad-36 seropositivity had a higher prevalence in obese children than in normal weight group (58.6 versus 41.4%, P = 0.007). Ad-36 seropositivity was associated with obesity (OR = 2.66, P = 0.01) and high-density lipoprotein <40 mg/dL (OR = 2.85, P = 0.03). The Ad-36 seropositive group had greater risk of 4 metabolic abnormalities compared with those children without none alteration. In summary, Ad-36 seropositivity was associated with obesity and low HDL-c levels in the sample of children studied. PMID:24324491

  11. Effects of potato spindle tuber viroid infection on tomato metabolic profile.

    Science.gov (United States)

    Bagherian, Seyed Ali Akbar; Hamzehzarghani, Habiballah; Izadpanah, Keramatollah; Djavaheri, Mohammad

    2016-08-20

    Viroids are the smallest plant pathogens consisting of a single stranded circular RNA molecule with a strong secondary structure, lacking a coat protein or any other proteins. The mechanism of viroid pathogenicity has remained unclear. Recent advances in instrumentation and data mining have made it possible to study the effects of various stresses on primary and secondary metabolisms. Here, we have utilized metabolic profiling approach to show how PSTVd infection alters tomato metabolic profile and the related pathways. Three terminal leaflets of third true leaf of 20-day-old tolerant tomato cultivar 'Moneymaker' were mechanically inoculated by PSTVd intermediate variant cDNAs and samples were taken from eighth leaf, 19days post-inoculation. Metabolites were extracted and analyzed by gas chromatography/mass spectrometry (GC/MS) and subjected to statistical data analysis. Affected pathways were identified by Pathway Tools program and were compared with microarray data previously reported. The study showed that 79 metabolites changed significantly and 23 pathways were identified in relation to these metabolites. Fourteen of these pathways were similar to those reported in other works. The altered pathways in PSTVd infected tomato leaves included, eight cutin and wax biosynthesis, seven pathways that produce defense related compounds, two energy generator pathways, three hormone biosynthesis pathways, two signal transduction pathways, and one nucleotide biosynthesis pathway. Our data on up/down-regulation of pathways supported the data produced on their corresponding gene(s) up/down-regulation. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Metabolic profile of santa inês ewes whith low body condition score during peripartum

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    Nayara Resende Nasciutti

    2012-02-01

    Full Text Available The objective of this study was to analyse the variations in the metabolic profile of protein, energy enzyme and mineral of Santa Inês ewes with low body condition score (BCS during peripartum. Blood samples were collected from 12 animals by jugular venipuncture to determine the serum biochemical profiles of protein, energy, mineral and enzyme metabolisms. Samples were collected on the following days: days 28, 21, 14, and 7 before lambing, at birth and, at days 2, 4, 7, 14, 21, and 28 postpartum (dpp. The samples were centrifuged and the serum analysed by Automated-Analyser. There was no alteration of the BCS during the 28 dpp, between 0.6 and 2.1 ± 2.4 ± 0.5, and was considered, as lean. The values of the total serum protein, globulin, albumin, and albumin/globulin ratio were reduced effective from the period before birth until 28dpp. The values of beta-hydroxybutyrate, calcium, phosphorus and magnesium remained below those of reference values. The concentrations of alanin aminotransferase (ALT were decreased particularly during the weeks before delivery. It was concluded that Santa Inês sheep with low body condition score demonstrated a reduction in the metabolism of proteins, energy, mineral and enzyme during peripartum.

  13. Dissection of the Mouse Pancreas for Histological Analysis and Metabolic Profiling.

    Science.gov (United States)

    Veite-Schmahl, Michelle J; Regan, Daniel P; Rivers, Adam C; Nowatzke, Joseph F; Kennedy, Michael A

    2017-08-19

    We have been investigating the pancreas specific transcription factor, 1a cre-recombinase; lox-stop-lox- Kristen rat sarcoma, glycine to aspartic acid at the 12 codon (Ptf1a cre/+ ;LSL-Kras G12D/+ ) mouse strain as a model of human pancreatic cancer. The goal of our current studies is to identify novel metabolic biomarkers of pancreatic cancer progression. We have performed metabolic profiling of urine, feces, blood, and pancreas tissue extracts, as well as histological analyses of the pancreas to stage the cancer progression. The mouse pancreas is not a well-defined solid organ like in humans, but rather is a diffusely distributed soft tissue that is not easily identified by individuals unfamiliar with mouse internal anatomy or by individuals that have little or no experience performing mouse organ dissections. The purpose of this article is to provide a detailed step-wise visual demonstration to guide novices in the removal of the mouse pancreas by dissection. This article should be especially valuable to students and investigators new to research that requires harvesting of the mouse pancreas by dissection for metabolic profiling or histological analyses.

  14. Hydrophilic interaction chromatography-mass spectrometry for anionic metabolic profiling of urine from antibiotic-treated rats

    NARCIS (Netherlands)

    Kok, Miranda G M; Swann, Jonathan R.; Wilson, Ian D.; Somsen, Govert W.; de Jong, Gerhardus J.

    2014-01-01

    Hydrophilic interaction chromatography-mass spectrometry (HILIC-MS) was used for anionic metabolic profiling of urine from antibiotic-treated rats to study microbial-host co-metabolism. Rats were treated with the antibiotics penicillin G and streptomycin sulfate for four or eight days and compared

  15. Metabolic profil in a group of obese Moroccan children enrolled in schools in the city of Rabat

    OpenAIRE

    Mouane, Nezha; Dekkaki, Imane Cherkaoui; Ettair, Said; Meskini, Toufik; Khalloufi, Nabil; Bouklouze, Aziz; Barkat, Amina

    2014-01-01

    Introduction To determine the metabolic profile in a group of obese children in Morocco. Methods The BMI, the waist circumference, the blood pressure and metabolic parameters in 73 children (37 obese and 36 normal) were compared. Results 80% of obese children had abdominal obesity (p

  16. Spatially matched in vivo and ex vivo MR metabolic profiles of prostate cancer - investigation of a correlation with Gleason score

    NARCIS (Netherlands)

    Selnaes, K.M.; Gribbestad, I.S.; Bertilsson, H.; Wright, A.; Angelsen, A.; Heerschap, A.; Tessem, M.B.

    2013-01-01

    MR metabolic profiling of the prostate is promising as an additional diagnostic approach to separate indolent from aggressive prostate cancer. The objective of this study was to assess the relationship between the Gleason score and the metabolic biomarker (choline + creatine + spermine)/citrate

  17. Site and strain-specific variation in gut microbiota profiles and metabolism in experimental mice.

    Directory of Open Access Journals (Sweden)

    Melissa K Friswell

    2010-01-01

    Full Text Available The gastrointestinal tract microbiota (GTM of mammals is a complex microbial consortium, the composition and activities of which influences mucosal development, immunity, nutrition and drug metabolism. It remains unclear whether the composition of the dominant GTM is conserved within animals of the same strain and whether stable GTMs are selected for by host-specific factors or dictated by environmental variables.The GTM composition of six highly inbred, genetically distinct strains of mouse (C3H, C57, GFEC, CD1, CBA nu/nu and SCID was profiled using eubacterial -specific PCR-DGGE and quantitative PCR of feces. Animals exhibited strain-specific fecal eubacterial profiles that were highly stable (c. >95% concordance over 26 months for C57. Analyses of mice that had been relocated before and after maturity indicated marked, reproducible changes in fecal consortia and that occurred only in young animals. Implantation of a female BDF1 mouse with genetically distinct (C57 and Agoutie embryos produced highly similar GTM profiles (c. 95% concordance between mother and offspring, regardless of offspring strain, which was also reflected in urinary metabolite profiles. Marked institution-specific GTM profiles were apparent in C3H mice raised in two different research institutions.Strain-specific data were suggestive of genetic determination of the composition and activities of intestinal symbiotic consortia. However, relocation studies and uterine implantation demonstrated the dominance of environmental influences on the GTM. This was manifested in large variations between isogenic adult mice reared in different research institutions.

  18. Importance of acylcarnitine profile analysis for disorders of lipid metabolism in adolescent patients with recurrent rhabdomyolysis: Report of two cases

    OpenAIRE

    Yasemin Topçu; Erhan Bayram; Pakize Karaoglu; Uluç Yis; Semra Hiz Kurul

    2014-01-01

    Metabolic myopathies due to disorders of lipid metabolism are a heterogeneous group of diseases. Newborns may present with hypotonia and convulsions, while progressive proximal muscle weakness or recurrent episodes of muscle weakness accompanied by rhabdomyolysis/myoglobinuria may be seen in older ages. There is little knowledge on detection of disorders of lipid metabolism by acylcarnitine profile (ACP) analysis by tandem mass spectrometry outside the neonatal period particularly in cases wi...

  19. Taxonomic and predicted metabolic profiles of the human gut microbiome in pre-Columbian mummies.

    Science.gov (United States)

    Santiago-Rodriguez, Tasha M; Fornaciari, Gino; Luciani, Stefania; Dowd, Scot E; Toranzos, Gary A; Marota, Isolina; Cano, Raul J

    2016-11-01

    Characterization of naturally mummified human gut remains could potentially provide insights into the preservation and evolution of commensal and pathogenic microorganisms, and metabolic profiles. We characterized the gut microbiome of two pre-Columbian Andean mummies dating to the 10-15th centuries using 16S rRNA gene high-throughput sequencing and metagenomics, and compared them to a previously characterized gut microbiome of an 11th century AD pre-Columbian Andean mummy. Our previous study showed that the Clostridiales represented the majority of the bacterial communities in the mummified gut remains, but that other microbial communities were also preserved during the process of natural mummification, as shown with the metagenomics analyses. The gut microbiome of the other two mummies were mainly comprised by Clostridiales or Bacillales, as demonstrated with 16S rRNA gene amplicon sequencing, many of which are facultative anaerobes, possibly consistent with the process of natural mummification requiring low oxygen levels. Metagenome analyses showed the presence of other microbial groups that were positively or negatively correlated with specific metabolic profiles. The presence of sequences similar to both Trypanosoma cruzi and Leishmania donovani could suggest that these pathogens were prevalent in pre-Columbian individuals. Taxonomic and functional profiling of mummified human gut remains will aid in the understanding of the microbial ecology of the process of natural mummification. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Protocol for quality control in metabolic profiling of biological fluids by U(H)PLC-MS.

    Science.gov (United States)

    Gika, Helen G; Zisi, Chrysostomi; Theodoridis, Georgios; Wilson, Ian D

    2016-01-01

    The process of untargeted metabolic profiling/phenotyping of complex biological matrices, i.e., biological fluids such as blood plasma/serum, saliva, bile, and tissue extracts, provides the analyst with a wide range of challenges. Not the least of these challenges is demonstrating that the acquired data are of "good" quality and provide the basis for more detailed multivariate, and other, statistical analysis necessary to detect, and identify, potential biomarkers that might provide insight into the process under study. Here straightforward and pragmatic "quality control (QC)" procedures are described that allow investigators to monitor the analytical processes employed for global, untargeted, metabolic profiling. The use of this methodology is illustrated with an example from the analysis of human urine where an excel spreadsheet of the preprocessed LC-MS output is provided with embedded macros, calculations and visualization plots that can be used to explore the data. Whilst the use of these procedures is exemplified on human urine samples, this protocol is generally applicable to metabonomic/metabolomic profiling of biofluids, tissue and cell extracts from many sources. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Subclinical hypothyroidism does not influence the metabolic and hormonal profile of women with PCOS.

    Science.gov (United States)

    Trakakis, Eftihios; Pergialiotis, Vasilios; Hatziagelaki, Erifili; Panagopoulos, Periklis; Salloum, Ioannis; Papantoniou, Nikolaos

    2017-06-23

    Background Subclinical hypothyroidism (SCH) is present in 5%-10% of polycystic ovary syndrome (PCOS) patients. To date, its impact on the metabolic and hormonal profile of those women remains controversial. The purpose of our study is to evaluate the impact of SCH on the glycemic, lipid and hormonal profile of PCOS patients. Materials and methods We conducted a prospective case control study of patients that attended the Department of Gynecological Endocrinology of our hospital. Results Overall, 280 women with PCOS were enrolled during a time period of 7 years (2009-2015). Twenty-one patients (7.5%) suffered from SCH. The anthropometric characteristics were comparable among women with PCOS and those with SCH + PCOS. The prevalence of acne, hirsutism and anovulation did not differ. Significant differences were observed in the 2-h oral glucose tolerance test (OGTT) (p = 0.003 for glucose and p = 0.046 for insulin). The QUICKI, Matsuda and homeostatic model assessment-insulin resistance (HOMA-IR) indices where, however, similar. No difference in serum lipids was observed. Slightly elevated levels of follicle stimulating hormone (FSH) and testosterone were noted. The remaining hormonal parameters remained similar among groups. Similarly, the ovarian volume and the endometrial thickness did not differ. Conclusions The impact of SCH on the metabolic and hormonal profile of PCOS patients seems to be negligible. Future studies are needed in the field and their conduct in a multi-institutional basis seems to be required, given the small prevalence of SCH among women with PCOS.

  2. Development of a Pipeline for Exploratory Metabolic Profiling of Infant Urine.

    Science.gov (United States)

    Jackson, Frances; Georgakopoulou, Nancy; Kaluarachchi, Manuja; Kyriakides, Michael; Andreas, Nicholas; Przysiezna, Natalia; Hyde, Matthew J; Modi, Neena; Nicholson, Jeremy K; Wijeyesekera, Anisha; Holmes, Elaine

    2016-09-02

    Numerous metabolic profiling pipelines have been developed to characterize the composition of human biofluids and tissues, the vast majority of these being for studies in adults. To accommodate limited sample volume and to take into account the compositional differences between adult and infant biofluids, we developed and optimized sample handling and analytical procedures for studying urine from newborns. A robust pipeline for metabolic profiling using NMR spectroscopy was established, encompassing sample collection, preparation, spectroscopic measurement, and computational analysis. Longitudinal samples were collected from five infants from birth until 14 months of age. Methods of extraction and effects of freezing and sample dilution were assessed, and urinary contaminants from breakdown of polymers in a range of diapers and cotton wool balls were identified and compared, including propylene glycol, acrylic acid, and tert-butanol. Finally, assessment of urinary profiles obtained over the first few weeks of life revealed a dramatic change in composition, with concentrations of phenols, amino acids, and betaine altering systematically over the first few months of life. Therefore, neonatal samples require more stringent standardization of experimental design, sample handling, and analysis compared to that of adult samples to accommodate the variability and limited sample volume.

  3. SEVERE OBESITY SHIFTS METABOLIC THRESHOLDS BUT DOES NOT ATTENUATE AEROBIC TRAINING ADAPTATIONS IN ZUCKER RATS

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    Thiago Santos Rosa

    2016-04-01

    Full Text Available Severe obesity affects metabolism with potential to influence the lactate and glycemic response to different exercise intensities in untrained and trained rats. Here we evaluated metabolic thresholds and maximal aerobic capacity in rats with severe obesity and lean counterparts at pre- and post-training. Zucker rats (obese: n = 10, lean: n = 10 were submitted to constant treadmill bouts, to determine the maximal lactate steady state, and an incremental treadmill test, to determine the lactate threshold, glycemic threshold and maximal velocity at pre and post 8 weeks of treadmill training. Velocities of the lactate threshold and glycemic threshold agreed with the maximal lactate steady state velocity on most comparisons. The maximal lactate steady state velocity occurred at higher percentage of the maximal velocity in Zucker rats at pre-training than the percentage commonly reported and used for training prescription for other rat strains (i.e., 60% (obese = 78±9% and lean = 68±5%, P 0.05, whereas increase in maximal velocity was greater in the obese group (P <0.05 vs. lean. In conclusion, lactate threshold, glycemic threshold and maximal lactate steady state occurred at similar exercise intensity in Zucker rats at pre- and post-training. Severe obesity shifted metabolic thresholds to higher exercise intensity at pre-training, but did not attenuate submaximal and maximal aerobic training adaptations.

  4. Severe Obesity Shifts Metabolic Thresholds but Does Not Attenuate Aerobic Training Adaptations in Zucker Rats

    Science.gov (United States)

    Rosa, Thiago S.; Simões, Herbert G.; Rogero, Marcelo M.; Moraes, Milton R.; Denadai, Benedito S.; Arida, Ricardo M.; Andrade, Marília S.; Silva, Bruno M.

    2016-01-01

    Severe obesity affects metabolism with potential to influence the lactate and glycemic response to different exercise intensities in untrained and trained rats. Here we evaluated metabolic thresholds and maximal aerobic capacity in rats with severe obesity and lean counterparts at pre- and post-training. Zucker rats (obese: n = 10, lean: n = 10) were submitted to constant treadmill bouts, to determine the maximal lactate steady state, and an incremental treadmill test, to determine the lactate threshold, glycemic threshold and maximal velocity at pre and post 8 weeks of treadmill training. Velocities of the lactate threshold and glycemic threshold agreed with the maximal lactate steady state velocity on most comparisons. The maximal lactate steady state velocity occurred at higher percentage of the maximal velocity in Zucker rats at pre-training than the percentage commonly reported and used for training prescription for other rat strains (i.e., 60%) (obese = 78 ± 9% and lean = 68 ± 5%, P 0.05), whereas increase in maximal velocity was greater in the obese group (P < 0.05 vs. lean). In conclusion, lactate threshold, glycemic threshold and maximal lactate steady state occurred at similar exercise intensity in Zucker rats at pre- and post-training. Severe obesity shifted metabolic thresholds to higher exercise intensity at pre-training, but did not attenuate submaximal and maximal aerobic training adaptations. PMID:27148063

  5. Chemotactic signal transduction and phosphate metabolism as adaptive strategies during citrus canker induction by Xanthomonas citri.

    Science.gov (United States)

    Moreira, Leandro Marcio; Facincani, Agda Paula; Ferreira, Cristiano Barbalho; Ferreira, Rafael Marine; Ferro, Maria Inês Tiraboshi; Gozzo, Fabio Cesar; de Oliveira, Julio Cezar Franco; Ferro, Jesus Aparecido; Soares, Márcia Regina

    2015-03-01

    The genome of Xanthomonas citri subsp. Citri strain 306 pathotype A (Xac) was completely sequenced more than 10 years; to date, few studies involving functional genomics Xac and its host compatible have been developed, specially related to adaptive events that allow the survival of Xac within the plant. Proteomic analysis of Xac showed that the processes of chemotactic signal transduction and phosphate metabolism are key adaptive strategies during the interaction of a pathogenic bacterium with its plant host. The results also indicate the importance of a group of proteins that may not be directly related to the classical virulence factors, but that are likely fundamental to the success of the initial stages of the infection, such as methyl-accepting chemotaxis protein (Mcp) and phosphate specific transport (Pst). Furthermore, the analysis of the mutant of the gene pstB which codifies to an ABC phosphate transporter subunit revealed a complete absence of citrus canker symptoms when inoculated in compatible hosts. We also conducted an in silico analysis which established the possible network of genes regulated by two-component systems PhoPQ and PhoBR (related to phosphate metabolism), and possible transcriptional factor binding site (TFBS) motifs of regulatory proteins PhoB and PhoP, detaching high degree of conservation of PhoB TFBS in 84 genes of Xac genome. This is the first time that chemotaxis signal transduction and phosphate metabolism were therefore indicated to be fundamental to the process of colonization of plant tissue during the induction of disease associated with Xanthomonas genus bacteria.

  6. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

    Science.gov (United States)

    Mella, Olav; Bruland, Ove; Risa, Kristin; Dyrstad, Sissel E.; Alme, Kine; Rekeland, Ingrid G.; Sapkota, Dipak; Røsland, Gro V.; Fosså, Alexander; Ktoridou-Valen, Irini; Lunde, Sigrid; Sørland, Kari; Lien, Katarina; Herder, Ingrid; Thürmer, Hanne; Gotaas, Merete E.; Baranowska, Katarzyna A.; Bohnen, Louis M.L.J.; Schäfer, Christoph; McCann, Adrian; Sommerfelt, Kristian; Helgeland, Lars; Ueland, Per M.; Dahl, Olav

    2016-01-01

    Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is a debilitating disease of unknown etiology, with hallmark symptoms including postexertional malaise and poor recovery. Metabolic dysfunction is a plausible contributing factor. We hypothesized that changes in serum amino acids may disclose specific defects in energy metabolism in ME/CFS. Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients. The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion. The amino acid changes could not be explained by symptom severity, disease duration, age, BMI, or physical activity level among patients. These findings are in agreement with the clinical disease presentation of ME/CFS, with inadequate ATP generation by oxidative phosphorylation and excessive lactate generation upon exertion. PMID:28018972

  7. Proteomic analysis of the metabolic adaptation of the biocontrol agent Pseudozyma flocculosa leading to glycolipid production

    Directory of Open Access Journals (Sweden)

    Bélanger Richard R

    2010-02-01

    Full Text Available Abstract The yeast-like epiphytic fungus Pseudozyma flocculosa is known to antagonize powdery mildew fungi through proliferation on colonies presumably preceded by the release of an antifungal glycolipid (flocculosin. In culture conditions, P. flocculosa can be induced to produce or not flocculosin through manipulation of the culture medium nutrients. In order to characterize and understand the metabolic changes in P. flocculosa linked to glycolipid production, we conducted a 2-DE proteomic analysis and compared the proteomic profile of P. flocculosa growing under conditions favoring the development of the fungus (control or conducive to flocculosin synthesis (stress. A large number of protein spots (771 were detected in protein extracts of the control treatment compared to only 435 matched protein spots in extracts of the stress cultures, which clearly suggests an important metabolic reorganization in slow-growing cells producing flocculosin. From the latter treatment, we were able to identify 21 protein spots that were either specific to the treatment or up-regulated significantly (2-fold increase. All of them were identified based on similarity between predicted ORF of the newly sequenced genome of P. flocculosa with Ustilago maydis' available annotated sequences. These proteins were associated with the carbon and fatty acid metabolism, and also with the filamentous change of the fungus leading to flocculosin production. This first look into the proteome of P. flocculosa suggests that flocculosin synthesis is elicited in response to specific stress or limiting conditions.

  8. Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism

    Directory of Open Access Journals (Sweden)

    Gabriel N. Aughey

    2014-10-01

    Full Text Available The essential metabolic enzyme CTP synthase (CTPsyn can be compartmentalised to form an evolutionarily-conserved intracellular structure termed the cytoophidium. Recently, it has been demonstrated that the enzymatic activity of CTPsyn is attenuated by incorporation into cytoophidia in bacteria and yeast cells. Here we demonstrate that CTPsyn is regulated in a similar manner in Drosophila tissues in vivo. We show that cytoophidium formation occurs during nutrient deprivation in cultured cells, as well as in quiescent and starved neuroblasts of the Drosophila larval central nervous system. We also show that cytoophidia formation is reversible during neurogenesis, indicating that filament formation regulates pyrimidine synthesis in a normal developmental context. Furthermore, our global metabolic profiling demonstrates that CTPsyn overexpression does not significantly alter CTPsyn-related enzymatic activity, suggesting that cytoophidium formation facilitates metabolic stabilisation. In addition, we show that overexpression of CTPsyn only results in moderate increase of CTP pool in human stable cell lines. Together, our study provides experimental evidence, and a mathematical model, for the hypothesis that inactive CTPsyn is incorporated into cytoophidia.

  9. Oxidative metabolic profiles of Brucella strains isolated from marine mammals: contribution to their species classification.

    Science.gov (United States)

    Jacques, Isabelle; Grayon, Maggy; Verger, Jean-Michel

    2007-05-01

    Since the 1990s, Brucella strains not matching the characteristics of any of the six conventional species have been isolated worldwide from marine mammals. In this study, 31 Brucella strains isolated from various marine mammals were examined for their oxidative metabolic pattern on 12 amino-acid and carbohydrate substrates. Three main oxidative profiles different from those of the Brucella terrestrial mammal strains were identified for the marine mammal strains: one gathering strains isolated from pinnipeds and two gathering strains from cetaceans. Thus, both oxidative metabolism results and previous molecular studies are in agreement with the proposal of two new Brucella species, Brucella pinnipediae and Brucella cetaceae, to classify the Brucella strains isolated from marine mammals, and are also in accordance with a classification of species of the Brucella genus based on host preference.

  10. Evaluation of 1H NMR metabolic profiling using biofluid mixture design.

    Science.gov (United States)

    Athersuch, Toby J; Malik, Shahid; Weljie, Aalim; Newton, Jack; Keun, Hector C

    2013-07-16

    A strategy for evaluating the performance of quantitative spectral analysis tools in conditions that better approximate background variation in a metabonomics experiment is presented. Three different urine samples were mixed in known proportions according to a {3, 3} simplex lattice experimental design and analyzed in triplicate by 1D (1)H NMR spectroscopy. Fifty-four urinary metabolites were subsequently quantified from the sample spectra using two methods common in metabolic profiling studies: (1) targeted spectral fitting and (2) targeted spectral integration. Multivariate analysis using partial least-squares (PLS) regression showed the latent structure of the spectral set recapitulated the experimental mixture design. The goodness-of-prediction statistic (Q(2)) of each metabolite variable in a PLS model was calculated as a metric for the reliability of measurement, across the sample compositional space. Several metabolites were observed to have low Q(2) values, largely as a consequence of their spectral resonances having low s/n or strong overlap with other sample components. This strategy has the potential to allow evaluation of spectral features obtained from metabolic profiling platforms in the context of the compositional background found in real biological sample sets, which may be subject to considerable variation. We suggest that it be incorporated into metabolic profiling studies to improve the estimation of matrix effects that confound accurate metabolite measurement. This novel method provides a rational basis for exploiting information from several samples in an efficient manner and avoids the use of multiple spike-in authentic standards, which may be difficult to obtain.

  11. [Profile of free fatty acids (FFA) in serum of young Colombians with obesity and metabolic syndrome].

    Science.gov (United States)

    Bermudez, J A; Velásquez, C M

    2014-12-01

    Obesity produces greater circulation of free fatty acids (FFA). In adults, the FFA composition changes in states of obesity; in adolescents, the results are contradictory. This study compare the FFA profile of obese youth with and without Metabolic Syndrome (MetS) and explore the association between FFA and metabolic alterations of obesity and MetS. A cross-sectional study with 96 young people between 10 and 18 years old was divided into three groups: 1) obese youth with MetS, 2) obese youth without MetS; and 3) adequate weight (AW), matched according to age, gender, pubertal maturation and socioeconomic stratum. The nutritional status was classified according to the body-mass index (BMI), according to the World Health Organization 2007 (WHO, 2007); the waist circumference (WC), adiposity, lipid profile, highly-sensitive reactive C protein (hsRCP), glucose, insulin and insulin resistance (IR), according to the homeostatic model assessment (HOMA Calculator Version 2.2.2). The FFA serum concentration was determined by gas chromatography. Both obese groups had higher adiposity, inflamation (hsRCP), FFA totals and frequency palmitoleic-16:Jn7, compared to AW. The obese with MetS presented more metabolic alterations, a greater amount of dihomo-γ-linolenic (DHGL-20:3n6) and a 20:3n6/18:2n6 relation, indicative of increased activity of A6 desaturase (D6D). The FFA totals, palmitoleic-l6:1n7, DHGL-20:3n6, D6D activity and hsRCP significantly correlated with variables of adiposity, IR and triglicerides. The results in obese with MetS corroborate the association among central obesity, inflammation and increased lipolysis in visceral adipose tissue and metabolic alterations.

  12. Metabolic profiling of residents in the vicinity of a petrochemical complex

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Tzu-Hsuen; Chung, Ming-Kei [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Lin, Ching-Yu [Institute of Environmental Health, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Chen, Shu-Ting; Wu, Kuen-Yuh [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Chan, Chang-Chuan, E-mail: ccchan@ntu.edu.tw [Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan (China)

    2016-04-01

    No previous studies have simultaneously measured the biomarkers of environmental exposure and metabolome perturbation in residents affected by industrial pollutants. This study aimed to investigate the metabolic effects of environmental pollutants such as vanadium and polycyclic aromatic hydrocarbons (PAHs) on residents in the vicinity of a petrochemical complex. The study subjects were 160 residents, including 80 high-exposure subjects exposed to high levels of vanadium and PAHs and 80 age- and gender-matched low-exposure subjects living within a 40-km radius of a petrochemical complex. The exposure biomarkers vanadium and 1-hydroxypyrene and four oxidative/nitrosative stress biomarkers were measured in these subjects. Plasma samples from the study subjects were also analyzed using {sup 1}H NMR spectroscopy for metabolic profiling. The results showed that the urinary levels of vanadium and 1-hydroxypyrene in the high-exposure subjects were 40- and 20-fold higher, respectively, than those in the low-exposure subjects. Higher urinary levels of stress biomarkers, including 8-OHdG, HNE-MA, 8-isoPF2α, and 8-NO{sub 2}Gua, were also observed among the high-exposure subjects compared with the low-exposure subjects. Partial least squares discriminant analysis of the plasma metabolome demonstrated a clear separation between the high- and low-exposure subjects; the intensities of amino acids and carbohydrate metabolites were lower in the high-exposure subjects compared with the low-exposure subjects. The exposure to vanadium and PAHs may cause a reduction in the levels of amino acids and carbohydrates by elevating PPAR and insulin signaling, as well as oxidative/nitrosative stress. - Highlights: • Metabolic effects when exposure to pollutants near a petrochemical complex • V and PAHs exposure associated with elevated oxidative/nitrosative stress responses • V and PAHs exposure related to reduced amino acid and carbohydrate levels • V and PAHs affect metabolic

  13. Land reclamation and short-term cultivation change soil microbial communities and bacterial metabolic profiles.

    Science.gov (United States)

    He, Xun-yang; Su, Yi-rong; Liang, Yue-ming; Chen, Xiang-bi; Zhu, Han-hua; Wang, Ke-lin

    2012-03-30

    Soil microbes play an important role in many critical ecosystem processes, but little is known about the effects of land reclamation and short-term cultivation on microbial communities in red soil. In this study, soil microbial communities under five land use patterns-artificial pine forest (Fp), tussock and shrub (TS), shrubbery (Sh), sugarcane (Su) and maize and cassava rotation (Ma)-were characterised by DNA fingerprinting and metabolic profiling to reveal how land reclamation and cultivation affect the underlying diversity and function of soil microbial communities in southwestern China. Eight years of reclamation and cultivation significantly affected population size, composition and structure, bacterial metabolic profiles and diversity values (Shannon-Wiener index) of soil microbial communities. Soil organic carbon and pH were the most important factors shaping the underlying microbial communities; however, with significant correlations between soil carbon/nitrogen ratio and bacterial taxonomic and metabolic diversities, soil total nitrogen was a potentially important factor for soil microbial composition and function, as well as soil moisture, cation exchange capacity and physical structure to a lesser extent. In addition, the lowest pH, lower nutrient availability and the most compact soil in pine forest resulted in the lowest microbial taxonomic and metabolic diversities among the five land use patterns studied. Soil organic carbon, nitrogen and pH appeared to be the most important factors influencing microbial biomass, composition and function in red soil of southwestern China. The study suggests that measures to lessen the impact of changes in this edaphic environment should be taken to avoid an imbalance of microbial function and improve ecological sustainability in southwestern China. Copyright © 2012 Society of Chemical Industry.

  14. The effectiveness of the individual approach in physical rehabilitation of men with metabolic syndrome to improve atherogenic lipid profile

    Directory of Open Access Journals (Sweden)

    Marina Elnikova

    2016-06-01

    Full Text Available Purpose: evaluation of the effectiveness of individual approach in physical rehabilitation of men with metabolic syndrome based on the dynamics of indicators of the atherogenic lipid profile. Material & Methods: theoretical analysis and compilation of scientific and methodical literature and internet providers; biochemical methods; methods of mathematical statistics. To study involved 60 men with metabolic syndrome. Results: application of individual approach in the long-term form of rehabilitant-rehabilitation interaction at the outpatient rehabilitation stage of men with the metabolic syndrome improves lipid profile, significantly reduces total cholesterol, low-density lipoprotein, triglycerides and increases high-density lipoprotein.

  15. Adaptive Hybrid Control of Vehicle Semiactive Suspension Based on Road Profile Estimation

    Directory of Open Access Journals (Sweden)

    Yechen Qin

    2015-01-01

    Full Text Available A new road estimation based suspension hybrid control strategy is proposed. Its aim is to adaptively change control gains to improve both ride comfort and road handling with the constraint of rattle space. To achieve this, analytical expressions for ride comfort, road handling, and rattle space with respect to road input are derived based on the hybrid control, and the problem is transformed into a MOOP (Multiobjective Optimization Problem and has been solved by NSGA-II (Nondominated Sorting Genetic Algorithm-II. A new road estimation and classification method, which is based on ANFIS (Adaptive Neurofuzzy Inference System and wavelet transforms, is then presented as a means of detecting the road profile level, and a Kalman filter is designed for observing unknown states. The results of simulations conducted with random road excitation show that the efficiency of the proposed control strategy compares favourably to that of a passive system.

  16. Effect of probiotics on metabolic profiles in type 2 diabetes mellitus

    Science.gov (United States)

    Li, Caifeng; Li, Xin; Han, Hongqiu; Cui, Hailong; Peng, Min; Wang, Guolin; Wang, Zhiqiang

    2016-01-01

    Abstract Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease which is imposing heavy burden on global health and economy. Recent studies indicate gut microbiota play important role on the pathogenesis and metabolic disturbance of T2DM. As an effective mean of regulating gut microbiota, probiotics are live micro-organisms that are believed to provide a specific health benefit on the host. Whether probiotic supplementation could improve metabolic profiles by modifying gut microbiota in T2DM or not is still in controversy. The aim of the study is to assess the effect of probiotic supplementation on metabolic profiles in T2DM. We searched PubMed, EMBASE, and Cochrane Library up to 12 April 2016. Two review authors independently assessed study eligibility, extracted data, and evaluated risk of bias of included studies. Data were pooled by using the random-effect model and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was assessed and quantified (I2). A total of 12 randomized controlled trials (RCTs) were included. Lipid profiles (n = 508) and fasting blood glucose (FBG) (n = 520) were reported in 9 trials; the homeostasis model of assessment for insulin resistance index (HOMA-IR) (n = 368) and glycosylated hemoglobin (HbA1c) (n = 380) were reported in 6 trials. Probiotics could alleviate FBG (SMD –0.61 mmol/L, 95% CI [–0.92, –0.30], P = 0.0001). Probiotics could increase high-density lipoprotein-cholesterol (HDL-C) (SMD 0.42 mmol/L, 95% CI [0.08, 0.76], P = 0.01). There were no significant differences in low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), HbA1c and HOMA-IR between the treatment group and the control group. Probiotics may improve glycemic control and lipid metabolism in T2DM. Application of probiotic agents might become a new method for glucose management in T2DM. PMID:27368052

  17. Metabolic adaptation to the aqueous leaf extract of Moringa oleifera Lam.-supplemented diet is related to the modulation of gut microbiota in mice.

    Science.gov (United States)

    Gao, Xiaoyu; Xie, Qiuhong; Liu, Ling; Kong, Ping; Sheng, Jun; Xiang, Hongyu

    2017-06-01

    The aqueous leaf extract of Moringa oleifera Lam. (LM-A) is reported to have many health beneficial bioactivities and no obvious toxicity, but have mild adverse effects. Little is known about the mechanism of these reported adverse effects. Notably, there has been no report about the influence of LM-A on intestinal microecology. In this study, animal experiments were performed to explore the relationships between metabolic adaptation to an LM-A-supplemented diet and gut microbiota changes. After 8-week feeding with normal chow diet, the body weight of mice entered a stable period, and one of the group received daily doses of 750-mg/kg body weight LM-A by gavage for 4 weeks (assigned as LM); the other group received the vehicle (assigned as NCD). The liver weight to body weight ratio was enhanced, and the ceca were enlarged in the LM group compared with the NCD group. LM-A-supplemented-diet mice elicited a uniform metabolic adaptation, including slightly influenced fasting glucose and blood lipid profiles, significantly reduced liver triglycerides content, enhanced serum lipopolysaccharide level, activated inflammatory responses in the intestine and liver, compromised gut barrier function, and broken intestinal homeostasis. Many metabolic changes in mice were significantly correlated with altered specific gut bacteria. Changes in Firmicutes, Eubacterium rectale/Clostridium coccoides group, Faecalibacterium prausnitzii, Akkermansia muciniphila, segmented filamentous bacteria, Enterococcus spp., and Sutterella spp. may play an important role in the process of host metabolic adaptation to LM-A administration. Our research provides an explanation of the adverse effects of LM-A administration on normal adult individuals in the perspective of microecology.

  18. Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism

    DEFF Research Database (Denmark)

    Hao, Qin; Yadav, Rachita; Basse, Astrid L.

    2015-01-01

    We applied digital gene expression profiling to determine the transcriptome of brown and white adipose tissues (BAT and WAT, respectively) during cold exposure. Male C57BL/6J mice were exposed to cold for 2 or 4 days. A notable induction of genes related to glucose uptake, glycolysis, glycogen...... exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating...

  19. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    Directory of Open Access Journals (Sweden)

    Samman S

    2014-06-01

    Full Text Available Samir Samman,1 Ben Crossett,2 Miles Somers,1 Kirstine J Bell,1 Nicole T Lai,1,3 David R Sullivan,3 Peter Petocz4 1Discipline of Nutrition and Metabolism, 2Discipline of Proteomics and Biotechnology, School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia; 3Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 4Department of Statistics, Macquarie University, Sydney, NSW, Australia Abstract: Amino acid (AA status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM or chicken (CM, and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014, with consistently higher changes observed after 60 minutes (P<0.001. Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the

  20. Skeletal Muscle Remodeling in Response to Eccentric vs. Concentric Loading: Morphological, Molecular, and Metabolic Adaptations

    Directory of Open Access Journals (Sweden)

    Martino V. Franchi

    2017-07-01

    Full Text Available Skeletal muscle contracts either by shortening or lengthening (concentrically or eccentrically, respectively; however, the two contractions substantially differ from one another in terms of mechanisms of force generation, maximum force production and energy cost. It is generally known that eccentric actions generate greater force than isometric and concentric contractions and at a lower metabolic cost. Hence, by virtue of the greater mechanical loading involved in active lengthening, eccentric resistance training (ECC RT is assumed to produce greater hypertrophy than concentric resistance training (CON RT. Nonetheless, prevalence of either ECC RT or CON RT in inducing gains in muscle mass is still an open issue, with some studies reporting greater hypertrophy with eccentric, some with concentric and some with similar hypertrophy within both training modes. Recent observations suggest that such hypertrophic responses to lengthening vs. shortening contractions are achieved by different adaptations in muscle architecture. Whilst the changes in muscle protein synthesis in response to acute and chronic concentric and eccentric exercise bouts seem very similar, the molecular mechanisms regulating the myogenic adaptations to the two distinct loading stimuli are still incompletely understood.Thus, the present review aims to, (a critically discuss the literature on the contribution of eccentric vs. concentric loading to muscular hypertrophy and structural remodeling, and, (b clarify the molecular mechanisms that may regulate such adaptations.We conclude that, when matched for either maximum load or work, similar increase in muscle size is found between ECC and CON RT. However, such hypertrophic changes appear to be achieved through distinct structural adaptations, which may be regulated by different myogenic and molecular responses observed between lengthening and shortening contractions.

  1. The New Weather Radar for America's Space Program in Florida: A Temperature Profile Adaptive Scan Strategy

    Science.gov (United States)

    Carey, L. D.; Petersen, W. A.; Deierling, W.; Roeder, W. P.

    2009-01-01

    A new weather radar is being acquired for use in support of America s space program at Cape Canaveral Air Force Station, NASA Kennedy Space Center, and Patrick AFB on the east coast of central Florida. This new radar replaces the modified WSR-74C at Patrick AFB that has been in use since 1984. The new radar is a Radtec TDR 43-250, which has Doppler and dual polarization capability. A new fixed scan strategy was designed to best support the space program. The fixed scan strategy represents a complex compromise between many competing factors and relies on climatological heights of various temperatures that are important for improved lightning forecasting and evaluation of Lightning Launch Commit Criteria (LCC), which are the weather rules to avoid lightning strikes to in-flight rockets. The 0 C to -20 C layer is vital since most generation of electric charge occurs within it and so it is critical in evaluating Lightning LCC and in forecasting lightning. These are two of the most important duties of 45 WS. While the fixed scan strategy that covers most of the climatological variation of the 0 C to -20 C levels with high resolution ensures that these critical temperatures are well covered most of the time, it also means that on any particular day the radar is spending precious time scanning at angles covering less important heights. The goal of this project is to develop a user-friendly, Interactive Data Language (IDL) computer program that will automatically generate optimized radar scan strategies that adapt to user input of the temperature profile and other important parameters. By using only the required scan angles output by the temperature profile adaptive scan strategy program, faster update times for volume scans and/or collection of more samples per gate for better data quality is possible, while maintaining high resolution at the critical temperature levels. The temperature profile adaptive technique will also take into account earth curvature and refraction

  2. The Antagonistic Effect of Mycotoxins Deoxynivalenol and Zearalenone on Metabolic Profiling in Serum and Liver of Mice

    Directory of Open Access Journals (Sweden)

    Jian Ji

    2017-01-01

    Full Text Available Metabolic profiling in liver and serum of mice was studied for the combined toxic effects of deoxynivalenol (DON and zearalenone (ZEN, through gas chromatography mass spectrum. The spectrum of serum and liver sample of mice, treated with individual 2 mg/kg DON, 20 mg/kg ZEN, and the combined DON + ZEN with final concentration 2 mg/kg DON and 20 mg/kg ZEN for 21 days, were deconvoluted, aligned and identified with MS DIAL. The data matrix was processed with univariate analysis and multivariate analysis for selection of metabolites with variable importance for the projection (VIP > 1, t-test p value < 0.05. The metabolic pathway analysis was performed with MetaMapp and drawn by CytoScape. Results show that the combined DON and ZEN treatment has an obvious “antagonistic effect” in serum and liver tissue metabolic profiling of mice. The blood biochemical indexes, like alkaline phosphatase, alanine transaminase, and albumin (ALB/globulin (GLO, reveal a moderated trend in the combined DON + ZEN treatment group, which is consistent with histopathological examination. The metabolic pathway analysis demonstrated that the combined DON and ZEN treatment could down-regulate the valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, and O-glycosyl compounds related glucose metabolism in liver tissue. The metabolic profiling in serum confirmed the finding that the combined DON and ZEN treatment has an “antagonistic effect” on liver metabolism of mice.

  3. Metabolic Profiles in Cell Lines Infected with Classical Swine Fever Virus

    Directory of Open Access Journals (Sweden)

    Jinding Chen

    2017-04-01

    Full Text Available Viruses require energy and biosynthetic precursors from host cells for replication. An understanding of the metabolic interplay between classical swine fever virus (CSFV and host cells is important for exploring the complex pathological mechanisms of classical swine fever (CSF. In the current study, and for the first time, we utilized an approach involving gas chromatography coupled with mass spectrometry (GC-MS to examine the metabolic profiles within PK-15 and 3D4/2 cells infected with CSFV. The differential metabolites of PK-15 cells caused by CSFV infection mainly included the decreased levels of glucose 6-phosphate [fold change (FC = −1.94] and glyceraldehyde-3-phosphate (FC = −1.83 during glycolysis, ribulose 5-phosphate (FC = −1.51 in the pentose phosphate pathway, guanosine (FC = −1.24 and inosine (FC = −1.16 during purine biosynthesis, but the increased levels of 2-ketoisovaleric acid (FC = 0.63 during the citrate cycle, and ornithine (FC = 0.56 and proline (FC = 0.62 during arginine and proline metabolism. However, metabolite changes caused by CSFV infection in 3D4/2 cells included the reduced glyceraldehyde-3-phosphate (FC = −0.77 and pyruvic acid (FC = −1.42 during glycolysis, 2-ketoglutaric acid (FC = −1.52 in the citrate cycle, and the elevated cytosine (FC = 2.15 during pyrimidine metabolism. Our data showed that CSFV might rebuild cellular metabolic programs, thus aiding viral replication. These findings may be important in developing targets for new biomarkers for the diagnosis and identification of enzyme inhibitors or metabolites as antiviral drugs, or screening viral gene products as vaccines.

  4. The metabolic profile of a rat model of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Yohei Tanada

    2017-05-01

    Full Text Available Background The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD with cardiorenal syndrome (CRS induced by prolonged hypertension. Methods We used inbred male Dahl salt-sensitive (DS rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group or a 0.3% NaCl diet as controls (low-salt; LS group. We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney. Results DS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA cycle, decreased. Conclusions DS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.

  5. PGC-1alpha in exercise- and exercise training-induced metabolic adaptations

    DEFF Research Database (Denmark)

    Jørgensen, Stine Ringholm

    (PGC)-1α is required for exercise-, exercise training- and fasting-induced mRNA and protein responses, respectively, of metabolic, angiogenic and gluconeogenic proteins in liver and adipose tissue in mice, 3) PGC-1α is required for both exercise training and resveratrol mediated prevention of age...... and interferes with the exercise-induced adaptive response in human skeletal muscle. Study II demonstrates that mouse liver glucose-6-phosphatase (G6Pase) mRNA content increased in recovery from acute exercise in both wildtype (WT) and PGC-1α knockout (KO) mice, while phosphoenolpyruvate carboxykinase (PEPCK......) and pyruvate carboxylase mRNA content did not change in either genotype. Exercise training increased PEPCK protein content in both WT and PGC-1α KO mice. In addition, the mRNA and protein content of cytochrome (Cyt) c and cytochrome c oxidase (COX) subunit I increased in response to acute exercise and exercise...

  6. Recovery of Phenotypes Obtained by Adaptive Evolution through Inverse Metabolic Engineering

    DEFF Research Database (Denmark)

    Hong, Kuk-Ki; Nielsen, Jens

    2012-01-01

    In a previous study, system level analysis of adaptively evolved yeast mutants showing improved galactose utilization revealed relevant mutations. The governing mutations were suggested to be in the Ras/PKA signaling pathway and ergosterol metabolism. Here, site-directed mutants having one...... of the mutations RAS2Lys77, RAS2Tyr112, and ERG5Pro370 were constructed and evaluated. The mutants were also combined with overexpression of PGM2, earlier proved as a beneficial target for galactose utilization. The constructed strains were analyzed for their gross phenotype, transcriptome and targeted metabolites......, and the results were compared to those obtained from reference strains and the evolved strains. The RAS2Lys77 mutation resulted in the highest specific galactose uptake rate among all of the strains with an increased maximum specific growth rate on galactose. The RAS2Tyr112 mutation also improved the specific...

  7. Cross cultural adaptations and psychometric domains of Brazilian version of PROFILE PD for Parkinson's disease.

    Science.gov (United States)

    Swarowsky, Alessandra; Fontana, Samanta Rattis Canterle Bez; Santos, Mariana Palla; Silva, Bruna Adriana Da; Spagnuolo, Gessyca; Ovando, Angélica Cristiane; Ilha, Jocemar

    2017-08-01

    The PROFILE PD scale was developed specifically to evaluate patients with Parkinson's disease (PD) within the context of the International Classification of Functioning, Disability and Health, directly applied to physical therapy practice. The study aimed to translate and cross-culturally adapt the PROFILE PD scale to Portuguese-Brazil, and to analyze its psychometric domains. Fifty participants with PD participated in the study. We assessed the clarity of the Brazilian version of the scale by physiotherapists, presence of floor and ceiling effects, interrater and test-retest reliabilities, in addition to discriminant, concurrent (UPDRS) and construct validity, internal consistence, minimal detectable change (MDC), and responsiveness. The scale was considered highly clear for physical therapists. The interrater ICC was 0.74 and Wk was 0.89 for the total score. For test-retest reliability, the total ICC score was 0.99. The analysis of concurrent validity showed the Spearman correlation between Brazilian version of PROFILE PD and UPDRS (ρ = 0.77; p Brazilian version of PROFILE PD was able to discriminate the subject with PD in mild and moderate stages, and in mild and severe stages. A high internal consistency was found (α = 0.99). MDC was 2.41 points and there were no floor and ceiling effects. Also, the scale was responsive to physical therapy intervention, with improvement in 8 points after two months (effect size = 0.85). The Brazilian version of PROFILE PD is an instrument reliable, valid, and responsive to physical therapy intervention, that can be used to quantify impairments and limitations in patients with PD and can provide an overall summary of the impact of disease, useful for physiotherapy practice. Implications for Rehabilitation PROFILE PD is a reliable and valid instrument to be applied in Brazilian Parkinson disease patients. This scale is design specially to be used in physical therapy practice within the contexts surrounding the

  8. Metabolic profiling approach to explore compounds related to the umami intensity of soy sauce.

    Science.gov (United States)

    Shiga, Kazuki; Yamamoto, Shinya; Nakajima, Ayako; Kodama, Yukako; Imamura, Miho; Sato, Tsuneo; Uchida, Riichiro; Obata, Akio; Bamba, Takeshi; Fukusaki, Eiichiro

    2014-07-23

    A metabolic profiling approach was employed to explore the compounds that affect the intensity of umami taste in soy sauce. Twenty-five kinds of soy sauces were analyzed using GC-MS and LC-MS, wherein measurement data for 427 compounds were obtained. The umami taste intensity of each soy sauce sample was also quantitated by sensory evaluation and a projection to latent structure (PLS) regression analysis was conducted using the compounds' measurements and umami taste intensity data. Variable importance for the projection (VIP) value obtained via PLS was used for the estimation of the relevance for umami taste intensity. N-(1-Deoxyfructos-1-yl)glutamic acid (Fru-Glu) had the highest VIP value, and addition of Fru-Glu to soy sauce increased umami taste intensity better than glutamic acid at the same concentration as confirmed by sensory evaluation. This study showed that the combination of metabolic profiling approach and sensory evaluation can be used effectively to determine compounds related to taste.

  9. Cytokine profile and clinical metabolic alterations in HIV-1 infected individuals with and without lipodistrophy

    Directory of Open Access Journals (Sweden)

    L. C. R. Pontes-Cardoso

    2007-01-01

    Full Text Available The extensive use of Highly Active Antiretroviral Therapy (HAART has transformed HIV infection into a chronic condition. Thus, metabolic alterations including lipodystrophy and dyslipidemia have been associated with the use of such medications. The objective of the present study was to analyze clinical metabolic alterations and the profile of TNF-alpha, IFN-Y, IL-2, IL-10, and TNF-alpha type II soluble receptor in serum of HIV-1 individuals with and without lipodystrophy. Eighty-four adults were evaluated, 42 males and 42 females, mean age 37 years, and HAART time of at least 15 months. Two groups were formed, G1: 42 individuals with lipodystrophy, and G2: 42 without lipodistropy. From the HAART used, stavudine was more associated with the lipodystrophy group and zidovudine with the non-lipodystrophy group. CD4 and CD8 values, viral load, glucose, albumin, and lipids were not different between groups, except for triglycerides, which were high in the lipodystrophy group, and HDL, whose concentration was reduced in G1. TNF-alpha, TNF-RII, and IL-10 profiles were high and had positive correlation; IL-2 and IFN-gamma had reduced levels in the lipodystrophy group. High TNF-alpha and its receptor levels seem to be associated with lipodystrophy development in individuals under HAART therapy.

  10. Studies of the transition cow under a pasture-based milk production system: metabolic profiles.

    Science.gov (United States)

    Cavestany, D; Blanc, J E; Kulcsar, M; Uriarte, G; Chilibroste, P; Meikle, A; Febel, H; Ferraris, A; Krall, E

    2005-02-01

    This study describes the effect of parity (multiparous versus primiparous) and body condition score (BCS) at calving ( or =3; scale 1-5) on variations of BCS, body weight (BW) and metabolic profiles in Holstein cows grazing on improved pastures. Forty-two cows were studied (21 multiparous and 21 primiparous) from 2 months before to 3 months after calving. BCS, BW and milk production were measured every 2 weeks. Blood samples were taken every 2 weeks to determine total protein, albumin, urea, non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHB), cholesterol, aspartate aminotransferase (AST), calcium, phosphorus and magnesium. Primiparous cows had lower BCS during the early postpartum (PP) period and produced less milk than multiparous. In primiparous cows NEFA concentrations were higher during the early postpartum period; BHB levels were similar in both categories during this period. Primiparous cows showed a more unbalanced metabolic profile than multiparous cows, reflecting that they are recovering from the loss of BCS after calving with less success.

  11. Effects of coronatine elicitation on growth and metabolic profiles of Lemna paucicostata culture.

    Science.gov (United States)

    Kim, Jin-Young; Kim, Hye-Youn; Jeon, Jun-Yeong; Kim, Dong-Min; Zhou, Yaoyao; Lee, Jae Soung; Lee, Heayyean; Choi, Hyung-Kyoon

    2017-01-01

    In this study, the effects of coronatine treatment on the growth, comprehensive metabolic profiles, and productivity of bioactive compounds, including phenolics and phytosterols, in whole plant cultures of Lemna paucicostata were investigated using gas chromatography-mass spectrometry (GC-MS) coupled with multivariate statistical analysis. To determine the optimal timing of coronatine elicitation, coronatine was added on days 0, 23, and 28 after inoculation. The total growth of L. paucicostata was not significantly different between the coronatine treated groups and the control. The coronatine treatment in L. paucicostata induced increases in the content of hydroxycinnamic acids, such as caffeic acid, isoferulic acid, ρ-coumaric acid, sinapic acid, and phytosterols, such as campesterol and β-sitosterol. The productivity of these useful metabolites was highest when coronatine was added on day 0 and harvested on day 32. These results suggest that coronatine treatment on day 0 activates the phenolic and phytosterol biosynthetic pathways in L. paucicostata to a greater extent than in the control. To the best of our knowledge, this is the first report to investigate the effects of coronatine on the alteration of metabolism in L. paucicostata based on GC-MS profiling. The results of this research provide a foundation for designing strategies for enhanced production of useful metabolites for pharmaceutical and nutraceutical industries by cultivation of L. paucicostata.

  12. Prenatal Psychosocial Profile: translation, cross-cultural adaptation and validation to its use in Brazil.

    Science.gov (United States)

    Weissheimer, Anne Marie; Mamede, Marli Villela

    2015-12-01

    To translate the Prenatal Psychosocial Profile (PPP) to be used in Brazil; to perform its cross-cultural adaptation; and to evaluate its reliability and validity. Methodological study. The study was conducted in 10 prenatal care clinics at the city of Porto Alegre/Brazil. 241 women pregnant women. The adaptation process consisted in: translation; first version synthesis; expert committee evaluation; back translation; pre-test of the PPP version in Portuguese (PPP-VP); validation; the data with the participants was collected in 2007, by trained student nurses that approached the women while they were waiting for prenatal consultation. The mean scores for all subscales were similar to the ones found by the original authors; internal consistency was verified through Cronbach׳s alpha, with values of 0.71 for the stress subscale; 0.96 for support from the partner; 0.96 for support from others; and 0.79 for self-esteem; validity was supported through factorial analysis; construct and criterion validities were also established. PPP-VP should be used as a tool to obtain a psychosocial profile which can lead to nursing interventions that will reduce health risk behaviours during pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Exercise-Induced Skeletal Muscle Remodeling and Metabolic Adaptation: Redox Signaling and Role of Autophagy

    Science.gov (United States)

    Giammarioli, Anna Maria; Chiandotto, Sergio; Spoletini, Ilaria

    2014-01-01

    Abstract Significance: Skeletal muscle is a highly plastic tissue. Exercise evokes signaling pathways that strongly modify myofiber metabolism and physiological and contractile properties of skeletal muscle. Regular physical activity is beneficial for health and is highly recommended for the prevention of several chronic conditions. In this review, we have focused our attention on the pathways that are known to mediate physical training-induced plasticity. Recent Advances: An important role for redox signaling has recently been proposed in exercise-mediated muscle remodeling and peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) activation. Still more currently, autophagy has also been found to be involved in metabolic adaptation to exercise. Critical Issues: Both redox signaling and autophagy are processes with ambivalent effects; they can be detrimental and beneficial, depending on their delicate balance. As such, understanding their role in the chain of events induced by exercise and leading to skeletal muscle remodeling is a very complicated matter. Moreover, the study of the signaling induced by exercise is made even more difficult by the fact that exercise can be performed with several different modalities, with this having different repercussions on adaptation. Future Directions: Unraveling the complexity of the molecular signaling triggered by exercise on skeletal muscle is crucial in order to define the therapeutic potentiality of physical training and to identify new pharmacological compounds that are able to reproduce some beneficial effects of exercise. In evaluating the effect of new “exercise mimetics,” it will also be necessary to take into account the involvement of reactive oxygen species, reactive nitrogen species, and autophagy and their controversial effects. Antioxid. Redox Signal. 21, 154–176. PMID:24450966

  14. Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum

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    Beisser Daniela

    2012-06-01

    Full Text Available Abstract Background Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade Milnesium tardigradum were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress. Results In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites and 4,378 edges (reactions. Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurable metabolism (e.g. glycolysis and amino acid anabolism during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from

  15. Body composition and metabolic profile in adults with vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Liane Murari ROCHA

    Full Text Available ABSTRACT Objective: To investigate the body composition and metabolic profile in individuals in terms of different concentrations of serum vitamin D, ranging from deficiency to sufficiency. Methods: A cross-sectional study of 106 adults of both genders, who were divided into three groups according to vitamin D levels: deficiency: <20ng/mL; insufficiency: 20-29.9ng/mL; and sufficiency: 30-100ng/mL. Anthropometric evaluation included weight, height, and body circumferences. Fat mass and lean mass were assessed using the Tetrapolar bioelectrical impedance method. Clinical and biochemical evaluations were also carried out. Insulin resistance was estimated using the Homeostasis Model Assessment Insulin index. Results: The analysis showed that the main alterations in individuals in the vitamin D deficiency group were higher triglycerides, very low density lipoprotein - cholesterol, fasting blood glucose, insulin, glycated hemoglobin, body mass index, body fat percentage, lean mass percentage, waist circumference, and Homeostasis Model Assessment Insulin than those of the vitamin D sufficient group (p<0.05. Conclusion: It was found that vitamin D deficiency causes important body composition and metabolic changes, which may lead to diseases such as diabetes Mellitus and metabolic syndrome.

  16. Urine metabolic profiling for the pathogenesis research of erosive oral lichen planus.

    Science.gov (United States)

    Li, Xu-Zhao; Yang, Xu-Yan; Wang, Yu; Zhang, Shuai-Nan; Zou, Wei; Wang, Yan; Li, Xiao-Nan; Wang, Ling-Shu; Zhang, Zhi-Gang; Xie, Liang-Zhen

    2017-01-01

    Oral lichen planus (OLP) is a relatively common chronic immune-pathological and inflammatory disease and potentially oral precancerous lesion. Erosive OLP patients show the higher rate of malignant transformation than patients with non-erosive OLP. Identifying the potential biomarkers related to erosive OLP may help to understand the pathogenesis of the diseases. Metabolic profiles were compared in control and patient subjects with erosive OLP by using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods An integrative analysis was used to identify the perturbed metabolic pathways and pathological processes that may be associated with the disease. In total, 12 modulated metabolites were identified and considered as the potential biomarkers of erosive OLP. Multiple metabolic pathways and pathological processes were involved in erosive OLP. The dysregulations of these metabolites could be used to explain the pathogenesis of the disease, which could also be the potential therapeutic targets for the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Maternal chromium restriction modulates miRNA profiles related to lipid metabolism disorder in mice offspring.

    Science.gov (United States)

    Zhang, Qian; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-08-01

    Increasing evidence shows that maternal nutrition status has a vital effect on offspring susceptibility to obesity. MicroRNAs are related to lipid metabolism processes. This study aimed to evaluate whether maternal chromium restriction could affect miRNA expression involved in lipid metabolism in offspring. Weaning C57BL/6J mice born from mothers fed with normal control diet or chromium-restricted diet were fed for 13 weeks. The adipose miRNA expression profile was analyzed by miRNA array analysis. At 16 weeks old, pups from dams fed with chromium-restricted diet exhibit higher body weight, fat weight, and serum TC, TG levels. Six miRNAs were identified as upregulated in the RC group compared with the CC group, whereas eight miRNAs were lower than the threshold level set in the RC group. In the validated target genes of these differentially expressed miRNA, the MAPK signaling pathway serves an important role in the influence of early life chromium-restricted diet on lipid metabolism through miRNA. Long-term programming on various specific miRNA and MAPK signaling pathway may be involved in maternal chromium restriction in the adipose of female offspring. Impact statement For the first time, our study demonstrates important miRNA differences in the effect of maternal chromium restriction in offspring. These miRNAs may serve as "bridges" between the mother and the offspring by affecting the MAPK pathway.

  18. Neonatal diethylstilbestrol exposure alters the metabolic profile of uterine epithelial cells

    Directory of Open Access Journals (Sweden)

    Yan Yin

    2012-11-01

    Developmental exposure to diethylstilbestrol (DES causes reproductive tract malformations, affects fertility and increases the risk of clear cell carcinoma of the vagina and cervix in humans. Previous studies on a well-established mouse DES model demonstrated that it recapitulates many features of the human syndrome, yet the underlying molecular mechanism is far from clear. Using the neonatal DES mouse model, the present study uses global transcript profiling to systematically explore early gene expression changes in individual epithelial and mesenchymal compartments of the neonatal uterus. Over 900 genes show differential expression upon DES treatment in either one or both tissue layers. Interestingly, multiple components of peroxisome proliferator-activated receptor-γ (PPARγ-mediated adipogenesis and lipid metabolism, including PPARγ itself, are targets of DES in the neonatal uterus. Transmission electron microscopy and Oil-Red O staining further demonstrate a dramatic increase in lipid deposition in uterine epithelial cells upon DES exposure. Neonatal DES exposure also perturbs glucose homeostasis in the uterine epithelium. Some of these neonatal DES-induced metabolic changes appear to last into adulthood, suggesting a permanent effect of DES on energy metabolism in uterine epithelial cells. This study extends the list of biological processes that can be regulated by estrogen or DES, and provides a novel perspective for endocrine disruptor-induced reproductive abnormalities.

  19. Profiling of cytosolic and peroxisomal acetyl-CoA metabolism in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Yun Chen

    Full Text Available As a key intracellular metabolite, acetyl-coenzyme A (acetyl-CoA plays a major role in various metabolic pathways that link anabolism and catabolism. In the yeast Saccharomyces cerevisiae, acetyl-CoA involving metabolism is compartmentalized, and may vary with the nutrient supply of a cell. Membranes separating intracellular compartments are impermeable to acetyl-CoA and no direct transport between the compartments occurs. Thus, without carnitine supply the glyoxylate shunt is the sole possible route for transferring acetyl-CoA from the cytosol or the peroxisomes into the mitochondria. Here, we investigate the physiological profiling of different deletion mutants of ACS1, ACS2, CIT2 and MLS1 individually or in combination under alternative carbon sources, and study how various mutations alter carbon distribution. Based on our results a detailed model of carbon distribution about cytosolic and peroxisomal acetyl-CoA metabolism in yeast is suggested. This will be useful to further develop yeast as a cell factory for the biosynthesis of acetyl-CoA-derived products.

  20. Metabolic profiles show specific mitochondrial toxicities in vitro in myotube cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu Qiuwei, E-mail: qiuwei_xu@merck.com; Vu, Heather; Liu Liping; Wang, Ting-Chuan; Schaefer, William H. [Merck Research Laboratories (United States)

    2011-04-15

    Mitochondrial toxicity has been a serious concern, not only in preclinical drug development but also in clinical trials. In mitochondria, there are several distinct metabolic processes including fatty acid {beta}-oxidation, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation (OXPHOS), and each process contains discrete but often intimately linked steps. Interruption in any one of those steps can cause mitochondrial dysfunction. Detection of inhibition to OXPHOS can be complicated in vivo because intermediate endogenous metabolites can be recycled in situ or circulated systemically for metabolism in other organs or tissues. Commonly used assays for evaluating mitochondrial function are often applied to ex vivo or in vitro samples; they include various enzymatic or protein assays, as well as functional assays such as measurement of oxygen consumption rate, membrane potential, or acidification rates. Metabolomics provides quantitative profiles of overall metabolic changes that can aid in the unraveling of explicit biochemical details of mitochondrial inhibition while providing a holistic view and heuristic understanding of cellular bioenergetics. In this paper, we showed the application of quantitative NMR metabolomics to in vitro myotube cells treated with mitochondrial toxicants, rotenone and antimycin A. The close coupling of the TCA cycle to the electron transfer chain (ETC) in OXPHOS enables specific diagnoses of inhibition to ETC complexes by discrete biochemical changes in the TCA cycle.

  1. Metabolic profiles from two different breakfast meals characterized by (1)H NMR-based metabolomics.

    Science.gov (United States)

    Rådjursöga, Millie; Karlsson, Göran B; Lindqvist, Helen M; Pedersen, Anders; Persson, Cecilia; Pinto, Rui Climaco; Ellegård, Lars; Winkvist, Anna

    2017-09-15

    It is challenging to measure dietary exposure with techniques that are both accurate and applicable to free-living individuals. We performed a cross-over intervention, with 24 healthy individuals, to capture the acute metabolic response of a cereal breakfast (CB) and an egg and ham breakfast (EHB). Fasting and postprandial urine samples were analyzed using (1)H nuclear magnetic resonance (NMR) spectroscopy and multivariate data analysis. Metabolic profiles were distinguished in relation to ingestion of either CB or EHB. Phosphocreatine/creatine and citrate were identified at higher concentrations after consumption of EHB. Beverage consumption (i.e., tea or coffee) could clearly be seen in the data. 2-furoylglycine and 5-hydroxymethyl-2-furoic acid - potential biomarkers for coffee consumption were identified at higher concentrations in coffee drinkers. Thus (1)H NMR urine metabolomics is applicable in the characterization of acute metabolic fingerprints from meal consumption and in the identification of metabolites that may serve as potential biomarkers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Metabolic profile and underlying improved bio-activity of Fructus aurantii immaturus by human intestinal bacteria.

    Science.gov (United States)

    Liu, Xing Yan; Fan, Meng Lin; Wang, Huai You; Yu, Bo Yang; Liu, Ji Hua

    2017-06-21

    Fructus aurantii immaturus (FAI) is the dried young fruit of Citrus aurantium L. or Citrus sinensis L. Osbeck. The purpose of this paper was to investigate the metabolic fate of FAI upon incubation with human intestinal bacteria, meanwhile to evaluate the antioxidant and anti-inflammatory activities of FAI and the transformed Fructus aurantii immaturus (TFAI). The water extract of FAI was anaerobically incubated with human intestinal bacterial suspensions for 48 h at 37 °C. Liquid chromatography-hybridised with quadrupole-time-of-flight mass spectrometry (LC-Q-TOF/MS) was applied to identify FAI metabolites. A total of 45 compounds were identified in FAI, eleven of which were metabolized by human intestinal bacteria. Nine major metabolites were identified as eriodictyol, naringenin, hesperetin, luteolin, apigenin, chryseriol, isosakuranetin, phloretin and diosmetin. The metabolic profile of FAI was elucidated on the basis of metabolite information. We found that the concentrations of acetic, propionic and butyric acids in FAI culture were all increased during fermentation relative to those of the control. Further bioactive evaluations showed that TFAI exhibited more potent antioxidant and anti-inflammatory abilities than FAI in vitro. Additionally, in vivo experiment confirmed that FAI significantly attenuated the blood endotoxin and TNF-α levels in the conventional rats compared to those of pseudo-germ-free (PGF) rats. This study revealed that metabolites may play a key role in the antioxidant and anti-inflammatory capacities of FAI.

  3. PROX1 Promotes Metabolic Adaptation and Fuels Outgrowth of Wnthigh Metastatic Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Simone Ragusa

    2014-09-01

    Full Text Available The Wnt pathway is abnormally activated in the majority of colorectal cancers, and significant knowledge has been gained in understanding its role in tumor initiation. However, the mechanisms of metastatic outgrowth in colorectal cancer remain a major challenge. We report that autophagy-dependent metabolic adaptation and survival of metastatic colorectal cancer cells is regulated by the target of oncogenic Wnt signaling, homeobox transcription factor PROX1, expressed by a subpopulation of colon cancer progenitor/stem cells. We identify direct PROX1 target genes and show that repression of a pro-apoptotic member of the BCL2 family, BCL2L15, is important for survival of PROX1+ cells under metabolic stress. PROX1 inactivation after the establishment of metastases prevented further growth of lesions. Furthermore, autophagy inhibition efficiently targeted metastatic PROX1+ cells, suggesting a potential therapeutic approach. These data identify PROX1 as a key regulator of the transcriptional network contributing to metastases outgrowth in colorectal cancer.

  4. Effects of phototherapy plus physical training on metabolic profile and quality of life in postmenopausal women.

    Science.gov (United States)

    Paolillo, Fernanda Rossi; Borghi-Silva, Audrey; Arena, Ross; Parizotto, Nivaldo Antonio; Kurachi, Cristina; Bagnato, Vanderlei Salvador

    2017-10-01

    A cluster of metabolic abnormalities are markedly higher among postmenopausal women. The present study evaluated the effects of infrared light emitting diode (LED) during treadmill training on multiple metabolic markers, body fat, dietary habits and quality of life in postmenopausal women. Forty-five postmenopausal women aged 50-60 years were randomly assigned to one of three groups, and of these, 30 women successfully completed the full study. The three groups were as follows: (i) the LED group, which performed treadmill training associated with phototherapy (n = 10); (ii) the exercise group, which carried out treadmill training only (n = 10); and (iii) the sedentary group, which neither performed physical training nor underwent phototherapy (n = 10). Training was performed over a period of six months, twice a week for 45 min per session at 85-90% of maximal heart rate (HRmax), which was obtained during a progressive exercise testing. The average HR and velocity during treadmill training were 144 ± 9 bpm and 5.8 ± 1.3 km/h for both trained groups. The irradiation parameters were 100 mW, 39 mW/cm(2) and 108 J/cm(2) for 45 min. Anthropometric data, skinfolds thickness, biochemical exams (lipid profile, glucose and insulin levels), dietary habits and quality of life were evaluated. The sum of skinfolds significantly improved in the exercise and sedentary groups (p quality of life improved in the LED group only, with a significant reduction in the total WHQ score (p training with or without phototherapy may improve the metabolic profile. In addition, phototherapy together with treadmill training prevented an increase in subcutaneous fat and facilitated an improved quality of life in postmenopausal women.

  5. Effects of black raspberry on lipid profiles and vascular endothelial function in patients with metabolic syndrome.

    Science.gov (United States)

    Jeong, Han Saem; Hong, Soon Jun; Lee, Tae-Bum; Kwon, Ji-Wung; Jeong, Jong Tae; Joo, Hyung Joon; Park, Jae Hyoung; Ahn, Chul-Min; Yu, Cheol Woong; Lim, Do-Sun

    2014-10-01

    Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p raspberry than in the placebo group. Increases in baFMD at the 12-week follow-up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12-week follow-up. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver.

    Science.gov (United States)

    Ferreira, Andréa G K; da Cunha, Aline A; Machado, Fernanda R; Pederzolli, Carolina D; Dalazen, Giovana R; de Assis, Adriano M; Lamers, Marcelo L; dos Santos, Marinilce F; Dutra-Filho, Carlos S; Wyse, Angela T S

    2012-01-01

    The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation. Copyright © 2011 Wiley Periodicals, Inc.

  7. Metabolic adaptation to chronic inhibition of mitochondrial protein synthesis in acute myeloid leukemia cells.

    Directory of Open Access Journals (Sweden)

    Bozhena Jhas

    Full Text Available Recently, we demonstrated that the anti-bacterial agent tigecycline preferentially induces death in leukemia cells through the inhibition of mitochondrial protein synthesis. Here, we sought to understand mechanisms of resistance to tigecycline by establishing a leukemia cell line resistant to the drug. TEX leukemia cells were treated with increasing concentrations of tigecycline over 4 months and a population of cells resistant to tigecycline (RTEX+TIG was selected. Compared to wild type cells, RTEX+TIG cells had undetectable levels of mitochondrially translated proteins Cox-1 and Cox-2, reduced oxygen consumption and increased rates of glycolysis. Moreover, RTEX+TIG cells were more sensitive to inhibitors of glycolysis and more resistant to hypoxia. By electron microscopy, RTEX+TIG cells had abnormally swollen mitochondria with irregular cristae structures. RNA sequencing demonstrated a significant over-representation of genes with binding sites for the HIF1α:HIF1β transcription factor complex in their promoters. Upregulation of HIF1α mRNA and protein in RTEX+TIG cells was confirmed by Q-RTPCR and immunoblotting. Strikingly, upon removal of tigecycline from RTEX+TIG cells, the cells re-established aerobic metabolism. Levels of Cox-1 and Cox-2, oxygen consumption, glycolysis, mitochondrial mass and mitochondrial membrane potential returned to wild type levels, but HIF1α remained elevated. However, upon re-treatment with tigecycline for 72 hours, the glycolytic phenotype was re-established. Thus, we have generated cells with a reversible metabolic phenotype by chronic treatment with an inhibitor of mitochondrial protein synthesis. These cells will provide insight into cellular adaptations used to cope with metabolic stress.

  8. Nitrogen Metabolism in Adaptation of Photosynthesis to Water Stress in Rice Grown under Different Nitrogen Levels

    Directory of Open Access Journals (Sweden)

    Chu Zhong

    2017-06-01

    Full Text Available To investigate the role of nitrogen (N metabolism in the adaptation of photosynthesis to water stress in rice, a hydroponic experiment supplying with low N (0.72 mM, moderate N (2.86 mM, and high N (7.15 mM followed by 150 g⋅L-1 PEG-6000 induced water stress was conducted in a rainout shelter. Water stress induced stomatal limitation to photosynthesis at low N, but no significant effect was observed at moderate and high N. Non-photochemical quenching was higher at moderate and high N. In contrast, relative excessive energy at PSII level (EXC was declined with increasing N level. Malondialdehyde and hydrogen peroxide (H2O2 contents were in parallel with EXC. Water stress decreased catalase and ascorbate peroxidase activities at low N, resulting in increased H2O2 content and severer membrane lipid peroxidation; whereas the activities of antioxidative enzymes were increased at high N. In accordance with photosynthetic rate and antioxidative enzymes, water stress decreased the activities of key enzymes involving in N metabolism such as glutamate synthase and glutamate dehydrogenase, and photorespiratory key enzyme glycolate oxidase at low N. Concurrently, water stress increased nitrate content significantly at low N, but decreased nitrate content at moderate and high N. Contrary to nitrate, water stress increased proline content at moderate and high N. Our results suggest that N metabolism appears to be associated with the tolerance of photosynthesis to water stress in rice via affecting CO2 diffusion, antioxidant capacity, and osmotic adjustment.

  9. Training-induced adaptation in purine metabolism in high-level sprinters vs. triathletes.

    Science.gov (United States)

    Zielinski, Jacek; Kusy, Krzysztof

    2012-02-01

    The aim of this study was to assess the effect of training loads on metabolic response of purine derivatives in highly trained sprinters (10 men, age range 20-29 yr) in a 1-yr cycle, compared with endurance-training mode in triathletes (10 men, age range 21-28 yr). A four-time measurement of respiratory parameters, plasma hypoxanthine (Hx) concentration, and erythrocyte hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity was administered in four characteristic training phases (general, specific, competition, and transition). A considerably lower postexercise plasma concentration of Hx in sprinters (8.1-18.0 μmol/l) than in triathletes (14.1-24.9 μmol/l) was demonstrated in all training phases. In both groups, a significant decrease in plasma Hx concentration in the competition phase and a considerable increase in the transition phase were observed. It was found that the resting erythrocyte HGPRT activity increased in the competition period and declined in the transition phase. Sprinters showed higher HGPRT activity (58.5-71.8 nmol IMP·mg Hb(-1)·h(-1)) than triathletes (55.8-66.6 nmol IMP·mg Hb(-1)·h(-1)) in all examinations. The results suggest a more effective use of anaerobic metabolic energy sources induced by sprint training characterized by higher amount of exercise in the anaerobic lactacid and the nonlactacid zone. The changes in plasma Hx concentration and erythrocyte HGPRT activity might serve as sensitive metabolic indicators in the training control, especially in sprint-trained athletes. These parameters may provide information about the energetic status of the muscles in highly trained athletes in which no significant adaptation changes are detected by means of commonly acknowledged biochemical and physiological parameters.

  10. Carotenoid metabolic profiling and transcriptome-genome mining reveal functional equivalence among blue-pigmented copepods and appendicularia.

    Science.gov (United States)

    Mojib, Nazia; Amad, Maan; Thimma, Manjula; Aldanondo, Naroa; Kumaran, Mande; Irigoien, Xabier

    2014-06-01

    The tropical oligotrophic oceanic areas are characterized by high water transparency and annual solar radiation. Under these conditions, a large number of phylogenetically diverse mesozooplankton species living in the surface waters (neuston) are found to be blue pigmented. In the present study, we focused on understanding the metabolic and genetic basis of the observed blue phenotype functional equivalence between the blue-pigmented organisms from the phylum Arthropoda, subclass Copepoda (Acartia fossae) and the phylum Chordata, class Appendicularia (Oikopleura dioica) in the Red Sea. Previous studies have shown that carotenoid-protein complexes are responsible for blue coloration in crustaceans. Therefore, we performed carotenoid metabolic profiling using both targeted and nontargeted (high-resolution mass spectrometry) approaches in four different blue-pigmented genera of copepods and one blue-pigmented species of appendicularia. Astaxanthin was found to be the principal carotenoid in all the species. The pathway analysis showed that all the species can synthesize astaxanthin from β-carotene, ingested from dietary sources, via 3-hydroxyechinenone, canthaxanthin, zeaxanthin, adonirubin or adonixanthin. Further, using de novo assembled transcriptome of blue A. fossae (subclass Copepoda), we identified highly expressed homologous β-carotene hydroxylase enzymes and putative carotenoid-binding proteins responsible for astaxanthin formation and the blue phenotype. In blue O. dioica (class Appendicularia), corresponding putative genes were identified from the reference genome. Collectively, our data provide molecular evidences for the bioconversion and accumulation of blue astaxanthin-protein complexes underpinning the observed ecological functional equivalence and adaptive convergence among neustonic mesozooplankton. © 2014 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  11. Metabolic profiling of urine and blood plasma in rat models of drug addiction on the basis of morphine, methamphetamine, and cocaine-induced conditioned place preference.

    Science.gov (United States)

    Zaitsu, Kei; Miyawaki, Izuru; Bando, Kiyoko; Horie, Hiroshi; Shima, Noriaki; Katagi, Munehiro; Tatsuno, Michiaki; Bamba, Takeshi; Sato, Takako; Ishii, Akira; Tsuchihashi, Hitoshi; Suzuki, Koichi; Fukusaki, Eiichiro

    2014-02-01

    The metabolic profiles of urine and blood plasma in drug-addicted rat models based on morphine (MOR), methamphetamine (MA), and cocaine (COC)-induced conditioned place preference (CPP) were investigated. Rewarding effects induced by each drug were assessed by use of the CPP model. A mass spectrometry (MS)-based metabolomics approach was applied to urine and plasma of MOR, MA, and COC-addicted rats. In total, 57 metabolites in plasma and 70 metabolites in urine were identified by gas chromatography-MS. The metabolomics approach revealed that amounts of some metabolites, including tricarboxylic acid cycle intermediates, significantly changed in the urine of MOR-addicted rats. This result indicated that disruption of energy metabolism is deeply relevant to MOR addiction. In addition, 3-hydroxybutyric acid, L-tryptophan, cystine, and n-propylamine levels were significantly changed in the plasma of MOR-addicted rats. Lactose, spermidine, and stearic acid levels were significantly changed in the urine of MA-addicted rats. Threonine, cystine, and spermidine levels were significantly increased in the plasma of COC-addicted rats. In conclusion, differences in the metabolic profiles were suggestive of different biological states of MOR, MA, and COC addiction; these may be attributed to the different actions of the drugs on the brain reward circuitry and the resulting adaptation. In addition, the results showed possibility of predict the extent of MOR addiction by metabolic profiling. This is the first study to apply metabolomics to CPP models of drug addiction, and we demonstrated that metabolomics can be a multilateral approach to investigating the mechanism of drug addiction.

  12. Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy.

    Directory of Open Access Journals (Sweden)

    Ji Soo Choi

    Full Text Available The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB samples using high-resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA. Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.

  13. Effective long term adaptation and metabolic state regulation of ski-racers

    Directory of Open Access Journals (Sweden)

    A.S. Bakhareva

    2016-06-01

    Full Text Available Purpose: to scientifically substantiate effective mechanisms of organism’s bio-chemical adaptation of ski-racers in competition period with the help of lipid peroxidation indicators, oxidative modification of proteins and activity of hypothalamus pituitary adrenocortical system. Material: in the research 14 sportsmen of 18-25 years’ age (combined team of university with different level of sportsmanship participated. Assessment of free radical oxidation, anti-oxidant system, cortisol level was fulfilled with the help of indicators’ quantitative analysis by bio-chemical methods applied to blood serum samples. Results: it was found that in the basis of bio-chemical changes under intensive physical loads is increase of catabolic processes’ speed. Change of organism’s metabolic orientation of ski racers at optimal level results in working muscles’ energy supply improvement, increase of energy systems’ power and sports efficiency. Conclusions: Application of interval trainings at stages of preparation to special significant competitions results in expected adaptation and increase of sports efficiency. We also showed their effective role in ensuring long term reactions, conditioning high sports efficiency.

  14. Hominids adapted to metabolize ethanol long before human-directed fermentation.

    Science.gov (United States)

    Carrigan, Matthew A; Uryasev, Oleg; Frye, Carole B; Eckman, Blair L; Myers, Candace R; Hurley, Thomas D; Benner, Steven A

    2015-01-13

    Paleogenetics is an emerging field that resurrects ancestral proteins from now-extinct organisms to test, in the laboratory, models of protein function based on natural history and Darwinian evolution. Here, we resurrect digestive alcohol dehydrogenases (ADH4) from our primate ancestors to explore the history of primate-ethanol interactions. The evolving catalytic properties of these resurrected enzymes show that our ape ancestors gained a digestive dehydrogenase enzyme capable of metabolizing ethanol near the time that they began using the forest floor, about 10 million y ago. The ADH4 enzyme in our more ancient and arboreal ancestors did not efficiently oxidize ethanol. This change suggests that exposure to dietary sources of ethanol increased in hominids during the early stages of our adaptation to a terrestrial lifestyle. Because fruit collected from the forest floor is expected to contain higher concentrations of fermenting yeast and ethanol than similar fruits hanging on trees, this transition may also be the first time our ancestors were exposed to (and adapted to) substantial amounts of dietary ethanol.

  15. Metabolic profiling for detection of Staphylococcus aureus infection and antibiotic resistance.

    Directory of Open Access Journals (Sweden)

    Henrik Antti

    Full Text Available Due to slow diagnostics, physicians must optimize antibiotic therapies based on clinical evaluation of patients without specific information on causative bacteria. We have investigated metabolomic analysis of blood for the detection of acute bacterial infection and early differentiation between ineffective and effective antibiotic treatment. A vital and timely therapeutic difficulty was thereby addressed: the ability to rapidly detect treatment failures because of antibiotic-resistant bacteria. Methicillin-resistant Staphylococcus aureus (MRSA and methicillin-sensitive S. aureus (MSSA were used in vitro and for infecting mice, while natural MSSA infection was studied in humans. Samples of bacterial growth media, the blood of infected mice and of humans were analyzed with combined Gas Chromatography/Mass Spectrometry. Multivariate data analysis was used to reveal the metabolic profiles of infection and the responses to different antibiotic treatments. In vitro experiments resulted in the detection of 256 putative metabolites and mice infection experiments resulted in the detection of 474 putative metabolites. Importantly, ineffective and effective antibiotic treatments were differentiated already two hours after treatment start in both experimental systems. That is, the ineffective treatment of MRSA using cloxacillin and untreated controls produced one metabolic profile while all effective treatment combinations using cloxacillin or vancomycin for MSSA or MRSA produced another profile. For further evaluation of the concept, blood samples of humans admitted to intensive care with severe sepsis were analyzed. One hundred thirty-three putative metabolites differentiated severe MSSA sepsis (n = 6 from severe Escherichia coli sepsis (n = 10 and identified treatment responses over time. Combined analysis of human, in vitro, and mice samples identified 25 metabolites indicative of effective treatment of S. aureus sepsis. Taken together, this

  16. Study of phytohormone profile and oxidative metabolism as key process to identification of salinity response in tomato commercial genotypes.

    Science.gov (United States)

    de la Torre-González, Alejandro; Navarro-León, Eloy; Albacete, Alfonso; Blasco, Begoña; Ruiz, Juan M

    2017-09-01

    Climatic change, intensive agriculture, and worsening water quality induce abiotic stress conditions for plants. Among these factors, salinity stress is a limit factor for plant growth. Therefore, the purpose of this study was to analyze the phytohormones role and oxidative metabolism in response to salt stress of two genotypes of tomato cv. Grand Brix and cv. Marmande RAF, the crops were carried out in a growth chamber. Salinity stress reduces biomass and relative growth rate (RGR) in both genotypes, this effect being greater in cv. Marmande RAF. These results, together with main stress indicator response, the O 2 .- , indicate that cv. Marmande RAF is more sensitive to Saline stress. Grand Brix showed less oxidative stress, because it presented greater detoxification of the O 2 - , due to SOD enzyme activity induction and greater antioxidant capacity. Furthermore, Grand Brix has a better hormonal profile adapted to salt stress resistance, the accumulation of IAA, GA4 and CKs and their beneficial role against oxidative stress could make the difference between resistance and sensitivity to salt stress. On the other hand, a lower ACC concentration, ethylene precursor, combined with a greater O 2 .- detoxification in the cv. Grand Brix could play a fundamental role in tolerance to saline stress. Besides, an increase in ABA levels promotes better stomatal closure, better photosynthesis control and a lower rate of water loss. This data could be essential to select plants with greater resistance to saline stress. Copyright © 2017. Published by Elsevier GmbH.

  17. Proteomic profiling of the effect of metabolic acidosis on the apical membrane of the proximal convoluted tubule

    Science.gov (United States)

    Walmsley, Scott J.; Freund, Dana M.

    2012-01-01

    The physiological response to the onset of metabolic acidosis requires pronounced changes in renal gene expression. Adaptations within the proximal convoluted tubule support the increased extraction of plasma glutamine and the increased synthesis and transport of glucose and of NH4+ and HCO3− ions. Many of these adaptations involve proteins associated with the apical membrane. To quantify the temporal changes in these proteins, proteomic profiling was performed using brush-border membrane vesicles isolated from proximal convoluted tubules (BBMVPCT) that were purified from normal and acidotic rats. This preparation is essentially free of contaminating apical membranes from other renal cortical cells. The analysis identified 298 proteins, 26% of which contained one or more transmembrane domains. Spectral counts were used to assess changes in protein abundance. The onset of acidosis produced a twofold, but transient, increase in the Na+-dependent glucose transporter and a more gradual, but sustained, increase (3-fold) in the Na+-dependent lactate transporter. These changes were associated with the loss of glycolytic and gluconeogenic enzymes that are contained in the BBMVPCT isolated from normal rats. In addition, the levels of γ-glutamyltranspeptidase increased twofold, while transporters that participate in the uptake of neutral amino acids, including glutamine, were decreased. These changes could facilitate the deamidation of glutamine within the tubular lumen. Finally, pronounced increases were also observed in the levels of DAB2 (3-fold) and myosin 9 (7-fold), proteins that may participate in endocytosis of apical membrane proteins. Western blot analysis and accurate mass and time analyses were used to validate the spectral counting. PMID:22357915

  18. Profiles of the biosynthesis and metabolism of pyridine nucleotides in potatoes (Solanum tuberosum L.).

    Science.gov (United States)

    Katahira, Riko; Ashihara, Hiroshi

    2009-12-01

    As part of a research program on nucleotide metabolism in potato tubers (Solanum tuberosum L.), profiles of pyridine (nicotinamide) metabolism were examined based on the in situ metabolic fate of radio-labelled precursors and the in vitro activities of enzymes. In potato tubers, [(3)H]quinolinic acid, which is an intermediate of de novo pyridine nucleotide synthesis, and [(14)C]nicotinamide, a catabolite of NAD, were utilised for pyridine nucleotide synthesis. The in situ tracer experiments and in vitro enzyme assays suggest the operation of multiple pyridine nucleotide cycles. In addition to the previously proposed cycle consisting of seven metabolites, we found a new cycle that includes newly discovered nicotinamide riboside deaminase which is also functional in potato tubers. This cycle bypasses nicotinamide and nicotinic acid; it is NAD --> nicotinamide mononucleotide --> nicotinamide riboside --> nicotinic acid riboside --> nicotinic acid mononucleotide --> nicotinic acid adenine dinucleotide --> NAD. Degradation of the pyridine ring was extremely low in potato tubers. Nicotinic acid glucoside is formed from nicotinic acid in potato tubers. Comparative studies of [carboxyl-(14)C]nicotinic acid metabolism indicate that nicotinic acid is converted to nicotinic acid glucoside in all organs of potato plants. Trigonelline synthesis from [carboxyl-(14)C]nicotinic acid was also found. Conversion was greater in green parts of plants, such as leaves and stem, than in underground parts of potato plants. Nicotinic acid utilised for the biosynthesis of these conjugates seems to be derived not only from the pyridine nucleotide cycle, but also from the de novo synthesis of nicotinic acid mononucleotide.

  19. Metabolic Profiling Reveals Effects of Age, Sexual Development and Neutering in Plasma of Young Male Cats.

    Directory of Open Access Journals (Sweden)

    David Allaway

    Full Text Available Neutering is a significant risk factor for obesity in cats. The mechanisms that promote neuter-associated weight gain are not well understood but following neutering, acute changes in energy expenditure and energy consumption have been observed. Metabolic profiling (GC-MS and UHPLC-MS-MS was used in a longitudinal study to identify changes associated with age, sexual development and neutering in male cats fed a nutritionally-complete dry diet to maintain an ideal body condition score. At eight time points, between 19 and 52 weeks of age, fasted blood samples were taken from kittens neutered at either 19 weeks of age (Early Neuter (EN, n = 8 or at 31 weeks of age (Conventional Neuter (CN, n = 7. Univariate and multivariate analyses were used to compare plasma metabolites (n = 370 from EN and CN cats. Age was the primary driver of variance in the plasma metabolome, including a developmental change independent of neuter group between 19 and 21 weeks in lysolipids and fatty acid amides. Changes associated with sexual development and its subsequent loss were also observed, with differences at some time points observed between EN and CN cats for 45 metabolites (FDR p<0.05. Pathway Enrichment Analysis also identified significant effects in 20 pathways, dominated by amino acid, sterol and fatty acid metabolism. Most changes were interpretable within the context of male sexual development, and changed following neutering in the CN group. Felinine metabolism in CN cats was the most significantly altered pathway, increasing during sexual development and decreasing acutely following neutering. Felinine is a testosterone-regulated, felid-specific glutathione derivative secreted in urine. Alterations in tryptophan, histidine and tocopherol metabolism observed in peripubertal cats may be to support physiological functions of glutathione following diversion of S-amino acids for urinary felinine secretion.

  20. Endobacteria affect the metabolic profile of their host Gigaspora margarita, an arbuscular mycorrhizal fungus.

    Science.gov (United States)

    Salvioli, Alessandra; Chiapello, Marco; Fontaine, Joel; Hadj-Sahraoui, Anissa Lounes; Grandmougin-Ferjani, Anne; Lanfranco, Luisa; Bonfante, Paola

    2010-08-01

    The aim of this paper was to understand whether the endobacterium identified as Candidatus Glomeribacter gigasporarum has an effect on the biology of its host, the arbuscular mycorrhizal fungus Gigaspora margarita, through the study of the modifications induced on the fungal proteome and lipid profile. The availability of G. margarita cured spores (i.e. spores that do not contain bacteria), represented a crucial tool to enable the comparison between two fungal homogeneous populations in the presence and the absence of the bacterial components. Our results demonstrate that the endobacterial presence leads to a modulation of fungal protein expression in all the different conditions we tested (quiescent, germinating and strigolactone-elicited germinating spores), and in particular after treatment with a strigolactone analogue. The fungal fatty acid profile resulted to be modified both quantitatively and qualitatively in the absence of endobacteria, being fatty acids less abundant in the cured spores. The results offer one of the first comparative metabolic studies of an AM fungus investigated under different physiological conditions, reveal that endobacteria have an important impact on the host fungal activity, influencing both protein expression and lipid profile, and suggest that the bacterial absence is perceived by G. margarita as a stimulus which activates stress-responsive proteins. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

  1. The Cinderella story of metabolic profiling: does metabolomics get to go to the functional genomics ball?

    Science.gov (United States)

    Griffin, Julian L

    2005-01-01

    To date most global approaches to functional genomics have centred on genomics, transcriptomics and proteomics. However, since a number of high-profile publications, interest in metabolomics, the global profiling of metabolites in a cell, tissue or organism, has been rapidly increasing. A range of analytical techniques, including 1H NMR spectroscopy, gas chromatography–mass spectrometry (GC–MS), liquid chromatography–mass spectrometry (LC–MS), Fourier Transform mass spectrometry (FT–MS), high performance liquid chromatography (HPLC) and electrochemical array (EC-array), are required in order to maximize the number of metabolites that can be identified in a matrix. Applications have included phenotyping of yeast, mice and plants, understanding drug toxicity in pharmaceutical drug safety assessment, monitoring tumour treatment regimes and disease diagnosis in human populations. These successes are likely to be built on as other analytical and bioinformatic approaches are developed to fully exploit the information obtained in metabolic profiles. To assist in this process, databases of metabolomic data will be necessary to allow the passage of information between laboratories. In this prospective review, the capabilities of metabolomics in the field of medicine will be assessed in an attempt to predict the impact this ‘Cinderella approach’ will have at the ‘functional genomic ball’. PMID:16553314

  2. Thermodynamically based profiling of drug metabolism and drug-drug metabolic interactions: a case study of acetaminophen and ethanol toxic interaction.

    Science.gov (United States)

    Yang, Feng; Beard, Daniel A

    2006-03-20

    Drug-drug metabolic interactions can result in unwanted side effects, including reduced drug efficacy and formation of toxic metabolic intermediates. In this work, thermodynamic constraints on non-equilibrium metabolite concentrations are used to reveal the biochemical interactions between the metabolic pathways of ethanol and acetaminophen (N-acetyl-p-aminophenol), two drugs known to interact unfavorably. It is known that many reactions of these pathways are coupled to the central energy metabolic reactions through a number of metabolites and the cellular redox potential. Based on these observations, a metabolic network model has been constructed and a database of thermodynamic properties for all participating metabolites and reactions has been compiled. Constraint-based computational analysis of the feasible metabolite concentrations reveals that the non-toxic pathways for APAP metabolism and the pathway for detoxifying N-acetyl-p-benzoquinoneimine (NAPQI) are inhibited by network interactions with ethanol metabolism. These results point to the potential utility of thermodynamically based profiling of metabolic network interactions in screening of drug candidates and analysis of potential toxicity.

  3. Assessment of epicardial fat volume and myocardial triglyceride content in severely obese subjects: relationship to metabolic profile, cardiac function and visceral fat

    National Research Council Canada - National Science Library

    Gaborit, B; Kober, F; Jacquier, A; Moro, P J; Cuisset, T; Boullu, S; Dadoun, F; Alessi, M-C; Morange, P; Clément, K; Bernard, M; Dutour, A

    2012-01-01

    To assess epicardial fat volume (EFV), myocardial TG content (MTGC) and metabolic profile in severely obese patients, and to determine whether ectopic fat depots are linked to metabolic disorders or myocardial function...

  4. 1H NMR-based profiling reveals differential immune-metabolic networks during influenza virus infection in obese mice.

    Directory of Open Access Journals (Sweden)

    J Justin Milner

    Full Text Available Obese individuals are at greater risk for death from influenza virus infection. Paralleling human evidence, obese mice are also more susceptible to influenza infection mortality. However, the underlying mechanisms driving greater influenza severity in the obese remain unclear. Metabolic profiling has been utilized in infectious disease models to enhance prognostic or diagnostic methods, and to gain insight into disease pathogenesis by providing a more global picture of dynamic infection responses. Herein, metabolic profiling was used to develop a deeper understanding of the complex processes contributing to impaired influenza protection in obese mice and to facilitate generation of new explanatory hypotheses. Diet-induced obese and lean mice were infected with influenza A/Puerto Rico/8/34. 1H nuclear magnetic resonance-based metabolic profiling of urine, feces, lung, liver, mesenteric white adipose tissue, bronchoalveolar lavage fluid and serum revealed distinct metabolic signatures in infected obese mice, including perturbations in nucleotide, vitamin, ketone body, amino acid, carbohydrate, choline and lipid metabolic pathways. Further, metabolic data was integrated with immune analyses to obtain a more comprehensive understanding of potential immune-metabolic interactions. Of interest, uncovered metabolic signatures in urine and feces allowed for discrimination of infection status in both lean and obese mice at an early influenza time point, which holds prognostic and diagnostic implications for this methodology. These results confirm that obesity causes distinct metabolic perturbations during influenza infection and provide a basis for generation of new hypotheses and use of this methodology in detection of putative biomarkers and metabolic patterns to predict influenza infection outcome.

  5. Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions

    Directory of Open Access Journals (Sweden)

    Fenja Klevenhusen

    2015-10-01

    Full Text Available Left displaced abomasum (LDA is a severe metabolic disease of cattle with a strong negative impact on production efficiency of dairy farms. Metabolic and inflammatory alterations associated with this disease have been reported in earlier studies, conducted mostly in large dairy farms. This research aimed to: (1 evaluate metabolic and inflammatory responses in dairy cows affected by LDA in small-scaled dairy farms; and (2 establish an Animals 2015, 5 1022 association between lactation number and milk production with the outcome of metabolic variables. The cows with LDA had lower serum calcium (Ca, but greater concentrations of non-esterified fatty acids (NEFA and beta-hydroxy-butyrate (BHBA, in particular when lactation number was >2. Cows with LDA showed elevated levels of aspartate aminotransferase, glutamate dehydrogenase, and serum amyloid A (SAA, regardless of lactation number. In addition, this study revealed strong associations between milk yield and the alteration of metabolic profile but not with inflammation in the sick cows. Results indicate metabolic alterations, liver damage, and inflammation in LDA cows kept under small-scale farm conditions. Furthermore, the data suggest exacerbation of metabolic profile and Ca metabolism but not of inflammation and liver health with increasing lactation number and milk yield in cows affected by LDA.

  6. Liver morphometrics and metabolic blood profile across divergent phenotypes for feed efficiency in the bovine.

    Science.gov (United States)

    Montanholi, Yuri Regis; Haas, Livia Sadocco; Swanson, Kendall Carl; Coomber, Brenda Lynn; Yamashiro, Shigeto; Miller, Stephen Paul

    2017-04-26

    Feed costs are a major expense in the production of beef cattle. Individual variation in the efficiency of feed utilization may be evident through feed efficiency-related phenotypes such as those related to major energetic sinks. Our objectives were to assess the relationships between feed efficiency with liver morphometry and metabolic blood profile in feedlot beef cattle. Two populations (A = 112 and B = 45) of steers were tested for feed efficiency. Blood from the 12 most (efficient) and 12 least feed inefficient (inefficient) steers from population A was sampled hourly over the circadian period. Blood plasma samples were submitted for analysis on albumin, aspartate aminotransferase, γ-glutamyl transpeptidase urea, cholesterol, creatinine, alkaline phosphatase, creatine kinase, lipase, carbon dioxide, β-hydroxybutyrate, acetate and bile acids. Liver tissue was also harvested from 24 steers that were blood sampled from population A and the 10 steers with divergent feed efficiency in each tail of population B was sampled for microscopy at slaughter. Photomicroscopy images were taken using the portal triad and central vein as landmarks. Histological quantifications included cross-sectional hepatocyte perimeter and area, hepatocyte nuclear area and nuclei area as proportion of the hepatocyte area. The least square means comparison between efficient and inefficient steers for productive performance and liver morphometry and for blood analytes data were analyzed using general linear model and mixed model procedures of SAS, respectively. No differences were observed for liver weight; however, efficient steers had larger hepatocyte (i.e. hepatocyte area at the porta triad 323.31 vs. 286.37 µm2) and nuclei dimensions at portal triad and central vein regions, compared with inefficient steers. The metabolic profile indicated efficient steers had lower albumin (36.18 vs. 37.65 g/l) and cholesterol (2.62 vs. 3.05 mmol/l) and higher creatinine (118.59 vs. 110.50

  7. Metabolic profiles of male meat eaters, fish eaters, vegetarians, and vegans from the EPIC-Oxford cohort12

    Science.gov (United States)

    Schmidt, Julie A; Rinaldi, Sabina; Ferrari, Pietro; Carayol, Marion; Achaintre, David; Scalbert, Augustin; Cross, Amanda J; Gunter, Marc J; Fensom, Georgina K; Appleby, Paul N; Key, Timothy J; Travis, Ruth C

    2015-01-01

    Background: Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic profiles than meat eaters. Objective: We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism between male meat eaters, fish eaters, vegetarians, and vegans from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. Design: In this cross-sectional study, concentrations of metabolites were measured by mass spectrometry in plasma from 379 men categorized according to their diet group. Differences in mean metabolite concentrations across diet groups were tested by using ANOVA, and a false discovery rate–controlling procedure was used to account for multiple testing. Principal component analysis was used to investigate patterns in metabolic profiles. Results: Concentrations of 79% of metabolites differed significantly by diet group. In the vast majority of these cases, vegans had the lowest concentration, whereas meat eaters most often had the highest concentrations of the acylcarnitines, glycerophospholipids, and sphingolipids, and fish eaters or vegetarians most often had the highest concentrations of the amino acids and a biogenic amine. A clear separation between patterns in the metabolic profiles of the 4 diet groups was seen, with vegans being noticeably different from the other groups because of lower concentrations of some glycerophospholipids and sphingolipids. Conclusions: Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of

  8. Metabolic profiles of male meat eaters, fish eaters, vegetarians, and vegans from the EPIC-Oxford cohort.

    Science.gov (United States)

    Schmidt, Julie A; Rinaldi, Sabina; Ferrari, Pietro; Carayol, Marion; Achaintre, David; Scalbert, Augustin; Cross, Amanda J; Gunter, Marc J; Fensom, Georgina K; Appleby, Paul N; Key, Timothy J; Travis, Ruth C

    2015-12-01

    Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic profiles than meat eaters. We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism between male meat eaters, fish eaters, vegetarians, and vegans from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. In this cross-sectional study, concentrations of metabolites were measured by mass spectrometry in plasma from 379 men categorized according to their diet group. Differences in mean metabolite concentrations across diet groups were tested by using ANOVA, and a false discovery rate-controlling procedure was used to account for multiple testing. Principal component analysis was used to investigate patterns in metabolic profiles. Concentrations of 79% of metabolites differed significantly by diet group. In the vast majority of these cases, vegans had the lowest concentration, whereas meat eaters most often had the highest concentrations of the acylcarnitines, glycerophospholipids, and sphingolipids, and fish eaters or vegetarians most often had the highest concentrations of the amino acids and a biogenic amine. A clear separation between patterns in the metabolic profiles of the 4 diet groups was seen, with vegans being noticeably different from the other groups because of lower concentrations of some glycerophospholipids and sphingolipids. Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of glycerophospholipids and sphingolipids in vegans.

  9. Metabolic Profiling and Antioxidant Assay of Metabolites from Three Radish Cultivars (Raphanus sativus).

    Science.gov (United States)

    Park, Chang Ha; Baskar, Thanislas Bastin; Park, Soo-Yun; Kim, Sun-Ju; Valan Arasu, Mariadhas; Al-Dhabi, Naif Abdullah; Kim, Jae Kwang; Park, Sang Un

    2016-01-28

    A total of 13 anthocyanins and 33 metabolites; including organic acids, phenolic acids, amino acids, organic compounds, sugar acids, sugar alcohols, and sugars, were profiled in three radish cultivars by using high-performance liquid chromatography (HPLC) and gas chromatography time-of-flight mass spectrometry (GC-TOFMS)-based metabolite profiling. Total phenolics and flavonoids and their in vitro antioxidant activities were assessed. Pelargonidins were found to be the major anthocyanin in the cultivars studied. The cultivar Man Tang Hong showed the highest level of anthocyanins (1.89 ± 0.07 mg/g), phenolics (0.0664 ± 0.0033 mg/g) and flavonoids (0.0096 ± 0.0004 mg/g). Here; the variation of secondary metabolites in the radishes is described, as well as their association with primary metabolites. The low-molecular-weight hydrophilic metabolite profiles were subjected to principal component analysis (PCA), hierarchical clustering analysis (HCA), Pearson's correlation analysis. PCA fully distinguished the three radish cultivars tested. The polar metabolites were strongly correlated between metabolites that participate in the TCA cycle. The chemometrics results revealed that TCA cycle intermediates and free phenolic acids as well as anthocyanins were higher in the cultivar Man Tang Hong than in the others. Furthermore; superoxide radical scavenging activities and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging were investigated to elucidate the antioxidant activity of secondary metabolites in the cultivars. Man Tang Hong showed the highest superoxide radical scavenging activity (68.87%) at 1000 μg/mL, and DPPH activity (20.78%), followed by Seo Ho and then Hong Feng No. 1. The results demonstrate that GC-TOFMS-based metabolite profiling, integrated with chemometrics, is an applicable method for distinguishing phenotypic variation and determining biochemical reactions connecting primary and secondary metabolism. Therefore; this study might provide

  10. Adaptive NetworkProfiler for Identifying Cancer Characteristic-Specific Gene Regulatory Networks.

    Science.gov (United States)

    Park, Heewon; Shimamura, Teppei; Imoto, Seiya; Miyano, Satoru

    2017-10-20

    There is currently much discussion about sample (patient)-specific gene regulatory network identification, since the efficiently constructed sample-specific gene networks lead to effective personalized cancer therapy. Although statistical approaches have been proposed for inferring gene regulatory networks, the methods cannot reveal sample-specific characteristics because the existing methods, such as an L1-type regularization, provide averaged results for all samples. Thus, we cannot reveal sample-specific characteristics in transcriptional regulatory networks. To settle on this issue, the NetworkProfiler was proposed based on the kernel-based L1-type regularization. The NetworkProfiler imposes a weight on each sample based on the Gaussian kernal function for controlling effect of samples on modeling a target sample, where the amount of weight depends on similarity of cancer characteristics between samples. The method, however, cannot perform gene regulatory network identification well for a target sample in a sparse region (i.e., for a target sample, there are only a few samples having a similar characteristic of the target sample, where the characteristic is considered as a modulator in sample-specific gene network construction), since a constant bandwidth in the Gaussian kernel function cannot effectively group samples for modeling a target sample in sparse region. The cancer characteristics, such as an anti-cancer drug sensitivity, are usually nonuniformly distributed, and thus modeling for samples in a sparse region is also a crucial issue. We propose a novel kernel-based L1-type regularization method based on a modified k-nearest neighbor (KNN)-Gaussian kernel function, called an adaptive NetworkProfiler. By using the modified KNN-Gaussian kernel function, our method provides robust results against the distribution of modulators, and properly groups samples according to a cancer characteristic for sample-specific analysis. Furthermore, we propose a sample

  11. Metabolic Profiling of Chicken Embryos Exposed to Perfluorooctanoic Acid (PFOA and Agonists to Peroxisome Proliferator-Activated Receptors.

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    Anna Mattsson

    Full Text Available Untargeted metabolic profiling of body fluids in experimental animals and humans exposed to chemicals may reveal early signs of toxicity and indicate toxicity pathways. Avian embryos develop separately from their mothers, which gives unique possibilities to study effects of chemicals during embryo development with minimal confounding factors from the mother. In this study we explored blood plasma and allantoic fluid from chicken embryos as matrices for revealing metabolic changes caused by exposure to chemicals during embryonic development. Embryos were exposed via egg injection on day 7 to the environmental pollutant perfluorooctanoic acid (PFOA, and effects on the metabolic profile on day 12 were compared with those caused by GW7647 and rosiglitazone, which are selective agonists to peroxisome-proliferator activated receptor α (PPARα and PPARγ, respectively. Analysis of the metabolite concentrations from allantoic fluid by Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA showed clear separation between the embryos exposed to GW7647, rosiglitazone, and vehicle control, respectively. In blood plasma only GW7647 caused a significant effect on the metabolic profile. PFOA induced embryo mortality and increased relative liver weight at the highest dose. Sublethal doses of PFOA did not significantly affect the metabolic profile in either matrix, although single metabolites appeared to be altered. Neonatal mortality by PFOA in the mouse has been suggested to be mediated via activation of PPARα. However, we found no similarity in the metabolite profile of chicken embryos exposed to PFOA with those of embryos exposed to PPAR agonists. This indicates that PFOA does not activate PPAR pathways in our model at concentrations in eggs and embryos well above those found in wild birds. The present study suggests that allantoic fluid and plasma from chicken embryos are useful and complementary matrices for exploring effects on the metabolic

  12. Metabolic modelling in a dynamic evolutionary framework predicts adaptive diversification of bacteria in a long-term evolution experiment.

    Science.gov (United States)

    Großkopf, Tobias; Consuegra, Jessika; Gaffé, Joël; Willison, John C; Lenski, Richard E; Soyer, Orkun S; Schneider, Dominique

    2016-08-20

    Predicting adaptive trajectories is a major goal of evolutionary biology and useful for practical applications. Systems biology has enabled the development of genome-scale metabolic models. However, analysing these models via flux balance analysis (FBA) cannot predict many evolutionary outcomes including adaptive diversification, whereby an ancestral lineage diverges to fill multiple niches. Here we combine in silico evolution with FBA and apply this modelling framework, evoFBA, to a long-term evolution experiment with Escherichia coli. Simulations predicted the adaptive diversification that occurred in one experimental population and generated hypotheses about the mechanisms that promoted coexistence of the diverged lineages. We experimentally tested and, on balance, verified these mechanisms, showing that diversification involved niche construction and character displacement through differential nutrient uptake and altered metabolic regulation. The evoFBA framework represents a promising new way to model biochemical evolution, one that can generate testable predictions about evolutionary and ecosystem-level outcomes.

  13. Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments.

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    Anubhav Srivastava

    2016-12-01

    Full Text Available Malaria parasites (Plasmodium spp. encounter markedly different (nutritional environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages. We show that glutamine serves as the predominant input into TCA metabolism in both asexual and sexual blood stages and is important for complete male gametogenesis. Glutamine catabolism, as well as key reactions in intermediary metabolism and CoA synthesis are also essential for ookinete to oocyst transition in the mosquito. These data extend our knowledge of Plasmodium metabolism and point towards possible targets for transmission-blocking intervention strategies. Furthermore, they highlight significant metabolic differences between Plasmodium species which are not easily anticipated based on genomics or transcriptomics studies and underline the importance of integration of metabolomics data with other platforms in order to better inform drug discovery and design.

  14. Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments.

    Science.gov (United States)

    Srivastava, Anubhav; Philip, Nisha; Hughes, Katie R; Georgiou, Konstantina; MacRae, James I; Barrett, Michael P; Creek, Darren J; McConville, Malcolm J; Waters, Andrew P

    2016-12-01

    Malaria parasites (Plasmodium spp.) encounter markedly different (nutritional) environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA) metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages. We show that glutamine serves as the predominant input into TCA metabolism in both asexual and sexual blood stages and is important for complete male gametogenesis. Glutamine catabolism, as well as key reactions in intermediary metabolism and CoA synthesis are also essential for ookinete to oocyst transition in the mosquito. These data extend our knowledge of Plasmodium metabolism and point towards possible targets for transmission-blocking intervention strategies. Furthermore, they highlight significant metabolic differences between Plasmodium species which are not easily anticipated based on genomics or transcriptomics studies and underline the importance of integration of metabolomics data with other platforms in order to better inform drug discovery and design.

  15. The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake.

    Science.gov (United States)

    Hopkins, M; Gibbons, C; Caudwell, P; Hellström, P M; Näslund, E; King, N A; Finlayson, G; Blundell, J E

    2014-05-01

    A decline in resting energy expenditure (REE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (EI). Thirty overweight and obese women (body mass index (BMI)=30.6±3.6 kg/m(2)) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, EI and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured REE was also calculated post intervention (MApost), with REE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI=31.0±3.9 kg/m(2)). Although mean predicted and measured REE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in REE (-102.9±77.5 kcal per day). MApost was associated with the change in leptin (r=0.47; P=0.04), and the change in resting fat (r=0.52; P=0.01) and carbohydrate oxidation (r=-0.44; P=0.02). Furthermore, MApost was also associated with the change in EI following EX (r=-0.44; P=0.01). Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in REE also experienced an upregulation in EI, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.

  16. Metabolic blood profile of beef heifers during oestrous and non-oestrous states.

    Science.gov (United States)

    Crane, E M; Munro, J C; Bourgon, S L; Diel de Amorim, M; Ventura, R; Fredeen, A H; Montanholi, Y R

    2016-10-01

    Haematological metabolic profiles in heifers could contribute to the development of proxies for oestrous detection and provide clues to further characterize biological changes during oestrus. One hundred and seven beef heifers were observed for oestrous behaviour twice daily for 124 days. Feed intake and productive performance (body weight and composition) traits were measured, and feed efficiency was determined using residual feed intake (kg DM/day). Blood plasma samples were collected when signs of oestrus were observed and every 30 ± 2 days. Heifers were considered in oestrus (n = 71) when plasma progesterone concentrations were Feed efficient heifers had greater levels of AST, cholesterol and GGT than inefficient heifers. Blood plasma parameters may be complementary to oestrous detection upon further validation; effects of age, feed efficiency, body size and body composition should be considered to optimize this haematological assessment. © 2016 Blackwell Verlag GmbH.

  17. Characterisation of metabolic profile of banana genotypes, aiming at biofortified Musa spp. cultivars.

    Science.gov (United States)

    Borges, Cristine Vanz; Amorim, Vanusia Batista de Oliveira; Ramlov, Fernanda; Ledo, Carlos Alberto da Silva; Donato, Marcela; Maraschin, Marcelo; Amorim, Edson Perito

    2014-02-15

    The banana is an important, widely consumed fruit, especially in areas of rampant undernutrition. Twenty-nine samples were analysed, including 9 diploids, 13 triploids and 7 tetraploids, in the Active Germplasm Bank, at Embrapa Cassava & Fruits, to evaluate the bioactive compounds. The results of this study reveal the presence of a diversity of bioactive compounds, e.g., catechins; they are phenolic compounds with high antioxidant potential and antitumour activity. In addition, accessions with appreciable amounts of pVACs were identified, especially compared with the main cultivars that are currently marketed. The ATR-FTIR, combined with principal components analysis, identified accessions with distinct metabolic profiles in the fingerprint regions of compounds important for human health. Likewise, starch fraction characterisation allowed discrimination of accessions according to their physical, chemical, and functional properties. The results of this study demonstrate that the banana has functional characteristics endowing it with the potential to promote human health. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Metabolic profile of the bioactive compounds of burdock (Arctium lappa) seeds, roots and leaves.

    Science.gov (United States)

    Ferracane, Rosalia; Graziani, Giulia; Gallo, Monica; Fogliano, Vincenzo; Ritieni, Alberto

    2010-01-20

    In this work the bioactive metabolic profile, the antioxidant activity and total phenolic content of burdock (Arctium lappa) seeds, leaves and roots were obtained. TEAC values and total phenolic content for hydro-alcoholic extracts of burdock ranged from 67.39 to 1.63 micromol Trolox equivalent/100g dry weight (DW), and from 2.87 to 45 g of gallic acid equivalent/100g DW, respectively. Phytochemical compounds were analyzed by liquid chromatography coupled to electrospray tandem mass spectrometry (LC/MS/MS) in negative mode. The main compounds of burdock extracts were caffeoylquinic acid derivatives, lignans (mainly arctiin) and various flavonoids. The occurrence of some phenolic acids (caffeic acid, chlorogenic acid and cynarin) in burdock seeds; arctiin, luteolin and quercetin rhamnoside in burdock roots; phenolic acids, quercetin, quercitrin and luteolin in burdock leaves was reported for the first time.

  19. Cross-platform metabolic profiling: application to the aquatic model organism Lymnaea stagnalis.

    Science.gov (United States)

    Tufi, Sara; Lamoree, Marja H; De Boer, Jacob; Leonards, Pim E G

    2015-03-01

    The freshwater pond snail Lymnaea stagnalis is used in several studies on molecular and behavioral neurobiology and ecotoxicology showing its successful application as a model organism. In the present study, a cross-platform metabolomic approach has been evaluated to characterize the organ molecular phenotypes of L. stagnalis central nervous system (CNS), digestive gland (DG), and albumen gland (AG). Two types of tissue disruption methods were evaluated of which beads beating was the preferred method. To obtain a broad picture of the hydrophilic and lipophilic metabolome, two complementary analytical platforms have been employed: liquid chromatography (LC) and gas chromatography (GC) coupled to high-resolution mass spectrometry. Furthermore, to increase the power to separate small polar metabolites, hydrophilic interaction liquid chromatography (HILIC) was applied. The analytical platform performances have been evaluated based on the metabolome coverage, number of molecular features, reproducibility, and multivariate data analysis (MVDA) clustering. This multiplatform approach is a starting point for future global metabolic profiling applications on L. stagnalis.

  20. An Inducible Operon Is Involved in Inulin Utilization in Lactobacillus plantarum Strains, as Revealed by Comparative Proteogenomics and Metabolic Profiling.

    Science.gov (United States)

    Buntin, Nirunya; Hongpattarakere, Tipparat; Ritari, Jarmo; Douillard, François P; Paulin, Lars; Boeren, Sjef; Shetty, Sudarshan A; de Vos, Willem M

    2017-01-15

    The draft genomes of Lactobacillus plantarum strains isolated from Asian fermented foods, infant feces, and shrimp intestines were sequenced and compared to those of well-studied strains. Among 28 strains of L. plantarum, variations in the genomic features involved in ecological adaptation were elucidated. The genome sizes ranged from approximately 3.1 to 3.5 Mb, of which about 2,932 to 3,345 protein-coding sequences (CDS) were predicted. The food-derived isolates contained a higher number of carbohydrate metabolism-associated genes than those from infant feces. This observation correlated to their phenotypic carbohydrate metabolic profile, indicating their ability to metabolize the largest range of sugars. Surprisingly, two strains (P14 and P76) isolated from fermented fish utilized inulin. β-Fructosidase, the inulin-degrading enzyme, was detected in the supernatants and cell wall extracts of both strains. No activity was observed in the cytoplasmic fraction, indicating that this key enzyme was either membrane-bound or extracellularly secreted. From genomic mining analysis, a predicted inulin operon of fosRABCDXE, which encodes β-fructosidase and many fructose transporting proteins, was found within the genomes of strains P14 and P76. Moreover, pts1BCA genes, encoding sucrose-specific IIBCA components involved in sucrose transport, were also identified. The proteomic analysis revealed the mechanism and functional characteristic of the fosRABCDXE operon involved in the inulin utilization of L. plantarum The expression levels of the fos operon and pst genes were upregulated at mid-log phase. FosE and the LPXTG-motif cell wall anchored β-fructosidase were induced to a high abundance when inulin was present as a carbon source. Inulin is a long-chain carbohydrate that may act as a prebiotic, which provides many health benefits to the host by selectively stimulating the growth and activity of beneficial bacteria in the colon. While certain lactobacilli can catabolize

  1. Functional genomic and metabolic studies of the adaptations of a prominent adult human gut symbiont, Bacteroides thetaiotaomicron, to the suckling period.

    Science.gov (United States)

    Bjursell, Magnus K; Martens, Eric C; Gordon, Jeffrey I

    2006-11-24

    The adult human gut microbiota is dominated by two divisions of Bacteria, the Bacteroidetes and the Firmicutes. Assembly of this community begins at birth through processes that remain largely undefined. In this report, we examine the adaptations of Bacteroides thetaiotaomicron, a prominent member of the adult distal intestinal microbiota, during the suckling and weaning periods. Germ-free NMRI mice were colonized at birth from their gnotobiotic mothers, who harbored this anaerobic Gram-negative saccharolytic bacterium. B. thetaiotaomicron was then harvested from the ceca of these hosts during the suckling period (postnatal day 17) and after weaning (postnatal day 30). Whole genome transcriptional profiles were obtained at these two time points using custom B. thetaiotaomicron GeneChips. Transcriptome-based in silico reconstructions of bacterial metabolism and gas chromatography-mass spectrometry and biochemical assays of carbohydrate utilization in vivo indicated that in the suckling gut B. thetaiotaomicron prefers host-derived polysaccharides, as well as mono- and oligosaccharides present in mother's milk. After weaning, B. thetaiotaomicron expands its metabolism to exploit abundant, plant-derived dietary polysaccharides. The bacterium's responses to postnatal alterations in its nutrient landscape involve expression of gene clusters encoding environmental sensors, outer membrane proteins involved in binding and import of glycans, and glycoside hydrolases. These expression changes are interpreted in light of a phylogenetic analysis that revealed unique expansions of related polysaccharide utilization loci in three human alimentary tract-associated Bacteroidetes, expansions that likely reflect the evolutionary adaptations of these species to different nutrient niches.

  2. Murine Cyp3a knockout chimeric mice with humanized liver: prediction of the metabolic profile of nefazodone in humans.

    Science.gov (United States)

    Nakada, Naoyuki; Kawamura, Akio; Kamimura, Hidetaka; Sato, Koya; Kazuki, Yasuhiro; Kakuni, Masakazu; Ohbuchi, Masato; Kato, Kota; Tateno, Chise; Oshimura, Mitsuo; Usui, Takashi

    2016-01-01

    Chimeric mice with humanized livers (PXB mice) are used to investigate the metabolism and pharmacokinetics of drugs in humans. However, residual murine enzymatic activities derived from the liver and the presence of mouse small intestinal metabolism can hamper the prediction of human drug metabolism. Recently murine Cytochrome P450 3a gene knockout chimeric mice with humanized livers (Cyp3a KO CM) were developed. To evaluate the prediction of drug metabolism, nefazodone (NEF) was administered orally at 10 mg/kg to the following mouse strains: Cyp3a KO CM, murine Cyp3a gene knockout (Cyp3a KO), PXB and severe combined immunodeficiency (SCID) mice. Liquid chromatography-mass spectrometry was used for metabolic profiling of plasma, urine and bile. The prediction of human metabolite levels such as hydroxy nefazodone (OH-NEF), triazoledione form (TD), m-chlorophenylpiperazine and dealkyl metabolites in Cyp3a KO CM was superior to that in Cyp3a KO, PXB or SCID mice. Further, clinical exposure levels of NEF, OH-NEF and TD were reproduced in Cyp3a KO CM. In contrast, NEF was rapidly metabolized to TD in both PXB and SCID mice but not in Cyp3a KO mice, suggesting that murine CYP3A is involved in the elimination of NEF in these mice. These findings demonstrate that the metabolic profile of NEF in Cyp3a KO CM differs qualitatively and quantitatively from that in PXB mice due to the higher metabolic rate of NEF and its metabolites via murine CYP3A. Therefore Cyp3a KO CM might be useful in predicting the metabolic profiles of drug candidates in humans. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Metagenomic insights into anaerobic metabolism along an Arctic peat soil profile.

    Directory of Open Access Journals (Sweden)

    David A Lipson

    Full Text Available A metagenomic analysis was performed on a soil profile from a wet tundra site in northern Alaska. The goal was to link existing biogeochemical knowledge of the system with the organisms and genes responsible for the relevant metabolic pathways. We specifically investigated how the importance of iron (Fe oxides and humic substances (HS as terminal electron acceptors in this ecosystem is expressed genetically, and how respiratory and fermentative processes varied with soil depth into the active layer and into the upper permafrost. Overall, the metagenomes reflected a microbial community enriched in a diverse range of anaerobic pathways, with a preponderance of known Fe reducing species at all depths in the profile. The abundance of sequences associated with anaerobic metabolic processes generally increased with depth, while aerobic cytochrome c oxidases decreased. Methanogenesis genes and methanogen genomes followed the pattern of CH4 fluxes: they increased steeply with depth into the active layer, but declined somewhat over the transition zone between the lower active layer and the upper permafrost. The latter was relatively enriched in fermentative and anaerobic respiratory pathways. A survey of decaheme cytochromes (MtrA, MtrC and their homologs revealed that this is a promising approach to identifying potential reducers of Fe(III or HS, and indicated a possible role for Acidobacteria as Fe reducers in these soils. Methanogens appear to coexist in the same layers, though in lower abundance, with Fe reducing bacteria and other potential competitors, including acetogens. These observations provide a rich set of hypotheses for further targeted study.

  4. Hierarchical Status Predicts Behavioral Vulnerability and Nucleus Accumbens Metabolic Profile Following Chronic Social Defeat Stress.

    Science.gov (United States)

    Larrieu, Thomas; Cherix, Antoine; Duque, Aranzazu; Rodrigues, João; Lei, Hongxia; Gruetter, Rolf; Sandi, Carmen

    2017-07-24

    Extensive data highlight the existence of major differences in individuals' susceptibility to stress [1-4]. While genetic factors [5, 6] and exposure to early life stress [7, 8] are key components for such neurobehavioral diversity, intriguing observations revealed individual differences in response to stress in inbred mice [9-12]. This raised the possibility that other factors might be critical in stress vulnerability. A key challenge in the field is to identify non-invasively risk factors for vulnerability to stress. Here, we investigated whether behavioral factors, emerging from preexisting dominance hierarchies, could predict vulnerability to chronic stress [9, 13-16]. We applied a chronic social defeat stress (CSDS) model of depression in C57BL/6J mice to investigate the predictive power of hierarchical status to pinpoint which individuals will exhibit susceptibility to CSDS. Given that the high social status of dominant mice would be the one particularly challenged by CSDS, we predicted and found that dominant individuals were the ones showing a strong susceptibility profile as indicated by strong social avoidance following CSDS, while subordinate mice were not affected. Data from (1)H-NMR spectroscopy revealed that the metabolic profile in the nucleus accumbens (NAc) relates to social status and vulnerability to stress. Under basal conditions, subordinates show lower levels of energy-related metabolites compared to dominants. In subordinates, but not dominants, levels of these metabolites were increased after exposure to CSDS. To the best of our knowledge, this is the first study that identifies non-invasively the origin of behavioral risk factors predictive of stress-induced depression-like behaviors associated with metabolic changes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. ADMINISTRATION OF EARLY POST-PARTUM ORAL DRENCH IN DAIRY COWS: EFFECTON METABOLIC PROFILE

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    R. Schallenberger Gonçalves

    2015-01-01

    Full Text Available Some prophylactic treatments have been proposed in high-yielding dairy cattle in order to minimize the effects of negative energy balance and some disturbances such as hypocalcaemia and ketosis. The objective of this study was to evaluate the effects of two doses of d rench within 24 h after calving on the metabolic profile and prevention of ketosis. a total of 48 cows from a herd in r io Grande do s ul state (southern Brazil was used in the study. The animals were randomly selected and treated orally with d rench ( n = 32, propylene glycol, electrolytes and choline in 40 L of water and water ( n = 16 used as control. Blood samples were collected by blood coccygeal venipuncture through a vacutainer plain system tubes. Biochemical determinations were performed in serum (albumin, urea, cholesterol, triglycerides, non-esterified fatty acids - ne F a -, calcium, phosphorus, magnesium, aspartate transaminase - as T- and gammaglutamyl- transferase -GGT- and a cow-side determination of beta-hydroxybutyrate (BHB was performed using the a bbot blood Precision Xtra system. a ll cows in the experiment had their milk production controlled. The d rench treatment produces a tendency to a better milk yield (32.5 vs 29.6 L/cow/day and helps to prevent subclinical ketosis, as indicated by a lesser prevalence of subclinical ketosis (29.7% vs 37.2% and mean values of BHB (1.19 vs 1.27 mmol/L as well as a lesser lipolysis as indicated by ne F a values (509 vs 1.560 μmol/L. The other components of the metabolic profile did not have substantial effects between treatments. i n short, on the conditions of the present work, the d rench treatment is an effective management tool for prevention of subclinical ketosis and severe lipolysis.

  6. Effects of meal frequency on metabolic profiles and substrate partitioning in lean healthy males.

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    Marjet J M Munsters

    Full Text Available The daily number of meals has an effect on postprandial glucose and insulin responses, which may affect substrate partitioning and thus weight control. This study investigated the effects of meal frequency on 24 h profiles of metabolic markers and substrate partitioning.Twelve (BMI:21.6 ± 0.6 kg/m(2 healthy male subjects stayed after 3 days of food intake and physical activity standardization 2 × 36 hours in a respiration chamber to measure substrate partitioning. All subjects randomly received two isoenergetic diets with a Low meal Frequency (3 ×; LFr or a High meal Frequency (14 ×; HFr consisting of 15 En% protein, 30 En% fat, and 55 En% carbohydrates. Blood was sampled at fixed time points during the day to measure metabolic markers and satiety hormones.Glucose and insulin profiles showed greater fluctuations, but a lower AUC of glucose in the LFr diet compared with the HFr diet. No differences between the frequency diets were observed on fat and carbohydrate oxidation. Though, protein oxidation and RMR (in this case SMR + DIT were significantly increased in the LFr diet compared with the HFr diet. The LFr diet increased satiety and reduced hunger ratings compared with the HFr diet during the day.The higher rise and subsequently fall of insulin in the LFr diet did not lead to a higher fat oxidation as hypothesized. The LFr diet decreased glucose levels throughout the day (AUC indicating glycemic improvements. RMR and appetite control increased in the LFr diet, which can be relevant for body weight control on the long term.ClinicalTrials.gov NCT01034293.

  7. Gender and functional CYP2C and NAT2 polymorphisms determine the metabolic profile of metamizole.

    Science.gov (United States)

    Martínez, Carmen; Andreu, Inmaculada; Amo, Gemma; Miranda, Miguel A; Esguevillas, Gara; Torres, María José; Blanca-López, Natalia; Blanca, Miguel; García-Martín, Elena; Agúndez, José A G

    2014-12-01

    Metamizole is a pain-killer drug that has been banned in some countries because of its toxicity, but it is still used in many countries due to its effective analgesic and antispasmodic properties. Although large variability in the biodisposition and adverse effects of metamizole are known, factors underlying this variability are poorly understood. We analyzed the urinary recovery of metabolites, as well as the association of these profiles with genetic and non-genetic factors, in a group of 362 healthy individuals. Gender and functional polymorphisms are strongly related to metabolic profiles. N-demethylation of the active metabolite MAA is diminished in carriers of the CYP2C19*2 allele and in NAT2-slow acetylators. Acetylation of the secondary metabolite AA is decreased in men, in drinkers and in NAT2-slow acetylators with a differential effect of NAT2*5 and NAT2*6 alleles. The formylation of MAA is diminished in older subjects and in carriers of defect CYP2C9 and CYP2C19 alleles. Two novel arachidonoyl metabolites were identified for the first time in humans. Women and NAT2-slow acetylators show higher concentrations, whereas the presence of the rapid CYP2C19*17 allele is associated with lower concentrations of these metabolites. All genetic associations show a gene-dose effect. We identified for the first time genetic and non-genetic factors related to the oxidative metabolism of analgesic drug metamizole, as well as new active metabolites in humans. The phenotypic and genetic factors identified in this study have a potential application as biomarkers of metamizole biotransformation and toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Monitoring of blood metabolic profile and milk quality of ewes during lactation in organic farming

    Directory of Open Access Journals (Sweden)

    Zvonko Antunović

    2017-01-01

    Full Text Available The aim of this research was to monitor the metabolic profile of blood and the quality of ewes’ milk during lactation in organic farming. Biological investigations were carried out on 32 clinically healthy Merinolandschaf ewes during the 3th lactation on the 20th, 60th and 100th day of lactation. Ewes’ milk was analyzed for the non fat dry matter, milk fat, protein, lactose, urea, the somatic cells count (SCC and te total viable cell number (CFU, as well as for the concentration of fatty acids, atherogenic (AI, thrombogenic (TI and Δ9-desaturase activity index. Concentrations of minerals (Ca-calcium, P-phosphorus-inorganic, Mg-magnesium, and Fe-iron, biochemical parameters (urea, glucose, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, total protein, albumin, globulin, NEFA-non-esterified fatty acids, BHBA-beta-hydroxybutyrate and enzyme activity (ALT-alanine aminotransferase, AST-aspartate aminotransferase, ALP-alkaline phosphatase, CK-creatine kinase and GGT-γ-glutamyl transferase were analyzed in blood serum. Chemical composition of milk differed among different stages of lactation, which was marked by the increased content of milk fat, the decreased urea concentration, as well as by numeorus changes of fatty acid concentration observed along with lactation progression. Number of SCC and CFU in milk increased during lactation. AT and TI were appropriate in all stages of lactation, which resulted in satisfactory quality of ewes’ milk from organic farming. Determined concentrations of certain biochemical parameters (NEFA, triglycerides, VLDL-cholesterol, Ca and Fe in blood of ewes originating from organic farming indicated lower deficit of energy during the 20th day of lactation, as well as a lack of Ca and Fe concentrations in blood, which most likely occurred due to higher loss through milk. Accordingly, the blood metabolic profile can be considered as an indicator for feeding and health status of ewes during lactation

  9. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

    Science.gov (United States)

    Pontzer, Herman; Durazo-Arvizu, Ramon; Dugas, Lara R; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Cooper, Richard S; Schoeller, Dale A; Luke, Amy

    2016-02-08

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Metabolic adaptations in the liver of born long-distance running mice.

    Science.gov (United States)

    Brenmoehl, Julia; Walz, Christina; Renne, Ulla; Ponsuksili, Siriluck; Wolf, Carola; Langhammer, Martina; Schwerin, Manfred; Hoeflich, Andreas

    2013-05-01

    Long-distance runners have increased needs of energy supply. To unravel genetically based mechanisms required for efficient energy supply, we have analyzed hepatic metabolism of mice characterized by the inborn capacity to perform as long-distance runners. The mouse model had been established by phenotypic selection for high treadmill performance for 90 generations and was characterized by approximately 3.8-fold higher running capacities (Dummerstorf high Treadmill Performance mouse line [DUhTP]) compared with unselected and also untrained controls (Dummerstorf Control mouse line [DUC]). From 7-wk-old male mice, serum and liver samples were collected and analyzed for messenger RNA, protein, and metabolite levels, respectively. In livers from DUhTP mice, we identified significantly higher messenger RNA transcript levels of peroxisome proliferator-activated receptor delta and higher protein levels of sirtuin-1, acetyl-CoA-synthetase, acetyl-CoA-carboxylase, phosphoenolpyruvate carboxykinase, and glutamate-dehydrogenase, suggesting higher gluconeogenesis and lipogenesis in DUhTP mice. In fact, higher hepatic levels of glycogen and triglycerides as well as higher concentrations of carbohydrate, fatty acid, and cholesterol metabolites were found in DUhTP mice. In parallel, in DUhTP mice, which did not have access to running wheels, a marked hyperlipidemia (cholesterol = 160% ± 8%, triglycerides = 174% ± 14% of controls, respectively), and abdominal obesity (DUhTP = 0.396 ± 0.019 g, DUC = 0.291 ± 0.019 g) were found. From our data, we conclude that the physiological basis of genetically fixed higher endurance-running performance in DUhTP marathon mouse is related to increased hepatic gluconeogenesis and lipogenesis. Expression of sirtuin 1 as well as of gluconeogenic and lipogenic key enzymes may be related to peroxisome proliferator-activated receptor delta. Metabolic adaptations presented in our study represent inborn features of superior endurance

  11. (Im) Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis

    NARCIS (Netherlands)

    He, F.; Fromion, V.; Westerhoff, H.V.

    2013-01-01

    Background: Metabolic control analysis (MCA) and supply-demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply-demand theory has not yet considered gene-expression regulation explicitly whilst a

  12. Metabolic responses of Quercus ilex seedlings to wounding analysed with nuclear magnetic resonance profiling.

    Science.gov (United States)

    Sardans, J; Gargallo-Garriga, A; Pérez-Trujillo, M; Parella, T J; Seco, R; Filella, I; Peñuelas, J

    2014-03-01

    Plants defend themselves against herbivory at several levels. One of these is the synthesis of inducible chemical defences. Using NMR metabolomic techniques, we studied the metabolic changes of plant leaves after a wounding treatment simulating herbivore attack in the Mediterranean sclerophyllous tree Quercus ilex. First, an increase in glucose content was observed in wounded plants. There was also an increase in the content of C-rich secondary metabolites such as quinic acid and quercitol, both related to the shikimic acid pathway and linked to defence against biotic stress. There was also a shift in N-storing amino acids, from leucine and isoleucine to asparagine and choline. The observed higher content of asparagine is related to the higher content of choline through serine that was proved to be the precursor of choline. Choline is a general anti-herbivore and pathogen deterrent. The study shows the rapid metabolic response of Q. ilex in defending its leaves, based on a rapid increase in the production of quinic acid, quercitol and choline. The results also confirm the suitability of (1)H NMR-based metabolomic profiling studies to detect global metabolome shifts after wounding stress in tree leaves, and therefore its suitability in ecometabolomic studies. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  13. Metabolic Profiling Reveals Effects of Age, Sexual Development and Neutering in Plasma of Young Male Cats.

    Science.gov (United States)

    Allaway, David; Gilham, Matthew S; Colyer, Alison; Jönsson, Thomas J; Swanson, Kelly S; Morris, Penelope J

    2016-01-01

    Neutering is a significant risk factor for obesity in cats. The mechanisms that promote neuter-associated weight gain are not well understood but following neutering, acute changes in energy expenditure and energy consumption have been observed. Metabolic profiling (GC-MS and UHPLC-MS-MS) was used in a longitudinal study to identify changes associated with age, sexual development and neutering in male cats fed a nutritionally-complete dry diet to maintain an ideal body condition score. At eight time points, between 19 and 52 weeks of age, fasted blood samples were taken from kittens neutered at either 19 weeks of age (Early Neuter (EN), n = 8) or at 31 weeks of age (Conventional Neuter (CN), n = 7). Univariate and multivariate analyses were used to compare plasma metabolites (n = 370) from EN and CN cats. Age was the primary driver of variance in the plasma metabolome, including a developmental change independent of neuter group between 19 and 21 weeks in lysolipids and fatty acid amides. Changes associated with sexual development and its subsequent loss were also observed, with differences at some time points observed between EN and CN cats for 45 metabolites (FDR pcats was the most significantly altered pathway, increasing during sexual development and decreasing acutely following neutering. Felinine is a testosterone-regulated, felid-specific glutathione derivative secreted in urine. Alterations in tryptophan, histidine and tocopherol metabolism observed in peripubertal cats may be to support physiological functions of glutathione following diversion of S-amino acids for urinary felinine secretion.

  14. Metabolic profiles of exercise in patients with McArdle disease or mitochondrial myopathy.

    Science.gov (United States)

    Delaney, Nigel F; Sharma, Rohit; Tadvalkar, Laura; Clish, Clary B; Haller, Ronald G; Mootha, Vamsi K

    2017-08-01

    McArdle disease and mitochondrial myopathy impair muscle oxidative phosphorylation (OXPHOS) by distinct mechanisms: the former by restricting oxidative substrate availability caused by blocked glycogen breakdown, the latter because of intrinsic respiratory chain defects. We applied metabolic profiling to systematically interrogate these disorders at rest, when muscle symptoms are typically minimal, and with exercise, when symptoms of premature fatigue and potential muscle injury are unmasked. At rest, patients with mitochondrial disease exhibit elevated lactate and reduced uridine; in McArdle disease purine nucleotide metabolites, including xanthine, hypoxanthine, and inosine are elevated. During exercise, glycolytic intermediates, TCA cycle intermediates, and pantothenate expand dramatically in both mitochondrial disease and control subjects. In contrast, in McArdle disease, these metabolites remain unchanged from rest; but urea cycle intermediates are increased, likely attributable to increased ammonia production as a result of exaggerated purine degradation. Our results establish skeletal muscle glycogen as the source of TCA cycle expansion that normally accompanies exercise and imply that impaired TCA cycle flux is a central mechanism of restricted oxidative capacity in this disorder. Finally, we report that resting levels of long-chain triacylglycerols in mitochondrial myopathy correlate with the severity of OXPHOS dysfunction, as indicated by the level of impaired O 2 extraction from arterial blood during peak exercise. Our integrated analysis of exercise and metabolism provides unique insights into the biochemical basis of these muscle oxidative defects, with potential implications for their clinical management.

  15. Metabolic profiles in serum of mouse after chronic exposure to drinking water.

    Science.gov (United States)

    Zhang, Yan; Wu, Bing; Zhang, Xuxiang; Li, Aimin; Cheng, Shupei

    2011-08-01

    The toxicity of Nanjing drinking water on mouse (Mus musculus) was detected by (1)H nuclear magnetic resonance (NMR)-based metabonomic method. Three groups of mice were fed with drinking water (produced by Nanjing BHK Water Plant), 3.8 μg/L benzo(a)pyrene as contrast, and clean water as control, respectively, for 90 days. It was observed that the levels of lactate, alanine, and creatinine in the mice fed with drinking water were increased and that of valine was decreased. The mice of drinking water group were successfully separated from control. The total concentrations of polycyclic aromatic hydrocarbons (PAHs), phthalates (PAEs), and other organic pollutants in the drinking water were 0.23 μg/L, 4.57 μg/L, and 0.34 μg/L, respectively. In this study, Nanjing drinking water was found to induce distinct perturbations of metabolic profiles on mouse including disorders of glucose-alanine cycle, branched-chain amino acid and energy metabolism, and dysfunction of kidney. This study suggests that metabonomic method is feasible and sensitive to evaluate potential toxic effects of drinking water.

  16. Metabolic profile of visual cortex in diabetic rats measured with in vivo proton MRS.

    Science.gov (United States)

    Li, Shuang; Wang, Xinghua; Yang, Junjie; Lei, Hao; Wang, Xuxia; Xiang, Yi

    2017-11-01

    The purpose of the present study was to characterize the metabolic profile of the visual cortex in streptozotocin-induced Type 1 diabetic rats by means of in vivo proton MRS. Several metabolite concentration ratios in the visual cortex were calculated. In addition, postmortem histologic analyses for retinal ganglion cell (RGC) loss, optic nerve injury and visual cortex alterations were monitored. The results showed that diabetes induced several changes in visual cortex metabolites, such as reduced N-acetylaspartate, glutamate, γ-aminobutyric acid, taurine and choline-containing compound levels. Nevertheless, myo-inositol levels increased significantly as compared with controls. Remarkable RGC loss and optic nerve degeneration were observed by morphological analysis. Moreover, the results showed significant neuronal loss and glial activation in the visual cortex. These findings indicated that, besides vascular abnormalities, neuronal loss and degeneration in the visual pathway were induced due to disrupted glucose homeostasis in diabetes. Metabolic or functional abnormalities were induced in cerebral neurons of the visual cortex by diabetes. Copyright © 2017 John Wiley & Sons, Ltd.

  17. [LEVELS OF OBESITY, METABOLIC PROFILE, CONSUMPTION OF TABACO AND BLOOD PRESSURE IN SEDENTARY YOUTHS].

    Science.gov (United States)

    Caamaño Navarrete, Felipe; Alarcón Hormazábal, Manuel; Delgado Floody, Pedro

    2015-11-01

    in Chile, the National Health Survey (ENS) conducted in 2009-2010 reported high prevalence of overweight, sedentary lifestyle, high cholesterol and metabolic syndrome in the population. to determine the prevalence in young sedentary obesity and consumption of tabaco and analyze their association with the metabolic profile, body fat percentage and blood pressure. 125 young sedentary, 26 men and 99 women, aged between 17 and 29 years old were evaluated. Body mass index (BMI), percent body fat (% fat), waist contour (CC), systolic and diastolic blood pressure, total cholesterol, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides: measurements were performed, glycemia and consumption of snuff. HDL-C (p = 0.000) and% MG (p = 0.043) were higher in women. 37.6% of young people turned smoker. 35, 2% of the sample showed excessive malnutrition. Obese subjects had higher levels: waist contour (p = 0.000) and% FM (p = 0.000). When analyzing obesity DC, this showed significant differences in BMI,% fat, systolic and diastolic blood pressure. BMI presented positive association with CC,% fat, total cholesterol, triglycerides, LDL, systolic and diastolic blood pressure (p tabaco in the study sample, while other variables are not high-risk categories, it is an opportune time to intervene and reverse these negative health trends now. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  18. Metabolomics-proteomics profiles delineate metabolic changes in kidney fibrosis disease.

    Science.gov (United States)

    Cao, Hongxin; Zhang, Aihua; Sun, Hui; Zhou, Xiaohang; Guan, Yu; Liu, Qi; Kong, Ling; Wang, Xijun

    2015-11-01

    Kidney fibrosis (KF) is a common process that leads to the progression of various types of kidney disease including kidney-yang deficiency syndrome, however, little is known regarding the underlying biology of this disorder. Fortunately, integrated omics approaches provide the molecule fingerprints related to the disease. In an attempt to address this issue, we integrated metabolomics-proteomics profiles analyzed pathogenic mechanisms of KF based on rat model. A total 37 serum differential metabolites were contributed to KF progress, involved several important metabolic pathways. Using iTRAQ-based quantitative proteomics analysis, 126 differential serum proteins were identified and provide valuable insight into the underlying mechanisms of KF. These proteins appear to be involved in complement and coagulation cascades, regulation of actin cytoskeleton, MAPK signaling pathway, RNA transport, etc. Interestingly, pathway/network analysis of integrated proteomics and metabolomics data firstly reveals that these signaling pathways were closely related with KF. It further indicated that most of these proteins play a pivotal role in the regulation of metabolism pathways. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Metabolic profile of dystrophic mdx mouse muscles analyzed with in vitro magnetic resonance spectroscopy (MRS).

    Science.gov (United States)

    Martins-Bach, Aurea B; Bloise, Antonio C; Vainzof, Mariz; Rahnamaye Rabbani, Said

    2012-10-01

    Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy characterized by progressive and irreversible degeneration of the muscles. The mdx mouse is the classical animal model for DMD, showing similar molecular and protein defects. The mdx mouse, however, does not show significant muscle weakness, and the diaphragm muscle is significantly more degenerated than skeletal muscles. In this work, (1)H magnetic resonance spectroscopy (MRS) was used to study the metabolic profile of quadriceps and diaphragm muscles from mdx and control mice. Using principal components analysis (PCA), the animals were separated into groups according to age and lineages. The classification was compared to histopathological analysis. Among the 24 metabolites identified from the nuclear MR spectra, only 19 were used by the PCA program for classification purposes. These can be important key biomarkers associated with the progression of degeneration in mdx muscles and with natural aging in control mice. Glutamate, glutamine, succinate, isoleucine, acetate, alanine and glycerol were increased in mdx samples as compared to control mice, in contrast to carnosine, taurine, glycine, methionine and creatine that were decreased. These results suggest that MRS associated with pattern recognition analysis can be a reliable tool to assess the degree of pathological and metabolic alterations in the dystrophic tissue, thereby affording the possibility of evaluation of beneficial effects of putative therapies. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Metabolic profiles of flooding-tolerant mechanism in early-stage soybean responding to initial stress.

    Science.gov (United States)

    Wang, Xin; Zhu, Wei; Hashiguchi, Akiko; Nishimura, Minoru; Tian, Jingkui; Komatsu, Setsuko

    2017-08-01

    Metabolomic analysis of flooding-tolerant mutant and abscisic acid-treated soybeans suggests that accumulated fructose might play a role in initial flooding tolerance through regulation of hexokinase and phosphofructokinase. Soybean is sensitive to flooding stress, which markedly reduces plant growth. To explore the mechanism underlying initial-flooding tolerance in soybean, mass spectrometry-based metabolomic analysis was performed using flooding-tolerant mutant and abscisic-acid treated soybeans. Among the commonly-identified metabolites in both flooding-tolerant materials, metabolites involved in carbohydrate and organic acid displayed same profile at initial-flooding stress. Sugar metabolism was highlighted in both flooding-tolerant materials with the decreased and increased accumulation of sucrose and fructose, respectively, compared to flooded soybeans. Gene expression of hexokinase 1 was upregulated in flooded soybean; however, it was downregulated in both flooding-tolerant materials. Metabolites involved in carbohydrate/organic acid and proteins related to glycolysis/tricarboxylic acid cycle were integrated. Increased protein abundance of phosphofructokinase was identified in both flooding-tolerant materials, which was in agreement with its enzyme activity. Furthermore, sugar metabolism was pointed out as the tolerant-responsive process at initial-flooding stress with the integration of metabolomics, proteomics, and transcriptomics. Moreover, application of fructose declined the increased fresh weight of plant induced by flooding stress. These results suggest that fructose might be the critical metabolite through regulation of hexokinase and phosphofructokinase to confer initial-flooding stress in soybean.

  1. Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    María B Cassera

    2007-06-01

    Full Text Available In Plasmodium falciparum, the formation of isopentenyl diphosphate and dimethylallyl diphosphate, central intermediates in the biosynthesis of isoprenoids, occurs via the methylerythritol phosphate (MEP pathway. Fosmidomycin is a specific inhibitor of the second enzyme of the MEP pathway, 1-deoxy-D-xylulose-5-phosphate reductoisomerase. We analyzed the effect of fosmidomycin on the levels of each intermediate and its metabolic requirement for the isoprenoid biosynthesis, such as dolichols and ubiquinones, throughout the intraerythrocytic cycle of P. falciparum. The steady-state RNA levels of the MEP pathway-associated genes were quantified by real-time polymerase chain reaction and correlated with the related metabolite levels. Our results indicate that MEP pathway metabolite peak precede maximum transcript abundance during the intraerythrocytic cycle. Fosmidomycin-treatment resulted in a decrease of the intermediate levels in the MEP pathway as well as in ubiquinone and dolichol biosynthesis. The MEP pathway associated transcripts were modestly altered by the drug, indicating that the parasite is not strongly responsive at the transcriptional level. This is the first study that compares the effect of fosmidomycin on the metabolic and transcript profiles in P. falciparum, which has only the MEP pathway for isoprenoid biosynthesis.

  2. Effect of fosmidomycin on metabolic and transcript profiles of the methylerythritol phosphate pathway in Plasmodium falciparum.

    Science.gov (United States)

    Cassera, María B; Merino, Emilio F; Peres, Valnice J; Kimura, Emilia A; Wunderlich, Gerhard; Katzin, Alejandro M

    2007-06-01

    In Plasmodium falciparum, the formation of isopentenyl diphosphate and dimethylallyl diphosphate, central intermediates in the biosynthesis of isoprenoids, occurs via the methylerythritol phosphate (MEP) pathway. Fosmidomycin is a specific inhibitor of the second enzyme of the MEP pathway, 1-deoxy-D-xylulose-5-phosphate reductoisomerase. We analyzed the effect of fosmidomycin on the levels of each intermediate and its metabolic requirement for the isoprenoid biosynthesis, such as dolichols and ubiquinones, throughout the intraerythrocytic cycle of P. falciparum. The steady-state RNA levels of the MEP pathway-associated genes were quantified by real-time polymerase chain reaction and correlated with the related metabolite levels. Our results indicate that MEP pathway metabolite peak precede maximum transcript abundance during the intraerythrocytic cycle. Fosmidomycin-treatment resulted in a decrease of the intermediate levels in the MEP pathway as well as in ubiquinone and dolichol biosynthesis. The MEP pathway associated transcripts were modestly altered by the drug, indicating that the parasite is not strongly responsive at the transcriptional level. This is the first study that compares the effect of fosmidomycin on the metabolic and transcript profiles in P. falciparum, which has only the MEP pathway for isoprenoid biosynthesis.

  3. Use of endometrial cytology and metabolic profiles for selection of embryo donor cows

    Directory of Open Access Journals (Sweden)

    F. Ismael Fernandez-Sanchez

    2014-07-01

    Full Text Available The aim of this study was to evaluate the use of endometrial cytology and metabolic profiles for selection of donor cows in embryo transfer programmes. For this purpose, 69 clinically healthy Holstein cows were enrolled in the study. At the start of the superovulation procedure (Day 0, blood and endometrial samples were obtained to determine metabolic and uterine status, respectively. The cows were then subjected to porcine follicle stimulating hormone (pFSH superovulation treatment, and embryos were recovered after 7 days. The mean number of embryos obtained per flush was 9.89±8.21 (4.63±5.34 viable embryos, 0.82±2.01 degenerated embryos and 4.57±6.44 unfertilized ova. The following statistically significant variables were entered in a regression model: beta-hydroxybutyrate, serum cholesterol, body condition, number of calvings and percentage of neutrophils. In almost all cases, the model explained some percentage of the variance: total number of embryos, 4.8% (p<0.05; number of degenerate embryos, 4.2% (p=0.051; and number of unfertilized ova, 14.2% (p<0.01. Statistical models for the percentage of viable embryos and unfertilized ova accounted for 24.0% and 29.4% of the variance, respectively, and both were statistically significant (p<0.01. The model for the percentage of degenerated embryos was statistically significant (p<0.05 and explained 4.4% of the variance. In conclusion, we have demonstrated that positive energy balance and healthy uterus can improve ovarian response and the proportion of viable embryos in cows. Efficient tools for monitoring the metabolic and uterine status should therefore be used in bovine embryo transfer programmes.

  4. Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors.

    Directory of Open Access Journals (Sweden)

    Pantelis Stavrinou

    Full Text Available Endogenous and exogenous compounds as well as carcinogens are metabolized and detoxified by phase I and II enzymes, the activity of which could be crucial to the inactivation and hence susceptibility to carcinogenic factors. The expression of these enzymes in human brain tumor tissue has not been investigated sufficiently. We studied the association between tumor pathology and the expression profile of seven phase I and II drug metabolizing genes (CYP1A1, CYP1B1, ALDH3A1, AOX1, GSTP1, GSTT1 and GSTM3 and some of their proteins.Using qRT-PCR and western blotting analysis the gene and protein expression in a cohort of 77 tumors were investigated. The major tumor subtypes were meningioma, astrocytoma and brain metastases, -the later all adenocarcinomas from a lung primary.Meningeal tumors showed higher expression levels for AOX1, CYP1B1, GSTM3 and GSTP1. For AOX1, GSTM and GSTP1 this could be verified on a protein level as well. A negative correlation between the WHO degree of malignancy and the strength of expression was identified on both transcriptional and translational level for AOX1, GSTM3 and GSTP1, although the results could have been biased by the prevalence of meningiomas and glioblastomas in the inevitably bipolar distribution of the WHO grades. A correlation between the gene expression and the protein product was observed for AOX1, GSTP1 and GSTM3 in astrocytomas.The various CNS tumors show different patterns of drug metabolizing gene expression. Our results suggest that the most important factor governing the expression of these enzymes is the histological subtype and to a far lesser extent the degree of malignancy itself.

  5. Gold nanoparticles improve metabolic profile of mice fed a high-fat diet.

    Science.gov (United States)

    Chen, Hui; Ng, Jane P M; Tan, Yi; McGrath, Kristine; Bishop, David P; Oliver, Brian; Chan, Yik Lung; Cortie, Michael B; Milthorpe, Bruce K; Valenzuela, Stella M

    2018-02-06

    Obesity is a high risk for multiple metabolic disorders due to excessive influx of energy, glucose and lipid, often from a western based diet. Low-grade inflammation plays a key role in the progression of such metabolic disorders. The anti-inflammatory property of gold compounds has been used in treating rheumatoid arthritis in the clinic. Previously we found that pure gold nanoparticles (AuNPs, 21 nm) also possess anti-inflammatory effects on the retroperitoneal fat tissue following intraperitoneal injection, by downregulating tumor necrosis factor (TNF) α. However, whether such an effect can change the risk of metabolic disorders in the obese has not been well studied. The study employed C57BL/6 mice fed a pellet high fat diet (HFD, 43% as fat) that were treated daily with AuNPs [low (HFD-LAu) or high (HFD-HAu) dose] via intraperitoneal injection for 9 weeks. In the in vitro study, RAW264.7 macrophages and 3T3-L1 adipocytes were cultured with low and high concentrations of AuNPs alone or together. The HFD-fed mice showed a significant increase in fat mass, glucose intolerance, dyslipidemia, and liver steatosis. The HFD-LAu group showed an 8% reduction in body weight, ameliorated hyperlipidemia, and normal glucose tolerance; while the HFD-HAu group had a 5% reduction in body weight with significant improvement in their glucose intolerance and hyperlipidemia. The underlying mechanism may be attributed to a reduction in adipose and hepatic local proinflammatory cytokine production, e.g. TNFα. In vitro studies of co-cultured murine RAW264.7 macrophage and 3T3-L1 adipocytes supported this proposed mechanism. AuNPs demonstrate a promising profile for potential management of obesity related glucose and lipid disorders and are useful as a research tool for the study of biological mechanisms.

  6. Yogurt consumption is associated with better diet quality and metabolic profile in American men and women

    Science.gov (United States)

    Wang, Huifen; Livingston, Kara A.; Fox, Caroline S.; Meigs, James B.; Jacques, Paul F.

    2013-01-01

    The evidence-based Dietary Guidelines for Americans recommends increasing the intake of fat-free or low-fat milk and milk products. However, yogurt, a nutrient-dense milk product, has been understudied. This cross-sectional study examined whether yogurt consumption was associated with better diet quality and metabolic profile among adults (n = 6526) participating in the Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-2005) cohorts. A validated food frequency questionnaire was used to assess dietary intake, and the Dietary Guidelines Adherence Index (DGAI) was used to measure overall diet quality. Standardized clinical examinations and laboratory tests were conducted. Generalized estimating equations examined the associations of yogurt consumption with diet quality and levels of metabolic factors. Approximately 64% of women (vs 41% of men) were yogurt consumers (ie, consumed >0 servings/week). Yogurt consumers had a higher DGAI score (ie, better diet quality) than nonconsumers. Adjusted for demographic and lifestyle factors and DGAI, yogurt consumers, compared with nonconsumers, had higher potassium intakes (difference, 0.12 g/d) and were 47%, 55%, 48%, 38%, and 34% less likely to have inadequate intakes (based on Dietary Reference Intake) of vitamins B2 and B12, calcium, magnesium, and zinc, respectively (all P ≤ .001). In addition, yogurt consumption was associated with lower levels of circulating triglycerides, glucose, and lower systolic blood pressure and insulin resistance (all P Yogurt is a good source of several micronutrients and may help to improve diet quality and maintain metabolic well-being as part of a healthy, energy-balanced dietary pattern. PMID:23351406

  7. Genetic diversity and metabolic profile of Salvia officinalis populations: implications for advanced breeding strategies.

    Science.gov (United States)

    Sarrou, Eirini; Ganopoulos, Ioannis; Xanthopoulou, Aliki; Masuero, Domenico; Martens, Stefan; Madesis, Panagiotis; Mavromatis, Athanasios; Chatzopoulou, Paschalina

    2017-08-01

    As a result of this work, we were able to characterize seven indigenous to Greece Salvia officinalis populations using genetic and metabolomic tools. These tools can be used to select the most promising genotypes, capable to design future breeding programs for high valuable varieties. An initial investigation was carried out to compare the genetic and metabolic diversity in S. officinalis grown in Greece and to discern the relationship between the two sets of data. Analysis of inter-simple sequence repeats (ISSR) revealed significant genetic differences among seven sage populations, which were grouped into three main clusters according to an UPGMA ISSR data-based dendrogram and Principle Coordinate Analysis. 80 loci were scored of which up to 90% were polymorphic at species level. According to the composition of their essential oil, the populations were classified into two chemotypes: 1.8 cineole/α-thujone and α-thujone/1.8 cineole. Additionally, a targeted ultra performance liquid chromatography (UPLC-MS/MS) method was used to qualify and quantify phenolic compounds in methanolic extracts of the seven sage genotypes according to which they were districted in six clusters among the sage populations. The main compounds characterizing the seven genotypes were rosmarinic acid and carnosol, followed by apigenin-7-O-glucoside (Ap7glc), and luteolin-7-O-glucoside (Lu7glc). The correlation between matrices obtained from ISSR data and metabolic profiles was non-significant. However, based on the differences in metabolic fingerprint, we aimed to define populations using as main selection criteria the high polyphenol content and desired essential oil composition, using state to the art analytical tools for the identification of parent lines for breeding programs.

  8. EnzDP: improved enzyme annotation for metabolic network reconstruction based on domain composition profiles.

    Science.gov (United States)

    Nguyen, Nam-Ninh; Srihari, Sriganesh; Leong, Hon Wai; Chong, Ket-Fah

    2015-10-01

    Determining the entire complement of enzymes and their enzymatic functions is a fundamental step for reconstructing the metabolic network of cells. High quality enzyme annotation helps in enhancing metabolic networks reconstructed from the genome, especially by reducing gaps and increasing the enzyme coverage. Currently, structure-based and network-based approaches can only cover a limited number of enzyme families, and the accuracy of homology-based approaches can be further improved. Bottom-up homology-based approach improves the coverage by rebuilding Hidden Markov Model (HMM) profiles for all known enzymes. However, its clustering procedure relies firmly on BLAST similarity score, ignoring protein domains/patterns, and is sensitive to changes in cut-off thresholds. Here, we use functional domain architecture to score the association between domain families and enzyme families (Domain-Enzyme Association Scoring, DEAS). The DEAS score is used to calculate the similarity between proteins, which is then used in clustering procedure, instead of using sequence similarity score. We improve the enzyme annotation protocol using a stringent classification procedure, and by choosing optimal threshold settings and checking for active sites. Our analysis shows that our stringent protocol EnzDP can cover up to 90% of enzyme families available in Swiss-Prot. It achieves a high accuracy of 94.5% based on five-fold cross-validation. EnzDP outperforms existing methods across several testing scenarios. Thus, EnzDP serves as a reliable automated tool for enzyme annotation and metabolic network reconstruction. Available at: www.comp.nus.edu.sg/~nguyennn/EnzDP .

  9. Adaptations in lipid metabolism of bovine adipose tissue in lactogenesis and lactation.

    Science.gov (United States)

    McNamara, J P; Hillers, J K

    1986-02-01

    The timing and magnitude of metabolic adaptations in adipose tissue during lactogenesis and lactation were determined in first lactation bovines. In vitro rates of lipogenesis and palmitate esterification were measured to estimate in vivo synthesis. Lipolysis was measured in the basal state and as maximally stimulated by norepinephrine or epinephrine to estimate physiological adaptations as well as the changes in catecholamine responsiveness. Subcutaneous adipose tissue was biopsied at -1, -0.5, +0.5, 1, 2, and 6 months from parturition. From 1 to 0.5 months prepartum there was a 54% reduction in lipogenesis, a 16% reduction in esterification, a 54 and 77% increase in norepinephrine- and epinephrine-stimulated free fatty acid (FFA) release, respectively, and a 28% increase in epinephrine-stimulated glycerol release. The immediate postpartum period (0.5 and 1 month) was marked by a decrease in lipogenesis to 5% and esterification to 50% of -1 month rates. During this period, norepinephrine-stimulated FFA release increased 50% above -1 month rates, epinephrine-stimulated FFA release increased 128%, and norepinephrine- and epinephrine-stimulated glycerol release increased 30 and 87%, respectively. Midlactation (2 and 6 months) was marked by a dramatic rebound in lipogenesis and esterification to 14-fold and 2.5-fold prepartum rates, respectively. Basal glycerol release doubled during this period, while basal FFA release declined to near prepartum levels. Catecholamine-stimulated FFA and glycerol release decreased from the peak during midlactation, but remained elevated compared to prepartum levels.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Adaptation to the Spanish population of the Substance Use Risk Profile Scale (SURPS) and psychometric properties.

    Science.gov (United States)

    Fernández-Calderón, Fermín; Díaz-Batanero, Carmen; Rojas-Tejada, Antonio J; Castellanos-Ryan, Natalie; Lozano-Rojas, Óscar M

    2017-07-14

    The identification of different personality risk profiles for substance misuse is useful in preventing substance-related problems. This study aims to test the psychometric properties of a new version of the Substance Use Risk Profile Scale (SURPS) for Spanish college students. Cross-sectional study with 455 undergraduate students from four Spanish universities. A new version of the SURPS, adapted to the Spanish population, was administered with the Beck Hopelessness Scale, the UPPS-P Impulsive Behavior Scale, the State-Trait Anxiety Inventory (STAI) and the Alcohol Use Disorders Identification Test (AUDIT). Internal consistency reliability ranged between 0.652 and 0.806 for the four SURPS subscales, while reliability estimated by split-half coefficients varied from 0.686 to 0.829. The estimated test-retest reliability ranged between 0.733 and 0.868. The expected four-factor structure of the original scale was replicated. As evidence of convergent validity, we found that the SURPS subscales were significantly associated with other conceptually-relevant personality scales and significantly associated with alcohol use measures in theoretically-expected ways. This SURPS version may be a useful instrument for measuring personality traits related to vulnerability to substance use and misuse when targeting personality with preventive interventions.

  11. Global Transcriptional Profiling of Diapause and Climatic Adaptation in Drosophila melanogaster.

    Science.gov (United States)

    Zhao, Xiaqing; Bergland, Alan O; Behrman, Emily L; Gregory, Brian D; Petrov, Dmitri A; Schmidt, Paul S

    2016-03-01

    Wild populations of the model organism Drosophila melanogaster experience highly heterogeneous environments over broad geographical ranges as well as over seasonal and annual timescales. Diapause is a primary adaptation to environmental heterogeneity, and in D. melanogaster the propensity to enter diapause varies predictably with latitude and season. Here we performed global transcriptomic profiling of naturally occurring variation in diapause expression elicited by short day photoperiod and moderately low temperature in two tissue types associated with neuroendocrine and endocrine signaling, heads, and ovaries. We show that diapause in D. melanogaster is an actively regulated phenotype at the transcriptional level, suggesting that diapause is not a simple physiological or reproductive quiescence. Differentially expressed genes and pathways are highly distinct in heads and ovaries, demonstrating that the diapause response is not uniform throughout the soma and suggesting that it may be comprised of functional modules associated with specific tissues. Genes downregulated in heads of diapausing flies are significantly enriched for clinally varying single nucleotide polymorphism (SNPs) and seasonally oscillating SNPs, consistent with the hypothesis that diapause is a driving phenotype of climatic adaptation. We also show that chromosome location-based coregulation of gene expression is present in the transcriptional regulation of diapause. Taken together, these results demonstrate that diapause is a complex phenotype actively regulated in multiple tissues, and support the hypothesis that natural variation in diapause propensity underlies adaptation to spatially and temporally varying selective pressures. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity

    Science.gov (United States)

    Shaham, Oded; Wei, Ru; Wang, Thomas J; Ricciardi, Catherine; Lewis, Gregory D; Vasan, Ramachandran S; Carr, Steven A; Thadhani, Ravi; Gerszten, Robert E; Mootha, Vamsi K

    2008-01-01

    Glucose ingestion after an overnight fast triggers an insulin-dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry-based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes—proteolysis, lipolysis, ketogenesis, and glycolysis—reflecting a switch from catabolism to anabolism. In pre-diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's 'insulin response profile', which could have value in predicting diabetes, its complications, and in guiding therapy. PMID:18682704

  13. PFAS profiles in three North Sea top predators: metabolic differences among species?

    Science.gov (United States)

    Galatius, Anders; Bossi, Rossana; Sonne, Christian; Rigét, Frank Farsø; Kinze, Carl Christian; Lockyer, Christina; Teilmann, Jonas; Dietz, Rune

    2013-11-01

    Profiles of seven compounds of perfluoro-alkyl substances (PFASs) were compared among three species of top predators from the Danish North Sea: the white-beaked dolphin (Lagenorhynchus albirostris), the harbor porpoise (Phocoena phocoena), and the harbor seal (Phoca vitulina). The seals had higher total burdens (757.8 ng g(-1) ww) than the dolphins (439.9 ng g(-1) ww) and the porpoises (355.8 ng g(-1) ww), probably a reflection of feeding closer to the shore and thus contamination sources. The most striking difference among the species was the relative contribution of perfluorooctanesulfonamide (PFOSA) to the profiles; the seals (0.1%) had much lower levels than porpoises (8.3%) and dolphins (26.0%). In combination with the values obtained from the literature, this result indicates that Carnivora species including Pinnipedia have a much higher capacity of transforming PFOSA to perfluorooctane sulfonic acid (PFOS) than cetacean species. Another notable difference among the species was that the two smaller species (seals and porpoises) with supposedly higher metabolic rates had lower concentrations of the perfluorinated carboxylic acids, which are generally more easily excreted than perfluorinated sulfonamides. Species-specific characteristics should be recognized when PFAS contamination in marine mammals is investigated, for example, several previous studies of PFASs in cetaceans have not quantified PFOSA.

  14. Soy Germ Protein With or Without-Zn Improve Plasma Lipid Profile in Metabolic Syndrome Women

    Directory of Open Access Journals (Sweden)

    HERY WINARSI

    2012-03-01

    Full Text Available The aim of this research was to determine the effect of soy germ protein on lipid profile of metabolic syndrome (MetS patients. Respondents were 30 women with criteria, i.e. blood glucose level > normal, body mass index > 25 kg/m2, hypertriglyceridemia, low cholesterol-HDL level, 40-65 years old, living in Purwokerto, and signed the informed consent. The project was approved by the ethics committee of the Medical Faculty from Gadjah Mada University-Yogyakarta. Respondents were divided into three randomly chosen groups consisting of ten women each. The first, second, and third groups were treated, respectively, with milk enriched soy germ protein plus Zn, milk enriched soy germ protein (without Zn, and placebo for two months. Blood samples were taken at baseline, one and two months after observation. Two months after observation the groups consuming milk enriched with soy germ protein, both with or without Zn, had their level of cholesterol-total decrease from 215.8 to 180.2 mg/dl (P = 0.03, triglyceride from 240.2 to 162.5 mg/dl (P = 0.02, and LDL from 154.01 to 93.85 mg/dl (P = 0.03. In contrast, HDL increased from 38.91 to 49.49 mg/dl (P = 0.0008. In conclusion, soy germ protein can improve lipid profile, thus it can inhibit atherosclerosis incident.

  15. High-Throughput Metabolic Profiling of Soybean Leaves by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

    Science.gov (United States)

    Yilmaz, Ali; Rudolph, Heather L; Hurst, Jerod J; Wood, Troy D

    2016-01-19

    As a relatively recent research field, plant metabolomics has gained increasing interest in the past few years and has been applied to answer biological questions through large-scale qualitative and quantitative analyses of the plant metabolome. The combination of sensitivity and selectivity offered by mass spectrometry (MS) for measurement of many metabolites in a single shot makes it an indispensable platform in metabolomics. In this regard, Fourier-transform ion cyclotron resonance (FTICR) has the unique advantage of delivering high mass resolving power and mass accuracy simultaneously, making it ideal for the study of complex mixtures such as plant extracts. Here we optimize soybean leaf extraction methods compatible with high-throughput reproducible MS-based metabolomics. In addition, matrix-assisted laser desorption ionization (MALDI) and direct LDI of soybean leaves are compared for metabolite profiling. The extraction method combined with electrospray (ESI)-FTICR is supported by the significant reduction of chlorophyll and its related metabolites as the growing season moves from midsummer to the autumn harvest day. To our knowledge for the first time, the use of ESI-FTICR MS and MALDI-FTICR MS is described in a complementary manner with the aim of metabolic profiling of plant leaves that have been collected at different time points during the growing season.

  16. Metabolic profiling and biological capacity of Pieris brassicae fed with kale (Brassica oleracea L. var. acephala).

    Science.gov (United States)

    Ferreres, Federico; Fernandes, Fátima; Oliveira, Jorge M A; Valentão, Patrícia; Pereira, José A; Andrade, Paula B

    2009-06-01

    Phenolic and organic acid profiles of aqueous extracts from Pieris brassicae material and the host kale (Brassica oleracea L. var. acephala) leaves were determined by HPLC/UV-DAD/MS(n)-ESI and HPLC-UV, respectively. The identified phenolics included acylated and nonacylated flavonoid glycosides, hydroxycinnamic acyl gentiobiosides, and sulphate phenolics. Kale exhibited the highest content (11g/kg lyophilized extract), while no phenolics were identified in the butterflies or exuviae. Nine different organic acids were characterized in the materials, with kale showing the highest amount (112g/kg lyophilized extract). With the exception of the exuviae extract, the rest were screened for bioactivity. Using spectrophotometric microassays, all exhibited antiradical capacity against DPPH and NO in a concentration-dependent way, whereas only kale and excrement extracts were active against superoxide. All displayed activity on intestinal smooth muscle, albeit with distinct relaxation-contraction profiles. Larvae and butterfly extracts were more efficacious for intestinal relaxation than was kale extract, whereas excrement extract evoked only contractions, thus evidencing their different compositions. Collectively, these results show that P. brassicae sequesters and metabolizes kale's phenolic compounds. Moreover, the extract's bioactivities suggest that they may constitute an interesting source of bioactive compounds whose complex chemical structures preclude either synthesis or isolation.

  17. Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma

    Science.gov (United States)

    Jalbert, Llewellyn E.; Elkhaled, Adam; Phillips, Joanna J.; Neill, Evan; Williams, Aurelia; Crane, Jason C.; Olson, Marram P.; Molinaro, Annette M.; Berger, Mitchel S.; Kurhanewicz, John; Ronen, Sabrina M.; Chang, Susan M.; Nelson, Sarah J.

    2017-03-01

    Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy.

  18. Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles

    Directory of Open Access Journals (Sweden)

    Cassandra Collins

    2017-09-01

    Full Text Available Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein, indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

  19. Frankincense and myrrh suppress inflammation via regulation of the metabolic profiling and the MAPK signaling pathway.

    Science.gov (United States)

    Su, Shulan; Duan, Jinao; Chen, Ting; Huang, Xiaochen; Shang, Erxin; Yu, Li; Wei, Kaifeng; Zhu, Yue; Guo, Jianming; Guo, Sheng; Liu, Pei; Qian, Dawei; Tang, Yuping

    2015-09-02

    Frankincense and myrrh are highly effective in treatment of inflammatory diseases, but lacking of thetherapy mechanisms. We undertook this study to evaluate the effects on Adjuvant-induced Arthritis(AIA) rats and to explore the underlying mechanisms by analyzing the metabolic profiling and signalingpathway evaluated by expression of inflammatory cytokines, c-jun and c-fos and corresponding phosphorylationlevels. [corrected]. The results stated the elevated expression levels of TNFα, PGE2, IL-2, NO, and MDA in serum and swelling paw of AIA rats were significantly decreased after treatment, which exerted more remarkable inhibitive effects of combined therapy. The metbolic profiling of plasma and urine were clearly improved and twenty-one potential biomarkers were identified. Moreover, the inhibited effects of five bioactive components on cytokine transcription in PHA stimulated-PBMC showed the MAPK pathway might account for this phenomenon with considerable reduction in phosphorylated forms of all the three MAPK (ERK1/2, p38 and JNK) and down regulation of c-jun and c-fos.

  20. Overlap in serum metabolic profiles between non-related diseases: Implications for LC-MS metabolomics biomarker discovery.

    Science.gov (United States)

    Lindahl, Anna; Forshed, Jenny; Nordström, Anders

    2016-09-23

    Untargeted metabolic profiling has generated large activity in the field of clinical biomarker discovery. Yet, no clinically approved metabolite biomarkers have emerged with failure in validation phases often being a reason. To investigate why, we have applied untargeted metabolic profiling in a retrospective cohort of serum samples representing non-related diseases. Age and gender matched samples from patients diagnosed with pneumonia, congestive heart failure, lymphoma and healthy controls were subject to comprehensive metabolic profiling using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The metabolic profile of each diagnosis was compared to the healthy control group and significant metabolites were filtered out using t-test with FDR correction. Metabolites found to be significant between each disease and healthy controls were compared and analyzed for overlap. Results show that despite differences in etiology and clinical disease presentation, the fraction of metabolites with an overlap between two or more diseases was 61%. A majority of these metabolites can be associated with immune responses thus representing non-disease specific events. We show that metabolic serum profiles from patients representing non-related diseases display very similar metabolic differences when compared to healthy controls. Many of the metabolites discovered as disease specific in this study have further been associated with other diseases in the literature. Based on our findings we suggest non-related disease controls in metabolomics biomarker discovery studies to increase the chances of a successful validation and future clinical applications. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Stepwise metabolic adaption from pure metabolization to balanced anaerobic growth on xylose explored for recombinant Saccharomyces cerevisiae.

    Science.gov (United States)

    Klimacek, Mario; Kirl, Elisabeth; Krahulec, Stefan; Longus, Karin; Novy, Vera; Nidetzky, Bernd

    2014-03-08

    To effectively convert lignocellulosic feedstocks to bio-ethanol anaerobic growth on xylose constitutes an essential trait that Saccharomyces cerevisiae strains normally do not adopt through the selective integration of a xylose assimilation route as the rate of ATP-formation is below energy requirements for cell maintenance (mATP). To enable cell growth extensive evolutionary and/or elaborate rational engineering is required. However the number of available strains meeting demands for process integration are limited. In this work evolutionary engineering in just two stages coupled to strain selection under strict anaerobic conditions was carried out with BP10001 as progenitor. BP10001 is an efficient (Yethanol = 0.35 g/g) but slow (qethanol = 0.05 ± 0.01 g/gBM/h) xylose-metabolizing recombinant strain of Saccharomyces cerevisiae that expresses an optimized yeast-type xylose assimilation pathway. BP10001 was adapted in 5 generations to anaerobic growth on xylose by prolonged incubation for 91 days in sealed flasks. Resultant strain IBB10A02 displayed a specific growth rate μ of 0.025 ± 0.002 h-1 but produced large amounts of glycerol and xylitol. In addition growth was strongly impaired at pH below 6.0 and in the presence of weak acids. Using sequential batch selection and IBB10A02 as basis, IBB10B05 was evolved (56 generations). IBB10B05 was capable of fast (μ = 0.056 ± 0.003 h-1; qethanol = 0.28 ± 0.04 g/gBM/h), efficient (Yethanol = 0.35 ± 0.02 g/g), robust and balanced fermentation of xylose. Importantly, IBB10A02 and IBB10B05 displayed a stable phenotype. Unlike BP10001 both strains displayed an unprecedented biphasic formation of glycerol and xylitol along the fermentation time. Transition from a glycerol- to a xylitol-dominated growth phase, probably controlled by CO2/HCO3-, was accompanied by a 2.3-fold increase of mATP while YATP (= 87 ± 7 mmolATP/gBM) remained unaffected. As long as glycerol

  2. Long-term high air pollution exposure induced metabolic adaptations in traffic policemen.

    Science.gov (United States)

    Tan, Chaochao; Wang, Yupeng; Lin, Mingyue; Wang, Zhu; He, Li; Li, Zhiyi; Li, Yu; Xu, Keqian

    2018-01-05

    To assess the adverse physiological changes induced by long-term exposure to PM2.5. Totally 183 traffic policemen and 88 office policemen as the control group, were enrolled in this study. The concentrations of PM2.5 in both the working places of traffic and office policemen were obtained. Detailed personal questionnaires and conventional laboratory tests including hematology, fasting blood glucose, blood lipids, liver, kidney, immunity and tumor-related markers were conducted on all participants of this study. A dose-response relationship between the FBG, HDL-c and CEA values and the PM2.5 exposure duration was observed. Multivariate analysis confirmed that one hour on duty outdoor per day for one year was associated with an increase in FBG of 0.005% (95% CI: 0.0004% to 0.009%), CEA of 0.012% (95% CI: 0.006% to 0.017%), and a decrease in HDL-C of 0.001% (95% CI: 0.00034% to 0.002%). Long-term high air pollution exposure may lead to metabolism adaptation and it is likely involved in the development of cardiovascular disease and diabetes mellitus. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Leishmania amazonensis: metabolic adaptations induced by resistance to an ABC transporter blocker.

    Science.gov (United States)

    Machuca, Claudia; Rodríguez, Adriana; Herrera, Marymar; Silva, Sonia; Ponte-Sucre, Alicia

    2006-09-01

    We compared growth rate, cell glucose turnover and expression of ATP-binding-cassette (ABC) transporters in Leishmania amazonensis (LTB0016; LTB) versus LTB(160) selected for resistance against the ABC transporter blocker glibenclamide. Additionally, we evaluated the influence of drug-resistance on Leishmania sensitivity against 2-mercaptoacetate and 2-deoxyglucose. Our data demonstrate that (1) LTB(160) and LTB constitutively express ABC transporters for neutral substrates, (2) glibenclamide resistance induces the expression of organic anion ABC transporters, members of the drug resistance associated transporters subfamily, (3) LTB(160) parasites use less glucose as energy substrate and exhibit a slower glucose uptake than LTB cells, and (4) LTB(160) parasites are less sensitive to 2-mercaptoacetate and 2-deoxyglucose than the glibenclamide-sensitive Leishmania LTB. Together these and previous results indicate that the metabolic adaptations expressed in drug-resistant LTB(160) differ from those described for mammalian drug resistant cells and constitute general mechanisms that underlie drug resistance in Leishmania and may be helpful for identifying alternative strategies to circumvent drug resistance in leishmaniasis.

  4. Metabolic profile at first-time schizophrenia diagnosis: a population-based cross-sectional study

    National Research Council Canada - National Science Library

    Horsdal, Henriette Thisted; Benros, Michael Erickson; Köhler-Forsberg, Ole; Krogh, Jesper; Gasse, Christiane

    2017-01-01

    ...: Schizophrenia and/or antipsychotic drug use are associated with metabolic abnormalities; however, knowledge regarding metabolic status and physician's monitoring of metabolic status at first schizophrenia diagnosis is sparse...

  5. IV. Discovery of CXCR3 antagonists substituted with heterocycles as amide surrogates: improved PK, hERG and metabolic profiles.

    Science.gov (United States)

    Nair, Anilkumar G; Wong, Michael K C; Shu, Youheng; Jiang, Yueheng; Jenh, Chung-Her; Kim, Seong Heon; Yang, De-Yi; Zeng, Qingbei; Shao, Yuefei; Zawacki, Lisa Guise; Duo, Jingqi; McGuinness, Brian F; Carroll, Carolyn Diianni; Hobbs, Doug W; Shih, Neng-Yang; Rosenblum, Stuart B; Kozlowski, Joseph A

    2014-02-15

    The structure-human CXCR3 binding affinity relationship of a series of pyridyl/pyrazinyl-piperazinyl-piperidine derivatives were explored with a focus to improve PK, hERG and metabolic profiles. Several small heterocycles were identified as amide surrogates, which minimized many potential metabolite issues. During the course of SAR development, we have observed the additive effect of desirable functional groups to improve hERG and PK profiles which lead to the discovery of many clinically developable CXCR3 antagonists with excellent overall profile. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Tailoring Nutritional Advice for Mexicans Based on Prevalence Profiles of Diet-Related Adaptive Gene Polymorphisms

    Directory of Open Access Journals (Sweden)

    Claudia Ojeda-Granados

    2017-11-01

    Full Text Available Diet-related adaptive gene (DRAG polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM and Mestizos who have variable AM, European (EUR and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA software, based on the published data of the MTHFR C677T (rs1801133, ABCA1 Arg230Cys (rs9282541, APOE T388C (rs429358/C526T (rs7412, LCT C-13910T (rs4988235 polymorphisms and AMY1 copy number variation (CNV. Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that

  7. Maternal prepregnancy BMI, offspring's early postnatal growth, and metabolic profile at age 5-6 years: the ABCD Study

    NARCIS (Netherlands)

    Oostvogels, Adriëtte J. J. M.; Stronks, Karien; Roseboom, Tessa J.; van der Post, Joris A. M.; van Eijsden, Manon; Vrijkotte, Tanja G. M.

    2014-01-01

    Maternal prepregnancy body mass index (pBMI) and offspring's accelerated postnatal growth have adverse consequences for later cardiometabolic health, but it is unknown how these two factors interact. To assess the association between maternal pBMI and offspring's metabolic profile at age 5-6 years

  8. Undiagnosed diabetes has poorer profiles for cardiovascular and metabolic markers than known diabetes: The Yuport Medical Checkup Center Study.

    Science.gov (United States)

    Ohara, Chisin; Inoue, Kazuo; Kashima, Saori; Inoue, Machiko; Akimoto, Kimihiko

    2013-08-01

    We compared cardiovascular and metabolic markers between undiagnosed and known diabetes among 3045 subjects who had voluntary health check and no cardiovascular disease. Subjects with undiagnosed diabetes had poorer profiles of these markers than those with known diabetes. Undiagnosed diabetes should be recognized as a condition with these risks. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. A recycling pathway for cyanogenic glycosides evidenced by the comparative metabolic profiling in three cyanogenic plant species

    DEFF Research Database (Denmark)

    Pičmanová, Martina; Neilson, Elizabeth H.; Motawia, Mohammed S.

    2015-01-01

    nitrogen at specific developmental stages. To investigate the presence of putative turnover products of cyanogenic glycosides, comparative metabolic profiling using LC-MS/MS and HR-MS complemented by ion-mobility mass spectrometry was carried out in three cyanogenic plant species: cassava, almond...

  10. Enantioselective Effects of Metalaxyl Enantiomers on Breast Cancer Cells Metabolic Profiling Using HPLC-QTOF-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Ping Zhang

    2017-01-01

    Full Text Available In this study, an integrative high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (HPLC-QTOF based metabolomics approach was performed to evaluate the enantioselective metabolic perturbations in MCF-7 cells after treatment with R-metalaxyl and S-metalaxyl, respectively. Untargeted metabolomics profile, multivariate pattern recognition, metabolites identification, and pathway analysis were determined after metalaxyl enantiomer exposure. Principal component analysis (PCA and partitial least-squares discriminant analysis (PLS-DA directly reflected the enantioselective metabolic perturbations induced by metalaxyl enantiomers. On the basis of multivariate statistical results, a total of 49 metabolites including carbohydrates, amino acids, nucleotides, fatty acids, organic acids, phospholipids, indoles, derivatives, etc. were found to be the most significantly changed metabolites and metabolic fluctuations caused by the same concentration of R-metalaxyl and S-metalaxyl were enantioselective. Pathway analysis indicated that R-metalaxyl and S-metalaxyl mainly affected the 7 and 10 pathways in MCF-7 cells, respectively, implying the perturbed pathways induced by metalaxyl enantiomers were also enantioselective. Furthermore, the significantly perturbed metabolic pathways were highly related to energy metabolism, amino acid metabolism, lipid metabolism, and antioxidant defense. Such results provide more specific insights into the enantioselective metabolic effects of chiral pesticides in breast cancer progression, reveal the underlying mechanisms, and provide available data for the health risk assessments of chiral environmental pollutants at the molecular level.

  11. Involvement of alternative oxidase (AOX) in adventitious rooting of Olea europaea L. microshoots is linked to adaptive phenylpropanoid and lignin metabolism.

    Science.gov (United States)

    Santos Macedo, E; Sircar, D; Cardoso, H G; Peixe, A; Arnholdt-Schmitt, B

    2012-09-01

    Alternative oxidase (AOX) has been proposed as a functional marker candidate in a number of events involving cell differentiation, including rooting efficiency in semi-hardwood shoot cuttings of olive (Olea europaea L.). To ascertain the general importance of AOX in olive rooting, the auxin-induced rooting process was studied in an in vitro system for microshoot propagation. Inhibition of AOX by salicylhydroxamic acid (SHAM) significantly reduced rooting efficiency. However, the inhibitor failed to exhibit any effect on the preceding calli stage. This makes the system appropriate for distinguishing dedifferentiation and de novo differentiation during root induction. Metabolite analyses of microshoots showed that total phenolics, total flavonoids and lignin contents were significantly reduced upon SHAM treatment. It was concluded that the influence of alternative respiration on root formation was associated to adaptive phenylpropanoid and lignin metabolism. Transcript profiles of two olive AOX genes (OeAOX1a and OeAOX2) were examined during the process of auxin-induced root induction. Both genes displayed stable transcript accumulation in semi-quantitative RT-PCR analysis during all experimental stages. In contrary, when the reverse primer for OeAOX2 was designed from the 3'-UTR instead of the ORF, differential transcript accumulation was observed suggesting posttranscriptional regulation of OeAOX2 during metabolic acclimation. This result confirms former observations in olive semi-hardwood shoot cuttings on differential OeAOX2 expression during root induction. It further points to the importance of future studies on the functional role of sequence and length polymorphisms in the 3'-UTR of this gene. The manuscript reports the general importance of AOX in olive adventitious rooting and the association of alternative respiration to adaptive phenylpropanoid and lignin metabolism.

  12. Features of Metabolic Processes in Children Born by Caesarean Section in the Early Adaptation Period: the Role of Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Т. S. Tumaeva

    2015-01-01

    Full Text Available Background: The postnatal adaptation comprises alteration of metabolic processes of a newborn, the disturbance of which can lead to dysfunction, and later — to the development of diseases. Objective: Our aim was to study the bond of cerebral ischemia in full-term children born by Caesarean section with the course of metabolic processes in the early neonatal period. Methods: A retrospective comparative study was conducted. Children born by Caesarean section, who had cerebral ischemia (n =120 and who didn't have it, (n = 150 were examined. Complex examination included an assessment of a number of factors: clinical, biochemical blood tests, acidbase balance, concentration of some hormones. Results: In children after Caesarean section with cerebral ischemia in the early period of adaptation we noted disturbances of the acid-base balance (BE 0.3 ± 1.9 mmol/l; р = 0.038, blood oxygenation (SaO2 79.7 ± 2.8%; р = 0.001, frank lactataemia (4.3 ± 1.8 mmol/l; р = 0.002, signs of a catabolic orientation of metabolism (hypoproteinemia, increased protein metabolism products, frank primary loss of body weight. The considerable changes of activity of the blood enzymes, disturbance of glucose metabolism indicated the lack of energy-dependent processes. Due to this, the hyperbilirubinemia and a hormonal imbalance were more often formed. Conclusion: Cerebral ischemia in children born by Caesarean section is a reason for the development of a metabolic disadaptation. The detection of disturbances of metabolic processes in the early neonatal period is necessary for a timely start of the correctional therapy in order to prevent the development of diseases in more distant periods of a child's life. 

  13. {sup 1}H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    Energy Technology Data Exchange (ETDEWEB)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D., E-mail: bernard.lemire@ualberta.ca [University of Alberta, Department of Biochemistry, School of Molecular and Systems Medicine (Canada)

    2011-04-15

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in {sup 1}H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  14. Pharmacokinetics and comparative metabolic profiling of iridoid enriched fraction of Picrorhiza kurroa - An Ayurvedic Herb.

    Science.gov (United States)

    Zahiruddin, Sultan; Khan, Washim; Nehra, Rinki; Alam, Md Javed; Mallick, Md Nasar; Parveen, Rabea; Ahmad, Sayeed

    2017-02-02

    Picrosides I, II and apocynin are the main active principles present in the roots and rhizomes of Picrorhiza kurroa Royle ex. Benth (Kutki). Ethno-medicinally, the plant is used for the treatment of liver, upper respiratory tract disorders and dyspepsia, since long in Ayurveda. This study attempts to determine the pharmacokinetic profile of picrosides I, II and apocynin in rats after oral administration of iridoid enriched fraction (IRF) and to recognize the pattern of its metabolites as such in IRF and in plasma. A simple, precise, specific and sensitive RP-HPLC method was developed for simultaneous quantification of picrosides I, II and apocynin in rat plasma and in plant extract. Acetonitrile (ACN) and water was used as a solvent system with a gradient elution for pharmacokinetic studies using HPLC-PDA (Flow rate: 1.0mL/min) and metabolic profiling through UPLC-MS (Flow rate: 0.5mL/min) in selected reaction monitoring. A comparative study was performed in order to recognize the pattern and fate of metabolites in rat plasma up to 24h after single oral administration of IRF. Developed method produced more than 85% recovery of the targeted metabolites in rat plasma. The content of picrosides I, II and apocynin in IRF were found 5.7%, 18.3% and 27.3% w/w, respectively. The mean plasma concentration versus time profiles of picroside I, II and apocynin resulted in peak plasma concentration (C max ) 244.9, 104.6 and 504.2ng/mL with half-life (t 1/2 ) 14, 8 and 6h, respectively. Other pharmacokinetic parameters such as time to reach C max (t max ), area under curve (AUC), absorption (k a ) and elimination (k e ) constant, volume of distribution (V d ) were also determined. Pattern recognition analysis showed fate of 18 metabolites in rat plasma up to 24h out of 26 present in IRF. The information gained from this study postulates the basic pharmacokinetic profiling of picroside I, II and apocynin as well as fate of other metabolites after oral administration of IRF

  15. Assessing long-term effects of eslicarbazepine acetate on lipid metabolism profile, sodium values and liver function tests.

    Science.gov (United States)

    Ley, M; Principe, A; Jiménez-Conde, J; Rocamora, R

    2015-09-01

    Older dibenzazepines with a carboxamide substitution have been demonstrated to cause deleterious effects on lipid metabolism profile, as well as frequent hyponatremia. The aim of our study is to assess the effects of eslicarbazepine acetate, a novel AED, on lipid metabolism profile, sodium values and liver function tests, as well as to compare them with previous effects of carbamazepine and oxcarbazepine. This report describes a retrospective cohort study of 108 patients who were treated with eslicarbazepine. Of these patients, 52% had switched to eslicarbazepine from prior treatment with carbamazepine or oxcarbazepine. Laboratory values concerning lipid metabolism profile, liver function tests and sodium were assessed before and after beginning/switching treatment. Patients who began treatment or whose treatment for dyslipidemia was modified during the study period were excluded from the analysis. Co-medications that could impact lipid metabolism profile, sodium or hepatic function were kept stable during the study period. The mean total cholesterol of the entire group decreased significantly from prior pathological to normal values after beginning/switching treatment. The percentage of patients with pathological values decreased. Patients switching from prior carboxamides also showed significant reductions in mean LDL and triglycerides. Patients beginning treatment without prior carboxamides did not develop dyslipidemia after titration. A tendency for an increased percentage of patients with hyponatremia was detected in both groups. Compared with older carboxamides, eslicarbazepine acetate exhibits a safer profile related to lipid metabolism. No relevant changes were detected in liver function tests. Consequently, a vascular risk factor could be avoided in patients with chronic epilepsy, while hyponatremia still needs to be ruled out. Prospective studies are still needed. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Effects of ACE inhibitors on insulin resistance and lipid profile in children with metabolic syndrome.

    Science.gov (United States)

    Bitkin, Eda Celebi; Boyraz, Mehmet; Taşkın, Necati; Akçay, Arzu; Ulucan, Korkut; Akyol, Mehmet Bedir; Akçay, Teoman

    2013-09-10

    The aim of this study was to evaluate the effects of using ACE inhibitors on insulin resistance, glucose metabolism, body fat composition, and lipid profile in children over 10 years of age with obesity-associated metabolic syndrome (MS). A total of 53 children with MS, who had been followed for at least one year were included in the study. The sample was divided into two groups: Group 1-30 obese children (13 female, 17 male) who were not using an ACE inhibitor and Group 2-23 obese children (13 female, 10 male) who were using an ACE inhibitor. Anthropometric and laboratory data obtained at baseline and at the 3rd, 6th, and 12th months of follow-up were compared in the two groups. Comparison of the data in the two groups at 3rd, 6th, and 12th months revealed no statistically significant differences in terms of weight standard deviation score (SDS), body mass index SDS, weight for height percentile, body fat percentage, and very low-density lipoprotein (VLDL)values. However, there were statistically significant differences in mean glucose and insulin levels, homeostasis model assessment for insulin resistance, LDL and high-density lipoprotein values, and highly significant differences in mean triglyceride values. The positive effects of ACE inhibitor drugs, particularly on hypertriglyceridemia and insulin resistance, might bring them forth as first-line drugs in the treatment of obese and hypertensive children. Randomized, controlled, double-blind, and long-term studies are needed for a definitive conclusion.

  17. Peripheral blood-derived cytokine gene polymorphisms and metabolic profile in women with polycystic ovary syndrome.

    Science.gov (United States)

    Sóter, Mirelle O; Ferreira, Cláudia N; Sales, Mariana F; Candido, Ana L; Reis, Fernando M; Milagres, Kátia S; Ronda, Carla; Silva, Ieda O; Sousa, Marinez O; Gomes, Karina B

    2015-12-01

    The imbalance between proinflammatory and anti-inflammatory pathways plays a role in polycystic ovary syndrome (PCOS) etiology. We aimed to investigate the relationship between polymorphisms of genes encoding inflammation-associated cytokines and the metabolic profile of Brazilian women with PCOS. Case-control study. The study included 196 women - 97 with PCOS (diagnosed based on Rotterdam criteria, 2003) and 99 age-matched, healthy women (controls). It was investigated polymorphisms in cytokines genes from peripheral blood-derived DNA by using PCR. The frequencies of alleles, genotypes, and phenotypes were similar between women with PCOS and controls. The GG genotype of the -179C/G polymorphism (IL6) was associated with higher glucose levels, while the GA and AA genotypes of the -1082A/G polymorphism (IL10), CT and TT genotypes of the -819A/T polymorphism (IL10), CA and AA genotypes of the -522A/G (IL10) polymorphism, and TA genotype of the +874T/A polymorphism (IFN-γ) were associated with lower total cholesterol and triglycerides levels. The GA genotype of the -1082A/G polymorphism (IL10) and the CC genotype of the 10T/C polymorphism (TGF-β1) were associated with lower and higher Ferriman indices, respectively, in women with PCOS. The AA genotype of the -1082A/G polymorphism (IL10) was associated with lower glucose levels, while the TC genotype of the 10T/C polymorphism (TGF-β1) was associated with a lower lipid accumulation product index and higher high-density lipoprotein cholesterol levels in the PCOS group. The genetic polymorphisms of cytokines are not associated with PCOS development, but may contribute to common metabolic disorders associated with PCOS. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Effects of 3-styrylchromones on metabolic profiles and cell death in oral squamous cell carcinoma cells

    Directory of Open Access Journals (Sweden)

    Hiroshi Sakagami

    2015-01-01

    Full Text Available 4H-1-benzopyran-4-ones (chromones are important naturally-distributing compounds. As compared with flavones, isoflavones and 2-styrylchromones, there are only few papers of 3-styrylchromones that have been published. We have previously reported that among fifteen 3-styrylchromone derivatives, three new synthetic compounds that have OCH3 group at the C-6 position of chromone ring, (E-3-(4-hydroxystyryl-6-methoxy-4H-chromen-4-one (compound 11, (E-6-methoxy-3-(4-methoxystyryl-4H-chromen-4-one (compound 4, (E-6-methoxy-3-(3,4,5-trimethoxystyryl-4H-chromen-4-one (compound 6 showed much higher cytotoxicities against four epithelial human oral squamous cell carcinoma (OSCC lines than human normal oral mesenchymal cells. In order to further confirm the tumor specificities of these compounds, we compared their cytotoxicities against both human epithelial malignant and non-malignant cells, and then investigated their effects on fine cell structures and metabolic profiles and cell death in human OSCC cell line HSC-2. Cytotoxicities of compounds 4, 6, 11 were assayed with MTT method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to CE-TOFMS analysis. Compounds 4, 6, 11 showed much weaker cytotoxicity against human oral keratinocyte and primary human gingival epithelial cells, as compared with HSC-2, confirming their tumor-specificity, whereas doxorubicin and 5-FU were highly cytotoxic to these normal epithelial cells, giving unexpectedly lower tumor-specificity. The most cytotoxic compound 11, induced the mitochondrial vacuolization, autophagy suppression followed by apoptosis induction, and changes in the metabolites involved in amino acid and glycerophospholipid metabolisms. Chemical modification of lead compound 11 may be a potential choice for designing new type of anticancer drugs.

  19. Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis

    Science.gov (United States)

    2012-01-01

    Background Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied with an increased risk of developing type 2 diabetes mellitus and cardiovascular disease; despite being a common condition, the pathogenesis of PCOS remains unclear. Our aim was to investigate the potential metabolic profiles for different phenotypes of PCOS, as well as for the early prognosis of complications. Methods A total of 217 women with PCOS and 48 healthy women as normal controls were studied. Plasma samples of subjects were tested using two different analytical platforms of metabolomics: 1H nuclear magnetic resonance (NMR) and gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS). Results Our results showed that carbohydrate, lipid and amino acid metabolisms were influenced in PCOS. The levels of lactate, long-chain fatty acids, triglyceride and very low-density lipoprotein were elevated, while glucose, phosphatidylcholine and high-density lipoprotein (HDL) concentrations were reduced in PCOS patients as compared with controls. Additionally, the levels of alanine, valine, serine, threonine, ornithine, phenylalanine, tyrosine and tryptophan were generally increased, whereas the levels of glycine and proline were significantly reduced in PCOS samples compared to controls. Furthermore, the ratio of branched-chain amino acid to aromatic amino acid concentrations (BCAA/AAA) in PCOS plasma was significantly reduced in PCOS patients and was insusceptible to obesity and insulin sensitivity. Conclusions Our results suggested that the enhanced glycolysis and inhibited tricarboxylic acid cycle (TAC) in women with PCOS. Decrease of BCAA/AAA ratio was directly correlated with the development of PCOS. Ovulatory dysfunction of PCOS patients was associated with raised production of serine, threonine, phenylalanine, tyrosine and ornithine. Elevated levels of valine and leucine, and decreased concentrations of glycine in PCOS plasma could contribute to insulin

  20. Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis.

    Science.gov (United States)

    Zhao, Yue; Fu, Li; Li, Rong; Wang, Li-Na; Yang, Yan; Liu, Na-Na; Zhang, Chun-Mei; Wang, Ying; Liu, Ping; Tu, Bin-Bin; Zhang, Xue; Qiao, Jie

    2012-11-30

    Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied with an increased risk of developing type 2 diabetes mellitus and cardiovascular disease; despite being a common condition, the pathogenesis of PCOS remains unclear. Our aim was to investigate the potential metabolic profiles for different phenotypes of PCOS, as well as for the early prognosis of complications. A total of 217 women with PCOS and 48 healthy women as normal controls were studied. Plasma samples of subjects were tested using two different analytical platforms of metabolomics: 1H nuclear magnetic resonance (NMR) and gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS). Our results showed that carbohydrate, lipid and amino acid metabolisms were influenced in PCOS. The levels of lactate, long-chain fatty acids, triglyceride and very low-density lipoprotein were elevated, while glucose, phosphatidylcholine and high-density lipoprotein (HDL) concentrations were reduced in PCOS patients as compared with controls. Additionally, the levels of alanine, valine, serine, threonine, ornithine, phenylalanine, tyrosine and tryptophan were generally increased, whereas the levels of glycine and proline were significantly reduced in PCOS samples compared to controls. Furthermore, the ratio of branched-chain amino acid to aromatic amino acid concentrations (BCAA/AAA) in PCOS plasma was significantly reduced in PCOS patients and was insusceptible to obesity and insulin sensitivity. Our results suggested that the enhanced glycolysis and inhibited tricarboxylic acid cycle (TAC) in women with PCOS. Decrease of BCAA/AAA ratio was directly correlated with the development of PCOS. Ovulatory dysfunction of PCOS patients was associated with raised production of serine, threonine, phenylalanine, tyrosine and ornithine. Elevated levels of valine and leucine, and decreased concentrations of glycine in PCOS plasma could contribute to insulin sensitivity and could be considered as the

  1. Potential of fermentation profiling via rapid measurement of amino acid metabolism by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Dalluge, Joseph J; Smith, Sean; Sanchez-Riera, Fernando; McGuire, Chris; Hobson, Russell

    2004-07-16

    Monitoring amino acid metabolism during fermentation has significant potential from the standpoint of strain selection, optimizing growth and production in host strains, and profiling microbial metabolism and growth state. A method has been developed based on rapid quantification of underivatized amino acids using liquid chromatography-electrospray tandem mass spectrometry (LC-MS-MS) to monitor the metabolism of 20 amino acids during microbial fermentation. The use of a teicoplanin-based chiral stationary phase coupled with electrospray tandem mass spectrometry allows complete amino acid analyses in less than 4 min. Quantification is accomplished using five isotopically labeled amino acids as internal standards. Because comprehensive chromatographic separation and derivatization are not required, analysis time is significantly less than traditional reversed- or normal-phase LC-based amino acid assays. Intra-sample precisions for amino acid measurements in fermentation supernatants using this method average 4.9% (R.S.D.). Inter-day (inter-fermentation) precisions for individual amino acid measurements range from 4.2 to 129% (R.S.D.). Calibration curves are linear over the range 0-300 microg/ml, and detection limits are estimated at 50-450 ng/ml. Data visualization techniques for constructing semi-quantitative fermentation profiles of nitrogen source utilization have also been developed and implemented, and demonstrate that amino acid profiles generally correlate with observed growth profiles. Further, cellular growth events, such as lag-time and cell lysis can be detected using this methodology. Correlation coefficients for the time profiles of each amino acid measured illustrate that while several amino acids are differentially metabolized in similar fermentations, a select group of amino acids display strong correlations in these samples, indicating a sub-population of analytes that may be most useful for fermentation profiling.

  2. Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism.

    Science.gov (United States)

    Germain, Arnaud; Ruppert, David; Levine, Susan M; Hanson, Maureen R

    2017-01-31

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a continuum spectrum disease without biomarkers or simple objective tests, and therefore relies on a diagnosis from a set of symptoms to link the assortment of brain and body disorders to ME/CFS. Although recent studies show various affected pathways, the underlying basis of ME/CFS has yet to be established. In this pilot study, we compare plasma metabolic signatures in a discovery cohort, 17 patients and 15 matched controls, and explore potential metabolic perturbations as the aftermath of the complex interactions between genes, transcripts and proteins. This approach to examine the complex array of symptoms and underlying foundation of ME/CFS revealed 74 differentially accumulating metabolites, out of 361 (P < 0.05), and 35 significantly altered after statistical correction (Q < 0.15). The latter list includes several essential energy-related compounds which could theoretically be linked to the general lack of energy observed in ME/CFS patients. Pathway analysis points to a few pathways with high impact and therefore potential disturbances in patients, mainly taurine metabolism and glycerophospholipid metabolism, combined with primary bile acid metabolism, as well as glyoxylate and dicarboxylate metabolism and a few other pathways, all involved broadly in fatty acid metabolism. Purines, including ADP and ATP, pyrimidines and several amino acid metabolic pathways were found to be significantly disturbed. Finally, glucose and oxaloacetate were two main metabolites affected that have a major effect on sugar and energy levels. Our work provides a prospective path for diagnosis and understanding of the underlying mechanisms of ME/CFS.

  3. Use of metabolic profiles in dairy cattle in tropical and subtropical countries on smallholder dairy farms.

    Science.gov (United States)

    Whitaker, D A; Goodger, W J; Garcia, M; Perera, B M; Wittwer, F

    1999-01-27

    Metabolic profile testing has generally been used as part of a multidisciplinary approach for dairy herds in temperate climates. Our goal was to evaluate the effectiveness of the technique for identifying constraints on productivity in small herds in environments less favorable for milk production. Metabolites tested were chosen for stability in the sample after collection of blood, ease of analysis and practical knowledge of the meaning of the results. Blood levels of five different metabolites in low-producing dairy cows belonging to smallholders in tropical and subtropical environments were measured. The study involved 13 projects with 80 cows in each, carried out in six Latin American, six Asian, and one southern European countries. Data were also collected on feeding, body condition score (BCS) and weight change, parasitism, and reproduction. In Chile, Mexico, Paraguay, Philippines, Uruguay, and Venezuela, globulin levels were high in > 17% of cows sampled on each occasion. Globulin levels were also high in Turkey and Vietnam on one or more occasions. In Paraguay, 49% of cows had high globulin levels at two to three months after calving. These results suggest that inflammatory disease was present to a potentially important degree, although this was not always investigated and not always taken into account. In all countries except Mexico and Venezuela, high beta-hydroxybutyrate (BHB) levels before calving in many cows highlighted the presence of condition loss in late pregnancy, an important potential constraint on productivity and fertility. Fewer cows showed high BHB levels in lactation, whereas change in BCS and weight was more sensitive for measuring negative energy balance. Urea concentrations were low in only small numbers of cows suggesting that dietary protein shortages were not common. Albumin values were low mainly in cows where globulin values were high and, hence, did not generally provide additional information. The exception was in China where

  4. The mRNA expression profile of metabolic genes relative to MHC isoform pattern in human skeletal muscles

    DEFF Research Database (Denmark)

    Plomgaard, Peter; Penkowa, Milena; Leick, Lotte

    2006-01-01

    The metabolic profile of rodent muscle is generally reflected in the myosin heavy chain (MHC) fiber-type composition. The present study was conducted to test the hypothesis that metabolic gene expression is not tightly coupled with MHC fiber-type composition for all genes in human skeletal muscle...... was more than twofold higher in soleus and vastus than in triceps. Contrary, phosphofructokinase and total lactate dehydrogenase (LDH) activity was approximately three- and twofold higher in triceps than in both soleus and vastus. Expression of metabolic genes was assessed by determining the mRNA content...... of a broad range of metabolic genes. The triceps muscle had two- to fivefold higher MHC IIa, phosphofructokinase, and LDH A mRNA content and two- to fourfold lower MHC I, lipoprotein lipase, CD36, hormone-sensitive lipase, and LDH B and hexokinase II mRNA than vastus lateralis or soleus. Interestingly...

  5. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing [181st Hospital Guangxi, Central Laboratory, Laboratory of Metabolic Diseases Research, Guangxi Province (China); Li, Liping [Guangxi Normal University, The Life Science College, Guangxi Province (China); Li, Wuxian [Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqiong Medical University, Chongqing (China); Dai, Yong [Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People' s Hospital), Shenzhen, Guangdong Province (China)

    2012-07-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH{sub 2}-CH = O), L5 lipids (-CH{sub 2}-C = O), and L3 lipids (-CH{sub 2}-CH{sub 2}-C = O) as well as lower levels of {beta}-glucose, {alpha}-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high

  6. NMR Metabolic profiling of green tea (Camellia sinensis L.) leaves grown at Kemuning, Indonesia

    Science.gov (United States)

    Wahyuni, D. S. C.; Kristanti, M. W.; Putri, R. K.; Rinanto, Y.

    2017-01-01

    Green tea (Camellia sinensis L.) has been famous as a beverage and natural medicine. It contains a broad range of primary and secondary metabolites i.e. polyphenols. Nuclear Magnetic Resonance (NMR) has been widely used for metabolic profiling in medicinal plants. It provides a very fast and detailed analysis of the biomolecular composition of crude extracts. Moreover, an NMR spectrum is a physical characteristic of a compound and thus highly reproducible. Therefore, this study aims to profile metabolites of three different varieties of green tea C. Sinensis grown in Kemuning, Middle Java. Three varieties of green tea collected on Kemuning (TR1 2025, Gambung 4/5, and Chiaruan 143) were used in this study. 1H-NMR spectra were recorded at 230C on a 400 MHz Agilent WB (Widebore). The analysis was performed on dried green tea leaves and analyzed by 1H-NMR, 2D-J-resolved and 1H-1H correlated spectroscopy (COSY). MestRenova version 11.0.0 applied to identify metabolites in samples. A 1H-NMR spectrum of tea showed amino acids and organic acids signal at the area δ 0.8-4.0. These were theanine, alanine, threonine, succinic acid, aspartic acid, lactic acid. Anomeric protons of carbohydrate were shown by the region of β-glucose, α-glucose, fructose and sucrose. The phenolic region was depicted at area δ 5.5-8.5. Epigallocatechin derivates and caffeine were detected in the tea leaves. The detail compound identification was observed and discussed in the text.

  7. Crassulacean Acid Metabolism and Epiphytism Linked to Adaptive Radiations in the Orchidaceae1[OA

    Science.gov (United States)

    Silvera, Katia; Santiago, Louis S.; Cushman, John C.; Winter, Klaus

    2009-01-01

    Species of the large family Orchidaceae display a spectacular array of adaptations and rapid speciations that are linked to several innovative features, including specialized pollination syndromes, colonization of epiphytic habitats, and the presence of Crassulacean acid metabolism (CAM), a water-conserving photosynthetic pathway. To better understand the role of CAM and epiphytism in the evolutionary expansion of tropical orchids, we sampled leaf carbon isotopic composition of 1,103 species native to Panama and Costa Rica, performed character state reconstruction and phylogenetic trait analysis of CAM and epiphytism, and related strong CAM, present in