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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. 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

  16. 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…

  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. 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.

  5. 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...

  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. 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

  10. [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

  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. 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

  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. 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.

  17. 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

  18. 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...

  19. 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...

  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. 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

  3. 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.

  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. 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)

  12. 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)

  13. 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

  14. 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

  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. 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...

  13. 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

  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. 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.

  16. 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

  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. 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.

  19. 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.

  20. 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

  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. 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.

  5. 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...

  6. 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...

  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. 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 ...

  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. 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...

  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. 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...

  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. 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.

  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. 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

  20. 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.

  1. 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

  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. 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

  4. 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

  5. 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.

  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. 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

  15. 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...

  16. 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...

  17. 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

  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. 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 ...

  20. 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.

  1. 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 ...

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  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. 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...

  12. 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

  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. 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....

  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. 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...

  11. 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...

  12. 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

  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. 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.

  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. 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.

  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. 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

  6. 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.

  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. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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...

  16. 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

  17. 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

  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. 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.

  2. 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

  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. 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...

  6. 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...

  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. 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.

  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. 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.

  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. 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

  19. 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.

  20. 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.

  1. 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.

  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. 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

  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. 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...

  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

    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.

  12. 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

  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 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...

  15. 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

  16. 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...

  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. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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)

  9. 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.

  10. 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)

  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. 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.

  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. 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

  20. 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

  1. 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.

  2. {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.

  3. 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.

  4. 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

  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. 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

  9. 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

  10. 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

  11. Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver

    Valproic acid (VPA) is used clinically to treat epilepsy, however it induces hepatotoxicity such as microvesicular steatosis. Acute hepatotoxicity of VPA has been well documented by biochemical studies and microarray analysis, but little is known about the chronic effects of VPA in the liver. In the present investigation, we profiled gene expression patterns in the mouse liver after subchronic treatment with VPA. VPA was administered orally at a dose of 100 mg/kg/day or 500 mg/kg/day to ICR mice, and the livers were obtained after 1, 2, or 4 weeks. The activities of serum liver enzymes did not change, whereas triglyceride concentration increased significantly. Microarray analysis revealed that 1325 genes of a set of 32,996 individual genes were VPA responsive when examined by two-way ANOVA (P 1.5). Consistent with our previous results obtained using an acute VPA exposure model (Lee et al., Toxicol Appl Pharmacol. 220:45-59, 2007), the most significantly over-represented biological terms for these genes included lipid, fatty acid, and steroid metabolism. Biological pathway analysis suggests that the genes responsible for increased biosynthesis of cholesterol and triglyceride, and for decreased fatty acid β-oxidation contribute to the abnormalities in lipid metabolism induced by subchronic VPA treatment. A comparison of the VPA-responsive genes in the acute and subchronic models extracted 15 commonly altered genes, such as Cyp4a14 and Adpn, which may have predictive power to distinguish the mode of action of hepatotoxicants. Our data provide a better understanding of the molecular mechanisms of VPA-induced hepatotoxicity and useful information to predict steatogenic hepatotoxicity

  12. Insights into the iron and sulfur energetic metabolism of Acidithiobacillus ferrooxidans by microarray transcriptome profiling

    R. Quatrini; C. Appia-Ayme; Y. Denis; J. Ratouchniak; F. Veloso; J. Valdes; C. Lefimil; S. Silver; F. Roberto; O. Orellana; F. Denizot; E. Jedlicki; D. Holmes; V. Bonnefoy

    2006-09-01

    Acidithiobacillus ferrooxidans is a well known acidophilic, chemolithoautotrophic, Gram negative, bacterium involved in bioleaching and acid mine drainage. In aerobic conditions, it gains energy mainly from the oxidation of ferrous iron and/or reduced sulfur compounds present in ores. After initial oxidation of the substrate, electrons from ferrous iron or sulfur enter respiratory chains and are transported through several redox proteins to oxygen. However, the oxidation of ferrous iron and reduced sulfur compounds has also to provide electrons for the reduction of NAD(P) that is subsequently required for many metabolic processes including CO2 fixation. To help to unravel the enzymatic pathways and the electron transfer chains involved in these processes, a genome-wide microarray transcript profiling analysis was carried out. Oligonucleotides corresponding to approximately 3000 genes of the A. ferrooxidans type strain ATCC23270 were spotted onto glass-slides and hybridized with cDNA retrotranscribed from RNA extracted from ferrous iron and sulfur grown cells. The genes which are preferentially transcribed in ferrous iron conditions and those preferentially transcribed in sulfur conditions were analyzed. The expression of a substantial number of these genes has been validated by real-time PCR, Northern blot hybridization and/or immunodetection analysis. Our results support and extend certain models of iron and sulfur oxidation and highlight previous observations regarding the possible presence of alternate electron pathways. Our findings also suggest ways in which iron and sulfur oxidation may be co-ordinately regulated. An accompanying paper (Appia-Ayme et al.) describes results pertaining to other metabolic functions.

  13. The mRNA expression profile of metabolic genes relative to MHC isoform pattern in human skeletal muscles

    Plomgaard, Peter; Penkowa, Milena; Leick, Lotte;

    2006-01-01

    The metabolic profile of rodent muscle is generally reflected in the myosin heavy chain (MHC) fiber-type composition. The present study was conducted to test the hypothesis that metabolic gene expression is not tightly coupled with MHC fiber-type composition for all genes in human skeletal muscle...... metabolism genes, which suggests that basal mRNA regulation of genes encoding mitochondrial proteins does not match the wide differences in mitochondrial content of these muscles....... of a broad range of metabolic genes. The triceps muscle had two- to fivefold higher MHC IIa, phosphofructokinase, and LDH A mRNA content and two- to fourfold lower MHC I, lipoprotein lipase, CD36, hormone-sensitive lipase, and LDH B and hexokinase II mRNA than vastus lateralis or soleus...

  14. Use of metabolic profiles in dairy cattle in tropical and subtropical countries on smallholder dairy farms.

    Whitaker, D A; Goodger, W J; Garcia, M; Perera, B M; Wittwer, F

    1999-01-27

    Metabolic profile testing has generally been used as part of a multidisciplinary approach for dairy herds in temperate climates. Our goal was to evaluate the effectiveness of the technique for identifying constraints on productivity in small herds in environments less favorable for milk production. Metabolites tested were chosen for stability in the sample after collection of blood, ease of analysis and practical knowledge of the meaning of the results. Blood levels of five different metabolites in low-producing dairy cows belonging to smallholders in tropical and subtropical environments were measured. The study involved 13 projects with 80 cows in each, carried out in six Latin American, six Asian, and one southern European countries. Data were also collected on feeding, body condition score (BCS) and weight change, parasitism, and reproduction. In Chile, Mexico, Paraguay, Philippines, Uruguay, and Venezuela, globulin levels were high in > 17% of cows sampled on each occasion. Globulin levels were also high in Turkey and Vietnam on one or more occasions. In Paraguay, 49% of cows had high globulin levels at two to three months after calving. These results suggest that inflammatory disease was present to a potentially important degree, although this was not always investigated and not always taken into account. In all countries except Mexico and Venezuela, high beta-hydroxybutyrate (BHB) levels before calving in many cows highlighted the presence of condition loss in late pregnancy, an important potential constraint on productivity and fertility. Fewer cows showed high BHB levels in lactation, whereas change in BCS and weight was more sensitive for measuring negative energy balance. Urea concentrations were low in only small numbers of cows suggesting that dietary protein shortages were not common. Albumin values were low mainly in cows where globulin values were high and, hence, did not generally provide additional information. The exception was in China where

  15. Use of metabolic profiles in dairy cattle in tropical and subtropical countries on smallholder dairy farms

    Metabolic profile testing has generally been used as part of a multi-disciplinary approach for dairy herds in temperate climates. Our goal was to evaluate the effectiveness of the technique for identifying constraints on productivity in small herds in environments less favourable for milk production. Metabolites tested were chosen for stability in the sample after collection of blood, ease of analysis and practical knowledge of the meaning of the results. Blood levels of five different metabolites in low producing dairy cows belonging to smallholders in tropical and subtropical environments were measured. The study involved 13 projects with 80 cows in each, carried out in six Latin American, six Asian and one southern European country. Data was also collected on feeding, body condition (BCS) and weight change, parasitism and reproduction. In Chile, Mexico, Paraguay, Philippines, Uruguay and Venezuela globulin levels were high in more than 17% of cows sampled on each occasion. Globulin levels were also high in Turkey and Viet Nam on one or more occasions. In Paraguay 49% of cows had high globulin levels at 2-3 months after calving. These results suggest that inflammatory disease was present to a potentially important degree, although this was not always investigated and not always taken into account. In all countries except Mexico and Venezuela high β-hydroxybutyrate (BHB) levels before calving in many cows highlighted the presence of condition loss in late pregnancy, an important potential constraint on productivity and fertility. Fewer cows showed high BHB levels in lactation where change in BCS and weight was more sensitive for measuring negative energy balance. Urea concentrations were only found to be low in small numbers of cows suggesting that dietary protein shortages were not common. Albumin values were low mainly in cows where globulin values were high and so did not generally provide additional information. The exception was in China where pregnant yaks

  16. Phylogeography, Salinity Adaptations and Metabolic Potential of the Candidate Division KB1 Bacteria Based on a Partial Single Cell Genome.

    Nigro, Lisa M; Hyde, Andrew S; MacGregor, Barbara J; Teske, Andreas

    2016-01-01

    Deep-sea hypersaline anoxic basins and other hypersaline environments contain abundant and diverse microbial life that has adapted to these extreme conditions. The bacterial Candidate Division KB1 represents one of several uncultured groups that have been consistently observed in hypersaline microbial diversity studies. Here we report the phylogeography of KB1, its phylogenetic relationships to Candidate Division OP1 Bacteria, and its potential metabolic and osmotic stress adaptations based on a partial single cell amplified genome of KB1 from Orca Basin, the largest hypersaline seafloor brine basin in the Gulf of Mexico. Our results are consistent with the hypothesis - previously developed based on (14)C incorporation experiments with mixed-species enrichments from Mediterranean seafloor brines - that KB1 has adapted its proteins to elevated intracellular salinity, but at the same time KB1 apparently imports glycine betaine; this compatible solute is potentially not limited to osmoregulation but could also serve as a carbon and energy source. PMID:27597842

  17. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH2-CH = O), L5 lipids (-CH2-C = O), and L3 lipids (-CH2-CH2-C = O) as well as lower levels of β-glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our research. These

  18. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing [181st Hospital Guangxi, Central Laboratory, Laboratory of Metabolic Diseases Research, Guangxi Province (China); Li, Liping [Guangxi Normal University, The Life Science College, Guangxi Province (China); Li, Wuxian [Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqiong Medical University, Chongqing (China); Dai, Yong [Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People' s Hospital), Shenzhen, Guangdong Province (China)

    2012-07-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH{sub 2}-CH = O), L5 lipids (-CH{sub 2}-C = O), and L3 lipids (-CH{sub 2}-CH{sub 2}-C = O) as well as lower levels of {beta}-glucose, {alpha}-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high

  19. Gene expression profiling in Entamoeba histolytica identifies key components in iron uptake and metabolism.

    Nora Adriana Hernández-Cuevas

    Full Text Available Entamoeba histolytica is an ameboid parasite that causes colonic dysentery and liver abscesses in humans. The parasite encounters dramatic changes in iron concentration during its invasion of the host, with relatively low levels in the intestinal lumen and then relatively high levels in the blood and liver. The liver notably contains sources of iron; therefore, the parasite's ability to use these sources might be relevant to its survival in the liver and thus the pathogenesis of liver abscesses. The objective of the present study was to identify factors involved in iron uptake, use and storage in E. histolytica. We compared the respective transcriptomes of E. histolytica trophozoites grown in normal medium (containing around 169 µM iron, low-iron medium (around 123 µM iron, iron-deficient medium (around 91 µM iron, and iron-deficient medium replenished with hemoglobin. The differentially expressed genes included those coding for the ATP-binding cassette transporters and major facilitator transporters (which share homology with bacterial siderophores and heme transporters and genes involved in heme biosynthesis and degradation. Iron deficiency was associated with increased transcription of genes encoding a subset of cell signaling molecules, some of which have previously been linked to adaptation to the intestinal environment and virulence. The present study is the first to have assessed the transcriptome of E. histolytica grown under various iron concentrations. Our results provide insights into the pathways involved in iron uptake and metabolism in this parasite.

  20. Dose-dependent effects of dietary zinc oxide on bacterial communities and metabolic profiles in the ileum of weaned pigs.

    Pieper, R; Vahjen, W; Neumann, K; Van Kessel, A G; Zentek, J

    2012-10-01

    Pharmacological levels of zinc oxide (ZnO) can improve the health of weaning piglets and influence the intestinal microbiota. This experiment aimed at studying the dose-response effect of five dietary concentrations of ZnO on small intestinal bacteria and metabolite profiles. Fifteen piglets, weaned at 25 ± 1 days of age, were allocated into five groups according to body weight and litter. Diets were formulated to contain 50 (basal diet), 150, 250, 1000 and 2500 mg zinc/kg by adding analytical-grade (>98% purity) ZnO to the basal diet and fed ad libitum for 14 days after a 7-day adaptation period on the basal diet. Ileal bacterial community profiles were analysed by denaturing gradient gel electrophoresis and selected bacterial groups quantified by real-time PCR. Concentrations of ileal volatile fatty acids (VFA), D- and L-lactate and ammonia were determined. Species richness, Shannon diversity and evenness were significantly higher at high ZnO levels. Quantitative PCR revealed lowest total bacterial counts in the 50 mg/kg group. Increasing ZnO levels led to an increase (p = 0.017) in enterobacteria from log 4.0 cfu/g digesta (50 mg/kg) to log 6.7 cfu/g digesta (2500 mg/kg). Lactic acid bacteria were not influenced (p = 0.687) and clostridial cluster XIVa declined (p = 0.035) at highest ZnO level. Concentration of total, D- and L-lactate and propionate was not affected (p = 0.736, p = 0.290 and p = 0.630), but concentrations of ileal total VFA, acetate and butyrate increased markedly from 50 to 150 mg/kg and decreased with further increasing zinc levels and reached low levels again at 2500 mg/kg (p = 0.048, p = 0.048 and p = 0.097). Ammonia decreased (p < 0.006) with increasing dietary ZnO level. In conclusion, increasing levels of dietary ZnO had strong and dose-dependent effects on ileal bacterial community composition and activity, suggesting taxonomic variation in metabolic response to ZnO. PMID:21929727

  1. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B.

    2015-01-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. PMID:26407887

  2. Metabolic adaptations of Azospirillum brasilense to oxygen stress by cell-to-cell clumping and flocculation.

    Bible, Amber N; Khalsa-Moyers, Gurusahai K; Mukherjee, Tanmoy; Green, Calvin S; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Hurst, Gregory B; Alexandre, Gladys

    2015-12-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. PMID:26407887

  3. INFLUENCE OF THE COMBINED ANTIHYPERTENSIVE THERAPY ON METABOLIC PROFILE AND CEREBRAL BLOOD FLOW IN PATIENTS WITH METABOLIC SYNDROME

    E. M. Idrisova; T. P. Kalashnikova; I. Yu. Efimova

    2016-01-01

    Aim. To study influence of the combined antihypertensive therapy on blood pressure (BP), glucose and lipid metabolism as well as cerebral blood flow in patients with metabolic syndrome (МS)Material and methods. 60 patients with MS aged of 35-65 y.o. were included in the study. 29 patients of the 1st group received verapamil SR (240 mg once daily) and indapamide retard (1,5 mg once daily). 31 patients of the 2nd group received verapamil SR (240 mg once daily) and enalapril (12,2±5,9 mg BID). A...

  4. Metabolic Profiling Directly from the Petri Dish Using Nanospray Desorption Electrospray Ionization Imaging Mass Spectrometry

    Watrous, Jeramie D.; Roach, Patrick J.; Heath, Brandi S.; Alexandrov, Theodore; Laskin, Julia; Dorrestein, Pieter C.

    2013-11-05

    Understanding molecular interaction pathways in complex biological systems constitutes a treasure trove of knowledge that might facilitate the specific, chemical manipulation of the countless microbiological systems that occur throughout our world. However, there is a lack of methodologies that allow the direct investigation of chemical gradients and interactions in living biological systems, in real time. Here, we report the use of nanospray desorption electrospray ionization (nanoDESI) imaging mass spectrometry for in vivo metabolic profiling of living bacterial colonies directly from the Petri dish with absolutely no sample preparation needed. Using this technique, we investigated single colonies of Shewanella oneidensis MR-1, Bacillus subtilis 3610, and Streptomyces coelicolor A3(2) as well as a mixed biofilm of S. oneidensis MR-1 and B. subtilis 3610. Data from B. subtilis 3610 and S. coelicolor A3(2) provided a means of validation for the method while data from S. oneidensis MR-1 and the mixed biofilm showed a wide range of compounds that this bacterium uses for the dissimilatory reduction of extracellular metal oxides, including riboflavin, iron-bound heme and heme biosynthetic intermediates, and the siderophore putrebactin.

  5. Metabolic profiling directly from the Petri dish using nanospray desorption electrospray ionization imaging mass spectrometry.

    Watrous, Jeramie; Roach, Patrick; Heath, Brandi; Alexandrov, Theodore; Laskin, Julia; Dorrestein, Pieter C

    2013-11-01

    Understanding molecular interaction pathways in complex biological systems constitutes a treasure trove of knowledge that might facilitate the specific, chemical manipulation of the countless microbiological systems that occur throughout our world. However, there is a lack of methodologies that allow the direct investigation of chemical gradients and interactions in living biological systems, in real time. Here, we report the use of nanospray desorption electrospray ionization (nanoDESI) imaging mass spectrometry for in vivo metabolic profiling of living bacterial colonies directly from the Petri dish with absolutely no sample preparation needed. Using this technique, we investigated single colonies of Shewanella oneidensis MR-1, Bacillus subtilis 3610, and Streptomyces coelicolor A3(2) as well as a mixed biofilm of S. oneidensis MR-1 and B. subtilis 3610. Data from B. subtilis 3610 and S. coelicolor A3(2) provided a means of validation for the method while data from S. oneidensis MR-1 and the mixed biofilm showed a wide range of compounds that this bacterium uses for the dissimilatory reduction of extracellular metal oxides, including riboflavin, iron-bound heme and heme biosynthetic intermediates, and the siderophore putrebactin. PMID:24047514

  6. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile

    Oskari Kilpeläinen, Tuomas; Zillikens, M Carola; Stančákova, Alena;

    2011-01-01

    Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14...... coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance....... genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and......Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14...

  7. Metabolic profiling of vitamin C deficiency in Gulo−/− mice using proton NMR spectroscopy

    Nutrient deficiencies are an ongoing problem in many populations and ascorbic acid is a key vitamin whose mild or acute absence leads to a number of conditions including the famously debilitating scurvy. As such, the biochemical effects of ascorbate deficiency merit ongoing scrutiny, and the Gulo knockout mouse provides a useful model for the metabolomic examination of vitamin C deficiency. Like humans, these animals are incapable of synthesizing ascorbic acid but with dietary supplements are otherwise healthy and grow normally. In this study, all vitamin C sources were removed after weaning from the diet of Gulo−/− mice (n = 7) and wild type controls (n = 7) for 12 weeks before collection of serum. A replicate study was performed with similar parameters but animals were harvested pre-symptomatically after 2–3 weeks. The serum concentration of 50 metabolites was determined by quantitative profiling of 1D proton NMR spectra. Multivariate statistical models were used to describe metabolic changes as compared to control animals; replicate study animals were used for external validation of the resulting models. The results of the study highlight the metabolites and pathways known to require ascorbate for proper flux.

  8. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.

    Kilpeläinen, Tuomas O; Zillikens, M Carola; Stančákova, Alena; Finucane, Francis M; Ried, Janina S; Langenberg, Claudia; Zhang, Weihua; Beckmann, Jacques S; Luan, Jian'an; Vandenput, Liesbeth; Styrkarsdottir, Unnur; Zhou, Yanhua; Smith, Albert Vernon; Zhao, Jing-Hua; Amin, Najaf; Vedantam, Sailaja; Shin, So-Youn; Haritunians, Talin; Fu, Mao; Feitosa, Mary F; Kumari, Meena; Halldorsson, Bjarni V; Tikkanen, Emmi; Mangino, Massimo; Hayward, Caroline; Song, Ci; Arnold, Alice M; Aulchenko, Yurii S; Oostra, Ben A; Campbell, Harry; Cupples, L Adrienne; Davis, Kathryn E; Döring, Angela; Eiriksdottir, Gudny; Estrada, Karol; Fernández-Real, José Manuel; Garcia, Melissa; Gieger, Christian; Glazer, Nicole L; Guiducci, Candace; Hofman, Albert; Humphries, Steve E; Isomaa, Bo; Jacobs, Leonie C; Jula, Antti; Karasik, David; Karlsson, Magnus K; Khaw, Kay-Tee; Kim, Lauren J; Kivimäki, Mika; Klopp, Norman; Kühnel, Brigitte; Kuusisto, Johanna; Liu, Yongmei; Ljunggren, Osten; Lorentzon, Mattias; Luben, Robert N; McKnight, Barbara; Mellström, Dan; Mitchell, Braxton D; Mooser, Vincent; Moreno, José Maria; Männistö, Satu; O'Connell, Jeffery R; Pascoe, Laura; Peltonen, Leena; Peral, Belén; Perola, Markus; Psaty, Bruce M; Salomaa, Veikko; Savage, David B; Semple, Robert K; Skaric-Juric, Tatjana; Sigurdsson, Gunnar; Song, Kijoung S; Spector, Timothy D; Syvänen, Ann-Christine; Talmud, Philippa J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Uitterlinden, André G; van Duijn, Cornelia M; Vidal-Puig, Antonio; Wild, Sarah H; Wright, Alan F; Clegg, Deborah J; Schadt, Eric; Wilson, James F; Rudan, Igor; Ripatti, Samuli; Borecki, Ingrid B; Shuldiner, Alan R; Ingelsson, Erik; Jansson, John-Olov; Kaplan, Robert C; Gudnason, Vilmundur; Harris, Tamara B; Groop, Leif; Kiel, Douglas P; Rivadeneira, Fernando; Walker, Mark; Barroso, Inês; Vollenweider, Peter; Waeber, Gérard; Chambers, John C; Kooner, Jaspal S; Soranzo, Nicole; Hirschhorn, Joel N; Stefansson, Kari; Wichmann, H-Erich; Ohlsson, Claes; O'Rahilly, Stephen; Wareham, Nicholas J; Speliotes, Elizabeth K; Fox, Caroline S; Laakso, Markku; Loos, Ruth J F

    2011-08-01

    Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance. PMID:21706003

  9. 1H NMR based metabolic profiling in the evaluation of Japanese green tea quality.

    Tarachiwin, Lucksanaporn; Ute, Koichi; Kobayashi, Akio; Fukusaki, Eiichiro

    2007-11-14

    Classification of tea quality is now mainly performed according to the sensory results by professional tea tasters. However, this evaluation method is inconsistent in differentiating their qualities. A combination of a (1)H NMR technique and a multivariate analysis was introduced to the quality evaluation of green tea by means of a metabolomic technique. A broad range of metabolites were detected by (1)H NMR spectrometry. The principal component analysis (PCA) was used to reduce the complexity of the (1)H NMR spectra data set and provided the quality discrimination result. It offered an extensive clue for classification and quality assessment without any prepurification method. A set of green teas from a Japanese tea contest were analyzed by (1)H NMR to classify the quality with respect to that judged by tea tasters and to conceive a quality prediction model. Metabolic profiling and fingerprinting of (1)H NMR spectra of green teas with different quality were studied. PCA showed a separation between the high- and the low-quality green teas. The taste marker compounds contributing to the discrimination of tea quality were identified. Reliable prediction models were obtained by the partial least-squares projection to latent structure (PLS) analysis together with a preprocessing filter of both orthogonal signal correction (OSC) and a combination between OSC and wavelet transform algorithms. PMID:17944534

  10. Metabolic profiling of vitamin C deficiency in Gulo-/- mice using proton NMR spectroscopy

    Duggan, Gavin E. [University of Calgary, Biochemistry Research Group, Department of Biological Sciences (Canada); Joan Miller, B.; Jirik, Frank R. [University of Calgary, Department of Biochemistry and Molecular Biology, The McCaig Institute for Bone and Joint Health (Canada); Vogel, Hans J., E-mail: vogel@ucalgary.ca [University of Calgary, Biochemistry Research Group, Department of Biological Sciences (Canada)

    2011-04-15

    Nutrient deficiencies are an ongoing problem in many populations and ascorbic acid is a key vitamin whose mild or acute absence leads to a number of conditions including the famously debilitating scurvy. As such, the biochemical effects of ascorbate deficiency merit ongoing scrutiny, and the Gulo knockout mouse provides a useful model for the metabolomic examination of vitamin C deficiency. Like humans, these animals are incapable of synthesizing ascorbic acid but with dietary supplements are otherwise healthy and grow normally. In this study, all vitamin C sources were removed after weaning from the diet of Gulo-/- mice (n = 7) and wild type controls (n = 7) for 12 weeks before collection of serum. A replicate study was performed with similar parameters but animals were harvested pre-symptomatically after 2-3 weeks. The serum concentration of 50 metabolites was determined by quantitative profiling of 1D proton NMR spectra. Multivariate statistical models were used to describe metabolic changes as compared to control animals; replicate study animals were used for external validation of the resulting models. The results of the study highlight the metabolites and pathways known to require ascorbate for proper flux.

  11. Metabolic profiling uncovers a phenotypic signature of small for gestational age in early pregnancy.

    Horgan, Richard P

    2012-01-31

    Being born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma samples from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.

  12. Second-generation antipsychotics in a tertiary care hospital: prescribing patterns, metabolic profiles, and drug interactions.

    Niedrig, David F; Gött, Carmen; Fischer, Anja; Müller, Sabrina T; Greil, Waldemar; Bucklar, Guido; Russmann, Stefan

    2016-01-01

    We carried out an observational study that analyzed population characteristics, metabolic profiles, potentially interacting pharmacotherapy, and related adverse events in second-generation antipsychotics (SGAs) users of a tertiary care hospital. Within our pharmacoepidemiological database derived from electronic medical records of 82,358 hospitalizations, we identified 1136 hospitalizations contributing 9165 patient-days with exposure to SGA. Blood pressure, blood glucose, lipids, and BMI had been documented in 97.7, 75.7, 24.6, and 77.4% of hospitalizations, respectively. Among these, the prevalence of hypertension, hyperglycemia, dyslipidemia, and BMI 30 kg/m or more was 36.9, 22.6, 61.1, and 23.1%, respectively. A total of 63.4, 70.8, and 37.1% of SGA users with hyperglycemia, dyslipidemia, and hypertension, respectively, received no pharmacotherapy for these conditions. We identified 614 patient-days with SGA plus formally contraindicated comedication and another 1066 patient-days with other high-risk combinations for QTc prolongation. Among those there was one case with associated neutropenia and four cases with abnormal QTc interval. However, specific monitoring for such adverse events was not documented in 45.5% of hospitalizations with contraindicated and 89.8% with high-risk QTc-prolonging combinations. Our study identified targets for improved monitoring and management in SGA users. These may be implemented as automated alerts into electronic prescribing systems and thereby efficiently support safer pharmacotherapy in clinical practice. PMID:26473524

  13. Effects of Regular Physical Exercises in the Water on the Metabolic Profile of Women with Abdominal Obesity

    Kasprzak Zbigniew

    2014-07-01

    Full Text Available Recreational physical exercise in the water is predominantly based on aerobic metabolism. Since it involves both carbohydrate and lipid sources of energy, aqua aerobics has a beneficial effect on metabolism of these substrates. The aim of the study was to assess the impact of a 3 month aqua aerobics training program on the metabolic profile of women with abdominal obesity. The study sample comprised 32 women aged 41-72 years. Somatic characteristics and variables characterizing carbohydrate and lipid metabolism were measured before the commencement and after the completion of the training program. During the 2nd measurement all mean anthropometric variables were found to be significantly lower (p<0.01. In the blood lipid profile, the concentrations of total cholesterol, LDL-cholesterol and HOMAIR were significantly lower (p<0.01. Furthermore, the levels of fasting triglycerides, glucose and insulin were reduced significantly (p<0.05 after the training program. The aqua aerobics program contributed to positive changes in lipid metabolism, anthropometric variables, as well as the fasting insulin, glucose levels and insulin resistance index in women with abdominal obesity.

  14. Urinary metabolic profile predicts high-fat diet sensitivity in the C57Bl6/J mouse.

    Fedry, Juliette; Blais, Anne; Even, Patrick C; Piedcoq, Julien; Fromentin, Gilles; Gaudichon, Claire; Azzout-Marniche, Dalila; Tomé, Daniel

    2016-05-01

    To prevent the development of adiposity-associated metabolic diseases, early biomarkers are needed. Such markers could bring insight to understand the complexity of susceptibility to obesity. Urine and plasma metabolomics fingerprints have been successfully associated with metabolic dysfunctions. Fat resistance (FR) was found to be associated with higher urinary levels of acylglycines and leucine. However, no differences were observed before the diet switch. In this context, we aimed at characterizing metabolic signatures predictive of resistance or sensitivity to fat in the C57Bl6/J mouse model. Urinary metabolic profiles of FR (n=15) and fat sensitivity (FS) mice (n=14) were performed on liquid chromatography-mass spectrometry. Urinary and plasma metabolic profiles were first collected at baseline (during low-fat diet), then after 10weeks of high-fat (HF) feeding. Mice were sorted a posteriori into FS and FR based on their final adiposity. After HF feeding for 10weeks, FS mice tended to have lower plasma levels of β-hydroxybutyrate than FR ones. Urinary metabolic profiles showed that baseline levels of octanoylglycine, leucine and valine were significantly lower in FS mice. Moreover, expressions in the adipose tissue of Baat and Glyat mRNA were lower in FS than in FR mice. In muscle, mRNA encoding CaD and UbE2b tended to be lower in FS mice than in FR mice (P=.056 and P=.071, respectively). The data show that lower levels of urinary octanoylglycine, leucine and valine are potential predictive biomarkers of FS and could be related to a lower stimulation in adipose acyl-coenzyme A conjugation to glycine and to muscle protein breakdown. PMID:27133427

  15. Cross-sectional and longitudinal comparisons of metabolic profiles between vegetarian and non-vegetarian subjects: a matched cohort study.

    Chiu, Yen-Feng; Hsu, Chih-Cheng; Chiu, Tina H T; Lee, Chun-Yi; Liu, Ting-Ting; Tsao, Chwen Keng; Chuang, Su-Chun; Hsiung, Chao A

    2015-10-28

    Several previous cross-sectional studies have shown that vegetarians have a better metabolic profile than non-vegetarians, suggesting that a vegetarian dietary pattern may help prevent chronic degenerative diseases. However, longitudinal studies on the impact of vegetarian diets on metabolic traits are scarce. We studied how several sub-types of vegetarian diets affect metabolic traits, including waist circumference, BMI, systolic blood pressure (SBP), diastolic blood pressure, fasting blood glucose, total cholesterol (TC), HDL, LDL, TAG and TC:HDL ratio, through both cross-sectional and longitudinal study designs. The study used the MJ Health Screening database, with data collected from 1994 to 2008 in Taiwan, which included 4415 lacto-ovo-vegetarians, 1855 lacto-vegetarians and 1913 vegans; each vegetarian was matched with five non-vegetarians based on age, sex and study site. In the longitudinal follow-up, each additional year of vegan diet lowered the risk of obesity by 7 % (95 % CI 0·88, 0·99), whereas each additional year of lacto-vegetarian diet lowered the risk of elevated SBP by 8 % (95 % CI 0·85, 0·99) and elevated glucose by 7 % (95 % CI 0·87, 0·99), and each additional year of ovo-lacto-vegetarian diet increased abnormal HDL by 7 % (95 % CI 1·03, 1·12), compared with non-vegetarians. In the cross-sectional comparisons, all sub-types of vegetarians had lower likelihoods of abnormalities compared with non-vegetarians on all metabolic traits (P<0·001 for all comparisons), except for HDL and TAG. The better metabolic profile in vegetarians is partially attributable to lower BMI. With proper management of TAG and HDL, along with caution about the intake of refined carbohydrates and fructose, a plant-based diet may benefit all aspects of the metabolic profile. PMID:26355190

  16. Elucidating the adaptation and temporal coordination of metabolic pathways using in-silico evolution

    Gottstein, W.; Müller, Stefan; Herzel, H.; Steuer, Ralf

    2014-01-01

    Roč. 117, mar (2014), s. 68-76. ISSN 0303-2647 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : evolutionary algorithms * flux-balance analysis * metabolic oscillations * metabolism * systems biology Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.548, year: 2014

  17. Pseudo-transition Analysis Identifies the Key Regulators of Dynamic Metabolic Adaptations from Steady-State Data.

    Gerosa, Luca; Haverkorn van Rijsewijk, Bart R B; Christodoulou, Dimitris; Kochanowski, Karl; Schmidt, Thomas S B; Noor, Elad; Sauer, Uwe

    2015-10-28

    Hundreds of molecular-level changes within central metabolism allow a cell to adapt to the changing environment. A primary challenge in cell physiology is to identify which of these molecular-level changes are active regulatory events. Here, we introduce pseudo-transition analysis, an approach that uses multiple steady-state observations of (13)C-resolved fluxes, metabolites, and transcripts to infer which regulatory events drive metabolic adaptations following environmental transitions. Pseudo-transition analysis recapitulates known biology and identifies an unexpectedly sparse, transition-dependent regulatory landscape: typically a handful of regulatory events drive adaptation between carbon sources, with transcription mainly regulating TCA cycle flux and reactants regulating EMP pathway flux. We verify these observations using time-resolved measurements of the diauxic shift, demonstrating that some dynamic transitions can be approximated as monotonic shifts between steady-state extremes. Overall, we show that pseudo-transition analysis can explore the vast regulatory landscape of dynamic transitions using relatively few steady-state data, thereby guiding time-consuming, hypothesis-driven molecular validations. PMID:27136056

  18. EXTREME METEOROLOGICAL CONDITIONS AND METABOLIC PROFILE IN HIGH YIELDING HOLSTEINFRIESIAN DAIRY COWS

    Z. GERGÁCZ

    2013-12-01

    Full Text Available The impact of two years (2002 and 2003 with different summer temperature extremes on variation in metabolic profile was analyzed in blood and urine samples taken from healthy, primiparous (n = 371 and multiparous (n = 795 high yielding Holstein-Friesian dairy cows. In this study main focus was lead on three most critical physiological phases, thus cows were assigned into three groups as follows: (1 dry cows for 10 days prior to calving; (2 cows 1-30 days after delivery, and (3 cows with more than 31 days post partum. Findings reveal clear response of the cows to heat in selected blood (hemoglobin, plasma aceto-acetic-acid, FFA, AST, glucose, urea and urine (pH, NABE and urea parameters. In the majority of cows, glucose and hemoglobin level, one of the most significant blood parameters, indicated symptoms of insufficient energy supply. Further metabolic indicators differed more or less from reference values depending on actual condition. Due to heat load dry matter intake has been decreased even by 10-15 per cent in primiparous cows. They were expected to increase body weight and size and simultaneously produce attain at large milk yields. In doing so that cows would have require large amount of nutrients. Out of parameters such as hemoglobin, glucose, FFA, AST and blood-urea differed from the reference values in most cases; however, this phenomenon seemed to be present in almost every case for hemoglobin and glucose. The lack of energy caused by heat stress can be contributed to the decrease of dry matter intake which has been indicated by the urea levels and pH both in blood and urine prevailing unfavorable and insufficient feeding practice. The results reconfirm the need to reconsider both the actual feeding practice (e.g. to increase of nutrient content in rations, reduce the intake of soluble proteins in rumen, pay attention of crude fiber in Total Mixed Rations (TMR, NDF and ADF, avoid overfeeding of inorganic buffers, to control moisture

  19. Metabolic product response profiles of Cherax quadricarinatus towards white spot syndrome virus infection.

    Fan, Weiwei; Ye, Yangfang; Chen, Zhen; Shao, Yina; Xie, Xiaolu; Zhang, Weiwei; Liu, Hai-Peng; Li, Chenghua

    2016-08-01

    White spot syndrome virus (WSSV) is one of the most devastating viral pathogens in both shrimp and crayfish farms, which often causes disease outbreak and leads to massive moralities with significant economic losses of aquaculture. However, limited research has been carried out on the intrinsic mechanisms toward WSSV challenge at the metabolic level. To gain comprehensive insight into metabolic responses induced by WSSV, we applied an NMR approach to investigate metabolic changes of crayfish gill and hepatopancreas infected by WSSV for 1, 6 and 12 h. In gill, an enhanced energy metabolism was observed in WSSV-challenged crayfish samples at 1 h, as marked by increased glucose, alanine, methionine, glutamate and uracil. Afterwards, energy metabolism, lipid metabolism as well as osmoregulation were markedly increased at 6 hpi, as shown by elevated glucose, alanine, methionine, fumarate, tyrosine, tryptophan, histidine, phosphorylcholine, betaine and uracil, whereas no obvious metabolites change was detected at 12 hpi. As for hepatopancreas, disturbed lipid metabolism and induced osmotic regulation was found at 6 hpi based on the metabolic biomarkers such as branched chain amino acids, threonine, alanine, methionine, glutamate, glutamine, tyrosine, phenylalanine, lactate and lipid. However, no obvious metabolic change was shown in hepatopancreas at both 1 hpi and 12 hpi. Taken together, our present results provided essential metabolic information about host-pathogen interactions in crayfish, which shed new light on our understanding of WSSV infection at metabolic level. PMID:27068762

  20. Metabolic Profiling of Dividing Cells in Live Rodent Brain by Proton Magnetic Resonance Spectroscopy (1HMRS) and LCModel Analysis

    Park, June-Hee; Lee, Hedok; Makaryus, Rany;

    2014-01-01

    RATIONALE: Dividing cells can be detected in the live brain by positron emission tomography or optical imaging. Here we apply proton magnetic resonance spectroscopy (1HMRS) and a widely used spectral fitting algorithm to characterize the effect of increased neurogenesis after electroconvulsive...... shock in the live rodent brain via spectral signatures representing mobile lipids resonating at ∼1.30 ppm. In addition, we also apply the same 1HMRS methodology to metabolically profile glioblastomas with actively dividing cells growing in RCAS-PDGF mice. METHODS: 1HMRS metabolic profiles were acquired...... on a 9.4T MRI instrument in combination with LCModel spectral analysis of: 1) rat brains before and after ECS or sham treatments and 2) RCAS-PDGF mice with glioblastomas and wild-type controls. Quantified 1HMRS data were compared to post-mortem histology. RESULTS: Dividing cells in the rat...

  1. (1)H-Nuclear Magnetic Resonance-Based Plasma Metabolic Profiling of Dairy Cows with Fatty Liver.

    Xu, Chuang; Sun, Ling-Wei; Xia, Cheng; Zhang, Hong-You; Zheng, Jia-San; Wang, Jun-Song

    2016-02-01

    Fatty liver is a common metabolic disorder of dairy cows during the transition period. Historically, the diagnosis of fatty liver has involved liver biopsy, biochemical or histological examination of liver specimens, and ultrasonographic imaging of the liver. However, more convenient and noninvasive methods would be beneficial for the diagnosis of fatty liver in dairy cows. The plasma metabolic profiles of dairy cows with fatty liver and normal (control) cows were investigated to identify new biomarkers using (1)H nuclear magnetic resonance. Compared with the control group, the primary differences in the fatty liver group included increases in β-hydroxybutyric acid, acetone, glycine, valine, trimethylamine-N-oxide, citrulline, and isobutyrate, and decreases in alanine, asparagine, glucose, γ-aminobutyric acid glycerol, and creatinine. This analysis revealed a global profile of endogenous metabolites, which may present potential biomarkers for the diagnosis of fatty liver in dairy cows. PMID:26732447

  2. Metabolic Symbiosis Enables Adaptive Resistance to Anti-angiogenic Therapy that Is Dependent on mTOR Signaling.

    Allen, Elizabeth; Miéville, Pascal; Warren, Carmen M; Saghafinia, Sadegh; Li, Leanne; Peng, Mei-Wen; Hanahan, Douglas

    2016-05-10

    Therapeutic targeting of tumor angiogenesis with VEGF inhibitors results in demonstrable, but transitory efficacy in certain human tumors and mouse models of cancer, limited by unconventional forms of adaptive/evasive resistance. In one such mouse model, potent angiogenesis inhibitors elicit compartmental reorganization of cancer cells around remaining blood vessels. The glucose and lactate transporters GLUT1 and MCT4 are induced in distal hypoxic cells in a HIF1α-dependent fashion, indicative of glycolysis. Tumor cells proximal to blood vessels instead express the lactate transporter MCT1, and p-S6, the latter reflecting mTOR signaling. Normoxic cancer cells import and metabolize lactate, resulting in upregulation of mTOR signaling via glutamine metabolism enhanced by lactate catabolism. Thus, metabolic symbiosis is established in the face of angiogenesis inhibition, whereby hypoxic cancer cells import glucose and export lactate, while normoxic cells import and catabolize lactate. mTOR signaling inhibition disrupts this metabolic symbiosis, associated with upregulation of the glucose transporter GLUT2. PMID:27134166

  3. Metabolic Profiling of a Corynebacterium Glutamicum DeltaprpD2 by GC-APCI High Resolution Q-TOF Analysis

    Zurek, G.; Persike, M.; Plassmeier, J.; Niehaus, K. (Kristian); Barsch, A.

    2011-01-01

    Metabolomics studies based on Gas chromatography–Mass spectrometry (GC-MS) are well established and typically employ electron impact (EI) ionisation. Target compounds of interest can be identified by comparison to commercial or public databases. Unfortunately, many possible biomarkers detected in metabolic profiling experiments cannot be identified due to the lack of reference spectra for a majority of biologically relevant compounds. Therefore, many possible biomarkers remain “unknowns” up t...

  4. Metabolic Profiling-based Data-mining for an Effective Chemical Combination to Induce Apoptosis of Cancer Cells

    Motofumi Kumazoe; Yoshinori Fujimura; Shiori Hidaka; Yoonhee Kim; Kanako Murayama; Mika Takai; Yuhui Huang; Shuya Yamashita; Motoki Murata; Daisuke Miura; Hiroyuki Wariishi; Mari Maeda-Yamamoto; Hirofumi Tachibana

    2015-01-01

    Green tea extract (GTE) induces apoptosis of cancer cells without adversely affecting normal cells. Several clinical trials reported that GTE was well tolerated and had potential anti-cancer efficacy. Epigallocatechin-3-O-gallate (EGCG) is the primary compound responsible for the anti-cancer effect of GTE; however, the effect of EGCG alone is limited. To identify GTE compounds capable of potentiating EGCG bioactivity, we performed metabolic profiling of 43 green tea cultivar panels by liquid ...

  5. Avocado Oil Supplementation Modifies Cardiovascular Risk Profile Markers in a Rat Model of Sucrose-Induced Metabolic Changes

    Octavio Carvajal-Zarrabal; Cirilo Nolasco-Hipolito; M. Guadalupe Aguilar-Uscanga; Guadalupe Melo-Santiesteban; Patricia M. Hayward-Jones; Barradas-Dermitz, Dulce M.

    2014-01-01

    The purpose of this study was to evaluate the effects of avocado oil administration on biochemical markers of cardiovascular risk profile in rats with metabolic changes induced by sucrose ingestion. Twenty-five rats were divided into five groups: a control group (CG; basic diet), a sick group (MC; basic diet plus 30% sucrose solution), and three other groups (MCao, MCac, and MCas; basic diet plus 30% sucrose solution plus olive oil and avocado oil extracted by centrifugation or using solvent,...

  6. Use of metabolic profiles and body condition scoring for the assessment of energy status of dairy cows

    Prodanović R.; Sladojević Ž.; Kirovski D.; Vujanac I.; Ivetić V.; Savić B.; Kureljušić B.; Stevančević M.

    2012-01-01

    The aim of this study was to assess the significance of body condition scoring and metabolic profile test for estimation of energy status of healthy high-yielding dairy cows. Twenty one healthy cows (primiparous and secundiparous) were divided into three groups: dry cows, early puerperal cows and early lactating cows. Cow’s energy status was estimated by the analysis of blood samples for beta-hydroxybutirate (BHBA) and glucose. Additionally, urea, total bil...

  7. Metabolic profiling of Rhodiola rosea rhizomes by 1H NMR spectroscopy

    Ioset, Karine Ndjoko; Nyberg, Nils T; Van Diermen, Daphne;

    2011-01-01

    Introduction - Rhodiola rosea is a broadly used medicinal plant with largely unexplored natural variability in secondary metabolite levels.Objective - The aim of this work was to develop a non-target procedure for (1)H NMR spectroscopic fingerprinting of rhizome extracts for pattern recognition...... demonstrated the usefulness of the established procedure for multivariate non-target (1)H NMR metabolic profiling of Rhodiola rosea. Copyright © 2010 John Wiley & Sons, Ltd....

  8. FGF21 as a Stress Hormone: The Roles of FGF21 in Stress Adaptation and the Treatment of Metabolic Diseases

    Kook Hwan Kim

    2014-08-01

    Full Text Available Fibroblast growth factor 21 (FGF21 is an endocrine hormone that is primarily expressed in the liver and exerts beneficial effects on obesity and related metabolic diseases. In addition to its remarkable pharmacologic actions, the physiological roles of FGF21 include the maintenance of energy homeostasis in the body in conditions of metabolic or environmental stress. The expression of FGF21 is induced in multiple organs in response to diverse physiological or pathological stressors, such as starvation, nutrient excess, autophagy deficiency, mitochondrial stress, exercise, and cold exposure. Thus, the FGF21 induction caused by stress plays an important role in adaptive response to these stimuli. Here, we highlight our current understanding of the functional importance of the induction of FGF21 by diverse stressors as a feedback mechanism that prevents excessive stress.

  9. Impact of Postovulatory Food Deprivation on the Ova Transport, Hormonal Profiles and Metabolic Changes in Sows

    Einarsson S

    2001-03-01

    Full Text Available The effect of food deprivation on ova transport, hormonal profiles and metabolic changes was studied in 20 crossbred multiparous sows during their second oestrus after weaning. To determine the time of ovulation, transrectal ultrasonographic examination was performed. The sows were divided into 2 groups, one control group (C-group, which was fed according to Swedish standards, and one experimental group (E-group. The E-group sows were deprived of food from the first morning meal after ovulation until slaughter. Blood samples were collected every second hour from about 12 h before expected ovulation in the second oestrus after weaning until slaughter and were analysed for progesterone, prostaglandin F2α-metabolite, insulin, glucose, free fatty acids and triglycerides. All sows were slaughtered approximately 48 h after ovulation and the genital tract was recovered. The isthmic part of the oviduct was divided into 3 equally long segments and flushed separately with phosphate buffered saline (PBS. Uterine horns were also flushed with PBS. A significantly greater number of ova were found in the first and second part of the isthmus in the E-group (p = 0.05 while in the C-group most of the ova were found in the third part of the isthmus or the uterus (p = 0.01. The level of prostaglandin F2α-metabolite was significantly higher in the E-group compared with the C-group. The concentration of progesterone increased in both groups after ovulation but there were no significant differences between the groups. The other blood parameters showed that the food-deprived sows were in a catabolic state. The 48 h period of fasting results, directly or indirectly in an delayed ova transport, which may be due to a delayed relaxation in the smooth circular muscle layer of the isthmus.

  10. (1H-NMR spectroscopy revealed Mycobacterium tuberculosis caused abnormal serum metabolic profile of cattle.

    Yingyu Chen

    Full Text Available To re-evaluate virulence of Mycobacterium tuberculosis (M. tb in cattle, we experimentally infected calves with M. tb andMycobacterium bovisvia intratracheal injection at a dose of 2.0×10(7 CFU and observed the animals for 33 weeks. The intradermal tuberculin test and IFN-γin vitro release assay showed that both M. tb and M. bovis induced similar responses. Immunohistochemical staining of pulmonary lymph nodes indicated that the antigen MPB83 of both M. tb and M. bovis were similarly distributed in the tissue samples. Histological examinations showed all of the infected groups exhibited neutrophil infiltration to similar extents. Although the infected cattle did not develop granulomatous inflammation, the metabolic profiles changed significantly, which were characterized by a change in energy production pathways and increased concentrations of N-acetyl glycoproteins. Glycolysis was induced in the infected cattle by decreased glucose and increased lactate content, and enhanced fatty acid β-oxidation was induced by decreased TG content, and decreased gluconeogenesis indicated by the decreased concentration of glucogenic and ketogenic amino acids promoted utilization of substances other than glucose as energy sources. In addition, an increase in acute phase reactive serum glycoproteins, together with neutrophil infiltration and increased of IL-1β production indicated an early inflammatory response before granuloma formation. In conclusion, this study indicated that both M. tb and M.bovis were virulent to cattle. Therefore, it is likely that cattle with M. tb infections would be critical to tuberculosis transmission from cattle to humans. Nuclear magnetic resonance was demonstrated to be an efficient method to systematically evaluate M. tb and M. bovi sinfection in cattle.

  11. Evaluation of sample preparation methods for nuclear magnetic resonance metabolic profiling studies with Eisenia fetida.

    Brown, Sarah A E; Simpson, André J; Simpson, Myrna J

    2008-04-01

    The earthworm Eisenia fetida is frequently used in ecotoxicological studies; however, it has not yet been investigated using proton nuclear magnetic resonance ((1)H NMR) metabolic profiling methods. The present study investigates the impact of depuration time, sample homogenization, and different extraction solvents on the quality and reproducibility of the (1)H NMR spectra of E. fetida with the goal of determining whether this species is suitable for future metabonomic studies. A depuration time of 96 h, followed by intact lyophilization before homogenization and extraction into a deuterium oxide (D(2)O)-based phosphate buffer, was found to produce extracts with excellent (1)H NMR reproducibility. The D(2)O buffer extracted the largest quantity of the widest variety of earthworm metabolites, which is consistent with the results from other studies using different earthworm species. Nuclear magnetic resonance assignments of the major metabolites in the D(2)O-based buffer also were performed and found to be similar to those for other earthworm species, such as Eisenia veneta, but also to have characteristic attributes in E. fetida. The major metabolites identified include amino acids (alanine, arginine, glutamic acid, glutamine, glycine, leucine, lysine, phenylalanine, serine, tyrosine, and valine), two sugars (glucose and maltose), the sugar alcohol mannitol, and the polyalcohol inositol. Two other earthworm species (Lumbricus rubellus and Lumbricus terrestris) also were examined using protocols developed for E. fetida, and of the three species, the (1)H NMR spectra of E. fetida had the least variation, indicating this species is well-suited for future metabolomic-based ecotoxicity studies. PMID:18333692

  12. Metabolic profiling of human brain metastases using in vivo proton MR spectroscopy at 3T

    Metastases to the central nervous system from different primary cancers are an oncologic challenge as the overall prognosis for these patients is generally poor. The incidence of brain metastases varies with type of primary cancer and is probably increasing due to improved therapies of extracranial metastases prolonging patient's overall survival and thereby time for brain metastases to develop. In addition, the greater access to improved neuroimaging techniques can provide earlier diagnosis. The aim of this study was to investigate the feasibility of using proton magnetic resonance spectroscopy (MRS) and multivariate analyses to characterize brain metastases originating from different primary cancers, to assess changes in spectra during radiation treatment and to correlate the spectra to clinical outcome after treatment. Patients (n = 26) with brain metastases were examined using single voxel MRS at a 3T clinical MR system. Five patients were excluded due to poor spectral quality. The spectra were obtained before start (n = 21 patients), immediately after (n = 6 patients) and two months after end of treatment (n = 4 patients). Principal component analysis (PCA) and partial least square regression analysis (PLS) were applied in order to identify clustering of spectra due to origin of metastases and to relate clinical outcome (survival) of the patients to spectral data from the first MR examination. The PCA results indicated that brain metastases from primary lung and breast cancer were separated into two clusters, while the metastases from malignant melanomas showed no uniformity. The PLS analysis showed a significant correlation between MR spectral data and survival five months after MRS before start of treatment. MRS determined metabolic profiles analysed by PCA and PLS might give valuable clinical information when planning and evaluating the treatment of brain metastases, and also when deciding to terminate further therapies

  13. Tumour xenograft detection through quantitative analysis of the metabolic profile of urine in mice

    Moroz, Jennifer [Department of Physics, University of Alberta, 11322-89 Avenue, Edmonton, Alberta T6G 2G7 (Canada); Turner, Joan [Department of Experimental Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Slupsky, Carolyn [Department of Nutrition, University of California, One Shields Avenue, Davis, CA 95616-8598 (United States); Fallone, Gino; Syme, Alasdair, E-mail: alasdair.syme@albertahealthservices.ca [Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)

    2011-02-07

    The metabolic content of urine from NIH III nude mice (n = 22) was analysed before and after inoculation with human glioblastoma multiforme (GBM) cancer cells. An age- and gender-matched control population (n = 14) was also studied to identify non-tumour-related changes. Urine samples were collected daily for 6 weeks, beginning 1 week before cell injection. Metabolite concentrations were obtained via targeted profiling with Chenomx Suite 5.1, based on nuclear magnetic resonance (NMR) spectra acquired on an Oxford 800 MHz cold probe NMR spectrometer. The Wilcoxon rank sum test was used to evaluate the significance of the change in metabolite concentration between the two time points. Both the metabolite concentrations and the ratios of pairs of metabolites were studied. The complicated inter-relationships between metabolites were assessed through partial least-squares discriminant analysis (PLS-DA). Receiver operating characteristic (ROC) curves were generated for all variables and the area under the curve (AUC) calculated. The data indicate that the number of statistically significant changes in metabolite concentrations was more pronounced in the tumour-bearing population than in the control animals. This was also true of the ratios of pairs of metabolites. ROC analysis suggests that the ratios were better able to differentiate between the pre- and post-injection samples compared to the metabolite concentrations. PLS-DA models produced good separation between the populations and had the best AUC results (all models exceeded 0.937). These results demonstrate that metabolomics may be used as a screening tool for GBM cells grown in xenograft models in mice.

  14. Metabolism

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood ...

  15. Regulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa biofilms to urinary tract-like conditions.

    Petra Tielen

    Full Text Available Biofilms of the Gram-negative bacterium Pseudomonas aeruginosa are one of the major causes of complicated urinary tract infections with detrimental outcome. To develop novel therapeutic strategies the molecular adaption strategies of P. aeruginosa biofilms to the conditions of the urinary tract were investigated thoroughly at the systems level using transcriptome, proteome, metabolome and enzyme activity analyses. For this purpose biofilms were grown anaerobically in artificial urine medium (AUM. Obtained data were integrated bioinformatically into gene regulatory and metabolic networks. The dominating response at the transcriptome and proteome level was the adaptation to iron limitation via the broad Fur regulon including 19 sigma factors and up to 80 regulated target genes or operons. In agreement, reduction of the iron cofactor-dependent nitrate respiratory metabolism was detected. An adaptation of the central metabolism to lactate, citrate and amino acid as carbon sources with the induction of the glyoxylate bypass was observed, while other components of AUM like urea and creatinine were not used. Amino acid utilization pathways were found induced, while fatty acid biosynthesis was reduced. The high amounts of phosphate found in AUM explain the reduction of phosphate assimilation systems. Increased quorum sensing activity with the parallel reduction of chemotaxis and flagellum assembly underscored the importance of the biofilm life style. However, reduced formation of the extracellular polysaccharide alginate, typical for P. aeruginosa biofilms in lungs, indicated a different biofilm type for urinary tract infections. Furthermore, the obtained quorum sensing response results in an increased production of virulence factors like the extracellular lipase LipA and protease LasB and AprA explaining the harmful cause of these infections.

  16. Profiling the Metabolism of Astragaloside IV by Ultra Performance Liquid Chromatography Coupled with Quadrupole/Time-of-Flight Mass Spectrometry

    Xu-Dong Cheng

    2014-11-01

    Full Text Available Astragaloside IV is a compound isolated from the Traditional Chinese Medicine Astragalus membranaceus, that has been reported to have bioactivities against cardiovascular disease and kidney disease. There is limited information on the metabolism of astragaloside IV, which impedes comprehension of its biological actions and pharmacology. In the present study, an ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS-based approach was developed to profile the metabolites of astragaloside IV in rat plasma, bile, urine and feces samples. Twenty-two major metabolites were detected. The major components found in plasma, bile, urine and feces included the parent chemical and phases I and II metabolites. The major metabolic reactions of astragaloside IV were hydrolysis, glucuronidation, sulfation and dehydrogenation. These results will help to improve understanding the metabolism and reveal the biotransformation profiling of astragaloside IV in vivo. The metabolic information obtained from our study will guide studies into the pharmacological activity and clinical safety of astragaloside IV.

  17. Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation

    Bible, Amber N.; Khalsa-Moyers, Gurusahai K.; Mukherjee, Tanmoy; Green, Calvin S.; Mishra, Priyanka; Purcell, Alicia; Aksenova, Anastasia; Gregory B Hurst; Alexandre, Gladys

    2015-01-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clum...

  18. Adaptation of the symbiotic Mesorhizobium-chickpea relationship to phosphate deficiency relies on reprogramming of whole-plant metabolism.

    Nasr Esfahani, Maryam; Kusano, Miyako; Nguyen, Kien Huu; Watanabe, Yasuko; Ha, Chien Van; Saito, Kazuki; Sulieman, Saad; Herrera-Estrella, Luis; Tran, L S

    2016-08-01

    Low inorganic phosphate (Pi) availability is a major constraint for efficient nitrogen fixation in legumes, including chickpea. To elucidate the mechanisms involved in nodule acclimation to low Pi availability, two Mesorhizobium-chickpea associations exhibiting differential symbiotic performances, Mesorhizobium ciceri CP-31 (McCP-31)-chickpea and Mesorhizobium mediterranum SWRI9 (MmSWRI9)-chickpea, were comprehensively studied under both control and low Pi conditions. MmSWRI9-chickpea showed a lower symbiotic efficiency under low Pi availability than McCP-31-chickpea as evidenced by reduced growth parameters and down-regulation of nifD and nifK These differences can be attributed to decline in Pi level in MmSWRI9-induced nodules under low Pi stress, which coincided with up-regulation of several key Pi starvation-responsive genes, and accumulation of asparagine in nodules and the levels of identified amino acids in Pi-deficient leaves of MmSWRI9-inoculated plants exceeding the shoot nitrogen requirement during Pi starvation, indicative of nitrogen feedback inhibition. Conversely, Pi levels increased in nodules of Pi-stressed McCP-31-inoculated plants, because these plants evolved various metabolic and biochemical strategies to maintain nodular Pi homeostasis under Pi deficiency. These adaptations involve the activation of alternative pathways of carbon metabolism, enhanced production and exudation of organic acids from roots into the rhizosphere, and the ability to protect nodule metabolism against Pi deficiency-induced oxidative stress. Collectively, the adaptation of symbiotic efficiency under Pi deficiency resulted from highly coordinated processes with an extensive reprogramming of whole-plant metabolism. The findings of this study will enable us to design effective breeding and genetic engineering strategies to enhance symbiotic efficiency in legume crops. PMID:27450089

  19. Disruption of the acyl-coa binding protein gene delays hepatic adaptation to metabolic changes at weaning

    Neess, Ditte; Bloksgaard, Maria; Sørensen, Signe Bek; Marcher, Ann-Britt; Elle, Ida C; Helledie, Torben; Due, Marianne; Pagmantidis, Vasileios; Finsen, Bente; Wilbertz, Johannes; Kruhoeffer, Mogens; Faergeman, Nils; Mandrup, Susanne

    2011-01-01

    , little is known about the in vivo function in mammalian cells. We have generated mice with targeted disruption of ACBP (ACBP-/-). These mice are viable and fertile and develop normally. However, around weaning the ACBP-/- mice go through a crisis with overall weakness, and a slightly decreased growth...... rate. Using microarray analysis we show that the liver of ACBP-/- mice display a significantly delayed adaptation to weaning with late induction of target genes of the sterol regulatory element binding protein (SREBP) family. As a result, hepatic de novo cholesterogenesis is decreased at weaning. The...... delayed induction of SREBP target genes around weaning is caused by a compromised processing and decreased expression of SREBP precursors leading to reduced binding of SREBP to target sites in chromatin. In conclusion, lack of ACBP interferes with the normal metabolic adaptation to weaning and leads to...

  20. Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

    Stengärde Lena

    2008-08-01

    Full Text Available Abstract Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations. Cows were examined and blood sampled every three weeks from four weeks ante partum (ap to nine weeks postpartum (pp. Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA, insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds.

  1. Transfer of Assembly Operations to New Workpiece Poses by Adaptation to the Desired Force Profile

    Nemec, Bojan; Abu-Dakka, Fares; Rytz, Jimmy Alison;

    2013-01-01

    In this paper we propose a new algorithm that can be used for adaptation of robot trajectories in automated assembly tasks. Initial trajectories and forces are obtained by demonstration and iteratively adapted to the specific environment configuration. The algorithm adapts Cartesian space trajector...

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

    Munch-Andersen, T.; Sorensen, K.; Andersen, L. B.; Aachmann-Andersen, N. J.; Aksglaede, L.; Juul, A.; Helge, Jørn Wulff

    2013-01-01

    Objective During recent decades, the prevalence of metabolic morbidity has increased rapidly in adult Greenlandic Inuit. To what extent this is also reflected in the juvenile Inuit population is unknown. The objective was, therefore, in the comparison with Danish children, to evaluate metabolic...... tendencies toward higher prevalence of diabetes and metabolic morbidity in the adult Greenlandic Inuit population may also be present in the Inuit children population....

  3. Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice

    Jackson, Kathryn C.; Wohlers, Lindsay M.; Richard M. Lovering; Schuh, Rosemary A.; Maher, Amy C.; Bonen, Arend; Koves, Timothy R.; Ilkayeva, Olga; Thomson, David M.; Muoio, Deborah M.; Spangenburg, Espen E.

    2012-01-01

    Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism coupled with altered mitochondrial function may also develop. The objective of this study was to use an integrative metabolic approach to identify potential areas of dysfunction that develop in skeletal muscle from ovariectomized (OVX) femal...

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

    Zou, Li-Hua; Liu, Jin-Ping; Zhang, Hao; Wu, Shu-Bin; Ji, Bing-Yang

    2016-01-01

    Background: Antegrade selective cerebral perfusion (ASCP) is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest (DHCA). However, brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology. Methods: To clarify the metabolomics profiling of ASCP, 12 New Zealand white rabbits were randomly assigned into 60 min DHCA with (DHCA+ASCP [DA] group, n = 6) and without (DHCA [D] group, n = 6) ASCP according to the random number table. ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery. Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass. The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry. Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites, and then Student's t-test was applied to test for statistical significance between the two groups. Results: Metabolic profiling of brain was distinctive significantly between the two groups (Q2Y = 0.88 for partial least squares-DA model). In comparing to group D, 62 definable metabolites were varied significantly after ASCP, which were mainly related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway, subdued anaerobic metabolism, and oxidative stress. In addition, L-kynurenine (P = 0.0019), 5-methoxyindole-3-acetic acid (P = 0.0499), and 5-hydroxyindole-3-acetic acid (P = 0.0495) in tryptophan metabolism pathways were decreased, and citrulline (P = 0.0158) in urea cycle was increased in group DA comparing to group D. Conclusions: The present study applied metabolomics analysis to identify the cerebral

  5. Metabolic profiles of dioscin in rats revealed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.

    Zhu, He; Xu, Jin-Di; Mao, Qian; Shen, Hong; Kong, Ming; Chen, Jian-Ping; Li, Song-Lin

    2015-09-01

    Dioscin (DIS), one of the most abundant bioactive steroidal saponins in Dioscorea sp., is used as a complementary medicine to treat coronary disease and angina pectoris in China. Although the pharmacological activities and pharmacokinetics of DIS have been well demonstrated, information regarding the final metabolic fates is very limited. This study investigated the in vivo metabolic profiles of DIS after oral administration by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method. The structures of the metabolites were identified and tentatively characterized by means of comparing the molecular mass, retention time and fragmentation pattern of the analytes with those of the parent compound. A total of eight metabolites, including seven phase I and one phase II metabolites, were detected and tentatively identified for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. In addition, a possible metabolic pathway on the biotransformation of DIS in vivo was proposed. This study provides valuable and new information on the metabolism of DIS, which will be helpful for further understanding its mechanism of action. PMID:25678372

  6. Noninvasive analysis of metabolic changes following nutrient input into diverse fish species, as investigated by metabolic and microbial profiling approaches

    Taiga Asakura

    2014-10-01

    Full Text Available An NMR-based metabolomic approach in aquatic ecosystems is valuable for studying the environmental effects of pharmaceuticals and other chemicals on fish. This technique has also contributed to new information in numerous research areas, such as basic physiology and development, disease, and water pollution. We evaluated the microbial diversity in various fish species collected from Japan’s coastal waters using next-generation sequencing, followed by evaluation of the effects of feed type on co-metabolic modulations in fish-microbial symbiotic ecosystems in laboratory-scale experiments. Intestinal bacteria of fish in their natural environment were characterized (using 16S rRNA genes for trophic level using pyrosequencing and noninvasive sampling procedures developed to study the metabolism of intestinal symbiotic ecosystems in fish reared in their environment. Metabolites in feces were compared, and intestinal contents and feed were annotated based on HSQC and TOCSY using SpinAssign and network analysis. Feces were characterized by species and varied greatly depending on the feeding types. In addition, feces samples demonstrated a response to changes in the time series of feeding. The potential of this approach as a non-invasive inspection technique in aquaculture is suggested.

  7. Transcriptome analysis of Salicornia europaea under saline conditions revealed the adaptive primary metabolic pathways as early events to facilitate salt adaptation.

    Pengxiang Fan

    Full Text Available BACKGROUND: Halophytes such as Salicornia europaea have evolved to exhibit unique mechanisms controlled by complex networks and regulated by numerous genes and interactions to adapt to habitats with high salinity. However, these mechanisms remain unknown. METHODS: To investigate the mechanism by which halophytes tolerate salt based on changes in the whole transcriptome, we performed transcriptome sequencing and functional annotation by database search. Using the unigene database, we conducted digital gene expression analysis of S. europaea at various time points after these materials were treated with NaCl. We also quantified ion uptakes. Gene functional enrichment analysis was performed to determine the important pathways involved in this process. RESULTS: A total of 57,151 unigenes with lengths of >300 bp were assembled, in which 57.5% of these unigenes were functionally annotated. Differentially expressed genes indicated that cell wall metabolism and lignin biosynthetic pathways were significantly enriched in S. europaea to promote the development of the xylem under saline conditions. This result is consistent with the increase in sodium uptake as ions pass through the xylem. Given that PSII efficiency remained unaltered, salt treatment activated the expression of electron transfer-related genes encoded by the chloroplast chromosome. Chlorophyll biosynthesis was also inhibited, indicating the energy-efficient state of the electron transfer system of S. europaea. CONCLUSIONS: The key function of adjusting important primary metabolic pathways in salt adaption was identified by analyzing the changes in the transcriptome of S. europaea. These pathways could involve unique salt tolerance mechanisms in halophytes. This study also provided information as the basis of future investigations on salt response genes in S. europaea. Ample gene resources were also provided to improve the genes responsible for the salt tolerance ability of crops.

  8. Metabolic profiling of plant extracts using direct-injection electrospray ionization mass spectrometry allows for high-throughput phenotypic characterization according to genetic and environmental effects.

    García-Flores, Martín; Juárez-Colunga, Sheila; García-Casarrubias, Adrián; Trachsel, Samuel; Winkler, Robert; Tiessen, Axel

    2015-01-28

    In comparison to the exponential increase of genotyping methods, phenotyping strategies are lagging behind in agricultural sciences. Genetic improvement depends upon the abundance of quantitative phenotypic data and the statistical partitioning of variance into environmental, genetic, and random effects. A metabolic phenotyping strategy was adapted to increase sample throughput while saving reagents, reducing cost, and simplifying data analysis. The chemical profiles of stem extracts from maize plants grown under low nitrogen (LN) or control trial (CT) were analyzed using optimized protocols for direct-injection electrospray ionization mass spectrometry (DIESI-MS). Specific ions significantly decreased or increased because of environmental (LN versus CT) or genotypic effects. Biochemical profiling with DIESI-MS had a superior cost-benefit compared to other standard analytical technologies (e.g., ultraviolet, near-infrared reflectance spectroscopy, high-performance liquid chromatography, and gas chromatography with flame ionization detection) routinely used for plant breeding. The method can be successfully applied in maize, strawberry, coffee, and other crop species. PMID:25588121

  9. Metabolic profiling reveals altered nitrogen nutrient regimes have diverse effects on the metabolism of hydroponically-grown tomato (Solanum lycopersicum) plants.

    Urbanczyk-Wochniak, Ewa; Fernie, Alisdair R

    2005-01-01

    The role of inorganic nitrogen assimilation in the production of amino acids is one of the most important biochemical processes in plants. For this reason, a detailed broad-range characterization of the metabolic response of tomato (Solanum lycopersicum) leaves to the alteration of nitrate level was performed. Tomato plants were grown hydroponically in liquid culture under three different nitrate regimes: saturated (8 mM NO3-), replete (4 mM NO3-) and deficient (0.4 mM NO3-). All treatments were performed under varied light intensity, with leaf samples being collected after 7, 14, and 21 d. In addition, the short-term response (after 1, 24, 48, and 94 h) to varying nutrient status was evaluated at the higher light intensity. GC-MS analysis of the levels of amino acids, tricarboxylic acid cycle intermediates, sugars, sugar alcohols, and representative compounds of secondary metabolism revealed substantial changes under the various growth regimes applied. The data presented here suggest that nitrate nutrition has wide-ranging effects on plant leaf metabolism with nitrate deficiency resulting in decreases in many amino and organic acids and increases in the level of several carbohydrates and phosphoesters, as well as a handful of secondary metabolites. These results are compared with previously reported transcript profiles of altered nitrogen regimes and discussed within the context of current models of carbon nitrogen interaction. PMID:15596475

  10. Identification and transcriptional profiling of Pseudomonas putida genes involved in furoic acid metabolism

    Furfural (2-furaldehyde) is a furan formed by dehydration of pentose sugars. Pseudomonas putida Fu1 metabolizes furfural through a pathway involving conversion to 2-oxoglutarate, via 2-furoic acid and Coenzyme A intermediates. To identify genes involved in furan metabolism, two P. putida transposo...

  11. Association between metabolic syndrome and depressive symptom profiles-Sex-specific?

    Marijnissen, Radboud M; Smits, Johanna E M P; Schoevers, Robert A; van den Brink, Rob H S; Holewijn, Suzanne; Franke, Barbara; de Graaf, Jacqueline; Oude Voshaar, Richard C

    2013-01-01

    Background: The association between depression and metabolic syndrome is becoming more obvious. Waist circumference (WC) might be the most important metabolic syndrome (MetS) feature in relation to late-life depression, with a possible mediating role for adiponectin. Methods: Cross-sectional populat

  12. Association between metabolic syndrome and depressive symptom profiles--sex-specific?

    Marijnissen, R.M.; Smits, J.E.; Schoevers, R.A.; Brink, R.H. van den; Holewijn, S.; Franke, B.; Graaf, J. de; Voshaar, R.C. Oude

    2013-01-01

    BACKGROUND: The association between depression and metabolic syndrome is becoming more obvious. Waist circumference (WC) might be the most important metabolic syndrome (MetS) feature in relation to late-life depression, with a possible mediating role for adiponectin. METHODS: Cross-sectional populat

  13. Differential metabolic and endocrine adaptations in llamas, sheep, and goats fed high- and low-protein grass-based diets.

    Kiani, A; Alstrup, L; Nielsen, M O

    2015-10-01

    This study aimed to elucidate whether distinct endocrine and metabolic adaptations provide llamas superior ability to adapt to low protein content grass-based diets as compared with the true ruminants. Eighteen adult, nonpregnant females (6 llamas, 6 goats, and 6 sheep) were fed either green grass hay with (HP) or grass seed straw (LP) in a cross-over design experiment over 2 periods of 21 d. Blood samples were taken on day 21 in each period at -30, 60, 150, and 240 min after feeding the morning meal and analyzed for plasma contents of glucose, triglyceride, nonesterified fatty acids, β-hydroxy butyrate (BOHB), urea, creatinine, insulin, and leptin. Results showed that llamas vs sheep and goats had higher plasma concentrations of glucose (7.1 vs 3.5 and 3.6 ± 0.18 mmol/L), creatinine (209 vs 110 and 103 ± 10 μmol/L), and urea (6.7 vs 5.6 and 4.9 ± 0.5 mmol/L) but lower leptin (0.33 vs 1.49 and 1.05 ± 0.1 ng/mL) and BOHB (0.05 vs 0.26 and 0.12 ± 0.02 mmol/L), respectively. BOHB in llamas was extremely low for a ruminating animal. Llamas showed that hyperglycemia coexisted with hyperinsulinemia (in general on the HP diet; postprandially on the LP diet). Llamas were clearly hypercreatinemic compared with the true ruminants, which became further exacerbated on the LP diet, where they also sustained plasma urea at markedly higher concentrations. However, llamas had markedly lower leptin concentrations than the true ruminants. In conclusion, llamas appear to have an intrinsic insulin resistant phenotype. Augmentation of creatinine and sustenance of elevated plasma urea concentrations in llamas when fed the LP diet must reflect distinct metabolic adaptations of intermediary protein and/or nitrogen metabolism, not observed in the true ruminants. These features can contribute to explain lower metabolic rates in llamas compared with the true ruminants, which must improve the chances of survival on low protein content diets. PMID:26073222

  14. Relationship between habitat, densities and metabolic profile in brown hares (Lepus europaeus Pallas

    Marco Bagliacca

    2010-01-01

    and best body conditions can be found in highlands, open fields with low tree presence and wooded borders, medium mixture soils, scarce predator presence and limited anthropogenic presence and with abundant water availability and shrubbiness. The study of the absolute values of metabolic profile, indicator of the physiological and nutritional condition of the reared animals, did not show any nutritional winter deficiency in wild hares and, as census data, should be repeated for several years since, probably, only their variations can be used as indicators of preliminary problems.

  15. Adapt

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  16. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells.

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N(8)-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  17. Tumour-specific metabolic adaptation to acidosis is coupled to epigenetic stability in osteosarcoma cells

    Chano, Tokuhiro; Avnet, Sofia; Kusuzaki, Katsuyuki; Bonuccelli, Gloria; Sonveaux, Pierre; Rotili, Dante; Mai, Antonello; Baldini, Nicola

    2016-01-01

    The glycolytic-based metabolism of cancers promotes an acidic microenvironment that is responsible for increased aggressiveness. However, the effects of acidosis on tumour metabolism have been almost unexplored. By using capillary electrophoresis with time-of-flight mass spectrometry, we observed a significant metabolic difference associated with glycolysis repression (dihydroxyacetone phosphate), increase of amino acid catabolism (phosphocreatine and glutamate) and urea cycle enhancement (arginino succinic acid) in osteosarcoma (OS) cells compared with normal fibroblasts. Noteworthy, metabolites associated with chromatin modification, like UDP-glucose and N8-acetylspermidine, decreased more in OS cells than in fibroblasts. COBRA assay and acetyl-H3 immunoblotting indicated an epigenetic stability in OS cells than in normal cells, and OS cells were more sensitive to an HDAC inhibitor under acidosis than under neutral pH. Since our data suggest that acidosis promotes a metabolic reprogramming that can contribute to the epigenetic maintenance under acidosis only in tumour cells, the acidic microenvironment should be considered for future therapies. PMID:27186436

  18. Genome-scale reconstruction of Salinispora tropica CNB-440 metabolism to study strain-specific adaptation.

    Contador, C A; Rodríguez, V; Andrews, B A; Asenjo, J A

    2015-11-01

    The first manually curated genome-scale metabolic model for Salinispora tropica strain CNB-440 was constructed. The reconstruction enables characterization of the metabolic capabilities for understanding and modeling the cellular physiology of this actinobacterium. The iCC908 model was based on physiological and biochemical information of primary and specialised metabolism pathways. The reconstructed stoichiometric matrix consists of 1169 biochemical conversions, 204 transport reactions and 1317 metabolites. A total of 908 structural open reading frames (ORFs) were included in the reconstructed network. The number of gene functions included in the reconstructed network corresponds to 20% of all characterized ORFs in the S. tropica genome. The genome-scale metabolic model was used to study strain-specific capabilities in defined minimal media. iCC908 was used to analyze growth capabilities in 41 different minimal growth-supporting environments. These nutrient sources were evaluated experimentally to assess the accuracy of in silico growth simulations. The model predicted no auxotrophies for essential amino acids, which was corroborated experimentally. The strain is able to use 21 different carbon sources, 8 nitrogen sources and 4 sulfur sources from the nutrient sources tested. Experimental observation suggests that the cells may be able to store sulfur. False predictions provided opportunities to gain new insights into the physiology of this species, and to gap fill the missing knowledge. The incorporation of modifications led to increased accuracy in predicting the outcome of growth/no growth experiments from 76 to 93%. iCC908 can thus be used to define the metabolic capabilities of S. tropica and guide and enhance the production of specialised metabolites. PMID:26459337

  19. Cerebrospinal fluid metabolic profiles in multiple sclerosis and degenerative dementias obtained by high resolution proton magnetic resonance spectroscopy

    We have analyzed the cerebrospinal fluid (CSF) of 19 patients with multiple sclerosis (MS), 12 patients with degenerative dementia and 17 control patients using in vitro high resolution proton magnetic resonance spectroscopy (MRS) at 400 MHz. The CSF metabolic profile is slightly modified in MS patients (increased lactate and fructose concentrations, decreased creatinine and phenylalanine concentrations) and is not correlated with the intensity of the intrathecal inflammation. Proton MRS of CSF does not differentiate relapsing-remitting MS and primary progressive MS. We have not detected any specific abnormal resonance in native or lyophilized CSF. The CSF metabolic profile of demented patients is much more altered (increased concentration of lactate, pyruvate, alanine, lysine, valine, leucine-isoleucine, tyrosine, glutamine) and is in agreement with a brain oxidative metabolism impairment as already described in Alzheimer's disease. Unassigned abnormal but non specific or constant resonances have been detected on MR spectra of demented patients. CSF inositol concentration is also increased in the CSF of patients with Alzheimer's disease. In vitro high resolution proton MRS of the CSF constitutes a new and original way to explore CSF for the differential and/or early diagnosis of dementias, as a complement to in vivo proton cerebral MRS. (authors). 22 refs., 4 figs., 2 tabs

  20. Metabolic and phylogenetic profile of bacterial community in Guishan coastal water (Pearl River Estuary), South China Sea

    Hu, Xiaojuan; Liu, Qing; Li, Zhuojia; He, Zhili; Gong, Yingxue; Cao, Yucheng; Yang, Yufeng

    2014-10-01

    Characteristics of a microbial community are important as they indicate the status of aquatic ecosystems. In the present study, the metabolic and phylogenetic profile of the bacterioplankton community in Guishan coastal water (Pearl River Estuary), South China Sea, at 12 sites (S1-S12) were explored by community-level physiological profiling (CLPP) with BIOLOG Eco-plate and denaturing gradient gel electrophoresis (DGGE). Our results showed that the core mariculture area (S6, S7 and S8) and the sites associating with human activity and sewage discharge (S11 and S12) had higher microbial metabolic capability and bacterial community diversity than others (S1-5, S9-10). Especially, the diversity index of S11 and S12 calculated from both CLPP and DGGE data ( H>3.2) was higher than that of others as sewage discharge may increase water nitrogen and phosphorus nutrient. The bacterial community structure of S6, S8, S11 and S12 was greatly influenced by total phosphorous, salinity and total nitrogen. Based on DGGE fingerprinting, proteobacteria, especially γ- and α-proteobacteria, were found dominant at all sites. In conclusion, the aquaculture area and wharf had high microbial metabolic capability. The structure and composition of bacterial community were closely related to the level of phosphorus, salinity and nitrogen.

  1. New generation NMR bioreactor coupled with high-resolution NMR spectroscopy leads to novel discoveries in Moorella thermoaceticum metabolic profiles

    Xue, Junfeng; Isern, Nancy G.; Ewing, R James; Liyu, Andrey V.; Sears, Jesse A.; Knapp, Harlan; Iversen, Jens; Sisk, Daniel R.; Ahring, Birgitte K.; Majors, Paul D.

    2014-06-20

    An in-situ nuclear magnetic resonance (NMR) bioreactor was developed and employed to monitor microbial metabolism under batch-growth conditions in real time. We selected Moorella thermoacetica ATCC 49707 as a test case. M. thermoacetica (formerly Clostridium thermoaceticum) is a strictly anaerobic, thermophilic, acetogenic, gram-positive bacterium with potential for industrial production of chemicals. The metabolic profiles of M. thermoacetica were characterized during growth in batch mode on xylose (a component of lignocellulosic biomass) using the new generation NMR bioreactor in combination with high-resolution, high sensitivity NMR (HR-NMR) spectroscopy. In-situ NMR measurements were performed using water-suppressed H-1 NMR spectroscopy at an NMR frequency of 500 MHz, and aliquots of the bioreactor contents were taken for 600 MHz HR-NMR spectroscopy at specific intervals to confirm metabolite identifications and expand metabolite coverage. M. thermoacetica demonstrated the metabolic potential to produce formate, ethanol and methanol from xylose, in addition to its known capability of producing acetic acid. Real-time monitoring of bioreactor conditions showed a temporary pH decrease, with a concomitant increase in formic acid during exponential growth. Fermentation experiments performed outside of the magnet showed that the strong magnetic field employed for NMR detection did not significantly affect cell metabolism. Use of the in-situ NMR bioreactor facilitated monitoring of the fermentation process in real time, enabling identification of intermediate and end-point metabolites and their correlation with pH and biomass produced during culture growth. Real-time monitoring of culture metabolism using the NMR bioreactor in combination with the HR-NMR spectroscopy will allow optimization of the metabolism of microorganisms producing valuable bioproducts.

  2. Dynamic Metabolic Profiles and Tissue-Specific Source Effects on the Metabolome of Developing Seeds of Brassica napus.

    Helin Tan

    Full Text Available Canola (Brassica napus is one of several important oil-producing crops, and the physiological processes, enzymes, and genes involved in oil synthesis in canola seeds have been well characterized. However, relatively little is known about the dynamic metabolic changes that occur during oil accumulation in seeds, as well as the mechanistic origins of metabolic changes. To explore the metabolic changes that occur during oil accumulation, we isolated metabolites from both seed and silique wall and identified and characterized them by using gas chromatography coupled with mass spectrometry (GC-MS. The results showed that a total of 443 metabolites were identified from four developmental stages. Dozens of these metabolites were differentially expressed during seed ripening, including 20 known to be involved in seed development. To investigate the contribution of tissue-specific carbon sources to the biosynthesis of these metabolites, we examined the metabolic changes of silique walls and seeds under three treatments: leaf-detachment (Ld, phloem-peeling (Pe, and selective silique darkening (Sd. Our study demonstrated that the oil content was independent of leaf photosynthesis and phloem transport during oil accumulation, but required the metabolic influx from the silique wall. Notably, Sd treatment resulted in seed senescence, which eventually led to a severe reduction of the oil content. Sd treatment also caused a significant accumulation of fatty acids (FA, organic acids and amino acids. Furthermore, an unexpected accumulation of sugar derivatives and organic acid was observed in the Pe- and Sd-treated seeds. Consistent with this, the expression of a subset of genes involved in FA metabolism, sugar and oil storage was significantly altered in Pe and Sd treated seeds. Taken together, our studies suggest the metabolite profiles of canola seeds dynamically varied during the course of oil accumulation, which may provide a new insight into the mechanisms

  3. New generation NMR bioreactor coupled with high-resolution NMR spectroscopy leads to novel discoveries in Moorella thermoacetica metabolic profiles.

    Xue, Junfeng; Isern, Nancy G; Ewing, R James; Liyu, Andrei V; Sears, Jesse A; Knapp, Harlan; Iversen, Jens; Sisk, Daniel R; Ahring, Birgitte K; Majors, Paul D

    2014-10-01

    An in situ nuclear magnetic resonance (NMR) bioreactor was developed and employed to monitor microbial metabolism under batch growth conditions in real time. We selected Moorella thermoacetica ATCC 49707 as a test case. M. thermoacetica (formerly Clostridium thermoaceticum) is a strictly anaerobic, thermophilic, acetogenic, gram-positive bacterium with potential for industrial production of chemicals. The metabolic profiles of M. thermoacetica were characterized during growth in batch mode on xylose (a component of lignocellulosic biomass) using the new generation NMR bioreactor in combination with high-resolution NMR (HR-NMR) spectroscopy. In situ NMR measurements were performed using water-suppressed H-1 NMR spectroscopy at 500 MHz, and aliquots of the bioreactor contents were taken for 600-MHz HR-NMR spectroscopy at specific intervals to confirm metabolite identifications and expand metabolite coverage. M. thermoacetica demonstrated the metabolic potential to produce formate, ethanol, and methanol from xylose, in addition to its known capability of producing acetic acid. Real-time monitoring of bioreactor conditions showed a temporary pH decrease, with a concomitant increase in formic acid during exponential growth. Fermentation experiments performed outside of the magnet showed that the strong magnetic field employed for NMR detection did not significantly affect cell metabolism. Use of the in situ NMR bioreactor facilitated monitoring of the fermentation process, enabling identification of intermediate and endpoint metabolites and their correlation with pH and biomass produced during culture growth. Real-time monitoring of culture metabolism using the NMR bioreactor in combination with HR-NMR spectroscopy will allow optimization of the metabolism of microorganisms producing valuable bioproducts. PMID:24946863

  4. ROLE OF PHYSICAL EXERCISE, FITNESS AND AEROBIC TRAINING IN TYPE 1 DIABETIC AND HEALTHY MEN IN RELATION TO THE LIPID PROFILE, LIPID PEROXIDATION AND THE METABOLIC SYNDROME

    David E. Laaksonen

    2003-06-01

    Full Text Available Dyslipidemia and possibly lipid peroxidation play important roles in the development of macro- and microvascular disease in type 1 diabetes mellitus. Little is known, however, of the role of aerobic exercise in dyslipidemia and resting and exercise-induced lipid peroxidation in type 1 diabetes. Despite the well-known effect of leisure-time physical activity (LTPA on components of the metabolic syndrome, little is known of the association of LTPA and cardiorespiratory fitness (maximal oxygen consumption, VO2max with development of the metabolic syndrome itself. A randomized controlled trial assessing the effect of a 12-16 week aerobic exercise program on VO2max and the lipid profile was carried out in otherwise healthy young men with type 1 diabetes. The effect of acute physical exercise on oxidative stress and antioxidant defenses and the relation to VO2max in men with type 1 diabetes was also evaluated. To test four recently proposed definitions by the World Health Organization (WHO and National Cholesterol Education Program (NCEP of the metabolic syndrome, the sensitivity and specificity of the definitions for prevalent and incident diabetes were assessed in a population-based cohort of middle-aged men. We also studied the associations of LTPA and cardiorespiratory fitness with prevalent and incident cases of the metabolic syndrome. A 12-16 week endurance exercise program produced antiatherogenic changes in lipid, lipoprotein and apolipoprotein levels in 20 type 1 diabetic men who for the most part were already physically active at baseline. The most favorable training-induced changes in the high-density lipoprotein cholesterol (HDL/low-density lipoprotein cholesterol (LDL and apolipoprotein A-I/apolipoprotein B ratios were in patients with low baseline HDL/LDL levels, likely the group with the most benefit to be gained by such changes. Plasma thiobarbituric acid reactive substances (TBARS, a measure of lipid peroxidation, was higher in nine

  5. Polymorphism profiling of nine high altitude relevant candidate gene loci in acclimatized sojourners and adapted natives

    Tomar, Arvind; Malhotra, Seema; Sarkar, Soma

    2015-01-01

    Background Sea level sojourners, on ascent to high altitude, undergo acclimatization through integrated physiological processes for defending the body against oxygen deprivation while the high altitude natives (resident population) are adapted to the prevailing hypobaric hypoxic condition through natural selection. Separating the acclimatization processes from adaptive changes and identifying genetic markers in lowlanders that may be beneficial for offsetting the high altitude hypoxic stress,...

  6. Untargeted Metabolic Profiling of Winery-Derived Biomass Waste Degradation by Penicillium chrysogenum.

    Karpe, Avinash V; Beale, David J; Godhani, Nainesh B; Morrison, Paul D; Harding, Ian H; Palombo, Enzo A

    2015-12-16

    Winery-derived biomass waste was degraded by Penicillium chrysogenum under solid state fermentation over 8 days in a (2)H2O-supplemented medium. Multivariate statistical analysis of the gas chromatography-mass spectrometry (GC-MS) data resulted in the identification of 94 significant metabolites, within 28 different metabolic pathways. The majority of biomass sugars were utilized by day 4 to yield products such as sugars, fatty acids, isoprenoids, and amino acids. The fungus was observed to metabolize xylose to xylitol, an intermediate of ethanol production. However, enzyme inhibition and autolysis were observed from day 6, indicating 5 days as the optimal time for fermentation. P. chrysogenum displayed metabolism of pentoses (to alcohols) and degraded tannins and lignins, properties that are lacking in other biomass-degrading ascomycetes. Rapid fermentation (3-5 days) may not only increase the pentose metabolizing efficiency but also increase the yield of medicinally important metabolites, such as syringate. PMID:26611372

  7. Transcriptome analysis of Escherichia coli O157:H7 grown in vitro in the sterile-filtrated cecal content of human gut microbiota associated rats reveals an adaptive expression of metabolic and virulence genes.

    Le Bihan, Guillaume; Jubelin, Grégory; Garneau, Philippe; Bernalier-Donadille, Annick; Martin, Christine; Beaudry, Francis; Harel, Josée

    2015-01-01

    In developed countries, enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a leading cause of bloody diarrhea and renal failures in human. Understanding strategies employed by EHEC to colonize the intestine is of major importance since to date no cure exists to eradicate the pathogen. In this study, the adaptive response of EHEC to the intestinal milieu conditioned by a human microbiota was examined. A transcriptomic analysis was performed on the EHEC strain EDL933 incubated in vitro in the sterile-filtrated cecal content of human microbiota-associated rats (HMC) compared with EDL933 incubated in the sterile-filtrated cecal content of germ-free rat (GFC). EDL933 switches from a glycolytic metabolic profile in the GFC to an anaplerotic metabolic profile in HMC. The expression of several catabolism genes was strongly affected such as those involved in the utilization of sugars, glycerol, N-acetylneuraminic acid, amino acids and secondary metabolites. Interestingly, expression level of critical EHEC O157:H7 virulence genes including genes from the locus of enterocyte effacement was reduced in HMC. Altogether, these results contribute to the understanding of EHEC adaptive response to a digestive content and highlight the ability of the microbiota to repress EHEC virulence gene expression. PMID:25290220

  8. Responses of mouse skeletal muscle to endurance exercise. Functional, metabolic, and genomic adaptations

    de Snoo, M.W.

    2009-01-01

    Endurance exercise is commonly known to improve skeletal muscle performance with respect to fatigue resistance. The exact mechanisms, however, as to how skeletal muscle adapts to increased physical demand are still largely unknown, despite extensive research. These processes were originally studied

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

    Leyla Baykal Selçuk; Deniz Aksu Arıca; Savaş Yaylı

    2016-01-01

    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...

  10. Metabolic profiles of biological aging in American Indians: The strong heart family study

    Zhao, Jinying; Zhu, Yun; Uppal, Karan; ViLinh T Tran; Yu, Tianwei; Lin, Jue; Matsuguchi, Tet; Blackburn, Elizabeth; Jones, Dean; Lee, Elisa T.; Howard, Barbara V.

    2014-01-01

    Short telomere length, a marker of biological aging, has been associated with age-related metabolic disorders. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolome of telomeric aging in human. Here we studied 423 apparently healthy American Indians participating in the Strong Family Heart Study. Leukocyte telomere length (LTL) was measured by qPCR. Metabolites in fasting plasma were detected by untargeted LC/MS. Associations of L...

  11. METABOLIC PROPERTIES OF RYE PRODUCTS Focusing on insulinaemia, glycaemic profile and appetite regulation in healthy subjects

    Rosén, Liza

    2011-01-01

    The prevalence of metabolic disorders, such as type 2 diabetes, cardiovascular diseases and the insulin resistance syndrome (IRS) are increasing worldwide. However, disturbances in the metabolic status can be prevented by changing the daily diet towards more whole grains, vegetables, legumes and dairy products. Also the dietary glycaemic- and insulinaemic indices of foods may play a role. Rye products are interesting in this context as they are usually consumed in wholegrain form and have bee...

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

    Jørgensen, Stine Ringholm

    training, respectively, in WT mice while there was no change in PGC-1α KO mice. Furthermore, fasting increased G6Pase and PEPCK mRNA content in both WT and PGC-1α KO mice. This implies that exercise- and exercise training-induced improvements in hepatic oxidative capacity, but not regulation......The aim of the present thesis was to investigate the hypotheses that 1) bed rest reduces metabolic and angiogenic proteins and changes microRNA (miRNA) content as well as alters exercise-induced mRNA responses in human skeletal muscle, 2) Peroxisome proliferator-activated receptor-γ coactivator...... (PGC)-1α is required for exercise-, exercise training- and fasting-induced mRNA and protein responses, respectively, of metabolic, angiogenic and gluconeogenic proteins in liver and adipose tissue in mice, 3) PGC-1α is required for both exercise training and resveratrol mediated prevention of age...

  13. Genomic profiling of carbohydrate metabolism in the ectomycorrhizal fungus Tuber melanosporum.

    Ceccaroli, P; Buffalini, M; Saltarelli, R; Barbieri, E; Polidori, E; Ottonello, S; Kohler, A; Tisserant, E; Martin, F; Stocchi, V

    2011-02-01

    • Primary carbohydrate metabolism plays a special role related to carbon/nitrogen exchange, as well as metabolic support of fruiting body development, in ectomycorrhizal macrofungi. In this study, we used information retrieved from the recently sequenced Tuber melanosporum genome, together with transcriptome analysis data and targeted validation experiments, to construct the first genome-wide catalogue of the proteins supporting carbohydrate metabolism in a plant-symbiotic ascomycete. • More than 100 genes coding for enzymes of the glycolysis, pentose phosphate, tricarboxylic acid, glyoxylate and methylcitrate pathways, glycogen, trehalose and mannitol metabolism and cell wall precursor were annotated. Transcriptional regulation of these pathways in different stages of the T. melanosporum lifecycle was investigated using whole-genome oligoarray expression data together with real-time reverse transcription-polymerase chain reaction analysis of selected genes. • The most significant results were the identification of methylcitrate cycle genes and of an acid invertase, the first enzyme of this kind to be described in a plant-symbiotic filamentous fungus. • A subset of transcripts coding for trehalose, glyoxylate and methylcitrate enzymes was up-regulated in fruiting bodies, whereas genes involved in mannitol and glycogen metabolism were preferentially expressed in mycelia and ectomycorrhizas, respectively. These data indicate a high degree of lifecycle stage specialization for particular branches of carbohydrate metabolism in T. melanosporum. PMID:21039570

  14. Metabolic profiling of the tissue-specific responses in mussel Mytilus galloprovincialis towards Vibrio harveyi challenge.

    Liu, Xiaoli; Ji, Chenglong; Zhao, Jianmin; Wang, Qing; Li, Fei; Wu, Huifeng

    2014-08-01

    Mussel Mytilus galloprovincialis is a marine aquaculture shellfish distributing widely along the coast in north China. In this work, we studied the differential metabolic responses induced by Vibrio harveyi in digestive gland and gill tissues from M. galloprovincialis using NMR-based metabolomics. The differential metabolic responses in the two tissue types were detected, except the similarly altered taurine and betaine. These metabolic responses suggested that V. harveyi mainly induced osmotic disruption and reduced energy demand via the metabolic pathways of glucose synthesis and ATP/AMP conversion in mussel digestive gland. In mussel gill tissues, V. harveyi basically caused osmotic stress and possible reduced energy demand as shown by the elevated phosphocholine that is involved in one of the metabolic pathways of ATP synthesis from ADP and phosphocholine. The altered mRNA expression levels of related genes (superoxide dismutase with copper and zinc, heat shock protein 90, defensin and lysozyme) suggested that V. harveyi induced clear oxidative and immune stresses in both digestive gland and gill tissues. However, the mRNA expression levels of both lysozyme and defensin in digestive gland were more significantly up-regulated than those in gill from V. harveyi-challenged mussel M. galloprovincialis, meaning that the immune organ, digestive gland, was more sensitive than gill. Overall, our results indicated that V. harveyi could induce tissue-specific metabolic responses in mussel M. galloprovincialis. PMID:24911264

  15. Gender-related effects on substrate utilization and metabolic adaptation in hairless spontaneously hypertensive rat

    Trnovská, J.; Šilhavý, Jan; Zídek, Václav; Šimáková, Miroslava; Mlejnek, Petr; Landa, Vladimír; Eigner, Sebastian; Eigner-Henke, Kateřina; Škop, V.; Oliyarnyk, O.; Kazdová, L.; Mráček, Tomáš; Houštěk, Josef; Pravenec, Michal

    2015-01-01

    Roč. 64, č. 1 (2015), s. 51-60. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GB14-36804G; GA ČR(CZ) GA13-04420S; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:61389005 Keywords : gender * hairless rat * metabolism * brown adipose tissue Subject RIV: ED - Physiology Impact factor: 1.293, year: 2014

  16. Adaptive evolution of energy metabolism genes and the origin of flight in bats

    Shen, Yong-Yi; Liang, Lu; Zhu, Zhou-Hai; Zhou, Wei-Ping; David M. Irwin; Zhang, Ya-Ping

    2010-01-01

    Bat flight poses intriguing questions about how flight independently developed in mammals. Flight is among the most energy-consuming activities. Thus, we deduced that changes in energy metabolism must be a primary factor in the origin of flight in bats. The respiratory chain of the mitochondrial produces 95% of the adenosine triphosphate (ATP) needed for locomotion. Because the respiratory chain has a dual genetic foundation, with genes encoded by both the mitochondrial and nuclear genomes, w...

  17. Exercise-Induced Skeletal Muscle Remodeling and Metabolic Adaptation: Redox Signaling and Role of Autophagy

    Ferraro, Elisabetta; Giammarioli, Anna Maria; Chiandotto, Sergio; Spoletini, Ilaria; Rosano, Giuseppe

    2014-01-01

    Significance: Skeletal muscle is a highly plastic tissue. Exercise evokes signaling pathways that strongly modify myofiber metabolism and physiological and contractile properties of skeletal muscle. Regular physical activity is beneficial for health and is highly recommended for the prevention of several chronic conditions. In this review, we have focused our attention on the pathways that are known to mediate physical training-induced plasticity. Recent Advances: An important role for redox ...

  18. A Novel Mathematical Model Describing Adaptive Cellular Drug Metabolism and Toxicity in the Chemoimmune System

    Tóth, Attila; Brózik, Anna; Szakács, Gergely; Sarkadi, Balázs; Hegedüs, Tamás

    2015-01-01

    Cells cope with the threat of xenobiotic stress by activating a complex molecular network that recognizes and eliminates chemically diverse toxic compounds. This “chemoimmune system” consists of cellular Phase I and Phase II metabolic enzymes, Phase 0 and Phase III ATP Binding Cassette (ABC) membrane transporters, and nuclear receptors regulating these components. In order to provide a systems biology characterization of the chemoimmune network, we designed a reaction kinetic model based on d...

  19. Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep.

    Khanal, Prabhat; Johnsen, Lærke; Axel, Anne Marie Dixen; Hansen, Pernille Willert; Kongsted, Anna Hauntoft; Lyckegaard, Nette Brinch; Nielsen, Mette Olaf

    2016-01-01

    We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 2½ years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights. PMID:27257993

  20. Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep.

    Prabhat Khanal

    Full Text Available We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin-pregnant ewes were fed NORM (100% of daily energy and protein requirements, LOW (50% of NORM or HIGH (150%/110% of energy/protein requirements diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF or moderate (CONV diets until 6 months of age, and a moderate (obesity correcting diet thereafter. At 2½ years of age (adulthood, plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights.

  1. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

    2014-09-15

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

  2. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue

  3. Effect of probiotics on metabolic profiles in type 2 diabetes mellitus: A meta-analysis of randomized, controlled trials.

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

    2016-06-01

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

  4. Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis

    Oliveira, Marina C.; Tavares, Luciana P.; Vago, Juliana P.; Batista, Nathália V.; Queiroz-Junior, Celso M.; Vieira, Angelica T.; Menezes, Gustavo B.; Sousa, Lirlândia P.; van de Loo, Fons A. J.; Teixeira, Mauro M.; Amaral, Flávio A.; Ferreira, Adaliene V. M.

    2016-01-01

    Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines. PMID:26742100

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

    Bakhareva A.S.; Isaev A.P.; Erlikh V.V.; Aminov A.S.

    2016-01-01

    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 wa...

  6. Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance

    Dulloo, Abdul G; Seydoux, Josiane; JACQUET, JEAN

    2005-01-01

    After decades of controversies about the quantitative importance of autoregulatory adjustments in energy expenditure in weight regulation, there is now increasing recognition that even subtle variations in thermogenesis could, in dynamic systems and over the long term, be important in determining weight maintenance in some and obesity in others. The main challenge nowadays is to provide a mechanistic explanation for the role of adaptive thermogenesis in attenuating and correcting deviations o...

  7. 1H NMR Metabolic Profiling of Biofluids from Rats with Gastric Mucosal Lesion and Electroacupuncture Treatment

    Jingjing Xu

    2015-01-01

    Full Text Available Gastric mucosal lesion (GML is a common gastrointestinal disorder with multiple pathogenic mechanisms in clinical practice. In traditional Chinese medicine (TCM, electroacupuncture (EA treatment has been proven as an effective therapy for GML, although the underlying healing mechanism is not yet clear. Here, we used proton nuclear magnetic resonance- (1H NMR- based metabolomic method to investigate the metabolic perturbation induced by GML and the therapeutic effect of EA treatment on stomach meridian (SM acupoints. Clear metabolic differences were observed between GML and control groups, and related metabolic pathways were discussed by means of online metabolic network analysis toolbox. By comparing the endogenous metabolites from GML and GML-SM groups, the disturbed pathways were partly recovered towards healthy state via EA treated on SM acupoints. Further comparison of the metabolic variations induced by EA stimulated on SM and the control gallbladder meridian (GM acupoints showed a quite similar metabolite composition except for increased phenylacetylglycine, 3,4-dihydroxymandelate, and meta-hydroxyphenylacetate and decreased N-methylnicotinamide in urine from rats with EA treated on SM acupoints. The current study showed the potential application of metabolomics in providing further insight into the molecular mechanism of acupuncture.

  8. Effects of herbage allowance of native grasslands in purebred and crossbred beef cows: metabolic, endocrine and hepatic gene expression profiles through the gestation-lactation cycle.

    Laporta, J; Astessiano, A L; López-Mazz, C; Soca, P; Espasandin, A C; Carriquiry, M

    2014-07-01

    Our objective was to evaluate the metabolic, endocrine and hepatic mRNA profiles through the gestation-lactation cycle in purebred (PU: Angus and Hereford) and crossbred (CR: reciprocal F1 crosses) mutliparous beef cows (n=32), grazing on two herbage allowances of native pastures (2.5 v. 4 kg dry matter/kg BW; LO v. HI) and their associations with cow's productive performance (calf birth weight, milk production and commencement of luteal activity). Cow BW, body condition score (BCS) and blood samples were collected monthly, starting at -165 days relative to calving (days), and every 2 weeks after calving until +60 days of lactation. Liver biopsies were collected at -165, -75, -45, -15±10, and +15 and +60±3 days. Metabolic, endocrine and hepatic gene expression profiles, and calf birth weight, milk yield and postpartum commencement of luteal activity were evaluated. Overall, the most pronounced changes in metabolic, endocrine and hepatic gene expression occurred during winter gestation (-165 to -45 days), when all cows experienced the onset of a negative energy balance (decreased BCS, glucose and insulin, and increased non-esterified fatty acid concentrations, Pcows. However, serum IGF-I concentrations and hepatic growth hormone receptor (GHR) and IGF1 mRNA decreased (Pcows. Although IGF-I concentrations decreased (Pcows, the typical molecular mechanism that control the uncoupling of the growth hormone-IGF1 axis during the transition period of the dairy cattle (reduced hepatic GHR1A and IGF-I mRNA) was not observed in this study. The hepatic mRNA expression of key transcripts involved in gluconeogenesis and fatty-acid oxidation were upregulated (Pcow groups). Particularly, acyl-CoA oxidase-1 mRNA was greater for CR than for PU cows during winter gestation (-75 and -45 days), and fibroblast growth factor-21 mRNA was downregulated (Pcows during the transition (-15 v. 15 days) and lactation period (+15 to +60 days, Pmilk yield and shorter commencement of luteal

  9. Xylem transcription profiles indicate potential metabolic responses for economically relevant characteristics of Eucalyptus species

    Salazar, Marcela Mendes; Nascimento, Leandro Costa; Camargo, Eduardo Leal Oliveira; Gonçalves, Danieli Cristina; Neto, Jorge Lepikson; Marques, Wesley Leoricy; Teixeira, Paulo José Pereira Lima; Mieczkowski, Piotr; Mondego, Jorge Maurício Costa; Carazzolle, Marcelo Falsarella; Deckmann, Ana Carolina; Pereira, Gonçalo Amarante Guimarães

    2013-01-01

    Background Eucalyptus is one of the most important sources of industrial cellulose. Three species of this botanical group are intensively used in breeding programs: E. globulus, E. grandis and E. urophylla. E. globulus is adapted to subtropical/temperate areas and is considered a source of high-quality cellulose; E. grandis grows rapidly and is adapted to tropical/subtropical climates; and E. urophylla, though less productive, is considered a source of genes related to robustness. Wood, or se...

  10. Differential Roles of the TRAF3 Adapter Protein in Adipogenesis and Glucose Metabolism

    Loo, Lotus Kyi

    2015-01-01

    The main goal of this project is to delineate the roles and mechanisms of constitutive type II nuclear factor-kappa B (NF-kB) activation on adipogenesis and glucose metabolism. Our laboratory has shown that the tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) is a critical negative modulator of type II NF-kB and TRAF3 knockout (TRAF3-/-) have constitutive activation of non canonical or type II NF-kB pathway. However, TRAF3-/- pups die within two weeks after birth and the funct...

  11. Metabolic profiling provides a system understanding of hypothyroidism in rats and its application.

    Si Wu

    Full Text Available BACKGROUND: Hypothyroidism is a chronic condition of endocrine disorder and its precise molecular mechanism remains obscure. In spite of certain efficacy of thyroid hormone replacement therapy in treating hypothyroidism, it often results in other side effects because of its over-replacement, so it is still urgent to discover new modes of treatment for hypothyroidism. Sini decoction (SND is a well-known formula of traditional Chinese medicine (TCM and is considered as efficient agents against hypothyroidism. However, its holistic effect assessment and mechanistic understanding are still lacking due to its complex components. METHODOLOGY/PRINCIPAL FINDINGS: A urinary metabonomic method based on ultra performance liquid chromatography coupled to mass spectrometry was employed to explore global metabolic characters of hypothyroidism. Three typical hypothyroidism models (methimazole-, propylthiouracil- and thyroidectomy-induced hypothyroidism were applied to elucidate the molecular mechanism of hypothyroidism. 17, 21, 19 potential biomarkers were identified with these three hypothyroidism models respectively, primarily involved in energy metabolism, amino acid metabolism, sphingolipid metabolism and purine metabolism. In order to avert the interference of drug interaction between the antithyroid drugs and SND, the thyroidectomy-induced hypothyroidism model was further used to systematically assess the therapeutic efficacy of SND on hypothyroidism. A time-dependent recovery tendency was observed in SND-treated group from the beginning of model to the end of treatment, suggesting that SND exerted a recovery effect on hypothyroidism in a time-dependent manner through partially regulating the perturbed metabolic pathways. CONCLUSIONS/SIGNIFICANCE: Our results showed that the metabonomic approach is instrumental to understand the pathophysiology of hypothyroidism and offers a valuable tool for systematically studying the therapeutic effects of SND on

  12. Metabolic and proteomic profiling of diapause in the aphid parasitoid Praon volucre.

    Hervé Colinet

    Full Text Available BACKGROUND: Diapause, a condition of developmental arrest and metabolic depression exhibited by a wide range of animals is accompanied by complex physiological and biochemical changes that generally enhance environmental stress tolerance and synchronize reproduction. Even though some aspects of diapause have been well characterized, very little is known about the full range of molecular and biochemical modifications underlying diapause in non-model organisms. METHODOLOGY/PRINCIPAL FINDINGS: In this study we focused on the parasitic wasp, Praon volucre that exhibits a pupal diapause in response to environmental signals. System-wide metabolic changes occurring during diapause were investigated using GC-MS metabolic fingerprinting. Moreover, proteomic changes were studied in diapausing versus non-diapausing phenotypes using a combination of two-dimensional differential gel electrophoresis (2D-DIGE and mass spectrometry. We found a reduction of Krebs cycle intermediates which most likely resulted from the metabolic depression. Glycolysis was galvanized, probably to favor polyols biosynthesis. Diapausing parasitoids accumulated high levels of cryoprotective polyols, especially sorbitol. A large set of proteins were modulated during diapause and these were involved in various functions such as remodeling of cytoskeleton and cuticle, stress tolerance, protein turnover, lipid metabolism and various metabolic enzymes. CONCLUSIONS/SIGNIFICANCE: The results presented here provide some first clues about the molecular and biochemical events that characterize the diapause syndrome in aphid parasitoids. These data are useful for probing potential commonality of parasitoids diapause with other taxa and they will help creating a general understanding of diapause underpinnings and a background for future interpretations.

  13. Metabolic effects of influenza virus infection in cultured animal cells: Intra- and extracellular metabolite profiling

    Genzel Yvonne

    2010-05-01

    Full Text Available Abstract Background Many details in cell culture-derived influenza vaccine production are still poorly understood and approaches for process optimization mainly remain empirical. More insights on mammalian cell metabolism after a viral infection could give hints on limitations and cell-specific virus production capacities. A detailed metabolic characterization of an influenza infected adherent cell line (MDCK was carried out based on extracellular and intracellular measurements of metabolite concentrations. Results For most metabolites the comparison of infected (human influenza A/PR/8/34 and mock-infected cells showed a very similar behavior during the first 10-12 h post infection (pi. Significant changes were observed after about 12 h pi: (1 uptake of extracellular glucose and lactate release into the cell culture supernatant were clearly increased in infected cells compared to mock-infected cells. At the same time (12 h pi intracellular metabolite concentrations of the upper part of glycolysis were significantly increased. On the contrary, nucleoside triphosphate concentrations of infected cells dropped clearly after 12 h pi. This behaviour was observed for two different human influenza A/PR/8/34 strains at slightly different time points. Conclusions Comparing these results with literature values for the time course of infection with same influenza strains, underline the hypothesis that influenza infection only represents a minor additional burden for host cell metabolism. The metabolic changes observed after12 h pi are most probably caused by the onset of apoptosis in infected cells. The comparison of experimental data from two variants of the A/PR/8/34 virus strain (RKI versus NIBSC with different productivities and infection dynamics showed comparable metabolic patterns but a clearly different timely behavior. Thus, infection dynamics are obviously reflected in host cell metabolism.

  14. A novel mathematical model describing adaptive cellular drug metabolism and toxicity in the chemoimmune system.

    Attila Tóth

    Full Text Available Cells cope with the threat of xenobiotic stress by activating a complex molecular network that recognizes and eliminates chemically diverse toxic compounds. This "chemoimmune system" consists of cellular Phase I and Phase II metabolic enzymes, Phase 0 and Phase III ATP Binding Cassette (ABC membrane transporters, and nuclear receptors regulating these components. In order to provide a systems biology characterization of the chemoimmune network, we designed a reaction kinetic model based on differential equations describing Phase 0-III participants and regulatory elements, and characterized cellular fitness to evaluate toxicity. In spite of the simplifications, the model recapitulates changes associated with acquired drug resistance and allows toxicity predictions under variable protein expression and xenobiotic exposure conditions. Our simulations suggest that multidrug ABC transporters at Phase 0 significantly facilitate the defense function of successive network members by lowering intracellular drug concentrations. The model was extended with a novel toxicity framework which opened the possibility of performing in silico cytotoxicity assays. The alterations of the in silico cytotoxicity curves show good agreement with in vitro cell killing experiments. The behavior of the simplified kinetic model suggests that it can serve as a basis for more complex models to efficiently predict xenobiotic and drug metabolism for human medical applications.

  15. MORBIDITY PROFILE, HEALTH SEEKING BEHAVIOUR AND HOME ENVIRONMENT SURVEY FOR ADAPTIVE MEASURES IN GERIATRIC POPULATION – URBAN COMMUNITY STUDY

    Warbhe Priya A, Warbhe Rupesh

    2015-10-01

    Full Text Available Background: Population ageing is a significant product of demographic transition. Declining fertility and improved health and longevity have generated rising proportions of the older population. Double burden of communicable and non-communicable diseases affects the geriatric segment of the population with variable health seeking behaviour. Objectives: To assess morbidity profile, health seeking behaviour and home environmental survey for adaptive measures in geriatric population from an urban community. Material and Methods: Cross-sectional study stratified systematic random sampling was applied. Research tool was interviewer based closed ended questionnaire. Adaptive measures as part of environment survey were assessed. Proportions and Pearson’s chi-square test were calculated. Results: 64.1% participants were from 60-69 years age category, 9.1% current smokers. 94.1% had 1-3 morbidities, 4.1% had 4-6 morbidities .37.3% gave a history of fall and 31.4% history of fracture. 13.6% cataract operation, 16.8% procedure for fracture.10% had dental procedure. 54.2% went to UHC and GOVT/BMC hospitals for treatment and 78.6% received both allopathic and ayurvedic treatment. History of fall was not associated with adaptive measures in the house (p=0.952. Conclusions: Majority of the participants suffered from old age related morbidities, hypertension emerged as a major morbidity. Most of the participants relied on government hospitals for treatment. Adaptive measures were lacking in most of the houses.

  16. The adaptive metabolic response involves specific protein glutathionylation during the filamentation process in the pathogen Candida albicans.

    Gergondey, R; Garcia, C; Serre, V; Camadro, J M; Auchère, F

    2016-07-01

    Candida albicans is an opportunist pathogen responsible for a large spectrum of infections, from superficial mycosis to the systemic disease candidiasis. Its ability to adopt various morphological forms, such as unicellular yeasts, filamentous pseudohyphae and hyphae, contributes to its ability to survive within the host. It has been suggested that the antioxidant glutathione is involved in the filamentation process. We investigated S-glutathionylation, the reversible binding of glutathione to proteins, and the functional consequences on C. albicans metabolic remodeling during the yeast-to-hyphae transition. Our work provided evidence for the specific glutathionylation of mitochondrial proteins involved in bioenergetics pathways in filamentous forms and a regulation of the main enzyme of the glyoxylate cycle, isocitrate lyase, by glutathionylation. Isocitrate lyase inactivation in the hyphal forms was reversed by glutaredoxin treatment, in agreement with a glutathionylation process, which was confirmed by proteomic data showing the binding of one glutathione molecule to the enzyme (data are available via ProteomeXchange with identifier PXD003685). We also assessed the effect of alternative carbon sources on glutathione levels and isocitrate lyase activity. Changes in nutrient availability led to morphological flexibility and were related to perturbations in glutathione levels and isocitrate lyase activity, confirming the key role of the maintenance of intracellular redox status in the adaptive metabolic strategy of the pathogen. PMID:27083931

  17. Association between muscle mass and adipo-metabolic profile: a cross-sectional study in older subjects

    Perna S

    2015-02-01

    Full Text Available Simone Perna,1,* Davide Guido,2,* Mario Grassi,2 Mariangela Rondanelli1 1Department of Public Health, Experimental and Forensic Medicine, School of Medicine, Endocrinology and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di Pavia, Pavia, Italy; 2Medical and Genomic Statistics Unit, Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy *These authors contributed equally to this work Background: Sarcopenia, the decrease in muscle mass and function, may lead to various negative health outcomes in elderly. The association among sarcopenia with adiposity and metabolic markers has rarely been studied in the elderly population, with controversial results. The aim of this study is to evaluate this relationship in older subjects.Methods: A cross-sectional study was conducted in 290 elderly patients, focusing on the possible association between muscle mass loss, assessed by relative skeletal muscle mass (RSMM, and an adipo-metabolic profile (AMP defined by adiposity and metabolic biochemical markers. Measurements of body composition were assessed by dual energy X-ray absorptiometry. Biochemical parameters, such as albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides, C-reactive protein, and homocysteine and its related markers (folate and vitamin B12 were measured. Using canonical correlation analysis and structural equation modeling, an individual score of AMP was created and correlated with RSMM.Results: The AMP–RSMM correlation was equal to +0.642 (95% confidence interval, +0.512 to +0.773; P<0.001. Hence, a negative association between sarcopenia severity and adiposity/metabolic biochemical markers was highlighted.Conclusion: This study contained a novel way to examine the relationship between the variables of interest based on a composite index of adiposity and metabolic conditions. Results shed light on the orientation and magnitude of

  18. Tissue-Specific Metabolic Profile Study of Moringa oleifera L. Using Nuclear Magnetic Resonance Spectroscopy

    Mahmud, Iqbal; Chowdhury, Kamal; Boroujerdi, Arezue

    2014-01-01

    Moringa oleifera, an important multipurpose crop, is rich in various phytochemicals: flavonoids, antioxidants, vitamins, minerals and carotenes. The purpose of this study was to profile the groups of metabolites in leaf and stem tissues of M. oleifera. Various sugars, amino acids, and organic acid derivatives were found in all of the M. oleifera tissues with different profiles/peak intensities depending on the tissue. 1D proton nuclear magnetic resonance (NMR) was applied for collecting metab...

  19. Uniform longitudinal beam profiles in the Fermilab Recycler using adaptive rf correction

    Hu, Martin; Broemmelsiek, Daniel Robert; Chase, Brian; Crisp, James L.; Eddy, Nathan; Joireman, Paul W.; Ng, King Yuen; /Fermilab

    2007-06-01

    The Fermilab Recycler Ring is a permanent magnet based 8 GeV anti-proton storage ring. A wideband RF system, driven with ARB's (ARBitrary waveform generators), allows the system to produce programmable barrier waveforms. Beam current profile distortion was observed, its origin verified both experimentally and theoretically, and an FPGA-based correction system was designed, tested and implemented to level the bunch profile.

  20. Partial restoration of dietary fat induced metabolic adaptations to training by 7 days of carbohydrate diet

    Helge, Jørn Wulff; Watt, Peter W; Richter, Erik A;

    2002-01-01

    -fat (Fat-CHO; 62% fat, 21% carbohydrate) and 6 a high-carbohydrate diet (CHO; 20% fat, 65% carbohydrate) for 7 wk, and thereafter both groups consumed the carbohydrate diet for an eighth week. Training was performed throughout. After 8 wk, during 60 min of exercise (71 +/- 1% pretraining maximal oxygen...... +/- 59 vs. 688 +/- 43 mmol/kg dry wt) in Fat-CHO than in CHO. In conclusion, shift to carbohydrate diet after prolonged adaptation to fat diet and training causes increased resting muscle glycogen levels but impaired leg glucose uptake and similar muscle glycogen breakdown, despite higher resting levels......, compared with when the carbohydrate diet is consumed throughout training....

  1. Effects of α-Tocopherol on Oxidative Status and Metabolic Profile in Overweight Women

    J. D. Méndez

    2007-12-01

    Full Text Available Despite extensive research, the effects of α-tocopherol supplementation remain controversial. Few studies have been focused on obese and overweight people. We examined the effects of α-tocopherol (AT on the oxidative status and metabolic profile in overweight women. Sixteen overweight women between the ages of 40-60 years old, received AT, 800 IU/day during 12 weeks, followed by a 6-week washout period. Blood samples were taken at the beginning and then every 6 weeks until the end of the study. AT, retinol, malondialdehyde (MDA, total antioxidant status (TAS, selenium-dependent glutathione peroxidase (GPx and CuZn-superoxide dismutase (SOD were quantified to evaluate the oxidative stress. The metabolic profile was estimated by measuring glycated hemoglobin (HbA1c in erythrocytes and glucose, phosphate, magnesium, lipid and lipoprotein concentrations in serum. Under AT administration HbA1c, serum- MDA levels and erythrocyte GPx activity were markedly reduced. TAS, AT and Mg2+ concentrations in serum and SOD activity in erythrocytes were higher after AT treatment. Body weight; glucose, lipid and retinol concentrations, or blood cells count were unchanged. Lipid peroxidation was considerably reduced in AT treated women and also improved serum antioxidant status was observed, but the imbalanced response between erythrocyte SOD and GPx activities could affect normal response to oxidative stress.

  2. Metabolic profiling using HPLC allows classification of drugs according to their mechanisms of action in HL-1 cardiomyocytes

    Along with hepatotoxicity, cardiotoxic side effects remain one of the major reasons for drug withdrawals and boxed warnings. Prediction methods for cardiotoxicity are insufficient. High content screening comprising of not only electrophysiological characterization but also cellular molecular alterations are expected to improve the cardiotoxicity prediction potential. Metabolomic approaches recently have become an important focus of research in pharmacological testing and prediction. In this study, the culture medium supernatants from HL-1 cardiomyocytes after exposure to drugs from different classes (analgesics, antimetabolites, anthracyclines, antihistamines, channel blockers) were analyzed to determine specific metabolic footprints in response to the tested drugs. Since most drugs influence energy metabolism in cardiac cells, the metabolite 'sub-profile' consisting of glucose, lactate, pyruvate and amino acids was considered. These metabolites were quantified using HPLC in samples after exposure of cells to test compounds of the respective drug groups. The studied drug concentrations were selected from concentration response curves for each drug. The metabolite profiles were randomly split into training/validation and test set; and then analysed using multivariate statistics (principal component analysis and discriminant analysis). Discriminant analysis resulted in clustering of drugs according to their modes of action. After cross validation and cross model validation, the underlying training data were able to predict 50%-80% of conditions to the correct classification group. We show that HPLC based characterisation of known cell culture medium components is sufficient to predict a drug's potential classification according to its mode of action.

  3. Gut microbiota can transfer fiber characteristics and lipid metabolic profiles of skeletal muscle from pigs to germ-free mice.

    Yan, Honglin; Diao, Hui; Xiao, Yi; Li, Wenxia; Yu, Bing; He, Jun; Yu, Jie; Zheng, Ping; Mao, Xiangbing; Luo, Yuheng; Zeng, Benhua; Wei, Hong; Chen, Daiwen

    2016-01-01

    Obesity causes changes in microbiota composition, and an altered gut microbiota can transfer obesity-associated phenotypes from donors to recipients. Obese Rongchang pigs (RP) exhibited distinct fiber characteristics and lipid metabolic profiles in their muscle compared with lean Yorkshire pigs (YP). However, whether RP have a different gut microbiota than YP and whether there is a relationship between the microbiota and muscle properties are poorly understood. The present study was conducted to test whether the muscle properties can be transferred from pigs to germ-free (GF) mice. High-throughput pyrosequencing confirms the presence of distinct core microbiota between pig breeds, with alterations in taxonomic distribution and modulations in β diversity. RP displayed a significant higher Firmicutes/Bacteroidetes ratio and apparent genera differences compared with YP. Transplanting the porcine microbiota into GF mice replicated the phenotypes of the donors. RP and their GF mouse recipients exhibited a higher body fat mass, a higher slow-contracting fiber proportion, a decreased fiber size and fast IIb fiber percentage, and enhanced lipogenesis in the gastrocnemius muscle. Furthermore, the gut microbiota composition of colonized mice shared high similarity with their donor pigs. Taken together, the gut microbiota of obese pigs intrinsically influences skeletal muscle development and the lipid metabolic profiles. PMID:27545196

  4. Inflammatory Cytokine Profile Associated with Metabolic Syndrome in Adult Patients with Type 1 Diabetes

    Aldo Ferreira-Hermosillo

    2015-01-01

    Full Text Available Objective. To compare the serum concentration of IL-6, IL-10, TNF, IL-8, resistin, and adiponectin in type 1 diabetic patients with and without metabolic syndrome and to determine the cut-off point of the estimated glucose disposal rate that accurately differentiated these groups. Design. We conducted a cross-sectional evaluation of all patients in our type 1 diabetes clinic from January 2012 to January 2013. Patients were considered to have metabolic syndrome when they fulfilled the joint statement criteria and were evaluated for clinical, biochemical, and immunological features. Methods. We determined serum IL-6, IL-8, IL-10, and TNF with flow cytometry and adiponectin and resistin concentrations with enzyme linked immunosorbent assay in patients with and without metabolic syndrome. We also compared estimated glucose disposal rate between groups. Results. We tested 140 patients. Forty-four percent fulfilled the metabolic syndrome criteria (n=61, 54% had central obesity, 30% had hypertriglyceridemia, 29% had hypoalphalipoproteinemia, and 19% had hypertension. We observed that resistin concentrations were higher in patients with MS. Conclusion. We found a high prevalence of MS in Mexican patients with T1D. The increased level of resistin may be related to the increased fat mass and could be involved in the development of insulin resistance.

  5. Global Profiling of Protein Lysine Malonylation in Escherichia coli Reveals Its Role in Energy Metabolism.

    Qian, Lili; Nie, Litong; Chen, Ming; Liu, Ping; Zhu, Jun; Zhai, Linhui; Tao, Sheng-Ce; Cheng, Zhongyi; Zhao, Yingming; Tan, Minjia

    2016-06-01

    Protein lysine malonylation is a recently identified post-translational modification (PTM), which is evolutionarily conserved from bacteria to mammals. Although analysis of lysine malonylome in mammalians suggested that this modification was related to energy metabolism, the substrates and biological roles of malonylation in prokaryotes are still poorly understood. In this study, we performed qualitative and quantitative analyses to globally identify lysine malonylation substrates in Escherichia coli. We identified 1745 malonylation sites in 594 proteins in E. coli, representing the first and largest malonylome data set in prokaryotes up to date. Bioinformatic analyses showed that lysine malonylation was significantly enriched in protein translation, energy metabolism pathways and fatty acid biosynthesis, implying the potential roles of protein malonylation in bacterial physiology. Quantitative proteomics by fatty acid synthase inhibition in both auxotrophic and prototrophic E. coli strains revealed that lysine malonylation is closely associated with E. coli fatty acid metabolism. Protein structural analysis and mutagenesis experiment suggested malonylation could impact enzymatic activity of citrate synthase, a key enzyme in citric acid (TCA) cycle. Further comparative analysis among lysine malonylome, succinylome and acetylome data showed that these three modifications could participate in some similar enriched metabolism pathways, but they could also possibly play distinct roles such as in fatty acid synthesis. These data expanded our knowledge of lysine malonylation in prokaryotes, providing a resource for functional study of lysine malonylation in bacteria. PMID:27183143

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

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

    2015-01-01

    exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating...

  7. Physical activity, heart rate, metabolic profile, and estradiol in premenopausal women

    Emaus, Aina; Veierød, Marit B; Furberg, Anne-Sofie;

    2008-01-01

    PURPOSE: To study whether physical inactive women with a tendency to develop metabolic syndrome have high levels of 17beta-estradiol (E2) of importance for breast cancer risk. METHODS: Two hundred and four healthy women of reproductive age were assessed for self-reported leisure-time physical...

  8. Unveiling the Metabolic Pathways Associated with the Adaptive Reduction of Cell Size During Vibrio harveyi Persistence in Seawater Microcosms.

    Kaberdin, Vladimir R; Montánchez, Itxaso; Parada, Claudia; Orruño, Maite; Arana, Inés; Barcina, Isabel

    2015-10-01

    Owing to their ubiquitous presence and ability to act as primary or opportunistic pathogens, Vibrio species greatly contribute to the diversity and evolution of marine ecosystems. This study was aimed at unveiling the cellular strategies enabling the marine gammaproteobacterium Vibrio harveyi to adapt and persist in natural aquatic systems. We found that, although V. harveyi incubation in seawater microcosm at 20 °C for 2 weeks did not change cell viability and culturability, it led to a progressive reduction in the average cell size. Microarray analysis revealed that this morphological change was accompanied by a profound decrease in gene expression affecting the central carbon metabolism, major biosynthetic pathways, and energy production. In contrast, V. harveyi elevated expression of genes closely linked to the composition and function of cell envelope. In addition to triggering lipid degradation via the β-oxidation pathway and apparently promoting the use of endogenous fatty acids as a major energy and carbon source, V. harveyi upregulated genes involved in ancillary mechanisms important for sustaining iron homeostasis, cell resistance to the toxic effect of reactive oxygen species, and recycling of amino acids. The above adaptation mechanisms and morphological changes appear to represent the major hallmarks of the initial V. harveyi response to starvation. PMID:25903990

  9. Involvement of anti-oxidative enzymes, photosynthetic pigments and flavonoid metabolism in the adaptation of Reaumuria soongorica to salt stress

    YuBing Liu; Bo Cao; MeiLing Liu

    2013-01-01

    Reaumuria soongorica is a short woody shrub widely found in semi-arid areas of China. It can survive severe environ-mental stress including high salinity in its natural habitat. Thus, we investigated the involvement of anti-oxidative enzymes, photosynthetic pigments and flavonoid metabolism in the adaptation of R. soongorica to saline environments. R. soon-gorica was treated with 0, 100, 200 and 400 mM NaCl solutions for 14 days. Soil salt content increased significantly by watering with high content of NaCl solution, and no variation between 8 and 14 days during treatment. The levels of pe-roxidation of lipid membranes (measured by malondialdehyde content) and the activities of three antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX)) increased under salt stress. Chlorophyll and carotenoid content decreased with increasing salt content. The ratio of Chl a/Chl b and carotenoid/Chl exhibited sig-nificant increase under 400 mM NaCl. However, total flavonoid and anthocyanin contents and key enzyme activities in the flavonoid pathway including phenylalanine ammonialyase (PAL) and Chalcone isomerase (CHI) decreased under salt stress. These findings possibly suggest that R. soongorica has an adaptation protection mechanism against salt-induced oxidative damage by inducing the activity of antioxidant enzymes and maintaining a steady level of carotenoid/Chl.

  10. Nuclear hormone receptors as mediators of metabolic adaptability following reproductive perturbations.

    Ratnappan, Ramesh; Ward, Jordan D; Yamamoto, Keith R; Ghazi, Arjumand

    2016-01-01

    Previously, we identified a group of nuclear hormone receptors (NHRs) that promote longevity in the nematode Caenorhabditis elegans following germline-stem cell (GSC) loss. This group included NHR-49, the worm protein that performs functions similar to vertebrate PPARα, a key regulator of lipid metabolism. We showed that NHR-49/PPARα enhances mitochondrial β-oxidation and fatty acid desaturation upon germline removal, and through the coordinated enhancement of these processes allows the animal to retain lipid homeostasis and undergo lifespan extension. NHR-49/PPARα expression is elevated in GSC-ablated animals, in part, by DAF-16/FOXO3A and TCER-1/TCERG1, two other conserved, pro-longevity transcriptional regulators that are essential for germline-less longevity. In exploring the roles of the other pro-longevity NHRs, we discovered that one of them, NHR-71/HNF4, physically interacted with NHR-49/PPARα. NHR-71/HNF4 did not have a broad impact on the expression of β-oxidation and desaturation targets of NHR-49/PPARα. But, both NHR-49/PPARα and NHR-71/HNF4 were essential for the increased expression of DAF-16/FOXO3A- and TCER-1/TCERG1-downstream target genes. In addition, nhr-49 inactivation caused a striking membrane localization of KRI-1, the only known common upstream regulator of DAF-16/FOXO3A and TCER-1/TCERG1, suggesting that it may operate in a positive feedback loop to potentiate the activity of this pathway. These data underscore how selective interactions between NHRs that function as nodes in metabolic networks, confer functional specificity in response to different physiological stimuli. PMID:27073739

  11. Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila.

    Williams, Stephanie; Dew-Budd, Kelly; Davis, Kristen; Anderson, Julie; Bishop, Ruth; Freeman, Kenda; Davis, Dana; Bray, Katherine; Perkins, Lauren; Hubickey, Joana; Reed, Laura K

    2015-12-01

    Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual's genetic and environmental context. PMID:26530416

  12. A comparative study of the metabolic profile, insulin sensitivity and inflammatory response between organically and conventionally managed dairy cattle during the periparturient period.

    Abuelo, A; Hernández, J; Benedito, J L; Castillo, C

    2014-09-01

    The number of organically managed cattle (OMC) within the European Union has increased tremendously in the last decade. However, there are still some concerns about animals under this farming system meeting their dietary requirements for milk production. The aim of this study was to compare the metabolic adaptations to the onset of lactation in three different herds, one conventional and two organic ones. Twenty-two conventionally managed cattle (CMC) and 20 from each organic farm were sampled throughout the periparturient period. These samplings were grouped into four different stages: (i) far-off dry, (ii) close-up dry, (iii) fresh and (iv) peak of lactation and compared among them. In addition, the results of periparturient animals were also compared within each management type with a control group (animals between the 4th and 5th months of pregnancy). Metabolic profiles were used to assess the health status of the herds, along with the quantification of the acute phase proteins haptoglobin and serum amyloid A, insulin and the calculation of different surrogate indices of insulin sensitivity. Generalised linear mixed models with repeated measurements were used to study the effect of the stage, management type or their interaction on the serum variables studied. The prevalence of subclinical ketosis was higher in OMC, although they showed better insulin sensitivity, a lower degree of inflammation and less liver injury, without a higher risk of macromineral deficiencies. Therefore, attention should be paid on organic farms to the nutritional management of cows around the time of calving in order to prevent the harmful consequences of excessive negative energy balance. Moreover, it must be taken into account that most of the common practices used to treat this condition in CMC are not allowed on a systematic basis in OMC. PMID:24916777

  13. Adaptive mutations in sugar metabolism restore growth on glucose in a pyruvate decarboxylase negative yeast strain

    Zhang, Yiming; Liu, Guodong; Engqvist, Martin K. M.;

    2015-01-01

    carbon source, and requires supplementation of C2 compounds to the medium in order to meet the requirement for cytosolic acetyl-CoA for biosynthesis of fatty acids and ergosterol. Results: In this study, a Pdc negative strain was adaptively evolved for improved growth in glucose medium via serial......Background: A Saccharomyces cerevisiae strain carrying deletions in all three pyruvate decarboxylase (PDC) genes (also called Pdc negative yeast) represents a non-ethanol producing platform strain for the production of pyruvate derived biochemicals. However, it cannot grow on glucose as the sole...... transfer, resulting in three independently evolved strains, which were able to grow in minimal medium containing glucose as the sole carbon source at the maximum specific rates of 0.138, 0.148, 0.141 h-1, respectively. Several genetic changes were identified in the evolved Pdc negative strains by genomic...

  14. Indigenous and adapted energy technologies and energy efficiency [Brazil: A country profile on sustainable energy development

    Brazil has significant experience in the development and use of innovative technologies. This chapter presents and discusses general aspects of indigenous and adapted energy technologies in Brazil and analyses of energy efficiencies of selected technologies. The most important technologies include sugar cane production and conversion to ethanol, hydropower, electricity transmission and offshore oil production

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

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

    2015-01-01

    of orientation, which provide a mathematical machinery for efficient and stable adaptation. Experimentally we show that the robot’s performance can be significantly improved within a few iteration steps, compensating for vision and other errors that might arise during the execution of the task. We also show...... that our methodology is suitable both for robots with admittance and for robots with impedance control....

  16. Educational Multimedia Profiling Recommendations for Device-Aware Adaptive Mobile Learning

    Moldovan, Arghir-Nicolae; Ghergulescu, Ioana; Muntean, Cristina Hava

    2014-01-01

    Mobile learning is seeing a fast adoption with the increasing availability and affordability of mobile devices such as smartphones and tablets. As the creation and consumption of educational multimedia content on mobile devices is also increasing fast, educators and mobile learning providers are faced with the challenge to adapt multimedia type…

  17. Profiling and Metabolism of Sterols in the Weaver Ant Genus Oecophylla.

    Vidkjær, Nanna H; Jensen, Karl-Martin V; Gislum, René; Fomsgaard, Inge S

    2016-01-01

    Sterols are essential to insects because they are vital for many biochemical processes, nevertheless insects cannot synthesize sterols but have to acquire them through their diet. Studies of sterols in ants are sparse and here the sterols of the weaver ant genus Oecophylla are identified for the first time. The sterol profile and the dietary sterols provided to a laboratory Oecophylla longinoda colony were analyzed. Most sterols originated from the diet, except one, which was probably formed via dealkylation in the ants and two sterols of fungal origin, which likely originate from hitherto unidentified endosymbionts responsible for supplying these two compounds. The sterol profile of a wild Oecophylla smaragdina colony was also investigated. Remarkable qualitative similarities were established between the two species despite the differences in diet, species, and origin. This may reflect a common sterol need/aversion in the weaver ants. Additionally, each individual caste of both species displayed unique sterol profiles. PMID:26996016

  18. Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and Pareto filters.

    Carlos Pozo

    Full Text Available Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study

  19. Comprehensive Analysis of PPARα-Dependent Regulation of Hepatic Lipid Metabolism by Expression Profiling

    Maryam Rakhshandehroo

    2007-09-01

    Full Text Available PPARα is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARα in hepatic lipid metabolism, many PPARα-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARα-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARα target genes, livers from several animal studies in which PPARα was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARα-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARα-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip, electron-transferring-flavoprotein β polypeptide (Etfb, electron-transferring-flavoprotein dehydrogenase (Etfdh, phosphatidylcholine transfer protein (Pctp, endothelial lipase (EL, Lipg, adipose triglyceride lipase (Pnpla2, hormone-sensitive lipase (HSL, Lipe, and monoglyceride lipase (Mgll. Using an in silico screening approach, one or more PPAR response elements (PPREs were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARα agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARα. Our study illustrates the power of transcriptional profiling to uncover novel PPARα-regulated genes and pathways in liver.

  20. Microbial metabolic profiles in Australian soils with varying crop management strategies

    Aldorri, Sind; McMillan, Mary; Pereg, Lily

    2015-04-01

    Cotton production belt in Australia is covering vast areas from subtropical to temperate and grassland. Soil types are mostly different variations of clay with mainly black, grey and red clay soil containing variable proportions of sand in it. Growers often grow cotton in rotation with other crops, such as wheat, beans and corn, and soil fertilization vary with a number of growers using organic amendments as a main or supplementary source of nutrients. We have collected soil samples from farms in different regions and with different crop management strategies and studied the metabolic signature of microbial communities using the Biolog Ecoplate system. The metabolic patterns, supplemented with molecular analysis of the community will further the understanding of the influence of crop and soil management on soil functions carried out by microbes.

  1. Development of a UHPLC method for the assessment of the metabolic profile of cinitapride.

    Marquez, Helena; Albertí, Joan; Salvà, Miquel; Saurina, Javier; Sentellas, Sonia

    2011-12-01

    An ultra high-performance liquid chromatographic method was developed to study the cinitapride metabolism. Metabolites were generated from the incubation of cinitapride with human liver microsomes. Cinitapride and its metabolites were separated by reversed-phase mode using a formate aqueous solution (pH 6.5) and acetonitrile as the components of the mobile phase. Chromatographic conditions, including the establishment of an elution gradient, were optimized for obtaining the maximum number of resolved components in the minimum analysis time. Experimental design and multicriteria decision-making strategies were utilized to facilitate the optimization of chromatographic conditions. Figures of merit were evaluated with cinitapride standards and incubated samples. Limits of detection are about 0.03 μmol/L, and repeatabilities are better than 0.06% for retention times and better than 3.5% for concentrations. The method was applied to characterize the in vitro cinitapride metabolism with human liver microsomes. PMID:21695682

  2. Nutrition, metabolic profiles and puberty in Brahman (Bos indicus) beef heifers.

    Samadi, F; Blache, D; Martin, G B; D'Occhio, M J

    2014-05-01

    The aim of the present study was to gain an improved understanding of the relationships between body weight (BW), body condition (BCS), and metabolic homeostasis, and the attainment of puberty in Brahman heifers in a subtropical environment. Brahman heifers (200±3kg BW; 2.00±0.0 BCS) were assigned to a moderate nutrition (MN, n=11) or improved nutrition (IN, n=11) treatment from 11 to 23 months-of-age. The heifers were monitored at regular intervals for circulating concentrations of GH, IGF-1, insulin, glucose and leptin, and ovarian follicular activity was recorded until the first ovulation. From approximately 16 months of age, heifers on IN had a greater (PBrahman heifers on IN had a metabolic homeostasis that was supportive of reproductive maturation and puberty. PMID:24725537

  3. Metabolic and Endocrine Profiles in Response to Systemic Infusion of Fructose and Glucose in Rhesus Macaques

    Adams, Sean H.; Stanhope, Kimber L.; Grant, Ryan W.; Cummings, Bethany P.; Havel, Peter J.

    2008-01-01

    Diurnal patterns of circulating leptin concentrations are attenuated after consumption of fructose-sweetened beverages compared with glucose-sweetened beverages, likely a result of limited postprandial glucose and insulin excursions after fructose. Differences in postprandial exposure of adipose tissue to peripheral circulating fructose and glucose or in adipocyte metabolism of the two sugars may also be involved. Thus, we compared plasma leptin concentrations after 6-h iv infusions of saline...

  4. Profiling the control of hepatic glucose and lipid metabolism for evaluating novel strategies of insulin delivery

    Soares, Ana Francisca Leal Silva

    2011-01-01

    Diabetes mellitus (DM) is a metabolic disorder that results from a dysfunction of insulin secretion (type 1) and/or sensitivity (type 2). Type 1 and in many cases type 2 diabetic patients require daily insulin injections to control blood glucose levels and retard the appearance of diabetes-related complications. The liver plays a central role in the context of whole-body glucose homoeostasis and fuel management in general. Under physiological conditions, insulin is released by the pancr...

  5. Morphometric Variables Related to Metabolic Profile in Captive Chimpanzees (Pan troglodytes)

    Andrade, Marcia CR; Higgins, Paul B.; Mattern, Vicki L; Garza, Melissa A De La; Brasky, Kathleen M.; Voruganti, V. Saroja; Comuzzie, Anthony G.

    2011-01-01

    Obesity is a risk factor for several diseases including type 2 diabetes and cardiovascular disease. The aim of this study was to compare the relationships of waist circumference and body weight with circulating markers of metabolic, cardiovascular, and hepatic function in chimpanzees (Pan troglodytes). After a 12-h fast, blood was collected from 39 adult captive chimpanzees for measurement of serum glucose, BUN, creatinine, albumin, cholesterol, ALT, AST, ALP, total and direct bilirubin, trig...

  6. Metabolic profile of phillyrin in rats obtained by UPLC-Q-TOF-MS.

    Wang, Hairong; Zhang, Xiaoxu; Jia, Peipei; Zhang, Yanfen; Tang, Siwen; Wang, Hongtao; Li, Song; Yu, Xinluan; Li, Yingfei; Zhang, Lantong

    2016-06-01

    Forsythia suspensa Vahl (Oleaceae) is an important original plant in traditional Chinese medicine. The air-dried fruits of Forsythia suspensa have long been used to relieve respiratory symptoms. Phillyrin is one of the main chemical constituent of Forsythia suspensa. A clear understanding of the metabolism of phillyrin is very important in rational clinical use and pharmacological research. In this study, the metabolism of phillyrin in rat was investigated for the first time using an ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) method. Bile, urine and feces were collected from rats after single-dose (10 mg/kg) orally administered phillyrin. Liquid-liquid extraction and ultrasonic extraction were used to prepare samples. UPLC-Q-TOF-MS analysis of the phillyrin samples showed that phillyrin was converted to a major metabolite, M26, which underwent deglucosidation, further dehydration and desaturation. A total of 34 metabolites were detected including 30 phase I and four phase II metabolites. The conjugation types and structure skeletons of the metabolites were preliminarily determined. Moreover, 28 new metabolites were reported for the first time. The main biotransformation route of phillyrin was identified as hydrolysis, oxidation and sulfation. These findings enhance our understanding of the metabolism and the real active structures of phillyrin. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26425840

  7. Coordinate changes in histone modifications, mRNA levels, and metabolite profiles in clonal INS-1 832/13 β-cells accompany functional adaptations to lipotoxicity.

    Malmgren, Siri; Spégel, Peter; Danielsson, Anders P H; Nagorny, Cecilia L; Andersson, Lotta E; Nitert, Marloes Dekker; Ridderstråle, Martin; Mulder, Hindrik; Ling, Charlotte

    2013-04-26

    Lipotoxicity is a presumed pathogenetic process whereby elevated circulating and stored lipids in type 2 diabetes cause pancreatic β-cell failure. To resolve the underlying molecular mechanisms, we exposed clonal INS-1 832/13 β-cells to palmitate for 48 h. We observed elevated basal insulin secretion but impaired glucose-stimulated insulin secretion in palmitate-exposed cells. Glucose utilization was unchanged, palmitate oxidation was increased, and oxygen consumption was impaired. Halting exposure of the clonal INS-1 832/13 β-cells to palmitate largely recovered all of the lipid-induced functional changes. Metabolite profiling revealed profound but reversible increases in cellular lipids. Glucose-induced increases in tricarboxylic acid cycle intermediates were attenuated by exposure to palmitate. Analysis of gene expression by microarray showed increased expression of 982 genes and decreased expression of 1032 genes after exposure to palmitate. Increases were seen in pathways for steroid biosynthesis, cell cycle, fatty acid metabolism, DNA replication, and biosynthesis of unsaturated fatty acids; decreases occurred in the aminoacyl-tRNA synthesis pathway. The activity of histone-modifying enzymes and histone modifications of differentially expressed genes were reversibly altered upon exposure to palmitate. Thus, Insig1, Lss, Peci, Idi1, Hmgcs1, and Casr were subject to epigenetic regulation. Our analyses demonstrate that coordinate changes in histone modifications, mRNA levels, and metabolite profiles accompanied functional adaptations of clonal β-cells to lipotoxicity. It is highly likely that these changes are pathogenetic, accounting for loss of glucose responsiveness and perturbed insulin secretion. PMID:23476019

  8. Coordinate Changes in Histone Modifications, mRNA Levels, and Metabolite Profiles in Clonal INS-1 832/13 β-Cells Accompany Functional Adaptations to Lipotoxicity*

    Malmgren, Siri; Spégel, Peter; Danielsson, Anders P.H.; Nagorny, Cecilia L.; Andersson, Lotta E.; Nitert, Marloes Dekker; Ridderstråle, Martin; Mulder, Hindrik; Ling, Charlotte

    2013-01-01

    Lipotoxicity is a presumed pathogenetic process whereby elevated circulating and stored lipids in type 2 diabetes cause pancreatic β-cell failure. To resolve the underlying molecular mechanisms, we exposed clonal INS-1 832/13 β-cells to palmitate for 48 h. We observed elevated basal insulin secretion but impaired glucose-stimulated insulin secretion in palmitate-exposed cells. Glucose utilization was unchanged, palmitate oxidation was increased, and oxygen consumption was impaired. Halting exposure of the clonal INS-1 832/13 β-cells to palmitate largely recovered all of the lipid-induced functional changes. Metabolite profiling revealed profound but reversible increases in cellular lipids. Glucose-induced increases in tricarboxylic acid cycle intermediates were attenuated by exposure to palmitate. Analysis of gene expression by microarray showed increased expression of 982 genes and decreased expression of 1032 genes after exposure to palmitate. Increases were seen in pathways for steroid biosynthesis, cell cycle, fatty acid metabolism, DNA replication, and biosynthesis of unsaturated fatty acids; decreases occurred in the aminoacyl-tRNA synthesis pathway. The activity of histone-modifying enzymes and histone modifications of differentially expressed genes were reversibly altered upon exposure to palmitate. Thus, Insig1, Lss, Peci, Idi1, Hmgcs1, and Casr were subject to epigenetic regulation. Our analyses demonstrate that coordinate changes in histone modifications, mRNA levels, and metabolite profiles accompanied functional adaptations of clonal β-cells to lipotoxicity. It is highly likely that these changes are pathogenetic, accounting for loss of glucose responsiveness and perturbed insulin secretion. PMID:23476019

  9. Optimization and evaluation of metabolite extraction protocols for untargeted metabolic profiling of liver samples by UPLC-MS.

    Masson, Perrine; Alves, Alexessander Couto; Ebbels, Timothy M D; Nicholson, Jeremy K; Want, Elizabeth J

    2010-09-15

    A series of six protocols were evaluated for UPLC-MS based untargeted metabolic profiling of liver extracts in terms of reproducibility and number of metabolite features obtained. These protocols, designed to extract both polar and nonpolar metabolites, were based on (i) a two stage extraction approach or (ii) a simultaneous extraction in a biphasic mixture, employing different volumes and combinations of extraction and resuspension solvents. A multivariate statistical strategy was developed to allow comparison of the multidimensional variation between the methods. The optimal protocol for profiling both polar and nonpolar metabolites was found to be an aqueous extraction with methanol/water followed by an organic extraction with dichloromethane/methanol, with resuspension of the dried extracts in methanol/water before UPLC-MS analysis. This protocol resulted in a median CV of feature intensities among experimental replicates of data demonstrate the robustness of the proposed protocol for extracting metabolites from liver samples and make it well suited for untargeted liver profiling in studies exploring xenobiotic hepatotoxicity and clinical investigations of liver disease. The generic nature of this protocol facilitates its application to other tissues, for example, brain or lung, enhancing its utility in clinical and toxicological studies. PMID:20715759

  10. Synergy between 13C-metabolic flux analysis and flux balance analysis for understanding metabolic adaption to anaerobiosis in e. coli

    Genome-based Flux Balance Analysis (FBA, constraints based flux analysis) and steady state isotopic-labeling-based Metabolic Flux Analysis (MFA) are complimentary approaches to predicting and measuring the operation and regulation of metabolic networks. Here a genome-derived model of E. coli metabol...

  11. Rapid temperature adaptation in trout: Alterations in membrane molecular species metabolism

    Williams, E.E.; Hazel, J.R. (Arizona State Univ., Tempe (United States))

    1991-03-11

    The ability of poikilotherms to change their membrane phospholipid composition in response to long term temperature change is well documented. Less understood are the changes which occur when rapid temperature fluctuations are encountered. The authors have followed the fate of 16:0/18:1 phosphatidylcholine (PC), radiocarbon labeled at the 18:1 acyl chain, in the plasma membranes of trout hepatocytes. After isolation by PC, 5%-10% of which was taken up into the plasma membranes. The cells were then divided into two groups and either held at acclimation temperature or transferred to 5C. After 1 hour at 20C or 5 hours at 5C the plasma membranes were isolated, the lipids extracted, and the PC fraction was resolved into its molecular species. The distribution of radiolabel between the warm and cold exposed cells was then determined. In both groups radioactivity was found in molecular species other than 16:0/18:1, however no radioactivity was found in lipids other than PC. Cold exposed cells contained less radioactivity in 18:2/18:2, 20:1/22:6, 16:0/18:2 and 18:0/18:1 PC than the warm cells, but contained more in 18:1/18:1 PC. These results indicate that the environmental temperature influences the rates of in situ desaturation, chain elongation, and intermolecular acyl chain regroupings. Subtle changes in molecular species metabolism might be important early steps in temperature acclimation.

  12. Role of Hypothalamic VGF in Energy Balance and Metabolic Adaption to Environmental Enrichment in Mice.

    Foglesong, Grant D; Huang, Wei; Liu, Xianglan; Slater, Andrew M; Siu, Jason; Yildiz, Vedat; Salton, Stephen R J; Cao, Lei

    2016-03-01

    Environmental enrichment (EE), a housing condition providing complex physical, social, and cognitive stimulation, leads to improved metabolic health and resistance to diet-induced obesity and cancer. One underlying mechanism is the activation of the hypothalamic-sympathoneural-adipocyte axis with hypothalamic brain-derived neurotrophic factor (BDNF) as the key mediator. VGF, a peptide precursor particularly abundant in the hypothalamus, was up-regulated by EE. Overexpressing BDNF or acute injection of BDNF protein to the hypothalamus up-regulated VGF, whereas suppressing BDNF signaling down-regulated VGF expression. Moreover, hypothalamic VGF expression was regulated by leptin, melanocortin receptor agonist, and food deprivation mostly paralleled to BDNF expression. Recombinant adeno-associated virus-mediated gene transfer of Cre recombinase to floxed VGF mice specifically decreased VGF expression in the hypothalamus. In contrast to the lean and hypermetabolic phenotype of homozygous germline VGF knockout mice, specific knockdown of hypothalamic VGF in male adult mice led to increased adiposity, decreased core body temperature, reduced energy expenditure, and impaired glucose tolerance, as well as disturbance of molecular features of brown and white adipose tissues without effects on food intake. However, VGF knockdown failed to block the EE-induced BDNF up-regulation or decrease of adiposity indicating a minor role of VGF in the hypothalamic-sympathoneural-adipocyte axis. Taken together, our results suggest hypothalamic VGF responds to environmental demands and plays an important role in energy balance and glycemic control likely acting in the melanocortin pathway downstream of BDNF. PMID:26730934

  13. Drug metabolism: Comparison of biodistribution profile of holmium in three different compositions in healthy Wistar rats.

    Cerqueira-Coutinho, Cristal; Vidal, Lluis Pascual; Pinto, Suyene Rocha; Santos-Oliveira, Ralph

    2016-06-01

    Radioisotope holmium is a candidate to be used in cancer treatment and diagnosis. There are different holmium salts and they present distinct solubility and consequently different biodistribution profiles. In this work, we aimed to evaluate the biodistribution profiles of two holmium salts (chloride and sulfate) and holmium nanoparticles (oxide) through an in vivo biodistribution assay using animal model. Samples were labeled with technetium-99m and administered in Wistar rats by retro-orbital route. Holmium chloride is highly soluble in water and it was quickly filtered by the kidneys while holmium sulfate that presents lower solubility in water was mainly found in the liver and the spleen. However, both the salts showed a similar biodistribution profile. On the other hand, holmium oxide showed a very different biodistribution profile since it seemed to interact with all organs. Due to its particle size range (approximately 100nm) it was not intensively filtered by the kidneys being found in high quantities in many organs, for this reason its use as a nanoradiopharmaceutical could be promising in the oncology field. PMID:26986812

  14. Towards real-time metabolic profiling of a biopsy specimen during a surgical operation by 1H high resolution magic angle spinning nuclear magnetic resonance: a case report

    Piotto Martial

    2012-01-01

    Full Text Available Abstract Introduction Providing information on cancerous tissue samples during a surgical operation can help surgeons delineate the limits of a tumoral invasion more reliably. Here, we describe the use of metabolic profiling of a colon biopsy specimen by high resolution magic angle spinning nuclear magnetic resonance spectroscopy to evaluate tumoral invasion during a simulated surgical operation. Case presentation Biopsy specimens (n = 9 originating from the excised right colon of a 66-year-old Caucasian women with an adenocarcinoma were automatically analyzed using a previously built statistical model. Conclusions Metabolic profiling results were in full agreement with those of a histopathological analysis. The time-response of the technique is sufficiently fast for it to be used effectively during a real operation (17 min/sample. Metabolic profiling has the potential to become a method to rapidly characterize cancerous biopsies in the operation theater.

  15. Differential effect of ultraviolet-B radiation on certain metabolic processes in a chromatically adapting Nostoc

    Tyagi, R.; Srinivas, G.; Vyas, D.; Kumar, A.; Kumar, H.D. (Banaras Hindu Univ., Varanasi (India))

    1992-03-01

    The impact of UV-B radiation on growth, pigmentation and certain physiological processes was studied in a N{sub 2}-fixing chromatically adapting cyanobacterium, Nostoc spongiaeforme. A brownish form (phycoerythrin rich) was found to be more tolerant to UV-B than the blue-green (phycocyanin rich) form of N. spongiaeforme. Continuous exposure to UV-B (5.5 W m{sup -2}) for 90 min caused complete killing of the blue-green strain whereas the brown strain showed complete loss of survival after 180 min. Pigment content was more strongly inhibited in the blue-green strain than in the brown. Nitrogenase activity was completely abolished in both strains within 35 min of UV-B treatment. Restoration of nitrogenase occurred upon transfer to fluorescent or incandescent light after a lag of 5-6 h, suggesting fresh synthesis of nitrogenase. In vivo nitrate reductase activity was stimulated by UV-B treatment, the degree of enhancement being significantly higher in the blue-green strain. {sup 14}CO{sub 2} uptake was also completely abolished by UV-B treatment in both strains. (author).

  16. NMR-based characterization of metabolic alterations in hypertension using an adaptive, intelligent binning algorithm.

    De Meyer, Tim; Sinnaeve, Davy; Van Gasse, Bjorn; Tsiporkova, Elena; Rietzschel, Ernst R; De Buyzere, Marc L; Gillebert, Thierry C; Bekaert, Sofie; Martins, José C; Van Criekinge, Wim

    2008-05-15

    As with every -omics technology, metabolomics requires new methodologies for data processing. Due to the large spectral size, a standard approach in NMR-based metabolomics implies the division of spectra into equally sized bins, thereby simplifying subsequent data analysis. Yet, disadvantages are the loss of information and the occurrence of artifacts caused by peak shifts. Here, a new binning algorithm, Adaptive Intelligent Binning (AI-Binning), which largely circumvents these problems, is presented. AI-Binning recursively identifies bin edges in existing bins, requires only minimal user input, and avoids the use of arbitrary parameters or reference spectra. The performance of AI-Binning is demonstrated using serum spectra from 40 hypertensive and 40 matched normotensive subjects from the Asklepios study. Hypertension is a major cardiovascular risk factor characterized by a complex biochemistry and, in most cases, an unknown origin. The binning algorithm resulted in an improved classification of hypertensive status compared with that of standard binning and facilitated the identification of relevant metabolites. Moreover, since the occurrence of noise variables is largely avoided, AI-Binned spectra can be unit-variance scaled. This enables the detection of relevant, low-intensity metabolites. These results demonstrate the power of AI-Binning and suggest the involvement of alpha-1 acid glycoproteins and choline biochemistry in hypertension. PMID:18419139

  17. Differential effect of ultraviolet-B radiation on certain metabolic processes in a chromatically adapting Nostoc

    The impact of UV-B radiation on growth, pigmentation and certain physiological processes was studied in a N2-fixing chromatically adapting cyanobacterium, Nostoc spongiaeforme. A brownish form (phycoerythrin rich) was found to be more tolerant to UV-B than the blue-green (phycocyanin rich) form of N. spongiaeforme. Continuous exposure to UV-B (5.5 W m-2) for 90 min caused complete killing of the blue-green strain whereas the brown strain showed complete loss of survival after 180 min. Pigment content was more strongly inhibited in the blue-green strain than in the brown. Nitrogenase activity was completely abolished in both strains within 35 min of UV-B treatment. Restoration of nitrogenase occurred upon transfer to fluorescent or incandescent light after a lag of 5-6 h, suggesting fresh synthesis of nitrogenase. In vivo nitrate reductase activity was stimulated by UV-B treatment, the degree of enhancement being significantly higher in the blue-green strain. 14CO2 uptake was also completely abolished by UV-B treatment in both strains. (author)

  18. Metabolic engineering and adaptive evolution for efficient production of D-lactic acid in Saccharomyces cerevisiae.

    Baek, Seung-Ho; Kwon, Eunice Y; Kim, Yong Hwan; Hahn, Ji-Sook

    2016-03-01

    There is an increasing demand for microbial production of lactic acid (LA) as a monomer of biodegradable poly lactic acid (PLA). Both optical isomers, D-LA and L-LA, are required to produce stereocomplex PLA with improved properties. In this study, we developed Saccharomyces cerevisiae strains for efficient production of D-LA. D-LA production was achieved by expressing highly stereospecific D-lactate dehydrogenase gene (ldhA, LEUM_1756) from Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 in S. cerevisiae lacking natural LA production activity. D-LA consumption after glucose depletion was inhibited by deleting DLD1 encoding D-lactate dehydrogenase and JEN1 encoding monocarboxylate transporter. In addition, ethanol production was reduced by deleting PDC1 and ADH1 genes encoding major pyruvate decarboxylase and alcohol dehydrogenase, respectively, and glycerol production was eliminated by deleting GPD1 and GPD2 genes encoding glycerol-3-phosphate dehydrogenase. LA tolerance of the engineered D-LA-producing strain was enhanced by adaptive evolution and overexpression of HAA1 encoding a transcriptional activator involved in weak acid stress response, resulting in effective D-LA production up to 48.9 g/L without neutralization. In a flask fed-batch fermentation under neutralizing condition, our evolved strain produced 112.0 g/L D-LA with a yield of 0.80 g/g glucose and a productivity of 2.2 g/(L · h). PMID:26596574

  19. The Effects of Sprint Interval vs. Continuous Endurance Training on Physiological And Metabolic Adaptations in Young Healthy Adults.

    Nalcakan, Gulbin Rudarli

    2014-12-01

    The purpose of this study was to compare the effects of sprint interval training (SIT) and continuous endurance training (CET) on selected anthropometric, aerobic, and anaerobic performance indices as well as the blood lipid profile, inflammatory and muscle damage markers in healthy young males. Fifteen recreationally active male volunteers (age: 21.7 ±2.2 years, body mass: 83.0 ±8.0 kg, body height: 1.82 ±0.05 m) were divided into two groups according to their initial VO2max levels. Training programs were conducted 3 times per week for 7 weeks. The SIT program consisted of 4-6 Wingate anaerobic sprints with a 4.5 min recovery, while CET consisted of 30-50 min cycling at 60% VO2max. Biochemical, anthropometric and fitness assessments were performed both pre and post-intervention. Significant improvements in VO2max, anaerobic power and capacity, and VO2 utilization during the submaximal workout and significant decreases in body fat and in waist circumference after the intervention occurred in both SIT and CET groups. Significantly greater gross efficiency was measured in the CET group. No differences in the lipid profile or serum levels of inflammatory, myocardial and skeletal muscle damage markers were observed after the training period. The study results agree with the effectiveness of a 30 s all-out training program with a reduced time commitment for anthropometric, aerobic and anaerobic adaptation and eliminate doubts about its safety as a model. PMID:25713670

  20. Metabolic Responses of Poplar to Apripona germari (Hope) as Revealed by Metabolite Profiling

    Lijuan Wang; Liangjian Qu; Liwei Zhang; Jianjun Hu; Fang Tang; Mengzhu Lu

    2016-01-01

    Plants have developed biochemical responses to adapt to biotic stress. To characterize the resistance mechanisms in poplar tree against Apripona germari, comprehensive metabolomic changes of poplar bark and xylem in response to A. germari infection were examined by gas chromatography time-of-flight mass spectrometry (GC–TOF/MS). It was found that, four days after feeding (stage I), A. germari infection brought about changes in various metabolites, such as phenolics, amino acids and sugars in ...

  1. Effect of adaptation to ethanol on cytoplasmic and membrane protein profiles of Oenococcus oeni

    Silveira, da, Fabio Land; Baumgärtner, M.; Rombouts, F. M.; Abee, T.

    2004-01-01

    The practical application of commercial malolactic starter cultures of Oenococcus oeni surviving direct inoculation in wine requires insight into mechanisms of ethanol toxicity and of acquired ethanol tolerance in this organism. Therefore, the site-specific location of proteins involved in ethanol adaptation, including cytoplasmic, membrane-associated, and integral membrane proteins, was investigated. Ethanol triggers alterations in protein patterns of O. oeni cells stressed with 12% ethanol ...

  2. Effect of Adaptation to Ethanol on Cytoplasmic and Membrane Protein Profiles of Oenococcus oeni

    2004-01-01

    The practical application of commercial malolactic starter cultures of Oenococcus oeni surviving direct inoculation in wine requires insight into mechanisms of ethanol toxicity and of acquired ethanol tolerance in this organism. Therefore, the site-specific location of proteins involved in ethanol adaptation, including cytoplasmic, membrane-associated, and integral membrane proteins, was investigated. Ethanol triggers alterations in protein patterns of O. oeni cells stressed with 12% ethanol ...

  3. Changes in C-N metabolism under elevated CO2 and temperature in Indian mustard (Brassica juncea L.): an adaptation strategy under climate change scenario.

    Seth, Chandra Shekhar; Misra, Virendra

    2014-11-01

    The present study was performed to investigate the possible role of carbon (C) and nitrogen (N) metabolism in adaptation of Indian mustard (Brassica juncea L.) growing under ambient (370 ± 15 ppm) and elevated CO2 (700 ± 15 ppm), and jointly in elevated CO2 and temperature (30/22 °C for day/night). The key enzymes responsible for C-N metabolism were studied in different samples of Brassica juncea L. collected from ambient (AMB), elevated (ELE) and ELExT growth conditions. Total percent amount of C and N in leaves were particularly estimated to establish a clear understanding of aforesaid metabolism in plant adaptation. Furthermore, key morphological and physiological parameters such as plant height, leaf area index, dry biomass, net photosynthetic rate, stomatal conductance, transpiration, total protein and chlorophyll contents were also studied in relation to C/N metabolism. The results indicated that the C-metabolizing enzymes, such as (ribulose-1,5-bisphosphate carboxylase/oxygenase, phosphoenolpyruvate carboxylase, malate dehydrogenase, NAD-malic enzyme, NADP-malic enzyme and citrate synthase) and the N-metabolizing enzymes, such as (aspartate amino transferase, glutamine synthetase, nitrate reductase and nitrite reductase) showed significantly (P ELE > ELExT > AMB growth conditions. This is also evident by significant (P < 0.05) increase in percent contents of C and N in leaves as per said order. These findings suggested that improved performance of C-N metabolism could be a possible approach for CO2 assimilation and adaptation in Brassica juncea L. against elevated CO2 and temperature prevailing in climate change scenarios. PMID:25246072

  4. Acylcarnitine Profiles in Acetaminophen Toxicity in the Mouse: Comparison to Toxicity, Metabolism and Hepatocyte Regeneration

    Jack Hinson

    2013-08-01

    Full Text Available High doses of acetaminophen (APAP result in hepatotoxicity that involves metabolic activation of the parent compound, covalent binding of the reactive intermediate N-acetyl-p-benzoquinone imine (NAPQI to liver proteins, and depletion of hepatic glutathione. Impaired fatty acid β-oxidation has been implicated in previous studies of APAP-induced hepatotoxicity. To better understand relationships between toxicity and fatty acid β-oxidation in the liver in APAP toxicity, metabolomic assays for long chain acylcarnitines were examined in relationship to established markers of liver toxicity, oxidative metabolism, and liver regeneration in a time course study in mice. Male B6C3F1 mice were treated with APAP (200 mg/kg IP or saline and sacrificed at 1, 2, 4, 8, 24 or 48 h after APAP. At 1 h, hepatic glutathione was depleted and APAP protein adducts were markedly increased. Alanine aminotransferase (ALT levels were elevated at 4 and 8 h, while proliferating cell nuclear antigen (PCNA expression, indicative of hepatocyte regeneration, was apparent at 24 h and 48 h. Elevations of palmitoyl, oleoyl and myristoyl carnitine were apparent by 2–4 h, concurrent with the onset of Oil Red O staining in liver sections. By 8 h, acylcarnitine levels were below baseline levels and remained low at 24 and 48 h. A partial least squares (PLS model suggested a direct association of acylcarnitine accumulation in serum to APAP protein adduct and hepatic glutathione levels in mice. Overall, the kinetics of serum acylcarnitines in APAP toxicity in mice followed a biphasic pattern involving early elevation after the metabolism phases of toxicity and later depletion of acylcarnitines.

  5. Mineral and metabolic profiles in tea leaves and flowers during flower development.

    Jia, Sisi; Wang, Yu; Hu, Jianhui; Ding, Zhaotang; Liang, Qing; Zhang, Yinfei; Wang, Hui

    2016-09-01

    Tea [Camellia sinensis (L.) O. Kuntze] is one of the most popular non-alcoholic beverage crops in the world, and the physiological processes and gene regulations involved in development in tea plants have been well characterized. However, relatively little is known about the metabolic changes combined with mineral distributions that occur during flower development. Here we detected the contents of 11 elements in tea leaves and flowers and found that, some of them, especially phosphorus, sulfur and copper, showed significant changes during tea flowering. We also detected 122 metabolites in tea leaves and flowers and found that, 72 of them showed significant differences between flowers and leaves, of which sugars, organic acids, and flavonoids dominated. The sugars, such as trehalose and galactose, all accumulated in tea flowers, and the organic acids, such as malic acid, citric acid and fumaric acid involved in TCA cycle. The flavonoids, like epicatechin, catechin gallate and epigallocatechin, were more abundant in leaves. Furthermore, we found that the contents of 33 metabolites changed during the development of flowers. Especially, citric acid, phenylalanine and most flavonoids decreased while fructose and galactose increased during flowering stages in flowers. We also analyzed the correlations between the ions and metabolites and found that, some mineral nutrients including phosphorus, sulfur, manganese and zinc had close relations to organic acids, flavonoids, sugars and several amino acids during flowering. We mapped the metabolic pathway according to the KEGG database. This work will serve as the foundation for a systems biology approach to the understanding of mineral metabolism. PMID:27372442

  6. The Variable Regions of Lactobacillus rhamnosus Genomes Reveal the Dynamic Evolution of Metabolic and Host-Adaptation Repertoires.

    Ceapa, Corina; Davids, Mark; Ritari, Jarmo; Lambert, Jolanda; Wels, Michiel; Douillard, François P; Smokvina, Tamara; de Vos, Willem M; Knol, Jan; Kleerebezem, Michiel

    2016-01-01

    Lactobacillus rhamnosus is a diverse Gram-positive species with strains isolated from different ecological niches. Here, we report the genome sequence analysis of 40 diverse strains of L. rhamnosus and their genomic comparison, with a focus on the variable genome. Genomic comparison of 40 L. rhamnosus strains discriminated the conserved genes (core genome) and regions of plasticity involving frequent rearrangements and horizontal transfer (variome). The L. rhamnosus core genome encompasses 2,164 genes, out of 4,711 genes in total (the pan-genome). The accessory genome is dominated by genes encoding carbohydrate transport and metabolism, extracellular polysaccharides (EPS) biosynthesis, bacteriocin production, pili production, the cas system, and the associated clustered regularly interspaced short palindromic repeat (CRISPR) loci, and more than 100 transporter functions and mobile genetic elements like phages, plasmid genes, and transposons. A clade distribution based on amino acid differences between core (shared) proteins matched with the clade distribution obtained from the presence-absence of variable genes. The phylogenetic and variome tree overlap indicated that frequent events of gene acquisition and loss dominated the evolutionary segregation of the strains within this species, which is paralleled by evolutionary diversification of core gene functions. The CRISPR-Cas system could have contributed to this evolutionary segregation. Lactobacillus rhamnosus strains contain the genetic and metabolic machinery with strain-specific gene functions required to adapt to a large range of environments. A remarkable congruency of the evolutionary relatedness of the strains' core and variome functions, possibly favoring interspecies genetic exchanges, underlines the importance of gene-acquisition and loss within the L. rhamnosus strain diversification. PMID:27358423

  7. Nutrient depletion and metabolic profiles in breast carcinoma cell lines measured with a label-free platform.

    Demmel, F; Brischwein, M; Wolf, P; Huber, F; Pfister, C; Wolf, B

    2015-07-01

    The response of two well-characterized human breast cancer cell lines (MCF-7 and MDA-MB-231) to a series of nutrient deficiencies is investigated with a label-free cell assay platform. The motivation of the research is to analyze adaptive responses of tumor cell metabolism and to find limiting conditions for cell survival. The platform measures extracellular values of pH and dissolved oxygen saturation to provide data of extracellular acidification rates and oxygen uptake rates. Additional electric cell substrate impedance sensing and bright-field cell imaging supports the data interpretation by providing information about cell morphological parameters. A sequential administration of nutrient depletions does not cause metabolic reprogramming, since the ratios of oxygen uptake to acidification return to their basal values. While the extracellular acidification drops sharply upon reduction of glucose and glutamine, the oxygen uptake is not affected. In contrast to other published data, cell death is not observed when both glucose and glutamine are depleted and cell proliferation is not inhibited, at least in MCF-7 cultures. It is assumed that residual concentrations of nutrients from the serum component are able to maintain cell viability when delivered regularly by active flow like in the cell assay platform, and, in a similar way, under physiological conditions. PMID:26015442

  8. An efficient xylose-fermenting recombinant Saccharomyces cerevisiae strain obtained through adaptive evolution and its global transcription profile

    Shen, Yu; Chen, Xiao; Peng, Bingyin; Chen, Liyuan; Hou, Jin; Bao, Xiaoming [Shandong Univ., Jinan (China). State Key Lab. of Microbial Technology

    2012-11-15

    Factors related to ethanol production from xylose in engineered Saccharomyces cerevisiae that contain an exogenous initial metabolic pathway are still to be elucidated. In the present study, a strain that expresses the xylose isomerase gene of Piromyces sp. Pi-xylA and overexpresses XKS1, RPE1, RKI1, TAL1, and TKL1, with deleted GRE3 and COX4 genes was constructed. The xylose utilization capacity of the respiratory deficiency strain was poor but improved via adaptive evolution in xylose. The {mu}{sub max} of the evolved strain in 20 gl{sup -1} xylose is 0.11 {+-} 0.00 h{sup -1}, and the evolved strain consumed 17.83 gl{sup -1} xylose within 72 h, with an ethanol yield of 0.43 gg{sup -1} total consumed sugars during glucose-xylose cofermentation. Global transcriptional changes and effect of several specific genes were studied. The result revealed that the increased xylose isomerase activity, the upregulation of enzymes involved in glycolysis and glutamate synthesis, and the downregulation of trehalose and glycogen synthesis, may have contributed to the improved xylose utilization of the strain. Furthermore, the deletion of PHO13 decreased the xylose growth in the respiration deficiency strain although deleting PHO13 can improve the xylose metabolism in other strains. (orig.)

  9. Metabolic Profile of Offspring from Diabetic Wistar Rats Treated with Mentha piperita (Peppermint)

    Barbalho, Sandra M.; Damasceno, Débora C; Ana Paula Machado Spada; Vanessa Sellis da Silva; Karla Aparecida Martuchi; Marie Oshiiwa; Flávia M. V. Farinazzi Machado; Claudemir Gregório Mendes

    2011-01-01

    This study aimed at evaluating glycemia and lipid profile of offspring from diabetic Wistar rats treated with Mentha piperita (peppermint) juice. Male offspring from nondiabetic dams (control group: 10 animals treated with water and 10 treated with peppermint juice) and from dams with streptozotocin-induced severe diabetes (diabetic group: 10 animals treated with water and 10 treated with peppermint juice) were used. They were treated during 30 days, and, after the treatment period, levels of...

  10. Gene expression profiling of sex differences in HIF1-dependent adaptive cardiac responses to chronic hypoxia

    Bohuslavová, Romana; Kolář, František; Kuthanová, Lada; Neckář, Jan; Tichopád, Aleš; Pavlínková, Gabriela

    2010-01-01

    Roč. 109, č. 4 (2010), s. 1195-1202. ISSN 8750-7587 R&D Projects: GA ČR GA301/09/0117 Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z50110509 Keywords : Hypoxia inducible factor 1 alpha * hypoxia * gene expression profiling Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.232, year: 2010

  11. 1H High Resolution Magic-Angle Coil Spinning (HR-MACS) µNMR Metabolic Profiling of whole Saccharomyces cervisiae cells: A Demonstrative Study

    AlanWong

    2014-01-01

    The low sensitivity of Nuclear Magnetic Resonance (NMR) is its prime shortcoming compared to other analytical methods for metabolomic studies. It relies on large sample volume (30–50 µl for HR-MAS) for rich metabolic profiling, hindering high-throughput screening especially when the sample requires a labor-intensive preparation or is a sacred specimen. This is indeed the case for some living organisms. This study evaluates a 1H HR-MAS approach for metabolic profiling of small volume (250 nl) ...

  12. Expression profiling of skeletal muscle following acute and chronic β2-adrenergic stimulation: implications for hypertrophy, metabolism and circadian rhythm

    Lynch Gordon S

    2009-09-01

    Full Text Available Abstract Background Systemic administration of β-adrenoceptor (β-AR agonists has been found to induce skeletal muscle hypertrophy and significant metabolic changes. In the context of energy homeostasis, the importance of β-AR signaling has been highlighted by the inability of β1-3-AR-deficient mice to regulate energy expenditure and susceptibility to diet induced obesity. However, the molecular pathways and gene expression changes that initiate and maintain these phenotypic modulations are poorly understood. Therefore, the aim of this study was to identify differential changes in gene expression in murine skeletal muscle associated with systemic (acute and chronic administration of the β2-AR agonist formoterol. Results Skeletal muscle gene expression (from murine tibialis anterior was profiled at both 1 and 4 hours following systemic administration of the β2-AR agonist formoterol, using Illumina 46K mouse BeadArrays. Illumina expression profiling revealed significant expression changes in genes associated with skeletal muscle hypertrophy, myoblast differentiation, metabolism, circadian rhythm, transcription, histones, and oxidative stress. Differentially expressed genes relevant to the regulation of muscle mass and metabolism (in the context of the hypertrophic phenotype were further validated by quantitative RT-PCR to examine gene expression in response to both acute (1-24 h and chronic administration (1-28 days of formoterol at multiple timepoints. In terms of skeletal muscle hypertrophy, attenuation of myostatin signaling (including differential expression of myostatin, activin receptor IIB, phospho-Smad3 etc was observed following acute and chronic administration of formoterol. Acute (but not chronic administration of formoterol also significantly induced the expression of genes involved in oxidative metabolism, including hexokinase 2, sorbin and SH3 domain containing 1, and uncoupling protein 3. Interestingly, formoterol

  13. Transcriptional Profiling of Hydrogen Production Metabolism of Rhodobacter capsulatus under Temperature Stress by Microarray Analysis.

    Gürgan, Muazzez; Erkal, Nilüfer Afşar; Özgür, Ebru; Gündüz, Ufuk; Eroglu, Inci; Yücel, Meral

    2015-01-01

    Biohydrogen is a clean and renewable form of hydrogen, which can be produced by photosynthetic bacteria in outdoor large-scale photobioreactors using sunlight. In this study, the transcriptional response of Rhodobacter capsulatus to cold (4 °C) and heat (42 °C) stress was studied using microarrays. Bacteria were grown in 30/2 acetate/glutamate medium at 30 °C for 48 h under continuous illumination. Then, cold and heat stresses were applied for two and six hours. Growth and hydrogen production were impaired under both stress conditions. Microarray chips for R. capsulatus were custom designed by Affymetrix (GeneChip®. TR_RCH2a520699F). The numbers of significantly changed genes were 328 and 293 out of 3685 genes under cold and heat stress, respectively. Our results indicate that temperature stress greatly affects the hydrogen production metabolisms of R. capsulatus. Specifically, the expression of genes that participate in nitrogen metabolism, photosynthesis and the electron transport system were induced by cold stress, while decreased by heat stress. Heat stress also resulted in down regulation of genes related to cell envelope, transporter and binding proteins. Transcriptome analysis and physiological results were consistent with each other. The results presented here may aid clarification of the genetic mechanisms for hydrogen production in purple non-sulfur (PNS) bacteria under temperature stress. PMID:26086826

  14. Metabolic Profiling and Quantification of Neurotransmitters in Mouse Brain by Gas Chromatography-Mass Spectrometry.

    Jäger, Christian; Hiller, Karsten; Buttini, Manuel

    2016-01-01

    Metabolites are key mediators of cellular functions, and have emerged as important modulators in a variety of diseases. Recent developments in translational biomedicine have highlighted the importance of not looking at just one disease marker or disease inducing molecule, but at populations thereof to gain a global understanding of cellular function in health and disease. The goal of metabolomics is the systematic identification and quantification of metabolite populations. One of the most pressing issues of our times is the understanding of normal and diseased nervous tissue functions. To ensure high quality data, proper sample processing is crucial. Here, we present a method for the extraction of metabolites from brain tissue, their subsequent preparation for non-targeted gas chromatography-mass spectrometry (GC-MS) measurement, as well as giving some guidelines for processing of raw data. In addition, we present a sensitive screening method for neurotransmitters based on GC-MS in selected ion monitoring mode. The precise multi-analyte detection and quantification of amino acid and monoamine neurotransmitters can be used for further studies such as metabolic modeling. Our protocol can be applied to shed light on nervous tissue function in health, as well as neurodegenerative disease mechanisms and the effect of experimental therapeutics at the metabolic level. © 2016 by John Wiley & Sons, Inc. PMID:27584556

  15. Metabolomic profiles reveal key metabolic changes in heat stress-treated mouse Sertoli cells.

    Xu, Bo; Chen, Minjian; Ji, Xiaoli; Yao, Mengmeng; Mao, Zhilei; Zhou, Kun; Xia, Yankai; Han, Xiao; Tang, Wei

    2015-10-01

    Heat stress (HS) is a potential harmful factor for male reproduction. However, the effect of HS on Sertoli cells is largely unknown. In this study, the metabolic changes in Sertoli cell line were analyzed after HS treatment. Metabolomic analysis revealed that carnitine, 2-hydroxy palmitic acid, nicotinic acid, niacinamide, adenosine monophosphate, glutamine and creatine were the key changed metabolites. We found the expression levels of BTB factors (Connexin43, ZO-1, Vimentin, Claudin1, Claudin5) were disrupted in TM-4 cells after HS treatment, which were recovered by the addition of carnitine. RT-PCR indicated that the mRNA levels of inflammatory cytokines (IL-1α, IL-1β, IL-6) were increased after HS treatment, and their related miRNAs (miR-132, miR-431, miR-543) levels were decreased. Our metabolomic data provided a novel understanding of metabolic changes in male reproductive cells after HS treatment and revealed that HS-induced changes of BTB factors and inflammatory status might be caused by the decreased carnitine after HS treatment. PMID:26165742

  16. Transcriptional Profiling of Hydrogen Production Metabolism of Rhodobacter capsulatus under Temperature Stress by Microarray Analysis

    Muazzez Gürgan

    2015-06-01

    Full Text Available Biohydrogen is a clean and renewable form of hydrogen, which can be produced by photosynthetic bacteria in outdoor large-scale photobioreactors using sunlight. In this study, the transcriptional response of Rhodobacter capsulatus to cold (4 °C and heat (42 °C stress was studied using microarrays. Bacteria were grown in 30/2 acetate/glutamate medium at 30 °C for 48 h under continuous illumination. Then, cold and heat stresses were applied for two and six hours. Growth and hydrogen production were impaired under both stress conditions. Microarray chips for R. capsulatus were custom designed by Affymetrix (GeneChip®. TR_RCH2a520699F. The numbers of significantly changed genes were 328 and 293 out of 3685 genes under cold and heat stress, respectively. Our results indicate that temperature stress greatly affects the hydrogen production metabolisms of R. capsulatus. Specifically, the expression of genes that participate in nitrogen metabolism, photosynthesis and the electron transport system were induced by cold stress, while decreased by heat stress. Heat stress also resulted in down regulation of genes related to cell envelope, transporter and binding proteins. Transcriptome analysis and physiological results were consistent with each other. The results presented here may aid clarification of the genetic mechanisms for hydrogen production in purple non-sulfur (PNS bacteria under temperature stress.

  17. A multivariate statistical analysis coming from the NMR metabolic profile of cherry tomatoes (The Sicilian Pachino case)

    Mallamace, Domenico; Corsaro, Carmelo; Salvo, Andrea; Cicero, Nicola; Macaluso, Andrea; Giangrosso, Giuseppe; Ferrantelli, Vincenzo; Dugo, Giacomo

    2014-05-01

    We have studied by means of High Resolution Magic Angle Spinning Nuclear Magnetic Resonance the metabolic profile of the famous Sicilian cherry tomato of Pachino. Thanks to its organoleptic and healthy properties, this particular foodstuff was the first tomato accredited by the European PGI (Protected Geographical Indication) certification of quality. Due to the relatively high price of the final product commercial frauds originated in the Italian and international markets. Hence, there is a growing interest to develop analytical techniques able to predict the origin of a tomato sample, indicating whether or not it originates from the area of Pachino, Sicily (Italy). In this paper we have determined the molar concentration of the metabolites constituent the PGI cherry tomato of Pachino. Furthermore, by means of a multivariate statistical analysis we have identified which metabolites are relevant for sample differentiation.

  18. Dynamics of bacterial metabolic profile and community structure during the mineralization of organic carbon in intensive swine farm wastewater

    Xiaoyan Ma

    2015-06-01

    Full Text Available Land application of intensive swine farm wastewater has raised serious environmental concerns due to the accumulation and microbially mediated transformation of large amounts of swine wastewater organic C (SWOC. Therefore, the study of SWOC mineralization and dynamics of wastewater microorganisms is essential to understand the environmental impacts of swine wastewater application. We measured the C mineralization of incubated swine wastewaters with high (wastewater H and low (wastewater L organic C concentrations. The dynamics of bacteria metabolic profile and community structure were also investigated. The results showed that SWOC mineralization was properly fitted by the two-simultaneous reactions model. The initial potential rate of labile C mineralization of wastewater H was 46% higher than that of wastewater L, whereas the initial potential rates of recalcitrant C mineralization of wastewaters H and L were both around 23 mg L-1 d-1. The bacterial functional and structural diversities significantly decreased for both the wastewaters during SWOC mineralization, and were all negatively correlated to specific UV absorbance (SUVA254; P < 0.01. The bacteria in the raw wastewaters exhibited functional similarity, and both metabolic profile and community structure changed with the mineralization of SWOC, mainly under the influence of SUVA254 (P < 0.001. These results suggested that SWOC mineralization was characterized by rapid mineralization of labile C and subsequent slow decomposition of recalcitrant C pool, and the quality of SWOC varied between the wastewaters with different amounts of organic C. The decreased bio-availability of dissolved organic matter affected the dynamics of wastewater bacteria during SWOC mineralization.

  19. Development of a Rapid Microbore Metabolic Profiling Ultraperformance Liquid Chromatography-Mass Spectrometry Approach for High-Throughput Phenotyping Studies.

    Gray, Nicola; Adesina-Georgiadis, Kyrillos; Chekmeneva, Elena; Plumb, Robert S; Wilson, Ian D; Nicholson, Jeremy K

    2016-06-01

    A rapid gradient microbore ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) method has been developed to provide a high-throughput analytical platform for the metabolic phenotyping of urine from large sample cohorts. The rapid microbore metabolic profiling (RAMMP) approach was based on scaling a conventional reversed-phase UPLC-MS method for urinary profiling from 2.1 mm × 100 mm columns to 1 mm × 50 mm columns, increasing the linear velocity of the solvent, and decreasing the gradient time to provide an analysis time of 2.5 min/sample. Comparison showed that conventional UPLC-MS and rapid gradient approaches provided peak capacities of 150 and 50, respectively, with the conventional method detecting approximately 19 000 features compared to the ∼6 000 found using the rapid gradient method. Similar levels of repeatability were seen for both methods. Despite the reduced peak capacity and the reduction in ions detected, the RAMMP method was able to achieve similar levels of group discrimination as conventional UPLC-MS when applied to rat urine samples obtained from investigative studies on the effects of acute 2-bromophenol and chronic acetaminophen administration. When compared to a direct infusion MS method of similar analysis time the RAMMP method provided superior selectivity. The RAMMP approach provides a robust and sensitive method that is well suited to high-throughput metabonomic analysis of complex mixtures such as urine combined with a 5-fold reduction in analysis time compared with the conventional UPLC-MS method. PMID:27116471

  20. Effect of the environment on the secondary metabolic profile of Tithonia diversifolia: a model for environmental metabolomics of plants

    Sampaio, Bruno Leite; Edrada-Ebel, Ruangelie; da Costa, Fernando Batista

    2016-07-01

    Tithonia diversifolia is an invasive weed commonly found in tropical ecosystems. In this work, we investigate the influence of different abiotic environmental factors on the plant’s metabolite profile by multivariate statistical analyses of spectral data deduced by UHPLC-DAD-ESI-HRMS and NMR methods. Different plant part samples of T. diversifolia which included leaves, stems, roots, and inflorescences were collected from two Brazilian states throughout a 24-month period, along with the corresponding monthly environmental data. A metabolomic approach employing concatenated LC-MS and NMR data was utilised for the first time to study the relationships between environment and plant metabolism. A seasonal pattern was observed for the occurrence of metabolites that included sugars, sesquiterpenes lactones and phenolics in the leaf and stem parts, which can be correlated to the amount of rainfall and changes in temperature. The distribution of the metabolites in the inflorescence and root parts were mainly affected by variation of some soil nutrients such as Ca, Mg, P, K and Cu. We highlight the environment-metabolism relationship for T. diversifolia and the combined analytical approach to obtain reliable data that contributed to a holistic understanding of the influence of abiotic environmental factors on the production of metabolites in various plant parts.

  1. Serum Leptin Levels in Polycystic Ovary Syndrome and Its Relationship with Metabolic and Hormonal Profile in Pakistani Females

    Mukhtiar Baig

    2014-01-01

    Full Text Available The study aimed to investigate the levels of serum leptin in PCOS females and to correlate it with metabolic and hormonal parameters. Sixty-two PCOS and ninety normal cycling (NC females with matched age and body mass index (BMI were recruited for this cross-sectional study. Serum leptin, FSH, LH, E2, free testosterone, progesterone, thyroid profile, and FBG levels were measured. The mean leptin levels in PCOS and NC were not significantly different (45.56 ng/mL ± 1.49 vs 41.78 ± 1.31 ng/mL, P>0.05; however, leptin levels showed a strong correlation with BMI in PCOS and NC group (r=0.77, P<0.0001; r=0.82, P<0.0001, resp.. High E2 levels in NC had a significant correlation with leptin whereas FBG correlated with leptin in PCOS (r=0.51, P=0.005. TSH had a substantial correlation (r=0.49, P<0.005; r=0.69, P<0.005 in PCOS and NC, respectively. There was no significant difference found in circulating leptin concentration between PCOS and NC subjects. Leptin levels in PCOS were related with metabolic impairments manifested by disturbance in FBG levels and impairment of reproductive functions in terms of reduced E2 secretion.

  2. Effect of the environment on the secondary metabolic profile of Tithonia diversifolia: a model for environmental metabolomics of plants

    Sampaio, Bruno Leite; Edrada-Ebel, RuAngelie; Da Costa, Fernando Batista

    2016-01-01

    Tithonia diversifolia is an invasive weed commonly found in tropical ecosystems. In this work, we investigate the influence of different abiotic environmental factors on the plant’s metabolite profile by multivariate statistical analyses of spectral data deduced by UHPLC-DAD-ESI-HRMS and NMR methods. Different plant part samples of T. diversifolia which included leaves, stems, roots, and inflorescences were collected from two Brazilian states throughout a 24-month period, along with the corresponding monthly environmental data. A metabolomic approach employing concatenated LC-MS and NMR data was utilised for the first time to study the relationships between environment and plant metabolism. A seasonal pattern was observed for the occurrence of metabolites that included sugars, sesquiterpenes lactones and phenolics in the leaf and stem parts, which can be correlated to the amount of rainfall and changes in temperature. The distribution of the metabolites in the inflorescence and root parts were mainly affected by variation of some soil nutrients such as Ca, Mg, P, K and Cu. We highlight the environment-metabolism relationship for T. diversifolia and the combined analytical approach to obtain reliable data that contributed to a holistic understanding of the influence of abiotic environmental factors on the production of metabolites in various plant parts. PMID:27383265

  3. Avocado Oil Supplementation Modifies Cardiovascular Risk Profile Markers in a Rat Model of Sucrose-Induced Metabolic Changes

    Octavio Carvajal-Zarrabal

    2014-01-01

    Full Text Available The purpose of this study was to evaluate the effects of avocado oil administration on biochemical markers of cardiovascular risk profile in rats with metabolic changes induced by sucrose ingestion. Twenty-five rats were divided into five groups: a control group (CG; basic diet, a sick group (MC; basic diet plus 30% sucrose solution, and three other groups (MCao, MCac, and MCas; basic diet plus 30% sucrose solution plus olive oil and avocado oil extracted by centrifugation or using solvent, resp.. Glucose, total cholesterol, triglycerides, phospholipids, low- and high-density lipoproteins (LDL, HDL, very low-density lipoprotein (VLDL, lactic dehydrogenase, creatine kinase, and high sensitivity C-reactive protein concentration were analyzed. Avocado oil reduces TG, VLDL, and LDL levels, in the LDL case significantly so, without affecting HDL levels. An effect was exhibited by avocado oil similar to olive oil, with no significant difference between avocado oil extracted either by centrifugation or solvent in myocardial injury biochemical indicators. Avocado oil decreased hs-CRP levels, indicating that inflammatory processes were partially reversed. These findings suggested that avocado oil supplementation has a positive health outcome because it reduces inflammatory events and produces positive changes in the biochemical indicators studied, related to the development of metabolic syndrome.

  4. Preparing Muscles for Diving: Age-Related Changes in Muscle Metabolic Profiles in Harp (Pagophilus groenlandicus) and Hooded (Cystophora cristata) Seals.

    Burns, J M; Lestyk, K; Freistroffer, D; Hammill, M O

    2015-01-01

    In adult marine mammals, muscles can sustain aerobic metabolism during dives in part because they contain large oxygen (O2) stores and metabolic rates are low. However, young pups have significantly lower tissue O2 stores and much higher mass-specific metabolic rates. To investigate how these differences may influence muscle function during dives, we measured the activities of enzymes involved in aerobic and anaerobic metabolic pathways (citrate synthase [CS], β-hydroxyacyl-coenzyme A dehydrogenase [HOAD], lactate dehydrogenase [LDH]) and the LDH isoform profile in six muscles from 41 harp (Pagophilus groenlandicus) and 30 hooded (Cystophora cristata) seals ranging in age from fetal to adult. All neonatal muscles had significantly higher absolute but lower metabolically scaled CS and HOAD activities than adults (∼ 70% and ∼ 85% lower, respectively). Developmental increases in LDH activity lagged that of aerobic enzymes and were not accompanied by changes in isozyme profile, suggesting that changes in enzyme concentration rather than structure determine activity levels. Biochemical maturation proceeded faster in the major locomotory muscles. In combination, findings suggest that pup muscles are unable to support strenuous aerobic exercise or rely heavily on anaerobic metabolism during early diving activities and that pups' high mass-specific metabolic rates may play a key role in limiting the ability of their muscles to support underwater foraging. PMID:25730272

  5. Transcript profiles uncover temporal and stress-induced changes of metabolic pathways in germinating sugar beet seeds

    Windhövel Andrea

    2008-12-01

    Full Text Available Abstract Background With a cultivation area of 1.75 Mio ha and sugar yield of 16.7 Mio tons in 2006, sugar beet is a crop of great economic importance in Europe. The productivity of sugar beet is determined significantly by seed vigour and field emergence potential; however, little is known about the molecular mechanisms underlying these traits. Both traits exhibit large variations within sugar beet germplasm that have been difficult to ascribe to either environmental or genetic causes. Among potential targets for trait improvement, an enhancement of stress tolerance is considered because of the high negative influence of environmental stresses on trait parameters. Extending our knowledge of genetic and molecular determinants of sugar beet germination, stress response and adaptation mechanisms would facilitate the detection of new targets for breeding crop with an enhanced field emergence potential. Results To gain insight into the sugar beet germination we initiated an analysis of gene expression in a well emerging sugar beet hybrid showing high germination potential under various environmental conditions. A total of 2,784 ESTs representing 2,251 'unigenes' was generated from dry mature and germinating seeds. Analysis of the temporal expression of these genes during germination under non-stress conditions uncovered drastic transcriptional changes accompanying a shift from quiescent to metabolically active stages of the plant life cycle. Assay of germination under stressful conditions revealed 157 genes showing significantly different expression patterns in response to stress. As deduced from transcriptome data, stress adaptation mechanisms included an alteration in reserve mobilization pathways, an accumulation of the osmoprotectant glycine betaine, late embryogenesis abundant proteins and detoxification enzymes. The observed transcriptional changes are supposed to be regulated by ABA-dependent signal transduction pathway. Conclusion This study

  6. Effect of silver nanoparticles on growth performance, metabolism and microbial profile of broiler chickens

    Pineda, Lane Manalili; Chwalibog, André; Sawosz, Ewa;

    2012-01-01

    Nano20, respectively) provided via the drinking water from day 7 to 36 post-hatching. Body weight and feed consumption were measured weekly. In addition, balance and respiration experiments were carried out to determine nitrogen (N) utilisation and energy retention. At days 22 and 36, blood samples and...... intestinal content were collected to evaluate the effects of AgNano on plasma concentration of immunoglobulins and the intestinal microflora, respectively. The provision of water solutions containing different concentrations of AgNano had no effect on postnatal growth performance and the energy metabolism of...... broiler chickens. However, in Group AgNano10 N intake (p = 0.05) and retention (p = 0.03) was increased, but N excretion and efficiency of utilisation was not affected. The populations of bacteria in the intestinal samples were not affected by AgNano supplementation. The concentration of immunoglobulin...

  7. Metabolic Profiling of Food Protective Cultures by in vitro NMR Spectroscopy

    Ebrahimi, Parvaneh

    -called protective cultures) has unexploited potential to inhibit the growth of pathogenic microorganisms and enhance the shelf life of the final food product. In order to apply biopreservation in food products effectively, detailed knowledge on the metabolism of protective cultures is required. The present Ph......Food spoilage is of major concern to the food industry, because it leads to considerable economic losses, a deteriorated environmental food-print, and to possible public health hazards. In order to limit food spoilage, research on the preservation of food products has always received particular...... attention by the food industry. Traditionally, such efforts have mainly relied on the application of chemical preservatives or drastic physical treatments. However, chemical preservatives are becoming increasingly unpopular by the consumers, and some have even proven to be toxic and linked to cancer and...

  8. Offspring body size and metabolic profile - effects of lifestyle intervention in obese pregnant women

    Tanvig, Mette; Jensen, Dorte Møller

    2014-01-01

    disturbances in the offspring. Pregnancy offers the opportunity to modify the intrauterine environment, and maternal lifestyle changes during gestation may confer health benefits to the child. The overall aim with this PhD thesis was to study the effects of maternal obesity on offspring body size and metabolic...... RCT offspring were similar, and no differences were detected between the RCT offspring and the external reference group of offspring of lean mothers. Lifestyle intervention in obese pregnant women has the potential to modify the intrauterine environment and confer long-term benefits to the child. In......Worldwide, the prevalence of obesity has reached epidemic proportions. In Denmark one third of all pregnant women are overweight and 12 % are obese. Perhaps even more concerning, a dramatic rise in the prevalence of childhood overweight and obesity has also been evident over recent decades. The...

  9. Metabolic profiling studies on the toxicological effects of realgar in rats by 1H NMR spectroscopy

    The toxicological effects of realgar after intragastrical administration (1 g/kg body weight) were investigated over a 21 day period in male Wistar rats using metabonomic analysis of 1H NMR spectra of urine, serum and liver tissue aqueous extracts. Liver and kidney histopathology examination and serum clinical chemistry analyses were also performed. 1H NMR spectra and pattern recognition analyses from realgar treated animals showed increased excretion of urinary Kreb's cycle intermediates, increased levels of ketone bodies in urine and serum, and decreased levels of hepatic glucose and glycogen, as well as hypoglycemia and hyperlipoidemia, suggesting the perturbation of energy metabolism. Elevated levels of choline containing metabolites and betaine in serum and liver tissue aqueous extracts and increased serum creatine indicated altered transmethylation. Decreased urinary levels of trimethylamine-N-oxide, phenylacetylglycine and hippurate suggested the effects on the gut microflora environment by realgar. Signs of impairment of amino acid metabolism were supported by increased hepatic glutamate levels, increased methionine and decreased alanine levels in serum, and hypertaurinuria. The observed increase in glutathione in liver tissue aqueous extracts could be a biomarker of realgar induced oxidative injury. Serum clinical chemistry analyses showed increased levels of lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase as well as increased levels of blood urea nitrogen and creatinine, indicating slight liver and kidney injury. The time-dependent biochemical variations induced by realgar were achieved using pattern recognition methods. This work illustrated the high reliability of NMR-based metabonomic approach on the study of the biochemical effects induced by traditional Chinese medicine

  10. Metabolic profiling reveals coordinated switches in primary carbohydrate metabolism in grape berry (Vitis vinifera L.), a non-climacteric fleshy fruit

    Dai, Z.; Leon, C.; Feil, R.; Lunn, J.; Delrot, S.; Gomes, E.

    2013-01-01

    Changes in carbohydrate metabolism during grape berry development play a central role in shaping the final composition of the fruit. The present work aimed to identify metabolic switches during grape development and to provide insights into the timing of developmental regulation of carbohydrate metabolism. Metabolites from central carbon metabolism were measured using high-pressure anion-exchange chromatography coupled to tandem mass spectrometry and enzymatic assays during the development of...

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

    Pereira Isabel

    2011-06-01

    Full Text Available 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 taken during the transition period and early lactation in both farms. Data was analyzed by farm using a repeated measures analyses including GH and IGF-I genotypes, days and interactions as fixed effects, sire and cow as random effects and calving date as covariate. Results and Discussion Frequencies of GH and IGF-I alleles were L:0.84, V:0.16 and A:0.60, B:0.40, respectively. The GH genotype was not associated with productive or reproductive variables, but interaction with days affected FCM yield in multiparous (farm 2 cows (LL yielded more than LV cows in early lactation. The GH genotype affected NEFA and IGF-I concentrations in farm 1 (LV had higher NEFA and lower IGF-I than LL cows suggesting a better energy status of LL cows. There was no effect of IGF-I genotype on productive variables, but a trend was found for FCM in farm 2 (AB cows yielded more than AA cows. IGF-I genotype affected calving first service interval in farm 1, and the interaction with days tended to affect FCM yield (AB cows had a shorter interval and yielded more FCM than BB cows. IGF-I genotype affected BHB, NEFA, and insulin concentrations in farm 1: primiparous BB cows had lower NEFA and BHB and higher insulin concentrations. In farm 2, there was no effect of IGF-I genotype, but there was an interaction with days on IGF-I concentration, suggesting a greater uncoupling somatropic axis in AB and BB than AA cows, being in accordance with greater FCM yield in AB cows. Conclusion The GH and

  12. Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia—A Case of Novel Weapons?

    Skoneczny, Dominik; Weston, Paul A.; Zhu, Xiaocheng; Gurr, Geoff M.; Callaway, Ragan M.; Weston, Leslie A.

    2015-01-01

    Metabolic profiling allows for simultaneous and rapid annotation of biochemically similar organismal metabolites. An effective platform for profiling of toxic pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) was developed using ultra high pressure liquid chromatography quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry. Field-collected populations of invasive Australian weeds, Echium plantagineum and E. vulgare were raised under controlled glasshouse conditions and surveyed for the presence of related PAs and PANOs in leaf tissues at various growth stages. Echium plantagineum possessed numerous related and abundant PANOs (>17) by seven days following seed germination, and these were also observed in rosette and flowering growth stages. In contrast, the less invasive E. vulgare accumulated significantly lower levels of most PANOs under identical glasshouse conditions. Several previously unreported PAs were also found at trace levels. Field-grown populations of both species were also evaluated for PA production and highly toxic echimidine N-oxide was amongst the most abundant PANOs in foliage of both species. PAs in field and glasshouse plants were more abundant in the more widely invasive species, E. plantagineum, and may provide competitive advantage by increasing the plant’s capacity to deter natural enemies in its invaded range through production of novel weapons. PMID:26561809

  13. Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia—A Case of Novel Weapons?

    Dominik Skoneczny

    2015-11-01

    Full Text Available Metabolic profiling allows for simultaneous and rapid annotation of biochemically similar organismal metabolites. An effective platform for profiling of toxic pyrrolizidine alkaloids (PAs and their N-oxides (PANOs was developed using ultra high pressure liquid chromatography quadrupole time-of-flight (UHPLC-QTOF mass spectrometry. Field-collected populations of invasive Australian weeds, Echium plantagineum and E. vulgare were raised under controlled glasshouse conditions and surveyed for the presence of related PAs and PANOs in leaf tissues at various growth stages. Echium plantagineum possessed numerous related and abundant PANOs (>17 by seven days following seed germination, and these were also observed in rosette and flowering growth stages. In contrast, the less invasive E. vulgare accumulated significantly lower levels of most PANOs under identical glasshouse conditions. Several previously unreported PAs were also found at trace levels. Field-grown populations of both species were also evaluated for PA production and highly toxic echimidine N-oxide was amongst the most abundant PANOs in foliage of both species. PAs in field and glasshouse plants were more abundant in the more widely invasive species, E. plantagineum, and may provide competitive advantage by increasing the plant’s capacity to deter natural enemies in its invaded range through production of novel weapons.

  14. Metabolic Profiling of Pyrrolizidine Alkaloids in Foliage of Two Echium spp. Invaders in Australia--A Case of Novel Weapons?

    Skoneczny, Dominik; Weston, Paul A; Zhu, Xiaocheng; Gurr, Geoff M; Callaway, Ragan M; Weston, Leslie A

    2015-01-01

    Metabolic profiling allows for simultaneous and rapid annotation of biochemically similar organismal metabolites. An effective platform for profiling of toxic pyrrolizidine alkaloids (PAs) and their N-oxides (PANOs) was developed using ultra high pressure liquid chromatography quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry. Field-collected populations of invasive Australian weeds, Echium plantagineum and E. vulgare were raised under controlled glasshouse conditions and surveyed for the presence of related PAs and PANOs in leaf tissues at various growth stages. Echium plantagineum possessed numerous related and abundant PANOs (>17) by seven days following seed germination, and these were also observed in rosette and flowering growth stages. In contrast, the less invasive E. vulgare accumulated significantly lower levels of most PANOs under identical glasshouse conditions. Several previously unreported PAs were also found at trace levels. Field-grown populations of both species were also evaluated for PA production and highly toxic echimidine N-oxide was amongst the most abundant PANOs in foliage of both species. PAs in field and glasshouse plants were more abundant in the more widely invasive species, E. plantagineum, and may provide competitive advantage by increasing the plant's capacity to deter natural enemies in its invaded range through production of novel weapons. PMID:26561809

  15. Role of Training and Detraining on Inflammatory and Metabolic Profile in Infarcted Rats: Influences of Cardiovascular Autonomic Nervous System

    Bruno Rodrigues

    2014-01-01

    Full Text Available The aim of this study was to evaluate the effects of exercise training (ET, 50–70% of VO2 max, 5 days/week and detraining (DT on inflammatory and metabolic profile after myocardial infarction (MI in rats. Male Wistar rats were divided into control (C, n=8, sedentary infarcted (SI, n=9, trained infarcted (TI,  n=10; 3 months of ET, and detrained infarcted (DI, n=11; 2 months of ET + 1 month of DT. After ET and DT protocols, ventricular function and inflammation, cardiovascular autonomic modulation (spectral analysis, and adipose tissue inflammation and lipolytic pathway were evaluated. ET after MI improved cardiac and vascular autonomic modulation, and these benefits were correlated with reduced inflammatory cytokines on the heart and adipose tissue. These positive changes were sustained even after 1 month of detraining. No expressive changes were observed in oxidative stress and lipolytic pathway in experimental groups. In conclusion, our results strongly suggest that the autonomic improvement promoted by ET, and maintained even after the detraining period, was associated with reduced inflammatory profile in the left ventricle and adipose tissue of rats subjected to MI. These data encourage enhancing cardiovascular autonomic function as a therapeutic strategy for the treatment of inflammatory process triggered by MI.

  16. Intrinsic and Tumor Microenvironment-Induced Metabolism Adaptations of T Cells and Impact on Their Differentiation and Function

    Kouidhi, Soumaya; Noman, Muhammad Zaeem; Kieda, Claudine; Elgaaied, Amel Benammar; Chouaib, Salem

    2016-01-01

    It is well recognized that the immune system and metabolism are highly integrated. In this context, multilevel interactions between metabolic system and T lymphocyte signaling and fate exist. This review will discuss different potential cell metabolism pathways involved in shaping T lymphocyte function and differentiation. We will also provide a general framework for understanding how tumor microenvironmental metabolism, associated with hypoxic stress, interferes with T-cell priming and expansion. How T-cell metabolism drives T-cell-mediated immunity and how the manipulation of metabolic programing for therapeutic purposes will be also discussed. PMID:27066006

  17. Factors Associated with Adiposity, Lipid Profile Disorders and the Metabolic Syndrome Occurrence in Premenopausal and Postmenopausal Women

    Suliga, Edyta; Kozieł, Dorota; Cieśla, Elżbieta; Rębak, Dorota; Głuszek, Stanisław

    2016-01-01

    The aim of the study was the assessment of the dependencies between a woman’s menopausal status and adiposity, lipid profile and metabolic syndrome occurrence, as well as finding out whether the correlations between the socio-demographic profile and lifestyle elements and adiposity, lipid profile and the risk of MetS are the same before and after menopause. A cross-sectional study was carried out on 3636 women, aged between 40–59, which involved a questionnaire interview, anthropometric measurements and fasting blood samples, on the basis of which the concentration of triglycerides, cholesterol and glucose was estimated. Before menopause, a greater adiposity (BMIβ = 0.08; %BFβ = 0.07; WCβ = 0.06) was characteristic for women living in a stable relationship than for single women. Women who smoked in the past were characterized by a higher BMI (β = 0.09) and WC (β = 0.06) in comparison with women who have never smoked, while after menopause a greater adiposity (%BFβ = 0.12) and a worse lipid profile (TCβ = 0.08; LDLβ = 0.07; HDLβ = -0.05; TGβ = 0.14) were present in women currently smoking, in comparison to women who have never smoked. After menopause, in women who had two or more children, a greater adiposity (BMIβ = 0.07 and 0.09; %BFβ = 0.05 and 0.07) and a higher risk of MetS (OR = 1.22, 95%CI: 1.03–1.44) was observed compared to nulliparous women, than before menopause. In women with a higher level of education, the risk of MetS after menopause was significantly lower compared with women with a lower level of education (OR = 0.74, 95%CI: 0.61–0.90). Physical activity after menopause had a higher influence on the decrease in the women’s adiposity (BMIβ = -0.11 v. -0.06; %BFβ = -0.11 v. -0.06; WCβ = -0.14 v. -0.08), than before menopause. In women not undergoing hormone replacement therapy, some of the socio-demographic factors and lifestyle elements affected adiposity, lipid profile and the risk of MetS differently before and after

  18. Comparative transcriptome profiling analyses during the lag phase uncover YAP1, PDR1, PDR3, RPN4, and HSF1 as key regulatory genes in genomic adaptation to the lignocellulose derived inhibitor HMF for Saccharomyces cerevisiae

    Liu Z Lewis

    2010-11-01

    Full Text Available Abstract Background The yeast Saccharomyces cerevisiae is able to adapt and in situ detoxify lignocellulose derived inhibitors such as furfural and HMF. The length of lag phase for cell growth in response to the inhibitor challenge has been used to measure tolerance of strain performance. Mechanisms of yeast tolerance at the genome level remain unknown. Using systems biology approach, this study investigated comparative transcriptome profiling, metabolic profiling, cell growth response, and gene regulatory interactions of yeast strains and selective gene deletion mutations in response to HMF challenges during the lag phase of growth. Results We identified 365 candidate genes and found at least 3 significant components involving some of these genes that enable yeast adaptation and tolerance to HMF in yeast. First, functional enzyme coding genes such as ARI1, ADH6, ADH7, and OYE3, as well as gene interactions involved in the biotransformation and inhibitor detoxification were the direct driving force to reduce HMF damages in cells. Expressions of these genes were regulated by YAP1 and its closely related regulons. Second, a large number of PDR genes, mainly regulated by PDR1 and PDR3, were induced during the lag phase and the PDR gene family-centered functions, including specific and multiple functions involving cellular transport such as TPO1, TPO4, RSB1, PDR5, PDR15, YOR1, and SNQ2, promoted cellular adaptation and survival in order to cope with the inhibitor stress. Third, expressed genes involving degradation of damaged proteins and protein modifications such as SHP1 and SSA4, regulated by RPN4, HSF1, and other co-regulators, were necessary for yeast cells to survive and adapt the HMF stress. A deletion mutation strain Δrpn4 was unable to recover the growth in the presence of HMF. Conclusions Complex gene interactions and regulatory networks as well as co-regulations exist in yeast adaptation and tolerance to the lignocellulose derived

  19. Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients.

    Mohtashami, Alireaz; Mahaki, Behzad; Azadbakht, Leila; Entezari, Mohammad Hasan

    2016-04-01

    Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients. PMID:27152298

  20. Effects of Bread with Nigella Sativa on Lipid Profiles, Apolipoproteins and Inflammatory Factor in Metabolic Syndrome Patients

    2016-01-01

    Nigella sativa (N.sativa) has been used in traditional medicine and many studies have been performed in different communities in order to reveal the effects of it on medical disorders and chronic diseases. The aim of this study was to investigate the effects of bread with N. Sativa on lipid profiles, apolipoproteins, and inflammatory factors in metabolic syndrome (MetS) patients. A randomized, double-blind, cross-over and clinical trial was conducted in 51 MetS patients of both sexes with age group of 20-65 years old in Chaloos, north of Iran. Patients were randomly divided in two groups. In phase 1, intervention group (A, n = 27) received daily a bread with N. sativa and wheat bran and control group (B, n = 24) received the same bread without N. sativa for 2 months. After 2 weeks of wash out period, phase 2 was started with switch the intervention between two groups. Measuring of lipid profiles, apolipoproteins and inflammatory factor was performed for all patients before and after two phases. In this study, treatment, sequence and time effects of intervention were evaluated and revealed that consumption of bread with N. sativa has no significant treatment and time effects on triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein (APO)-A, APO-B and high-sensitivity C-reactive protein (p > 0.05). Sequence effect was significant on CHOL, LDL, APO-A, and APO-B (p 0.05). Consumption of bread with N. sativa has no a significant effect on lipid profiles, apolipoproteins and inflammatory factor in MetS patients. PMID:27152298

  1. The Effects of Sprint Interval vs. Continuous Endurance Training on Physiological and Metabolic Adaptations in Young Healthy Adults

    Nalcakan Gulbin Rudarli

    2014-12-01

    Full Text Available The purpose of this study was to compare the effects of sprint interval training (SIT and continuous endurance training (CET on selected anthropometric, aerobic, and anaerobic performance indices as well as the blood lipid profile, inflammatory and muscle damage markers in healthy young males. Fifteen recreationally active male volunteers (age: 21.7 ±2.2 years, body mass: 83.0 ±8.0 kg, body height: 1.82 ±0.05 m were divided into two groups according to their initial VO2max levels. Training programs were conducted 3 times per week for 7 weeks. The SIT program consisted of 4-6 Wingate anaerobic sprints with a 4.5 min recovery, while CET consisted of 30-50 min cycling at 60% VO2max. Biochemical, anthropometric and fitness assessments were performed both pre and post-intervention. Significant improvements in VO2max, anaerobic power and capacity, and VO2 utilization during the submaximal workout and significant decreases in body fat and in waist circumference after the intervention occurred in both SIT and CET groups. Significantly greater gross efficiency was measured in the CET group. No differences in the lipid profile or serum levels of inflammatory, myocardial and skeletal muscle damage markers were observed after the training period. The study results agree with the effectiveness of a 30 s all-out training program with a reduced time commitment for anthropometric, aerobic and anaerobic adaptation and eliminate doubts about its safety as a model.

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

    Clarisse Noel Ayina Ayina Lissock

    2011-09-01

    Full Text Available < 0.001 respectively. However, total Cholesterol (TC and LDL-c were significantly higher in urban than in rural men (p<0.001 and p=0.005 and women (p <0.001 respectively. Diabetes� rate in this population was 6.6%. This rate was higher in the rural (8.3% than in the urban area (6.0%. Age and RHR were significantly higher in diabetic women than in non-diabetics (p=0.007; p=0.032 respectively. In a multiple regression, age was an independent predictor of SBP, DBP and RHR in the entire population. Age predicted blood glucose in rural women only. BMI, WC and BF% were independent predictors of RHR in rural population, especially in men. WC and BF% predicted DBP in rural men only. Anthropometric parameters did not predict the lipid profile.

  3. Metabolic Profile of Offspring from Diabetic Wistar Rats Treated with Mentha piperita (Peppermint

    Sandra M. Barbalho

    2011-01-01

    Full Text Available This study aimed at evaluating glycemia and lipid profile of offspring from diabetic Wistar rats treated with Mentha piperita (peppermint juice. Male offspring from nondiabetic dams (control group: 10 animals treated with water and 10 treated with peppermint juice and from dams with streptozotocin-induced severe diabetes (diabetic group: 10 animals treated with water and 10 treated with peppermint juice were used. They were treated during 30 days, and, after the treatment period, levels of glycemia, triglycerides, total cholesterol, and fractions were analyzed in the adult phase. The offspring from diabetic dams treated with peppermint showed significantly reduced levels of glucose, cholesterol, LDL-c, and triglycerides and significant increase in HDL-c levels. The use of the M. piperita juice has potential as culturally appropriate strategy to aid in the prevention of DM, dyslipidemia, and its complications.

  4. Developing an Adaptive Exposure Model to Support the Generation of Country Disaster Risk Profiles

    Gunasekera, Rashmin; Ishizawa, Oscar; Aubrecht, Christoph; Pita, Gonzalo; Pomonis, Antonios; Fane, Kayoum; Murray, Siobhan; Blankespoor, Brian

    2014-05-01

    Probabilistic disaster risk profiles provide estimates of potential damage to property and life caused by adverse natural hazards. A Country Disaster Risk Profile (CDRP), which is a coarse level analysis, presents an estimate of risk at the national level. We define the exposure model in that context as a geo-referenced database of assets at risk at a 1-km grid level, capturing important attributes such as geographical location, urban/rural classification, type of occupancy (e.g. residential and non-residential), building typology (e.g. wood, steel, masonry), and aggregated asset value. We present here a sensitivity analysis of key parameters of the exposure model developed in relation to CDRPs. Specifically, we analyse the sensitivity in characterisation of built up areas, and associated disaggregation of assets. We evaluate this by comparing datasets such as Modis 500m (2010), Landscan (2012), BuREF (2012), and GUF (2013). We also present a method to integrate exterior wall and roof type typologies to assess vulnerability of buildings to both earthquakes and hurricanes. Finally, developments in determining replacement value of buildings from national and sub national datasets are presented. Integration of all these developments together produces an exposure model. The sensitivity of such a model output is even more crucial in risk analysis of Small Island States (SIS), and we highlight this with case studies from the Caribbean region. This resultant gridded exposure database could be convolved with hazard and vulnerability components to create CDRPs for multiple hazards that include earthquake, flood and windstorms. The findings, interpretations, and conclusions expressed in this paper are entirely those of the authors. They do not necessarily represent the views of the International Bank for Reconstruction and Development/World Bank and its affiliated organizations, or those of the Executive Directors of the World Bank or the governments they represent.

  5. Chemical fingerprint and metabolic profile analysis of ethyl acetate fraction of Gastrodia elata by ultra performance liquid chromatography/quadrupole-time of flight mass spectrometry.

    Tang, Chunlan; Wang, Li; Liu, Xinxin; Cheng, Mengchun; Xiao, Hongbin

    2016-02-01

    The chemical fingerprint and metabolic profile of traditional Chinese medicine is very complicated and has been a great challenge. In the present study, chemical fingerprint of ethyl acetate fraction of Gastrodia elata (EtAcGE) and metabolic profile of rat plasma sample after intragastric administration of EtAcGE (2.5g/kg) were investigated using ultra-high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC/Q-TOF MS). A total of 38 chemical constituents of EtAcGE were identified by comparing their retention time, accurate molecular mass and characteristic fragment ions with those of references, or tentatively characterized by comparing molecular formula, fragment ions with that of known compound or information available in literature. And 40 compounds were detected in dosed rat plasma sample, including 16 prototypes and 24 metabolites underwent metabolic process of glucuronidation, glucosylation, sulfation, methylation, hydroxylation, dehydrogenation or mixed modes. The metabolic "soft spots" was hydroxyl or carboxy group. This is the first research for chemical fingerprint and metabolic profile of EtAcGE, which lay a foundation for the further investigation of EtAcGE. PMID:26621783

  6. Metabolism profiles of nuciferine in rats using ultrafast liquid chromatography with tandem mass spectrometry.

    Ye, Lin-Hu; Xiao, Bing-Xin; Liao, Yong-Hong; Liu, Xin-Min; Pan, Rui-Le; Chang, Qi

    2016-08-01

    Nuciferine (NF) is one of the main aporphine alkaloids existing in the traditional Chinese medicine Folium Nelumbinis (lotus leaves). Modern pharmacological studies have demonstrated that NF has a broad spectrum of bioactivities, such as anti-HIV and anti-hyperlipidemic effects, and has been recommended as a leading compound for new drug development. However, the metabolites and biotransformation pathway of NF in vivo have not yet been comprehensively investigated. The present study was performed to identify the metabolites of NF for exploring in vivo fates. Rat plasma and urine samples were collected after oral administration and prepared by liquid-liquid extraction with ethyl acetate. A method based on ultrafast liquid chromatography with tandem mass spectrometry was applied to identify the metabolites. Q1 (first quadrupole) full scan combined with a multiple reaction monitoring (MRM) survey scan were used for the detection of metabolites. MRM-information-dependent acquisition of enhanced product ions was used for the structural identification of detected metabolites. A total of 10 metabolites were identified, including phase I (demethylation, oxidation and dehydrogenation) and phase II (glucuronidation, sulfation and glutathione) biotransformation products. Demethylation is the main metabolic pathway of NF in the body. These results can help in improving understanding of the disposition and pharmacological mechanism of NF in the body. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26682724

  7. Safety profile of anakinra in the management of rheumatologic, metabolic and autoinflammatory disorders.

    Lopalco, Giuseppe; Rigante, Donato; Giannini, Margherita; Galeazzi, Mauro; Lapadula, Giovanni; Iannone, Florenzo; Cantarini, Luca

    2016-01-01

    Anakinra is a biologic response modifier that competitively antagonises the biologic effects of interleukin-1, the ancestor pleiotropic proinflammatory cytokine produced by numerous cell types, found in excess in the serum, synovial fluid and any involved tissues of patients with many inflammatory diseases. The magnitude of the risk of different infections, including Mycobacterium tuberculosis (Mtb) infection, associated with the large use of anakinra in many rheumatologic, metabolic or autoinflammatory disorders is still unknown. In addition, it is unclear whether this effect is modified by the concomitant use of antirheumatic drugs and corticosteroids. The rates of development of Mtb disease in patients treated with anakinra due to rheumatoid arthritis, systemic autoinflammatory diseases, Schnitzler's syndrome, Behçet's disease, adult-onset Still disease, systemic juvenile idiopathic arthritis, gout and diabetes mellitus have been usually very low. However, clinicians must carefully weigh the benefits of biological drugs against their risks, particularly in patients prone to infections. Additional data are needed to understand whether this risk of Mtb infection and reactivation are representative of a class effect related to biologics or whether anakinra bears specifically an intrinsic lower risk in comparison with other biologic drugs. PMID:26940286

  8. Metabolic Profiling of Major Vitamin D Metabolites Using Diels-Alder Derivatization and Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

    Biologically active forms of vitamin D are important analytical targets both in research and in clinical practice. Typically, each of the vitamin D metabolites is best analyzed by individual assay. However, current LC-MS technologies allow simultaneous metabolic profiling of entire biochemical pathw...

  9. Cultural Adaptation in Translation of Company Profiles%公司简介翻译中的文化顺应

    吴青茹

    2014-01-01

    公司简介用来宣传介绍公司情况以吸引潜在顾客。由于中西文化的差异,在翻译公司简介的过程中译者应充分考虑文化因素,从历史传统、风俗习惯、宗教信仰和价值观三个方面让译文顺应目的语的文化语境,更好地传递信息,达到宣传的目的。%A company profile is brief introduction to a company which provides information about the product range or services that a company offers, and states the corporate values to invite potential buyers to contact it. As there are differences between Chi⁃nese Culture and Western Culture, translator should consider the culture influence when do the translation of company profile, making adaptation to accord with the cultural context of target language from three aspects: historical traditions, customs and conventions, religions and values. Thus information can transmit to the target language reader smoothly and the goal of company file can be achieved.

  10. Effect of Ramadan Fasting on Anthropometric Measures and Metabolic Profiles among Type 2 Diabetic Subjects

    Ajit Kumar Paul

    2015-05-01

    Full Text Available Background: Fasting from dawn to dusk during the month of Holy Ramadan is obligatory for all healthy adult Muslims. Individuals are exempted from fasting if they are suffering from an illness that could be adversely affected by fasting. Although The Quran exempts sick people from fasting, many Muslim diabetic patients may not perceive themselves as sick and are keenly interested to fast. But they fast without proper medical guidance exposing themselves to certain risks as a direct consequence of fasting. So we designed this study to assess the impact of fasting during Ramadan and to evaluate the effects of fasting on their biochemical profiles in patients with diabetes. Objective: The objective of this study was to investigate whether Ramadan fasting has any effect on body weight, blood pressure, fasting glucose, HbA1C, serum lipids, serum creatinine among type 2 diabetic patients. Materials and Methods: Fifty two stable outpatients with type 2 diabetes with intention to fast were studied in the month of Ramadan 1434 Hijri calendar year (11th July to 9th August, 2013 at two points of time: one week before Ramadan (visit 1 and within last 3 days before the end of Ramadan (visit 2. During each visit the height, body weight and blood pressure were recorded. Blood samples were collected for fasting glucose, HbA1C, total cholesterol, triglyceride, high density and low density lipoprotein cholesterol and creatinine. Data were analyzed by Student’s paired t-test using SPSS system and results were expressed as mean ± SD. Probability values were considered to be significant if it was less than 0.05. Results: There were 30 (62.8% males and 22 (37.2% females with a mean age of 54.7 ± 11.55 (range 35–80 years and mean duration of diabetes was 5.5 ± 5.2 years (range 9 months–18 years. In this study mean weight of the patients decreased significantly from 60.5 ± 12.6 kg to 58.5 ± 11.3 kg (p<0.001. Blood pressure reduced but not significantly

  11. The metabolic profile of growing lambs fed diets rich in unsaturated fatty acids.

    Steppa, R; Szkudelska, K; Wójtowski, J; Stanisz, M; Szumacher-Strabel, M; Czyżak-Runowska, G; Cieślak, A; Markiewicz-Kęszycka, M; Pietrzak, M

    2014-10-01

    The effect of two diets enriched with unsaturated fatty acids--one containing the addition of dried distillers grains with solubles (DGS) and the other the addition of false flax--Camelina sativa cake (CS)--on some metabolic parameters and hormone concentration in growing lambs was determined in this experiment. A total of 21 ram lambs of the Polish Whiteheaded mutton sheep were divided into three groups (the control, receiving DGS and CS). The diets were administered to animals for 6 weeks. During the experiment, peripheral blood was collected. Glucose (GL), total cholesterol (CH), triglycerides (TG), free fatty acids (FFA), insulin (IN), leptin (LE), triiodothyronine (T3) and thyroxine (T4) were assayed in serum. The age-dependent reduction in CH and TG limited by both experimental diets were observed. A significant increase in FFA concentration was observed in samples collected in the last, that is, third, time period. This was most probably caused by a 12-h pre-slaughter fasting period. A significantly lower dynamic of FFA increase in that experimental period was found in animals receiving the experimental feed. Insulin concentration in DGS-receiving lambs was increased, in contrast to the CS-receiving lambs, in which it was lower when compared to the control. LE concentration was decreased by both experimental diets, more markedly in the DGS-receiving animals. No differences between the experimental groups and the control were observed in T3 and T4 concentrations. The effect of 12-h pre-slaughter fasting was statistically highly significant for the levels of examined blood markers and hormones, except for TG and IN in the group of lambs receiving the experimental diet with CS. PMID:24387699

  12. Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

    Sorribas Albert

    2009-11-01

    Full Text Available Abstract Background Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements. Results We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA representation. The optimization task is posed as a nonconvex nonlinear programming (NLP problem that is solved by an outer-approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in Saccharomyces cerevisiae. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast Saccharomyces cerevisiae to heat shock Conclusion Our results

  13. New Features on the Environmental Regulation of Metabolism Revealed by Modeling the Cellular Proteomic Adaptations Induced by Light, Carbon, and Inorganic Nitrogen in Chlamydomonas reinhardtii.

    Gérin, Stéphanie; Leprince, Pierre; Sluse, Francis E; Franck, Fabrice; Mathy, Grégory

    2016-01-01

    Microalgae are currently emerging to be very promising organisms for the production of biofuels and high-added value compounds. Understanding the influence of environmental alterations on their metabolism is a crucial issue. Light, carbon and nitrogen availability have been reported to induce important metabolic adaptations. So far, the influence of these variables has essentially been studied while varying only one or two environmental factors at the same time. The goal of the present work was to model the cellular proteomic adaptations of the green microalga Chlamydomonas reinhardtii upon the simultaneous changes of light intensity, carbon concentrations (CO2 and acetate), and inorganic nitrogen concentrations (nitrate and ammonium) in the culture medium. Statistical design of experiments (DOE) enabled to define 32 culture conditions to be tested experimentally. Relative protein abundance was quantified by two dimensional differential in-gel electrophoresis (2D-DIGE). Additional assays for respiration, photosynthesis, and lipid and pigment concentrations were also carried out. A hierarchical clustering survey enabled to partition biological variables (proteins + assays) into eight co-regulated clusters. In most cases, the biological variables partitioned in the same cluster had already been reported to participate to common biological functions (acetate assimilation, bioenergetic processes, light harvesting, Calvin cycle, and protein metabolism). The environmental regulation within each cluster was further characterized by a series of multivariate methods including principal component analysis and multiple linear regressions. This metadata analysis enabled to highlight the existence of a clear regulatory pattern for every cluster and to mathematically simulate the effects of light, carbon, and nitrogen. The influence of these environmental variables on cellular metabolism is described in details and thoroughly discussed. This work provides an overview of the

  14. Profiling of genes central to human mitochondrial energy metabolism following low intensity laser irradiation

    Houreld, Nicolette N.; Masha, Roland; Abrahamse, Heidi

    2012-09-01

    Background: Wound healing involves three overlapping phases: inflammation, granulation and tissue remodelling. If this process is disrupted, delayed wound healing ensues, a common complication seen in diabetic patients. Low intensity laser irradiation (LILI) has been found to promote healing in such patients. However, the exact mechanisms of action are poorly understood. Purpose: This study aimed to profile the expression of key genes involved in mitochondrial respiration. Materials and Methods: Diabetic wounded fibroblast cells were exposed to a wavelength of 660 nm and a fluence of 5 J/cm2 and incubated for 30 min. Total RNA was isolated and 1 μg reverse transcribed into cDNA which was used for real-time polymerase chain reaction (PCR) array analysis. The array contained genes important for each of the mitochondrial complexes involved in the electron transport chain (ETC). Adenosine triphosphate (ATP) levels were also determined post-irradiation by ATP luminescence. Results: Genes involved in complex IV (cytochrome c oxidase), COX6B2 and COX6C, and PPA1 which is involved in complex V (ATP synthase) were significantly up-regulated. There was a significant increase in ATP levels in diabetic wounded cells post-irradiation. Discussion and Conclusion: LILI stimulates the ETC at a transcriptional level, resulting in an increase in ATP. This study helps understand the mechanisms of LILI in diabetic wound healing, and gives information on activation of genes in response to LILI.

  15. Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

    Iagher Fabiola

    2011-04-01

    Full Text Available Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG (4 mg/g body weight was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C, coconut fat-treated normal weight group (CO, fish oil-treated normal weight group (FO, obese control group (Ob, coconut fat-treated obese group (ObCO and fish oil-treated obese group (ObFO. Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30% and triacylglycerol (TG; 33% compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

  16. Metabolic profiles using (1)H-nuclear magnetic resonance spectroscopy in postpartum dairy cows with ovarian inactivity.

    Xu, Chuchu; Xia, Cheng; Sun, Yuhang; Xiao, Xinhuan; Wang, Gang; Fan, Ziling; Shu, Shi; Zhang, Hongyou; Xu, Chuang; Yang, Wei

    2016-10-01

    To understand the differences in metabolic changes between cows with ovarian inactivity and estrus cows, we selected cows at 60-90 days postpartum from an intensive dairy farm. According to clinical manifestations, B-ultrasound scan, rectal examination, 10 cows were assigned to the estrus group (A) and 10 to the ovarian inactivity group (B). All plasma samples were analyzed by (1)H-nuclear magnetic resonance spectroscopy to compare plasma metabolomic profiles between the groups. We used multivariate pattern recognition to screen for different metabolites in plasma of anestrus cows. Compared with normal estrous cows, there were abnormalities in 12 kinds of metabolites in postpartum cows with ovarian inactivity (|r|> 0.602), including an increase in acetic acid (r = -0.817), citric acid (r = -0.767), and tyrosine (r = -0.714), and a decrease in low-density lipoprotein (r = 0.820), very low-density lipoprotein (r = 0.828), lipids (r = 0.769), alanine (r = 0.816), pyruvate (r = 0.721), creatine (r = 0.801), choline (r = 0.639), phosphorylcholine (r = 0.741), and glycerophosphorylcholine (r = 0.881). These metabolites were closely related to abnormality of glucose, amino acid, lipoprotein and choline metabolism, which may disturb the normal estrus. The decrease in plasma creatine and the increase in tyrosine were new changes for ovarian inactivity of postpartum cows. The decrease in plasma creatine and choline and the increase in tyrosine and p-hydroxyphenylalanine in cows with ovarian inactivity provide new directions for research on the mechanism of ovarian inactivity in cows. PMID:27291083

  17. Protective properties of radio-chemoresistant glioblastoma stem cell clones are associated with metabolic adaptation to reduced glucose dependence.

    Fei Ye

    Full Text Available Glioblastoma stem cells (GSC are a significant cell model for explaining brain tumor recurrence. However, mechanisms underlying their radiochemoresistance remain obscure. Here we show that most clonogenic cells in GSC cultures are sensitive to radiation treatment (RT with or without temozolomide (TMZ. Only a few single cells survive treatment and regain their self-repopulating capacity. Cells re-populated from treatment-resistant GSC clones contain more clonogenic cells compared to those grown from treatment-sensitive GSC clones, and repeated treatment cycles rapidly enriched clonogenic survival. When compared to sensitive clones, resistant clones exhibited slower tumor development in animals. Upregulated genes identified in resistant clones via comparative expression microarray analysis characterized cells under metabolic stress, including blocked glucose uptake, impaired insulin/Akt signaling, enhanced lipid catabolism and oxidative stress, and suppressed growth and inflammation. Moreover, many upregulated genes highlighted maintenance and repair activities, including detoxifying lipid peroxidation products, activating lysosomal autophagy/ubiquitin-proteasome pathways, and enhancing telomere maintenance and DNA repair, closely resembling the anti-aging effects of caloric/glucose restriction (CR/GR, a nutritional intervention that is known to increase lifespan and stress resistance in model organisms. Although treatment-introduced genetic mutations were detected in resistant clones, all resistant and sensitive clones were subclassified to either proneural (PN or mesenchymal (MES glioblastoma subtype based on their expression profiles. Functional assays demonstrated the association of treatment resistance with energy stress, including reduced glucose uptake, fatty acid oxidation (FAO-dependent ATP maintenance, elevated reactive oxygen species (ROS production and autophagic activity, and increased AMPK activity and NAD(+ levels accompanied by

  18. Comparative transcripts profiling of fruit mesocarp and endocarp relevant to secondary metabolism by suppression subtractive hybridization in Azadirachta indica (neem).

    Narnoliya, Lokesh K; Rajakani, Raja; Sangwan, Neelam S; Gupta, Vikrant; Sangwan, Rajender S

    2014-05-01

    Azadirachta indica (neem) is a medicinally important plant that is valued for its bioactive secondary metabolites. Higher levels of the bioactive phytochemicals are accumulated in fruits than in other tissues. In the present study, a total of 387 and 512 ESTs, respectively, from endocarp and mesocarp of neem fruits were isolated and analyzed. Out of them 318 ESTs (82.17%) clones from endocarp and 418 ESTs (81.64%) from mesocarp encoded putative proteins that could be classified into three major gene ontology categories: biological process, molecular function and cellular component. From the analyses of contigs, 73 unigenes from the forward subtracted library and 35 unigenes from the reverse subtracted library were obtained. The ESTs from mesocarp encoded cytochrome P450 enzymes, which indicated hydroxylation to be a major metabolic event and that biogeneration of hydroxylated neem fruit phytochemicals was differentially regulated with developmental stage-specificity of synthesis. Through this study, we present the first report of any gene expression data in neem tissues. Neem hydroxy-methyl glutaryl-coenzyme A reductase (NHMGR) gene was used as expressing control vis-a-vis subtracted tissues. NHMGR was present in fruit, endocarp and mesocarp tissues, but absent in subtractive libraries, revealing that it was successfully eliminated during subtraction. Eight genes of interest from subtracted libraries were profiled for their expression in fruit, mesocarp and endocarp. Expression profiles validated the quality of the libraries and functional diversity of the tissues. The subtractive cDNA library and EST database described in this study represent a valuable transcript sequence resource for future research aimed at improving the economically important medicinal plant. PMID:24477588

  19. Pea fiber and wheat bran fiber show distinct metabolic profiles in rats as investigated by a 1H NMR-based metabolomic approach.

    Guangmang Liu

    Full Text Available This study aimed to examine the effect of pea fiber (PF and wheat bran fiber (WF supplementation in rat metabolism. Rats were assigned randomly to one of three dietary groups and were given a basal diet containing 15% PF, 15% WF, or no supplemental fiber. Urine and plasma samples were analyzed by NMR-based metabolomics. PF significantly increased the plasma levels of 3-hydroxybutyrate, and myo-inositol as well as the urine levels of alanine, hydroxyphenylacetate, phenylacetyglycine, and α-ketoglutarate. However, PF significantly decreased the plasma levels of isoleucine, leucine, lactate, and pyruvate as well as the urine levels of allantoin, bile acids, and trigonelline. WF significantly increased the plasma levels of acetone, isobutyrate, lactate, myo-inositol, and lipids as well as the urine levels of alanine, lactate, dimethylglycine, N-methylniconamide, and α-ketoglutarate. However, WF significantly decreased the plasma levels of amino acids, and glucose as well as the urine levels of acetate, allantoin, citrate, creatine, hippurate, hydroxyphenylacetate, and trigonelline. Results suggest that PF and WF exposure can promote antioxidant activity and can exhibit common systemic metabolic changes, including lipid metabolism, energy metabolism, glycogenolysis and glycolysis metabolism, protein biosynthesis, and gut microbiota metabolism. PF can also decrease bile acid metabolism. These findings indicate that different fiber diet may cause differences in the biofluid profile in rats.

  20. The gut microbiome of the sea urchin, Lytechinus variegatus, from its natural habitat demonstrates selective attributes of microbial taxa and predictive metabolic profiles.

    Hakim, Joseph A; Koo, Hyunmin; Kumar, Ranjit; Lefkowitz, Elliot J; Morrow, Casey D; Powell, Mickie L; Watts, Stephen A; Bej, Asim K

    2016-09-01

    In this paper, we describe the microbial composition and their predictive metabolic profile in the sea urchin Lytechinus variegatus gut ecosystem along with samples from its habitat by using NextGen amplicon sequencing and downstream bioinformatics analyses. The microbial communities of the gut tissue revealed a near-exclusive abundance of Campylobacteraceae, whereas the pharynx tissue consisted of Tenericutes, followed by Gamma-, Alpha- and Epsilonproteobacteria at approximately equal capacities. The gut digesta and egested fecal pellets exhibited a microbial profile comprised of Gammaproteobacteria, mainly Vibrio, and Bacteroidetes. Both the seagrass and surrounding sea water revealed Alpha- and Betaproteobacteria. Bray-Curtis distances of microbial communities indicated a clustering profile with low intrasample variation. Predictive metagenomics performed on the microbial communities revealed that the gut tissue had high relative abundances of metabolisms assigned to the KEGG-Level-2 designation of energy metabolisms compared to the gut digesta, which had higher carbohydrate, amino acid and lipid metabolisms. Overall, the results of this study elaborate the spatial distribution of microbial communities in the gut ecosystem of L. variegatus, and specifically a selective attribute for Campylobacteraceae in the gut tissue. Also, the predictive functional significance of bacterial communities in uniquely compartmentalized gut ecosystems of L. variegatus has been described. PMID:27368709

  1. Metabolic profile modifications in milk after enrofloxacin administration studied by liquid chromatography coupled with high resolution mass spectrometry.

    Junza, A; Saurina, J; Barrón, D; Minguillón, C

    2016-08-19

    High resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was used in the search and identification of metabolites in raw milk from cows medicated with enrofloxacin. Data consisting of m/z features were taken throughout the entire chromatogram of milk samples from medicated animals and were compared with blank samples. Twenty six different compounds were identified. Some of them were attributed to structures related to enrofloxacin while others were dipeptides or tripeptides. Additionally, enrofloxacin was administered in a controlled treatment for three days. Milk was collected daily from the first day of treatment and until four days after in the search for the identified compounds. The obtained data were chemometrically treated by Principal Component Analysis. Samples were classified by this method into three different groups corresponding to days 1-2, day 3 and days 4-7 considering the different concentration profile evolution of metabolites during the days studied. Tentative metabolic pathways were designed to rationalize the presence of the newly identified compounds. PMID:27425761

  2. Antioxidant activity, cytotoxic activity and metabolic profiling of juices obtained from saffron (Crocus sativus L.) floral by-products.

    Tuberoso, Carlo I G; Rosa, Antonella; Montoro, Paola; Fenu, Maurizio Antonio; Pizza, Cosimo

    2016-05-15

    Juices obtained from cold-pressed saffron (Crocus sativus L.) floral by-products were evaluated as a potential source of compounds with antioxidant and cytotoxic activities. Floral by-products were split in two batches for extraction 24 and 48h after flower harvesting, respectively. The in vitro anti-oxidant activity of these extracts was tested using the FRAP and DPPH assays, and two biological models of lipid oxidation (activity in preventing cholesterol degradation and protection against Cu(2+)-mediated degradation of the liposomal unsaturated fatty acids). The cytotoxic activity was evaluated using the MTT assay. The results show that extracts obtained 48h post-harvest contained higher levels of total polar phenols and had the highest antioxidant activity in all of the performed assays. The LC-DAD and LC-ESI-(HR)MS(n) metabolic profiles showed high levels of kaempferol derivatives and anthocyanins. This study suggests that juices from saffron floral by-products could potentially be used to develop new products for the food and health industry. PMID:26775939

  3. Global metabolic profiling using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

    Qi, Yunpeng; Song, Yunlong; Gu, Haiwei; Fan, Guorong; Chai, Yifeng

    2014-01-01

    Currently, liquid chromatography-mass spectrometry (LC-MS) is one of the most important analytical technologies for detecting hundreds of metabolites in the field of metabolomics. A recent advance in LC that has impacted metabolomics is the development of UPLC (ultra-performance liquid chromatography). In this chapter, we describe the analytical methodologies for the global metabolic profiling of serum, urine, and tissue samples using UPLC-Q-TOF (quadrupole-time-of-flight)-MS. Aqueous metabolites are extracted after adding methanol/acetonitrile/acetone and then analyzed by UPLC-MS under positive and/or negative ionization mode. With the aid of multivariate statistical analysis, separation between various groups can be observed in the score plots, and biomarkers are screened in the loading/weight/VIP (variable importance in the projection) scatterplots. Furthermore, putative markers can be identified through comparison with the authentic standards based on tandem mass spectrometry (MS/MS) fragmentation pattern and LC retention. We expect that our protocol, with modifications if necessary, can be useful in many metabolomics studies and a wide range of research areas related to small molecules and LC-MS. PMID:25270920

  4. Metabolic Heat Stress Adaption in Transition Cows: Differences in Macronutrient Oxidation between Late-Gestating and Early-Lactating German Holstein Dairy Cows.

    Ole Lamp

    Full Text Available High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS and one pair-fed (PF at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1, cows were challenged for 6 days (P2 by heat stress (temperature humidity index (THI = 76 or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows.

  5. Dynamic metabolic profiling of urine biomarkers in rats with alcohol‑induced liver damage following treatment with Zhi‑Zi‑Da‑Huang decoction.

    An, Li; Lang, Qiaoling; Shen, Wenbin; Shi, Qingshui; Feng, Fang

    2016-09-01

    Alcoholic liver disease (ALD) is a leading cause of liver‑associated morbidity and mortality. Zhi‑Zi‑Da‑Huang decoction (ZZDHD), a traditional Chinese medicine formula, has been frequently used to treat or alleviate the symptoms of the various stages of ALD. To identify metabolic changes and the ZZDHD mechanism of action on ALD, potential urine biomarkers involved in the effects of ZZDHD were identified. Additionally, dynamic metabolomic profiles were systematically analyzed using nuclear magnetic resonance (NMR) spectroscopy in conjunction with statistical analysis. Alcohol administration to experimental rats disrupted multiple metabolic pathways, including methionine, gut bacterial, energy and amino acid metabolism. However, ZZDHD relieved certain effects of alcohol on the metabolism and regulated changes in potential characteristic biomarkers, including dimethylglycine, hippurate, lactate and creatine. The present study investigated time‑dependent metabolomic changes in the development of alcohol‑induced liver injury, including the effect of ZZDHD intervention. These findings elucidated important information regarding the metabolic responses to the protective effects of ZZDHD. 1H NMR‑based metabolomics method a reliable and useful tool for determining the metabolic progression of alcohol‑induced liver injury and elucidating the underlying mechanisms of the effect of traditional Chinese medicine formulas. This study also demonstrated that NMR‑based metabolomics approach is a powerful tool for understanding the molecular basis of pathogenesis and drug intervention processes. PMID:27430289

  6. CRITICAL POINTS IN THE FEEDING OF HIGH YIELDING DAIRY COWS IN ASSOCIATION WITH BCS AND METABOLIC PROFILE TEST

    Z. GERGÁCZ

    2013-07-01

    Full Text Available The aim of the study was to analyse the relationship between the body condition and the results of metabolic profile tests done in the milk (DIM of dairy cows in different days. Moreover, critical points in the early pre- and postpartum period were also analysed. In the experiment, blood and urine samples were taken from 1984 clinically healthy cows (from 49 large scale dairy farms in Hungary, selected randomly from various groups of cows with different physiological stage of lactation and gestation, 3-5 hours after the morning feeding. During the experiment body condition scoring (BCS was measured on 1-5 scale, as well. It was concluded, that the BCS (body condition score decreased from the 1st day of lactation (3.48 onwards till the 44th day (2.65 and slightly increased till the day 218 (2.89. The haemoglobin value and the glucose concentration in blood samples were ranging within the physiological range and followed the tendency of BCS and the relationship between them and DIM was (P<0.001. There was a close negative correlation between the NEFA (non-esterified-fatty-acid concentration in blood samples and BCS change and it was found that these values were significantly different (P<0.01 compared to the DIM. The aceto-acetic acid concentration exceeded the upper limit of the physiological range indicating hyperketonaemia at DIM 18. The AST (aspartate aminotransferase, liver-enzyme activity value exceeded the upper limit of physiological range and followed the tendency of BCS change . The urea concentration in the blood exceeded the upper limit of the physiological range in all cows. The NABE (net acid-base empty value in the urine samples indicated acid load in the first two groups of samples (pre-, and post calving. During factor analysis I could differentiate three group factors and one individual. The most important factor is the acid-based factor (with urine pH and NEBA. The results of the present study also confirm that the body

  7. The metabolic effects of di (2-ethyl hexyl phthalate medium dose on lipid profiles in serum and liver tissue

    Buang Y

    2011-02-01

    Full Text Available Background: Di (2-ethyl hexyl phthalate is the most widely used  plasticizer in blood storage bag for transfusion. This substance can modify lipid metabolism. This study was aimed to elucidate the metabolic effects of di (2-ethyl hexyl phthalate medium dose on lipid profiles in serum and liver tissue.Methods: Sprague Dawley rats were fed 1.0 % di (2-ethyl hexyl phthalate diet (DEHP group, n=5 or a non-supplemented diet (control group, n=5 for 10 days. The rats were allowed to freely access each food. Serum lipid concentrations were measured using enzyme assay kits. Lipids of liver tissues were extracted and the lipid contents were determined. A peach of liver was prepared to determine the activities of malic enzyme and carnitine palmitoyl transferase-1 (CPT-1.Results: Serum lipid concentrations (mg/dL of DEHP group decreased compared to control (P<0.05. The serum triglyceride (TG concentrations of control and DEHP groups were respectively (100.5±16.5 and (31.2±1.7; phospholipid (PL, (143.3±7.8 and (88.9±3.2; total cholesterol, (88.7±4.6 and (51.9±2.3. The liver TG content of control and DEHP group (mg/g liver were respectively, (40.8±4.4 and (23.7±1.3; liver cholesterol were (3.36±0.29 and (2.33±0.23; and the liver PL were (36.5±1.0 and (41.7±0.6. Malic enzyme and CPT-1 activities (nmol/min/mg protein of DEHP group increased compared to control (P<0.05, in which their increases were approximately by 4.35- and 2.33-folds,  respectively.Conclusion: The di (2-ethyl hexyl phthalate medium dose attenuates lipids secretion from the liver cells into the bloodstream. The increase of liver PL level accompanied with the promotions of malic enzyme and the CPT-1 activities are the key factors of the dietary di (2-ethyl hexyl phthalate effects in rats to attenuate the lipid secretions from the livers. (Med J Indones 2011; 20:20-6Keywords: Di (2-ethyl hexyl phthalate, hyperphospholipids, lipolysis, liver lipids, serum lipids

  8. Microbial and metabolic profiling reveal strong influence of water table and land-use patterns on classification of degraded tropical peatlands

    S. Mishra

    2013-08-01

    Full Text Available Tropical peatlands from Southeast Asia are undergoing extensive drainage, deforestation and degradation for agriculture and human settlement purposes. This is resulting in biomass loss and subsidence of peat from its oxidation. Molecular profiling approaches were used to understand the relative influences of different land-use patterns, hydrological and physiochemical parameters on the state of degraded tropical peatlands. As microbial communities play a critical role in biogeochemical cascades in the functioning of peatlands, we used microbial and metabolic profiles as surrogates of community structure and functions, respectively. Profiles were generated from 230 bacterial 16S rDNA fragments and 145 metabolic markers of 46 samples from ten sites, including those from above and below water table in a contiguous area of 48 km2 covering five land-use types. These were degraded forest, degraded land, oil palm plantation, mixed crop plantation and settlements. Bacterial profiles were most influenced by variations in water table and land-use patterns, followed by age of drainage and peat thickness in that order. Bacterial profiling revealed differences in sites, based on the duration and frequency of water table fluctuations and on oxygen availability. Bacterial and metabolic profiles of degraded forest and mixed crop plantations were most diverse compared to other land-use types. Metabolic profiling, being closely associated with biogeochemical functions could distinguish communities not only based on land-use types but also their geographic locations, thus providing a finer resolution than bacterial profiles. Agricultural inputs, such as nitrates were highly associated with bacterial community structure of oil palm plantations, whereas phosphates and dissolved organic carbon influenced those from mixed crop plantations and settlements. Our results provide a basis for adopting molecular marker-based approaches to classify peatlands and determine

  9. Indicadores metabólicos en razas lecheras especializadas en condiciones tropicales en Colombia Metabolic profile in dairy cows under tropical conditions in Colombia

    Rómulo Campos G

    2007-06-01

    Full Text Available Se ha seleccionado un alto número de razas bovinas para producción de leche, sin embargo, las de origen Bos taurus no han logrado adaptarse a las condiciones tropicales. El objetivo del trabajo fue analizar el comportamiento metabólico de siete razas (Ayrshire, Girolando, Holstein Friesian, Jersey, Lucerna, Pardo Suizo y Simenthal a través de 15 metabolitos. Se emplearon 28 animales por raza, distribuidos en cuatro grupos fisiológicos: novillas, inicio y final de lactancia y vacas secas (final de gestación. Los valores medios de los indicadores metabólicos fueron: BOH 0.5 mmol/l; glucosa 2.8 mmol/l; colesterol 2.5 mmol/l; potasio 4.1 mmol/l; calcio 2.0 mmol/l; fósforo inorgánico 1.7 mmol/l; magnesio 1.1 mmol/l; proteínas totales 66.2 mg/dl; albúmina 25.8 mg/dl; globulinas 40.2 mg/dl; creatinina 109 µmol/l; BUN 3.8 mmol/l; ALT 32.2 UI/l; AST 56.6 UI/l; GGT 12.3 UI/l; bilirrubina total 0.2 µmol/l; bilirrubina conjugada 0.08 µmol/l. Los valores medios de la condición corporal y el hematocrito fueron 3.25% y 27.0% respectivamente. Se encontraron diferencias estadísticas significativas entre grupos raciales y entre grupos de producción. Los animales de menor peso metabólico (Jersey presentaron mejor homeostasis que los de pesos mayores (Simenthal, Holstein.High numbers of bovine breeds have been selected as milk producers, but those derived from the Bos taurus breeds have been unable to adapt to tropical conditions. The aim of this work was to analyze the metabolic profile of the seven breeds (Ayrshire, Girolando, Holstein Friesian, Jersey , Lucerna, Brown Swiss and Simmental through the use of 15 metabolites. For each breed, 28 animals were used, divided into four physiological different groups: heifers, cows from the first stages and last stages of the lactation process and dry cows. The mean values of metabolites indicators were as follow: BOH 0.5 mmol/l; glucose 2.8 mmol/l; cholesterol 2.5 mmol/l; potassium 4.1 mmol/l; calcium 2

  10. 1H High Resolution Magic-Angle Coil Spinning (HR-MACS) - NMR Metabolic Profiling of whole Saccharomyces cervisiae cells: A Demonstrative Study

    Wong, Alan; Boutin, Celine; Aguiar, Pedro

    2014-06-01

    The low sensitivity of Nuclear Magnetic Resonance (NMR) is its prime shortcoming compared to other analytical methods for metabolomic studies. It relies on large sample volume (30-50 µl for HR-MAS) for rich metabolic profiling, hindering high-throughput screening especially when the sample requires a labor-intensive preparation or is a sacred specimen. This is indeed the case for some living organisms. This study evaluates a 1H HR-MAS approach for metabolic profiling of small volume (250 nl) whole bacterial cells, Saccharomyces cervisiae, using an emerging micro-NMR technology: high-resolution magic-angle coil spinning (HR-MACS). As a demonstrative study for whole cells, we perform two independent metabolomics studies identifying the significant metabolites associated with osmotic stress and aging.

  11. 1H High Resolution Magic-Angle Coil Spinning (HR-MACS µNMR Metabolic Profiling of whole Saccharomyces cervisiae cells: A Demonstrative Study

    Alan eWong

    2014-06-01

    Full Text Available The low sensitivity of Nuclear Magnetic Resonance (NMR is its prime shortcoming compared to other analytical methods for metabolomic studies. It relies on large sample volume (30–50 µl for HR-MAS for rich metabolic profiling, hindering high-throughput screening especially when the sample requires a labor-intensive preparation or is a sacred specimen. This is indeed the case for some living organisms. This study evaluates a 1H HR-MAS approach for metabolic profiling of small volume (250 nl whole bacterial cells, Saccharomyces cervisiae, using an emerging micro-NMR technology: high-resolution magic-angle coil spinning (HR-MACS. As a demonstrative study for whole cells, we perform two independent metabolomics studies identifying the significant metabolites associated with osmotic stress and aging.

  12. Hepatic transcriptome profiling identifies differences in expression of genes associated with changes in metabolism and postnatal growth between Hereford and Holstein-Friesian bulls.

    Lisowski, Pawel; Kościuczuk, Ewa M; Gościk, Joanna; Pierzchała, Mariusz; Rowińska, Barbara; Zwierzchowski, Lech

    2014-04-01

    This study examined liver transcriptomic profiles of cattle distinctly different in meat and milk production capacity. It was performed on bulls of two different genetic backgrounds: Herefords (H), a meat breed, and Holstein-Friesians (HF), a dairy breed. Using bovine long oligo-microarrays and qPCR, we identified 128 genes that are differentially expressed between the two breeds. In H bulls, we observed up-regulation of genes involved in fatty acid biosynthesis and lipid metabolism (CD36, CAT, HSD3B1, FABP1, ACAA1) and involved in insulin signaling (INSR, INSIG2, NR4A1) and down-regulation of genes involved in somatotropic axis signaling (IGF1, GHR, IGFBP3) as compared to HF. Transcriptome profiling of these two breeds allowed us to pinpoint the transcriptional differences between Holstein and Hereford bulls at hepatic level associated with changes in metabolism and postnatal growth. PMID:24304134

  13. Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models

    Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood. The concentrations of choline-derived metabolites were determined in xenografted primary human breast carcinomas, representing basal-like and luminal-like subtypes. Quantification of metabolites in fresh frozen tissue was performed using high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS). The expression of genes involved in phosphatidylcholine (PtdCho) metabolism was retrieved from whole genome expression microarray analyses. The metabolite profiles from xenografts were compared with profiles from human breast cancer, sampled from patients with estrogen/progesterone receptor positive (ER+/PgR+) or triple negative (ER-/PgR-/HER2-) breast cancer. In basal-like xenografts, glycerophosphocholine (GPC) concentrations were higher than phosphocholine (PCho) concentrations, whereas this pattern was reversed in luminal-like xenografts. These differences may be explained by lower choline kinase (CHKA, CHKB) expression as well as higher PtdCho degradation mediated by higher expression of phospholipase A2 group 4A (PLA2G4A) and phospholipase B1 (PLB1) in the basal-like model. The glycine concentration was higher in the basal-like model. Although glycine could be derived from energy metabolism pathways, the gene expression data suggested a metabolic shift from PtdCho synthesis to glycine formation in basal-like xenografts. In agreement with results from the xenograft models, tissue samples from triple negative breast carcinomas had higher GPC/PCho ratio than samples from ER+/PgR+ carcinomas, suggesting that the choline metabolism in the experimental models is representative for luminal-like and basal-like human breast cancer. The differences in choline metabolite

  14. Metabolic profile in two physically active Inuit groups consuming either a western or a traditional Inuit diet

    Thor Munch-Andersen

    2012-03-01

    Full Text Available Objectives: To evaluate the effect of regular physical activity on metabolic risk factors and blood pressure in Inuit with high BMI consuming a western diet (high amount of saturated fatty acids and carbohydrates with a high glycemic index. Study design: Cross sectional study, comparing Inuit eating a western diet with Inuit eating a traditional diet. Methods: Two physically active Greenland Inuit groups consuming different diet, 20 eating a traditional diet (Qaanaaq and 15 eating a western diet (TAB, age (mean (range; 38, (22–58 yrs, BMI; 28 (20–40 were subjected to an oral glucose tolerance test (OGTT, blood sampling, maximal oxygen uptake test, food interview/collection and monitoring of physical activity. Results: All Inuit had a normal OGTT. Fasting glucose (mmol/l, HbA1c (%, total cholesterol (mmol/l and HDL-C (mmol/l were for Qaanaaq women: 4.8±0.2, 5.3±0.1, 4.96±0.42, 1.34±0.06, for Qaanaaq men: 4.9±0.1, 5.7±0.1, 5.08±0.31, 1.28±0.09, for TAB women: 5.1±0.2, 5.3±0.1, 6.22±0.39, 1.86±0.13, for TAB men: 5.1±0.2, 5.3±0.1, 6.23±0.15, 1.60±0.10. No differences were found in systolic or diastolic blood pressure between the groups. There was a more adverse distribution of small dense LDL-C particles and higher total cholesterol and HDL-C concentration in the western diet group. Conclusions: Diabetes or impaired glucose tolerance was not found in the Inuit consuming either the western or the traditional diet, and this could, at least partly, be due to the high amount of regular daily physical activity. However, when considering the total cardio vascular risk profile the Inuit consuming a western diet had a less healthy profile than the Inuit consuming a traditional diet.

  15. Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a double-blind, randomized, open-label study

    Wani RA

    2015-03-01

    Full Text Available Rayees Ahmad Wani, Mansoor Ahmad Dar, Rajesh Kumar Chandel, Yasir Hassan Rather, Inaamul Haq, Arshad Hussain, Altaf Ahmad MallaDepartment of Psychiatry, Government Medical College, Srinagar, Jammu and Kashmir, IndiaBackground: Patients with schizophrenia suffer high rates of metabolic derangements on some antipsychotic medications that predispose them to cardiovascular diseases. Keeping this fact in mind, we planned this open-label study to see the effect on various metabolic parameters after switching stable schizophrenia subjects, who had developed metabolic syndrome on olanzapine, to aripiprazole.Methods: Sixty-two patients with schizophrenia who were stable on olanzapine and were fulfilling modified National Cholesterol Education Program (NCEP Adult Treatment Panel III (ATP-III criteria for the presence of metabolic syndrome were enrolled on the study. Patients were randomly assigned either to switch to aripiprazole or to stay on olanzapine, on a 1:1 basis. Cross-tapering over a period of 1 month was done while switching patients to aripiprazole. Laboratory assessment for metabolic parameters was done at baseline, 8 weeks, and 24 weeks after enrollment; efficacy assessment was done using the Positive and Negative Syndrome Scale (PANSS at baseline and 24 weeks, the Clinical Global Impressions severity subscale (CGI-S at baseline, and the Clinical Global Impressions improvement subscale (CGI-I at 24 weeks.Results: All parameters of metabolic syndrome (waist circumference, blood pressure, triglyceride level, fasting blood glucose, and high-density lipoprotein cholesterol kept deteriorating in the stay group, compared with a continuous improvement in the switch group over time. At the end of the study, 26 patients (100% from the stay group and 15 patients (42.8% from switch group met the modified NCEP ATP-III criteria for presence of metabolic syndrome (P<0.001. There were no statistically significant differences between groups in

  16. Characterization of in vitro metabolic profiles of cinitapride obtained with liver microsomes of humans and various mammal species using UHPLC and chemometric methods for data analysis.

    Marquez, Helena; Albertí, Joan; Salvà, Miquel; Saurina, Javier; Sentellas, Sonia

    2012-05-01

    An ultra-high performance liquid chromatographic method has been utilized to obtain metabolic profiles of cinitapride with liver microsomes of humans and various mammal species such as rats, mice, mini pigs, dogs, and monkeys. Metabolites have been generated by incubation of cinitapride in the presence of microsomes using nicotinamide adenine dinucleotide phosphate as a cofactor. Incubation times from 15 to 60 min have been assayed. Cinitapride and its metabolites have been separated by reversed-phase C(18) mode using ammonium formate aqueous solution (pH 6.5) and acetonitrile as the components of the mobile phase. Concentrations of metabolites in the incubated samples have resulted in an excellent source of multivariate data to be used to extract metabolic information. Statistic parameters and principal component analysis have been used to compare the in vitro metabolism of humans with the other species. PMID:22362276

  17. Effect of Levan Supplement in Orange Juice on Weight, Gastrointestinal Symptoms and Metabolic Profile of Healthy Subjects: Results of an 8-Week Clinical Trial

    Nachum Vaisman; Mira Arbiv; Etty Naor; Evgenia Rokhkind; Ira Akiva; Yami Shapira; Eva Niv

    2012-01-01

    Levan is a commonly used dietary fiber of the fructans group. Its impact on health remains undetermined. This double blind controlled study aimed to investigate the effect of 8 weeks’ daily consumption of 500 mL of natural orange juice enriched with 11.25 g of levan compared to the same amount of natural orange juice without levan on weight, gastrointestinal symptoms and metabolic profiles of 48 healthy volunteers. The statistical analyses compared between- and within-group findings at baseli...

  18. Global Metabolic Regulation of the Snow Alga Chlamydomonas nivalis in Response to Nitrate or Phosphate Deprivation by a Metabolome Profile Analysis

    Na Lu; Jun-Hui Chen; Dong Wei; Feng Chen; Gu Chen

    2016-01-01

    In the present work, Chlamydomonas nivalis, a model species of snow algae, was used to illustrate the metabolic regulation mechanism of microalgae under nutrient deprivation stress. The seed culture was inoculated into the medium without nitrate or phosphate to reveal the cell responses by a metabolome profile analysis using gas chromatography time-of-flight mass spectrometry (GC/TOF-MS). One hundred and seventy-one of the identified metabolites clustered into five groups by the orthogonal pa...

  19. Organic and inorganic sources of zinc, copper and selenium in diets for dairy cows: intake, blood metabolic profile, milk yield and composition

    Cristina Simões Cortinhas; José Esler de Freitas Júnior; Julianne de Rezende Naves; Marco Aurélio de Felicio Porcionato; Luís Felipe Prada e Silva; Francisco Palma Rennó; Marcos Veiga dos Santos

    2012-01-01

    The present study was carried out with the objective of evaluating the effects of feeding dairy cows with organic or inorganic sources of zinc (Zn), copper (Cu) and selenium (Se) on blood concentrations of these minerals, blood metabolic profiles, nutrient intake and milk yield and composition. Nineteen Holstein cows were selected and randomly assigned to two groups for receiving organic (n = 9) or inorganic (n = 10) sources of Zn, Cu and Se from 60 days before the expected date of calving to...

  20. Effects of Various Dietary Amino Acid Preparations for Phenylketonuric Patients on the Metabolic Profiles along with Postprandial Insulin and Ghrelin Responses

    Weigel, Corina; Rauh, Manfred; Kiener, C.; Rascher, Wolfgang; Knerr, Ina

    2013-01-01

    Aim: We investigated the metabolic profiles along with insulin and ghrelin responses following ingestion of various amino acid (AA) substitutes commonly used in the treatment of phenylketonuria to study the effects of added macronutrients. Methods: Twenty healthy and 6 phenylketonuric adults ingested AA mixtures with or without carbohydrates and fat (Anamix, Easiphen, or p-am 3; 0.35 g AA/kg body weight); milk powder shakes were used for control purposes. Serum AA, glucose, urea, insulin, and...

  1. Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

    Nanyang Yu; Si Wei; Meiying Li; Jingping Yang; Kan Li; Ling Jin; Yuwei Xie; Giesy, John P; Xiaowei Zhang; Hongxia Yu

    2016-01-01

    Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of expos...

  2. Identification of Key Licorice Constituents Which Interact with Cytochrome P450: Evaluation by LC/MS/MS Cocktail Assay and Metabolic Profiling

    Qiao, Xue; Ji, Shuai; Yu, Si-wang; Lin, Xiong-hao; Jin, Hong-wei; Duan, Yao-kai; Zhang, Liang-Ren; Guo, De-an; Ye, Min

    2013-01-01

    Licorice has been shown to affect the activities of several cytochrome P450 enzymes. This study aims to identify the key constituents in licorice which may affect these activities. Bioactivity assay was combined with metabolic profiling to identify these compounds in several complex licorice extracts. Firstly, the inhibition potencies of 40 pure licorice compounds were tested using an liquid chromatography/tandem mass spectrometry cocktail method. Significant inhibitors of human P450 isozymes...

  3. Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

    Yu, Nanyang; Wei, Si; Li, Meiying; Yang, Jingping; Li, Kan; Jin, Ling; Xie, Yuwei; Giesy, John P.; Zhang, Xiaowei; Yu, Hongxia

    2016-04-01

    Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects.

  4. A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles

    Sugimoto Masahiro

    2006-07-01

    Full Text Available Abstract Background In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems. Results The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations. Conclusion The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.

  5. Effects of Perfluorooctanoic Acid on Metabolic Profiles in Brain and Liver of Mouse Revealed by a High-throughput Targeted Metabolomics Approach

    Yu, Nanyang; Wei, Si; Li, Meiying; Yang, Jingping; Li, Kan; Jin, Ling; Xie, Yuwei; Giesy, John P.; Zhang, Xiaowei; Yu, Hongxia

    2016-01-01

    Perfluorooctanoic acid (PFOA), a perfluoroalkyl acid, can result in hepatotoxicity and neurobehavioral effects in animals. The metabolome, which serves as a connection among transcriptome, proteome and toxic effects, provides pathway-based insights into effects of PFOA. Since understanding of changes in the metabolic profile during hepatotoxicity and neurotoxicity were still incomplete, a high-throughput targeted metabolomics approach (278 metabolites) was used to investigate effects of exposure to PFOA for 28 d on brain and liver of male Balb/c mice. Results of multivariate statistical analysis indicated that PFOA caused alterations in metabolic pathways in exposed individuals. Pathway analysis suggested that PFOA affected metabolism of amino acids, lipids, carbohydrates and energetics. Ten and 18 metabolites were identified as potential unique biomarkers of exposure to PFOA in brain and liver, respectively. In brain, PFOA affected concentrations of neurotransmitters, including serotonin, dopamine, norepinephrine, and glutamate in brain, which provides novel insights into mechanisms of PFOA-induced neurobehavioral effects. In liver, profiles of lipids revealed involvement of β-oxidation and biosynthesis of saturated and unsaturated fatty acids in PFOA-induced hepatotoxicity, while alterations in metabolism of arachidonic acid suggesting potential of PFOA to cause inflammation response in liver. These results provide insight into the mechanism and biomarkers for PFOA-induced effects. PMID:27032815

  6. Organic and inorganic sources of zinc, copper and selenium in diets for dairy cows: intake, blood metabolic profile, milk yield and composition

    Cristina Simões Cortinhas

    2012-06-01

    Full Text Available The present study was carried out with the objective of evaluating the effects of feeding dairy cows with organic or inorganic sources of zinc (Zn, copper (Cu and selenium (Se on blood concentrations of these minerals, blood metabolic profiles, nutrient intake and milk yield and composition. Nineteen Holstein cows were selected and randomly assigned to two groups for receiving organic (n = 9 or inorganic (n = 10 sources of Zn, Cu and Se from 60 days before the expected date of calving to 80 days of lactation. Samples of feed, orts and milk were collected for analysis. Body condition score (BCS was determined and blood samples were collected for analysis of Zn, Cu and Se concentrations, as well as for metabolic profile. Supplying organic or inorganic sources of Zn, Cu, and Se did not affect dry matter and nutrient intake, blood metabolic profile, milk yield and composition, plasma concentration of these minerals, and BCS or change the BCS in cows from 60 days before the expected date of calving to 80 days of lactation. An effect of time was observed on all feed intake variables, plasma concentrations of Zn and Se, milk yield, milk protein content, BCS and change in BCS.

  7. Metabolic and proteomic adaptation of Lactobacillus rhamnosus strains during growth under cheese-like environmental conditions compared to de Man, Rogosa, and Sharpe medium.

    Bove, Claudio Giorgio; De Angelis, Maria; Gatti, Monica; Calasso, Maria; Neviani, Erasmo; Gobbetti, Marco

    2012-11-01

    The aim of this study was to demonstrate the metabolic and proteomic adaptation of Lactobacillus rhamnosus strains, which were isolated at different stages of Parmigiano Reggiano cheese ripening. Compared to de Man, Rogosa, and Sharpe (MRS) broth, cultivation under cheese-like conditions (cheese broth, CB) increased the number of free amino acids used as carbon sources. Compared with growth on MRS or pasteurized and microfiltrated milk, all strains cultivated in CB showed a low synthesis of d,l-lactic acid and elevated levels of acetic acid. The proteomic maps of the five representative strains, showing different metabolic traits, were comparatively determined after growth on MRS and CB media. The amount of intracellular and cell-associated proteins was affected by culture conditions and diversity between strains, depending on their time of isolation. Protein spots showing decreased (62 spots) or increased (59 spot) amounts during growth on CB were identified using MALDI-TOF-MS/MS or LC-nano-ESI-MS/MS. Compared with cultivation on MRS broth, the L. rhamnosus strains cultivated under cheese-like conditions had modified amounts of some proteins responsible for protein biosynthesis, nucleotide, and carbohydrate metabolisms, the glycolysis pathway, proteolytic activity, cell wall, and exopolysaccharide biosynthesis, cell regulation, amino acid, and citrate metabolism, oxidation/reduction processes, and stress responses. PMID:22965658

  8. High-intensity interval training-induced metabolic adaptation coupled with an increase in Hif-1α and glycolytic protein expression.

    Abe, Takaaki; Kitaoka, Yu; Kikuchi, Dale Manjiro; Takeda, Kohei; Numata, Osamu; Takemasa, Tohru

    2015-12-01

    It is known that repeated bouts of high-intensity interval training (HIIT) lead to enhanced levels of glycolysis, glycogenesis, and lactate transport proteins in skeletal muscle; however, little is known about the molecular mechanisms underlying these adaptations. To decipher the mechanism leading to improvement of skeletal muscle glycolytic capacity associated with HIIT, we examined the role of hypoxia-inducible factor-1α (Hif-1α), the major transcription factor regulating the expression of genes related to anaerobic metabolism, in the adaptation to HIIT. First, we induced Hif-1α accumulation using ethyl 3,4-dihydroxybenzoate (EDHB) to assess the potential role of Hif-1α in skeletal muscle. Treatment with EDHB significantly increased the protein levels of Hif-1α in gastrocnemius muscles, accompanied by elevated expression of genes related to glycolysis, glycogenesis, and lactate transport. Daily administration of EDHB for 1 wk resulted in elevated glycolytic enzyme activity in gastrocnemius muscles. Second, we examined whether a single bout of HIIT could induce Hif-1α protein accumulation and subsequent increase in the expression of genes related to anaerobic metabolism in skeletal muscle. We observed that the protein levels of Hif-1α and expression of the target genes were elevated 3 h after an acute bout of HIIT in gastrocnemius muscles. Last, we examined the effects of long-term HIIT. We found that long-term HIIT increased the basal levels of Hif-1α as well as the glycolytic capacity in gastrocnemius muscles. Our results suggest that Hif-1α is a key regulator in the metabolic adaptation to high-intensity training. PMID:26429867

  9. Glucose homeostasis and metabolic adaptation in the pregnant and lactating sheep are affected by the level of nutrition previously provided during her late fetal life

    Husted, Sanne Munch; Nielsen, Mette Olaf; Blache, D;

    2008-01-01

    This study investigated whether undernutrition (UN) during late fetal life can programme the subsequent adult life adaptation of glucose homeostasis and metabolism during pregnancy and lactation. Twenty-four primiparous experimental ewes were used. Twelve had been exposed to a prenatal NORM level...... of nutrition (maternal diet approximately 15 MJME/d) and 12 to a LOW level of nutrition (maternal diet approximately 7 MJME/d) during the last 6 weeks pre-partum. The experimental ewes were subjected to two intravenous glucose tolerance tests (IGTT) in late gestation (one prior to (G-IGTT) and one by...

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

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

    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 cattl...

  11. Metabolic profiling study on potential toxicity and immunotoxicity-biomarker discovery in rats treated with cyclophosphamide using HPLC-ESI-IT-TOF-MS.

    Li, Jing; Lin, Wensi; Lin, Weiwei; Xu, Peng; Zhang, Jianmei; Yang, Haisong; Ling, Xiaomei

    2015-05-01

    Despite the recent advances in understanding toxicity mechanism of cyclophosphamide (CTX), the development of biomarkers is still essential. CTX-induced immunotoxicity in rats by a metabonomics approach was investigated using high-performance liquid chromatography coupled with ion trap time-of-flight mass spectrometry (HPLC-ESI-IT-TOF-MS). The rats were orally administered CTX (30 mg/kg/day) for five consecutive days, and on the fifth day samples of urine, thymus and spleen were collected and analyzed. A significant difference in metabolic profiling was observed between the CTX-treated group and the control group by partial least squares-discriminant analysis (PLS-DA), which indicated that metabolic disturbances of immunotoxicity in CTX-treated rats had occurred. One potential biomarker in spleen, three in urine and three in thymus were identified. It is suggested that the CTX-toxicity mechanism may involve the modulation of tryptophan metabolism, phospholipid metabolism and energy metabolism. This research can help to elucidate the CTX-influenced pathways at a low dose and can further help to indicate the patients' pathological status at earlier stages of toxicological progression after drug administration. PMID:25322901

  12. Metabolic profiling in Maturity-onset diabetes of the young (MODY and young onset type 2 diabetes fails to detect robust urinary biomarkers.

    Anna L Gloyn

    Full Text Available It is important to identify patients with Maturity-onset diabetes of the young (MODY as a molecular diagnosis determines both treatment and prognosis. Genetic testing is currently expensive and many patients are therefore not assessed and are misclassified as having either type 1 or type 2 diabetes. Biomarkers could facilitate the prioritisation of patients for genetic testing. We hypothesised that patients with different underlying genetic aetiologies for their diabetes could have distinct metabolic profiles which may uncover novel biomarkers. The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK or hepatocyte nuclear factor 1 alpha (HNF1A, type 2 diabetes (T2D and normoglycaemic control subjects. Urinary metabolic profiling by Nuclear Magnetic Resonance (NMR and ultra performance liquid chromatography hyphenated to Q-TOF mass spectrometry (UPLC-MS was performed in a Discovery set of subjects with HNF1A-MODY (n = 14, GCK-MODY (n = 17, T2D (n = 14 and normoglycaemic controls (n = 34. Data were used to build a valid partial least squares discriminate analysis (PLS-DA model where HNF1A-MODY subjects could be separated from the other diabetes subtypes. No single metabolite contributed significantly to the separation of the patient groups. However, betaine, valine, glycine and glucose were elevated in the urine of HNF1A-MODY subjects compared to the other subgroups. Direct measurements of urinary amino acids and betaine in an extended dataset did not support differences between patients groups. Elevated urinary glucose in HNF1A-MODY is consistent with the previously reported low renal threshold for glucose in this genetic subtype. In conclusion, we report the first metabolic profiling study in monogenic diabetes and show that, despite the distinct biochemical pathways affected, there are unlikely to be robust urinary biomarkers which distinguish monogenic

  13. RNA profiles of porcine embryos during genome activation reveal complex metabolic switch sensitive to in vitro conditions

    Østrup, Olga; Olbricht, Gayla; Østrup, Esben;

    2013-01-01

    a handful of reports characterize changing transcriptome profiles and resulting metabolic changes in cleavage stage embryos. The aims of the current study were to investigate RNA profiles of in vivo developed (ivv) and in vitro produced (ivt) porcine embryos before (2-cell stage) and after (late 4...... they originate from oocyte and are imposed either before oocyte aspiration or during in vitro maturation. IVT embryos have altered content of apoptotic factors, cell cycle regulation factors and spindle components, and transcription factors, which all may contribute to reduced developmental competence...... of embryos produced in vitro. Overall, our data are in good accordance with previously published, genome-wide profiling data in other species. Moreover, comparison with mouse and human embryos showed striking overlap in functional annotation of transcripts during the EGA, suggesting conserved basic...

  14. Effect of calcium-vitamin D supplementation on metabolic profiles in pregnant women at risk for pre-eclampsia: a randomized placebo-controlled trial.

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

    2012-04-01

    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-eclampsia. This randomized single-blind controlled clinical trial was performed among 49 pregnant women at risk for pre-eclampsia, primigravida, aged 18-35 year old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to consume the placebo (n = 25) or calcium-vitamin D supplements (n = 24) for 9 weeks. Calcium-vitamin D supplements were containing 500 mg carbonate calcium plus 200 IU vitamin D3. Fasting blood samples were taken at baseline and after 9 week intervention to measures of Fasting Plasma Glucose (FPG) and serum lipid profiles. Consumption of calcium-vitamin D supplements resulted in decreased FPG and serum triglycerides levels as compared to the placebo (-9.1 vs. 0.5 mg dL(-1); p = 0.03, -11.7 vs. 49.9 mg dL(-1); p = 0.001, respectively). No significant differences were found comparing calcium-vitamin D supplements and the placebo in terms of their effect on serum total-, HDL-, LDL-cholesterol levels. Within-group differences in the placebo group revealed a significant increase in serum triglycerides levels (+49.9 mg dL(-1), p < 0.0001). In conclusion, consumption of calcium-vitamin D supplements for 9 weeks during pregnancy among pregnant women at risk for pre-eclampsia resulted in decreased FPG and serum triglycerides levels as compared to the placebo group, but could not affect serum total-, HDL-, LDL-cholesterol levels. PMID:24163957

  15. Evolution of the biochemical profile of children treated or undergoing treatment for moderate or severe stunting: consequences of metabolic programming?

    Jullyana F.R. Alves

    2014-07-01

    Full Text Available OBJECTIVE: to evaluate changes in the biochemical profile of children treated or being treated for moderate or severe stunting in a nutrition recovery and education center. METHODS: this was a retrospective longitudinal study of 263 children treated at this center between August of 2008 to August of 2011, aged 1 to 6 years, diagnosed with moderate (z-score of height-for-age [HAZ] < -2 or severe stunting (HAZ < -3. Data were collected on socioeconomic conditions, dietary habits, and biochemical changes, as well as height according to age. RESULTS: the nutritional intervention showed an increase in HAZ of children with moderate (0.51 ± 0.4, p = 0.001 and severe (0.91 ± 0.7, p = 0.001 stunting during the monitoring. Increased levels of insulin-like growth factor 1 (IGF-1 (initial: 71.7 ng/dL; final: 90.4 ng/dL; p = 0.01 were also observed, as well as a reduction in triglycerides (TG in both severely (initial: 91.8 mg/dL; final: 79.1 mg/dL; p = 0.01 and in moderately malnourished children (initial: 109.2 mg/dL; final 88.7 mg/dL; p = 0.01, and a significant increase in high-density lipoprotein cholesterol HDL-C only in the third year of intervention (initial: 31.4 mg/dL; final: 42.2 mg/dL. The values of total cholesterol (TC and low-density lipoprotein cholesterol (LDL-C levels remained high throughout the treatment (initial: 165.1 mg/dL; final: 163.5 mg/dL and initial: 109.0 mg/dL; final: 107.3 mg/dL, respectively. CONCLUSION: the nutritional treatment for children with short stature was effective in reducing stunting and improving TG and HDL-C after three years of intervention. However, the levels of LDL-C and TC remained high even in treated children. It is therefore speculated that these changes may result from metabolic programming due to malnutrition.

  16. Sultr4;1 mutant seeds of Arabidopsis have an enhanced sulphate content and modified proteome suggesting metabolic adaptations to altered sulphate compartmentalization

    Belghazi Maya

    2010-04-01

    Full Text Available Abstract Background Sulphur is an essential macronutrient needed for the synthesis of many cellular components. Sulphur containing amino acids and stress response-related compounds, such as glutathione, are derived from reduction of root-absorbed sulphate. Sulphate distribution in cell compartments necessitates specific transport systems. The low-affinity sulphate transporters SULTR4;1 and SULTR4;2 have been localized to the vacuolar membrane, where they may facilitate sulphate efflux from the vacuole. Results In the present study, we demonstrated that the Sultr4;1 gene is expressed in developing Arabidopsis seeds to a level over 10-fold higher than the Sultr4;2 gene. A characterization of dry mature seeds from a Sultr4;1 T-DNA mutant revealed a higher sulphate content, implying a function for this transporter in developing seeds. A fine dissection of the Sultr4;1 seed proteome identified 29 spots whose abundance varied compared to wild-type. Specific metabolic features characteristic of an adaptive response were revealed, such as an up-accumulation of various proteins involved in sugar metabolism and in detoxification processes. Conclusions This study revealed a role for SULTR4;1 in determining sulphate content of mature Arabidopsis seeds. Moreover, the adaptive response of sultr4;1 mutant seeds as revealed by proteomics suggests a function of SULTR4;1 in redox homeostasis, a mechanism that has to be tightly controlled during development of orthodox seeds.

  17. The role of free fatty acids in the inflammatory and cardiometabolic profile in adolescents with metabolic syndrome engaged in interdisciplinary therapy.

    Masquio, Deborah Cristina Landi; de Piano-Ganen, Aline; Oyama, Lila Missae; Campos, Raquel Munhoz da Silveira; Santamarina, Aline Boveto; de Souza, Gabriel Inácio de Morais Honorato; Gomes, Aline Dal'Olio; Moreira, Renata Guimarães; Corgosinho, Flávia Campos; do Nascimento, Claudia Maria Oller; Tock, Lian; Tufik, Sergio; de Mello, Marco Túlio; Dâmaso, Ana R

    2016-07-01

    The purpose of the present study was to evaluate if interdisciplinary therapy can influence the cardiometabolic and serum free fatty acid profile. The second aim was to evaluate if there is an association between serum free fatty acids, inflammation and cardiometabolic biomarkers in obese adolescents with and without metabolic syndrome submitted to a long-term interdisciplinary therapy. The study involved 108 postpuberty obese adolescents, who were divided according to metabolic syndrome (MetS) diagnosis: MetS (n=32) and Non-MetS (n=76). The interdisciplinary therapy consisted of a 1-year period of nutrition, psychology, physical exercise and clinical support. After therapy, both groups improved metabolic, inflammatory (leptin, adiponectin, leptin/adiponectin ratio, adiponectin/leptin ratio and C-reactive protein) and cardiometabolic profile (PAI-1 and ICAM). Metabolic syndrome prevalence reduced from 28.70% to 12.96%. Both groups reduced myristic acid (C14:0) and increased docosahexaenoic acid (DHA, C22:6n3), heneicosapentaenoic acid (HPA, C21:5n3) and arachidonic acid (C20:4n6). After adjustment for metabolic syndrome and the number of metabolic syndrome parameters, multiple regression analysis showed that changes in VCAM and PAI-1 were negatively associated with changes in cis-linoleic acid (C18:2n6c). Additionally, changes in trans-linoleic acid (C18:2n6t) were also positively associated with these biomarkers. Moreover, leptin and leptin/adiponectin ratio were negatively associated with changes in docosapentaenoic acid (DPA, C22:5n3) and stearidonic acid (SDA, C18:4n3). Adiponectin/leptin ratio was positively associated with docosapentaenoic acid (DPA, C22:5n3). Changes in adiponectin were positively correlated with changes in omega 3, such as heneicosapentaenoic acid (HPA, C21:5n3) and docosapentaenoic acid (DPA, C22:5n3). Results support that interdisciplinary therapy can control inflammatory and cardiometabolic profile in obese adolescents. Moreover, serum

  18. GeneChip expression profiling reveals the alterations of energy metabolism related genes in osteocytes under large gradient high magnetic fields.

    Wang, Yang; Chen, Zhi-Hao; Yin, Chun; Ma, Jian-Hua; Li, Di-Jie; Zhao, Fan; Sun, Yu-Long; Hu, Li-Fang; Shang, Peng; Qian, Ai-Rong

    2015-01-01

    The diamagnetic levitation as a novel ground-based model for simulating a reduced gravity environment has recently been applied in life science research. In this study a specially designed superconducting magnet with a large gradient high magnetic field (LG-HMF), which can provide three apparent gravity levels (μ-g, 1-g, and 2-g), was used to simulate a space-like gravity environment. Osteocyte, as the most important mechanosensor in bone, takes a pivotal position in mediating the mechano-induced bone remodeling. In this study, the effects of LG-HMF on gene expression profiling of osteocyte-like cell line MLO-Y4 were investigated by Affymetrix DNA microarray. LG-HMF affected osteocyte gene expression profiling. Differentially expressed genes (DEGs) and data mining were further analyzed by using bioinfomatic tools, such as DAVID, iReport. 12 energy metabolism related genes (PFKL, AK4, ALDOC, COX7A1, STC1, ADM, CA9, CA12, P4HA1, APLN, GPR35 and GPR84) were further confirmed by real-time PCR. An integrated gene interaction network of 12 DEGs was constructed. Bio-data mining showed that genes involved in glucose metabolic process and apoptosis changed notablly. Our results demostrated that LG-HMF affected the expression of energy metabolism related genes in osteocyte. The identification of sensitive genes to special environments may provide some potential targets for preventing and treating bone loss or osteoporosis. PMID:25635858

  19. Aging Increases Susceptibility to High Fat Diet-Induced Metabolic Syndrome in C57BL/6 Mice: Improvement in Glycemic and Lipid Profile after Antioxidant Therapy

    Valéria Nunes-Souza

    2016-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has been considered a novel component of the metabolic syndrome (MetS, with the oxidative stress participating in its progression. This study aimed to evaluate the metabolic profile in young and old mice with MetS, and the effects of apocynin and tempol on glycemic and lipid parameters. Young and old C57BL/6 mice with high fat diet- (HFD- induced MetS received apocynin and tempol 50 mg·kg−1/day in their drinking water for 10 weeks. After HFD, the young group showed elevated fasting glucose, worsened lipid profile in plasma, steatosis, and hepatic lipid peroxidation. Nevertheless, the old group presented significant increase in fasting insulin levels, insulin resistance, plasma and hepatic lipid peroxidation, and pronounced steatosis. The hepatic superoxide dismutase and catalase activity did not differ between the groups. Tempol and apocynin seemed to prevent hepatic lipid deposition in both groups. Furthermore, apocynin improved glucose tolerance and insulin sensitivity in old mice. In summary, old mice are more susceptible to HFD-induced metabolic changes than their young counterparts. Also, the antioxidant therapy improved insulin sensitivity and glucose tolerance, and in addition, apocynin seemed to prevent the HFD-induced hepatic fat deposition, suggesting an important role of oxidative stress in the induction of NAFLD.

  20. Effect of Resistance Training and Various Sources of Protein Supplementation on Body Fat Mass and Metabolic Profile in Sarcopenic Overweight Older Adult Men: A Pilot Study.

    Maltais, Mathieu L; Perreault, Karine; Courchesne-Loyer, Alexandre; Lagacé, Jean Christophe; Barsalani, Razieh; Dionne, Isabelle J

    2016-02-01

    The decrease in resting energy expenditure (REE) and fat oxidation with aging is associated with an increase in fat mass (FM), and both could be prevented by exercise such as resistance training. Dairy consumption has also been shown to promote FM loss in different subpopulations and to be positively associated with fat oxidation. Therefore, we sought to determine whether resistance exercise combined with dairy supplementation could have an additive impact on FM and energy metabolism, especially in individuals with a deficit in muscle mass. Twenty-six older overweight sarcopenic men (65 ± 5 years old) were recruited for the study. They participated in 4 months of resistance exercise and were randomized into three groups for postexercise shakes (control, dairy, and nondairy isocaloric and isoprotein supplement with 375 ml and ~280 calories per shake). Body composition was measured by dual X-ray absorptiometry and REE by indirect calorimetry. Fasting glucose, insulin, leptin, inflammatory profile, and blood lipid profile were also measured. Significant decreases were observed with FM only in the dairy supplement group; no changes were observed for any other variables. To conclude, FM may decrease without changes in metabolic parameters during resistance training and dairy supplementation with no caloric restriction without having any impact on metabolic properties. More studies are warranted to explain this significant decrease in FM. PMID:26894503