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Sample records for adaptation metabolic profiling

  1. Metabolism as means for hypoxia adaptation: metabolic profiling and flux balance analysis

    Paternostro Giovanni

    2009-09-01

    Full Text Available Abstract Background Cellular hypoxia is a component of many diseases, but mechanisms of global hypoxic adaptation and resistance are not completely understood. Previously, a population of Drosophila flies was experimentally selected over several generations to survive a chronically hypoxic environment. NMR-based metabolomics, combined with flux-balance simulations of genome-scale metabolic networks, can generate specific hypotheses for global reaction fluxes within the cell. We applied these techniques to compare metabolic activity during acute hypoxia in muscle tissue of adapted versus "naïve" control flies. Results Metabolic profiles were gathered for adapted and control flies after exposure to acute hypoxia using 1H NMR spectroscopy. Principal Component Analysis suggested that the adapted flies are tuned to survive a specific oxygen level. Adapted flies better tolerate acute hypoxic stress, and we explored the mechanisms of this tolerance using a flux-balance model of central metabolism. In the model, adapted flies produced more ATP per glucose and created fewer protons than control flies, had lower pyruvate carboxylase flux, and had greater usage of Complex I over Complex II. Conclusion We suggest a network-level hypothesis of metabolic regulation in hypoxia-adapted flies, in which lower baseline rates of biosynthesis in adapted flies draws less anaplerotic flux, resulting in lower rates of glycolysis, less acidosis, and more efficient use of substrate during acute hypoxic stress. In addition we suggest new specific hypothesis, which were found to be consistent with existing data.

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

    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.

  3. Metabolic Adaptation to Muscle Ischemia

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

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

    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 t...

  5. Mitochondrial function adaptations to changed metabolic conditions

    Bakkman, Linda

    2010-01-01

    The skeletal muscle mitochondria play a decisive role for the metabolic capacity of the body. A capability to adapt to changed metabolic conditions and energy demands is crucial for weight control and physical exercise. The aim of this thesis was to describe how the mitochondria adapt its function to different environmental conditions and changed metabolic demands. In study I, the aim was to evaluate mitochondrial adaptations to hypoxic exercise. The effect of one-legged...

  6. Adaptive diversity: hormones and metabolism in freshwaters.

    Laudet, Vincent

    2010-12-01

    Genes underlying the evolution of morphological traits have recently been identified in a number of model species. In the stickleback, the metabolic adaptations to a freshwater habitat have now been linked to a well-known hormonal system. PMID:21145015

  7. Metabolic Profiling of Alpine and Ecuadorian Lichens

    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.

  8. Adaptive evolution of complex innovations through stepwise metabolic niche expansion.

    Szappanos, Balázs; Fritzemeier, Jonathan; Csörgő, Bálint; Lázár, Viktória; Lu, Xiaowen; Fekete, Gergely; Bálint, Balázs; Herczeg, Róbert; Nagy, István; Notebaart, Richard A; Lercher, Martin J; Pál, Csaba; Papp, Balázs

    2016-01-01

    A central challenge in evolutionary biology concerns the mechanisms by which complex metabolic innovations requiring multiple mutations arise. Here, we propose that metabolic innovations accessible through the addition of a single reaction serve as stepping stones towards the later establishment of complex metabolic features in another environment. We demonstrate the feasibility of this hypothesis through three complementary analyses. First, using genome-scale metabolic modelling, we show that complex metabolic innovations in Escherichia coli can arise via changing nutrient conditions. Second, using phylogenetic approaches, we demonstrate that the acquisition patterns of complex metabolic pathways during the evolutionary history of bacterial genomes support the hypothesis. Third, we show how adaptation of laboratory populations of E. coli to one carbon source facilitates the later adaptation to another carbon source. Our work demonstrates how complex innovations can evolve through series of adaptive steps without the need to invoke non-adaptive processes. PMID:27197754

  9. The metabolic profile of long-lived Drosophila melanogaster

    Sarup, Pernille Merete; Pedersen, Simon Metz; Nielsen, Niels Christian; Malmendal, Anders; Loeschcke, Volker

    2012-01-01

    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 and...

  10. Phthalate Exposure Changes the Metabolic Profile of Cardiac Muscle Cells

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

    2012-01-01

    Background: 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. Objectives: 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. Methods: N...

  11. Discrete Model Reference Adaptive Control System for Automatic Profiling Machine

    Peng Song; Guo-kai Xu; Xiu-chun Zhao

    2012-01-01

    Automatic profiling machine is a movement system that has a high degree of parameter variation and high frequency of transient process, and it requires an accurate control in time. In this paper, the discrete model reference adaptive control system of automatic profiling machine is discussed. Firstly, the model of automatic profiling machine is presented according to the parameters of DC motor. Then the design of the discrete model reference adaptive control is proposed, and the control rules...

  12. Development of personalised functional foods needs metabolic profiling

    Claus, Sandrine Paule

    2014-01-01

    Purpose of review There is growing interest in applying metabolic profiling technologies to food science as this approach is now embedded into the foodomics toolbox. This review aims at exploring how metabolic profiling can be applied to the development of functional foods. Recent findings One of the biggest challenges of modern nutrition is to propose a healthy diet to populations worldwide that must suit high inter-individual variability driven by complex gene-nutrient-environment...

  13. Metabolic adaptations for desert survival in the Bedouin goat.

    Choshniak, I; Ben-Kohav, N; Taylor, C R; Robertshaw, D; Barnes, R J; Dobson, A; Belkin, V; Shkolnik, A

    1995-05-01

    Energy conservation is a key adaptation for desert survival in the Bedouin goat. When food is scarce, metabolism is reduced and body weight can be maintained indefinitely on less than one-half of normal intake. We hypothesized that metabolism would be turned down during both rest and exercise, but it was not. It was low when animals rested and returned to normal during exercise. We expected catecholamines and thyroid hormones would modulate metabolism, but they did not. The reduction in metabolism preceded any change in thyroid hormone concentrations, and infusions of epinephrine did not restore reduced metabolism to normal levels. Finally, we expected the gut would be the major organ system involved in the metabolic reduction because less food is eaten, processed, and absorbed. Contrary to our expectations, we found that muscle is the primary organ system responsible for the reduction. It appears that the adaptations of the Bedouin goat for surviving on limited food supplies involve different organ systems and different modulators to reduce metabolism from those known for other mammals. PMID:7771568

  14. An Enhanced Profile Management System to Support Adaptability

    Chen Ting; Yang Yun

    2008-01-01

    An integrated management architecture which called Adaptive Agent and Profile Management System (AAPMS) was proposed here. Using this system, users can get an adaptive service list according to their current condition (terminal capability, user preference, etc.). After choosing a service, the users only need to download a simple service agent to their mobile device and install it, and then the service agent will connect to the corresponding service provider. The users and the service providers can also manage their profiles using AAPMS.

  15. Energetic Metabolism and Biochemical Adaptation: A Bird Flight Muscle Model

    Rioux, Pierre; Blier, Pierre U.

    2006-01-01

    The main objective of this class experiment is to measure the activity of two metabolic enzymes in crude extract from bird pectoral muscle and to relate the differences to their mode of locomotion and ecology. The laboratory is adapted to stimulate the interest of wildlife management students to biochemistry. The enzymatic activities of cytochrome…

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

    Rommelaere, Samuel; Millet, Virginie; Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie; Tailleux, Anne; Staels, Bart; Galland, Franck; Naquet, Philippe

    2014-01-01

    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. PMID:25141153

  17. MetAssimulo:Simulation of Realistic NMR Metabolic Profiles

    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

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

    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.

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

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

    2012-01-01

    known transcription regulation network. Interactions across multiple levels of regulation were involved in adaptive changes that could also be achieved by controlling single genes. Our analysis suggests that global trade-offs and evolutionary constraints provide incentives to favor complex control......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 and...... model-based data analyses of dynamic transcript, protein, and metabolite abundances and promoter activities. Adaptation to malate was rapid and primarily controlled posttranscriptionally compared with the slow, mainly transcriptionally controlled adaptation to glucose that entailed nearly half of the...

  20. Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting

    Rommelaere, Samuel; Millet, Virginie; Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie

    2014-01-01

    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...

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

    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. PMID:25773945

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

    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.

  3. Lipid Profile and Leptin Levels in Patients with Metabolic Syndrome

    This paper should be cited as: Esmaeili R, Hassanzadeh, T . [ Lipid Profile and Leptin Levels in Patients with Metabolic Syndrome ]. mljgoums . 201 4 ; 8 ( 3 : 23 - 29 [Article in Persian] Esmaeili, R.

    2014-09-01

    Full Text Available Background and Objective: Metabolic syndrome called a cluster of several metabolic disorders is associated with increased risk of cardiovascular diseases. Genetic differences in leptin receptor gene are related with the concentration and activity of leptin in that these discrepancies can influence lipid levels. We aimed to determine the association between the leptin receptor gene polymorphism on serum lipid profile and leptin activity in metabolic syndrome patients. Material and Methods: This case-control study was conducted on 200 patients with metabolic syndrome and 200 healthy individuals. Polymerase Chain Reaction (PCR and Restriction Fragment Length Polymorphisms (RFLP were used to determine genotypic distribution and allelic frequencies of polymorphisms, respectively. The plasma leptin activity was measured by a kit in a fluorescence spectrometer, and Lipid concentration by routine biochemical and enzymatic assays. Results: Two groups had significant differences in all measured factors such as lipid profiles, fast blood sugar, waist circumference, blood pressure and leptin concentration (P< 0.05. Conclusion: Given that the two groups had significant differences in blood and body measurements, no role of K656N polymorphism was observed. Overall, Lys656Asn (K656N polymorphism of leptin receptor gene is not associated with serum lipid profile and leptin activity with metabolic syndrome.

  4. Intercultural Profiles and Adaptation Among Immigrant and Autochthonous Adolescents

    Cristiano Inguglia; Pasquale Musso

    2015-01-01

    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...

  5. Adaptive Guidance based on Context Profile for Software Process Modeling

    Hamid Khemissa

    2012-07-01

    Full Text Available This paper aims to define an adaptive guidance for software process modeling. The proposed guidance approach is based on development’s profile context (actor’s role in the process, actor’s qualification and related activities in progress. We introduce new guidance concepts through adaptive guidance meta-model (AGM allowing specific assistance interventions (corrective, constructive and automatic guidance. We illustrate our guidance approach using SPEM formalism extended with these new guidance concepts.

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

    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.

  7. Learner Profile Management for Collaborative Adaptive eLearning Application

    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...... adaptive hypermedia systems. Existing Web Service standards, however, only provide very basic features and leave out many important issues like transactional management. In this paper we propose a mechanism for enabling consistency maintenance of Learner Profiles shared between collaborating adaptive...... learning systems....

  8. Adaptive Sensing Based on Profiles for Sensor Systems

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

    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. PMID:25566668

  10. How the edaphic Bacillus megaterium strain Mes11 adapts its metabolism to the herbicide mesotrione pressure

    Toxicity of pesticides towards microorganisms can have a major impact on ecosystem function. Nevertheless, some microorganisms are able to respond quickly to this stress by degrading these molecules. The edaphic Bacillus megaterium strain Mes11 can degrade the herbicide mesotrione. In order to gain insight into the cellular response involved, the intracellular proteome of Mes11 exposed to mesotrione was analyzed using the two-dimensional differential in-gel electrophoresis (2D-DIGE) approach coupled with mass spectrometry. The results showed an average of 1820 protein spots being detected. The gel profile analyses revealed 32 protein spots whose abundance is modified after treatment with mesotrione. Twenty spots could be identified, leading to 17 non redundant proteins, mainly involved in stress, metabolic and storage mechanisms. These findings clarify the pathways used by B. megaterium strain Mes11 to resist and adapt to the presence of mesotrione. - Highlights: • Bacillus megaterium strain Mes11 is able to degrade the herbicide mesotrione. • The response to mesotrione stress was studied by a differential proteomic approach. • Adaptation to mesotrione involves stress, central metabolism and storage proteins. • Some identified proteins could be directly involved in mesotrione degradation. - Metabolism adaptation of the mesotrione-degrading Bacillus megaterium to the mesotrione herbicide stress

  11. Adaptive Benefits of Storage Strategy and Dual AMPK/TOR Signaling in Metabolic Stress Response.

    Pfeuty, Benjamin; Thommen, Quentin

    2016-01-01

    Cellular metabolism must ensure that supply of nutrient meets the biosynthetic and bioenergetic needs. Cells have therefore developed sophisticated signaling and regulatory pathways in order to cope with dynamic fluctuations of both resource and demand and to regulate accordingly diverse anabolic and catabolic processes. Intriguingly, these pathways are organized around a relatively small number of regulatory hubs, such as the highly conserved AMPK and TOR kinase families in eukaryotic cells. Here, the global metabolic adaptations upon dynamic environment are investigated using a prototypical model of regulated metabolism. In this model, the optimal enzyme profiles as well as the underlying regulatory architecture are identified by combining perturbation and evolutionary methods. The results reveal the existence of distinct classes of adaptive strategies, which differ in the management of storage reserve depending on the intensity of the stress and in the regulation of ATP-producing reaction depending on the nature of the stress. The regulatory architecture that optimally implements these adaptive features is characterized by a crosstalk between two specialized signaling pathways, which bears close similarities with the sensing and regulatory properties of AMPK and TOR pathways. PMID:27505075

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

    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

  13. Metabolic profiling distinguishes three subtypes of Alzheimer's disease.

    Bredesen, Dale E

    2015-08-01

    The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization. PMID:26343025

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

    Alagna Fiammetta; Mariotti Roberto; Panara Francesco; Caporali Silvia; Urbani Stefania; Veneziani Gianluca; Esposto Sonia; Taticchi Agnese; Rosati Adolfo; Rao Rosa; Perrotta Gaetano; Servili Maurizio; Baldoni Luciana

    2012-01-01

    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, demethyloleu...

  15. Determination of Ancylostoma caninum ova viability using metabolic profiling.

    Gyawali, P; Beale, D J; Ahmed, W; Karpe, A V; Magalhaes, R J Soares; Morrison, P D; Palombo, E A

    2016-09-01

    Differentiation between viable and non-viable hookworm ova in environmental samples is necessary in order to implement strategies to mitigate re-infections in endemic regions. In this study, an untargeted metabolic profiling method was developed that utilised gas chromatography-mass spectrometry (GC-MS) in order to investigate hookworm ova viability. Ancylostoma caninum was used to investigate the metabolites within viable and non-viable ova. Univariate and multivariate statistical analyses of the data resulted in the identification of 53 significant metabolites across all hookworm ova samples. The major compounds observed in viable and non-viable hookworm ova were tetradecanoic acid, commonly known as myristic acid [fold change (FC) = 0.4], and dodecanoic acid, commonly known as lauric acid (FC = 0.388). Additionally, the viable ova had self-protecting metabolites such as prostaglandins, a typical feature absent in non-viable ova. The results of this study demonstrate that metabolic profiling using GC-MS methods can be used to determine the viability of canine hookworm ova. Further studies are needed to assess the applicability of metabolic profiling using GC-MS to detect viable hookworm ova in the mixed (viable and non-viable) populations from environmental samples and identify the metabolites specific to human hookworm species. PMID:27236650

  16. Adaptation from interactions between metabolism and behaviour: self-sensitive behaviour in protocells

    Egbert, Matthew

    2012-01-01

    This thesis considers the relationship between adaptive behaviour and metabolism, using theoretical arguments supported by computational models to demonstrate mechanisms of adaptation that are uniquely available to systems based upon the metabolic organisation of self-production. It is argued how, by being sensitive to their metabolic viability, an organism can respond to the quality of its environment with respect to its metabolic well-being. This makes possible simple but powerful ‘self...

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

    Verma-Gaur, Jiyoti; Qu, Yue; Harrison, Paul F.; Lo, Tricia L.; Quenault, Tara; Dagley, Michael J.; Bellousoff, Matthew; Powell, David R; Beilharz, Traude H.; Traven, Ana

    2015-01-01

    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 change...

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

    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. PMID:27247643

  19. Intercultural Profiles and Adaptation Among Immigrant and Autochthonous Adolescents

    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.

  20. Isotopologue profiling of the listerial N-metabolism.

    Kutzner, Erika; Kern, Tanja; Felsl, Angela; Eisenreich, Wolfgang; Fuchs, Thilo M

    2016-04-01

    The nitrogen (N-) sources and the relative contribution of a nitrogenous nutrient to the N-pool of the gram-positive pathogen Listeria monocytogenes are largely unknown. Therefore, (15) N-isotopologue profiling was established to study the N-metabolism of L. monocytogenes. The pathogen was grown in a defined minimal medium supplemented with potential (15) N-labeled nutrients. The bacteria were harvested and hydrolysed under acidic conditions, and the resulting amino acids were analysed by GC-MS, revealing (15) N-enrichments and isotopomeric compositions of amino acids. The differential (15) N-profiles showed the substantial and simultaneous usage of ammonium, glutamine, methionine, and, to a lower extent, the branched-chain amino acids valine, leucine, and isoleucine for anabolic purposes, with a significant preference for ammonium. In contrast, arginine, histidine and cysteine were directly incorporated into proteins. L. monocytogenes is able to replace glutamine with ethanolamine or glucosamine as amino donors for feeding the core N-metabolism. Perturbations of N-fluxes caused by gene deletions demonstrate the involvement of ethanolamine ammonia lyase, and suggest a role of the regulator GlnK of L. monocytogenes distinct from that of Escherichia coli. The metabolism of nitrogenous nutrients reflects the high flexibility of this pathogenic bacterium in exploiting N-sources that could also be relevant for its proliferation during infection. PMID:26699934

  1. Magnetic resonance imaging of tumor oxygenation and metabolic profile

    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...

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

    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.

  3. Functional profiling of cyanobacterial genomes and its role in ecological adaptations.

    Prabha, Ratna; Singh, Dhananjaya P; Somvanshi, Pallavi; Rai, Anil

    2016-09-01

    With the availability of complete genome sequences of many cyanobacterial species, it is becoming feasible to study the broad prospective of the environmental adaptation and the overall changes at transcriptional and translational level in these organisms. In the evolutionary phase, niche-specific competitive forces have resulted in specific features of the cyanobacterial genomes. In this study, functional composition of the 84 different cyanobacterial genomes and their adaptations to different environments was examined by identifying the genomic composition for specific cellular processes, which reflect their genomic functional profile and ecological adaptation. It was identified that among cyanobacterial genomes, metabolic genes have major share over other categories and differentiation of genomic functional profile was observed for the species inhabiting different habitats. The cyanobacteria of freshwater and other habitats accumulate large number of poorly characterized genes. Strain specific functions were also reported in many cyanobacterial members, of which an important feature was the occurrence of phage-related sequences. From this study, it can be speculated that habitat is one of the major factors in giving the shape of functional composition of cyanobacterial genomes towards their ecological adaptations. PMID:27408818

  4. Raster image adaptation for mobile devices using profiles

    Rosenbaum, René; Hamann, Bernd

    2012-02-01

    Focusing on digital imagery, this paper introduces a strategy to handle heterogeneous hardware in mobile environments. Constrained system resources of most mobile viewing devices require contents that are tailored to the requirements of the user and the capabilities of the device. Appropriate image adaptation is still an unsolved research question. Due to the complexity of the problem, available solutions are either too resource-intensive or inflexible to be more generally applicable. The proposed approach is based on scalable image compression and progressive refinement as well as data and user profiles. A scalable image is created once and used multiple times for different kinds of devices and user requirements. Profiles available on the server side allow for an image representation that is adapted to the most important resources in mobile computing: screen space, computing power, and the volume of the transmitted data. Options for progressively refining content thereby allow for a fluent viewing experience during adaptation. Due to its flexibility and low complexity, the proposed solution is much more general compared to related approaches. To document the advantages of our approach we provide empirical results obtained in experiments with an implementation of the method.

  5. Metabolic and antioxidant profiles of herbal infusions and decoctions.

    Fotakis, Charalambos; Tsigrimani, Diamantina; Tsiaka, Thalia; Lantzouraki, Dimitra Z; Strati, Irini F; Makris, Constantinos; Tagkouli, Dimitra; Proestos, Charalampos; Sinanoglou, Vassilia J; Zoumpoulakis, Panagiotis

    2016-11-15

    This study implements NMR metabolomics and spectrophotometric studies (Folin-Ciocalteu, FRAP, ABTS) to infusions and decoctions of ten plant species in order to assess and compare the metabolic and antioxidant profiles for each botanical family. Multivariate and univariate data analyses highlighted the differences among the samples and pinpointed specific classes of compounds for each plant species as well as infusions and decoctions. The identified phenolic compounds by NMR, as well as the antioxidant profile, framed a trend of increased values in infusions compared to the decoctions. Moreover, the infusion procedure positively affected the extractability of the phenolic compounds compared to decoctions. The highest total phenolic content was found in Mentha spicata, while the lowest in Matricaria chamomilla preparations, irrespective of the preparation method. The preparation time for the decoctions was examined showing that the 15min preparations were generally found richer in phenolics and of higher antioxidant capacity. PMID:27283718

  6. The adaptability of career decision-making profiles.

    Gadassi, Reuma; Gati, Itamar; Dayan, Amira

    2012-10-01

    The Career Decision-Making Profiles questionnaire (CDMP; Gati, Landman, Davidovitch, Asulin-Peretz, & Gadassi, 2010) uses a new model for characterizing the way individuals make decisions based on the simultaneous use of 11 dimensions. The present study investigated which pole of each dimension is more adaptive. Using the data of 383 young adults who were about to make a career choice, we assessed the individuals' decision status and the associations of the dimensions Emotional and Personality-related Career decision-making Difficulties (EPCD; Saka, Gati, & Kelly, 2008) and personality factors (NEO Personality Inventory-Revised; Costa & McCrae, 1992). The results suggest that, as hypothesized, comprehensive Information gathering, analytic Information processing, a more internal Locus of control, more Effort invested, less Procrastination, greater Speed of making the final decision, less Dependence on others, and less Desire to please others were more adaptive in making career decisions. However, contrary to our hypotheses, high Aspiration for an ideal occupation was more adaptive for the decision-making process, Willingness to compromise was not associated with more adaptive decision making, and the results regarding Consulting with others were mixed. Gender differences in the CDMP dimensions and counseling implications are discussed. PMID:22746185

  7. Metabolic Profiling Regarding Pathogenesis of Idiopathic Pulmonary Fibrosis.

    Kang, Yun Pyo; Lee, Sae Bom; Lee, Ji-Min; Kim, Hyung Min; Hong, Ji Yeon; Lee, Won Jun; Choi, Chang Woo; Shin, Hwa Kyun; Kim, Do-Jin; Koh, Eun Suk; Park, Choon-Sik; Kwon, Sung Won; Park, Sung-Woo

    2016-05-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease characterized by fibrosis of the lung parenchyma and loss of lung function. IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair process including uncontrolled proliferation of lung (myo) fibroblasts and excessive deposition of extracellular matrix proteins in the interstitial space; however, the pathogenic pathways involved in IPF have not been fully elucidated. In this study, we attempted to characterize metabolic changes of lung tissues involved in the pathogenesis of IPF using gas chromatography-mass spectrometry-based metabolic profiling. Partial least-squares discriminant analysis (PLS-DA) model generated from metabolite data was able to discriminate between the control subjects and IPF patients (R(2)X = 0.37, R(2)Y = 0.613 and Q(2) (cumulative) = 0.54, receiver operator characteristic AUC > 0.9). We discovered 25 metabolite signatures of IPF using both univariate and multivariate statistical analyses (FDR 1). These metabolite signatures indicated alteration in metabolic pathways: adenosine triphosphate degradation pathway, glycolysis pathway, glutathione biosynthesis pathway, and ornithine aminotransferase pathway. The results could provide additional insight into understanding the disease and potential for developing biomarkers. PMID:27052453

  8. LC–MS-based metabolomics in profiling of drug metabolism and bioactivation

    Feng Li; Frank J. Gonzalez; Xiaochao Ma

    2012-01-01

    Since metabolism significantly affects drug safety and efficacy, determining the metabolic profile of a drug is a critical part of drug development. The application of an LC–MS-based metabolomic approach has gained more widespread use in identifying drug metabolites, developing metabolic maps and lending clues to mechanisms of bioactivation. Thus, the LC–MS-based metabolomic approach is a powerful tool for profiling of drug metabolism and bioactivation.

  9. INFLUENCE FEEDING AND TRAINING ON THE METABOLIC PROFIL SPORT HORSES

    M HALO

    2010-06-01

    Full Text Available In a group of 11 sport horses, the effect of the traianig process, inclunding training and resting periods, on the metabolic profile. Training proces was divided into four part: I. End of the sport season, II. End of the resting period, III. End of the quantitative training charged and IV. End of the qualitative training charged. The level glucose in the blood serum of the observed horses was stated within the reference limits, with the tendency towards the inncreased values in the 2-st and 4-st period (4,34 – 5,03 mmol.l-1. The average values global lipid and cholesterol was stated whitin the reference limits.

  10. Cold adaptation increases rates of nutrient flow and metabolic plasticity during cold exposure in Drosophila melanogaster.

    Williams, Caroline M; McCue, Marshall D; Sunny, Nishanth E; Szejner-Sigal, Andre; Morgan, Theodore J; Allison, David B; Hahn, Daniel A

    2016-09-14

    Metabolic flexibility is an important component of adaptation to stressful environments, including thermal stress and latitudinal adaptation. A long history of population genetic studies suggest that selection on core metabolic enzymes may shape life histories by altering metabolic flux. However, the direct relationship between selection on thermal stress hardiness and metabolic flux has not previously been tested. We investigated flexibility of nutrient catabolism during cold stress in Drosophila melanogaster artificially selected for fast or slow recovery from chill coma (i.e. cold-hardy or -susceptible), specifically testing the hypothesis that stress adaptation increases metabolic turnover. Using (13)C-labelled glucose, we first showed that cold-hardy flies more rapidly incorporate ingested carbon into amino acids and newly synthesized glucose, permitting rapid synthesis of proline, a compound shown elsewhere to improve survival of cold stress. Second, using glucose and leucine tracers we showed that cold-hardy flies had higher oxidation rates than cold-susceptible flies before cold exposure, similar oxidation rates during cold exposure, and returned to higher oxidation rates during recovery. Additionally, cold-hardy flies transferred compounds among body pools more rapidly during cold exposure and recovery. Increased metabolic turnover may allow cold-adapted flies to better prepare for, resist and repair/tolerate cold damage. This work illustrates for the first time differences in nutrient fluxes associated with cold adaptation, suggesting that metabolic costs associated with cold hardiness could invoke resource-based trade-offs that shape life histories. PMID:27605506

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

    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. PMID:26635840

  12. Study of protein and metabolic profile of sugarcane workers

    Full text: The National Alcohol Program (Proalcool) is a successful Brazilian renewable fuel initiative aiming to reduce the country's oil dependence. Producing ethanol from sugar cane, the program has shown positive results although accompanied by potential damage. The environmental impact mainly derives from the particulate matter emissions due to sugarcane burning, which is potentially harmful to human health. The physical activity of sugarcane workers is repetitive and exhaustive and is carried out in presence of dust, smoke and soot. The efforts by the sugarcane workers during the labor process result in increased risks of nervous, respiratory and cardiovascular system diseases and also in premature death. The aim of the present study was to investigate the effect of occupational stress on protein and metabolic profile of sugarcane workers. Forty serum samples were analyzed by 1-DE and LC MS/MS proteomic shotgun strategy and nuclear magnetic resonance (NMR). A set of proteins was found to be altered in workers after crops when compared with controls. The analysis of NMR spectra by Chenomx also showed differences in the expression of metabolites. For example, lactate displayed higher levels in control subjects than in sugarcane workers, and vice versa for the acetate. The concentrations of the two metabolites were lower after the crop, except in the case of acetate, which remained uniform in the control subjects before and after the crop. The present findings can have important application for rational designs of preventive measures and early disease detection in sugarcane workers. (author)

  13. Study of protein and metabolic profile of sugarcane workers

    Polachini, G.M.; Tajara, E.H. [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil); Santos, U.P. [Universidade de Sao Paulo (USP), SP (Brazil); Zeri, A.C.M.; Paes Leme, A.F. [Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, SP (Brazil)

    2012-07-01

    Full text: The National Alcohol Program (Proalcool) is a successful Brazilian renewable fuel initiative aiming to reduce the country's oil dependence. Producing ethanol from sugar cane, the program has shown positive results although accompanied by potential damage. The environmental impact mainly derives from the particulate matter emissions due to sugarcane burning, which is potentially harmful to human health. The physical activity of sugarcane workers is repetitive and exhaustive and is carried out in presence of dust, smoke and soot. The efforts by the sugarcane workers during the labor process result in increased risks of nervous, respiratory and cardiovascular system diseases and also in premature death. The aim of the present study was to investigate the effect of occupational stress on protein and metabolic profile of sugarcane workers. Forty serum samples were analyzed by 1-DE and LC MS/MS proteomic shotgun strategy and nuclear magnetic resonance (NMR). A set of proteins was found to be altered in workers after crops when compared with controls. The analysis of NMR spectra by Chenomx also showed differences in the expression of metabolites. For example, lactate displayed higher levels in control subjects than in sugarcane workers, and vice versa for the acetate. The concentrations of the two metabolites were lower after the crop, except in the case of acetate, which remained uniform in the control subjects before and after the crop. The present findings can have important application for rational designs of preventive measures and early disease detection in sugarcane workers. (author)

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

    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. PMID:25820686

  15. Metabolomic and Proteomic Profiles Reveal the Dynamics of Primary Metabolism during Seed Development of Lotus (Nelumbo nucifera).

    Wang, Lei; Fu, Jinlei; Li, Ming; Fragner, Lena; Weckwerth, Wolfram; Yang, Pingfang

    2016-01-01

    Sacred lotus (Nelumbo nucifera) belongs to the Nelumbonaceae family. Its seeds are widely consumed in Asian countries as snacks or even medicine. Besides the market value, lotus seed also plays a crucial role in the 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 corresponded 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 metabolic 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 acid 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 a reference data set for the evaluation of primary metabolism during lotus seed development. PMID:27375629

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

    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

  17. Dynamical feedback between circadian clock and sucrose availability explains adaptive response of starch metabolism to various photoperiods

    Francois Gabriel Feugier

    2013-01-01

    Full Text Available Plants deal with resource management during all their life. During the day they feed on photosynthetic carbon, sucrose, while storing a part into starch for night use. Careful control of carbon partitioning, starch degradation and sucrose export rates is crucial to avoid carbon starvation, insuring optimal growth whatever the photoperiod. Efficient regulation of these key metabolic rates can give an evolutionary advantage to plants. Here we propose a model of adaptive starch metabolism in response to various photoperiods. We assume the three key metabolic rates to be circadian regulated in leaves and that their phases of oscillations are shifted in response to sucrose starvation. We performed gradient descents for various photoperiod conditions to find the corresponding optimal sets of phase shifts that minimize starvation. Results at convergence were all consistent with experimental data: i diurnal starch profile showed linear increase during the day and linear decrease at night; ii shorter photoperiod tended to increase starch synthesis speed while decreasing its degradation speed during the longer night; iii sudden early dusk showed slower starch degradation during the longer night. Profiles that best explained observations corresponded to circadian regulation of all rates. This theoretical study would establish a framework for future research on feedback between starch metabolism and circadian clock as well as plant productivity.

  18. Metabolic insight into mechanisms of high-altitude adaptation in Tibetans

    Ge, Ri-Li; Simonson, Tatum S.; Cooksey, Robert C.; Tanna, Uran; Qin, Ga; Huff, Chad D.; WITHERSPOON, DAVID J.; Xing, Jinchuan; Zhengzhong, Bai; Prchal, Josef T.; Jorde, Lynn B.; McClain, Donald A.

    2012-01-01

    Recent studies have identified genes involved in high-altitude adaptation in Tibetans. Genetic variants/haplotypes within regions containing three of these genes (EPAS1, EGLN1, and PPARA) are associated with relatively decreased hemoglobin levels observed in Tibetans at high altitude, providing corroborative evidence for genetic adaptation to this extreme environment. The mechanisms that afford adaptation to high-altitude hypoxia, however, remain unclear. Considering the strong metabolic dema...

  19. A Supporting System for Adaptive Peer Review based on Learners' Profiles

    Crespo García, Raquel; Pardo Sánchez, Abelardo

    2010-01-01

    Intelligent tutoring systems cover a wide range of educational processes. There are however scarce attempts to apply those principles for adapting peer review processes according to the student's profile in the educational settings. In this paper, the Adaptive Peer Review methodology is reviewed, paying special attention to the problem of building the student profile. A supporting system based on such Adaptive Peer Review methodology is then introduced, which should facilitate teachers the ad...

  20. Exercise, PGC-1α and metabolic adaptation in skeletal muscle

    Yan, Zhen

    2009-01-01

    Endurance exercise promotes skeletal muscle adaptation, and exercise-induced peroxisome proliferator-activated receptor γ co-activator-1α (Pgc-1α) gene expression may play a pivotal role in the adaptive processes. Recent applications of mouse genetic models and in vivo imaging in exercise studies started to delineate the signaling-transcription pathways that are involved in the regulation of the Pgc-1α gene. These studies revealed the importance of p38 mitogen-activated protein kinase (MAPK)/...

  1. Metabolic profiling distinguishes three subtypes of Alzheimer's disease

    Bredesen, Dale E.

    2015-01-01

    The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report tha...

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

    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.

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

    Fentz, Joachim

    A bout of exercise potently stimulates skeletal muscle energy metabolism. The ATP turnover may rise up to0 ~100 fold compared to the resting state and this presents a substantial stress on skeletal muscle ATP regeneration. To prepare for future events of metabolic stress, the muscle increases its...

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

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

    2016-01-01

    Objectives: 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. Methods: 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 ...

  5. Metabolic adaptation of skeletal muscles to gravitational unloading

    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

  6. Cold adaptation mechanisms in the ghost moth Hepialus xiaojinensis: Metabolic regulation and thermal compensation.

    Zhu, Wei; Zhang, Huan; Li, Xuan; Meng, Qian; Shu, Ruihao; Wang, Menglong; Zhou, Guiling; Wang, Hongtuo; Miao, Lin; Zhang, Jihong; Qin, Qilian

    2016-02-01

    Ghost moths (Lepidoptera: Hepialidae) are cold-adapted stenothermal species inhabiting alpine meadows on the Tibetan Plateau. They have an optimal developmental temperature of 12-16°C but can maintain feeding and growth at 0°C. Their survival strategies have received little attention, but these insects are a promising model for environmental adaptation. Here, biochemical adaptations and energy metabolism in response to cold were investigated in larvae of the ghost moth Hepialus xiaojinensis. Metabolic rate and respiratory quotient decreased dramatically with decreasing temperature (15-4°C), suggesting that the energy metabolism of ghost moths, especially glycometabolism, was sensitive to cold. However, the metabolic rate at 4°C increased with the duration of cold exposure, indicating thermal compensation to sustain energy budgets under cold conditions. Underlying regulation strategies were studied by analyzing metabolic differences between cold-acclimated (4°C for 48h) and control larvae (15°C). In cold-acclimated larvae, the energy generating pathways of carbohydrates, instead of the overall consumption of carbohydrates, was compensated in the fat body by improving the transcription of related enzymes. The mobilization of lipids was also promoted, with higher diacylglycerol, monoacylglycerol and free fatty acid content in hemolymph. These results indicated that cold acclimation induced a reorganization on metabolic structure to prioritise energy metabolism. Within the aerobic process, flux throughout the tricarboxylic acid (TCA) cycle was encouraged in the fat body, and the activity of α-ketoglutarate dehydrogenase was the likely compensation target. Increased mitochondrial cristae density was observed in the midgut of cold-acclimated larvae. The thermal compensation strategies in this ghost moth span the entire process of energy metabolism, including degration of metabolic substrate, TCA cycle and oxidative phosphorylation, and from an energy budget

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

    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....

  8. Predicting enzyme targets for cancer drugs by profiling human Metabolic reactions in NCI-60 cell lines

    Ching Wai-Ki

    2010-10-01

    Full Text Available Abstract Background Drugs can influence the whole metabolic system by targeting enzymes which catalyze metabolic reactions. The existence of interactions between drugs and metabolic reactions suggests a potential way to discover drug targets. Results In this paper, we present a computational method to predict new targets for approved anti-cancer drugs by exploring drug-reaction interactions. We construct a Drug-Reaction Network to provide a global view of drug-reaction interactions and drug-pathway interactions. The recent reconstruction of the human metabolic network and development of flux analysis approaches make it possible to predict each metabolic reaction's cell line-specific flux state based on the cell line-specific gene expressions. We first profile each reaction by its flux states in NCI-60 cancer cell lines, and then propose a kernel k-nearest neighbor model to predict related metabolic reactions and enzyme targets for approved cancer drugs. We also integrate the target structure data with reaction flux profiles to predict drug targets and the area under curves can reach 0.92. Conclusions The cross validations using the methods with and without metabolic network indicate that the former method is significantly better than the latter. Further experiments show the synergism of reaction flux profiles and target structure for drug target prediction. It also implies the significant contribution of metabolic network to predict drug targets. Finally, we apply our method to predict new reactions and possible enzyme targets for cancer drugs.

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

    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

  10. Metabolic profiling as a tool for prioritizing antimicrobial compounds

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

    2016-01-01

    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 different

  11. Profiles of School Adaptation: Social, Behavioral and Academic Functioning in Sexually Abused Girls

    Daignault, Isabelle V.; Hebert, Martine

    2009-01-01

    Objectives: The short-term outcomes of child sexual abuse (CSA) on academic, behavioral and social adaptation at school were examined in order to: (1) document the proportion of sexually abused (SA) girls struggling in school and define the nature of their difficulties, (2) explore whether different profiles of school adaptation could be…

  12. Adaptative diversity of calcium metabolism in gammarus fossarum populations

    Analysis of Gammarus fossarum populations from mountain torrents in the Grenoble region reveals some morphological and eco physiological diversity which appears to be related to the calcium concentration of the water after both field and laboratory experimentation. Animals from waters with a high calcium concentration (located in Chartreuse and Vercors) show larger size and a longer molt cycle than those from low calcium concentrated waters (located in Belledonne); their calcium balance during the molt cycle is different. Translocation experiments confirm these differences: a significant increase of the duration of the molt cycle is observed in animals translocated to lower calcium concentrated waters and vice-versa whereas no significant difference is observed between controls and animals translocated within comparably calcium concentrated waters. The causes of such an adaptative diversity between Gammarus fossarum populations will be researched at the genetic level, namely through mitochondrial DNA investigations. (author). 25 refs., 2 tabs., 2 figs

  13. Determination of free energy profiles by repository based adaptive umbrella sampling: Bridging nonequilibrium and quasiequilibrium simulations

    Zheng, Han; Zhang, Yingkai

    2008-01-01

    We propose a new adaptive sampling approach to determine free energy profiles with molecular dynamics simulations, which is called as “repository based adaptive umbrella sampling” (RBAUS). Its main idea is that a sampling repository is continuously updated based on the latest simulation data, and the accumulated knowledge and sampling history are then employed to determine whether and how to update the biasing umbrella potential for subsequent simulations. In comparison with other adaptive me...

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

    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...

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

    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

  16. Distribution of Metabolically Active Prokaryotes (Archaea and Bacteria) throughout the Profiles of Chernozem and Brown Semidesert Soil

    Semenov, M. V.; Manucharova, N. A.; Stepanov, A. L.

    2016-02-01

    The distribution of metabolically active cells of archaea and bacteria in the profiles of typical chernozems (Voronezh oblast) and brown semidesert soils (Astrakhan oblast) of natural and agricultural ecosystems was studied using the method of fluorescent in situ hybridization (FISH). The studied soils differed sharply in the microbial biomass and in the numbers of metabolically active cells of archaea and bacteria. The number of active bacterial cells was 3.5-7.0 times greater than that of archaea. In the arable chernozem, the numbers of active cells of archaea and bacteria were 2.6 and 1.5 times, respectively, lower than those in the chernozem under the shelterbelt. The agricultural use of the brown semidesert soil had little effect on the abundances of bacteria and archaea. The soil organic carbon content was the major factor controlling the numbers of metabolically active cells of both domains. However, the dependence of the abundance of bacteria on the organic matter content was more pronounced. The decrease in the organic carbon and total nitrogen contents down the soil profiles was accompanied by the decrease in the bacteria: archaea ratio attesting to a better adaptation of archaea to the permanent deficiency of carbon and nitrogen. The bacteria: archaea ratio can serve as an ecotrophic indicator of the state of soil microbial communities.

  17. Metabolic adaptation in transplastomic plants massively accumulating recombinant proteins.

    Julia Bally

    Full Text Available BACKGROUND: Recombinant chloroplasts are endowed with an astonishing capacity to accumulate foreign proteins. However, knowledge about the impact on resident proteins of such high levels of recombinant protein accumulation is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Here we used proteomics to characterize tobacco (Nicotiana tabacum plastid transformants massively accumulating a p-hydroxyphenyl pyruvate dioxygenase (HPPD or a green fluorescent protein (GFP. While under the conditions used no obvious modifications in plant phenotype could be observed, these proteins accumulated to even higher levels than ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco, the most abundant protein on the planet. This accumulation occurred at the expense of a limited number of leaf proteins including Rubisco. In particular, enzymes involved in CO(2 metabolism such as nuclear-encoded plastidial Calvin cycle enzymes and mitochondrial glycine decarboxylase were found to adjust their accumulation level to these novel physiological conditions. CONCLUSIONS/SIGNIFICANCE: The results document how protein synthetic capacity is limited in plant cells. They may provide new avenues to evaluate possible bottlenecks in recombinant protein technology and to maintain plant fitness in future studies aiming at producing recombinant proteins of interest through chloroplast transformation.

  18. On the accessibility of adaptive phenotypes of a bacterial metabolic network.

    Wilfred Ndifon

    2009-08-01

    Full Text Available The mechanisms by which adaptive phenotypes spread within an evolving population after their emergence are understood fairly well. Much less is known about the factors that influence the evolutionary accessibility of such phenotypes, a pre-requisite for their emergence in a population. Here, we investigate the influence of environmental quality on the accessibility of adaptive phenotypes of Escherichia coli's central metabolic network. We used an established flux-balance model of metabolism as the basis for a genotype-phenotype map (GPM. We quantified the effects of seven qualitatively different environments (corresponding to both carbohydrate and gluconeogenic metabolic substrates on the structure of this GPM. We found that the GPM has a more rugged structure in qualitatively poorer environments, suggesting that adaptive phenotypes could be intrinsically less accessible in such environments. Nevertheless, on average approximately 74% of the genotype can be altered by neutral drift, in the environment where the GPM is most rugged; this could allow evolving populations to circumvent such ruggedness. Furthermore, we found that the normalized mutual information (NMI of genotype differences relative to phenotype differences, which measures the GPM's capacity to transmit information about phenotype differences, is positively correlated with (simulation-based estimates of the accessibility of adaptive phenotypes in different environments. These results are consistent with the predictions of a simple analytic theory that makes explicit the relationship between the NMI and the speed of adaptation. The results suggest an intuitive information-theoretic principle for evolutionary adaptation; adaptation could be faster in environments where the GPM has a greater capacity to transmit information about phenotype differences. More generally, our results provide insight into fundamental environment-specific differences in the accessibility of adaptive

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

    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.

  20. Adaptive robust control of longitudinal and transverse electron beam profiles

    Rezaeizadeh, Amin; Schilcher, Thomas; Smith, Roy S.

    2016-05-01

    Feedback control of the longitudinal and transverse electron beam profiles are considered to be critical for beam control in accelerators. In the feedback scheme, the longitudinal or transverse beam profile is measured and compared to a desired profile to give an error estimate. The error is then used to act on the appropriate actuators to correct the profile. The role of the transverse feedback is to steer the beam in a particular trajectory, known as the "orbit." The common approach for orbit correction is based on approximately inverting the response matrix, and in the best case, involves regulating or filtering the singular values. In the current contribution, a more systematic and structured way of handling orbit correction is introduced giving robustness against uncertainties in the response matrix. Moreover, the input bounds are treated to avoid violating the limits of the corrector currents. The concept of the robust orbit correction has been successfully tested at the SwissFEL injector test facility. In the SwissFEL machine, a photo-injector laser system extracts electrons from a cathode and a similar robust control method is developed for the longitudinal feedback control of the current profile of the electron bunch. The method manipulates the angles of the crystals in the laser system to produce a desired charge distribution over the electron bunch length. This approach paves the way towards automation of laser pulse stacking.

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

    Albert Sundrum

    2015-10-01

    Full Text Available 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 Animals 2015, 5 979 and their large variations on various scales contradict any attempts to predict the outcome of animals’ adaptation in a farm specific situation. Any attempts to reduce the prevalence of metabolic disorders and associated production diseases should rely on continuous and comprehensive monitoring with appropriate indicators on the farm level. Furthermore, low levels of disorders and diseases should be seen as a further significant goal which carries weight in addition to productivity goals. In the long run, low disease levels can only be expected when farmers realize that they can gain a competitive advantage over competitors with higher levels of disease.

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

    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.

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

    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

  4. Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise

    Jørgensen, Sebastian Beck; Richter, Erik; Wojtaszewski, Jørgen

    2006-01-01

    The 5'-AMP-activated protein kinase (AMPK) is a potent regulator of skeletal muscle metabolism and gene expression. AMPK is activated both in response to in vivo exercise and ex vivo contraction. AMPK is therefore believed to be an important signalling molecule in regulating muscle metabolism...... furthermore discuss the possible role of AMPK as a master switch in skeletal muscle metabolism with the main focus on AMPK in metabolic regulation during muscle work. Finally, AMPK has a well established role in regulating expression of genes encoding various enzymes in muscle, and this issue is discussed in...... during exercise as well as in adaptation of skeletal muscle to exercise training. The first part of this review is focused on different mechanisms regulating AMPK activity during muscle work such as alterations in nucleotide concentrations, availability of energy substrates and upstream AMPK kinases. We...

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

    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.

  6. Genome-Wide Fitness and Expression Profiling Implicate Mga2 in Adaptation to Hydrogen Peroxide

    Ryan Kelley; Trey Ideker

    2009-01-01

    Caloric restriction extends lifespan, an effect once thought to involve attenuation of reactive oxygen species (ROS) generated by aerobic metabolism. However, recent evidence suggests that caloric restriction may in fact raise ROS levels, which in turn provides protection from acute doses of oxidant through a process called adaptation. To shed light on the molecular mechanisms of adaptation, we designed a series of genome-wide deletion fitness and mRNA expression screens to identify genes inv...

  7. Global urinary metabolic profiling procedures using gas chromatography-mass spectrometry.

    Chan, Eric Chun Yong; Pasikanti, Kishore Kumar; Nicholson, Jeremy K

    2011-10-01

    The role of urinary metabolic profiling in systems biology research is expanding. This is because of the use of this technology for clinical diagnostic and mechanistic studies and for the development of new personalized health care and molecular epidemiology (population) studies. The methodologies commonly used for metabolic profiling are NMR spectroscopy, liquid chromatography mass spectrometry (LC/MS) and gas chromatography-mass spectrometry (GC/MS). In this protocol, we describe urine collection and storage, GC/MS and data preprocessing methods, chemometric data analysis and urinary marker metabolite identification. Results obtained using GC/MS are complementary to NMR and LC/MS. Sample preparation for GC/MS analysis involves the depletion of urea via treatment with urease, protein precipitation with methanol, and trimethylsilyl derivatization. The protocol described here facilitates the metabolic profiling of ∼400-600 metabolites in 120 urine samples per week. PMID:21959233

  8. Metabolic model-based integration of microbiome taxonomic and metabolomic profiles elucidates mechanistic links between ecological and metabolic variation

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

    2016-01-19

    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-meta-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 contributors. Focusing on two independent vaginal microbiome datasets, 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 significantly contribute to these predictions. Interestingly, our analysis also detects metabolites for which predicted variation negatively correlates with measured variation, suggesting environmental control points of community metabolism. Applying this framework to gut microbiome datasets reveals similar trends,including prediction of bile acid metabolite shifts. This framework is an important first step towards a system-level multi-omic integration and an improved mechanistic understanding of the microbiome activity and dynamics in health and disease.

  9. A Metabolic Profiling Strategy for the Dissection of Plant Defense against Fungal Pathogens

    Aliferis, Konstantinos A.; Faubert, Denis; Jabaji, Suha

    2014-01-01

    Here we present a metabolic profiling strategy employing direct infusion Orbitrap mass spectrometry (MS) and gas chromatography-mass spectrometry (GC/MS) for the monitoring of soybean's (Glycine max L.) global metabolism regulation in response to Rhizoctonia solani infection in a time-course. Key elements in the approach are the construction of a comprehensive metabolite library for soybean, which accelerates the steps of metabolite identification and biological interpretation of results, and...

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

    Handlos, L. N.; Witte, D. R.; Mwaniki, D. L.; Bolt, M. K.; Kilonzo, B.; Friis, H.; Hansen, A. W.; Borch-Johnsen, K.; Tetens, Inge; Christensen, 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....... WC is useful in clinical practice for the diagnosis of metabolically unhealthy fat accumulation in an African setting. Read More: http://informahealthcare.com/doi/abs/10.3109/03014460.2012.720279...

  11. Effects of Cadmium Exposure on Growth and Metabolic Profile of Bermudagrass [Cynodon dactylon (L.) Pers.

    Yan Xie; Longxing Hu; Zhimin Du; Xiaoyan Sun; Erick Amombo; Jibiao Fan; Jinmin Fu

    2014-01-01

    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 ...

  12. Mutations in leaf starch metabolism modulate the diurnal root growth profiles of Arabidopsis thaliana

    Yazdanbakhsh, Nima; FISAHN, JOACHIM

    2011-01-01

    Roots of Arabidopsis thaliana exhibit stable diurnal growth profiles that are controlled by the circadian clock. Here we describe the effects of mutations in leaf starch metabolism on the diurnal root growth characteristics of Arabidopsis thaliana. High temporal and spatial resolution video imaging was performed to quantify the growth kinetics of Arabidopsis wild-type as well as pgm, sex1, mex1, dpe1 and dpe2 starch metabolism mutants grown in three different photoperiods. As a result, root g...

  13. Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

    Roze Ludmila V

    2010-08-01

    Full Text Available Abstract Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine; we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1 Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2 VeA coordinates the

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

    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.

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

    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.

  16. Review: Microfluidic Applications in Metabolomics and Metabolic Profiling

    Kraly, James R.; Holcomb, Ryan E.; Guan, Qian; Charles S. Henry

    2009-01-01

    Metabolomics is an emerging area of research focused on measuring small molecules in biological samples. There are a number of different types of metabolomics, ranging from global profiling of all metabolites in a single sample to measurement of a selected group of analytes. Microfluidics and related technologies have been used in this research area with good success. The aim of this review article is to summarize the use of microfluidics in metabolomics. Direct application of microfluidics t...

  17. Metabolic profiling as a tool for prioritizing antimicrobial compounds

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

    2016-01-01

    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 differentially produced compounds as potential biomarkers. Here, we review NMR- and MS-based metabolomics as technologies to facilitate the identification of novel antimicrobial natural products from microb...

  18. Metabolic profiles of dystrophin and utrophin expression in mouse models of Duchenne muscular dystrophy.

    Griffin, J L; Sang, E; Evens, T; Davies, K; Clarke, K

    2002-10-23

    Metabolic profiles from (1)H nuclear magnetic resonance spectroscopy have been used to describe both one and two protein systems in four mouse models related to Duchenne muscular dystrophy using the pattern recognition technique partial least squares. Robust statistical models were built for extracts and intact cardiac tissue, distinguishing mice according to expression of dystrophin. Using metabolic profiles of diaphragm, models were built describing dystrophin and utrophin, a dystrophin related protein, expression. Increased utrophin expression counteracted some of the deficits associated with dystrophic tissue. This suggests the method may be ideal for following treatment regimes such as gene therapy. PMID:12387876

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

    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.

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

    Heroven, Ann Kathrin; Dersch, Petra

    2014-01-01

    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 Yersinia pseudotuberculosis and Yersinia enterocolitica and the causative agent of plague, Yersinia 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 interbacterial 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. PMID:25368845

  1. The evolution of control and distribution of adaptive mutations in a metabolic pathway.

    Wright, Kevin M; Rausher, Mark D

    2010-02-01

    In an attempt to understand whether it should be expected that some genes tend to be used disproportionately often by natural selection, we investigated two related phenomena: the evolution of flux control among enzymes in a metabolic pathway and properties of adaptive substitutions in pathway enzymes. These two phenomena are related by the principle that adaptive substitutions should occur more frequently in enzymes with greater flux control. Predicting which enzymes will be preferentially involved in adaptive evolution thus requires an evolutionary theory of flux control. We investigated the evolution of enzyme control in metabolic pathways with two models of enzyme kinetics: metabolic control theory (MCT) and Michaelis-Menten saturation kinetics (SK). Our models generate two main predictions for pathways in which reactions are moderately to highly irreversible: (1) flux control will evolve to be highly unequal among enzymes in a pathway and (2) upstream enzymes evolve a greater control coefficient then those downstream. This results in upstream enzymes fixing the majority of beneficial mutations during adaptive evolution. Once the population has reached high fitness, the trend is reversed, with the majority of neutral/slightly deleterious mutations occurring in downstream enzymes. These patterns are the result of three factors (the first of these is unique to the MCT simulations while the other two seem to be general properties of the metabolic pathways): (1) the majority of randomly selected, starting combinations of enzyme kinetic rates generate pathways that possess greater control for the upstream enzymes compared to downstream enzymes; (2) selection against large pools of intermediate substrates tends to prevent majority control by downstream enzymes; and (3) equivalent mutations in enzyme kinetic rates have the greatest effect on flux for enzymes with high levels of flux control, and these enzymes will accumulate adaptive substitutions, strengthening their

  2. Increased plasma leptin attenuates adaptive metabolism in early lactating dairy cows.

    Ehrhardt, Richard A; Foskolos, Andreas; Giesy, Sarah L; Wesolowski, Stephanie R; Krumm, Christopher S; Butler, W Ronald; Quirk, Susan M; Waldron, Matthew R; Boisclair, Yves R

    2016-05-01

    Mammals meet the increased nutritional demands of lactation through a combination of increased feed intake and a collection of adaptations known as adaptive metabolism (e.g., glucose sparing via insulin resistance, mobilization of endogenous reserves, and increased metabolic efficiency via reduced thyroid hormones). In the modern dairy cow, adaptive metabolism predominates over increased feed intake at the onset of lactation and develops concurrently with a reduction in plasma leptin. To address the role of leptin in the adaptive metabolism of early lactation, we asked which adaptations could be countered by a constant 96-h intravenous infusion of human leptin (hLeptin) starting on day 8 of lactation. Compared to saline infusion (Control), hLeptin did not alter energy intake or milk energy output but caused a modest increase in body weight loss. hLeptin reduced plasma glucose by 9% and hepatic glycogen content by 73%, and these effects were associated with a 17% increase in glucose disposal during an insulin tolerance test. hLeptin attenuated the accumulation of triglyceride in the liver by 28% in the absence of effects on plasma levels of the anti-lipolytic hormone insulin or plasma levels of free fatty acids, a marker of lipid mobilization from adipose tissue. Finally, hLeptin increased the plasma concentrations of T4 and T3 by nearly 50% without affecting other neurally regulated hormones (i.e., cortisol and luteinizing hormone (LH)). Overall these data implicate the periparturient reduction in plasma leptin as one of the signals promoting conservation of glucose and energy at the onset of lactation in the energy-deficient dairy cow. PMID:26957637

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

    Verma-Gaur, Jiyoti; Qu, Yue; Harrison, Paul F; Lo, Tricia L; Quenault, Tara; Dagley, Michael J; Bellousoff, Matthew; Powell, David R; Beilharz, Traude H; Traven, Ana

    2015-10-01

    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. PMID:26474309

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

    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.

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

    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

  6. Adaptive super-twisting observer for estimation of random road excitation profile in automotive suspension systems.

    Rath, J J; Veluvolu, K C; Defoort, M

    2014-01-01

    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. PMID:24683321

  7. Metabolic Dysfunction in Heart Failure: Diagnostic, Prognostic, and Pathophysiologic Insights From Metabolomic Profiling.

    Hunter, Wynn G; Kelly, Jacob P; McGarrah, Robert W; Kraus, William E; Shah, Svati H

    2016-06-01

    Metabolic impairment is an intrinsic component of heart failure (HF) pathophysiology. Although initially conceived as a myocardial defect, metabolic dysfunction is now recognized as a systemic process with complex interplay between the myocardium and peripheral tissues and organs. Specifically, HF-associated metabolic dysfunction includes alterations in substrate utilization, insulin resistance, defects in energy production, and imbalanced anabolic-catabolic signaling leading to cachexia. Each of these metabolic abnormalities is associated with significant morbidity and mortality in patients with HF; however, their detection and therapeutic management remains challenging. Given the difficulty in obtaining human cardiac tissue for research purposes, peripheral blood metabolomic profiling, a well-established approach for characterizing small-molecule metabolite intermediates from canonical biochemical pathways, may be a useful technology for dissecting biomarkers and mechanisms of metabolic impairment in HF. In this review, metabolic abnormalities in HF will be discussed with particular emphasis on the application of metabolomic profiling to detecting, risk stratifying, and identifying novel targets for metabolic therapy in this heterogeneous population. PMID:27216948

  8. In Vivo NMR Metabolic Profiling of Fabrea salina Reveals Sequential Defense Mechanisms against Ultraviolet Radiation

    Marangoni, Roberto; Paris, Debora; Melck, Dominique; Fulgentini, Lorenzo; Colombetti, Giuliano; Motta, Andrea

    2011-01-01

    Fabrea salina is a hypersaline ciliate that is known to be among the strongest ultraviolet (UV)-resistant microorganisms; however, the molecular mechanisms of this resistance are almost unknown. By means of in vivo NMR spectroscopy, we determined the metabolic profile of living F. salina cells exposed to visible light and to polychromatic UV-B + UV-A + Vis radiation for several different exposure times. We used unsupervised pattern-recognition analysis to compare these profiles and discovered...

  9. Rural and urban differences in metabolic profiles in a Cameroonian population

    Clarisse Noel Ayina Ayina Lissock; Eugene Sobngwi; Eliane Ngassam; Laurent Serge Etoundi Ngoa

    2011-01-01

    Introduction The difference between modern lifestyle in urban areas and the traditional way of life in rural areas may affect the population's health in developing countries proportionally. In this study, we sought to describe and compare the metabolic (fasting blood sugar and lipid profile) profile in an urban and rural sample of a Cameroonian population, and study the association to anthropometric risk factors of obesity. Methods 332 urban and 120 rural men and women originating from the Sa...

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

    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.

  11. Validation Through Simulations of a Cn2 Profiler for the ESO/VLT Adaptive Optics Facility

    Garcia-Rissmann, A; Kolb, J; Louarn, M Le; Madec, P -Y; Neichel, B

    2015-01-01

    The Adaptive Optics Facility (AOF) project envisages transforming one of the VLT units into an adaptive telescope and providing its ESO (European Southern Observatory) second generation instruments with turbulence corrected wavefronts. For MUSE and HAWK-I this correction will be achieved through the GALACSI and GRAAL AO modules working in conjunction with a 1170 actuators Deformable Secondary Mirror (DSM) and the new Laser Guide Star Facility (4LGSF). Multiple wavefront sensors will enable GLAO and LTAO capabilities, whose performance can greatly benefit from a knowledge about the stratification of the turbulence in the atmosphere. This work, totally based on end-to-end simulations, describes the validation tests conducted on a Cn2 profiler adapted for the AOF specifications. Because an absolute profile calibration is strongly dependent on a reliable knowledge of turbulence parameters r0 and L0, the tests presented here refer only to normalized output profiles. Uncertainties in the input parameters inherent t...

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

    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.

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

    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

  14. Adaptive Control Model Reveals Systematic Feedback and Key Molecules in Metabolic Pathway Regulation

    Quo, Chang F.; Moffitt, Richard A; Merrill, Alfred H.; Wang, May D.

    2011-01-01

    Robust behavior in metabolic pathways resembles stabilized performance in systems under autonomous control. This suggests we can apply control theory to study existing regulation in these cellular networks. Here, we use model-reference adaptive control (MRAC) to investigate the dynamics of de novo sphingolipid synthesis regulation in a combined theoretical and experimental case study. The effects of serine palmitoyltransferase over-expression on this pathway are studied in vitro using human e...

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

    Ann Kathrin eHeroven; Petra eDersch

    2014-01-01

    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 tis...

  16. Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.

    Peliciari-Garcia, Rodrigo A; Goel, Mehak; Aristorenas, Jonathan A; Shah, Krishna; He, Lan; Yang, Qinglin; Shalev, Anath; Bailey, Shannon M; Prabhu, Sumanth D; Chatham, John C; Gamble, Karen L; Young, Martin E

    2016-10-01

    A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26721420

  17. Metabolic profiling as a tool for prioritizing antimicrobial compounds.

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

    2016-03-01

    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 differentially produced compounds as potential biomarkers. Here, we review NMR- and MS-based metabolomics as technologies to facilitate the identification of novel antimicrobial natural products from microbial sources. Approaches to elicit the production of poorly expressed (cryptic) molecules are thereby a key to allow statistical analysis of samples to identify bioactive markers, while connection of compounds to their biosynthetic gene cluster is a determining step in elucidating the biosynthetic pathway and allows downstream process optimization and upscaling. The review focuses on approaches built around NMR-based metabolomics, which enables efficient dereplication and guided fractionation of (antimicrobial) compounds. PMID:26335567

  18. Understanding developmental and adaptive cues in pine through metabolite profiling and co-expression network analysis

    Cañas, Rafael A.; Canales, Javier; Muñoz-Hernández, Carmen; Granados, Jose M.; Ávila, Concepción; García-Martín, María L.; Cánovas, Francisco M.

    2015-01-01

    Conifers include long-lived evergreen trees of great economic and ecological importance, including pines and spruces. During their long lives conifers must respond to seasonal environmental changes, adapt to unpredictable environmental stresses, and co-ordinate their adaptive adjustments with internal developmental programmes. To gain insights into these responses, we examined metabolite and transcriptomic profiles of needles from naturally growing 25-year-old maritime pine (Pinus pinaster L....

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

    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.

  20. Biological and behavioral modifiers of urinary arsenic metabolic profiles in a U.S. population

    Biological and behavioral modifiers of urinary arsenic metabolic profiles in a U.S. population David J. Thomas – ISTD, NHEERL Edward F. Hudgens – EHPD, NHEERL John Rogers - Westat Relations between intensity of arsenic exposure from home tap water and levels of inorganic As ...

  1. Effect of opium on glucose metabolism and lipid profiles in rats with streptozotocin-induced diabetes

    Sadeghian, Saeed; Boroumand, Mohammad Ali; Sotoudeh-Anvari, Maryam; Rahbani, Shahram; Sheikhfathollahi, Mahmood; Abbasi, Ali

    2009-01-01

    Background: This experimental study was performed to determine the impact of opium use on serum lipid profile and glucose metabolism in rats with streptozotocin-induced diabetes. Material and methods: To determine the effect of opium, 20 male rats were divided into control (n = 10) and opium-treated

  2. Yogurt consumption is associated with better diet quality and metabolic profile in American men and women

    Low-fat dairy products may be beneficial for health, but few studies have specifically focused on yogurt. We examined whether yogurt consumption was associated with better dietary patterns, diet quality, and metabolic profile. This cross-sectional study included the adults (n=6526) participating in ...

  3. Adaptive changes in basal metabolic rate and thermogenesis in chronic undernutrition

    Metabolic adaptation during chronic undernutrition represents a complex integration of several processes which affect the total energy expenditure of the individual. Basal metabolic rate (BMR) is reduced; reductions in BMR per unit fat free mass (FFM) is difficult to demonstrate. BMR changes in undernutrition reflect the low body weight as well as alterations in the composition of the FFM; more specifically changes in the ratio of viscera to muscle compartments of the FFM. Thermogenic responses to norepinephrine are transiently suppressed but recover rapidly on repeated stimulation. Dietary thermogenesis is enhanced possible the result of increases in tissue synthesis within the body. Changes in BMR and thermogenesis suggestive of an increase in metabolic efficiency is thus difficult to demonstrate in chronic undernutrition. (author). 15 refs, 2 figs, 7 tabs

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

    Ursula Sonnewald

    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

  5. Metabolic adaptation and trophic strategies of soil bacteria - C1- metabolism and sulfur chemolithotrophy in Starkeya novella

    UlrikeKappler

    2013-10-01

    Full Text Available The highly diverse and metabolically versatile microbial communities found in soil environments are major contributors to the global carbon, nitrogen and sulfur cycles. We have used a combination of genome –based pathway analysis with proteomics and gene expression studies to investigate metabolic adaptation in a representative of these bacteria, Starkeya novella, which was originally isolated from agricultural soil. This bacterium was the first facultative sulfur chemolithoautotroph that was isolated and it is also able to grow with methanol and on over 39 substrates as a heterotroph. However, using glucose, fructose, methanol, thiosulfate as well as combinations of the carbon compounds with thiosulfate as growth substrates we have demonstrated here that contrary to the previous classification, S. novella is not a facultative sulfur chemolitho- and methylotroph, as the enzyme systems required for these two growth modes as always expressed at high levels. This is typical for key metabolic pathways. In addition enzymes for various pathways of carbon dioxide fixation were always expressed at high levels, even during heterotrophic growth on glucose or fructose, which suggests a role for these pathways beyond the generation of reduced carbon units for cell growth, possibly in redox balancing of metabolism. Our results then indicate that S. novella, a representative of the Xanthobacteraceae family of methylotrophic soil and freshwater dwelling bacteria, employs a mixotrophic growth strategy under all conditions tested here. As a result the contribution of this bacterium to either carbon sequestration or the release of climate active substances could vary very quickly, which has direct implications for the modelling of such processes if mixotrophy proves to be the main growth strategy for large populations of soil bacteria.

  6. Metabonomic profiling of human placentas reveals different metabolic patterns among subtypes of neural tube defects.

    Chi, Yi; Pei, Lijun; Chen, Gong; Song, Xinming; Zhao, Aihua; Chen, Tianlu; Su, Mingming; Zhang, Yinan; Liu, Jianmeng; Ren, Aiguo; Zheng, Xiaoying; Xie, Guoxiang; Jia, Wei

    2014-02-01

    Neural tube defects (NTDs) are one of the most common types of birth defects with a complex etiology. We have previously profiled serum metabolites of pregnant women in Lvliang prefecture, Shanxi Province of China, which revealed distinct metabolic changes in pregnant women with NTDs outcome. Here we present a metabonomics study of human placentas of 144 pregnant women with normal pregnancy outcome and 115 pregnant women affected with NTDs recruited from four rural counties (Pingding, Xiyang, Taigu, and Zezhou) of Shanxi Province, the area with the highest prevalence worldwide. A panel of 19 metabolites related to one-carbon metabolism was also quantitatively determined. We observed obvious differences in global metabolic profiles and one-carbon metabolism among three subtypes of NTDs, anencephaly (Ane), spina bifida (SB), and Ane complicated with SB (Ane & SB) via mass-spectrometry-based metabonomics approach. Disturbed carbohydrate, amino acid, lipid, and nucleic acid metabolism were identified. Placental transport of amino acids might be depressed in Ane and Ane & SB group. Deficiency of choline contributes to Ane and Ane & SB pathogenesis via different metabolic pathways. The formation of NTDs seemed to be weakly related to folates. The metabonomic analysis reveals that the physiological and biochemical processes of the three subtypes of NTDs might be different and the subtype condition should be considered for the future investigation of NTDs. PMID:24397701

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

    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.

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

    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

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

    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.

  10. Metabolic profiling of biofilm bacteria known to cause microbial influenced corrosion.

    Beale, D J; Morrison, P D; Key, C; Palombo, E A

    2014-01-01

    This study builds upon previous research that demonstrated the simplicity of obtaining metabolite profiles of bacteria in urban water networks, by using the metabolic profile of bacteria extracted from a reticulation pipe biofilm, which is known to cause microbial influenced corrosion (MIC). The extracellular metabolites of the isolated bacteria, and those bacteria in consortium, were analysed in isolation, and after exposure to low levels of copper. Applying chemometric analytical methodologies to the metabolomic data, we were able to better understand the profile of the isolated biofilm bacteria, which were differentiated according to their activity and copper exposure. It was found that the metabolic activity of the isolated bacteria and the bacteria in consortium varied according to the bacterium's ability to metabolise copper. This demonstrates the power of metabolomic techniques for the discrimination of water reticulation biofilms comprising similar bacteria in consortium, but undergoing different physico-chemical activities, such as corrosion and corrosion inhibition. PMID:24434961

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

    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

  12. Metabolic profiles of male meat eaters, fish eaters, vegetarians, and vegans from the EPIC-Oxford cohort 1 2

    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 betw...

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

    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

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

    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

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

    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. PMID:25090149

  16. Adaptive neuro-fuzzy inference system for temperature and humidity profile retrieval from microwave radiometer observations

    Ramesh, K.; Kesarkar, A. P.; Bhate, J.; Venkat Ratnam, M.; Jayaraman, A.

    2015-01-01

    The retrieval of accurate profiles of temperature and water vapour is important for the study of atmospheric convection. Recent development in computational techniques motivated us to use adaptive techniques in the retrieval algorithms. In this work, we have used an adaptive neuro-fuzzy inference system (ANFIS) to retrieve profiles of temperature and humidity up to 10 km over the tropical station Gadanki (13.5° N, 79.2° E), India. ANFIS is trained by using observations of temperature and humidity measurements by co-located Meisei GPS radiosonde (henceforth referred to as radiosonde) and microwave brightness temperatures observed by radiometrics multichannel microwave radiometer MP3000 (MWR). ANFIS is trained by considering these observations during rainy and non-rainy days (ANFIS(RD + NRD)) and during non-rainy days only (ANFIS(NRD)). The comparison of ANFIS(RD + NRD) and ANFIS(NRD) profiles with independent radiosonde observations and profiles retrieved using multivariate linear regression (MVLR: RD + NRD and NRD) and artificial neural network (ANN) indicated that the errors in the ANFIS(RD + NRD) are less compared to other retrieval methods. The Pearson product movement correlation coefficient (r) between retrieved and observed profiles is more than 92% for temperature profiles for all techniques and more than 99% for the ANFIS(RD + NRD) technique Therefore this new techniques is relatively better for the retrieval of temperature profiles. The comparison of bias, mean absolute error (MAE), RMSE and symmetric mean absolute percentage error (SMAPE) of retrieved temperature and relative humidity (RH) profiles using ANN and ANFIS also indicated that profiles retrieved using ANFIS(RD + NRD) are significantly better compared to the ANN technique. The analysis of profiles concludes that retrieved profiles using ANFIS techniques have improved the temperature retrievals substantially; however, the retrieval of RH by all techniques considered in this paper (ANN, MVLR and

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

    Jonathan J Hansen

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

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

    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.

  19. Metabolic Profiling of Somatic Tissues from Monochamus alternatus (Coleoptera: Cerambycidae Reveals Effects of Irradiation on Metabolism

    Liangjian Qu

    2014-06-01

    Full Text Available A high-level of sexual sterility is of importance for the sterile insect technique (SIT. However, the use of high-dose-intensity gamma radiation to induce sterility has negative impacts not only on reproductive cells but also on somatic cells. In this study, we investigated the metabolite differences in somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated male Monochamus alternatus, an important vector of the pathogenic nematode, Bursaphelenchus xylophilus, which kills Asian pines. The results showed that metabolite levels changed moderately in the 20-Gy samples but were markedly altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively. Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but were not changed significantly in the 20-Gy samples. The comprehensive metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic pathways involved in the life process. The findings presented in this manuscript will contribute to our knowledge of the characteristic metabolic changes associated with gamma-radiation-induced damage to somatic cells and will allow for better exploration of the SIT for the control of this target pest.

  20. Metabolic profiling of somatic tissues from Monochamus alternatus (Coleoptera: Cerambycidae) reveals effects of irradiation on metabolism.

    Qu, Liangjian; Wang, Lijuan; Wang, Qinghua; Wang, Yuzhu; Zhang, Yongan

    2014-01-01

    A high-level of sexual sterility is of importance for the sterile insect technique (SIT). However, the use of high-dose-intensity gamma radiation to induce sterility has negative impacts not only on reproductive cells but also on somatic cells. In this study, we investigated the metabolite differences in somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated male Monochamus alternatus, an important vector of the pathogenic nematode, Bursaphelenchus xylophilus, which kills Asian pines. The results showed that metabolite levels changed moderately in the 20-Gy samples but were markedly altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively. Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but were not changed significantly in the 20-Gy samples. The comprehensive metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic pathways involved in the life process. The findings presented in this manuscript will contribute to our knowledge of the characteristic metabolic changes associated with gamma-radiation-induced damage to somatic cells and will allow for better exploration of the SIT for the control of this target pest. PMID:24937685

  1. Transcriptome profile of liver at different physiological stages reveals potential mode for lipid metabolism in laying hens

    Li, Hong; Wang, Taian; Xu, Chunlin; Wang, Dandan; Ren, Junxiao; Li, Yanmin; Tian, Yadong; Wang, Yanbin; Jiao, Yuping; Kang, Xiangtao; Liu, Xiaojun

    2015-01-01

    Background Liver is an important metabolic organ that plays a critical role in lipid synthesis, degradation, and transport; however, the molecular regulatory mechanisms of lipid metabolism remain unclear in chicken. In this study, RNA-Seq technology was used to investigate differences in expression profiles of hepatic lipid metabolism-related genes and associated pathways between juvenile and laying hens. The study aimed to broaden the understanding of liver lipid metabolism in chicken, and t...

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

    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.

  3. Streptococcus agalactiae adapts to glucose stress conditions by modulating gene expression profile

    Di Palo, Benedetta

    2012-01-01

    Diabetes mellitus is considered a risk factor for Group B Streptococcus (GBS) infections. Typically, this pathology is associated to high glucose levels in the bloodstream. Although clinical evidences support this notion, the physiological mechanisms underlying GBS adaptation to such conditions are not yet defined. In the attempt to address this issue, we performed comparative global gene expression analysis of GBS grown under glucose-stress conditions and observed that a number of metabolic ...

  4. Metabolic Profile Changes of CCl₄-Liver Fibrosis and Inhibitory Effects of Jiaqi Ganxian Granule.

    Wang, Ge; Li, Zehao; Li, Hao; Li, Lidan; Li, Jian; Yu, Changyuan

    2016-01-01

    Jiaqi Ganxian Granule (JGG) is a famous traditional Chinese medicine, which has been long used in clinical practice for treating liver fibrosis. However, the mechanism underlying its anti-hepatic fibrosis is still not clear. In this study, an Ultra-Performance Liquid Chromatography-Time-Of-Flight Mass Spectrometry (UPLC-TOF-MS)-based metabolomics strategy was used to profile the metabolic characteristic of serum obtained from a carbon tetrachloride (CCl₄)-induced hepatic fibrosis model in Sprague-Dawley (SD) rats with JGG treatment. Through Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA), it was shown that metabolic perturbations induced by CCl₄ were inhibited after treatment of JGG, for 17 different metabolites related to CCl₄. Among these compounds, the change tendency of eight potential drug targets was restored after the intervention with JGG. The current study indicates that JGG has a significant anti-fibrosis effect on CCl₄-induced liver fibrosis in rats, which might be by regulating the dysfunction of sphingolipid metabolism, glycerophospholipid metabolism, N-acylethanolamine biosynthesis, fat digestion and absorption, while glycerophospholipid metabolism played vital roles in the inhibitory effects of JGG on hepatic fibrosis according to Metabolic Pathway Analysis (MetPA). Our findings indicated that the metabolomics approach may provide a useful tool for exploring potential biomarkers involved in hepatic fibrosis and elucidate the mechanisms underlying the action of therapies used in traditional Chinese medicine. PMID:27248993

  5. Nuclear Magnetic Resonance (NMR) Spectroscopy For Metabolic Profiling of Medicinal Plants and Their Products.

    Kumar, Dinesh

    2016-09-01

    NMR spectroscopy has multidisciplinary applications, including excellent impact in metabolomics. The analytical capacity of NMR spectroscopy provides information for easy qualitative and quantitative assessment of both endogenous and exogenous metabolites present in biological samples. The complexity of a particular metabolite and its contribution in a biological system are critically important for understanding the functional state that governs the organism's phenotypes. This review covers historical aspects of developments in the NMR field, its applications in chemical profiling, metabolomics, and quality control of plants and their derived medicines, foods, and other products. The bottlenecks of NMR in metabolic profiling are also discussed, keeping in view the future scope and further technological interventions. PMID:26575437

  6. Co-evolution of Hormone Metabolism and Signaling Networks Expands Plant Adaptive Plasticity.

    Weng, Jing-Ke; Ye, Mingli; Li, Bin; Noel, Joseph P

    2016-08-11

    Classically, hormones elicit specific cellular responses by activating dedicated receptors. Nevertheless, the biosynthesis and turnover of many of these hormone molecules also produce chemically related metabolites. These molecules may also possess hormonal activities; therefore, one or more may contribute to the adaptive plasticity of signaling outcomes in host organisms. Here, we show that a catabolite of the plant hormone abscisic acid (ABA), namely phaseic acid (PA), likely emerged in seed plants as a signaling molecule that fine-tunes plant physiology, environmental adaptation, and development. This trait was facilitated by both the emergence-selection of a PA reductase that modulates PA concentrations and by the functional diversification of the ABA receptor family to perceive and respond to PA. Our results suggest that PA serves as a hormone in seed plants through activation of a subset of ABA receptors. This study demonstrates that the co-evolution of hormone metabolism and signaling networks can expand organismal resilience. PMID:27518563

  7. Metabolic profiling of muscle contraction in lean compared with obese rodents

    John P. Thyfault; Cree, Melanie G.; Tapscott, Edward B.; Bell, Jill A.; Koves, Timothy R.; Ilkayeva, Olga; Wolfe, Robert R.; Dohm, G. Lynis; Muoio, Deborah M.

    2010-01-01

    Interest in the pathophysiological relevance of intramuscular triacylglycerol (IMTG) accumulation has grown from numerous studies reporting that abnormally high glycerolipid levels in tissues of obese and diabetic subjects correlate negatively with glucose tolerance. Here, we used a hindlimb perfusion model to examine the impact of obesity and elevated IMTG levels on contraction-induced changes in skeletal muscle fuel metabolism. Comprehensive lipid profiling was performed on gastrocnemius mu...

  8. Perturbation in kidney lipid metabolic profiles in diabetic rats with reference to alcoholic oxidative stress

    K. R. Shanmugam; Ramakrishna, C. H.; K Mallikarjuna; Reddy, K. Sathyavelu

    2009-01-01

    Diabetes is a major threat to global public health, and the number of diabetic patients is rapidly increasing worldwide. Evidence suggests that oxidative stress is involved in the pathophysiology of diabetic complications and alcoholic diseases. The aim of this study is to find out the impact of alcohol on lipid metabolic profiles in kidney tissue under streptozotocin induced diabetic condition. No study has been reported so far on the effect of alcohol on diabetic condition and also with ref...

  9. Early weaning and concentrate supplementation on the performance and metabolic profile of grazing lambs

    Sergio Rodrigo Fernandes

    2012-05-01

    Full Text Available This study was designed to investigate the effect of early weaning and concentrate supplementation on performance and metabolic profile of lambs in four production systems on pasture: suckling lambs not supplemented until slaughter; suckling lambs supplemented with concentrate in creep feeding until slaughter; early weaned lambs not supplemented until slaughter; early weaned lambs supplemented with concentrate until slaughter. Performance was assessed by average daily gain (ADG and body condition score (BCS measurements. Metabolic profile was delineated by measuring serum albumin, urea, creatinine, cholesterol, glucose and aspartate aminotransferase. Weaning reduced ADG by 92 g/d and the ADG for weaned and suckling lambs were 113 g/d and 205 g/d, respectively. Supplementation increased ADG by 117 g/d and the ADG was 99 g/d for non-supplemented and 216 g/d for supplemented lambs. Body weight and BCS at the end of trial were lower in weaned and non-supplemented animals (20.7 kg and 1.5 points, and higher in those on creep feeding (35.3 kg and 3.3 points. Weaning decreased serum levels of albumin, cholesterol and aspartate aminotransferase. Supplementation increased serum albumin and decreased serum aspartate aminotransferase. Serum urea was not affected by weaning or supplementation and remained high during the trial. Serum creatinine and glucose were lower in weaned and non-supplemented lambs. Early weaning generates unsuitable metabolic profile and low performance and may not be recommended as single strategy to produce lambs on pasture. Concentrate supplementation has similar response to suckling on the performance and metabolic profile of animals, and may be considered an efficient strategy to improve the nutritional status of early weaned lambs.

  10. A comparative study on lifestyle and metabolic profile in normal and obese individuals

    Revathi R, Swetha S, MeghalathaTS, Arunakumari R

    2013-01-01

    Background/Aim: The aim of the present study was to evaluate the lifestyle and metabolic profiles in normal and obese. Material and Methods: A cross sectional study design was employed. Information on body weight, height, body fat, food choices, diet and physical activity behavior were collected by a questionnaire among 100 obese adults aged 18-35 years and compared with healthy individuals as controls. Blood samples were collected to analyze blood glucose, heamoglobin and total cholesterol....

  11. Yogurt consumption is associated with better diet quality and metabolic profile in American men and women

    Wang, Huifen; Livingston, Kara A.; Fox, Caroline S; Meigs, James B.; Jacques, Paul F.

    2012-01-01

    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 questionna...

  12. Racial Disparities between the Sex Steroid Milieu and the Metabolic Risk Profile

    Loreto Jackson; Ronald Goldberg; Robert Ross; Arlette Perry; Xuewen Wang

    2010-01-01

    Aims and Method. The present study examined the relationship between the metabolic risk profile (MRP) and total testosterone (TT) and free testosterone using the free androgen index (FAI) and sex hormone binding globulin (SHBG) in 36 Caucasian American (CA) and 30 African-American (AA) women volunteering for a weight loss study. Results. After controlling for age, significant relationships were found between TT and diastolic blood pressure (P = .004 and P = .015 in CA and AA women, resp.). Ad...

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

    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

  14. Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

    Hu Song

    2012-01-01

    Full Text Available Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA. Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1 and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms.

  15. Serum metabolic profiling of human gastric cancer based on gas chromatography/mass spectrometry

    Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS) was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA). Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV) of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP) value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1) and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms

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

    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.

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

    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

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

    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.

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

    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. PMID:25465889

  20. Metabolic modelling reveals the specialization of secondary replicons for niche adaptation in Sinorhizobium meliloti.

    diCenzo, George C; Checcucci, Alice; Bazzicalupo, Marco; Mengoni, Alessio; Viti, Carlo; Dziewit, Lukasz; Finan, Turlough M; Galardini, Marco; Fondi, Marco

    2016-01-01

    The genome of about 10% of bacterial species is divided among two or more large chromosome-sized replicons. The contribution of each replicon to the microbial life cycle (for example, environmental adaptations and/or niche switching) remains unclear. Here we report a genome-scale metabolic model of the legume symbiont Sinorhizobium meliloti that is integrated with carbon utilization data for 1,500 genes with 192 carbon substrates. Growth of S. meliloti is modelled in three ecological niches (bulk soil, rhizosphere and nodule) with a focus on the role of each of its three replicons. We observe clear metabolic differences during growth in the tested ecological niches and an overall reprogramming following niche switching. In silico examination of the inferred fitness of gene deletion mutants suggests that secondary replicons evolved to fulfil a specialized function, particularly host-associated niche adaptation. Thus, genes on secondary replicons might potentially be manipulated to promote or suppress host interactions for biotechnological purposes. PMID:27447951

  1. Metabolic profiling of a range of peach fruit varieties reveals high metabolic diversity and commonalities and differences during ripening.

    Monti, Laura L; Bustamante, Claudia A; Osorio, Sonia; Gabilondo, Julieta; Borsani, Julia; Lauxmann, Martin A; Maulión, Evangelina; Valentini, Gabriel; Budde, Claudio O; Fernie, Alisdair R; Lara, María V; Drincovich, María F

    2016-01-01

    Peach (Prunus persica) fruits from different varieties display differential organoleptic and nutritional properties, characteristics related to their chemical composition. Here, chemical biodiversity of peach fruits from fifteen varieties, at harvest and after post-harvest ripening, was explored by gas chromatography-mass spectrometry. Metabolic profiling revealed that metabolites involved in organoleptic properties (sugars, organic and amino acids), stress tolerance (raffinose, galactinol, maltitol), and with nutritional properties (amino, caffeoylquinic and dehydroascorbic acids) displayed variety-dependent levels. Peach varieties clustered into four groups: two groups of early-harvest varieties with higher amino acid levels; two groups of mid- and late-harvest varieties with higher maltose levels. Further separation was mostly dependent on organic acids/raffinose levels. Variety-dependent and independent metabolic changes associated with ripening were detected; which contribute to chemical diversity or can be used as ripening markers, respectively. The great variety-dependent diversity in the content of metabolites that define fruit quality reinforces metabolomics usage as a tool to assist fruit quality improvement in peach. PMID:26213052

  2. User Profile-Driven Data Warehouse Summary for Adaptive OLAP Queries

    Rym Khemiri; Fadila Bentayeb

    2013-01-01

    Data warehousing is an essential element of decision support systems. It aims at enabling the user knowledge to make better and faster daily business decisions. To improve this decision support system and to give more and more relevant information to the user, the need to integrate user's profiles into the data warehouse process becomes crucial. In this paper, we propose to exploit users' preferences as a basis for adapting OLAP (On-Line Analytical Processing) queries to the user. For this, w...

  3. Unsupervised principal component analysis of NMR metabolic profiles for the assessment of substantial equivalence of transgenic grapes (Vitis vinifera).

    Picone, Gianfranco; Mezzetti, Bruno; Babini, Elena; Capocasa, Franco; Placucci, Giuseppe; Capozzi, Francesco

    2011-09-14

    Substantial equivalence is a key concept in the evaluation of unintended and potentially harmful metabolic impact consequent to a genetic modification of food. The application of unsupervised multivariate data analysis to the metabolic profiles is expected to improve the effectiveness of such evaluation. The present study uses NMR spectra of hydroalcoholic extracts, as holistic representations of the metabolic profiles of grapes, to evaluate the effect of the insertion of one or three copies of the DefH9-iaaM construct in plants of Silcora and Thompson Seedless cultivars. The comparison of the metabolic profiles of transgenic derivatives with respect to their corresponding natural lines pointed out that the overall metabolic changes occur in the same direction, independent of the host genotype, although the two cultivars are modified to different extents. A higher number of copies not only produces a larger effect but also modifies the whole pattern of perturbed metabolites. PMID:21806070

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

    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

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

    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.

  6. Effects of sildenafil on lipid profile and glycemic control in patients with type 2 diabetes mellitus and metabolic syndrome

    Haedar Abdulhafith Al-biati

    2014-12-01

    Conclusion: We have provided the first evidence that sildenafil therapy improve glycemic control, lipid profile and body mass index in diabetic patients with metabolic syndrome. [Int J Basic Clin Pharmacol 2014; 3(6.000: 1048-1051

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

    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. PMID:25403594

  8. Evaluation and characterization of bacterial metabolic dynamics with a novel profiling technique, real-time metabolotyping.

    Shinji Fukuda

    Full Text Available BACKGROUND: Environmental processes in ecosystems are dynamically altered by several metabolic responses in microorganisms, including intracellular sensing and pumping, battle for survival, and supply of or competition for nutrients. Notably, intestinal bacteria maintain homeostatic balance in mammals via multiple dynamic biochemical reactions to produce several metabolites from undigested food, and those metabolites exert various effects on mammalian cells in a time-dependent manner. We have established a method for the analysis of bacterial metabolic dynamics in real time and used it in combination with statistical NMR procedures. METHODOLOGY/PRINCIPAL FINDINGS: We developed a novel method called real-time metabolotyping (RT-MT, which performs sequential (1H-NMR profiling and two-dimensional (2D (1H, (13C-HSQC (heteronuclear single quantum coherence profiling during bacterial growth in an NMR tube. The profiles were evaluated with such statistical methods as Z-score analysis, principal components analysis, and time series of statistical TOtal Correlation SpectroScopY (TOCSY. In addition, using 2D (1H, (13C-HSQC with the stable isotope labeling technique, we observed the metabolic kinetics of specific biochemical reactions based on time-dependent 2D kinetic profiles. Using these methods, we clarified the pathway for linolenic acid hydrogenation by a gastrointestinal bacterium, Butyrivibrio fibrisolvens. We identified trans11, cis13 conjugated linoleic acid as the intermediate of linolenic acid hydrogenation by B. fibrisolvens, based on the results of (13C-labeling RT-MT experiments. In addition, we showed that the biohydrogenation of polyunsaturated fatty acids serves as a defense mechanism against their toxic effects. CONCLUSIONS: RT-MT is useful for the characterization of beneficial bacterium that shows potential for use as probiotic by producing bioactive compounds.

  9. Influence of the RelA activity on E. coli metabolism by metabolite profiling of glucose-limited chemostat cultures

    Sónia Carneiro; Villas-Bôas, Silas G.; Ferreira, Eugénio C.; Isabel Rocha

    2012-01-01

    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 metabolit...

  10. Thermal and metabolic adaptation to first cold-water immersion in juvenile penguins.

    Barré, H; Roussel, B

    1986-09-01

    Juvenile king and macaroni penguins are terrestrial seabirds and must face an intensive and prolonged energetic demand during their passage from shore to marine life in cold subantarctic seawater. Evidence for progressive thermal adaptation was sought by measurement of metabolic rate (MR) and body (Tb) and skin (Tsk) temperatures in unrestrained, fully immersed penguins. Steady-state responses obtained after the 3rd h of immersion in never-immersed (NI) penguins were compared with those of penguins acclimatized to seawater temperature (A). NI macaroni penguins, unlike NI king penguins, showed a fall in Tb on their first immersion but, once acclimatized, were able to maintain their homeothermy due to an increase (greater than 3.2 W/kg) in regulatory thermogenesis. In NI king penguins, during a simulation of seawater adaptation by 10 successive immersions, MR at 7 degrees C water temperature (Tw) rose from 6.0 to 9.4 W/kg (becoming 3-5 times higher than in air), whereas Tb rose from 37.6 to 38.4 degrees C. In both species occurrence of peak MR at much lower Tw, progressive increase in thermogenesis capacity, and lower conductance in water after adaptation to marine life (28 and 36% less in A king and macaroni penguins, respectively) showed that the passage from shore to marine life consisted of a true cold acclimatization. PMID:3752279

  11. Fetal endocrine and metabolic adaptations to hypoxia: the role of the hypothalamic-pituitary-adrenal axis.

    Newby, Elizabeth A; Myers, Dean A; Ducsay, Charles A

    2015-09-01

    In utero, hypoxia is a significant yet common stress that perturbs homeostasis and can occur due to preeclampsia, preterm labor, maternal smoking, heart or lung disease, obesity, and high altitude. The fetus has the extraordinary capacity to respond to stress during development. This is mediated in part by the hypothalamic-pituitary-adrenal (HPA) axis and more recently explored changes in perirenal adipose tissue (PAT) in response to hypoxia. Obvious ethical considerations limit studies of the human fetus, and fetal studies in the rodent model are limited due to size considerations and major differences in developmental landmarks. The sheep is a common model that has been used extensively to study the effects of both acute and chronic hypoxia on fetal development. In response to high-altitude-induced, moderate long-term hypoxia (LTH), both the HPA axis and PAT adapt to preserve normal fetal growth and development while allowing for responses to acute stress. Although these adaptations appear beneficial during fetal development, they may become deleterious postnatally and into adulthood. The goal of this review is to examine the role of the HPA axis in the convergence of endocrine and metabolic adaptive responses to hypoxia in the fetus. PMID:26173460

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

    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 t

  13. Inner workings of thrombolites: spatial gradients of metabolic activity as revealed by metatranscriptome profiling

    Mobberley, J. M.; Khodadad, C. L. M.; Visscher, P. T.; Reid, R. P.; Hagan, P.; Foster, J. S.

    2015-07-01

    Microbialites are sedimentary deposits formed by the metabolic interactions of microbes and their environment. These lithifying microbial communities represent one of the oldest ecosystems on Earth, yet the molecular mechanisms underlying the function of these communities are poorly understood. In this study, we used comparative metagenomic and metatranscriptomic analyses to characterize the spatial organization of the thrombolites of Highborne Cay, The Bahamas, an actively forming microbialite system. At midday, there were differences in gene expression throughout the spatial profile of the thrombolitic mat with a high abundance of transcripts encoding genes required for photosynthesis, nitrogen fixation and exopolymeric substance production in the upper three mm of the mat. Transcripts associated with denitrification and sulfate reduction were in low abundance throughout the depth profile, suggesting these metabolisms were less active during midday. Comparative metagenomics of the Bahamian thrombolites with other known microbialite ecosystems from across the globe revealed that, despite many shared core pathways, the thrombolites represented genetically distinct communities. This study represents the first time the metatranscriptome of living microbialite has been characterized and offers a new molecular perspective on those microbial metabolisms, and their underlying genetic pathways, that influence the mechanisms of carbonate precipitation in lithifying microbial mat ecosystems.

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

    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.

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

    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.

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

    Xie, Yan; Hu, Longxing; Du, Zhimin; Sun, Xiaoyan; Amombo, Erick; Fan, Jibiao; Fu, Jinmin

    2014-01-01

    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. PMID:25545719

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

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

    2011-01-01

    Abstract 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...

  18. Gene regulatory and metabolic adaptation processes of Dinoroseobacter shibae DFL12T during oxygen depletion.

    Laass, Sebastian; Kleist, Sarah; Bill, Nelli; Drüppel, Katharina; Kossmehl, Sebastian; Wöhlbrand, Lars; Rabus, Ralf; Klein, Johannes; Rohde, Manfred; Bartsch, Annekathrin; Wittmann, Christoph; Schmidt-Hohagen, Kerstin; Tielen, Petra; Jahn, Dieter; Schomburg, Dietmar

    2014-05-01

    Metabolic flexibility is the key to the ecological success of the marine Roseobacter clade bacteria. We investigated the metabolic adaptation and the underlying changes in gene expression of Dinoroseobacter shibae DFL12(T) to anoxic life by a combination of metabolome, proteome, and transcriptome analyses. Time-resolved studies during continuous oxygen depletion were performed in a chemostat using nitrate as the terminal electron acceptor. Formation of the denitrification machinery was found enhanced on the transcriptional and proteome level, indicating that D. shibae DFL12(T) established nitrate respiration to compensate for the depletion of the electron acceptor oxygen. In parallel, arginine fermentation was induced. During the transition state, growth and ATP concentration were found to be reduced, as reflected by a decrease of A578 values and viable cell counts. In parallel, the central metabolism, including gluconeogenesis, protein biosynthesis, and purine/pyrimidine synthesis was found transiently reduced in agreement with the decreased demand for cellular building blocks. Surprisingly, an accumulation of poly-3-hydroxybutanoate was observed during prolonged incubation under anoxic conditions. One possible explanation is the storage of accumulated metabolites and the regeneration of NADP(+) from NADPH during poly-3-hydroxybutanoate synthesis (NADPH sink). Although D. shibae DFL12(T) was cultivated in the dark, biosynthesis of bacteriochlorophyll was increased, possibly to prepare for additional energy generation via aerobic anoxygenic photophosphorylation. Overall, oxygen depletion led to a metabolic crisis with partly blocked pathways and the accumulation of metabolites. In response, major energy-consuming processes were reduced until the alternative respiratory denitrification machinery was operative. PMID:24648520

  19. Raman-based noninvasive metabolic profile evaluation of in vitro bovine embryos

    dos Santos, Érika Cristina; Martinho, Herculano; Annes, Kelly; da Silva, Thais; Soares, Carlos Alexandre; Leite, Roberta Ferreira; Milazzotto, Marcella Pecora

    2016-07-01

    The timing of the first embryonic cell divisions may predict the ability of an embryo to establish pregnancy. Similarly, metabolic profiles may be markers of embryonic viability. However, in bovine, data about the metabolomics profile of these embryos are still not available. In the present work, we describe Raman-based metabolomic profiles of culture media of bovine embryos with different developmental kinetics (fast x slow) throughout the in vitro culture. The principal component analysis enabled us to classify embryos with different developmental kinetics since they presented specific spectroscopic profiles for each evaluated time point. We noticed that bands at 1076 cm-1 (lipids), 1300 cm-1 (Amide III), and 2719 cm-1 (DNA nitrogen bases) gave the most relevant spectral features, enabling the separation between fast and slow groups. Bands at 1001 cm-1 (phenylalanine) and 2892 cm-1 (methylene group of the polymethylene chain) presented specific patterns related to embryonic stage and can be considered as biomarkers of embryonic development by Raman spectroscopy. The culture media analysis by Raman spectroscopy proved to be a simple and sensitive technique that can be applied with high efficiency to characterize the profiles of in vitro produced bovine embryos with different development kinetics and different stages of development.

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

    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. PMID:27559027

  1. Metabolic profiling reveals growth related FAME productivity and quality of Chlorella sorokiniana with different inoculum sizes.

    Lu, Shuhuan; Wang, Jiangxin; Niu, Yanhong; Yang, Jie; Zhou, Jian; Yuan, Yingjin

    2012-07-01

    Inoculum size strongly affects cell growth and lipid accumulation of microalgae, one of the most potential biodiesel feedstock, however, the metabolic mechanism(s) of the lipid biosynthesis upon inoculum size has not been fully explored yet. The effects of inoculum size on cell growth, lipid accumulation, and metabolic changes of a green microalga Chlorella sorokiniana were investigated. In our experimental range of inoculum size, the productivity and the cetane number (CN) of fatty acid methyl esters (FAME) increased with increasing initial cell density, and the inoculum of 1 × 10(7) cells mL(-1) processed much higher productivity (up to 2.02-fold) and CN (up to 1.19-fold) of the FAME than the others. A significant correlation between the metabolic profile and quantity and quality of lipid production was revealed by partial least-squares to latent structures (PLS) analysis, and 15 key metabolites were identified. Most of those metabolites were involved in the photosynthetically fixed carbon metabolism. Furthermore, light intensity as one of the vital limitation factors for the high inoculum size cultivation was evaluated by illumination assay and the results revealed that increasing light intensity could improve the polyunsaturated fatty acids composition and lipid accumulation of C. sorokiniana. The lipid productivity of the culture was improved by 71.21% with the light intensity of 110 µmol m(-2) s(-1), compared to that under the irradiance of 65 µmol m(-2) s(-1). PMID:22252441

  2. A metabolic profiling strategy for the dissection of plant defense against fungal pathogens.

    Konstantinos A Aliferis

    Full Text Available Here we present a metabolic profiling strategy employing direct infusion Orbitrap mass spectrometry (MS and gas chromatography-mass spectrometry (GC/MS for the monitoring of soybean's (Glycine max L. global metabolism regulation in response to Rhizoctonia solani infection in a time-course. Key elements in the approach are the construction of a comprehensive metabolite library for soybean, which accelerates the steps of metabolite identification and biological interpretation of results, and bioinformatics tools for the visualization and analysis of its metabolome. The study of metabolic networks revealed that infection results in the mobilization of carbohydrates, disturbance of the amino acid pool, and activation of isoflavonoid, α-linolenate, and phenylpropanoid biosynthetic pathways of the plant. Components of these pathways include phytoalexins, coumarins, flavonoids, signaling molecules, and hormones, many of which exhibit antioxidant properties and bioactivity helping the plant to counterattack the pathogen's invasion. Unraveling the biochemical mechanism operating during soybean-Rhizoctonia interaction, in addition to its significance towards the understanding of the plant's metabolism regulation under biotic stress, provides valuable insights with potential for applications in biotechnology, crop breeding, and agrochemical and food industries.

  3. A metabolic profiling strategy for the dissection of plant defense against fungal pathogens.

    Aliferis, Konstantinos A; Faubert, Denis; Jabaji, Suha

    2014-01-01

    Here we present a metabolic profiling strategy employing direct infusion Orbitrap mass spectrometry (MS) and gas chromatography-mass spectrometry (GC/MS) for the monitoring of soybean's (Glycine max L.) global metabolism regulation in response to Rhizoctonia solani infection in a time-course. Key elements in the approach are the construction of a comprehensive metabolite library for soybean, which accelerates the steps of metabolite identification and biological interpretation of results, and bioinformatics tools for the visualization and analysis of its metabolome. The study of metabolic networks revealed that infection results in the mobilization of carbohydrates, disturbance of the amino acid pool, and activation of isoflavonoid, α-linolenate, and phenylpropanoid biosynthetic pathways of the plant. Components of these pathways include phytoalexins, coumarins, flavonoids, signaling molecules, and hormones, many of which exhibit antioxidant properties and bioactivity helping the plant to counterattack the pathogen's invasion. Unraveling the biochemical mechanism operating during soybean-Rhizoctonia interaction, in addition to its significance towards the understanding of the plant's metabolism regulation under biotic stress, provides valuable insights with potential for applications in biotechnology, crop breeding, and agrochemical and food industries. PMID:25369450

  4. Metabolic profiling of a mapping population exposes new insights in the regulation of seed metabolism and seed, fruit, and plant relations.

    David Toubiana

    Full Text Available To investigate the regulation of seed metabolism and to estimate the degree of metabolic natural variability, metabolite profiling and network analysis were applied to a collection of 76 different homozygous tomato introgression lines (ILs grown in the field in two consecutive harvest seasons. Factorial ANOVA confirmed the presence of 30 metabolite quantitative trait loci (mQTL. Amino acid contents displayed a high degree of variability across the population, with similar patterns across the two seasons, while sugars exhibited significant seasonal fluctuations. Upon integration of data for tomato pericarp metabolite profiling, factorial ANOVA identified the main factor for metabolic polymorphism to be the genotypic background rather than the environment or the tissue. Analysis of the coefficient of variance indicated greater phenotypic plasticity in the ILs than in the M82 tomato cultivar. Broad-sense estimate of heritability suggested that the mode of inheritance of metabolite traits in the seed differed from that in the fruit. Correlation-based metabolic network analysis comparing metabolite data for the seed with that for the pericarp showed that the seed network displayed tighter interdependence of metabolic processes than the fruit. Amino acids in the seed metabolic network were shown to play a central hub-like role in the topology of the network, maintaining high interactions with other metabolite categories, i.e., sugars and organic acids. Network analysis identified six exceptionally highly co-regulated amino acids, Gly, Ser, Thr, Ile, Val, and Pro. The strong interdependence of this group was confirmed by the mQTL mapping. Taken together these results (i reflect the extensive redundancy of the regulation underlying seed metabolism, (ii demonstrate the tight co-ordination of seed metabolism with respect to fruit metabolism, and (iii emphasize the centrality of the amino acid module in the seed metabolic network. Finally, the study

  5. CS-16THE eEF2 KINASE IS CRITICAL FOR BRAIN TUMOURS ADAPTATION TO METABOLIC STRESS

    Leprivier, Gabriel; Remke, Marc; Rotblat, Barak; Agnihotri, Sameer; Kool, Marcel; Derry, Brent; Pfister, Stefan; Taylor, Michael D.; Sorensen, Poul H.

    2014-01-01

    During tumour progression, brain tumour cells are exposed to metabolic stress, such as nutrient deprivation, due to abnormal tumour vasculature. The ability of tumour cells to respond and manage reduced nutrient availability has a strong impact on tumour outcome. The molecular pathways supporting metabolic adaptation of brain tumour cells to nutrient stress represent potential therapeutic targets which are still not well defined. We report that the translation elongation factor 2 (eEF2) kinas...

  6. Dynamical feedback between circadian clock and sucrose availability explains adaptive response of starch metabolism to various photoperiods

    Feugier, François G.; Satake, Akiko

    2013-01-01

    Plants deal with resource management during all their life. During the day they feed on photosynthetic carbon, sucrose, while storing a part into starch for night use. Careful control of carbon partitioning, starch degradation, and sucrose export rates is crucial to avoid carbon starvation, insuring optimal growth whatever the photoperiod. Efficient regulation of these key metabolic rates can give an evolutionary advantage to plants. Here we propose a model of adaptive starch metabolism in re...

  7. Metabolic adaptations of skeletal muscle to voluntary wheel running exercise in hypertensive heart failure rats

    Schultz, R L; Kullman, E L; Waters, Ryan;

    2013-01-01

    The Spontaneously Hypertensive Heart Failure (SHHF) rat mimics the human progression of hypertension from hypertrophy to heart failure. However, it is unknown whether SHHF animals can exercise at sufficient levels to observe beneficial biochemical adaptations in skeletal muscle. Thirty-seven female...... SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function and...... expression, and glycogen utilization. The SHHFex rats ran a greater distance and duration as compared to the WFex rats (P<0.05), but the WFex rats ran at a faster speed (P<0.05). Skeletal muscle citrate synthase and beta-hydroxyacyl-CoA dehydrogenase enzyme activity was not altered in the SHHFex group, but...

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

    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

  9. Vitamin C improves basal metabolic rate and lipid profile in alloxan-induced diabetes mellitus in rats

    D U Owu; A B Antai; K H Udofia; A O Obembe; K O Obasi; M U Eteng

    2006-12-01

    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. by gavage for four weeks to diabetic rats after which the resting metabolic rate and plasma lipid profile was determined. The results showed that vitamin C administration significantly ( < 0.01) reduced the resting metabolic rate in diabetic rats; and also lowered plasma triglyceride, total cholesterol and low-density lipoprotein cholesterol. These results suggest that the administration of vitamin C in this model of established diabetes mellitus might be beneficial for the restoration of basal metabolic rate and improvement of lipid profile. This may at least in part reduce the risk of cardiovascular events seen in diabetes mellitus.

  10. Urinary Metabolomic Approach Provides New Insights into Distinct Metabolic Profiles of Glutamine and N-Carbamylglutamate Supplementation in Rats.

    Liu, Guangmang; Cao, Wei; Fang, Tingting; Jia, Gang; Zhao, Hua; Chen, Xiaoling; Wu, Caimei; Wang, Jing

    2016-01-01

    Glutamine and N-carbamylglutamate can enhance growth performance and health in animals, but the underlying mechanisms are not yet elucidated. This study aimed to investigate the effect of glutamine and N-carbamylglutamate supplementation in rat metabolism. Thirty rats were fed a control, glutamine, or N-carbamylglutamate diet for four weeks. Urine samples were analyzed by nuclear magnetic resonance (NMR)-based metabolomics, specifically high-resolution ¹H NMR metabolic profiling combined with multivariate data analysis. Glutamine significantly increased the urine levels of acetamide, acetate, citrulline, creatinine, and methymalonate, and decreased the urine levels of ethanol and formate (p glutamine and N-carbamylglutamate could modify urinary metabolome related to nitrogen metabolism and gut microbiota metabolism. Moreover, N-carbamylglutamate could alter energy and lipid metabolism. These findings indicate that different arginine precursors may lead to differences in the biofluid profile in rats. PMID:27527211

  11. A GC-MS metabolic profiling study of plasma samples from mice on low- and high-fat diets.

    Spagou, Konstantina; Theodoridis, Georgios; Wilson, Ian; Raikos, Nikolaos; Greaves, Peter; Edwards, Richard; Nolan, Barbara; Klapa, Maria I

    2011-05-15

    Metabolic profiling of biofluids, based on the quantitative analysis of the concentration profile of their free low molecular mass metabolites, has been playing increasing role employed as a means to gain understanding of the progression of metabolic disorders, including obesity. Chromatographic methods coupled with mass spectrometry have been established as a strategy for metabolic profiling. Among these, GC-MS, targeting mainly the primary metabolism intermediates, offers high sensitivity, good peak resolution and extensive databases. However, the derivatization step required for many involatile metabolites necessitates specific data validation, normalization and analysis protocols to ensure accurate and reproducible performance. In this study, the GC-MS metabolic profiles of plasma samples from mice maintained on 12- or 15-month long low (10 kcal%) or high (60 kcal%) fat diets were obtained. The profiles of the trimethylsilyl(TMS)-methoxime(MeOx) derivatives of the free polar metabolites were acquired through GC-(ion trap)MS, using [U-(13)C]-glucose as the internal standard. After the application of a recently developed data correction and normalization/filtering protocol for GC-MS metabolomic datasets, the profiles of 48 out of the 77 detected metabolites were used in multivariate statistical analysis. Data mining suggested a decrease in the activity of the energy metabolism with age. In addition, the metabolic profiles indicated the presence of subpopulations with different physiology within the high- and low-fat diet mice, which correlated well with the difference in body weight among the animals and current knowledge about hyperglycemic conditions. PMID:21388899

  12. Effective long term adaptation and metabolic state regulation of ski-racers

    Bakhareva A.S.

    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.

  13. A Robust Adaptive Sliding Mode Control for PMLSM with Variable Velocity Profile Over Wide Range

    Payam Ghaebi Panah

    2015-07-01

    Full Text Available An adaptive robust variable structure speed controller is designed for wide range of desired velocity control of a Permanent Magnet Linear Synchronous Motor (PMLSM. This is performed for comprehensive nonlinear model of PMLSM including non-idealities such as detent force, parameter uncertainty, unpredicted disturbance and nonlinear friction. The proposed method is based on the robust Sliding Mode Control (SMC in combination with an adaptive strategy for a wide range of velocity. The simulation results are provided for the above mentioned comprehensive model of PMLSM with a variable velocity profile. Moreover, as an evaluation criterion, a Proportional-Integral (PI controller is designed whose parameters are optimally tuned by the Particle Swarm Optimization (PSO algorithm for better comparison.

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

    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.

  15. Metabolic profiling of the protozoan parasite Entamoeba invadens revealed activation of unpredicted pathway during encystation.

    Ghulam Jeelani

    Full Text Available Encystation, which is cellular differentiation from the motile, proliferative, labile trophozoite form to the dormant, resistant cyst form, is a crucial process found in parasitic and free-living protozoa such as Entamoeba, Giardia, Acanthamoeba, and Balamuthia. Since encystation is an essential process to deal with the adverse external environmental changes during the life cycle, and often integral to the transmission of the diseases, biochemical understanding of the process potentially provides useful measures against the infections caused by this group of protozoa. In this study, we investigated metabolic and transcriptomic changes that occur during encystation in Entamoeba invadens, the reptilian sibling of mammal-infecting E. histolytica, using capillary electrophoresis-tandem mass spectrometry-based metabolite profiling and DNA microarray-based expression profiling. As the encystation progressed, the levels of majority of metabolites involved in glycolysis and nucleotides drastically decreased, indicating energy generation is ceased. Furthermore, the flux of glycolysis was redirected toward chitin wall biosynthesis. We found remarkable temporal increases in biogenic amines such as isoamylamine, isobutylamine, and cadaverine, during the early period of encystation, when the trophozoites form large multicellular aggregates (precyst. We also found remarkable induction of γ-aminobutyric acid (GABA during encystation. This study has unveiled for the first time the dynamics of the transcriptional and metabolic regulatory networks during encystation, and should help in better understanding of the process in pathogenic eukaryotes, and further development of measures controlling infections they cause.

  16. High-resolution magic-angle-spinning NMR spectroscopy for metabolic profiling of intact tissues.

    Beckonert, Olaf; Coen, Muireann; Keun, Hector C; Wang, Yulan; Ebbels, Timothy M D; Holmes, Elaine; Lindon, John C; Nicholson, Jeremy K

    2010-06-01

    Metabolic profiling, metabolomic and metabonomic studies require robust study protocols for any large-scale comparisons and evaluations. Detailed methods for solution-state NMR spectroscopy have been summarized in an earlier protocol. This protocol details the analysis of intact tissue samples by means of high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy and we provide a detailed description of sample collection, preparation and analysis. Described here are (1)H NMR spectroscopic techniques such as the standard one-dimensional, relaxation-edited, diffusion-edited and two-dimensional J-resolved pulse experiments, as well as one-dimensional (31)P NMR spectroscopy. These are used to monitor different groups of metabolites, e.g., sugars, amino acids and osmolytes as well as larger molecules such as lipids, non-invasively. Through the use of NMR-based diffusion coefficient and relaxation times measurements, information on molecular compartmentation and mobility can be gleaned. The NMR methods are often combined with statistical analysis for further metabonomics analysis and biomarker identification. The standard acquisition time per sample is 8-10 min for a simple one-dimensional (1)H NMR spectrum, giving access to metabolite information while retaining tissue integrity and hence allowing direct comparison with histopathology and MRI/MRS findings or the evaluation together with biofluid metabolic-profiling data. PMID:20539278

  17. Web Log Pre-processing and Analysis for Generation of Learning Profiles in Adaptive E-learning

    Radhika M. Pai; Sucheta V. Kolekar; Manohara Pai M.M.

    2016-01-01

    Adaptive E-learning Systems (AESs) enhance the efficiency of online courses in education by providing personalized contents and user interfaces that changes according to learner’s requirements and usage patterns. This paper presents the approach to generate learning profile of each learner which helps to identify the learning styles and provide Adaptive User Interface which includes adaptive learning components and learning material. The proposed method analyzes the captured web usage data to...

  18. Metabolic profiles show specific mitochondrial toxicities in vitro in myotube cells

    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.

  19. MDG-1, an Ophiopogon polysaccharide, alleviates hyperlipidemia in mice based on metabolic profile of bile acids.

    Shi, Linlin; Wang, Jie; Wang, Yuan; Feng, Yi

    2016-10-01

    Hyperlipidemia is a chronic metabolic disorder with systemic complications that is prevalent worldwide. MDG-1, a water-soluble β-d-fructan polysaccharide from Ophiopogon japonicas has potent hypolipidemic and weight-control effects. The present study aimed to investigate the effects of MDG-1 on lipid metabolic disorders in diet-induced obese mice based on the metabolic profile of bile acids. C57BL/6 mice were treated with a low-fat diet, high-fat diet or high fat mixed with 1‰ (w/w) MDG-1 diet for 12 weeks. The results showed that MDG-1 inhibited body weight gain and lowered serum and liver total cholesterol contents in obese mice. In addition, MDG-1 could adsorb bile acids in the gut lumen and reduce their reabsorption, thus promoting cholesterol catabolism. Furthermore, MDG-1 inhibited the expression of the farnesoid X receptor, but activated the liver X receptor. Our findings shed new light on the mechanism of MDG-1 in the control of lipids. PMID:27312615

  20. Profiling of cytosolic and peroxisomal acetyl-CoA metabolism in Saccharomyces cerevisiae.

    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.

  1. Association between sedentary behavior and anthropometric and metabolic profiles among adolescents

    Roseane de Fátima Guimarães

    2013-12-01

    Full Text Available The purpose of this study was to establish the association between sedentary behavior and the anthropometric and metabolic profiles within a sample group of 572 adolescents from public schools in the city of Curitiba, State of Paraná, Brazil. Approximately 8 ml of blood was drawn to measure total cholesterol (TC, LDL-c, HDL-c, triglycerides, and glucose. Stature and body mass were measured to calculate the body mass index. Information about the subjects' socioeconomic status, physical activity level, sedentary behavior, eating frequency, as well as personal information was obtained through questionnaires. Descriptive statistics, measures of central tendency and percentage score, and Binary Logistic Regression were used to obtain the odds ratio with a CI of 95% and p<0.05. Half of the girls had TC levels classified as borderline or altered, and total screen time presented a significant association between the metabolic variables analyzed in the study. We conclude that girls had TC levels less favorable than that of the boys and that screen time is associated with some metabolic variables.

  2. Metabolic profiles show specific mitochondrial toxicities in vitro in myotube cells

    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 β-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.

  3. LOSS OF CARDIAC METABOLIC ADAPTATION AND DYSFUNCTION OF THE HEART WITH WESTERN DIET IN THE OBESE ZUCKER RAT

    The normal heart sustains its work output through changing the proportion of substrates it oxidizes depending on fuel supply. This metabolic adaptation is thought to be regulated at a transcriptional level by the peroxisome proliferator-activated receptor alpha (PPAR-alpha). We proposed that obesity...

  4. 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.

    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. PMID:23912828

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

    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

  6. Magnetic resonance metabolic profiling of breast cancer tissue obtained with core needle biopsy for predicting pathologic response to neoadjuvant chemotherapy.

    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.

  7. Metabolic profiling for detection of Staphylococcus aureus infection and antibiotic resistance.

    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

  8. Hepatic drug metabolizing profile of Flinders Sensitive Line rat model of depression.

    Kotsovolou, Olga; Ingelman-Sundberg, Magnus; Lang, Matti A; Marselos, Marios; Overstreet, David H; Papadopoulou-Daifoti, Zoi; Johanson, Inger; Fotopoulos, Andrew; Konstandi, Maria

    2010-08-16

    The Flinders Sensitive Line (FSL) rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed patients and has been very effective in screening antidepressants. Major factor that determines the effectiveness and toxicity of a drug is the drug metabolizing capacity of the liver. Therefore, in order to discriminate possible differentiation in the hepatic drug metabolism between FSL rats and Sprague-Dawley (SD) controls, their hepatic metabolic profile was investigated in this study. The data showed decreased glutathione (GSH) content and glutathione S-transferase (GST) activity and lower expression of certain major CYP enzymes, including the CYP2B1, CYP2C11 and CYP2D1 in FSL rats compared to SD controls. In contrast, p-nitrophenol hydroxylase (PNP), 7-ethoxyresorufin-O-dealkylase (EROD) and 16alpha-testosterone hydroxylase activities were higher in FSL rats. Interestingly, the wide spread environmental pollutant benzo(alpha)pyrene (B(alpha)P) induced CYP1A1, CYP1A2, CYP2B1/2 and ALDH3c at a lesser extend in FSL than in SD rats, whereas the antidepressant mirtazapine (MIRT) up-regulated CYP1A1/2, CYP2C11, CYP2D1, CYP2E1 and CYP3A1/2, mainly, in FSL rats. The drug also further increased ALDH3c whereas suppressed GSH content in B(alpha)P-exposed FSL rats. In conclusion, several key enzymes of the hepatic biotransformation machinery are differentially expressed in FSL than in SD rats, a condition that may influence the outcome of drug therapy. The MIRT-induced up-regulation of several drug-metabolizing enzymes indicates the critical role of antidepressant treatment that should be always taken into account in the designing of treatment and interpretation of insufficient pharmacotherapy or drug toxicity. PMID:20595028

  9. Cerebral Metabolic Profiling of Hypothermic Circulatory Arrest with and Without Antegrade Selective Cerebral Perfusion: Evidence from Nontargeted Tissue Metabolomics in a Rabbit Model

    Li-Hua Zou

    2016-01-01

    Conclusions: The present study applied metabolomics analysis to identify the cerebral metabolic profiling in rabbits with ASCP, and the results may shed new lights that cerebral metabolism is better preserved by ASCP compared with DHCA alone.

  10. Fluorescent profiling of modular biosynthetic enzymes by complementary metabolic and activity based probes.

    Meier, Jordan L; Mercer, Andrew C; Burkart, Michael D

    2008-04-23

    The study of the enzymes responsible for natural product biosynthesis has proven a valuable source of new enzymatic activities and been applied to a number of biotechnology applications. Protein profiling could prove highly complementary to genetics based approaches by allowing us to understand the activity, transcriptional control, and post-translational modification of these enzymes in their native and dynamic proteomic environments. Here we present a method for the fluorescent profiling of PKS, NRPS, and FAS multidomain modular synthases in their whole proteomes using complementary metabolic and activity based probes. After first examining the reactivity of these activity based probes with a variety of purified recombinant PKS, NRPS, and FAS enzymes in vitro, we apply this duel labeling strategy to the analysis of modular synthases in a human breast cancer cell line and two strains of the natural product producer Bacillus subtilis. Collectively, these studies demonstrate that complementary protein profiling approaches can prove highly useful in the identification and assignment of inhibitor specificity and domain structure of these modular biosynthetic enzymes. PMID:18376827

  11. Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions.

    Klevenhusen, Fenja; Humer, Elke; Metzler-Zebeli, Barbara; Podstatzky-Lichtenstein, Leopold; Wittek, Thomas; Zebeli, Qendrim

    2015-01-01

    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. PMID:26479481

  12. Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions

    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.

  13. Effect of Calcium-vitamin D Supplementation on Metabolic Profiles in Pregnant Women at Risk for Pre-eclampsia: A Randomized Placebo-controlled Trial

    Sima-Sadat Sabihi; Hassan Khorammian; Zahra Heidarzadeh; Zohreh Tabassi; Zatollah Asemi; Mansooreh Samimi

    2012-01-01

    Increased metabolic profiles during pregnancy are associated with an increased risk of maternal and neonatal morbidity and remain a significant medical challenge. To our knowledge, no reports are available indicating the effects of calcium-vitamin D supplementation on metabolic profiles among pregnant women at risk for pre-eclampsia. This study was designed to determine the effects of consumption calcium-vitamin D supplements on metabolic profiles among Iranian pregnant women at risk for pre-...

  14. Metabolic and endocrine profiles and reproductive parameters in dairy cows under grazing conditions: effect of polymorphisms in somatotropic axis genes

    Pereira Isabel; Ramos Juan; Carriquiry Mariana; Ruprechter Gretel; Ana Meikle

    2011-01-01

    Abstract Background The present study hypothesized that GH-AluI and IGF-I-SnabI polymorphisms do change the metabolic/endocrine profiles in Holstein cows during the transition period, which in turn are associated with productive and reproductive parameters. Methods Holstein cows (Farm 1, primiparous cows, n = 110, and Farm 2, multiparous cows, n = 76) under grazing conditions were selected and GH and IGF-I genotypes were determined. Blood samples for metabolic/endocrine determinations were ta...

  15. Metabolic Profiling of Chicken Embryos Exposed to Perfluorooctanoic Acid (PFOA) and Agonists to Peroxisome Proliferator-Activated Receptors

    Mattsson, Anna; Kärrman, Anna; Pinto, Rui; Brunström, Björn

    2015-01-01

    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 ex...

  16. Effect of age on 6-mercaptopurine metabolic profile during the maintenance phase in children with acute lymphoblastic leukaemia

    DZHANGt; AGILBER; KYAKOUBEN; YMEDARD; EVILMER; EJACQZ-AIGRAIN

    2004-01-01

    INTRODUCTION: 6-Mercaptopurine (6-MP) is a thiopurine analogue administered for the treatment of acute lymphoblastic leukaemia (ALL). It is an inactive pro-drug that undergoes extensive metabolism resulting in the formation of active metabolites 6-thioguanine nucleotides (6-TGN) and inactive 6-mercaptopurine methylated metabolites (6-MMP) under the genetic control of the enzyme thiopurine methyltransferase (TPMT). 6-MP metabolic profile (6-MMP/6-TGN) was proposed as a tool to

  17. Metabolic Profiling of Chicken Embryos Exposed to Perfluorooctanoic Acid (PFOA) and Agonists to Peroxisome Proliferator-Activated Receptors

    Mattsson, Anna; Kärrman, Anna; Pinto, Rui; Brunström, Björn

    2015-01-01

    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 profile resulting

  18. Metabolic Profiling of Chicken Embryos Exposed to Perfluorooctanoic Acid (PFOA) and Agonists to Peroxisome Proliferator-Activated Receptors.

    Mattsson, Anna; Kärrman, Anna; Pinto, Rui; Brunström, Björn

    2015-01-01

    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 profile resulting

  19. Metabolic Profiling of Chicken Embryos Exposed to Perfluorooctanoic Acid (PFOA and Agonists to Peroxisome Proliferator-Activated Receptors.

    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

  20. Hypoadiponectinemia in overweight children contributes to a negative metabolic risk profile 6 years later

    Kynde, Iben; Heitmann, Berit L; Bygbjerg, Ib C;

    2009-01-01

    follow-up data 6 years later (n = 169). Cardiometabolic risk profile was calculated using a continuous composite score derived from summing of 6 factors standardized to the sample means (Z scores): body mass index, homeostasis model assessment of insulin resistance, total serum cholesterol to serum high......Prognostic biomarkers are needed to identify children at increased cardiometabolic risk. The objective was to study whether markers of metabolism and inflammation, for example, circulating plasma adiponectin, leptin, interleukin-8, and hepatocyte growth factor, are associated with cardiometabolic......-density lipoprotein cholesterol ratio, serum triglycerides, systolic blood pressure, and the reciprocal value of fitness (maximum watts per kilogram). Overweight was defined using international classification of body mass index cutoff points for children. Plasma adiponectin, leptin, interleukin-8, and hepatocyte...

  1. Integrative Phosphoproteomics Links IL-23R Signaling with Metabolic Adaptation in Lymphocytes.

    Lochmatter, Corinne; Fischer, Roman; Charles, Philip D; Yu, Zhanru; Powrie, Fiona; Kessler, Benedikt M

    2016-01-01

    Interleukin (IL)-23 mediated signal transduction represents a major molecular mechanism underlying the pathology of inflammatory bowel disease, Crohn's disease and ulcerative colitis. In addition, emerging evidence supports the role of IL-23-driven Th17 cells in inflammation. Components of the IL-23 signaling pathway, such as IL-23R, JAK2 and STAT3, have been characterized, but elements unique to this network as compared to other interleukins have not been readily explored. In this study, we have undertaken an integrative phosphoproteomics approach to better characterise downstream signaling events. To this end, we performed and compared phosphopeptide and phosphoprotein enrichment methodologies after activation of T lymphocytes by IL-23. We demonstrate the complementary nature of the two phosphoenrichment approaches by maximizing the capture of phosphorylation events. A total of 8202 unique phosphopeptides, and 4317 unique proteins were identified, amongst which STAT3, PKM2, CDK6 and LASP-1 showed induction of specific phosphorylation not readily observed after IL-2 stimulation. Interestingly, quantitative analysis revealed predominant phosphorylation of pre-existing STAT3 nuclear subsets in addition to translocation of phosphorylated STAT3 within 30 min after IL-23 stimulation. After IL-23R activation, a small subset of PKM2 also translocates to the nucleus and may contribute to STAT3 phosphorylation, suggesting multiple cellular responses including metabolic adaptation. PMID:27080861

  2. Locomotor, cardiocirculatory and metabolic adaptations to training in Andalusian and Anglo-Arabian horses.

    Muñoz, A; Santisteban, R; Rubio, M D; Agüera, E I; Escribano, B M; Castejón, F M

    1999-02-01

    The effects of two training programmes in 20 Andalusian and 12 Anglo-Arabian horses were evaluated by an increasing intensity work test at velocities of 4, 5, 6, 7 and 8 m sec(-1). Heart rate was monitored and blood samples were drawn at rest and after each velocity to analyse packed cell volume, haemoglobin concentration, plasma lactate and potassium levels. Furthermore, the programmes were video-taped and stride length, duration and frequency, stance (restraint and propulsion), swing phase durations and stride vertical component were measured. The training protocol of the Andalusian horses produced significant decreases in the cardiovascular, haematological and metabolic responses to exercise. Locomotory training adaptation consisted of an increased stride frequency and a reduced stride length and vertical stride component. The last variable was the limiting factor of stride length both before and after training in the Andalusian horses. A different training protocol for show-jumping competition in Anglo-Arabian horses failed to show significant differences in the studied parameters to the work test, although an increase in stride length at velocities of over 6 m sec(-1) was observed. Stride vertical component did not have an effect on the physiological response to exercise, either before or after training. PMID:10088708

  3. Metabolic profile of dystrophic mdx mouse muscles analyzed with in vitro magnetic resonance spectroscopy (MRS).

    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. PMID:22673895

  4. Metabolic profiles in serum of mouse after chronic exposure to drinking water.

    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. PMID:21172972

  5. Evaluation of hyperandrogenemia and metabolic risk profile in women with postadolescent acne

    Leyla Baykal Selçuk

    2016-06-01

    Full Text Available Background and Design: Postadolescent acne is a disease with relapses frequently seen in women. Treatment is difficult. In our study, we aimed to investigate the clinical and biochemical characteristics of hyperandrogenism and the prevalence of metabolic disorders, such as metabolic syndrome (MS and dyslipidemia in women with postadolescent acne. Materials and Methods: This study was conducted on 50 women who attended our department with the complaint of postadolescent acne between July 2014 and December 2014. The presence of androgenetic alopecia (AGA, hirsutism, polycystic ovary syndrome (PCOS, MS, dyslipidemia, and obesity was evaluated. Results: Seborrhea was present in 56%, hirsutism in 40%, AGA in 26%, and PCOS in 24% of women with postadolescent acne. The prevalence of MS and dyslipidemia was 24% and 44%, respectively. The prevalence of MS was significantly higher in patients with AGA and hirsutism. There was no association of MS with menstrual irregularity and PCOS. There was no significant association of dyslipidemia with AGA, hirsutism, PCOS, and menstrual irregularity. Conclusion: Clinical symptoms of hyperandrogenism, such as hirsutism, AGA, and PCOS were more common in women with postadolescent acne but androgenic hormone profile abnormalities were minimal. As a result, postadolescent acne resistant to treatment may be considered as an early marker in the early diagnosis of PCOS in women to prevent the development of type 2 diabetes mellitus, MS and hypercholesterolemia.

  6. Hydrogen isotopic profile in the characterization of sugars. Influence of the metabolic pathway.

    Zhang, Ben-Li; Billault, Isabelle; Li, Xiaobao; Mabon, Françoise; Remaud, Gérald; Martin, Maryvonne L

    2002-03-13

    The site-specific natural hydrogen isotope ratios of plant metabolites determined by 2H nuclear magnetic resonance (SNIF-NMR method) can provide powerful criteria for inferring mechanistic and environmental effects on biosynthetic pathways. This work examines the potential of isotopic profiles for the main constituents of carbohydrates, glucose and fructose, to distinguish different photosynthetic pathways. An appropriate analytical strategy, involving three suitable isotopic probes, has been elaborated with a view to measuring simultaneously, in conditions devoid of isotopic perturbations, all (or nearly all) of the carbon-bound hydrogen isotope ratios. It is shown that the type of photosynthetic metabolism, either C3 (sugar beet, orange, and grape), C4 (maize and sugar cane), or CAM (pineapple), and the physiological status of the precursor plant exert strong influences on the deuterium distribution in the sugar molecules. Consequently, this isotopic fingerprint may be a rich source of information for the comparison of mechanisms in metabolic pathways. In addition, it can provide complementary criteria to ethanol as a probe for the origin of sugars. PMID:11879039

  7. Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts.

    Beckonert, Olaf; Keun, Hector C; Ebbels, Timothy M D; Bundy, Jacob; Holmes, Elaine; Lindon, John C; Nicholson, Jeremy K

    2007-01-01

    Metabolic profiling, metabolomic and metabonomic studies mainly involve the multicomponent analysis of biological fluids, tissue and cell extracts using NMR spectroscopy and/or mass spectrometry (MS). We summarize the main NMR spectroscopic applications in modern metabolic research, and provide detailed protocols for biofluid (urine, serum/plasma) and tissue sample collection and preparation, including the extraction of polar and lipophilic metabolites from tissues. 1H NMR spectroscopic techniques such as standard 1D spectroscopy, relaxation-edited, diffusion-edited and 2D J-resolved pulse sequences are widely used at the analysis stage to monitor different groups of metabolites and are described here. They are often followed by more detailed statistical analysis or additional 2D NMR analysis for biomarker discovery. The standard acquisition time per sample is 4-5 min for a simple 1D spectrum, and both preparation and analysis can be automated to allow application to high-throughput screening for clinical diagnostic and toxicological studies, as well as molecular phenotyping and functional genomics. PMID:18007604

  8. Residual feed intake and hematological and metabolic blood profiles of lle de France lambs

    Edson Ferraz Evaristo de Paula

    2013-11-01

    Full Text Available The objectives of this study were to estimate the phenotypic correlations of residual feed intake (RFI and gross feed efficiency (GFE with hematological and metabolic blood profiles of lambs and to determine the differences for these traits in animals of different RFI classes. Twenty Ile de France male lambs, 115±8 days of age and 31.3±4.1 kg of body weight (means ± SD, were individually housed and their dry matter intake was measured over 65 days. They were weighed every 13 days to determine the average daily weight gain and two blood samples were collected at the last two weighings (at 07h30 for analysis of blood variables. The animals were divided into two classes: negative RFI (most efficient: 0.5 SD above the mean; n=8. There were associations among RFI and the serum metabolic variables for albumin (rRFI = 0.74 and creatinine (rRFI = -0.45 and between GFE and serum albumin (rGFE = -0.70. Less efficient animals as measured by RFI had higher serum albumin and lower creatinine levels and showed a tendency to have a greater concentration of total plasma protein. Other serum biochemical parameters were not correlated with GFE and RFI, and no differences between RFI classes were found. There was a correlation between the percentage of eosinophils and RFI (rRFI = -0.65, and such more efficient animals had a higher proportion of these cells and a trend to have a lower percentage of monocytes. This study provided evidence indicating associations between RFI and protein metabolism, as reflected by the serum albumin and creatinine. The hematological findings suggest that RFI is related to susceptibility of lambs to stressand should provide a basis for further research in this regard.

  9. Expression Profile of Genes Related to Drug Metabolism in Human Brain Tumors.

    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.

  10. Proton magnetic resonance spectroscopy (MRS) of metastatic brain tumors. Variations of metabolic profile

    Spectroscopic imaging can be helpful for the noninvasive identification of parenchymal brain tumors. The objective of the present study was the characterization of the metabolic profile of intracranial metastases, based on proton magnetic resonance spectroscopy (MRS). One hundred and four metastatic brain tumors were evaluated by long-echo (TR, 2000 ms; TE, 136 ms) single-voxel volume-selected proton MRS. In 83 patients the tumor fraction within the MRS voxel constituted more than 50%. Compared to normal brain, the tumors showed statistically significant decreases of N-acetylaspartate (P<0.0001), creatine (P<0.0001), and the [NAA]/choline-containing compounds ratio (P<0.0001), increases of [Cho] (P<0.0001) and the mobile lipids/[Cr] ratio (P<0.0001) and the lactate/[Cr] ratio (P<0.05), and the more frequent presence of [Lip] (P<0.0001) and [Lac] (P<0.0001) resonances. However, the majority of these differences were lost when data for patients whose tumor fraction within the MRS voxel constituted less than 50% were analyzed separately. Determination of the predominant metabolite peak on the MR spectrum [NAA, Cho, Lip] permitted us to define three general metabolic patterns of brain metastases, which, showed statistically significant associations with the size of the neoplasm (P<0.001), type of its contrast enhancement (P<0.01), and the extent of perilesional edema (P<0.05). Proton MRS can define metabolically different subsets of metastatic brain tumors, and these characteristics should be taken into consideration during the differential diagnosis of parenchymal brain lesions. (author)

  11. Use of endometrial cytology and metabolic profiles for selection of embryo donor cows

    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.

  12. Profile and prevalence of aspirin resistance in patients with metabolic syndrome

    Zhaoping Liu; Yang Yu; Yuanjie Mao; Xinhua Wang; Jianzhong Wang; Yong Huo

    2008-01-01

    Objective Aspirin has been used extensively in primary and secondary prevention of cardiovascular disease,particularly for subjects at high risk such as metabolic syndrome.However,the responsiveness to aspirin treatment may vary among individuals.The present study was conducted to investigate the profile and prevalence of aspirin resistance in patients with metabolic syndrome.Methods In 221 consecutive patients,platelet aggregation induced by arachidonic acid (0.5mg/ml) was assessed after 10 days of aspirin treatment (200mg/d).Aspirin resistance was defined as mean optical platelet aggregation =20%.Results Aspirin resistance occurred in 39 patients (17.6%).Serum fibrinogen level was higher in patients with than in those without aspirin resistance (2.6_+0.4g/l vs 2.4±0.4g/L,P=0.017).The 2 groups,aspirin resistance group and no aspirin resistance group,did not differ significantly,with regard to gender,age,body mass index,waist-hip ratio,blood pressure level,serum cholesterol level and history of myocardial or cerebral infarction.Multivariate logistic regression analysis revealed that only serum fibrinogen level entered the model (odds ratio 2.973,p=0.023).Subgroup analysis further showed that aspirin resistance occurred more in male patients with myocardial infarction (50% vs14.5%,P=0.02) and in female patients with diastolic blood pressure=85mmHg (34% vs 15.5%,P=0.043).But after multifactor logistic regression,in women blood pressure=85mmHg was not a predictor any more.Conclusions In patients with metabolic syndrome,aspirin resistance is not uncommon,especially for men with history of myocardial infarction.Patients with aspirin resistance have an increased serum fibrinogen level.(J Geriatr Cardio12008;5:7-10)

  13. EnzDP: improved enzyme annotation for metabolic network reconstruction based on domain composition profiles.

    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 . PMID:26542446

  14. Metabolic Profile and Inflammatory Responses in Dairy Cows with Left Displaced Abomasum Kept under Small-Scaled Farm Conditions

    Klevenhusen, Fenja; Humer, Elke; Metzler-Zebeli, Barbara; Podstatzky-Lichtenstein, Leopold; Wittek, Thomas; Zebeli, Qendrim

    2015-01-01

    Simple Summary This research established an association between lactation number and milk production and metabolic and inflammatory responses in high-producing dairy cows affected by left abomasal displacement in small-scaled dairy farms. The study showed metabolic alterations, liver damage, and inflammation in the sick cows, which were further exacerbated with increasing lactation number and milk yield of the cows. Abstract 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 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. PMID:26479481

  15. In vivo NMR metabolic profiling of Fabrea salina reveals sequential defense mechanisms against ultraviolet radiation.

    Marangoni, Roberto; Paris, Debora; Melck, Dominique; Fulgentini, Lorenzo; Colombetti, Giuliano; Motta, Andrea

    2011-01-01

    Fabrea salina is a hypersaline ciliate that is known to be among the strongest ultraviolet (UV)-resistant microorganisms; however, the molecular mechanisms of this resistance are almost unknown. By means of in vivo NMR spectroscopy, we determined the metabolic profile of living F. salina cells exposed to visible light and to polychromatic UV-B + UV-A + Vis radiation for several different exposure times. We used unsupervised pattern-recognition analysis to compare these profiles and discovered some metabolites whose concentration changed specifically upon UV exposure and in a dose-dependent manner. This variation was interpreted in terms of a two-phase cell reaction involving at least two different pathways: an early response consisting of degradation processes, followed by a late response activating osmoprotection mechanisms. The first step alters the concentration of formate, acetate, and saturated fatty-acid metabolites, whereas the osmoprotection modifies the activity of betaine moieties and other functionally related metabolites. In the latter pathway, alanine, proline, and sugars suggest a possible incipient protein synthesis as defense and/or degeneration mechanisms. We conclude that NMR spectroscopy on in vivo cells is an optimal approach for investigating the effect of UV-induced stress on the whole metabolome of F. salina because it minimizes the invasiveness of the measurement. PMID:21190674

  16. Soy Germ Protein With or Without-Zn Improve Plasma Lipid Profile in Metabolic Syndrome Women

    SIWI PRAMATAMA MARS WIJAYANTI

    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.

  17. Metabolism

    ... also influenced by body composition — people with more muscle and less fat generally have higher BMRs. previous continue Things That Can Go Wrong With Metabolism Most of the time your metabolism works effectively ...

  18. Metabolism

    2008-01-01

    2008255 Serum adiponectin level declines in the elderly with metabolic syndrome.WU Xiaoyan(吴晓琰),et al.Dept Geriatr,Huashan Hosp,Fudan UnivShanghai200040.Chin J Geriatr2008;27(3):164-167.Objective To investigate the correlation between ser-um adiponectin level and metabolic syndrome in the elderly·Methods Sixty-one subjects with metabolic syndrome and140age matched subjects without metabolic

  19. Adaptation of chondrocytes to low oxygen tension: relationship between hypoxia and cellular metabolism.

    Rajpurohit, R; Koch, C J; Tao, Z; Teixeira, C M; Shapiro, I M

    1996-08-01

    In endochondral bone, the growth cartilage is the site of rapid growth. Since the vascular supply to the cartilage is limited, it is widely assumed that cells of the cartilage are hypoxic and that limitations in the oxygen supply regulate the energetic state of the maturing cells. In this report, we evaluate the effects of oxygen tension on chondrocyte energy metabolism, thiol status, and expression of transcription elements, HIF and AP-1. Imposition of an hypoxic environment on cultured chondrocytes caused a proportional increase in glucose utilization and elevated levels of lactate synthesis. Although we observed a statistical increase in the activities of phosphofructokinase, pyruvate kinase, lactate dehydrogenase, and creatine kinase after exposure to lowered oxygen concentrations, the effect was small. The cultured cells exhibited a decreased utilization of glutamine, possibly due to down regulation of mitochondrial function and inhibition of oxidative deamination. With respect to total energy generation, we noted that these cells are quite capable of maintaining the energy charge of the cell at low oxygen tensions. Indeed, no changes in the absolute quantity of adenine nucleotides or the energy charge ratio was observed. Hypoxia caused a decrease in the glutathione content of cultured chondrocytes and a concomitant rise in cell and medium cysteine levels. It is likely that the fall in cell glutathione level is due to decreased synthesis of the tripeptide under reduced oxygen stress and the limited supply of glutamate. The observed rise in cellular and medium cysteine levels probably reflects an increase in the rate of degradation of glutathione and a decrease in synthesis of the peptide. To explore how cells transduce these metabolic effects, gel retardation assays were used to study chondrocyte HIF and AP-1 binding activities. Chondrocyte nuclear preparations bound an HIF-oligonucleotide; however, at low oxygen tensions, no increase in HIF binding was

  20. The correlation of sodium and potassium metabolism with the level of energy consumption in man during adaptation to heat

    Afanasyev, B. G.; Zhestovskiy, V. A.

    1978-01-01

    The sodium and potassium metabolism was studied in a thermal chamber at 35 deg and 80 percent relative humidity in 8 men for a period of 6 days. The control group (3 subjects) were outside of the chamber at a comfortable ambient temperature. The intracellular sodium and potassium metabolism were assessed based on their content in the erythrocytes. The finding was that during adaptation to heat, a considerable amount of sodium was excreted by the body in the sweat and urine (about 1/3 of the sodium content of the human body) as compared with its intake and the amount of potassium retained in the body. Changes in the concentration of sodium and potassium may serve as indexes of the state of adaptation processes during constant exposure to heat.

  1. Interactive effects of age and multi-gene profile on motor learning and sensorimotor adaptation.

    Noohi, Fatemeh; Boyden, Nate B; Kwak, Youngbin; Humfleet, Jennifer; Müller, Martijn L T M; Bohnen, Nicolaas I; Seidler, Rachael D

    2016-04-01

    The interactive association of age and dopaminergic polymorphisms on cognitive function has been studied extensively. However, there is limited research on whether age interacts with the association between genetic polymorphisms and motor learning. We examined a group of young and older adults' performance in three motor tasks: explicit sequence learning, visuomotor adaptation, and grooved pegboard. We assessed whether individuals' motor learning and performance were associated with their age and genotypes. We selected three genetic polymorphisms: Catechol-O-Methyl Transferase (COMT val158met) and Dopamine D2 Receptor (DRD2 G>T), which are involved with dopaminergic regulation, and Brain Derived Neurotrophic Factor (BDNF val66met) that modulates neuroplasticity and has been shown to interact with dopaminergic genes. Although the underlying mechanisms of the function of these three genotypes are different, the high performance alleles of each have been linked to better learning and performance. We created a composite polygene score based on the Number of High Performance Alleles (NHPA) that each individual carried. We found several associations between genetic profile, motor performance, and sensorimotor adaptation. More importantly, we found that this association varies with age, task type, and engagement of implicit versus explicit learning processes. PMID:26926580

  2. Elevated dopamine concentration in light-adapted zebrafish retinas is correlated with increased dopamine synthesis and metabolism.

    Connaughton, Victoria P; Wetzell, Bradley; Arneson, Lynne S; DeLucia, Vittoria; Riley, Anthony L

    2015-10-01

    Probing zebrafish (Danio rerio) retinal cryostat sections, collected either 8 h into the light or dark cycle, with an antibody against tyrosine hydroxylase (TH) identified a single population of immunopositive cells in the inner retina. However, the observed labeling patterns were not identical in both sets of tissues - label intensity was brighter in light-adapted tissue. This difference was quantified by probing western blots of retinal homogenates with the same TH antibody, which showed that TH expression increased by 42% in light-adapted tissue. High-performance liquid chromatography with electrochemical detection revealed that the concentrations of both dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) are also elevated in light-adapted zebrafish retinal tissue. Dopamine levels increased by 14% and DOPAC levels increased by 25% when measured in retinal homogenates harvested during the light cycle. These results indicate that dopamine levels in zebrafish retina are significantly increased in light-adapted tissue. The increase in dopamine content is correlated with an increase in both TH and DOPAC, suggesting that changes in dopamine concentration are due to light-adaptive changes in the synthesis, release and metabolism of dopamine. Dopamine concentration is elevated in lighted-adapted zebrafish retinas. This increase is correlated with an increase in both tyrosine hydroxylase (TH) and DOPAC (3,4-dihydroxyphenylacetic acid), suggesting that changes in dopamine concentration are due to light-adaptive changes in the synthesis, release and metabolism of dopamine. This is applicable to studies examining retinal mutants, the role of dopamine in disease or visual system development. PMID:26212704

  3. {sup 1}H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    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.

  4. 1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    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 1H 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.

  5. Exploring the molecular and metabolic factors contributing to the adaptation of maize seedlings to nitrate limitation

    Ashraf eEl-Kereamy

    2011-09-01

    Full Text Available Crop production on soils containing sub-optimal levels of nitrogen (N severely compromises yield potential. The development of plant varieties displaying high N use efficiency (NUE will optimize N fertilizer use and reduce the environmental damage caused by excess N application. Maize is one of the most important crops cultivated worldwide. Identification of the genotypes with an enhanced NUE in the field is both time and resource consuming and sometime is difficult due to the regulation in the biotechnology programs. Identification of traits associated with adaptation to N limitation at an early vegetative stage which could reflect NUE at maturity is in need. We developed a hydroponic growth system and used it to test two genotypes that were different in their NUE at maturity under N limitation. One genotype SRG-200 showed a higher NUE than the other genotype SRG-100 and we used its hybrid SRG-150 as a reference for NUE. A number of phenotypic, molecular and metabolic factors were tested using these three genetic lines at an early vegetative stage to determine which of these could be more indicative of predicting improved NUE at an early seedling stage. These include a transcriptional analysis which showed that the higher NUE in SRG-200 genotype is associated with higher transcript levels for the genes involved in nitrate transport, N assimilation and GS and that the SRG-200 genotype maintained higher sugar content in leaves. Those identified in this study could be useful indicators for selecting promising maize lines at early stages to help develop elite varieties showing an enhanced NUE.

  6. Metabolic adaptation of Ralstonia solanacearum during plant infection: a methionine biosynthesis case study.

    Laure Plener

    Full Text Available MetE and MetH are two distinct enzymes that catalyze a similar biochemical reaction during the last step of methionine biosynthesis, MetH being a cobalamin-dependent enzyme whereas MetE activity is cobalamin-independent. In this work, we show that the last step of methionine synthesis in the plant pathogen Ralstonia solanacearum is under the transcriptional control of the master pathogenicity regulator HrpG. This control is exerted essentially on metE expression through the intermediate regulator MetR. Expression of metE is strongly and specifically induced in the presence of plant cells in a hrpG- and metR-dependent manner. metE and metR mutants are not auxotrophic for methionine and not affected for growth inside the plant but produce significantly reduced disease symptoms on tomato whereas disruption of metH has no impact on pathogenicity. The finding that the pathogen preferentially induces metE expression rather than metH in the presence of plant cells is indicative of a probable metabolic adaptation to physiological host conditions since this induction of metE occurs in an environment in which cobalamin, the required co-factor for MetH, is absent. It also shows that MetE and MetH are not functionally redundant and are deployed during specific stages of the bacteria lifecycle, the expression of metE and metH being controlled by multiple and distinct signals.

  7. Comparative genome analysis reveals metabolic versatility and environmental adaptations of Sulfobacillus thermosulfidooxidans strain ST.

    Xue Guo

    Full Text Available The genus Sulfobacillus is a cohort of mildly thermophilic or thermotolerant acidophiles within the phylum Firmicutes and requires extremely acidic environments and hypersalinity for optimal growth. However, our understanding of them is still preliminary partly because few genome sequences are available. Here, the draft genome of Sulfobacillus thermosulfidooxidans strain ST was deciphered to obtain a comprehensive insight into the genetic content and to understand the cellular mechanisms necessary for its survival. Furthermore, the expressions of key genes related with iron and sulfur oxidation were verified by semi-quantitative RT-PCR analysis. The draft genome sequence of Sulfobacillus thermosulfidooxidans strain ST, which encodes 3225 predicted coding genes on a total length of 3,333,554 bp and a 48.35% G+C, revealed the high degree of heterogeneity with other Sulfobacillus species. The presence of numerous transposases, genomic islands and complete CRISPR/Cas defence systems testifies to its dynamic evolution consistent with the genome heterogeneity. As expected, S. thermosulfidooxidans encodes a suit of conserved enzymes required for the oxidation of inorganic sulfur compounds (ISCs. The model of sulfur oxidation in S. thermosulfidooxidans was proposed, which showed some different characteristics from the sulfur oxidation of Gram-negative A. ferrooxidans. Sulfur oxygenase reductase and heterodisulfide reductase were suggested to play important roles in the sulfur oxidation. Although the iron oxidation ability was observed, some key proteins cannot be identified in S. thermosulfidooxidans. Unexpectedly, a predicted sulfocyanin is proposed to transfer electrons in the iron oxidation. Furthermore, its carbon metabolism is rather flexible, can perform the transformation of pentose through the oxidative and non-oxidative pentose phosphate pathways and has the ability to take up small organic compounds. It encodes a multitude of heavy metal

  8. Perilipin 5 is dispensable for normal substrate metabolism and in the adaptation of skeletal muscle to exercise training.

    Mohktar, Ruzaidi A M; Montgomery, Magda K; Murphy, Robyn M; Watt, Matthew J

    2016-07-01

    Cytoplasmic lipid droplets provide a reservoir for triglyceride storage and are a central hub for fatty acid trafficking in cells. The protein perilipin 5 (PLIN5) is highly expressed in oxidative tissues such as skeletal muscle and regulates lipid metabolism by coordinating the trafficking and the reversible interactions of effector proteins at the lipid droplet. PLIN5 may also regulate mitochondrial function, although this remains unsubstantiated. Hence, the aims of this study were to examine the role of PLIN5 in the regulation of skeletal muscle substrate metabolism during acute exercise and to determine whether PLIN5 is required for the metabolic adaptations and enhancement in exercise tolerance following endurance exercise training. Using muscle-specific Plin5 knockout mice (Plin5(MKO)), we show that PLIN5 is dispensable for normal substrate metabolism during exercise, as reflected by levels of blood metabolites and rates of glycogen and triglyceride depletion that were indistinguishable from control (lox/lox) mice. Plin5(MKO) mice exhibited a functional impairment in their response to endurance exercise training, as reflected by reduced maximal running capacity (20%) and reduced time to fatigue during prolonged submaximal exercise (15%). The reduction in exercise performance was not accompanied by alterations in carbohydrate and fatty acid metabolism during submaximal exercise. Similarly, mitochondrial capacity (mtDNA, respiratory complex proteins, citrate synthase activity) and mitochondrial function (oxygen consumption rate in muscle fiber bundles) were not different between lox/lox and Plin5(MKO) mice. Thus, PLIN5 is dispensable for normal substrate metabolism during exercise and is not required to promote mitochondrial biogenesis or enhance the cellular adaptations to endurance exercise training. PMID:27189934

  9. Metabolic Profiling and Antioxidant Assay of Metabolites from Three Radish Cultivars (Raphanus sativus).

    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

    2016-01-01

    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. Metabolic Profiling and Antioxidant Assay of Metabolites from Three Radish Cultivars (Raphanus sativus

    Chang Ha Park

    2016-01-01

    Full Text Available 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