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Sample records for metabolism ccm supported

  1. CCM key comparison CCM.D-K4 'Hydrometer'

    Lorefice, S.; Becerra, L. O.; Lenard, E.; Lee, Y. J.; Lee, W. G.; Madec, T.; Meury, P. A.; Caceres, J.; Santos, C.; Vamossy, C.; Man, J.; Fen, K.; Toda, K.; Wright, J.; Bettin, H.; Toth, H.

    2016-01-01

    added to this comparison so that all participants were engaged after the breakage of the 9340171 artefact. A particularly good agreement was found among the results provided by most of the participants, even if some systematic differences and either underestimated or overestimated uncertainties of the submitted results can be identified with respect to the KCRVs. In general the deviations of the laboratory results to the KCRVs are within of 1/3rd to 1/4th of a scale division and the uncertainty at 95% is usually within half a division. During the analysis of the submitted results, a systematic difference between the first and last immersed mark was also noted, possibly due to a temperature gradient along the stem and/or wetting of the stem around the tested mark, and therefore a corrected claimed uncertainty from each laboratory is expected. However this comparison may help the laboratories to solve some residual or marginal problems as well as to better understand the uncertainty components. The comparison fully supports the calibration measurement capabilities table in the BIPM key comparison database (KCDB). The results can be used to link regional comparisons to this CCM key comparison Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  2. CCM in the FUV

    Cartledge, S. I. B.; Clayton, G. C.; Gordon, K. D.

    2005-12-01

    Over 90% of Milky Way extinction curves sampled from IR through UV wavelengths (UV coverage by IUE) conform to the CCM family of curves based on R(V), a single parameter linked to grain size. The far-ultraviolet (FUV) portion of this formulation, however, was based only on a few sight lines observed by Copernicus, and it has recently been shown that in certain cases CCM does not predict extinction in the FUV as accurately as it does at longer wavelengths. In this poster paper, we present preliminary results from our examination of the agreement between all publicly-available FUSE FUV spectra of reddened O and B stars and their corresponding extinction curves inferred from longer wavelength fluxes. The eventual goal of our project is to reformulate CCM, particularly in the FUV where we have compiled more than 90 sight lines observed by FUSE. We are also exploring correlations between bulk sight line properties and the form of the reconstituted CCM curves.

  3. iCCM

    school level (with 6 days statutory iCCM training)2 to be able to manage uncomplicated ... debate that has received less attention has been a failure to demonstrate, or .... qualitative evidence from a pilot study in Tanzania. J Health Commun.

  4. L3:PHI.CMD.P13.02 Support for CILC L1 Milestone Using STAR-CCM+

    Slattery, Stuart R.; Gurecky, William L.

    2016-01-01

    This report documents work performed to support Consortium for the Advanced Simulation of LWRs (CASL) modeling of Chalk River Unidentified Deposit (CRUD) Induced Power Shift (CIPS) and CRUD Induced Local Corrosion (CILC) using the Cicada package. The work documented here is intended to complement current and future CIPS and CILC modeling activities in CASL. We provide tools for crud and corrosion-related simulation and analysis by developing a better understanding of the interplay between the coupled physics that describe the phenomena at different time and length scales. We intend to use these models to better inform future simulation capability and development.

  5. L3:PHI.CMD.P13.02 Support for CILC L1 Milestone Using STAR-CCM+

    Slattery, Stuart R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gurecky, William L. [Univ. of Texas, Austin, TX (United States)

    2016-10-07

    This report documents work performed to support Consortium for the Advanced Simulation of LWRs (CASL) modeling of Chalk River Unidentified Deposit (CRUD) Induced Power Shift (CIPS) and CRUD Induced Local Corrosion (CILC) using the Cicada package. The work documented here is intended to complement current and future CIPS and CILC modeling activities in CASL. We provide tools for crud and corrosion-related simulation and analysis by developing a better understanding of the interplay between the coupled physics that describe the phenomena at different time and length scales. We intend to use these models to better inform future simulation capability and development.

  6. Structural determinants of the outer shell of β-carboxysomes in Synechococcus elongatus PCC 7942: roles for CcmK2, K3-K4, CcmO, and CcmL.

    Benjamin D Rae

    Full Text Available Cyanobacterial CO(2-fixation is supported by a CO(2-concentrating mechanism which improves photosynthesis by saturating the primary carboxylating enzyme, ribulose 1, 5-bisphosphate carboxylase/oxygenase (RuBisCO, with its preferred substrate CO(2. The site of CO(2-concentration is a protein bound micro-compartment called the carboxysome which contains most, if not all, of the cellular RuBisCO. The shell of β-type carboxysomes is thought to be composed of two functional layers, with the inner layer involved in RuBisCO scaffolding and bicarbonate dehydration, and the outer layer in selective permeability to dissolved solutes. Here, four genes (ccmK2-4, ccmO, whose products were predicted to function in the outer shell layer of β-carboxysomes from Synechococcus elongatus PCC 7942, were investigated by analysis of defined genetic mutants. Deletion of the ccmK2 and ccmO genes resulted in severe high-CO(2-requiring mutants with aberrant carboxysomes, whilst deletion of ccmK3 or ccmK4 resulted in cells with wild-type physiology and normal ultrastructure. However, a tandem deletion of ccmK3-4 resulted in cells with wild-type carboxysome structure, but physiologically deficient at low CO(2 conditions. These results revealed the minimum structural determinants of the outer shell of β-carboxysomes from this strain: CcmK2, CcmO and CcmL. An accessory set of proteins was required to refine the function of the pre-existing shell: CcmK3 and CcmK4. These data suggested a model for the facet structure of β-carboxysomes with CcmL forming the vertices, CcmK2 forming the bulk facet, and CcmO, a "zipper protein," interfacing the edges of carboxysome facets.

  7. Coolant channel module CCM

    Hoeld, Alois

    2007-01-01

    A complete and detailed description of the theoretical background of an '(1D) thermal-hydraulic drift-flux based mixture-fluid' coolant channel model and its resulting module CCM will be presented. The objective of this module is to simulate as universally as possible the steady state and transient behaviour of the key characteristic parameters of a single- or two-phase fluid flowing within any type of heated or non-heated coolant channel. Due to the possibility that different flow regimes can appear along any channel, such a 'basic (BC)' 1D channel is assumed to be subdivided into a number of corresponding sub-channels (SC-s). Each SC can belong to only two types of flow regime, an SC with just a single-phase fluid, containing exclusively either sub-cooled water or superheated steam, or an SC with a two-phase mixture flow. After an appropriate nodalisation of such a BC (and therefore also its SC-s) a 'modified finite volume method' has been applied for the spatial discretisation of the partial differential equations (PDE-s) which represent the basic conservation equations of thermal-hydraulics. Special attention had to be given to the possibility of variable SC entrance or outlet positions (which describe boiling boundaries or mixture levels) and thus the fact that an SC can even disappear or be created anew. The procedure yields for each SC type (and thus the entire BC), a set of non-linear ordinary 1st order differential equations (ODE-s). To link the resulting mean nodal with the nodal boundary function values, both of which are present in the discretised differential equations, a special quadratic polygon approximation procedure (PAX) had to be constructed. Together with the very thoroughly tested packages for drift-flux, heat transfer and single- and two-phase friction factors this procedure represents the central part of the here presented 'Separate-Region' approach, a theoretical model which provides the basis to the very effective working code package CCM

  8. Identification of a novel gene cluster in the upstream region of the S-layer gene sbpA involved in cell wall metabolism of Lysinibacillus sphaericus CCM 2177 and characterization of the recombinantly produced autolysin and pyruvyl transferase.

    Pleschberger, Magdalena; Hildner, Florian; Rünzler, Dominik; Gelbmann, Nicola; Mayer, Harald F; Sleytr, Uwe B; Egelseer, Eva M

    2013-05-01

    The S-layer protein SbpA of Lysinibacillus sphaericus CCM 2177 assembles into a square (p4) lattice structure and recognizes a pyruvylated secondary cell wall polymer (SCWP) as the proper anchoring structure to the rigid cell wall layer. Sequencing of 8,004 bp in the 5'-upstream region of the S-layer gene sbpA led to five ORFs-encoding proteins involved in cell wall metabolism. After cloning and heterologous expression of ORF1 and ORF5 in Escherichia coli, the recombinant autolysin rAbpA and the recombinant pyruvyl transferase rCsaB were isolated, purified, and correct folding was confirmed by circular dichroism. Although rAbpA encoded by ORF1 showed amidase activity, it could attack whole cells of Ly. sphaericus CCM 2177 only after complete extraction of the S-layer lattice. Despite the presence of three S-layer-homology motifs on the N-terminal part, rAbpA did not show detectable affinity to peptidoglycan-containing sacculi, nor to isolated SCWP. As the molecular mass of the autolysin lies above the molecular exclusion limit of the S-layer, AbpA is obviously trapped within the rigid cell wall layer by the isoporous protein lattice. Immunogold-labeling of ultrathin-sectioned whole cells of Ly. sphaericus CCM 2177 with a polyclonal rabbit antiserum raised against rCsaB encoded by ORF5, and cell fractionation experiments demonstrated that the pyruvyl transferase was located in the cytoplasm, but not associated with cell envelope components including the plasma membrane. In enzymatic assays, rCsaB clearly showed pyruvyl transferase activity. By using RT-PCR, specific transcripts for each ORF could be detected. Cotranscription could be confirmed for ORF2 and ORF3.

  9. CEAI: CCM based Email Authorship Identification Model

    Nizamani, Sarwat; Memon, Nasrullah

    2013-01-01

    In this paper we present a model for email authorship identification (EAI) by employing a Cluster-based Classification (CCM) technique. Traditionally, stylometric features have been successfully employed in various authorship analysis tasks; we extend the traditional feature-set to include some...... more interesting and effective features for email authorship identification (e.g. the last punctuation mark used in an email, the tendency of an author to use capitalization at the start of an email, or the punctuation after a greeting or farewell). We also included Info Gain feature selection based...... reveal that the proposed CCM-based email authorship identification model, along with the proposed feature set, outperforms the state-of-the-art support vector machine (SVM)-based models, as well as the models proposed by Iqbal et al. [1, 2]. The proposed model attains an accuracy rate of 94% for 10...

  10. Provider Experiences with Chronic Care Management (CCM) Services and Fees: A Qualitative Research Study.

    O'Malley, Ann S; Sarwar, Rumin; Keith, Rosalind; Balke, Patrick; Ma, Sai; McCall, Nancy

    2017-12-01

    Support for ongoing care management and coordination between office visits for patients with multiple chronic conditions has been inadequate. In January 2015, Medicare introduced the Chronic Care Management (CCM) payment policy, which reimburses providers for CCM activities for Medicare beneficiaries occurring outside of office visits. To explore the experiences, facilitators, and challenges of practices providing CCM services, and their implications going forward. Semi-structured telephone interviews from January to April 2016 with 71 respondents. Sixty billing and non-billing providers and practice staff knowledgeable about their practices' CCM services, and 11 professional society representatives. Practice respondents noted that most patients expressed positive views of CCM services. Practice respondents also perceived several patient benefits, including improved adherence to treatment, access to care team members, satisfaction, care continuity, and care coordination. Facilitators of CCM provision included having an in-practice care manager, patient-centered medical home recognition, experience developing care plans, patient trust in their provider, and supplemental insurance to cover CCM copayments. Most billing practices reported few problems obtaining patients' consent for CCM, though providers felt that CMS could better facilitate consent by marketing CCM's goals to beneficiaries. Barriers reported by professional society representatives and by billing and non-billing providers included inadequacy of CCM payments to cover upfront investments for staffing, workflow modification, and time needed to manage complex patients. Other barriers included inadequate infrastructure for health information exchange with other providers and limited electronic health record capabilities for documenting and updating care plans. Practices owned by hospital systems and large medical groups faced greater bureaucracy in implementing CCM than did smaller, independent practices

  11. Spontaneous non-canonical assembly of CcmK hexameric components from β-carboxysome shells of cyanobacteria.

    Luis F Garcia-Alles

    Full Text Available CcmK proteins are major constituents of icosahedral shells of β-carboxysomes, a bacterial microcompartment that plays a key role for CO2 fixation in nature. Supported by the characterization of bidimensional (2D layers of packed CcmK hexamers in crystal and electron microscopy structures, CcmK are assumed to be the major components of icosahedral flat facets. Here, we reassessed the validity of this model by studying CcmK isoforms from Synechocystis sp. PCC6803. Native mass spectrometry studies confirmed that CcmK are hexamers in solution. Interestingly, potential pre-assembled intermediates were also detected with CcmK2. Atomic-force microscopy (AFM imaging under quasi-physiological conditions confirmed the formation of canonical flat sheets with CcmK4. Conversely, CcmK2 formed both canonical and striped-patterned patches, while CcmK1 assembled into remarkable supra-hexameric curved honeycomb-like mosaics. Mutational studies ascribed the propensity of CcmK1 to form round assemblies to a combination of two features shared by at least one CcmK isoform in most β-cyanobacteria: a displacement of an α helical portion towards the hexamer edge, where a potential phosphate binding funnel forms between packed hexamers, and the presence of a short C-terminal extension in CcmK1. All-atom molecular dynamics supported a contribution of phosphate molecules sandwiched between hexamers to bend CcmK1 assemblies. Formation of supra-hexameric curved structures could be reproduced in coarse-grained simulations, provided that adhesion forces to the support were weak. Apart from uncovering unprecedented CcmK self-assembly features, our data suggest the possibility that transitions between curved and flat assemblies, following cargo maturation, could be important for the biogenesis of β-carboxysomes, possibly also of other BMC.

  12. Final report on CCM key comparison CCM.D-K2: Comparison of liquid density standards

    Bettin, Horst; Jacques, Claude; Zelenka, Zoltán; Fujii, Ken-ichi; Kuramoto, Naoki; Chang, Kyung-Ho; Lee, Yong Jae; Becerra, Luis Omar; Domostroeva, Natalia

    2013-01-01

    The results are presented of the key comparison CCM.D-K2 that covered the density measurements of four liquids: the density of water at 20 °C, of pentadecane at 15 °C, 20 °C, 40 °C and 60°C, of tetrachloroethlyene at 5 °C and 20 °C and of a viscous oil at 20 °C. Seven national metrology institutes measured the densities at atmospheric pressure by hydrostatic weighing of solid density standards in the time interval from 27 April 2004 to 28 June 2004. Since the participants were asked not to include components for a possible drift or inhomogeneity of the liquid in their uncertainty budget, these uncertainty contributions are investigated for the final evaluation of the data. For this purpose, results of stability and homogeneity measurements of the pilot laboratory are used. The participants decided not to include a possible drift of the liquid's density since no significant drift could be detected, and the influence of the drift and its uncertainty are negligible. Similarly, the inhomogeneity of the water and pentadecane samples is not significant and has no influence on the evaluation. Thus, it was neglected. Only the inhomogeneities of tetrachloroethylene and of the viscous oil were significant. Consequently, they were included in the evaluation. With one or two exceptions, the results show good agreement among the participants. Only in the case of water are the results clearly discrepant. The key comparison reference values were calculated by the weighted mean (taking into account a small correlation between two participants) in the case of consistent results. Otherwise the Procedure B of Cox was used. The expanded uncertainties of all reference densities are below 1 × 10-5 in relative terms. This satisfies the needs of all customers who wish to calibrate or check liquid density measuring instruments such as oscillation-type density meters. The comparison fully supports the calibration measurement capabilities table in the BIPM key comparison database

  13. CCM: A Text Classification Method by Clustering

    Nizamani, Sarwat; Memon, Nasrullah; Wiil, Uffe Kock

    2011-01-01

    In this paper, a new Cluster based Classification Model (CCM) for suspicious email detection and other text classification tasks, is presented. Comparative experiments of the proposed model against traditional classification models and the boosting algorithm are also discussed. Experimental results...... show that the CCM outperforms traditional classification models as well as the boosting algorithm for the task of suspicious email detection on terrorism domain email dataset and topic categorization on the Reuters-21578 and 20 Newsgroups datasets. The overall finding is that applying a cluster based...

  14. STAR-CCM+ Verification and Validation Plan

    Pointer, William David [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-09-30

    The commercial Computational Fluid Dynamics (CFD) code STAR-CCM+ provides general purpose finite volume method solutions for fluid dynamics and energy transport. This document defines plans for verification and validation (V&V) of the base code and models implemented within the code by the Consortium for Advanced Simulation of Light water reactors (CASL). The software quality assurance activities described herein are port of the overall software life cycle defined in the CASL Software Quality Assurance (SQA) Plan [Sieger, 2015]. STAR-CCM+ serves as the principal foundation for development of an advanced predictive multi-phase boiling simulation capability within CASL. The CASL Thermal Hydraulics Methods (THM) team develops advanced closure models required to describe the subgrid-resolution behavior of secondary fluids or fluid phases in multiphase boiling flows within the Eulerian-Eulerian framework of the code. These include wall heat partitioning models that describe the formation of vapor on the surface and the forces the define bubble/droplet dynamic motion. The CASL models are implemented as user coding or field functions within the general framework of the code. This report defines procedures and requirements for V&V of the multi-phase CFD capability developed by CASL THM. Results of V&V evaluations will be documented in a separate STAR-CCM+ V&V assessment report. This report is expected to be a living document and will be updated as additional validation cases are identified and adopted as part of the CASL THM V&V suite.

  15. CEAI: CCM-based email authorship identification model

    Sarwat Nizamani

    2013-11-01

    Full Text Available In this paper we present a model for email authorship identification (EAI by employing a Cluster-based Classification (CCM technique. Traditionally, stylometric features have been successfully employed in various authorship analysis tasks; we extend the traditional feature set to include some more interesting and effective features for email authorship identification (e.g., the last punctuation mark used in an email, the tendency of an author to use capitalization at the start of an email, or the punctuation after a greeting or farewell. We also included Info Gain feature selection based content features. It is observed that the use of such features in the authorship identification process has a positive impact on the accuracy of the authorship identification task. We performed experiments to justify our arguments and compared the results with other base line models. Experimental results reveal that the proposed CCM-based email authorship identification model, along with the proposed feature set, outperforms the state-of-the-art support vector machine (SVM-based models, as well as the models proposed by Iqbal et al. (2010, 2013 [1,2]. The proposed model attains an accuracy rate of 94% for 10 authors, 89% for 25 authors, and 81% for 50 authors, respectively on Enron dataset, while 89.5% accuracy has been achieved on authors’ constructed real email dataset. The results on Enron dataset have been achieved on quite a large number of authors as compared to the models proposed by Iqbal et al. [1,2].

  16. Modulators of arginine metabolism support cancer immunosurveillance

    Freschi Massimo

    2009-01-01

    Full Text Available Abstract Background Tumor-associated accrual of myeloid derived suppressor cells (MDSC in the blood, lymphoid organs and tumor tissues may lead to perturbation of the arginine metabolism and impairment of the endogenous antitumor immunity. The objective of this study was to evaluate whether accumulation of MDSC occurred in Th2 prone BALB/c and Th1 biased C57BL/6 mice bearing the C26GM colon carcinoma and RMA T lymphoma, respectively, and to investigate whether N(G nitro-L-arginine methyl ester (L-NAME and sildenafil, both modulators of the arginine metabolism, restored antitumor immunity. Results We report here that MDSC accumulate in the spleen and blood of mice irrespective of the mouse and tumor model used. Treatment of tumor-bearing mice with either the phosphodiesterase-5 inhibitor sildenafil or the nitric-oxide synthase (NOS inhibitor L-NAME significantly restrained tumor growth and expanded the tumor-specific immune response. Conclusion Our data emphasize the role of MDSC in modulating the endogenous tumor-specific immune response and underline the anti-neoplastic therapeutic potential of arginine metabolism modulators.

  17. Teelthandleiding korrelmais en Corn Cob Mix (CCM) - voedingsaspecten

    Brink, van den L.; Groten, J.A.M.

    2005-01-01

    Korrelmaïs wordt overwegend verwerkt in mengvoer voor pluimvee en varkens. CCM wordt hoofdzakelijk vervoederd aan varkens, maar daarnaast ook aan rundvee. MKS is voornamelijk bestemd voor rundvee en paarden

  18. Potential of Lactobacillus plantarum ccm 3627 and Lactobacillus brevis ccm 1815 for fermentation of cereal substrates

    Kvetoslava Romanová

    2017-01-01

    Full Text Available Lactobacillus is the most representative strain in a group of lactic acid bacteria, which perform an essential role in the preservation and production of wholesome foods. Lactic acid fermentation is the oldest traditional method for preparation of fermented vegetables, meat products, dairy products and cereal foods. Cereal grains are considered to be one of the most important sources of dietary proteins, carbohydrates, vitamins, minerals and fibre for people. The main exploitation of cereals is to prepare sourdough, which is a mixture of wheat, rye or other cereal flour with water and contains yeasts and lactobacilli. The basic biochemical changes that occur in sourdough bread fermentation are acidification of the dough with organic acids produced by the lactobacilli and leavening with carbon dioxide produced by the yeast and the lactobacilli. Acidification perhaps initiate enzymatic processes of proteins and phytates degradation. Lactobacilli produce various enzymes which make flavour precursors, improve of mineral bioavailability or degrade celiac active peptides, because some species of lactobacilli produce specific peptidases during growth, which are capable to hydrolyze hardly cleavable, celiac-active proline-rich peptides. Microbial fermentation with selected strains of lactobacilli may be new alternative approach for modification of gluten by hydrolysis. In this paper are described growth characteristics and intracellular aminopeptidases activities of Lactobacillus plantarum CCM 3627 and Lactobacillus brevis CCM 1815. Work was focused on characterization of the lactobacilli for potential usage as a starter culture in further fermentation experiments.

  19. Montreal Protocol Benefits simulated with CCM SOCOL

    T. Egorova

    2013-04-01

    Full Text Available Ozone depletion is caused by the anthropogenic increase of halogen-containing species in the atmosphere, which results in the enhancement of the concentration of reactive chlorine and bromine in the stratosphere. To reduce the influence of anthropogenic ozone-depleting substances (ODS, the Montreal Protocol was agreed by Governments in 1987, with several Amendments and Adjustments adopted later. In order to assess the benefits of the Montreal Protocol and its Amendments and Adjustments (MPA on ozone and UV radiation, two different runs of the chemistry-climate model (CCM SOCOL have been carried out. The first run was driven by the emission of ozone depleting substances (ODS prescribed according to the restrictions of the MPA. For the second run we allow the ODS to grow by 3% annually. We find that the MPA would have saved up to 80% of the global annual total ozone by the end of the 21st century. Our calculations also show substantial changes of the stratospheric circulation pattern as well as in surface temperature and precipitations that could occur in the world without MPA implementations. To illustrate the changes in UV radiation at the surface and to emphasise certain features, which can only be seen for some particular regions if the influence of the cloud cover changes is accounted for, we calculate geographical distribution of the erythemally weighted irradiance (Eery. For the no Montreal Protocol simulation Eery increases by factor of 4 to 16 between the 1970s and 2100. For the scenario including the Montreal Protocol it is found that UV radiation starts to decrease in 2000, with continuous decline of 5% to 10% at middle latitudes in the both Northern and Southern Hemispheres.

  20. iCCM policy analysis: strategic contributions to understanding its character, design and scale up in sub-Saharan Africa.

    George, Asha; Rodríguez, Daniela C; Rasanathan, Kumanan; Brandes, Neal; Bennett, Sara

    2015-12-01

    Pneumonia, diarrhoea and malaria remain leading causes of death for children under 5 years of age and access to effective and appropriate treatment for sick children is extremely low where it is needed most. Integrated community case management (iCCM) enables community health workers to provide basic lifesaving treatment for sick children living in remote communities for these diseases. While many governments in sub-Saharan Africa recently changed policies to support iCCM, large variations in implementation remain. As a result, the collaboration represented in this supplement examined the policy processes underpinning iCCM through qualitative case study research in six purposively identified countries (Niger, Burkina Faso, Mali, Kenya, Malawi and Mozambique) and the global context. We introduce the supplement, by reviewing how policy analysis can inform: (a) how we frame iCCM and negotiate its boundaries, (b) how we tailor iCCM for national health systems and (c) how we foster accountability and learning for iCCM. In terms of framing, iCCM boundaries reflect how an array of actors use evidence to prioritize particular aspects of child mortality (lack of access to treatment), and how this underpins the ability to reach consensus and legitimate specific policy enterprises. When promoted at national level, contextual health system factors, such as the profile of CHWs and the history of primary health care, cannot be ignored. Adaptation to these contextual realities may lead to unintended consequences not forseen by technical or managerial expertize alone. Further scaling up of iCCM requires understanding of the political accountabilities involved, how ownership can be fostered and learning for improved policies and programs sustained. Collectively these articles demonstrate that iCCM, although often compartmentalized as a technical intervention, also reflects the larger and messier real world of health politics, policy and practice, for which policy analysis is vital

  1. Laboratory evaluation of a new strain CCM 8367 of Isaria fumosorosea (syn. Paecilomyces fumosoroseus) on Spodoptera littoralis (Boisd.)

    Hussein, Hany; Zemek, Rostislav; Habuštová, Oxana; Prenerová, Eva; Adel, M. M.

    2013-01-01

    Roč. 46, č. 11 (2013), s. 1307-1319 ISSN 0323-5408 R&D Projects: GA MŠk 2B06005 Institutional support: RVO:60077344 Keywords : entomopathogenic fungi * Isaria fumosorosea * CCM 8367 Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection

  2. Validation of Slosh Modeling Approach Using STAR-CCM+

    Benson, David J.; Ng, Wanyi

    2018-01-01

    Without an adequate understanding of propellant slosh, the spacecraft attitude control system may be inadequate to control the spacecraft or there may be an unexpected loss of science observation time due to higher slosh settling times. Computational fluid dynamics (CFD) is used to model propellant slosh. STAR-CCM+ is a commercially available CFD code. This paper seeks to validate the CFD modeling approach via a comparison between STAR-CCM+ liquid slosh modeling results and experimental, empirically, and analytically derived results. The geometries examined are a bare right cylinder tank and a right cylinder with a single ring baffle.

  3. Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

    Sousa, Cristovão M; Biancur, Douglas E; Wang, Xiaoxu; Halbrook, Christopher J; Sherman, Mara H; Zhang, Li; Kremer, Daniel; Hwang, Rosa F; Witkiewicz, Agnes K; Ying, Haoqiang; Asara, John M; Evans, Ronald M; Cantley, Lewis C; Lyssiotis, Costas A; Kimmelman, Alec C

    2016-08-25

    Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour’s dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

  4. Teelthandleiding korrelmais en Corn Cob Mix (CCM) - bemesting

    Brink, van den L.; Groten, J.A.M.

    2005-01-01

    De bemesting van korrelmaïs, CCM en MKS komt grotendeels overeen met die van snijmaïs. Voor de bemestingsadviezen wordt dan ook verwezen naar http://www.handboeksnijmais.nl/. Er zijn echter voor de situatie van twee of meer jaren achter elkaar telen van het gewas wel enkele aanpassingen nodig. Dit

  5. Can CCM law properly represent all extinction curves?

    Geminale, Anna; Popowski, Piotr

    2005-01-01

    We present the analysis of a large sample of lines of sight with extinction curves covering wavelength range from near-infrared (NIR) to ultraviolet (UV). We derive total to selective extinction ratios based on the Cardelli, Clayton and Mathis (1989, CCM) law, which is typically used to fit the extinction data both for diffuse and dense interstellar medium. We conclude that the CCM law is able to fit most of the extinction curves in our sample. We divide the remaining lines of sight with peculiar extinction into two groups according to two main behaviors: a) the optical/IR or/and UV wavelength region cannot be reproduced by the CCM formula; b) the optical/NIR and UV extinction data are best fit by the CCM law with different values of R v . We present examples of such curves. The study of both types of peculiar cases can help us to learn about the physical processes that affect dust in the interstellar medium, e.g., formation of mantles on the surface of grains, evaporation, growing or shattering

  6. CCM-R: Secure Counter Synchronization for IoT Wireless Link

    Roy, Upal; Yin, Jiachen; Andersen, Birger

    2016-01-01

    In this paper we propose and evaluate a new version of the CCM mode of operation, CCM-R, which isan extended and alternate version of the original CBC-MAC with Counter Mode(CCM) that was created to address the problem of counter synchronization. While CCM is considered secure when used/implemente...... it suitable for low-power wireless IoT devices....

  7. Costs of implementing integrated community case management (iCCM) in six African countries: implications for sustainability.

    Daviaud, Emmanuelle; Besada, Donnela; Leon, Natalie; Rohde, Sarah; Sanders, David; Oliphant, Nicholas; Doherty, Tanya

    2017-06-01

    Sub-Saharan Africa still reports the highest rates of under-five mortality. Low cost, high impact interventions exist, however poor access remains a challenge. Integrated community case management (iCCM) was introduced to improve access to essential services for children 2-59 months through diagnosis, treatment and referral services by community health workers for malaria, pneumonia and diarrhea. This paper presents the results of an economic analysis of iCCM implementation in regions supported by UNICEF in six countries and assesses country-level scale-up implications. The paper focuses on costs to provider (health system and donors) to inform planning and budgeting, and does not cover cost-effectiveness. The analysis combines annualised set-up costs and 1 year implementation costs to calculate incremental economic and financial costs per treatment from a provider perspective. Affordability is assessed by calculating the per capita financial cost of the program as a percentage of the public health expenditure per capita. Time and financial implications of a 30% increase in utilization were modeled. Country scale-up is modeled for all children under 5 in rural areas. Utilization of iCCM services varied from 0.05 treatment/y/under-five in Ethiopia to over 1 in Niger. There were between 10 and 603 treatments/community health worker (CHW)/y. Consultation cost represented between 93% and 22% of economic costs per treatment influenced by the level of utilization. Weighted economic cost per treatment ranged from US$ 13 (2015 USD) in Ghana to US$ 2 in Malawi. CHWs spent from 1 to 9 hours a week on iCCM. A 30% increase in utilization would add up to 2 hours a week, but reduce cost per treatment (by 20% in countries with low utilization). Country scale up would amount to under US$ 0.8 per capita total population (US$ 0.06-US$0.74), between 0.5% and 2% of public health expenditure per capita but 8% in Niger. iCCM addresses unmet needs and impacts on under 5 mortality. An

  8. Contemporary commercial music (CCM) survey: who's teaching what in nonclassical music.

    LoVetri, Jeannette L; Weekly, Edrie Means

    2003-06-01

    Currently, there is an increasing interest in and demand for training in a wide variety of nonclassical music--contemporary commercial music (CCM)--and most particularly for music theater. A survey of singing teachers was completed to elucidate their training, education, and experience with and methods of teaching CCM. Teachers were at colleges, universities, and conservatories as well as in private studios, both nationally and in several foreign countries. A substantial percentage of those teaching CCM had neither formal education in teaching it nor professional experience. Many of the respondents indicated conflict between classical and CCM styles. Respondents were generally familiar with voice science and voice medicine as well as certain CCM terminology. Teachers expressed an interest in obtaining more information, with an emphasis on healthy vocal production. These results are discussed, as well as implications for the singing teacher who desires specific training to teach CCM.

  9. Calcium absorption from apple and orange juice fortified with calcium citrate malate (CCM).

    Andon, M B; Peacock, M; Kanerva, R L; De Castro, J A

    1996-06-01

    Determine calcium (Ca) absorption from Ca fortified orange and apple juice. Absorbability was assessed by measuring 45Ca absorption in healthy women (mean age 57 years, n = 57/group) and whole body 47Ca retention in adult female beagle dogs (n = 6/group) and young adult male rats (n = 6/group). Women received 6.24 mmol (250 mg) Ca as calcium citrate malate fortified orange juice (CCM-OJ) or apple juice (CCM-AJ). Dogs received 3.12 mmol (125 mg) Ca as CCM-OJ or CCM-AJ. Rats were administered 0.15 mmol (6 mg) Ca as either milk, CCM-OJ, or CCM-AJ. Additional 47Ca whole body retention experiments in rats measured the effects of differences in the carbohydrate and organic acid contents of the juices on Ca absorption. Mean +/- SEM percent Ca fractional absorption was greater (p composition of Ca fortified juices, we found that the greater fructose and lower organic acid content of apple juice accounted for its greater Ca absorbability. CCM fortified versions of orange and apple juice have high Ca absorbability and are potentially important vehicles for increasing dietary Ca intake. The greater Ca absorption from CCM-AJ compared with CCM-OJ is accounted for by differences in the carbohydrate and organic acid content of the juices. These data suggest that by modifying common beverage ingredients, products with even greater Ca absorbability could be formulated.

  10. Significance of family and peer support for metabolic control of type 1 diabetes in adolescents

    Đurović Dušanka

    2009-01-01

    Full Text Available The aim of the paper was to explore the significance of family and peer support for metabolic control of Type 1 diabetes in adolescents. Metabolic control refers to maintenance of acceptable blood glucose level thus diminishing risk for chronic complications. It involves regular insulin shots, measuring blood glucose and keeping diary, as the daily based self-control. Regular visits to endocrinologist and screening for chronic complications are compulsory. The sample comprised 79 adolescents age 10-17 years with diagnose of Type 1 diabetes and properly treated at the institute. The sample was divided in two groups - with good (N=40 and poor (N=39 metabolic control. A criterium for good metabolic control was glycosilated hemoglobin less than 7,6%. Social support was measured by Social Support Scale consisting of two parts - the first for estimation of registered family support (based upon modified Perceived Social Support Family Scale and the second for estimation of registered friends' support (modified Perceived Social Support Friend Scale. Adolescents with good metabolic control referred statistically more significant social support in the family, unlike the group with poor metabolic control. Considering peer social support, there was no statistically significant difference. Positive family history for diabetes also appeared to be directly linked to good metabolic control.

  11. Relaunch of the official community health worker programme in Mozambique: is there a sustainable basis for iCCM policy?

    Chilundo, Baltazar Gm; Cliff, Julie L; Mariano, Alda Re; Rodríguez, Daniela C; George, Asha

    2015-12-01

    In Mozambique, integrated community case management (iCCM) of diarrhoea, malaria and pneumonia is embedded in the national community health worker (CHW) programme, mainstreaming it into government policy and service delivery. Since its inception in 1978, the CHW programme has functioned unevenly, was suspended in 1989, but relaunched in 2010. To assess the long-term success of iCCM in Mozambique, this article addresses whether the current CHW programme exhibits characteristics that facilitate or impede its sustainability. We undertook a qualitative case study based on document review (n = 54) and key informant interviews (n = 21) with respondents from the Ministry of Health (MOH), multilateral and bilateral agencies and non-governmental organizations (NGOs) in Maputo in 2012. Interviews were mostly undertaken in Portuguese and all were coded using NVivo. A sustainability framework guided thematic analysis according to nine domains: strategic planning, organizational capacity, programme adaptation, programme monitoring and evaluation, communications, funding stability, political support, partnerships and public health impact. Government commitment was high, with the MOH leading a consultative process in Maputo and facilitating successful technical coordination. The MOH made strategic decisions to pay CHWs, authorize their prescribing abilities, foster guidance development, support operational planning and incorporate previously excluded 'old' CHWs. Nonetheless, policy negotiations excluded certain key actors and uncertainty remains about CHW integration into the civil service and their long-term retention. In addition, reliance on NGOs and donor funding has led to geographic distortions in scaling up, alongside challenges in harmonization. Finally, dependence on external funding, when both external and government funding are declining, may hamper sustainability. Our analysis represents a nuanced assessment of the various domains that influence CHW programme

  12. Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

  13. An investigation of the Archean climate using the NCAR CCm

    Jenkins, G.S.

    1991-01-01

    The Archean (2.5 to 3.8 billion years ago) is of interest climatically, because of the 'Faint-Young Sun Paradox', which can be characterized by the Sun's reduced energy output. This lower energy output leads to a frozen planet if the climate existed as it does today. But, the geologic record shows that water was flowing at the earth's surface 3.8 billion years ago. Energy Balance Models (EBMs) and one-dimensional radiative-convective (1DRC) models predict a frozen planet for this time period, unless large carbon dioxide (CO2) concentrations exist in the Archean atmosphere. The goal is to explore the Archean climate with the National Center for Atmospheric Research (NCAR), Community Climate Model (CCM). The search for negative feedbacks to explain the 'Faint-Young Sun Paradox' is the thrust of this study. This study undertakes a series of sensitivity simulations which first explores individual factors that may be important for the Archean. They include rotation rate, lower solar luminosity, and land fraction. Then, these climatic factors along with higher CO2 concentrations are combined into a set of experiments. A faster rotation rate may have existed in the Archean. The faster rotation rate simulations show warmer globally averaged surface temperatures that are caused by a 20 percent decrease in the total cloud fraction. The smaller cloud fraction is brought about by dynamical changes. A global ocean is a possibility for the Archean. A global ocean simulation predicts 4 K increase in global mean surface temperatures compared to the present-day climate control

  14. How Energy Metabolism Supports Cerebral Function: Insights from 13C Magnetic Resonance Studies In vivo

    Sarah Sonnay

    2017-05-01

    Full Text Available Cerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-twentieth century the idea that brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis. Moreover, brain energy metabolism was demonstrated to be compartmentalized in neurons and astrocytes, and astrocytic glycolysis was proposed to serve the energetic demands of glutamatergic activity. Shedding light on the role of astrocytes in brain metabolism, the earlier picture of astrocytes being restricted to a scaffold-associated function in the brain is now out of date. With the development and optimization of non-invasive techniques, such as nuclear magnetic resonance spectroscopy (MRS, several groups have worked on assessing cerebral metabolism in vivo. In this context, 1H MRS has allowed the measurements of energy metabolism-related compounds, whose concentrations can vary under different brain activation states. 1H-[13C] MRS, i.e., indirect detection of signals from 13C-coupled 1H, together with infusion of 13C-enriched glucose has provided insights into the coupling between neurotransmission and glucose oxidation. Although these techniques tackle the coupling between neuronal activity and metabolism, they lack chemical specificity and fail in providing information on neuronal and glial metabolic pathways underlying those processes. Currently, the improvement of detection modalities (i.e., direct detection of 13C isotopomers, the progress in building adequate mathematical models along with the increase in magnetic field strength now available render possible detailed compartmentalized metabolic flux characterization. In particular, direct 13C MRS offers more detailed dataset acquisitions and provides information on metabolic interactions between neurons and astrocytes, and their role in supporting neurotransmission. Here

  15. Gender difference in the association between social support and metabolic syndrome in Japan: the 'enkai' effect?

    Ikeda, Ai; Kawachi, Ichiro; Iso, Hiroyasu; Inoue, Manami; Tsugane, Shoichiro

    2011-01-01

    Recent reports have found an association between social support and reduced prevalence of metabolic syndrome (or its components) in the West; however, no study has been carried out in Asian populations. The authors examined 12,537 men and women who were part of the Japan Public Health Center-based Prospective Study initiated in 1993. Perceived emotional support was assessed through questionnaire as receipt of confidant support and esteem support from family members or friends. Metabolic syndrome was defined based on the modified criteria of the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) and International Diabetes Federation (IDF), while its components were obtained through health examinations conducted during the same year as the questionnaire. The authors found an association between social support and metabolic syndrome among Japanese men that was in the opposite direction to what has previously been reported in western studies. Among men, the multivariate ORs and 95% CIs for metabolic syndrome in the lowest versus highest level of social support was 0.75 (0.58 to 0.97) based on AHA/NHLBI criteria and 0.69 (0.51 to 0.92) based on IDF criteria. Among women, the authors found no association between social support and metabolic syndrome. In this study, men with higher social support appeared to engage in heavier drinking and also reported a higher fat intake pattern, both of which may increase the risk of metabolic syndrome mainly through overweight. Our findings lend weight to the notion that the pattern of association between social support and health outcomes is both culturally contingent and gender-specific.

  16. Exercise as an intervention for the age-related decline in brain metabolic support

    Brenda J Anderson

    2010-08-01

    Full Text Available To identify interventions for brain aging, we must first identify the processes in which we hope to intervene. Brain aging is a period of decreasing functional capacity and increasing vulnerability, which reflect a reduction in morphological organization and perhaps degeneration. Since life is ultimately dependent upon the ability to maintain cellular organization through metabolism, this review explores evidence for a decline in neural metabolic support during aging, which includes a reduction in whole brain cerebral blood flow, and cellular metabolic capacity. Capillary density may also decrease with age, although the results are less clear. Exercise may be a highly effective intervention for brain aging, because it improves the cardiovascular system as a whole, and increases regional capillary density and neuronal metabolic capacity. Although the evidence is strongest for motor regions, more work may yield additional evidence for exercise-related improvement in metabolic support in non-motor regions. The protective effects of exercise may be specific to brain region and the type of insult. For example, exercise protects striatal cells from ischemia, but it produces mixed results after hippocampal seizures. Exercise can improve metabolic support and bioenergetic capacity in adult animals, but it remains to be determined whether it has similar effects in aging animals. What is clear is that exercise can influence the multiple levels of support necessary for maintaining optimal neuronal function, which is unique among proposed interventions for aging.

  17. Effects of velocity and weight support on ground reaction forces and metabolic power during running.

    Grabowski, Alena M; Kram, Rodger

    2008-08-01

    The biomechanical and metabolic demands of human running are distinctly affected by velocity and body weight. As runners increase velocity, ground reaction forces (GRF) increase, which may increase the risk of an overuse injury, and more metabolic power is required to produce greater rates of muscular force generation. Running with weight support attenuates GRFs, but demands less metabolic power than normal weight running. We used a recently developed device (G-trainer) that uses positive air pressure around the lower body to support body weight during treadmill running. Our scientific goal was to quantify the separate and combined effects of running velocity and weight support on GRFs and metabolic power. After obtaining this basic data set, we identified velocity and weight support combinations that resulted in different peak GRFs, yet demanded the same metabolic power. Ideal combinations of velocity and weight could potentially reduce biomechanical risks by attenuating peak GRFs while maintaining aerobic and neuromuscular benefits. Indeed, we found many combinations that decreased peak vertical GRFs yet demanded the same metabolic power as running slower at normal weight. This approach of manipulating velocity and weight during running may prove effective as a training and/or rehabilitation strategy.

  18. The module CCM for the simulation of the thermal-hydraulic situation within a coolant channel

    Hoeld, A.

    2000-01-01

    A coolant channel module (Cc) will be presented which aim is to simulate, in a very general way, the thermal-hydraulic behaviour of single- and two-phase fluids flowing along a heated (or cooled) vertical, inclined or horizontal coolant channel. It is based on a theoretical drift-flux supported 3-equation mixture-fluid model describing the steady state and transient behaviour of characteristic thermal-hydraulic parameters of a single- and two-phase flow within such a channel. The module can be applied as an element within an overall theoretical model for large and complex plant assemblies (PWR and BWR core channels, parallel channels in 3D cores, primary and secondary sides of different steam generators types etc.). The model refers to a general (basic) coolant channel (BC) which can consists of different flow regimes. The BC has thus to be subdivided accordingly into a number of subchannels (SC-s). All of them can belong, however, to only two types of SC-s (single-phase fluid with subcooled water or superheated steam or a two-phase flow regime). For both of them the possibility of variable entrance or outlet positions has to be considered. For discretization purposes the BC (and thus also the SC-s) have to be subdivided into a number of (BC and SC) nodes, discretizing thus the conservation equations for mass, energy and momentum along these nodes by applying a very general spatial procedure, namely a 'modified finite volume method'. A special quadratic polygon approximation method (PAX procedure) helps then to establish a connection between nodal boundary and mean nodal parameters. Considering their constitutive equations (among them an adequate drift-flux correlation package) yields finally a set of non-linear algebraic and non-linear ordinary differential equations for the characteristic parameters of each of these SC nodes (mass flow, pressure drop, coolant temperature and/or void fraction). Based on this theory a code package (CCM) could be established

  19. Training, supervision and quality of care in selected integrated community case management (iCCM) programmes: A scoping review of programmatic evidence.

    Bosch-Capblanch, Xavier; Marceau, Claudine

    2014-12-01

    included additional support of equipment and supplies, seemed to improve selected quality of care outcomes. However, current evaluation and reporting practices need to be revised in a new research agenda to address the methodological challenges of iCCM evaluations.

  20. Training, supervision and quality of care in selected integrated community case management (iCCM) programmes: A scoping review of programmatic evidence

    Bosch–Capblanch, Xavier; Marceau, Claudine

    2014-01-01

    components of training, supervision, which included additional support of equipment and supplies, seemed to improve selected quality of care outcomes. However, current evaluation and reporting practices need to be revised in a new research agenda to address the methodological challenges of iCCM evaluations. PMID:25520793

  1. Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses.

    Thwe, Phyu M; Pelgrom, Leonard; Cooper, Rachel; Beauchamp, Saritha; Reisz, Julie A; D'Alessandro, Angelo; Everts, Bart; Amiel, Eyal

    2017-09-05

    Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. We demonstrate that DCs possess intracellular glycogen stores and that cell-intrinsic glycogen metabolism supports the early effector functions of TLR-activated DCs. Inhibition of glycogenolysis significantly attenuates TLR-mediated DC maturation and impairs their ability to initiate lymphocyte activation. We further report that DCs exhibit functional compartmentalization of glucose- and glycogen-derived carbons, where these substrates preferentially contribute to distinct metabolic pathways. This work provides novel insights into nutrient homeostasis in DCs, demonstrating that differential utilization of glycogen and glucose metabolism regulates their optimal immune function. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. CCM proteins control endothelial β1 integrin dependent response to shear stress

    Zuzana Macek Jilkova

    2014-11-01

    Full Text Available Hemodynamic shear stress from blood flow on the endothelium critically regulates vascular function in many physiological and pathological situations. Endothelial cells adapt to shear stress by remodeling their cytoskeletal components and subsequently by changing their shape and orientation. We demonstrate that β1 integrin activation is critically controlled during the mechanoresponse of endothelial cells to shear stress. Indeed, we show that overexpression of the CCM complex, an inhibitor of β1 integrin activation, blocks endothelial actin rearrangement and cell reorientation in response to shear stress similarly to β1 integrin silencing. Conversely, depletion of CCM2 protein leads to an elongated “shear-stress-like” phenotype even in the absence of flow. Taken together, our findings reveal the existence of a balance between positive extracellular and negative intracellular signals, i.e. shear stress and CCM complex, for the control of β1 integrin activation and subsequent adaptation of vascular endothelial cells to mechanostimulation by fluid shear stress.

  3. Basal metabolic state governs AIF-dependent growth support in pancreatic cancer cells

    Scott, Andrew J.; Wilkinson, Amanda S.; Wilkinson, John C.

    2016-01-01

    Apoptosis-inducing factor (AIF), named for its involvement in cell death pathways, is a mitochondrial protein that regulates metabolic homeostasis. In addition to supporting the survival of healthy cells, AIF also plays a contributory role to the development of cancer through its enzymatic activity, and we have previously shown that AIF preferentially supports advanced-stage prostate cancer cells. Here we further evaluated the role of AIF in tumorigenesis by exploring its function in pancreatic cancer, a disease setting that most often presents at an advanced stage by the time of diagnosis. A bioinformatics approach was first employed to investigate AIF mRNA transcript levels in pancreatic tumor specimens vs. normal tissues. AIF-deficient pancreatic cancer cell lines were then established via lentiviral infection. Immunoblot analysis was used to determine relative protein quantities within cells. Cell viability was measured by flow cytometry; in vitro and Matrigel™ growth/survival using Coulter™ counting and phase contrast microscopy; and glucose consumption in the absence and presence of Matrigel™ using spectrophotometric methods. Archival gene expression data revealed a modest elevation of AIF transcript levels in subsets of pancreatic tumor specimens, suggesting a possible role in disease progression. AIF expression was then suppressed in a panel of five pancreatic cancer cell lines that display diverse metabolic phenotypes. AIF ablation selectively crippled the growth of cells in vitro in a manner that directly correlated with the loss of mitochondrial respiratory chain subunits and altered glucose metabolism, and these effects were exacerbated in the presence of Matrigel™ substrate. This suggests a critical metabolic role for AIF to pancreatic tumorigenesis, while the spectrum of sensitivities to AIF ablation depends on basal cellular metabolic phenotypes. Altogether these data indicate that AIF supports the growth and survival of metabolically defined

  4. Novel functions of CCM1 delimit the relationship of PTB/PH domains.

    Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

    2017-10-01

    Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and

  5. A decision-support system for sustainable urban metabolism in Europe

    Gonzalez, Ainhoa, E-mail: ainhoag@yahoo.com [Trinity Centre for Biodiversity Research, School of Natural Sciences, Trinity College Dublin, College Green, Dublin 2 (Ireland); Donnelly, Alison, E-mail: donnelac@tcd.ie [Centre for the Environment, School of Natural Sciences, Trinity College Dublin (Ireland); Jones, Mike, E-mail: mike.jones@tcd.ie [Discipline of Botany, School of Natural Sciences, Trinity College Dublin (Ireland); Chrysoulakis, Nektarios, E-mail: zedd2@iacm.forth.gr [Foundation for Research and Technology-Hellas, Institute of Applied and Computational Mathematics (Greece); Lopes, Myriam, E-mail: myr@ua.pt [Departamento de Ambiente e Ordenamento and CESAM, University of Aveiro (Portugal)

    2013-01-15

    Urban metabolism components define the energy and material exchanges within a city and, therefore, can provide valuable information on the environmental quality of urban areas. Assessing the potential impact of urban planning alternatives on urban metabolism components (such as energy, water, carbon and pollutants fluxes) can provide a quantitative estimation of their sustainability performance. Urban metabolism impact assessment can, therefore, contribute to the identification of sustainable urban structures with regards, for example, to building types, materials and layout, as well as to location and capacity of transportation and infrastructural developments. In this way, it enables the formulation of planning and policy recommendations to promote efficient use of resources and enhance environmental quality in urban areas. The European FP7 project BRIDGE (sustainaBle uRban plannIng Decision support accountinG for urban mEtabolism) has developed a decision-support system (DSS) that systematically integrates urban metabolism components into impact assessment processes with the aim of accurately quantifying the potential effects of proposed planning interventions. The DSS enables integration of multiple spatial and non-spatial datasets (e.g. physical flows of energy and material with variables of social and economic change) in a systematic manner to obtain spatially defined assessment results and to thus inform planners and decision-makers. This multi-criteria approach also enables incorporation of stakeholders' perceptions in order to prioritise decisive assessment criteria. This paper describes the methodological framework used to develop the DSS and critically examines the results of its practical application in five European cities. - Highlights: Black-Right-Pointing-Pointer Urban metabolism in sustainability assessment of planning alternatives. Black-Right-Pointing-Pointer European FP7 project applied to 5 real life case studies across Europe. Black

  6. A decision-support system for sustainable urban metabolism in Europe

    González, Ainhoa; Donnelly, Alison; Jones, Mike; Chrysoulakis, Nektarios; Lopes, Myriam

    2013-01-01

    Urban metabolism components define the energy and material exchanges within a city and, therefore, can provide valuable information on the environmental quality of urban areas. Assessing the potential impact of urban planning alternatives on urban metabolism components (such as energy, water, carbon and pollutants fluxes) can provide a quantitative estimation of their sustainability performance. Urban metabolism impact assessment can, therefore, contribute to the identification of sustainable urban structures with regards, for example, to building types, materials and layout, as well as to location and capacity of transportation and infrastructural developments. In this way, it enables the formulation of planning and policy recommendations to promote efficient use of resources and enhance environmental quality in urban areas. The European FP7 project BRIDGE (sustainaBle uRban plannIng Decision support accountinG for urban mEtabolism) has developed a decision-support system (DSS) that systematically integrates urban metabolism components into impact assessment processes with the aim of accurately quantifying the potential effects of proposed planning interventions. The DSS enables integration of multiple spatial and non-spatial datasets (e.g. physical flows of energy and material with variables of social and economic change) in a systematic manner to obtain spatially defined assessment results and to thus inform planners and decision-makers. This multi-criteria approach also enables incorporation of stakeholders' perceptions in order to prioritise decisive assessment criteria. This paper describes the methodological framework used to develop the DSS and critically examines the results of its practical application in five European cities. - Highlights: ► Urban metabolism in sustainability assessment of planning alternatives. ► European FP7 project applied to 5 real life case studies across Europe. ► Decision support system enables incorporating scientific

  7. Investigating the thermal hydraulic performance of spacer grid with mixing vanes using STAR-CCM+ and MATRA

    Agbodemegbe, V. Y.

    2014-07-01

    Enhancement of heat transfer for flow through rod bundles is linked to the extent and sustainability of mixing in the flow geometry. Spacer grids used as support for rod bundles in nuclear reactors, when attached with ditferent designs of mixing vanes promote turbulent mixing by inducing swirl or forced lateral convection that improves mixing within or between sub-channels. The improved turbulent mixing raises the margin of the onset of critical heat flux in light water reactors (LWR) and also ensures a higher fuel cycle economy. To optimize design of mixing vanes and performance of spacer grids with mixing vanes, computational fluid dynamic simulations arc carried out on new designs and validated experimentally prior to industrial application. In the present study, computational fluid dynamic simulation using STAR-CCM+ and sub-channel analysis with MATRA were performed for flow of water through a 5 X 5 rod bundle geometry for which the rod to rod pitch to diameter ratio was 1.33 and the wall to rod pitch to diameter ratio was 0.74. The two layer k-epsilon turbulence model with an all- y + automatic wall treatment function in STAR-CCM+ were adopted for an isothermal single phase flow through the geometry with imposed cyclic periodic and non-cyclic periodic interface boundary conditions. The objective was to primarily investigate the detail flow behavior in rod bundle in the presence of spacer grids with and without attached mixing vanes. Furthermore, the present study also investigated the extent of turbulent mixing and lateral mass flux induced by the mixing vanes through comparative analysis of parametric trends for spacer grid with and without mixing vanes. New models and empirical correlations for describing the mixing vanes effects were also developed. These semi-empirical correlations improved the prediction for lateral mass flux due to turbulence, fraction of flow diverted through gaps and cross-flow resistance coefficients. Validation of simulation results

  8. Data in support of metabolic reprogramming in transformed mouse cortical astrocytes: A proteomic study

    Azeddine Bentaib

    2015-03-01

    Full Text Available 2D-DIGE analysis coupled with mass spectrometry is a global, without a priori, comparative proteomic approach particularly suited to identify and quantify enzymes isoforms and structural proteins, thus making it an efficient tool for the characterization of the changes in cell phenotypes that occur in physiological and pathological conditions. In this data article in support of the research article entitled “Metabolic reprogramming in transformed mouse cortical astrocytes: a proteomic study” [1] we illustrate the changes in protein profile that occur during the metabolic reprogramming undergone by cultured mouse astrocytes in a model of in-vitro cancerous transformation [2].

  9. Structure/Function of the Novel Proteins LCIB and LCIC in the Chlamydomonas CCM

    Martin, Spalding H. [Iowa State Univ., Ames, IA (United States). Dept. of Genetics, Development and Cell Biology

    2017-05-09

    The goal of this project was to investigate the function of two novel proteins, LCIB and LCIC, which together form an essential protein complex that is required for function of a carbon-dioxide-concentrating mechanism (CCM) required by microalgae to grow in environments where carbon dioxide levels are at or below air equilibration levels.

  10. Flyback CCM inverter for AC module applications: iterative learning control and convergence analysis

    Lee, Sung-Ho; Kim, Minsung

    2017-12-01

    This paper presents an iterative learning controller (ILC) for an interleaved flyback inverter operating in continuous conduction mode (CCM). The flyback CCM inverter features small output ripple current, high efficiency, and low cost, and hence it is well suited for photovoltaic power applications. However, it exhibits the non-minimum phase behaviour, because its transfer function from control duty to output current has the right-half-plane (RHP) zero. Moreover, the flyback CCM inverter suffers from the time-varying grid voltage disturbance. Thus, conventional control scheme results in inaccurate output tracking. To overcome these problems, the ILC is first developed and applied to the flyback inverter operating in CCM. The ILC makes use of both predictive and current learning terms which help the system output to converge to the reference trajectory. We take into account the nonlinear averaged model and use it to construct the proposed controller. It is proven that the system output globally converges to the reference trajectory in the absence of state disturbances, output noises, or initial state errors. Numerical simulations are performed to validate the proposed control scheme, and experiments using 400-W AC module prototype are carried out to demonstrate its practical feasibility.

  11. Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass.

    Spinelli, Jessica B; Yoon, Haejin; Ringel, Alison E; Jeanfavre, Sarah; Clish, Clary B; Haigis, Marcia C

    2017-11-17

    Ammonia is a ubiquitous by-product of cellular metabolism; however, the biological consequences of ammonia production are not fully understood, especially in cancer. We found that ammonia is not merely a toxic waste product but is recycled into central amino acid metabolism to maximize nitrogen utilization. In our experiments, human breast cancer cells primarily assimilated ammonia through reductive amination catalyzed by glutamate dehydrogenase (GDH); secondary reactions enabled other amino acids, such as proline and aspartate, to directly acquire this nitrogen. Metabolic recycling of ammonia accelerated proliferation of breast cancer. In mice, ammonia accumulated in the tumor microenvironment and was used directly to generate amino acids through GDH activity. These data show that ammonia is not only a secreted waste product but also a fundamental nitrogen source that can support tumor biomass. Copyright © 2017, American Association for the Advancement of Science.

  12. FOREWORD: CCM Second International Seminar: Pressure Metrology from 1 kPa to 1 GPa

    Molinar, G. F.

    1994-01-01

    , it was at a high level. This special issue of Metrologia brings together all the seminar papers accepted for publication after a careful review process controlled directly by the organizing committee of the seminar and the Metrologia editor. I feel that we have succeeded reasonably well. The papers published here focus on important achievements in pressure measurements and the main problems which the scientific community is working to resolve in the future. Various achievements are reported, ranging from a general improvement in accuracy to new devices and techniques. I would like to thank all those who helped with this seminar. First, the members of the organizing committee: Chairman of the CCM Medium Pressure Work ing Group, P Stuart, (NPL, UK); J Bonhoure (BIPM); V Borovkov (VNIIFTRI, Russia); C Ehrlich (NIST, USA); J Jager (PTB, Germany); J C Legras (LNE); Chairman of the CCM Low Pressure Working Group, C Tilford (NIST, USA); S Yamamoto (NRLM, Japan); R Wirniewski (WUT, Poland); not forgetting the institutions that allowed them to spend considerable time on the preparation and organization of the seminar. I extend my thanks to V E Bean (NIST, USA), A Ooiwa (NRLM, Japan), and A J Rostocki (WUT, Poland), who joined the organizing committee as guest editors and helped to see the papers presented at the seminar through the review process and into print. Many thanks are also due to A Bryden, Director of the Laboratoire National d'Essais, and to J C Legras of the LNE Pressure Laboratory, for hosting the seminar and for taking care of all practical problems. A special thanks to T J Quinn, Director of the Bureau International des Poids et Mesures, for his continuous support and encouragement in the preparation of the seminar. Grateful thanks to Desgranges et Huot, France, for their hospitality in Paris; and to D-H Instruments Co., USA, and Ruska Co., USA, which sponsored the seminar through their fmancial support for the publication of these Proceedings. A special

  13. Metabolism

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  14. Predicting metabolic syndrome using decision tree and support vector machine methods

    Farzaneh Karimi-Alavijeh

    2016-06-01

    Full Text Available BACKGROUND: Metabolic syndrome which underlies the increased prevalence of cardiovascular disease and Type 2 diabetes is considered as a group of metabolic abnormalities including central obesity, hypertriglyceridemia, glucose intolerance, hypertension, and dyslipidemia. Recently, artificial intelligence based health-care systems are highly regarded because of its success in diagnosis, prediction, and choice of treatment. This study employs machine learning technics for predict the metabolic syndrome. METHODS: This study aims to employ decision tree and support vector machine (SVM to predict the 7-year incidence of metabolic syndrome. This research is a practical one in which data from 2107 participants of Isfahan Cohort Study has been utilized. The subjects without metabolic syndrome according to the ATPIII criteria were selected. The features that have been used in this data set include: gender, age, weight, body mass index, waist circumference, waist-to-hip ratio, hip circumference, physical activity, smoking, hypertension, antihypertensive medication use, systolic blood pressure (BP, diastolic BP, fasting blood sugar, 2-hour blood glucose, triglycerides (TGs, total cholesterol, low-density lipoprotein, high density lipoprotein-cholesterol, mean corpuscular volume, and mean corpuscular hemoglobin. Metabolic syndrome was diagnosed based on ATPIII criteria and two methods of decision tree and SVM were selected to predict the metabolic syndrome. The criteria of sensitivity, specificity and accuracy were used for validation. RESULTS: SVM and decision tree methods were examined according to the criteria of sensitivity, specificity and accuracy. Sensitivity, specificity and accuracy were 0.774 (0.758, 0.74 (0.72 and 0.757 (0.739 in SVM (decision tree method. CONCLUSION: The results show that SVM method sensitivity, specificity and accuracy is more efficient than decision tree. The results of decision tree method show that the TG is the most

  15. Predicting metabolic syndrome using decision tree and support vector machine methods.

    Karimi-Alavijeh, Farzaneh; Jalili, Saeed; Sadeghi, Masoumeh

    2016-05-01

    Metabolic syndrome which underlies the increased prevalence of cardiovascular disease and Type 2 diabetes is considered as a group of metabolic abnormalities including central obesity, hypertriglyceridemia, glucose intolerance, hypertension, and dyslipidemia. Recently, artificial intelligence based health-care systems are highly regarded because of its success in diagnosis, prediction, and choice of treatment. This study employs machine learning technics for predict the metabolic syndrome. This study aims to employ decision tree and support vector machine (SVM) to predict the 7-year incidence of metabolic syndrome. This research is a practical one in which data from 2107 participants of Isfahan Cohort Study has been utilized. The subjects without metabolic syndrome according to the ATPIII criteria were selected. The features that have been used in this data set include: gender, age, weight, body mass index, waist circumference, waist-to-hip ratio, hip circumference, physical activity, smoking, hypertension, antihypertensive medication use, systolic blood pressure (BP), diastolic BP, fasting blood sugar, 2-hour blood glucose, triglycerides (TGs), total cholesterol, low-density lipoprotein, high density lipoprotein-cholesterol, mean corpuscular volume, and mean corpuscular hemoglobin. Metabolic syndrome was diagnosed based on ATPIII criteria and two methods of decision tree and SVM were selected to predict the metabolic syndrome. The criteria of sensitivity, specificity and accuracy were used for validation. SVM and decision tree methods were examined according to the criteria of sensitivity, specificity and accuracy. Sensitivity, specificity and accuracy were 0.774 (0.758), 0.74 (0.72) and 0.757 (0.739) in SVM (decision tree) method. The results show that SVM method sensitivity, specificity and accuracy is more efficient than decision tree. The results of decision tree method show that the TG is the most important feature in predicting metabolic syndrome. According

  16. A Unified Voltage Harmonic Control Strategy for Coordinated Compensation with VCM and CCM Converters

    Zhao, Xin; Meng, Lexuan; Xie, Chuan

    2018-01-01

    -controlled mode (VCM) and current-controlled mode (CCM), need to cooperatively provide the compensation function. Aiming at this objective, this paper proposes a unified voltage harmonic mitigation strategy for VCM and CCM converters with high harmonic current sharing accuracy. Another advantage of the proposal......Harmonics have been considered as one of the major issues in modern power grids. Considering the high penetration level of power electronic converter interfaced distributed generators (DGs), it is of interest to provide ancillary services through DG interfacing converters, such as harmonic...... compensation. In case of that, multiple DG interfacing converters are utilized to compensate harmonics, and the compensation effort should be properly shared among these converters. However, it is rarely considered in existing literatures that converters operating in different modes, such as voltage...

  17. Myocardial Oxidative Metabolism and Protein Synthesis during Mechanical Circulatory Support by Extracorporeal Membrane Oxygenation

    Priddy, MD, Colleen M.; Kajimoto, Masaki; Ledee, Dolena; Bouchard, Bertrand; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-02-01

    Extracorporeal membrane oxygenation (ECMO) provides mechanical circulatory support essential for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative. We focused on the amino acid leucine, and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart (i) the fractional contribution of leucine (FcLeucine) and pyruvate (FCpyruvate) to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and (ii) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 hours of normal circulation or ECMO) and intracoronary infusion [13C6,15N]-L-leucine (3.7 mM) alone or with [2-13C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (~ 40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. Conclusion: The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining (i) metabolic flexibility indicated by ability to respond to pyruvate, and (ii) a normal or increased capacity for global protein synthesis, suggesting an improved protein balance.

  18. Metabolism

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  19. Estimate of Leaf Chlorophyll and Nitrogen Content in Asian Pear (Pyrus serotina Rehd. by CCM-200

    Mostafa GHASEMI

    2011-03-01

    Full Text Available In many cases evaluation of chlorophyll and nitrogen content in plants need to destructive methods, more time and organic solvents. Application of chlorophyll meters save time and resources. The aim of this study was estimating of chlorophyll and nitrogen content in Asian pear leaves using non-destructive method and rapid quantification of chlorophyll by chlorophyll content meter (CCM-200. This study was conducted on 8 years old Asian pear trees during June 2008 in Tehran, Iran. To develop our regression model, the chlorophyll meter data were correlated with extracted chlorophyll and nitrogen content data obtained from DMSO and Kejeldal methods, respectively. The results showed that, there was positive and linear correlation between CCM-200 data and chlorophyll a (R�=0.7183, chlorophyll b (R�=0.8523, total chlorophyll (R�=0.90, and total nitrogen content (R�=0.76 in Asian pear leaves. Thus, it can be concluded that, CCM-200 can be used in order to predict both chlorophyll and nitrogen content in Asian pear leaves.

  20. Evaluation of stability of interface between CCM (Co-Cr-Mo) UCLA abutment and external hex implant.

    Yoon, Ki-Joon; Park, Young-Bum; Choi, Hyunmin; Cho, Youngsung; Lee, Jae-Hoon; Lee, Keun-Woo

    2016-12-01

    The purpose of this study is to evaluate the stability of interface between Co-Cr-Mo (CCM) UCLA abutment and external hex implant. Sixteen external hex implant fixtures were assigned to two groups (CCM and Gold group) and were embedded in molds using clear acrylic resin. Screw-retained prostheses were constructed using CCM UCLA abutment and Gold UCLA abutment. The external implant fixture and screw-retained prostheses were connected using abutment screws. After the abutments were tightened to 30 Ncm torque, 5 kg thermocyclic functional loading was applied by chewing simulator. A target of 1.0 × 10 6 cycles was applied. After cyclic loading, removal torque values were recorded using a driving torque tester, and the interface between implant fixture and abutment was evaluated by scanning electronic microscope (SEM). The means and standard deviations (SD) between the CCM and Gold groups were analyzed with independent t-test at the significance level of 0.05. Fractures of crowns, abutments, abutment screws, and fixtures and loosening of abutment screws were not observed after thermocyclic loading. There were no statistically significant differences at the recorded removal torque values between CCM and Gold groups ( P >.05). SEM analysis revealed that remarkable wear patterns were observed at the abutment interface only for Gold UCLA abutments. Those patterns were not observed for other specimens. Within the limit of this study, CCM UCLA abutment has no statistically significant difference in the stability of interface with external hex implant, compared with Gold UCLA abutment.

  1. Mouse preimplantation embryo responses to culture medium osmolarity include increased expression of CCM2 and p38 MAPK activation

    Watson Andrew J

    2007-01-01

    Full Text Available Abstract Background Mechanisms that confer an ability to respond positively to environmental osmolarity are fundamental to ensuring embryo survival during the preimplantation period. Activation of p38 mitogen-activated protein kinase (MAPK occurs following exposure to hyperosmotic treatment. Recently, a novel scaffolding protein called Osmosensing Scaffold for MEKK3 (OSM was linked to p38 MAPK activation in response to sorbitol-induced hypertonicity. The human ortholog of OSM is cerebral cavernous malformation 2 (CCM2. The present study was conducted to investigate whether CCM2 is expressed during mouse preimplantation development and to determine whether this scaffolding protein is associated with p38 MAPK activation following exposure of preimplantation embryos to hyperosmotic environments. Results Our results indicate that Ccm2 along with upstream p38 MAPK pathway constituents (Map3k3, Map2k3, Map2k6, and Map2k4 are expressed throughout mouse preimplantation development. CCM2, MAP3K3 and the phosphorylated forms of MAP2K3/MAP2K6 and MAP2K4 were also detected throughout preimplantation development. Embryo culture in hyperosmotic media increased p38 MAPK activity in conjunction with elevated CCM2 levels. Conclusion These results define the expression of upstream activators of p38 MAPK during preimplantation development and indicate that embryo responses to hyperosmotic environments include elevation of CCM2 and activation of p38 MAPK.

  2. On the cradle of CCM research: discovery, development, and challenges ahead.

    Kaplan, Aaron

    2017-06-01

    Herein, 40 years after its discovery, I briefly and critically survey the development of ideas that propelled research on CO2-concentrating mechanisms (CCMs; a term proposed by Dean Price) of phytoplankton, mainly focusing on cyanobacteria. This is not a comprehensive review on CCM research, but a personal view on the past developments and challenges that lie ahead. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Improving effectiveness in e-marketing communication for Chinese SMEs: 2CCM

    Zhao, Ying

    2014-01-01

    The purpose of this thesis was to come up with perspectives on improving effective-ness in e-marketing communication for Chinese SMEs. The aim of this thesis was to analyze Chinese e-marketing communication channels and message delivery. This thesis was done for 2CCM, which is an online store for selling fashionable and stylish high-end products. The thesis was roughly divided into two parts which were theoretical part and rec-ommendations. The theoretical part introduced the concept, Ch...

  4. Analysis of Low-Speed Stall Aerodynamics of a Business Jets Wing Using STAR-CCM+

    Bui, Trong

    2016-01-01

    Reynolds-Averaged Navier-Stokes (RANS) computational fluid dynamics (CFD) analysis was conducted: to study the low-speed stall aerodynamics of a GIII aircrafts swept wing modified with (1) a laminar-flow wing glove, or (2) a seamless flap. The stall aerodynamics of these two different wing configurations were analyzed and compared with the unmodified baseline wing for low-speed flight. The Star-CCM+ polyhedral unstructured CFD code was first validated for wing stall predictions using the wing-body geometry from the First AIAA CFD High-Lift Prediction Workshop.

  5. Decision support for large-scale remediation strategies by fused urban metabolism and life cycle assessment

    Ohms, Pernille; Andersen, Camilla; Landgren, Mathilde

    2018-01-01

    Purpose: This paper seeks to identify the most environmental friendly way of conducting a refurbishment of Broendby Strand, with focus on PCB remediation. The actual identification is conducted by comparing four remediation techniques using urban metabolism fused with life cycle assessment (UM......-LCA) in combination with information relating to cost and efficiency of the compared techniques. The methodological goal of our paper is to test UM-LCA as a decision support tool and discuss application of the method in relation to large refurbishment projects. Methods: To assess the environmental performance of PCB......-remediation techniques, the UM-LCA method was applied. By combining UM and LCA methodologies, the total environmental impact potentials of the remediation techniques were calculated. To build an inventory for each technique, we contacted and interviewed experts and studied existing literature, cases, and projects...

  6. Impact of Amazon deforestation on climate simulations using the NCAR CCM2/BATS model

    Hahmann, A.N.; Dickinson, R.E. [Univ. of Arizona, Tucson, AZ (United States)

    1996-12-31

    Model validation and results are briefly presented for a simulation of deforestation of the Amazon rainforest. This initial study is made using assumptions regarding deforestation similar to those in earlier studies with several versions of the NCAR Community Climate Model (CCM) couples to the Biosphere-Atmosphere Transfer Scheme (BATS). The model used is a revised version of the NCAR CCM Version 2 coupled to BATS Version 1e. This paper discusses the portion of validation dealing with the distribution of precipitation; the simulation displays very good agreement with observed rainfall rates for the austral summer. Preliminary results from an 8-year simulation of deforestation are similar to that of previous studies. Annual precipitation and evaporation are reduced, while surface air temperatures show a slight increase. A substantial bimodal pattern appears in the results, with the Amazon decrease of precipitation and temperature increase accompanied by changes in the opposite sign to the southeast of the Amazon. Similar patterns have occurred in other studies, but not always in exactly the same locations. Evidently, how much of the region of rainfall increase occurs in the deforested area over the Amazon strongly affects the inferred statistics. It is likely that this pattern depends on the model control climatology and possibly other features. 16 refs., 2 figs., 2 tabs.

  7. Evidence that the tri-cellular metabolism of N-acetylaspartate functions as the brain's "operating system": how NAA metabolism supports meaningful intercellular frequency-encoded communications.

    Baslow, Morris H

    2010-11-01

    N-acetylaspartate (NAA), an acetylated derivative of L-aspartate (Asp), and N-acetylaspartylglutamate (NAAG), a derivative of NAA and L-glutamate (Glu), are synthesized by neurons in brain. However, neurons cannot catabolize either of these substances, and so their metabolism requires the participation of two other cell types. Neurons release both NAA and NAAG to extra-cellular fluid (ECF) upon stimulation, where astrocytes, the target cells for NAAG, hydrolyze it releasing NAA back into ECF, and oligodendrocytes, the target cells for NAA, hydrolyze it releasing Asp to ECF for recycling to neurons. This sequence is unique as it is the only known amino acid metabolic cycle in brain that requires three cell types for its completion. The results of this cycling are two-fold. First, neuronal metabolic water is transported to ECF for its removal from brain. Second, the rate of neuronal activity is coupled with focal hyperemia, providing stimulated neurons with the energy required for transmission of meaningful frequency-encoded messages. In this paper, it is proposed that the tri-cellular metabolism of NAA functions as the "operating system" of the brain, and is essential for normal cognitive and motor activities. Evidence in support of this hypothesis is provided by the outcomes of two human inborn errors in NAA metabolism.

  8. Metabolic modelling to support long term strategic decisions on water supply systems

    Ciriello, Valentina; Felisa, Giada; Lauriola, Ilaria; Pomanti, Flavio; Di Federico, Vittorio

    2017-04-01

    Water resources are essential for the economic development and sustenance of anthropic activities belonging to the civil, agricultural and industrial sectors. Nevertheless, availability of water resources is not uniformly distributed in space and time. Moreover, the increasing water demand, mainly due to population growth and expansion of agricultural crops, may cause increasing water stress conditions, if combined with the effects of climate change. Under these circumstances, it is necessary to improve the resilience of water supply systems both in terms of infrastructures and environmental compliance. Metabolic modelling approaches represent a flexible tool able to provide support to decision making in the long term, based on sustainability criteria. These approaches mimic the water supply network through a set of material and energy fluxes that interact and influence each other. By analyzing these fluxes, a suite of key performance indicators is evaluated in order to identify which kind of interventions may be applied to increase the sustainability of the system. Here, we adopt these concepts to analyze the water supply network of Reggio-Emilia (Italy) which is supported by water withdrawals from both surface water and groundwater bodies. We analyze different scenarios, including possible reduction of water withdrawals from one of the different sources as a consequence of a decrease in water availability under present and future scenarios. On these basis, we identify preventive strategies for a dynamic management of the water supply system.

  9. Verteerbaarheid en voederwaarde van diverse kwaliteiten graskuil en van CCM bij biologische zeugen = Digestibility and nutritive value of several qualities of grass silage and of CCM in organic housed gestating sows

    Peet-Schwering, van der C.M.C.; Binnendijk, G.P.; Diepen, van J.T.M.

    2010-01-01

    The chemical composition, digestibility and energy value of five qualities of grass silage and of CCM (Corn cob mix) were investigated in organic housed gestating sows. The dry matter content of the five grass silages varied between 21.3 and 24.9%. The energy value per kg dry matter varied between

  10. FOREWORD: The 4th CCM International Conference on Pressure Metrology from Ultra-High Vacuum to Very High Pressures (10-9 Pa to 109 Pa)

    Legras, Jean-Claude; Jousten, Karl; Severn, Ian

    2005-12-01

    , particularly Gianfranco Molinar who offered much advice based on experience of organizing the previous conference. Special thanks must also be made to Mitsuru Tanaka, President of the CCM, and Andrew Wallard, Director of the BIPM, for their support of the event. The event was coordinated by Jasmina Bolfek-Radovani, of the Institute of Physics, without whose tireless efforts the event would not have been as successful. The production of this issue of Metrologia would not have been possible without the help and support of its editor, Jeffrey Williams. The National Measurement System Directorate of the Department of Trade and Industry supported the conference and it was sponsored by DH Instruments and BOC Edwards. Additional financial assistance was also received from Chell Instruments Ltd, DH-Budenberg, GE Infrastructure Sensing, Hi-Pro Pressure Products Ltd, Kurt J Lesker Company Ltd and Leybold Vacuum UK Ltd. Finally we would like to thank all of the conference participants who made the event both technically stimulating and enjoyable. By the time the next CCM Pressure conference is held in Berlin in 2011, pressure science and technology will undoubtedly have moved on still further and we may see the culmination of work to realize primary pressure standards by more fundamental methods.

  11. Assessing Intraseasonal Variability Produced by Several Deep Convection Schemes in the NCAR CCM3.6

    Maloney, E. D.

    2001-05-01

    The Hack, Zhang/McFarlane, and McRAS convection schemes produce very different simulations of intraseasonal variability in the NCAR CCM3.6. A robust analysis of simulation performance requires an expanded set of diagnostics. The use of only one criterion to analyze model Madden-Julian oscillation (MJO) variability, such as equatorial zonal wind variability, may give a misleading impression of model performance. Schemes that produce strong variability in zonal winds may sometimes lack a corresponding coherent signal in precipitation, suggesting that model convection and the large-scale circulation are not as strongly coupled as observed. The McRAS scheme, which includes a parametrization of unsaturated convective downdrafts, produces the best simulation of intraseasonal variability of the three schemes used. Downdrafts in McRAS create a moister equatorial troposphere, which increases equatorial convection. Composite analysis indicates a strong dependence of model intraseasonal variability on the frictional convergence mechanism, which may also be important in nature. The McRAS simulation has limitations, however. Indian Ocean variability is weak, and anomalous convection extends too far east across the Pacific. The dependence of convection on surface friction is too strong, and causes enhanced MJO convection to be associated with low-level easterly wind perturbations, unlike observed MJO convection. Anomalous vertical advection associated with surface convergence influences model convection by moistening the lower troposphere. Based on the work of Hendon (2000), coupling to an interactive ocean is unlikely to change the performance of the CCM3 with McRAS, due to the phase relationship between anomalous convection and zonal winds. Use of the analysis tools presented here indicates areas for improvement in the parametrization of deep convection by atmospheric GCMs.

  12. Nuclear reactor multi-physics simulations with coupled MCNP5 and STAR-CCM+

    Cardoni, Jeffrey Neil; Rizwan-uddin

    2011-01-01

    The MCNP5 Monte Carlo particle transport code has been coupled to the computational fluid dynamics code, STAR-CCM+, to provide a high fidelity multi-physics simulation tool for pressurized water nuclear reactors. The codes are executed separately and coupled externally through a Perl script. The Perl script automates the exchange of temperature, density, and volumetric heating information between the codes using ASCII text data files. Fortran90 and Java utility programs assist job automation with data post-processing and file management. The MCNP5 utility code, MAKXSF, pre-generates temperature dependent cross section libraries for the thermal feedback calculations. The MCNP5–STAR-CCM+ coupled simulation tool, dubbed MULTINUKE, was applied to a steady state, PWR cell model to demonstrate its usage and capabilities. The demonstration calculation showed reasonable results that agree with PWR values typically reported in literature. Temperature and fission reaction rate distributions were realistic and intuitive. Reactivity coefficients were also deemed reasonable in comparison to historically reported data. The demonstration problem consisted of 9,984 CFD cells and 7,489 neutronic cells. MCNP5 tallied fission energy deposition over 3,328 UO_2 cells. The coupled solution converged within eight hours and in three MULTINUKE iterations. The simulation was carried out on a 64 bit, quad core, Intel 2.8 GHz microprocessor with 1 GB RAM. The simulations on a quad core machine indicated that a massively parallelized implementation of MULTINUKE can be used to assess larger multi-million cell models. (author)

  13. STAR-CCM+ (CFD) Calculations and Validation L3:VVI.H2L.P15.02

    Gilkey, Lindsay [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-09-05

    This milestone presents a demonstration of the High-to-Low (Hi2Lo) process in the VVI focus area. Validation and additional calculations with the commercial computational fluid dynamics code, STAR-CCM+, were performed using a 5x5 fuel assembly with non-mixing geometry and spacer grids. This geometry was based on the benchmark experiment provided by Westinghouse. Results from the simulations were compared to existing experimental data and to the subchannel thermal-hydraulics code COBRA-TF (CTF). An uncertainty quantification (UQ) process was developed for the STAR-CCM+ model and results of the STAR UQ were communicated to CTF. Results from STAR-CCM+ simulations were used as experimental design points in CTF to calibrate the mixing parameter β and compared to results obtained using experimental data points. This demonstrated that CTF’s β parameter can be calibrated to match existing experimental data more closely. The Hi2Lo process for the STAR-CCM+/CTF code coupling was documented in this milestone and closely linked L3:VVI.H2LP15.01 milestone report.

  14. Economic evaluation of Cardiac Contractility Modulation (CCM therapy with the optimizer IVs in the management of heart failure patients

    Nikos Maniadakis

    2015-01-01

    The present analysis indicates that CCM may be cost-effective therapy. This early conclusion should be viewed in the light of the caveats of the modeling methods used, due to data availability limitations. Long-term studies directly collecting hospitalization and mortality data should be undertaken to provide more robust evidence.

  15. Gas Furnace with Pulsed Feeding of the Heating Agent for Volume Precision Heat Treatment of CCM Rolls

    Moroz, V. I.; Egorova, V. M.; Gusev, S. V.

    2001-05-01

    A standard chamber batch furnace of the Severstal' plant has been modified for precision heat treatment of CCM rolls. The certification tests of a charge of rolls from steel 24KhM1F have shown the technical and economical advantages of the new design.

  16. Simulation of the modern arctic climate by the NCAR CCM1

    Bromwich, David H.; Tzeng, Ren-Yow; Parish, Thomas, R.

    1994-01-01

    The National Center of Atmospheric Research (NCAR) Community Climate Model Version 1 (CCM1's) simulation of the modern arctic climate is evaluated by comparing a five-year seasonal cycle simulation with the European Center for Medium-Range Weather Forecasts (ECMWF) global analyses. The sea level pressure (SLP), storm tracks, vertical cross section of height, 500-hPa height, total energy budget, and moisture budget are analyzed to investigate the biases in the simulated arctic climate. The results show that the model simulates anomalously low SLP, too much storm activity, and anomalously strong baroclinicity to the west of Greenland and vice versa to the east of Greenland. This bias is mainly attributed to the model's topographic representation of Greenland. First, the broadened Greenland topography in the model distorts the path of cyclone waves over the North Atlantic Ocean. Second, the model oversimulates the ridge over Greenland, which intensifies its blocking effect and steers the cyclone waves clockwise around it and hence produces an artificial circum-Greenland trough. These biases are significantly alleviated when the horizontal resolution increases to T42. Over the Arctic basin, the model simulates large amounts of low-level (stratus) clouds in winter and almost no stratus in summer, which is opposite to the observations. This bias is mainly due to the location of the simulated SLP features and the negative anomaly of storm activity, which prevent the transport of moisture into this region during summer but favor this transport in winter. The moisture budget analysis shows that the model's net annual precipitation (P-E) between 70 deg N and the North Pole is 6.6 times larger than the observations and the model transports six times more moisture into this region. The bias in the advection term is attributed to the positive moisture fixer scheme and the distorted flow pattern. However, the excessive moisture transport into the Arctic basin does not solely

  17. Diagnostics of the Tropical Tropopause Layer from in-situ observations and CCM data

    C. M. Volk

    2009-12-01

    Full Text Available A suite of diagnostics is applied to in-situ aircraft measurements and one Chemistry-Climate Model (CCM data to characterize the vertical structure of the Tropical Tropopause Layer (TTL. The diagnostics are based on vertical tracer profiles and relative vertical tracer gradients, using tropopause-referenced coordinates, and tracer-tracer relationships in the tropical Upper Troposphere/Lower Stratosphere (UT/LS.

    Observations were obtained during four tropical campaigns performed from 1999 to 2006 with the research aircraft Geophysica and have been compared to the output of the ECHAM5/MESSy CCM. The model vertical resolution in the TTL (~500 m allows for appropriate comparison with high-resolution aircraft observations and the diagnostics used highlight common TTL features between the model and the observational data.

    The analysis of the vertical profiles of water vapour, ozone, and nitrous oxide, in both the observations and the model, shows that concentration mixing ratios exhibit a strong gradient change across the tropical tropopause, due to the role of this latter as a transport barrier and that transition between the tropospheric and stratospheric regimes occurs within a finite layer. The use of relative vertical ozone and carbon monoxide gradients, in addition to the vertical profiles, helps to highlight the region where this transition occurs and allows to give an estimate of its thickness. The analysis of the CO-O3 and H2O-O3 scatter plots and of the Probability Distribution Function (PDF of the H2O-O3 pair completes this picture as it allows to better distinguish tropospheric and stratospheric regimes that can be identified by their different chemical composition.

    The joint analysis and comparison of observed and modelled data allows to state that the model can represent the background TTL structure and its seasonal variability rather accurately. The model

  18. A comparison of ANSYS Fluent and STAR-CCM+ simulations for a tangent ogive slender body with a structured mesh at incompressible flow conditions

    Schoombie, Janine

    2017-10-01

    Full Text Available -CCM+ (1) • Why STAR-CCM+? – In 2017 only a STAR-CCM+ v11.06 commercial licence was available – Didn’t want to start from scratch – Test solver with identical mesh STEP 1: • Import Fluent .cas files - Imported as a volume mesh - No mesh continuum... stream_source_info Schoombie_19954_2017.pdf.txt stream_content_type text/plain stream_size 3069 Content-Encoding UTF-8 stream_name Schoombie_19954_2017.pdf.txt Content-Type text/plain; charset=UTF-8 A comparison of ANSYS...

  19. Nutrition and the science of disease prevention: a systems approach to support metabolic health

    Bennett, Brian J.; Hall, Kevin D.; Hu, Frank B.; McCartney, Anne L.; Roberto, Christina

    2017-01-01

    Progress in nutritional science, genetics, computer science, and behavioral economics can be leveraged to address the challenge of noncommunicable disease. This report highlights the connection between nutrition and the complex science of preventing disease and discusses the promotion of optimal metabolic health, building on input from several complementary disciplines. The discussion focuses on (1) the basic science of optimal metabolic health, including data from gene–diet interactions, microbiome, and epidemiological research in nutrition, with the goal of defining better targets and interventions, and (2) how nutrition, from pharma to lifestyle, can build on systems science to address complex issues. PMID:26415028

  20. Health benefits observed after probiotic Lactobacillus fermentum CCM 7421 application in dogs.

    Strompfová, Viola; Kubašová, Ivana; Lauková, Andrea

    2017-08-01

    The importance of the intestinal microbiota has attracted much interest in recent years particularly with respect to ways in which the microbiota can be manipulated in order to improve health. Improving gut health through the use of probiotic microorganisms has become an area of research activity in both human and animal nutrition. However, the amount of research using companion animals is insufficient. The present review evaluates and compares the effects achieved after application of canine-derived probiotic strain Lactobacillus fermentum CCM 7421 to healthy dogs as well as to dogs suffering from gastrointestinal disorders. The experiments involved varying duration of application (4 days-14 days), dosage (10 7 -10 9  CFU), form of application (fresh culture or lyophilized from) or combination with natural substances. Results from nine independent studies show the ability of probiotic strains to establish themselves in the canine gastrointestinal tract, alter the composition of intestinal microbiota and metabolites (organic acids), and modulate the physiology (serum biochemical parameters) and immunity parameters in dogs. Almost all observed effects were irrespective of dose or duration of probiotic administration.

  1. Biocompatibility of metal injection molded versus wrought ASTM F562 (MP35N) and ASTM F1537 (CCM) cobalt alloys.

    Chen, Hao; Sago, Alan; West, Shari; Farina, Jeff; Eckert, John; Broadley, Mark

    2011-01-01

    We present a comparative analysis between biocompatibility test results of wrought and Metal Injection Molded (MIM) ASTM F562-02 UNS R30035 (MP35N) and F1537 UNS R31538 (CCM) alloy samples that have undergone the same generic orthopedic implant's mechanical, chemical surface pre-treatment, and a designed pre-testing sample preparation method. Because the biocompatibility properties resulting from this new MIM cobalt alloy process are not well understood, we conducted tests to evaluate cytotoxicity (in vitro), hemolysis (in vitro), toxicity effects (in vivo), tissue irritation level (in vivo), and pyrogenicity count (in vitro) on such samples. We show that our developed MIM MP35N and CCM materials and treatment processes are biocompatible, and that both the MIM and wrought samples, although somewhat different in microstructure and surface, do not show significant differences in biocompatibility.

  2. Dynamic changes in energy metabolism upon embryonic stem cell differentiation support developmental toxicant identification

    Dartel, van D.A.M.; Schulpen, S.H.; Theunissen, P.T.; Bunschoten, A.; Piersma, A.H.; Keijer, J.

    2014-01-01

    Embryonic stem cells (ESC) are widely used to study embryonic development and to identify developmental toxicants. Particularly, the embryonic stem cell test (EST) is well known as in vitro model to identify developmental toxicants. Although it is clear that energy metabolism plays a crucial role in

  3. Immune-Challenged Fish Up-Regulate Their Metabolic Scope to Support Locomotion.

    Camille Bonneaud

    Full Text Available Energy-based trade-offs occur when investment in one fitness-related trait diverts energy away from other traits. The extent to which such trade-offs are shaped by limits on the rate of conversion of energy ingested in food (e.g. carbohydrates into chemical energy (ATP by oxidative metabolism rather than by the amount of food ingested in the first place is, however, unclear. Here we tested whether the ATP required for mounting an immune response will lead to a trade-off with ATP available for physical activity in mosquitofish (Gambusia holbrooki. To this end, we challenged fish either with lipopolysaccharide (LPS from E. coli or with Sheep Red Blood Cells (SRBC, and measured oxygen consumption at rest and during swimming at maximum speed 24h, 48h and 7 days post-challenge in order to estimate metabolic rates. Relative to saline-injected controls, only LPS-injected fish showed a significantly greater resting metabolic rate two days post-challenge and significantly higher maximal metabolic rates two and seven days post-challenge. This resulted in a significantly greater metabolic scope two days post-challenge, with LPS-fish transiently overcompensating by increasing maximal ATP production more than would be required for swimming in the absence of an immune challenge. LPS-challenged fish therefore increased their production of ATP to compensate physiologically for the energetic requirements of immune functioning. This response would avoid ATP shortages and allow fish to engage in an aerobically-challenging activity (swimming even when simultaneously mounting an immune response. Nevertheless, relative to controls, both LPS- and SRBC-fish displayed reduced body mass gain one week post-injection, and LPS-fish actually lost mass. The concomitant increase in metabolic scope and reduced body mass gain of LPS-challenged fish indicates that immune-associated trade-offs are not likely to be shaped by limited oxidative metabolic capacities, but may instead

  4. Laboratory Evaluation of Isaria fumosorosea CCM 8367 and Steinernema feltiae Ustinov against Immature Stages of the Colorado Potato Beetle

    Hussein, Hany M.; Skoková Habuštová, Oxana; Půža, Vladimír; Zemek, Rostislav

    2016-01-01

    The Colorado potato beetle, Leptinotarsa decemlineata, has developed resistance to most registered pesticides and has become one of the most difficult insect pests to control. Development of new biopesticides targeting this pest might solve the resistance problem and contribute to sustainable crop production. Laboratory experiments were conducted to assess the efficacy of Isaria fumosorosea (syn. Paecilomyces fumosoroseus) strain CCM 8367 against L. decemlineata when applied alone or combined with the entomopathogenic nematode Steinernema feltiae. The last-instar larvae of the Colorado potato beetle showed the highest susceptibility to I. fumosorosea followed by pre-pupae and pupae. The median lethal concentration (LC50) was estimated to be 1.03×106 blastospores/ml. The strain CCM 8367 was more virulent, causing 92.6% mortality of larvae (LT50 = 5.0 days) compared to the reference strain Apopka 97, which caused 54.5% mortality (LT50 = 7.0 days). The combined application of the fungus with the nematodes increased the mortality up to 98.0%. The best results were obtained when S. feltiae was applied simultaneously with I. fumosorosea (LT50 = 2.0 days); later application negatively affected both the penetration rate and the development of the nematodes. We can conclude that the strain CCM 8367 of I. fumosorosea is a prospective biocontrol agent against immature stages of L. decemlineata. For higher efficacy, application together with an entomopathogenic nematode is recommended. PMID:27015633

  5. Laboratory Evaluation of Isaria fumosorosea CCM 8367 and Steinernema feltiae Ustinov against Immature Stages of the Colorado Potato Beetle.

    Hany M Hussein

    Full Text Available The Colorado potato beetle, Leptinotarsa decemlineata, has developed resistance to most registered pesticides and has become one of the most difficult insect pests to control. Development of new biopesticides targeting this pest might solve the resistance problem and contribute to sustainable crop production. Laboratory experiments were conducted to assess the efficacy of Isaria fumosorosea (syn. Paecilomyces fumosoroseus strain CCM 8367 against L. decemlineata when applied alone or combined with the entomopathogenic nematode Steinernema feltiae. The last-instar larvae of the Colorado potato beetle showed the highest susceptibility to I. fumosorosea followed by pre-pupae and pupae. The median lethal concentration (LC50 was estimated to be 1.03×106 blastospores/ml. The strain CCM 8367 was more virulent, causing 92.6% mortality of larvae (LT50 = 5.0 days compared to the reference strain Apopka 97, which caused 54.5% mortality (LT50 = 7.0 days. The combined application of the fungus with the nematodes increased the mortality up to 98.0%. The best results were obtained when S. feltiae was applied simultaneously with I. fumosorosea (LT50 = 2.0 days; later application negatively affected both the penetration rate and the development of the nematodes. We can conclude that the strain CCM 8367 of I. fumosorosea is a prospective biocontrol agent against immature stages of L. decemlineata. For higher efficacy, application together with an entomopathogenic nematode is recommended.

  6. Effectiveness of using pure copper and silver coupon corrosivity monitoring (CCM) metal strips to measure the severity levels of air pollutants in indoor and outdoor atmospheres

    Foax, LJ

    2008-10-01

    Full Text Available Severity levels of air pollutants rich in oxides, chlorides and sulphides were successfully measured in indoor and outdoor atmospheres using pure copper and silver coupon corrosivity monitoring (CCM) metal strips when the maximum exposure periods...

  7. In situ dynamics of O2, pH and cyanobacterial transcripts associated with CCM, photosynthesis and detoxification of ROS

    Jensen, Sheila I; Steunou, Anne-Soisig; Bhaya, Devaki

    2011-01-01

    The relative abundance of transcripts encoding proteins involved in inorganic carbon concentrating mechanisms (CCM), detoxification of reactive oxygen species (ROS) and photosynthesis in the thermophilic cyanobacterium Synechococcus OS-B' was measured in hot spring microbial mats over two diel...

  8. Contribution of family social support to the metabolic control of people with diabetes mellitus: A randomized controlled clinical trial.

    Gomes, Lilian Cristiane; Coelho, Anna Claudia Martins; Gomides, Danielle Dos Santos; Foss-Freitas, Maria Cristina; Foss, Milton César; Pace, Ana Emilia

    2017-08-01

    This randomized controlled clinical trial aimed to evaluate the contribution of family social support to the clinical/metabolic control of people with type 2 diabetes mellitus. Diabetes mellitus is a chronic disease that requires continuous care in order for individuals to reach glycemic control, the primordial goal of treatment. Family social support is essential to the development of care skills and their maintenance. However, there are few studies that investigate the contribution of family social support to diabetes control. The study was developed between June 2011 and May 2013, and included 164 people who were randomized using simple randomization. The intervention group differed from the control group in that it included a family caregiver, who was recognized by the patient as a source of social support. The educational interventions received by people with diabetes mellitus were used as the basis of the education provided through telephone calls to patients' family members and caregivers, and their purpose was to encourage dialogue between the patients and their relatives about the topics related to diabetes. Regarding the clinical impact, the results showed that there was a greater reduction in blood pressure and glycated hemoglobin in the intervention group than in the control group, showing a positive effect on the control of the disease. Families should be incorporated into the care of people with diabetes mellitus and especially in health care programs, in particular those that can promote different forms of social support to strengthen the bond between family members. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Optimization of analysis best-estimate of a fuel element BWR with Code STAR-CCM+; Optimizacion del analisis best-estimate de un elemento combustible BWR con el codigo STAR-CCM+

    Morgado Canada, E.; Concejal Barmejo, A.; Jimenez Varas, G.; Solar Martinez, A.

    2014-07-01

    The objective of the project is the evaluation of the code STAR-CCM +, as well as the establishment of guidelines and standardized procedures for the discretization of the area of study and the selection of physical models suitable for the simulation of BWR fuel. For this purpose several of BFBT experiments have simulated [1] provide a data base for the development of experiments for measuring distribution of fractions of holes to changes in power in order to find the most appropriate models for the simulation of the problem. (Author)

  10. Human breath analysis may support the existence of individual metabolic phenotypes.

    Pablo Martinez-Lozano Sinues

    Full Text Available The metabolic phenotype varies widely due to external factors such as diet and gut microbiome composition, among others. Despite these temporal fluctuations, urine metabolite profiling studies have suggested that there are highly individual phenotypes that persist over extended periods of time. This hypothesis was tested by analyzing the exhaled breath of a group of subjects during nine days by mass spectrometry. Consistent with previous metabolomic studies based on urine, we conclude that individual signatures of breath composition exist. The confirmation of the existence of stable and specific breathprints may contribute to strengthen the inclusion of breath as a biofluid of choice in metabolomic studies. In addition, the fact that the method is rapid and totally non-invasive, yet individualized profiles can be tracked, makes it an appealing approach.

  11. Demand generation and social mobilisation for integrated community case management (iCCM) and child health: Lessons learned from successful programmes in Niger and Mozambique.

    Sharkey, Alyssa B; Martin, Sandrine; Cerveau, Teresa; Wetzler, Erica; Berzal, Rocio

    2014-12-01

    We present the approaches used in and outcomes resulting from integrated community case management (iCCM) programmes in Niger and Mozambique with a strong focus on demand generation and social mobilisation. We use a case study approach to describe the programme and contextual elements of the Niger and Mozambique programmes. Awareness and utilisation of iCCM services and key family practices increased following the implementation of the Niger and Mozambique iCCM and child survival programmes, as did care-seeking within 24 hours and care-seeking from appropriate, trained providers in Mozambique. These approaches incorporated interpersonal communication activities and community empowerment/participation for collective change, partnerships and networks among key stakeholder groups within communities, media campaigns and advocacy efforts with local and national leaders. iCCM programmes that train and equip community health workers and successfully engage and empower community members to adopt new behaviours, have appropriate expectations and to trust community health workers' ability to assess and treat illnesses can lead to improved care-seeking and utilisation, and community ownership for iCCM.

  12. Demand generation and social mobilisation for integrated community case management (iCCM and child health: Lessons learned from successful programmes in Niger and Mozambique

    Alyssa B Sharkey

    2014-11-01

    Full Text Available We present the approaches used in and outcomes resulting from integrated community case management (iCCM programmes in Niger and Mozambique with a strong focus on demand generation and social mobilisation. We use a case study approach to describe the programme and contextual elements of the Niger and Mozambique programmes. Awareness and utilisation of iCCM services and key family practices increased following the implementation of the Niger and Mozambique iCCM and child survival programmes, as did care–seeking within 24 hours and care–seeking from appropriate, trained providers in Mozambique. These approaches incorporated interpersonal communication activities and community empowerment/participation for collective change, partnerships and networks among key stakeholder groups within communities, media campaigns and advocacy efforts with local and national leaders. iCCM programmes that train and equip community health workers and successfully engage and empower community members to adopt new behaviours, have appropriate expectations and to trust community health workers’ ability to assess and treat illnesses can lead to improved care–seeking and utilisation, and community ownership for iCCM.

  13. Pantothenate kinase 1 is required to support the metabolic transition from the fed to the fasted state.

    Roberta Leonardi

    2010-06-01

    Full Text Available Coenzyme A (CoA biosynthesis is regulated by the pantothenate kinases (PanK, of which there are four active isoforms. The PanK1 isoform is selectively expressed in liver and accounted for 40% of the total PanK activity in this organ. CoA synthesis was limited using a Pank1(-/- knockout mouse model to determine whether the regulation of CoA levels was critical to liver function. The elimination of PanK1 reduced hepatic CoA levels, and fasting triggered a substantial increase in total hepatic CoA in both Pank1(-/- and wild-type mice. The increase in hepatic CoA during fasting was blunted in the Pank1(-/- mouse, and resulted in reduced fatty acid oxidation as evidenced by abnormally high accumulation of long-chain acyl-CoAs, acyl-carnitines, and triglycerides in the form of lipid droplets. The Pank1(-/- mice became hypoglycemic during a fast due to impaired gluconeogenesis, although ketogenesis was normal. These data illustrate the importance of PanK1 and elevated liver CoA levels during fasting to support the metabolic transition from glucose utilization and fatty acid synthesis to gluconeogenesis and fatty acid oxidation. The findings also suggest that PanK1 may be a suitable target for therapeutic intervention in metabolic disorders that feature hyperglycemia and hypertriglyceridemia.

  14. Persuasive user experiences of a health Behavior Change Support System: A 12-month study for prevention of metabolic syndrome.

    Karppinen, Pasi; Oinas-Kukkonen, Harri; Alahäivälä, Tuomas; Jokelainen, Terhi; Keränen, Anna-Maria; Salonurmi, Tuire; Savolainen, Markku

    2016-12-01

    Obesity has become a severe health problem in the world. Even a moderate 5% weight loss can significantly reduce the prevalence of metabolic syndrome, which can be vital for preventing comorbidities caused by the obesity. Health Behavior Change Support Systems (hBCSS) emphasize an autogenous approach, where an individual uses the system to influence one's own attitude or behavior to achieve his or her own goal. Regardless of promising results, such health interventions technology has often been considered merely as a tool for delivering content that has no effect or value of its own. More research on actual system features is required. The objective of this study is to describe how users perceive persuasive software features designed and implemented into a support system. The research medium in this study is a web-based information system designed as a lifestyle intervention for participants who are at risk of developing a metabolic syndrome or who are already suffering from it. The system was designed closely following the principles of the Persuasive Systems Design (PSD) model and the Behavior Change Support Systems (BCSS) framework. A total of 43 system users were interviewed for this study during and after a 52 week intervention period. In addition, the system's login data and subjects' Body Mass Index (BMI) measures were used to interpret the results. This study explains in detail how the users perceived using the system and its persuasive features. Self-monitoring, reminders, and tunneling were perceived as especially beneficial persuasive features. The need for social support appeared to grow along the duration of the intervention. Unobtrusiveness was found to be very important in all stages of the intervention rather than only at the beginning. Persuasive software features have power to affect individuals' health behaviors. Through their systematicity the PSD model and the BCSS framework provide effective support for the design and development of

  15. SulfoSYS (Sulfolobus Systems Biology): towards a silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation

    Albers, S.V.; Birkeland, N.K.; Driessen, A.J.M.; Gertig, S.; Haferkamp, P.; Klenk, H.P.; Kouril, T.; Manica, A.; Pham, T.K.; Ruoff, P.; Schleper, C.; Schomburg, D.; Sharkey, K.; Siebers, B.; Sierocinski, P.; Steur, R.; Oost, van der J.; Westerhoff, H.V.; Wieloch, P.; Wright, P.C.; Zaparty, M.

    2009-01-01

    SulfoSYS (Sulfolobus Systems Biology) focuses on the study of the CCM (central carbohydrate metabolism) of Sulfolobus solfataricus and its regulation under temperature variation at the systems level. In Archaea, carbohydrates are metabolized by modifications of the classical pathways known from

  16. Sulfosys (Sulfolobus Systems Biology): towards a silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation.

    Albers, S.V.; Birkeland, N.K.; Driessen, A.J.; Gertig, S.; Haferkamp, P.; Klenk, H.P.; Kouril, T.; Manica, A.; Pham, T.K.; Ruoff, P.; Schleper, C.; Schomburg, D.; Sharkey, K.J.; Siebers, B.; Sierocinski, P.; Steuer, R.; van der Oost, J.; Westerhoff, H.V.; Wieloch, P.; Wright, P.C.; Zaparty, M.

    2009-01-01

    SulfoSYS (Sulfolobus Systems Biology) focuses on the study of the CCM (central carbohydrate metabolism) of Sulfolobus solfataricus and its regulation under temperature variation at the systems level. In Archaea, carbohydrates are metabolized by modifications of the classical pathways known from

  17. SulfoSYS (Sulfolobus Systems Biology) : towards a silicon cell model for the central carbohydrate metabolism of the archaeon Sulfolobus solfataricus under temperature variation

    Albers, Sonja-Verena; Birkeland, Nils-Kare; Driessen, Arnold J. M.; Gertig, Susanne; Haferkamp, Patrick; Klenk, Hans-Peter; Kouril, Theresa; Manica, Andrea; Pham, Trong K.; Ruoff, Peter; Schleper, Christa; Schomburg, Dietmar; Sharkey, Kieran J.; Siebers, Bettina; Sierocinski, Pawel; Steuer, Ralf; van der Oost, John; Westerhoff, Hans V.; Wieloch, Patricia; Wright, Phillip C.; Zaparty, Melanie; Birkeland, Nils-Kåre

    SulfoSYS (Sulfolobus Systems Biology) focuses on the study of the CCM (central carbohydrate metabolism) of Sulfolobus solfataricus and its regulation under temperature variation at the systems level. in Archaea, carbohydrates are metabolized by modifications of the classical pathways known from

  18. The incidences of oxidative –stress occurrence following two metabolic support measures in critically ill patients

    Mojtaba Mojtahedzadeh

    2013-02-01

    Full Text Available Background: A high percentage of patients admitted to the intensive care unit (ICU have systemic inflammatory response syndrome (SIRS criteria. Free radicals play an important role in initiation and development of SIRS. The purpose of this study was to assess and compare the molecular changes of cellular antioxidant power in patients with SIRS who received enteral nutrition (EN or EN combined with parenteral nutrition (PN. Methods: Two groups of 10 patients were enrolled in this randomized, controlled clinical trial. Those in the treatment group received EN+PN and the control group received only EN. Venous blood samples were taken just prior to initiation of nutritional support and then 24, 48 and 72 hours following entry into the study for examination of antioxidant parameters including total thiol, total antioxidant capacity and lipid peroxidation. Results: The two supportive regimens had different affects on total antioxidant capacity (P=0.005. In the EN group the amount of total antioxidant capacity was not significantly different in different days (P>0.05, but in the EN+PN group it was significantly different on third and forth days as compared to the first day. The two other parameters had no significant differences between the two groups. Conclusion: These results are suggesting that an increase in oxidative stress bio-markers are not necessarily related to the route of pharmaconutrition and may occur independently during metabolic support measures. Keywords: Parenteral Nutrition, Enteral Nitrition, Systemic Inflammatory Response Syndrome, Oxidative stress

  19. Supportive Management of Mucositis and Metabolic Derangements in Head and Neck Cancer Patients

    Bonomi, Marcelo; Batt, Katharine

    2015-01-01

    Oral mucositis (OM) is among the most undesirable, painful, and expensive toxicities of cytotoxic cancer therapy, and is disheartening for patients and frustrating for caregivers. Accurate assessment of the incidence of OM has been elusive, but accumulating data suggests that reported OM frequency is significantly less than its actual occurrence. It has been suggested that over 90% of head and neck cancer (HNC) patients receiving radiotherapy (RT) with concurrent cisplatin experience severe OM with symptoms of extreme pain, mucosal ulceration and consequent limitations in swallowing and achieving adequate nutritional intake. This panoply of symptoms inevitably impacts a patients’ quality of life and their willingness to continue treatment. In spite of all the advances made in understanding the pathophysiology of OM, there is still no prophylactic therapy with proven efficacy. Strategies to limit the extent of OM and to manage its symptomatology include basic oral care, supportive medications, nutritional support and targeting aggressive treatments to high-risk patients. This review focuses on OM recognition, preventive measurements, and symptom-management strategies

  20. Supportive Management of Mucositis and Metabolic Derangements in Head and Neck Cancer Patients

    Bonomi, Marcelo, E-mail: mbonomi@wakehealth.edu; Batt, Katharine [Section of Hematology and Medical Oncology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 (United States)

    2015-09-03

    Oral mucositis (OM) is among the most undesirable, painful, and expensive toxicities of cytotoxic cancer therapy, and is disheartening for patients and frustrating for caregivers. Accurate assessment of the incidence of OM has been elusive, but accumulating data suggests that reported OM frequency is significantly less than its actual occurrence. It has been suggested that over 90% of head and neck cancer (HNC) patients receiving radiotherapy (RT) with concurrent cisplatin experience severe OM with symptoms of extreme pain, mucosal ulceration and consequent limitations in swallowing and achieving adequate nutritional intake. This panoply of symptoms inevitably impacts a patients’ quality of life and their willingness to continue treatment. In spite of all the advances made in understanding the pathophysiology of OM, there is still no prophylactic therapy with proven efficacy. Strategies to limit the extent of OM and to manage its symptomatology include basic oral care, supportive medications, nutritional support and targeting aggressive treatments to high-risk patients. This review focuses on OM recognition, preventive measurements, and symptom-management strategies.

  1. Low Earth orbit journey and ground simulations studies point out metabolic changes in the ESA life support organism Rhodospirillum rubrum

    Mastroleo, Felice; Leys, Natalie; Benotmane, Rafi; Vanhavere, Filip; Janssen, Ann; Hendrickx, Larissa; Wattiez, Ruddy; Mergeay, Max

    MELiSSA (Micro-Ecological Life Support System Alternative) is a project of closed regenerative life support system for future space flights developed by the European Space Agency. It consists of interconnected processes (i.e. bioreactors, higher plant compartments, filtration units,..) targeting the total recycling of organic waste into oxygen, water and food. Within the MELiSSA loop, the purple non-sulfur alpha-proteobacterium R. rubrum ATCC25903 is used to convert fatty acids released from the upstream raw waste digesting reactor to CO2 and biomass, and to complete the mineralization of aminoacids into NH4+ that will be forwarded to the nitrifying compartment. Among the numerous challenges of the project, the functional stability of the bioreactors in long term and under space flight conditions is of paramount importance for the efficiency of the life support system and consequently the crew safety. Therefore, the physiological and metabolic changes induced by space flight were investigated for R. rubrum. The bacterium grown on solid medium during 2 different 10-day space flights to the ISS (MES- SAGE2, BASE-A experiments) were compared to cells grown on Earth 1 g gravity or modeled microgravity and normal Earth radiation or simulated space flight radiation conditions in order to relate each single stress to its respective cellular response. For simulating the radiation environment, pure gamma and neutron sources were combined, while simulation of changes in gravity where performed using the Random Positioning Machine technology. Transcriptome analysis using R. rubrum total genome DNA-chip showed up-regulation of genes involved in oxidative stress response after a 10-day mission inside the ISS, without loss of viability. As an example, alkyl hydroperoxide reductase, thioredoxin reductase and bacterioferritin genes are least 2 fold induced although the radiation dose experienced by the bacterium (4 mSv) is very low compared to its radiotolerance (D10 = 100 Sv

  2. Beneficiary effect of Commiphora mukul ethanolic extract against high fructose diet induced abnormalities in carbohydrate and lipid metabolism in wistar rats

    Ramesh Bellamkonda

    2018-01-01

    Full Text Available The present study was proposed to elucidate the effect of Commiphora mukul gum resin elthanolic extract treatment on alterations in carbohydrate and lipid metabolisms in rats fed with high-fructose diet. Male Wistar rats were divided into four groups: two of these groups (group C and C+CM were fed with standard pellet diet and the other two groups (group F and F+CM were fed with high fructose (66 % diet. C. mukul suspension in 5% Tween-80 in distilled water (200 mg/kg body weight/day was administered orally to group C+CM and group F+CM. At the end of 60-day experimental period, biochemical parameters related to carbohydrate and lipid metabolisms were assayed. C. mukul treatment completely prevented the fructose-induced increased body weight, hyperglycemia, and hypertriglyceridemia. Hyperinsulinemia and insulin resistance observed in group F decreased significantly with C. mukul treatment in group F+CM. The alterations observed in the activities of enzymes of carbohydrate and lipid metabolisms and contents of hepatic tissue lipids in group F rats were significantly restored to near normal values by C. mukul treatment in group F+CM. In conclusion, our study demonstrated that C. mukul treatment is effective in preventing fructose-induced insulin resistance and hypertriglyceridemia while attenuating the fructose induced alterations in carbohydrate and lipid metabolisms by the extract which was further supported by histopathological results from liver samples which showed regeneration of the hepatocytes. This study suggests that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it.

  3. Biodistribution of 99mTc labelled anti TAG 72 chimeric McAb ccM4 in nude mice and preliminary clinical study

    Ma Qingjie; Zhao Jie; Zhang Yingnan; Gao Fengtong; Liu Shuqing

    1995-01-01

    Chimeric McAb ccM 4 was labelled with 99m Tc by direct method. The antibody was reduced by molar excess 2-mercaptoethanol (2-ME; Ab, 1000:1). The reduced ccM 4 chimeric McAb was mixed with 99m Tc reduced by SnCl 2 and 99m Tc labelling efficiency was 98%. The immunoreactivity did not change after labelling. The biodistribution of 99m Tc-ccM 4 was performed in nude mice and patients with stomach carcinoma. There was significantly more radioactivity in tumor than in the rest of the body in nude mice. Radioimmunoimaging of ccM 4 in 10 patients of gastric cancer was also presented

  4. Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

    Fero Matthew

    2011-10-01

    Full Text Available Abstract Background The response of mammalian glial cells to chronic degeneration and trauma is hypothesized to be incompatible with support of neuronal function in the central nervous system (CNS and retina. To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (p27 or Cdkn1b in the adult mouse and determined the outcome on retinal structure and function. Results p27-deficient Müller glia reentered the cell cycle, underwent aberrant migration, and enhanced their expression of intermediate filament proteins, all of which are characteristics of Müller glia in a reactive state. Surprisingly, neuroglial interactions, retinal electrophysiology, and visual acuity were normal. Conclusion The benign outcome of proliferative reactive Müller gliosis suggests that reactive glia display context-dependent, graded and dynamic phenotypes and that reactivity in itself is not necessarily detrimental to neuronal function.

  5. Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.

    Nengyi Zhang

    2010-04-01

    Full Text Available Central carbon metabolism (CCM is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays, the most diverse model crop species, to study the genetics of CCM is a particularly attractive system.We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 1.1.1.41, in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis, the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication.Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites.

  6. Pressurized Martian-Like Pure CO2 Atmosphere Supports Strong Growth of Cyanobacteria, and Causes Significant Changes in their Metabolism

    Murukesan, Gayathri; Leino, Hannu; Mäenpää, Pirkko; Ståhle, Kurt; Raksajit, Wuttinun; Lehto, Harry J.; Allahverdiyeva-Rinne, Yagut; Lehto, Kirsi

    2016-03-01

    Surviving of crews during future missions to Mars will depend on reliable and adequate supplies of essential life support materials, i.e. oxygen, food, clean water, and fuel. The most economical and sustainable (and in long term, the only viable) way to provide these supplies on Martian bases is via bio-regenerative systems, by using local resources to drive oxygenic photosynthesis. Selected cyanobacteria, grown in adequately protective containment could serve as pioneer species to produce life sustaining substrates for higher organisms. The very high (95.3 %) CO2 content in Martian atmosphere would provide an abundant carbon source for photo-assimilation, but nitrogen would be a strongly limiting substrate for bio-assimilation in this environment, and would need to be supplemented by nitrogen fertilizing. The very high supply of carbon, with rate-limiting supply of nitrogen strongly affects the growth and the metabolic pathways of the photosynthetic organisms. Here we show that modified, Martian-like atmospheric composition (nearly 100 % CO2) under various low pressure conditions (starting from 50 mbar to maintain liquid water, up to 200 mbars) supports strong cellular growth. Under high CO2 / low N2 ratio the filamentous cyanobacteria produce significant amount of H2 during light due to differentiation of high amount of heterocysts.

  7. Dynamic metabolism modelling of urban water services--demonstrating effectiveness as a decision-support tool for Oslo, Norway.

    Venkatesh, G; Sægrov, Sveinung; Brattebø, Helge

    2014-09-15

    Urban water services are challenged from many perspectives and different stakeholders demand performance improvements along economic, social and environmental dimensions of sustainability. In response, urban water utilities systematically give more attention to criteria such as water safety, climate change adaptation and mitigation, environmental life cycle assessment (LCA), total cost efficiency, and on how to improve their operations within the water-energy-carbon nexus. The authors of this paper collaborated in the development of a 'Dynamic Metabolism Model' (DMM). The model is developed for generic use in the sustainability assessment of urban water services, and it has been initially tested for the city of Oslo, Norway. The purpose has been to adopt a holistic systemic perspective to the analysis of metabolism and environmental impacts of resource flows in urban water and wastewater systems, in order to offer a tool for the examination of future strategies and intervention options in such systems. This paper describes the model and its application to the city of Oslo for the analysis time period 2013-2040. The external factors impacting decision-making and interventions are introduced along with realistic scenarios developed for the testing, after consultation with officials at the Oslo Water and Wastewater Works (Norway). Possible interventions that the utility intends to set in motion are defined and numerically interpreted for incorporation into the model, and changes in the indicator values over the time period are determined. This paper aims to demonstrate the effectiveness and usefulness of the DMM, as a decision-support tool for water-wastewater utilities. The scenarios considered and interventions identified do not include all possible scenarios and interventions that can be relevant for water-wastewater utilities. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Uncertainties in modelling Mt. Pinatubo eruption with 2-D AER model and CCM SOCOL

    Kenzelmann, P.; Weisenstein, D.; Peter, T.; Luo, B. P.; Rozanov, E.; Fueglistaler, S.; Thomason, L. W.

    2009-04-01

    measurements and from AER model calculation serve as input for the 3D chemistry climate model (CCM) SOCOL [Schraner et al., 2008]. The heating rates, calculated with SOCOL, are compared with a reference radiative transfer model LibRadtran [Mayer and Kylling, 2005]. This comparison suggests that SOCOL underestimates the net heating rate by 10-20%. In stark contrast, the temperature increase in the lower stratosphere due to absorption of longwave and near infrared radiation is overestimated by all SOCOL scenarios. This lets us conclude that SOCOL, and similarly other state-of-the-art CCMs, misrepresent processes required to model the effect of volcanic eruptions on the lower stratosphere and tropopause region. Possible reasons for model deficiencies could be too coarse vertical resolution or missing dynamical feedbacks near the tropopause and in the lower stratosphere. Another important feature is the warming of the tropical troposphere, which is present in the model simulation but was not observed with comparable amplitude in reality. The heating of the lower stratosphere in the models leads to an increase of stratospheric water vapour and influences the radiative and chemical properties of the stratosphere. Eyring, V. et al (2006), Assessment of temperature, trace species, and ozone in chemistry-climate model simulations of the recent past, Journal of Geophysical Research-Atmospheres, 111, D22,308. Guo, S., G. J. S. Bluth, W. I. Rose, I. M. Watson, and A. J. Prata (2004), Re-evaluation of SO2 release of the 15 June 1991 Pinatubo eruption using ultraviolet and infrared satellite sensors, Geochemistry Geophysics Geosystems, 5. Mayer, B., and A. Kylling (2005), Technical note: The libRadtran software package for radiative transfer calculations - description and examples of use, Atmos. Chem. Phys, 5, 1855-1877. McCormick, M. P. (1992), Initial assessment of the stratospheric and climatic impact of the 1991 Mount- Pinatubo eruption - prologue, Geophysical Research Letters, 19 (2

  9. CCM Continuity Constraint Method: A finite-element computational fluid dynamics algorithm for incompressible Navier-Stokes fluid flows

    Williams, P. T. [Univ. of Tennessee, Knoxville, TN (United States)

    1993-09-01

    As the field of computational fluid dynamics (CFD) continues to mature, algorithms are required to exploit the most recent advances in approximation theory, numerical mathematics, computing architectures, and hardware. Meeting this requirement is particularly challenging in incompressible fluid mechanics, where primitive-variable CFD formulations that are robust, while also accurate and efficient in three dimensions, remain an elusive goal. This dissertation asserts that one key to accomplishing this goal is recognition of the dual role assumed by the pressure, i.e., a mechanism for instantaneously enforcing conservation of mass and a force in the mechanical balance law for conservation of momentum. Proving this assertion has motivated the development of a new, primitive-variable, incompressible, CFD algorithm called the Continuity Constraint Method (CCM). The theoretical basis for the CCM consists of a finite-element spatial semi-discretization of a Galerkin weak statement, equal-order interpolation for all state-variables, a 0-implicit time-integration scheme, and a quasi-Newton iterative procedure extended by a Taylor Weak Statement (TWS) formulation for dispersion error control. Original contributions to algorithmic theory include: (a) formulation of the unsteady evolution of the divergence error, (b) investigation of the role of non-smoothness in the discretized continuity-constraint function, (c) development of a uniformly H1 Galerkin weak statement for the Reynolds-averaged Navier-Stokes pressure Poisson equation, (d) derivation of physically and numerically well-posed boundary conditions, and (e) investigation of sparse data structures and iterative methods for solving the matrix algebra statements generated by the algorithm.

  10. Preliminary evidences of CCM operation and its down regulation in relation to increasing CO2 levels in natural phytoplankton assemblages from the coastal waters of Bay of Bengal

    Biswas, Haimanti; Rahman Shaik, Aziz Ur; Bandyopadhyay, Debasmita

    2014-05-01

    Bay of Bengal (BoB), a low productive part of the North Indian Ocean, often possesses low CO2 levels in its surface water and diatoms dominate the phytoplankton communities. Virtually no studies are available from this area reporting how this diatom dominated phytoplankton community would respond any increase in dissolved CO2 levels either naturally or anthopogenically. In most of the marine phytoplankton, the inefficiency of the sole carbon fixing enzyme Rubisco necessitates the need of concentrating dissolved inorganic carbon (DIC) (mostly as HCO3) inside the cell in excess of the ambient water concentrations in order to maintain high rate of photosynthesis under low CO2 levels through an energy consuming carbon concentration mechanisms (CCMs). The ubiquitous enzyme carbonic anhydrase (CA) plays a vital role in CCMs by converting HCO3- to CO2 and usually utilizes the trace metal zinc (Zn) as a cofactor. However, it is evident in many marine phytoplankton species that with increasing external CO2 levels, CCMs can be down-regulated leading to energetic savings which can be reallocated to growth; although exceptions occur. Hence, in order to predict their responses to the projected changes, it is imperative to understand their carbon metabolism patterns. We have conducted a series of incubation experiments in microcosms with natural phytoplankton communities from the coastal waters of BoB under different CO2 levels. Our results revealed that the rate of net photosynthetic oxygen evolution and biomass build-up increased in response to increasing CO2 levels. The depletion in δ13CPOM values were more in the high CO2 treatments relative to the low CO2 treated cells (control), indicating that dissolved CO2 uptake was higher when CO2 levels were increased. When additional Zn was added to the low CO2 treated cells, net photosynthetic oxygen evolution rate was increased significantly than that of the untreated control. It is likely that upon the supply of Zn under low CO2

  11. Evaluation of Acoustic Emission NDE of Composite Crew Module Service Module/Alternate Launch Abort System (CCM SM/ALAS) Test Article Failure Tests

    Horne, Michael R.; Madaras, Eric I.

    2010-01-01

    Failure tests of CCM SM/ALAS (Composite Crew Module Service Module / Alternate Launch Abort System) composite panels were conducted during July 10, 2008 and July 24, 2008 at Langley Research Center. This is a report of the analysis of the Acoustic Emission (AE) data collected during those tests.

  12. Spatial distribution and deployment of community-based distributors implementing integrated community case management (iCCM): Geographic information system (GIS) mapping study in three South Sudan states.

    Pratt, Abigail; Dale, Martin; Olivi, Elena; Miller, Jane

    2014-12-01

    In late 2012 and in conjunction with South Sudan's Ministry of Health - National Malaria Control Program, PSI (Population Services International) conducted a comprehensive mapping exercise to assess geographical coverage of its integrated community case management (iCCM) program and consider scope for expansion. The operational research was designed to provide evidence and support for low-cost mapping and monitoring systems, demonstrating the use of technology to enhance the quality of programming and to allow for the improved allocation of resources through appropriate and need-based deployment of community-based distributors (CBDs). The survey took place over the course of three months and program staff gathered GPS (global positioning system) data, along with demographic data, for over 1200 CBDs and 111 CBD supervisors operating in six counties in South Sudan. Data was collated, cleaned and quality assured, input into an Excel database, and subsequently uploaded to geographic information system (GIS) for spatial analysis and map production. The mapping results showed that over three-quarters of CBDs were deployed within a five kilometer radius of a health facility or another CBD, contrary to program planning and design. Other characteristics of the CBD and CBD supervisor profiles (age, gender, literacy) were more closely matched with other regional programs. The results of this mapping exercise provided a valuable insight into the contradictions found between a program "deployment plan" and the realities observed during field implementation. It also highlighted an important need for program implementers and national-level strategy makers to consider the natural and community-driven diffusion of CBDs, and take into consideration the strength of the local health facilities when developing a deployment plan.

  13. Setting global research priorities for integrated community case management (iCCM: Results from a CHNRI (Child Health and Nutrition Research Initiative exercise

    Kerri Wazny

    2014-11-01

    Full Text Available Aims: to systematically identify global research gaps and resource priorities for integrated community case management (iCCM. Methods: an iCCM Child Health and Nutrition Research Initiative (CHNRI Advisory Group, in collaboration with the Community Case Management Operational Research Group (CCM ORG identified experts to participate in a CHNRI research priority setting exercise. These experts generated and systematically ranked research questions for iCCM. Research questions were ranked using a “Research Priority Score” (RPS and the “Average Expert Agreement” (AEA was calculated for every question. Our groups of experts were comprised of both individuals working in Ministries of Health or Non Governmental Organizations (NGOs in low– and middle–income countries (LMICs and individuals working in high–income countries (HICs in academia or NGO headquarters. A Spearman's Rho was calculated to determine the correlation between the two groups' research questions' ranks. Results: The overall RPS ranged from 64.58 to 89.31, with a median score of 81.43. AEA scores ranged from 0.54 to 0.86. Research questions involving increasing the uptake of iCCM services, research questions concerning the motivation, retention, training and supervision of Community Health Workers (CHWs and concerning adding additional responsibilities including counselling for infant and young child feeding (IYCF and treatment of severe acute malnutrition (SAM ranked highly. There was weak to moderate, statistically significant, correlation between scores by representatives of high–income countries and those working in–country or regionally (Spearman's ρ = 0.35034, P < 0.01. Conclusions: Operational research to determine optimal training, supervision and modes of motivation and retention for the CHW is vital for improving iCCM, globally, as is research to motivate caregivers to take advantage of iCCM services. Experts working in–country or regionally in

  14. Kinetics, bioavailability, and metabolism of RRR-alpha-tocopherol in humans supports lower requirement for vitamin E

    Kinetic models enable nutrient needs and kinetic behaviors to be quantified and provide mechanistic insights into metabolism. Therefore, we modeled and quantified the kinetics, bioavailability and metabolism of RRR-alpha-tocopherol in 12 healthy adults. Six men and six women, aged 27 ± 6 y, each i...

  15. Genome Sequence of Rhodococcus erythropolis Strain CCM2595, a Phenol Derivative-Degrading Bacterium

    Strnad, Hynek; Pátek, Miroslav; Fousek, Jan; Szököl, Juraj; Ulbrich, P.; Nešvera, Jan; Pačes, Václav; Vlček, Čestmír

    2014-01-01

    Roč. 2, č. 2 (2014) ISSN 2169-8287 R&D Projects: GA ČR GA13-28283S; GA MŠk 2B08062 Institutional support: RVO:68378050 ; RVO:61388971 Keywords : Rhodococcus erythropolis * genome sequence Subject RIV: EB - Genetics ; Molecular Biology

  16. Chemical cleavage reactions of DNA on solid support: application in mutation detection

    Cotton Richard GH

    2003-05-01

    Full Text Available Abstract Background The conventional solution-phase Chemical Cleavage of Mismatch (CCM method is time-consuming, as the protocol requires purification of DNA after each reaction step. This paper describes a new version of CCM to overcome this problem by immobilizing DNA on silica solid supports. Results DNA test samples were loaded on to silica beads and the DNA bound to the solid supports underwent chemical modification reactions with KMnO4 (potassium permanganate and hydroxylamine in 3M TEAC (tetraethylammonium chloride solution. The resulting modified DNA was then simultaneously cleaved by piperidine and removed from the solid supports to afford DNA fragments without the requirement of DNA purification between reaction steps. Conclusions The new solid-phase version of CCM is a fast, cost-effective and sensitive method for detection of mismatches and mutations.

  17. A new version of the CNRM Chemistry-Climate Model, CNRM-CCM: description and improvements from the CCMVal-2 simulations

    M. Michou

    2011-10-01

    Full Text Available This paper presents a new version of the Météo-France CNRM Chemistry-Climate Model, so-called CNRM-CCM. It includes some fundamental changes from the previous version (CNRM-ACM which was extensively evaluated in the context of the CCMVal-2 validation activity. The most notable changes concern the radiative code of the GCM, and the inclusion of the detailed stratospheric chemistry of our Chemistry-Transport model MOCAGE on-line within the GCM. A 47-yr transient simulation (1960–2006 is the basis of our analysis. CNRM-CCM generates satisfactory dynamical and chemical fields in the stratosphere. Several shortcomings of CNRM-ACM simulations for CCMVal-2 that resulted from an erroneous representation of the impact of volcanic aerosols as well as from transport deficiencies have been eliminated.

    Remaining problems concern the upper stratosphere (5 to 1 hPa where temperatures are too high, and where there are biases in the NO2, N2O5 and O3 mixing ratios. In contrast, temperatures at the tropical tropopause are too cold. These issues are addressed through the implementation of a more accurate radiation scheme at short wavelengths. Despite these problems we show that this new CNRM CCM is a useful tool to study chemistry-climate applications.

  18. Comparison of the seasonal climate simulated by the pattern CCM3 and the data of the reanalysis NCEP/NCAR with the observed data of the temperature of the air and the precipitation in Colombia

    Leon Aristizabal, Gloria Esperanza; Zea Mazo, Jorge Anibal

    2001-01-01

    In this work we carry out a comparison of the simulations of the climatic model CCM3, the data of the NCEP/NCAR Reanalysis and real data, by the practical significance of the model based on the observed differences

  19. [Difficulties and concerns identified by Puerto Rican youth with insulin-dependent diabetes mellitus (IDDM): their relationship with metabolic control, hopelessness, social support, and depressive symptoms].

    Rosselló, Jeannette; Maysonet Guzmán, Marielisa

    2006-12-01

    Insulin-dependent diabetes mellitus (IDDM) is a chronic health condition that affects 18 of every 100,000 Puerto Rican youth. Few research studies have been performed on the problems that youth with diabetes encounter and how they are related to adherence to treatment and adequate metabolic control. Adequate metabolic control is associated with fewer short and long-term medical complications, as well as better quality of life. Adapting to the demands and stressors associated with IDDM and its treatment is a task that can prove to be difficult for youth with diabetes due to having to make adjustments, alterations, and following a prescribed regimen in their daily activities. The main purpose of this investigation was to explore difficulties and worries identified by Puerto Rican youth with IDDM. This study examined whether there is a relationship between difficulties and worries, and adequate metabolic control, hopelessness, social support and depressive symptomatology. One hundred and one youth with IDDM between the ages of 8 and 17 (45 male, 56 female) were evaluated. Analysis of frequencies, correlations, and comparison tests were performed by group (gender, age, diabetes duration, and metabolic control. Results reveal that some of the difficulties identified by Puerto Rican youth with IDDM were: not eating candy and/or cake, self-monitoring blood glucose at school, doing things on time, and waking up early. Among the worries they reported were: insulin reactions and thinking that they might have to go to the hospital.

  20. The logics of metabolic regulation in bacteria challenges biosensor-based metabolic engineering

    Matthieu Jules

    2017-12-01

    Full Text Available Synthetic Biology (SB aims at the rational design and engineering of novel biological functions and systems. By facilitating the engineering of living organisms, SB promises to facilitate the development of many new applications for health, biomanufacturing, and the environment. Over the last decade, SB promoted the construction of libraries of components enabling the fine-tuning of genetic circuits expression and the development of novel genome engineering methodologies for many organisms of interest. SB thus opened new perspectives in the field of metabolic engineering, which was until then mainly limited to (overproducing naturally synthesized metabolic compounds. To engineer efficient cell factories, it is key to precisely reroute cellular resources from the central carbon metabolism (CCM to the synthetic circuitry. This task is however difficult as there is still significant lack of knowledge regarding both the function of several metabolic components and the regulation of the CCM fluxes for many industrially important bacteria. Pyruvate is a pivotal metabolite at the heart of the CCM and a key precursor for the synthesis of several commodity compounds and fine chemicals. Numerous bacterial species can also use it as a carbon source when present in the environment but bacterial, pyruvate-specific uptake systems were to be discovered. This is an issue for metabolic engineering as one can imagine to make use of pyruvate transport systems to replenish synthetic metabolic pathways towards the synthesis of chemicals of interest. Here we describe a recent study (MBio 8(5: e00976-17, which identified and characterized a pyruvate transport system in the Gram-positive (G+ve bacterium Bacillus subtilis, a well-established biotechnological workhorse for the production of enzymes, fine chemicals and antibiotics. This study also revealed that the activity of the two-component system (TCS responsible for its induction is retro-inhibited by the level of

  1. Reduction of statistic scale applied to data of the CCM3 to generate data of temperature of the air in surface

    Molina Lizcano Alicia; Bernal Suarez, Nestor Ricardo; Martinez Collantes, Jorge; Pabon Jose Daniel; Vega Rodriguez, Emel

    2000-01-01

    The technique is applied of statistical down scaling to find the relations between the variables simulated by a Climate Community Model, in its third version (CCM3) available on the closest grid points near three stations in the Guajira region in north-eastern Colombia, and the surface temperature at those stations. As training (or calibrating)period we chose the years from 1969 to 1990, while the phase of assessment was from 1991 to 1998. The method used was the canonical correlation analysis (CCA) The results were good insofar as the relations obtained approximate satisfactorily the real behaviour of the surface air temperature at the three stations

  2. Supplement to CCM.D-K4 'Hydrometer' report: linkage of EURAMET.M.D-K4 comparison, SIM.M.D-K4 comparison and the supplementary SIM.M.D-S2 to CCM.D-K4 'Hydrometer'

    Lorefice, S.; Becerra, L. O.

    2017-01-01

    Evaluation of different types of comparisons to a common set of reference values of a CIPM key comparison is essential to satisfy the concept of the CIPM Mutual Recognition Arrangement (CIPM MRA), where the DoEs of any participant who took part in comparisons should be within the Calibration and Measurement Capability (CMC) section of the CIPM MRA Key Comparison Data Base. The subject of this supplementary report is therefore to present the equivalence of each National Metrological Institute (NMI) participant in the CCM.D-K4 'Hydrometer' key comparison, which was performed in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20 °C, and the linkage of the European and Inter-American NMI results performed in the RMO.M.D-K4 comparisons as well as those of the supplementary SIM.M.D-S2 to the common set of KCRVs of the CCM.D-K4 'Hydrometer'. The linking procedure has been obtained by numerical simulation, based on the Monte Carlo method, in which the differences in the results of the different comparison between the intended laboratory and one or more linking laboratory/ies, which took part in both comparisons, are correlated with a continuous function describing the DoEs of the linking laboratory/ies with respect to the common set of KCRVs of the CCM.D-K4. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  3. The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure

    Goliasch, Georg; Khorsand, Aliasghar; Sochor, Heinz; Schmidinger, Herwig; Graf, Senta; Schuetz, Matthias; Karanikas, Georgios; Khazen, Cesar; Wolzt, Michael

    2012-01-01

    Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO 2 ) in patients with chronic heart failure using 11 C-acetate positron emission tomography (PET). We prospectively enrolled 21 patients with severe heart failure. 11 C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. Under resting conditions, the values of myocardial blood flow (MBF), MVO 2 and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 ± 0.18 ml min -1 g -1 with the device off and 0.80 ± 0.15 ml min -1 g -1 with the device on (p = 0.818), MVO 2 was 6.81 ± 1.69 ml/min/100 g with the device off and 7.15 ± 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 ± 1.14 mmHg ml/m 2 with the device off and 5.21 ± 1.36 mmHg ml/m 2 with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO 2 and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. These results indicate that CCM does not induce increased MVO 2 , even under stress conditions. (orig.)

  4. The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure

    Goliasch, Georg; Khorsand, Aliasghar; Sochor, Heinz; Schmidinger, Herwig; Graf, Senta [Vienna General Hospital/Medical University of Vienna, Department of Cardiology, Vienna (Austria); Schuetz, Matthias; Karanikas, Georgios [Vienna General Hospital/Medical University of Vienna, Department of Nuclear Medicine, Vienna (Austria); Khazen, Cesar [Vienna General Hospital/ Medical University of Vienna, Department of Cardiothoracic Surgery, Vienna (Austria); Wolzt, Michael [Vienna General Hospital/Medical University of Vienna, Department of Cardiology, Vienna (Austria); Vienna General Hospital/ Medical University of Vienna, Department of Clinical Pharmacology, Vienna (Austria)

    2012-03-15

    Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO{sub 2}) in patients with chronic heart failure using {sup 11}C-acetate positron emission tomography (PET). We prospectively enrolled 21 patients with severe heart failure. {sup 11}C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. Under resting conditions, the values of myocardial blood flow (MBF), MVO{sub 2} and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 {+-} 0.18 ml min{sup -1} g{sup -1} with the device off and 0.80 {+-} 0.15 ml min{sup -1} g{sup -1} with the device on (p = 0.818), MVO{sub 2} was 6.81 {+-} 1.69 ml/min/100 g with the device off and 7.15 {+-} 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 {+-} 1.14 mmHg ml/m{sup 2} with the device off and 5.21 {+-} 1.36 mmHg ml/m{sup 2} with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO{sub 2} and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. These results indicate that CCM does not induce increased MVO{sub 2}, even under stress conditions. (orig.)

  5. Guidelines for specialized nutritional and metabolic support in the critically-ill patient: update. Consensus SEMICYUC-SENPE: neurocritical patient.

    Acosta Escribano, J; Herrero Meseguer, I; Conejero García-Quijada, R

    2011-11-01

    Neurocritical patients require specialized nutritional support due to their intense catabolism and prolonged fasting. The preferred route of nutrient administration is the gastrointestinal route, especially the gastric route. Alternatives are the transpyloric route or mixed enteral-parenteral nutrition if an effective nutritional volume of more than 60% cannot be obtained. Total calorie intake ranges from 20-30 kcal/kg/day, depending on the period of the clinical course, with protein intake higher than 20% of total calories (hyperproteic diet). Nutritional support should be initiated early. The incidence of gastrointestinal complications is generally higher to other critically-ill patients, the most frequent complication being an increase in gastric residual volume. As in other critically-ill patients, glycemia should be closely monitored and maintained below 150 mg/dL.

  6. A demonstration of mobile phone deployment to support the treatment of acutely ill children under five in Bushenyi district, Uganda.

    Kabakyenga, Jerome; Barigye, Celestine; Brenner, Jennifer; Maling, Samuel; Buchner, Denise; Nettle-Aquirre, Alberto; Singhal, Nalini; Kyomuhangi, Teddy; Tumusiime, David; Finch, Janet; MacLeod, Stuart

    2016-03-01

    Benefits of mobile phone deployment for children mobile phone use. Impact was assessed by quantitative measures and qualitative evaluation through household surveys, focus group discussions, and key informant interviews. CHWs in targeted sites improved child healthcare through mobile phone use coupled with iCCM. Of acutely ill children, 92.6% were correctly managed. Significant improvements in clinical outcomes compared to those obtained by CHWs with enhanced iCCM training alone were unproven in this limited demonstration. Nonetheless, qualitative evaluation showed gains in treatment planning, supply management, and logistical efficiency. Provider confidence and communications were enhanced as was ease and accuracy of record keeping. Mobile phones appear synergistic with iCCM to bolster basic supportive care for acutely ill children provided by CHWs. The full impact of expanded mobile phone deployment warrants further evaluation prior to scaling up in low-resource settings.

  7. The S-layer homology domain-containing protein SlhA from Paenibacillus alvei CCM 2051(T) is important for swarming and biofilm formation.

    Janesch, Bettina; Koerdt, Andrea; Messner, Paul; Schäffer, Christina

    2013-01-01

    Swarming and biofilm formation have been studied for a variety of bacteria. While this is well investigated for Gram-negative bacteria, less is known about Gram-positive bacteria, including Paenibacillus alvei, a secondary invader of diseased honeybee colonies infected with Melissococcus pluton, the causative agent of European foulbrood (EFB). Paenibacillus alvei CCM 2051(T) is a Gram-positive bacterium which was recently shown to employ S-layer homology (SLH) domains as cell wall targeting modules to display proteins on its cell surface. This study deals with the newly identified 1335-amino acid protein SlhA from P. alvei which carries at the C‑terminus three consecutive SLH-motifs containing the predicted binding sequences SRGE, VRQD, and LRGD instead of the common TRAE motif. Based on the proof of cell surface location of SlhA by fluorescence microscopy using a SlhA-GFP chimera, the binding mechanism was investigated in an in vitro assay. To unravel a putative function of the SlhA protein, a knockout mutant was constructed. Experimental data indicated that one SLH domain is sufficient for anchoring of SlhA to the cell surface, and the SLH domains of SlhA recognize both the peptidoglycan and the secondary cell wall polymer in vitro. This is in agreement with previous data from the S-layer protein SpaA, pinpointing a wider utilization of that mechanism for cell surface display of proteins in P. alvei. Compared to the wild-type bacterium ΔslhA revealed changed colony morphology, loss of swarming motility and impaired biofilm formation. The phenotype was similar to that of the flagella knockout Δhag, possibly due to reduced EPS production influencing the functionality of the flagella of ΔslhA. This study demonstrates the involvement of the SLH domain-containing protein SlhA in swarming and biofilm formation of P. alvei CCM 2051(T).

  8. The S-layer homology domain-containing protein SlhA from Paenibacillus alvei CCM 2051(T is important for swarming and biofilm formation.

    Bettina Janesch

    Full Text Available Swarming and biofilm formation have been studied for a variety of bacteria. While this is well investigated for Gram-negative bacteria, less is known about Gram-positive bacteria, including Paenibacillus alvei, a secondary invader of diseased honeybee colonies infected with Melissococcus pluton, the causative agent of European foulbrood (EFB.Paenibacillus alvei CCM 2051(T is a Gram-positive bacterium which was recently shown to employ S-layer homology (SLH domains as cell wall targeting modules to display proteins on its cell surface. This study deals with the newly identified 1335-amino acid protein SlhA from P. alvei which carries at the C‑terminus three consecutive SLH-motifs containing the predicted binding sequences SRGE, VRQD, and LRGD instead of the common TRAE motif. Based on the proof of cell surface location of SlhA by fluorescence microscopy using a SlhA-GFP chimera, the binding mechanism was investigated in an in vitro assay. To unravel a putative function of the SlhA protein, a knockout mutant was constructed. Experimental data indicated that one SLH domain is sufficient for anchoring of SlhA to the cell surface, and the SLH domains of SlhA recognize both the peptidoglycan and the secondary cell wall polymer in vitro. This is in agreement with previous data from the S-layer protein SpaA, pinpointing a wider utilization of that mechanism for cell surface display of proteins in P. alvei. Compared to the wild-type bacterium ΔslhA revealed changed colony morphology, loss of swarming motility and impaired biofilm formation. The phenotype was similar to that of the flagella knockout Δhag, possibly due to reduced EPS production influencing the functionality of the flagella of ΔslhA.This study demonstrates the involvement of the SLH domain-containing protein SlhA in swarming and biofilm formation of P. alvei CCM 2051(T.

  9. Different gene-expression profiles for the poorly differentiated carcinoma and the highly differentiated papillary adenocarcinoma in mammary glands support distinct metabolic pathways

    Eilon, Tali; Barash, Itamar

    2008-01-01

    Deregulation of Stat5 in the mammary gland of transgenic mice causes tumorigenesis. Poorly differentiated carcinoma and highly differentiated papillary adenocarcinoma tumors evolve. To distinguish the genes and elucidate the cellular processes and metabolic pathways utilized to preserve these phenotypes, gene-expression profiles were analyzed. Mammary tumors were excised from transgenic mice carrying a constitutively active variant of Stat5, or a Stat5 variant lacking s transactivation domain. These tumors displayed either the carcinoma or the papillary adenocarcinoma phenotypes. cRNAs, prepared from each tumor were hybridized to an Affymetrix GeneChip ® Mouse Genome 430A 2.0 array. Gene-ontology analysis, hierarchical clustering and biological-pathway analysis were performed to distinct the two types of tumors. Histopathology and immunofluorescence staining complemented the comparison between the tumor phenotypes. The nucleus-cytoskeleton-plasma membrane axis is a major target for differential gene expression between phenotypes. In the carcinoma, stronger expression of genes coding for specific integrins, cytoskeletal proteins and calcium-binding proteins highlight cell-adhesion and motility features of the tumor cells. This is supported by the higher expression of genes involved in O-glycan synthesis, TGF-β, activin, their receptors and Smad3, as well as the Notch ligands and members of the γ-secretase complex that enable Notch nuclear localization. The Wnt pathway was also a target for differential gene expression. Higher expression of genes encoding the degradation complex of the canonical pathway and limited TCF expression in the papillary adenocarcinoma result in membranal accumulation of β-catenin, in contrast to its nuclear translocation in the carcinoma. Genes involved in cell-cycle arrest at G1 and response to DNA damage were more highly expressed in the papillary adenocarcinomas, as opposed to favored G2/M regulation in the carcinoma tumors. At least

  10. Distribution and phylogenies of enzymes of the Embden-Meyerhof-Parnas pathway from archaea and hyperthermophilic bacteria support a gluconeogenic origin of metabolism

    Ron S. Ronimus

    2003-01-01

    Full Text Available Enzymes of the gluconeogenic/glycolytic pathway (the Embden-Meyerhof-Parnas (EMP pathway, the reductive tricarboxylic acid cycle, the reductive pentose phosphate cycle and the Entner-Doudoroff pathway are widely distributed and are often considered to be central to the origins of metabolism. In particular, several enzymes of the lower portion of the EMP pathway (the so-called trunk pathway, including triosephosphate isomerase (TPI; EC 5.3.1.1, glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12/13, phosphoglycerate kinase (PGK; EC 2.7.2.3 and enolase (EC 4.2.1.11, are extremely well conserved and universally distributed among the three domains of life. In this paper, the distribution of enzymes of gluconeogenesis/glycolysis in hyperthermophiles—microorganisms that many believe represent the least evolved organisms on the planet—is reviewed. In addition, the phylogenies of the trunk pathway enzymes (TPIs, GAPDHs, PGKs and enolases are examined. The enzymes catalyzing each of the six-carbon transformations in the upper portion of the EMP pathway, with the possible exception of aldolase, are all derived from multiple gene sequence families. In contrast, single sequence families can account for the archaeal and hyperthermophilic bacterial enzyme activities of the lower portion of the EMP pathway. The universal distribution of the trunk pathway enzymes, in combination with their phylogenies, supports the notion that the EMP pathway evolved in the direction of gluconeogenesis, i.e., from the bottom up.

  11. Environmental stressors and cardio-metabolic disease: part I-epidemiologic evidence supporting a role for noise and air pollution and effects of mitigation strategies.

    Münzel, Thomas; Sørensen, Mette; Gori, Tommaso; Schmidt, Frank P; Rao, Xiaoquan; Brook, Jeffrey; Chen, Lung Chi; Brook, Robert D; Rajagopalan, Sanjay

    2017-02-21

    Traffic noise and air pollution together represent the two most important environmental risk factors in urbanized societies. The first of this two-part review discusses the epidemiologic evidence in support of the existence of an association between these risk factors with cardiovascular and metabolic disease. While independent effects of these risk factors have now clearly been shown, recent studies also suggest that the two exposures may interact with each other and with traditional risk factors such as hypertension and type 2 diabetes. From a societal and policy perspective, the health effects of both air pollution and traffic noise are observed for exposures well below the thresholds currently accepted as being safe. Current gaps in knowledge, effects of intervention and their impact on cardiovascular disease, will be discussed in the last section of this review. Increased awareness of the societal burden posed by these novel risk factors and acknowledgement in traditional risk factor guidelines may intensify the efforts required for effective legislation to reduce air pollution and noise. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

  12. Assessment of a simplified set of momentum closure relations for low volume fraction regimes in STAR-CCM+ and OpenFOAM

    Sugrue, Rosemary; Magolan, Ben; Lubchenko, Nazar; Baglietto, Emilio

    2017-01-01

    Highlights: •A simplified set of momentum closures – Bubbly And Moderate void Fraction (BAMF) – is proposed. •BAMF model is assessed by simulation of 12 cases from the Liu and Bankoff experimental database. •Portability between STAR-CCM+ and OpenFOAM CFD softwares is demonstrated. •Both CFD softwares yield mean flow predictions in close agreement with experimental results. -- Abstract: Multiphase computational fluid dynamics (M-CFD) modeling approaches provide three-dimensional resolution of complex two-phase flow and boiling heat transfer phenomena, which makes them an invaluable tool for nuclear reactor design applications. By virtue of the Eulerian-Eulerian spatial and temporal averaging framework, additional terms manifest in the phase momentum equations that require closure through prescription of interfacial forces in the stream-wise and lateral flow directions, as well as in the near-wall region. These momentum closures are critical to M-CFD prediction of mean flow profiles, including velocity and volume fraction distributions, and yet while an overwhelming number of them has been developed, no consensus exists on how to assemble them to achieve a simplified set of closures that is numerically robust and extensible to a wide array of flow configurations; further, no consistent demonstration has been shown of the cross-code portability of these closures between CFD softwares. To address these challenges, we propose in this work a simplified set of momentum closures for stream-wise drag and lateral redistribution mechanisms—collectively referred to as the Bubbly And Moderate void Fraction (BAMF) model—and assess its performance by simulation of 12 cases from the Liu and Bankoff experimental database using STAR-CCM+ and OpenFOAM. Both CFD softwares yield mean flow predictions that are in close agreement with the experimental results, and also in close agreement with each other. These results confirm the effectiveness of the BAMF model and its

  13. Effects of temperature, pH and NaCl content on in vitro putrescine and cadaverine production through the growth of Serratia marcescens CCM 303.

    Bubelová, Zuzana; Buňka, František; Taťáková, Monika; Štajnochová, Kateřina; Purevdorj, Khatantuul; Buňková, Leona

    2015-01-01

    The aim of this study was to evaluate the combined effect of temperature (10, 20 and 37°C), pH (4, 5, 6, 7 and 8), and NaCl content (0, 1, 3, 4, 5 and 6% w/v) on the growth and putrescine and cadaverine production of Serratia marcescens CCM 303 under model conditions. The decarboxylase activity of S. marcescens was monitored in broth after cultivation. The cultivation medium was enriched with selected amino acids (ornithine, arginine and lysine; 0.2% w/v each) serving as precursors of biogenic amines. Levels of putrescine and cadaverine in broth were analysed by high-performance liquid chromatography after pre-column derivatisation with o-phthalaldehyde reagent. S. marcescens produced higher amounts of putrescine (up to 2096.8 mg L(-1)) compared to cadaverine content (up to 343.3 mg L(-1)) in all cultivation media. The highest putrescine and cadaverine concentrations were reached during cultivation at 10-20°C, pH 5-7 and NaCl content 1-3% w/v. On the other hand, the highest BAs production of individual cell (recalculated based on a cell; so called "yield factor") was observed at 10°C, pH 4 and salt concentration 3-5% w/v as a response to environmental stress.

  14. Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D₃, and vitamin K₁ produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome.

    Lamb, Joseph J; Holick, Michael F; Lerman, Robert H; Konda, Veera R; Minich, Deanna M; Desai, Anuradha; Chen, Tai C; Austin, Melissa; Kornberg, Jacob; Chang, Jyh-Lurn; Hsi, Alex; Bland, Jeffrey S; Tripp, Matthew L

    2011-05-01

    Metabolic syndrome poses additional risk for postmenopausal women who are already at risk for osteoporosis. We hypothesized that a nutritional supplement containing anti-inflammatory phytochemicals and essential bone nutrients would produce a favorable bone biomarker profile in postmenopausal women with metabolic syndrome. In this 14-week, randomized trial, 51 women were instructed to consume a modified Mediterranean-style, low-glycemic-load diet and to engage in aerobic exercise. Those in the intervention arm (n = 25) additionally received 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D₃, and 500 μg vitamin K₁ twice daily. Forty-five women completed the study. Baseline nutrient intake did not differ between arms. Compared with baseline, the intervention arm exhibited an approximate 25% mean decrease (P vitamin D₃, and vitamin K₁ produced a more favorable bone biomarker profile indicative of healthy bone metabolism in postmenopausal women with metabolic syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Laboratory evaluation of Isaria fumosorosea CCM 8367 and Steinernema feltiae Ustinov against immature stages of the Colorado potato beetle

    Hussein, Hany; Skoková Habuštová, Oxana; Půža, Vladimír; Zemek, Rostislav

    2016-01-01

    Roč. 11, č. 3 (2016), č. článku e0152399. E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) EE2.3.30.0032 Grant - others:Ministerstvo zemědělství(CZ) 206553/2011-MZE-17253; Ministerstvo školství, mládeže a tělovýchovy(CZ) CZ.1.07/2.4.00/12.0082 Institutional support: RVO:60077344 Keywords : Isaria fumosorosea * Steinernema feltiae * Colorado potato beetle Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection Impact factor: 2.806, year: 2016 http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0152399

  16. VRML metabolic network visualizer.

    Rojdestvenski, Igor

    2003-03-01

    A successful date collection visualization should satisfy a set of many requirements: unification of diverse data formats, support for serendipity research, support of hierarchical structures, algorithmizability, vast information density, Internet-readiness, and other. Recently, virtual reality has made significant progress in engineering, architectural design, entertainment and communication. We experiment with the possibility of using the immersive abstract three-dimensional visualizations of the metabolic networks. We present the trial Metabolic Network Visualizer software, which produces graphical representation of a metabolic network as a VRML world from a formal description written in a simple SGML-type scripting language.

  17. Analysis of the behavior of the flow of refrigerant through the bottom head and the impact of the removal of holes in the side panel of the MAEF-2012 with the code CFD STAR-CCM+; Analisis del comportamiento del flujo de refrigerante a traves del cabezal inferior y el impacto de la supresion de los taladros en el faldon lateral del MAEF-2012 con el codigo CFD STAR-CCM+

    Barrera, J.; Corpa, R.

    2013-07-01

    The scope of this work consists in the study of different pairs of lower headers with a dynamical code detail like the STAR-CCM + v8, to identify and study the consequences of changes in the distribution of flow and variation in the pressure drop of fluid passing through them, as well as check the absence of impact from the point of view of safety.

  18. Genome scale metabolic modeling of cancer

    Nilsson, Avlant; Nielsen, Jens

    2017-01-01

    of metabolism which allows simulation and hypotheses testing of metabolic strategies. It has successfully been applied to many microorganisms and is now used to study cancer metabolism. Generic models of human metabolism have been reconstructed based on the existence of metabolic genes in the human genome......Cancer cells reprogram metabolism to support rapid proliferation and survival. Energy metabolism is particularly important for growth and genes encoding enzymes involved in energy metabolism are frequently altered in cancer cells. A genome scale metabolic model (GEM) is a mathematical formalization...

  19. Quality improvement practices to institutionalize supply chain best practices for iCCM: Evidence from Rwanda and Malawi.

    Chandani, Yasmin; Duffy, Malia; Lamphere, Barbara; Noel, Megan; Heaton, Alexis; Andersson, Sarah

    2017-11-01

    Supply chain bottlenecks that prevent community health workers (CHWs) from accessing essential medicines significantly increase under-5 child mortality, particularly in poor and rural areas. Using implementation research, interventions aimed at improving supply chain practices and access to medicines were tested in Malawi and Rwanda. These interventions included simple demand-based resupply procedures, using mobile technology and traditional methods for communication, and multilevel, performance-driven quality improvement (QI) teams. Mixed-method evaluations were conducted at baseline (2010), midline (2013), and endline (2014). Baseline assessments identified common bottlenecks and established performance levels. Midline assessments identified which intervention package had the greatest impact. Endline surveys measured the progress of scale-up and institutionalization of each innovation. In both Rwanda and Malawi CHWs, health center staff, and district managers all cited many benefits of the establishment of resupply procedures and QI teams: such as providing structure and processes, a means to analyze and discuss problems and enhance collaboration between staff. Implementing simple, streamlined, demand-based resupply procedures formed the basis for informed and regular resupply, and increased the visibility of appropriate and timely community logistics data. QI teams played a critical role in reinforcing resupply procedures and routinely unlocking the bottlenecks that prevent the continuous flow of critical health products. While simple, streamlined, demand-based resupply procedures provide the basis for regular, functional, and efficient resupply of CHWs, the procedures alone are not sufficient to create consistent change in product availability. Supporting these procedures with multilevel QI teams reinforces the correct and consistent use of resupply procedures. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Bifidobacterium longum CCM 7952 Promotes Epithelial Barrier Function and Prevents Acute DSS-Induced Colitis in Strictly Strain-Specific Manner.

    Dagmar Srutkova

    Full Text Available Reduced microbial diversity has been associated with inflammatory bowel disease (IBD and probiotic bacteria have been proposed for its prevention and/or treatment. Nevertheless, comparative studies of strains of the same subspecies for specific health benefits are scarce. Here we compared two Bifidobacterium longum ssp. longum strains for their capacity to prevent experimental colitis.Immunomodulatory properties of nine probiotic bifidobacteria were assessed by stimulation of murine splenocytes. The immune responses to B. longum ssp. longum CCM 7952 (Bl 7952 and CCDM 372 (Bl 372 were further characterized by stimulation of bone marrow-derived dendritic cell, HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS-induced colitis was used to compare their beneficial effects in vivo.The nine bifidobacteria exhibited strain-specific abilities to induce cytokine production. Bl 372 induced higher levels of both pro- and anti-inflammatory cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved expression of tight junction proteins. Importantly, Bl 7952 improved intestinal barrier function as demonstrated by reduced FITC-dextran levels in serum.We have shown that Bl 7952, but not Bl 372, protected mice from the development of experimental colitis. Our data suggest that although some immunomodulatory properties might be widespread among the genus Bifidobacterium, others may be rare and characteristic only for a specific strain. Therefore, careful selection might be crucial in providing beneficial outcome in clinical trials with probiotics in IBD.

  1. Astrocytes and energy metabolism.

    Prebil, Mateja; Jensen, Jørgen; Zorec, Robert; Kreft, Marko

    2011-05-01

    Astrocytes are glial cells, which play a significant role in a number of processes, including the brain energy metabolism. Their anatomical position between blood vessels and neurons make them an interface for effective glucose uptake from blood. After entering astrocytes, glucose can be involved in different metabolic pathways, e.g. in glycogen production. Glycogen in the brain is localized mainly in astrocytes and is an important energy source in hypoxic conditions and normal brain functioning. The portion of glucose metabolized into glycogen molecules in astrocytes is as high as 40%. It is thought that the release of gliotransmitters (such as glutamate, neuroactive peptides and ATP) into the extracellular space by regulated exocytosis supports a significant part of communication between astrocytes and neurons. On the other hand, neurotransmitter action on astrocytes has a significant role in brain energy metabolism. Therefore, understanding the astrocytes energy metabolism may help understanding neuron-astrocyte interactions.

  2. Metabolic Syndrome

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  3. Neutron–gamma discrimination based on the support vector machine method

    Yu, Xunzhen; Zhu, Jingjun; Lin, ShinTed; Wang, Li; Xing, Haoyang; Zhang, Caixun; Xia, Yuxi; Liu, Shukui; Yue, Qian; Wei, Weiwei; Du, Qiang; Tang, Changjian

    2015-01-01

    In this study, the combination of the support vector machine (SVM) method with the moment analysis method (MAM) is proposed and utilized to perform neutron/gamma (n/γ) discrimination of the pulses from an organic liquid scintillator (OLS). Neutron and gamma events, which can be firmly separated on the scatter plot drawn by the charge comparison method (CCM), are detected to form the training data set and the test data set for the SVM, and the MAM is used to create the feature vectors for individual events in the data sets. Compared to the traditional methods, such as CCM, the proposed method can not only discriminate the neutron and gamma signals, even at lower energy levels, but also provide the corresponding classification accuracy for each event, which is useful in validating the discrimination. Meanwhile, the proposed method can also offer a predication of the classification for the under-energy-limit events

  4. Validation of the space fields and the median zonal of the temperature of the air in surface and of the precipitation in Colombia, simulated by the pattern CCM3 and the data of the NCEP/NCAR Reanalysis

    Zea Mazo, Jorge Anibal; Leon Aristizabal Gloria Esperanza; Eslava Ramirez, Jesus Antonio

    2001-01-01

    This work presents an analysis of the basic fields of the surface temperature and the precipitation for the national territory, from two sources of information: the data originated by the national meteorological network and the generated ones at world-wide level by means of the NCEP/NCAR Reanalysis project for the assimilation of data coming from diverse world-wide networks. With them reference scenes are constructed to validate the CCM3 model which is used like tool for the projection of the climatic change in Colombia

  5. CONFERENCE NOTE: Comité Consultatif pour la Masse et les grandeurs apparentées (CCM), High Pressure and Medium Pressure Working Groups, Second International Seminar on Pressure Metrology from 1 kPa to 1 GPa

    1992-01-01

    The seminar will be held from 2 to 4 June 1993, preceding the next meeting of the CCM, at the Laboratoire National d'Essais (LNE), 1 rue Gaston Boissier, 75015 Paris, France. Scope of the Seminar The purpose of the seminar is to review the state of the art of pressure measurements in the 1 kPa to 1 GPa range and to present original and innovative contributions from standards laboratories and industry. Main Topics The seminar will be organized in six sessions as follows: Liquid-column manometers Piston gauge pressure standards Properties of liquids and gases relevant to pressure metrology Pressure transducers and transfer standards Pressure standard comparison (methods and results) Dynamic pressure measurements. Each topic will be introduced by a review paper presented by a session chairman. A final session, coordinated by Dr G F Molinar (IMGC), Chairman of the CCM High Pressure Working Group, and Dr P Stuart (NPL), Chairman of the CCM Medium Pressure Working Group, will deal with: Actual limits of accuracy of static pressure measurements in fluid media Fundamental problems in pressure metrology between I kPa and 1 GPa. Call for Papers Papers should be prepared for oral presentation and will be refereed by the session chairmen. The Proceedings will be published as a special issue of Metrologia. Papers should be written according to the instructions for authors printed on the inside back cover of this journal. A one-page abstract should be sent to Dr Molinar at the IMGC, to arrive before 31 January 1993. A participation fee of 900 FFr (175 US) will be charged. This will cover general expenses and a copy of the Proceedings. Hotel reservations, meals and transport are not included. Organizers For further information please contact: 1993 CCM Pressure Seminar, Dr G F Molinar, Istituto di Metrologia "G Colonnetti", Strada delle Cacce 73, 1-10135 Torino, Italy telephone (39) 11 39771; telex 212209 IMGCTO-I; fax (39) 11 346761. Contact at the LNE: J C Legras, telephone (33

  6. CLINICAL PRACTICE GUIDELINES FOR THE PERIOPERATIVE NUTRITIONAL, METABOLIC, AND NONSURGICAL SUPPORT OF THE BARIATRIC SURGERY PATIENT—2013 UPDATE: COSPONSORED BY AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, THE OBESITY SOCIETY, AND AMERICAN SOCIETY FOR METABOLIC & BARIATRIC SURGERY★

    Mechanick, Jeffrey I.; Youdim, Adrienne; Jones, Daniel B.; Garvey, W. Timothy; Hurley, Daniel L.; McMahon, M. Molly; Heinberg, Leslie J.; Kushner, Robert; Adams, Ted D.; Shikora, Scott; Dixon, John B.; Brethauer, Stacy

    2014-01-01

    The development of these updated guidelines was commissioned by the AACE, TOS, and ASMBS Board of Directors and adheres to the AACE 2010 protocol for standardized production of clinical practice guidelines (CPG). Each recommendation was re-evaluated and updated based on the evidence and subjective factors per protocol. Examples of expanded topics in this update include: the roles of sleeve gastrectomy, bariatric surgery in patients with type-2 diabetes, bariatric surgery for patients with mild obesity, copper deficiency, informed consent, and behavioral issues. There are 74 recommendations (of which 56 are revised and 2 are new) in this 2013 update, compared with 164 original recommendations in 2008. There are 403 citations, of which 33 (8.2%) are EL 1, 131 (32.5%) are EL 2, 170 (42.2%) are EL 3, and 69 (17.1%) are EL 4. There is a relatively high proportion (40.4%) of strong (EL 1 and 2) studies, compared with only 16.5% in the 2008 AACE- TOS-ASMBS CPG. These updated guidelines reflect recent additions to the evidence base. Bariatric surgery remains a safe and effective intervention for select patients with obesity. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues. PMID:23529351

  7. Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and Nonsurgical Support of the Bariatric Surgery Patient—2013 Update: Cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery*

    Mechanick, Jeffrey I.; Youdim, Adrienne; Jones, Daniel B.; Garvey, W. Timothy; Hurley, Daniel L.; McMahon, Molly; Heinberg, Leslie J.; Kushner, Robert; Adams, Ted D.; Shikora, Scott; Dixon, John B.; Brethauer, Stacy

    2014-01-01

    The development of these updated guidelines was commissioned by the AACE, TOS, and ASMBS Board of Directors and adheres to the AACE 2010 protocol for standardized production of clinical practice guidelines (CPG). Each recommendation was re-evaluated and updated based on the evidence and subjective factors per protocol. Examples of expanded topics in this update include: the roles of sleeve gastrectomy, bariatric surgery in patients with type-2 diabetes, bariatric surgery for patients with mild obesity, copper deficiency, informed consent, and behavioral issues. There are 74 recommendations (of which 56 are revised and 2 are new) in this 2013 update, compared with 164 original recommendations in 2008. There are 403 citations, of which 33 (8.2%) are EL 1, 131 (32.5%) are EL 2, 170 (42.2%) are EL 3, and 69 (17.1%) are EL 4. There is a relatively high proportion (40.4%) of strong (EL 1 and 2) studies, compared with only 16.5% in the 2008 AACE-TOS-ASMBS CPG. These updated guidelines reflect recent additions to the evidence base. Bariatric surgery remains a safe and effective intervention for select patients with obesity. A team approach to perioperative care is mandatory with special attention to nutritional and metabolic issues. PMID:23529939

  8. Nutritional support in children under metabolic stress Soporte nutricional en el niño con estrés metabólico

    María Elsy Sepúlveda Hincapié

    1999-04-01

    Full Text Available A review is presented on metabolic changes that occur in children under stress, and on the organs that are affected by the response to it; also considered are the different resources that are presently available in order to maintain nutrition in these children and to improve their probabilities of recovery. Se hace una revisión acerca de los cambios metabólicos que ocurren en el niño durante el estrés y los órganos que se afectan en su respuesta; se tienen en cuenta además, los diferentes recursos que actualmente se pueden utilizar con el fin de mantener la nutrición del niño durante este tipo de situación, mejorando sus posibilidades de recuperación.

  9. The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

    Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

    2016-05-01

    Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. © 2016 John Wiley & Sons Ltd.

  10. Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria

    Solverson, Patrick; Murali, Sangita G.; Brinkman, Adam S.; Nelson, David W.; Clayton, Murray K.; Yen, Chi-Liang Eric

    2012-01-01

    Phenylketonuria (PKU) is caused by a mutation in the phenylalanine (phe) hydroxylase gene and requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to AA formula. Our objective was to compare growth, body composition, and energy balance in Pahenu2 (PKU) and wild-type mice fed low-phe GMP, low-phe AA, or high-phe casein diets from 3–23 wk of age. The 2 × 2 × 3 design included main effects of genotype, sex, and diet. Fat and lean mass were assessed by dual-energy X-ray absorptiometry, and acute energy balance was assessed by indirect calorimetry. PKU mice showed growth and lean mass similar to wild-type littermates fed the GMP or AA diets; however, they exhibited a 3–15% increase in energy expenditure, as reflected in oxygen consumption, and a 3–30% increase in food intake. The GMP diet significantly reduced energy expenditure, food intake, and plasma phe concentration in PKU mice compared with the casein diet. The high-phe casein diet or the low-phe AA diet induced metabolic stress in PKU mice, as reflected in increased energy expenditure and intake of food and water, increased renal and spleen mass, and elevated plasma cytokine concentrations consistent with systemic inflammation. The low-phe GMP diet significantly attenuated these adverse effects. Moreover, total fat mass, %body fat, and the respiratory exchange ratio (CO2 produced/O2 consumed) were significantly lower in PKU mice fed GMP compared with AA diets. In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice. PMID:22297302

  11. What is Metabolic Syndrome?

    ... Intramural Research Home / Metabolic Syndrome Metabolic Syndrome Also known as What Is Metabolic syndrome ... metabolic risk factors to be diagnosed with metabolic syndrome. Metabolic Risk Factors A Large Waistline Having a large ...

  12. Effectiveness of a Peer Support Programme versus Usual Care in Disease Management of Diabetes Mellitus Type 2 regarding Improvement of Metabolic Control: A Cluster-Randomised Controlled Trial.

    Johansson, Tim; Keller, Sophie; Winkler, Henrike; Ostermann, Thomas; Weitgasser, Raimund; Sönnichsen, Andreas C

    2016-01-01

    Testing the effectiveness of peer support additionally to a disease management programme (DMP) for type 2 diabetes patients. Unblinded cluster-randomised controlled trial (RCT) involving 49 general practices, province of Salzburg, Austria. All patients enrolled in the DMP were eligible, n = 337 participated (intervention: 148 in 19 clusters; control: 189 in 20 clusters). The peer support intervention ran over 24 months and consisted of peer supporter recruitment and training, and group meetings weekly for physical exercise and monthly for discussion of diabetes related topics. At two-year follow-up, adjusted analysis revealed a nonsignificant difference in HbA1c change of 0.14% (21.97 mmol/mol) in favour of the intervention (95% CI -0.08 to 0.36%, p = 0.22). Baseline values were 7.02 ± 1.25% in the intervention and 7.08 ± 1.25 in the control group. None of the secondary outcome measures showed significant differences except for improved quality of life (EQ-5D-VAS) in controls (4.3 points on a scale of 100; 95% CI 0.08 to 8.53, p = 0.046) compared to the intervention group. Our peer support intervention as an additional DMP component showed no significant effect on HbA1c and secondary outcome measures. Further RTCs with a longer follow-up are needed to reveal whether peer support will have clinically relevant effects. This trial has been registered with Current Controlled Trials Ltd. (ISRCTN10291077).

  13. [Metabolic acidosis].

    Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

    2016-01-01

    Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

  14. Drug Metabolism

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  15. Drug Metabolism

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  16. Metabolic Myopathies.

    Tarnopolsky, Mark A

    2016-12-01

    Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

  17. Animal metabolism

    Walburg, H.E.

    1977-01-01

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144 Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95 Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  18. Cancer Cell Metabolism: One Hallmark, Many Faces

    Cantor, Jason R.; Sabatini, David M.

    2012-01-01

    Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such chang...

  19. [Metabolic myopathies].

    Papazian, Óscar; Rivas-Chacón, Rafael

    2013-09-06

    To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

  20. Nucleotide Metabolism

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolis...

  1. Metabolic changes in malnutrition.

    Emery, P W

    2005-10-01

    This paper is concerned with malnutrition caused by inadequate intake of all the major nutrients rather than deficiency diseases relating to a single micronutrient. Three common situations are recognised: young children in third world countries with protein-energy malnutrition; adults in the same countries who are chronically adapted to subsisting on marginally inadequate diets; and patients who become malnourished as a result of chronic diseases. In all these situations infectious diseases are often also present, and this complicates the interpretation of biochemical and physiological observations. The metabolic response to starvation is primarily concerned with maintaining a supply of water-soluble substrates to supply energy to the brain. Thus there is an initial rise in metabolic rate, reflecting gluconeogenic activity. As fasting progresses, gluconeogenesis is suppressed to minimise muscle protein breakdown and ketones become the main fuel for the brain. With chronic underfeeding the basal metabolic rate per cell appears to fall, but the mechanistic basis for this is not clear. The main adaptation to chronic energy deficiency is slow growth and low adult body size, although the reduction in energy requirement achieved by this is partially offset by the preservation of the more metabolically active organs at the expense of muscle, which has a lower metabolic rate. The interaction between malnutrition and the metabolic response to trauma has been studied using an animal model. The rise in energy expenditure and urinary nitrogen excretion following surgery were significantly attenuated in malnourished rats, suggesting that malnutrition impairs the ability of the body to mobilise substrates to support inflammatory and reparative processes. However, the healing process in wounded muscle remained unimpaired in malnutrition, suggesting that this process has a high biological priority.

  2. Metabolic Surgery

    Pareek, Manan; Schauer, Philip R; Kaplan, Lee M

    2018-01-01

    The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown...... the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity....... Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further...

  3. Metabolic Syndrome

    Sevil Ikinci

    2010-10-01

    Full Text Available Metabolic Syndrome is a combination of risk factors including common etiopathogenesis. These risk factors play different roles in occurence of atherosclerotic diseases, type 2 diabetes, and cancers. Although a compromise can not be achieved on differential diagnosis for MS, the existence of any three criterias enable to diagnose MS. These are abdominal obesity, dislipidemia (hypertrigliceridemia, hypercholesterolemia, and reduced high density lipoprotein hypertension, and elevated fasting blood glucose. According to the results of Metabolic Syndrome Research (METSAR, the overall prevalence of MS in Turkey is 34%; in females 40%, and in males it is 28%. As a result of “Western” diet, and increased frequency of obesity, MS is observed in children and in adolescents both in the world and in Turkey. Resulting in chronic diseases, it is thought that the syndrome can be prevented by healthy lifestyle behaviours. [TAF Prev Med Bull 2010; 9(5.000: 535-540

  4. Sleep and metabolic function.

    Morselli, Lisa L; Guyon, Aurore; Spiegel, Karine

    2012-01-01

    Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper airway obstruction leading to intermittent hypoxemia and sleep fragmentation, has also become highly prevalent as a consequence of the epidemic of obesity and has been shown to contribute, in a vicious circle, to the metabolic disturbances observed in obese patients. In this article, we summarize the current data supporting the role of sleep in the regulation of glucose homeostasis and the hormones involved in the regulation of appetite. We also review the results of the epidemiologic and laboratory studies that investigated the impact of sleep duration and quality on the risk of developing diabetes and obesity, as well as the mechanisms underlying this increased risk. Finally, we discuss how obstructive sleep apnea affects glucose metabolism and the beneficial impact of its treatment, the continuous positive airway pressure. In conclusion, the data available in the literature highlight the importance of getting enough good sleep for metabolic health.

  5. Cellular metabolism

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  6. The Evidence-base for Using Ontologies and Semantic Integration Methodologies to Support Integrated Chronic Disease Management in Primary and Ambulatory Care: Realist Review. Contribution of the IMIA Primary Health Care Informatics WG.

    Liyanage, H; Liaw, S-T; Kuziemsky, C; Terry, A L; Jones, S; Soler, J K; de Lusignan, S

    2013-01-01

    Most chronic diseases are managed in primary and ambulatory care. The chronic care model (CCM) suggests a wide range of community, technological, team and patient factors contribute to effective chronic disease management. Ontologies have the capability to enable formalised linkage of heterogeneous data sources as might be found across the elements of the CCM. To describe the evidence base for using ontologies and other semantic integration methods to support chronic disease management. We reviewed the evidence-base for the use of ontologies and other semantic integration methods within and across the elements of the CCM. We report them using a realist review describing the context in which the mechanism was applied, and any outcome measures. Most evidence was descriptive with an almost complete absence of empirical research and important gaps in the evidence-base. We found some use of ontologies and semantic integration methods for community support of the medical home and for care in the community. Ubiquitous information technology (IT) and other IT tools were deployed to support self-management support, use of shared registries, health behavioural models and knowledge discovery tools to improve delivery system design. Data quality issues restricted the use of clinical data; however there was an increased use of interoperable data and health system integration. Ontologies and semantic integration methods are emergent with limited evidence-base for their implementation. However, they have the potential to integrate the disparate community wide data sources to provide the information necessary for effective chronic disease management.

  7. Penicillin G acylase from Achromobacter sp CCM 4824 An efficient biocatalyst for syntheses of beta-lactam antibiotics under conditions employed in large-scale processes

    Bečka, Stanislav; Štěpánek, Václav; Vyasarayani, W. R.; Grulich, Michal; Maršálek, Jaroslav; Plháčková, Kamila; Dobišová, Marie; Marešová, Helena; Plačková, Martina; Valešová, Renata; Palyzová, Andrea; Datla, A.; Ashar, T. K.; Kyslík, Pavel

    2014-01-01

    Roč. 98, č. 3 (2014), s. 1195-1203 ISSN 0175-7598 Institutional support: RVO:61388971 Keywords : Achromobacter sp. * Penicillin G acylase * beta-Lactam antibiotics Subject RIV: EE - Microbiology, Virology Impact factor: 3.337, year: 2014

  8. Potential of the strain of entomopathogenic fungus Isaria fumosorosea CCM 8637 as a biological control agent against Cameraria ohridella and other pests

    Zemek, Rostislav; Prenerová, Eva; Awad, Mona; Hussein, Hany

    2012-01-01

    Roč. 15, - (2012), s. 79-80 ISSN 1335-258X R&D Projects: GA MŠk 2B06005 Grant - others:European Social Fund(CZ) CZ.1.07/2.4.00/12.0082 Institutional support: RVO:60077344 Keywords : biological control * horse chestnut leaf miner * Colorado potato beatle

  9. Metabolic syndrome in hyperprolactinemia

    Andersen, Marianne; Glintborg, Dorte

    2018-01-01

    The metabolic syndrome (MetS) is a conglomerate of clinical findings that convey into increased morbidity and mortality from type 2 diabetes mellitus (T2D) and cardiovascular disease. Hyperprolactinemia (hyperPRL) is associated with components of MetS, especially during pregnancy. Endogenous levels...... in patients with T2D. HyperPRL is a biomarker for decreased dopaminergic tonus in the hypothalamic-pituitary circuit. Patients with a prolactinoma, patients with schizophrenia and/or T2D often have disturbances in this balance and the finding of lower prolactin (PRL) levels in polycystic ovary syndrome (PCOS......) may indicate increased dopaminergic tonus. Recent studies supported that PRL levels within or above reference range may be differently related to MetS. In healthy study populations and in PCOS, PRL levels were inversely associated with metabolic risk markers. Ongoing research on PRL fragments...

  10. Calcium metabolism in birds.

    de Matos, Ricardo

    2008-01-01

    Calcium is one of the most important plasma constituents in mammals and birds. It provides structural strength and support (bones and eggshell) and plays vital roles in many of the biochemical reactions in the body. The control of calcium metabolism in birds is highly efficient and closely regulated in a number of tissues, primarily parathyroid gland, intestine, kidney, and bone. The hormones with the greatest involvement in calcium regulation in birds are parathyroid hormone, 1,25-dihydroxyvitamin D(3) (calcitriol), and estrogen, with calcitonin playing a minor and uncertain role. The special characteristics of calcium metabolism in birds, mainly associated with egg production, are discussed, along with common clinical disorders secondary to derangements in calcium homeostasis.

  11. A Metabolic Race

    A.M.S. Costa et al.

    2017-07-01

    Full Text Available Metabolic Syndrome describes a set of metabolic risk factors that manifest in an individual and some aspects contribute to its appearance: genetic, overweight and the absence of physical activity. So, a board game was created to simulate the environment and routine experienced by UFF students that could contribute  to the development of Metabolic Syndrome. Players move along a simplified map of Niterói city, where places as Antônio Pedro Hospital (HUAP are pointed out. OBJECTIVES: This project aimed to develop an educational game to consolidate Metabolic Syndrome biochemical events. MATERIAL E METHODS: Each group receives a board, pins, dice, question, challenge and diagnostics cards. One student performs the family doctor function, responsable for delivering cards, reading activities and providing diagnosis to players when game is over.The scoring system is based on 3 criteria for Metabolic Syndrome diagnosis: glycemia, abdominal obesity and HDL cholesterol. At the end of game, it is possible to calculate the rates of each player and provide proportional diagnosis. The winner is the healthiest that first arrives at HUAP. RESULTS AND DISCUSSION: The game was applied to 50 students and only 10% classified the subject-matter as difficult. This finding highlight the need to establish new methods to enhance the teaching and learning process and decrease the students’ dificulties. Students evaluated the game as an important educational support and 85% of them agreed it complements  and consolidate the content discussed in classroom. Finally, the game was very highly rated by students according to their perception about their own performance while playing.  In addition, 95 % students pointed they would play again and 98% said they think games are able to optimize learning. CONCLUSIONS: It was possible not only to approximate biochemical phenomena to the students’ daily life, but also to solidify the theoretical concepts in a dynamic and fun

  12. Immunoreactive proteins of Bifidobacterium longum ssp. longum CCM 7952 and Bifidobacterium longum ssp. longum CCDM 372 identified by gnotobiotic mono-colonized mice sera, immune rabbit sera and nonimmune human sera.

    Sabina Górska

    2016-09-01

    Full Text Available The Bifidobacteria show great diversity in the cell surface architecture which may influence the physicochemical properties of the bacterial cell and strain specific properties. The immunomodulatory role of bifidobacteria has been extensively studied, however studies on the immunoreactivity of their protein molecules are very limited. Here, we compared six different methods of protein isolation and purification and we report identification of immunogenic and immunoreactive protein of two human Bifidobacterium longum ssp. longum strains. We evaluated potential immunoreactive properties of proteins employing polyclonal sera obtained from germ free mouse, rabbit and human. The protein yield was isolation method-dependent and the reactivity of proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and have them sequenced. Among the immunoreactive proteins we identified enolase, aspartokinase, pyruvate kinase, DnaK (B. longum ssp. longum CCM 7952 and sugar ABC transporter ATP-binding protein, phosphoglycerate kinase, peptidoglycan synthethase penicillin-binding protein 3, transaldolase, ribosomal proteins and glyceraldehyde 3-phosphate dehydrogenase (B. longum ssp. longum CCDM 372.

  13. Immunoreactive Proteins of Bifidobacterium longum ssp. longum CCM 7952 and Bifidobacterium longum ssp. longum CCDM 372 Identified by Gnotobiotic Mono-Colonized Mice Sera, Immune Rabbit Sera and Non-immune Human Sera.

    Górska, Sabina; Dylus, Ewa; Rudawska, Angelika; Brzozowska, Ewa; Srutkova, Dagmar; Schwarzer, Martin; Razim, Agnieszka; Kozakova, Hana; Gamian, Andrzej

    2016-01-01

    The Bifidobacteria show great diversity in the cell surface architecture which may influence the physicochemical properties of the bacterial cell and strain specific properties. The immunomodulatory role of bifidobacteria has been extensively studied, however studies on the immunoreactivity of their protein molecules are very limited. Here, we compared six different methods of protein isolation and purification and we report identification of immunogenic and immunoreactive protein of two human Bifidobacterium longum ssp. longum strains. We evaluated potential immunoreactive properties of proteins employing polyclonal sera obtained from germ free mouse, rabbit and human. The protein yield was isolation method-dependent and the reactivity of proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and have them sequenced. Among the immunoreactive proteins we identified enolase, aspartokinase, pyruvate kinase, DnaK ( B. longum ssp. longum CCM 7952) and sugar ABC transporter ATP-binding protein, phosphoglycerate kinase, peptidoglycan synthethase penicillin-binding protein 3, transaldolase, ribosomal proteins and glyceraldehyde 3-phosphate dehydrogenase ( B. longum ssp. longum CCDM 372).

  14. Nutrigenetics of the lipoprotein metabolism.

    Garcia-Rios, Antonio; Perez-Martinez, Pablo; Delgado-Lista, Javier; Lopez-Miranda, Jose; Perez-Jimenez, Francisco

    2012-01-01

    It is well known that lipid metabolism is a cornerstone in the development of the commonest important chronic diseases worldwide, such as obesity, cardiovascular disease, or metabolic syndrome. In this regard, the area of lipid and lipoprotein metabolism is one of the areas in which the understanding of the development and progression of those metabolic disorders has been studied in greater depth. Thus, growing evidence has demonstrated that while universal recommendations might be appropriate for the general population, in this area there is great variability among individuals, related to a combination of environmental and genetic factors. Moreover, the interaction between genetic and dietary components has helped in understanding this variability. Therefore, with further study into the interaction between the most important genetic markers or single-nucleotide polymorphisms (SNPs) and diet, it may be possible to understand the variability in lipid metabolism, which could lead to an increase in the use of personalized nutrition as the best support to combat metabolic disorders. This review discusses some of the evidence in which candidate SNPs can affect the key players of lipid metabolism and how their phenotypic manifestations can be modified by dietary intake. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Inherited metabolic disorders in Thailand.

    Wasant, Pornswan; Svasti, Jisnuson; Srisomsap, Chantragan; Liammongkolkul, Somporn

    2002-08-01

    The study of inborn errors of metabolism (IEM) in Thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn Research Institute) and abroad (Japan and the United States). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in Thailand, research and pilot studies in newborn screening in Thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj Hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).

  16. Cancer cell metabolism: one hallmark, many faces.

    Cantor, Jason R; Sabatini, David M

    2012-10-01

    Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes within the metabolic program of a cancer cell can dictate by what means proliferative rewiring is driven, and can also impart heterogeneity in the metabolic dependencies of the cell. A better understanding of this heterogeneity may enable the development and optimization of therapeutic strategies that target tumor metabolism.

  17. Introduction of mobile phones for use by volunteer community health workers in support of integrated community case management in Bushenyi District, Uganda: development and implementation process.

    Tumusiime, David Katuruba; Agaba, Gad; Kyomuhangi, Teddy; Finch, Jan; Kabakyenga, Jerome; MacLeod, Stuart

    2014-01-01

    A substantial literature suggests that mobile phones have great potential to improve management and survival of acutely ill children in rural Africa. The national strategy of the Ugandan Ministry of Health calls for employment of volunteer community health workers (CHWs) in implementation of Integrated Community Case Management (iCCM) of common illnesses (diarrhea, acute respiratory infection, pneumonia, fever/malaria) affecting children under five years of age. A mobile phone enabled system was developed within iCCM aiming to improve access by CHWs to medical advice and to strengthen reporting of data on danger signs and symptoms for acutely ill children under five years of age. Herein critical steps in development, implementation, and integration of mobile phone technology within iCCM are described. Mechanisms to improve diagnosis, treatment and referral of sick children under five were defined. Treatment algorithms were developed by the project technical team and mounted and piloted on the mobile phones, using an iterative process involving technical support personnel, health care providers, and academic support. Using a purposefully developed mobile phone training manual, CHWs were trained over an intensive five-day course to make timely diagnoses, recognize clinical danger signs, communicate about referrals and initiate treatment with appropriate essential drugs. Performance by CHWs and the accuracy and completeness of their submitted data was closely monitored post training test period and during the subsequent nine month community trial. In the full trial, the number of referrals and correctly treated children, based on the agreed treatment algorithms, was recorded. Births, deaths, and medication stocks were also tracked. Seven distinct phases were required to develop a robust mobile phone enabled system in support of the iCCM program. Over a nine month period, 96 CHWs were trained to use mobile phones and their competence to initiate a community trial was

  18. Carbohydrate Metabolism Disorders

    ... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose (a type of sugar). If ...

  19. Comprehensive metabolic panel

    Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... Chernecky CC, Berger BJ. Comprehensive metabolic panel (CMP) - blood. In: ... Tests and Diagnostic Procedures . 6th ed. St Louis, MO: ...

  20. CCM - Understanding and working with Competencies

    HR Department

    2011-01-01

    Find out what competencies are, make them come to life by sharing your experience with colleagues, and understand what they represent in our work environment. All staff members are encouraged to attend. Register here for sessions in June.

  1. CCM - Understanding and working with Competencies

    HR Department

    2011-01-01

    Find out what competencies are, make them come to life by sharing your experience with colleagues, and understand what they represent in our work environment. All staff members are encouraged to attend. Register here for sessions in March and April.

  2. Energy Metabolism Impairment in Migraine.

    Cevoli, Sabina; Favoni, Valentina; Cortelli, Pietro

    2018-06-22

    Migraine is a common disabling neurological disorder which is characterised by recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an update overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold create metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Insights into Brain Glycogen Metabolism

    Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2016-01-01

    Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

  4. Inflammation and metabolic disorders.

    Navab, Mohamad; Gharavi, Nima; Watson, Andrew D

    2008-07-01

    Poor nutrition, overweight and obesity have increasingly become a public health concern as they affect many metabolic disorders, including heart disease, diabetes, digestive system disorders, and renal failure. Study of the effects of life style including healthy nutrition will help further elucidate the mechanisms involved in the adverse effects of poor nutrition. Unhealthy life style including poor nutrition can result in imbalance in our oxidation/redox systems. Lipids can undergo oxidative modification by lipoxygenases, cyclooxygenases, myeloperoxidase, and other enzymes. Oxidized phospholipids can induce inflammatory molecules in the liver and other organs. This can contribute to inflammation, leading to coronary heart disease, stroke, renal failure, inflammatory bowl disease, metabolic syndrome, bone and joint disorders, and even certain types of cancer. Our antioxidant and antiinflammatory defense mechanisms contribute to a balance between the stimulators and the inhibitors of inflammation. Beyond a point, however, these systems might be overwhelmed and eventually fail. High-density lipoprotein is a potent inhibitor of the formation of toxic oxidized lipids. High-density lipoprotein is also an effective system for stimulating the genes whose products are active in the removal, inactivation, and elimination of toxic lipids. Supporting the high-density lipoprotein function should help maintain the balance in these systems. It is hoped that the present report would elucidate some of the ongoing work toward this goal.

  5. Treatment of metabolic syndrome.

    Wagh, Arati; Stone, Neil J

    2004-03-01

    The metabolic syndrome is intended to identify patients who have increased risk of diabetes and/or a cardiac event due to the deleterious effects of weight gain, sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol Education Program's Adult Treatment Panel III definition uses easily measured clinical findings of increased abdominal circumference, elevated triglycerides, low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or elevated blood pressure. Three of these five are required for diagnosis. The authors also note that other definitions of metabolic syndrome focus more on insulin resistance and its key role in this syndrome. This review focuses on how treatment might affect each of the five components. Abdominal obesity can be treated with a variety of lower calorie diets along with regular exercise. Indeed, all of the five components of the metabolic syndrome are improved by even modest amounts of weight loss achieved with diet and exercise. For those with impaired fasting glucose tolerance, there is good evidence that a high fiber, low saturated fat diet with increased daily exercise can reduce the incidence of diabetes by almost 60%. Of note, subjects who exercise the most, gain the most benefit. Metformin has also been shown to be helpful in these subjects. Thiazolidinedione drugs may prove useful, but further studies are needed. Although intensified therapeutic lifestyle change will help the abnormal lipid profile, some patients may require drug therapy. This review also discusses the use of statins, fibrates, and niacin. Likewise, while hypertension in the metabolic syndrome benefits from therapeutic lifestyle change, physicians should also consider angiotensin converting enzyme inhibitor drugs or angiotensin receptor blockers, due to their effects on preventing complications of diabetes, such as progression of diabetic nephropathy and due to their effects on regression of left ventricular hypertrophy. Aspirin

  6. Haloacetonitriles: metabolism and toxicity.

    Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

    2009-01-01

    The haloacetonitriles (HANs) exist in drinking water exclusively as byproducts of disinfection. HANs are found in drinking water more often, and in higher concentrations, when surface water is treated by chloramination. Human exposure occurs through consumption of finished drinking water; oral and dermal contact also occurs, and results from showering, swimming and other activities. HANs are reactive and are toxic to gastrointestinal tissues following oral administration. Such toxicity is characterized by GSH depletion, increased lipid peroxidation, and covalent binding of HAN-associated radioactivity to gut tissues. The presence of GSH in cells is an important protective mechanism against HAN toxicity; depletion of cellular GSH results in increased toxicity. Some studies have demonstrated an apparently synergistic effect between ROS and HAN administration, that may help explain effects observed in GI tissues. ROS are produced in gut tissues, and in vitro evidence indicates that ROS may contribute to the degradation and formation of reactive intermediates from HANs. The rationale for ROS involvement may involve HAN-induced depletion of GSH and the role of GSH in scavenging ROS. In addition to effects on GI tissues, studies show that HAN-derived radiolabel is found covalently bound to proteins and DNA in several organs and tissues. The addition of antioxidants to biologic systems protects against HAN-induced DNA damage. The protection offered by antioxidants supports the role of oxidative stress and the potential for a threshold in han-induced toxicity. However, additional data are needed to substantiate evidence for such a threshold. HANs are readily absorbed from the GI tract and are extensively metabolized. Elimination occurs primarily in urine, as unconjugated one-carbon metabolites. Evidence supports the involvement of mixed function oxidases, the cytochrome P450 enzyme family and GST, in HAN metabolism. Metabolism represents either a detoxification or

  7. Metabolism and disease

    Grodzicker, Terri; Stewart, David J; Stillman, Bruce

    2011-01-01

    ...), cellular, organ system (cardiovascular, bone), and organismal (timing and life span) scales. Diseases impacted by metabolic imbalance or dysregulation that were covered in detail included diabetes, obesity, metabolic syndrome, and cancer...

  8. Metabolic Engineering X Conference

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  9. Altered metabolism in cancer

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  10. Engineering Cellular Metabolism

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  11. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate.

    Ward, Patrick S; Thompson, Craig B

    2012-03-20

    Cancer metabolism has long been equated with aerobic glycolysis, seen by early biochemists as primitive and inefficient. Despite these early beliefs, the metabolic signatures of cancer cells are not passive responses to damaged mitochondria but result from oncogene-directed metabolic reprogramming required to support anabolic growth. Recent evidence suggests that metabolites themselves can be oncogenic by altering cell signaling and blocking cellular differentiation. No longer can cancer-associated alterations in metabolism be viewed as an indirect response to cell proliferation and survival signals. We contend that altered metabolism has attained the status of a core hallmark of cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R.; Jijakli, Kenan; Salehi-Ashtiani, Kourosh

    2014-01-01

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

  13. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R. [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates); Jijakli, Kenan [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates); Engineering Division, Biofinery, Manhattan, KS (United States); Salehi-Ashtiani, Kourosh, E-mail: ksa3@nyu.edu [Division of Science and Math, New York University Abu Dhabi, Abu Dhabi (United Arab Emirates); Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi Institute, Abu Dhabi (United Arab Emirates)

    2014-12-10

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

  14. Drug discovery strategies in the field of tumor energy metabolism: Limitations by metabolic flexibility and metabolic resistance to chemotherapy.

    Amoedo, N D; Obre, E; Rossignol, R

    2017-08-01

    The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro. Such contradictory findings raised several questions concerning the optimization of drug discovery strategies in the field of cancer metabolism. For instance, the cell culture models in 2D or 3D might already show strong limitations to mimic the tumor micro- and macro-environment. The microenvironment of tumors is composed of cancer cells of variegated metabolic profiles, supporting local metabolic exchanges and symbiosis, but also of immune cells and stroma that further interact with and reshape cancer cell metabolism. The macroenvironment includes the different tissues of the organism, capable of exchanging signals and fueling the tumor 'a distance'. Moreover, most metabolic targets were identified from their increased expression in tumor transcriptomic studies, or from targeted analyses looking at the metabolic impact of particular oncogenes or tumor suppressors on selected metabolic pathways. Still, very few targets were identified from in vivo analyses of tumor metabolism in patients because such studies are difficult and adequate imaging methods are only currently being developed for that purpose. For instance, perfusion of patients with [ 13 C]-glucose allows deciphering the metabolomics of tumors and opens a new area in the search for effective targets. Metabolic imaging with positron emission tomography and other techniques that do not involve [ 13 C] can also be used to evaluate tumor

  15. Metabolic Effects of Intermittent Fasting.

    Patterson, Ruth E; Sears, Dorothy D

    2017-08-21

    The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as sleep. If proven to be efficacious, these eating regimens offer promising nonpharmacological approaches to improving health at the population level, with multiple public health benefits.

  16. [Menopause and metabolic syndrome].

    Meirelles, Ricardo M R

    2014-03-01

    The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.

  17. Metabolism and virulence in Neisseria meningitidis

    Christoph eSchoen

    2014-08-01

    Full Text Available A longstanding question in infection biology addresses the genetic basis for invasive behaviour in commensal pathogens. A prime example for such a pathogen is Neisseria meningitidis. On the one hand it is a harmless commensal bacterium exquisitely adapted to humans, and on the other hand it sometimes behaves like a ferocious pathogen causing potentially lethal disease such as sepsis and acute bacterial meningitis. Despite the lack of a classical repertoire of virulence genes in N. meningitidis separating commensal from invasive strains, molecular epidemiology suggests that carriage and invasive strains belong to genetically distinct populations. In recent years, it has become increasingly clear that metabolic adaptation enables meningococci to exploit host resources, supporting the concept of nutritional virulence as a crucial determinant of invasive capability. Here, we discuss the contribution of core metabolic pathways in the context of colonization and invasion with special emphasis on results from genome-wide surveys. The metabolism of lactate, the oxidative stress response, and, in particular, glutathione metabolism as well as the denitrification pathway provide examples of how meningococcal metabolism is intimately linked to pathogenesis. We further discuss evidence from genome-wide approaches regarding potential metabolic differences between strains from hyperinvasive and carriage lineages and present new data assessing in vitro growth differences of strains from these two populations. We hypothesize that strains from carriage and hyperinvasive lineages differ in the expression of regulatory genes involved particularly in stress responses and amino acid metabolism under infection conditions.

  18. Metabolic syndrome and menopause

    Jouyandeh, Zahra; Nayebzadeh, Farnaz; Qorbani, Mostafa; Asadi, Mojgan

    2013-01-01

    Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3) criteria t...

  19. [Regulation of terpene metabolism

    Croteau, R.

    1991-01-01

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target regulatory'' enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C[sub 15]-C[sub 30]) produced by oil glands.

  20. [Metabolic functions and sport].

    Riviere, Daniel

    2004-01-01

    Current epidemiological studies emphasize the increased of metabolic diseases of the adults, such as obesity, type-2 diabetes and metabolic syndromes. Even more worrying is the rising prevalence of obesity in children. It is due more to sedentariness, caused more by inactivity (television, video, games, etc.) than by overeating. Many studies have shown that regular physical activities benefit various bodily functions including metabolism. After dealing with the major benefits of physical exercise on some adult metabolic disorders, we focus on the prime role played by physical activity in combating the public health problem of childhood obesity.

  1. Mathematical modelling of metabolism

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

    Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology....... available. Both stoichiometric and kinetic models have been used to investigate the metabolism, which has resulted in defining the optimal fermentation conditions, as well as in directing the genetic changes to be introduced in order to obtain a good producer strain or cell line. With the increasing...

  2. Famine versus feast: understanding the metabolism of tumors in vivo.

    Mayers, Jared R; Vander Heiden, Matthew G

    2015-03-01

    To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo. Whole-body metabolism and tumor heterogeneity also influence the metabolism of tumor cells, and successful targeting of metabolism for cancer therapy will require an understanding of tumor metabolism in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. [Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus of the Spanish Society of Intensive Care Medicine and Coronary Units-Spanish Society of Parenteral and Enteral Nutrition (SEMICYUC-SENPE): neurocritical patient].

    Acosta Escribano, J; Herrero Meseguer, I; Conejero García-Quijada, R

    2011-11-01

    Neurocritical patients require specialized nutritional support due to their intense catabolism and prolonged fasting. The preferred route of nutrient administration is the gastrointestinal route, especially the gastric route. Alternatives are the transpyloric route or mixed enteral-parenteral nutrition if an effective nutritional volume of more than 60% cannot be obtained. Total calore intake ranges from 20-30 kcal/kg/day, depending on the period of the clinical course, with protein intake higher than 20% of total calories (hyperproteic diet). Nutritional support should be initiated early. The incidence of gastrointestinal complications is generally higher to other critically-ill patients, the most frequent complication being an increase in gastric residual volume. As in other critically-ill patients, glycemia should be closely monitored and maintained below 150 mg/dL. Copyright © 2011 Sociedad Española de Medicina Intensiva, Critica y Unidades Coronarias (SEMICYUC) and Elsevier España, S.L. All rights reserved.

  4. Fluoroacetylcarnitine: metabolism and metabolic effects in mitochondria

    Bremer, J; Davis, E J

    1973-01-01

    The metabolism and metabolic effects of fluoroacetylcarnitine have been investigated. Carnitineacetyltransferase transfers the fluoro-acetyl group of fluoroacetylcarnitine nearly as rapidly to CoA as the acetyl group of acetylcarnitine. Fluorocitrate is then formed by citrate synthase, but this second reaction is relatively slow. The fluorocitrate formed intramitochondrially inhibits the metabolism of citrate. In heart and skeletal muscle mitochondria the accumulated citrate inhibits citrate synthesis and the ..beta..-oxidation of fatty acids. Free acetate is formed, presumably because accumulated acetyl-CoA is hydrolyzed. In liver mitochondria the accumulation of citrate leads to a relatively increased rate of ketogenesis. Increased ketogenesis is obtained also upon the addition of citrate to the reaction mixture.

  5. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pha...

  6. Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate

    Ward, Patrick S.; Thompson, Craig B.

    2012-01-01

    Cancer metabolism has long been equated with aerobic glycolysis, seen by early biochemists as primitive and inefficient. Despite these early beliefs, the metabolic signatures of cancer cells are not passive responses to damaged mitochondria, but result from oncogene-directed metabolic reprogramming required to support anabolic growth. Recent evidence suggests that metabolites themselves can be oncogenic by altering cell signaling and blocking cellular differentiation. No longer can cancer-ass...

  7. Tech Support.

    Beem, Kate

    2002-01-01

    Discusses technology-support issues, including staff training, cost, and outsourcing. Describes how various school districts manage technology-support services. Features the Technology Support Index, developed by the International Society for Technology in Education, to gauge the operation of school district technology-support programs. (PKP)

  8. Fatty acid metabolism: target for metabolic syndrome

    Wakil, Salih J.; Abu-Elheiga, Lutfi A.

    2009-01-01

    Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They...

  9. Gout and Metabolic Syndrome: a Tangled Web.

    Thottam, Gabrielle E; Krasnokutsky, Svetlana; Pillinger, Michael H

    2017-08-26

    The complexity of gout continues to unravel with each new investigation. Gout sits at the intersection of multiple intrinsically complex processes, and its prevalence, impact on healthcare costs, and association with important co-morbidities make it increasingly relevant. The association between gout and type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease, renal disease, and obesity suggest that either gout, or its necessary precursor hyperuricemia, may play an important role in the manifestations of the metabolic syndrome. In this review, we analyze the complex interconnections between gout and metabolic syndrome, by reviewing gout's physiologic and epidemiologic relationships with its major co-morbidities. Increasing evidence supports gout's association with metabolic syndrome. More specifically, both human studies and animal models suggest that hyperuricemia may play a role in promoting inflammation, hypertension and cardiovascular disease, adipogenesis and lipogenesis, insulin and glucose dysregulation, and liver disease. Fructose ingestion is associated with increased rates of hypertension, weight gain, impaired glucose tolerance, and dyslipidemia and is a key driver of urate biosynthesis. AMP kinase (AMPK) is a central regulator of processes that tend to mitigate against the metabolic syndrome. Within hepatocytes, leukocytes, and other cells, a fructose/urate metabolic loop drives key inhibitors of AMPK, including AMP deaminase and fructokinase, that may tilt the balance toward metabolic syndrome progression. Preliminary evidence suggests that agents that block the intracellular synthesis of urate may restore AMPK activity and help maintain metabolic homeostasis. Gout is both an inflammatory and a metabolic disease. With further investigation of urate's role, the possibility of proper gout management additionally mitigating metabolic syndrome is an evolving and important question.

  10. Gastric emptying, glucose metabolism and gut hormones

    Vermeulen, Mechteld A R; Richir, Milan C; Garretsen, Martijn K

    2011-01-01

    To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant and carb......To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant...... and carbohydrate content. However, gastric emptying of fluids is influenced by its nutrient composition; hence, safety of preoperative carbohydrate loading should be confirmed. Because gut hormones link carbohydrate metabolism and gastric emptying, hormonal responses were studied....

  11. Investigation of metabolic encephalopathy

    cycle defects is the X-linked recessive disorder, ornithine ... life, or if the child is fed the compounds that they are unable .... as learning difficulties, drowsiness and avoidance of ... Table 2. Laboratory investigation of suspected metabolic encephalopathy. Laboratory .... Clinical approach to treatable inborn metabolic diseases:.

  12. Metabolic regulation of inflammation.

    Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

    2017-05-01

    Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

  13. Metabolic syndrome and menopause

    Jouyandeh Zahra

    2013-01-01

    Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

  14. The Hunger Games: p53 regulates metabolism upon serine starvation.

    Tavana, Omid; Gu, Wei

    2013-02-05

    Cancer cells reprogram their metabolism to support a high proliferative rate. A new study shows that, upon serine starvation, the tumor suppressor p53 activates p21 to shift metabolic flux from purine biosynthesis to glutathione production, which enhances cellular proliferation and viability by combating ROS (Maddocks et al., 2013). Copyright © 2013 Elsevier Inc. All rights reserved.

  15. The role of gut microbiota in human metabolism

    Vrieze, A.

    2013-01-01

    This thesis supports the hypothesis that gut microbiota can be viewed as an ‘exteriorised organ’ that contributes to energy metabolism and the modulation of our immune system. Following Koch’s postulates, it has now been shown that gut microbiota are associated with metabolic disease and that these

  16. Drug metabolism in birds

    Pan, Huo Ping; Fouts, James R.

    1979-01-01

    Papers published over 100 years since the beginning of the scientific study of drug metabolism in birds were reviewed. Birds were found to be able to accomplish more than 20 general biotransformation reactions in both functionalization and conjugation. Chickens were the primary subject of study but over 30 species of birds were used. Large species differences in drug metabolism exist between birds and mammals as well as between various birds, these differences were mostly quantitative. Qualitative differences were rare. On the whole, drug metabolism studies in birds have been neglected as compared with similar studies on insects and mammals. The uniqueness of birds and the advantages of using birds in drug metabolism studies are discussed. Possible future studies of drug metabolism in birds are recommended.

  17. Metabolic imaging using SPECT

    Taki, Junichi; Matsunari, Ichiro

    2007-01-01

    In normal condition, the heart obtains more than two-thirds of its energy from the oxidative metabolism of long chain fatty acids, although a wide variety of substrates such as glucose, lactate, ketone bodies and amino acids are also utilised. In ischaemic myocardium, on the other hand, oxidative metabolism of free fatty acid is suppressed and anaerobic glucose metabolism plays a major role in residual oxidative metabolism. Therefore, metabolic imaging can be an important technique for the assessment of various cardiac diseases and conditions. In SPECT, several iodinated fatty acid traces have been introduced and studied. Of these, 123 I-labelled 15-(p-iodophenyl)3-R, S-methylpentadecanoic acid (BMIPP) has been the most commonly used tracer in clinical studies, especially in some of the European countries and Japan. In this review article, several fatty acid tracers for SPECT are characterised, and the mechanism of uptake and clinical utility of BMIPP are discussed in detail. (orig.)

  18. Mycobacterium tuberculosis Metabolism

    Warner, Digby F.

    2015-01-01

    Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host–pathogen interaction through modulation of metabolic functions. PMID:25502746

  19. Metabolic Engineering VII Conference

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  20. Metabolic imaging using PET

    Kudo, Takashi

    2007-01-01

    There is growing evidence that myocardial metabolism plays a key role not only in ischaemic heart disease but also in a variety of diseases which involve myocardium globally, such as heart failure and diabetes mellitus. Understanding myocardial metabolism in such diseases helps to elucidate the pathophysiology and assists in making therapeutic decisions. As well as providing information on regional changes, PET can deliver quantitative information about both regional and global changes in metabolism. This capability of quantitative measurement is one of the major advantages of PET along with physiological positron tracers, especially relevant in evaluating diseases which involve the whole myocardium. This review discusses major PET tracers for metabolic imaging and their clinical applications and contributions to research regarding ischaemic heart disease and other diseases such as heart failure and diabetic heart disease. Future applications of positron metabolic tracers for the detection of vulnerable plaque are also highlighted briefly. (orig.)

  1. Metabolic costs of hybridization in newts

    Gvoždík, Lumír

    2012-01-01

    Roč. 61, 3-4 (2012), s. 197-201 ISSN 0139-7893 R&D Projects: GA ČR GAP506/10/2170; GA MŠk LC06073 Institutional support: RVO:68081766 Keywords : oxygen consumption * energetic metabolism * hybrids * Triturus * amphibians * mitonuclear interactions * reproductive barriers Subject RIV: EG - Zoology Impact factor: 0.494, year: 2012

  2. The energy metabolism of megacities

    Facchini, Angelo; Kennedy, Chris; Stewart, Iain; Mele, Renata

    2017-01-01

    Highlights: • Energy metabolism leads to a better management of energy use in megacities. • Insights on strategies to improve energy efficiency and reduce resource consumption. • We find a regionalization of energy flows and sectoral energy use. • Scaling law for energy Vs density suggests strategies for compact cities planning. • Supports development of models to reduce GHG emissions and increase resilience. - Abstract: Due to their sheer size and complexity, megacities are extreme examples in which both negative and positive aspects of urbanization co-exist and are amplified. Especially in emerging countries they are becoming the dominant paradigm of the future urbanization, representing a sustainability challenge both from the point of view of energy and resource consumption, and from the point of view of climate change adaptation and mitigation. In this paper we compare the energy metabolism in 27 of the world’s megacities including details of mobile and stationary energy consumption patterns, fuels used, as well as end-use patterns and electricity generation mix. Our results show that per capita total energy consumption scales with urban population density according to a power law characterized by the universal −3/4 scaling, pointing out that compact cities are more energy efficient with respect to dispersed cities. By comparing energy sources and sectoral end use, also focusing on electricity use and generation source, we found a significant regionalization of energy metabolism, and we discuss the implication for resilience, infrastructure planning, GHG emissions, and policies for infrastructure decarbonization. The comparison of the energy metabolism can lead to a more appropriate management of energy use patterns and electricity generation mix in megacities, giving insights on strategies to improve urban energy efficiency and reducing environmental pressure of megacities.

  3. Signaling Pathways Regulating Redox Balance in Cancer Metabolism.

    De Santis, Maria Chiara; Porporato, Paolo Ettore; Martini, Miriam; Morandi, Andrea

    2018-01-01

    The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells' demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions.

  4. Nutritional Support

    Nutritional support is therapy for people who cannot get enough nourishment by eating or drinking. You may need ... absorb nutrients through your digestive system You receive nutritional support through a needle or catheter placed in your ...

  5. SBOLme: a Repository of SBOL Parts for Metabolic Engineering

    Kuwahara, Hiroyuki; Cui, Xuefeng; Umarov, Ramzan; Grunberg, Raik; Myers, Chris J.; Gao, Xin

    2017-01-01

    The Synthetic Biology Open Language (SBOL) is a community-driven open language to promote standardization in synthetic biology. To support the use of SBOL in metabolic engineering, we developed SBOLme, the first open-access repository of SBOL 2

  6. Lipoprotein metabolism indicators improve cardiovascular risk prediction.

    Daniël B van Schalkwijk

    Full Text Available BACKGROUND: Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to investigate whether lipoprotein metabolism indicators can improve cardiovascular risk prediction and therapy management. METHODS AND RESULTS: We calculated lipoprotein metabolism indicators for 1981 subjects (145 cases, 1836 controls from the Framingham Heart Study offspring cohort in which NMR lipoprotein profiles were measured. We applied a statistical learning algorithm using a support vector machine to select conventional risk factors and lipoprotein metabolism indicators that contributed to predicting risk for general cardiovascular disease. Risk prediction was quantified by the change in the Area-Under-the-ROC-Curve (ΔAUC and by risk reclassification (Net Reclassification Improvement (NRI and Integrated Discrimination Improvement (IDI. Two VLDL lipoprotein metabolism indicators (VLDLE and VLDLH improved cardiovascular risk prediction. We added these indicators to a multivariate model with the best performing conventional risk markers. Our method significantly improved both CVD prediction and risk reclassification. CONCLUSIONS: Two calculated VLDL metabolism indicators significantly improved cardiovascular risk prediction. These indicators may help to reduce prescription of unnecessary cholesterol-lowering medication, reducing costs and possible side-effects. For clinical application, further validation is required.

  7. Metabolic disorders in menopause

    Grzegorz Stachowiak

    2015-04-01

    Full Text Available Metabolic disorders occurring in menopause, including dyslipidemia, disorders of carbohydrate metabolism (impaired glucose tolerance – IGT, type 2 diabetes mellitus – T2DM or components of metabolic syndrome, constitute risk factors for cardiovascular disease in women. A key role could be played here by hyperinsulinemia, insulin resistance and visceral obesity, all contributing to dyslipidemia, oxidative stress, inflammation, alter coagulation and atherosclerosis observed during the menopausal period. Undiagnosed and untreated, metabolic disorders may adversely affect the length and quality of women’s life. Prevention and treatment preceded by early diagnosis should be the main goal for the physicians involved in menopausal care. This article represents a short review of the current knowledge concerning metabolic disorders (e.g. obesity, polycystic ovary syndrome or thyroid diseases in menopause, including the role of a tailored menopausal hormone therapy (HT. According to current data, HT is not recommend as a preventive strategy for metabolic disorders in menopause. Nevertheless, as part of a comprehensive strategy to prevent chronic diseases after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered (after balancing benefits/risks and excluding women with absolute contraindications to this therapy. Life-style modifications, with moderate physical activity and healthy diet at the forefront, should be still the first choice recommendation for all patients with menopausal metabolic abnormalities.

  8. Metabolic Diet App Suite for inborn errors of amino acid metabolism.

    Ho, Gloria; Ueda, Keiko; Houben, Roderick F A; Joa, Jeff; Giezen, Alette; Cheng, Barbara; van Karnebeek, Clara D M

    2016-03-01

    An increasing number of rare inborn errors of metabolism (IEMs) are amenable to targeted metabolic nutrition therapy. Daily adherence is important to attain metabolic control and prevent organ damage. This is challenging however, given the lack of information of disorder specific nutrient content of foods, the limited availability and cost of specialty products as well as difficulties in reliable calculation and tracking of dietary intake and targets. To develop apps for all inborn errors of amino acid metabolism for which the mainstay of treatment is a medical diet, and obtain patient and family feedback throughout the process to incorporate this into subsequent versions. The Metabolic Diet App Suite was created with input from health care professionals as a free, user-friendly, online tool for both mobile devices and desktop computers (http://www.metabolicdietapp.org) for 15 different IEMs. General information is provided for each IEM with links to useful online resources. Nutrient information is based on the MetabolicPro™, a North American food database compiled by the Genetic Metabolic Dietitians International (GMDI) Technology committee. After user registration, a personalized dashboard and management plan including specific nutrient goals are created. Each Diet App has a user-friendly interface and the functions include: nutrient intake counts, adding your own foods and homemade recipes and, managing a daily food diary. Patient and family feedback was overall positive and specific suggestions were used to further improve the App Suite. The Metabolic Diet App Suite aids individuals affected by IEMs to track and plan their meals. Future research should evaluate its impact on patient adherence, metabolic control, quality of life and health-related outcomes. The Suite will be updated and expanded to Apps for other categories of IEMs. Finally, this Suite is a support tool only, and does not replace medical/metabolic nutrition professional advice. Copyright

  9. Human Body Exergy Metabolism

    Mady, Carlos Eduardo Keutenedjian

    2013-01-01

    The exergy analysis of the human body is a tool that can provide indicators of health and life quality. To perform the exergy balance it is necessary to calculate the metabolism on an exergy basis, or metabolic exergy, although there is not yet consensus in its calculation procedure. Hence, the aim of this work is to provide a general method to evaluate this physical quantity for human body based on indirect calorimetry data. To calculate the metabolism on an exergy basis it is necessary to d...

  10. Hypothalamic control of energy and glucose metabolism.

    Sisley, Stephanie; Sandoval, Darleen

    2011-09-01

    The central nervous system (CNS), generally accepted to regulate energy homeostasis, has been implicated in the metabolic perturbations that either cause or are associated with obesity. Normally, the CNS receives hormonal, metabolic, and neuronal input to assure adequate energy levels and maintain stable energy homeostasis. Recent evidence also supports that the CNS uses these same inputs to regulate glucose homeostasis and this aspect of CNS regulation also becomes impaired in the face of dietary-induced obesity. This review focuses on the literature surrounding hypothalamic regulation of energy and glucose homeostasis and discusses how dysregulation of this system may contribute to obesity and T2DM.

  11. Supporting Families to Support Students

    Kelly, John; Rossen, Eric; Cowan, Katherine C.

    2018-01-01

    Collaboration between students' families and the school is an essential component to promoting student mental and behavioral health. Many schools structure their mental health services using a Multi-Tiered System of Supports that offers three different tiers of support from universal supports to personalized help for students with serious…

  12. What is Nutrition & Metabolism?

    Feinman Richard D

    2004-08-01

    Full Text Available Abstract A new Open Access journal, Nutrition & Metabolism (N&M will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.

  13. Epigenetics and Cellular Metabolism

    Wenyi Xu

    2016-01-01

    Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

  14. Amino Acid Metabolism Disorders

    ... this process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form ...

  15. The metabolic radiotherapy

    Begon, F.; Gaci, M.

    1993-01-01

    In this article, the authors recall the principles of the metabolic radiotherapy and present these main applications in the treatment of thyroid cancers, hyperthyroidism, polycythemia, arthritis, bone metastases, adrenergic neoplasms. They also present the radioimmunotherapy

  16. Engineering of metabolic control

    Liao, James C.

    2004-03-16

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  17. Oxidative metabolism in muscle.

    Ferrari, M; Binzoni, T; Quaresima, V

    1997-01-01

    Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantage...

  18. Tumor Macroenvironment and Metabolism

    Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S.; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-01-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organ...

  19. It must be my metabolism: Metabolic control of mind

    Dana M Small

    2014-07-01

    participant ingested the same caloric dose during conditioning, changes in plasma glucose depended upon individual differences in glucose absorption/metabolism. Therefore, these findings provide indirect, and yet convincing, support for our hypothesis that glucose metabolism regulates response to calorie-predictive flavors in brain reward circuits. We can therefore conclude that, at least for carbohydrates, responses to calorie predictive food cues reflect the learned association between the cue and its ability to result in a change in blood glucose. This finding has important implications for understanding how the modern food environment promotes weight gain. Carbohydrates now come in forms and doses not experienced during our evolutionary past. Not only are calories increased, but the way in which they are metabolized differs. For example, calories ingested in liquid form are trafficked through the gut faster than solids (e.g. 18. Might this influence metabolic regulation of reward circuits? Certainly it stands to reason that larger loads delivered more quickly to the circulation might increase the metabolic impact and hence more efficiently engage reward circuits to enhance food cue reactivity and promote eating in the absence of hunger. In summary, our result indicates that, as in the rodent model, metabolic response drives the reinforcement potency of carbohydrates and regulates food cue reactivity. We conclude that not only are modern foods more caloric, but in addition their increased metabolic impact drives reward circuits and may therefore promote intake by enhancing food cue reactivity. Our finding further suggests that metabolic regulation of reward circuits may differ in individuals with altered glucose metabolism, such as type II diabetes, offering a potential mechanism by which they become susceptible to weight gain.

  20. Ca-48 metabolism studies

    Van der Merwe, D.G.

    1987-03-01

    Calcium metabolism has been studied in depth physiologically and is a relatively well-understood element in biochemistry and medicine. There is still only restricted knowledge of the metabolic fate of calcium in normal and abnormal paediatric subjects. The latter is partially owing to inadequate techniques for tracing and modelling calcium pathways in children. The advent of radioactive tracers has unquestionably enhanced medical research and improved the quality of many metabolic studies. The present study was aimed at the development, promotion and justification of a new tracer technique using the stable isotope, calcium-48. The obvious advantages of such a technique are its harmlessness tothe subject, its applicability to both short- and long-term studies as well as its usefulness to the study for which it was originally motivated, viz research defining the actual relationship between a calcium-deficient diet and the occurrence of rickets in rural Black children in South Africa. Exploratory instrumental analyses were performed specifically with serum samples. This proved successful enough to develop a less specific pre-concentration technique which improved the sensitivity and reduces the cost of doing calcium-48 metabolism studies. The results of a simple metabolic study are presented whereby the scope of the technique is demonstrated in a real situation. The possibilities and limitations of double-isotope metabolic studies are discussed, particularly with regard to strontium as the second tracer

  1. Roadway supports

    Stassen, P

    1980-01-01

    Support systems in stone drifts and tunnels are discussed. Timber supports, steel arches, cold-bent sheet-metal arches, shotcrete and combined support arrangements are described. Brickwork and reinforced concrete are also covered. Supports in roadways leading to the face and in-seam roads are discussed including timber supports, steel arches, articulated arches on timber chocks, support accessories and the withdrawal and reshaping of arches. The subject of strata bolting, the aims of strata bolting, methods of strata bolting, systems of rock-bolting, end plates and wire mesh, and bolt and anchorage monitoring are also discussed. Injection techniques, injection parameters, injection methods, grouts, includes an example of the application of injection techniques are covered and combined injection/dowelling arrangements are examined. (55 refs.) (In French)

  2. LakeMetabolizer: An R package for estimating lake metabolism from free-water oxygen using diverse statistical models

    Winslow, Luke; Zwart, Jacob A.; Batt, Ryan D.; Dugan, Hilary; Woolway, R. Iestyn; Corman, Jessica; Hanson, Paul C.; Read, Jordan S.

    2016-01-01

    Metabolism is a fundamental process in ecosystems that crosses multiple scales of organization from individual organisms to whole ecosystems. To improve sharing and reuse of published metabolism models, we developed LakeMetabolizer, an R package for estimating lake metabolism from in situ time series of dissolved oxygen, water temperature, and, optionally, additional environmental variables. LakeMetabolizer implements 5 different metabolism models with diverse statistical underpinnings: bookkeeping, ordinary least squares, maximum likelihood, Kalman filter, and Bayesian. Each of these 5 metabolism models can be combined with 1 of 7 models for computing the coefficient of gas exchange across the air–water interface (k). LakeMetabolizer also features a variety of supporting functions that compute conversions and implement calculations commonly applied to raw data prior to estimating metabolism (e.g., oxygen saturation and optical conversion models). These tools have been organized into an R package that contains example data, example use-cases, and function documentation. The release package version is available on the Comprehensive R Archive Network (CRAN), and the full open-source GPL-licensed code is freely available for examination and extension online. With this unified, open-source, and freely available package, we hope to improve access and facilitate the application of metabolism in studies and management of lentic ecosystems.

  3. Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes.

    Allison, Katrina E; Coomber, Brenda L; Bridle, Byram W

    2017-10-01

    Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and up-regulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system. Immune checkpoint blockade provides an example of how metabolism can be differentially impacted to impair cancer cells but support T cells. Implications for research with metabolic inhibitors are discussed. © 2017 John Wiley & Sons Ltd.

  4. Melatonin, mitochondria, and the metabolic syndrome.

    Cardinali, Daniel P; Vigo, Daniel E

    2017-11-01

    A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.

  5. 胃癌术后肠内营养支持对患者人体成分及能量代谢变化的影响%Patients with gastric cancer postoperative enteral nutrition support on body composition and the change of energy metabolism

    李雪娇; 黄迎春; 彭南海; 刘思彤

    2015-01-01

    Objective: To investigate the effect of enteral nutrition support on the changes of body element and energy metabolism in patients with gastric cancer after operation.Methods:Prospective selected from 182 cases of postoperative patients with gastric cancer, including 140 patients accept enteral nutrition and related nursing care before discharge and 42 patients who did not receive enteral nutrition support from February 2013 to July 2015. Two groups of patients atfer surgery followed up by the nutritional support of nursing team, and use the human body composition analyzer and indirect energy metabolism instrument measuring body composition, observed and compared patients after accept nutrition support their muscle, body fat, protein, weight, BMI changes. Results:Atfer 3 months of enteral nutrition support, treatment group to check the patients’ weight, BMI, skeletal muscle, protein, body cell mass (BCM), intracellular water (ICW) is significantly higher than before enteral nutrition therapy, patients with edema degree reduced, the difference was statistically significant (P0.05); 140 cases receiving enteral nutrition support after gastric cancer patients with no after nutritional support treatment of 42 cases of postoperative gastric cancer patients compared, its weight, skeletal muscle, protein, around the upper arm (AC), upper arm around fat-free (AMC) significantly less high nutritional support group, the difference was statistically significant (P0.05).Conclusion: Atfer 3 months of enteral nutrition support, postoperative gastric cancer patients of energy metabolism and body composition than before treatment signiifcantly were improved.%目的:了解肠内营养支持治疗对胃癌术后患者人体成份变化及能量代谢的影响。方法:前瞻性选取2013年2月至2015年7月南京军区南京总医院收治的182例胃癌术后患者,其中140例患者于出院前开始对其实施肠内营养及相关护理,42例患者未接受肠内营

  6. Relationship among social support, treatment adherence and metabolic control of diabetes mellitus patients Relación entre apoyo social, adhesión al tratamiento y control metabólico de personas con Diabetes Mellitus Relação entre apoio social, adesão aos tratamentos e controle metabólico de pessoas com diabetes mellitus

    Lilian Cristiane Gomes-Villas Boas

    2012-02-01

    Full Text Available This cross-sectional and quantitative study aimed to analyze the relationship among social support, adherence to non-pharmacological (diet and physical exercise and pharmacological treatments (insulin and/or oral anti-diabetic medication and clinical and metabolic control of 162 type 2 diabetes mellitus patients. Data were collected through instruments validated for Brazil. Social support was directly correlated with treatment adherence. Adherence to non-pharmacological treatment was inversely correlated with body mass index, and medication adherence was inversely correlated with diastolic blood pressure. There were no associations between social support and clinical and metabolic control variables. Findings indicate that social support can be useful to achieve treatment adherence. Studies with other designs should be developed to broaden the analysis of relations between social support and other variables.El presente estudio objetivó analizar la relación entre apoyo social, adhesión a los tratamientos no medicamentoso (dieta y ejercicio físico y medicamentoso(insulina y/o antidiabéticos orales y control clínico-metabólico de 162 personas con diabetes mellitus tipo 2. Se trata de un estudio seccional, de abordaje cuantitativo. Los datos fueron recolectados por medio de instrumentos validados. El apoyo social tuvo correlación directa con la adhesión al tratamiento. Se observó correlación inversa entre adhesión al tratamiento no medicamentoso y índice de masa corporal, así como entre adhesión medicamentosa y presión arterial diastólica. No hubo asociaciones entre apoyo social y variables de control clínico-metabólico. Se concluye que el apoyo social podrá ser útil para obtener la adhesión a los tratamientos. Estudios con otros delineamientos deben ser desarrollados, a fin de ampliar el análisis de las relaciones entre apoyo social y otras variables.O presente estudo objetivou analisar a relação entre apoio social, ades

  7. Vertigo and metabolic disorders.

    Santos, Maruska D' Aparecida; Bittar, Roseli Saraiva Moreira

    2012-01-01

    Metabolic disorders are accepted by many authors as being responsible for balance disorders. Because of the importance of metabolic disorders in the field of labyrinthine dysfunction, we decided to assess the prevalence of carbohydrates, lipids and thyroid hormones disorders in our patients with vestibular diseases. The study evaluates the metabolic profile of 325 patients with vertigo who sought the Otolaryngology Department of the University of São Paulo in the Hospital das Clínicas da Universidade de São Paulo. The laboratory tests ordered according to the classical research protocol were: low-density lipoprotein cholesterol fraction, TSH, T3, T4 and fasting blood sugar level. The metabolic disorders found and the ones that were observed in the general population were compared. The high level of low-density lipoprotein cholesterol, the altered levels of thyroid hormones, the higher prevalence of diabetes mellitus were the most significant changes found in the group of study. The higher amount of metabolic disorders in patients with vertigo disease reinforces the hypothesis of its influence on the etiopathogenesis of cochleovestibular symptoms.

  8. Metabolic surgery: quo vadis?

    Ramos-Leví, Ana M; Rubio Herrera, Miguel A

    2014-01-01

    The impact of bariatric surgery beyond its effect on weight loss has entailed a change in the way of regarding it. The term metabolic surgery has become more popular to designate those interventions that aim at resolving diseases that have been traditionally considered as of exclusive medical management, such as type 2 diabetes mellitus (T2D). Recommendations for metabolic surgery have been largely addressed and discussed in worldwide meetings, but no definitive consensus has been reached yet. Rates of diabetes remission after metabolic surgery have been one of the most debated hot topics, with heterogeneity being a current concern. This review aims to identify and clarify controversies regarding metabolic surgery, by focusing on a critical analysis of T2D remission rates achieved with different bariatric procedures, and using different criteria for its definition. Indications for metabolic surgery for patients with T2D who are not morbidly obese are also discussed. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  9. Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health

    Ribas-Latre, Aleix; Eckel-Mahan, Kristin

    2016-01-01

    Background While additional research is needed, a number of large epidemiological studies show an association between circadian disruption and metabolic disorders. Specifically, obesity, insulin resistance, cardiovascular disease, and other signs of metabolic syndrome all have been linked to circadian disruption in humans. Studies in other species support this association and generally reveal that feeding that is not in phase with the external light/dark cycle, as often occurs with night or rotating shift workers, is disadvantageous in terms of energy balance. As food is a strong driver of circadian rhythms in the periphery, understanding how nutrient metabolism drives clocks across the body is important for dissecting out why circadian misalignment may produce such metabolic effects. A number of circadian clock proteins as well as their accessory proteins (such as nuclear receptors) are highly sensitive to nutrient metabolism. Macronutrients and micronutrients can function as zeitgebers for the clock in a tissue-specific way and can thus impair synchrony between clocks across the body, or potentially restore synchrony in the case of circadian misalignment. Circadian nuclear receptors are particularly sensitive to nutrient metabolism and can alter tissue-specific rhythms in response to changes in the diet. Finally, SNPs in human clock genes appear to be correlated with diet-specific responses and along with chronotype eventually may provide valuable information from a clinical perspective on how to use diet and nutrition to treat metabolic disorders. Scope of review This article presents a background of the circadian clock components and their interrelated metabolic and transcriptional feedback loops, followed by a review of some recent studies in humans and rodents that address the effects of nutrient metabolism on the circadian clock and vice versa. We focus on studies in which results suggest that nutrients provide an opportunity to restore or, alternatively

  10. Neuron-glia metabolic coupling and plasticity.

    Magistretti, Pierre J

    2006-06-01

    The coupling between synaptic activity and glucose utilization (neurometabolic coupling) is a central physiological principle of brain function that has provided the basis for 2-deoxyglucose-based functional imaging with positron emission tomography (PET). Astrocytes play a central role in neurometabolic coupling, and the basic mechanism involves glutamate-stimulated aerobic glycolysis; the sodium-coupled reuptake of glutamate by astrocytes and the ensuing activation of the Na-K-ATPase triggers glucose uptake and processing via glycolysis, resulting in the release of lactate from astrocytes. Lactate can then contribute to the activity-dependent fuelling of the neuronal energy demands associated with synaptic transmission. An operational model, the 'astrocyte-neuron lactate shuttle', is supported experimentally by a large body of evidence, which provides a molecular and cellular basis for interpreting data obtained from functional brain imaging studies. In addition, this neuron-glia metabolic coupling undergoes plastic adaptations in parallel with adaptive mechanisms that characterize synaptic plasticity. Thus, distinct subregions of the hippocampus are metabolically active at different time points during spatial learning tasks, suggesting that a type of metabolic plasticity, involving by definition neuron-glia coupling, occurs during learning. In addition, marked variations in the expression of genes involved in glial glycogen metabolism are observed during the sleep-wake cycle, with in particular a marked induction of expression of the gene encoding for protein targeting to glycogen (PTG) following sleep deprivation. These data suggest that glial metabolic plasticity is likely to be concomitant with synaptic plasticity.

  11. Constraining Genome-Scale Models to Represent the Bow Tie Structure of Metabolism for 13C Metabolic Flux Analysis

    Tyler W. H. Backman

    2018-01-01

    Full Text Available Determination of internal metabolic fluxes is crucial for fundamental and applied biology because they map how carbon and electrons flow through metabolism to enable cell function. 13 C Metabolic Flux Analysis ( 13 C MFA and Two-Scale 13 C Metabolic Flux Analysis (2S- 13 C MFA are two techniques used to determine such fluxes. Both operate on the simplifying approximation that metabolic flux from peripheral metabolism into central “core” carbon metabolism is minimal, and can be omitted when modeling isotopic labeling in core metabolism. The validity of this “two-scale” or “bow tie” approximation is supported both by the ability to accurately model experimental isotopic labeling data, and by experimentally verified metabolic engineering predictions using these methods. However, the boundaries of core metabolism that satisfy this approximation can vary across species, and across cell culture conditions. Here, we present a set of algorithms that (1 systematically calculate flux bounds for any specified “core” of a genome-scale model so as to satisfy the bow tie approximation and (2 automatically identify an updated set of core reactions that can satisfy this approximation more efficiently. First, we leverage linear programming to simultaneously identify the lowest fluxes from peripheral metabolism into core metabolism compatible with the observed growth rate and extracellular metabolite exchange fluxes. Second, we use Simulated Annealing to identify an updated set of core reactions that allow for a minimum of fluxes into core metabolism to satisfy these experimental constraints. Together, these methods accelerate and automate the identification of a biologically reasonable set of core reactions for use with 13 C MFA or 2S- 13 C MFA, as well as provide for a substantially lower set of flux bounds for fluxes into the core as compared with previous methods. We provide an open source Python implementation of these algorithms at https://github.com/JBEI/limitfluxtocore.

  12. Flux Balance Analysis of Cyanobacterial Metabolism.The Metabolic Network of Synechocystis sp. PCC 6803

    Knoop, H.; Gründel, M.; Zilliges, Y.; Lehmann, R.; Hoffmann, S.; Lockau, W.; Steuer, Ralf

    2013-01-01

    Roč. 9, č. 6 (2013), e1003081-e1003081 ISSN 1553-7358 R&D Projects: GA MŠk(CZ) EE2.3.20.0256 Institutional support: RVO:67179843 Keywords : SP STRAIN PCC-6803 * SP ATCC 51142 * photoautotrophic metabolism * anacystis-nidulans * reconstructions * pathway * plants * models * growth Subject RIV: EI - Biotechnology ; Bionics Impact factor: 4.829, year: 2013

  13. Metabolism of phencyclidine

    Hoag, M.K.P.

    1987-01-01

    Phencyclidine (PCP) is a drug of abuse which may produce, in some users, a persistent schizophreniform psychosis. The possibility that long term effects of PCP are mediated by metabolic activation of the parent compound to reactive species is consistent with the demonstration of metabolism-dependent covalent binding of radiolabeled PCP in vivo and in vitro to macromolecules in rodent lung, liver, and kidney. Formation of the electrophilic iminium ion metabolite of PCP is believed to be critical for covalent binding since binding was inhibited by cyanide ion at concentrations which did not inhibit metabolism of PCP but did trap the iminium ion to form the corresponding alpha-aminonitrile. The present studies were designed to characterize further the biological fate of PCP by identifying possible macromolecular targets of the reactive metabolite(s)

  14. Supporting Information

    U.S. Environmental Protection Agency — This is the supporting information for the journal article. This dataset is associated with the following publication: Rankin, K., S. Mabury, T. Jenkins, and J....

  15. Supporting Info

    U.S. Environmental Protection Agency — Supporting Info. This dataset is associated with the following publication: Washington , J., and T. Jenkins. Abiotic Hydrolysis of Fluorotelomer-Based Polymers as a...

  16. Supporting Info

    U.S. Environmental Protection Agency — Supporting Information. This dataset is associated with the following publication: Washington , J., T. Jenkins, and E. Weber. Identification of Unsaturated and 2H...

  17. Triglyceride metabolism in exercising muscle.

    Watt, Matthew J; Cheng, Yunsheng

    2017-10-01

    Triglycerides are stored within lipid droplets in skeletal muscle and can be hydrolyzed to produce fatty acids for energy production through β-oxidation and oxidative phosphorylation. While there was some controversy regarding the quantitative importance of intramyocellular triglyceride (IMTG) as a metabolic substrate, recent advances in proton magnetic resonance spectroscopy and confocal microscopy support earlier tracer and biopsy studies demonstrating a substantial contribution of IMTG to energy production, particularly during moderate-intensity endurance exercise. This review provides an update on the understanding of IMTG utilization during exercise, with a focus on describing the key regulatory proteins that control IMTG breakdown and how these proteins respond to acute exercise and in the adaptation to exercise training. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Urea metabolism in plants.

    Witte, Claus-Peter

    2011-03-01

    Urea is a plant metabolite derived either from root uptake or from catabolism of arginine by arginase. In agriculture, urea is intensively used as a nitrogen fertilizer. Urea nitrogen enters the plant either directly, or in the form of ammonium or nitrate after urea degradation by soil microbes. In recent years various molecular players of plant urea metabolism have been investigated: active and passive urea transporters, the nickel metalloenzyme urease catalyzing the hydrolysis of urea, and three urease accessory proteins involved in the complex activation of urease. The degradation of ureides derived from purine breakdown has long been discussed as a possible additional metabolic source for urea, but an enzymatic route for the complete hydrolysis of ureides without a urea intermediate has recently been described for Arabidopsis thaliana. This review focuses on the proteins involved in plant urea metabolism and the metabolic sources of urea but also addresses open questions regarding plant urea metabolism in a physiological and agricultural context. The contribution of plant urea uptake and metabolism to fertilizer urea usage in crop production is still not investigated although globally more than half of all nitrogen fertilizer is applied to crops in the form of urea. Nitrogen use efficiency in crop production is generally well below 50% resulting in economical losses and creating ecological problems like groundwater pollution and emission of nitric oxides that can damage the ozone layer and function as greenhouse gasses. Biotechnological approaches to improve fertilizer urea usage bear the potential to increase crop nitrogen use efficiency. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  19. Nitrile Metabolizing Yeasts

    Bhalla, Tek Chand; Sharma, Monica; Sharma, Nitya Nand

    Nitriles and amides are widely distributed in the biotic and abiotic components of our ecosystem. Nitrile form an important group of organic compounds which find their applications in the synthesis of a large number of compounds used as/in pharmaceutical, cosmetics, plastics, dyes, etc>. Nitriles are mainly hydro-lyzed to corresponding amide/acid in organic chemistry. Industrial and agricultural activities have also lead to release of nitriles and amides into the environment and some of them pose threat to human health. Biocatalysis and biotransformations are increasingly replacing chemical routes of synthesis in organic chemistry as a part of ‘green chemistry’. Nitrile metabolizing organisms or enzymes thus has assumed greater significance in all these years to convert nitriles to amides/ acids. The nitrile metabolizing enzymes are widely present in bacteria, fungi and yeasts. Yeasts metabolize nitriles through nitrilase and/or nitrile hydratase and amidase enzymes. Only few yeasts have been reported to possess aldoxime dehydratase. More than sixty nitrile metabolizing yeast strains have been hither to isolated from cyanide treatment bioreactor, fermented foods and soil. Most of the yeasts contain nitrile hydratase-amidase system for metabolizing nitriles. Transformations of nitriles to amides/acids have been carried out with free and immobilized yeast cells. The nitrilases of Torulopsis candida>and Exophiala oligosperma>R1 are enantioselec-tive and regiospecific respectively. Geotrichum>sp. JR1 grows in the presence of 2M acetonitrile and may have potential for application in bioremediation of nitrile contaminated soil/water. The nitrilase of E. oligosperma>R1 being active at low pH (3-6) has shown promise for the hydroxy acids. Immobilized yeast cells hydrolyze some additional nitriles in comparison to free cells. It is expected that more focus in future will be on purification, characterization, cloning, expression and immobilization of nitrile metabolizing

  20. Immunoreactive Proteins of Bifidobacterium longum ssp longum CCM 7952 and Bifidobacterium longum ssp longum CCDM 372 Identified by Gnotobiotic Mono-Colonized Mice Sera, Immune Rabbit Sera and Non-immune Human Sera

    Górska, S.; Dylus, E.; Rudawska, A.; Brzozowska, E.; Šrůtková, Dagmar; Schwarzer, Martin; Razim, A.; Kozáková, Hana; Gamian, A.

    2016-01-01

    Roč. 7, SEP 29 (2016), s. 1537 ISSN 1664-302X R&D Projects: GA MŠk(CZ) 7AMB16PL006 Institutional support: RVO:61388971 Keywords : Bifidobacterium * probiotics * moonlighting proteins Subject RIV: EE - Microbiology, Virology Impact factor: 4.076, year: 2016

  1. [Nutritional support in sepsis].

    Ortiz Leyba, C; López Martínez, J; Blesa Malpica, A L

    2005-06-01

    Although it is considered that metabolic and nutritional support must be part of the management of septic patients, it has not been conclusively shown that nutritional support will improve survival or complications from sepsis. Specific data on this issue are scarce since there are few studies that have investigated specialized nutritional support in septic patients. Thus, most of the recommendations are based on outcomes obtained in severely ill patients with different pathologies. It is assumed that nutritional support should be carried out through the enteral route whenever possible, as in other critically ill patients. The energetic waste in these patients is highly variable, although in general terms the hypermetabolic situation may be classified as moderate. An adjustment factor of 1.25-1.30 is recommended for the Harris-Benedict's equation to calculate the caloric intake. Septic patients should receive a hyperproteic intake. The amount of glucose administered should not exceed 70% of non-protein calories, and lipids intake should not exceed 40%. With regards to micronutrients, it is recommended to increase the supply of those with antioxidant properties (vitamin E, carotenes, vitamin C, selenium). There are data to consider that the use of diets enriched with pharmaco-nutrients (both with parenteral and enteral routes) may be beneficial in septic patients, although there is some controversy when interpreting the outcomes.

  2. Nitrate-containing beetroot enhances myocyte metabolism and mitochondrial content

    Vaughan, Roger A.; Gannon, Nicholas P.; Carriker, Colin R.

    2015-01-01

    Beetroot (甜菜 tián cài) juice consumption is of current interest for improving aerobic performance by acting as a vasodilator and possibly through alterations in skeletal muscle metabolism and physiology. This work explored the effects of a commercially available beetroot supplement on metabolism, gene expression, and mitochondrial content in cultured myocytes. C2C12 myocytes were treated with various concentrations of the beetroot supplement for various durations. Glycolytic metabolism and oxidative metabolism were quantified via measurement of extracellular acidification and oxygen consumption, respectively. Metabolic gene expression was measured using quantitative reverse transcription–polymerase chain reaction, and mitochondrial content was assessed with flow cytometry and confocal microscopy. Cells treated with beetroot exhibited significantly increased oxidative metabolism, concurrently with elevated metabolic gene expression including peroxisome proliferator-activated receptor gamma coactivator-1 alpha, nuclear respiratory factor 1, mitochondrial transcription factor A, and glucose transporter 4, leading to increased mitochondrial biogenesis. Our data show that treatment with a beetroot supplement increases basal oxidative metabolism. Our observations are also among the first to demonstrate that beetroot extract is an inducer of metabolic gene expression and mitochondrial biogenesis. These observations support the need for further investigation into the therapeutic and pharmacological effects of nitrate-containing supplements for health and athletic benefits. PMID:26870674

  3. Hypothyroidism in metabolic syndrome

    Sunil Kumar Kota

    2012-01-01

    Full Text Available Aim: Metabolic syndrome (MetS and hypothyroidism are well established forerunners of atherogenic cardiovascular disease. Considerable overlap occurs in the pathogenic mechanisms of atherosclerotic cardiovascular disease by metabolic syndrome and hypothyroidism. Insulin resistance has been studied as the basic pathogenic mechanism in metabolic syndrome. [1] This cross sectional study intended to assess thyroid function in patients with metabolic syndrome and to investigate the association between hypothyroidism and metabolic syndrome. Materials and Methods: One hundred patients with metabolic syndrome who fulfilled the National Cholesterol Education Program- Adult Treatment Panel (NCEP-ATP III criteria [ 3 out of 5 criteria positive namely blood pressure ≥ 130/85 mm hg or on antihypertensive medications, fasting plasma glucose > 100 mg/dl or on anti-diabetic medications, fasting triglycerides > 150 mg/dl, high density lipoprotein cholesterol (HDL-C 102 cms in men and 88 cms in women] were included in the study group. [2] Fifty patients who had no features of metabolic syndrome (0 out of 5 criteria for metabolic syndrome were included in the control group. Patients with liver disorders, renal disorders, congestive cardiac failure, pregnant women, patients on oral contraceptive pills, statins and other medications that alter thyroid functions and lipid levels and those who are under treatment for any thyroid related disorder were excluded from the study. Acutely ill patients were excluded taking into account sick euthyroid syndrome. Patients were subjected to anthropometry, evaluation of vital parameters, lipid and thyroid profile along with other routine laboratory parameters. Students t-test, Chi square test and linear regression, multiple logistic regression models were used for statistical analysis. P value < 0.05 was considered significant. Results: Of the 100 patients in study group, 55 were females (55% and 45 were males (45%. Of the 50

  4. Metabolic complications in oncology

    Sycova-Mila, Z.

    2012-01-01

    Currently, a lot of space and time is devoted to the therapy of oncologic diseases itself. To reach the good therapy results, complex care of the oncologic patient is needed. Management of complications linked with the disease itself and management of complications emerged after administration of chemotherapy, radiotherapy or targeted therapy, plays a significant role. In addition to infectious, hematological, neurological, cardiac or other complications, metabolic complications are relatively extensive and serious. One of the most frequent metabolic complications in oncology is tumor lysis syndrome, hyperuricemia, hypercalcaemia and syndrome of inappropriate secretion of antidiuretic hormone. (author)

  5. Prokaryote metabolism activity

    Biederman, Lori

    2017-01-01

    I wrote this activity to emphasize that prokaryotic organisms can carry out 6 different types of metabolisms (as presented in Freeman’s Biological Science textbook) and this contrasts to eukaryotes, which can only use 2 metabolism pathways (photoautotroph and heterotroph).    For in class materials I remove the  red box (upper right corner) and print slides 3-10, place them back-to-back and laminate them.  The students get a key (slide 2) and a two-sided organism sheet...

  6. Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

    Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

    2017-07-01

    The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Data supporting study of Ecosystem Metabolism in Pensacola Bay estuary

    U.S. Environmental Protection Agency — These files house the data collected during 2013 in lower Pensacola Bay. The data were used to estimate aquatic primary production and respiration. This dataset is...

  8. Visual cycle and its metabolic support in gecko photoreceptors.

    Kolesnikov, A V; Ala-Laurila, P; Shukolyukov, S A; Crouch, R K; Wiggert, B; Estevez, M E; Govardovskii, V I; Cornwall, M C

    2007-02-01

    Photoreceptors of nocturnal geckos are transmuted cones that acquired rod morphological and physiological properties but retained cone-type phototransduction proteins. We have used microspectrophotometry and microfluorometry of solitary isolated green-sensitive photoreceptors of Tokay gecko to study the initial stages of the visual cycle within these cells. These stages are the photolysis of the visual pigment, the reduction of all-trans retinal to all-trans retinol, and the clearance of all-trans retinol from the outer segment (OS) into the interphotoreceptor space. We show that the rates of decay of metaproducts (all-trans retinal release) and retinal-to-retinol reduction are intermediate between those of typical rods and cones. Clearance of retinol from the OS proceeds at a rate that is typical of rods and is greatly accelerated by exposure to interphotoreceptor retinoid-binding protein, IRBP. The rate of retinal release from metaproducts is independent of the position within the OS, while its conversion to retinol is strongly spatially non-uniform, being the fastest at the OS base and slowest at the tip. This spatial gradient of retinol production is abolished by dialysis of saponin-permeabilized OSs with exogenous NADPH or substrates for its production by the hexose monophosphate pathway (NADP+glucose-6-phosphate or 6-phosphogluconate, glucose-6-phosphate alone). Following dialysis by these agents, retinol production is accelerated by several-fold compared to the fastest rates observed in intact cells in standard Ringer solution. We propose that the speed of retinol production is set by the availability of NADPH which in turn depends on ATP supply within the outer segment. We also suggest that principal source of this ATP is from mitochondria located within the ellipsoid region of the inner segment.

  9. Primary Metabolic Pathways and Metabolic Flux Analysis

    Villadsen, John

    2015-01-01

    his chapter introduces the metabolic flux analysis (MFA) or stoichiometry-based MFA, and describes the quantitative basis for MFA. It discusses the catabolic pathways in which free energy is produced to drive the cell-building anabolic pathways. An overview of these primary pathways provides...... the reader who is primarily trained in the engineering sciences with atleast a preliminary introduction to biochemistry and also shows how carbon is drained off the catabolic pathways to provide precursors for cell mass building and sometimes for important industrial products. The primary pathways...... to be examined in the following are: glycolysis, primarily by the EMP pathway, but other glycolytic pathways is also mentioned; fermentative pathways in which the redox generated in the glycolytic reactions are consumed; reactions in the tricarboxylic acid (TCA) cycle, which produce biomass precursors and redox...

  10. Sleep and Metabolism: An Overview

    Sunil Sharma

    2010-01-01

    Full Text Available Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism.

  11. Metabolic Signaling and Therapy of Lung Cancer

    2013-09-01

    report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by...which makes them attractive therapeutic targets. However, the development of targeted agents in lung cancer is still in its infancy, despite the...notion that metabolites can act as signaling molecules in distant metabolic pathways is gaining significant attentionand support (Figure 1A). Some of the

  12. Energy Metabolism and Human Dosimetry of Tritium

    Galeriu, D.; Takeda, H.; Melintescu, A.; Trivedi, A.

    2005-01-01

    In the frame of current revision of human dosimetry of 14 C and tritium, undertaken by the International Commission of Radiological Protection, we propose a novel approach based on energy metabolism and a simple biokinetic model for the dynamics of dietary intake (organic 14 C, tritiated water and Organically Bound Tritium-OBT). The model predicts increased doses for HTO and OBT comparing to ICRP recommendations, supporting recent findings

  13. Neonatal nutrition and metabolism

    Thureen, Patti J; Hay, William W

    2006-01-01

    ..., the volume highlights the important longterm effects of fetal and neonatal growth on health in later life. In addition, there are very practical chapters on methods and techniques for assessing nutritional status, body composition, and evaluating metabolic function. Written by an authoritative, international team of cont...

  14. Insect flight muscle metabolism

    Horst, D.J. van der; Beenakkers, A.M.Th.; Marrewijk, W.J.A. van

    1984-01-01

    The flight of an insect is of a very complicated and extremely energy-demanding nature. Wingbeat frequency may differ between various species but values up to 1000 Hz have been measured. Consequently metabolic activity may be very high during flight and the transition from rest to flight is

  15. Synthetic Metabolic Pathways

    topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

  16. Metabolism of femoxetine

    Larsson, H.; Lund, J.

    1981-01-01

    The metabolism of femoxetine, a serotonin uptake inhibitor, has been investigated in rats, dogs, monkeys, and human subjects using two 14 C-femoxetine compounds with labelling in different positions. The metabolic pathways were oxidations (and glucuronidation) and demethylation, both reactions most probably taking place in the liver. Nearly all femoxetine was metabolised, and the same metabolites were found in urine from all four species. Only a small percentage of the radioactivity excreted in the urine was not identified. Rat and dog excreted more N-oxide than monkey and man, while most of the radioactivity (60-100%) in these two species was excreted as two hydroxy metabolites. The metabolic pattern in monkey and man was very similar. About 50% was excreted in these two species as one metabolite, formed by demethylation of a methoxy group. A demethylation of a N-CH 3 group formed an active metabolite, norfemoxetine. The excretion of this metabolite in urine from man varied from 0 to 18% of the dose between individuals. Most of the radioactivity was excreted with the faeces in rat and dog, while monkey and man excreted most of the radioactivity in urine. This difference in excretion route might be explained by the difference in the metabolic pattern. No dose dependency was observed in any of the three animal species investigated. (author)

  17. Tumor macroenvironment and metabolism.

    Al-Zoughbi, Wael; Al-Zhoughbi, Wael; Huang, Jianfeng; Paramasivan, Ganapathy S; Till, Holger; Pichler, Martin; Guertl-Lackner, Barbara; Hoefler, Gerald

    2014-04-01

    In this review we introduce the concept of the tumor macroenvironment and explore it in the context of metabolism. Tumor cells interact with the tumor microenvironment including immune cells. Blood and lymph vessels are the critical components that deliver nutrients to the tumor and also connect the tumor to the macroenvironment. Several factors are then released from the tumor itself but potentially also from the tumor microenvironment, influencing the metabolism of distant tissues and organs. Amino acids, and distinct lipid and lipoprotein species can be essential for further tumor growth. The role of glucose in tumor metabolism has been studied extensively. Cancer-associated cachexia is the most important tumor-associated systemic syndrome and not only affects the quality of life of patients with various malignancies but is estimated to be the cause of death in 15%-20% of all cancer patients. On the other hand, systemic metabolic diseases such as obesity and diabetes are known to influence tumor development. Furthermore, the clinical implications of the tumor macroenvironment are explored in the context of the patient's outcome with special consideration for pediatric tumors. Finally, ways to target the tumor macroenvironment that will provide new approaches for therapeutic concepts are described. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Metabolic Diseases of Muscle

    ... here and still get the great care and treatment I received in Michigan.” MDA Is Here to Help You T he Muscular Dystrophy Association offers a vast array of services to help you and your family deal with metabolic diseases of muscle. The staff at your local MDA office is ...

  19. Dysregulated metabolism contributes to oncogenesis

    Hirschey, Matthew D.; DeBerardinis, Ralph J.; Diehl, Anna Mae E.; Drew, Janice E.; Frezza, Christian; Green, Michelle F.; Jones, Lee W.; Ko, Young H.; Le, Anne; Lea, Michael A.; Locasale, Jason W.; Longo, Valter D.; Lyssiotis, Costas A.; McDonnell, Eoin; Mehrmohamadi, Mahya; Michelotti, Gregory; Muralidhar, Vinayak; Murphy, Michael P.; Pedersen, Peter L.; Poore, Brad; Raffaghello, Lizzia; Rathmell, Jeffrey C.; Sivanand, Sharanya; Vander Heiden, Matthew G.; Wellen, Kathryn E.

    2015-01-01

    Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review “Hallmarks of Cancer”, where the dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results suggest that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. PMID:26454069

  20. Cerebral ketone body metabolism.

    Morris, A A M

    2005-01-01

    Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids. The rate of cerebral KB metabolism depends primarily on the concentration in blood; high concentrations occur during fasting and on a high-fat diet. Cerebral KB metabolism is also regulated by the permeability of the blood-brain barrier (BBB), which depends on the abundance of monocarboxylic acid transporters (MCT1). The BBB's permeability to KBs increases with fasting in humans. In rats, permeability increases during the suckling period, but human neonates have not been studied. Monocarboxylic acid transporters are also present in the plasma membranes of neurons and glia but their role in regulating KB metabolism is uncertain. Finally, the rate of cerebral KB metabolism depends on the activities of the relevant enzymes in brain. The activities vary with age in rats, but reliable results are not available for humans. Cerebral KB metabolism in humans differs from that in the rat in several respects. During fasting, for example, KBs supply more of the brain's energy in humans than in the rat. Conversely, KBs are probably used more extensively in the brain of suckling rats than in human neonates. These differences complicate the interpretation of rodent studies. Most patients with inborn errors of ketogenesis develop normally, suggesting that the only essential role for KBs is as an alternative fuel during illness or prolonged fasting. On the other hand, in HMG-CoA lyase deficiency, imaging generally shows asymptomatic white-matter abnormalities. The ability of KBs to act as an alternative fuel explains the effectiveness of the ketogenic diet in GLUT1 deficiency, but its effectiveness in epilepsy remains unexplained.

  1. Pipe support

    Pollono, L.P.

    1979-01-01

    A pipe support for high temperature, thin-walled piping runs such as those used in nuclear systems is described. A section of the pipe to be suppported is encircled by a tubular inner member comprised of two walls with an annular space therebetween. Compacted load-bearing thermal insulation is encapsulated within the annular space, and the inner member is clamped to the pipe by a constant clamping force split-ring clamp. The clamp may be connected to pipe hangers which provide desired support for the pipe

  2. Assessment of a pioneer metabolic information service in Brazil.

    Brustolin, Silvia; Souza, Carolina; Puga, Ana Cristina; Refosco, Lilia; Pires, Ricardo; Peres, Rossana; Giugliani, Roberto

    2006-01-01

    The Information Service on Inborn Errors of Metabolism (SIEM), a pioneer toll-free service in both Brazil and South America, is based in Porto Alegre, Southern Brazil. SIEM has been operating since October 2001 providing support to health care professionals involved in the diagnosis and management of suspected metabolic diseases. We analyzed the demographic and clinical characteristics of the 376 consults received and followed in the first two and half years of SIEM. Our results show that the suspicion of a metabolic disease was most often associated with neurological symptoms. Among the consults, 24.4% were eventually confirmed as inborn errors of metabolism (IEM), with organic acidurias and amino acid disorders being the two most frequent diagnostic groups. Our conclusion shows this kind of service to provide helpful support to the diagnosis and acute management of IEM, especially to health professionals working in developing countries who are often far from reference centers.

  3. Can you boost your metabolism?

    ... this page: //medlineplus.gov/ency/patientinstructions/000893.htm Can you boost your metabolism? To use the sharing ... boosting metabolism than tactics that work. Some myths can backfire. If you think you are burning more ...

  4. Human drug metabolism: an introduction

    Coleman, Michael D

    2010-01-01

    ... metabolism and its impact on patient welfare. After underlining the relationship between efficacy, toxicity and drug concentration, the book then considers how metabolizing systems operate and how they impact upon drug concentration...

  5. Supporting ATLAS

    maximilien brice

    2003-01-01

    Eighteen feet made of stainless steel will support the barrel ATLAS detector in the cavern at Point 1. In total, the ATLAS feet system will carry approximately 6000 tons, and will give the same inclination to the detector as the LHC accelerator.

  6. Supporting Transition

    Qureshi, Asima; Petrucco, James

    2018-01-01

    Meadowbrook Primary School has explored the use of The Teacher Assessment in Primary Science (TAPS) to support transition, initially for transfer to secondary school and now for transition from Early Years Foundation Stage (EYFS) into Key Stage 1 (ages 5-7). This article will consider an example of a secondary transition project and discuss the…

  7. Sleep and Metabolism: An Overview

    Sharma, Sunil; Kavuru, Mani

    2010-01-01

    Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways i...

  8. Energy Metabolism in the Liver

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, p...

  9. SBOLme: a Repository of SBOL Parts for Metabolic Engineering

    Kuwahara, Hiroyuki

    2017-01-12

    The Synthetic Biology Open Language (SBOL) is a community-driven open language to promote standardization in synthetic biology. To support the use of SBOL in metabolic engineering, we developed SBOLme, the first open-access repository of SBOL 2-compliant biochemical parts for a wide range of metabolic engineering applications. The URL of our repository is http://www.cbrc.kaust.edu.sa/sbolme.

  10. Epigenetics and a new look on metabolic syndrome

    Kuneš, Jaroslav; Vaněčková, Ivana; Mikulášková, Barbora; Behuliak, Michal; Maletínská, L.; Zicha, Josef

    2015-01-01

    Roč. 64, č. 5 (2015), s. 611-620 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NV15-25396A; GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : metabolic syndrome * epigenetic s * transgenerational inheritance * gene-environmental interactions * obesity * hypertension Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.643, year: 2015

  11. Epigenetics and a new look on metabolic syndrome

    Kuneš, Jaroslav; Vaněčková, I.; Mikulášková, Barbora; Behuliak, M.; Maletínská, Lenka; Zicha, J.

    2015-01-01

    Roč. 64, č. 5 (2015), s. 611-620 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : metabolic syndrome * epigenetic s * transgenerational inheritance * gene-environmental interactions * obesity * hypertension Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.643, year: 2015 http://www.biomed.cas.cz/physiolres/pdf/64/64_611.pdf

  12. Plausible role for CHW peer support groups in increasing care-seeking in an integrated community case management project in Rwanda: a mixed methods evaluation

    Langston, Anne; Weiss, Jennifer; Landegger, Justine; Pullum, Thomas; Morrow, Melanie; Kabadege, Melene; Mugeni, Catherine; Sarriot, Eric

    2014-01-01

    ABSTRACT Background: The Kabeho Mwana project (2006–2011) supported the Rwanda Ministry of Health (MOH) in scaling up integrated community case management (iCCM) of childhood illness in 6 of Rwanda's 30 districts. The project trained and equipped community health workers (CHWs) according to national guidelines. In project districts, Kabeho Mwana staff also trained CHWs to conduct household-level health promotion and established supervision and reporting mechanisms through CHW peer support groups (PSGs) and quality improvement systems. Methods: The 2005 and 2010 Demographic and Health Surveys were re-analyzed to evaluate how project and non-project districts differed in terms of care-seeking for fever, diarrhea, and acute respiratory infection symptoms and related indicators. We developed a logit regression model, controlling for the timing of the first CHW training, with the district included as a fixed categorical effect. We also analyzed qualitative data from the final evaluation to examine factors that may have contributed to improved outcomes. Results: While there was notable improvement in care-seeking across all districts, care-seeking from any provider for each of the 3 conditions, and for all 3 combined, increased significantly more in the project districts. CHWs contributed a larger percentage of consultations in project districts (27%) than in non-project districts (12%). Qualitative data suggested that the PSG model was a valuable sub-level of CHW organization associated with improved CHW performance, supervision, and social capital. Conclusions: The iCCM model implemented by Kabeho Mwana resulted in greater improvements in care-seeking than those seen in the rest of the country. Intensive monitoring, collaborative supervision, community mobilization, and CHW PSGs contributed to this success. The PSGs were a unique contribution of the project, playing a critical role in improving care-seeking in project districts. Effective implementation of iCCM

  13. Pulmonary metabolism of foreign compounds: Its role in metabolic activation

    Cohen, G.M.

    1990-01-01

    The lung has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity of many pulmonary toxins. Environmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity

  14. Does caffeine alter muscle carbohydrate and fat metabolism during exercise?

    Graham, Terry E; Battram, Danielle S; Dela, Flemming

    2008-01-01

    and carbohydrate metabolism. While caffeine certainly mobilizes fatty acids from adipose tissue, rarely have measures of the respiratory exchange ratio indicated an increase in fat oxidation. However, this is a difficult measure to perform accurately during exercise, and small changes could be physiologically...... important. The few studies examining human muscle metabolism directly have also supported the fact that there is no change in fat or carbohydrate metabolism, but these usually have had a small sample size. We combined the data from muscle biopsy analyses of several similar studies to generate a sample size...

  15. Human drug metabolism: an introduction

    Coleman, Michael D

    2010-01-01

    ..., both under drug pressure and during inhibition. Factors affecting drug metabolism, such as genetic polymorphisms, age and diet are discussed and how metabolism can lead to toxicity is explained. The book concludes with the role of drug metabolism in the commercial development of therapeutic agents as well as the pharmacology of some illicit drugs.

  16. Mechanisms of carbon dioxide acquisition and CO2 sensing in marine diatoms: a gateway to carbon metabolism.

    Matsuda, Yusuke; Hopkinson, Brian M; Nakajima, Kensuke; Dupont, Christopher L; Tsuji, Yoshinori

    2017-09-05

    Diatoms are one of the most successful marine eukaryotic algal groups, responsible for up to 20% of the annual global CO 2 fixation. The evolution of a CO 2 -concentrating mechanism (CCM) allowed diatoms to overcome a number of serious constraints on photosynthesis in the marine environment, particularly low [CO 2 ] aq in seawater relative to concentrations required by the CO 2 fixing enzyme, ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), which is partly due to the slow diffusion rate of CO 2 in water and a limited CO 2 formation rate from [Formula: see text] in seawater. Diatoms use two alternative strategies to take up dissolved inorganic carbon (DIC) from the environment: one primarily relies on the direct uptake of [Formula: see text] through plasma-membrane type solute carrier (SLC) 4 family [Formula: see text] transporters and the other is more reliant on passive diffusion of CO 2 formed by an external carbonic anhydrase (CA). Bicarbonate taken up into the cytoplasm is most likely then actively transported into the chloroplast stroma by SLC4-type transporters on the chloroplast membrane system. Bicarbonate in the stroma is converted into CO 2 only in close proximity to RubisCO preventing unnecessary CO 2 leakage. CAs play significant roles in mobilizing DIC as it is progressively moved towards the site of fixation. However, the evolutionary types and subcellular locations of CAs are not conserved between different diatoms, strongly suggesting that this DIC mobilization strategy likely evolved multiple times with different origins. By contrast, the recent discovery of the thylakoid luminal θ-CA indicates that the strategy to supply CO 2 to RubisCO in the pyrenoid may be very similar to that of green algae, and strongly suggests convergent coevolution in CCM function of the thylakoid lumen not only among diatoms but among eukaryotic algae in general. In this review, both experimental and corresponding theoretical models of the diatom CCMs are

  17. Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease

    Michelle E. Watts

    2018-06-01

    Full Text Available Dynamic metabolic changes occurring in neurons are critically important in directing brain plasticity and cognitive function. In other tissue types, disruptions to metabolism and the resultant changes in cellular oxidative state, such as increased reactive oxygen species (ROS or induction of hypoxia, are associated with cellular stress. In the brain however, where drastic metabolic shifts occur to support physiological processes, subsequent changes to cellular oxidative state and induction of transcriptional sensors of oxidative stress likely play a significant role in regulating physiological neuronal function. Understanding the role of metabolism and metabolically-regulated genes in neuronal function will be critical in elucidating how cognitive functions are disrupted in pathological conditions where neuronal metabolism is affected. Here, we discuss known mechanisms regulating neuronal metabolism as well as the role of hypoxia and oxidative stress during normal and disrupted neuronal function. We also summarize recent studies implicating a role for metabolism in regulating neuronal plasticity as an emerging neuroscience paradigm.

  18. Microglia energy metabolism in metabolic disorder.

    Kalsbeek, Martin J T; Mulder, Laurie; Yi, Chun-Xia

    2016-12-15

    Microglia are the resident macrophages of the CNS, and are in charge of maintaining a healthy microenvironment to ensure neuronal survival. Microglia carry out a non-stop patrol of the CNS, make contact with neurons and look for abnormalities, all of which requires a vast amount of energy. This non-signaling energy demand increases after activation by pathogens, neuronal damage or other kinds of stimulation. Of the three major energy substrates - glucose, fatty acids and glutamine - glucose is crucial for microglia survival and several glucose transporters are expressed to supply sufficient glucose influx. Fatty acids are another source of energy for microglia and have also been shown to strongly influence microglial immune activity. Glutamine, although possibly suitable for use as an energy substrate by microglia, has been shown to have neurotoxic effects when overloaded. Microglial fuel metabolism might be associated with microglial reactivity under different pathophysiological conditions and a microglial fuel switch may thus be the underlying cause of hypothalamic dysregulation, which is associated with obesity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Inborn errors of metabolism: a clinical overview

    Ana Maria Martins

    1999-11-01

    Full Text Available CONTEXT: Inborn errors of metabolism cause hereditary metabolic diseases (HMD and classically they result from the lack of activity of one or more specific enzymes or defects in the transportation of proteins. OBJECTIVES: A clinical review of inborn errors of metabolism (IEM to give a practical approach to the physician with figures and tables to help in understanding the more common groups of these disorders. DATA SOURCE: A systematic review of the clinical and biochemical basis of IEM in the literature, especially considering the last ten years and a classic textbook (Scriver CR et al, 1995. SELECTION OF STUDIES: A selection of 108 references about IEM by experts in the subject was made. Clinical cases are presented with the peculiar symptoms of various diseases. DATA SYNTHESIS: IEM are frequently misdiagnosed because the general practitioner, or pediatrician in the neonatal or intensive care units, does not think about this diagnosis until the more common cause have been ruled out. This review includes inheritance patterns and clinical and laboratory findings of the more common IEM diseases within a clinical classification that give a general idea about these disorders. A summary of treatment types for metabolic inherited diseases is given. CONCLUSIONS: IEM are not rare diseases, unlike previous thinking about them, and IEM patients form part of the clientele in emergency rooms at general hospitals and in intensive care units. They are also to be found in neurological, pediatric, obstetrics, surgical and psychiatric clinics seeking diagnoses, prognoses and therapeutic or supportive treatment.

  20. Spectrum of metabolic myopathies.

    Angelini, Corrado

    2015-04-01

    Metabolic myopathies are disorders of utilization of carbohydrates or fat in muscles. The acute nature of energy failure is manifested either by a metabolic crisis with weakness, sometimes associated with respiratory failure, or by myoglobinuria. A typical disorder where permanent weakness occurs is glycogenosis type II (GSDII or Pompe disease) both in infantile and late-onset forms, where respiratory insufficiency is manifested by a large number of cases. In GSDII the pathogenetic mechanism is still poorly understood, and has to be attributed more to structural muscle alterations, possibly in correlation to macro-autophagy, rather than to energetic failure. This review is focused on recent advances about GSDII and its treatment, and the most recent notions about the management and treatment of other metabolic myopathies will be briefly reviewed, including glycogenosis type V (McArdle disease), glycogenosis type III (debrancher enzyme deficiency or Cori disease), CPT-II deficiency, and ETF-dehydrogenase deficiency (also known as riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency or RR-MADD). The discovery of the genetic defect in ETF dehydrogenase confirms the etiology of this syndrome. Other metabolic myopathies with massive lipid storage and weakness are carnitine deficiency, neutral lipid storage-myopathy (NLSD-M), besides RR-MADD. Enzyme replacement therapy is presented with critical consideration and for each of the lipid storage disorders, representative cases and their response to therapy is included. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

  1. Epigenetics and Cellular Metabolism

    Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

  2. Microbial Metabolism in Serpentinite Fluids

    Crespo-Medina, M.; Brazelton, W. J.; Twing, K. I.; Kubo, M.; Hoehler, T. M.; Schrenk, M. O.

    2013-12-01

    Serpentinization is the process in which ultramafic rocks, characteristic of the upper mantle, react with water liberating mantle carbon and reducing power to potenially support chemosynthetic microbial communities. These communities may be important mediators of carbon and energy exchange between the deep Earth and the surface biosphere. Our work focuses on the Coast Range Ophiolite Microbial Observatory (CROMO) in Northern California where subsurface fluids are accessible through a series of wells. Preliminary analyses indicate that the highly basic fluids (pH 9-12) have low microbial diversity, but there is limited knowledge about the metabolic capabilities of these communties. Metagenomic data from similar serpentine environments [1] have identified Betaproteobacteria belonging to the order Burkholderiales and Gram-positive bacteria from the order Clostridiales as key components of the serpentine microbiome. In an effort to better characterize the microbial community, metabolism, and geochemistry at CROMO, fluids from two representative wells (N08B and CSWold) were sampled during recent field campaigns. Geochemical characterization of the fluids includes measurements of dissolved gases (H2, CO, CH4), dissolved inorganic and organic carbon, volatile fatty acids, and nutrients. The wells selected can be differentiated in that N08B had higher pH (10-11), lower dissolved oxygen, and cell counts ranging from 105-106 cells mL-1 of fluid, with an abundance of the betaproteobacterium Hydrogenophaga. In contrast, fluids from CSWold have slightly lower pH (9-9.5), DO, and conductivity, as well as higher TDN and TDP. CSWold fluid is also characterized for having lower cell counts (~103 cells mL-1) and an abundance of Dethiobacter, a taxon within the phylum Clostridiales. Microcosm experiments were conducted with the purpose of monitoring carbon fixation, methanotrophy and metabolism of small organic compounds, such as acetate and formate, while tracing changes in fluid

  3. Circadian physiology of metabolism.

    Panda, Satchidananda

    2016-11-25

    A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes. Experimental animal models and epidemiological data indicate that chronic circadian rhythm disruption increases the risk of metabolic diseases. Conversely, time-restricted feeding, which imposes daily cycles of feeding and fasting without caloric reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases. These findings highlight an integrative role of circadian rhythms in physiology and offer a new perspective for treating chronic diseases in which metabolic disruption is a hallmark. Copyright © 2016, American Association for the Advancement of Science.

  4. Maternal cardiac metabolism in pregnancy

    Liu, Laura X.; Arany, Zolt

    2014-01-01

    Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal ‘invasion’ profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology. PMID:24448314

  5. Imaging metabolic heterogeneity in cancer.

    Sengupta, Debanti; Pratx, Guillem

    2016-01-06

    As our knowledge of cancer metabolism has increased, it has become apparent that cancer metabolic processes are extremely heterogeneous. The reasons behind this heterogeneity include genetic diversity, the existence of multiple and redundant metabolic pathways, altered microenvironmental conditions, and so on. As a result, methods in the clinic and beyond have been developed in order to image and study tumor metabolism in the in vivo and in vitro regimes. Both regimes provide unique advantages and challenges, and may be used to provide a picture of tumor metabolic heterogeneity that is spatially and temporally comprehensive. Taken together, these methods may hold the key to appropriate cancer diagnoses and treatments in the future.

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

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

    2014-08-01

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

  7. Tumor Metabolism of Malignant Gliomas

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang, E-mail: deliang.guo@osumc.edu [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center & Arthur G James Cancer Hospital, Columbus, OH 43012 (United States)

    2013-11-08

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  8. Tumor Metabolism of Malignant Gliomas

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang

    2013-01-01

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation

  9. Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling.

    Cuperlovic-Culf, Miroslava

    2018-01-11

    Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies.

  10. Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling

    Cuperlovic-Culf, Miroslava

    2018-01-01

    Machine learning uses experimental data to optimize clustering or classification of samples or features, or to develop, augment or verify models that can be used to predict behavior or properties of systems. It is expected that machine learning will help provide actionable knowledge from a variety of big data including metabolomics data, as well as results of metabolism models. A variety of machine learning methods has been applied in bioinformatics and metabolism analyses including self-organizing maps, support vector machines, the kernel machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning has also been utilized to take advantage of the increasing availability of genomics and metabolomics data for the optimization of metabolic network models and their analysis. In this context, machine learning has aided the development of metabolic networks, the calculation of parameters for stoichiometric and kinetic models, as well as the analysis of major features in the model for the optimal application of bioreactors. Examples of this very interesting, albeit highly complex, application of machine learning for metabolism modeling will be the primary focus of this review presenting several different types of applications for model optimization, parameter determination or system analysis using models, as well as the utilization of several different types of machine learning technologies. PMID:29324649

  11. Evidence for transgenerational metabolic programming in Drosophila

    Jessica L. Buescher

    2013-09-01

    Worldwide epidemiologic studies have repeatedly demonstrated an association between prenatal nutritional environment, birth weight and susceptibility to adult diseases including obesity, cardiovascular disease and type 2 diabetes. Despite advances in mammalian model systems, the molecular mechanisms underlying this phenomenon are unclear, but might involve programming mechanisms such as epigenetics. Here we describe a new system for evaluating metabolic programming mechanisms using a simple, genetically tractable Drosophila model. We examined the effect of maternal caloric excess on offspring and found that a high-sugar maternal diet alters body composition of larval offspring for at least two generations, augments an obese-like phenotype under suboptimal (high-calorie feeding conditions in adult offspring, and modifies expression of metabolic genes. Our data indicate that nutritional programming mechanisms could be highly conserved and support the use of Drosophila as a model for evaluating the underlying genetic and epigenetic contributions to this phenomenon.

  12. Anthelmintic metabolism in parasitic helminths: proteomic insights.

    Brophy, Peter M; MacKintosh, Neil; Morphew, Russell M

    2012-08-01

    Anthelmintics are the cornerstone of parasitic helminth control. Surprisingly, understanding of the biochemical pathways used by parasitic helminths to detoxify anthelmintics is fragmented, despite the increasing global threat of anthelmintic resistance within the ruminant and equine industries. Reductionist biochemistry has likely over-estimated the enzymatic role of glutathione transferases in anthelmintic metabolism and neglected the potential role of the cytochrome P-450 superfamily (CYPs). Proteomic technologies offers the opportunity to support genomics, reverse genetics and pharmacokinetics, and provide an integrated insight into both the cellular mechanisms underpinning response to anthelmintics and also the identification of biomarker panels for monitoring the development of anthelmintic resistance. To date, there have been limited attempts to include proteomics in anthelmintic metabolism studies. Optimisations of membrane, post-translational modification and interaction proteomic technologies in helminths are needed to especially study Phase I CYPs and Phase III ABC transporter pumps for anthelmintics and their metabolites.

  13. Uncovering transcriptional regulation of metabolism by using metabolic network topology

    Patil, Kiran Raosaheb; Nielsen, Jens

    2005-01-01

    in the metabolic network that follow a common transcriptional response. Thus, the algorithm enables identification of so-called reporter metabolites (metabolites around which the most significant transcriptional changes occur) and a set of connected genes with significant and coordinated response to genetic......Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional...... therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns...

  14. The Association of Arsenic Exposure and Arsenic Metabolism with the Metabolic Syndrome and its Individual Components: Prospective Evidence from the Strong Heart Family Study.

    Spratlen, Miranda J; Grau-Perez, Maria; Best, Lyle G; Yracheta, Joseph; Lazo, Mariana; Vaidya, Dhananjay; Balakrishnan, Poojitha; Gamble, Mary V; Francesconi, Kevin A; Goessler, Walter; Cole, Shelley A; Umans, Jason G; Howard, Barbara V; Navas-Acien, Ana

    2018-03-15

    Inorganic arsenic exposure is ubiquitous and both exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. The association between arsenic exposure and arsenic metabolism with metabolic syndrome and its individual components, however, is relatively unknown. We used poisson regression with robust variance to evaluate the association between baseline arsenic exposure (urine arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident metabolic syndrome and its individual components (elevated waist circumference, elevated triglycerides, reduced HDL, hypertension, elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort in American Indian communities (baseline visits in 1998-1999 and 2001-2003, follow-up visits in 2001-2003 and 2006-2009). 32% of participants developed metabolic syndrome over follow-up. An IQR increase in arsenic exposure was associated with 1.19 (95% CI: 1.01, 1.41) greater risk for elevated fasting plasma glucose but not with other individual components or overall metabolic syndrome. Arsenic metabolism, specifically lower MMA% and higher DMA% was associated with higher risk of overall metabolic syndrome and elevated waist circumference, but not with any other component. These findings support there is a contrasting and independent association between arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.

  15. Supporting ATLAS

    2003-01-01

    Eighteen feet made of stainless steel will support the barrel ATLAS detector in the cavern at Point 1. In total, the ATLAS feet system will carry approximately 6000 tons, and will give the same inclination to the detector as the LHC accelerator. The installation of the feet is scheduled to finish during January 2004 with an installation precision at the 1 mm level despite their height of 5.3 metres. The manufacture was carried out in Russia (Company Izhorskiye Zavody in St. Petersburg), as part of a Russian and JINR Dubna in-kind contribution to ATLAS. Involved in the installation is a team from IHEP-Protvino (Russia), the ATLAS technical co-ordination team at CERN, and the CERN survey team. In all, about 15 people are involved. After the feet are in place, the barrel toroid magnet and the barrel calorimeters will be installed. This will keep the ATLAS team busy for the entire year 2004.

  16. Redesign of the Human Metabolic Simulator

    Duffield, Bruce; Jeng, Frank; Lange, Kevin

    2004-01-01

    The National Aeronautics and Space Administration (NASA) is currently building a Human Metabolic Simulator (HMS) at the Johnson Space Center as part of the Advanced Life Support Air Revitalization Technology Evaluation Facility (ARTEF). The purpose of ARTEF is to evaluate Environmental Control and Life Support System Technologies for Advanced Missions. The HMS is needed to reproduce the primary metabolic effects of human respiration on an enclosed atmosphere when humans cannot be present and the impact of human presence on the system is required. A HMS was designed, built and successfully operated in 2000 but larger crew size requirements and the expense of upgrade of the current system necessitate redesign. This paper addresses the redesign. Several concepts were considered, ranging from chemical oxidation of a hydrocarbon like ethanol or ethyl acetate to carbon dioxide and water, oxidation of an iron-containing compound, or by using a fuel cell. For reasons of cost, simplicity, safety and other factors, the concept chosen includes: a molecular sieve packaged as an industrial oxygen concentrator to remove oxygen from the atmosphere, with direct carbon dioxide, water and heat injection. The water injection is done via heating water to steam with a heat exchanger and thermal effects are handled by directly adding heat to the air stream with a second heat exchanger. Both heat exchangers are supplied by a hot oil loop. The amount of oxygen removal, carbon dioxide addition, water addition and heat addition were calculated using metabolic profiles for respiration and heat, calculated using a series of empirical equations developed for International Space Station (ISS). Sketches of the Human Metabolic Simulator and the hot oil bath loop used to supply heat to the heat exchangers are included

  17. Metabolic assessments during extra-vehicular activity

    Osipov, Yu. Yu.; Spichkov, A. N.; Filipenkov, S. N.

    Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha'(ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO 2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

  18. Metal metabolism and toxicity

    Bhattacharyya, M.H.; Larsen, R.P.; Whelton, B.D.; Moretti, E.S.; Peterson, D.P.; Oldham, R.D.

    1985-01-01

    This research focuses on the role of pregnancy and lactation in susceptibility to the toxic effects of cadmium and lead. Responses under investigation include lead-induced changes in pathways for vitamin D and calcium metabolism and cadmium-induced alterations in kidney function and skeletal structure. The second area focuses on the gastrointestinal absorption of plutonium and other actinide elements. Studies currently being conducted in nonhuman primates to develop a procedure to determine GI absorption values of uranium and plutonium that does not require sacrifice of the animal. 6 refs

  19. Connecting Myokines and Metabolism

    Rexford S. Ahima

    2015-09-01

    Full Text Available Skeletal muscle is the largest organ of the body in non-obese individuals and is now considered to be an endocrine organ. Hormones (myokines secreted by skeletal muscle mediate communications between muscle and liver, adipose tissue, brain, and other organs. Myokines affect muscle mass and myofiber switching, and have profound effects on glucose and lipid metabolism and inflammation, thus contributing to energy homeostasis and the pathogenesis of obesity, diabetes, and other diseases. In this review, we summarize recent findings on the biology of myokines and provide an assessment of their potential as therapeutic targets.

  20. Novel Composite Membrane for Space Life Supporting System, Phase I

    National Aeronautics and Space Administration — Space life-supporting systems require effective removal of metabolic CO2 from the cabin atmosphere with minimal loss of O2. Conventional techniques, using either...

  1. Metabolic syndrome, diet and exercise.

    De Sousa, Sunita M C; Norman, Robert J

    2016-11-01

    Polycystic ovary syndrome (PCOS) is associated with a range of metabolic complications including insulin resistance (IR), obesity, dyslipidaemia, hypertension, obstructive sleep apnoea (OSA) and non-alcoholic fatty liver disease. These compound risks result in a high prevalence of metabolic syndrome and possibly increased cardiovascular (CV) disease. As the cardiometabolic risk of PCOS is shared amongst the different diagnostic systems, all women with PCOS should undergo metabolic surveillance though the precise approach differs between guidelines. Lifestyle interventions consisting of increased physical activity and caloric restriction have been shown to improve both metabolic and reproductive outcomes. Pharmacotherapy and bariatric surgery may be considered in resistant metabolic disease. Issues requiring further research include the natural history of PCOS-associated metabolic disease, absolute CV risk and comparative efficacy of lifestyle interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Metabolic Reprogramming in Thyroid Carcinoma

    Raquel Guimaraes Coelho

    2018-03-01

    Full Text Available Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer.

  3. Metabolic Reprogramming in Thyroid Carcinoma

    Coelho, Raquel Guimaraes; Fortunato, Rodrigo S.; Carvalho, Denise P.

    2018-01-01

    Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer. PMID:29629339

  4. Horizontal and vertical growth of S. cerevisiae metabolic network.

    Grassi, Luigi

    2011-10-14

    BACKGROUND: The growth and development of a biological organism is reflected by its metabolic network, the evolution of which relies on the essential gene duplication mechanism. There are two current views about the evolution of metabolic networks. The retrograde model hypothesizes that a pathway evolves by recruiting novel enzymes in a direction opposite to the metabolic flow. The patchwork model is instead based on the assumption that the evolution is based on the exploitation of broad-specificity enzymes capable of catalysing a variety of metabolic reactions. RESULTS: We analysed a well-studied unicellular eukaryotic organism, S. cerevisiae, and studied the effect of the removal of paralogous gene products on its metabolic network. Our results, obtained using different paralog and network definitions, show that, after an initial period when gene duplication was indeed instrumental in expanding the metabolic space, the latter reached an equilibrium and subsequent gene duplications were used as a source of more specialized enzymes rather than as a source of novel reactions. We also show that the switch between the two evolutionary strategies in S. cerevisiae can be dated to about 350 million years ago. CONCLUSIONS: Our data, obtained through a novel analysis methodology, strongly supports the hypothesis that the patchwork model better explains the more recent evolution of the S. cerevisiae metabolic network. Interestingly, the effects of a patchwork strategy acting before the Euascomycete-Hemiascomycete divergence are still detectable today.

  5. Citrus Flavonoids as Regulators of Lipoprotein Metabolism and Atherosclerosis.

    Mulvihill, Erin E; Burke, Amy C; Huff, Murray W

    2016-07-17

    Citrus flavonoids are polyphenolic compounds with significant biological properties. This review summarizes recent advances in understanding the ability of citrus flavonoids to modulate lipid metabolism, other metabolic parameters related to the metabolic syndrome, and atherosclerosis. Citrus flavonoids, including naringenin, hesperitin, nobiletin, and tangeretin, have emerged as potential therapeutics for the treatment of metabolic dysregulation. Epidemiological studies reveal an association between the intake of citrus flavonoid-containing foods and a decreased incidence of cardiovascular disease. Studies in cell culture and animal models, as well as a limited number of clinical studies, reveal the lipid-lowering, insulin-sensitizing, antihypertensive, and anti-inflammatory properties of citrus flavonoids. In animal models, supplementation of rodent diets with citrus flavonoids prevents hepatic steatosis, dyslipidemia, and insulin resistance primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver, adipose, kidney, and the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have not been completely established, although several potential targets have been identified. In mouse models, citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters as well as through direct impact on the vessel wall. Recent studies support a role for citrus flavonoids in the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity, and atherosclerosis. Larger human studies examining dose, bioavailability, efficacy, and safety are required to promote the development of these promising therapeutic agents.

  6. Metabolic topography of Parkinsonism

    Kim, Jae Seung [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson disorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkinsonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, and assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of Parkinsonism.

  7. Drug metabolism and ageing.

    Wynne, Hilary

    2005-06-01

    Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24-35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

  8. Metabolic topography of Parkinsonism

    Kim, Jae Seung

    2007-01-01

    Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson disorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkinsonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, and assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of Parkinsonism

  9. Metabolic regulation of yeast

    Fiechter, A.

    1982-12-01

    Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

  10. Biochemical Hypermedia: Galactose Metabolism.

    J.K. Sugai

    2013-05-01

    Full Text Available Introduction: Animations of biochemical processes and virtual laboratory environments lead to true molecular simulations. The use of interactive software’s in education can improve cognitive capacity, better learning and, mainly, it makes information acquisition easier. Material and Methods: This work presents the development of a biochemical hypermedia to understanding of the galactose metabolism. It was developed with the help of concept maps, ISIS Draw, ADOBE Photoshop and FLASH MX Program. Results and Discussion: A step by step animation process shows the enzymatic reactions of galactose conversion to glucose-1-phosphate (to glycogen synthesis, glucose-6-phosphate (glycolysis intermediary, UDP-galactose (substrate to mucopolysaccharides synthesis and collagen’s glycosylation. There are navigation guide that allow scrolling the mouse over the names of the components of enzymatic reactions of via the metabolism of galactose. Thus, explanatory text box, chemical structures and animation of the actions of enzymes appear to navigator. Upon completion of the module, the user’s response to the proposed exercise can be checked immediately through text box with interactive content of the answer. Conclusion: This hypermedia was presented for undergraduate students (UFSC who revealed that it was extremely effective in promoting the understanding of the theme.

  11. [Metabolic bone disease osteomalacia].

    Reuss-Borst, M A

    2014-05-01

    Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases.

  12. Supportive care in radiation oncology

    Rotman, M.; John, M.

    1987-01-01

    The radiation therapist, concerned with the disease process and all the technical intricacies of treatment, has usually not been involved in managing the supportive aspects of caring for the patient. Yet, of the team of medical specialists and allied health personnel required in oncology, the radiation therapist is the one most responsible for overseeing the total care of the cancer patient. At times this might include emotional support, prevention and correction of tissue dysfunction, augmentation of nutrition, metabolic and electrolyte regulation, rehabilitation, and vocational support. This chapter is a brief overview of a considerable volume of literature that has occupied the interest of a rather small group of physicians, nutritionists, and psychologists. The discussion highlights the special management problems of the normal-tissue effects of radiation, the related nutritional aspects of cancer care, and certain emotional and pathologic considerations

  13. Metabolic rates of giant pandas inform conservation strategies

    Fei, Yuxiang; Hou, Rong; Spotila, James R.; Paladino, Frank V.; Qi, Dunwu; Zhang, Zhihe

    2016-01-01

    The giant panda is an icon of conservation and survived a large-scale bamboo die off in the 1980s in China. Captive breeding programs have produced a large population in zoos and efforts continue to reintroduce those animals into the wild. However, we lack sufficient knowledge of their physiological ecology to determine requirements for survival now and in the face of climate change. We measured resting and active metabolic rates of giant pandas in order to determine if current bamboo resources were sufficient for adding additional animals to populations in natural reserves. Resting metabolic rates were somewhat below average for a panda sized mammal and active metabolic rates were in the normal range. Pandas do not have exceptionally low metabolic rates. Nevertheless, there is enough bamboo in natural reserves to support both natural populations and large numbers of reintroduced pandas. Bamboo will not be the limiting factor in successful reintroduction. PMID:27264109

  14. Metabolic rates of giant pandas inform conservation strategies

    Fei, Yuxiang; Hou, Rong; Spotila, James R.; Paladino, Frank V.; Qi, Dunwu; Zhang, Zhihe

    2016-06-01

    The giant panda is an icon of conservation and survived a large-scale bamboo die off in the 1980s in China. Captive breeding programs have produced a large population in zoos and efforts continue to reintroduce those animals into the wild. However, we lack sufficient knowledge of their physiological ecology to determine requirements for survival now and in the face of climate change. We measured resting and active metabolic rates of giant pandas in order to determine if current bamboo resources were sufficient for adding additional animals to populations in natural reserves. Resting metabolic rates were somewhat below average for a panda sized mammal and active metabolic rates were in the normal range. Pandas do not have exceptionally low metabolic rates. Nevertheless, there is enough bamboo in natural reserves to support both natural populations and large numbers of reintroduced pandas. Bamboo will not be the limiting factor in successful reintroduction.

  15. Support facilities

    Williamson, F.S.; Blomquist, J.A.; Fox, C.A.

    1977-01-01

    Computer support is centered on the Remote Access Data Station (RADS), which is equipped with a 1000 lpm printer, 1000 cpm reader, and a 300 cps paper tape reader with 500-foot spools. The RADS is located in a data preparation room with four 029 key punches (two of which interpret), a storage vault for archival magnetic tapes, card files, and a 30 cps interactive terminal principally used for job inquiry and routing. An adjacent room provides work space for users, with a documentation library and a consultant's office, plus file storage for programs and their documentations. The facility has approximately 2,600 square feet of working laboratory space, and includes two fully equipped photographic darkrooms, sectioning and autoradiographic facilities, six microscope cubicles, and five transmission electron microscopes and one Cambridge scanning electron microscope equipped with an x-ray energy dispersive analytical system. Ancillary specimen preparative equipment includes vacuum evaporators, freeze-drying and freeze-etching equipment, ultramicrotomes, and assorted photographic and light microscopic equipment. The extensive physical plant of the animal facilities includes provisions for holding all species of laboratory animals under controlled conditions of temperature, humidity, and lighting. More than forty rooms are available for studies of the smaller species. These have a potential capacity of more than 75,000 mice, or smaller numbers of larger species and those requiring special housing arrangements. There are also six dog kennels to accommodate approximately 750 dogs housed in runs that consist of heated indoor compartments and outdoor exercise areas

  16. 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.

  17. Gut Microbiota and Metabolic Disorders

    Kyu Yeon Hur

    2015-06-01

    Full Text Available Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders.

  18. Clinical update on metabolic syndrome

    Juan Diego Hernández-Camacho

    2017-12-01

    Full Text Available Metabolic syndrome has been defined as a global issue since it affects a lot of people. Numerous factors are involved in metabolic syndrome development. It has been described that metabolic syndrome has negative consequences on health. Consequently, a lot of treatments have been proposed to palliate it such as drugs, surgery or life style changes where nutritional habits have shown to be an important point in its management. The current study reviews the literature existing about the actual epidemiology of metabolic syndrome, the components involucrate in its appearance and progression, the clinical consequences of metabolic syndrome and the nutritional strategies reported in its remission. A bibliographic search in PubMed and Medline was performed to identify eligible studies. Authors obtained that metabolic syndrome is present in population from developed and undeveloped areas in a huge scale. Environmental and genetic elements are involucrate in metabolic syndrome development. Metabolic syndrome exponentially increased risk of cardiovascular disease, some types of cancers, diabetes mellitus type 2, sleep disturbances, etc. Nutritional treatments play a crucial role in metabolic syndrome prevention, treatment and recovery.

  19. A state of the art of metabolic networks of unicellular microalgae and cyanobacteria for biofuel production.

    Baroukh, Caroline; Muñoz-Tamayo, Rafael; Steyer, Jean-Philippe; Bernard, Olivier

    2015-07-01

    The most promising and yet challenging application of microalgae and cyanobacteria is the production of renewable energy: biodiesel from microalgae triacylglycerols and bioethanol from cyanobacteria carbohydrates. A thorough understanding of microalgal and cyanobacterial metabolism is necessary to master and optimize biofuel production yields. To this end, systems biology and metabolic modeling have proven to be very efficient tools if supported by an accurate knowledge of the metabolic network. However, unlike heterotrophic microorganisms that utilize the same substrate for energy and as carbon source, microalgae and cyanobacteria require light for energy and inorganic carbon (CO2 or bicarbonate) as carbon source. This double specificity, together with the complex mechanisms of light capture, makes the representation of metabolic network nonstandard. Here, we review the existing metabolic networks of photoautotrophic microalgae and cyanobacteria. We highlight how these networks have been useful for gaining insight on photoautotrophic metabolism. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  20. Metabolic Regulation of Histone Acetyltransferases by Endogenous Acyl-CoA Cofactors

    Montgomery, David C.; Sorum, Alexander W.; Guasch, Laura; Nicklaus, Marc C.; Meier, Jordan L.

    2015-01-01

    The finding that chromatin modifications are sensitive to changes in cellular cofactor levels potentially links altered tumor cell metabolism and gene expression. However, the specific enzymes and metabolites that connect these two processes remain obscure. Characterizing these metabolic-epigenetic axes is critical to understanding how metabolism supports signaling in cancer, and developing therapeutic strategies to disrupt this process. Here, we describe a chemical approach to define the met...

  1. Metabolic interrelationships software application: Interactive learning tool for intermediary metabolism

    A.J.M. Verhoeven (Adrie); M. Doets (Mathijs); J.M.J. Lamers (Jos); J.F. Koster (Johan)

    2005-01-01

    textabstractWe developed and implemented the software application titled Metabolic Interrelationships as a self-learning and -teaching tool for intermediary metabolism. It is used by undergraduate medical students in an integrated organ systems-based and disease-oriented core curriculum, which

  2. Metabolism during hypodynamia

    Federov, I. V.

    1980-01-01

    Physical immobilization, inaction due to space travel, a sedentary occupation, or bed confinement due to a chronic illness elicit similar alternations in the metabolism of man and animals (rat, rabbit, dog, mouse). After a preliminary period of weight loss, there is eventually weight gain due to increased lipid storage. Protein catabolism is enhanced and anabolism depressed, with elevated urinary excretion of amino acids, creatine, and ammonia. Glycogen stores are depleted and glyconeogenesis is accelerated. Polyuria develops with subsequent redistribution of body fluids in which the blood volume of the systemic circulation is decreased and that of pulmonary circulation increased. This results in depressed production of vasopressin by the posterior pituitary which further enhances urinary water and salt loss.

  3. Olfaction Under Metabolic Influences

    2012-01-01

    Recently published work and emerging research efforts have suggested that the olfactory system is intimately linked with the endocrine systems that regulate or modify energy balance. Although much attention has been focused on the parallels between taste transduction and neuroendocrine controls of digestion due to the novel discovery of taste receptors and molecular components shared by the tongue and gut, the equivalent body of knowledge that has accumulated for the olfactory system, has largely been overlooked. During regular cycles of food intake or disorders of endocrine function, olfaction is modulated in response to changing levels of various molecules, such as ghrelin, orexins, neuropeptide Y, insulin, leptin, and cholecystokinin. In view of the worldwide health concern regarding the rising incidence of diabetes, obesity, and related metabolic disorders, we present a comprehensive review that addresses the current knowledge of hormonal modulation of olfactory perception and how disruption of hormonal signaling in the olfactory system can affect energy homeostasis. PMID:22832483

  4. Metabolic syndrome and asthma.

    Garmendia, Jenny V; Moreno, Dolores; Garcia, Alexis H; De Sanctis, Juan B

    2014-01-01

    Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.

  5. Early anaerobic metabolisms

    Canfield, Donald Eugene; Rosing, Minik T; Bjerrum, Christian

    2006-01-01

    probably driven by the cycling of H2 and Fe2+ through primary production conducted by anoxygenic phototrophs. Interesting and dynamic ecosystems would have also been driven by the microbial cycling of sulphur and nitrogen species, but their activity levels were probably not so great. Despite the diversity......Before the advent of oxygenic photosynthesis, the biosphere was driven by anaerobic metabolisms. We catalogue and quantify the source strengths of the most probable electron donors and electron acceptors that would have been available to fuel early-Earth ecosystems. The most active ecosystems were...... of potential early ecosystems, rates of primary production in the early-Earth anaerobic biosphere were probably well below those rates observed in the marine environment. We shift our attention to the Earth environment at 3.8Gyr ago, where the earliest marine sediments are preserved. We calculate, consistent...

  6. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism.

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.

  7. Lactate rescues neuronal sodium homeostasis during impaired energy metabolism

    Karus, Claudia; Ziemens, Daniel; Rose, Christine R

    2015-01-01

    Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle. PMID:26039160

  8. Adaptations of energy metabolism during cerebellar neurogenesis are co-opted in medulloblastoma.

    Tech, Katherine; Deshmukh, Mohanish; Gershon, Timothy R

    2015-01-28

    Recent studies show that metabolic patterns typical of cancer cells, including aerobic glycolysis and increased lipogenesis, are not unique to malignancy, but rather originate in physiologic development. In the postnatal brain, where sufficient oxygen for energy metabolism is scrupulously maintained, neural progenitors nevertheless metabolize glucose to lactate and prioritize lipid synthesis over fatty acid oxidation. Medulloblastoma, a cancer of neural progenitors that is the most common malignant brain tumor in children, recapitulates the metabolic phenotype of brain progenitor cells. During the physiologic proliferation of neural progenitors, metabolic enzymes generally associated with malignancy, including Hexokinase 2 (Hk2) and Pyruvate kinase M2 (PkM2) configure energy metabolism to support growth. In these non-malignant cells, expression of Hk2 and PkM2 is driven by transcriptional regulators that are typically identified as oncogenes, including N-myc. Importantly, N-myc continues to drive Hk2 and PkM2 in medulloblastoma. Similarly E2F transcription factors and PPARγ function in both progenitors and medulloblastoma to optimize energy metabolism to support proliferation. These findings show that the "metabolic transformation" that is a hallmark of cancer is not specifically limited to cancer. Rather, metabolic transformation represents a co-opting of developmental programs integral to physiologic growth. Despite their physiologic origins, the molecular mechanisms that mediate metabolic transformation may nevertheless present ideal targets for novel anti-tumor therapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. [Regulation of terpene metabolism

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C[sub 15] C[sub 20], C[sub 30], C[sub 40]) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C[sub 15]) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  10. SU-E-J-102: Separation of Metabolic Supply and Demand: From Power Grid Economics to Cancer Metabolism

    Epstein, T; Xu, L; Gillies, R; Gatenby, R [Moffitt Cancer Center and Research Institute, Tampa, FL (United States)

    2014-06-01

    Purpose: To study a new model of glucose metabolism which is primarily governed by the timescale of the energetic demand and not by the oxygen level, and its implication on cancer metabolism (Warburg effect) Methods: 1) Metabolic profiling of membrane transporters activity in several cell lines, which represent the spectrum from normal breast epithelium to aggressive, metastatic cancer, using Seahorse XF reader.2) Spatial localization of oxidative and non-oxidative metabolic components using immunocytochemical imaging of the glycolytic ATP-producing enzyme, pyruvate kinase and mitochondria. 3) Finite element simulations of coupled partial differential equations using COMSOL and MATLAB. Results: Inhibition or activation of pumps on the cell membrane led to reduction or increase in aerobic glycolysis, respectively, while oxidative phosphorylation remained unchanged. These results were consistent with computational simulations of changes in short-timescale demand for energy by cell membrane processes. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. These predictions were confirmed experimentally. Conclusion: The results in this work support a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Similar to power grid economics, optimal metabolic control requires the two pathways, even in normoxic conditions, to match two different types of energy demands. Cells use aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism to meet short-timescale energy demands, mainly from membrane transport activities, even in the presence of oxygen. This model provides a mechanism for the origin of the Warburg effect in cancer cells. Here, the Warburg effect emerges during carcinogenesis is a physiological

  11. SU-E-J-102: Separation of Metabolic Supply and Demand: From Power Grid Economics to Cancer Metabolism

    Epstein, T; Xu, L; Gillies, R; Gatenby, R

    2014-01-01

    Purpose: To study a new model of glucose metabolism which is primarily governed by the timescale of the energetic demand and not by the oxygen level, and its implication on cancer metabolism (Warburg effect) Methods: 1) Metabolic profiling of membrane transporters activity in several cell lines, which represent the spectrum from normal breast epithelium to aggressive, metastatic cancer, using Seahorse XF reader.2) Spatial localization of oxidative and non-oxidative metabolic components using immunocytochemical imaging of the glycolytic ATP-producing enzyme, pyruvate kinase and mitochondria. 3) Finite element simulations of coupled partial differential equations using COMSOL and MATLAB. Results: Inhibition or activation of pumps on the cell membrane led to reduction or increase in aerobic glycolysis, respectively, while oxidative phosphorylation remained unchanged. These results were consistent with computational simulations of changes in short-timescale demand for energy by cell membrane processes. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. These predictions were confirmed experimentally. Conclusion: The results in this work support a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Similar to power grid economics, optimal metabolic control requires the two pathways, even in normoxic conditions, to match two different types of energy demands. Cells use aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism to meet short-timescale energy demands, mainly from membrane transport activities, even in the presence of oxygen. This model provides a mechanism for the origin of the Warburg effect in cancer cells. Here, the Warburg effect emerges during carcinogenesis is a physiological

  12. Metabolic syndrome in urban DRDO population

    Prakash P Bellubbi

    2015-01-01

    Full Text Available Metabolic syndrome is a common condition occurring all over the world which is also known by other terminology such as Dysmetabolic syndrome, Syndrome X, Insulin Resistance syndrome, Obesity syndrome, or Reaven′s syndrome. Metabolic syndrome is constituted by a group of Risk Factors such as Trunkal Obesity, Impaired or Altered Glucose Tolerance, Dyslipidemia and Hypertension. Individuals with these risk factors are at a greater risk of developing a cardiovascular disease or Type 2 Diabetes. NCEP, National Heart, lung and Blood Institute, National Institutes of Health periodically publishes ATP clinical updates as warranted by advances in the cholesterol management. Each of the guideline reports -ATP I, II and III - has a major thrust in Cardiovascular Risk Management. While some of the features of ATP I and ATP II are shared by ATP III guidelines, there are some salient differences. ATP III focuses on Multiple risk factors and recommends the use ofFramingham projections of 10 year absolute risk, modifies lipid and lipoprotein classification and supports for implementation of a revised schedule for screening and Therapeutic Life-style Changes. DRDO has embarked upon a program to assess the occupational health risk and the coronary risk status of the DRDO and defence employees. The present paper describes incidence of Metabolic Syndrome amongst the DRDO and Defence employees, using the ATP III guidelines and importance of calculating the absolute coronary risk status of these personnel.

  13. A CASE OF METABOLIC SYNDROME

    Khoo Ee Ming; Rabia Khatoon

    2006-01-01

    This case report illustrates a 40-year-old woman who presented with chest discomfort that was subsequently diagnosed to have metabolic syndrome. Metabolic syndrome is a common condition associated with increased cardiovascular morbidity and mortality. As primary care providers, we should be detect this condition early, intervene and prevent appropriately before complications occur.

  14. Artificial Promoters for Metabolic Optimization

    Jensen, Peter Ruhdal; Hammer, Karin

    1998-01-01

    In this article, we review some of the expression systems that are available for Metabolic Control Analysis and Metabolic Engineering, and examine their advantages and disadvantages in different contexts. In a recent approach, artificial promoters for modulating gene expression in micro-organisms...

  15. Metabolic alterations in dialysis patients

    Drechsler, Christiane

    2010-01-01

    Assessing metabolic risk in dialysis patients, three main aspects are important: a) the pathophysiologic effects of metabolic disturbances as known from the general population are unlikely to completely reverse once patients reach dialysis. b) Specific additional problems related to chronic kidney

  16. Selected Metabolic Responses to Skateboarding

    Hetzler, Ronald K.; Hunt, Ian; Stickley, Christopher D.; Kimura, Iris F.

    2011-01-01

    Despite the popularity of skateboarding worldwide, the authors believe that no previous studies have investigated the metabolic demands associated with recreational participation in the sport. Although metabolic equivalents (METs) for skateboarding were published in textbooks, the source of these values is unclear. Therefore, the rise in…

  17. Gait Dynamics and Locomotor Metabolism

    2014-12-01

    26 47. Taylor CR, Heglund NC, Maloiy GMO . Energetics and mechanics of terrestrial locomotion. I. Metabolic energy consumption as a function of...San Diego, CA: Academic Press, 1994. 110 47. Taylor CR, Heglund NC, Maloiy GMO . Energetics and mechanics of terrestrial locomotion. I. Metabolic

  18. Metabolic network prediction through pairwise rational kernels.

    Roche-Lima, Abiel; Domaratzki, Michael; Fristensky, Brian

    2014-09-26

    Metabolic networks are represented by the set of metabolic pathways. Metabolic pathways are a series of biochemical reactions, in which the product (output) from one reaction serves as the substrate (input) to another reaction. Many pathways remain incompletely characterized. One of the major challenges of computational biology is to obtain better models of metabolic pathways. Existing models are dependent on the annotation of the genes. This propagates error accumulation when the pathways are predicted by incorrectly annotated genes. Pairwise classification methods are supervised learning methods used to classify new pair of entities. Some of these classification methods, e.g., Pairwise Support Vector Machines (SVMs), use pairwise kernels. Pairwise kernels describe similarity measures between two pairs of entities. Using pairwise kernels to handle sequence data requires long processing times and large storage. Rational kernels are kernels based on weighted finite-state transducers that represent similarity measures between sequences or automata. They have been effectively used in problems that handle large amount of sequence information such as protein essentiality, natural language processing and machine translations. We create a new family of pairwise kernels using weighted finite-state transducers (called Pairwise Rational Kernel (PRK)) to predict metabolic pathways from a variety of biological data. PRKs take advantage of the simpler representations and faster algorithms of transducers. Because raw sequence data can be used, the predictor model avoids the errors introduced by incorrect gene annotations. We then developed several experiments with PRKs and Pairwise SVM to validate our methods using the metabolic network of Saccharomyces cerevisiae. As a result, when PRKs are used, our method executes faster in comparison with other pairwise kernels. Also, when we use PRKs combined with other simple kernels that include evolutionary information, the accuracy

  19. The use of metabolic balance studies in the objective discrimination between intestinal insufficiency and intestinal failure

    Prahm, August P; Brandt, Christopher F; Askov-Hansen, Carsten

    2017-01-01

    Background: In research settings that use metabolic balance studies (MBSs) of stable adult patients with short bowel syndrome, intestinal failure (IF) and dependence on parenteral support (PS) have been defined objectively as energy absorption metabolic rate (BMR), wet......, to objectivize the cause of nutritional dyshomeostasis (oral failure, malabsorption, or both), and to quantify the effects of treatment....

  20. Effects of independently altering body weight and body mass on the metabolic cost of running

    Teunissen, L.P.J.; Grabowski, A.; Kram, R.

    2011-01-01

    The metabolic cost of running is substantial, despite the savings from elastic energy storage and return. Previous studies suggest that generating vertical force to support body weight and horizontal forces to brake and propel body mass are the major determinants of the metabolic cost of running. In

  1. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill

    2015-01-01

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular...

  2. Aspects involved in the (patho)physiology of the metabolic syndrome

    Duivenvoorden, Ilse

    2006-01-01

    The metabolic syndrome is an increasing problem in our Western society. Many of the features of the metabolic syndrome, like obesity, insulin resistance, dyslipidemia, and hepatic steatosis are established risk factors for cardiovascular disease. Growing evidence supports the important role of body

  3. 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

  4. Modelling central metabolic fluxes by constraint-based optimization reveals metabolic reprogramming of developing Solanum lycopersicum (tomato) fruit.

    Colombié, Sophie; Nazaret, Christine; Bénard, Camille; Biais, Benoît; Mengin, Virginie; Solé, Marion; Fouillen, Laëtitia; Dieuaide-Noubhani, Martine; Mazat, Jean-Pierre; Beauvoit, Bertrand; Gibon, Yves

    2015-01-01

    Modelling of metabolic networks is a powerful tool to analyse the behaviour of developing plant organs, including fruits. Guided by our current understanding of heterotrophic metabolism of plant cells, a medium-scale stoichiometric model, including the balance of co-factors and energy, was constructed in order to describe metabolic shifts that occur through the nine sequential stages of Solanum lycopersicum (tomato) fruit development. The measured concentrations of the main biomass components and the accumulated metabolites in the pericarp, determined at each stage, were fitted in order to calculate, by derivation, the corresponding external fluxes. They were used as constraints to solve the model by minimizing the internal fluxes. The distribution of the calculated fluxes of central metabolism were then analysed and compared with known metabolic behaviours. For instance, the partition of the main metabolic pathways (glycolysis, pentose phosphate pathway, etc.) was relevant throughout fruit development. We also predicted a valid import of carbon and nitrogen by the fruit, as well as a consistent CO2 release. Interestingly, the energetic balance indicates that excess ATP is dissipated just before the onset of ripening, supporting the concept of the climacteric crisis. Finally, the apparent contradiction between calculated fluxes with low values compared with measured enzyme capacities suggest a complex reprogramming of the metabolic machinery during fruit development. With a powerful set of experimental data and an accurate definition of the metabolic system, this work provides important insight into the metabolic and physiological requirements of the developing tomato fruits. © 2014 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

  5. Oral cancer cells may rewire alternative metabolic pathways to survive from siRNA silencing of metabolic enzymes

    Zhang, Min; Chai, Yang D; Brumbaugh, Jeffrey; Liu, Xiaojun; Rabii, Ramin; Feng, Sizhe; Misuno, Kaori; Messadi, Diana; Hu, Shen

    2014-01-01

    Cancer cells may undergo metabolic adaptations that support their growth as well as drug resistance properties. The purpose of this study is to test if oral cancer cells can overcome the metabolic defects introduced by using small interfering RNA (siRNA) to knock down their expression of important metabolic enzymes. UM1 and UM2 oral cancer cells were transfected with siRNA to transketolase (TKT) or siRNA to adenylate kinase (AK2), and Western blotting was used to confirm the knockdown. Cellular uptake of glucose and glutamine and production of lactate were compared between the cancer cells with either TKT or AK2 knockdown and those transfected with control siRNA. Statistical analysis was performed with student T-test. Despite the defect in the pentose phosphate pathway caused by siRNA knockdown of TKT, the survived UM1 or UM2 cells utilized more glucose and glutamine and secreted a significantly higher amount of lactate than the cells transferred with control siRNA. We also demonstrated that siRNA knockdown of AK2 constrained the proliferation of UM1 and UM2 cells but similarly led to an increased uptake of glucose/glutamine and production of lactate by the UM1 or UM2 cells survived from siRNA silencing of AK2. Our results indicate that the metabolic defects introduced by siRNA silencing of metabolic enzymes TKT or AK2 may be compensated by alternative feedback metabolic mechanisms, suggesting that cancer cells may overcome single defective pathways through secondary metabolic network adaptations. The highly robust nature of oral cancer cell metabolism implies that a systematic medical approach targeting multiple metabolic pathways may be needed to accomplish the continued improvement of cancer treatment

  6. [Hypovitaminosis D and metabolic syndrome].

    Miñambres, Inka; de Leiva, Alberto; Pérez, Antonio

    2014-12-23

    Metabolic syndrome and hypovitaminosis D are 2 diseases with high prevalence that share several risk factors, while epidemiological evidence shows they are associated. Although the mechanisms involved in this association are not well established, hypovitaminosis D is associated with insulin resistance, decreased insulin secretion and activation of the renin-angiotensin system, mechanisms involved in the pathophysiology of metabolic syndrome. However, the apparent ineffectiveness of vitamin D supplementation on metabolic syndrome components, as well as the limited information about the effect of improving metabolic syndrome components on vitamin D concentrations, does not clarify the direction and the mechanisms involved in the causal relationship between these 2 pathologies. Overall, because of the high prevalence and the epidemiological association between both diseases, hypovitaminosis D could be considered a component of the metabolic syndrome. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  7. Vitamin A Metabolism: An Update

    William S. Blaner

    2011-01-01

    Full Text Available Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years.

  8. The metabolic switch of cancer

    Yuting Ma

    2017-03-01

    Full Text Available Although remarkable progress has been made in oncology research, cancer is still a leading cause of death worldwide. It is well recognized that cancer is a genetic disease, yet metabolic alterations or reprogramming are the major phenotypes associated with the (epi-genetic modifications of cancer cells. Thus, understanding the metabolic changes of tumor cells will facilitate the diagnosis of cancer, alleviate drug resistance and provide novel druggable targets that can lead to cures for cancer. The first Sino-US Symposium on Cancer Metabolism was held in Chongqing on October 10th and 11th, with the theme of “cancer metabolism and precision cancer therapy”. The symposium brought about a dozen keynote speakers each from the US and mainland China, as well as one hundred delegates with an interest in cancer metabolism. This short article will briefly summarize the advances reported during this meeting.

  9. Variation in winter metabolic reduction between sympatric amphibians

    Podhajský, Luděk; Gvoždík, Lumír

    2016-01-01

    Roč. 201, November (2016), s. 110-114 ISSN 1095-6433 R&D Projects: GA ČR(CZ) GA15-07140S Institutional support: RVO:68081766 Keywords : Caloric reserves * Ichthyosaura * Lissotriton * Metabolic rate * Newt * Oxygen consumption * Respirometry * Salamander * Thermal sensitivity * Wintering Subject RIV: EG - Zoology Impact factor: 1.812, year: 2016

  10. Constitutive Reprogramming of Fibroblast Mitochondrial Metabolism in Pulmonary Hypertension

    Plecitá-Hlavatá, Lydie; Tauber, Jan; Li, M.; Zhang, H.; Flockton, A. R.; Pullamsetti, S. S.; Chelladurai, P.; D'Alessandro, A.; El Kasmi, K. C.; Ježek, Petr; Stenmark, K. R.

    2016-01-01

    Roč. 55, č. 1 (2016), s. 47-57 ISSN 1044-1549 R&D Projects: GA MŠk(CZ) LH11055; GA MŠk(CZ) LH15071 Institutional support: RVO:67985823 Keywords : mitochondria * complex I * oxidative metabolism * pulmonary hypertension * adventitial fibroblasts Subject RIV: ED - Physiology Impact factor: 4.100, year: 2016

  11. Metabolic pathways of benzimidazole anthelmintics in harebell (Campanula rotundifolia)

    Stuchlíková, L.; Jirásko, R.; Skálová, L.; Pavlík, F.; Szotáková, B.; Holčapek, M.; Vaněk, Tomáš; Podlipná, Radka

    2016-01-01

    Roč. 157, AUG (2016), s. 10-17 ISSN 0045-6535 R&D Projects: GA ČR(CZ) GA15-05325S Institutional support: RVO:61389030 Keywords : Drug metabolism * Biotransformation * Albendazole Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.208, year: 2016

  12. Activating transcription factor 3 regulates immune and metabolic homeostasis

    Ryneš, J.; Donohoe, C. D.; Frommolt, P.; Brodesser, S.; Jindra, Marek; Uhlířová, M.

    2012-01-01

    Roč. 32, č. 19 (2012), s. 3949-3962 ISSN 0270-7306 R&D Projects: GA ČR(CZ) GD204/09/H058 Institutional support: RVO:60077344 Keywords : metabolic homeostasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.372, year: 2012

  13. Opposite metabolic responses of shoots and roots to drought

    Gargallo-Garriga, A.; Sardans, J.; Pérez-Trujillo, M.; Rivas-Ubach, A.; Oravec, Michal; Večeřová, Kristýna; Urban, Otmar; Jentsch, A.; Kreyling, J.; Beierkuhnlein, C.; Parella, T.; Penuelas, J.

    2014-01-01

    Roč. 4, č. 6829 (2014), s. 1-7 ISSN 2045-2322 Grant - others:AV ČR(CZ) M200871201 Institutional support: RVO:67179843 Keywords : shoot and roots * autotrophic and heterotrophic organs * environmental change * growth metabolism * water and nutirens Subject RIV: EH - Ecology, Behaviour Impact factor: 5.578, year: 2014

  14. A clustering analysis of lipoprotein diameters in the metabolic syndrome

    The presence of smaller low-density lipoproteins (LDL) has been associated with atherosclerosis risk, and the insulin resistance (IR) underlying the metabolic syndrome (MetS). In addition, some research has supported the association of very low-, low- and high-density lipoprotein (VLDL HDL) particle...

  15. Updating on Italian stroke units: the "CCM study".

    Guidetti, D; Spallazzi, M; Toni, D; Rota, E; Morelli, N; Immovilli, P; Baldereschi, M; Polizzi, B M; Ferro, S; Inzitari, D

    2013-07-01

    The stroke units (SUs) have been demonstrated to be efficient and cost effective for acute stroke care. Nevertheless, the level of stroke unit implementation in Italy does not correspond to expectations yet. This study is a survey, which aims at assessing the current status of in-hospital stroke care in the Italian regions and at updating SUs. The survey was conducted by means of a semi-structured questionnaire, based on 18 stroke care "quality indicators", submitted to all the Italian centres that had taken part in the SITS-MOST study, and to other centres advised by the coordinator of SITS studies and by regional opinion leaders of stroke. SUs were defined as acute wards, with stroke-dedicated beds and dedicated teams that had been formally authorised to administer rt-PA. A statistical analysis was performed by a descriptive statistics and logistic regression model. The study was carried out from November 2009 to September 2010. A total of 168 forms were sent out and 153 replies received. Seven centres, which had not performed any thrombolytic treatment, and 16 which did not fulfil the criteria for the definition of SU were excluded from the study. Most of the centres reported more than 100 stroke patient admissions per year, i.e., 122 (84%) from 100 to 500, 18 (12%) more than 500. The 19% of the centres admitted more than 30% of patients within 3 h from the symptom onset and only 30% admitted more than 30% of patients within 4.5 h. The mean number of thrombolyses performed in the last 6 months was 10 for centres with a doctor on duty 24 h a day, 6 for those that have a doctor on duty from 8 a.m. to 8 p.m. and a doctor on call for night, and 5 for centres with a doctor on call 24 h a day. The territorial distribution of the SUs is remarkably heterogeneous: 87 SUs (67%) are located in the North of Italy, 28 (22%) in the central part of Italy and only 15 (11%) in the South. The last few years have witnessed a rise in both the diffusion of SUs and access to thrombolytic therapy in Italy. Despite this, there are a few large areas, mostly in the south, where the requirements of healthcare legislation are not met, and access to a dedicated SU and thrombolytic treatment is still limited and poor.

  16. The CCM Model: A Management Approach to Performance Optimization

    Geroy, Gary D.; Bray, Amber; Venneberg, Donald L.

    2005-01-01

    Three leadership styles are frequently discussed in the literature today: transactional, transformational, and most recently--transcendental. Managers may be able to put transactional, transformational, and transcendental leadership style theories into practice without inventing a new set of processes and procedures to achieve individual follower…

  17. Double silencing of relevant genes suggests the existence of the direct link between DNA replication/repair and central carbon metabolism in human fibroblasts.

    Wieczorek, Aneta; Fornalewicz, Karolina; Mocarski, Łukasz; Łyżeń, Robert; Węgrzyn, Grzegorz

    2018-04-15

    Genetic evidence for a link between DNA replication and glycolysis has been demonstrated a decade ago in Bacillus subtilis, where temperature-sensitive mutations in genes coding for replication proteins could be suppressed by mutations in genes of glycolytic enzymes. Then, a strong influence of dysfunctions of particular enzymes from the central carbon metabolism (CCM) on DNA replication and repair in Escherichia coli was reported. Therefore, we asked if such a link occurs only in bacteria or it is a more general phenomenon. Here, we demonstrate that effects of silencing (provoked by siRNA) of expression of genes coding for proteins involved in DNA replication and repair (primase, DNA polymerase ι, ligase IV, and topoisomerase IIIβ) on these processes (less efficient entry into the S phase of the cell cycle and decreased level of DNA synthesis) could be suppressed by silencing of specific genes of enzymes from CMM. Silencing of other pairs of replication/repair and CMM genes resulted in enhancement of the negative effects of lower expression levels of replication/repair genes. We suggest that these results may be proposed as a genetic evidence for the link between DNA replication/repair and CMM in human cells, indicating that it is a common biological phenomenon, occurring from bacteria to humans. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Clinical Decision Support to Implement CYP2D6 Drug-Gene Interaction.

    Caraballo, Pedro J; Parkulo, Mark; Blair, David; Elliott, Michelle; Schultz, Cloann; Sutton, Joseph; Rao, Padma; Bruflat, Jamie; Bleimeyer, Robert; Crooks, John; Gabrielson, Donald; Nicholson, Wayne; Rohrer Vitek, Carolyn; Wix, Kelly; Bielinski, Suzette J; Pathak, Jyotishman; Kullo, Iftikhar

    2015-01-01

    The level of CYP2D6 metabolic activity can be predicted by pharmacogenomic testing, and concomitant use of clinical decision support has the potential to prevent adverse effects from those drugs metabolized by this enzyme. Our initial findings after implementation of clinical decision support alerts integrated in the electronic health records suggest high feasibility, but also identify important challenges.

  19. Metabolic Syndrome and Neuroprotection

    Melisa Etchegoyen

    2018-04-01

    Full Text Available Introduction: Over the years the prevalence of metabolic syndrome (MetS has drastically increased in developing countries as a major byproduct of industrialization. Many factors, such as the consumption of high-calorie diets and a sedentary lifestyle, bolster the spread of this disorder. Undoubtedly, the massive and still increasing incidence of MetS places this epidemic as an important public health issue. Hereon we revisit another outlook of MetS beyond its classical association with cardiovascular disease (CVD and Diabetes Mellitus Type 2 (DM2, for MetS also poses a risk factor for the nervous tissue and threatens neuronal function. First, we revise a few essential concepts of MetS pathophysiology. Second, we explore some neuroprotective approaches in MetS pertaining brain hypoxia. The articles chosen for this review range from the years 1989 until 2017; the selection criteria was based on those providing data and exploratory information on MetS as well as those that studied innovative therapeutic approaches.Pathophysiology: The characteristically impaired metabolic pathways of MetS lead to hyperglycemia, insulin resistance (IR, inflammation, and hypoxia, all closely associated with an overall pro-oxidative status. Oxidative stress is well-known to cause the wreckage of cellular structures and tissue architecture. Alteration of the redox homeostasis and oxidative stress alter the macromolecular array of DNA, lipids, and proteins, in turn disrupting the biochemical pathways necessary for normal cell function.Neuroprotection: Different neuroprotective strategies are discussed involving lifestyle changes, medication aimed to mitigate MetS cardinal symptoms, and treatments targeted toward reducing oxidative stress. It is well-known that the routine practice of physical exercise, aerobic activity in particular, and a complete and well-balanced nutrition are key factors to prevent MetS. Nevertheless, pharmacological control of MetS as a whole and

  20. Metabolic Heat Regenerated Temperature Swing Adsorption for CO2, Thermal and Humidity Control, Phase I

    National Aeronautics and Space Administration — Metabolic heat regenerated Temperature Swing Adsorption (MTSA) technology is proposed for a Portable Life Support System to remove and reject heat and carbon dioxide...

  1. Metabolic heat production by human and animal populations in cities

    Stewart, Iain D.; Kennedy, Chris A.

    2017-07-01

    Anthropogenic heating from building energy use, vehicle fuel consumption, and human metabolism is a key term in the urban energy budget equation. Heating from human metabolism, however, is often excluded from urban energy budgets because it is widely observed to be negligible. Few reports for low-latitude cities are available to support this observation, and no reports exist on the contribution of domestic animals to urban heat budgets. To provide a more comprehensive view of metabolic heating in cities, we quantified all terms of the anthropogenic heat budget at metropolitan scale for the world's 26 largest cities, using a top-down statistical approach. Results show that metabolic heat release from human populations in mid-latitude cities (e.g. London, Tokyo, New York) accounts for 4-8% of annual anthropogenic heating, compared to 10-45% in high-density tropical cities (e.g. Cairo, Dhaka, Kolkata). Heat release from animal populations amounts to <1% of anthropogenic heating in all cities. Heat flux density from human and animal metabolism combined is highest in Mumbai—the world's most densely populated megacity—at 6.5 W m-2, surpassing heat production by electricity use in buildings (5.8 W m-2) and fuel combustion in vehicles (3.9 W m-2). These findings, along with recent output from global climate models, suggest that in the world's largest and most crowded cities, heat emissions from human metabolism alone can force measurable change in mean annual temperature at regional scale.

  2. Deranged Cardiac Metabolism and the Pathogenesis of Heart Failure

    2016-01-01

    Activation of the neuro-hormonal system is a pathophysiological consequence of heart failure. Neuro-hormonal activation promotes metabolic changes, such as insulin resistance, and determines an increased use of non-carbohydrate substrates for energy production. Fasting blood ketone bodies as well as fat oxidation are increased in patients with heart failure, yielding a state of metabolic inefficiency. The net result is additional depletion of myocardial adenosine triphosphate, phosphocreatine and creatine kinase levels with further decreased efficiency of mechanical work. In this context, manipulation of cardiac energy metabolism by modification of substrate use by the failing heart has produced positive clinical results. The results of current research support the concept that shifting the energy substrate preference away from fatty acid metabolism and towards glucose metabolism could be an effective adjunctive treatment in patients with heart failure. The additional use of drugs able to partially inhibit fatty acids oxidation in patients with heart failure may therefore yield a significant protective effect for clinical symptoms and cardiac function improvement, and simultaneously ameliorate left ventricular remodelling. Certainly, to clarify the exact therapeutic role of metabolic therapy in heart failure, a large multicentre, randomised controlled trial should be performed. PMID:28785448

  3. A Synthetic Alternative to Canonical One-Carbon Metabolism.

    Bouzon, Madeleine; Perret, Alain; Loreau, Olivier; Delmas, Valérie; Perchat, Nadia; Weissenbach, Jean; Taran, Frédéric; Marlière, Philippe

    2017-08-18

    One-carbon metabolism is an ubiquitous metabolic pathway that encompasses the reactions transferring formyl-, hydroxymethyl- and methyl-groups bound to tetrahydrofolate for the synthesis of purine nucleotides, thymidylate, methionine and dehydropantoate, the precursor of coenzyme A. An alternative cyclic pathway was designed that substitutes 4-hydroxy-2-oxobutanoic acid (HOB), a compound absent from known metabolism, for the amino acids serine and glycine as one-carbon donors. It involves two novel reactions, the transamination of l-homoserine and the transfer of a one-carbon unit from HOB to tetrahydrofolate releasing pyruvate as coproduct. Since canonical reactions regenerate l-homoserine from pyruvate by carboxylation and subsequent reduction, every one-carbon moiety made available for anabolic reactions originates from CO 2 . The HOB-dependent pathway was established in an Escherichia coli auxotroph selected for prototrophy using long-term cultivation protocols. Genetic, metabolic and biochemical evidence support the emergence of a functional HOB-dependent one-carbon pathway achieved with the recruitment of the two enzymes l-homoserine transaminase and HOB-hydroxymethyltransferase and of HOB as an essential metabolic intermediate. Escherichia coli biochemical reprogramming was achieved by minimally altering canonical metabolism and leveraging on natural selection mechanisms, thereby launching the resulting strain on an evolutionary trajectory diverging from all known extant species.

  4. Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP

    Jarmon G. Lees

    2017-01-01

    Full Text Available Metabolism is central to embryonic stem cell (ESC pluripotency and differentiation, with distinct profiles apparent under different nutrient milieu, and conditions that maintain alternate cell states. The significance of altered nutrient availability, particularly oxygen, and metabolic pathway activity has been highlighted by extensive studies of their impact on preimplantation embryo development, physiology, and viability. ESC similarly modulate their metabolism in response to altered metabolite levels, with changes in nutrient availability shown to have a lasting impact on derived cell identity through the regulation of the epigenetic landscape. Further, the preferential use of glucose and anaplerotic glutamine metabolism serves to not only support cell growth and proliferation but also minimise reactive oxygen species production. However, the perinuclear localisation of spherical, electron-poor mitochondria in ESC is proposed to sustain ESC nuclear-mitochondrial crosstalk and a mitochondrial-H2O2 presence, to facilitate signalling to support self-renewal through the stabilisation of HIFα, a process that may be favoured under physiological oxygen. The environment in which a cell is grown is therefore a critical regulator and determinant of cell fate, with metabolism, and particularly mitochondria, acting as an interface between the environment and the epigenome.

  5. Metabolic reprogramming during neuronal differentiation.

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.

  6. Noise effect in metabolic networks

    Zheng-Yan, Li; Zheng-Wei, Xie; Tong, Chen; Qi, Ouyang

    2009-01-01

    Constraint-based models such as flux balance analysis (FBA) are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution and natural selection, this model successfully predicts most cellular behaviours in growth rate. However, the model ignores the fact that cells can change their cellular metabolic states during evolution, leaving optimal metabolic states unstable. Here, we consider all the cellular processes that change metabolic states into a single term 'noise', and assume that cells change metabolic states by randomly walking in feasible solution space. By simulating a state of a cell randomly walking in the constrained solution space of metabolic networks, we found that in a noisy environment cells in optimal states tend to travel away from these points. On considering the competition between the noise effect and the growth effect in cell evolution, we found that there exists a trade-off between these two effects. As a result, the population of the cells contains different cellular metabolic states, and the population growth rate is at suboptimal states. (cross-disciplinary physics and related areas of science and technology)

  7. Xenobiotic Metabolism and Gut Microbiomes.

    Anubhav Das

    Full Text Available Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs also indicate geographic as well as age specific trends.

  8. Acyl-Lipid Metabolism

    Li-Beisson, Yonghua; Shorrosh, Basil; Beisson, Fred; Andersson, Mats X.; Arondel, Vincent; Bates, Philip D.; Baud, Sébastien; Bird, David; DeBono, Allan; Durrett, Timothy P.; Franke, Rochus B.; Graham, Ian A.; Katayama, Kenta; Kelly, Amélie A.; Larson, Tony; Markham, Jonathan E.; Miquel, Martine; Molina, Isabel; Nishida, Ikuo; Rowland, Owen; Samuels, Lacey; Schmid, Katherine M.; Wada, Hajime; Welti, Ruth; Xu, Changcheng; Zallot, Rémi; Ohlrogge, John

    2013-01-01

    Acyl lipids in Arabidopsis and all other plants have a myriad of diverse functions. These include providing the core diffusion barrier of the membranes that separates cells and subcellular organelles. This function alone involves more than 10 membrane lipid classes, including the phospholipids, galactolipids, and sphingolipids, and within each class the variations in acyl chain composition expand the number of structures to several hundred possible molecular species. Acyl lipids in the form of triacylglycerol account for 35% of the weight of Arabidopsis seeds and represent their major form of carbon and energy storage. A layer of cutin and cuticular waxes that restricts the loss of water and provides protection from invasions by pathogens and other stresses covers the entire aerial surface of Arabidopsis. Similar functions are provided by suberin and its associated waxes that are localized in roots, seed coats, and abscission zones and are produced in response to wounding. This chapter focuses on the metabolic pathways that are associated with the biosynthesis and degradation of the acyl lipids mentioned above. These pathways, enzymes, and genes are also presented in detail in an associated website (ARALIP: http://aralip.plantbiology.msu.edu/). Protocols and methods used for analysis of Arabidopsis lipids are provided. Finally, a detailed summary of the composition of Arabidopsis lipids is provided in three figures and 15 tables. PMID:23505340

  9. Sphingolipid metabolism diseases.

    Kolter, Thomas; Sandhoff, Konrad

    2006-12-01

    Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated "cross correction", gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT.

  10. Physics of metabolic organization

    Jusup, Marko; Sousa, Tânia; Domingos, Tiago; Labinac, Velimir; Marn, Nina; Wang, Zhen; Klanjšček, Tin

    2017-03-01

    We review the most comprehensive metabolic theory of life existing to date. A special focus is given to the thermodynamic roots of this theory and to implications that the laws of physics-such as the conservation of mass and energy-have on all life. Both the theoretical foundations and biological applications are covered. Hitherto, the foundations were more accessible to physicists or mathematicians, and the applications to biologists, causing a dichotomy in what always should have been a single body of work. To bridge the gap between the two aspects of the same theory, we (i) adhere to the theoretical formalism, (ii) try to minimize the amount of information that a reader needs to process, but also (iii) invoke examples from biology to motivate the introduction of new concepts and to justify the assumptions made, and (iv) show how the careful formalism of the general theory enables modular, self-consistent extensions that capture important features of the species and the problem in question. Perhaps the most difficult among the introduced concepts, the utilization (or mobilization) energy flow, is given particular attention in the form of an original and considerably simplified derivation. Specific examples illustrate a range of possible applications-from energy budgets of individual organisms, to population dynamics, to ecotoxicology.

  11. The metabolism of biphenyl

    Meyer, T.; Aarbakke, J.; Scheline, R.R.

    1976-01-01

    The metabolic disposition of 14 C-biphenyl in the rat was studied by liquid scintillation counting. The rats were given an oral dose of 14 C-biphenyl (100 mg/kg, 0.7-1.0 μci) and the total excretion of radioactivity after 96 hrs was 92.2% of the dose. Urinary excretion accounted for 84.8% and faecal excretion for 7.3% of the dose. Most of this radioactivity, 75.8% and 5.8% respectively, was excreted within 24 hrs. Only trace amounts of 14 CO 2 were detected in the expired air and 0.6% of the dose was found to be still present in the rats 96 hrs after biphenyl administration. Extraction and fractionation of the 24 hrs urine samples showed that the largest fraction (nearly 30% of the dose) consisted of conjugated phenolic metabolites. Acidic metabolites accounted for a quarter of the dose and the low levels of expired 14 CO 2 indicated that these were not products resulting from extensive degradation and decarboxylation. (author)

  12. Carbohydrate metabolism in catfish

    Saad, C.R.; Lovell, R.T.

    2002-01-01

    Radiolabeled (U- 14 C)-glucose was incorporated in diets and forced-fed to channel catfish and was observed for a 24 hour period. About 95% of fed labeled (U- 14 C)-glucose was absorbed by catfish, showing a high digestibility of glucose. The amounts of 14 C excreted over 24 h as carbon dioxide were 49% and amounts excreted in urine were 3.5%. The amount retained as protein, fat glycogen and other organic compounds were 8.2, 1.2, 6.5 and 32.1 % respectively, for the 24 hour period. The blood concentration of 14 C reached a maximum 2.5 hour after feeding (U- 14 C)-glucose, then gradually decreased. Based on tissue concentrations of 14 C, glycogen was an immediate storage site for absorbed glucose, but 14 C- glycogen in liver decreased rapidly. Glucose was quickly and heavily converted into triglyceride, indicating that fat is an important intermediate in the metabolism of glucose in channel catfish. 14 C-fat in the serum and liver were transferred to the adipose tissue in the muscle and mesentery about 10 hours after feeding. (Author)

  13. Linking neuronal brain activity to the glucose metabolism.

    Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

    2013-08-29

    Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

  14. Energy Metabolism in the Liver

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

  15. Mathematical modeling of cancer metabolism.

    Medina, Miguel Ángel

    2018-04-01

    Systemic approaches are needed and useful for the study of the very complex issue of cancer. Modeling has a central position in these systemic approaches. Metabolic reprogramming is nowadays acknowledged as an essential hallmark of cancer. Mathematical modeling could contribute to a better understanding of cancer metabolic reprogramming and to identify new potential ways of therapeutic intervention. Herein, I review several alternative approaches to metabolic modeling and their current and future impact in oncology. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. An Integrative Approach to Energy Carbon and Redox Metabolism In Cyanobacterium Synechocystis

    Dr. Ross Overbeek

    2003-06-30

    The main objectives for the first year were to produce a detailed metabolic reconstruction of synechocystis sp.pcc6803 especially in interrelated arrears of photosynthesis respiration and central carbon metabolism to support a more complete understanding and modeling of this organism. Additionally, IG, Inc. provided detailed bioinformatic analysis of selected functional systems related to carbon and energy generation and utilization, and of the corresponding pathways functional roles and individual genes to support wet lab experiments by collaborators.

  17. Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

    Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O.

    2016-01-01

    The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology. PMID:27911809

  18. metabolicMine: an integrated genomics, genetics and proteomics data warehouse for common metabolic disease research.

    Lyne, Mike; Smith, Richard N; Lyne, Rachel; Aleksic, Jelena; Hu, Fengyuan; Kalderimis, Alex; Stepan, Radek; Micklem, Gos

    2013-01-01

    Common metabolic and endocrine diseases such as diabetes affect millions of people worldwide and have a major health impact, frequently leading to complications and mortality. In a search for better prevention and treatment, there is ongoing research into the underlying molecular and genetic bases of these complex human diseases, as well as into the links with risk factors such as obesity. Although an increasing number of relevant genomic and proteomic data sets have become available, the quantity and diversity of the data make their efficient exploitation challenging. Here, we present metabolicMine, a data warehouse with a specific focus on the genomics, genetics and proteomics of common metabolic diseases. Developed in collaboration with leading UK metabolic disease groups, metabolicMine integrates data sets from a range of experiments and model organisms alongside tools for exploring them. The current version brings together information covering genes, proteins, orthologues, interactions, gene expression, pathways, ontologies, diseases, genome-wide association studies and single nucleotide polymorphisms. Although the emphasis is on human data, key data sets from mouse and rat are included. These are complemented by interoperation with the RatMine rat genomics database, with a corresponding mouse version under development by the Mouse Genome Informatics (MGI) group. The web interface contains a number of features including keyword search, a library of Search Forms, the QueryBuilder and list analysis tools. This provides researchers with many different ways to analyse, view and flexibly export data. Programming interfaces and automatic code generation in several languages are supported, and many of the features of the web interface are available through web services. The combination of diverse data sets integrated with analysis tools and a powerful query system makes metabolicMine a valuable research resource. The web interface makes it accessible to first

  19. Plant metabolic modeling: achieving new insight into metabolism and metabolic engineering.

    Baghalian, Kambiz; Hajirezaei, Mohammad-Reza; Schreiber, Falk

    2014-10-01

    Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology. © 2014 American Society of Plant Biologists. All rights reserved.

  20. Metabolism of Ca and Sr in late adult life

    Newton, D.; Harrison, G.E.; Rundo, J.; Kang, C.; Warner, A.J.

    1990-01-01

    Data are presented on the metabolism of Ca and Sr in a healthy male volunteer who, in a series of investigations conducted between the ages of 53 and 82 y, received controlled intakes of 45 Ca, 47 Ca, or 85 Sr. No age-related trends were established, either in factors affecting the skeletal deposition of the tracers or in their subsequent retention studied for up to 462 d after intake. The data thus lend support to an important working postulate in the ICRP's model of alkaline earth metabolism

  1. In silico prediction of xenobiotic metabolism in humans

    Mu, Fangping [Los Alamos National Laboratory

    2009-01-01

    Xenobiotic metabolism in humans is catalyzed by a few enzymes with broad substrate specificities, which provide the overall broad chemical specificity for nearly all xenobiotics that humans encounter. Xenobiotic metabolism are classified into functional group biotransformations. Based on bona fide reactions and negative examples for each reaction class, support vector machine (SVM) classifiers are built. The input to SVM is a set of atomic and molecular features to define the electrostatic, steric, energetic, geometrical and topological environment of the atoms in the reaction center under the molecule. Results show that the overall sensitivity and specificity of classifiers is around 87%.

  2. Metabolic Syndrome in Nurses

    María Escasany

    2014-01-01

    Full Text Available Objectives: To estimate the prevalence of metabolic syndrome (MS in female nurses in the Hospital Juan A. Fernandez (HJAF, Buenos Aires, Argentina, and to determine whether work, rest, diet, and health, are predictive of it.Materials and methods: For the first objective, a descriptive, observational and cross-sectional study was conducted, and for the second, a multivariate cross-sectional observational multivariate analysis was made comparing independent samples. A total of 192 nurses were studied between October 2008 and March 2009. They completed a questionnaire that include indicators that could be predictors of MS. Anthropometric measurements, including blood pressure were taken, was well as a blood sample to analyze fasting glucose, HDL-C and plasma triglycerides.Results: It was found that 35% and 41% of nurses were overweight and obese, respectively. A total of 92% had centro-abdominal obesity. The prevalence of MS found was 33.3% (95%CI, 26.7 to 40.5. Those who had this disease were between 53±9 years. Statistically significant differences were found in the bivariate analysis between MS and the variables, age, length of service, time worked during night shift, and academic studies.Conclusions: The prevalence of MS was 64/192 in HJAF nurses (33.3% I 95%CI, 26.7-40.5. There were no statistically significant differences with the indicators of, age, “time worked during night shift”, and “studies”. These results suggest that age is the most important variable in predicting the onset of MS in the population of nurses.

  3. Testosterone and metabolic syndrome

    Glenn R Cunningham

    2015-04-01

    Full Text Available Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS. Many of the components are accepted risk factors for cardiovascular disease (CVD. Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT and sex hormone binding globulin (SHBG levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

  4. The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture.

    Caetano-Anollés, Gustavo; Kim, Hee Shin; Mittenthal, Jay E

    2007-05-29

    Metabolism represents a complex collection of enzymatic reactions and transport processes that convert metabolites into molecules capable of supporting cellular life. Here we explore the origins and evolution of modern metabolism. Using phylogenomic information linked to the structure of metabolic enzymes, we sort out recruitment processes and discover that most enzymatic activities were associated with the nine most ancient and widely distributed protein fold architectures. An analysis of newly discovered functions showed enzymatic diversification occurred early, during the onset of the modern protein world. Most importantly, phylogenetic reconstruction exercises and other evidence suggest strongly that metabolism originated in enzymes with the P-loop hydrolase fold in nucleotide metabolism, probably in pathways linked to the purine metabolic subnetwork. Consequently, the first enzymatic takeover of an ancient biochemistry or prebiotic chemistry was related to the synthesis of nucleotides for the RNA world.

  5. Topological analysis of metabolic control.

    Sen, A K

    1990-12-01

    A topological approach is presented for the analysis of control and regulation in metabolic pathways. In this approach, the control structure of a metabolic pathway is represented by a weighted directed graph. From an inspection of the topology of the graph, the control coefficients of the enzymes are evaluated in a heuristic manner in terms of the enzyme elasticities. The major advantage of the topological approach is that it provides a visual framework for (1) calculating the control coefficients of the enzymes, (2) analyzing the cause-effect relationships of the individual enzymes, (3) assessing the relative importance of the enzymes in metabolic regulation, and (4) simplifying the structure of a given pathway, from a regulatory viewpoint. Results are obtained for (a) an unbranched pathway in the absence of feedback the feedforward regulation and (b) an unbranched pathway with feedback inhibition. Our formulation is based on the metabolic control theory of Kacser and Burns (1973) and Heinrich and Rapoport (1974).

  6. Neuroinflammatory basis of metabolic syndrome.

    Purkayastha, Sudarshana; Cai, Dongsheng

    2013-10-05

    Inflammatory reaction is a fundamental defense mechanism against threat towards normal integrity and physiology. On the other hand, chronic diseases such as obesity, type 2 diabetes, hypertension and atherosclerosis, have been causally linked to chronic, low-grade inflammation in various metabolic tissues. Recent cross-disciplinary research has led to identification of hypothalamic inflammatory changes that are triggered by overnutrition, orchestrated by hypothalamic immune system, and sustained through metabolic syndrome-associated pathophysiology. While continuing research is actively trying to underpin the identity and mechanisms of these inflammatory stimuli and actions involved in metabolic syndrome disorders and related diseases, proinflammatory IκB kinase-β (IKKβ), the downstream nuclear transcription factor NF-κB and some related molecules in the hypothalamus were discovered to be pathogenically significant. This article is to summarize recent progresses in the field of neuroendocrine research addressing the central integrative role of neuroinflammation in metabolic syndrome components ranging from obesity, glucose intolerance to cardiovascular dysfunctions.

  7. Metabolic Resistance in Bed Bugs

    Omprakash Mittapalli

    2011-03-01

    Full Text Available Blood-feeding insects have evolved resistance to various insecticides (organochlorines, pyrethroids, carbamates, etc. through gene mutations and increased metabolism. Bed bugs (Cimex lectularius are hematophagous ectoparasites that are poised to become one of the major pests in households throughout the United States. Currently, C. lectularius has attained a high global impact status due to its sudden and rampant resurgence. Resistance to pesticides is one factor implicated in this phenomenon. Although much emphasis has been placed on target sensitivity, little to no knowledge is available on the role of key metabolic players (e.g., cytochrome P450s and glutathione S-transferases towards pesticide resistance in C. lectularius. In this review, we discuss different modes of resistance (target sensitivity, penetration resistance, behavioral resistance, and metabolic resistance with more emphasis on metabolic resistance.

  8. Exercise training in metabolic myopathies

    Vissing, J

    2016-01-01

    metabolic adaptations, such as increased dependence on glycogen use and a reduced capacity for fatty acid oxidation, which is detrimental in GSDs. Training has not been studied systematically in any FAODs and in just a few GSDs. However, studies on single bouts of exercise in most metabolic myopathies show......Metabolic myopathies encompass muscle glycogenoses (GSD) and disorders of muscle fat oxidation (FAOD). FAODs and GSDs can be divided into two main clinical phenotypes; those with static symptoms related to fixed muscle weakness and atrophy, and those with dynamic, exercise-related symptoms...... that are brought about by a deficient supply of ATP. Together with mitochondrial myopathies, metabolic myopathies are unique among muscle diseases, as the limitation in exercise performance is not solely caused by structural damage of muscle, but also or exclusively related to energy deficiency. ATP consumption...

  9. Histone variants and lipid metabolism

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  10. Metabolic pancreatitis: Etiopathogenesis and management

    Sunil Kumar Kota

    2013-01-01

    Full Text Available Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis. Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson′s disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

  11. B-12 vitamin metabolism disorders

    Fabriciova, K.; Bzduch, V.; Behulova, D.; Skodova, J.; Holesova, D.; Ostrozlikova, M.; Schmidtova, K.; Kozich, V.

    2012-01-01

    Vitamin B-12 – cobalamin (Cbl) is a water soluble vitamin, which is synthesized by lower organisms. It cannot be synthesized by plants and higher organisms. Problem in the metabolic pathway of Cbl can be caused by its deficiency or by the deficiency of its last metabolites – adenosylcobalamin and methylcobalamin. Both reasons are presented by errors in the homocysteine and methylmalonyl-coenzyme A metabolism. Clinical symptoms of the Cbl metabolism disorders are: different neurological disorders, changes in haematological status (megaloblastic anemia, pancytopenia), symptoms of gastrointestinal tract (glossitis, loss of appetite, diarrhea) and changes in the immune system. In the article the authors describe the causes of Cbl metabolism disorders, its different diagnosis and treatment. They introduce the group of patients with these disorders, who were taken care of in the I st Paediatric Department of University Children Hospital for the last 5 years. (author)

  12. Human drug metabolism: an introduction

    Coleman, Michael D

    2010-01-01

    Human Drug Metabolism, An Introduction, Second Edition provides an accessible introduction to the subject and will be particularly invaluable to those who already have some understanding of the life sciences...

  13. Metabolic Effects of Ketogenic Diets

    J Gordon Millichap

    1989-01-01

    The results of 24 metabolic profiles performed on 55 epileptic children receiving the classical ketogenic diet, the MCT diet, a modified MCT diet, and normal diets are reported from the University Department of Paediatrics, John Radcliffe Hospital, Oxford, England.

  14. Substrate kinetics in patients with disorders of skeletal muscle metabolism.

    Ørngreen, Mette Cathrine

    2016-07-01

    The main purpose of the following studies was to investigate pathophysiological mechanisms in fat and carbohydrate metabolism and effect of nutritional interventions in patients with metabolic myopathies and in patients with severe muscle wasting. Yet there is no cure for patients with skeletal muscle disorders. The group of patients is heterozygous and this thesis is focused on patients with metabolic myopathies and low muscle mass due to severe muscle wasting. Disorders of fatty acid oxidation (FAO) are, along with myophosphorylase deficiency (McArdle disease), the most common inborn errors of metabolism leading to recurrent episodes of rhabdomyolysis in adults. Prolonged exercise, fasting, and fever are the main triggering factors for rhabdomyolysis in these conditions, and can be complicated by acute renal failure. Patients with low muscle mass are in risk of loosing their functional skills and depend on a wheel chair and respiratory support. We used nutritional interventions and metabolic studies with stable isotope technique and indirect calorimetry in patients with metabolic myopathies and patients with low muscle mass to get information of the metabolism of the investigated diseases, and to gain knowledge of the biochemical pathways of intermediary metabolism in human skeletal muscle. We have shown that patients with fat metabolism disorders in skeletal muscle affecting the transporting enzyme of fat into the mitochondria (carnitine palmitoyltransferase II deficiency) and affecting the enzyme responsible for breakdown of the long-chain fatty acids (very long chain acyl-CoA dehydrogenase deficiency) have a normal fatty acid oxidation at rest, but enzyme activity is too low to increase fatty acid oxidation during exercise. Furthermore, these patients benefit from a carbohydrate rich diet. Oppositely is exercise capacity worsened by a fat-rich diet in these patients. The patients also benefit from IV glucose, however, when glucose is given orally just before

  15. [Endocrinological diseases, metabolic diseases, sexuality].

    Lemaire, Antoine

    2014-10-01

    Sexuality is regularly evaluated in media surveys. Relations between sexual problems and some chronic pathologies as diabetes or metabolic syndrome have been brought to light. Androgen deficiency in the aging male has become a topic of increasing interest. Hormones play an important role in sexual function and relation between hormonal status and metabolic data are now well established. Copyright © 2014. Published by Elsevier Masson SAS.

  16. Evolution of metabolic network organization

    Bonchev Danail

    2010-05-01

    Full Text Available Abstract Background Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. By selecting taxa representative of different lineages or lifestyles and using a comprehensive set of descriptors of the structure and complexity of their metabolic networks, one can highlight both qualitative and quantitative differences in the metabolic organization of species subject to distinct evolutionary paths or environmental constraints. Results We used a novel representation of metabolic networks, termed network of interacting pathways or NIP, to focus on the modular, high-level organization of the metabolic capabilities of the cell. Using machine learning techniques we identified the most relevant aspects of cellular organization that change under evolutionary pressures. We considered the transitions from prokarya to eukarya (with a focus on the transitions among the archaea, bacteria and eukarya, from unicellular to multicellular eukarya, from free living to host-associated bacteria, from anaerobic to aerobic, as well as the acquisition of cell motility or growth in an environment of various levels of salinity or temperature. Intuitively, we expect organisms with more complex lifestyles to have more complex and robust metabolic networks. Here we demonstrate for the first time that such organisms are not only characterized by larger, denser networks of metabolic pathways but also have more efficiently organized cross communications, as revealed by subtle changes in network topology. These changes are unevenly distributed among metabolic pathways, with specific categories of pathways being promoted to more central locations as an answer to environmental constraints. Conclusions Combining methods from graph theory and machine learning, we have shown here that evolutionary pressures not only affects gene and protein sequences, but also specific details of the complex wiring of functional modules

  17. Energy metabolism in the liver.

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic function is controlled by insulin and other metabolic hormones. Glucose is converted into pyruvate through glycolysis in the cytoplasm, and pyruvate is subsequently oxidized in the mitochondria to generate ATP through the TCA cycle and oxidative phosphorylation. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and/or cholesterol esters in hepatocytes. These complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as very low-density lipoprotein particles. In the fasted state, the liver secretes glucose through both glycogenolysis and gluconeogenesis. During pronged fasting, hepatic gluconeogenesis is the primary source for endogenous glucose production. Fasting also promotes lipolysis in adipose tissue, resulting in release of nonesterified fatty acids which are converted into ketone bodies in hepatic mitochondria though β-oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver energy metabolism is tightly regulated by neuronal and hormonal signals. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis but suppresses gluconeogenesis, and glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze key steps of metabolic pathways, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases. © 2014 American Physiological Society.

  18. Drug treatment of metabolic syndrome.

    Altabas, Velimir

    2013-08-01

    The metabolic syndrome is a constellation of risk factors for cardiovascular diseases including: abdominal obesity, a decreased ability to metabolize glucose (increased blood glucose levels and/or presence of insulin resistance), dyslipidemia, and hypertension. Patients who have developed this syndrome have been shown to be at an increased risk of developing cardiovascular disease and/or type 2 diabetes. Genetic factors and the environment both are important in the development of the metabolic syndrome, influencing all single components of this syndrome. The goals of therapy are to treat the underlying cause of the syndrome, to reduce morbidity, and to prevent complications, including premature death. Lifestyle modification is the preferred first-step treatment of the metabolic syndrome. There is no single effective drug treatment affecting all components of the syndrome equally known yet. However, each component of metabolic syndrome has independent goals to be achieved, so miscellaneous types of drugs are used in the treatment of this syndrome, including weight losing drugs, antidiabetics, antihypertensives, antilipemic and anticlothing drugs etc. This article provides a brief insight into contemporary drug treatment of components the metabolic syndrome.

  19. Epilepsy and astrocyte energy metabolism.

    Boison, Detlev; Steinhäuser, Christian

    2018-06-01

    Epilepsy is a complex neurological syndrome characterized by neuronal hyperexcitability and sudden, synchronized electrical discharges that can manifest as seizures. It is now increasingly recognized that impaired astrocyte function and energy homeostasis play key roles in the pathogenesis of epilepsy. Excessive neuronal discharges can only happen, if adequate energy sources are made available to neurons. Conversely, energy depletion during seizures is an endogenous mechanism of seizure termination. Astrocytes control neuronal energy homeostasis through neurometabolic coupling. In this review, we will discuss how astrocyte dysfunction in epilepsy leads to distortion of key metabolic and biochemical mechanisms. Dysfunctional glutamate metabolism in astrocytes can directly contribute to neuronal hyperexcitability. Closure of astrocyte intercellular gap junction coupling as observed early during epileptogenesis limits activity-dependent trafficking of energy metabolites, but also impairs clearance of the extracellular space from accumulation of K + and glutamate. Dysfunctional astrocytes also increase the metabolism of adenosine, a metabolic product of ATP degradation that broadly inhibits energy-consuming processes as an evolutionary adaptation to conserve energy. Due to the critical role of astroglial energy homeostasis in the control of neuronal excitability, metabolic therapeutic approaches that prevent the utilization of glucose might represent a potent antiepileptic strategy. In particular, high fat low carbohydrate "ketogenic diets" as well as inhibitors of glycolysis and lactate metabolism are of growing interest for the therapy of epilepsy. © 2017 Wiley Periodicals, Inc.

  20. Metabolic syndrome and cardiovascular risk

    Abdullah M Alshehri

    2010-01-01

    Full Text Available The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol, elevated blood pressure, impaired glucose tolerance, and central obesity is now classified as metabolic syndrome, also called syndrome X. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria for use in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general, they include a combination of multiple and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics, commonly manifest a prothrombotic state as well as and a proinflammatory state. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB, increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C. The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of atherosclerotic cardiovascular disease (ASCVD risk factors, that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to the components of the syndrome present as well as the other, non-metabolic syndrome risk factors in a particular person.

  1. Metabolic syndrome and cardiovascular risk

    Abdullah M Alshehri

    2010-11-01

    Full Text Available The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol, elevated blood pressure, impaired glucose tolerance, and central obesity is now classified as metabolic syndrome, also called syndrome X. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria for use in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general, they include a combination of multiple and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics, commonly manifest a prothrombotic state as well as and a proinflammatory state. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB, increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C. The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of atherosclerotic cardiovascular disease (ASCVD risk factors, that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to the components of the syndrome present as well as the other, non-metabolic syndrome risk factors in a particular person.

  2. Energy metabolism and the metabolic syndrome: does a lower basal metabolic rate signal recovery following weight loss?

    Soares, Mario J; Cummings, Nicola K; Ping-Delfos, Wendy L Chan She

    2011-01-01

    To determine whether basal metabolic rate (BMR) was causally related to MetS, and to study the role of gender in this relationship. Seventy-two Caucasian subjects (43 women, 29 men) had changes in basal metabolic rate (BMR), carbohydrate oxidation rate (COR), fat oxidation rate (FOR) and prevalence of the metabolic syndrome (MetS) assessed in response to weight loss. There was a significant gender×MetS interaction in BMR at the start. Women with MetS had higher adjusted BMR, whilst men with MetS had lower adjusted BMR than their respective counterparts. Weight loss resulted in a significant decrease in fat mass (-5.2±0.31 kg, p=0.001), fat free mass (-2.3±0.27 kg, p=0.001), BMR (-549±58 kJ/d, p=0.001) and a decreased proportion of MetS (22/72, χ(2)=0.005). Subjects who recovered from MetS after weight loss (RMS) had ∼250 kJ/d significantly lower adjusted BMR compared to those who were never MetS (NMS, p=0.046) and those who still had MetS (MetS+, p=0.047). Regression analysis showed that change (Δ) in BMR was best determined by Δglucose×gender interaction (r(2)=23%), ΔFOR (r(2)=20.3%), ΔCOR (r(2)=19.4%) and Δtriglycerides (r(2)=7.8%). There is a sexual dimorphism of BMR in MetS. Overall, the data support the notion that alterations in BMR may be central to the etiopathogenesis of MetS. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  3. Symptoms and Diagnosis of Metabolic Syndrome

    ... Thromboembolism Aortic Aneurysm More Symptoms and Diagnosis of Metabolic Syndrome Updated:Apr 13,2017 What are the symptoms ... Syndrome? This content was last reviewed August 2016. Metabolic Syndrome • Home • About Metabolic Syndrome • Why Metabolic Syndrome Matters • ...

  4. Food for thought: Impact of metabolism on neuronal excitability.

    Katsu-Jiménez, Yurika; Alves, Renato M P; Giménez-Cassina, Alfredo

    2017-11-01

    Neuronal excitability is a highly demanding process that requires high amounts of energy and needs to be exquisitely regulated. For this reason, brain cells display active energy metabolism to support their activity. Independently of their roles as energy substrates, compelling evidence shows that the nature of the fuels that neurons use contribute to fine-tune neuronal excitability. Crosstalk of neurons with glial populations also plays a prominent role in shaping metabolic flow in the brain. In this review, we provide an overview on how different carbon substrates and metabolic pathways impact neurotransmission, and the potential implications for neurological disorders in which neuronal excitability is deregulated, such as epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

    Olivier F. Noel

    2016-01-01

    Full Text Available Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.

  6. Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis.

    de Leeuw, Christiaan; Goudriaan, Andrea; Smit, August B; Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M; Verheijen, Mark H G; Posthuma, Danielle

    2015-11-01

    Tourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls. The gene sets included specific synaptic, astrocytic, oligodendrocyte and microglial functions. We report association of Tourette syndrome with a set of genes involved in astrocyte function, specifically in astrocyte carbohydrate metabolism. This association is driven primarily by a subset of 33 genes involved in glycolysis and glutamate metabolism through which astrocytes support synaptic function. Our results indicate for the first time that the process of astrocyte-neuron metabolic coupling may be an important contributor to Tourette syndrome pathogenesis.

  7. Towards systems metabolic engineering in Pichia pastoris.

    Schwarzhans, Jan-Philipp; Luttermann, Tobias; Geier, Martina; Kalinowski, Jörn; Friehs, Karl

    2017-11-01

    The methylotrophic yeast Pichia pastoris is firmly established as a host for the production of recombinant proteins, frequently outperforming other heterologous hosts. Already, a sizeable amount of systems biology knowledge has been acquired for this non-conventional yeast. By applying various omics-technologies, productivity features have been thoroughly analyzed and optimized via genetic engineering. However, challenging clonal variability, limited vector repertoire and insufficient genome annotation have hampered further developments. Yet, in the last few years a reinvigorated effort to establish P. pastoris as a host for both protein and metabolite production is visible. A variety of compounds from terpenoids to polyketides have been synthesized, often exceeding the productivity of other microbial systems. The clonal variability was systematically investigated and strategies formulated to circumvent untargeted events, thereby streamlining the screening procedure. Promoters with novel regulatory properties were discovered or engineered from existing ones. The genetic tractability was increased via the transfer of popular manipulation and assembly techniques, as well as the creation of new ones. A second generation of sequencing projects culminated in the creation of the second best functionally annotated yeast genome. In combination with landmark physiological insights and increased output of omics-data, a good basis for the creation of refined genome-scale metabolic models was created. The first application of model-based metabolic engineering in P. pastoris showcased the potential of this approach. Recent efforts to establish yeast peroxisomes for compartmentalized metabolite synthesis appear to fit ideally with the well-studied high capacity peroxisomal machinery of P. pastoris. Here, these recent developments are collected and reviewed with the aim of supporting the establishment of systems metabolic engineering in P. pastoris. Copyright © 2017. Published

  8. Targeting Lipid Metabolic Reprogramming as Anticancer Therapeutics

    Cha, Ji-Young; Lee, Ho-Jae

    2016-01-01

    Cancer cells rewire their metabolism to satisfy the demands of growth and survival, and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. Lipid metabolism is pivotal in cellular process that converts nutrients into energy, building blocks for membrane biogenesis and the generation of signaling molecules. Accumulating evidence suggests that cancer cells show alterations in different aspects of lipid metabolism. The changes in lipid metabolism of cancer cells c...

  9. Group Decision Process Support

    Gøtze, John; Hijikata, Masao

    1997-01-01

    Introducing the notion of Group Decision Process Support Systems (GDPSS) to traditional decision-support theorists.......Introducing the notion of Group Decision Process Support Systems (GDPSS) to traditional decision-support theorists....

  10. 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

    2016-05-01

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

  11. Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes.

    Nissen, Jakob D; Pajęcka, Kamilla; Stridh, Malin H; Skytt, Dorte M; Waagepetersen, Helle S

    2015-12-01

    Astrocytes take up glutamate in the synaptic area subsequent to glutamatergic transmission by the aid of high affinity glutamate transporters. Glutamate is converted to glutamine or metabolized to support intermediary metabolism and energy production. Glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) catalyze the reversible reaction between glutamate and α-ketoglutarate, which is the initial step for glutamate to enter TCA cycle metabolism. In contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and aspartate. We have investigated the role of GDH in astrocyte glutamate and glucose metabolism employing siRNA mediated knock down (KD) of GDH in cultured astrocytes using stable and radioactive isotopes for metabolic mapping. An increased level of aspartate was observed upon exposure to [U-(13) C]glutamate in astrocytes exhibiting reduced GDH activity. (13) C Labeling of aspartate and TCA cycle intermediates confirmed that the increased amount of aspartate is associated with elevated TCA cycle flux from α-ketoglutarate to oxaloacetate, i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient astrocytes as observed by increased de novo synthesis of aspartate via pyruvate carboxylation. In the absence of glucose, lactate production from glutamate via malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies reveal that metabolism via GDH serves an important anaplerotic role by adding net carbon to the TCA cycle. A reduction in GDH activity seems to cause the astrocytes to up-regulate activity in pathways involved in maintaining the amount of TCA cycle intermediates such as pyruvate carboxylation as well as utilization of alternate substrates such as branched chain amino acids. © 2015 Wiley Periodicals, Inc.

  12. Metabolic Profiles of Brain Metastases

    Tone F. Bathen

    2013-01-01

    Full Text Available Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS to correlate the metabolic profiles to clinical and pathological information. Biopsy samples of human brain metastases (n = 49 were investigated. A significant correlation between lipid signals and necrosis in brain metastases was observed (p < 0.01, irrespective of their primary origin. The principal component analysis (PCA showed that brain metastases from malignant melanomas cluster together, while lung carcinomas were metabolically heterogeneous and overlap with other subtypes. Metastatic melanomas have higher amounts of glycerophosphocholine than other brain metastases. A significant correlation between microscopically visible lipid droplets estimated by Nile Red staining and MR visible lipid signals was observed in metastatic lung carcinomas (p = 0.01, indicating that the proton MR visible lipid signals arise from cytoplasmic lipid droplets. MRS-based metabolomic profiling is a useful tool for exploring the metabolic profiles of metastatic brain tumors.

  13. Autophagic pathways and metabolic stress.

    Kaushik, S; Singh, R; Cuervo, A M

    2010-10-01

    Autophagy is an essential intracellular process that mediates degradation of intracellular proteins and organelles in lysosomes. Autophagy was initially identified for its role as alternative source of energy when nutrients are scarce but, in recent years, a previously unknown role for this degradative pathway in the cellular response to stress has gained considerable attention. In this review, we focus on the novel findings linking autophagic function with metabolic stress resulting either from proteins or lipids. Proper autophagic activity is required in the cellular defense against proteotoxicity arising in the cytosol and also in the endoplasmic reticulum, where a vast amount of proteins are synthesized and folded. In addition, autophagy contributes to mobilization of intracellular lipid stores and may be central to lipid metabolism in certain cellular conditions. In this review, we focus on the interrelation between autophagy and different types of metabolic stress, specifically the stress resulting from the presence of misbehaving proteins within the cytosol or in the endoplasmic reticulum and the stress following a lipogenic challenge. We also comment on the consequences that chronic exposure to these metabolic stressors could have on autophagic function and on how this effect may underlie the basis of some common metabolic disorders. © 2010 Blackwell Publishing Ltd.

  14. Gut microbiota and metabolic syndrome.

    Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

    2014-11-21

    Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal "superorganism" seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host's immune system could culminate in the intestinal translocation of bacterial fragments and the development of "metabolic endotoxemia", leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.

  15. Metabolic syndrome in patients with ischemic heart disease

    Yasmin, S.; Naveed, T.; Shakoor, T.

    2008-01-01

    To determine the frequency of metabolic syndrome in patients with Ischemic Heart Disease (IHD). Cross-sectional, descriptive study. A total of 100 subjects with ischemic heart disease, fulfilling the inclusion criteria, were enrolled in the study. Demographic data (age and gender) and the 5 component conditions of the metabolic syndrome were noted. Subjects were physically assessed for the abdominal obesity, based on waist circumference. Fasting blood samples for glucose and lipid profile in first 24 hours after acute coronary insult were drawn and tested in central laboratory. Variables were processed for descriptive statistics. In this study population, 68% were male and 32% were female with mean age of 52 +-13.6 years in men and 56 +- 12.5 years in women. Frequency of metabolic syndrome was 32% in men and 28% in women. It increased with age. The highest rate of metabolic syndrome was in men diagnosed as STEMI (odds ratio: 3.39, 95% CI=1.36-8.41). Frequency of metabolic syndrome was high among the patients with IHD. It supports the potential for preventive efforts in persons with high-risk of IHD. (author)

  16. Automated Screening for Three Inborn Metabolic Disorders: A Pilot Study

    Kavitha S

    2006-12-01

    Full Text Available Background: Inborn metabolic disorders (IMDs form a large group of rare, but often serious, metabolic disorders. Aims: Our objective was to construct a decision tree, based on classification algorithm for the data on three metabolic disorders, enabling us to take decisions on the screening and clinical diagnosis of a patient. Settings and Design: A non-incremental concept learning classification algorithm was applied to a set of patient data and the procedure followed to obtain a decision on a patient’s disorder. Materials and Methods: Initially a training set containing 13 cases was investigated for three inborn errors of metabolism. Results: A total of thirty test cases were investigated for the three inborn errors of metabolism. The program identified 10 cases with galactosemia, another 10 cases with fructosemia and the remaining 10 with propionic acidemia. The program successfully identified all the 30 cases. Conclusions: This kind of decision support systems can help the healthcare delivery personnel immensely for early screening of IMDs.

  17. Telmisartan as metabolic modulator: a new perspective in sports doping?

    Sanchis-Gomar, Fabian; Lippi, Giuseppe

    2012-03-01

    The World Antidoping Agency (WADA) has introduced some changes in the 2012 prohibited list. Among the leading innovations to the rules are that both 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (peroxisome proliferator-activated receptor-δ [PPAR-δ]-5' adenosine monophosphate-activated protein kinase [AMPK] agonist) and GW1516 (PPAR-δ-agonist) are no longer categorized as gene doping substances in the new 2012 prohibited list but as metabolic modulators in the class "Hormone and metabolic modulators." This may also be valid for the angotensin II receptor blocker telmisartan. It has recently been shown that telmisartan might induce similar biochemical, biological, and metabolic changes (e.g., mitochondrial biogenesis and changes in skeletal muscle fiber type) as those reported for the former call of substances. We suspect that metabolic modulators abuse such as telmisartan might become a tangible threat in sports and should be thereby targeted as an important antidoping issue. The 2012 WADA prohibited list does not provide telmisartan for a potential doping drug, but arguments supporting the consideration to include them among "metabolic modulators" are at hand.

  18. Obesity and metabolic syndrome in COPD: Is exercise the answer?

    James, Benjamin D; Jones, Amy V; Trethewey, Ruth E; Evans, Rachael A

    2018-05-01

    Approximately half of all patients with chronic obstructive pulmonary disease (COPD) attending pulmonary rehabilitation (PR) programmes are overweight or obese which negatively impacts upon dyspnoea and exercise tolerance particularly when walking. Within the obese population (without COPD), the observed heterogeneity in prognosis is in part explained by the variability in the risk of developing cardiovascular disease or diabetes (cardiometabolic risk) leading to the description of metabolic syndrome. In obesity alone, high-intensity aerobic training can support healthy weight loss and improve the constituent components of metabolic syndrome. Those with COPD, obesity and/or metabolic syndrome undergoing PR appear to do as well in traditional outcomes as their normal-weight metabolically healthy peers in terms of improvement of symptoms, health-related quality of life and exercise performance, and should therefore not be excluded. To broaden the benefit of PR, for this complex population, we should learn from the extensive literature examining the effects of exercise in obesity and metabolic syndrome discussed in this review and optimize the exercise strategy to improve these co-morbid conditions. Standard PR outcomes could be expanded to include cardiometabolic risk reduction to lower future morbidity and mortality; to this end exercise may well be the answer.

  19. Metabolic acclimation to excess light intensity in Chlamydomonas reinhardtii.

    Davis, Maria C; Fiehn, Oliver; Durnford, Dion G

    2013-07-01

    There are several well-described acclimation responses to excess light in green algae but the effect on metabolism has not been thoroughly investigated. This study examines the metabolic changes during photoacclimation to high-light (HL) stress in Chlamydomonas reinhardtii using nuclear magnetic resonance and mass spectrometry. Using principal component analysis, a clear metabolic response to HL intensity was observed on global metabolite pools, with major changes in the levels of amino acids and related nitrogen metabolites. Amino acid pools increased during short-term photoacclimation, but were especially prominent in HL-acclimated cultures. Unexpectedly, we observed an increase in mitochondrial metabolism through downstream photorespiratory pathways. The expression of two genes encoding key enzymes in the photorespiratory pathway, glycolate dehydrogenase and malate synthase, were highly responsive to the HL stress. We propose that this pathway contributes to metabolite pools involved in nitrogen assimilation and may play a direct role in photoacclimation. Our results suggest that primary and secondary metabolism is highly pliable and plays a critical role in coping with the energetic imbalance during HL exposure and a necessary adjustment to support an increased growth rate that is an effective energy sink for the excess reducing power generated during HL stress. © 2013 John Wiley & Sons Ltd.

  20. Metabolism of methylamine in the tea plant (Thea sinensis L.)

    Suzuki, Takeo

    1973-01-01

    1. The metabolism of methylamine in excised shoot tips of tea was studied with micromolar amounts of [14C]methylamine. Of the [14C]methylamine supplied 57% was utilized by tea shoots during the 10h experimental period. 2. The main products of [14C]methylamine metabolism in tea shoots were serine, γ-glutamylmethylamide, theobromine, caffeine and CO2. There was also incorporation of the label into glutamate, aspartate, RNA purine nucleotides and S-adenosylmethionine. 3. The formation of methylamine from γ-glutamylmethylamide was confirmed by feeding tea shoots with γ-glutamyl[14C]methylamide. The products of γ-glutamyl[14C]methylamide metabolism in tea plants were serine, theobromine, caffeine, glutamate and aspartate. 4. The results indicate that the oxidation of methylamine to formaldehyde is the first step of methylamine utilization. Labelled formaldehyde released by the metabolism of methylamine leads to the incorporation of the label into metabolites on the C1 pathways of this compound. It is also suggested that formaldehyde is further oxidized via formate to CO2. 5. The role of γ-glutamylmethylamide in methylamine metabolism in tea plants is discussed. 6. Results support the view that theobromine is the immediate precursor of caffeine. PMID:4721610

  1. Secondary psychosis induced by metabolic disorders

    Olivier eBonnot

    2015-05-01

    Full Text Available Metabolic disorders are not well recognized by psychiatrists as a possible source of secondary psychoses. Inborn errors of metabolism (IEMs are not frequent. Although, their prompt diagnosis may lead to suitable treatments. IEMs are well known to paediatricians, in particular for their most serious forms, having an early expression most of the time. Recent years discoveries have unveiled later expression forms, and sometimes, very discreet first physical signs. There is a growing body of evidence that supports the hypothesis that IEMs can manifest as atypical psychiatric symptoms, even in the absence of clear neurological symptoms. In the present review, we propose a detailed overview at schizophrenia-like and autism-like symptoms that can lead practitioners to bear in mind an IEM. Other psychiatric manifestations are also found, as behavioral., cognitive, learning and mood disorders. However, they are less frequent. Ensuring an accurate IEM diagnosis, in front of these psychiatric symptoms should be a priority, in order to grant suitable and valuable treatment for these pathologies.

  2. Impact of Dietary Polyphenols on Carbohydrate Metabolism

    Kati Hanhineva

    2010-03-01

    Full Text Available Polyphenols, including flavonoids, phenolic acids, proanthocyanidins and resveratrol, are a large and heterogeneous group of phytochemicals in plant-based foods, such as tea, coffee, wine, cocoa, cereal grains, soy, fruits and berries. Growing evidence indicates that various dietary polyphenols may influence carbohydrate metabolism at many levels. In animal models and a limited number of human studies carried out so far, polyphenols and foods or beverages rich in polyphenols have attenuated postprandial glycemic responses and fasting hyperglycemia, and improved acute insulin secretion and insulin sensitivity. The possible mechanisms include inhibition of carbohydrate digestion and glucose absorption in the intestine, stimulation of insulin secretion from the pancreatic b-cells, modulation of glucose release from the liver, activation of insulin receptors and glucose uptake in the insulin-sensitive tissues, and modulation of intracellular signalling pathways and gene expression. The positive effects of polyphenols on glucose homeostasis observed in a large number of in vitro and animal models are supported by epidemiological evidence on polyphenol-rich diets. To confirm the implications of polyphenol consumption for prevention of insulin resistance, metabolic syndrome and eventually type 2 diabetes, human trials with well-defined diets, controlled study designs and clinically relevant end-points together with holistic approaches e.g., systems biology profiling technologies are needed.

  3. Identification of the Mitochondrial Heme Metabolism Complex.

    Medlock, Amy E; Shiferaw, Mesafint T; Marcero, Jason R; Vashisht, Ajay A; Wohlschlegel, James A; Phillips, John D; Dailey, Harry A

    2015-01-01

    Heme is an essential cofactor for most organisms and all metazoans. While the individual enzymes involved in synthesis and utilization of heme are fairly well known, less is known about the intracellular trafficking of porphyrins and heme, or regulation of heme biosynthesis via protein complexes. To better understand this process we have undertaken a study of macromolecular assemblies associated with heme synthesis. Herein we have utilized mass spectrometry with coimmunoprecipitation of tagged enzymes of the heme biosynthetic pathway in a developing erythroid cell culture model to identify putative protein partners. The validity of these data obtained in the tagged protein system is confirmed by normal porphyrin/heme production by the engineered cells. Data obtained are consistent with the presence of a mitochondrial heme metabolism complex which minimally consists of ferrochelatase, protoporphyrinogen oxidase and aminolevulinic acid synthase-2. Additional proteins involved in iron and intermediary metabolism as well as mitochondrial transporters were identified as potential partners in this complex. The data are consistent with the known location of protein components and support a model of transient protein-protein interactions within a dynamic protein complex.

  4. DNA methylation in metabolic disorders

    Barres, Romain; Zierath, Juleen R

    2011-01-01

    DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports...... have provided evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, which suggests that DNA methylation is a more dynamic process than previously appreciated. Because of the importance of lifestyle factors in metabolic disorders, DNA methylation provides...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders....

  5. Metabolism and dosimetry of tritium

    Hill, R.L.; Johnson, J.R.

    1993-01-01

    This document was prepared as a review of the current knowledge of tritium metabolism and dosimetry. The physical, chemical, and metabolic characteristics of various forms of tritium are presented as they pertain to performing dose assessments for occupational workers and for the general public. For occupational workers, the forms of tritium discussed include tritiated water, elemental tritium gas, skin absorption from elemental tritium gas-contaminated surfaces, organically bound tritium in pump oils, solvents and other organic compounds, metal tritides, and radioluminous paints. For the general public, age-dependent tritium metabolism is reviewed, as well as tritiated water, elemental tritium gas, organically bound tritium, organically bound tritium in food-stuffs, and tritiated methane. 106 refs

  6. Novel genes in LDL metabolism

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism. RECENT FINDINGS: The genetic loci for ATP-binding cassette......-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most...... of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol...

  7. Flux networks in metabolic graphs

    Warren, P B; Queiros, S M Duarte; Jones, J L

    2009-01-01

    A metabolic model can be represented as a bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a conserved metabolite property such as molecular weight. A similar flux network can be constructed by combining the primal and dual solutions to the linear programming problem that typically arises in constraint-based modelling. Such constructions may help with the visualization of flux distributions in complex metabolic networks. The analysis also explains the strong correlation observed between metabolite shadow prices (the dual linear programming variables) and conserved metabolite properties. The methods were applied to recent metabolic models for Escherichia coli, Saccharomyces cerevisiae and Methanosarcina barkeri. Detailed results are reported for E. coli; similar results were found for other organisms

  8. Ontogenic changes in selenite metabolism in rats

    Ostadalova, I.; Babicky, A.; Kopoldova, J.

    1982-01-01

    Radioselenium concentration and excretion was studied after administration of 75 Se-labelled selenite to male rats during ontogeny. The concentration of radioselenium in individual organs decreases with increasing age. The largest differences between young and adults were in the quantity and quality of excreted substances. During 2 h after the administration of 20 μmol selenite/kg young rats excreted 2.4% of the dose, essentially in the urine only, whilst adults excreted a total of 11%, distributed equally in breath and urine. The part excreted as methylated metabolites was 0.1% of the administered dose in young and 6.3% in adult rats. These results support the hypothesis that the differences in the sensitivity to the toxic action of selenite between young and adult rats can be due to ontogenic differences in selenium metabolism. (orig.)

  9. Metabolic and nutritional aspects of cancer.

    Krawczyk, Joanna; Kraj, Leszek; Ziarkiewicz, Mateusz; Wiktor-Jędrzejczak, Wiesław

    2014-08-22

    Cancer, being in fact a generalized disease involving the whole organism, is most frequently associated with metabolic deregulation, a latent inflammatory state and anorexia of various degrees. The pathogenesis of this disorder is complex, with multiple dilemmas remaining unsolved. The clinical consequences of the above-mentioned disturbances include cancer-related cachexia and anorexia-cachexia syndrome. These complex clinical entities worsen the prognosis, and lead to deterioration of the quality of life and performance status, and thus require multimodal treatment. Optimal therapy should include nutritional support coupled with pharmacotherapy targeted at underlying pathomechanisms of cachexia. Nevertheless, many issues still need explanation, and efficacious and comprehensive therapy of cancer-related cachexia remains a future objective.

  10. Epileptic Focus and Alteration of Metabolism

    Otáhal, Jakub; Folbergrová, Jaroslava; Kovacs, R.; Kunz, W.S.; Maggio, N.

    2014-01-01

    Roč. 114, č. 2014 (2014), s. 209-243 ISSN 0074-7742 R&D Projects: GA ČR(CZ) GAP303/10/0999; GA ČR(CZ) GA309/05/2015; GA ČR(CZ) GA309/08/0292; GA ČR(CZ) GAP302/10/0971; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14489; GA ČR(CZ) GA14-02634S Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : epilepsy * epileptogenesis * cerebral blood flow * blood brain barrier * reactive oxygen species * energy metabolism * mitochondria * oxidative posttranslational modifications * mtDNA mutations * pharmacoresistance Subject RIV: FH - Neurology Impact factor: 1.921, year: 2014

  11. Effects of hypoglycaemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose.

    Amaral, Ana I

    2013-07-01

    Hypoglycaemia is characterized by decreased blood glucose levels and is associated with different pathologies (e.g. diabetes, inborn errors of metabolism). Depending on its severity, it might affect cognitive functions, including impaired judgment and decreased memory capacity, which have been linked to alterations of brain energy metabolism. Glucose is the major cerebral energy substrate in the adult brain and supports the complex metabolic interactions between neurons and astrocytes, which are essential for synaptic activity. Therefore, hypoglycaemia disturbs cerebral metabolism and, consequently, neuronal function. Despite the high vulnerability of neurons to hypoglycaemia, important neurochemical changes enabling these cells to prolong their resistance to hypoglycaemia have been described. This review aims at providing an overview over the main metabolic effects of hypoglycaemia on neurons, covering in vitro and in vivo findings. Recent studies provided evidence that non-glucose substrates including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, are metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycaemia. One of the pathways likely implicated in the process is the pyruvate recycling pathway, which allows for the full oxidation of glutamate and glutamine. The operation of this pathway in neurons, particularly after hypoglycaemia, has been re-confirmed recently using metabolic modelling tools (i.e. Metabolic Flux Analysis), which allow for a detailed investigation of cellular metabolism in cultured cells. Overall, the knowledge summarized herein might be used for the development of potential therapies targeting neuronal protection in patients vulnerable to hypoglycaemic episodes.

  12. Computational Modelling of the Metabolic States Regulated by the Kinase Akt

    Ettore eMosca

    2012-11-01

    Full Text Available Signal transduction pathways and gene regulation determine a major reorganization of metabolic activities in order to support cell proliferation. Protein Kinase B (PKB, also known as Akt, participates in the PI3K/Akt/mTOR pathway, a master regulator of aerobic glycolysis and cellular biosynthesis, two activities shown by both normal and cancer proliferating cells. Not surprisingly considering its relevance for cellular metabolism, Akt/PKB is often found hyperactive in cancer cells. In the last decade, many efforts have been made to improve the understanding of the control of glucose metabolism and the identification of a therapeutic window between proliferating cancer cells and proliferating normal cells. In this context, we have modelled the link between the PI3K/Akt/mTOR pathway, glycolysis, lactic acid production and nucleotide biosynthesis. We used a computational model in order to compare two metabolic states generated by the specific variation of the metabolic fluxes regulated by the activity of the PI3K/Akt/mTOR pathway. One of the two states represented the metabolism of a growing cancer cell characterised by aerobic glycolysis and cellular biosynthesis, while the other state represented the same metabolic network with a reduced glycolytic rate and a higher mitochondrial pyruvate metabolism, as reported in literature in relation to the activity of the PI3K/Akt/mTOR. Some steps that link glycolysis and pentose phosphate pathway revealed their importance for controlling the dynamics of cancer glucose metabolism.

  13. The criteria for metabolic syndrome and the national health screening and education system in Japan

    Kazumasa Yamagishi

    2017-01-01

    Full Text Available Two major definitions of metabolic syndrome have been proposed. One focuses on the accumulation of risk factors, a measure used by the American Heart Association (AHA and the National Heart, Lung, and Blood Institute (NHLBI; the other focuses on abdominal obesity, a measure used by the International Diabetes Federation (IDF and the Japanese government. The latter definition takes waist circumference (WC into consideration as an obligatory component, whereas the former does not. In 2009, the IDF, NHLBI, AHA, and other organizations attempted to unify these criteria; as a result, WC is no longer an obligatory component of those systems, while it remains obligatory in the Japanese criteria. In 2008, a new Japanese cardiovascular screening and education system focused on metabolic syndrome was launched. People undergoing screening are classified into three groups according to the presence of abdominal obesity and the number of metabolic risk factors, and receive health educational support from insurers. This system has yielded several beneficial outcomes: the visibility of metabolic syndrome at the population level has drastically improved; preventive measures have been directed toward metabolic syndrome, which is expected to become more prevalent in future generations; and a post-screening education system has been established. However, several problems with the current system have been identified and are under debate. In this review, we discuss topics related to metabolic syndrome, including (1 the Japanese criteria for metabolic syndrome; (2 metabolic syndrome and the universal health screening and education system; and (3 recent debates about Japanese criteria for metabolic syndrome.

  14. 'Biomoleculas': cellular metabolism didactic software

    Menghi, M L; Novella, L P; Siebenlist, M R

    2007-01-01

    'Biomoleculas' is a software that deals with topics such as the digestion, cellular metabolism and excretion of nutrients. It is a pleasant, simple and didactic guide, made by and for students. In this program, each biomolecule (carbohydrates, lipids and proteins) is accompanied until its degradation and assimilation by crossing and interrelating the different metabolic channels to finally show the destination of the different metabolites formed and the way in which these are excreted. It is used at present as a teaching-learning process tool by the chair of Physiology and Biophysics at the Facultad de Ingenieria - Universidad Nacional de Entre Rios

  15. Serotonin metabolism in rat brain

    Schutte, H.H.

    1976-01-01

    The metabolism of serotonin in rat brain was studied by measuring specific activities of tryptophan in plasma and of serotonin, 5-hydroxyindole acetic acid and tryptophan in the brain after intravenous injection of tritiated tryptophan. For a detailed analysis of the specific activities, a computer simulation technique was used. It was found that only a minor part of serotonin in rat brain is synthesized from tryptophan rapidly transported from the blood. It is suggested that the brain tryptophan originates from brain proteins. It was also found that the serotonin in rat brain is divided into more than one metabolic compartment

  16. Incidence and Major Metabolic Risk Factors of Metabolic Syndrome ...

    The study involved 300 (92 males and 208 females) type 2 diabetic patients and was conducted at the Tamale Teaching/Regional Hospital from June 2006 to May 2007. Metabolic syndrome was diagnosed using the National Cholesterol Education Programme, Adult Treatment Panel III (2001) criteria. The incidence of the ...

  17. Substrate metabolism in the metabolic response to injury

    Romijn, J. A.

    2000-01-01

    In healthy subjects the metabolic response to starvation invokes regulatory mechanisms aimed at conservation of protein mass. This response is characterized by a decrease in energy expenditure and a progressive decrease in urinary N excretion. Many non-endocrine diseases induce anorexia and a

  18. Enantiomeric metabolic interactions and stereoselective human methadone metabolism.

    Totah, Rheem A; Allen, Kyle E; Sheffels, Pamela; Whittington, Dale; Kharasch, Evan D

    2007-04-01

    Methadone is administered as a racemate, although opioid activity resides in the R-enantiomer. Methadone disposition is stereoselective, with considerable unexplained variability in clearance and plasma R/S ratios. N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. CYP2B6 metabolism was stereoselective. CYP2C19 was less active, and stereoselectivity was opposite that for CYP2B6. CYP3A4 was not stereoselective. With all three isoforms, enantiomer N-dealkylation rates in the racemate were lower than those of (R)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (R-methadone) or (S)-(6-dimethyamino-4,4-diphenyl-heptan-3-one) hydrochloride (S-methadone) alone, suggesting an enantiomeric interaction and mutual metabolic inhibition. For CYP2B6, the interaction between enantiomers was stereoselective, with S-methadone as a more potent inhibitor of R-methadone N-demethylation than R-of S-methadone. In contrast, enantiomer interactions were not stereoselective with CYP2C19 or CYP3A4. For all three cytochromes P450, methadone N-demethylation was best described by two-site enzyme models with competitive inhibition. There were minor model differences between cytochromes P450 to account for stereoselectivity of metabolism and enantiomeric interactions. Changes in plasma R/S methadone ratios observed after rifampin or troleandomycin pretreatment in humans in vivo were successfully predicted by CYP2B6- but not CYP3A4-catalyzed methadone N-demethylation. CYP2B6 is a predominant catalyst of stereoselective methadone metabolism in vitro. In vivo, CYP2B6 may be a major determinant of methadone metabolism and disposition, and CYP2B6 activity and stereoselective metabolic

  19. [Gut microbiota and immune crosstalk in metabolic disease].

    Burcelin, Rémy

    2017-01-01

    , and hepatic steatosis, the mechanisms causal to the disease could be related to the translocation of microbiota from the gut to the tissues, which induces inflammation. The mechanisms regulating such a process are based on the crosstalk between the gut microbiota and the host immune system. The hologenome theory of evolution supports this concept and implies that therapeutic strategies aiming to control glycemia should take into account both the gut microbiota and the host immune system. This review discusses the latest evidence regarding the bidirectional impact of the gut microbiota on host immune system crosstalk for the control of metabolic disease, hyperglycemia, and obesity. To avoid redundancies with the literature, we will focus our attention on the intestinal immune system, identifying evidence for the generation of novel therapeutic strategies, which could be based on the control of the translocation of gut bacteria to tissues. Such novel strategies should hamper the role played by gut microbiota dysbiosis on the development of metabolic inflammation. Recent evidence in rodents allows us to conclude that an impaired intestinal immune system characterizes and could be causal in the development of metabolic disease. The fine understanding of the molecular mechanisms should allow for the development of a first line of treatment for metabolic disease and its co-morbidities. © Société de Biologie, 2017.

  20. Actionable Metabolic Pathways in Heart Failure and Cancer—Lessons From Cancer Cell Metabolism

    Anja Karlstaedt

    2018-06-01

    Full Text Available Recent advances in cancer cell metabolism provide unprecedented opportunities for a new understanding of heart metabolism and may offer new approaches for the treatment of heart failure. Key questions driving the cancer field to understand how tumor cells reprogram metabolism and to benefit tumorigenesis are also applicable to the heart. Recent experimental and conceptual advances in cancer cell metabolism provide the cardiovascular field with the unique opportunity to target metabolism. This review compares cancer cell metabolism and cardiac metabolism with an emphasis on strategies of cellular adaptation, and how to exploit metabolic changes for therapeutic benefit.

  1. Lipid signaling in adipose tissue: Connecting inflammation & metabolism

    Masoodi, M.; Kuda, Ondřej; Rossmeisl, Martin; Flachs, Pavel; Kopecký, Jan

    2015-01-01

    Roč. 1851, č. 4 (2015), s. 503-518 ISSN 1388-1981 R&D Projects: GA ČR(CZ) GA13-00871S; GA MŠk(CZ) 7E12073; GA MŠk(CZ) LH14040 Institutional support: RVO:67985823 Keywords : adipocyte * futile substrate cycle * macrophage Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.779, year: 2015

  2. Partitioning the Metabolic Cost of Human Running: A Task-by-Task Approach

    Arellano, Christopher J.; Kram, Rodger

    2014-01-01

    Compared with other species, humans can be very tractable and thus an ideal “model system” for investigating the metabolic cost of locomotion. Here, we review the biomechanical basis for the metabolic cost of running. Running has been historically modeled as a simple spring-mass system whereby the leg acts as a linear spring, storing, and returning elastic potential energy during stance. However, if running can be modeled as a simple spring-mass system with the underlying assumption of perfect elastic energy storage and return, why does running incur a metabolic cost at all? In 1980, Taylor et al. proposed the “cost of generating force” hypothesis, which was based on the idea that elastic structures allow the muscles to transform metabolic energy into force, and not necessarily mechanical work. In 1990, Kram and Taylor then provided a more explicit and quantitative explanation by demonstrating that the rate of metabolic energy consumption is proportional to body weight and inversely proportional to the time of foot-ground contact for a variety of animals ranging in size and running speed. With a focus on humans, Kram and his colleagues then adopted a task-by-task approach and initially found that the metabolic cost of running could be “individually” partitioned into body weight support (74%), propulsion (37%), and leg-swing (20%). Summing all these biomechanical tasks leads to a paradoxical overestimation of 131%. To further elucidate the possible interactions between these tasks, later studies quantified the reductions in metabolic cost in response to synergistic combinations of body weight support, aiding horizontal forces, and leg-swing-assist forces. This synergistic approach revealed that the interactive nature of body weight support and forward propulsion comprises ∼80% of the net metabolic cost of running. The task of leg-swing at most comprises ∼7% of the net metabolic cost of running and is independent of body weight support and forward

  3. Effects of independently altering body weight and body mass on the metabolic cost of running.

    Teunissen, Lennart P J; Grabowski, Alena; Kram, Rodger

    2007-12-01

    The metabolic cost of running is substantial, despite the savings from elastic energy storage and return. Previous studies suggest that generating vertical force to support body weight and horizontal forces to brake and propel body mass are the major determinants of the metabolic cost of running. In the present study, we investigated how independently altering body weight and body mass affects the metabolic cost of running. Based on previous studies, we hypothesized that reducing body weight would decrease metabolic rate proportionally, and adding mass and weight would increase metabolic rate proportionally. Further, because previous studies show that adding mass alone does not affect the forces generated on the ground, we hypothesized that adding mass alone would have no substantial effect on metabolic rate. We manipulated the body weight and body mass of 10 recreational human runners and measured their metabolic rates while they ran at 3 m s(-1). We reduced weight using a harness system, increased mass and weight using lead worn about the waist, and increased mass alone using a combination of weight support and added load. We found that net metabolic rate decreased in less than direct proportion to reduced body weight, increased in slightly more than direct proportion to added load (added mass and weight), and was not substantially different from normal running with added mass alone. Adding mass alone was not an effective method for determining the metabolic cost attributable to braking/propelling body mass. Runners loaded with mass alone did not generate greater vertical or horizontal impulses and their metabolic costs did not substantially differ from those of normal running. Our results show that generating force to support body weight is the primary determinant of the metabolic cost of running. Extrapolating our reduced weight data to zero weight suggests that supporting body weight comprises at most 74% of the net cost of running. However, 74% is probably an

  4. A support shield for a powered support

    Korczynski, P; Rojicek, P

    1982-08-31

    The subject of this invention is a support shield for a powered support. This shield resists creep of the coal from the longwall face, including an inclined longwall. It involves an arrangement wherein the distributor hinge is separated into upper and lower sections. The lower section holds a second hinge and the end of the rod of the pressure cylinder, one end of which is connected to the roof support. An advantage of the support is that compared to existing supports, it is self-advancing and holds stopes with coal which slopes in its formation or has inrushes. To a certain degree it prevents the stope space from ejecting fine pieces of rock from the longwall roof using an inter-timber support between the powered support and the stope. The support shield is moved by a simple system of levers which makes it possible, using a pressurized cylinder, to transmit a significant force to the coal stope. In this case, when the coal inrushes exceed the designed capabilities of the shield, a wooden extension piece is placed between the support and the face, through which the support pressure is applied.

  5. Metabolic engineering in methanotrophic bacteria

    Kalyuzhnaya, MG; Puri, AW; Lidstrom, ME

    2015-05-01

    Methane, as natural gas or biogas, is the least expensive source of carbon for (bio)chemical synthesis. Scalable biological upgrading of this simple alkane to chemicals and fuels can bring new sustainable solutions to a number of industries with large environmental footprints, such as natural gas/petroleum production, landfills, wastewater treatment, and livestock. Microbial biocatalysis with methane as a feedstock has been pursued off and on for almost a half century, with little enduring success. Today, biological engineering and systems biology provide new opportunities for metabolic system modulation and give new optimism to the concept of a methane-based bio-industry. Here we present an overview of the most recent advances pertaining to metabolic engineering of microbial methane utilization. Some ideas concerning metabolic improvements for production of acetyl-CoA and pyruvate, two main precursors for bioconversion, are presented. We also discuss main gaps in the current knowledge of aerobic methane utilization, which must be solved in order to release the full potential of methane-based biosystems. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  6. Nutrition, Epigenetics, and Metabolic Syndrome

    Wang, Junjun; Wu, Zhenlong; Li, Defa; Li, Ning; Dindot, Scott V.; Satterfield, M. Carey; Bazer, Fuller W.; Wu, Guoyao

    2012-01-01

    Significance: Epidemiological and animal studies have demonstrated a close link between maternal nutrition and chronic metabolic disease in children and adults. Compelling experimental results also indicate that adverse effects of intrauterine growth restriction on offspring can be carried forward to subsequent generations through covalent modifications of DNA and core histones. Recent Advances: DNA methylation is catalyzed by S-adenosylmethionine-dependent DNA methyltransferases. Methylation...

  7. Iodine metabolism and food needs

    Mornex, R.

    1992-01-01

    Iodine is an element that is necessary for the growth and mental development of a child and for the maintenance of the activity of all cells at all ages. In this article, the author recalls the iodine sources, its metabolism and the food needs and contributions

  8. Synthetic biology and metabolic engineering.

    Stephanopoulos, Gregory

    2012-11-16

    Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

  9. Dithiobiuret metabolism in the rat

    Williams, K.D.; Porter, W.R.; Peterson, R.E.

    1982-01-01

    Our main objective was to describe the metabolism of dithiobiuret (DTB) in the adult, male rat. Based on the thin-layer chromatographic analysis of urine from animals treated with [ 14 C] or [ 35 S] labeled DTB, two pathways for metabolism are proposed. One pathway is reversible and involves the oxidation of DTB to thiuret and the reduction of thiuret back to DTB. The other pathway consists of the desulfurization of DTB to monothiobiuret. The liver appears to desulfurate DTB because DTB-derived [35S] was eliminated from the liver more rapidly than [ 14 C]. The liver was the only tissue where the elimination kinetics of [ 35 S] and [ 14 C] DTB were different. DTB-derived radioactivity in urine that co-chromatographed with DTB, monothiobiuret, thiuret and sulfate was quantitated along with that of three uncharacterized metabolites. The presence of these unknown metabolites suggests that DTB metabolism is complex. The present study is the first description of the metabolic fate of DTB in the rat and serves as a starting point for determining whether DTB neurotoxicity is caused by the parent compound or a metabolite

  10. Cancer Metabolism: A Modeling Perspective

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells...

  11. MicroRNAs in Metabolism

    Vienberg, Sara; Geiger, Julian; Madsen, Søren

    2017-01-01

    roles in cholesterol and lipid metabolism, whereas miR-103 and -107 regulates hepatic insulin sensitivity. In muscle tissue a defined number of miRNAs (miR-1, miR-133, mir-206) control myofiber type switch and induce myogenic differentiation programs. Similarly, in adipose tissue a defined number of mi...

  12. Bile Acid Metabolism and Signaling

    Chiang, John Y. L.

    2015-01-01

    Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. PMID:23897684

  13. Absorption and Metabolism of Xanthophylls

    Eiichi Kotake-Nara

    2011-06-01

    Full Text Available Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

  14. Absorption and metabolism of xanthophylls.

    Kotake-Nara, Eiichi; Nagao, Akihiko

    2011-01-01

    Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

  15. Modifying factors for metabolic parameters

    Inaba, Jiro

    1990-01-01

    Studies on factors which influence the metabolic parameter for calculation of radiation doses from intakes of radionuclides are very important for estimation of the doses for the general public, because the present procedures recommended by the International Commission on Radiological Protection is for occupationally exposed workers and the underlying metabolic and dosimetric models have been developed from studies on adult man and experiments on adult animals and from observations on radionuclides in physico-chemically simple form. Many factors have been reported to influence the metabolic parameters. Among them, the food-chain involvement of radionuclides and the age-dependence in humans and animals are most significant as environmental and physiological factor, respectively. In connection with the age-dependence of dose calculation, the ICRP started a new programme. They organized a Task Group on Age-Dependent Dose-Factors where relevant information on metabolic and biokinetic parameters are presently being reviewed for development of a set of dose factors for the following age-groups: infant, 1-year-old, 5-year-old, 10-year-old, 15-year-old, and ICRP Reference Man. The first stage of the work is for age-dependent integrated organ and effective dose factors for radioisotopes of the following elements: hydrogen, carbon, iodine, cesium, strontium, plutonium and americium. (author)

  16. SIRT1 and metabolic syndrome

    Katarzyna Mac-Marcjanek

    2011-04-01

    Full Text Available Both obesity and type 2 diabetes mellitus, two major components of metabolic syndrome, become healthepidemics in the world. Over the past decade, advances in understanding the role of some regulators participatingin lipid and carbohydrate homeostasis have been made.Of them, SIRT1, the mammalian orthologue of the yeast Sir2 protein has been identified. SIRT1 is a nuclearNAD+-dependent deacetylase that targets many transcriptional modulators, including PPAR-α and -γ (peroxisomeproliferator-activated receptors α and γ, PGC-1α (PPAR-γ coactivator-1α, FOXO (forkhead box O proteins,and nuclear factor κB (NF-κB, thereby this enzyme mediates a wide range of physiological processes like apoptosis,fat metabolism, glucose homeostasis, and neurodegeneration.In this article, we discuss how SIRT1 regulates lipid and carbohydrate metabolism, and insulin secretion indifferent metabolic organs/tissue, including liver, muscle, pancreas, and fat. Additionally, the role of this enzymein reduction of inflammatory signalling is highlighted.

  17. Metabolism of phthalates in humans

    Frederiksen, Hanne; Skakkebaek, Niels E; Andersson, Anna-Maria

    2007-01-01

    on the foetal testis and they are similar to those seen in humans with testicular dysgenesis syndrome. Therefore, exposure of the human foetus and infants to phthalates via maternal exposure is a matter of concern. The metabolic pathways of phthalate metabolites excreted in human urine are partly known for some...

  18. Bone scintigraphy and metabolic disorders

    Mari', C.; Catafau, A.; Carrio', I.

    1999-01-01

    The paper discusses the main clinical value of bone scan in metabolic bone disease: its detection of focal conditions or focal complications of such generalized disease, its most common use of being the detection of fractures in osteoporosis, pseudofractures in osteomalacia and the evaluation of Paget's disease

  19. Bone scintigraphy and metabolic disorders

    Mari' , C.; Catafau, A.; Carrio' , I. [Hospital de Sant Pau, Barcelone (Spain). Serv. of Nuclear Medicine

    1999-09-01

    The paper discusses the main clinical value of bone scan in metabolic bone disease: its detection of focal conditions or focal complications of such generalized disease, its most common use of being the detection of fractures in osteoporosis, pseudo fractures in osteomalacia and the evaluation of Paget's disease.

  20. Development of radiometric assays for quantification of enzyme activities of the key enzymes of thyroid hormones metabolism

    Pavelka, Stanislav

    2014-01-01

    Roč. 63, Suppl.1 (2014), S133-S140 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 7AMB12SK158; GA ČR(CZ) GA304/08/0256 Institutional support: RVO:67985823 Keywords : enzyme * metabolism * radiometric assay * thyroid hormone Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.293, year: 2014

  1. Exogenous Classic Phytohormones Have Limited Regulatory Effects on Fructan and Primary Carbohydrate Metabolism in Perennial Ryegrass (Lolium perenne L.)

    Gasperl, A.; Morvan-Bertrand, A.; Prud'homme, M. P.; van der Graaff, E.; Roitsch, Thomas

    2016-01-01

    Roč. 6, jan (2016), s. 1251 ISSN 1664-462X R&D Projects: GA MŠk(CZ) LO1415 Institutional support: RVO:67179843 Keywords : enzymatic activity * fructan exohydrolase * fructan metabolism * fructosyltransferase * perennial ryegrass * phytohormones * primary carbohydrate metabolism Subject RIV: ED - Physiology Impact factor: 4.298, year: 2016

  2. Quantification of patterns of regional cardiac metabolism

    Lear, J.L.; Ackermann, R.F.

    1990-01-01

    To quantitatively map and compare patterns of regional cardiac metabolism with greater spatial resolution than is possible with positron emission tomography (PET), the authors developed autoradiographic techniques for use with combinations of radiolabeled fluorodeoxyglucose (FDG), glucose (GLU), and acetate (ACE) and applied the techniques to normal rats. Kinetic models were developed to compare GLU-based oxidative glucose metabolism with FDG-based total glucose metabolism (oxidative plus anaerobic) and to compare ACE-based overall oxidative metabolism with FDG-based total glucose metabolism. GLU-based metabolism generally paralleled FDG-based metabolism, but divergence occurred in certain structures such as the papillary muscles, where FDG-based metabolism was much greater. ACE-based metabolism also generally paralleled FDG-based metabolism, but again, the papillary muscles had relatively greater FDG-based metabolism. These discrepancies between FDG-based metabolism and GLU- or ACE-based metabolism suggest the presence of high levels of anaerobic glycolysis. Thus, the study indicates that anaerobic glycolysis, in addition to occurring in ischemic or stunned myocardium (as has been shown in recent PET studies), occurs normally in specific cardiac regions, despite the presence of abundant oxygen

  3. Feasible metabolisms in high pH springs of the Philippines.

    Cardace, Dawn; Meyer-Dombard, D'Arcy R; Woycheese, Kristin M; Arcilla, Carlo A

    2015-01-01

    A field campaign targeting high pH, H2-, and CH4-emitting serpentinite-associated springs in the Zambales and Palawan Ophiolites of the Philippines was conducted in 2012-2013, and enabled description of several springs sourced in altered pillow basalts, gabbros, and peridotites. We combine field observations of pH, temperature, conductivity, dissolved oxygen, and oxidation-reduction potential with analyses of major ions, dissolved inorganic carbon, dissolved organic carbon, and dissolved gas phases in order to model the activities of selected phases important to microbial metabolism, and to rank feasible metabolic reactions based on energy yield. We document changing geochemical inventories in these springs between sampling years, and examine how the environment supports or prevents the function of certain microbial metabolisms. In all, this geochemistry-based assessment of feasible metabolisms indicates methane cycling, hydrogen oxidation, some iron and sulfur metabolisms, and ammonia oxidation are feasible reactions in this continental site of serpentinization.

  4. Cerebral Metabolism and the Role of Glucose Control in Acute Traumatic Brain Injury.

    Buitrago Blanco, Manuel M; Prashant, Giyarpuram N; Vespa, Paul M

    2016-10-01

    This article reviews key concepts of cerebral glucose metabolism, neurologic outcomes in clinical trials, the biology of the neurovascular unit and its involvement in secondary brain injury after traumatic brain insults, and current scientific and clinical data that demonstrate a better understanding of the biology of metabolic dysfunction in the brain, a concept now known as cerebral metabolic energy crisis. The use of neuromonitoring techniques to better understand the pathophysiology of the metabolic crisis is reviewed and a model that summarizes the triphasic view of cerebral metabolic disturbance supported by existing scientific data is outlined. The evidence is summarized and a template for future research provided. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Uric acid in metabolic syndrome: From an innocent bystander to a central player

    Kanbay, Mehmet; Jensen, Thomas; Solak, Yalcin; Le, Myphuong; Roncal-Jimenez, Carlos; Rivard, Chris; Lanaspa, Miguel A.; Nakagawa, Takahiko; Johnson, Richard J.

    2016-01-01

    Uric acid, once viewed as an inert metabolic end-product of purine metabolism, has been recently incriminated in a number of chronic disease states, including hypertension, metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and chronic kidney disease. Several experimental and clinical studies support a role for uric acid as a contributory causal factor in these conditions. Here we discuss some of the major mechanisms linking uric acid to metabolic and cardiovascular diseases. At this time the key to understanding the importance of uric acid in these diseases will be the conduct of large clinical trials in which the effect of lowering uric acid on hard clinical outcomes is assessed. Elevated uric acid may turn out to be one of the more important remediable risk factors for metabolic and cardiovascular diseases. PMID:26703429

  6. "Metabolic staging" after major trauma - a guide for clinical decision making?

    Moore Ernest E

    2010-06-01

    Full Text Available Abstract Metabolic changes after major trauma have a complex underlying pathophysiology. The early posttraumatic stress response is associated with a state of hyperinflammation, with increased oxygen consumption and energy expenditure. This hypercatabolic state must be recognized early and mandates an early nutritional management strategy. A proactive concept of early enteral "immunonutrition" in severely injured patients, is aimed at counterbalancing the negative aspects of hyperinflammation and hypercatabolism in order to reduce the risk of late complications, including infections and posttraumatic organ failure. Recently, the concept of "metabolic staging" has been advocated, which takes into account the distinct inflammatory phases and metabolic phenotypes after major trauma, including the "ischemia/reperfusion phenotype", the "leukocytic phenotype", and the "angiogenic phenotype". The potential clinical impact of metabolic staging, and of an appropriately adapted "metabolic control" and nutritional support, remains to be determined.

  7. Resistance to Antiangiogenic Therapies by Metabolic Symbiosis in Renal Cell Carcinoma PDX Models and Patients

    Gabriela Jiménez-Valerio

    2016-05-01

    Full Text Available Antiangiogenic drugs are used clinically for treatment of renal cell carcinoma (RCC as a standard first-line treatment. Nevertheless, these agents primarily serve to stabilize disease, and resistance eventually develops concomitant with progression. Here, we implicate metabolic symbiosis between tumor cells distal and proximal to remaining vessels as a mechanism of resistance to antiangiogenic therapies in patient-derived RCC orthoxenograft (PDX models and in clinical samples. This metabolic patterning is regulated by the mTOR pathway, and its inhibition effectively blocks metabolic symbiosis in PDX models. Clinically, patients treated with antiangiogenics consistently present with histologic signatures of metabolic symbiosis that are exacerbated in resistant tumors. Furthermore, the mTOR pathway is also associated in clinical samples, and its inhibition eliminates symbiotic patterning in patient samples. Overall, these data support a mechanism of resistance to antiangiogenics involving metabolic compartmentalization of tumor cells that can be inhibited by mTOR-targeted drugs.

  8. Certification of support services

    Hroch, A.; Osusky, V.

    2006-01-01

    In this paper the process of certification of support services in the Slovenske elektrarne, a. s. is described. The nuclear power plants are also included into support services. Provisions and economic aspects of support services are discussed

  9. Evidence of circadian rhythm, oxygen regulation capacity, metabolic repeatability and positive correlations between forced and spontaneous maximal metabolic rates in lake sturgeon Acipenser fulvescens.

    Jon C Svendsen

    Full Text Available Animal metabolic rate is variable and may be affected by endogenous and exogenous factors, but such relationships remain poorly understood in many primitive fishes, including members of the family Acipenseridae (sturgeons. Using juvenile lake sturgeon (Acipenser fulvescens, the objective of this study was to test four hypotheses: 1 A. fulvescens exhibits a circadian rhythm influencing metabolic rate and behaviour; 2 A. fulvescens has the capacity to regulate metabolic rate when exposed to environmental hypoxia; 3 measurements of forced maximum metabolic rate (MMR(F are repeatable in individual fish; and 4 MMR(F correlates positively with spontaneous maximum metabolic rate (MMR(S. Metabolic rates were measured using intermittent flow respirometry, and a standard chase protocol was employed to elicit MMR(F. Trials lasting 24 h were used to measure standard metabolic rate (SMR and MMR(S. Repeatability and correlations between MMR(F and MMR(S were analyzed using residual body mass corrected values. Results revealed that A. fulvescens exhibit a circadian rhythm in metabolic rate, with metabolism peaking at dawn. SMR was unaffected by hypoxia (30% air saturation (O(2sat, demonstrating oxygen regulation. In contrast, MMR(F was affected by hypoxia and decreased across the range from 100% O(2sat to 70% O(2sat. MMR(F was repeatable in individual fish, and MMR(F correlated positively with MMR(S, but the relationships between MMR(F and MMR(S were only revealed in fish exposed to hypoxia or 24 h constant light (i.e. environmental stressor. Our study provides evidence that the physiology of A. fulvescens is influenced by a circadian rhythm and suggests that A. fulvescens is an oxygen regulator, like most teleost fish. Finally, metabolic repeatability and positive correlations between MMR(F and MMR(S support the conjecture that MMR(F represents a measure of organism performance that could be a target of natural selection.

  10. Identification of microRNAs controlling hepatic mRNA levels for metabolic genes during the metabolic transition from embryonic to posthatch development in the chicken.

    Hicks, Julie A; Porter, Tom E; Liu, Hsiao-Ching

    2017-09-05

    The transition from embryonic to posthatch development in the chicken represents a massive metabolic switch from primarily lipolytic to primarily lipogenic metabolism. This metabolic switch is essential for the chick to successfully transition from the metabolism of stored egg yolk to the utilization of carbohydrate-based feed. However, regulation of this metabolic switch is not well understood. We hypothesized that microRNAs (miRNAs) play an important role in the metabolic switch that is essential to efficient growth of chickens. We used high-throughput RNA sequencing to characterize expression profiles of mRNA and miRNA in liver during late embryonic and early posthatch development of the chicken. This extensive data set was used to define the contributions of microRNAs to the metabolic switch during development that is critical to growth and nutrient utilization in chickens. We found that expression of over 800 mRNAs and 30 miRNAs was altered in the embryonic liver between embryonic day 18 and posthatch day 3, and many of these differentially expressed mRNAs and miRNAs are associated with metabolic processes. We confirmed the regulation of some of these mRNAs by miRNAs expressed in a reciprocal pattern using luciferase reporter assays. Finally, through the use of yeast one-hybrid screens, we identified several proteins that likely regulate expression of one of these important miRNAs. Integration of the upstream regulatory mechanisms governing miRNA expression along with monitoring the downstream effects of this expression will ultimately allow for the construction of complete miRNA regulatory networks associated with the hepatic metabolic switch in chickens. Our findings support a key role for miRNAs in controlling the metabolic switch that occurs between embryonic and posthatch development in the chicken.

  11. Abdominal obesity and metabolic syndrome: exercise as medicine?

    Paley, Carole A; Johnson, Mark I

    2018-01-01

    Metabolic syndrome is defined as a cluster of at least three out of five clinical risk factors: abdominal (visceral) obesity, hypertension, elevated serum triglycerides, low serum high-density lipoprotein (HDL) and insulin resistance. It is estimated to affect over 20% of the global adult population. Abdominal (visceral) obesity is thought to be the predominant risk factor for metabolic syndrome and as predictions estimate that 50% of adults will be classified as obese by 2030 it is likely that metabolic syndrome will be a significant problem for health services and a drain on health economies.Evidence shows that regular and consistent exercise reduces abdominal obesity and results in favourable changes in body composition. It has therefore been suggested that exercise is a medicine in its own right and should be prescribed as such. This review provides a summary of the current evidence on the pathophysiology of dysfunctional adipose tissue (adiposopathy). It describes the relationship of adiposopathy to metabolic syndrome and how exercise may mediate these processes, and evaluates current evidence on the clinical efficacy of exercise in the management of abdominal obesity. The review also discusses the type and dose of exercise needed for optimal improvements in health status in relation to the available evidence and considers the difficulty in achieving adherence to exercise programmes. There is moderate evidence supporting the use of programmes of exercise to reverse metabolic syndrome although at present the optimal dose and type of exercise is unknown. The main challenge for health care professionals is how to motivate individuals to participate and adherence to programmes of exercise used prophylactically and as a treatment for metabolic syndrome.

  12. Metabolic heat production by human and animal populations in cities.

    Stewart, Iain D; Kennedy, Chris A

    2017-07-01

    Anthropogenic heating from building energy use, vehicle fuel consumption, and human metabolism is a key term in the urban energy budget equation. Heating from human metabolism, however, is often excluded from urban energy budgets because it is widely observed to be negligible. Few reports for low-latitude cities are available to support this observation, and no reports exist on the contribution of domestic animals to urban heat budgets. To provide a more comprehensive view of metabolic heating in cities, we quantified all terms of the anthropogenic heat budget at metropolitan scale for the world's 26 largest cities, using a top-down statistical approach. Results show that metabolic heat release from human populations in mid-latitude cities (e.g. London, Tokyo, New York) accounts for 4-8% of annual anthropogenic heating, compared to 10-45% in high-density tropical cities (e.g. Cairo, Dhaka, Kolkata). Heat release from animal populations amounts to heating in all cities. Heat flux density from human and animal metabolism combined is highest in Mumbai-the world's most densely populated megacity-at 6.5 W m -2 , surpassing heat production by electricity use in buildings (5.8 W m -2 ) and fuel combustion in vehicles (3.9 W m -2 ). These findings, along with recent output from global climate models, suggest that in the world's largest and most crowded cities, heat emissions from human metabolism alone can force measurable change in mean annual temperature at regional scale.

  13. Ovarian tumor-initiating cells display a flexible metabolism

    Anderson, Angela S. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Roberts, Paul C. [Biomedical Science and Pathobiology, Virginia Tech, Blacksburg, VA (United States); Frisard, Madlyn I. [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Hulver, Matthew W., E-mail: hulvermw@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States); Schmelz, Eva M., E-mail: eschmelz@vt.edu [Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA (United States)

    2014-10-15

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L{sub FFLv} (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth.

  14. Ovarian tumor-initiating cells display a flexible metabolism

    Anderson, Angela S.; Roberts, Paul C.; Frisard, Madlyn I.; Hulver, Matthew W.; Schmelz, Eva M.

    2014-01-01

    An altered metabolism during ovarian cancer progression allows for increased macromolecular synthesis and unrestrained growth. However, the metabolic phenotype of cancer stem or tumor-initiating cells, small tumor cell populations that are able to recapitulate the original tumor, has not been well characterized. In the present study, we compared the metabolic phenotype of the stem cell enriched cell variant, MOSE-L FFLv (TIC), derived from mouse ovarian surface epithelial (MOSE) cells, to their parental (MOSE-L) and benign precursor (MOSE-E) cells. TICs exhibit a decrease in glucose and fatty acid oxidation with a concomitant increase in lactate secretion. In contrast to MOSE-L cells, TICs can increase their rate of glycolysis to overcome the inhibition of ATP synthase by oligomycin and can increase their oxygen consumption rate to maintain proton motive force when uncoupled, similar to the benign MOSE-E cells. TICs have an increased survival rate under limiting conditions as well as an increased survival rate when treated with AICAR, but exhibit a higher sensitivity to metformin than MOSE-E and MOSE-L cells. Together, our data show that TICs have a distinct metabolic profile that may render them flexible to adapt to the specific conditions of their microenvironment. By better understanding their metabolic phenotype and external environmental conditions that support their survival, treatment interventions can be designed to extend current therapy regimens to eradicate TICs. - Highlights: • Ovarian cancer TICs exhibit a decreased glucose and fatty acid oxidation. • TICs are more glycolytic and have highly active mitochondria. • TICs are more resistant to AICAR but not metformin. • A flexible metabolism allows TICs to adapt to their microenvironment. • This flexibility requires development of specific drugs targeting TIC-specific changes to prevent recurrent TIC outgrowth

  15. Obestatin as a regulator of adipocyte metabolism and adipogenesis

    Gurriarán-Rodríguez, Uxía; Al-Massadi, Omar; Roca-Rivada, Arturo; Crujeiras, Ana Belén; Gallego, Rosalía; Pardo, Maria; Seoane, Luisa Maria; Pazos, Yolanda; Casanueva, Felipe F; Camiña, Jesús P

    2011-01-01

    Abstract The role of obestatin, a 23-amino-acid peptide encoded by the ghrelin gene, on the control of the metabolism of pre-adipocyte and adipocytes as well as on adipogenesis was determined. For in vitro assays, pre-adipocyte and adipocyte 3T3-L1 cells were used to assess the obestatin effect on cell metabolism and adipogenesis based on the regulation of the key enzymatic nodes, Akt and AMPK and their downstream targets. For in vivo assays, white adipose tissue (WAT) was obtained from male rats under continuous subcutaneous infusion of obestatin. Obestatin activated Akt and its downstream targets, GSK3α/β, mTOR and S6K1, in 3T3-L1 adipocyte cells. Simultaneously, obestatin inactivated AMPK in this cell model. In keeping with this, ACC phosphorylation was also decreased. This fact was confirmed in vivo in white adipose tissue (omental, subcutaneous and gonadal) obtained from male rats under continuous sc infusion of obestatin (24 and 72 hrs). The relevance of obestatin as regulator of adipocyte metabolism was supported by AS160 phosphorylation, GLUT4 translocation and augment of glucose uptake in 3T3-L1 adipocyte cells. In contrast, obestatin failed to modify translocation of fatty acid transporters, FATP1, FATP4 and FAT/CD36, to plasma membrane. Obestatin treatment in combination with IBMX and DEX showed to regulate the expression of C/EBPα, C/EBPβ, C/EBPδ and PPARγ promoting adipogenesis. Remarkable, preproghrelin expression, and thus obestatin expression, increased during adipogenesis being sustained throughout terminal differentiation. Neutralization of endogenous obestatin secreted by 3T3-L1 cells by anti-obestatin antibody decreased adipocyte differentiation. Furthermore, knockdown experiments by preproghrelin siRNA supported that obestatin contributes to adipogenesis. In summary, obestatin promotes adipogenesis in an autocrine/paracrine manner, being a regulator of adipocyte metabolism. These data point to a putative role in the pathogenesis of

  16. A central role of eNOS in the protective effect of wine against metabolic syndrome.

    Leighton, Federico; Miranda-Rottmann, Soledad; Urquiaga, Inés

    2006-01-01

    The positive health effects derived from moderate wine consumption are pleiotropic. They appear as improvements in cardiovascular risk factors such as plasma lipids, haemostatic mechanisms, endothelial function and antioxidant defences. The active principles would be ethanol and mainly polyphenols. Results from our and other laboratories support the unifying hypothesis that the improvements in risk factors after red wine consumption are mediated by endothelial nitric oxide synthase (eNOS). Many genes are involved, but the participation of eNOS would be a constant feature. The metabolic syndrome is a cluster of metabolic risk factors associated with high risk of cardiovascular disease (CVD). The National Cholesterol Education Programmmes Adult Treatment Panel III (NCEPATP III) clinical definition of the metabolic syndrome requires the presence of at least three risk factors, from among abdominal obesity, high plasma triacylglycerols, low plasma HDL, high blood pressure and high fasting plasma glucose. The molecular mechanisms responsible for the metabolic syndrome are not known. Since metabolic syndrome apparently affects 10-30% of the population in the world, research on its pathogenesis and control is needed. The recent finding that eNOS knockout mice present a cluster of cardiovascular risk factors comparable to those of the metabolic syndrome suggests that defects in eNOS function may cause human metabolic syndrome. These mice are hypertensive, insulin resistant and dyslipidemic. Further support for a pathogenic role of eNOS comes from the finding in humans that eNOS polymorphisms associate with insulin resistance and diabetes, with hypertension, with inflammatory and oxidative stress markers and with albuminuria. So, the data sustain the hypothesis that eNOS enhancement should reduce metabolic syndrome incidence and its consequences. Therefore red wine, since it enhances eNOS function, should be considered as a potential tool for the control of metabolic

  17. Albumin metabolism in health and disease

    Kirsch, R E; Saunders, S J; Brock, J F [Cape Town Univ. (South Africa). Dept. of Medicine

    1979-11-24

    Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed.

  18. Fifteen years experience: Egyptian metabolic lab

    Ekram M. Fateen

    2014-08-20

    Aug 20, 2014 ... defective enzymes or transport proteins which results in a block of the metabolic pathway and accumulation ... The detection of metabolic disorder is done ..... [42] Wood TC, Harvey K, Beck M, Burin MG, Chien YH, Church HJ,.

  19. Albumin metabolism in health and disease

    Kirsch, R.E.; Saunders, S.J.; Brock, J.F.

    1979-01-01

    Studies performed at the University of Cape Town on the metabolism of albumin have been reviewed. The control of albumin metabolism in protein energy malnutrition, in acute exposure to alcohol and after partial hepatectomy in the rat is discussed

  20. Modelling of the metabolism of Zymomonas mobilis

    Posten, C; Thoma, M

    1986-01-01

    In order to optimize fermentations with respect to media, reactor configuration, and control a structured model of the metabolism of Zymononas mobilis has been developed. The model is based on structure of metabolism, rate limiting steps, energy balance and metabolic elemental balances. A three-fold effect of ethanol has been observed concerning substrate-turnover, ammonia uptake and energy consumption. In addition to the metabolic view a structured cell-membrane-model should be considered.