WorldWideScience

Sample records for understanding metabolic adaption

  1. Metabolic Adaptation to Muscle Ischemia

    Science.gov (United States)

    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.

  2. Adaptations in the energy metabolism of parasites

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    Science.gov (United States)

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

  4. Understanding Regulation of Metabolism through Feasibility Analysis

    NARCIS (Netherlands)

    Nikerel, I.E.; Berkhout, J.; Hu, F.; Teusink, B.; Reinders, M.J.T.; De Ridder, D.

    2012-01-01

    Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but

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

    Science.gov (United States)

    Crewther, Blair; Cronin, John; Keogh, Justin

    2006-01-01

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

  6. Understanding climate change adaptation and adaptive capacity: synthesis report

    Energy Technology Data Exchange (ETDEWEB)

    Patino, L. [Policy Research Initiative, Government of Canada, Ottawa, ON (Canada)

    2010-09-15

    In 2007, the Natural Resources Canada (NRCan) Climate Change Impacts and Adaptation Division (CCIAD) offered its support to research projects that were involved in understanding and improving adaptation and adaptive capacity and contributed to climate change decision-making and policy development in Canada. 20 research projects were commissioned by the CCIAD. With the collaboration of NRCan, the principal findings raised by the commissioned projects were synthesized by the Policy Research Initiative (PRI). Common themes and main messages are introduced in this synthesis report, and policy and program aspects that promote adaptive capacity to climate change in Canada are identified. Common themes and important messages emerging from the research projects, as well as the processes and barriers to adaptation and adaptive capacity identified in the commissioned projects, were discussed during a workshop held in Ottawa in 2009. Five main themes and four common barriers to adaptation were found. 25 refs.

  7. Understanding Regulation of Metabolism through Feasibility Analysis

    Science.gov (United States)

    Nikerel, Emrah; Berkhout, Jan; Hu, Fengyuan; Teusink, Bas; Reinders, Marcel J. T.; de Ridder, Dick

    2012-01-01

    Understanding cellular regulation of metabolism is a major challenge in systems biology. Thus far, the main assumption was that enzyme levels are key regulators in metabolic networks. However, regulation analysis recently showed that metabolism is rarely controlled via enzyme levels only, but through non-obvious combinations of hierarchical (gene and enzyme levels) and metabolic regulation (mass action and allosteric interaction). Quantitative analyses relating changes in metabolic fluxes to changes in transcript or protein levels have revealed a remarkable lack of understanding of the regulation of these networks. We study metabolic regulation via feasibility analysis (FA). Inspired by the constraint-based approach of Flux Balance Analysis, FA incorporates a model describing kinetic interactions between molecules. We enlarge the portfolio of objectives for the cell by defining three main physiologically relevant objectives for the cell: function, robustness and temporal responsiveness. We postulate that the cell assumes one or a combination of these objectives and search for enzyme levels necessary to achieve this. We call the subspace of feasible enzyme levels the feasible enzyme space. Once this space is constructed, we can study how different objectives may (if possible) be combined, or evaluate the conditions at which the cells are faced with a trade-off among those. We apply FA to the experimental scenario of long-term carbon limited chemostat cultivation of yeast cells, studying how metabolism evolves optimally. Cells employ a mixed strategy composed of increasing enzyme levels for glucose uptake and hexokinase and decreasing levels of the remaining enzymes. This trade-off renders the cells specialized in this low-carbon flux state to compete for the available glucose and get rid of over-overcapacity. Overall, we show that FA is a powerful tool for systems biologists to study regulation of metabolism, interpret experimental data and evaluate hypotheses. PMID

  8. Adaptive Evolution of Phosphorus Metabolism in Prochlorococcus

    DEFF Research Database (Denmark)

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

    2016-01-01

    Inorganic phosphorus is scarce in the eastern Mediterranean Sea, where the high-light-adapted ecotype HLI of the marine picocyanobacterium Prochlorococcus marinus thrives. Physiological and regulatory control of phosphorus acquisition and partitioning has been observed in HLI both in culture...... and in the field; however, the optimization of phosphorus metabolism and associated gains for its phosphorus-limited-growth (PLG) phenotype have not been studied. Here, we reconstructed a genome-scale metabolic network of the HLI axenic strain MED4 (iJC568), consisting of 568 metabolic genes in relation to 794...... through drastic depletion of phosphorus-containing biomass components but also through network-wide reductions in phosphate-reaction participation and the loss of a key enzyme, succinate dehydrogenase. These alterations occur despite the stringency of having relatively few pathway redundancies...

  9. Understanding the adaptive approach to thermal comfort

    Energy Technology Data Exchange (ETDEWEB)

    Humphreys, M.A. [Oxford Univ. (United Kingdom). Centre for the Study of Christianity and Culture; Nicol, J.F. [Oxford Brookes Univ. (United Kingdom). School of Architecture

    1998-10-01

    This paper explains the adaptive approach to thermal comfort, and an adaptive model for thermal comfort is presented. The model is an example of a complex adaptive system (Casti 1996) whose equilibria are determined by the restrictions acting upon it. People`s adaptive actions are generally effective in securing comfort, which occurs at a wide variety of indoor temperatures. These comfort temperatures depend upon the circumstances in which people live, such as the climate and the heating or cooling regime. The temperatures may be estimated from the mean outdoor temperature and the availability of a heating or cooling plant. The evaluation of the parameters of the adaptive model requires cross-sectional surveys to establish current norms and sequential surveys (with and without intervention) to evaluate the rapidity of people`s adaptive actions. Standards for thermal comfort will need revision in the light of the adaptive approach. Implications of the adaptive model for the HVAC industry are noted.

  10. Understanding Controversies in Urban Climate Change Adaptation

    DEFF Research Database (Denmark)

    Baron, Nina; Petersen, Lars Kjerulf

    2015-01-01

    This article explores the controversies that exist in urban climate change adaptation and how these controversies influence the role of homeowners in urban adaptation planning. A concrete SUDS project in a housing cooperative in Copenhagen has been used as a case study thereby investigating the m...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

    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.

  13. Metabolic profiling reveals ethylene mediated metabolic changes and a coordinated adaptive mechanism of 'Jonagold' apple to low oxygen stress.

    Science.gov (United States)

    Bekele, Elias A; Beshir, Wasiye F; Hertog, Maarten L A T M; Nicolai, Bart M; Geeraerd, Annemie H

    2015-11-01

    Apples are predominantly stored in controlled atmosphere (CA) storage to delay ripening and prolong their storage life. Profiling the dynamics of metabolic changes during ripening and CA storage is vital for understanding the governing molecular mechanism. In this study, the dynamics of the primary metabolism of 'Jonagold' apples during ripening in regular air (RA) storage and initiation of CA storage was profiled. 1-Methylcyclopropene (1-MCP) was exploited to block ethylene receptors and to get insight into ethylene mediated metabolic changes during ripening of the fruit and in response to hypoxic stress. Metabolic changes were quantified in glycolysis, the tricarboxylic acid (TCA) cycle, the Yang cycle and synthesis of the main amino acids branching from these metabolic pathways. Partial least square discriminant analysis of the metabolic profiles of 1-MCP treated and control apples revealed a metabolic divergence in ethylene, organic acid, sugar and amino acid metabolism. During RA storage at 18°C, most amino acids were higher in 1-MCP treated apples, whereas 1-aminocyclopropane-1-carboxylic acid (ACC) was higher in the control apples. The initial response of the fruit to CA initiation was accompanied by an increase of alanine, succinate and glutamate, but a decline in aspartate. Furthermore, alanine and succinate accumulated to higher levels in control apples than 1-MCP treated apples. The observed metabolic changes in these interlinked metabolites may indicate a coordinated adaptive strategy to maximize energy production. © 2015 Scandinavian Plant Physiology Society.

  14. Dissecting the genetic and metabolic mechanisms of adaptation to the knockout of a major metabolic enzyme in Escherichia coli

    DEFF Research Database (Denmark)

    Long, Christopher P.; Gonzalez, Jacqueline E.; Feist, Adam M.

    2018-01-01

    Unraveling the mechanisms of microbial adaptive evolution following genetic or environmental challenges is of fundamental interest in biological science and engineering. When the challenge is the loss of a metabolic enzyme, adaptive responses can also shed significant insight into metabolic...

  15. Using Data to Understand How to Better Design Adaptive Learning

    Science.gov (United States)

    Liu, Min; Kang, Jina; Zou, Wenting; Lee, Hyeyeon; Pan, Zilong; Corliss, Stephanie

    2017-01-01

    There is much enthusiasm in higher education about the benefits of adaptive learning and using big data to investigate learning processes to make data-informed educational decisions. The benefits of adaptive learning to achieve personalized learning are obvious. Yet, there lacks evidence-based research to understand how data such as user behavior…

  16. Building Research Capacity to Understand and Adapt to Climate ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Building Research Capacity to Understand and Adapt to Climate Change in the Indus Basin ... Eleven world-class research teams set to improve livestock vaccine development ... Building resilience through socially equitable climate action.

  17. Three good reasons for heart surgeons to understand cardiac metabolism.

    Science.gov (United States)

    Doenst, Torsten; Bugger, Heiko; Schwarzer, Michael; Faerber, Gloria; Borger, Michael A; Mohr, Friedrich W

    2008-05-01

    It is the principal goal of cardiac surgeons to improve or reinstate contractile function with, through or after a surgical procedure on the heart. Uninterrupted contractile function of the heart is irrevocably linked to the uninterrupted supply of energy in the form of ATP. Thus, it would appear natural that clinicians interested in myocardial contractile function are interested in the way the heart generates ATP, i.e. the processes generally referred to as energy metabolism. Yet, it may appear that the relevance of energy metabolism in cardiac surgery is limited to the area of cardioplegia, which is a declining research interest. It is the goal of this review to change this trend and to illustrate the role and the therapeutic potential of metabolism and metabolic interventions for management. We present three compelling reasons why cardiac metabolism is of direct, practical interest to the cardiac surgeon and why a better understanding of energy metabolism might indeed result in improved surgical outcomes: (1) To understand cardioplegic arrest, ischemia and reperfusion, one needs a working knowledge of metabolism; (2) hyperglycemia is an underestimated and modifiable risk factor; (3) acute metabolic interventions can be effective in patients undergoing cardiac surgery.

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

    Science.gov (United States)

    Rioux, Pierre; Blier, Pierre U.

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Samuel Rommelaere

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

  20. Metabolic adaption of ethanol-tolerant Clostridium thermocellum.

    Directory of Open Access Journals (Sweden)

    Xinshu Zhu

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

  1. Understanding Plant Nitrogen Metabolism through Metabolomics and Computational Approaches

    Directory of Open Access Journals (Sweden)

    Perrin H. Beatty

    2016-10-01

    Full Text Available A comprehensive understanding of plant metabolism could provide a direct mechanism for improving nitrogen use efficiency (NUE in crops. One of the major barriers to achieving this outcome is our poor understanding of the complex metabolic networks, physiological factors, and signaling mechanisms that affect NUE in agricultural settings. However, an exciting collection of computational and experimental approaches has begun to elucidate whole-plant nitrogen usage and provides an avenue for connecting nitrogen-related phenotypes to genes. Herein, we describe how metabolomics, computational models of metabolism, and flux balance analysis have been harnessed to advance our understanding of plant nitrogen metabolism. We introduce a model describing the complex flow of nitrogen through crops in a real-world agricultural setting and describe how experimental metabolomics data, such as isotope labeling rates and analyses of nutrient uptake, can be used to refine these models. In summary, the metabolomics/computational approach offers an exciting mechanism for understanding NUE that may ultimately lead to more effective crop management and engineered plants with higher yields.

  2. [Roles of organic acid metabolism in plant adaptation to nutrient deficiency and aluminum toxicity stress].

    Science.gov (United States)

    Wang, Jianfei; Shen, Qirong

    2006-11-01

    Organic acids not only act as the intermediates in carbon metabolism, but also exert key roles in the plant adaptation to nutrient deficiency and metal stress and in the plant-microbe interactions at root-soil interface. From the viewpoint of plant nutrition, this paper reviewed the research progress on the formation and physiology of organic acids in plant, and their functions in nitrogen metabolism, phosphorus and iron uptake, aluminum tolerance, and soil ecology. New findings in the membrane transport of organic acids and the biotechnological manipulation of organic acids in transgenic model were also discussed. This novel perspectives of organic acid metabolism and its potential manipulation might present a possibility to understand the fundamental aspects of plant physiology, and lead to the new strategies to obtain crop varieties better adapted to environmental and metal stress.

  3. An Adaptive Laboratory Evolution Method to Accelerate Autotrophic Metabolism

    DEFF Research Database (Denmark)

    Zhang, Tian; Tremblay, Pier-Luc

    2018-01-01

    Adaptive laboratory evolution (ALE) is an approach enabling the development of novel characteristics in microbial strains via the application of a constant selection pressure. This method is also an efficient tool to acquire insights on molecular mechanisms responsible for specific phenotypes. ALE...... autotrophically and reducing CO2 into acetate more efficiently. Strains developed via this ALE method were also used to gain knowledge on the autotrophic metabolism of S. ovata as well as other acetogenic bacteria....

  4. Building Research Capacity to Understand and Adapt to Climate ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Building Research Capacity to Understand and Adapt to Climate Change in the Indus Basin ... Site internet ... L'honorable Chrystia Freeland, ministre du Commerce international, a annoncé le lancement d'un nouveau projet financé par le ...

  5. Perspectives in metabolic engineering: understanding cellular regulation towards the control of metabolic routes.

    Science.gov (United States)

    Zadran, Sohila; Levine, Raphael D

    2013-01-01

    Metabolic engineering seeks to redirect metabolic pathways through the modification of specific biochemical reactions or the introduction of new ones with the use of recombinant technology. Many of the chemicals synthesized via introduction of product-specific enzymes or the reconstruction of entire metabolic pathways into engineered hosts that can sustain production and can synthesize high yields of the desired product as yields of natural product-derived compounds are frequently low, and chemical processes can be both energy and material expensive; current endeavors have focused on using biologically derived processes as alternatives to chemical synthesis. Such economically favorable manufacturing processes pursue goals related to sustainable development and "green chemistry". Metabolic engineering is a multidisciplinary approach, involving chemical engineering, molecular biology, biochemistry, and analytical chemistry. Recent advances in molecular biology, genome-scale models, theoretical understanding, and kinetic modeling has increased interest in using metabolic engineering to redirect metabolic fluxes for industrial and therapeutic purposes. The use of metabolic engineering has increased the productivity of industrially pertinent small molecules, alcohol-based biofuels, and biodiesel. Here, we highlight developments in the practical and theoretical strategies and technologies available for the metabolic engineering of simple systems and address current limitations.

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

    Science.gov (United States)

    Sundrum, Albert

    2015-10-09

    Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. They mainly derive from difficulties the animals have in adapting to changes and disturbances occurring both outside and inside the organisms and due to varying gaps between nutrient supply and demand. Adaptation is a functional and target-oriented process involving the whole organism and thus cannot be narrowed down to single factors. Most problems which challenge the organisms can be solved in a number of different ways. To understand the mechanisms of adaptation, the interconnectedness of variables and the nutrient flow within a metabolic network need to be considered. Metabolic disorders indicate an overstressed ability to balance input, partitioning and output variables. Dairy cows will more easily succeed in adapting and in avoiding dysfunctional processes in the transition period when the gap between nutrient and energy demands and their supply is restricted. Dairy farms vary widely in relation to the living conditions of the animals. The complexity of nutritional and metabolic processes Animals 2015, 5 979 and their large variations on various scales contradict any attempts to predict the outcome of animals' adaptation in a farm specific situation. Any attempts to reduce the prevalence of metabolic disorders and associated production diseases should rely on continuous and comprehensive monitoring with appropriate indicators on the farm level. Furthermore, low levels of disorders and diseases should be seen as a further significant goal which carries weight in addition to productivity goals. In the long run, low disease levels can only be expected when farmers realize that they can gain a competitive advantage over competitors with higher levels of disease.

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

    Directory of Open Access Journals (Sweden)

    Albert Sundrum

    2015-10-01

    Full Text Available Metabolic disorders are a key problem in the transition period of dairy cows and often appear before the onset of further health problems. They mainly derive from difficulties the animals have in adapting to changes and disturbances occurring both outside and inside the organisms and due to varying gaps between nutrient supply and demand. Adaptation is a functional and target-oriented process involving the whole organism and thus cannot be narrowed down to single factors. Most problems which challenge the organisms can be solved in a number of different ways. To understand the mechanisms of adaptation, the interconnectedness of variables and the nutrient flow within a metabolic network need to be considered. Metabolic disorders indicate an overstressed ability to balance input, partitioning and output variables. Dairy cows will more easily succeed in adapting and in avoiding dysfunctional processes in the transition period when the gap between nutrient and energy demands and their supply is restricted. Dairy farms vary widely in relation to the living conditions of the animals. The complexity of nutritional and metabolic processes Animals 2015, 5 979 and their large variations on various scales contradict any attempts to predict the outcome of animals’ adaptation in a farm specific situation. Any attempts to reduce the prevalence of metabolic disorders and associated production diseases should rely on continuous and comprehensive monitoring with appropriate indicators on the farm level. Furthermore, low levels of disorders and diseases should be seen as a further significant goal which carries weight in addition to productivity goals. In the long run, low disease levels can only be expected when farmers realize that they can gain a competitive advantage over competitors with higher levels of disease.

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

    Science.gov (United States)

    Sundrum, Albert

    2015-01-01

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

  9. Metabolic phenotyping of various tea (Camellia sinensis L.) cultivars and understanding of their intrinsic metabolism.

    Science.gov (United States)

    Ji, Hyang-Gi; Lee, Yeong-Ran; Lee, Min-Seuk; Hwang, Kyeong Hwan; Kim, Eun-Hee; Park, Jun Seong; Hong, Young-Shick

    2017-10-15

    Recently, we selected three tea (Camellia sinensis) cultivars that are rich in taste, epigallocatechin-3-O-gallate (EGCG) and epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3″Me) and then cultivated them through asexual propagation by cutting in the same region. In the present study, proton nuclear magnetic resonance ( 1 H NMR)-based metabolomics was applied to characterize the metabotype and to understand the metabolic mechanism of these tea cultivars including wild type tea. Of the tea leaf metabolite variations, reverse associations of amino acid metabolism with catechin compound metabolism were found in the rich-taste, and EGCG- and EGCG3″Me-rich tea cultivars. Indeed, the metabolism of individual catechin compounds in the EGCG3″Me-rich cultivar differed from those of other tea cultivars. The current study highlights the distinct metabolism of various tea cultivars newly selected for cultivation and the important role of metabolomics in understanding the metabolic mechanism. Thus, comprehensive metabotyping is a useful method to assess and then develop a new plant cultivar. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Preparing for Local Adaptation: Understanding Flood Risk Perceptions in Pittsburgh

    Science.gov (United States)

    Klima, K.; Wong-Parodi, G.

    2015-12-01

    The City of Pittsburgh experiences numerous floods every year. Aging and insufficient infrastructure contribute to flash floods and to over 20 billion gallons of combined sewer overflows annually, contaminating Pittsburgh's streets, basements, and waterways. Climate change is expected to further exacerbate this problem by causing more intense and more frequent extreme precipitation events in Western Pennsylvania. For a stormwater adaptation plan to be implemented effectively, the City will need informed public support. One way to achieve public understanding and support is through effective communication of the risks, benefits, and uncertainties of local flooding hazards and adaptation methods. In order to develop these communications effectively, the city and its partners will need to know what knowledge and attitudes the residents of Pittsburgh already hold about flood risks. Here we seek to (1) identify Pittsburgh residents' knowledge level, risk perception and attitudes towards flooding and storm water management, and (2) pre-test communications meant to inform and empower Pittsburghers about flood risks and adaptation strategies. We conduct a city-wide survey of 10,000 Pittsburgh renters and homeowners from four life situations: high risk, above poverty; high-risk, below poverty; low risk, above poverty; and low-risk, below poverty. Mixed media recruitment strategies (online and paper-based solicitations guided/organized by community organizations) assist in reaching all subpopulations. Preliminary results suggest participants know what stormwater runoff is, but have a weak understanding of how stormwater interacts with natural and built systems. Furthermore, although participants have a good understanding of the difference between green and gray infrastructure, this does not translate into a change in their willingness to pay for green infrastructure adaptation. This suggests additional communications about flood risks and adaptation strategies.

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

    Directory of Open Access Journals (Sweden)

    Ann Kathrin eHeroven

    2014-10-01

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

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

    Science.gov (United States)

    Heroven, Ann Kathrin; Dersch, Petra

    2014-01-01

    Deciphering the principles how pathogenic bacteria adapt their metabolism to a specific host microenvironment is critical for understanding bacterial pathogenesis. The enteric pathogenic Yersinia species Yersinia pseudotuberculosis and Yersinia enterocolitica and the causative agent of plague, Yersinia pestis, are able to survive in a large variety of environmental reservoirs (e.g., soil, plants, insects) as well as warm-blooded animals (e.g., rodents, pigs, humans) with a particular preference for lymphatic tissues. In order to manage rapidly changing environmental conditions and interbacterial competition, Yersinia senses the nutritional composition during the course of an infection by special molecular devices, integrates this information and adapts its metabolism accordingly. In addition, nutrient availability has an impact on expression of virulence genes in response to C-sources, demonstrating a tight link between the pathogenicity of yersiniae and utilization of nutrients. Recent studies revealed that global regulatory factors such as the cAMP receptor protein (Crp) and the carbon storage regulator (Csr) system are part of a large network of transcriptional and posttranscriptional control strategies adjusting metabolic changes and virulence in response to temperature, ion and nutrient availability. Gained knowledge about the specific metabolic requirements and the correlation between metabolic and virulence gene expression that enable efficient host colonization led to the identification of new potential antimicrobial targets. PMID:25368845

  13. Metabolic adaptation of a human pathogen during chronic infections - a systems biology approach

    DEFF Research Database (Denmark)

    Thøgersen, Juliane Charlotte

    modeling to uncover how human pathogens adapt to the human host. Pseudomonas aeruginosa infections in cystic fibrosis patients are used as a model system for under-­‐ standing these adaptation processes. The exploratory systems biology approach facilitates identification of important phenotypes...... by classical molecular biology approaches where genes and reactions typically are investigated in a one to one relationship. This thesis is an example of how mathematical approaches and modeling can facilitate new biologi-­‐ cal understanding and provide new surprising ideas to important biological processes....... and metabolic pathways that are necessary or related to establishment of chronic infections. Archetypal analysis showed to be successful in extracting relevant phenotypes from global gene expression da-­‐ ta. Furthermore, genome-­‐scale metabolic modeling showed to be useful in connecting the genotype...

  14. Understanding specificity in metabolic pathways-Structural biology of human nucleotide metabolism

    International Nuclear Information System (INIS)

    Welin, Martin; Nordlund, Paer

    2010-01-01

    Interactions are the foundation of life at the molecular level. In the plethora of activities in the cell, the evolution of enzyme specificity requires the balancing of appropriate substrate affinity with a negative selection, in order to minimize interactions with other potential substrates in the cell. To understand the structural basis for enzyme specificity, the comparison of structural and biochemical data between enzymes within pathways using similar substrates and effectors is valuable. Nucleotide metabolism is one of the largest metabolic pathways in the human cell and is of outstanding therapeutic importance since it activates and catabolises nucleoside based anti-proliferative drugs and serves as a direct target for anti-proliferative drugs. In recent years the structural coverage of the enzymes involved in human nucleotide metabolism has been dramatically improved and is approaching completion. An important factor has been the contribution from the Structural Genomics Consortium (SGC) at Karolinska Institutet, which recently has solved 33 novel structures of enzymes and enzyme domains in human nucleotide metabolism pathways and homologs thereof. In this review we will discuss some of the principles for substrate specificity of enzymes in human nucleotide metabolism illustrated by a selected set of enzyme families where a detailed understanding of the structural determinants for specificity is now emerging.

  15. Preparing for local adaptation: Understanding flood risk perceptions in Pittsburgh

    Science.gov (United States)

    Wong-Parodi, G.; Klima, K.

    2016-12-01

    In cities such as Pittsburgh, aging and insufficient infrastructure contributes to flashfloods and numerous combined sewer overflows annually, contaminating streets, basements and waterways. Climate change is expected to further exacerbate this problem by causing more intense and more frequent extreme events in Western Pennsylvania. For a storm water adaptation plan to be implemented successfully, the City of Pittsburgh will need informed public support. One way to achieve public understanding and support is through effective communication of the risks, benefits, and uncertainties of local flooding hazards and adaptation methods. In order to develop risk communications effectively, the City and its partners will need to know what knowledge and attitudes the residents of Pittsburgh already hold about flood risks. To that end we surveyed 1,376 Pittsburgh residents on a variety of flood risk topics through an online or paper survey in Fall 2015. On balance, residents were relatively knowledgeable about storm water and see the City's current infrastructure as being inadequate to meet future risk. Moreover, they see the risk of runoff events as increasing and especially among those who live in hazardous flood areas. Residents expressed interest in having a dedicated fund to deal with runoff events. Among those queried about their willingness-to-pay, those asked to pay $15 were most interested in a dedicated fund and for green infrastructure (as opposed to gray infrastructure) in particular. Finally, while most residents favored green infrastructure in terms of its attractiveness and perceived affects on mitigating climate change many did not see it as effective at addressing flooding as gray infrastructure. We found people understand the risk and are open to doing something about it. However, more guidance and information on appropriate ways to adapt locally in terms that make sense to residents could enhance informed support for adaptation measures.

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

    Directory of Open Access Journals (Sweden)

    Dorian S Houser

    2013-11-01

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

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

    Science.gov (United States)

    Houser, Dorian S; Champagne, Cory D; Crocker, Daniel E

    2013-11-01

    Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies.

  18. Metabolic characteristics of keto-adapted ultra-endurance runners.

    Science.gov (United States)

    Volek, Jeff S; Freidenreich, Daniel J; Saenz, Catherine; Kunces, Laura J; Creighton, Brent C; Bartley, Jenna M; Davitt, Patrick M; Munoz, Colleen X; Anderson, Jeffrey M; Maresh, Carl M; Lee, Elaine C; Schuenke, Mark D; Aerni, Giselle; Kraemer, William J; Phinney, Stephen D

    2016-03-01

    Many successful ultra-endurance athletes have switched from a high-carbohydrate to a low-carbohydrate diet, but they have not previously been studied to determine the extent of metabolic adaptations. Twenty elite ultra-marathoners and ironman distance triathletes performed a maximal graded exercise test and a 180 min submaximal run at 64% VO2max on a treadmill to determine metabolic responses. One group habitually consumed a traditional high-carbohydrate (HC: n=10, %carbohydrate:protein:fat=59:14:25) diet, and the other a low-carbohydrate (LC; n=10, 10:19:70) diet for an average of 20 months (range 9 to 36 months). Peak fat oxidation was 2.3-fold higher in the LC group (1.54±0.18 vs 0.67±0.14 g/min; P=0.000) and it occurred at a higher percentage of VO2max (70.3±6.3 vs 54.9±7.8%; P=0.000). Mean fat oxidation during submaximal exercise was 59% higher in the LC group (1.21±0.02 vs 0.76±0.11 g/min; P=0.000) corresponding to a greater relative contribution of fat (88±2 vs 56±8%; P=0.000). Despite these marked differences in fuel use between LC and HC athletes, there were no significant differences in resting muscle glycogen and the level of depletion after 180 min of running (-64% from pre-exercise) and 120 min of recovery (-36% from pre-exercise). Compared to highly trained ultra-endurance athletes consuming an HC diet, long-term keto-adaptation results in extraordinarily high rates of fat oxidation, whereas muscle glycogen utilization and repletion patterns during and after a 3 hour run are similar. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Understanding barriers to implementation of an adaptive land management program

    Science.gov (United States)

    Jacobson, S.K.; Morris, J.K.; Sanders, J.S.; Wiley, E.N.; Brooks, M.; Bennetts, R.E.; Percival, H.F.; Marynowski, S.

    2006-01-01

    The Florida Fish and Wildlife Conservation Commission manages over 650,000 ha, including 26 wildlife management and environmental areas. To improve management, they developed an objective-based vegetation management (OBVM) process that focuses on desired conditions of plant communities through an adaptive management framework. Our goals were to understand potential barriers to implementing OBVM and to recommend strategies to overcome barriers. A literature review identified 47 potential barriers in six categories to implementation of adaptive and ecosystem management: logistical, communication, attitudinal, institutional, conceptual, and educational. We explored these barriers through a bureau-wide survey of 90 staff involved in OBVM and personal interviews with area managers, scientists, and administrators. The survey incorporated an organizational culture assessment instrument to gauge how institutional factors might influence OBVM implementation. The survey response rate was 69%. Logistics and communications were the greatest barriers to implementing OBVM. Respondents perceived that the agency had inadequate resources for implementing OBVM and provided inadequate information. About one-third of the respondents believed OBVM would decrease their job flexibility and perceived greater institutional barriers to the approach. The 43% of respondents who believed they would have more responsibility under OBVM also had greater attitudinal barriers. A similar percentage of respondents reported OBVM would not give enough priority to wildlife. Staff believed that current agency culture was hierarchical but preferred a culture that would provide more flexibility for adaptive management and would foster learning from land management activities. In light of the barriers to OBVM, we recommend the following: (1) mitigation of logistical barriers by addressing real and perceived constraints of staff, funds, and other resources in a participatory manner; (2) mitigation of

  20. Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance

    Science.gov (United States)

    2016-01-01

    Ageing and lifespan are strongly affected by metabolism. The maximal possible uptake of oxygen is not only a good predictor of performance in endurance sports, but also of life expectancy. Figuratively speaking, healthy ageing is a competitive sport. Although the root cause of ageing is damage to macromolecules, it is the balance with repair processes that is decisive. Reduced or intermittent nutrition, hormones and intracellular signalling pathways that regulate metabolism have strong effects on ageing. Homeostatic regulatory processes tend to keep the environment of the cells within relatively narrow bounds. On the other hand, the body is constantly adapting to physical activity and food consumption. Spontaneous fluctuations in heart rate and other processes indicate youth and health. A (homeo)dynamic aspect of homeostasis deteriorates with age. We are now in a position to develop computational models of human metabolism and the dynamics of heart rhythm and oxygen transport that will advance our understanding of ageing. Computational modelling of the connections between dietary restriction, metabolism and protein turnover may increase insight into homeostasis of the proteins in our body. In this way, the computational reconstruction of human physiological processes, the Physiome, can help prevent frailty and age-related disease. PMID:27051508

  1. Understanding the Generation of Network Bursts by Adaptive Oscillatory Neurons

    Directory of Open Access Journals (Sweden)

    Tanguy Fardet

    2018-02-01

    Full Text Available Experimental and numerical studies have revealed that isolated populations of oscillatory neurons can spontaneously synchronize and generate periodic bursts involving the whole network. Such a behavior has notably been observed for cultured neurons in rodent's cortex or hippocampus. We show here that a sufficient condition for this network bursting is the presence of an excitatory population of oscillatory neurons which displays spike-driven adaptation. We provide an analytic model to analyze network bursts generated by coupled adaptive exponential integrate-and-fire neurons. We show that, for strong synaptic coupling, intrinsically tonic spiking neurons evolve to reach a synchronized intermittent bursting state. The presence of inhibitory neurons or plastic synapses can then modulate this dynamics in many ways but is not necessary for its appearance. Thanks to a simple self-consistent equation, our model gives an intuitive and semi-quantitative tool to understand the bursting behavior. Furthermore, it suggests that after-hyperpolarization currents are sufficient to explain bursting termination. Through a thorough mapping between the theoretical parameters and ion-channel properties, we discuss the biological mechanisms that could be involved and the relevance of the explored parameter-space. Such an insight enables us to propose experimentally-testable predictions regarding how blocking fast, medium or slow after-hyperpolarization channels would affect the firing rate and burst duration, as well as the interburst interval.

  2. Role of hormones in cartilage and joint metabolism: understanding an unhealthy metabolic phenotype in osteoarthritis.

    Science.gov (United States)

    Bay-Jensen, Anne C; Slagboom, Eline; Chen-An, Pingping; Alexandersen, Peter; Qvist, Per; Christiansen, Claus; Meulenbelt, Ingrid; Karsdal, Morten A

    2013-05-01

    Joint health is affected by local and systemic hormones. It is well accepted that systemic factors regulate the metabolism of joint tissues, and that substantial cross-talk between tissues actively contributes to homeostasis. In the current review, we try to define a subtype of osteoarthritis (OA), metabolic OA, which is dependent on an unhealthy phenotype. Peer-reviewed research articles and reviews were reviewed and summarized. Only literature readily available online, either by download or by purchase order, was included. OA is the most common joint disease and is more common in women after menopause. OA is a disease that affects the whole joint, including cartilage, subchondral bone, synovium, tendons, and muscles. The clinical endpoints of OA are pain and joint space narrowing, which is characterized by cartilage erosion and subchondral sclerosis, suggesting that cartilage is a central tissue of joint health. Thus, the joint, more specifically the cartilage, may be considered a target of endocrine function in addition to the well-described traditional risk factors of disease initiation and progression such as long-term loading of the joint due to obesity. Metabolic syndrome affects a range of tissues and may in part be molecularly described as a dysregulation of cytokines, adipokines, and hormones (e.g., estrogen and thyroid hormone). Consequently, metabolic imbalance may both directly and indirectly influence joint health and cartilage turnover, altering the progression of diseases such as OA. There is substantial evidence for a connection between metabolic health and development of OA. We propose that more focus be directed to understanding this connection to improve the management of menopausal health and associated comorbidities.

  3. Understanding Coral's Short-term Adaptive Ability to Changing Environment

    Science.gov (United States)

    Tisthammer, K.; Richmond, R. H.

    2016-02-01

    Corals in Maunalua Bay, Hawaii are under chronic pressures from sedimentation and terrestrial runoffs containing multiple pollutants as a result of large scale urbanization that has taken place in the last 100 years. However, some individual corals thrive despite the prolonged exposure to these environmental stressors, which suggests that these individuals may have adapted to withstand such stressors. A recent survey showed that the lobe coral Porites lobata from the `high-stress' nearshore site had an elevated level of stress ixnduced proteins, compared to those from the `low-stress,' less polluted offshore site. To understand the genetic basis for the observed differential stress responses between the nearshore and offshore P. lobata populations, an analysis of the lineage-scale population genetic structure, as well as a reciprocal transplant experiment were conducted. The result of the genetic analysis revealed a clear genetic differentiation between P. lobata from the nearshore site and the offshore site. Following the 30- day reciprocal transplant experiment, protein expression profiles and other stress-related physiological characteristics were compared between the two populations. The experimental results suggest that the nearshore genotype can cope better with sedimentation/pollutants than the offshore genotype. This indicates that the observed genetic differentiation is due to selection for tolerance to these environmental stressors. Understanding the little-known, linage-scale genetic variation in corals offers a critical insight into their short-term adaptive ability, which is indispensable for protecting corals from impending environmental and climate change. The results of this study also offer a valuable tool for resource managers to make effective decisions on coral reef conservation, such as designing marine protected areas that incorporate and maintain such genetic diversity, and establishing acceptable pollution run-off levels.

  4. Understanding extreme sea levels for coastal impact and adaptation analysis

    Science.gov (United States)

    Wahl, T.; Haigh, I. D.; Nicholls, R. J.; Arns, A.; Hinkel, J.; Dangendorf, S.; Slangen, A.

    2016-12-01

    Coastal impact and adaptation assessments require detailed knowledge on extreme sea levels, because increasing damage due to extreme events, such as storm surges and tropical cyclones, is one of the major consequences of sea level rise and climate change. In fact, the IPCC has highlighted in its AR4 report that "societal impacts of sea level change primarily occur via the extreme levels rather than as a direct consequence of mean sea level changes". Over the last few decades, substantial research efforts have been directed towards improved understanding of past and future mean sea level; different scenarios were developed with process-based or semi-empirical models and used for coastal impact assessments at various spatial scales to guide coastal management and adaptation efforts. The uncertainties in future sea level rise are typically accounted for by analyzing the impacts associated with a range of scenarios leading to a vertical displacement of the distribution of extreme sea-levels. And indeed most regional and global studies find little or no evidence for changes in storminess with climate change, although there is still low confidence in the results. However, and much more importantly, there is still a limited understanding of present-day extreme sea-levels which is largely ignored in most impact and adaptation analyses. The two key uncertainties stem from: (1) numerical models that are used to generate long time series of extreme sea-levels. The bias of these models varies spatially and can reach values much larger than the expected sea level rise; but it can be accounted for in most regions making use of in-situ measurements; (2) Statistical models used for determining present-day extreme sea-level exceedance probabilities. There is no universally accepted approach to obtain such values for flood risk assessments and while substantial research has explored inter-model uncertainties for mean sea level, we explore here, for the first time, inter

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

    Science.gov (United States)

    Mouradov, Aidyn; Spangenberg, German

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Aidyn eMouradov

    2014-11-01

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

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

    OpenAIRE

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

    2013-01-01

    Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the no...

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xiaodong Zai

    2017-11-01

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

  10. A mathematical analysis of adaptations to the metabolic fate of fructose in essential fructosuria subjects.

    Science.gov (United States)

    Allen, R J; Musante, Cynthia J

    2018-04-17

    Fructose is a major component of Western diets and is implicated in the pathogenesis of obesity and type 2 diabetes. In response to an oral challenge, the majority of fructose is cleared during "first-pass" liver metabolism, primarily via phosphorylation by ketohexokinase (KHK). A rare benign genetic deficiency in KHK, called essential fructosuria (EF), leads to altered fructose metabolism. The only reported symptom of EF is the appearance of fructose in the urine following either oral or intravenous fructose administration. Here we develop and use a mathematical model to investigate the adaptations to altered fructose metabolism in people with EF. Firstly, the model is calibrated to fit available data in normal healthy subjects. Then, to mathematically represent EF subjects we systematically implement metabolic adaptations such that model simulations match available data for this phenotype. We hypothesize that these modifications represent the major metabolic adaptations present in these subjects. This modeling approach suggests that several other aspects of fructose metabolism, beyond hepatic KHK deficiency, are altered and contribute to the etiology of this benign condition. Specifically, we predict that fructose absorption into the portal vein is altered, peripheral metabolism is slowed, renal re-absorption of fructose is mostly ablated and that alternate pathways for hepatic metabolism of fructose are up-regulated. Moreover, these findings have implications for drug discovery and development, suggesting that the therapeutic targeting of fructose metabolism could lead to unexpected metabolic adaptations, potentially due to a physiological response to high fructose conditions.

  11. Metabolic adaptations and reduced respiration of the copepod ...

    African Journals Online (AJOL)

    The results reveal a reduction by 96% of metabolic rate in deep-living, diapausing C5s relative to surface-dwelling, active individuals. Only 14.4% of this metabolic reduction is explained by the lower ambient temperature at depth and a Q10 value of 2.34. Therefore, the major fraction (81.6%) of the metabolic reduction is ...

  12. Metabolic and adaptive immune responses induced in mice infected ...

    African Journals Online (AJOL)

    This study investigated metabolic and immuno-inflammatory responses of mice infected with tissue-dwelling larvae of Trichinella zimbabwensis and explored the relationship between infection, metabolic parameters and Th1/Th17 immune responses. Sixty (60) female BALB/c mice aged between 6 to 8 weeks old were ...

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

    NARCIS (Netherlands)

    Martín-Tereso López, J.

    2010-01-01

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

  14. Understanding sustainability from an exergetic frame in complex adaptive systems

    International Nuclear Information System (INIS)

    Aguilar Hernandez, Glem Alonso

    2017-01-01

    The concept of sustainability was developed from thermodynamic properties applied to complex adaptive systems. The origins of the perception about sustainable development and limitation in its application to analyze the interaction between a system and its surroundings were described. The properties of a complex adaptive system were taken as basis to determine how a system can to be affected by the resources restriction and irreversibility of the processes. The complex adaptive system was understood using the first and second law of thermodynamics, generating a conceptual framework to define the sustainability of a system. The contributions developed by exergy were shown to analyze the sustainability of systems in an economic, social and environmental context [es

  15. Metabolic flexibility as an adaptation to energy resources and requirements in health and disease.

    Science.gov (United States)

    Smith, Reuben L; Soeters, Maarten R; Wüst, Rob C I; Houtkooper, Riekelt H

    2018-04-24

    The ability to efficiently adapt metabolism by substrate sensing, trafficking, storage and utilization, dependent on availability and requirement is known as metabolic flexibility. In this review, we discuss the breadth and depth of metabolic flexibility and its impact on health and disease. Metabolic flexibility is essential to maintain energy homeostasis in times of either caloric excess or caloric restriction, and in times of either low or high energy demand, such as during exercise. The liver, adipose tissue and muscle govern systemic metabolic flexibility and manage nutrient sensing, uptake, transport, storage and expenditure by communication via endocrine cues. At a molecular level, metabolic flexibility relies on the configuration of metabolic pathways which is regulated by key metabolic enzymes and transcription factors, many of which interact closely with the mitochondria. Disrupted metabolic flexibility, or metabolic inflexibility, however, is associated with many pathological conditions including metabolic syndrome, type 2 diabetes mellitus, and cancer. Multiple factors like dietary composition and feeding frequency, exercise training, and use of pharmacological compounds influence metabolic flexibility and will be discussed here. Lastly, we outline important advances in metabolic flexibility research and discuss medical horizons and translational aspects.

  16. A pan-genomic approach to understand the basis of host adaptation in Achromobacter.

    Science.gov (United States)

    Jeukens, J; Freschi, L; Vincent, A T; Emond-Rheault, J G; Kukavica-Ibrulj, I; Charette, S J; Levesque, R C

    2017-04-05

    Over the past decade, there has been a rising interest in Achromobacter sp., an emerging opportunistic pathogen responsible for nosocomial and cystic fibrosis (CF) lung infections. Species of this genus are ubiquitous in the environment, can outcompete resident microbiota, and are resistant to commonly used disinfectants as well as antibiotics. Nevertheless, the Achromobacter genus suffers from difficulties in diagnosis, unresolved taxonomy and limited understanding of how it adapts to the CF lung, not to mention other host environments. The goals of this first genus-wide comparative genomics study were to clarify the taxonomy of this genus and identify genomic features associated with pathogenicity and host adaptation. This was done with a widely applicable approach based on pan-genome analysis. First, using all publicly available genomes, a combination of phylogenetic analysis based on 1,780 conserved genes with average nucleotide identity and accessory genome composition allowed the identification of a largely clinical lineage composed of A. xylosoxidans A insuavis A. dolens and A. ruhlandii. Within this lineage, we identified 35 positively selected genes involved in metabolism, regulation and efflux-mediated antibiotic resistance. Second, resistome analysis showed that this clinical lineage carried additional antibiotic resistance genes compared to other isolates. Finally, we identified putative mobile elements that contribute 53% of the genus's resistome and support horizontal gene transfer between Achromobacter and other ecologically similar genera. This study provides strong phylogenetic and pan-genomic bases to motivate further research on Achromobacter, and contributes to the understanding of opportunistic pathogen evolution. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  17. Glucocorticoids, metabolic adaptations and recovery : studies in specific mouse models

    NARCIS (Netherlands)

    Auvinen, Hanna Elina

    2013-01-01

    Today’s Western society and work promotes a sedentary lifestyle. This, coupled with high caloric food availability has increased obesity followed by an increased prevalence of the metabolic syndrome (MetS), type 2 diabetes (T2D) and cardiovascular diseases (CVD). Epidemiological data show a clear

  18. Understanding global health governance as a complex adaptive system.

    Science.gov (United States)

    Hill, Peter S

    2011-01-01

    The transition from international to global health reflects the rapid growth in the numbers and nature of stakeholders in health, as well as the constant change embodied in the process of globalisation itself. This paper argues that global health governance shares the characteristics of complex adaptive systems, with its multiple and diverse players, and their polyvalent and constantly evolving relationships, and rich and dynamic interactions. The sheer quantum of initiatives, the multiple networks through which stakeholders (re)configure their influence, the range of contexts in which development for health is played out - all compound the complexity of this system. This paper maps out the characteristics of complex adaptive systems as they apply to global health governance, linking them to developments in the past two decades, and the multiple responses to these changes. Examining global health governance through the frame of complexity theory offers insight into the current dynamics of governance, and while providing a framework for making meaning of the whole, opens up ways of accessing this complexity through local points of engagement.

  19. Biochemist-Tree: Using Modular Origami to Understand the Integration of Intermediary Metabolism

    Science.gov (United States)

    Sharp, Duncan

    2013-01-01

    Intermediary metabolism can be a complex area to study due to the inherent modularity of the catabolic biochemical processes. This article outlines a novel, cost-effective, and universally applicable teaching activity to enhance students understanding of the inter-relationship between the key processes of intermediary metabolism. A simple origami…

  20. Quantifying environmental adaptation of metabolic pathways in metagenomics

    DEFF Research Database (Denmark)

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

    2009-01-01

    of particular pathways and subnetworks reflects the adaptation of microbial communities across environments and habitats-i.e., how network dynamics relates to environmental features. Previous research has treated environments as discrete, somewhat simplified classes (e.g., terrestrial vs. marine), and searched...... multiple, continuously varying factors defining an environment to the extent of particular microbial pathways present in a geographic site. Moreover, rather than looking only at individual correlations (one-to-one), we adapted canonical correlation analysis and related techniques to define an ensemble...

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

    Science.gov (United States)

    Huang, Helen J.

    2013-01-01

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

  2. Role of metabolic stress for enhancing muscle adaptations: Practical applications

    OpenAIRE

    de Freitas, Marcelo Conrado; Gerosa-Neto, Jose; Zanchi, Nelo Eidy; Lira, Fabio Santos; Rossi, Fabr?cio Eduardo

    2017-01-01

    Metabolic stress is a physiological process that occurs during exercise in response to low energy that leads to metabolite accumulation [lactate, phosphate inorganic (Pi) and ions of hydrogen (H+)] in muscle cells. Traditional exercise protocol (i.e., Resistance training) has an important impact on the increase of metabolite accumulation, which influences hormonal release, hypoxia, reactive oxygen species (ROS) production and cell swelling. Changes in acute exercise routines, such as intensit...

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    The 5'-AMP-activated protein kinase (AMPK) is a potent regulator of skeletal muscle metabolism and gene expression. AMPK is activated both in response to in vivo exercise and ex vivo contraction. AMPK is therefore believed to be an important signalling molecule in regulating muscle metabolism...... during exercise as well as in adaptation of skeletal muscle to exercise training. The first part of this review is focused on different mechanisms regulating AMPK activity during muscle work such as alterations in nucleotide concentrations, availability of energy substrates and upstream AMPK kinases. We...... in relation to adaptation of skeletal muscle to exercise training....

  4. Parametric recursive system identification and self-adaptive modeling of the human energy metabolism for adaptive control of fat weight.

    Science.gov (United States)

    Őri, Zsolt P

    2017-05-01

    A mathematical model has been developed to facilitate indirect measurements of difficult to measure variables of the human energy metabolism on a daily basis. The model performs recursive system identification of the parameters of the metabolic model of the human energy metabolism using the law of conservation of energy and principle of indirect calorimetry. Self-adaptive models of the utilized energy intake prediction, macronutrient oxidation rates, and daily body composition changes were created utilizing Kalman filter and the nominal trajectory methods. The accuracy of the models was tested in a simulation study utilizing data from the Minnesota starvation and overfeeding study. With biweekly macronutrient intake measurements, the average prediction error of the utilized carbohydrate intake was -23.2 ± 53.8 kcal/day, fat intake was 11.0 ± 72.3 kcal/day, and protein was 3.7 ± 16.3 kcal/day. The fat and fat-free mass changes were estimated with an error of 0.44 ± 1.16 g/day for fat and -2.6 ± 64.98 g/day for fat-free mass. The daily metabolized macronutrient energy intake and/or daily macronutrient oxidation rate and the daily body composition change from directly measured serial data are optimally predicted with a self-adaptive model with Kalman filter that uses recursive system identification.

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

    Directory of Open Access Journals (Sweden)

    Anna Koczula

    2017-02-01

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

  6. The Factor Inhibiting HIF Asparaginyl Hydroxylase Regulates Oxidative Metabolism and Accelerates Metabolic Adaptation to Hypoxia.

    Science.gov (United States)

    Sim, Jingwei; Cowburn, Andrew S; Palazon, Asis; Madhu, Basetti; Tyrakis, Petros A; Macías, David; Bargiela, David M; Pietsch, Sandra; Gralla, Michael; Evans, Colin E; Kittipassorn, Thaksaon; Chey, Yu C J; Branco, Cristina M; Rundqvist, Helene; Peet, Daniel J; Johnson, Randall S

    2018-04-03

    Animals require an immediate response to oxygen availability to allow rapid shifts between oxidative and glycolytic metabolism. These metabolic shifts are highly regulated by the HIF transcription factor. The factor inhibiting HIF (FIH) is an asparaginyl hydroxylase that controls HIF transcriptional activity in an oxygen-dependent manner. We show here that FIH loss increases oxidative metabolism, while also increasing glycolytic capacity, and that this gives rise to an increase in oxygen consumption. We further show that the loss of FIH acts to accelerate the cellular metabolic response to hypoxia. Skeletal muscle expresses 50-fold higher levels of FIH than other tissues: we analyzed skeletal muscle FIH mutants and found a decreased metabolic efficiency, correlated with an increased oxidative rate and an increased rate of hypoxic response. We find that FIH, through its regulation of oxidation, acts in concert with the PHD/vHL pathway to accelerate HIF-mediated metabolic responses to hypoxia. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Adapting to a Challenging Fieldwork: Understanding the Ingredients

    Directory of Open Access Journals (Sweden)

    Emily Raphael-Greenfield

    2017-01-01

    Full Text Available Two occupational therapy students were assigned to an inpatient psychiatric unit for their first Level 1 fieldwork. With limited on-site supervision provided, they looked to each other for peer support and collaboration in assisting one patient with severe depression who was considered the “sickest patient on the unit.” The students were able to work together and make a positive intervention with this patient despite their novice status. Understanding what each of them brought personally to this experience as well as the nature of their working relationship and their use of concepts taught in the classroom has important implications for occupational therapy education. One of the profession’s goals in acute psychiatric settings is to engage clients in meaningful occupations to facilitate rehabilitation and the recovery process. The two students skillfully employed the concepts of emotional intelligence, cultural competence, and therapeutic use of self and demonstrated their comfort with technology and spirituality to facilitate his occupational reengagement. By examining this case report through the lens of the literature on emotional intelligence, cultural competence, and therapeutic use of self, the ingredients of their clinical reasoning becomes more transparent and available to other occupational therapy educational programs.

  8. Monoterpenol Oxidative Metabolism: Role in Plant Adaptation and Potential Applications

    Science.gov (United States)

    Ilc, Tina; Parage, Claire; Boachon, Benoît; Navrot, Nicolas; Werck-Reichhart, Danièle

    2016-01-01

    Plants use monoterpenols as precursors for the production of functionally and structurally diverse molecules, which are key players in interactions with other organisms such as pollinators, flower visitors, herbivores, fungal, or microbial pathogens. For humans, many of these monoterpenol derivatives are economically important because of their pharmaceutical, nutraceutical, flavor, or fragrance applications. The biosynthesis of these derivatives is to a large extent catalyzed by enzymes from the cytochrome P450 superfamily. Here we review the knowledge on monoterpenol oxidative metabolism in plants with special focus on recent elucidations of oxidation steps leading to diverse linalool and geraniol derivatives. We evaluate the common features between oxidation pathways of these two monoterpenols, such as involvement of the CYP76 family, and highlight the differences. Finally, we discuss the missing steps and other open questions in the biosynthesis of oxygenated monoterpenol derivatives. PMID:27200002

  9. Adaptation of red cell enzymes and intermediates in metabolic disorders.

    Science.gov (United States)

    Goebel, K M; Goebel, F D; Neitzert, A; Hausmann, L; Schneider, J

    1975-01-01

    The metabolic activity of the red cell glycolytic pathway hexose monophosphate shunt (HMP) with dependent glutathione system was studied in patients with hyperthyroidism (n = 10), hyperlipoproteinemia (n = 16), hypoglycemia (n = 25) and hyperglycemia (n = 23). In uncontrolled diabetics and patients with hyperthyroidism the mean value of glucose phosphate isomerase (GPI), glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR) was increased, whereas these enzyme activities were reduced in patients with hypoglycemia. Apart from a few values of hexokinase (HK) which were lower than normal the results in hyperlipoproteinemia patients remained essentially unchanged, including the intermediates such as 2,3-diphosphoglycerate (2,3-DPG), adenosine triphosphate (ATP) and reduced glutathione (GSH). While increased rates of 2,3-DPG and ATP in hypoglycemia patients were obtained, these substrates were markedly reduced in diabetics.

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

    Science.gov (United States)

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

    2011-01-01

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

  11. RNA metabolism in Xylella fastidiosa during cold adaptation and survival responses

    Science.gov (United States)

    Fastidious plant pathogen Xylella fastidiosa has a reduced ability to adapt to cold temperatures, limiting persistence in perennial hosts, such as grapevine, growing in colder regions. RNA metabolism is an essential part of bacterial response to low temperature, including inducible expression of RNA...

  12. Adaptation of metabolism and evaporative water loss along an aridity gradient

    NARCIS (Netherlands)

    Tieleman, BI; Williams, JB; Bloomer, P

    2003-01-01

    Broad-scale comparisons of birds indicate the possibility of adaptive modification of basal metabolic rate (BMR) and total evaporative water loss (TEWL) in species from desert environments, but these might be confounded by phylogeny or phenotypic plasticity. This study relates variation in avian BMR

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Yeast cell factories encounter physical and chemical stresses when used for industrial production of fuels and chemicals. These stresses reduce productivity and increase bioprocess costs. Understanding the mechanisms of the stress response is essential for improving cellular robustness in platform...... strains. We investigated the three most commonly encountered industrial stresses for yeast (ethanol, salt, and temperature) to identify the mechanisms of general and stress-specific responses under chemostat conditions in which specific growth rate–dependent changes are eliminated. By applying systems...

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

    DEFF Research Database (Denmark)

    Fentz, Joachim

    in response to 4 weeks of voluntary running wheel exercise training. However, the acute exercise-induced increase in mRNA expression of several metabolic and mitochondrial marker genes is impaired in the mice lacking AMPKα1 and α2. In addition to the two studies and some currently unpublished data this thesis...

  15. Metabolic heat production and thermal conductance are mass-independent adaptations to thermal environment in birds and mammals.

    Science.gov (United States)

    Fristoe, Trevor S; Burger, Joseph R; Balk, Meghan A; Khaliq, Imran; Hof, Christian; Brown, James H

    2015-12-29

    The extent to which different kinds of organisms have adapted to environmental temperature regimes is central to understanding how they respond to climate change. The Scholander-Irving (S-I) model of heat transfer lays the foundation for explaining how endothermic birds and mammals maintain their high, relatively constant body temperatures in the face of wide variation in environmental temperature. The S-I model shows how body temperature is regulated by balancing the rates of heat production and heat loss. Both rates scale with body size, suggesting that larger animals should be better adapted to cold environments than smaller animals, and vice versa. However, the global distributions of ∼9,000 species of terrestrial birds and mammals show that the entire range of body sizes occurs in nearly all climatic regimes. Using physiological and environmental temperature data for 211 bird and 178 mammal species, we test for mass-independent adaptive changes in two key parameters of the S-I model: basal metabolic rate (BMR) and thermal conductance. We derive an axis of thermal adaptation that is independent of body size, extends the S-I model, and highlights interactions among physiological and morphological traits that allow endotherms to persist in a wide range of temperatures. Our macrophysiological and macroecological analyses support our predictions that shifts in BMR and thermal conductance confer important adaptations to environmental temperature in both birds and mammals.

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

    Directory of Open Access Journals (Sweden)

    Xin Fang

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

  17. Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells

    LENUS (Irish Health Repository)

    Burleigh, Susan C

    2011-10-18

    Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry.

  18. Ask yeast how to burn your fats: lessons learned from the metabolic adaptation to salt stress.

    Science.gov (United States)

    Pascual-Ahuir, Amparo; Manzanares-Estreder, Sara; Timón-Gómez, Alba; Proft, Markus

    2018-02-01

    Here, we review and update the recent advances in the metabolic control during the adaptive response of budding yeast to hyperosmotic and salt stress, which is one of the best understood signaling events at the molecular level. This environmental stress can be easily applied and hence has been exploited in the past to generate an impressively detailed and comprehensive model of cellular adaptation. It is clear now that this stress modulates a great number of different physiological functions of the cell, which altogether contribute to cellular survival and adaptation. Primary defense mechanisms are the massive induction of stress tolerance genes in the nucleus, the activation of cation transport at the plasma membrane, or the production and intracellular accumulation of osmolytes. At the same time and in a coordinated manner, the cell shuts down the expression of housekeeping genes, delays the progression of the cell cycle, inhibits genomic replication, and modulates translation efficiency to optimize the response and to avoid cellular damage. To this fascinating interplay of cellular functions directly regulated by the stress, we have to add yet another layer of control, which is physiologically relevant for stress tolerance. Salt stress induces an immediate metabolic readjustment, which includes the up-regulation of peroxisomal biomass and activity in a coordinated manner with the reinforcement of mitochondrial respiratory metabolism. Our recent findings are consistent with a model, where salt stress triggers a metabolic shift from fermentation to respiration fueled by the enhanced peroxisomal oxidation of fatty acids. We discuss here the regulatory details of this stress-induced metabolic shift and its possible roles in the context of the previously known adaptive functions.

  19. Understanding the metabolic fate and assessing the biosafety of MnO nanoparticles by metabonomic analysis

    International Nuclear Information System (INIS)

    Li, Jinquan; Feng, Jianghua; Chen, Zhong; Zhao, Zhenghuan; Gao, Jinhao

    2013-01-01

    Recently, some types of MnO nanoparticle (Mn-NP) with favorable imaging capacity have been developed to improve the biocompatible profile of the existing Mn-based MRI contrast agent Mn-DPDP; however, the overall bio-effects and potential toxicity remain largely unknown. In this study, 1 H NMR-based metabolic profiling, integrated with traditional biochemical analysis and histopathological examinations, was used to investigate the absorption, distribution, metabolism, excretion and toxicity of Mn-NPs as candidates for MRI contrast agent. The metabolic responses in biofluids (plasma and urine) and tissues (liver, spleen, kidney, lung and brain) from rats could be divided into four classes following Mn-NP administration: Mn biodistribution-dependent, time-dependent, dose-dependent and complicated metabolic variations. The variations of these metabolites involved in lipid, energy, amino acid and other nutrient metabolism, which disclosed the metabolic fate and biological effects of Mn-NPs in rats. The changes of metabolic profile implied that the disturbance and impairment of biological functions induced by Mn-NP exposure were correlated with the particle size and the surface chemistry of nanoparticles. Integration of metabonomic technology with traditional methods provides a promising tool to understand the toxicological behavior of biomedical nanomaterials and will result in informed decision-making during drug development. (paper)

  20. Understanding Climate Adaptation on Public Lands in the Upper Midwest: Implications for Monitoring and Tracking Progress

    Science.gov (United States)

    Anhalt-Depies, Christine M.; Knoot, Tricia Gorby; Rissman, Adena R.; Sharp, Anthony K.; Martin, Karl J.

    2016-05-01

    There are limited examples of efforts to systematically monitor and track climate change adaptation progress in the context of natural resource management, despite substantial investments in adaptation initiatives. To better understand the status of adaptation within state natural resource agencies, we utilized and problematized a rational decision-making framework to characterize adaptation at the level of public land managers in the Upper Midwest. We conducted in-depth interviews with 29 biologists and foresters to provide an understanding of managers' experiences with, and perceptions of, climate change impacts, efforts towards planning for climate change, and a full range of actions implemented to address climate change. While the majority of managers identified climate change impacts affecting their region, they expressed significant uncertainty in interpreting those signals. Just under half of managers indicated planning efforts are underway, although most planning is remote from local management. Actions already implemented include both forward-looking measures and those aimed at coping with current impacts. In addition, cross-scale dynamics emerged as an important theme related to the overall adaptation process. The results hold implications for tracking future progress on climate change adaptation. Common definitions or measures of adaptation (e.g., presence of planning documents) may need to be reassessed for applicability at the level of public land managers.

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

    Directory of Open Access Journals (Sweden)

    Balraj Singh

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

  2. Selection of Metastatic Breast Cancer Cells Based on Adaptability of Their Metabolic State

    Science.gov (United States)

    Singh, Balraj; Tai, Karen; Madan, Simran; Raythatha, Milan R.; Cady, Amanda M.; Braunlin, Megan; Irving, LaTashia R.; Bajaj, Ankur; Lucci, Anthony

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rui V. Simões

    2015-08-01

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

  4. Recent Advances in Understanding of Kinetic Interplay Between Phase II Metabolism and Efflux Transport.

    Science.gov (United States)

    Wang, Shuai; Xing, Huijie; Zhao, Mengjing; Lu, Danyi; Li, Zhijie; Dong, Dong; Wu, Baojian

    2016-01-01

    Mechanistic understanding of the metabolism-transport interplay assumes great importance in pharmaceutical fields because the knowledge can help to interpret drug/xenobiotic metabolism and disposition studies as well as the drug-drug interactions in vivo. About 10 years ago, it started to recognize that cellular phase II metabolism is strongly influenced by the excretion (efflux transport) of generated metabolites, a kinetic phenomenon termed "phase II metabolism-transport interplay". This interplay is believed to have significant effects on the pharmacokinetics (bioavailability) of drugs/chemicals undergoing phase II metabolism. In this article, we review the studies investigating the phase II metabolism-transport interplay using cell models, perfused rat intestine, and intact rats. The potential confounding factors in exploring such interplay is also summarized. Moreover, the mechanism underlying the phase II metabolism-transport interplay is discussed. Various studies with engineered cells and rodents have demonstrated that there is an interaction (interplay) between phase II enzymes and efflux transporters. This type of interplay mainly refers to the dependence of phase II (conjugative) metabolism on the activities of efflux transporters. In general, inhibiting efflux transporters or decreasing their expression causes the reductions in metabolite excretion, apparent excretion clearance (CLapp) and total metabolism (fmet), as well as an increase in the intracellular level of metabolite (Ci). The deconjugation mediated by hydrolase (acting as a "bridge") is essential for the interplay to play out based on pharmacokinetic modeling/simulations, cell and animal studies. The hydrolases bridge the two processes (i.e., metabolite formation and excretion) and enable the interplay thereof (a bridging effect). Without the bridge, metabolite formation is independent on its downstream process excretion, thus impact of metabolite excretion on its formation is impossible

  5. Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene.

    Directory of Open Access Journals (Sweden)

    Pep Charusanti

    2010-11-01

    Full Text Available Bacterial survival requires adaptation to different environmental perturbations such as exposure to antibiotics, changes in temperature or oxygen levels, DNA damage, and alternative nutrient sources. During adaptation, bacteria often develop beneficial mutations that confer increased fitness in the new environment. Adaptation to the loss of a major non-essential gene product that cripples growth, however, has not been studied at the whole-genome level. We investigated the ability of Escherichia coli K-12 MG1655 to overcome the loss of phosphoglucose isomerase (pgi by adaptively evolving ten replicates of E. coli lacking pgi for 50 days in glucose M9 minimal medium and by characterizing endpoint clones through whole-genome re-sequencing and phenotype profiling. We found that 1 the growth rates for all ten endpoint clones increased approximately 3-fold over the 50-day period; 2 two to five mutations arose during adaptation, most frequently in the NADH/NADPH transhydrogenases udhA and pntAB and in the stress-associated sigma factor rpoS; and 3 despite similar growth rates, at least three distinct endpoint phenotypes developed as defined by different rates of acetate and formate secretion. These results demonstrate that E. coli can adapt to the loss of a major metabolic gene product with only a handful of mutations and that adaptation can result in multiple, alternative phenotypes.

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

    Directory of Open Access Journals (Sweden)

    Vande Wouwer, A.

    2010-01-01

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

  7. Understanding the role of p53 in adaptive response to radiation-induced germline mutations

    International Nuclear Information System (INIS)

    Langlois, N.L.; Quinn, J.S.; Somers, C.M.; Boreham, D.R.; Mitchel, R.E.J.

    2003-01-01

    Full text: Radiation-induced adaptive response is now a widely studied area of radiation biology. Studies have demonstrated reduced levels of radiation-induced biological damage when an 'adaptive dose' is given before a higher 'challenge dose' compared to when the challenge dose is given alone. It has been shown in some systems to be a result of inducible cellular repair systems. The adaptive response has been clearly demonstrated in many model systems, however its impact on heritable effects in the mammalian germline has never been studied. Expanded Simple Tandem Repeat (ESTR) loci have been used as markers demonstrating that induced heritable mutations in mice follow a dose-response relationship. Recent data in our laboratory show preliminary evidence of radiation-induced adaptive response suppressing germline mutations at ESTR loci in wild type mice. The frequency of heritable mutations was significantly reduced when a priming dose of 0.1 Gy was given 24 hours prior to a 1 Gy acute challenging dose. We are now conducting a follow-up study to attempt to understand the mechanism of this adaptive response. P53 is known to play a significant role in governing apoptosis, DNA repair and cancer induction. In order to determine what function p53 has in the adaptive response for heritable mutations, we have mated radiation treated Trp53+/- male mice (C57Bl) to untreated, normal females (C57Bl). Using DNA fingerprinting, we are investigating the rate of inherited radiation-induced mutations on pre- and post-meiotic radiation-treated gametocytes by examining mutation frequencies in offspring DNA. If p53 is integral in the mechanism of adaptive response, we should not see an adaptive response in radiation-induced heritable mutations in these mice. This research is significant in that it will provide insight to understanding the mechanism behind radiation-induced adaptive response in the mammalian germline

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

    International Nuclear Information System (INIS)

    Shetty, P.S.

    1993-01-01

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

  9. Independent AMP and NAD signaling regulates C2C12 differentiation and metabolic adaptation.

    Science.gov (United States)

    Hsu, Chia George; Burkholder, Thomas J

    2016-12-01

    The balance of ATP production and consumption is reflected in adenosine monophosphate (AMP) and nicotinamide adenine dinucleotide (NAD) content and has been associated with phenotypic plasticity in striated muscle. Some studies have suggested that AMPK-dependent plasticity may be an indirect consequence of increased NAD synthesis and SIRT1 activity. The primary goal of this study was to assess the interaction of AMP- and NAD-dependent signaling in adaptation of C2C12 myotubes. Changes in myotube developmental and metabolic gene expression were compared following incubation with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and nicotinamide mononucleotide (NMN) to activate AMPK- and NAD-related signaling. AICAR showed no effect on NAD pool or nampt expression but significantly reduced histone H3 acetylation and GLUT1, cytochrome C oxidase subunit 2 (COX2), and MYH3 expression. In contrast, NMN supplementation for 24 h increased NAD pool by 45 % but did not reduce histone H3 acetylation nor promote mitochondrial gene expression. The combination of AMP and NAD signaling did not induce further metabolic adaptation, but NMN ameliorated AICAR-induced myotube reduction. We interpret these results as indication that AMP and NAD contribute to C2C12 differentiation and metabolic adaptation independently.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

    Steffensen, John Fleng

    2002-01-01

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

  12. Understanding the transformation of climate futures. A conceptual framework illustrated with urban adaptation policy

    NARCIS (Netherlands)

    Boezeman, D.F.

    2016-01-01

    Projects in which science-based futures are produced indicating the relevant impacts of climatic changes are proliferating, in tandem with the increasing attention for climate change adaptation. Constructionist science studies have put forward the concept of ‘co-production’ to understand how

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

    Directory of Open Access Journals (Sweden)

    Reser Jared

    2009-02-01

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

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

    Science.gov (United States)

    Reser, Jared Edward

    2009-02-28

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

  15. Metabolic Profiling Provides a System Understanding of Hypothyroidism in Rats and Its Application

    Science.gov (United States)

    Dong, Xin; Zhu, Zhenyu; Li, Wuhong; Lou, Ziyang; Chai, Yifeng

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Guolin Li

    2018-01-01

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

  17. Metabonomics of ageing - Towards understanding metabolism of a long and healthy life.

    Science.gov (United States)

    Martin, Francois-Pierre J; Montoliu, Ivan; Kussmann, Martin

    2017-07-01

    Systems biology approaches have been increasingly employed in clinical studies to enhance our understanding of the role of genetics, environmental factors and their interactions on nutritional, health and disease status. Amongst the new omics technologies, metabonomics has emerged as a robust platform to capture metabolic and nutritional requirements by enabling, in a minimally invasive fashion, the monitoring of a wide range of biochemical compounds. Their variations reflect comprehensively the various molecular regulatory processes, which are tightly controlled and under the influence of genetics, diet, gut microbiota and other environmental factors. They are providing key insights into complex metabolic phenomena as well as into differences and specificities at individual and population level. The aim of this review is to evaluate promising metabolic insights towards understanding metabolism of a long and healthy life from pre-clinical and clinical metabonomics studies. We will also discuss analytical approaches to enable data integration, with an emphasis on the longitudinal component. Herein, we will illustrate current examples, challenges and perspectives in the applications of metabonomics monitoring and modelling approaches in the context of healthy ageing research. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2013-01-01

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

  19. Translational approaches to understanding metabolic dysfunction and cardiovascular consequences of obstructive sleep apnea

    Science.gov (United States)

    Polotsky, Vsevolod Y.; O'Donnell, Christopher P.; Cravo, Sergio L.; Lorenzi-Filho, Geraldo; Machado, Benedito H.

    2015-01-01

    Obstructive sleep apnea (OSA) is known to be independently associated with several cardiovascular diseases including hypertension, myocardial infarction, and stroke. To determine how OSA can increase cardiovascular risk, animal models have been developed to explore the underlying mechanisms and the cellular and end-organ targets of the predominant pathophysiological disturbance in OSA–intermittent hypoxia. Despite several limitations in translating data from animal models to the clinical arena, significant progress has been made in our understanding of how OSA confers increased cardiovascular risk. It is clear now that the hypoxic stress associated with OSA can elicit a broad spectrum of pathological systemic events including sympathetic activation, systemic inflammation, impaired glucose and lipid metabolism, and endothelial dysfunction, among others. This review provides an update of the basic, clinical, and translational advances in our understanding of the metabolic dysfunction and cardiovascular consequences of OSA and highlights the most recent findings and perspectives in the field. PMID:26232233

  20. Understanding adaptation and transformation through indigenous practice: the case of the Guna of Panama

    Directory of Open Access Journals (Sweden)

    Marina J. Apgar

    2015-03-01

    Full Text Available Resilience is emerging as a promising vehicle for improving management of social-ecological systems that can potentially lead to more sustainable arrangements between environmental and social spheres. Central to an understanding of how to support resilience is the need to understand social change and its links with adaptation and transformation. Our aim is to contribute to insights about and understanding of underlying social dynamics at play in social-ecological systems. We argue that longstanding indigenous practices provide opportunities for investigating processes of adaptation and transformation. We use in-depth analysis of adaptation and transformation through engagement in participatory action research, focusing on the role of cultural and social practices among the Guna indigenous peoples in Panama. Our findings reveal that cultural practices facilitating leadership development, personhood development, and social networking are critical for enabling both adaptation and transformation. Further, we argue that Guna ritual practice builds additional skills, such as critical self-reflection and creative innovation, that are important for supporting the deeper changes required by transformation.

  1. Understanding arsenic metabolism through spectroscopic determination of arsenic in human urine

    OpenAIRE

    Brima, Eid I.; Jenkins, Richard O.; Haris, Parvez I.

    2006-01-01

    In this review we discuss a range of spectroscopic techniques that are currently used for analysis of arsenic in human urine for understanding arsenic metabolism and toxicity, especially in relation to genetics/ethnicity, ingestion studies and exposure to arsenic through drinking water and diet. Spectroscopic techniques used for analysis of arsenic in human urine include inductively coupled plasma mass spectrometry (ICP-MS), hydride generation atomic absorption spectrometry (HG-AAS), hydride ...

  2. Non-Neuronal Cells in the Hypothalamic Adaptation to Metabolic Signals

    Science.gov (United States)

    Freire-Regatillo, Alejandra; Argente-Arizón, Pilar; Argente, Jesús; García-Segura, Luis Miguel; Chowen, Julie A.

    2017-01-01

    Although the brain is composed of numerous cell types, neurons have received the vast majority of attention in the attempt to understand how this organ functions. Neurons are indeed fundamental but, in order for them to function correctly, they rely on the surrounding “non-neuronal” cells. These different cell types, which include glia, epithelial cells, pericytes, and endothelia, supply essential substances to neurons, in addition to protecting them from dangerous substances and situations. Moreover, it is now clear that non-neuronal cells can also actively participate in determining neuronal signaling outcomes. Due to the increasing problem of obesity in industrialized countries, investigation of the central control of energy balance has greatly increased in attempts to identify new therapeutic targets. This has led to interesting advances in our understanding of how appetite and systemic metabolism are modulated by non-neuronal cells. For example, not only are nutrients and hormones transported into the brain by non-neuronal cells, but these cells can also metabolize these metabolic factors, thus modifying the signals reaching the neurons. The hypothalamus is the main integrating center of incoming metabolic and hormonal signals and interprets this information in order to control appetite and systemic metabolism. Hence, the factors transported and released from surrounding non-neuronal cells will undoubtedly influence metabolic homeostasis. This review focuses on what is known to date regarding the involvement of different cell types in the transport and metabolism of nutrients and hormones in the hypothalamus. The possible involvement of non-neuronal cells, in particular glial cells, in physiopathological outcomes of poor dietary habits and excess weight gain are also discussed. PMID:28377744

  3. Adaptive trade-offs in juvenile salmonid metabolism associated with habitat partitioning between coho salmon and steelhead trout in coastal streams.

    Science.gov (United States)

    Van Leeuwen, Travis E; Rosenfeld, Jordan S; Richards, Jeffrey G

    2011-09-01

    1. Adaptive trade-offs are fundamental to the evolution of diversity and the coexistence of similar taxa and occur when complimentary combinations of traits maximize efficiency of resource exploitation or survival at different points on environmental gradients. 2. Standard metabolic rate (SMR) is a key physiological trait that reflects adaptations to baseline metabolic performance, whereas active metabolism reflects adaptations to variable metabolic output associated with performance related to foraging, predator avoidance, aggressive interactions or migratory movements. Benefits of high SMR and active metabolism may change along a resource (productivity) gradient, indicating that a trade-off exists among active metabolism, resting metabolism and energy intake. 3. We measured and compared SMR, maximal metabolic rate (MMR), aerobic scope (AS), swim performance (UCrit) and growth of juvenile hatchery and wild steelhead and coho salmon held on high- and low-food rations in order to better understand the potential significance of variation in SMR to growth, differentiation between species, and patterns of habitat use along a productivity gradient. 4. We found that differences in SMR, MMR, AS, swim performance and growth rate between steelhead trout and coho salmon were reduced in hatchery-reared fish compared with wild fish. Wild steelhead had a higher MMR, AS, swim performance and growth rate than wild coho, but adaptations between species do not appear to involve differences in SMR or to trade-off increased growth rate against lower swim performance, as commonly observed for high-growth strains. Instead, we hypothesize that wild steelhead may be trading off higher growth rate for lower food consumption efficiency, similar to strategies adopted by anadromous vs. resident brook trout and Atlantic salmon vs. brook trout. This highlights potential differences in food consumption and digestion strategies as cryptic adaptations ecologically differentiating salmonid species

  4. Secondary metabolism and antioxidants are involved in environmental adaptation and stress tolerance in lettuce.

    Science.gov (United States)

    Oh, Myung-Min; Trick, Harold N; Rajashekar, C B

    2009-01-30

    Lettuce (Lactuca sativa) plants grown in a protective environment, similar to in vitro conditions, were acclimated in a growth chamber and subjected to water stress to examine the activation of genes involved in secondary metabolism and biosynthesis of antioxidants. The expression of phenylalanine ammonia-lyase (PAL), gamma-tocopherol methyl transferase (gamma-TMT) and l-galactose dehydrogenase (l-GalDH) genes involved in the biosynthesis of phenolic compounds, alpha-tocopherol and ascorbic acid, respectively, were determined during plant adaptation. These genes were activated in tender plants, grown under protective conditions, when exposed to normal growing conditions in a growth chamber. A large increase in transcript level for PAL, a key gene in the phenylpropanoid pathway leading to the biosynthesis of a wide array of phenolics and flavonoids, was observed within 1h of exposure of tender plants to normal growing conditions. Plant growth, especially the roots, was retarded in tender plants when exposed to normal growing conditions. Furthermore, exposure of both protected and unprotected plants to water stress resulted in the activation of PAL. PAL inhibition by 2-aminoindan-2-phosphonic acid (AIP) rendered these plants more sensitive to chilling and heat shock treatments. These results suggest that activation of secondary metabolism as well as the antioxidative metabolism is an integral part of plant adaptation to normal growing conditions in lettuce plants.

  5. Application of meta-omics techniques to understand greenhouse gas emissions originating from ruminal metabolism.

    Science.gov (United States)

    Wallace, Robert J; Snelling, Timothy J; McCartney, Christine A; Tapio, Ilma; Strozzi, Francesco

    2017-01-16

    Methane emissions from ruminal fermentation contribute significantly to total anthropological greenhouse gas (GHG) emissions. New meta-omics technologies are beginning to revolutionise our understanding of the rumen microbial community structure, metabolic potential and metabolic activity. Here we explore these developments in relation to GHG emissions. Microbial rumen community analyses based on small subunit ribosomal RNA sequence analysis are not yet predictive of methane emissions from individual animals or treatments. Few metagenomics studies have been directly related to GHG emissions. In these studies, the main genes that differed in abundance between high and low methane emitters included archaeal genes involved in methanogenesis, with others that were not apparently related to methane metabolism. Unlike the taxonomic analysis up to now, the gene sets from metagenomes may have predictive value. Furthermore, metagenomic analysis predicts metabolic function better than only a taxonomic description, because different taxa share genes with the same function. Metatranscriptomics, the study of mRNA transcript abundance, should help to understand the dynamic of microbial activity rather than the gene abundance; to date, only one study has related the expression levels of methanogenic genes to methane emissions, where gene abundance failed to do so. Metaproteomics describes the proteins present in the ecosystem, and is therefore arguably a better indication of microbial metabolism. Both two-dimensional polyacrylamide gel electrophoresis and shotgun peptide sequencing methods have been used for ruminal analysis. In our unpublished studies, both methods showed an abundance of archaeal methanogenic enzymes, but neither was able to discriminate high and low emitters. Metabolomics can take several forms that appear to have predictive value for methane emissions; ruminal metabolites, milk fatty acid profiles, faecal long-chain alcohols and urinary metabolites have all

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

    Science.gov (United States)

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

    2017-07-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  8. Understanding Indian Institutional Networks and Participation in Water Management Adaptation to Climate Change

    Science.gov (United States)

    Azhoni, A.; Holman, I.; Jude, S.

    2014-12-01

    Adaptation to climate change for water management involves complex interactions between different actors and sectors. The need to understand the relationships between key stakeholder institutions (KSIs) is increasingly recognized. The complexity of water management in India has meant that enhancing adaptive capacity through improved inter-institutional networks remains a challenge for both government and non-governmental institutions. To analyse such complex inter-actions this study has used Social Network and Stakeholder Analysis tools to quantify the participation of, and interactions between, each KSI in the climate change adaptation and water discourse based on keyword analysis of their online presence. Using NodeXL, a Social Network Analysis tool, network diagrams have been used to evaluate the inter-relationships between these KSIs. Semi-structured interviews were conducted with twenty-five KSIs to identify the main barriers to adaptation and to triangulate the findings of the e-documents analysis. The analysis found that there is an inverse relationship between institutions' reference to water and climate change in their web-documents. Most institutions emphasize mitigation rather than adaptation. Bureaucratic delays, poor coordination between the KSIs, unclear policies and systemic deficiencies are identified as key barriers to improving adaptive capacity within water management to climate change. However, the increasing attention being given to the perceived climate change impacts on the water sector and improving the inter-institutional networks are some of the opportunities for Indian water institutions. Although websites of Union Government Institutions seldom directly hyperlink to one another, they are linked through "bridging" websites which have the potential to act as brokers for enhancing adaptive capacity. The research has wider implications for analysis of complex inter-disciplinary and inter-institutional issues involving multi stakeholders.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function...... robust amounts of aerobic activity, voluntary wheel running exercise was not sufficiently intense to improve the oxidative capacity of skeletal muscle in adult SHHF animals, indicating an inability to compensate for declining heart function by improving peripheral oxidative adaptations in the skeletal...

  10. Polar Microalgae: New Approaches towards Understanding Adaptations to an Extreme and Changing Environment

    Directory of Open Access Journals (Sweden)

    Barbara R. Lyon

    2014-01-01

    Full Text Available Polar Regions are unique and highly prolific ecosystems characterized by extreme environmental gradients. Photosynthetic autotrophs, the base of the food web, have had to adapt physiological mechanisms to maintain growth, reproduction and metabolic activity despite environmental conditions that would shut-down cellular processes in most organisms. High latitudes are characterized by temperatures below the freezing point, complete darkness in winter and continuous light and high UV in the summer. Additionally, sea-ice, an ecological niche exploited by microbes during the long winter seasons when the ocean and land freezes over, is characterized by large salinity fluctuations, limited gas exchange, and highly oxic conditions. The last decade has been an exciting period of insights into the molecular mechanisms behind adaptation of microalgae to the cryosphere facilitated by the advancement of new scientific tools, particularly “omics” techniques. We review recent insights derived from genomics, transcriptomics, and proteomics studies. Genes, proteins and pathways identified from these highly adaptable polar microbes have far-reaching biotechnological applications. Furthermore, they may provide insights into life outside this planet, as well as glimpses into the past. High latitude regions also have disproportionately large inputs into global biogeochemical cycles and are the region most sensitive to climate change.

  11. Comparative metabolic responses and adaptive strategies of wheat (Triticum aestivum) to salt and alkali stress.

    Science.gov (United States)

    Guo, Rui; Yang, Zongze; Li, Feng; Yan, Changrong; Zhong, Xiuli; Liu, Qi; Xia, Xu; Li, Haoru; Zhao, Long

    2015-07-07

    It is well known that salinization (high-pH) has been considered as a major environmental threat to agricultural systems. The aim of this study was to investigate the differences between salt stress and alkali stress in metabolic profiles and nutrient accumulation of wheat; these parameters were also evaluated to determine the physiological adaptive mechanisms by which wheat tolerates alkali stress. The harmful effect of alkali stress on the growth and photosynthesis of wheat were stronger than those of salt stress. High-pH of alkali stress induced the most of phosphate and metal ions to precipitate; as a result, the availability of nutrients significantly declined. Under alkali stress, Ca sharply increased in roots, however, it decreased under salt stress. In addition, we detected the 75 metabolites that were different among the treatments according to GC-MS analysis, including organic acids, amino acids, sugars/polyols and others. The metabolic data showed salt stress and alkali stress caused different metabolic shifts; alkali stress has a stronger injurious effect on the distribution and accumulation of metabolites than salt stress. These outcomes correspond to specific detrimental effects of a highly pH environment. Ca had a significant positive correlation with alkali tolerates, and increasing Ca concentration can immediately trigger SOS Na exclusion system and reduce the Na injury. Salt stress caused metabolic shifts toward gluconeogenesis with increased sugars to avoid osmotic stress; energy in roots and active synthesis in leaves were needed by wheat to develop salt tolerance. Alkali stress (at high pH) significantly inhibited photosynthetic rate; thus, sugar production was reduced, N metabolism was limited, amino acid production was reduced, and glycolysis was inhibited.

  12. The kidney of chicken adapts to chronic metabolic acidosis: in vivo and in vitro studies.

    Science.gov (United States)

    Craan, A G; Lemieux, G; Vinay, P; Gougoux, A

    1982-08-01

    Renal adaptation to chronic metabolic acidosis was studies in Arbor Acre hens receiving ammonium chloride by stomach tube 0.75 g/kg/day during 6 days. During a 14-day study, it was shown that the animals could excrete as much as 60% of the acid load during ammonium chloride administration. At the same time urate excretion fell markedly but the renal contribution to urate excretion (14%) did not change. During acidosis, blood glutamine increased twofold and the tissue concentration of glutamine rose in both liver and kidney. Infusion of L-glutamine led to increased ammonia excretion and more so in acidotic animals. Glutaminase I, glutamate dehydrogenase, alanine aminotransferase (GPT), and malic enzyme activities increased in the kidney during acidosis but phosphoenolpyruvate carboxykinase (PEPCK) activity did not change. Glutaminase I was not found in the liver, but hepatic glutamine synthetase rose markedly during acidosis. Glutamine synthetase was not found in the kidney. Renal tubules incubated with glutamine and alanine were ammoniagenic and gluconeogenic to the same degree as rat tubules with the same increments in acidosis. Lactate was gluconeogenic without increment during acidosis. The present study indicates that the avian kidney adapts to chronic metabolic acidosis with similarities and differences when compared to dog and rat. Glutamine originating from the liver appears to be the major ammoniagenic substrate. Our data also support the hypothesis that hepatic urate synthesis is decreased during acidosis.

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

    Science.gov (United States)

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

    2017-08-29

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

  14. Adaptive changes in NAD+ metabolism in ultraviolet light-irradiated murine lymphoma cells

    International Nuclear Information System (INIS)

    Kleczkowska, H.E.; Szumiel, I.; Althaus, F.R.

    1990-01-01

    We have determined the ability of UV254nm-irradiated murine lymphoma cells to adapt their NAD+ metabolism to the increased NAD+ consumption for the poly ADP-ribosylation of chromatin proteins. Two murine lymphoma sublines with differential UV-sensitivity and poly(ADP-ribose) turnover were used as a model system. The first subline, designated LY-R is UV254nm-sensitive and tumorigenic in DBA/2 mice. The second subline, LY-S is UV254nm-resistant and nontumorigenic. Following treatment of these cells with 2 mM benzamide, an inhibitor of the NAD(+)-utilizing enzyme poly(ADP-ribose) polymerase, NAD+ levels slowly increased up to about 160% of control levels after 3 hours. When benzamide was added to these cultures 20 min after UV254nm irradiation, a dramatic transient increase of NAD+ levels was observed within 4 min in LY-R cells and more moderately in LY-S cells. At later times after UV254nm irradiation, the NAD+ levels increased in both sublines reaching up to 200% of the concentrations prior to benzamide treatment. These results demonstrate an adaptative response of NAD+ metabolism to UV254nm irradiation. In parallel, we observed a differential repartitioning of ADP-ribosyl residues between the NAD+ and poly(ADP-ribose) pools of LY-R and LY-S cells that correlates with the differential UV sensitivity of these cells

  15. Using community archetypes to better understand differential community adaptation to wildfire risk.

    Science.gov (United States)

    Carroll, Matthew; Paveglio, Travis

    2016-06-05

    One of the immediate challenges of wildfire management concerns threats to human safety and property in residential areas adjacent to non-cultivated vegetation. One approach for relieving this problem is to increase human community 'adaptiveness' to deal with the risk and reality of fire in a variety of landscapes. The challenge in creating 'fire-adapted communities' (FACs) is the great diversity in character and make-up of populations at risk from wildfire. This paper outlines a recently developed categorization scheme for Wildland-Urban Interface (WUI) communities based on a larger conceptual approach for understanding how social diversity is likely to influence the creation of FACs. The WUI categorization scheme situates four community archetypes on a continuum that recognizes dynamic change in human community functioning. We use results from the WUI classification scheme to outline key characteristics associated with each archetype and results from recent case studies to demonstrate the diversity across WUI communities. Differences among key characteristics of local social context will likely result in the need for different adaptation strategies to wildfire. While the WUI archetypes described here may not be broadly applicable to other parts of the world, we argue that the conceptual approach and strategies for systematically documenting local influences on wildfire adaptation have potential for broad application.This article is part of the themed issue 'The interaction of fire and mankind'. © 2016 The Author(s).

  16. Microbial Metabolism in Soil at Subzero Temperatures: Adaptation Mechanisms Revealed by Position-Specific 13C Labeling

    Directory of Open Access Journals (Sweden)

    Ezekiel K. Bore

    2017-05-01

    Full Text Available Although biogeochemical models designed to simulate carbon (C and nitrogen (N dynamics in high-latitude ecosystems incorporate extracellular parameters, molecular and biochemical adaptations of microorganisms to freezing remain unclear. This knowledge gap hampers estimations of the C balance and ecosystem feedback in high-latitude regions. To analyze microbial metabolism at subzero temperatures, soils were incubated with isotopomers of position-specifically 13C-labeled glucose at three temperatures: +5 (control, -5, and -20°C. 13C was quantified in CO2, bulk soil, microbial biomass, and dissolved organic carbon (DOC after 1, 3, and 10 days and also after 30 days for samples at -20°C. Compared to +5°C, CO2 decreased 3- and 10-fold at -5 and -20°C, respectively. High 13C recovery in CO2 from the C-1 position indicates dominance of the pentose phosphate pathway at +5°C. In contrast, increased oxidation of the C-4 position at subzero temperatures implies a switch to glycolysis. A threefold higher 13C recovery in microbial biomass at -5 than +5°C points to synthesis of intracellular compounds such as glycerol and ethanol in response to freezing. Less than 0.4% of 13C was recovered in DOC after 1 day, demonstrating complete glucose uptake by microorganisms even at -20°C. Consequently, we attribute the fivefold higher extracellular 13C in soil than in microbial biomass to secreted antifreeze compounds. This suggests that with decreasing temperature, intracellular antifreeze protection is complemented by extracellular mechanisms to avoid cellular damage by crystallizing water. The knowledge of sustained metabolism at subzero temperatures will not only be useful for modeling global C dynamics in ecosystems with periodically or permanently frozen soils, but will also be important in understanding and controlling the adaptive mechanisms of food spoilage organisms.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful...... tumour tissue in vivo and that FoxO3A short-hairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia....... reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes...... cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic...

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

    Directory of Open Access Journals (Sweden)

    Sissel J. Moltu

    2014-05-01

    Full Text Available Objectives: Early nutrition influences metabolic programming and long-term health. We explored the urinary metabolite profiles of 48 premature infants (birth weight < 1500 g randomized to an enhanced or a standard diet during neonatal hospitalization. Methods: Metabolomics using nuclear magnetic resonance spectroscopy (NMR was conducted on urine samples obtained during the first week of life and thereafter fortnightly. Results: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group. Enhanced nutrition did not appear to affect the urine profiles to an extent exceeding individual variation. However, in all infants the glucogenic amino acids glycine, threonine, hydroxyproline and tyrosine increased substantially during the early postnatal period, along with metabolites of the tricarboxylic acid cycle (succinate, oxoglutarate, fumarate and citrate. The metabolite changes correlated with postmenstrual age. Moreover, we observed elevated threonine and glycine levels in first-week urine samples of the small for gestational age (SGA; birth weight < 10th percentile for gestational age as compared to the appropriate for gestational age infants. Conclusion: This first nutri-metabolomics study in premature infants demonstrates that the physiological adaptation during the fetal-postnatal transition as well as maturation influences metabolism during the breastfeeding period. Elevated glycine and threonine levels were found in the first week urine samples of the SGA infants and emerged as potential biomarkers of an altered metabolic phenotype.

  19. Dynamic scenario of metabolic pathway adaptation in tumors and therapeutic approach.

    Science.gov (United States)

    Peppicelli, Silvia; Bianchini, Francesca; Calorini, Lido

    2015-01-01

    Cancer cells need to regulate their metabolic program to fuel several activities, including unlimited proliferation, resistance to cell death, invasion and metastasis. The aim of this work is to revise this complex scenario. Starting from proliferating cancer cells located in well-oxygenated regions, they may express the so-called "Warburg effect" or aerobic glycolysis, meaning that although a plenty of oxygen is available, cancer cells choose glycolysis, the sole pathway that allows a biomass formation and DNA duplication, needed for cell division. Although oxygen does not represent the primary font of energy, diffusion rate reduces oxygen tension and the emerging hypoxia promotes "anaerobic glycolysis" through the hypoxia inducible factor-1α-dependent up-regulation. The acquired hypoxic phenotype is endowed with high resistance to cell death and high migration capacities, although these cells are less proliferating. Cells using aerobic or anaerobic glycolysis survive only in case they extrude acidic metabolites acidifying the extracellular space. Acidosis drives cancer cells from glycolysis to OxPhos, and OxPhos transforms the available alternative substrates into energy used to fuel migration and distant organ colonization. Thus, metabolic adaptations sustain different energy-requiring ability of cancer cells, but render them responsive to perturbations by anti-metabolic agents, such as inhibitors of glycolysis and/or OxPhos.

  20. Understanding role of genome dynamics in host adaptation of gut commensal, L. reuteri

    Directory of Open Access Journals (Sweden)

    Shikha Sharma

    2017-10-01

    Full Text Available Lactobacillus reuteri is a gram-positive gut commensal and exhibits noteworthy adaptation to its vertebrate hosts. Host adaptation is often driven by inter-strain genome dynamics like expansion of insertion sequences that lead to acquisition and loss of gene(s and creation of large dynamic regions. In this regard we carried in-house genome sequencing of large number of L. reuteri strains origination from human, chicken, pig and rodents. We further next generation sequence data in understanding invasion and expansion of an IS element in shaping genome of strains belonging to human associated lineage. Finally, we share our experience in high-throughput genomic library preparation and generating high quality sequence data of a very low GC bacterium like L. reuteri.

  1. New features on the environmental regulation of metabolism revealed by modeling the cellular proteomic adaptations induced by light, carbon and inorganic nitrogen in Chlamydomonas reinhardtii

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    Stéphanie Gérin

    2016-08-01

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

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

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    Martino V. Franchi

    2017-07-01

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

  3. Rapid adaptation of the stimulatory effect of CO2 on brain norepinephrine metabolism.

    Science.gov (United States)

    Stone, E A

    1983-12-01

    The present study examined the effects of exposure of rats to elevated environmental levels of CO2 on norepinephrine metabolism in the hypothalamus and other regions of the brain. In confirmation of previous findings by others CO2 at 10 or 15% was found to elevate both dopa accumulation after dopa decarboxylase inhibition and norepinephrine utilization after tyrosine hydroxylase inhibition. These effects however were found to be transient occurring only during the first 30 min of 2.5 h exposure. In this regard CO2 differs from another form of stress, restraint which produces a sustained 2.5 h increase of dopa accumulation and NE accumulation. Restraint was also more effective than CO2 in depleting endogenous stores of hypothalamic NE. The factor responsible for the adaptation of the catecholamine response to CO2 was not identified although it was shown not to be hypothermia and it was reversed by a 2 h CO2-free recovery period.

  4. Thermophilic Adaptation in Prokaryotes Is Constrained by Metabolic Costs of Proteostasis

    Science.gov (United States)

    Venev, Sergey V; Zeldovich, Konstantin B

    2018-01-01

    Abstract Prokaryotes evolved to thrive in an extremely diverse set of habitats, and their proteomes bear signatures of environmental conditions. Although correlations between amino acid usage and environmental temperature are well-documented, understanding of the mechanisms of thermal adaptation remains incomplete. Here, we couple the energetic costs of protein folding and protein homeostasis to build a microscopic model explaining both the overall amino acid composition and its temperature trends. Low biosynthesis costs lead to low diversity of physical interactions between amino acid residues, which in turn makes proteins less stable and drives up chaperone activity to maintain appropriate levels of folded, functional proteins. Assuming that the cost of chaperone activity is proportional to the fraction of unfolded client proteins, we simulated thermal adaptation of model proteins subject to minimization of the total cost of amino acid synthesis and chaperone activity. For the first time, we predicted both the proteome-average amino acid abundances and their temperature trends simultaneously, and found strong correlations between model predictions and 402 genomes of bacteria and archaea. The energetic constraint on protein evolution is more apparent in highly expressed proteins, selected by codon adaptation index. We found that in bacteria, highly expressed proteins are similar in composition to thermophilic ones, whereas in archaea no correlation between predicted expression level and thermostability was observed. At the same time, thermal adaptations of highly expressed proteins in bacteria and archaea are nearly identical, suggesting that universal energetic constraints prevail over the phylogenetic differences between these domains of life. PMID:29106597

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

    Directory of Open Access Journals (Sweden)

    Bélanger Richard R

    2010-02-01

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

  6. Neuron specific metabolic adaptations following multi-day exposures to oxygen glucose deprivation.

    Science.gov (United States)

    Zeiger, Stephanie L H; McKenzie, Jennifer R; Stankowski, Jeannette N; Martin, Jacob A; Cliffel, David E; McLaughlin, BethAnn

    2010-11-01

    Prior exposure to sub toxic insults can induce a powerful endogenous neuroprotective program known as ischemic preconditioning. Current models typically rely on a single stress episode to induce neuroprotection whereas the clinical reality is that patients may experience multiple transient ischemic attacks (TIAs) prior to suffering a stroke. We sought to develop a neuron-enriched preconditioning model using multiple oxygen glucose deprivation (OGD) episodes to assess the endogenous protective mechanisms neurons implement at the metabolic and cellular level. We found that neurons exposed to a five minute period of glucose deprivation recovered oxygen utilization and lactate production using novel microphysiometry techniques. Using the non-toxic and energetically favorable five minute exposure, we developed a preconditioning paradigm where neurons are exposed to this brief OGD for three consecutive days. These cells experienced a 45% greater survival following an otherwise lethal event and exhibited a longer lasting window of protection in comparison to our previous in vitro preconditioning model using a single stress. As in other models, preconditioned cells exhibited mild caspase activation, an increase in oxidized proteins and a requirement for reactive oxygen species for neuroprotection. Heat shock protein 70 was upregulated during preconditioning, yet the majority of this protein was released extracellularly. We believe coupling this neuron-enriched multi-day model with microphysiometry will allow us to assess neuronal specific real-time metabolic adaptations necessary for preconditioning. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Nitrogen Metabolism in Adaptation of Photosynthesis to Water Stress in Rice Grown under Different Nitrogen Levels

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    Chu Zhong

    2017-06-01

    Full Text Available To investigate the role of nitrogen (N metabolism in the adaptation of photosynthesis to water stress in rice, a hydroponic experiment supplying with low N (0.72 mM, moderate N (2.86 mM, and high N (7.15 mM followed by 150 g⋅L-1 PEG-6000 induced water stress was conducted in a rainout shelter. Water stress induced stomatal limitation to photosynthesis at low N, but no significant effect was observed at moderate and high N. Non-photochemical quenching was higher at moderate and high N. In contrast, relative excessive energy at PSII level (EXC was declined with increasing N level. Malondialdehyde and hydrogen peroxide (H2O2 contents were in parallel with EXC. Water stress decreased catalase and ascorbate peroxidase activities at low N, resulting in increased H2O2 content and severer membrane lipid peroxidation; whereas the activities of antioxidative enzymes were increased at high N. In accordance with photosynthetic rate and antioxidative enzymes, water stress decreased the activities of key enzymes involving in N metabolism such as glutamate synthase and glutamate dehydrogenase, and photorespiratory key enzyme glycolate oxidase at low N. Concurrently, water stress increased nitrate content significantly at low N, but decreased nitrate content at moderate and high N. Contrary to nitrate, water stress increased proline content at moderate and high N. Our results suggest that N metabolism appears to be associated with the tolerance of photosynthesis to water stress in rice via affecting CO2 diffusion, antioxidant capacity, and osmotic adjustment.

  8. Adaptive clinical trial designs with pre-specified rules for modifying the sample size: understanding efficient types of adaptation.

    Science.gov (United States)

    Levin, Gregory P; Emerson, Sarah C; Emerson, Scott S

    2013-04-15

    Adaptive clinical trial design has been proposed as a promising new approach that may improve the drug discovery process. Proponents of adaptive sample size re-estimation promote its ability to avoid 'up-front' commitment of resources, better address the complicated decisions faced by data monitoring committees, and minimize accrual to studies having delayed ascertainment of outcomes. We investigate aspects of adaptation rules, such as timing of the adaptation analysis and magnitude of sample size adjustment, that lead to greater or lesser statistical efficiency. Owing in part to the recent Food and Drug Administration guidance that promotes the use of pre-specified sampling plans, we evaluate alternative approaches in the context of well-defined, pre-specified adaptation. We quantify the relative costs and benefits of fixed sample, group sequential, and pre-specified adaptive designs with respect to standard operating characteristics such as type I error, maximal sample size, power, and expected sample size under a range of alternatives. Our results build on others' prior research by demonstrating in realistic settings that simple and easily implemented pre-specified adaptive designs provide only very small efficiency gains over group sequential designs with the same number of analyses. In addition, we describe optimal rules for modifying the sample size, providing efficient adaptation boundaries on a variety of scales for the interim test statistic for adaptation analyses occurring at several different stages of the trial. We thus provide insight into what are good and bad choices of adaptive sampling plans when the added flexibility of adaptive designs is desired. Copyright © 2012 John Wiley & Sons, Ltd.

  9. The gut microbiota and metabolic disease: current understanding and future perspectives.

    Science.gov (United States)

    Arora, T; Bäckhed, F

    2016-10-01

    The human gut microbiota has been studied for more than a century. However, of nonculture-based techniques exploiting next-generation sequencing for analysing the microbiota, development has renewed research within the field during the past decade. The observation that the gut microbiota, as an environmental factor, contributes to adiposity has further increased interest in the field. The human microbiota is affected by the diet, and macronutrients serve as substrates for many microbially produced metabolites, such as short-chain fatty acids and bile acids, that may modulate host metabolism. Obesity predisposes towards type 2 diabetes and cardiovascular disease. Recently, it has been established that levels of butyrate-producing bacteria are reduced in patients with type 2 diabetes, whereas levels of Lactobacillus sp. are increased. Recent data suggest that the reduced levels of butyrate-producing bacteria might be causally linked to type 2 diabetes. Bariatric surgery, which promotes long-term weight loss and diabetes remission, alters the gut microbiota in both mice and humans. Furthermore, by transferring the microbiota from postbariatric surgery patients to mice, it has been demonstrated that an altered microbiota may contribute to the improved metabolic phenotype following this intervention. Thus, greater understanding of alterations of the gut microbiota, in combination with dietary patterns, may provide insights into how the gut microbiota contributes to disease progression and whether it can be exploited as a novel diagnostic, prognostic and therapeutic target. © 2016 The Association for the Publication of the Journal of Internal Medicine.

  10. Adaptation to metabolic dysfunction during aging: Making the best of a bad situation.

    Science.gov (United States)

    Jazwinski, S Michal; Jiang, James C; Kim, Sangkyu

    2017-07-29

    Mitochondria play a central role in energy metabolism in the process of oxidative phosphorylation. As importantly, they are key in several anabolic processes, including amino acid biosynthesis, nucleotide biosynthesis, heme biosynthesis, and the formation of iron‑sulfur clusters. Mitochondria are also engaged in waste removal in the urea cycle. Their activity can lead to the formation of reactive oxygen species which have damaging effects in the cell. These organelles are dynamic, undergoing cycles of fission and fusion which can be coupled to their removal by mitophagy. In addition to these widely recognized processes, mitochondria communicate with other subcellular compartments. Various components of mitochondrial complexes are encoded by either the nuclear or the mitochondrial genome necessitating coordination between these two organelles. This article reviews another form of communication between the mitochondria and the nucleus, in which the dysfunction of the former triggers changes in the expression of nuclear genes to compensate for it. The most extensively studied of these signaling pathways is the retrograde response whose effectors and downstream targets have been characterized. This response extends yeast replicative lifespan by adapting the organism to the mitochondrial dysfunction. Similar responses have been found in several other organisms, including mammals. Declining health and function during human aging incurs energetic costs. This compensation plays out differently in males and females, and variation in nuclear genes whose products affect mitochondrial function influences the outcome. Thus, the theme of mitochondria-nucleus communication as an adaptive response during aging appears very widespread. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration

    Science.gov (United States)

    Stewart, Randi

    2012-01-01

    Among organ systems, skeletal muscle is perhaps the most structurally specialized. The remarkable subcellular architecture of this tissue allows it to empower movement with instructions from motor neurons. Despite this high degree of specialization, skeletal muscle also has intrinsic signaling mechanisms that allow adaptation to long-term changes in demand and regeneration after acute damage. The second messenger adenosine 3′,5′-monophosphate (cAMP) not only elicits acute changes within myofibers during exercise but also contributes to myofiber size and metabolic phenotype in the long term. Strikingly, sustained activation of cAMP signaling leads to pronounced hypertrophic responses in skeletal myofibers through largely elusive molecular mechanisms. These pathways can promote hypertrophy and combat atrophy in animal models of disorders including muscular dystrophy, age-related atrophy, denervation injury, disuse atrophy, cancer cachexia, and sepsis. cAMP also participates in muscle development and regeneration mediated by muscle precursor cells; thus, downstream signaling pathways may potentially be harnessed to promote muscle regeneration in patients with acute damage or muscular dystrophy. In this review, we summarize studies implicating cAMP signaling in skeletal muscle adaptation. We also highlight ligands that induce cAMP signaling and downstream effectors that are promising pharmacological targets. PMID:22354781

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

    Directory of Open Access Journals (Sweden)

    A.S. Bakhareva

    2016-06-01

    Full Text Available Purpose: to scientifically substantiate effective mechanisms of organism’s bio-chemical adaptation of ski-racers in competition period with the help of lipid peroxidation indicators, oxidative modification of proteins and activity of hypothalamus pituitary adrenocortical system. Material: in the research 14 sportsmen of 18-25 years’ age (combined team of university with different level of sportsmanship participated. Assessment of free radical oxidation, anti-oxidant system, cortisol level was fulfilled with the help of indicators’ quantitative analysis by bio-chemical methods applied to blood serum samples. Results: it was found that in the basis of bio-chemical changes under intensive physical loads is increase of catabolic processes’ speed. Change of organism’s metabolic orientation of ski racers at optimal level results in working muscles’ energy supply improvement, increase of energy systems’ power and sports efficiency. Conclusions: Application of interval trainings at stages of preparation to special significant competitions results in expected adaptation and increase of sports efficiency. We also showed their effective role in ensuring long term reactions, conditioning high sports efficiency.

  13. The Recent Understanding of the Neurotrophin's Role in Skeletal Muscle Adaptation

    Directory of Open Access Journals (Sweden)

    Kunihiro Sakuma

    2011-01-01

    Full Text Available This paper summarizes the various effects of neurotrophins in skeletal muscle and how these proteins act as potential regulators of the maintenance, function, and regeneration of skeletal muscle fibers. Increasing evidence suggests that this family of neurotrophic factors influence not only the survival and function of innervating motoneurons but also the development and differentiation of myoblasts and muscle fibers. Muscle contractions (e.g., exercise produce BDNF mRNA and protein in skeletal muscle, and the BDNF seems to play a role in enhancing glucose metabolism and may act for myokine to improve various brain disorders (e.g., Alzheimer's disease and major depression. In adults with neuromuscular disorders, variations in neurotrophin expression are found, and the role of neurotrophins under such conditions is beginning to be elucidated. This paper provides a basis for a better understanding of the role of these factors under such pathological conditions and for treatment of human neuromuscular disease.

  14. Advances in computational metabolomics and databases deepen the understanding of metabolisms.

    Science.gov (United States)

    Tsugawa, Hiroshi

    2018-01-29

    Mass spectrometry (MS)-based metabolomics is the popular platform for metabolome analyses. Computational techniques for the processing of MS raw data, for example, feature detection, peak alignment, and the exclusion of false-positive peaks, have been established. The next stage of untargeted metabolomics would be to decipher the mass fragmentation of small molecules for the global identification of human-, animal-, plant-, and microbiota metabolomes, resulting in a deeper understanding of metabolisms. This review is an update on the latest computational metabolomics including known/expected structure databases, chemical ontology classifications, and mass spectrometry cheminformatics for the interpretation of mass fragmentations and for the elucidation of unknown metabolites. The importance of metabolome 'databases' and 'repositories' is also discussed because novel biological discoveries are often attributable to the accumulation of data, to relational databases, and to their statistics. Lastly, a practical guide for metabolite annotations is presented as the summary of this review. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. The contribution of mathematical modeling to understanding the dynamic aspects of rumen metabolism

    Directory of Open Access Journals (Sweden)

    André Bannink

    2016-11-01

    Full Text Available All rumen models cover the main drivers of variation in rumen function, which are feed intake, the differences between feedstuffs and feeds in their intrinsic rumen degradation characteristics, and fractional outflow rate of fluid and particulate matter. Dynamic modeling approaches are best suited to the prediction of more nuanced responses in rumen metabolism, and represent the dynamics of the interaction between substrates and micro-organisms and inter-microbial interactions. The concepts of dynamics are discussed for the case of rumen starch digestion as influenced by starch intake rate and frequency of feed intake, and for the case of fermentation of fiber in the large intestine. Adding representations of new functional classes of micro-organisms (i.e. with new characteristics from the perspective of whole rumen function in rumen models only delivers new insights if complemented by the dynamics of their interactions with other functional classes. Rumen fermentation conditions have to be represented due to their profound impact on the dynamics of substrate degradation and microbial metabolism. Although the importance of rumen acidity is generally acknowledged, more emphasis is needed on predicting its variation as well as variation in the processes that underlie rumen fluid dynamics. The rumen wall has an important role in adapting to rapid changes in the rumen environment, clearing of volatile fatty acids (VFA, and maintaining rumen pH within limits. Dynamics of rumen wall epithelia and its role in VFA absorption needs to be better represented in models which aim to predict rumen responses across nutritional or physiological states. For a detailed prediction of rumen N balance there is merit in a dynamic modeling approach compared to the static approaches adopted in current protein evaluation systems. Improvement is needed on previous attempts to predict rumen VFA profiles, and this should be pursued by introducing factors that relate more

  16. Toward a conceptual understanding of acute cultural adaptation: A preliminary examination of ACA in female swimming

    DEFF Research Database (Denmark)

    Ryba, Tatiana; Haapanen, Saara; Mosek, Shwiko

    2012-01-01

    This paper considers a novel approach to researching adaptation in transnational athletes. The first part introduces a conceptualisation of acute cultural adaptation (ACA), which extends the current literature in sport psychology by offering original insights into mechanisms underpinning adaptive...

  17. Force-induced bone growth and adaptation: A system theoretical approach to understanding bone mechanotransduction

    International Nuclear Information System (INIS)

    Maldonado, Solvey; Findeisen, Rolf

    2010-01-01

    The modeling, analysis, and design of treatment therapies for bone disorders based on the paradigm of force-induced bone growth and adaptation is a challenging task. Mathematical models provide, in comparison to clinical, medical and biological approaches an structured alternative framework to understand the concurrent effects of the multiple factors involved in bone remodeling. By now, there are few mathematical models describing the appearing complex interactions. However, the resulting models are complex and difficult to analyze, due to the strong nonlinearities appearing in the equations, the wide range of variability of the states, and the uncertainties in parameters. In this work, we focus on analyzing the effects of changes in model structure and parameters/inputs variations on the overall steady state behavior using systems theoretical methods. Based on an briefly reviewed existing model that describes force-induced bone adaptation, the main objective of this work is to analyze the stationary behavior and to identify plausible treatment targets for remodeling related bone disorders. Identifying plausible targets can help in the development of optimal treatments combining both physical activity and drug-medication. Such treatments help to improve/maintain/restore bone strength, which deteriorates under bone disorder conditions, such as estrogen deficiency.

  18. Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments.

    Science.gov (United States)

    Srivastava, Anubhav; Philip, Nisha; Hughes, Katie R; Georgiou, Konstantina; MacRae, James I; Barrett, Michael P; Creek, Darren J; McConville, Malcolm J; Waters, Andrew P

    2016-12-01

    Malaria parasites (Plasmodium spp.) encounter markedly different (nutritional) environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA) metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages. We show that glutamine serves as the predominant input into TCA metabolism in both asexual and sexual blood stages and is important for complete male gametogenesis. Glutamine catabolism, as well as key reactions in intermediary metabolism and CoA synthesis are also essential for ookinete to oocyst transition in the mosquito. These data extend our knowledge of Plasmodium metabolism and point towards possible targets for transmission-blocking intervention strategies. Furthermore, they highlight significant metabolic differences between Plasmodium species which are not easily anticipated based on genomics or transcriptomics studies and underline the importance of integration of metabolomics data with other platforms in order to better inform drug discovery and design.

  19. Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments.

    Directory of Open Access Journals (Sweden)

    Anubhav Srivastava

    2016-12-01

    Full Text Available Malaria parasites (Plasmodium spp. encounter markedly different (nutritional environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages. We show that glutamine serves as the predominant input into TCA metabolism in both asexual and sexual blood stages and is important for complete male gametogenesis. Glutamine catabolism, as well as key reactions in intermediary metabolism and CoA synthesis are also essential for ookinete to oocyst transition in the mosquito. These data extend our knowledge of Plasmodium metabolism and point towards possible targets for transmission-blocking intervention strategies. Furthermore, they highlight significant metabolic differences between Plasmodium species which are not easily anticipated based on genomics or transcriptomics studies and underline the importance of integration of metabolomics data with other platforms in order to better inform drug discovery and design.

  20. Adaptive Changes in Basal Metabolic Rate in Humans in Different Eco-Geographical Areas.

    Science.gov (United States)

    Maximov, Arkady L; Belkin, Victor Sh; Kalichman, Leonid; Kobyliansky, Eugene D

    2015-12-01

    Our aim was to establish whether the human basal metabolic rate (BMR) shifts towards the reduction of vital functions as an adaptation response to extreme environmental conditions. Data was collected in arid and Extreme North zones. The arid zone samples included Bedouins living in the Sinai Peninsula in Egypt, Turkmen students, the Pedagogical University of Chardzhou, Turkmenistan born Russians and Russian soldiers. Soldiers were divided into 3 groups according to the length of their tour of duty in the area: 1st group: up to six months, 2nd group: up to 2 years and the 3rd group: 3-5 years. The Extreme North samples comprised Chukchi natives, 1st generation Russian immigrants born in the area and 3 groups of soldiers comparable to the soldiers from Turkmenistan. BMR values of the new recruits had the highest values of total and relative BMR (1769 ± 16 and 28.3 ± 0.6, correspondingly). The total and relative BMR tended to decrease within a longer adaptation period. The BMR values of officers who served >3 years in Turkmenistan were very similar to the Turkmenistan born Russians (1730 ± 14 vs. 1726 ± 18 and 26.5 ± 0.6 vs. 27.3 ± 0.7, correspondingly). Similarly, in Chukotka, the highest relative BMR was found in the new recruits, serving up to 6 months (28.1 ± 0.7) and was significantly (p BMR was virtually similar in Russian officers serving > 3 years, compared to the middle-aged Chukchi or Chukotka-born Russians (25.8 ± 0.5 vs. 25.6 ± 0.5 and 25.5 ± 0.6, correspondingly). The BMR parameters demonstrated a stronger association with body weight than with age. In extreme environmental conditions, migrant populations showed a decrease in BMR, thus reducing its vital functions. The BMR reduction effect with the adequate adaptive transformation is likely to be the key strategy for developing programs to facilitate human and animal adaptation to extreme factors. This process is aimed at preserving the optimum energy balance and homeostasis while minimizing

  1. Adaptation to climate change and climate variability: The importance of understanding agriculture as performance

    OpenAIRE

    Crane, T.A.; Roncoli, C.; Hoogenboom, G.

    2011-01-01

    Most climate change studies that address potential impacts and potential adaptation strategies are largely based on modelling technologies. While models are useful for visualizing potential future outcomes and evaluating options for potential adaptation, they do not adequately represent and integrate adaptive human agency. Richards’ concept of ‘agriculture as performance’ is useful in counterbalancing the modelling approach to adaptation because it highlights how adaptive processes and techno...

  2. Understanding the adaptive growth strategy of Lactobacillus plantarum by in silico optimisation.

    NARCIS (Netherlands)

    Teusink, B.; Wiersma, A.; Jacobs, L.; Notebaart, R.A.; Smid, E.J.

    2009-01-01

    In the study of metabolic networks, optimization techniques are often used to predict flux distributions, and hence, metabolic phenotype. Flux balance analysis in particular has been successful in predicting metabolic phenotypes. However, an inherent limitation of a stoichiometric approach such as

  3. Understanding the Adaptive Growth Strategy of Lactobacillus plantarum by In Silico Optimisation

    NARCIS (Netherlands)

    Teusink, B.; Wiersma, A.; Jacobs, L.; Notebaart, R.A.; Smid, E.J.

    2009-01-01

    In the study of metabolic networks, optimization techniques are often used to predict flux distributions, and hence, metabolic phenotype. Flux balance analysis in particular has been successful in predicting metabolic phenotypes. However, an inherent limitation of a stoichiometric approach such as

  4. Cannabimimetic phytochemicals in the diet - an evolutionary link to food selection and metabolic stress adaptation?

    Science.gov (United States)

    Gertsch, Jürg

    2017-06-01

    The endocannabinoid system (ECS) is a major lipid signalling network that plays important pro-homeostatic (allostatic) roles not only in the nervous system but also in peripheral organs. There is increasing evidence that there is a dietary component in the modulation of the ECS. Cannabinoid receptors in hominids co-evolved with diet, and the ECS constitutes a feedback loop for food selection and energy metabolism. Here, it is postulated that the mismatch of ancient lipid genes of hunter-gatherers and pastoralists with the high-carbohydrate diet introduced by agriculture could be compensated for via dietary modulation of the ECS. In addition to the fatty acid precursors of endocannabinoids, the potential role of dietary cannabimimetic phytochemicals in agriculturist nutrition is discussed. Dietary secondary metabolites from vegetables and spices able to enhance the activity of cannabinoid-type 2 (CB 2 ) receptors may provide adaptive metabolic advantages and counteract inflammation. In contrast, chronic CB 1 receptor activation in hedonic obese individuals may enhance pathophysiological processes related to hyperlipidaemia, diabetes, hepatorenal inflammation and cardiometabolic risk. Food able to modulate the CB 1 /CB 2 receptor activation ratio may thus play a role in the nutrition transition of Western high-calorie diets. In this review, the interplay between diet and the ECS is highlighted from an evolutionary perspective. The emerging potential of cannabimimetic food as a nutraceutical strategy is critically discussed. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

  5. Optical imaging of metabolic adaptability in metastatic and non-metastatic breast cancer

    Science.gov (United States)

    Rebello, Lisa; Rajaram, Narasimhan

    2018-02-01

    Accurate methods for determining metastatic risk from the primary tumor are crucial for patient survival. Cell metabolism could potentially be used as a marker of metastatic risk. Optical imaging of the endogenous fluorescent molecules nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) provides a non-destructive and label-free method for determining cell metabolism. The optical redox ratio (FAD/FAD+NADH) is sensitive to the balance between glycolysis and oxidative phosphorylation (OXPHOS). We have previously established that hypoxia-reoxygenation stress leads to metastatic potential-dependent changes in optical redox ratio. The objective of this study was to monitor the changes in optical redox ratio in breast cancer cells in response to different periods of hypoxic stress as well various levels of hypoxia to establish an optimal protocol. We measured the optical redox ratio of highly metastatic 4T1 murine breast cancer cells under normoxic conditions and after exposure to 30, 60, and 120 minutes of 0.5% O2. This was followed by an hour of reoxygenation. We found an increase in the optical redox ratio following reoxygenation from hypoxia for all durations. Statistically significant differences were observed at 60 and 120 minutes (p˂0.01) compared with normoxia, implying an ability to adapt to OXPHOS after reoxygenation. The switch to OXPHOS has been shown to be a key promoter of cell invasion. We will present our results from these investigations in human breast cancer cells as well as non-metastatic breast cancer cells exposed to various levels of hypoxia.

  6. Neuronal Calcium Signaling in Metabolic Regulation and Adaptation to Nutrient Stress.

    Science.gov (United States)

    Jayakumar, Siddharth; Hasan, Gaiti

    2018-01-01

    All organisms can respond physiologically and behaviorally to environmental fluxes in nutrient levels. Different nutrient sensing pathways exist for specific metabolites, and their inputs ultimately define appropriate nutrient uptake and metabolic homeostasis. Nutrient sensing mechanisms at the cellular level require pathways such as insulin and target of rapamycin (TOR) signaling that integrates information from different organ systems like the fat body and the gut. Such integration is essential for coordinating growth with development. Here we review the role of a newly identified set of integrative interneurons and the role of intracellular calcium signaling within these neurons, in regulating nutrient sensing under conditions of nutrient stress. A comparison of the identified Drosophila circuit and cellular mechanisms employed in this circuit, with vertebrate systems, suggests that the identified cell signaling mechanisms may be conserved for neural circuit function related to nutrient sensing by central neurons. The ideas proposed are potentially relevant for understanding the molecular basis of metabolic disorders, because these are frequently linked to nutritional stress.

  7. Improving conservation outcomes with a new paradigm for understanding species’ fundamental and realized adaptive capacity

    Science.gov (United States)

    Beever, Erik; O’Leary, John; Mengelt, Claudia; West, Jordan M.; Julius, Susan; Green, Nancy; Magness, Dawn; Petes, Laura E.; Stein, Bruce A.; Nicotra, Adrienne B; Hellmann, Jessica J; Robertson, Amanda L; Staudinger, Michelle D.; Rosenberg, Andrew A.; Babij, Eleanora; Brennan, Jean; Schuurman, Gregor W.; Hofmann, Gretchen E

    2016-01-01

    Worldwide, many species are responding to ongoing climate change with shifts in distribution, abundance, phenology, or behavior. Consequently, natural-resource managers face increasingly urgent conservation questions related to biodiversity loss, expansion of invasive species, and deteriorating ecosystem services. We argue that our ability to address these questions is hampered by the lack of explicit consideration of species’ adaptive capacity (AC). AC is the ability of a species or population to cope with climatic changes and is characterized by three fundamental components: phenotypic plasticity, dispersal ability, and genetic diversity. However, few studies simultaneously address all elements; often, AC is confused with sensitivity or omitted altogether from climate-change vulnerability assessments. Improved understanding, consistent definition, and comprehensive evaluations of AC are needed. Using classic ecological-niche theory as an analogy, we propose a new paradigm that considers fundamental and realized AC: the former reflects aspects inherent to species, whereas the latter denotes how extrinsic factors constrain AC to what is actually expressed or observed. Through this conceptualization, we identify ecological attributes contributing to AC, outline areas of research necessary to advance understanding of AC, and provide examples demonstrating how the inclusion of AC can better inform conservation and natural-resource management.

  8. Comparative shotgun proteomic analysis of wild and domesticated Opuntia spp. species shows a metabolic adaptation through domestication.

    Science.gov (United States)

    Pichereaux, Carole; Hernández-Domínguez, Eric E; Santos-Diaz, Maria Del Socorro; Reyes-Agüero, Antonio; Astello-García, Marizel; Guéraud, Françoise; Negre-Salvayre, Anne; Schiltz, Odile; Rossignol, Michel; Barba de la Rosa, Ana Paulina

    2016-06-30

    The Opuntia genus is widely distributed in America, but the highest richness of wild species are found in Mexico, as well as the most domesticated Opuntia ficus-indica, which is the most domesticated species and an important crop in agricultural economies of arid and semiarid areas worldwide. During domestication process, the Opuntia morphological characteristics were favored, such as less and smaller spines in cladodes and less seeds in fruits, but changes at molecular level are almost unknown. To obtain more insights about the Opuntia molecular changes through domestication, a shotgun proteomic analysis and database-dependent searches by homology was carried out. >1000 protein species were identified and by using a label-free quantitation method, the Opuntia proteomes were compared in order to identify differentially accumulated proteins among wild and domesticated species. Most of the changes were observed in glucose, secondary, and 1C metabolism, which correlate with the observed protein, fiber and phenolic compounds accumulation in Opuntia cladodes. Regulatory proteins, ribosomal proteins, and proteins related with response to stress were also observed in differential accumulation. These results provide new valuable data that will help to the understanding of the molecular changes of Opuntia species through domestication. Opuntia species are well adapted to dry and warm conditions in arid and semiarid regions worldwide, and they are highly productive plants showing considerable promises as an alternative food source. However, there is a gap regarding Opuntia molecular mechanisms that enable them to grow in extreme environmental conditions and how the domestication processes has changed them. In the present study, a shotgun analysis was carried out to characterize the proteomes of five Opuntia species selected by its domestication degree. Our results will help to a better understanding of proteomic features underlying the selection and specialization under

  9. Insights into metabolism and sodium chloride adaptability of carbaryl degrading halotolerant Pseudomonas sp. strain C7.

    Science.gov (United States)

    Trivedi, Vikas D; Bharadwaj, Anahita; Varunjikar, Madhushri S; Singha, Arminder K; Upadhyay, Priya; Gautam, Kamini; Phale, Prashant S

    2017-08-01

    Pseudomonas sp. strain C7 isolated from sediment of Thane creek near Mumbai, India, showed the ability to grow on glucose and carbaryl in the presence of 7.5 and 3.5% of NaCl, respectively. It also showed good growth in the absence of NaCl indicating the strain to be halotolerant. Increasing salt concentration impacted the growth on carbaryl; however, the specific activity of various enzymes involved in the metabolism remained unaffected. Among various enzymes, 1-naphthol 2-hydroxylase was found to be sensitive to chloride as compared to carbaryl hydrolase and gentisate 1,2-dioxygenase. The intracellular concentration of Cl - ions remained constant (6-8 mM) for cells grown on carbaryl either in the presence or absence of NaCl. Thus the ability to adapt to the increasing concentration of NaCl is probably by employing chloride efflux pump and/or increase in the concentration of osmolytes as mechanism for halotolerance. The halotolerant nature of the strain will be beneficial to remediate carbaryl from saline agriculture fields, ecosystems and wastewaters.

  10. Adaptation of metabolism and evaporative water loss along an aridity gradient.

    Science.gov (United States)

    Tieleman, B Irene; Williams, Joseph B; Bloomer, Paulette

    2003-01-22

    Broad-scale comparisons of birds indicate the possibility of adaptive modification of basal metabolic rate (BMR) and total evaporative water loss (TEWL) in species from desert environments, but these might be confounded by phylogeny or phenotypic plasticity. This study relates variation in avian BMR and TEWL to a continuously varying measure of environment, aridity. We test the hypotheses that BMR and TEWL are reduced along an aridity gradient within the lark family (Alaudidae), and investigate the role of phylogenetic inertia. For 12 species of lark, BMR and TEWL decreased along a gradient of increasing aridity, a finding consistent with our proposals. We constructed a phylogeny for 22 species of lark based on sequences of two mitochondrial genes, and investigated whether phylogenetic affinity played a part in the correlation of phenotype and environment. A test for serial independence of the data for mass-corrected TEWL and aridity showed no influence of phylogeny on our findings. However, we did discover a significant phylogenetic effect in mass-corrected data for BMR, a result attributable to common phylogenetic history or to common ecological factors. A test of the relationship between BMR and aridity using phylogenetic independent constrasts was consistent with our previous analysis: BMR decreased with increasing aridity.

  11. Clear differences in metabolic and morphological adaptations of akinetes of two Nostocales living in different habitats.

    Science.gov (United States)

    Perez, Rebeca; Forchhammer, Karl; Salerno, Graciela; Maldener, Iris

    2016-02-01

    Akinetes are resting spore-like cells formed by some heterocyst-forming filamentous cyanobacteria for surviving long periods of unfavourable conditions. We studied the development of akinetes in two model strains of cyanobacterial cell differentiation, the planktonic freshwater Anabaena variabilis ATCC 29413 and the terrestrial or symbiotic Nostoc punctiforme ATCC 29133, in response to low light and phosphate starvation. The best trigger of akinete differentiation of Anabaena variabilis was low light; that of N. punctiforme was phosphate starvation. Light and electron microscopy revealed that akinetes of both species differed from vegetative cells by their larger size, different cell morphology and large number of intracellular granules. Anabaena variabilis akinetes had a multilayer envelope; those of N. punctiforme had a simpler envelope. During akinete development of Anabaena variabilis, the amount of the storage compounds cyanophycin and glycogen increased transiently, whereas in N. punctiforme, cyanophycin and lipid droplets increased transiently. Photosynthesis and respiration decreased during akinete differentiation in both species, and remained at a low level in mature akinetes. The clear differences in the metabolic and morphological adaptations of akinetes of the two species could be related to their different lifestyles. The results pave the way for genetic and functional studies of akinete differentiation in these species.

  12. For a better understanding of adaptive capacity to climate change: a research framework

    International Nuclear Information System (INIS)

    Magnan, Alexandre

    2010-05-01

    It is generally accepted that there exists a systematic link between a low level of adaptive capacity and a low level of development, which thus implies that the poor inevitably have low adaptive capacities. We argue here that this viewpoint is biased because adaptation to climate change is not solely determined by economic and technological capacities. Many other characteristics of a community can play a major role in its ability to react to and anticipate climate changes (e.g. the territorial identity or the social relationships). From our point of view, this limited view of adaptive capacity is related to a relative immaturity of the science of adaptation, a discipline that analyses the processes and determinants of adaptive capacity. This can be explained by the fact that there are currently few existing frameworks for studying adaptive capacity. This paper consists in a proposal for a research framework which is based upon four main fields of investigation: (i) the influential factors of adaptive capacity and their interactions, (ii) the relevant spatial and temporal scales of adaptive capacity, (iii) the links between adaptive capacity, vulnerability and the level of development and (iv) the theoretical links between adaptation and sustainability. These four fields of research should bring new knowledge on adaptive capacity and feed a more general reflection on the adaptation pathways for dealing with climate change. (author)

  13. Understanding the relationship between the variability in agrometeorological indices and adaptation practices across the Canadian Prairies

    Science.gov (United States)

    Chipanshi, A.; Qi, D.; Zhang, Y.; Cherneski, P.

    2017-12-01

    In an attempt to understand how agriculture will adapt to the changing and variable climate, crop based agrometeorological indices including the Effective Growing Degree Days (EGDDs), Growing Season Length (GSL), Heat waves, Water Demand (Precipitation - Evapotranspiration) and the Standardized Precipitation Evapotranspiration Index (SPEI) were analyzed in terms of frequency, duration and trend over a 63-year timeframe (1950 to 2012) from the Canadian Prairies and related to crop production. The heat based indices (EGDD, GSL and Heat waves) increased over the analysis period due to an upward increase in the observed mean temperature. The change was most noticeable in the northern portion of the study area where agriculture is limited by insufficient heat units under the present climate. Heat waves became more frequent in the southern parts of the study area (there were more days above the 30oC threshold). Water availability as assessed from water demand (P-PE) and SPEI trended downward especially in Alberta and Saskatchewan. In spite of the increased severity and frequency in water deficits, there was a noticeable reduction in the variability of crop yield over time. This was attributed to the increased adaptive capacity that has been gained through the use of improved seed hybrids, fertilizer, the use of fungicides and adoption of best management practices such as zero till and direct seeding. After crop yields were de-trended to remove effects of technology, the cumulative precipitation during the growing season explained the majority of the variance in crop yield. This initial analysis has set the stage for analyzing the characteristics of agrometeorological indices under climate change scenarios and how accumulated precipitation during the growing season will affect crop yield and production.

  14. Understanding stakeholder preferences for flood adaptation alternatives with natural capital implications

    Directory of Open Access Journals (Sweden)

    Jonathon R. Loos

    2016-09-01

    Full Text Available Inland flood risks are defined by a range of environmental and social factors, including land use and floodplain management. Shifting patterns of storm intensity and precipitation, attributed to climate change, are exacerbating flood risk in regions across North America. Strategies for adapting to growing flood risks and climate change must account for a community's specific vulnerabilities, and its local economic, environmental, and social conditions. Through a stakeholder-engaged methodology, we designed an interactive decision exercise to enable stakeholders to evaluate alternatives for addressing specific community flood vulnerabilities. We used a multicriteria framework to understand what drives stakeholder preferences for flood mitigation and adaptation alternatives, including ecosystem-based projects. Results indicated strong preferences for some ecosystem-based projects that utilize natural capital, generated a useful discussion on the role of individual values in driving decisions and a critique of local environmental and hazard planning procedure, and uncovered support for a river management alternative that had previously been considered socially infeasible. We conclude that a multicriteria decision framework may help ensure that the multiple benefit qualities of natural capital projects are considered by decision makers. Application of a utility function can demonstrate the role of individual decision-maker values in decision outcomes and help illustrate why one alternative may be a better choice than another. Although designing an efficient and accurate multicriteria exercise is quite challenging and often data intensive, we imagine that this method is applicable elsewhere. It may be especially suitable to group decisions that involve varying levels of expertise and competing values, as is often the case in planning for the ecological and human impacts of climate change.

  15. How low can you go? An adaptive energetic framework for interpreting basal metabolic rate variation in endotherms.

    Science.gov (United States)

    Swanson, David L; McKechnie, Andrew E; Vézina, François

    2017-12-01

    Adaptive explanations for both high and low body mass-independent basal metabolic rate (BMR) in endotherms are pervasive in evolutionary physiology, but arguments implying a direct adaptive benefit of high BMR are troublesome from an energetic standpoint. Here, we argue that conclusions about the adaptive benefit of BMR need to be interpreted, first and foremost, in terms of energetics, with particular attention to physiological traits on which natural selection is directly acting. We further argue from an energetic perspective that selection should always act to reduce BMR (i.e., maintenance costs) to the lowest level possible under prevailing environmental or ecological demands, so that high BMR per se is not directly adaptive. We emphasize the argument that high BMR arises as a correlated response to direct selection on other physiological traits associated with high ecological or environmental costs, such as daily energy expenditure (DEE) or capacities for activity or thermogenesis. High BMR thus represents elevated maintenance costs required to support energetically demanding lifestyles, including living in harsh environments. BMR is generally low under conditions of relaxed selection on energy demands for high metabolic capacities (e.g., thermoregulation, activity) or conditions promoting energy conservation. Under these conditions, we argue that selection can act directly to reduce BMR. We contend that, as a general rule, BMR should always be as low as environmental or ecological conditions permit, allowing energy to be allocated for other functions. Studies addressing relative reaction norms and response times to fluctuating environmental or ecological demands for BMR, DEE, and metabolic capacities and the fitness consequences of variation in BMR and other metabolic traits are needed to better delineate organismal metabolic responses to environmental or ecological selective forces.

  16. Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics.

    Science.gov (United States)

    Chicco, Adam J; Le, Catherine H; Gnaiger, Erich; Dreyer, Hans C; Muyskens, Jonathan B; D'Alessandro, Angelo; Nemkov, Travis; Hocker, Austin D; Prenni, Jessica E; Wolfe, Lisa M; Sindt, Nathan M; Lovering, Andrew T; Subudhi, Andrew W; Roach, Robert C

    2018-05-04

    Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project. In contrast to the view that hypoxia down-regulates aerobic metabolism, results show that mitochondria play a central role in muscle hypoxia adaptation by supporting higher resting phosphorylation potential and enhancing the efficiency of long-chain acylcarnitine oxidation. This directs increases in muscle glucose toward pentose phosphate and one-carbon metabolism pathways that support cytosolic redox balance and help mitigate the effects of increased protein and purine nucleotide catabolism in hypoxia. Muscle accumulation of free amino acids favor these adjustments by coordinating cytosolic and mitochondrial pathways to rid the cell of excess nitrogen, but might ultimately limit muscle oxidative capacity in vivo Collectively, these studies illustrate how an integration of aerobic and anaerobic metabolism is required for physiological hypoxia adaptation in skeletal muscle, and highlight protein catabolism and allosteric regulation as unexpected orchestrators of metabolic remodeling in this context. These findings have important implications for the management of hypoxia-related diseases and other conditions associated with chronic catabolic stress. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Metabolomics by proton nuclear magnetic resonance spectroscopy of the response to chloroethylnitrosourea reveals drug efficacy and tumor adaptive metabolic pathways.

    Science.gov (United States)

    Morvan, Daniel; Demidem, Aicha

    2007-03-01

    Metabolomics of tumors may allow discovery of tumor biomarkers and metabolic therapeutic targets. Metabolomics by two-dimensional proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy was applied to investigate metabolite disorders following treatment by chloroethylnitrosourea of murine B16 melanoma (n = 33) and 3LL pulmonary carcinoma (n = 31) in vivo. Treated tumors of both types resumed growth after a delay. Nitrosoureas provoke DNA damage but the metabolic consequences of genotoxic stress are little known yet. Although some differences were observed in the metabolite profile of untreated tumor types, the prominent metabolic features of the response to nitrosourea were common to both. During the growth inhibition phase, there was an accumulation of glucose (more than x10; P < 0.05), glutamine (x3 to 4; P < 0.01), and aspartate (x2 to 5; P < 0.01). This response testified to nucleoside de novo synthesis down-regulation and drug efficacy. However, this phase also involved the increase in alanine (P < 0.001 in B16 melanoma), the decrease in succinate (P < 0.001), and the accumulation of serine-derived metabolites (glycine, phosphoethanolamine, and formate; P < 0.01). This response witnessed the activation of pathways implicated in energy production and resumption of nucleotide de novo synthesis, thus metabolic pathways of DNA repair and adaptation to treatment. During the growth recovery phase, it remained polyunsaturated fatty acid accumulation (x1.5 to 2; P < 0.05) and reduced utilization of glucose compared with glutamine (P < 0.05), a metabolic fingerprint of adaptation. Thus, this study provides the proof of principle that metabolomics of tumor response to an anticancer agent may help discover metabolic pathways of drug efficacy and adaptation to treatment.

  18. Adaptation to climate change and climate variability:The importance of understanding agriculture as performance

    NARCIS (Netherlands)

    Crane, T.A.; Roncoli, C.; Hoogenboom, G.

    2011-01-01

    Most climate change studies that address potential impacts and potential adaptation strategies are largely based on modelling technologies. While models are useful for visualizing potential future outcomes and evaluating options for potential adaptation, they do not adequately represent and

  19. Jatropha curcas, a biofuel crop: functional genomics for understanding metabolic pathways and genetic improvement.

    Science.gov (United States)

    Maghuly, Fatemeh; Laimer, Margit

    2013-10-01

    Jatropha curcas is currently attracting much attention as an oilseed crop for biofuel, as Jatropha can grow under climate and soil conditions that are unsuitable for food production. However, little is known about Jatropha, and there are a number of challenges to be overcome. In fact, Jatropha has not really been domesticated; most of the Jatropha accessions are toxic, which renders the seedcake unsuitable for use as animal feed. The seeds of Jatropha contain high levels of polyunsaturated fatty acids, which negatively impact the biofuel quality. Fruiting of Jatropha is fairly continuous, thus increasing costs of harvesting. Therefore, before starting any improvement program using conventional or molecular breeding techniques, understanding gene function and the genome scale of Jatropha are prerequisites. This review presents currently available and relevant information on the latest technologies (genomics, transcriptomics, proteomics and metabolomics) to decipher important metabolic pathways within Jatropha, such as oil and toxin synthesis. Further, it discusses future directions for biotechnological approaches in Jatropha breeding and improvement. © 2013 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Going beyond energy intensity to understand the energy metabolism of nations: The case of Argentina

    International Nuclear Information System (INIS)

    Recalde, Marina; Ramos-Martin, Jesús

    2012-01-01

    The link between energy consumption and economic growth has been widely studied in the economic literature. Understanding this relationship is important from both an environmental and a socio-economic point of view, as energy consumption is crucial to economic activity and human environmental impact. This relevance is even higher for developing countries, since energy consumption per unit of output varies through the phases of development, increasing from an agricultural stage to an industrial one and then decreasing for certain service based economies. In the Argentinean case, the relevance of energy consumption to economic development seems to be particularly important. While energy intensity seems to exhibit a U-Shaped curve from 1990 to 2003 decreasing slightly after that year, total energy consumption increases along the period of analysis. Why does this happen? How can we relate this result with the sustainability debate? All these questions are very important due to Argentinean hydrocarbons dependence and due to the recent reduction in oil and natural gas reserves, which can lead to a lack of security of supply. In this paper we study Argentinean energy consumption pattern for the period 1990–2007, to discuss current and future energy and economic sustainability. To this purpose, we developed a conventional analysis, studying energy intensity, and a non conventional analysis, using the Multi-Scale Integrated Analysis of Societal and Ecosystem Metabolism (MuSIASEM) accounting methodology. Both methodologies show that the development process followed by Argentina has not been good enough to assure sustainability in the long term. Instead of improving energy use, energy intensity has increased. The current composition of its energy mix, and the recent economic crisis in Argentina, as well as its development path, are some of the possible explanations. -- Highlights: ► We analyze Argentinean energy consumption and social metabolism using MuSIASEM.

  1. Metabolism

    Science.gov (United States)

    ... 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 ...

  2. Understanding the physiology and adaptation of staphylococci: a post-genomic approach.

    Science.gov (United States)

    Becker, Karsten; Bierbaum, Gabriele; von Eiff, Christof; Engelmann, Susanne; Götz, Friedrich; Hacker, Jörg; Hecker, Michael; Peters, Georg; Rosenstein, Ralf; Ziebuhr, Wilma

    2007-11-01

    Staphylococcus aureus as well as coagulase-negative staphylococci are medically highly important pathogens characterized by an increasing resistance rate toward many antibiotics. Although normally being skin and mucosa commensals, some staphylococcal species and strains have the capacity to cause a wide range of infectious diseases. Many of these infections affect immunocompromised patients in hospitals. However, community-acquired staphylococcal infections due to resistant strains are also currently on the rise. In the light of this development, there is an urgent need for novel anti-staphylococcal therapeutic and prevention strategies for which a better understanding of the physiology of these bacteria is an essential prerequisite. Within the past years, staphylococci have been in the focus of genomic research, resulting in the determination and publication of a range of full-genome sequences of different staphylococcal species and strains which provided the basis for the design and application of DNA microarrays and other genomic tools. Here we summarize the results of the project group 'Staphylococci' within the research network 'Pathogenomics' giving new insights into the genome structure, molecular epidemiology, physiology, and genetic adaptation of both S. aureus and coagulase-negative staphylococci.

  3. Venom Resistance as a Model for Understanding the Molecular Basis of Complex Coevolutionary Adaptations.

    Science.gov (United States)

    Holding, Matthew L; Drabeck, Danielle H; Jansa, Sharon A; Gibbs, H Lisle

    2016-11-01

    SynopsisVenom and venom resistance are molecular phenotypes widely considered to have diversified through coevolution between predators and prey. However, while evolutionary and functional studies on venom have been extensive, little is known about the molecular basis, variation, and complexity of venom resistance. We review known mechanisms of venom resistance and relate these mechanisms to their predicted impact on coevolutionary dynamics with venomous enemies. We then describe two conceptual approaches which can be used to examine venom/resistance systems. At the intraspecific level, tests of local adaptation in venom and resistance phenotypes can identify the functional mechanisms governing the outcomes of coevolution. At deeper evolutionary timescales, the combination of phylogenetically informed analyses of protein evolution coupled with studies of protein function promise to elucidate the mode and tempo of evolutionary change on potentially coevolving genes. We highlight case studies that use each approach to extend our knowledge of these systems as well as address larger questions about coevolutionary dynamics. We argue that resistance and venom are phenotypic traits which hold exceptional promise for investigating the mechanisms, dynamics, and outcomes of coevolution at the molecular level. Furthermore, extending the understanding of single gene-for-gene interactions to the whole resistance and venom phenotypes may provide a model system for examining the molecular and evolutionary dynamics of complex multi-gene interactions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  4. Applying a complex adaptive system's understanding of health to primary care [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Johannes Bircher

    2016-09-01

    Full Text Available This paper explores the diagnostic and therapeutic potential of a new concept of health. Investigations into the nature of health have led to a new definition that explains health as a complex adaptive system (CAS and is based on five components (a-e. Humans like all biological creatures must satisfactorily respond to (a the demands of life. For this purpose they need (b a biologically given potential (BGP and (c a personally acquired potential (PAP. These properties of individuals are embedded within (d social and (e environmental determinants of health. Between these five components of health there are 10 complex interactions that justify viewing health as a CAS. In each patient, the current state of health as a CAS evolved from the past, will move forward to a new future, and has to be analyzed and treated as an autonomous whole. A diagnostic procedure is suggested as follows: together with the patient, the five components and 10 complex interactions are assessed. This may help patients to better understand their situations and to recognize possible next steps that may be useful in order to evolve toward better health by themselves. In this process mutual trust in the patient-physician interaction is critical. The described approach offers new possibilities for helping patients improve their health prospects.

  5. Understanding alternative fluxes/effluxes through comparative metabolic pathway analysis of phylum actinobacteria using a simplified approach.

    Science.gov (United States)

    Verma, Mansi; Lal, Devi; Saxena, Anjali; Anand, Shailly; Kaur, Jasvinder; Kaur, Jaspreet; Lal, Rup

    2013-12-01

    Actinobacteria are known for their diverse metabolism and physiology. Some are dreadful human pathogens whereas some constitute the natural flora for human gut. Therefore, the understanding of metabolic pathways is a key feature for targeting the pathogenic bacteria without disturbing the symbiotic ones. A big challenge faced today is multiple drug resistance by Mycobacterium and other pathogens that utilize alternative fluxes/effluxes. With the availability of genome sequence, it is now feasible to conduct the comparative in silico analysis. Here we present a simplified approach to compare metabolic pathways so that the species specific enzyme may be traced and engineered for future therapeutics. The analyses of four key carbohydrate metabolic pathways, i.e., glycolysis, pyruvate metabolism, tri carboxylic acid cycle and pentose phosphate pathway suggest the presence of alternative fluxes. It was found that the upper pathway of glycolysis was highly variable in the actinobacterial genomes whereas lower glycolytic pathway was highly conserved. Likewise, pentose phosphate pathway was well conserved in contradiction to TCA cycle, which was found to be incomplete in majority of actinobacteria. The clustering based on presence and absence of genes of these metabolic pathways clearly revealed that members of different genera shared identical pathways and, therefore, provided an easy method to identify the metabolic similarities/differences between pathogenic and symbiotic organisms. The analyses could identify isoenzymes and some key enzymes that were found to be missing in some pathogenic actinobacteria. The present work defines a simple approach to explore the effluxes in four metabolic pathways within the phylum actinobacteria. The analysis clearly reflects that actinobacteria exhibit diverse routes for metabolizing substrates. The pathway comparison can help in finding the enzymes that can be used as drug targets for pathogens without effecting symbiotic organisms

  6. Actionable Metabolic Pathways in Heart Failure and Cancer—Lessons From Cancer Cell Metabolism

    Directory of Open Access Journals (Sweden)

    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.

  7. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota.

    Science.gov (United States)

    Serino, Matteo; Luche, Elodie; Gres, Sandra; Baylac, Audrey; Bergé, Mathieu; Cenac, Claire; Waget, Aurelie; Klopp, Pascale; Iacovoni, Jason; Klopp, Christophe; Mariette, Jerome; Bouchez, Olivier; Lluch, Jerome; Ouarné, Francoise; Monsan, Pierre; Valet, Philippe; Roques, Christine; Amar, Jacques; Bouloumié, Anne; Théodorou, Vassilia; Burcelin, Remy

    2012-04-01

    The gut microbiota, which is considered a causal factor in metabolic diseases as shown best in animals, is under the dual influence of the host genome and nutritional environment. This study investigated whether the gut microbiota per se, aside from changes in genetic background and diet, could sign different metabolic phenotypes in mice. The unique animal model of metabolic adaptation was used, whereby C57Bl/6 male mice fed a high-fat carbohydrate-free diet (HFD) became either diabetic (HFD diabetic, HFD-D) or resisted diabetes (HFD diabetes-resistant, HFD-DR). Pyrosequencing of the gut microbiota was carried out to profile the gut microbial community of different metabolic phenotypes. Inflammation, gut permeability, features of white adipose tissue, liver and skeletal muscle were studied. Furthermore, to modify the gut microbiota directly, an additional group of mice was given a gluco-oligosaccharide (GOS)-supplemented HFD (HFD+GOS). Despite the mice having the same genetic background and nutritional status, a gut microbial profile specific to each metabolic phenotype was identified. The HFD-D gut microbial profile was associated with increased gut permeability linked to increased endotoxaemia and to a dramatic increase in cell number in the stroma vascular fraction from visceral white adipose tissue. Most of the physiological characteristics of the HFD-fed mice were modulated when gut microbiota was intentionally modified by GOS dietary fibres. The gut microbiota is a signature of the metabolic phenotypes independent of differences in host genetic background and diet.

  8. Imaging the NADH:NAD+ Homeostasis for Understanding the Metabolic Response of Mycobacterium to Physiologically Relevant Stresses.

    Science.gov (United States)

    Bhat, Shabir A; Iqbal, Iram K; Kumar, Ashwani

    2016-01-01

    The NADH:NAD + ratio is the primary indicator of the metabolic state of bacteria. NAD(H) homeostasis is critical for Mycobacterium tuberculosis (Mtb) survival and is thus considered an important drug target, but the spatio-temporal measurements of NAD(H) remain a challenge. Genetically encoded fluorescent biosensors of the NADH:NAD + ratios were recently described, paving the way for investigations of the metabolic state of pathogens during infection. Here we have adapted the genetically encoded biosensor Peredox for measurement of the metabolic state of Mtb in vitro and during infection of macrophage cells. Using Peredox, here we show that inhibition of the electron transport chain, disruption of the membrane potential and proton gradient, exposure to reactive oxygen species and treatment with antimycobacterial drugs led to the accumulation of NADH in mycobacterial cells. We have further demonstrated that Mtb residing in macrophages displays higher NADH:NAD + ratios, that may indicate a metabolic stress faced by the intracellular Mtb. We also demonstrate that the Mtb residing in macrophages display a metabolic heterogeneity, which may perhaps explain the tolerance displayed by intracellular Mtb. Next we studied the effect of immunological modulation by interferon gamma on metabolism of intracellular Mtb, since macrophage activation is known to restrict mycobacterial growth. We observed that activation of resting macrophages with interferon-gamma results in higher NADH:NAD + levels in resident Mtb cells. We have further demonstrated that exposure of Isoniazid, Bedaquiline, Rifampicin, and O-floxacin results in higher NADH:NAD + ratios in the Mtb residing in macrophages. However, intracellular Mtb displays lower NADH:NAD + ratio upon exposure to clofazimine. In summary, we have generated reporter strains capable of measuring the metabolic state of Mtb cells in vitro and in vivo with spatio-temporal resolution. We believe that this tool will facilitate further

  9. Adaptive radiation versus 'radiation' and 'explosive diversification': why conceptual distinctions are fundamental to understanding evolution.

    Science.gov (United States)

    Givnish, Thomas J

    2015-07-01

    Adaptive radiation is the rise of a diversity of ecological roles and role-specific adaptations within a lineage. Recently, some researchers have begun to use 'adaptive radiation' or 'radiation' as synonymous with 'explosive species diversification'. This essay aims to clarify distinctions between these concepts, and the related ideas of geographic speciation, sexual selection, key innovations, key landscapes and ecological keys. Several examples are given to demonstrate that adaptive radiation and explosive diversification are not the same phenomenon, and that focusing on explosive diversification and the analysis of phylogenetic topology ignores much of the rich biology associated with adaptive radiation, and risks generating confusion about the nature of the evolutionary forces driving species diversification. Some 'radiations' involve bursts of geographic speciation or sexual selection, rather than adaptive diversification; some adaptive radiations have little or no effect on speciation, or even a negative effect. Many classic examples of 'adaptive radiation' appear to involve effects driven partly by geographic speciation, species' dispersal abilities, and the nature of extrinsic dispersal barriers; partly by sexual selection; and partly by adaptive radiation in the classical sense, including the origin of traits and invasion of adaptive zones that result in decreased diversification rates but add to overall diversity. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

  10. Transcriptomic study to understand thermal adaptation in a high temperature-tolerant strain of Pyropia haitanensis.

    Science.gov (United States)

    Wang, Wenlei; Teng, Fei; Lin, Yinghui; Ji, Dehua; Xu, Yan; Chen, Changsheng; Xie, Chaotian

    2018-01-01

    Pyropia haitanensis, a high-yield commercial seaweed in China, is currently undergoing increasing levels of high-temperature stress due to gradual global warming. The mechanisms of plant responses to high temperature stress vary with not only plant type but also the degree and duration of high temperature. To understand the mechanism underlying thermal tolerance in P. haitanensis, gene expression and regulation in response to short- and long-term temperature stresses (SHS and LHS) was investigated by performing genome-wide high-throughput transcriptomic sequencing for a high temperature tolerant strain (HTT). A total of 14,164 differential expression genes were identified to be high temperature-responsive in at least one time point by high-temperature treatment, representing 41.10% of the total number of unigenes. The present data indicated a decrease in the photosynthetic and energy metabolic rates in HTT to reduce unnecessary energy consumption, which in turn facilitated in the rapid establishment of acclimatory homeostasis in its transcriptome during SHS. On the other hand, an increase in energy consumption and antioxidant substance activity was observed with LHS, which apparently facilitates in the development of resistance against severe oxidative stress. Meanwhile, ubiquitin-mediated proteolysis, brassinosteroids, and heat shock proteins also play a vital role in HTT. The effects of SHS and LHS on the mechanism of HTT to resist heat stress were relatively different. The findings may facilitate further studies on gene discovery and the molecular mechanisms underlying high-temperature tolerance in P. haitanensis, as well as allow improvement of breeding schemes for high temperature-tolerant macroalgae that can resist global warming.

  11. Adaptation and Mitigation in Agriculture: A Review of Synergies and Tradeoffs and How EO Could Improve Understanding and Outcomes

    Science.gov (United States)

    Barbieri, L.; Wollenberg, E.

    2017-12-01

    We present a review of the published literature on agricultural adaptation and mitigation, and report on the current evidence as to whether changes in agricultural practices meant to achieve mitigation or adaptation goals can be dual purpose: simultaneously reducing greenhouse gas (GHG) emissions and helping to facilitate adaptation. We characterize the spatio-temporal and system trends in how adaptation and mitigation outcomes are being achieved, and report on the current technical and knowledge gaps that exist and where Earth observations (EO) could improve our understanding. Agriculture contributes 12% GHG emissions globally, roughly one third from the developing world. Nearly 70% of the technical mitigation potential in agriculture sector occurs in these countries, however, while the mitigation potential is high, agricultural productivity also relies heavily on climate factors. With climate change, agricultural systems already, and will increasingly, need to adapt to extreme events and variability in temperatures and precipitation. This underscores the importance of implementing agricultural practices that can both reduce GHG emissions and help facilitate adaptation. Until recently, these objectives have been treated separately, but policy makers are increasingly calling for a joint approach to improve synergies, and avoid tradeoffs. There remain many complications in considering a joint approach: lack of clear conceptual frameworks, knowledge gaps in scientific understanding and evidence associated with adaptation and mitigation outcomes, and the abilities and motivations of stakeholders to consider both objectives. We review 56 peer-reviewed publications and present results from an in-depth analysis to answer two major concerns: to what extent is evidence provided for claims of synergistic outcomes, and what uncertainty surrounds this evidence. Our results show that only 21% of studies empirically measured both mitigation and adaptation outcomes, and claims

  12. Understanding the adaptation deficit: why are poor countries more vulnerable to climate events than rich countries?

    OpenAIRE

    Samuel Fankhauser; Thomas K. J. McDermott

    2014-01-01

    Poor countries are more heavily affected by extreme weather events and future climate change than rich countries. This discrepancy is sometimes known as an adaptation deficit. This paper analyses the link between income and adaptation to climate events theoretically and empirically. We postulate that the adaptation deficit is due to two factors: A demand effect, whereby the demand for the good �climate security� increases with income, and an efficiency effect, which works as a spill-over exte...

  13. mTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation.

    Science.gov (United States)

    Sinclair, Charles; Bommakanti, Gayathri; Gardinassi, Luiz; Loebbermann, Jens; Johnson, Matthew Joseph; Hakimpour, Paul; Hagan, Thomas; Benitez, Lydia; Todor, Andrei; Machiah, Deepa; Oriss, Timothy; Ray, Anuradha; Bosinger, Steven; Ravindran, Rajesh; Li, Shuzhao; Pulendran, Bali

    2017-09-08

    Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103 + DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b + DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (T H 2) to neutrophilic T H 17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  14. Understanding the leaky engineering pipeline: Motivation and job adaptability of female engineers

    Science.gov (United States)

    Saraswathiamma, Manjusha Thekkedathu

    This dissertation is a mixed-method study conducted using qualitative grounded theory and quantitative survey and correlation approaches. This study aims to explore the motivation and adaptability of females in the engineering profession and to develop a theoretical framework for both motivation and adaptability issues. As a result, this study endeavors to design solutions for the low enrollment and attenuation of female engineers in the engineering profession, often referred to as the "leaky female engineering pipeline." Profiles of 123 female engineers were studied for the qualitative approach, and 98 completed survey responses were analyzed for the quantitative approach. The qualitative, grounded-theory approach applied the constant comparison method; open, axial, and selective coding was used to classify the information in categories, sub-categories, and themes for both motivation and adaptability. The emergent themes for decisions motivating female enrollment include cognitive, emotional, and environmental factors. The themes identified for adaptability include the seven job adaptability factors: job satisfaction, risk- taking attitude, career/skill development, family, gender stereotyping, interpersonal skills, and personal benefit, as well as the self-perceived job adaptability factor. Illeris' Three-dimensional Learning Theory was modified as a model for decisions motivating female enrollment. This study suggests a firsthand conceptual parallelism of McClusky's Theory of Margin for the adaptability of female engineers in the profession. Also, this study attempted to design a survey instrument to measure job adaptability of female engineers. The study identifies two factors that are significantly related to job adaptability: interpersonal skills (related.

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

    Science.gov (United States)

    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.

  16. Adaptive Planning: Understanding Organizational Workload to Capability/ Capacity through Modeling and Simulation

    Science.gov (United States)

    Hase, Chris

    2010-01-01

    In August 2003, the Secretary of Defense (SECDEF) established the Adaptive Planning (AP) initiative [1] with an objective of reducing the time necessary to develop and revise Combatant Commander (COCOM) contingency plans and increase SECDEF plan visibility. In addition to reducing the traditional plan development timeline from twenty-four months to less than twelve months (with a goal of six months)[2], AP increased plan visibility to Department of Defense (DoD) leadership through In-Progress Reviews (IPRs). The IPR process, as well as the increased number of campaign and contingency plans COCOMs had to develop, increased the workload while the number of planners remained fixed. Several efforts from collaborative planning tools to streamlined processes were initiated to compensate for the increased workload enabling COCOMS to better meet shorter planning timelines. This paper examines the Joint Strategic Capabilities Plan (JSCP) directed contingency planning and staffing requirements assigned to a combatant commander staff through the lens of modeling and simulation. The dynamics of developing a COCOM plan are captured with an ExtendSim [3] simulation. The resulting analysis provides a quantifiable means by which to measure a combatant commander staffs workload associated with development and staffing JSCP [4] directed contingency plans with COCOM capability/capacity. Modeling and simulation bring significant opportunities in measuring the sensitivity of key variables in the assessment of workload to capability/capacity analysis. Gaining an understanding of the relationship between plan complexity, number of plans, planning processes, and number of planners with time required for plan development provides valuable information to DoD leadership. Through modeling and simulation AP leadership can gain greater insight in making key decisions on knowing where to best allocate scarce resources in an effort to meet DoD planning objectives.

  17. Process Network Approach to Understanding How Forest Ecosystems Adapt to Changes

    Science.gov (United States)

    Kim, J.; Yun, J.; Hong, J.; Kwon, H.; Chun, J.

    2011-12-01

    Sustainability challenges are transforming science and its role in society. Complex systems science has emerged as an inevitable field of education and research, which transcends disciplinary boundaries and focuses on understanding of the dynamics of complex social-ecological systems (SES). SES is a combined system of social and ecological components and drivers that interact and give rise to results, which could not be understood on the basis of sociological or ecological considerations alone. However, both systems may be viewed as a network of processes, and such a network hierarchy may serve as a hinge to bridge social and ecological systems. As a first step toward such effort, we attempted to delineate and interpret such process networks in forest ecosystems, which play a critical role in the cycles of carbon and water from local to global scales. These cycles and their variability, in turn, play an important role in the emergent and self-organizing interactions between forest ecosystems and their environment. Ruddell and Kumar (2009) define a process network as a network of feedback loops and the related time scales, which describe the magnitude and direction of the flow of energy, matter, and information between the different variables in a complex system. Observational evidence, based on micrometeorological eddy covariance measurements, suggests that heterogeneity and disturbances in forest ecosystems in monsoon East Asia may facilitate to build resilience for adaptation to change. Yet, the principles that characterize the role of variability in these interactions remain elusive. In this presentation, we report results from the analysis of multivariate ecohydrologic and biogeochemical time series data obtained from temperate forest ecosystems in East Asia based on information flow statistics.

  18. Understanding real-life website adaptations by investigating the relations between user behavior and user experience

    NARCIS (Netherlands)

    Graus, M.P.; Willemsen, M.C.; Swelsen, K.J.M.; Ricci, F.; Bontcheva, K.; Conlan, O; Lawless, S

    2015-01-01

    We study how a website adaptation based on segment predictions from click streams affects visitor behavior and user experience. Through statistical analysis we investigate how the adaptation changed actual behavior. Through structural equation modeling of subjective experience we answer why the

  19. Career Adaptability: A Qualitative Understanding from the Stories of Older Women

    Science.gov (United States)

    McMahon, Mary; Watson, Mark; Bimrose, Jenny

    2012-01-01

    This article reports on an international qualitative study investigating career pathways through the stories of transition and adaptability of older women. Informed by grounded theory, the study explored how this group of women coped with and adapted to changes and transitions related to career. Data were gathered by means of interviews with 36…

  20. Understanding the Leaky Engineering Pipeline: Motivation and Job Adaptability of Female Engineers

    Science.gov (United States)

    Saraswathiamma, Manjusha Thekkedathu

    2010-01-01

    This dissertation is a mixed-method study conducted using qualitative grounded theory and quantitative survey and correlation approaches. This study aims to explore the motivation and adaptability of females in the engineering profession and to develop a theoretical framework for both motivation and adaptability issues. As a result, this study…

  1. Analysis of farm performance in Europe under different climate and management conditions to improve understanding of adaptive capacity

    NARCIS (Netherlands)

    Reidsma, P.; Ewert, F.; Oude Lansink, A.

    2007-01-01

    The aim of this paper is to improve understanding of the adaptive capacity of European agriculture to climate change. Extensive data on farm characteristics of individual farms from the Farm Accountancy Data Network (FADN) have been combined with climatic and socio-economic data to analyze the

  2. Heterogeneity in a Suburban River Network: Understanding the Impact of Fluvial Wetlands on Dissolved Oxygen and Metabolism in Headwater Streams

    Science.gov (United States)

    Cain, J. S.; Wollheim, W. M.; Sheehan, K.; Lightbody, A.

    2014-12-01

    Low dissolved oxygen content in rivers threatens fish populations, aquatic organisms, and the health of entire ecosystems. River systems with high fluvial wetland abundance and organic matter, may result in high metabolism that in conjunction with low re-aeration rates, lead to low oxygen conditions. Increasing abundance of beaver ponds in many areas may exacerbate this phenomenon. This research aims to understand the impact of fluvial wetlands, including beaver ponds, on dissolved oxygen (D.O.) and metabolism throughout the headwaters of the Ipswich R. watershed, MA, USA. In several fluvial wetland dominated systems, we measured diel D.O. and metabolism in the upstream inflow, the surface water transient storage zones of fluvial wetland sidepools, and at the outflow to understand how the wetlands modify dissolved oxygen. D.O. was also measured longitudinally along entire surface water flow paths (x-y km long) to determine how low levels of D.O. propagate downstream. Nutrient samples were also collected to understand how their behavior was related to D.O. behavior. Results show that D.O. in fluvial wetlands has large swings with periods of very low D.O. at night. D.O. swings were also seen in downstream outflow, though lagged and somewhat attenuated. Flow conditions affect the level of inundation and the subsequent effects of fluvial wetlands on main channel D.O.. Understanding the D.O. behavior throughout river systems has important implications for the ability of river systems to remove anthropogenic nitrogen.

  3. Metabolic adaptations in models of fatty liver disease : Of mice and math

    NARCIS (Netherlands)

    Hijmans, Brenda

    2017-01-01

    The increasing incidence of overweight is accompanied by a plethora of medical symptoms together called the metabolic syndrome. Non-alcoholic fatty liver disease, characterized by persistent storage of lipids in the liver, is regarded as the hepatic component of the metabolic syndrome. An imbalance

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

    Czech Academy of Sciences Publication Activity Database

    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

  5. A review of human factors challenges of complex adaptive systems: discovering and understanding chaos in human performance.

    Science.gov (United States)

    Karwowski, Waldemar

    2012-12-01

    In this paper, the author explores a need for a greater understanding of the true nature of human-system interactions from the perspective of the theory of complex adaptive systems, including the essence of complexity, emergent properties of system behavior, nonlinear systems dynamics, and deterministic chaos. Human performance, more often than not, constitutes complex adaptive phenomena with emergent properties that exhibit nonlinear dynamical (chaotic) behaviors. The complexity challenges in the design and management of contemporary work systems, including service systems, are explored. Examples of selected applications of the concepts of nonlinear dynamics to the study of human physical performance are provided. Understanding and applications of the concepts of theory of complex adaptive and dynamical systems should significantly improve the effectiveness of human-centered design efforts of a large system of systems. Performance of many contemporary work systems and environments may be sensitive to the initial conditions and may exhibit dynamic nonlinear properties and chaotic system behaviors. Human-centered design of emergent human-system interactions requires application of the theories of nonlinear dynamics and complex adaptive system. The success of future human-systems integration efforts requires the fusion of paradigms, knowledge, design principles, and methodologies of human factors and ergonomics with those of the science of complex adaptive systems as well as modern systems engineering.

  6. Metabolism

    Science.gov (United States)

    ... 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 ...

  7. Understanding and applying principles of social cognition and decision making in adaptive environmental governance

    Science.gov (United States)

    Environmental governance systems are under greater pressure to adapt and to cope with increased social and ecological uncertainty from stressors like climate change. We review principles of social cognition and decision making that shape and constrain how environmental governance...

  8. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting.

    Science.gov (United States)

    Anton, Stephen D; Moehl, Keelin; Donahoo, William T; Marosi, Krisztina; Lee, Stephanie A; Mainous, Arch G; Leeuwenburgh, Christiaan; Mattson, Mark P

    2018-02-01

    Intermittent fasting (IF) is a term used to describe a variety of eating patterns in which no or few calories are consumed for time periods that can range from 12 hours to several days, on a recurring basis. This review is focused on the physiological responses of major organ systems, including the musculoskeletal system, to the onset of the metabolic switch: the point of negative energy balance at which liver glycogen stores are depleted and fatty acids are mobilized (typically beyond 12 hours after cessation of food intake). Emerging findings suggest that the metabolic switch from glucose to fatty acid-derived ketones represents an evolutionarily conserved trigger point that shifts metabolism from lipid/cholesterol synthesis and fat storage to mobilization of fat through fatty acid oxidation and fatty acid-derived ketones, which serve to preserve muscle mass and function. Thus, IF regimens that induce the metabolic switch have the potential to improve body composition in overweight individuals. Moreover, IF regimens also induce the coordinated activation of signaling pathways that optimize physiological function, enhance performance, and slow aging and disease processes. Future randomized controlled IF trials should use biomarkers of the metabolic switch (e.g., plasma ketone levels) as a measure of compliance and of the magnitude of negative energy balance during the fasting period. © 2017 The Obesity Society.

  9. Flipping the Metabolic Switch: Understanding and Applying Health Benefits of Fasting

    Science.gov (United States)

    Anton, Stephen D.; Moehl, Keelin; Donahoo, William T.; Marosi, Krisztina; Lee, Stephanie; Mainous, Arch G.; Leeuwenburgh, Christiaan; Mattson, Mark P.

    2017-01-01

    Intermittent fasting (IF) is a term used to describe a variety of eating patterns in which no or few calories are consumed for time periods that can range from 12 hours to several days, on a recurring basis. Here we focus on the physiological responses of major organ systems, including the musculoskeletal system, to the onset of the metabolic switch – the point of negative energy balance at which liver glycogen stores are depleted and fatty acids are mobilized (typically beyond 12 hours after cessation of food intake). Emerging findings suggest the metabolic switch from glucose to fatty acid-derived ketones represents an evolutionarily conserved trigger point that shifts metabolism from lipid/cholesterol synthesis and fat storage to mobilization of fat through fatty acid oxidation and fatty-acid derived ketones, which serve to preserve muscle mass and function. Thus, IF regimens that induce the metabolic switch have the potential to improve body composition in overweight individuals. Moreover, IF regimens also induce the coordinated activation of signaling pathways that optimize physiological function, enhance performance, and slow aging and disease processes. Future randomized controlled IF trials should use biomarkers of the metabolic switch (e.g., plasma ketone levels) as a measure of compliance and the magnitude of negative energy balance during the fasting period. PMID:29086496

  10. Metabolic adaptations may counteract ventilatory adaptations of intermittent hypoxic exposure during submaximal exercise at altitudes up to 4000 m.

    Directory of Open Access Journals (Sweden)

    Martin Faulhaber

    Full Text Available Intermittent hypoxic exposure (IHE has been shown to induce aspects of altitude acclimatization which affect ventilatory, cardiovascular and metabolic responses during exercise in normoxia and hypoxia. However, knowledge on altitude-dependent effects and possible interactions remains scarce. Therefore, we determined the effects of IHE on cardiorespiratory and metabolic responses at different simulated altitudes in the same healthy subjects. Eight healthy male volunteers participated in the study and were tested before and 1 to 2 days after IHE (7 × 1 hour at 4500 m. The participants cycled at 2 submaximal workloads (corresponding to 40% and 60% of peak oxygen uptake at low altitude at simulated altitudes of 2000 m, 3000 m, and 4000 m in a randomized order. Gas analysis was performed and arterial oxygen saturation, blood lactate concentrations, and blood gases were determined during exercise. Additionally baroreflex sensitivity, hypoxic and hypercapnic ventilatory response were determined before and after IHE. Hypoxic ventilatory response was increased after IHE (p<0.05. There were no altitude-dependent changes by IHE in any of the determined parameters. However, blood lactate concentrations and carbon dioxide output were reduced; minute ventilation and arterial oxygen saturation were unchanged, and ventilatory equivalent for carbon dioxide was increased after IHE irrespective of altitude. Changes in hypoxic ventilatory response were associated with changes in blood lactate (r = -0.72, p<0.05. Changes in blood lactate correlated with changes in carbon dioxide output (r = 0.61, p<0.01 and minute ventilation (r = 0.54, p<0.01. Based on the present results it seems that the reductions in blood lactate and carbon dioxide output have counteracted the increased hypoxic ventilatory response. As a result minute ventilation and arterial oxygen saturation did not increase during submaximal exercise at simulated altitudes between 2000 m and 4000 m.

  11. [Hemodynamics, the autonomic nervous system and water metabolism as criteria for developing the general adaptation syndrome in pregnant women].

    Science.gov (United States)

    Gur'ianov, V A; Shepetovskaia, N L; Pivovarova, G M; Tolmachev, G N; Volodin, A V

    2007-01-01

    By taking into account the fact that the autonomic nervous and cardiovascular systems (ANS and CVS) are the major links of development of the general adaptation syndrome in pregnancy, which are affected by all the processes involved in the development of the syndrome, the author analyzed the state of these systems in healthy non-pregnant and pregnant women (HNPW and HPW) and in pregnant women with gestosis. HNPW were found to have already a prerequisite for impairing pregnancy adaptive processes as ANS and CVS dysfunction. In HPW, these impairments were more pronounced. In the pregnant women, impaired adaptive processes manifested themselves as excess sympathicotonia in 72% and parasympathicotonia in 23% of cases despite the treatment performed, which was accompanied by hypokinetic hemodynamics in 53 and 50%, respectively. In hyper- and eukinetic hemodynamics, there were no physiologically required decreases in total peripheral vascular resistance while in hypokinetic hemodynamics, there was its pathological increase. Such disorders enhance the significance of abdominal compartment syndrome, aortocaval compression, ischemia-reperfusion, hydrodynamic and membranogenic (capillary leakage) factors of impaired water metabolism, which contributes to adaptation derangement. Based on the findings, the authors have created a developmental modulation algorithm for the general adaptation syndrome by completed pregnancy and surgical delivery.

  12. Adaptation.

    Science.gov (United States)

    Broom, Donald M

    2006-01-01

    The term adaptation is used in biology in three different ways. It may refer to changes which occur at the cell and organ level, or at the individual level, or at the level of gene action and evolutionary processes. Adaptation by cells, especially nerve cells helps in: communication within the body, the distinguishing of stimuli, the avoidance of overload and the conservation of energy. The time course and complexity of these mechanisms varies. Adaptive characters of organisms, including adaptive behaviours, increase fitness so this adaptation is evolutionary. The major part of this paper concerns adaptation by individuals and its relationships to welfare. In complex animals, feed forward control is widely used. Individuals predict problems and adapt by acting before the environmental effect is substantial. Much of adaptation involves brain control and animals have a set of needs, located in the brain and acting largely via motivational mechanisms, to regulate life. Needs may be for resources but are also for actions and stimuli which are part of the mechanism which has evolved to obtain the resources. Hence pigs do not just need food but need to be able to carry out actions like rooting in earth or manipulating materials which are part of foraging behaviour. The welfare of an individual is its state as regards its attempts to cope with its environment. This state includes various adaptive mechanisms including feelings and those which cope with disease. The part of welfare which is concerned with coping with pathology is health. Disease, which implies some significant effect of pathology, always results in poor welfare. Welfare varies over a range from very good, when adaptation is effective and there are feelings of pleasure or contentment, to very poor. A key point concerning the concept of individual adaptation in relation to welfare is that welfare may be good or poor while adaptation is occurring. Some adaptation is very easy and energetically cheap and

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

    Science.gov (United States)

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

    2015-12-01

    The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacterium Azospirillum brasilense navigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motile A. brasilense cells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilic A. brasilense cells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. The effect of problem posing and problem solving with realistic mathematics education approach to the conceptual understanding and adaptive reasoning

    Science.gov (United States)

    Mahendra, Rengga; Slamet, Isnandar; Budiyono

    2017-12-01

    One of the difficulties of students in learning mathematics is on the subject of geometry that requires students to understand abstract things. The aim of this research is to determine the effect of learning model Problem Posing and Problem Solving with Realistic Mathematics Education Approach to conceptual understanding and students' adaptive reasoning in learning mathematics. This research uses a kind of quasi experimental research. The population of this research is all seventh grade students of Junior High School 1 Jaten, Indonesia. The sample was taken using stratified cluster random sampling technique. The test of the research hypothesis was analyzed by using t-test. The results of this study indicate that the model of Problem Posing learning with Realistic Mathematics Education Approach can improve students' conceptual understanding significantly in mathematics learning. In addition tu, the results also showed that the model of Problem Solving learning with Realistic Mathematics Education Approach can improve students' adaptive reasoning significantly in learning mathematics. Therefore, the model of Problem Posing and Problem Solving learning with Realistic Mathematics Education Approach is appropriately applied in mathematics learning especially on the subject of geometry so as to improve conceptual understanding and students' adaptive reasoning. Furthermore, the impact can improve student achievement.

  15. Understanding and applying principles of social cognition and decision making in adaptive environmental governance

    Directory of Open Access Journals (Sweden)

    Daniel A. DeCaro

    2017-03-01

    Full Text Available Environmental governance systems are under greater pressure to adapt and to cope with increased social and ecological uncertainty from stressors like climate change. We review principles of social cognition and decision making that shape and constrain how environmental governance systems adapt. We focus primarily on the interplay between key decision makers in society and legal systems. We argue that adaptive governance must overcome three cooperative dilemmas to facilitate adaptation: (1 encouraging collaborative problem solving, (2 garnering social acceptance and commitment, and (3 cultivating a culture of trust and tolerance for change and uncertainty. However, to do so governance systems must cope with biases in people's decision making that cloud their judgment and create conflict. These systems must also satisfy people's fundamental needs for self-determination, fairness, and security, ensuring that changes to environmental governance are perceived as legitimate, trustworthy, and acceptable. We discuss the implications of these principles for common governance solutions (e.g., public participation, enforcement and conclude with methodological recommendations. We outline how scholars can investigate the social cognitive principles involved in cases of adaptive governance.

  16. Genome-driven evolutionary game theory helps understand the rise of metabolic interdependencies in microbial communities.

    Science.gov (United States)

    Zomorrodi, Ali R; Segrè, Daniel

    2017-11-16

    Metabolite exchanges in microbial communities give rise to ecological interactions that govern ecosystem diversity and stability. It is unclear, however, how the rise of these interactions varies across metabolites and organisms. Here we address this question by integrating genome-scale models of metabolism with evolutionary game theory. Specifically, we use microbial fitness values estimated by metabolic models to infer evolutionarily stable interactions in multi-species microbial "games". We first validate our approach using a well-characterized yeast cheater-cooperator system. We next perform over 80,000 in silico experiments to infer how metabolic interdependencies mediated by amino acid leakage in Escherichia coli vary across 189 amino acid pairs. While most pairs display shared patterns of inter-species interactions, multiple deviations are caused by pleiotropy and epistasis in metabolism. Furthermore, simulated invasion experiments reveal possible paths to obligate cross-feeding. Our study provides genomically driven insight into the rise of ecological interactions, with implications for microbiome research and synthetic ecology.

  17. Understanding and managing disturbances in insulin metabolism and body weight in women with polycystic ovary syndrome.

    Science.gov (United States)

    Moran, L; Norman, R J

    2004-10-01

    Polycystic ovary syndrome (PCOS) is a common clinical and metabolic condition in women of reproductive age. It is associated with short-term reproductive and long-term metabolic dysfunction. Treatment has traditionally focused on fertility and hormonal therapy. However, general obesity, central obesity and insulin resistance are strongly implicated in its aetiology and improving these factors has proved highly successful in some clinical situations, reducing the need for costly assisted reproduction. A low-fat, high-carbohydrate diet is thought to improve insulin sensitivity, aid in weight loss and reduction of metabolic and reproductive symptoms and improve the long-term maintenance of a reduced weight. However, there has been recent community interest in adopting a protocol advocating a moderate increase in dietary protein for improving weight loss and PCOS symptoms. Altering the glycaemic index of the diet has also received considerable attention as a regime for promoting satiety and reducing metabolic risk factors for type 2 diabetes mellitus and cardiovascular disease. Exercise and other lifestyle changes are essential for altering the short- and long-term effects of PCOS. It is vital that the efficacy of these strategies is assessed so that accurate medical and dietetic advice can be given both to patients and to the health-care community.

  18. Adaptation

    International Development Research Centre (IDRC) Digital Library (Canada)

    building skills, knowledge or networks on adaptation, ... the African partners leading the AfricaAdapt network, together with the UK-based Institute of Development Studies; and ... UNCCD Secretariat, Regional Coordination Unit for Africa, Tunis, Tunisia .... 26 Rural–urban Cooperation on Water Management in the Context of.

  19. Metabolic Adaptation of Human CD4+ and CD8+ T-Cells to T-Cell Receptor-Mediated Stimulation

    Directory of Open Access Journals (Sweden)

    Nicholas Jones

    2017-11-01

    Full Text Available Linking immunometabolic adaptation to T-cell function provides insight for the development of new therapeutic approaches in multiple disease settings. T-cell activation and downstream effector functions of CD4+ and CD8+ T-cells are controlled by the strength of interaction between the T-cell receptor (TCR and peptides presented by human leukocyte antigens (pHLA. The role of TCR–pHLA interactions in modulating T-cell metabolism is unknown. Here, for the first time, we explore the relative contributions of the main metabolic pathways to functional responses in human CD4+ and CD8+ T-cells. Increased expression of hexokinase II accompanied by higher basal glycolysis is demonstrated in CD4+ T-cells; cytokine production in CD8+ T-cells is more reliant on oxidative phosphorylation. Using antigen-specific CD4+ and CD8+ T-cell clones and altered peptide ligands, we demonstrate that binding affinity tunes the underlying metabolic shift. Overall, this study provides important new insight into how metabolic pathways are controlled during antigen-specific activation of human T-cells.

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

    Directory of Open Access Journals (Sweden)

    Francois Gabriel Feugier

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Elizabeth Allen

    2016-05-01

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

  2. Proceedings of the adapting to climate change in Canada 2005 conference : understanding risks and building capacity

    International Nuclear Information System (INIS)

    2005-01-01

    This four-day conference provided a national forum for researchers and decision-makers from a variety of disciplines to share information and results on climate change. Sponsored by Natural Resources Canada's Climate Change Impacts and Adaptation Program, the conference explored ways to improve knowledge of Canada's vulnerability to climate change, to better assess the benefits and risks of climate change and to examine policies and options through which decisions on adaptation can be made. Conference topics included issues such as global warming; sustainable development; climate change and agriculture; adaptation strategies; water, coastline and marine management and climate change; municipal level management and climate change; climate change and health issues; and many other topics related to climate change. The conference featured paper and poster presentations, opening remarks, and panel discussions. A total of 118 conference papers and 46 conference posters were presented at the conference of which 17 have been catalogued separately in this database. refs., tabs., figs

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

    DEFF Research Database (Denmark)

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

    The Chinese hamster ovary (CHO) cell line is the predominant mammalian cell factory for production of therapeutic glycoproteins. In this work, we aimed to study bottlenecks in the secretory pathway associated with the production of human erythropoietin (EPO) in CHO cells. In connection to this, we...... discovered indications of metabolic adaptation of the amino acid catabolism in favor of heterologous protein production. We established a panel of stably EPO expressing CHO-K1 clones spanning a 25-fold productivity range and characterized the clones in batch and chemostat cultures. For this, we employed...... a multi-omic physiological characterization including metabolic foot printing of amino acids, metabolite fingerprinting of glycolytic intermediates, NAD(P)H-/NAD(P)+ and adenosine nucleotide phosphates. We used qPCR, qRT-PCR, western blots and Affymetrix CHO microarrays to assess EPO gene copy numbers...

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

    Directory of Open Access Journals (Sweden)

    Petra Tielen

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

  5. Regulatory and Metabolic Networks for the Adaptation of Pseudomonas aeruginosa Biofilms to Urinary Tract-Like Conditions

    Science.gov (United States)

    Dohnt, Katrin; Haddad, Isam; Jänsch, Lothar; Klein, Johannes; Narten, Maike; Pommerenke, Claudia; Scheer, Maurice; Schobert, Max; Schomburg, Dietmar; Thielen, Bernhard; Jahn, Dieter

    2013-01-01

    Biofilms of the Gram-negative bacterium Pseudomonas aeruginosa are one of the major causes of complicated urinary tract infections with detrimental outcome. To develop novel therapeutic strategies the molecular adaption strategies of P. aeruginosa biofilms to the conditions of the urinary tract were investigated thoroughly at the systems level using transcriptome, proteome, metabolome and enzyme activity analyses. For this purpose biofilms were grown anaerobically in artificial urine medium (AUM). Obtained data were integrated bioinformatically into gene regulatory and metabolic networks. The dominating response at the transcriptome and proteome level was the adaptation to iron limitation via the broad Fur regulon including 19 sigma factors and up to 80 regulated target genes or operons. In agreement, reduction of the iron cofactor-dependent nitrate respiratory metabolism was detected. An adaptation of the central metabolism to lactate, citrate and amino acid as carbon sources with the induction of the glyoxylate bypass was observed, while other components of AUM like urea and creatinine were not used. Amino acid utilization pathways were found induced, while fatty acid biosynthesis was reduced. The high amounts of phosphate found in AUM explain the reduction of phosphate assimilation systems. Increased quorum sensing activity with the parallel reduction of chemotaxis and flagellum assembly underscored the importance of the biofilm life style. However, reduced formation of the extracellular polysaccharide alginate, typical for P. aeruginosa biofilms in lungs, indicated a different biofilm type for urinary tract infections. Furthermore, the obtained quorum sensing response results in an increased production of virulence factors like the extracellular lipase LipA and protease LasB and AprA explaining the harmful cause of these infections. PMID:23967252

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

    Science.gov (United States)

    Tielen, Petra; Rosin, Nathalie; Meyer, Ann-Kathrin; Dohnt, Katrin; Haddad, Isam; Jänsch, Lothar; Klein, Johannes; Narten, Maike; Pommerenke, Claudia; Scheer, Maurice; Schobert, Max; Schomburg, Dietmar; Thielen, Bernhard; Jahn, Dieter

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-08-09

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

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

    DEFF Research Database (Denmark)

    Neess, Ditte; Bloksgaard, Maria; Sørensen, Signe Bek

    2011-01-01

    The acyl-CoA binding protein/diazepam binding inhibitor (ACBP/DBI) is an intracellular protein that binds C14-C22 acyl-CoA esters and is thought to act as an acyl-CoA transporter. In vitro analyses have indicated that ACBP can transport acyl-CoA esters between different enzymatic systems; however....... The delayed induction of SREBP target genes around weaning is caused by a compromised processing and decreased expression of SREBP precursors leading to reduced binding of SREBP to target sites in chromatin. In conclusion, lack of ACBP interferes with the normal metabolic adaptation to weaning and leads...

  9. In search of an adaptive social-ecological approach to understanding a tropical city

    Science.gov (United States)

    A.E. Lugo; C.M. Concepcion; L.E. Santiago-Acevedo; T.A. Munoz-Erickson; J.C. Verdejo Ortiz; R. Santiago-Bartolomei; J. Forero-Montana; C.J. Nytch; H. Manrique; W. Colon-Cortes

    2012-01-01

    This essay describes our effort to develop a practical approach to the integration of the social and ecological sciences in the context of a Latin-American city such as San Juan, Puerto Rico. We describe our adaptive social-ecological approach in the historical context of the developing paradigms of the Anthropocene, new integrative social and ecological sciences, and...

  10. Adaptation, expertise, and giftedness: towards an understanding of cortical, subcortical, and cerebellar network contributions.

    Science.gov (United States)

    Koziol, Leonard F; Budding, Deborah Ely; Chidekel, Dana

    2010-12-01

    Current cortico-centric models of cognition lack a cohesive neuroanatomic framework that sufficiently considers overlapping levels of function, from "pathological" through "normal" to "gifted" or exceptional ability. While most cognitive theories presume an evolutionary context, few actively consider the process of adaptation, including concepts of neurodevelopment. Further, the frequent co-occurrence of "gifted" and "pathological" function is difficult to explain from a cortico-centric point of view. This comprehensive review paper proposes a framework that includes the brain's vertical organization and considers "giftedness" from an evolutionary and neurodevelopmental vantage point. We begin by discussing the current cortico-centric model of cognition and its relationship to intelligence. We then review an integrated, dual-tiered model of cognition that better explains the process of adaptation by simultaneously allowing for both stimulus-based processing and higher-order cognitive control. We consider the role of the basal ganglia within this model, particularly in relation to reward circuitry and instrumental learning. We review the important role of white matter tracts in relation to speed of adaptation and development of behavioral mastery. We examine the cerebellum's critical role in behavioral refinement and in cognitive and behavioral automation, particularly in relation to expertise and giftedness. We conclude this integrated model of brain function by considering the savant syndrome, which we believe is best understood within the context of a dual-tiered model of cognition that allows for automaticity in adaptation as well as higher-order executive control.

  11. Understanding Attention to Adaptive Hints in Educational Games: An Eye-Tracking Study

    Science.gov (United States)

    Conati, Cristina; Jaques, Natasha; Muir, Mary

    2013-01-01

    This paper presents a user study that investigates the factors affecting student attention to user-adaptive hints during interaction with an educational computer game. The study focuses on Prime Climb, an educational game designed to provide individualized support for learning number factorization skills in the form of textual hints based on a…

  12. Complexity in practice: understanding primary care as a complex adaptive system

    Directory of Open Access Journals (Sweden)

    Beverley Ellis

    2010-06-01

    Conclusions The results are real-world exemplars of the emergent properties of complex adaptive systems. Improving clinical governance in primary care requires both complex social interactions and underpinning informatics. The socio-technical lessons learned from this research should inform future management approaches.

  13. Using brain potentials to understand prism adaptation: the error-related negativity and the P300

    Directory of Open Access Journals (Sweden)

    Stephane Joseph Maclean

    2015-06-01

    Full Text Available Prism adaptation (PA is both a perceptual-motor learning task as well as a promising rehabilitation tool for visuo-spatial neglect (VSN – a spatial attention disorder often experienced after stroke resulting in slowed and/or inaccurate motor responses to contralesional targets. During PA, individuals are exposed to prism-induced shifts of the visual-field while performing a visuo-guided reaching task. After adaptation, with goggles removed, visuo-motor responding is shifted to the opposite direction of that initially induced by the prisms. This visuo-motor aftereffect has been used to study visuo-motor learning and adaptation and has been applied clinically to reduce VSN severity by improving motor responding to stimuli in contralesional (usually left-sided space. In order to optimize PA’s use for VSN patients, it is important to elucidate the neural and cognitive processes that alter visuomotor function during PA. In the present study, healthy young adults underwent PA while event-related potentials (ERPs were recorded at the termination of each reach (screen-touch, then binned according to accuracy (hit vs. miss and phase of exposure block (early, middle, late. Results show that two ERP components were evoked by screen-touch: an early error-related negativity (ERN, and a P300. The ERN was consistently evoked on miss trials during adaptation, while the P300 amplitude was largest during the early phase of adaptation for both hit and miss trials. This study provides evidence of two neural signals sensitive to visual feedback during PA that may sub-serve changes in visuomotor responding. Prior ERP research suggests that the ERN reflects an error processing system in medial-frontal cortex, while the P300 is suggested to reflect a system for context updating and learning. Future research is needed to elucidate the role of these ERP components in improving visuomotor responses among individuals with VSN.

  14. Using brain potentials to understand prism adaptation: the error-related negativity and the P300.

    Science.gov (United States)

    MacLean, Stephane J; Hassall, Cameron D; Ishigami, Yoko; Krigolson, Olav E; Eskes, Gail A

    2015-01-01

    Prism adaptation (PA) is both a perceptual-motor learning task as well as a promising rehabilitation tool for visuo-spatial neglect (VSN)-a spatial attention disorder often experienced after stroke resulting in slowed and/or inaccurate motor responses to contralesional targets. During PA, individuals are exposed to prism-induced shifts of the visual-field while performing a visuo-guided reaching task. After adaptation, with goggles removed, visuomotor responding is shifted to the opposite direction of that initially induced by the prisms. This visuomotor aftereffect has been used to study visuomotor learning and adaptation and has been applied clinically to reduce VSN severity by improving motor responding to stimuli in contralesional (usually left-sided) space. In order to optimize PA's use for VSN patients, it is important to elucidate the neural and cognitive processes that alter visuomotor function during PA. In the present study, healthy young adults underwent PA while event-related potentials (ERPs) were recorded at the termination of each reach (screen-touch), then binned according to accuracy (hit vs. miss) and phase of exposure block (early, middle, late). Results show that two ERP components were evoked by screen-touch: an error-related negativity (ERN), and a P300. The ERN was consistently evoked on miss trials during adaptation, while the P300 amplitude was largest during the early phase of adaptation for both hit and miss trials. This study provides evidence of two neural signals sensitive to visual feedback during PA that may sub-serve changes in visuomotor responding. Prior ERP research suggests that the ERN reflects an error processing system in medial-frontal cortex, while the P300 is suggested to reflect a system for context updating and learning. Future research is needed to elucidate the role of these ERP components in improving visuomotor responses among individuals with VSN.

  15. Understanding the socio-institutional context to support adaptation for future water security in forest landscapes

    Directory of Open Access Journals (Sweden)

    Tahia Devisscher

    2016-12-01

    Full Text Available During the first half of the 21st century, socioeconomic development is expected to contribute faster and to a greater extent to global water stress than climate change. Consequently, we aimed to identify conditions that can facilitate local adaptation planning for future water security, accounting for the socio-institutional context, developmental needs, and interests affecting water use and management. Our study focused on three forest landscapes in Latin America where water stress was identified as a current concern potentially leading to future social conflict if not addressed. In the three sites, we adopted a participatory approach to implement a systematic diagnostic framework for the analysis of socio-institutional barriers and opportunities influencing local adaptation decision making. This novel application enabled science-society engagement in which civil society organizations were coleading the research. The field methods we used involved participatory social network mapping, semistructured interviews, and validation workshops. Our study generated insights into several interventions that could help overcome barriers affecting the adaptation decision-making process, particularly in the diagnosis and early planning phases. Points of intervention included fostering local participation and dialogue to facilitate coproduction of knowledge, and strengthening the role of key central actors in the water governance networks. These key actors are currently bridging multiple interests, information sources, and governance levels, and thus, they could become agents of change that facilitate local adaptation processes. Working jointly with civil society to frame the research proved effective to increase awareness about water issues, which related not only to the technological, economic, and political aspects of water, but also to organizational processes. The involvement of civil society created genuine interest in building further capacity for

  16. Obese and anorexic yeasts: experimental models to understand the metabolic syndrome and lipotoxicity.

    Science.gov (United States)

    Kohlwein, Sepp D

    2010-03-01

    Lipotoxicity is the pathological consequence of lipid overflow in non-adipose tissue, mediated through reactive lipid moieties which may even lead to lipid-induced cell death (lipoapoptosis). This derailment of cellular and organismal fat homeostasis is the consequence of obesity due to continued over-feeding, and contributes substantially to the pathogenesis of insulin resistance, type 2 diabetes mellitus and cardiovascular disease, which are all components of the metabolic syndrome. Now, does yeast, a single-celled eukaryote, ever suffer from the metabolic syndrome and what can we potentially learn from studies in this organism about the underlying molecular mechanism that lead to lipid-associated pathologies in human cells? In this review I will summarize the remarkably conserved metabolic and regulatory processes relevant to establishing cellular energy and lipid homeostasis, as well as recent findings that provide detailed insights into the molecular mechanisms underlying fat-induced cellular malfunction and cell death, with potential implications also for mammalian cells. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  17. Total thyroidectomy: a clue to understanding the metabolic changes induced by subclinical hyperthyroidism?

    Science.gov (United States)

    Bel Lassen, Pierre; Kyrilli, Aglaia; Lytrivi, Maria; Ruiz Patino, Maria; Corvilain, Bernard

    2017-02-01

    The effects of endogenous subclinical hyperthyroidism (eSCH) on heart and bone have been well documented. There are only limited data available regarding the impact of eSCH on weight regulation and lipid metabolism. Our aim was to evaluate the changes in body weight and metabolic parameters after total thyroidectomy in patients with pre-operative eSCH compared with pre-operative patients with euthyroid (EUT). A retrospective study of 505 patients who underwent total thyroidectomy for benign multinodular goitre in an academic hospital in Brussels (Belgium) was performed. Two hundred and 25 patients were included (eSCH group: n = 74; EUT group: n = 151). The mean follow-up time was 26·1 ± 0·8 months and was similar in both groups. Absolute BMI gain was significantly greater in the eSCH group than in the EUT group (1·11 ± 0·17 vs 0·33 ± 0·13 kg/m 2 ; P = 0·003). A significant increase in LDL cholesterol was observed in the eSCH group (16·1 ± 3·8 mg/dl; P effect of eSCH on body weight regulation and lipid metabolism. © 2016 John Wiley & Sons Ltd.

  18. Cultivating Resilience in Families Who Foster: Understanding How Families Cope and Adapt Over Time.

    Science.gov (United States)

    Lietz, Cynthia A; Julien-Chinn, Francie J; Geiger, Jennifer M; Hayes Piel, Megan

    2016-12-01

    Families who foster offer essential care for children and youth when their own parents are unable to provide for their safety and well-being. Foster caregivers face many challenges including increased workload, emotional distress, and the difficulties associated with health and mental health problems that are more common in children in foster care. Despite these stressors, many families are able to sustain fostering while maintaining or enhancing functioning of their unit. This qualitative study applied an adaptational process model of family resilience that emerged in previous studies to examine narratives of persistent, long-term, and multiple fostering experiences. Data corroborated previous research in two ways. Family resilience was again described as a transactional process of coping and adaptation that evolves over time. This process was cultivated through the activation of 10 family strengths that are important in different ways, during varied phases. © 2016 Family Process Institute.

  19. SANParks, people and adaptive management: Understanding a diverse field of practice during changing times

    Directory of Open Access Journals (Sweden)

    Louise K. Swemmer

    2011-05-01

    Conservation implications: Benefit sharing through biodiversity conservation has been shown to be crucial for the long-term success of protected areas, but the practicalities of implementing this are thwart with challenges. Despite this, SANParks is attempting to facilitate and promote benefits through conservation, specifically in the sense of benefits that support livelihoods whilst reducing vulnerability. With this in mind, we acknowledge the importance of the concepts of scale, resilience, complexity and adaptive learning for, and during, this process.

  20. Understanding Migration as an Adaptation in Deltas Using a Bayesian Network Model

    Science.gov (United States)

    Lázár, A. N.; Adams, H.; de Campos, R. S.; Mortreux, C. C.; Clarke, D.; Nicholls, R. J.; Amisigo, B. A.

    2016-12-01

    Deltas are hotspots of high population density, fertile lands and dramatic environmental and anthropogenic pressures and changes. Amongst other environmental factors, sea level rise, soil salinization, water shortages and erosion threaten people's livelihoods and wellbeing. As a result, there is a growing concern that significant environmental change induced migration might occur from these areas. Migration, however, is already happening for economic, education and other reasons (e.g. livelihood change, marriage, planned relocation, etc.). Migration hence has multiple, interlinked drivers and depending on the perspective, can be considered as a positive or negative phenomenon. The DECCMA project (Deltas, Vulnerability & Climate Change: Migration & Adaptation) studies migration as part of a suite of adaptation options available to the coastal populations in the Ganges delta in Bangladesh, the Mahanadi delta in India and the Volta delta in Ghana. It aims to develop a holistic framework of analysis that assesses the impact of climate and environmental change on the migration patterns of these areas. This assessment framework will couple environmental, socio-economics and governance dimensions in an attempt to synthesise drivers and barriers and allow testing of plausible future scenarios. One of the integrative methods of DECCMA is a Bayesian Belief Network (BBN) model describing the decision-making of a coastal household. BBN models are built on qualitative and quantitative observations/expert knowledge and describe the probability of different events/responses etc. BBN models are especially useful to capture uncertainties of large systems and engaging with stakeholders. The DECCMA BBN model is based on household survey results from delta migrant sending areas. This presentation will describe model elements (livelihood sensitivity to climate change, local and national adaptation options, household characteristics/attitude, social networks, household decision) and

  1. Adaptive plasticity of skeletal muscle energetics in hibernating frogs: mitochondrial proton leak during metabolic depression.

    Science.gov (United States)

    Boutilier, Robert G; St-Pierre, Julie

    2002-08-01

    The common frog (Rana temporaria) spends the coldest months of each year overwintering in ice-covered ponds where temperatures can vary from 0.5 to 4.0 degrees C. Over the course of a winter season, the animals enter progressively into a state of metabolic depression that relies almost exclusively on aerobic production of ATP. However, if aerobic metabolism is threatened, for example by increasingly hypoxic conditions, decreases in the animal's metabolic rate can reach upwards of 75% compared with the 50% decrease seen during normoxia. Under these conditions, the major proportion of the overall reduction in whole-animal metabolic rate can be accounted for by metabolic suppression of the skeletal muscle (which makes up approximately 40% of body mass). Little is known about the properties of mitochondria during prolonged periods of metabolic depression, so we have examined several aspects of mitochondrial metabolism in the skeletal muscle of frogs over periods of hibernation of up to 4 months. Mitochondria isolated from the skeletal muscle of frogs hibernating in hypoxic water show a considerable reorganisation of function compared with those isolated from normoxic submerged animals at the same temperature (3 degrees C). Both the active (state 3) and resting (state 4) respiration rates of mitochondria decrease during hypoxic, but not normoxic, hibernation. In addition, the affinity of mitochondria for oxygen increases during periods of acute hypoxic stress during normoxic hibernation as well as during long-term hibernation in hypoxic water. The decrease in mitochondrial state 4 respiration rates during hypoxic hibernation evidently occurs through a reduction in electron-transport chain activity, not through a lowered proton conductance of the mitochondrial inner membrane. The reduced aerobic capacity of frog skeletal muscle during hypoxic hibernation is accompanied by lowered activities of key enzymes of mitochondrial metabolism caused by changes in the intrinsic

  2. Socio-ecological Typologies for Understanding Adaptive Capacity of a Region to Natural Disasters

    Science.gov (United States)

    Surendran Nair, S.; Preston, B. L.; King, A. W.; Mei, R.

    2015-12-01

    It is expected that the frequency and magnitude of extreme climatic events will increase in coming decades with an anticipated increase in losses from climate hazards. In the Gulf Coastal region of the United States, climate hazards/disasters are common including hurricanes, drought and flooding. However, the capacity to adapt to extreme climatic events varies across the region. This adaptive capacity is linked to the magnitude of the extreme event, exposed infrastructure, and the socio-economic conditions across the region. This study uses hierarchical clustering to quantitatively integrates regional socioeconomic and biophysical factors and develop socio-ecological typologies (SET). The biophysical factors include climatic and topographic variables, and the socio-economic variables include human capital, social capital and man-made resources (infrastructure) of the region. The types of the SET are independent variables in a statistical model of a regional variable of interest. The methodology was applied to US Gulf States to evaluate the social and biophysical determinants of the regional variation in social vulnerability and economic loss to climate hazards. The results show that the SET explains much of the regional variation in social vulnerability, effectively capturing its determinants. In addition, the SET also explains of the variability in economic loss to hazards across of the region. The approach can thus be used to prioritize adaptation strategies to reduce vulnerability and loss across the region.

  3. A problem-oriented approach to understanding adaptation: lessons learnt from Alpine Shire, Victoria Australia.

    Science.gov (United States)

    Roman, Carolina

    2010-05-01

    Climate change is gaining attention as a significant strategic issue for localities that rely on their business sectors for economic viability. For businesses in the tourism sector, considerable research effort has sought to characterise the vulnerability to the likely impacts of future climate change through scenarios or ‘end-point' approaches (Kelly & Adger, 2000). Whilst useful, there are few demonstrable case studies that complement such work with a ‘start-point' approach that seeks to explore contextual vulnerability (O'Brien et al., 2007). This broader approach is inclusive of climate change as a process operating within a biophysical system and allows recognition of the complex interactions that occur in the coupled human-environmental system. A problem-oriented and interdisciplinary approach was employed at Alpine Shire, in northeast Victoria Australia, to explore the concept of contextual vulnerability and adaptability to stressors that include, but are not limited to climatic change. Using a policy sciences approach, the objective was to identify factors that influence existing vulnerabilities and that might consequently act as barriers to effective adaptation for the Shire's business community involved in the tourism sector. Analyses of results suggest that many threats, including the effects climate change, compete for the resources, strategy and direction of local tourism management bodies. Further analysis of conditioning factors revealed that many complex and interacting factors define the vulnerability and adaptive capacity of the Shire's tourism sector to the challenges of global change, which collectively have more immediate implications for policy and planning than long-term future climate change scenarios. An approximation of the common interest, i.e. enhancing capacity in business acumen amongst tourism operators, would facilitate adaptability and sustainability through the enhancement of social capital in this business community. Kelly, P

  4. Adapt

    Science.gov (United States)

    Bargatze, L. F.

    2015-12-01

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

  5. Metabolic and endocrine adaptations to fasting in lean and obese individuals

    NARCIS (Netherlands)

    Wijngaarden, Marjolein A.

    2015-01-01

    In this thesis we examined several effects of fasting in lean and obese individuals. As expected, both the hormonal response as well as the metabolic shift from glucose towards lipid oxidation was impaired in obese individuals. At baseline, mitochondrial protein content in skeletal muscle of obese

  6. A transcription factor links growth rate and metabolism in the hypersaline adapted archaeon Halobacterium salinarum.

    Science.gov (United States)

    Todor, Horia; Dulmage, Keely; Gillum, Nicholas; Bain, James R; Muehlbauer, Michael J; Schmid, Amy K

    2014-09-01

    Co-ordinating metabolism and growth is a key challenge for all organisms. Despite fluctuating environments, cells must produce the same metabolic outputs to thrive. The mechanisms underlying this 'growth homeostasis' are known in bacteria and eukaryotes, but remain unexplored in archaea. In the model archaeon Halobacterium salinarum, the transcription factor TrmB regulates enzyme-coding genes in diverse metabolic pathways in response to glucose. However, H. salinarum is thought not to catabolize glucose. To resolve this discrepancy, we demonstrate that TrmB regulates the gluconeogenic production of sugars incorporated into the cell surface S-layer glycoprotein. Additionally, we show that TrmB-DNA binding correlates with instantaneous growth rate, likely because S-layer glycosylation is proportional to growth. This suggests that TrmB transduces a growth rate signal to co-regulated metabolic pathways including amino acid, purine, and cobalamin biosynthesis. Remarkably, the topology and function of this growth homeostatic network appear conserved across domains despite extensive alterations in protein components. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

  7. Modeling Phenotypic Metabolic Adaptations of Mycobacterium tuberculosis H37Rv under Hypoxia

    Science.gov (United States)

    2012-09-13

    Parish T, Brown AC (2008) Mycobacteria protocols. New York, NY: Humana Press. 19. Voskuil MI, Schnappinger D, Visconti KC, Harrell MI, Dolganov GM...Genomics Hum Genet 2: 343–372. 31. Kell DB (2006) Systems biology, metabolic modelling and metabolomics in drug discovery and development. Drug Discov

  8. Recent developments in our understanding of the implications of traditional African medicine on drug metabolism.

    Science.gov (United States)

    Gouws, Chrisna; Hamman, Josias H

    2018-02-01

    The use of traditional herbal medicines has become increasingly popular globally, but in some countries, it is the main or sometimes even the only healthcare service available in the most rural areas. This is especially true for Africa where herbal medicines form a key component of traditional medicinal practices and there is access to a diversity of medicinal plants. Although many benefits have been derived from the use of traditional herbal medicines, many concerns are associated with their use of which herb-drug interactions have been identified to have a rising impact on patient treatment outcome. One type of pharmacokinetic interaction involves the modulation of drug metabolizing enzymes, which may result in enhanced or reduced bioavailability of co-administered drugs. Areas covered: This review highlights the current information available on drug metabolism-associated information with regards to traditional African medicines related to some of the most prevalent diseases burdening the African continent. Expert opinion: It is clear from previous studies that enzyme modulation by traditional African medicines plays a significant role in the pharmacokinetics of some co-administered drugs, but more research is needed to provide detailed information on these interactions, specifically for treatment of prevalent diseases such as tuberculosis and hypertension.

  9. Understanding bistability in yeast glycolysis using general properties of metabolic pathways.

    Science.gov (United States)

    Planqué, Robert; Bruggeman, Frank J; Teusink, Bas; Hulshof, Josephus

    2014-09-01

    Glycolysis is the central pathway in energy metabolism in the majority of organisms. In a recent paper, van Heerden et al. showed experimentally and computationally that glycolysis can exist in two states, a global steady state and a so-called imbalanced state. In the imbalanced state, intermediary metabolites accumulate at low levels of ATP and inorganic phosphate. It was shown that Baker's yeast uses a peculiar regulatory mechanism--via trehalose metabolism--to ensure that most yeast cells reach the steady state and not the imbalanced state. Here we explore the apparent bistable behaviour in a core model of glycolysis that is based on a well-established detailed model, and study in great detail the bifurcation behaviour of solutions, without using any numerical information on parameter values. We uncover a rich suite of solutions, including so-called imbalanced states, bistability, and oscillatory behaviour. The techniques employed are generic, directly suitable for a wide class of biochemical pathways, and could lead to better analytical treatments of more detailed models. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Application of the ''bootstrap'' technique to understanding cerebral interregional metabolic relationships

    International Nuclear Information System (INIS)

    Metter, E.J.; Riege, W.H.; Kuhl, D.E.; Phelps, M.E.

    1984-01-01

    The authors' previous studies using (F18)-flourodeoxyglucose with positron computed tomography examined region to region metabolic correlations in (1) normal subjects, (2) normal elderly versus younger individuals, and (3) Alzheimer's, Huntington's and Parkinson's Diseases. Variations in the correlation matrices suggested differences in how brain regions function together. An alternative explanation was that the distribution of each matrix was not distinctly different, and the observations represented variations from the same distribution. To examine this tissue, the authors focused on the observation of differences in the total number of reliable correlations (i.e. correlations with r representing a p .01 uncorrected for the number of correlations) between the groups. For example in Parkinson Disease a total of 12 reliable correlations were found, as compared to 34 in Alzheimer's Disease. Four groups were compared including normal elderly, normal young, Alzheimer and Parkinson's Diseases. For each group, random samples were drawn from the studied subjects, and correlation matrices were calculated from the new samples. 508 matrices were calculated for the two normal groups, and 1016 were calculated for the Alzheimer's and Parkinson's groups. The total number of reliable correlations were counted for each matrix and the distribution of these counts were examined. Distinct differences were found in the mean, median and mode for each group. In particular, Parkinson's Disease peaked the earliest of the four groups, while Alzheimer's peaked the latest. The findings demonstrated that the metabolic data for each group were derived from different populations

  11. Final Report: Filling Knowledge Gaps in Biological Networks: Integrated Global Approaches to Understand H{sub 2} Metabolism in Chlamydomonas Reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Grossman, Arthur

    2012-05-01

    The major goal of our part of this project has been to generate mutants in fermentation metabolism and begin to decipher how lesions in the pathways associated with fermentation metabolism impact both H{sub 2} production and the production of other metabolites that accumulate as cells become anoxic. We are also trying to understand how metabolic pathways are regulated as O{sub 2} in the environment becomes depleted.

  12. Adaptive learning can result in a failure to profit from good conditions: implications for understanding depression.

    Science.gov (United States)

    Trimmer, Pete C; Higginson, Andrew D; Fawcett, Tim W; McNamara, John M; Houston, Alasdair I

    2015-04-26

    Depression is a major medical problem diagnosed in an increasing proportion of people and for which commonly prescribed psychoactive drugs are frequently ineffective. Development of treatment options may be facilitated by an evolutionary perspective; several adaptive reasons for proneness to depression have been proposed. A common feature of many explanations is that depressive behaviour is a way to avoid costly effort where benefits are small and/or unlikely. However, this viewpoint fails to explain why low mood persists when the situation improves. We investigate whether a behavioural rule that is adapted to a stochastically changing world can cause inactivity which appears similar to the effect of depression, in that it persists after the situation has improved. We develop an adaptive learning model in which an individual has repeated choices of whether to invest costly effort that may result in a net benefit. Investing effort also provides information about the current conditions and rates of change of the conditions. An individual following the optimal behavioural strategy may sometimes remain inactive when conditions are favourable (i.e. when it would be better to invest effort) when it is poorly informed about the current environmental state. Initially benign conditions can predispose an individual to inactivity after a relatively brief period of negative experiences. Our approach suggests that the antecedent factors causing depressed behaviour could go much further back in an individual s history than is currently appreciated. The insights from our approach have implications for the ongoing debate about best treatment options for patients with depressive symptoms. © The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  13. Adaptive interaction a utility maximization approach to understanding human interaction with technology

    CERN Document Server

    Payne, Stephen J

    2013-01-01

    This lecture describes a theoretical framework for the behavioural sciences that holds high promise for theory-driven research and design in Human-Computer Interaction. The framework is designed to tackle the adaptive, ecological, and bounded nature of human behaviour. It is designed to help scientists and practitioners reason about why people choose to behave as they do and to explain which strategies people choose in response to utility, ecology, and cognitive information processing mechanisms. A key idea is that people choose strategies so as to maximise utility given constraints. The frame

  14. Sulfur Metabolism of Hydrogenovibrio thermophilus Strain S5 and Its Adaptations to Deep-Sea Hydrothermal Vent Environment

    Directory of Open Access Journals (Sweden)

    Lijing Jiang

    2017-12-01

    Full Text Available Hydrogenovibrio bacteria are ubiquitous in global deep-sea hydrothermal vents. However, their adaptations enabling survival in these harsh environments are not well understood. In this study, we characterized the physiology and metabolic mechanisms of Hydrogenovibrio thermophilus strain S5, which was first isolated from an active hydrothermal vent chimney on the Southwest Indian Ridge. Physiological characterizations showed that it is a microaerobic chemolithomixotroph that can utilize sulfide, thiosulfate, elemental sulfur, tetrathionate, thiocyanate or hydrogen as energy sources and molecular oxygen as the sole electron acceptor. During thiosulfate oxidation, the strain produced extracellular sulfur globules 0.7–6.0 μm in diameter that were mainly composed of elemental sulfur and carbon. Some organic substrates including amino acids, tryptone, yeast extract, casamino acids, casein, acetate, formate, citrate, propionate, tartrate, succinate, glucose and fructose can also serve as carbon sources, but growth is weaker than under CO2 conditions, indicating that strain S5 prefers to be chemolithoautotrophic. None of the tested organic carbons could function as energy sources. Growth tests under various conditions confirmed its adaption to a mesophilic mixing zone of hydrothermal vents in which vent fluid was mixed with cold seawater, preferring moderate temperatures (optimal 37°C, alkaline pH (optimal pH 8.0, microaerobic conditions (optimal 4% O2, and reduced sulfur compounds (e.g., sulfide, optimal 100 μM. Comparative genomics showed that strain S5 possesses more complex sulfur metabolism systems than other members of genus Hydrogenovibrio. The genes encoding the intracellular sulfur oxidation protein (DsrEF and assimilatory sulfate reduction were first reported in the genus Hydrogenovibrio. In summary, the versatility in energy and carbon sources, and unique physiological properties of this bacterium have facilitated its adaptation to deep

  15. Phylogeography, salinity adaptations and metabolic potential of the Candidate Division KB1 Bacteria based on a partial single cell genome.

    Directory of Open Access Journals (Sweden)

    Lisa M Nigro

    2016-08-01

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

  16. Paving a Path to Understanding Metabolic Responses to Iron Bioavailability: Global Proteomic Analysis of Crocosphaera watsonii

    Science.gov (United States)

    Gauglitz, J.; McIlvin, M. R.; Moran, D. M.; Waterbury, J. B.; Saito, M. A.

    2016-02-01

    Marine diazotrophic cyanobacteria provide a key source of new nitrogen into the oceans and are important contributors to primary production. The geographic distribution of these cyanobacteria is impacted by available iron and phosphorus as well as environmental conditions such as temperature, however available iron concentrations are thought to be particularly critical due to the high demand for iron in cellular processes. Iron bioavailability and microorganismal adaptations to low iron environments may thus play a key role in dictating community structure, however the mechanisms by which cyanobacteria acquire iron and regulate its uptake are not well defined. In this study, the unicellular diazotroph, Crocosphaera watsonii WH8501, was acclimated to a range of bioavailable iron concentrations (from 0.001nM to 8.13nM Fe') using trace metal clean culturing techniques and the proteomes were analyzed by LC/MS-MS. Physiological and proteomic data indicate three distinct phenotypic ranges: iron-replete, iron-limited, and iron-starved. Trends in photosynthetic, carbon fixation and iron storage proteins across the iron gradient indicate that the C. watsonii proteome responds directly to iron availability. Further analysis of relative protein expression, which describes the physiological state of the cell, will lead to insights into how C. watsonii is able to adapt to iron-limited conditions and the resulting biogeochemical implications will be discussed.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    +/- 59 vs. 688 +/- 43 mmol/kg dry wt) in Fat-CHO than in CHO. In conclusion, shift to carbohydrate diet after prolonged adaptation to fat diet and training causes increased resting muscle glycogen levels but impaired leg glucose uptake and similar muscle glycogen breakdown, despite higher resting levels...

  18. Aging and longevity of yeast colony populations: metabolic adaptation and differentiation

    Czech Academy of Sciences Publication Activity Database

    Váchová, Libuše; Palková, Z.

    2011-01-01

    Roč. 39, - (2011), s. 1471-1475 ISSN 0300-5127 R&D Projects: GA ČR GA204/08/0718; GA MŠk(CZ) LC531 Institutional research plan: CEZ:AV0Z50200510 Keywords : adaptation and longevity * ammonia signalling * quorum sensing Subject RIV: EE - Microbiology, Virology Impact factor: 3.711, year: 2011

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

    Czech Academy of Sciences Publication Activity Database

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

    2015-01-01

    Roč. 64, č. 1 (2015), s. 51-60 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GB14-36804G; GA ČR(CZ) GA13-04420S; GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:61389005 Keywords : gender * hairless rat * metabolism * brown adipose tissue Subject RIV: ED - Physiology Impact factor: 1.643, year: 2015

  20. Metabolic adaptation in the crew of the Hesperides on their Antarctic journey.

    Science.gov (United States)

    Fernández-Riestra, Francisco A; Garcés, Carmen; Lahoz, Carlos; Lasunción, Miguel A; Castilla, Patricia; Viturro, Enrique; Cano, Beatriz; de Oya, Manuel

    2006-10-01

    We studied the metabolic changes that took place in the crew of the Hesperides vessel in their 2001-2002 Antarctic journey, comparing two periods differing in diet and physical activity. Lipid profile, vitamin and hormone levels were analyzed in 17 subjects who completed the study in its two phases. In phase I the participants spent 47 days sailing with hard work and rough seas, and the diet was rich in fat and poor in fresh foods. In this phase, glucose decreased and HDL-cholesterol, apo-AI, and TSH increased. Plasma retinol and alpha-tocopherol levels remained stable, gamma-tocopherol, alpha-carotene and beta-carotene significantly decreased, and lycopene significantly increased. Phase II lasted 49 days including a 7-day long stop in port. This meant that a more varied diet was available and fresh foods were present in the hold. There was also less extreme physical activity. The metabolic pattern changed direction, glucose rose, HDL-cholesterol and apo-AI decreased and the levels of the vitamins that dropped in phase I started to increase. Lycopene significantly decreased. Contrary to popular beliefs about navigation at extreme latitudes, the metabolic changes described may be explained by the intense physical activity in a cold environment and a high-fat diet poor in fresh products.

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

    Directory of Open Access Journals (Sweden)

    Gabriel N. Aughey

    2014-10-01

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

  2. Understanding the effect of adaptive preference elicitation methods on user satisfaction of a recommender system

    NARCIS (Netherlands)

    Knijnenburg, B.P.; Willemsen, M.C.

    2009-01-01

    In a recommender system that suggests options based on user attribute weights, the method of preference elicitation (PE) employed by a recommender system can influence users' satisfaction with the system, as well as the perceived usefulness and the understandability of the system. Specifically, we

  3. Response of Estrogen-related Receptor Alpha (ERRα to Endurance Training and its Participation in Endurance Training-induced Adaptations in Lipid Metabolism in Skeletal Muscle of Male Wistar rats

    Directory of Open Access Journals (Sweden)

    Soheil Aminizadeh

    2017-08-01

    Conclusion: In sum, expression of ERRα is a trainable factor and its changes are parallel with the increase in expression of lipid metabolism indexes; so, it could have a direct role in endurance training-induced adaptation in fat metabolism.

  4. Towards the understanding of microbial metabolism in relation to microbial enhanced oil recovery

    DEFF Research Database (Denmark)

    Halim, Amalia Yunita; Nielsen, Sidsel Marie; Nielsen, Kristian Fog

    2017-01-01

    In this study, Bacillus licheniformis 421 was used as a model organism to understand the effects of microbial cell growth and metabolite production under anaerobic conditions in relation to microbial enhanced oil recovery. The bacterium was able to grow anaerobically on different carbon compounds...

  5. Understanding extreme sea levels for broad-scale coastal impact and adaptation analysis

    Science.gov (United States)

    Wahl, T.; Haigh, I. D.; Nicholls, R. J.; Arns, A.; Dangendorf, S.; Hinkel, J.; Slangen, A. B. A.

    2017-07-01

    One of the main consequences of mean sea level rise (SLR) on human settlements is an increase in flood risk due to an increase in the intensity and frequency of extreme sea levels (ESL). While substantial research efforts are directed towards quantifying projections and uncertainties of future global and regional SLR, corresponding uncertainties in contemporary ESL have not been assessed and projections are limited. Here we quantify, for the first time at global scale, the uncertainties in present-day ESL estimates, which have by default been ignored in broad-scale sea-level rise impact assessments to date. ESL uncertainties exceed those from global SLR projections and, assuming that we meet the Paris agreement goals, the projected SLR itself by the end of the century in many regions. Both uncertainties in SLR projections and ESL estimates need to be understood and combined to fully assess potential impacts and adaptation needs.

  6. NMR-based metabonomics for understanding the influence of dormant female genital tuberculosis on metabolism of the human endometrium.

    Science.gov (United States)

    Subramani, E; Jothiramajayam, M; Dutta, M; Chakravorty, D; Joshi, M; Srivastava, S; Mukherjee, A; Datta Ray, C; Chakravarty, B N; Chaudhury, K

    2016-04-01

    Does investigation of metabolic perturbations in endometrial tissue of women with dormant genital tuberculosis (GTB) during the window of implantation (WOI) assist in improving the understanding of endometrial receptivity? In dormant GTB cases significant alterations in endometrial tissue metabolites occur, largely related to energy metabolism and amino acid biosynthesis in dormant GTB cases. As an intracellular pathogen, Mycobacterium tuberculosis strongly influences the metabolism of host cells causing metabolic dysregulation. It is also accepted that dormant GTB impairs the receptive status of the endometrium. Global metabolic profiling is useful for an understanding of disease progression and distinguishing between diseased and non-diseased groups. Endometrial tissue samples were collected from patients reporting at the tertiary infertility care center during the period September 2011-March 2013. Women having tested positive for GTB were considered as the study group (n = 24). Normal healthy women undergoing sterilization (n = 26) and unexplained infertile women with repeated IVF failure (n = 21) volunteered to participate as controls. Endometrial tissue samples were collected 6-10 days after confirmation of ovulation. PCR and BACTEC-460 culture were used for diagnosing GTB. Proton nuclear magnetic resonance (1H NMR) spectra of tissue were recorded using a 700 MHz Bruker Avance AV III spectrometer. Following phase and baseline correction of all NMR spectra by Bruker Topspin 2.1 software, spectral peak alignment of the data was performed. Multivariate analysis was applied to all spectra and individual metabolites identified and multiple correlation analysis was performed. Leucine, isoleucine, acetate, lactate, glutamate, glutamine, methionine, lysine, creatine, glycogen, glycine, proline and choline were found to be significantly increased (P < 0.05) in endometrial tissue of women with dormant GTB compared with unexplained infertile women with repeated

  7. Understanding system dynamics of an adaptive enzyme network from globally profiled kinetic parameters.

    Science.gov (United States)

    Chiang, Austin W T; Liu, Wei-Chung; Charusanti, Pep; Hwang, Ming-Jing

    2014-01-15

    A major challenge in mathematical modeling of biological systems is to determine how model parameters contribute to systems dynamics. As biological processes are often complex in nature, it is desirable to address this issue using a systematic approach. Here, we propose a simple methodology that first performs an enrichment test to find patterns in the values of globally profiled kinetic parameters with which a model can produce the required system dynamics; this is then followed by a statistical test to elucidate the association between individual parameters and different parts of the system's dynamics. We demonstrate our methodology on a prototype biological system of perfect adaptation dynamics, namely the chemotaxis model for Escherichia coli. Our results agreed well with those derived from experimental data and theoretical studies in the literature. Using this model system, we showed that there are motifs in kinetic parameters and that these motifs are governed by constraints of the specified system dynamics. A systematic approach based on enrichment statistical tests has been developed to elucidate the relationships between model parameters and the roles they play in affecting system dynamics of a prototype biological network. The proposed approach is generally applicable and therefore can find wide use in systems biology modeling research.

  8. PP064. Total vascular resistances in early pregnancy: A key to understand abnormal cardiovascular adaptation associated with spontaneous abortion.

    Science.gov (United States)

    Lo Presti, Damiano; Scala, Roberta Licia; Tiralongo, Grazia Maria; Pisani, Ilaria; Gagliardi, Giulia; Novelli, Gian Paolo; Vasapollo, Barbara; Valensise, Herbert

    2013-04-01

    From early pregnancy, maternal hemodynamic profile begins to change. The absence of these changes leads to increased risk of complication during the gestation. Aim of this study is to understand in early pregnancy the behaviour of total vascular resistances (TVR) as a sign of maternal cardiovascular adaptation to pregnancy. A cross section study was conducted. We followed 160 healthy women with singleton pregnancy during the first trimester of gestation. We evaluated cardiac output (CO) and TVR at 7, 9 and 11 weeks of gestation. We obtained the following haemodynamic measurements with the USCOM system, a non invasive method: heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), CO and TVR. 160 healthy pregnant women were selected, 8 patients, were excluded for a bad signal. Absolute values of the haemodynamic measures are shown in Fig. 1. 41 patients underwent spontaneous embryonic demise. This last group of patients showed in 54% (group A) TVR values within the normal limits (TVR1200) and CO values below the normal adaptation to pregnancy. Table 1 shows hemodynamic measures for the group A and group B; we found differences in term of CO, TVR and PAS between the two groups. Elevated TVR might indicate an abnormal vascular adaptation already in first weeks of pregnancy. Moreover, in women who undergo to abortion, elevated TVR could be use to distinguish genetic or environmental causes of miscarriage. Copyright © 2013. Published by Elsevier B.V.

  9. Cell Wall Remodeling by a Synthetic Analog Reveals Metabolic Adaptation in Vancomycin Resistant Enterococci.

    Science.gov (United States)

    Pidgeon, Sean E; Pires, Marcos M

    2017-07-21

    Drug-resistant bacterial infections threaten to overburden our healthcare system and disrupt modern medicine. A large class of potent antibiotics, including vancomycin, operate by interfering with bacterial cell wall biosynthesis. Vancomycin-resistant enterococci (VRE) evade the blockage of cell wall biosynthesis by altering cell wall precursors, rendering them drug insensitive. Herein, we reveal the phenotypic plasticity and cell wall remodeling of VRE in response to vancomycin in live bacterial cells via a metabolic probe. A synthetic cell wall analog was designed and constructed to monitor cell wall structural alterations. Our results demonstrate that the biosynthetic pathway for vancomycin-resistant precursors can be hijacked by synthetic analogs to track the kinetics of phenotype induction. In addition, we leveraged this probe to interrogate the response of VRE cells to vancomycin analogs and a series of cell wall-targeted antibiotics. Finally, we describe a proof-of-principle strategy to visually inspect drug resistance induction. Based on our findings, we anticipate that our metabolic probe will play an important role in further elucidating the interplay among the enzymes involved in the VRE biosynthetic rewiring.

  10. Cardiovascular and metabolic adaptations in horses competing in cross-country events.

    Science.gov (United States)

    Muñoz, A; Riber, C; Santisteban, R; Rubio, M D; Agüera, E I; Castejón, F M

    1999-01-01

    The cardiovascular and metabolic response to two cross-country events (CC*: preliminary level and CC*** advanced level) were analysed in 8 male eventing horses (4 Anglo-Hunter and 4 Anglo-Arabian). This study focused on the establishment of the main metabolic pathways involved in the muscle energy resynthesis during the competitions. Heart rate (HR) was recorded throughout the CC events. Jugular venous blood samples were withdrawn before the warm-up period, immediately after the competitions and at 5 and 10 min in the recuperation period. The following haematological parameters were studied: red blood cells (RBC), packed cell volume (PCV), haemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cells (WBC), and number and percentages of lymphocytes (LYM) and granulocytes and monocytes (GRAN). One fraction of blood was centrifuged and, in plasma, lactate (LA), total plasma protein (TPP) and the rate of LA disappearance were determined. The competitions induced significant increases in RBC, Hb, PCV, MCV and TPP. Plasma LA response exceeded the anaerobic threshold of 4 mmol/l, reaching a maximum level of 13.3 mmol/l. HR ranged from 140 to more than 200 bpm, peaking at 230 bpm, revealing a limitation in the oxygen supply to the working muscles. It was concluded that muscle energy resynthesis during a CC event is provided both through oxidative processes and glycolysis with LA formation. Therefore, both stamina and power exercises are required for eventing horses.

  11. The Mediator subunit MDT-15 confers metabolic adaptation to ingested material.

    Directory of Open Access Journals (Sweden)

    Stefan Taubert

    2008-02-01

    Full Text Available In eukaryotes, RNA polymerase II (Pol(II dependent gene expression requires accessory factors termed transcriptional coregulators. One coregulator that universally contributes to Pol(II-dependent transcription is the Mediator, a multisubunit complex that is targeted by many transcriptional regulatory factors. For example, the Caenorhabditis elegans Mediator subunit MDT-15 confers the regulatory actions of the sterol response element binding protein SBP-1 and the nuclear hormone receptor NHR-49 on fatty acid metabolism. Here, we demonstrate that MDT-15 displays a broader spectrum of activities, and that it integrates metabolic responses to materials ingested by C. elegans. Depletion of MDT-15 protein or mutation of the mdt-15 gene abrogated induction of specific detoxification genes in response to certain xenobiotics or heavy metals, rendering these animals hypersensitive to toxin exposure. Intriguingly, MDT-15 appeared to selectively affect stress responses related to ingestion, as MDT-15 functional defects did not abrogate other stress responses, e.g., thermotolerance. Together with our previous finding that MDT-15:NHR-49 regulatory complexes coordinate a sector of the fasting response, we propose a model whereby MDT-15 integrates several transcriptional regulatory pathways to monitor both the availability and quality of ingested materials, including nutrients and xenobiotic compounds.

  12. Fibroblast growth factor 21 participates in adaptation to endoplasmic reticulum stress and attenuates obesity-induced hepatic metabolic stress.

    Science.gov (United States)

    Kim, Seong Hun; Kim, Kook Hwan; Kim, Hyoung-Kyu; Kim, Mi-Jeong; Back, Sung Hoon; Konishi, Morichika; Itoh, Nobuyuki; Lee, Myung-Shik

    2015-04-01

    Fibroblast growth factor 21 (FGF21) is an endocrine hormone that exhibits anti-diabetic and anti-obesity activity. FGF21 expression is increased in patients with and mouse models of obesity or nonalcoholic fatty liver disease (NAFLD). However, the functional role and molecular mechanism of FGF21 induction in obesity or NAFLD are not clear. As endoplasmic reticulum (ER) stress is triggered in obesity and NAFLD, we investigated whether ER stress affects FGF21 expression or whether FGF21 induction acts as a mechanism of the unfolded protein response (UPR) adaptation to ER stress induced by chemical stressors or obesity. Hepatocytes or mouse embryonic fibroblasts deficient in UPR signalling pathways and liver-specific eIF2α mutant mice were employed to investigate the in vitro and in vivo effects of ER stress on FGF21 expression, respectively. The in vivo importance of FGF21 induction by ER stress and obesity was determined using inducible Fgf21-transgenic mice and Fgf21-null mice with or without leptin deficiency. We found that ER stressors induced FGF21 expression, which was dependent on a PKR-like ER kinase-eukaryotic translation factor 2α-activating transcription factor 4 pathway both in vitro and in vivo. Fgf21-null mice exhibited increased expression of ER stress marker genes and augmented hepatic lipid accumulation after tunicamycin treatment. However, these changes were attenuated in inducible Fgf21-transgenic mice. We also observed that Fgf21-null mice with leptin deficiency displayed increased hepatic ER stress response and liver injury, accompanied by deteriorated metabolic variables. Our results suggest that FGF21 plays an important role in the adaptive response to ER stress- or obesity-induced hepatic metabolic stress.

  13. Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity.

    Science.gov (United States)

    Epel, Elissa S; Lithgow, Gordon J

    2014-06-01

    The rate of biological aging is modulated in part by genes interacting with stressor exposures. Basic research has shown that exposure to short-term stress can strengthen cellular responses to stress ("hormetic stress"). Hormetic stress promotes longevity in part through enhanced activity of molecular chaperones and other defense mechanisms. In contrast, prolonged exposure to stress can overwhelm compensatory responses ("toxic stress") and shorten lifespan. One key question is whether the stressors that are well understood in basic models of aging can help us understand psychological stressors and human health. The psychological stress response promotes regulatory changes important in aging (e.g., increases in stress hormones, inflammation, oxidative stress, insulin). The negative effects of severe stress are well documented in humans. Potential positive effects of acute stress (stress resistance) are less studied, especially at the cellular level. Can stress resistance slow the rate of aging in humans, as it does in model organisms? If so, how can we promote stress resistance in humans? We urge a new research agenda embracing the continuum from cellular stress to psychological stress, using basic and human research in tandem. This will require interdisciplinary novel approaches that hold much promise for understanding and intervening in human chronic disease. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Coping with the Forced Swim Stressor: Towards Understanding an Adaptive Mechanism.

    Science.gov (United States)

    de Kloet, E R; Molendijk, M L

    2016-01-01

    In the forced swim test (FST) rodents progressively show increased episodes of immobility if immersed in a beaker with water from where escape is not possible. In this test, a compound qualifies as a potential antidepressant if it prevents or delays the transition to this passive (energy conserving) behavioural style. In the past decade however the switch from active to passive "coping" was used increasingly to describe the phenotype of an animal that has been exposed to a stressful history and/or genetic modification. A PubMed analysis revealed that in a rapidly increasing number of papers (currently more than 2,000) stress-related immobility in the FST is labeled as a depression-like phenotype. In this contribution we will examine the different phases of information processing during coping with the forced swim stressor. For this purpose we focus on the action of corticosterone that is mediated by the closely related mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in the limbic brain. The evidence available suggests a model in which we propose that the limbic MR-mediated response selection operates in complementary fashion with dopaminergic accumbens/prefrontal executive functions to regulate the transition between active and passive coping styles. Upon rescue from the beaker the preferred, mostly passive, coping style is stored in the memory via a GR-dependent action in the hippocampal dentate gyrus. It is concluded that the rodent's behavioural response to a forced swim stressor does not reflect depression. Rather the forced swim experience provides a unique paradigm to investigate the mechanistic underpinning of stress coping and adaptation.

  15. A reduced amino acid alphabet for understanding and designing protein adaptation to mutation.

    Science.gov (United States)

    Etchebest, C; Benros, C; Bornot, A; Camproux, A-C; de Brevern, A G

    2007-11-01

    Protein sequence world is considerably larger than structure world. In consequence, numerous non-related sequences may adopt similar 3D folds and different kinds of amino acids may thus be found in similar 3D structures. By grouping together the 20 amino acids into a smaller number of representative residues with similar features, sequence world simplification may be achieved. This clustering hence defines a reduced amino acid alphabet (reduced AAA). Numerous works have shown that protein 3D structures are composed of a limited number of building blocks, defining a structural alphabet. We previously identified such an alphabet composed of 16 representative structural motifs (5-residues length) called Protein Blocks (PBs). This alphabet permits to translate the structure (3D) in sequence of PBs (1D). Based on these two concepts, reduced AAA and PBs, we analyzed the distributions of the different kinds of amino acids and their equivalences in the structural context. Different reduced sets were considered. Recurrent amino acid associations were found in all the local structures while other were specific of some local structures (PBs) (e.g Cysteine, Histidine, Threonine and Serine for the alpha-helix Ncap). Some similar associations are found in other reduced AAAs, e.g Ile with Val, or hydrophobic aromatic residues Trp with Phe and Tyr. We put into evidence interesting alternative associations. This highlights the dependence on the information considered (sequence or structure). This approach, equivalent to a substitution matrix, could be useful for designing protein sequence with different features (for instance adaptation to environment) while preserving mainly the 3D fold.

  16. Speech understanding in background noise with the two-microphone adaptive beamformer BEAM in the Nucleus Freedom Cochlear Implant System.

    Science.gov (United States)

    Spriet, Ann; Van Deun, Lieselot; Eftaxiadis, Kyriaky; Laneau, Johan; Moonen, Marc; van Dijk, Bas; van Wieringen, Astrid; Wouters, Jan

    2007-02-01

    This paper evaluates the benefit of the two-microphone adaptive beamformer BEAM in the Nucleus Freedom cochlear implant (CI) system for speech understanding in background noise by CI users. A double-blind evaluation of the two-microphone adaptive beamformer BEAM and a hardware directional microphone was carried out with five adult Nucleus CI users. The test procedure consisted of a pre- and post-test in the lab and a 2-wk trial period at home. In the pre- and post-test, the speech reception threshold (SRT) with sentences and the percentage correct phoneme scores for CVC words were measured in quiet and background noise at different signal-to-noise ratios. Performance was assessed for two different noise configurations (with a single noise source and with three noise sources) and two different noise materials (stationary speech-weighted noise and multitalker babble). During the 2-wk trial period at home, the CI users evaluated the noise reduction performance in different listening conditions by means of the SSQ questionnaire. In addition to the perceptual evaluation, the noise reduction performance of the beamformer was measured physically as a function of the direction of the noise source. Significant improvements of both the SRT in noise (average improvement of 5-16 dB) and the percentage correct phoneme scores (average improvement of 10-41%) were observed with BEAM compared to the standard hardware directional microphone. In addition, the SSQ questionnaire and subjective evaluation in controlled and real-life scenarios suggested a possible preference for the beamformer in noisy environments. The evaluation demonstrates that the adaptive noise reduction algorithm BEAM in the Nucleus Freedom CI-system may significantly increase the speech perception by cochlear implantees in noisy listening conditions. This is the first monolateral (adaptive) noise reduction strategy actually implemented in a mainstream commercial CI.

  17. Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver.

    Science.gov (United States)

    Theurey, Pierre; Tubbs, Emily; Vial, Guillaume; Jacquemetton, Julien; Bendridi, Nadia; Chauvin, Marie-Agnès; Alam, Muhammad Rizwan; Le Romancer, Muriel; Vidal, Hubert; Rieusset, Jennifer

    2016-04-01

    Mitochondria-associated endoplasmic reticulum membranes (MAM) play a key role in mitochondrial dynamics and function and in hepatic insulin action. Whereas mitochondria are important regulators of energy metabolism, the nutritional regulation of MAM in the liver and its role in the adaptation of mitochondria physiology to nutrient availability are unknown. In this study, we found that the fasted to postprandial transition reduced the number of endoplasmic reticulum-mitochondria contact points in mouse liver. Screening of potential hormonal/metabolic signals revealed glucose as the main nutritional regulator of hepatic MAM integrity both in vitro and in vivo Glucose reduced organelle interactions through the pentose phosphate-protein phosphatase 2A (PP-PP2A) pathway, induced mitochondria fission, and impaired respiration. Blocking MAM reduction counteracted glucose-induced mitochondrial alterations. Furthermore, disruption of MAM integrity mimicked effects of glucose on mitochondria dynamics and function. This glucose-sensing system is deficient in the liver of insulin-resistant ob/ob and cyclophilin D-KO mice, both characterized by chronic disruption of MAM integrity, mitochondrial fission, and altered mitochondrial respiration. These data indicate that MAM contribute to the hepatic glucose-sensing system, allowing regulation of mitochondria dynamics and function during nutritional transition. Chronic disruption of MAM may participate in hepatic mitochondrial dysfunction associated with insulin resistance. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  18. Metabolic adaptations to short-term every-other-day feeding in long-living Ames dwarf mice.

    Science.gov (United States)

    Brown-Borg, Holly M; Rakoczy, Sharlene

    2013-09-01

    Restrictive dietary interventions exert significant beneficial physiological effects in terms of aging and age-related disease in many species. Every other day feeding (EOD) has been utilized in aging research and shown to mimic many of the positive outcomes consequent with dietary restriction. This study employed long living Ames dwarf mice subjected to EOD feeding to examine the adaptations of the oxidative phosphorylation and antioxidative defense systems to this feeding regimen. Every other day feeding lowered liver glutathione (GSH) concentrations in dwarf and wild type (WT) mice but altered GSH biosynthesis and degradation in WT mice only. The activities of liver OXPHOS enzymes and corresponding proteins declined in WT mice fed EOD while in dwarf animals, the levels were maintained or increased with this feeding regimen. Antioxidative enzymes were differentially affected depending on the tissue, whether proliferative or post-mitotic. Gene expression of components of liver methionine metabolism remained elevated in dwarf mice when compared to WT mice as previously reported however, enzymes responsible for recycling homocysteine to methionine were elevated in both genotypes in response to EOD feeding. The data suggest that the differences in anabolic hormone levels likely affect the sensitivity of long living and control mice to this dietary regimen, with dwarf mice exhibiting fewer responses in comparison to WT mice. These results provide further evidence that dwarf mice may be better protected against metabolic and environmental perturbations which may in turn, contribute to their extended longevity. © 2013.

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

    DEFF Research Database (Denmark)

    Jørgensen, Stine Ringholm

    and interferes with the exercise-induced adaptive response in human skeletal muscle. Study II demonstrates that mouse liver glucose-6-phosphatase (G6Pase) mRNA content increased in recovery from acute exercise in both wildtype (WT) and PGC-1α knockout (KO) mice, while phosphoenolpyruvate carboxykinase (PEPCK......) and pyruvate carboxylase mRNA content did not change in either genotype. Exercise training increased PEPCK protein content in both WT and PGC-1α KO mice. In addition, the mRNA and protein content of cytochrome (Cyt) c and cytochrome c oxidase (COX) subunit I increased in response to acute exercise and exercise...

  20. Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells.

    Science.gov (United States)

    Sandbichler, Adolf M; Jansen, Bianca; Peer, Bettina A; Paulitsch, Monika; Pelster, Bernd; Egg, Margit

    2018-01-01

    Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts. Circadian oscillations of core clock gene mRNA´s were assessed using realtime qPCR with subsequent cosine wave fit analysis. Here we show that under normoxia primary metabolic activity of cells predominately occurs during day time and that after acute hypoxia of two hours, administrated immediately before each sampling point, steady state concentrations of glycolytic key metabolites such as glucose and lactate reveal to be highly rhythmic, following a circadian pattern with highest levels during the night periods and reflecting the circadian variation of the cellular response to hypoxia. Remarkably, rhythms in glycolysis are transferred to cellular energy states under normoxic conditions, so that ADP/ATP ratios oscillate as well, which is the first evidence for cycling ADP/ATP pools in a metazoan cell line to our knowledge. Furthermore, the hypoxia induced alterations in rhythms of glycolysis lead to the alignment of three major cellular redox systems, namely the circadian oscillations of NAD+/NADH and NADP+/NADPH ratios and of increased nocturnal levels of oxidized peroxiredoxins, resulting in a highly

  1. Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells

    Directory of Open Access Journals (Sweden)

    Adolf M. Sandbichler

    2018-04-01

    Full Text Available Background/Aims: Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. Methods: For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts. Circadian oscillations of core clock gene mRNA´s were assessed using realtime qPCR with subsequent cosine wave fit analysis. Results: Here we show that under normoxia primary metabolic activity of cells predominately occurs during day time and that after acute hypoxia of two hours, administrated immediately before each sampling point, steady state concentrations of glycolytic key metabolites such as glucose and lactate reveal to be highly rhythmic, following a circadian pattern with highest levels during the night periods and reflecting the circadian variation of the cellular response to hypoxia. Remarkably, rhythms in glycolysis are transferred to cellular energy states under normoxic conditions, so that ADP/ATP ratios oscillate as well, which is the first evidence for cycling ADP/ATP pools in a metazoan cell line to our knowledge. Furthermore, the hypoxia induced alterations in rhythms of glycolysis lead to the alignment of three major cellular redox systems, namely the circadian oscillations of NAD+/NADH and NADP+/NADPH ratios and of increased nocturnal levels

  2. Productivity of selected plant species adapted to arid regions. [Crassulacean metabolizing plants; Agave deserti and Ferocactus acanthodes

    Energy Technology Data Exchange (ETDEWEB)

    Nobel, P.S.

    1980-01-01

    The biomass potential of selected arid region species for alcohol production merits careful consideration. The basis for this interest is the current low agronomic use of arid lands and the potential productivity of certain species adapted to these lands. Plants displaying Crassulacean acid metabolism (CAM) are particularly interesting with reference to biomass for fuel in regions with low rainfall, because plants with this photosynthetic process are strikingly efficient in water requirements. For CAM plants, CO/sub 2/ fixation occurs primarily at night, when tissue surface temperature and hence transpirational water loss is less than daytime values. For Agave deserti in the Sonoran desert, the water-use efficiency (mass of CO/sub 2/ fixed/mass of water transpired) over an entire year is an order of magnitude or more larger than for C-3 and C-4 plants. This indicates how well adapted CAM species are to arid regions. The potential productivity per unit land area of CAM plants is fairly substantial and, therefore, of considerable economic interest for arid areas where growth of agricultural plants is minimal.

  3. Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.

    Science.gov (United States)

    Gürke, Jacqueline; Hirche, Frank; Thieme, René; Haucke, Elisa; Schindler, Maria; Stangl, Gabriele I; Fischer, Bernd; Navarrete Santos, Anne

    2015-01-01

    During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling.

  4. Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.

    Directory of Open Access Journals (Sweden)

    Jacqueline Gürke

    Full Text Available During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2, branched chain ketoacid dehydrogenase (Bckdha and dehydrolipoyl dehydrogenase (Dld, were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling.

  5. The Role of Isocitrate Lyase (ICL1) in the Metabolic Adaptation of Candida albicans Biofilms

    Science.gov (United States)

    Ishola, Oluwaseun Ayodeji; Ting, Seng Yeat; Tabana, Yasser M; Ahmed, Mowaffaq Adam; Yunus, Muhammad Amir; Mohamed, Rafeezul; Lung Than, Leslie Thian; Sandai, Doblin

    2016-01-01

    Background A major characteristic of Candida biofilm cells that differentiates them from free-floating cells is their high tolerance to antifungal drugs. This high resistance is attributed to particular biofilm properties, including the accumulation of extrapolymeric substances, morphogenetic switching, and metabolic flexibility. Objectives This study evaluated the roles of metabolic processes (in particular the glyoxylate cycle) on biofilm formation, antifungal drug resistance, morphology, and cell wall components. Methods Growth, adhesion, biofilm formation, and cell wall carbohydrate composition were quantified for isogenic Candida albicans ICL1/ICL1, ICL1/icl1, and icl1/icl1 strains. The morphology and topography of these strains were compared by light microscopy and scanning electron microscopy. FKS1 (glucan synthase), ERG11 (14-α-demethylase), and CDR2 (efflux pump) mRNA levels were quantified using qRT-PCR. Results The ICL1/icl1 and icl1/icl1 strains formed similar biofilms and exhibited analogous drug-tolerance levels to the control ICL1/ICL1 strains. Furthermore, the drug sequestration ability of β-1, 3-glucan, a major carbohydrate component of the extracellular matrix, was not impaired. However, the inactivation of ICL1 did impair morphogenesis. ICL1 deletion also had a considerable effect on the expression of the FKS1, ERG11, and CDR2 genes. FKS1 and ERG11 were upregulated in ICL1/icl1 and icl1/icl1 cells throughout the biofilm developmental stages, and CDR2 was upregulated at the early phase. However, their expression was downregulated compared to the control ICL1/ICL1 strain. Conclusions We conclude that the glyoxylate cycle is not a specific determinant of biofilm drug resistance. PMID:27800147

  6. Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model

    Directory of Open Access Journals (Sweden)

    Fang-Hui Li

    2018-05-01

    Full Text Available The effects of high-intensity interval (HIIT and moderate-intensity continuous training (MICT on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance (1H NMR spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague–Dawley rats were separated into three groups: sedentary control (SED, MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by 1H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, 1H NMR spectroscopy and multivariate

  7. Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model.

    Science.gov (United States)

    Li, Fang-Hui; Li, Tao; Ai, Jing-Yi; Sun, Lei; Min, Zhu; Duan, Rui; Zhu, Ling; Liu, Yan-Ying; Liu, Timon Cheng-Yi

    2018-01-01

    The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance ( 1 H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague-Dawley rats were separated into three groups: sedentary control (SED), MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by 1 H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio) in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, 1 H NMR spectroscopy and multivariate statistical

  8. Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach.

    Science.gov (United States)

    Chen, Meimei; Yang, Fafu; Yang, Xuemei; Lai, Xinmei; Gao, Yuxing

    2016-12-16

    Metabolic syndrome (MS) is becoming a worldwide health problem. Wendan decoction (WDD)-a famous traditional Chinese medicine formula-has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

  9. Systematic Understanding of Mechanisms of a Chinese Herbal Formula in Treatment of Metabolic Syndrome by an Integrated Pharmacology Approach

    Directory of Open Access Journals (Sweden)

    Meimei Chen

    2016-12-01

    Full Text Available Metabolic syndrome (MS is becoming a worldwide health problem. Wendan decoction (WDD—a famous traditional Chinese medicine formula—has been extensively employed to relieve syndromes related to MS in clinical practice in China. However, its pharmacological mechanisms still remain vague. In this study, a comprehensive approach that integrated chemomics, principal component analysis, molecular docking simulation, and network analysis was established to elucidate the multi-component and multi-target mechanism of action of WDD in treatment of MS. The compounds in WDD were found to possess chemical diversity, complexity and drug-likeness compared to MS drugs. Six nuclear receptors were obtained to have strong binding affinity with 217 compounds of five herbs in WDD. The importance roles of targets and herbs were also identified due to network parameters. Five compounds from Radix Glycyrrhizae Preparata can hit all six targets, which can assist in screening new MS drugs. The pathway network analysis demonstrated that the main pharmacological effects of WDD might lie in maintaining lipid and glucose metabolisms and anticancer activities as well as immunomodulatory and hepatoprotective effects. This study provided a comprehensive system approach for understanding the multi-component, multi-target and multi-pathway mechanisms of WDD during the treatment of MS.

  10. A Computational Model of Hepatic Energy Metabolism: Understanding Zonated Damage and Steatosis in NAFLD.

    Directory of Open Access Journals (Sweden)

    William B Ashworth

    2016-09-01

    Full Text Available In non-alcoholic fatty liver disease (NAFLD, lipid build-up and the resulting damage is known to occur more severely in pericentral cells. Due to the complexity of studying individual regions of the sinusoid, the causes of this zone specificity and its implications on treatment are largely ignored. In this study, a computational model of liver glucose and lipid metabolism is presented which treats the sinusoid as the repeating unit of the liver rather than the single hepatocyte. This allows for inclusion of zonated enzyme expression by splitting the sinusoid into periportal to pericentral compartments. By simulating insulin resistance (IR and high intake diets leading to the development of steatosis in the model, we identify key differences between periportal and pericentral cells accounting for higher susceptibility to pericentral steatosis. Secondly, variation between individuals is seen in both susceptibility to steatosis and in its development across the sinusoid. Around 25% of obese individuals do not show excess liver fat, whilst 16% of lean individuals develop NAFLD. Furthermore, whilst pericentral cells tend to show higher lipid levels, variation is seen in the predominant location of steatosis from pericentral to pan-sinusoidal or azonal. Sensitivity analysis was used to identify the processes which have the largest effect on both total hepatic triglyceride levels and on the sinusoidal location of steatosis. As is seen in vivo, steatosis occurs when simulating IR in the model, predominantly due to increased uptake, along with an increase in de novo lipogenesis. Additionally, concentrations of glucose intermediates including glycerol-3-phosphate increased when simulating IR due to inhibited glycogen synthesis. Several differences between zones contributed to a higher susceptibility to steatosis in pericentral cells in the model simulations. Firstly, the periportal zonation of both glycogen synthase and the oxidative phosphorylation

  11. A Computational Model of Hepatic Energy Metabolism: Understanding Zonated Damage and Steatosis in NAFLD

    Science.gov (United States)

    Ashworth, William B.; Bogle, I. David L.

    2016-01-01

    In non-alcoholic fatty liver disease (NAFLD), lipid build-up and the resulting damage is known to occur more severely in pericentral cells. Due to the complexity of studying individual regions of the sinusoid, the causes of this zone specificity and its implications on treatment are largely ignored. In this study, a computational model of liver glucose and lipid metabolism is presented which treats the sinusoid as the repeating unit of the liver rather than the single hepatocyte. This allows for inclusion of zonated enzyme expression by splitting the sinusoid into periportal to pericentral compartments. By simulating insulin resistance (IR) and high intake diets leading to the development of steatosis in the model, we identify key differences between periportal and pericentral cells accounting for higher susceptibility to pericentral steatosis. Secondly, variation between individuals is seen in both susceptibility to steatosis and in its development across the sinusoid. Around 25% of obese individuals do not show excess liver fat, whilst 16% of lean individuals develop NAFLD. Furthermore, whilst pericentral cells tend to show higher lipid levels, variation is seen in the predominant location of steatosis from pericentral to pan-sinusoidal or azonal. Sensitivity analysis was used to identify the processes which have the largest effect on both total hepatic triglyceride levels and on the sinusoidal location of steatosis. As is seen in vivo, steatosis occurs when simulating IR in the model, predominantly due to increased uptake, along with an increase in de novo lipogenesis. Additionally, concentrations of glucose intermediates including glycerol-3-phosphate increased when simulating IR due to inhibited glycogen synthesis. Several differences between zones contributed to a higher susceptibility to steatosis in pericentral cells in the model simulations. Firstly, the periportal zonation of both glycogen synthase and the oxidative phosphorylation enzymes meant that the

  12. Proteomics and metabolomics characterizing the pathophysiology of adaptive reactions to the metabolic challenges during the transition from late pregnancy to early lactation in dairy cows.

    Science.gov (United States)

    Ceciliani, Fabrizio; Lecchi, Cristina; Urh, Christiane; Sauerwein, Helga

    2018-04-30

    The transition from late pregnancy to early lactation is a critical period in a dairy cow's life due to the rapidly increasing drain of nutrients from the maternal organism towards the foetus and into colostrum and milk. In order to cope with the challenges of parturition and lactation, comprehensive adaptive reactions comprising the endocrine and the immune system need to be accomplished. There is high variation in this coping ability and both metabolic and infectious diseases, summarized as "production diseases", such as hypocalcaemia (milk fever), fatty liver syndrome, laminitis and ketosis, may occur and impact welfare, productive lifespan and economic outcomes. Proteomics and metabolomics have emerged as valuable techniques to characterize proteins and metabolite assets from tissue and biological fluids, such as milk, blood and urine. In this review we provide an overview on metabolic status and physiological changes during the transition period and the related production diseases in dairy cows, and summarize the state of art on proteomics and metabolomics of biological fluids and tissues involved in metabolic stress during the peripartum period. We also provide a current and prospective view of the application of the recent achievements generated by omics for biomarker discovery and their potential in diagnosis. For high-yielding dairy cows there are several "occupational diseases" that occur mainly during the metabolic challenges related to the transition from pregnancy to lactation. Such diseases and their sequelae form a major concern for dairy production, and often lead to early culling of animals. Beside the economical perspective, metabolic stress may severely influence animal welfare. There is a multitude of studies about the metabolic backgrounds of such so called production diseases like ketosis, fatty liver, or hypocalcaemia, although the investigations aiming to assess the complexity of the pathophysiological reactions are largely focused on gene

  13. Understanding energy consumption behaviors in order to adapt demand response measures

    Energy Technology Data Exchange (ETDEWEB)

    Vassileva, Iana; Wallin, Fredrik; Dahlquist, Erik [Malardalen University (Sweden)], email: iana.vassileva@mdh.se, email: fredrik.wallin@mdh.se, email: erik.dahlquist@mdh.se

    2011-07-01

    When new price strategies and other demand-response measures are being established, it is important that amounts of electricity consumed and the potential for consumer participation be given serious consideration. It is important to encourage consumers to use less electricity if sustainable use of energy is to be achieved. Demand-response is a key component of the smart grids concept. So it is vital to get a comprehensive understanding of how different processes and factors influence the end use of energy. This paper presents an in-depth analysis of questionnaire responses from 2000 households in Vaxjo, Sweden. It sheds new light on the energy consumption behaviors of Swedish householders. Since 2008 Vaxjo householder customers have been able to check their own daily electricity consumption and get advice and tips, via a website provided by the local energy company, on how to lower the use of electricity. At the present time, of those responding to the questionnaire, this website is visited more frequently by people who live in houses than in apartments.

  14. Understanding of human metabolic pathways of different sub-classes of phenols from Arbutus unedo fruit after an acute intake.

    Science.gov (United States)

    Mosele, Juana I; Macià, Alba; Motilva, María-José

    2016-03-01

    Arbutus unedo is a small Mediterranean fruit, commonly named strawberry tree, which is a rich source of different sub-classes of phenolic compounds, the more representative being the gallic acid derivatives, including its mono and oligomeric forms esterified with quinic and shikimic acids. In addition, galloyl derivatives, particularly gallotannins, described in A. unedo, are part of a very selective phenolic group, present in a reduced number of plant-products. The aim of the present study is to provide a better understanding of human metabolic pathways of different sub-classes of phenols from the A. unedo fruit after an acute intake by healthy adults. Therefore, the A. unedo phenolic metabolites were studied in whole blood samples (0 to 24 h), urine (24 h) and feces (12 and 24 h). Special focus was placed on the application of dried blood spot (DBS) cards for the sample collection and for the analysis of phenolic metabolites in whole blood samples. The results of the blood analysis revealed two peaks for the maximum concentrations of the main phenolic metabolites. Furthermore, it is appropriate to highlight the application of DBS cards as an efficient and accurate way to collect blood samples in post-prandial bioavailability studies. The analysis of urine (24 h) gave a wide range of phenolic metabolites showing the extensive metabolism that A. unedo phenolic compounds underwent in the human body. The results of the study provide a relevant contribution to the understanding of the in vivo human bioavailability of phenolic compounds, especially galloyl derivatives, a singular phenolic sub-group present in the A. unedo fruit.

  15. Adaptative increase of ornithine production and decrease of ammonia metabolism in rat colonocytes after hyperproteic diet ingestion.

    Science.gov (United States)

    Mouillé, Béatrice; Robert, Véronique; Blachier, François

    2004-08-01

    Chronic high-protein consumption leads to increased concentrations of NH(4)(+)/NH(3) in the colon lumen. We asked whether this increase has consequences on colonic epithelial cell metabolism. Rats were fed isocaloric diets containing 20 (P20) or 58% (P58) casein as the protein source for 7 days. NH(4)(+)/NH(3) concentration in the colonic lumen and in the colonic vein blood as well as ammonia metabolism by isolated surface colonic epithelial cells was determined. After 2 days of consumption of the P58 diet, marked increases of luminal and colonic vein blood NH(4)(+)/NH(3) concentrations were recorded when compared with the values obtained in the P20 group. Colonocytes recovered from the P58 group were characterized at that time and thereafter by an increased capacity for l-ornithine and urea production through arginase (P diet consumption, however, the ammonia metabolism into l-citrulline was found lower (P < 0.01) when compared with the values measured in the colonocytes recovered from the P20 group despite any decrease in the related enzymatic activities (i.e., carbamoyl-phosphate synthetase I and ornithine carbamoyl transferase). This decrease was found to coincide with a return of blood NH(4)(+)/NH(3) concentration in colonic portal blood to values close to the one recorded in the P20 group. In response to increased NH(4)(+)/NH(3) concentration in the colon, the increased capacity of the colonocytes to synthesize l-ornithine is likely to correspond to an elevated l-ornithine requirement for the elimination of excessive blood ammonia in the liver urea cycle. Moreover, in the presence of NH(4)Cl, colonocytes diminished their synthesis capacity of l-citrulline from l-ornithine, allowing a lower cellular utilization of this latter amino acid. These results are discussed in relationship with an adaptative process that would be related to both interorgan metabolism and to the role of the colonic epithelium as a first line of defense toward luminal NH(4)(+)/NH(3

  16. Understanding Institutional Adaptation to Climate Change: Social Resilience and Adaptive Governance Capacities of the Nature Based Tourism Institutions in the Annapurna Conservation Area, Nepal

    OpenAIRE

    Lama, Anu Kumari

    2016-01-01

    The global-local sustainable development and climate change adaptation policy, and the emerging political discourse on the value of local Adaptation, have positioned the local institutions and their governance space within the strategic enclaves of multilevel governance system. Such shifts have transformed the context for sustainable Nature Based Tourism (NBT) development and adaptation in Nepal in general, and its protected areas, in particular. The emerging institutional adaptation discours...

  17. The woodrat gut microbiota as an experimental system for understanding microbial metabolism of dietary toxins

    Directory of Open Access Journals (Sweden)

    Kevin D. Kohl

    2016-07-01

    Full Text Available The microbial communities inhabiting the alimentary tracts of mammals, particularly those of herbivores, are estimated to be one of the densest microbial reservoirs on Earth. The significance of these gut microbes in influencing the physiology, ecology and evolution of their hosts is only beginning to be realized. To understand the microbiome of herbivores with a focus on nutritional ecology, while evaluating the roles of host evolution and environment in sculpting microbial diversity, we have developed an experimental system consisting of the microbial communities of several species of herbivorous woodrats (genus Neotoma that naturally feed on a variety of dietary toxins. We designed this system to investigate the long-standing, but experimentally neglected hypothesis that ingestion of toxic diets by herbivores is facilitated by the gut microbiota. Like several other rodent species, the woodrat stomach has a sacculated, nongastric foregut portion. We have documented a dense and diverse community of microbes in the woodrat foregut, with several genera potentially capable of degrading dietary toxins and/or playing a role in stimulating hepatic detoxification enzymes of the host. The biodiversity of these gut microbes appears to be a function of host evolution, ecological experience and diet, such that dietary toxins increase microbial diversity in hosts with experience with these toxins while novel toxins depress microbial diversity. These microbial communities are critical to the ingestion of a toxic diet as reducing the microbial community with antibiotics impairs the host’s ability to feed on dietary toxins. Furthermore, the detoxification capacity of gut microbes can be transferred from Neotoma both intra and interspecifically to naïve animals that lack ecological and evolutionary history with these toxins. In addition to advancing our knowledge of complex host-microbes interactions, this system holds promise for identifying microbes that

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

    Science.gov (United States)

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

    2016-01-01

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

  19. Understanding the dynamics of the Seguro Popular de Salud policy implementation in Mexico from a complex adaptive systems perspective.

    Science.gov (United States)

    Nigenda, Gustavo; González-Robledo, Luz María; Juárez-Ramírez, Clara; Adam, Taghreed

    2016-05-13

    In 2003, Mexico's Seguro Popular de Salud (SPS), was launched as an innovative financial mechanism implemented to channel new funds to provide health insurance to 50 million Mexicans and to reduce systemic financial inequities. The objective of this article is to understand the complexity and dynamics that contributed to the adaptation of the policy in the implementation stage, how these changes occurred, and why, from a complex and adaptive systems perspective. A complex adaptive systems (CAS) framework was used to carry out a secondary analysis of data obtained from four SPS's implementation evaluations. We first identified key actors, their roles, incentives and power, and their responses to the policy and guidelines. We then developed a causal loop diagram to disentangle the feedback dynamics associated with the modifications of the policy implementation which we then analyzed using a CAS perspective. Implementation variations were identified in seven core design features during the first 10 years of implementation period, and in each case, the SPS's central coordination introduced modifications in response to the reactions of the different actors. We identified several CAS phenomena associated with these changes including phase transitions, network emergence, resistance to change, history dependence, and feedback loops. Our findings generate valuable lessons to policy implementation processes, especially those involving a monetary component, where the emergence of coping mechanisms and other CAS phenomena inevitably lead to modifications of policies and their interpretation by those who implement them. These include the difficulty of implementing strategies that aim to pool funds through solidarity among beneficiaries where the rich support the poor when there are no incentives for the rich to do so. Also, how resistance to change and history dependence can pose significant challenges to implementing changes, where the local actors use their significant power

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-03-01

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

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

    International Nuclear Information System (INIS)

    Tyagi, R.; Srinivas, G.; Vyas, D.; Kumar, A.; Kumar, H.D.

    1992-01-01

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

  2. iRESM INITIATIVE UNDERSTANDING DECISION SUPPORT NEEDS FOR CLIMATE CHANGE MITIGATION AND ADAPTATION --US Midwest Region—

    Energy Technology Data Exchange (ETDEWEB)

    Rice, Jennie S.; Runci, Paul J.; Moss, Richard H.; Anderson, Kate L.

    2010-10-01

    The impacts of climate change are already affecting human and environmental systems worldwide, yet many uncertainties persist in the prediction of future climate changes and impacts due to limitations in scientific understanding of relevant causal factors. In particular, there is mounting urgency to efforts to improve models of human and environmental systems at the regional scale, and to integrate climate, ecosystem and energy-economic models to support policy, investment, and risk management decisions related to climate change mitigation (i.e., reducing greenhouse gas emissions) and adaptation (i.e., responding to climate change impacts). The Pacific Northwest National Laboratory (PNNL) is developing a modeling framework, the integrated Regional Earth System Model (iRESM), to address regional human-environmental system interactions in response to climate change and the uncertainties therein. The framework will consist of a suite of integrated models representing regional climate change, regional climate policy, and the regional economy, with a focus on simulating the mitigation and adaptation decisions made over time in the energy, transportation, agriculture, and natural resource management sectors.

  3. Exotic species as models to understand biocultural adaptation: Challenges to mainstream views of human-nature relations.

    Directory of Open Access Journals (Sweden)

    Aline Dourado Sena Gama

    Full Text Available A central argument in the research on traditional knowledge, which persists in the scientific literature, is that the entrance of exotic plants in local medical systems is directly associated with acculturation. However, this logic has put an end for a long period to efforts to understand why such species have so successfully entered socio-ecological systems or even their real role in such systems. This study provides evidence that (1 in some socio-environmental contexts, exotic medicinal species usually confer greater adaptive advantages to local populations, and (2 despite their general importance, exotic species only excel in medical systems when cost-benefit ratio is favorable to them. Thus, in order to avoid the loss of knowledge about native plants and to ensure biocultural conservation, it is necessary to create strategies to amplify the advantages of these species.

  4. Research on operation and maintenance support system adaptive to human recognition and understanding in human-centered plant

    International Nuclear Information System (INIS)

    Numano, Masayoshi; Matsuoka, Takeshi; Mitomo, N.

    2004-01-01

    As a human-centered plant, advanced nuclear power plant needs appropriate role sharing between human and mobile intelligent agents. Human-machine cooperation for plant operation and maintenance activities is also required with an advanced interface. Plant's maintenance is programmed using mobile robots working under the radiation environments instead of human beings. Operation and maintenance support system adaptive to human recognition and understanding should be developed to establish adequate human and machine interface so as to induce human capabilities to the full and enable human to take responsibility for plan's operation. Plant's operation and maintenance can be cooperative activities between human and intelligent automonous agents having surveillance and control functions. Infrastructure of multi-agent simulation system for the support system has been investigated and developed based on work plans derived from the scheduler. (T. Tanaka)

  5. Adaptation by Stealth: Understanding climate information use across scales and decision spaces in water management in the United States

    Science.gov (United States)

    Kirchhoff, C.; Vang Rasmussen, L.; Lemos, M. C.

    2016-12-01

    While there has been considerable focus on understanding how factors related to the creation of climate knowledge affect its uptake and use, less attention has been paid to the actors, decisions, and processes through which climate information supports, or fails to support, action. This is particularly the case concerning how different scales of decision-making influence information uptake. In this study, we seek to understand how water and resource managers' decision space influences climate information use in two Great Lakes watersheds. We find that despite the availability of tailored climate information, actual use of information in decision making remains low. Reasons include: a) lack of willingness to place climate on agendas because local managers perceive climate change as politically risky and a difficult and intangible problem; b) lack of formal mandate or authority at the city and county scale to translate climate information into on-the-ground action, c) problems with the information itself, and d) perceived lack of demand for climate information by those managers who have the mandate and authority (e.g. at the state level) to use (or help others use) climate information. Our findings suggest that 1) climate scientists and information brokers should produce information that meets a range of decision needs and reserve intensive tailoring efforts for decision makers who have authority and willingness to employ climate information, 2) without support from higher levels of decision-making (e.g. state) it is unlikely that climate information use for adaptation decisions will accelerate significantly in the next few years, and 3) the trend towards adopting more sustainability and resilience practices over climate-specific actions should be supported as an important component of the climate adaptation repertoire.

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

    Science.gov (United States)

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

    2016-07-02

    Lactobacillus rhamnosus is a diverse Gram-positive species with strains isolated from different ecological niches. Here, we report the genome sequence analysis of 40 diverse strains of L. rhamnosus and their genomic comparison, with a focus on the variable genome. Genomic comparison of 40 L. rhamnosus strains discriminated the conserved genes (core genome) and regions of plasticity involving frequent rearrangements and horizontal transfer (variome). The L. rhamnosus core genome encompasses 2,164 genes, out of 4,711 genes in total (the pan-genome). The accessory genome is dominated by genes encoding carbohydrate transport and metabolism, extracellular polysaccharides (EPS) biosynthesis, bacteriocin production, pili production, the cas system, and the associated clustered regularly interspaced short palindromic repeat (CRISPR) loci, and more than 100 transporter functions and mobile genetic elements like phages, plasmid genes, and transposons. A clade distribution based on amino acid differences between core (shared) proteins matched with the clade distribution obtained from the presence-absence of variable genes. The phylogenetic and variome tree overlap indicated that frequent events of gene acquisition and loss dominated the evolutionary segregation of the strains within this species, which is paralleled by evolutionary diversification of core gene functions. The CRISPR-Cas system could have contributed to this evolutionary segregation. Lactobacillus rhamnosus strains contain the genetic and metabolic machinery with strain-specific gene functions required to adapt to a large range of environments. A remarkable congruency of the evolutionary relatedness of the strains' core and variome functions, possibly favoring interspecies genetic exchanges, underlines the importance of gene-acquisition and loss within the L. rhamnosus strain diversification. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  7. Metabolic Symbiosis and Immunomodulation: How Tumor Cell-Derived Lactate May Disturb Innate and Adaptive Immune Responses

    Directory of Open Access Journals (Sweden)

    Alexandre Morrot

    2018-03-01

    Full Text Available The tumor microenvironment (TME is composed by cellular and non-cellular components. Examples include the following: (i bone marrow-derived inflammatory cells, (ii fibroblasts, (iii blood vessels, (iv immune cells, and (v extracellular matrix components. In most cases, this combination of components may result in an inhospitable environment, in which a significant retrenchment in nutrients and oxygen considerably disturbs cell metabolism. Cancer cells are characterized by an enhanced uptake and utilization of glucose, a phenomenon described by Otto Warburg over 90 years ago. One of the main products of this reprogrammed cell metabolism is lactate. “Lactagenic” or lactate-producing cancer cells are characterized by their immunomodulatory properties, since lactate, the end product of the aerobic glycolysis, besides acting as an inducer of cellular signaling phenomena to influence cellular fate, might also play a role as an immunosuppressive metabolite. Over the last 10 years, it has been well accepted that in the TME, the lactate secreted by transformed cells is able to compromise the function and/or assembly of an effective immune response against tumors. Herein, we will discuss recent advances regarding the deleterious effect of high concentrations of lactate on the tumor-infiltrating immune cells, which might characterize an innovative way of understanding the tumor-immune privilege.

  8. Adapting capillary gel electrophoresis as a sensitive, high-throughput method to accelerate characterization of nucleic acid metabolic enzymes.

    Science.gov (United States)

    Greenough, Lucia; Schermerhorn, Kelly M; Mazzola, Laurie; Bybee, Joanna; Rivizzigno, Danielle; Cantin, Elizabeth; Slatko, Barton E; Gardner, Andrew F

    2016-01-29

    Detailed biochemical characterization of nucleic acid enzymes is fundamental to understanding nucleic acid metabolism, genome replication and repair. We report the development of a rapid, high-throughput fluorescence capillary gel electrophoresis method as an alternative to traditional polyacrylamide gel electrophoresis to characterize nucleic acid metabolic enzymes. The principles of assay design described here can be applied to nearly any enzyme system that acts on a fluorescently labeled oligonucleotide substrate. Herein, we describe several assays using this core capillary gel electrophoresis methodology to accelerate study of nucleic acid enzymes. First, assays were designed to examine DNA polymerase activities including nucleotide incorporation kinetics, strand displacement synthesis and 3'-5' exonuclease activity. Next, DNA repair activities of DNA ligase, flap endonuclease and RNase H2 were monitored. In addition, a multicolor assay that uses four different fluorescently labeled substrates in a single reaction was implemented to characterize GAN nuclease specificity. Finally, a dual-color fluorescence assay to monitor coupled enzyme reactions during Okazaki fragment maturation is described. These assays serve as a template to guide further technical development for enzyme characterization or nucleoside and non-nucleoside inhibitor screening in a high-throughput manner. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Understanding urban water performance at the city-region scale using an urban water metabolism evaluation framework.

    Science.gov (United States)

    Renouf, Marguerite A; Kenway, Steven J; Lam, Ka Leung; Weber, Tony; Roux, Estelle; Serrao-Neumann, Silvia; Choy, Darryl Low; Morgan, Edward A

    2018-06-15

    Water sensitive interventions are being promoted to reduce the adverse impacts of urban development on natural water cycles. However it is currently difficult to know the best strategy for their implementation because current and desired urban water performance is not well quantified. This is particularly at the city-region scale, which is important for strategic urban planning. This work aimed to fill this gap by quantifying the water performance of urban systems within city-regions using 'urban water metabolism' evaluation, to inform decisions about water sensitive interventions. To do this we adapted an existing evaluation framework with new methods. In particular, we used land use data for defining system boundaries, and for estimating natural hydrological flows. The criteria for gauging the water performance were water efficiency (in terms of water extracted externally) and hydrological performance (how much natural hydrological flows have changed relative to a nominated pre-urbanised state). We compared these performance criteria for urban systems within three Australian city-regions (South East Queensland, Melbourne and Perth metropolitan areas), under current conditions, and after implementation of example water sensitive interventions (demand management, rainwater/stormwater harvesting, wastewater recycling and increasing perviousness). The respective water efficiencies were found to be 79, 90 and 133 kL/capita/yr. In relation to hydrological performance, stormwater runoff relative to pre-urbanised flows was of most note, estimated to be 2-, 6- and 3- fold, respectively. The estimated performance benefits from water sensitive interventions suggested different priorities for each region, and that combined implementation of a range of interventions may be necessary to make substantive gains in performance. We concluded that the framework is suited to initial screening of the type and scale of water sensitive interventions needed to achieve desired water

  10. Maize source leaf adaptation to nitrogen deficiency affects not only nitrogen and carbon metabolism but also control of phosphate homeostasis.

    Science.gov (United States)

    Schlüter, Urte; Mascher, Martin; Colmsee, Christian; Scholz, Uwe; Bräutigam, Andrea; Fahnenstich, Holger; Sonnewald, Uwe

    2012-11-01

    Crop plant development is strongly dependent on the availability of nitrogen (N) in the soil and the efficiency of N utilization for biomass production and yield. However, knowledge about molecular responses to N deprivation derives mainly from the study of model species. In this article, the metabolic adaptation of source leaves to low N was analyzed in maize (Zea mays) seedlings by parallel measurements of transcriptome and metabolome profiling. Inbred lines A188 and B73 were cultivated under sufficient (15 mM) or limiting (0.15 mM) nitrate supply for up to 30 d. Limited availability of N caused strong shifts in the metabolite profile of leaves. The transcriptome was less affected by the N stress but showed strong genotype- and age-dependent patterns. N starvation initiated the selective down-regulation of processes involved in nitrate reduction and amino acid assimilation; ammonium assimilation-related transcripts, on the other hand, were not influenced. Carbon assimilation-related transcripts were characterized by high transcriptional coordination and general down-regulation under low-N conditions. N deprivation caused a slight accumulation of starch but also directed increased amounts of carbohydrates into the cell wall and secondary metabolites. The decrease in N availability also resulted in accumulation of phosphate and strong down-regulation of genes usually involved in phosphate starvation response, underlining the great importance of phosphate homeostasis control under stress conditions.

  11. Methanogenic H2 syntrophy among thermophiles: a model of metabolism, adaptation and survival in the subsurface

    Science.gov (United States)

    Topcuoglu, B. D.; Stewart, L. C.; Butterfield, D. A.; Huber, J. A.; Holden, J. F.

    2016-12-01

    Approximately 1 giga ton (Gt, 1015 g) of CH4 is formed globally per year from H2, CO2 and acetate through methanogenesis, largely by methanogens growing in syntrophic association with anaerobic microbes that hydrolyze and ferment biopolymers. However, our understanding of methanogenesis in hydrothermal regions of the subseafloor and potential syntrophic methanogenesis at thermophilic temperatures (i.e., >50°C) is nascent. In this study, the growth of natural assemblages of thermophilic methanogens from Axial Seamount was primarily limited by H2 availability. Heterotrophs supported thermophilic methanogenesis by H2 syntrophy in microcosm incubations of hydrothermal fluids at 55°C and 80°C supplemented with tryptone only. Based on 16S rRNA gene sequencing, only heterotrophic archaea that produce H2, H2-consuming methanogens, and sulfate reducing archaea were found in 80°C tryptone microcosms from Marker 113 vent. No bacteria were found. In 55°C tryptone microcosms, sequences were found from H2-producing bacteria and H2-consuming methanogens and sulfate-reducing bacteria. In order to model the impact of H2 syntrophy at hyperthemophilic temperatures, a co-culture was established consisting of the H2-producing hyperthermophilic heterotroph Thermococcus paralvinellae and a H2-consuming hyperthermophilic methanogen Methanocaldococcus bathoardescens. When grown alone in a chemostat, the growth rates and steady-state cell concentrations of T. paralvinellae decreased significantly when a high H2 (70 µM) background was present. H2 inhibition was ameliorated by the production of formate, but in silico modeling suggests less energetic yield for the cells. H2 syntrophy relieved H2 inhibition for both the heterotroph and the methanogenic partners. The results demonstrate that thermophilic H2 syntrophy can support methanogenesis within natural microbial assemblages and may be an important alternative energy source for thermophilic autotrophs in marine geothermal environments.

  12. The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome.

    Science.gov (United States)

    Daskalakis, Nikolaos P; Bagot, Rosemary C; Parker, Karen J; Vinkers, Christiaan H; de Kloet, E R

    2013-09-01

    Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual's predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Cellular Assays for Ferredoxins: A Strategy for Understanding Electron Flow through Protein Carriers That Link Metabolic Pathways.

    Science.gov (United States)

    Atkinson, Joshua T; Campbell, Ian; Bennett, George N; Silberg, Jonathan J

    2016-12-27

    The ferredoxin (Fd) protein family is a structurally diverse group of iron-sulfur proteins that function as electron carriers, linking biochemical pathways important for energy transduction, nutrient assimilation, and primary metabolism. While considerable biochemical information about individual Fd protein electron carriers and their reactions has been acquired, we cannot yet anticipate the proportion of electrons shuttled between different Fd-partner proteins within cells using biochemical parameters that govern electron flow, such as holo-Fd concentration, midpoint potential (driving force), molecular interactions (affinity and kinetics), conformational changes (allostery), and off-pathway electron leakage (chemical oxidation). Herein, we describe functional and structural gaps in our Fd knowledge within the context of a sequence similarity network and phylogenetic tree, and we propose a strategy for improving our understanding of Fd sequence-function relationships. We suggest comparing the functions of divergent Fds within cells whose growth, or other measurable output, requires electron transfer between defined electron donor and acceptor proteins. By comparing Fd-mediated electron transfer with biochemical parameters that govern electron flow, we posit that models that anticipate energy flow across Fd interactomes can be built. This approach is expected to transform our ability to anticipate Fd control over electron flow in cellular settings, an obstacle to the construction of synthetic electron transfer pathways and rational optimization of existing energy-conserving pathways.

  14. Understanding Students' Adaptation to Graduate School: An Integration of Social Support Theory and Social Learning Theory

    Science.gov (United States)

    Tsay, Crystal Han-Huei

    2012-01-01

    The contemporary business world demands adaptive individuals (Friedman & Wyman, 2005). Adaptation is essential for any life transition. It often involves developing coping mechanisms, strategies, and seeking of social support. Adaptation occurs in many settings from moving to a new culture, taking a new job, starting or finishing an…

  15. Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis.

    Science.gov (United States)

    Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral

    2012-04-01

    The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

  16. Adapting public policy theory for public health research: A framework to understand the development of national policies on global health.

    Science.gov (United States)

    Jones, Catherine M; Clavier, Carole; Potvin, Louise

    2017-03-01

    National policies on global health appear as one way that actors from health, development and foreign affairs sectors in a country coordinate state action on global health. Next to a burgeoning literature in which international relations and global governance theories are employed to understand global health policy and global health diplomacy at the international level, little is known about policy processes for global health at the national scale. We propose a framework of the policy process to understand how such policies are developed, and we identify challenges for public health researchers integrating conceptual tools from political science. We developed the framework using a two-step process: 1) reviewing literature to establish criteria for selecting a theoretical framework fit for this purpose, and 2) adapting Real-Dato's synthesis framework to integrate a cognitive approach to public policy within a constructivist perspective. Our framework identifies multiple contexts as part of the policy process, focuses on situations where actors work together to make national policy on global health, considers these interactive situations as spaces for observing external influences on policy change and proposes policy design as the output of the process. We suggest that this framework makes three contributions to the conceptualisation of national policy on global health as a research object. First, it emphasizes collective action over decisions of individual policy actors. Second, it conceptualises the policy process as organised interactive spaces for collaboration rather than as stages of a policy cycle. Third, national decision-making spaces are opportunities for transferring ideas and knowledge from different sectors and settings, and represent opportunities to identify international influences on a country's global health policy. We discuss two sets of challenges for public health researchers using interdisciplinary approaches in policy research. Copyright

  17. Understanding the interplay of carbon and nitrogen supply for ectoines production and metabolic overflow in high density cultures of Chromohalobacter salexigens.

    Science.gov (United States)

    Salar-García, María J; Bernal, Vicente; Pastor, José M; Salvador, Manuel; Argandoña, Montserrat; Nieto, Joaquín J; Vargas, Carmen; Cánovas, Manuel

    2017-02-08

    The halophilic bacterium Chromohalobacter salexigens has been proposed as promising cell factory for the production of the compatible solutes ectoine and hydroxyectoine. This bacterium has evolved metabolic adaptations to efficiently grow under high salt concentrations by accumulating ectoines as compatible solutes. However, metabolic overflow, which is a major drawback for the efficient conversion of biological feedstocks, occurs as a result of metabolic unbalances during growth and ectoines production. Optimal production of ectoines is conditioned by the interplay of carbon and nitrogen metabolisms. In this work, we set out to determine how nitrogen supply affects the production of ectoines. Chromohalobacter salexigens was challenged to grow in media with unbalanced carbon/nitrogen ratio. In C. salexigens, overflow metabolism and ectoines production are a function of medium composition. At low ammonium conditions, the growth rate decreased importantly, up to 80%. Shifts in overflow metabolism were observed when changing the C/N ratio in the culture medium. 13 C-NMR analysis of ectoines labelling revealed a high metabolic rigidity, with almost constant flux ratios in all conditions assayed. Unbalanced C/N ratio led to pyruvate accumulation, especially upon N-limitation. Analysis of an ect - mutant demonstrated the link between metabolic overflow and ectoine biosynthesis. Under non ectoine synthesizing conditions, glucose uptake and metabolic overflow decreased importantly. Finally, in fed-batch cultures, biomass yield was affected by the feeding scheme chosen. High growth (up to 42.4 g L -1 ) and volumetric ectoine yields (up to 4.21 g L -1 ) were obtained by minimizing metabolite overflow and nutrient accumulation in high density cultures in a low nitrogen fed-batch culture. Moreover, the yield coefficient calculated for the transformation of glucose into biomass was 30% higher in fed-batch than in the batch culture, demonstrating that the metabolic

  18. Recent advances in cancer metabolism: a technological perspective.

    Science.gov (United States)

    Kang, Yun Pyo; Ward, Nathan P; DeNicola, Gina M

    2018-04-16

    Cancer cells are highly dependent on metabolic pathways to sustain both their proliferation and adaption to harsh microenvironments. Thus, understanding the metabolic reprogramming that occurs in tumors can provide critical insights for the development of therapies targeting metabolism. In this review, we will discuss recent advancements in metabolomics and other multidisciplinary techniques that have led to the discovery of novel metabolic pathways and mechanisms in diverse cancer types.

  19. The Effect of a Three-Week Adaptation to a Low Carbohydrate/High Fat Diet on Metabolism and Cognitive Performance

    Science.gov (United States)

    1990-04-11

    similar to that seen in starvation (5,21), hypocaloric weight loss diets (4, 29) and carbohydrate deprivation (12, 27, 28). Our subjects exhibited a...E.A.H. Sims. Comparison of carbohydrate-containing and carbohydrate-restricted hypocaloric diets in the treatment of obesity. J Clin Invest. 68:399-404...D-A247 575 . THE EFFECT OF A THREE-WEEK ADAPTATION TO A LOW CARBOHYDRATE / HIGH FAT DIET ON METABOLISM AND COGNITIVE PERFORMANCE C. G. GRAY 0. G

  20. A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land.

    Science.gov (United States)

    Emiliani, Giovanni; Fondi, Marco; Fani, Renato; Gribaldo, Simonetta

    2009-02-16

    The pioneering ancestor of land plants that conquered terrestrial habitats around 500 million years ago had to face dramatic stresses including UV radiation, desiccation, and microbial attack. This drove a number of adaptations, among which the emergence of the phenylpropanoid pathway was crucial, leading to essential compounds such as flavonoids and lignin. However, the origin of this specific land plant secondary metabolism has not been clarified. We have performed an extensive analysis of the taxonomic distribution and phylogeny of Phenylalanine Ammonia Lyase (PAL), which catalyses the first and essential step of the general phenylpropanoid pathway, leading from phenylalanine to p-Coumaric acid and p-Coumaroyl-CoA, the entry points of the flavonoids and lignin routes. We obtained robust evidence that the ancestor of land plants acquired a PAL via horizontal gene transfer (HGT) during symbioses with soil bacteria and fungi that are known to have established very early during the first steps of land colonization. This horizontally acquired PAL represented then the basis for further development of the phenylpropanoid pathway and plant radiation on terrestrial environments. Our results highlight a possible crucial role of HGT from soil bacteria in the path leading to land colonization by plants and their subsequent evolution. The few functional characterizations of sediment/soil bacterial PAL (production of secondary metabolites with powerful antimicrobial activity or production of pigments) suggest that the initial advantage of this horizontally acquired PAL in the ancestor of land plants might have been either defense against an already developed microbial community and/or protection against UV.

  1. A horizontal gene transfer at the origin of phenylpropanoid metabolism: a key adaptation of plants to land

    Directory of Open Access Journals (Sweden)

    Gribaldo Simonetta

    2009-02-01

    Full Text Available Abstract Background The pioneering ancestor of land plants that conquered terrestrial habitats around 500 million years ago had to face dramatic stresses including UV radiation, desiccation, and microbial attack. This drove a number of adaptations, among which the emergence of the phenylpropanoid pathway was crucial, leading to essential compounds such as flavonoids and lignin. However, the origin of this specific land plant secondary metabolism has not been clarified. Results We have performed an extensive analysis of the taxonomic distribution and phylogeny of Phenylalanine Ammonia Lyase (PAL, which catalyses the first and essential step of the general phenylpropanoid pathway, leading from phenylalanine to p-Coumaric acid and p-Coumaroyl-CoA, the entry points of the flavonoids and lignin routes. We obtained robust evidence that the ancestor of land plants acquired a PAL via horizontal gene transfer (HGT during symbioses with soil bacteria and fungi that are known to have established very early during the first steps of land colonization. This horizontally acquired PAL represented then the basis for further development of the phenylpropanoid pathway and plant radiation on terrestrial environments. Conclusion Our results highlight a possible crucial role of HGT from soil bacteria in the path leading to land colonization by plants and their subsequent evolution. The few functional characterizations of sediment/soil bacterial PAL (production of secondary metabolites with powerful antimicrobial activity or production of pigments suggest that the initial advantage of this horizontally acquired PAL in the ancestor of land plants might have been either defense against an already developed microbial community and/or protection against UV. Reviewers This article was reviewed by Purificación López-García, Janet Siefert, and Eugene Koonin.

  2. Eriophorum angustifolium and Lolium perenne metabolic adaptations to metals- and metalloids-induced anomalies in the vicinity of a chemical industrial complex.

    Science.gov (United States)

    Anjum, Naser A; Ahmad, Iqbal; Rodrigues, Sónia M; Henriques, Bruno; Cruz, Nuno; Coelho, Cláudia; Pacheco, Mário; Duarte, Armando C; Pereira, Eduarda

    2013-01-01

    As plants constitute the foundation of the food chain, concerns have been raised about the possibility of toxic concentrations of metals and metalloids being transported from plants to the higher food chain strata. In this perspective, the use of important phytotoxicity endpoints may be of utmost significance in assessing the hazardous nature of metals and metalloids and also in developing ecological soil screening levels. The current study aimed to investigate the role of glutathione (GSH) and its associated enzymes in the metabolic adaptation of two grass species namely Eriophorum angustifolium Honck. and Lolium perenne L. to metals and metalloids stress in the vicinity of a chemical industrial complex (Estarreja, Portugal). Soil and plant samples were collected from contaminated (C) and non-contaminated (reference, R) sites, respectively, near and away from the Estarreja Chemical Complex, Portugal. Soils (from 0 to 10 and 10 to 20 cm depths) were analyzed for pH, organic carbon, and metals and metalloids concentrations. Plant samples were processed fresh for physiological and biochemical estimations, while oven-dried plant samples were used for metals and metalloids determinations following standard methodologies. Both soils and plants from the industrial area exhibited differential concentrations of major metals and metalloids including As, Cu, Hg, Pb, and Zn. In particular, L. perenne shoot displayed significantly higher and lower concentrations of Pb and As, respectively at contaminated site (vs. E. angustifolium). Irrespective of sites, L. perenne shoot exhibited significantly higher total GSH pool, oxidized glutathione (GSSG) and oxidized protein (vs. E. angustifolium). Additionally, severe damages to photosynthetic pigments, proteins, cellular membrane integrity (in terms of electrolyte leakage), and lipid peroxidation were also perceptible in L. perenne shoot. Contrarily, irrespective of the sites, activities of catalase and GSH-regenerating enzyme, GSH

  3. Metabolic Adaptation, a Specialized Leaf Organ Structure and Vascular Responses to Diurnal N2 Fixation by Nostoc azollae Sustain the Astonishing Productivity of Azolla Ferns without Nitrogen Fertilizer.

    Science.gov (United States)

    Brouwer, Paul; Bräutigam, Andrea; Buijs, Valerie A; Tazelaar, Anne O E; van der Werf, Adrie; Schlüter, Urte; Reichart, Gert-Jan; Bolger, Anthony; Usadel, Björn; Weber, Andreas P M; Schluepmann, Henriette

    2017-01-01

    Sustainable agriculture demands reduced input of man-made nitrogen (N) fertilizer, yet N 2 fixation limits the productivity of crops with heterotrophic diazotrophic bacterial symbionts. We investigated floating ferns from the genus Azolla that host phototrophic diazotrophic Nostoc azollae in leaf pockets and belong to the fastest growing plants. Experimental production reported here demonstrated N-fertilizer independent production of nitrogen-rich biomass with an annual yield potential per ha of 1200 kg -1 N fixed and 35 t dry biomass. 15 N 2 fixation peaked at noon, reaching 0.4 mg N g -1 dry weight h -1 . Azolla ferns therefore merit consideration as protein crops in spite of the fact that little is known about the fern's physiology to enable domestication. To gain an understanding of their nitrogen physiology, analyses of fern diel transcript profiles under differing nitrogen fertilizer regimes were combined with microscopic observations. Results established that the ferns adapted to the phototrophic N 2 -fixing symbionts N. azollae by (1) adjusting metabolically to nightly absence of N supply using responses ancestral to ferns and seed plants; (2) developing a specialized xylem-rich vasculature surrounding the leaf-pocket organ; (3) responding to N-supply by controlling transcripts of genes mediating nutrient transport, allocation and vasculature development. Unlike other non-seed plants, the Azolla fern clock is shown to contain both the morning and evening loops; the evening loop is known to control rhythmic gene expression in the vasculature of seed plants and therefore may have evolved along with the vasculature in the ancestor of ferns and seed plants.

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

    Science.gov (United States)

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

    2017-06-01

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

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

    Science.gov (United States)

    Derno, Michael; Otten, Winfried; Mielenz, Manfred; Nürnberg, Gerd

    2015-01-01

    High ambient temperatures have severe adverse effects on biological functions of high-yielding dairy cows. The metabolic adaption to heat stress was examined in 14 German Holsteins transition cows assigned to two groups, one heat-stressed (HS) and one pair-fed (PF) at the level of HS. After 6 days of thermoneutrality and ad libitum feeding (P1), cows were challenged for 6 days (P2) by heat stress (temperature humidity index (THI) = 76) or thermoneutral pair-feeding in climatic chambers 3 weeks ante partum and again 3 weeks post-partum. On the sixth day of each period P1 or P2, oxidative metabolism was analyzed for 24 hours in open circuit respiration chambers. Water and feed intake, vital parameters and milk yield were recorded. Daily blood samples were analyzed for glucose, β-hydroxybutyric acid, non-esterified fatty acids, urea, creatinine, methyl histidine, adrenaline and noradrenaline. In general, heat stress caused marked effects on water homeorhesis with impairments of renal function and a strong adrenergic response accompanied with a prevalence of carbohydrate oxidation over fat catabolism. Heat-stressed cows extensively degraded tissue protein as reflected by the increase of plasma urea, creatinine and methyl histidine concentrations. However, the acute metabolic heat stress response in dry cows differed from early-lactating cows as the prepartal adipose tissue was not refractory to lipolytic, adrenergic stimuli, and the rate of amino acid oxidation was lower than in the postpartal stage. Together with the lower endogenous metabolic heat load, metabolic adaption in dry cows is indicative for a higher heat tolerance and the prioritization of the nutritional requirements of the fast-growing near-term fetus. These findings indicate that the development of future nutritional strategies for attenuating impairments of health and performance due to ambient heat requires the consideration of the physiological stage of dairy cows. PMID:25938406

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

    Science.gov (United States)

    Lamp, Ole; Derno, Michael; Otten, Winfried; Mielenz, Manfred; Nürnberg, Gerd; Kuhla, Björn

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ole Lamp

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

  8. The importance of socio-ecological system dynamics in understanding adaptation to global change in the forestry sector.

    Science.gov (United States)

    Blanco, Victor; Brown, Calum; Holzhauer, Sascha; Vulturius, Gregor; Rounsevell, Mark D A

    2017-07-01

    Adaptation is necessary to cope with or take advantage of the effects of climate change on socio-ecological systems. This is especially important in the forestry sector, which is sensitive to the ecological and economic impacts of climate change, and where the adaptive decisions of owners play out over long periods of time. Relatively little is known about how successful these decisions are likely to be in meeting demands for ecosystem services in an uncertain future. We explore adaptation to global change in the forestry sector using CRAFTY-Sweden; an agent-based model that represents large-scale land-use dynamics, based on the demand and supply of ecosystem services. Future impacts and adaptation within the Swedish forestry sector were simulated for scenarios of socio-economic change (Shared Socio-economic Pathways) and climatic change (Representative Concentration Pathways, for three climate models), between 2010 and 2100. Substantial differences were found in the competitiveness and coping ability of land owners implementing different management strategies through time. Generally, multi-objective management was found to provide the best basis for adaptation. Across large regions, however, a combination of management strategies was better at meeting ecosystem service demands. Results also show that adaptive capacity evolves through time in response to external (global) drivers and interactions between individual actors. This suggests that process-based models are more appropriate for the study of autonomous adaptation and future adaptive and coping capacities than models based on indicators, discrete time snapshots or exogenous proxies. Nevertheless, a combination of planned and autonomous adaptation by institutions and forest owners is likely to be more successful than either group acting alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Effects of Castration on Expression of Lipid Metabolism Genes in the Liver of Korean Cattle

    OpenAIRE

    Baik, Myunggi; Nguyen, Trang Hoa; Jeong, Jin Young; Piao, Min Yu; Kang, Hyeok Joong

    2015-01-01

    Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p

  10. Dominance as adaptive stressing and ranking of males, serving to allocate reproduction by differential self-suppressed fertility: towards a fully biological understanding of social systems.

    Science.gov (United States)

    Moxon, Steve

    2009-07-01

    Dominance is a biological concept of an asymmetric 'power' relationship between (any pair of) individuals, as a result of previous encounters with others biasing likelihood of contesting. That this requires dedicated neural structure shows that dominance is adaptive; and it is usually thought that fitness is increased through dominance (hierarchy) minimising mutually unproductive contest over resources, and/or determining access to or control over resources. But highly inconsistent data indicates that this operational definition is too wide, and given clear evidence that dominance is invariably same-sex, it would seem instead to function primarily to allocate reproduction. Dominance contest exposes individual differences in metabolic vigor especially, but also in various other, including sophisticated attributes; and by a self-organising process there is ranking of same-sex individuals in a hierarchy. But this achieves nothing in itself without an integral mechanism of corresponding individual variable self-suppression of the physiology re reproduction--and mate choice with rank as the criteria. Reproductive suppression would appear to vary along a continuum, from in some species (most 'cooperative breeders') a 100% reproductive skew with total suppression of all individuals bar the sole breeder to, in most others, a gradient down the length of the dominance hierarchy. The mechanism in most species is directly either hormonal or pheromonal, on top of an indirect consequence of the stress caused by relatively low rank. Dominance would seem to have evolved as a major instrument of the proposed 'genetic filter' function of the male, whereby in effect accumulated deleterious genetic material is 'quarantined' in the male half of the lineage from where it is purged, so as to keep this source of reproductive logjam away from females, thereby to avoid amplifying the problem of the female being necessarily the limiting factor in reproduction. The theory makes predictions

  11. Understanding the determinants of selectivity in drug metabolism through modeling of dextromethorphan oxidation by cytochrome P450

    Science.gov (United States)

    Oláh, Julianna; Mulholland, Adrian J.; Harvey, Jeremy N.

    2011-01-01

    Cytochrome P450 enzymes play key roles in the metabolism of the majority of drugs. Improved models for prediction of likely metabolites will contribute to drug development. In this work, two possible metabolic routes (aromatic carbon oxidation and O-demethylation) of dextromethorphan are compared using molecular dynamics (MD) simulations and density functional theory (DFT). The DFT results on a small active site model suggest that both reactions might occur competitively. Docking and MD studies of dextromethorphan in the active site of P450 2D6 show that the dextromethorphan is located close to heme oxygen in a geometry apparently consistent with competitive metabolism. In contrast, calculations of the reaction path in a large protein model [using a hybrid quantum mechanical–molecular mechanics (QM/MM) method] show a very strong preference for O-demethylation, in accordance with experimental results. The aromatic carbon oxidation reaction is predicted to have a high activation energy, due to the active site preventing formation of a favorable transition-state structure. Hence, the QM/MM calculations demonstrate a crucial role of many active site residues in determining reactivity of dextromethorphan in P450 2D6. Beyond substrate binding orientation and reactivity of Compound I, successful metabolite predictions must take into account the detailed mechanism of oxidation in the protein. These results demonstrate the potential of QM/MM methods to investigate specificity in drug metabolism. PMID:21444768

  12. A 7-day high protein hypocaloric diet promotes cellular metabolic adaptations and attenuates lean mass loss in healthy males

    OpenAIRE

    Matthew Furber; Ana Anton-Solanas; Emma Koppe; Charlotte Ashby; Michael Roberts; Justin Roberts

    2017-01-01

    Mitochondrial quantity and density are associated with increased oxidative metabolism. It has been demonstrated that a hypocaloric high fat/low carbohydrate (HF/LC) diet can up-regulate transcriptional markers of mitochondrial biogenesis; this was yet to be explored in vivo subsequent to a high protein/low carbohydrate (HP/LC) diet. Thus the aims of the study were to explore such diets on transcriptional markers or mitochondrial biogenesis, body composition and resting metabolic rate (RMR). F...

  13. III. Cellular ultrastructures in situ as key to understanding tumor energy metabolism: biological significance of the Warburg effect.

    Science.gov (United States)

    Witkiewicz, Halina; Oh, Phil; Schnitzer, Jan E

    2013-01-01

    Despite the universality of metabolic pathways, malignant cells were found to have their metabolism reprogrammed to generate energy by glycolysis even under normal oxygen concentrations (the Warburg effect). Therefore, the pathway energetically 18 times less efficient than oxidative phosphorylation was implicated to match increased energy requirements of growing tumors. The paradox was explained by an abnormally high rate of glucose uptake, assuming unlimited availability of substrates for tumor growth in vivo. However, ultrastructural analysis of tumor vasculature morphogenesis showed that the growing tissue regions did not have continuous blood supply and intermittently depended on autophagy for survival. Erythrogenic autophagy, and resulting ATP generation by glycolysis, appeared critical to initiating vasculature formation where it was missing. This study focused on ultrastructural features that reflected metabolic switch from aerobic to anaerobic. Morphological differences between and within different types of cells were evident in tissue sections. In cells undergoing nucleo-cytoplasmic conversion into erythrosomes (erythrogenesis), gradual changes led to replacing mitochondria with peroxisomes, through an intermediate form connected to endoplasmic reticulum. Those findings related to the issue of peroxisome biogenesis and to the phenomenon of hemogenic endothelium. Mitochondria were compacted also during mitosis. In vivo, cells that lost and others that retained capability to use oxygen coexisted side-by-side; both types were important for vasculature morphogenesis and tissue growth. Once passable, the new vasculature segment could deliver external oxygen and nutrients. Nutritional and redox status of microenvironment had similar effect on metabolism of malignant and non-malignant cells demonstrating the necessity to maintain structure-energy equivalence in all living cells. The role of glycolysis in initiating vasculature formation, and in progression of

  14. Unexpected metabolic disorders induced by endocrine disruptors in Xenopus tropicalis provide new lead for understanding amphibian decline.

    Science.gov (United States)

    Regnault, Christophe; Usal, Marie; Veyrenc, Sylvie; Couturier, Karine; Batandier, Cécile; Bulteau, Anne-Laure; Lejon, David; Sapin, Alexandre; Combourieu, Bruno; Chetiveaux, Maud; Le May, Cédric; Lafond, Thomas; Raveton, Muriel; Reynaud, Stéphane

    2018-05-08

    Despite numerous studies suggesting that amphibians are highly sensitive to endocrine disruptors (EDs), both their role in the decline of populations and the underlying mechanisms remain unclear. This study showed that frogs exposed throughout their life cycle to ED concentrations low enough to be considered safe for drinking water, developed a prediabetes phenotype and, more commonly, a metabolic syndrome. Female Xenopus tropicalis exposed from tadpole stage to benzo( a )pyrene or triclosan at concentrations of 50 ng⋅L -1 displayed glucose intolerance syndrome, liver steatosis, liver mitochondrial dysfunction, liver transcriptomic signature, and pancreatic insulin hypersecretion, all typical of a prediabetes state. This metabolic syndrome led to progeny whose metamorphosis was delayed and occurred while the individuals were both smaller and lighter, all factors that have been linked to reduced adult recruitment and likelihood of reproduction. We found that F 1 animals did indeed have reduced reproductive success, demonstrating a lower fitness in ED-exposed Xenopus Moreover, after 1 year of depuration, Xenopus that had been exposed to benzo( a )pyrene still displayed hepatic disorders and a marked insulin secretory defect resulting in glucose intolerance. Our results demonstrate that amphibians are highly sensitive to EDs at concentrations well below the thresholds reported to induce stress in other vertebrates. This study introduces EDs as a possible key contributing factor to amphibian population decline through metabolism disruption. Overall, our results show that EDs cause metabolic disorders, which is in agreement with epidemiological studies suggesting that environmental EDs might be one of the principal causes of metabolic disease in humans.

  15. CD36-dependent Regulation of Muscle FoxO1 and PDK4 in the PPARδ/β-mediated Adaptation to Metabolic Stress*

    OpenAIRE

    Nahlé, Zaher; Hsieh, Michael; Pietka, Terri; Coburn, Chris T.; Grimaldi, Paul A.; Zhang, Michael Q.; Das, Debopriya; Abumrad, Nada A.

    2008-01-01

    The transcription factor FoxO1 contributes to the metabolic adaptation to fasting by suppressing muscle oxidation of glucose, sparing it for glucose-dependent tissues. Previously, we reported that FoxO1 activation in C2C12 muscle cells recruits the fatty acid translocase CD36 to the plasma membrane and increases fatty acid uptake and oxidation. This, together with FoxO1 induction of lipoprotein lipase, would promote the reliance on fatty acid utilization characteristic of the fasted muscle. H...

  16. Understanding the Representative Gut Microbiota Dysbiosis in Metformin-Treated Type 2 Diabetes Patients Using Genome-Scale Metabolic Modeling

    Directory of Open Access Journals (Sweden)

    Dorines Rosario

    2018-06-01

    Full Text Available Dysbiosis in the gut microbiome composition may be promoted by therapeutic drugs such as metformin, the world’s most prescribed antidiabetic drug. Under metformin treatment, disturbances of the intestinal microbes lead to increased abundance of Escherichia spp., Akkermansia muciniphila, Subdoligranulum variabile and decreased abundance of Intestinibacter bartlettii. This alteration may potentially lead to adverse effects on the host metabolism, with the depletion of butyrate producer genus. However, an increased production of butyrate and propionate was verified in metformin-treated Type 2 diabetes (T2D patients. The mechanisms underlying these nutritional alterations and their relation with gut microbiota dysbiosis remain unclear. Here, we used Genome-scale Metabolic Models of the representative gut bacteria Escherichia spp., I. bartlettii, A. muciniphila, and S. variabile to elucidate their bacterial metabolism and its effect on intestinal nutrient pool, including macronutrients (e.g., amino acids and short chain fatty acids, minerals and chemical elements (e.g., iron and oxygen. We applied flux balance analysis (FBA coupled with synthetic lethality analysis interactions to identify combinations of reactions and extracellular nutrients whose absence prevents growth. Our analyses suggest that Escherichia sp. is the bacteria least vulnerable to nutrient availability. We have also examined bacterial contribution to extracellular nutrients including short chain fatty acids, amino acids, and gasses. For instance, Escherichia sp. and S. variabile may contribute to the production of important short chain fatty acids (e.g., acetate and butyrate, respectively involved in the host physiology under aerobic and anaerobic conditions. We have also identified pathway susceptibility to nutrient availability and reaction changes among the four bacteria using both FBA and flux variability analysis. For instance, lipopolysaccharide synthesis, nucleotide sugar

  17. Mixed methods approach to understanding farmer and agricultural advisor perceptions of climate change and adaptation in Vermont, United States

    Science.gov (United States)

    Rachel E. Schattman; V. Ernesto Méndez; Scott C. Merrill; Asim Zia

    2018-01-01

    The relationships among farmers' belief in climate change, perceptions of climate-related risk, and use of climate adaptation practices is a growing topic of interest in U.S. scholarship. The northeast region is not well represented in the literature, although it is highly agricultural and will likely face climaterelated risks that differ from those faced in other...

  18. Establishment and metabolic analysis of a model microbial community for understanding trophic and electron accepting interactions of subsurface anaerobic environments

    Directory of Open Access Journals (Sweden)

    Yang Zamin K

    2010-05-01

    Full Text Available Abstract Background Communities of microorganisms control the rates of key biogeochemical cycles, and are important for biotechnology, bioremediation, and industrial microbiological processes. For this reason, we constructed a model microbial community comprised of three species dependent on trophic interactions. The three species microbial community was comprised of Clostridium cellulolyticum, Desulfovibrio vulgaris Hildenborough, and Geobacter sulfurreducens and was grown under continuous culture conditions. Cellobiose served as the carbon and energy source for C. cellulolyticum, whereas D. vulgaris and G. sulfurreducens derived carbon and energy from the metabolic products of cellobiose fermentation and were provided with sulfate and fumarate respectively as electron acceptors. Results qPCR monitoring of the culture revealed C. cellulolyticum to be dominant as expected and confirmed the presence of D. vulgaris and G. sulfurreducens. Proposed metabolic modeling of carbon and electron flow of the three-species community indicated that the growth of C. cellulolyticum and D. vulgaris were electron donor limited whereas G. sulfurreducens was electron acceptor limited. Conclusions The results demonstrate that C. cellulolyticum, D. vulgaris, and G. sulfurreducens can be grown in coculture in a continuous culture system in which D. vulgaris and G. sulfurreducens are dependent upon the metabolic byproducts of C. cellulolyticum for nutrients. This represents a step towards developing a tractable model ecosystem comprised of members representing the functional groups of a trophic network.

  19. Quality of life, psychological adjustment, and adaptive functioning of patients with intoxication-type inborn errors of metabolism - a systematic review.

    Science.gov (United States)

    Zeltner, Nina A; Huemer, Martina; Baumgartner, Matthias R; Landolt, Markus A

    2014-10-25

    In recent decades, considerable progress in diagnosis and treatment of patients with intoxication-type inborn errors of metabolism (IT-IEM) such as urea cycle disorders (UCD), organic acidurias (OA), maple syrup urine disease (MSUD), or tyrosinemia type 1 (TYR 1) has resulted in a growing group of long-term survivors. However, IT-IEM still require intense patient and caregiver effort in terms of strict dietetic and pharmacological treatment, and the threat of metabolic crises is always present. Furthermore, crises can affect the central nervous system (CNS), leading to cognitive, behavioural and psychiatric sequelae. Consequently, the well-being of the patients warrants consideration from both a medical and a psychosocial viewpoint by assessing health-related quality of life (HrQoL), psychological adjustment, and adaptive functioning. To date, an overview of findings on these topics for IT-IEM is lacking. We therefore aimed to systematically review the research on HrQoL, psychological adjustment, and adaptive functioning in patients with IT-IEM. Relevant databases were searched with predefined keywords. Study selection was conducted in two steps based on predefined criteria. Two independent reviewers completed the selection and data extraction. Eleven articles met the inclusion criteria. Studies were of varying methodological quality and used different assessment measures. Findings on HrQoL were inconsistent, with some showing lower and others showing higher or equal HrQoL for IT-IEM patients compared to norms. Findings on psychological adjustment and adaptive functioning were more consistent, showing mostly either no difference or worse adjustment of IT-IEM patients compared to norms. Single medical risk factors for HrQoL, psychological adjustment, or adaptive functioning have been addressed, while psychosocial risk factors have not been addressed. Data on HrQoL, psychological adjustment, and adaptive functioning for IT-IEM are sparse. Studies are inconsistent in

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

    DEFF Research Database (Denmark)

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

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Chinese hamster ovary (CHO) cells are the preferred production host for many therapeutic proteins. The production of heterologous proteins in CHO cells imposes a burden on the host cell metabolism and impact cellular physiology on a global scale. In this work, a multi-omics approach was applied...

  2. Adaptations in the glucose metabolism of procyclic Trypanosoma brucei isolates from Tsetse flies and during differentiation of bloodstream forms.

    NARCIS (Netherlands)

    van Grinsven, K.W.A.; van den Abbeele, J.; van den Bossche, P.; van Hellemond, J.J.; Tielens, A.G.M.

    2009-01-01

    Procyclic forms of Trypanosoma brucei isolated from the midguts of infected tsetse flies, or freshly transformed from a strain that is close to field isolates, do not use a complete Krebs cycle. Furthermore, short stumpy bloodstream forms produce acetate and are apparently metabolically preadapted

  3. Addressing unknown constants and metabolic network behaviors through petascale computing: understanding H2 production in green algae

    International Nuclear Information System (INIS)

    Chang, Christopher; Alber, David; Graf, Peter; Kim, Kwiseon; Seibert, Michael

    2007-01-01

    The Genomics Revolution has resulted in a massive and growing quantity of whole-genome DNA sequences, which encode the metabolic catalysts necessary for life. However, gene annotations can rarely be complete, and measurement of the kinetic constants associated with the encoded enzymes can not possibly keep pace, necessitating the use of careful modeling to explore plausible network behaviors. Key challenges are (1) quantitatively formulating kinetic laws governing each transformation in a fixed model network; (2) characterizing the stable solution (if any) of the associated ordinary differential equations (ODEs); (3) fitting the latter to metabolomics data as it becomes available; and (4) optimizing a model output against the possible space of kinetic parameters, with respect to properties such as robustness of network response, or maximum consumption/production. This SciDAC-2 project addresses this large-scale uncertainty in the genome-scale metabolic network of the water-splitting, H 2 -producing green alga Chlamydomonas reinhardtii. Each metabolic transformation is formulated as an irreversible steady-state process, such that the vast literature on known enzyme mechanisms may be incorporated directly. To start, glycolysis, the tricarboxylic acid cycle, and basic fermentation pathways have been encoded in Systems Biology Markup Language (SBML) with careful annotation and consistency with the KEGG database, yielding a model with 3 compartments, 95 species, 38 reactions, and 109 kinetic constants. To study and optimize such models with a view toward larger models, we have developed a system which takes as input an SBML model, and automatically produces C code that when compiled and executed optimizes the model's kinetic parameters according to test criteria. We describe the system and present numerical results. Further development, including overlaying of a parallel multistart algorithm, will allow optimization of thousands of parameters on high-performance systems

  4. Addressing unknown constants and metabolic network behaviors through petascale computing: understanding H{sub 2} production in green algae

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Christopher; Alber, David; Graf, Peter; Kim, Kwiseon; Seibert, Michael [National Renewable Energy Laboratory (NREL), Golden, CO 80401 (United States)

    2007-07-15

    The Genomics Revolution has resulted in a massive and growing quantity of whole-genome DNA sequences, which encode the metabolic catalysts necessary for life. However, gene annotations can rarely be complete, and measurement of the kinetic constants associated with the encoded enzymes can not possibly keep pace, necessitating the use of careful modeling to explore plausible network behaviors. Key challenges are (1) quantitatively formulating kinetic laws governing each transformation in a fixed model network; (2) characterizing the stable solution (if any) of the associated ordinary differential equations (ODEs); (3) fitting the latter to metabolomics data as it becomes available; and (4) optimizing a model output against the possible space of kinetic parameters, with respect to properties such as robustness of network response, or maximum consumption/production. This SciDAC-2 project addresses this large-scale uncertainty in the genome-scale metabolic network of the water-splitting, H{sub 2}-producing green alga Chlamydomonas reinhardtii. Each metabolic transformation is formulated as an irreversible steady-state process, such that the vast literature on known enzyme mechanisms may be incorporated directly. To start, glycolysis, the tricarboxylic acid cycle, and basic fermentation pathways have been encoded in Systems Biology Markup Language (SBML) with careful annotation and consistency with the KEGG database, yielding a model with 3 compartments, 95 species, 38 reactions, and 109 kinetic constants. To study and optimize such models with a view toward larger models, we have developed a system which takes as input an SBML model, and automatically produces C code that when compiled and executed optimizes the model's kinetic parameters according to test criteria. We describe the system and present numerical results. Further development, including overlaying of a parallel multistart algorithm, will allow optimization of thousands of parameters on high

  5. Less-than-expected weight loss in normal-weight women undergoing caloric restriction and exercise is accompanied by preservation of fat-free mass and metabolic adaptations.

    Science.gov (United States)

    Koehler, K; De Souza, M J; Williams, N I

    2017-03-01

    Normal-weight women frequently restrict their caloric intake and exercise, but little is known about the effects on body weight, body composition and metabolic adaptations in this population. We conducted a secondary analysis of data from a randomized controlled trial in sedentary normal-weight women. Women were assigned to a severe energy deficit (SEV: -1062±80 kcal per day; n=9), a moderate energy deficit (MOD: -633±71 kcal per day; n=7) or energy balance (BAL; n=9) while exercising five times per week for 3 months. Outcome variables included changes in body weight, body composition, resting metabolic rate (RMR) and metabolic hormones associated with energy conservation. Weight loss occurred in SEV (-3.7±0.9 kg, P0.33). RMR decreased by -6±2% in MOD (P=0.020). In SEV, RMR did not change on a group level (P=0.66), but participants whose RMR declined lost more weight (P=0.020) and had a higher baseline RMR (P=0.026) than those whose RMR did not decrease. Characteristic changes in leptin (P=0.003), tri-iodothyronine (P=0.013), insulin-like growth factor-1 (P=0.016) and ghrelin (P=0.049) occurred only in SEV. The energy deficit and adaptive changes in RMR explained 54% of the observed weight loss. In normal-weight women, caloric restriction and exercise resulted in less-than-predicted weight loss. In contrast to previous literature, weight loss consisted almost exclusively of fat mass, whereas fat-free mass was preserved.

  6. Involvement of alternative oxidase (AOX) in adventitious rooting of Olea europaea L. microshoots is linked to adaptive phenylpropanoid and lignin metabolism.

    Science.gov (United States)

    Santos Macedo, E; Sircar, D; Cardoso, H G; Peixe, A; Arnholdt-Schmitt, B

    2012-09-01

    Alternative oxidase (AOX) has been proposed as a functional marker candidate in a number of events involving cell differentiation, including rooting efficiency in semi-hardwood shoot cuttings of olive (Olea europaea L.). To ascertain the general importance of AOX in olive rooting, the auxin-induced rooting process was studied in an in vitro system for microshoot propagation. Inhibition of AOX by salicylhydroxamic acid (SHAM) significantly reduced rooting efficiency. However, the inhibitor failed to exhibit any effect on the preceding calli stage. This makes the system appropriate for distinguishing dedifferentiation and de novo differentiation during root induction. Metabolite analyses of microshoots showed that total phenolics, total flavonoids and lignin contents were significantly reduced upon SHAM treatment. It was concluded that the influence of alternative respiration on root formation was associated to adaptive phenylpropanoid and lignin metabolism. Transcript profiles of two olive AOX genes (OeAOX1a and OeAOX2) were examined during the process of auxin-induced root induction. Both genes displayed stable transcript accumulation in semi-quantitative RT-PCR analysis during all experimental stages. In contrary, when the reverse primer for OeAOX2 was designed from the 3'-UTR instead of the ORF, differential transcript accumulation was observed suggesting posttranscriptional regulation of OeAOX2 during metabolic acclimation. This result confirms former observations in olive semi-hardwood shoot cuttings on differential OeAOX2 expression during root induction. It further points to the importance of future studies on the functional role of sequence and length polymorphisms in the 3'-UTR of this gene. The manuscript reports the general importance of AOX in olive adventitious rooting and the association of alternative respiration to adaptive phenylpropanoid and lignin metabolism.

  7. Adaptive Activation of a Stress Response Pathway Improves Learning and Memory Through Gs and β-Arrestin-1-Regulated Lactate Metabolism.

    Science.gov (United States)

    Dong, Jun-Hong; Wang, Yi-Jing; Cui, Min; Wang, Xiao-Jing; Zheng, Wen-Shuai; Ma, Ming-Liang; Yang, Fan; He, Dong-Fang; Hu, Qiao-Xia; Zhang, Dao-Lai; Ning, Shang-Lei; Liu, Chun-Hua; Wang, Chuan; Wang, Yue; Li, Xiang-Yao; Yi, Fan; Lin, Amy; Kahsai, Alem W; Cahill, Thomas Joseph; Chen, Zhe-Yu; Yu, Xiao; Sun, Jin-Peng

    2017-04-15

    Stress is a conserved physiological response in mammals. Whereas moderate stress strengthens memory to improve reactions to previously experienced difficult situations, too much stress is harmful. We used specific β-adrenergic agonists, as well as β 2 -adrenergic receptor (β2AR) and arrestin knockout models, to study the effects of adaptive β2AR activation on cognitive function using Morris water maze and object recognition experiments. We used molecular and cell biological approaches to elucidate the signaling subnetworks. We observed that the duration of the adaptive β2AR activation determines its consequences on learning and memory. Short-term formoterol treatment, for 3 to 5 days, improved cognitive function; however, prolonged β2AR activation, for more than 6 days, produced harmful effects. We identified the activation of several signaling networks downstream of β2AR, as well as an essential role for arrestin and lactate metabolism in promoting cognitive ability. Whereas Gs-protein kinase A-cyclic adenosine monophosphate response element binding protein signaling modulated monocarboxylate transporter 1 expression, β-arrestin-1 controlled expression levels of monocarboxylate transporter 4 and lactate dehydrogenase A through the formation of a β-arrestin-1/phospho-mitogen-activated protein kinase/hypoxia-inducible factor-1α ternary complex to upregulate lactate metabolism in astrocyte-derived U251 cells. Conversely, long-term treatment with formoterol led to the desensitization of β2ARs, which was responsible for its decreased beneficial effects. Our results not only revealed that β-arrestin-1 regulated lactate metabolism to contribute to β2AR functions in improved memory formation, but also indicated that the appropriate management of one specific stress pathway, such as through the clinical drug formoterol, may exert beneficial effects on cognitive abilities. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

  8. A tribute to Ulrich Heber (1930-2016) for his contribution to photosynthesis research: understanding the interplay between photosynthetic primary reactions, metabolism and the environment.

    Science.gov (United States)

    Dietz, Karl-Josef; Krause, G Heinrich; Siebke, Katharina; Krieger-Liszkay, Anja

    2018-07-01

    The dynamic and efficient coordination of primary photosynthetic reactions with leaf energization and metabolism under a wide range of environmental conditions is a fundamental property of plants involving processes at all functional levels. The present historical perspective covers 60 years of research aiming to understand the underlying mechanisms, linking major breakthroughs to current progress. It centers on the contributions of Ulrich Heber who had pioneered novel concepts, fundamental methods, and mechanistic understanding of photosynthesis. An important first step was the development of non-aqueous preparation of chloroplasts allowing the investigation of chloroplast metabolites ex vivo (meaning that the obtained results reflect the in vivo situation). Later on, intact chloroplasts, retaining their functional envelope membranes, were isolated in aqueous media to investigate compartmentation and exchange of metabolites between chloroplasts and external medium. These studies elucidated metabolic interaction between chloroplasts and cytoplasm during photosynthesis. Experiments with isolated intact chloroplasts clarified that oxygenation of ribulose-1.5-bisphosphate generates glycolate in photorespiration. The development of non-invasive optical methods enabled researchers identifying mechanisms that balance electron flow in the photosynthetic electron transport system avoiding its over-reduction. Recording chlorophyll a (Chl a) fluorescence allowed one to monitor, among other parameters, thermal energy dissipation by means of 'nonphotochemical quenching' of the excited state of Chl a. Furthermore, studies both in vivo and in vitro led to basic understanding of the biochemical mechanisms of freezing damage and frost tolerance of plant leaves, to SO 2 tolerance of tree leaves and dehydrating lichens and mosses.

  9. The contribution of experimental in vivo models to understanding the mechanisms of adaptation to mechanical loading in bone

    Directory of Open Access Journals (Sweden)

    Lee B Meakin

    2014-10-01

    Full Text Available Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading.Jiri Heřt introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gauges to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced.Experiments combining strain gauge instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats and mice has yielded significant insight into the control of strain-related adaptive (remodeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice which is now the model of choice for many studies. Together such studies have demonstrated that; over the physiological strain range, bone’s mechanically-adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles and that these are most effective when interrupted by short periods of

  10. The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone

    Science.gov (United States)

    Meakin, Lee B.; Price, Joanna S.; Lanyon, Lance E.

    2014-01-01

    Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading. Jiri Hert introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gages to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced. Experiments combining strain gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice, which is now the model of choice for many studies. Together such studies have demonstrated that over the physiological strain range, bone’s mechanically adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles, and that these are most effective when interrupted by short periods of rest between them

  11. Adaptive metabolic response to 4 weeks of sugar-sweetened beverage consumption in healthy, lightly active individuals and chronic high glucose availability in primary human myotubes.

    Science.gov (United States)

    Sartor, Francesco; Jackson, Matthew J; Squillace, Cesare; Shepherd, Anthony; Moore, Jonathan P; Ayer, Donald E; Kubis, Hans-Peter

    2013-04-01

    Chronic sugar-sweetened beverage (SSB) consumption is associated with obesity and type 2 diabetes mellitus (T2DM). Hyperglycaemia contributes to metabolic alterations observed in T2DM, such as reduced oxidative capacity and elevated glycolytic and lipogenic enzyme expressions in skeletal muscle tissue. We aimed to investigate the metabolic alterations induced by SSB supplementation in healthy individuals and to compare these with the effects of chronic hyperglycaemia on primary muscle cell cultures. Lightly active, healthy, lean subjects (n = 11) with sporadic soft drink consumption underwent a 4-week SSB supplementation (140 ± 15 g/day, ~2 g glucose/kg body weight/day, glucose syrup). Before and after the intervention, body composition, respiratory exchange ratio (RER), insulin sensitivity, muscle metabolic gene and protein expression were assessed. Adaptive responses to hyperglycaemia (7 days, 15 mM) were tested in primary human myotubes. SSB supplementation increased fat mass (+1.0 kg, P < 0.05), fasting RER (+0.12, P < 0.05), fasting glucose (+0.3 mmol/L, P < 0.05) and muscle GAPDH mRNA expressions (+0.94 AU, P < 0.05). PGC1α mRNA was reduced (-0.20 AU, P < 0.05). Trends were found for insulin resistance (+0.16 mU/L, P = 0.09), and MondoA protein levels (+1.58 AU, P = 0.08). Primary myotubes showed elevations in GAPDH, ACC, MondoA and TXNIP protein expressions (P < 0.05). Four weeks of SSB supplementation in healthy individuals shifted substrate metabolism towards carbohydrates, increasing glycolytic and lipogenic gene expression and reducing mitochondrial markers. Glucose-sensing protein MondoA might contribute to this shift, although further in vivo evidence is needed to corroborate this.

  12. Adaptation of Bacillus subtilis carbon core metabolism to simultaneous nutrient limitation and osmotic challenge : a multi-omics perspective

    NARCIS (Netherlands)

    Kohlstedt, Michael; Sappa, Praveen K; Meyer, Hanna; Maaß, Sandra; Zaprasis, Adrienne; Hoffmann, Tamara; Becker, Judith; Steil, Leif; Hecker, Michael; van Dijl, Jan Maarten; Lalk, Michael; Mäder, Ulrike; Stülke, Jörg; Bremer, Erhard; Völker, Uwe; Wittmann, Christoph

    The Gram-positive bacterium Bacillus subtilis encounters nutrient limitations and osmotic stress in its natural soil ecosystem. To ensure survival and sustain growth, highly integrated adaptive responses are required. Here, we investigated the system-wide response of B.subtilis to different,

  13. Global Metabolic Reconstruction and Metabolic Gene Evolution in the Cattle Genome

    Science.gov (United States)

    Kim, Woonsu; Park, Hyesun; Seo, Seongwon

    2016-01-01

    The sequence of cattle genome provided a valuable opportunity to systematically link genetic and metabolic traits of cattle. The objectives of this study were 1) to reconstruct genome-scale cattle-specific metabolic pathways based on the most recent and updated cattle genome build and 2) to identify duplicated metabolic genes in the cattle genome for better understanding of metabolic adaptations in cattle. A bioinformatic pipeline of an organism for amalgamating genomic annotations from multiple sources was updated. Using this, an amalgamated cattle genome database based on UMD_3.1, was created. The amalgamated cattle genome database is composed of a total of 33,292 genes: 19,123 consensus genes between NCBI and Ensembl databases, 8,410 and 5,493 genes only found in NCBI or Ensembl, respectively, and 266 genes from NCBI scaffolds. A metabolic reconstruction of the cattle genome and cattle pathway genome database (PGDB) was also developed using Pathway Tools, followed by an intensive manual curation. The manual curation filled or revised 68 pathway holes, deleted 36 metabolic pathways, and added 23 metabolic pathways. Consequently, the curated cattle PGDB contains 304 metabolic pathways, 2,460 reactions including 2,371 enzymatic reactions, and 4,012 enzymes. Furthermore, this study identified eight duplicated genes in 12 metabolic pathways in the cattle genome compared to human and mouse. Some of these duplicated genes are related with specific hormone biosynthesis and detoxifications. The updated genome-scale metabolic reconstruction is a useful tool for understanding biology and metabolic characteristics in cattle. There has been significant improvements in the quality of cattle genome annotations and the MetaCyc database. The duplicated metabolic genes in the cattle genome compared to human and mouse implies evolutionary changes in the cattle genome and provides a useful information for further research on understanding metabolic adaptations of cattle. PMID

  14. Radiohistochemical investigations into the central nervous sialoglycoconjugate metabolism of dormice (Glis glis) in different stages of adaptation

    International Nuclear Information System (INIS)

    Mehlfeld, R.

    1988-01-01

    Twenty adult dormice (Glis glis, Gliridae) were used to measure seasonal and temperature-related variations of sialoglycoconjugates in the central nervous system. The study had two different aims: On the one hand, biochemical and radiochemical methods of separation were used to investigate 10 cerebral regions for any changes in their individual contents of proteins and protein-bound sialic acids and for alterations in the ganglioside pattern of neurons as well as the time curves plotted for the uptake of a specific ganglioside tracer, 14C-N-Ac-mannosamine, that may possibly arise in response to seasonal and temperature-dependent adaptations. In addition, 32 central cerebral regions were examined for dormice showing different stages of adaptation (winter versus summer) to determine in autoradiograms that percentage share of integrated optical density (IOD), which accounts for the radioactively labelled proportions of TCA/PTA-soluble compounds, sialoglycolipids and sialoglycoproteins plus asialocompounds in the total radioactivity. (orig./ECB) [de

  15. A 7-day high protein hypocaloric diet promotes cellular metabolic adaptations and attenuates lean mass loss in healthy males

    Directory of Open Access Journals (Sweden)

    Matthew Furber

    2017-08-01

    Full Text Available Mitochondrial quantity and density are associated with increased oxidative metabolism. It has been demonstrated that a hypocaloric high fat/low carbohydrate (HF/LC diet can up-regulate transcriptional markers of mitochondrial biogenesis; this was yet to be explored in vivo subsequent to a high protein/low carbohydrate (HP/LC diet. Thus the aims of the study were to explore such diets on transcriptional markers or mitochondrial biogenesis, body composition and resting metabolic rate (RMR. Forty-five healthy male participants were randomly assigned one of four intervention diets: eucaloric high protein low carbohydrate (PRO-EM, hypocaloric high protein low carbohydrate (PRO-ER, eucaloric high carbohydrate (CHO-EM or hypocaloric high carbohydrate (CHO-ER. The macronutrient ratio of the high protein diet and high carbohydrate diets was 40:30:30% and 10:60:30% (PRO:CHO:FAT respectively. Energy intake for the hypocaloric diets were calculated to match resting metabolic rate. Participants visited the laboratory on 3 occasions each separated by 7 days. On each visit body composition, resting metabolic rate and a muscle biopsy from the vastus lateralis was collected. Prior to visit 1 and 2 habitual diet was consumed which was used as a control, between visit 2 and 3 the intervention diet was consumed continuously for 7-days. No group × time effect was observed, however in the PRO-ER group a significant increase in AMPK, PGC-1α, SIRT1 and SIRT3 mRNA expression was observed post diet intervention groups (p < 0.05. No change was observed in any of the transcriptional markers in the other 3 groups. Despite ∼30% reduction in calorie intake no difference in lean mass (LM loss was observed between the PRO-ER and CHO-EM groups. The results from this study suggest that a 7-day a high protein low carbohydrate hypocaloric diet increased AMPK, SIRT1 and PGC-1 α mRNA expression at rest, and also suggest that increased dietary protein may attenuate LM mass

  16. Past and future corollaries of theories on causes of metabolic syndrome and obesity related co-morbidities part 2: a composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    Science.gov (United States)

    McGill, Anne-Thea

    2014-01-01

    Metabolic syndrome (MetS) predicts type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer, and their rates have escalated over the last few decades. Obesity related co-morbidities also overlap the concept of the metabolic syndrome (MetS). However, understanding of the syndrome's underlying causes may have been misapprehended. The current paper follows on from a theory review by McGill, A-T in Archives of Public Health, 72: 30. This accompanying paper utilises research on human evolution and new biochemistry to theorise on why MetS and obesity arise and how they affect the population. The basis of this composite unifying theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals. In humans who consume a nutritious diet, the NRF2 system has become highly energy efficient. Other relevant human-specific co-adaptations are explored. In order to 'test' this composite unifying theory it is important to show that the hypothesis and sub-theories pertain throughout the whole of human evolution and history up till the current era. Corollaries of the composite unifying theory of MetS are examined with respect to past under-nutrition and malnutrition since agriculture began 10,000 years ago. The effects of man-made pollutants on degenerative change are examined. Projections are then made from current to future patterns on the state of 'insufficient micronutrient and/or unbalanced high energy malnutrition with central obesity and metabolic dysregulation' or 'malnubesity'. Forecasts

  17. Using an adaptive expertise lens to understand the quality of teachers' classroom implementation of computer-supported complex systems curricula in high school science

    Science.gov (United States)

    Yoon, Susan A.; Koehler-Yom, Jessica; Anderson, Emma; Lin, Joyce; Klopfer, Eric

    2015-05-01

    Background: This exploratory study is part of a larger-scale research project aimed at building theoretical and practical knowledge of complex systems in students and teachers with the goal of improving high school biology learning through professional development and a classroom intervention. Purpose: We propose a model of adaptive expertise to better understand teachers' classroom practices as they attempt to navigate myriad variables in the implementation of biology units that include working with computer simulations, and learning about and teaching through complex systems ideas. Sample: Research participants were three high school biology teachers, two females and one male, ranging in teaching experience from six to 16 years. Their teaching contexts also ranged in student achievement from 14-47% advanced science proficiency. Design and methods: We used a holistic multiple case study methodology and collected data during the 2011-2012 school year. Data sources include classroom observations, teacher and student surveys, and interviews. Data analyses and trustworthiness measures were conducted through qualitative mining of data sources and triangulation of findings. Results: We illustrate the characteristics of adaptive expertise of more or less successful teaching and learning when implementing complex systems curricula. We also demonstrate differences between case study teachers in terms of particular variables associated with adaptive expertise. Conclusions: This research contributes to scholarship on practices and professional development needed to better support teachers to teach through a complex systems pedagogical and curricular approach.

  18. Rhizobium leguminosarum bv. viciae 3841 Adapts to 2,4-Dichlorophenoxyacetic Acid with "Auxin-Like" Morphological Changes, Cell Envelope Remodeling and Upregulation of Central Metabolic Pathways.

    Directory of Open Access Journals (Sweden)

    Supriya V Bhat

    Full Text Available There is a growing need to characterize the effects of environmental stressors at the molecular level on model organisms with the ever increasing number and variety of anthropogenic chemical pollutants. The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D, as one of the most widely applied pesticides in the world, is one such example. This herbicide is known to have non-targeted undesirable effects on humans, animals and soil microbes, but specific molecular targets at sublethal levels are unknown. In this study, we have used Rhizobium leguminosarum bv. viciae 3841 (Rlv as a nitrogen fixing, beneficial model soil organism to characterize the effects of 2,4-D. Using metabolomics and advanced microscopy we determined specific target pathways in the Rlv metabolic network and consequent changes to its phenotype, surface ultrastructure, and physical properties during sublethal 2,4-D exposure. Auxin and 2,4-D, its structural analogue, showed common morphological changes in vitro which were similar to bacteroids isolated from plant nodules, implying that these changes are related to bacteroid differentiation required for nitrogen fixation. Rlv showed remarkable adaptation capabilities in response to the herbicide, with changes to integral pathways of cellular metabolism and the potential to assimilate 2,4-D with consequent changes to its physical and structural properties. This study identifies biomarkers of 2,4-D in Rlv and offers valuable insights into the mode-of-action of 2,4-D in soil bacteria.

  19. Metabolic Alterations Caused by KRAS Mutations in Colorectal Cancer Contribute to Cell Adaptation to Glutamine Depletion by Upregulation of Asparagine Synthetase

    Directory of Open Access Journals (Sweden)

    Kosuke Toda

    2016-11-01

    Full Text Available A number of clinical trials have shown that KRAS mutations of colorectal cancer (CRC can predict a lack of responses to anti-epidermal growth factor receptor–based therapy. Recently, there have been several studies to elucidate metabolism reprogramming in cancer. However, it remains to be investigated how mutated KRAS can coordinate the metabolic shift to sustain CRC tumor growth. In this study, we found that KRAS mutation in CRC caused alteration in amino acid metabolism. KRAS mutation causes a marked decrease in aspartate level and an increase in asparagine level in CRC. Using several human CRC cell lines and clinical specimens of primary CRC, we demonstrated that the expression of asparagine synthetase (ASNS, an enzyme that synthesizes asparagine from aspartate, was upregulated by mutated KRAS and that ASNS expression was induced by KRAS-activated signaling pathway, in particular PI3K-AKT-mTOR pathway. Importantly, we demonstrated that KRAS-mutant CRC cells could become adaptive to glutamine depletion through asparagine biosynthesis by ASNS and that asparagine addition could rescue the inhibited growth and viability of cells grown under the glutamine-free condition in vitro. Notably, a pronounced growth suppression of KRAS-mutant CRC was observed upon ASNS knockdown in vivo. Furthermore, combination of L-asparaginase plus rapamycin markedly suppressed the growth of KRAS-mutant CRC xenografts in vivo, whereas either L-asparaginase or rapamycin alone was not effective. These results indicate ASNS might be a novel therapeutic target against CRCs with mutated KRAS.

  20. ISC1-dependent metabolic adaptation reveals an indispensable role for mitochondria in induction of nuclear genes during the diauxic shift in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kitagaki, Hiroshi; Cowart, L Ashley; Matmati, Nabil; Montefusco, David; Gandy, Jason; de Avalos, Silvia Vaena; Novgorodov, Sergei A; Zheng, Jim; Obeid, Lina M; Hannun, Yusuf A

    2009-04-17

    Growth of Saccharomyces cerevisiae following glucose depletion (the diauxic shift) depends on a profound metabolic adaptation accompanied by a global reprogramming of gene expression. In this study, we provide evidence for a heretofore unsuspected role for Isc1p in mediating this reprogramming. Initial studies revealed that yeast cells deleted in ISC1, the gene encoding inositol sphingolipid phospholipase C, which resides in mitochondria in the post-diauxic phase, showed defective aerobic respiration in the post-diauxic phase but retained normal intrinsic mitochondrial functions, including intact mitochondrial DNA, normal oxygen consumption, and normal mitochondrial polarization. Microarray analysis revealed that the Deltaisc1 strain failed to up-regulate genes required for nonfermentable carbon source metabolism during the diauxic shift, thus suggesting a mechanism for the defective supply of respiratory substrates into mitochondria in the post-diauxic phase. This defect in regulating nuclear gene induction in response to a defect in a mitochondrial enzyme raised the possibility that mitochondria may initiate diauxic shift-associated regulation of nucleus-encoded genes. This was established by demonstrating that in respiratory-deficient petite cells these genes failed to be up-regulated across the diauxic shift in a manner similar to the Deltaisc1 strain. Isc1p- and mitochondrial function-dependent genes significantly overlapped with Adr1p-, Snf1p-, and Cat8p-dependent genes, suggesting some functional link among these factors. However, the retrograde response was not activated in Deltaisc1, suggesting that the response of Deltaisc1 cannot be simply attributed to mitochondrial dysfunction. These results suggest a novel role for Isc1p in allowing the reprogramming of gene expression during the transition from anaerobic to aerobic metabolism.

  1. Understanding Perceptions of Climate Change, Priorities, and Decision-Making among Municipalities in Lima, Peru to Better Inform Adaptation and Mitigation Planning.

    Science.gov (United States)

    Siña, Mariella; Wood, Rachel C; Saldarriaga, Enrique; Lawler, Joshua; Zunt, Joseph; Garcia, Patricia; Cárcamo, César

    2016-01-01

    Climate change poses multiple risks to the population of Lima, the largest city and capital of Peru, located on the Pacific coast in a desert ecosystem. These risks include increased water scarcity, increased heat, and the introduction and emergence of vector-borne and other climate sensitive diseases. To respond to these threats, it is necessary for the government, at every level, to adopt more mitigation and adaptation strategies. Here, focus groups were conducted with representatives from five Lima municipalities to determine priorities, perception of climate change, and decision-making processes for implementing projects within each municipality. These factors can affect the ability and desire of a community to implement climate change adaptation and mitigation strategies. The results show that climate change and other environmental factors are of relatively low priority, whereas public safety and water and sanitation services are of highest concern. Perhaps most importantly, climate change is not well understood among the municipalities. Participants had trouble distinguishing climate change from other environmental issues and did not fully understand its causes and effects. Greater understanding of what climate change is and why it is important is necessary for it to become a priority for the municipalities. Different aspects of increased climate change awareness seem to be connected to having experienced extreme weather events, whether related or not to climate change, and to higher socioeconomic status.

  2. Stomatal density and metabolic determinants mediate salt stress adaptation and water use efficiency in basil (Ocimum basilicum L.).

    Science.gov (United States)

    Barbieri, Giancarlo; Vallone, Simona; Orsini, Francesco; Paradiso, Roberta; De Pascale, Stefania; Negre-Zakharov, Florence; Maggio, Albino

    2012-11-15

    Increasing salinity tolerance and water-use efficiency in crop plants are two major challenges that agriculture must face in the next decades. Many physiological mechanisms and molecular components mediating crop response to environmental stresses have been identified. However, the functional inter-links between stress adaptation responses have not been completely understood. Using two basil cultivars (Napoletano and Genovese) with contrasting ability to respond to salt stress, here we demonstrate that reduced stomatal density, high ascorbate level and polyphenol oxidase (PPO) activity coordinately contribute to improve basil adaptation and water use efficiency (WUE) in saline environment. The constitutively reduced stomatal density was associated with a "delayed" accumulation of stress molecules (and growth inhibiting signals) such as abscisic acid (ABA) and proline, in the more tolerant Genovese. Leaf volatile profiling also revealed cultivar-specific patterns, which may suggest a role for the volatile phenylpropanoid eugenol and monoterpenes in conferring stress tolerance via antioxidant and signalling functions. Copyright © 2012 Elsevier GmbH. All rights reserved.

  3. Acrolein-stressed threshold adaptation alters the molecular and metabolic bases of an engineered Saccharomyces cerevisiae to improve glutathione production.

    Science.gov (United States)

    Zhou, Wenlong; Yang, Yan; Tang, Liang; Cheng, Kai; Li, Changkun; Wang, Huimin; Liu, Minzhi; Wang, Wei

    2018-03-14

    Acrolein (Acr) was used as a selection agent to improve the glutathione (GSH) overproduction of the prototrophic strain W303-1b/FGP PT . After two rounds of adaptive laboratory evolution (ALE), an unexpected result was obtained wherein identical GSH production was observed in the selected isolates. Then, a threshold selection mechanism of Acr-stressed adaption was clarified based on the formation of an Acr-GSH adduct, and a diffusion coefficient (0.36 ± 0.02 μmol·min -1 ·OD 600 -1 ) was calculated. Metabolomic analysis was carried out to reveal the molecular bases that triggered GSH overproduction. The results indicated that all three precursors (glutamic acid (Glu), glycine (Gly) and cysteine (Cys)) needed for GSH synthesis were at a relativity higher concentration in the evolved strain and that the accumulation of homocysteine (Hcy) and cystathionine might promote Cys synthesis and then improve GSH production. In addition to GSH and Cys, it was observed that other non-protein thiols and molecules related to ATP generation were at obviously different levels. To divert the accumulated thiols to GSH biosynthesis, combinatorial strategies, including deletion of cystathionine β-lyase (STR3), overexpression of cystathionine γ-lyase (CYS3) and cystathionine β-synthase (CYS4), and reduction of the unfolded protein response (UPR) through up-regulation of protein disulphide isomerase (PDI), were also investigated.

  4. Can increases in capillarization explain the early adaptations in metabolic regulation in human muscle to short-term training?

    Science.gov (United States)

    Green, Howard J; Burnett, Margaret; Kollias, Helen; Ouyang, Jing; Smith, Ian; Tupling, Susan

    2012-05-01

    To investigate the hypothesis that increases in fibre capillary density would precede increases in oxidative potential following training onset, tissue was extracted from the vastus lateralis prior to (0 days) and following 3 and 6 consecutive days of submaximal cycle exercise (2 h·day(-1)). Participants were untrained males (age = 21.4 ± 0.58 years; peak oxygen consumption = 46.2 ± 1.6 mL·kg(-1)·min(-1); mean ± standard error (SE)). Tissue was assessed for succinic dehydrogenase activity (SDH) by microphotometry and indices of capillarization based on histochemically assessed area and capillary counts (CC) in specific fibre types. Three days of training (n = 13) resulted in a generalized decrease (p metabolic alterations that also result.

  5. Filling Knowledge Gaps in Biological Networks: integrating global approaches to understand H2 metabolism in Chlamydomonas reinhardtii - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Posewitz, Matthew C

    2011-06-30

    The green alga Chlamydomonas reinhardtii (Chlamydomonas) has numerous genes encoding enzymes that function in fermentative pathways. Among these genes, are the [FeFe]-hydrogenases, pyruvate formate lyase, pyruvate ferredoxin oxidoreductase, acetate kinase, and phosphotransacetylase. We have systematically undertaken a series of targeted mutagenesis approaches to disrupt each of these key genes and omics techniques to characterize alterations in metabolic flux. Funds from DE-FG02-07ER64423 were specifically leveraged to generate mutants with disruptions in the genes encoding the [FeFe]-hydrogenases HYDA1 and HYDA2, pyruvate formate lyase (PFL1), and in bifunctional alcohol/aldehyde alcohol dehydrogenase (ADH1). Additionally funds were used to conduct global transcript profiling experiments of wildtype Chlamydomonas cells, as well as of the hydEF-1 mutant, which is unable to make H2 due to a lesion in the [FeFe]-hydrogenase biosynthetic pathway. In the wildtype cells, formate, acetate and ethanol are the dominant fermentation products with traces of CO2 and H2 also being produced. In the hydEF-1 mutant, succinate production is increased to offset the loss of protons as a terminal electron acceptor. In the pfl-1 mutant, lactate offsets the loss of formate production, and in the adh1-1 mutant glycerol is made instead of ethanol. To further probe the system, we generated a double mutant (pfl1-1 adh1) that is unable to synthesize both formate and ethanol. This strain, like the pfl1 mutants, secreted lactate, but also exhibited a significant increase in the levels of extracellular glycerol, acetate, and intracellular reduced sugars, and a decline in dark, fermentative H2 production. Whereas wild-type Chlamydomonas fermentation primarily produces formate and ethanol, the double mutant performs a complete rerouting of the glycolytic carbon to lactate and glycerol. Lastly, transcriptome data have been analysed for both the wildtype and hydEF-1, that correlate with our

  6. Concentration-related metabolic rate and behavioral thermoregulatory adaptations to serial administrations of nitrous oxide in rats

    Science.gov (United States)

    2018-01-01

    Background Initial administration of ≥60% nitrous oxide (N2O) to rats evokes hypothermia, but after repeated administrations the gas instead evokes hyperthermia. This sign reversal is driven mainly by increased heat production. To determine whether rats will behaviorally oppose or assist the development of hyperthermia, we previously performed thermal gradient testing. Inhalation of N2O at ≥60% causes rats to select cooler ambient temperatures both during initial administrations and during subsequent administrations in which the hyperthermic state exists. Thus, an available behavioral response opposes (but does not completely prevent) the acquired hyperthermia that develops over repeated high-concentration N2O administrations. However, recreational and clinical uses of N2O span a wide range of concentrations. Therefore, we sought to determine the thermoregulatory adaptations to chronic N2O administration over a wide range of concentrations. Methods This study had two phases. In the first phase we adapted rats to twelve 3-h N2O administrations at either 0%, 15%, 30%, 45%, 60% or 75% N2O (n = 12 per group); outcomes were core temperature (via telemetry) and heat production (via respirometry). In the second phase, we used a thermal gradient (range 8°C—38°C) to assess each adapted group’s thermal preference, core temperature and locomotion on a single occasion during N2O inhalation at the assigned concentration. Results In phase 1, repeated N2O administrations led to dose related hyperthermic and hypermetabolic states during inhalation of ≥45% N2O compared to controls (≥ 30% N2O compared to baseline). In phase 2, rats in these groups selected cooler ambient temperatures during N2O inhalation but still developed some hyperthermia. However, a concentration-related increase of locomotion was evident in the gradient, and theoretical calculations and regression analyses both suggest that locomotion contributed to the residual hyperthermia. Conclusions Acquired

  7. A Phytochemical-Sensing Strategy Based on Mass Spectrometry Imaging and Metabolic Profiling for Understanding the Functionality of the Medicinal Herb Green Tea.

    Science.gov (United States)

    Fujimura, Yoshinori; Miura, Daisuke; Tachibana, Hirofumi

    2017-09-27

    Low-molecular-weight phytochemicals have health benefits and reduce the risk of diseases, but the mechanisms underlying their activities have remained elusive because of the lack of a methodology that can easily visualize the exact behavior of such small molecules. Recently, we developed an in situ label-free imaging technique, called mass spectrometry imaging, for visualizing spatially-resolved biotransformations based on simultaneous mapping of the major bioactive green tea polyphenol and its phase II metabolites. In addition, we established a mass spectrometry-based metabolic profiling technique capable of evaluating the bioactivities of diverse green tea extracts, which contain multiple phytochemicals, by focusing on their compositional balances. This methodology allowed us to simultaneously evaluate the relative contributions of the multiple compounds present in a multicomponent system to its bioactivity. This review highlights small molecule-sensing techniques for visualizing the complex behaviors of herbal components and linking such information to an enhanced understanding of the functionalities of multicomponent medicinal herbs.

  8. Carbon-Water-Nitrogen relationships between lichens and the atmosphere: Tools to understand metabolism and ecosystem change

    Directory of Open Access Journals (Sweden)

    Cristina Máguas

    2013-04-01

    Full Text Available Due to the close linking between the biosphere and atmosphere, there are clear impacts of changes in climate, atmospheric deposition of nutrients/pollutants and land use (Global Changes on the terrestrial biosphere. Lichens, with a direct dependence on atmospheric conditions, are much more affected by their immediate microclimate than by the ecosystem’s prevailing macroclimate. In contrast to higher plants, poikilohydric organisms have different mechanisms of water and CO2 exchange. The application of stable isotopes to the understanding of the mechanisms that are fundamental to lichen gas exchange and water uptake is a promising tool for the evaluation of lichen response to environmental changes. Indeed, lichens have been shown to be influenced by a large number of natural and anthropogenic environmental factors, serving as ecological indicators. Thus, we may use these organisms to model the impact of key global change drivers, such as nitrogen deposition and biodiversity changes, at local scale. Particularly useful is the application of the Lichen Diversity Value (LDV in order to evaluate the impact of global drivers. Moreover, it has been shown that these indices, associated with main photobiont types, green-algae (LDVch or cyanobacteria (LDVcyh, and/or nitrophilous versus oligotrophic species, were good candidates as ecological indicators. Besides mapping with high spatial resolution the effects of climate alterations, lichen functional groups could also be used as an early-warning system in order to detect the first effects of climate change in ecosystems before sudden shifts occur on other components that may be less sensitive. Clearly, lichens possess the adequate traits to be used as powerful indicators of complex interactions between atmosphere and biosphere, and thus can generate potentially interesting models for global change drivers.

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

    Directory of Open Access Journals (Sweden)

    Nalcakan Gulbin Rudarli

    2014-12-01

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

  10. Respiratory muscle hemodynamic and metabolic adaptations to 16 weeks of training in varsity soccer players: near-infrared spectroscopy measurements during lung function tests (Conference Presentation)

    Science.gov (United States)

    Harris, R. Luke; Grob, Tanya; Sandhu, Komal; Schwab, Timothy

    2017-02-01

    The purpose of this study was to test the hypothesis that mobile, wireless near-infrared spectroscopy (NIRS) instruments can be used during standard lung function tests to measure adaptations in respiratory muscle metabolism over weeks to months. In eight varsity soccer players at 0 weeks and after 16 weeks of routine training, commercially available mobile, wireless NIRS instruments were used to measure oxygenation and hemodynamics in the sternocleidomastoid (SCM, accessory inspiration muscle). During maximal expiratory pressure (MEP) and forced vital capacity (FVC) maneuvers we determined peak or antipeak changes relative to baseline in oxygenation and hemodynamics: Δ%Sat (muscle oxygen saturation), ΔtHb (total hemoglobin), ΔO2Hb (oxygenated hemoglobin), and ΔHHb (deoxygenated hemoglobin). Subjects reported that the average training load was 13.3 h/week during the 16 study weeks, compared to 10.4 h/week during 12 prior weeks. After 16 weeks of training compared to 0 weeks we found statistically significant increases in SCM Δ%Sat (57.7%), ΔtHb (55.3%), and ΔO2Hb (56.7%) during MEP maneuvers, and in SCM Δ%Sat (64.8%), ΔtHb (29.4%), and ΔO2Hb (51.6%) during FVC maneuvers. Our data provide preliminary evidence that NIRS measurements during standard lung function tests are sufficiently sensitive to detect improvements or declines in respiratory muscle metabolism over periods of weeks to months due to training, disease, and rehabilitation exercise.

  11. AMPK-α2 is involved in exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following high-fat diet.

    Science.gov (United States)

    Abbott, Marcia J; Turcotte, Lorraine P

    2014-10-15

    AMP-activated protein kinase (AMPK) has been studied extensively and postulated to be a target for the treatment and/or prevention of metabolic disorders such as insulin resistance. Exercise training has been deemed a beneficial treatment for obesity and insulin resistance. Furthermore, exercise is a feasible method to combat high-fat diet (HFD)-induced alterations in insulin sensitivity. The purpose of this study was to determine whether AMPK-α2 activity is required to gain beneficial effects of exercise training with high-fat feeding. Wild-type (WT) and AMPK-α2 dominant-negative (DN) male mice were fed standard diet (SD), underwent voluntary wheel running (TR), fed HFD, or trained with HFD (TR + HFD). By week 6, TR, irrespective of genotype, decreased blood glucose and increased citrate synthase activity in both diet groups and decreased insulin levels in HFD groups. Hindlimb perfusions were performed, and, in WT mice with SD, TR increased insulin-mediated palmitate uptake (76.7%) and oxidation (>2-fold). These training-induced changes were not observed in the DN mice. With HFD, TR decreased palmitate oxidation (61-64%) in both WT and DN and increased palmitate uptake (112%) in the WT with no effects on palmitate uptake in the DN. With SD, TR increased ERK1/2 and JNK1/2 phosphorylation, regardless of genotype. With HFD, TR reduced JNK1/2 phosphorylation, regardless of genotype, carnitine palmitoyltransferase 1 expression in WT, and CD36 expression in both DN and WT. These data suggest that low AMPK-α2 signaling disrupts, in part, the exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following HFD. Copyright © 2014 the American Physiological Society.

  12. SNP discovery in candidate adaptive genes using exon capture in a free-ranging alpine ungulate

    Science.gov (United States)

    Gretchen H. Roffler; Stephen J. Amish; Seth Smith; Ted Cosart; Marty Kardos; Michael K. Schwartz; Gordon Luikart

    2016-01-01

    Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identify SNP markers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein-coding...

  13. Physical Forces Modulate Oxidative Status and Stress Defense Meditated Metabolic Adaptation of Yeast Colonies: Spaceflight and Microgravity Simulations

    Science.gov (United States)

    Hammond, Timothy G.; Allen, Patricia L.; Gunter, Margaret A.; Chiang, Jennifer; Giaever, Guri; Nislow, Corey; Birdsall, Holly H.

    2018-05-01

    Baker's yeast ( Saccharomyces cerevisiae) has broad genetic homology to human cells. Although typically grown as 1-2mm diameter colonies under certain conditions yeast can form very large (10 + mm in diameter) or `giant' colonies on agar. Giant yeast colonies have been used to study diverse biomedical processes such as cell survival, aging, and the response to cancer pharmacogenomics. Such colonies evolve dynamically into complex stratified structures that respond differentially to environmental cues. Ammonia production, gravity driven ammonia convection, and shear defense responses are key differentiation signals for cell death and reactive oxygen system pathways in these colonies. The response to these signals can be modulated by experimental interventions such as agar composition, gene deletion and application of pharmaceuticals. In this study we used physical factors including colony rotation and microgravity to modify ammonia convection and shear stress as environmental cues and observed differences in the responses of both ammonia dependent and stress response dependent pathways We found that the effects of random positioning are distinct from rotation. Furthermore, both true and simulated microgravity exacerbated both cellular redox responses and apoptosis. These changes were largely shear-response dependent but each model had a unique response signature as measured by shear stress genes and the promoter set which regulates them These physical techniques permitted a graded manipulation of both convection and ammonia signaling and are primed to substantially contribute to our understanding of the mechanisms of drug action, cell aging, and colony differentiation.

  14. Physical Forces Modulate Oxidative Status and Stress Defense Meditated Metabolic Adaptation of Yeast Colonies: Spaceflight and Microgravity Simulations

    Science.gov (United States)

    Hammond, Timothy G.; Allen, Patricia L.; Gunter, Margaret A.; Chiang, Jennifer; Giaever, Guri; Nislow, Corey; Birdsall, Holly H.

    2017-12-01

    Baker's yeast (Saccharomyces cerevisiae) has broad genetic homology to human cells. Although typically grown as 1-2mm diameter colonies under certain conditions yeast can form very large (10 + mm in diameter) or `giant' colonies on agar. Giant yeast colonies have been used to study diverse biomedical processes such as cell survival, aging, and the response to cancer pharmacogenomics. Such colonies evolve dynamically into complex stratified structures that respond differentially to environmental cues. Ammonia production, gravity driven ammonia convection, and shear defense responses are key differentiation signals for cell death and reactive oxygen system pathways in these colonies. The response to these signals can be modulated by experimental interventions such as agar composition, gene deletion and application of pharmaceuticals. In this study we used physical factors including colony rotation and microgravity to modify ammonia convection and shear stress as environmental cues and observed differences in the responses of both ammonia dependent and stress response dependent pathways We found that the effects of random positioning are distinct from rotation. Furthermore, both true and simulated microgravity exacerbated both cellular redox responses and apoptosis. These changes were largely shear-response dependent but each model had a unique response signature as measured by shear stress genes and the promoter set which regulates them These physical techniques permitted a graded manipulation of both convection and ammonia signaling and are primed to substantially contribute to our understanding of the mechanisms of drug action, cell aging, and colony differentiation.

  15. NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus

    Science.gov (United States)

    Cantó, Carles; Menzies, Keir; Auwerx, Johan

    2015-01-01

    NAD+ has emerged as a vital cofactor that can rewire metabolism, activate sirtuins and maintain mitochondrial fitness through mechanisms such as the mitochondrial unfolded protein response. This improved understanding of NAD+ metabolism revived interest in NAD+ boosting strategies to manage a wide spectrum of diseases, ranging from diabetes to cancer. In this review, we summarize how NAD+ metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited. PMID:26118927

  16. Understanding water deficit stress-induced changes in the basic metabolism of higher plants - biotechnologically and sustainably improving agriculture and the ecoenvironment in arid regions of the globe.

    Science.gov (United States)

    Shao, Hong-Bo; Chu, Li-Ye; Jaleel, C Abdul; Manivannan, P; Panneerselvam, R; Shao, Ming-An

    2009-01-01

    Water is vital for plant growth, development and productivity. Permanent or temporary water deficit stress limits the growth and distribution of natural and artificial vegetation and the performance of cultivated plants (crops) more than any other environmental factor. Productive and sustainable agriculture necessitates growing plants (crops) in arid and semiarid regions with less input of precious resources such as fresh water. For a better understanding and rapid improvement of soil-water stress tolerance in these regions, especially in the water-wind eroded crossing region, it is very important to link physiological and biochemical studies to molecular work in genetically tractable model plants and important native plants, and further extending them to practical ecological restoration and efficient crop production. Although basic studies and practices aimed at improving soil water stress resistance and plant water use efficiency have been carried out for many years, the mechanisms involved at different scales are still not clear. Further understanding and manipulating soil-plant water relationships and soil-water stress tolerance at the scales of ecology, physiology and molecular biology can significantly improve plant productivity and environmental quality. Currently, post-genomics and metabolomics are very important in exploring anti-drought gene resources in various life forms, but modern agriculturally sustainable development must be combined with plant physiological measures in the field, on the basis of which post-genomics and metabolomics have further practical prospects. In this review, we discuss physiological and molecular insights and effects in basic plant metabolism, drought tolerance strategies under drought conditions in higher plants for sustainable agriculture and ecoenvironments in arid and semiarid areas of the world. We conclude that biological measures are the bases for the solutions to the issues relating to the different types of

  17. Rational and design of an overfeeding protocol in constitutional thinness: Understanding the physiology, metabolism and genetic background of resistance to weight gain.

    Science.gov (United States)

    Ling, Yiin; Galusca, Bogdan; Hager, Jorg; Feasson, Leonard; Valsesia, Armand; Epelbaum, Jacques; Alexandre, Virginie; Wynn, Emma; Dinet, Cécile; Palaghiu, Radu; Peoc'h, Michel; Boirie, Yves; Montaurier, Christophe; Estour, Bruno; Germain, Natacha

    2016-10-01

    Constitutional thinness (CT) is a natural state of underweight (13-17.5kg/m 2 ) without the presence of any eating disorders and abnormal hormonal profile, and with preserved menses in women. We previously conducted a four-week fat overfeeding study showing weight gain resistance in CT women and one of our main results was the identification of an energy gap: a positive energy balance (higher energy intake than energy expenditure). This new overfeeding study is designed to confirm the energy gap and propose mechanistic hypothesis. A 2-week overfeeding (daily consumption of one bottle of Renutryl ® Booster (600kcal, 30g protein, 72g carbohydrate, 21g fat) on top of the dietary intake) is performed to compare 15 women and men in each CT group (Body Mass Index [BMI]controls (BMI 20-25kg/m 2 ). Bodyweight, food intake, energy expenditure (canopy, calorimetric chamber and Actiheart), body composition (DXA), appetite regulatory hormone profiles after a test meal, proteomics, metabolomics, urinary metabolic profiles, stool microbiome and lipids, fat and muscle transcriptomics are monitored before and after overfeeding. Data inter-linking will be able to be established with results of this study. The findings could possibly open to therapeutic approaches to help CT patients to gain weight as well as provide a better understanding of energy regulation with regard to treat obesity (resistance to weight loss), a mirror image of CT (resistance to weight gain). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. A Phytochemical-Sensing Strategy Based on Mass Spectrometry Imaging and Metabolic Profiling for Understanding the Functionality of the Medicinal Herb Green Tea

    Directory of Open Access Journals (Sweden)

    Yoshinori Fujimura

    2017-09-01

    Full Text Available Low-molecular-weight phytochemicals have health benefits and reduce the risk of diseases, but the mechanisms underlying their activities have remained elusive because of the lack of a methodology that can easily visualize the exact behavior of such small molecules. Recently, we developed an in situ label-free imaging technique, called mass spectrometry imaging, for visualizing spatially-resolved biotransformations based on simultaneous mapping of the major bioactive green tea polyphenol and its phase II metabolites. In addition, we established a mass spectrometry-based metabolic profiling technique capable of evaluating the bioactivities of diverse green tea extracts, which contain multiple phytochemicals, by focusing on their compositional balances. This methodology allowed us to simultaneously evaluate the relative contributions of the multiple compounds present in a multicomponent system to its bioactivity. This review highlights small molecule-sensing techniques for visualizing the complex behaviors of herbal components and linking such information to an enhanced understanding of the functionalities of multicomponent medicinal herbs.

  19. A LysR-Type Transcriptional Regulator, RovM, Senses Nutritional Cues Suggesting that It Is Involved in Metabolic Adaptation of Yersinia pestis to the Flea Gut.

    Directory of Open Access Journals (Sweden)

    Viveka Vadyvaloo

    Full Text Available Yersinia pestis has evolved as a clonal variant of Yersinia pseudotuberculosis to cause flea-borne biofilm-mediated transmission of the bubonic plague. The LysR-type transcriptional regulator, RovM, is highly induced only during Y. pestis infection of the flea host. RovM homologs in other pathogens regulate biofilm formation, nutrient sensing, and virulence; including in Y. pseudotuberculosis, where RovM represses the major virulence factor, RovA. Here the role that RovM plays during flea infection was investigated using a Y. pestis KIM6+ strain deleted of rovM, ΔrovM. The ΔrovM mutant strain was not affected in characteristic biofilm gut blockage, growth, or survival during single infection of fleas. Nonetheless, during a co-infection of fleas, the ΔrovM mutant exhibited a significant competitive fitness defect relative to the wild type strain. This competitive fitness defect was restored as a fitness advantage relative to the wild type in a ΔrovM mutant complemented in trans to over-express rovM. Consistent with this, Y. pestis strains, producing elevated transcriptional levels of rovM, displayed higher growth rates, and differential ability to form biofilm in response to specific nutrients in comparison to the wild type. In addition, we demonstrated that rovA was not repressed by RovM in fleas, but that elevated transcriptional levels of rovM in vitro correlated with repression of rovA under specific nutritional conditions. Collectively, these findings suggest that RovM likely senses specific nutrient cues in the flea gut environment, and accordingly directs metabolic adaptation to enhance flea gut colonization by Y. pestis.

  20. Effects of starvation, refeeding, and insulin on energy-linked metabolic processes in catfish (Rhamdia hilarii) adapted to a carbohydrate-rich diet

    International Nuclear Information System (INIS)

    Machado, C.R.; Garofalo, M.A.; Roselino, J.E.; Kettelhut, I.C.; Migliorini, R.H.

    1988-01-01

    The effects of starvation and of a short period of refeeding on energy-linked metabolic processes, as well as the effects of insulin administration, were investigated in an omnivorous fish (catfish, Rhamdia hilarii) previously adapted to a carbohydrate-rich diet. Following food deprivation blood sugar levels declined progressively to about 50% of fed values after 30 days. During the same period plasma free fatty acid (FFA) concentration increased twofold. Starvation resulted in reduced concentrations of lipid and glycogen in the liver and of glycogen, lipid, and protein in white muscle. However, taking into account the initial and final concentrations of tissue constituents, the liver weight, and the large fractions of body weight represented by muscle, it could be estimated that most of the energy utilized during starvation derived from the catabolism of muscle lipid and protein. Refeeding starved fishes for 48 hr induced several-fold increases in the rates of in vivo and in vitro incorporation of [14C]glucose into liver and muscle lipid and of [14C]glycine into liver and muscle protein. Incorporation of [14C]glucose into liver glycogen was also increased. However; refeeding did not affect the incorporation of labeled glucose into muscle glycogen, neither in vivo nor in vitro. Administration of pharmacological doses of insulin to normally fed catfishes resulted in marked increases in the in vivo incorporation of 14C from glucose into lipid and protein in both liver and muscle. In contrast, labeled glucose incorporation into muscle glycogen was not affected by insulin and label incorporation into liver glycogen was actually lower than that in noninjected controls

  1. Late gestation under- and overnutrition have differential impacts when combined with a post-natal obesogenic diet on glucose-lactate-insulin adaptations during metabolic challenges in adolescent sheep

    DEFF Research Database (Denmark)

    Khanal, Prabhat; Axel, Anne Marie Dixen; Kongsted, Anna Hauntoft

    2015-01-01

    AIM: To determine whether late gestation under- and overnutrition programme metabolic plasticity in a similar way, and whether metabolic responses to an obesogenic diet in early post-natal life depend on the foetal nutrition history. METHODS: In a 3 × 2 factorial design, twin-pregnant ewes were......) or conventional (CONV; N = 35) diets from 3 days to 6 months of age (around puberty). Then intravenous glucose (GTT; overnight fasted), insulin (ITT; fed) and propionate (gluconeogenetic precursor; PTT; both fed and fasted) tolerance tests were conducted to evaluate (hepatic) metabolic plasticity. RESULTS......: Prenatal malnutrition differentially impacted adaptations of particularly plasma lactate followed by glucose, cholesterol and insulin. This was most clearly expressed during PTT in fasted lambs and much less during ITT and GTT. In fasted lambs, propionate induced more dramatic increases in lactate than...

  2. Exercise Intensity Modulation of Hepatic Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Fábio S. Lira

    2012-01-01

    Full Text Available Lipid metabolism in the liver is complex and involves the synthesis and secretion of very low density lipoproteins (VLDL, ketone bodies, and high rates of fatty acid oxidation, synthesis, and esterification. Exercise training induces several changes in lipid metabolism in the liver and affects VLDL secretion and fatty acid oxidation. These alterations are even more conspicuous in disease, as in obesity, and cancer cachexia. Our understanding of the mechanisms leading to metabolic adaptations in the liver as induced by exercise training has advanced considerably in the recent years, but much remains to be addressed. More recently, the adoption of high intensity exercise training has been put forward as a means of modulating hepatic metabolism. The purpose of the present paper is to summarise and discuss the merit of such new knowledge.

  3. [Influence of age and degree of compensation of carbohydrate metabolism on metabolic changes in blood of women patients with type 2 diabetes].

    Science.gov (United States)

    Mikashinovich, Z I; Ishonina, O G; Krivolapova, E G

    The purpose of this study was a comprehensive analysis of various aspects of metabolism of erythrocytes in women with type 2 diabetes, according to the age characteristics of compensation of carbohydrate metabolism. The obtained results, based on the nature of changes in parameters of carbohydrate and energy metabolism, gas transport and antioxidant systems of blood, contribute to the understanding of the role of metabolic changes in red blood cells, leading to changes in their biological properties, severity of which reflects the adaptive capacity of the organism in terms of hyperglycemia in different age groups in type 2 diabetes.

  4. Convergent Metabolic Specialization through Distinct Evolutionary Paths in Pseudomonas aeruginosa.

    Science.gov (United States)

    La Rosa, Ruggero; Johansen, Helle Krogh; Molin, Søren

    2018-04-10

    surprising that conclusions from our investigations of bacterial evolution in the CF model system are different from what has been concluded from laboratory experiments. The analysis presented here of the metabolic and regulatory driving forces leading to successful adaptation to a new environment provides an important insight into the role of metabolism and its regulatory mechanisms for successful adaptation of microorganisms in dynamic and complex environments. Understanding the trajectories of adaptation, as well as the mechanisms behind slow growth and rewiring of regulatory and metabolic networks, is a key element to understand the adaptive robustness and evolvability of bacteria in the process of increasing their in vivo fitness when conquering new territories. Copyright © 2018 La Rosa et al.

  5. Unraveling lipid metabolism in lipid-dependent pathogenic Malassezia yeasts

    OpenAIRE

    Celis Ramirez, A.M.

    2017-01-01

    Malassezia yeasts are lipid-dependent fungal species that are common members of the human and animal skin microbiota. The lipid-dependency is a crucial trait in the adaptation process to grow on the skin but also plays a role in their pathogenic life style. Malassezia species can cause several skin infections like dandruff or seborrheic dermatitis but also bloodstream infections. Understanding the lipid metabolism in Malassezia is essential to understand its life style as skin commensal and p...

  6. Understanding Resilience

    Directory of Open Access Journals (Sweden)

    Gang eWu

    2013-02-01

    Full Text Available Resilience is the ability to adapt successfully in the face of stress and adversity. Stressful life events, trauma and chronic adversity can have a substantial impact on brain function and structure, and can result in the development of PTSD, depression and other psychiatric disorders. However, most individuals do not develop such illnesses after experiencing stressful life events, and are thus thought to be resilient. Resilience as successful adaptation relies on effective responses to environmental challenges and ultimate resistance to the deleterious effects of stress, therefore a greater understanding of the factors that promote such effects is of great relevance. This review focuses on recent findings regarding genetic, epigenetic, developmental, psychosocial and neurochemical factors that are considered essential contributors to the development of resilience. Neural circuits and pathways involved in mediating resilience are also discussed. The growing understanding of resilience factors will hopefully lead to the development of new pharmacological and psychological interventions for enhancing resilience and mitigating the untoward consequences.

  7. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    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/

  8. Climate. For a successful change. Volume 1: How to commit one's territory in an adaptation approach. Volume 2: How to implement a territorial project which integrates adaptation. Volume 3: How to understand the complexity of climate change - Scientific issues

    International Nuclear Information System (INIS)

    2013-12-01

    The first volume presents the climate issue as a world issue as well as a local issue (historic context of adaptation to climate change effects, legal obligation for local communities, indicators of direct and indirect effects of climate change, economic impacts), and presents adaptation as a way of action at a local level (definition of a strategy, articulation between works on greenhouse gas emissions and those on adaptation, actions to be implemented, action follow-up and adjustment). The second volume describes how to communicate and talk about climate change, and more specifically about the above-mentioned issues (reality of climate change, indirect and direct effects, obligations and responsibilities for local communities, economic impacts). It addresses the issue of climate change in the Rhone-Alpes region: adaptation within the regional scheme on climate, air and energy (SRCAE), role of local communities. It presents an action methodology: to inform and organise, to prepare the mobilisation of actors, to prepare the territory vulnerability diagnosis, to define the adaptation strategy, and to implement, follow-up and assess the action. The third volume proposes a set of sheets containing scientific information and data related to climate change: factors of climate variability, current global warming, greenhouse gases and aerosols, physical-chemical principles involved in greenhouse effect, carbon sinks and carbon sources, effects of land assignment and agriculture, combined effects of mankind actions on the atmosphere, climate change and oceans, climate change and cryo-sphere, climate change and biodiversity, extreme meteorological and climate events and their consequences

  9. Obesity-driven gut microbiota inflammatory pathways to metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Luiz Henrique Agra eCavalcante-Silva

    2015-11-01

    Full Text Available The intimate interplay between immune system, metabolism and gut microbiota plays an important role in controlling metabolic homeostasis and possible obesity development. Obesity involves impairment of immune response affecting both innate and adaptive immunity. The main factors involved in the relationship of obesity with inflammation have not been completely elucidated. On the other hand, gut microbiota, via innate immune receptors, has emerged as one of the key factors regulating events triggering acute inflammation associated with obesity and metabolic syndrome. Inflammatory disorders lead to several signalling transduction pathways activation, inflammatory cytokine, chemokine production and cell migration, which in turn cause metabolic dysfunction. Inflamed adipose tissue, with increased macrophages infiltration, is associated with impaired preadipocyte development and differentiation to mature adipose cells, leading to ectopic lipid accumulation and insulin resistance. This review focuses on the relationship between obesity and inflammation, which is essential to understand the pathological mechanisms governing metabolic syndrome.

  10. Role and function of short chain fatty acids in rumen epithelial metabolism, development and importance of the rumen epithelium in understanding control of transcriptome

    Science.gov (United States)

    The epithelial lining of the rumen is uniquely placed to have impact on the nutrient metabolism of the animal. The symbiotic relationship with the microbial populations that inhabit the rumen, serves to provide a constant supply of nutrients from roughage that would otherwise be unusable. Metaboli...

  11. Cerebral metabolism in dogs assessed by 18F-FDG PET. A pilot study to understand physiological changes in behavioral disorders in dogs

    International Nuclear Information System (INIS)

    Irimajiri, Mami; Jaeger, C.B.; Luescher, A.U.; Miller, M.A.; Hutchins, G.D.; Green, M.A.

    2010-01-01

    The positron emission tomography (PET) imaging technique, which is utilized in human behavior and psychiatric disorder research, was performed on the brains of clinically normal mixed breed dogs, 3 hound-type (long floppy ears) mixed breed dogs and 3 non-hound retriever-type mixed breed dogs. Glucose metabolism was obtained with F-18 fluorodeoxyglucose (FDG), and quantitative analysis was performed by standardized uptake value (SUV) measurement. Magnetic resonance (MR) images were obtained in each dog, and these images were superimposed on PET images to identify anatomical locations. The glucose metabolism in each region of interest was compared between the three hound-type dogs and 3 non-hound-type dogs. The two anatomically different types of dog were compared to assess whether breed-typical behavioral tendencies (e.g., sniffing behavior in hound-type dogs, staring and retrieving in Labrador-type dogs) are reflected in baseline brain metabolic activity. There were no significant differences between the hound-type dogs and non-hound-type dogs in cerebral SUV values. These data might serve as normal canine cerebral metabolism data for FDG PET studies in dogs and form the basis for investigations into behavioral disorders in dogs such as compulsive disorder, anxiety disorders and cognitive dysfunction. (author)

  12. Early metabolic adaptation in C57BL/6 mice resistant to high fat diet induced weight gain involves an activation of mitochondrial oxidative pathways.

    Science.gov (United States)

    Boulangé, Claire L; Claus, Sandrine P; Chou, Chieh J; Collino, Sebastiano; Montoliu, Ivan; Kochhar, Sunil; Holmes, Elaine; Rezzi, Serge; Nicholson, Jeremy K; Dumas, Marc E; Martin, François-Pierre J

    2013-04-05

    We investigated the short-term (7 days) and long-term (60 days) metabolic effect of high fat diet induced obesity (DIO) and weight gain in isogenic C57BL/6 mice and examined the specific metabolic differentiation between mice that were either strong-responders (SR), or non-responders (NR) to weight gain. Mice (n = 80) were fed a standard chow diet for 7 days prior to randomization into a high-fat (HF) (n = 56) or a low-fat (LF) (n = 24) diet group. The (1)H NMR urinary metabolic profiles of LF and HF mice were recorded 7 and 60 days after the diet switch. On the basis of the body weight gain (BWG) distribution of HF group, we identified NR mice (n = 10) and SR mice (n = 14) to DIO. Compared with LF, HF feeding increased urinary excretion of glycine conjugates of β-oxidation intermediate (hexanoylglycine), branched chain amino acid (BCAA) catabolism intermediates (isovalerylglycine, α-keto-β-methylvalerate and α-ketoisovalerate) and end-products of nicotinamide adenine dinucleotide (NAD) metabolism (N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide) suggesting up-regulation of mitochondrial oxidative pathways. In the HF group, NR mice excreted relatively more hexanoylglycine, isovalerylglycine, and fewer tricarboxylic acid (TCA) cycle intermediate (succinate) in comparison to SR mice. Thus, subtle regulation of ketogenic pathways in DIO may alleviate the saturation of the TCA cycle and mitochondrial oxidative metabolism.

  13. Effectiveness of Adaptive Concept Maps for Promoting Conceptual Understanding: Findings from a Design-Based Case Study of a Learner-Centered Tool

    Science.gov (United States)

    Moore, Jacob; Williams, Christopher B.; North, Christopher; Johri, Aditya; Paretti, Marie

    2015-01-01

    Traditional instructional materials such as textbooks contain significant educational content, but the navigational mechanisms to access that content are limited and, more importantly, not designed with learning in mind. To address this gap, we present the Adaptive Map, a novel organization and navigation tool designed to help students better…

  14. Breeding poplars with durable resistance to Melampsora larici-populina leaf rust: a multidisciplinary approach to understand and delay pathogen adaptation

    Science.gov (United States)

    V. Jorge Dowkiw; M. Villar; E. Voisin; V. Guérin; P. Faivre-Rampant; A. Bresson; F. Bitton; S. Duplessis; P. Frey; B. Petre; C. Guinet; C. Xhaard; B. Fabre; F. Halkett; C. Plomion; C. Lalanne; C. Bastien

    2012-01-01

    During the last decades, European poplar breeders learned the hard way that Melampsora larici-populina (commonly abbreviated as Mlp…) has an impressive adaptive potential (McDonald and Linde 2002). This fungal pathogen defeated all the deployed cultivars carrying qualitative (i.e., complete) resistances inherited from the...

  15. Cellular energy metabolism in T-lymphocytes.

    Science.gov (United States)

    Gaber, Timo; Strehl, Cindy; Sawitzki, Birgit; Hoff, Paula; Buttgereit, Frank

    2015-01-01

    Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.

  16. Improving lactate metabolism in an intensified CHO culture process: productivity and product quality considerations.

    Science.gov (United States)

    Xu, Sen; Hoshan, Linda; Chen, Hao

    2016-11-01

    In this study, we discussed the development and optimization of an intensified CHO culture process, highlighting medium and control strategies to improve lactate metabolism. A few strategies, including supplementing glucose with other sugars (fructose, maltose, and galactose), controlling glucose level at Productivity and product quality attributes differences between batch, fed-batch, and concentrated fed-batch cultures were discussed. The importance of process and cell metabolism understanding when adapting the existing process to a new operational mode was demonstrated in the study.

  17. Short-term high fat-feeding results in morphological and metabolic adaptations in the skeletal muscle of C57BL/6J mice

    NARCIS (Netherlands)

    Wilde, de J.; Mohren, R.; Berg, van den S.; Boekschoten, M.V.; Willems van Dijk, K.; Groot, de P.J.; Müller, M.R.; Mariman, E.; Smit, E.

    2008-01-01

    The prevalence of the metabolic syndrome (MS) is rapidly increasing all over the world. Consequently, there is an urgent need for more effective intervention strategies. Both animal and human studies indicate that lipid oversupply to skeletal muscle can result in insulin resistance which is one of

  18. Glucagon-Like Peptide 2 Stimulates Postresection Intestinal Adaptation in Preterm Pigs by Affecting Proteins Related to Protein, Carbohydrate, and Sulphur Metabolism

    DEFF Research Database (Denmark)

    Jiang, Pingping; Vegge, Andreas; Thymann, Thomas

    2017-01-01

    cellular structural proteins, while the added GLP-2 treatment affected proteins involved in protein processing and the metabolism of protein, carbohydrate, and sulphur. CONCLUSION: In the first days following resection, proteins affected by resection plus GLP-2 treatment differed markedly from those...

  19. Metabolic cold adaptation and aerobic performance of blue mussels (Mytilus edulis) along a temperature gradient into the High Arctic region

    DEFF Research Database (Denmark)

    Thyrring, Jakob; Rysgaard, Søren; Blicher, Martin

    2015-01-01

    and plasticity of blue mussels across latitudes spanning from 56 to 77ºN. This indicates that low ocean temperature per se does not constrain metabolic activity of Mytilus in the Arctic; rather, we speculate that maturation of reproductive tissues, larval supply and annual energy budgets are the most relevant...

  20. Middle-aged overweight South Asian men exhibit a different metabolic adaptation to short-term energy restriction compared with Europeans

    NARCIS (Netherlands)

    Bakker, L.E.; Guigas, B.; Schinkel, L.D. van; Zon, G.C. van der; Streefland, T.C.; Klinken, J.B. van; Jonker, J.T.; Lamb, H.J.; Smit, J.W.A.; Pijl, H.; Meinders, A.E.; Jazet, I.M.

    2015-01-01

    AIMS/HYPOTHESIS: South Asians have a higher risk of developing type 2 diabetes than Europeans. The underlying cause of this excess risk is still poorly understood but might be related to differences in the regulation of energy/nutrient-sensing pathways in metabolic tissues and subsequent changes in

  1. Recent advances in understanding the genetic resources of sheep breeds locally-adapted to the UK uplands : opportunities they offer for sustainable productivity.

    Directory of Open Access Journals (Sweden)

    Dianna eBowles

    2015-02-01

    Full Text Available Locally adapted breeds of livestock are of considerable interest since they represent potential reservoirs of adaptive fitness traits that may contribute to the future of sustainable productivity in a changing climate.Recent research, involving three hill sheep breeds geographically concentrated in the northern uplands of the UK has revealed the extent of their genetic diversity from one another and from other breeds. Results from the use of SNPs, microsatellites and retrovirus insertions are reviewed in the context of related studies on sheep breeds world-wide to highlight opportunities offered by the genetic resources of locally adapted hill breeds. One opportunity concerns reduced susceptibility to Maedi-Visna, a lentivirus with massive impacts on sheep health and productivity globally. In contrast to many mainstream breeds used in farming, each of the hill breeds analysed are likely to be far less susceptible to the disease threat. A different opportunity, relating specifically to the Herdwick breed, is the extent to which the genome of the breed has retained primitive features, no longer present in other mainland breeds of sheep in the UK and offering a new route for discovering unique genetic traits of use to agriculture.

  2. Diabetic db/db mice do not develop heart failure upon pressure overload: a longitudinal in vivo PET, MRI, and MRS study on cardiac metabolic, structural, and functional adaptations.

    Science.gov (United States)

    Abdurrachim, Desiree; Nabben, Miranda; Hoerr, Verena; Kuhlmann, Michael T; Bovenkamp, Philipp; Ciapaite, Jolita; Geraets, Ilvy M E; Coumans, Will; Luiken, Joost J F P; Glatz, Jan F C; Schäfers, Michael; Nicolay, Klaas; Faber, Cornelius; Hermann, Sven; Prompers, Jeanine J

    2017-08-01

    Heart failure is associated with altered myocardial substrate metabolism and impaired cardiac energetics. Comorbidities like diabetes may influence the metabolic adaptations during heart failure development. We quantified to what extent changes in substrate preference, lipid accumulation, and energy status predict the longitudinal development of hypertrophy and failure in the non-diabetic and the diabetic heart. Transverse aortic constriction (TAC) was performed in non-diabetic (db/+) and diabetic (db/db) mice to induce pressure overload. Magnetic resonance imaging, 31P magnetic resonance spectroscopy (MRS), 1H MRS, and 18F-fluorodeoxyglucose-positron emission tomography (PET) were applied to measure cardiac function, energy status, lipid content, and glucose uptake, respectively. In vivo measurements were complemented with ex vivo techniques of high-resolution respirometry, proteomics, and western blotting to elucidate the underlying molecular pathways. In non-diabetic mice, TAC induced progressive cardiac hypertrophy and dysfunction, which correlated with increased protein kinase D-1 (PKD1) phosphorylation and increased glucose uptake. These changes in glucose utilization preceded a reduction in cardiac energy status. At baseline, compared with non-diabetic mice, diabetic mice showed normal cardiac function, higher lipid content and mitochondrial capacity for fatty acid oxidation, and lower PKD1 phosphorylation, glucose uptake, and energetics. Interestingly, TAC affected cardiac function only mildly in diabetic mice, which was accompanied by normalization of phosphorylated PKD1, glucose uptake, and cardiac energy status. The cardiac metabolic adaptations in diabetic mice seem to prevent the heart from failing upon pressure overload, suggesting that restoring the balance between glucose and fatty acid utilization is beneficial for cardiac function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions

  3. Camelid genomes reveal evolution and adaptation to desert environments.

    Science.gov (United States)

    Wu, Huiguang; Guang, Xuanmin; Al-Fageeh, Mohamed B; Cao, Junwei; Pan, Shengkai; Zhou, Huanmin; Zhang, Li; Abutarboush, Mohammed H; Xing, Yanping; Xie, Zhiyuan; Alshanqeeti, Ali S; Zhang, Yanru; Yao, Qiulin; Al-Shomrani, Badr M; Zhang, Dong; Li, Jiang; Manee, Manee M; Yang, Zili; Yang, Linfeng; Liu, Yiyi; Zhang, Jilin; Altammami, Musaad A; Wang, Shenyuan; Yu, Lili; Zhang, Wenbin; Liu, Sanyang; Ba, La; Liu, Chunxia; Yang, Xukui; Meng, Fanhua; Wang, Shaowei; Li, Lu; Li, Erli; Li, Xueqiong; Wu, Kaifeng; Zhang, Shu; Wang, Junyi; Yin, Ye; Yang, Huanming; Al-Swailem, Abdulaziz M; Wang, Jun

    2014-10-21

    Bactrian camel (Camelus bactrianus), dromedary (Camelus dromedarius) and alpaca (Vicugna pacos) are economically important livestock. Although the Bactrian camel and dromedary are large, typically arid-desert-adapted mammals, alpacas are adapted to plateaus. Here we present high-quality genome sequences of these three species. Our analysis reveals the demographic history of these species since the Tortonian Stage of the Miocene and uncovers a striking correlation between large fluctuations in population size and geological time boundaries. Comparative genomic analysis reveals complex features related to desert adaptations, including fat and water metabolism, stress responses to heat, aridity, intense ultraviolet radiation and choking dust. Transcriptomic analysis of Bactrian camels further reveals unique osmoregulation, osmoprotection and compensatory mechanisms for water reservation underpinned by high blood glucose levels. We hypothesize that these physiological mechanisms represent kidney evolutionary adaptations to the desert environment. This study advances our understanding of camelid evolution and the adaptation of camels to arid-desert environments.

  4. Understanding arsenic metabolism through a comparative study of arsenic levels in the urine, hair and fingernails of healthy volunteers from three unexposed ethnic groups in the United Kingdom

    International Nuclear Information System (INIS)

    Brima, Eid I.; Haris, Parvez I.; Jenkins, Richard O.; Polya, Dave A.; Gault, Andrew G.; Harrington, Chris F.

    2006-01-01

    Very little is known about arsenic (As) metabolism in healthy populations that are not exposed to high concentrations of As in their food or water. Here we present a study with healthy volunteers from three different ethnic groups, residing in Leicester, UK, which reveals statistically significant differences in the levels of total As in urine and fingernail samples. Urine (n = 63), hair (n = 36) and fingernail (n = 36) samples from Asians, Somali Black-Africans and Whites were analysed using inductively coupled plasma mass spectrometry (ICP-MS) and graphite furnace atomic absorption spectroscopy (GF-AAS). The results clearly show that the total concentrations of As in urine and fingernail samples of a Somali Black-African population (urine 7.2 μg/g creatinine; fingernails 723.1 μg/kg) are significantly (P 0.05) in the level of As in the hair samples from these three groups; Somali Black-Africans (116.0 μg/kg), Asians (117.4 μg/kg) and Whites (141.2 μg/kg). Significantly different levels of total As in fingernail and urine and a higher percentage of urinary DMA in the Somali Black-Africans are suggestive of a different pattern of As metabolism in this ethnic group

  5. Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance

    DEFF Research Database (Denmark)

    Vollaard, Niels B J; Constantin-Teodosiu, Dimitru; Fredriksson, Katarina

    2009-01-01

    It has not been established which physiological processes contribute to endurance training-related changes (Delta) in aerobic performance. For example, the relationship between intramuscular metabolic responses at the intensity used during training and improved human functional capacity has...... not been examined in a longitudinal study. In the present study we hypothesized that improvements in aerobic capacity (Vo(2max)) and metabolic control would combine equally to explain enhanced aerobic performance. Twenty-four sedentary males (24 +/- 2 yr; 1.81 +/- 0.08 m; 76.6 +/- 11.3 kg) undertook...... unrelated to the change in aerobic performance. The maximal parameters DeltaVe(max) and DeltaVeq(max) (DeltaVe/Vo(2max)) accounted for 64% of the variance in DeltaVo(2max) (P

  6. Metabolic switches and adaptations deduced from the proteomes of Streptomyces coelicolor wild type and phoP mutant grown in batch culture.

    Science.gov (United States)

    Thomas, Louise; Hodgson, David A; Wentzel, Alexander; Nieselt, Kay; Ellingsen, Trond E; Moore, Jonathan; Morrissey, Edward R; Legaie, Roxane; Wohlleben, Wolfgang; Rodríguez-García, Antonio; Martín, Juan F; Burroughs, Nigel J; Wellington, Elizabeth M H; Smith, Margaret C M

    2012-02-01

    Bacteria in the genus Streptomyces are soil-dwelling oligotrophs and important producers of secondary metabolites. Previously, we showed that global messenger RNA expression was subject to a series of metabolic and regulatory switches during the lifetime of a fermentor batch culture of Streptomyces coelicolor M145. Here we analyze the proteome from eight time points from the same fermentor culture and, because phosphate availability is an important regulator of secondary metabolite production, compare this to the proteome of a similar time course from an S. coelicolor mutant, INB201 (ΔphoP), defective in the control of phosphate utilization. The proteomes provide a detailed view of enzymes involved in central carbon and nitrogen metabolism. Trends in protein expression over the time courses were deduced from a protein abundance index, which also revealed the importance of stress pathway proteins in both cultures. As expected, the ΔphoP mutant was deficient in expression of PhoP-dependent genes, and several putatively compensatory metabolic and regulatory pathways for phosphate scavenging were detected. Notably there is a succession of switches that coordinately induce the production of enzymes for five different secondary metabolite biosynthesis pathways over the course of the batch cultures.

  7. Teaching Teaching & Understanding Understanding

    DEFF Research Database (Denmark)

    2006-01-01

    "Teaching Teaching & Understanding Understanding" is a 19-minute award-winning short-film about teaching at university and higher-level educational institutions. It is based on the "Constructive Alignment" theory developed by Prof. John Biggs. The film delivers a foundation for understanding what...

  8. Determinate primary root growth as an adaptation to aridity in Cactaceae: towards an understanding of the evolution and genetic control of the trait.

    Science.gov (United States)

    Shishkova, Svetlana; Las Peñas, María Laura; Napsucialy-Mendivil, Selene; Matvienko, Marta; Kozik, Alex; Montiel, Jesús; Patiño, Anallely; Dubrovsky, Joseph G

    2013-07-01

    Species of Cactaceae are well adapted to arid habitats. Determinate growth of the primary root, which involves early and complete root apical meristem (RAM) exhaustion and differentiation of cells at the root tip, has been reported for some Cactoideae species as a root adaptation to aridity. In this study, the primary root growth patterns of Cactaceae taxa from diverse habitats are classified as being determinate or indeterminate, and the molecular mechanisms underlying RAM maintenance in Cactaceae are explored. Genes that were induced in the primary root of Stenocereus gummosus before RAM exhaustion are identified. Primary root growth was analysed in Cactaceae seedlings cultivated in vertically oriented Petri dishes. Differentially expressed transcripts were identified after reverse northern blots of clones from a suppression subtractive hybridization cDNA library. All species analysed from six tribes of the Cactoideae subfamily that inhabit arid and semi-arid regions exhibited determinate primary root growth. However, species from the Hylocereeae tribe, which inhabit mesic regions, exhibited mostly indeterminate primary root growth. Preliminary results suggest that seedlings of members of the Opuntioideae subfamily have mostly determinate primary root growth, whereas those of the Maihuenioideae and Pereskioideae subfamilies have mostly indeterminate primary root growth. Seven selected transcripts encoding homologues of heat stress transcription factor B4, histone deacetylase, fibrillarin, phosphoethanolamine methyltransferase, cytochrome P450 and gibberellin-regulated protein were upregulated in S. gummosus root tips during the initial growth phase. Primary root growth in Cactoideae species matches their environment. The data imply that determinate growth of the primary root became fixed after separation of the Cactiodeae/Opuntioideae and Maihuenioideae/Pereskioideae lineages, and that the genetic regulation of RAM maintenance and its loss in Cactaceae is

  9. Can adaptive threshold-based metabolic tumor volume (MTV) and lean body mass corrected standard uptake value (SUL) predict prognosis in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy?

    Science.gov (United States)

    Akagunduz, Ozlem Ozkaya; Savas, Recep; Yalman, Deniz; Kocacelebi, Kenan; Esassolak, Mustafa

    2015-11-01

    To evaluate the predictive value of adaptive threshold-based metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax) and maximum lean body mass corrected SUV (SULmax) measured on pretreatment positron emission tomography and computed tomography (PET/CT) imaging in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy. Pretreatment PET/CT of the 62 patients with locally advanced head and neck cancer who were treated consecutively between May 2010 and February 2013 were reviewed retrospectively. The maximum FDG uptake of the primary tumor was defined according to SUVmax and SULmax. Multiple threshold levels between 60% and 10% of the SUVmax and SULmax were tested with intervals of 5% to 10% in order to define the most suitable threshold value for the metabolic activity of each patient's tumor (adaptive threshold). MTV was calculated according to this value. We evaluated the relationship of mean values of MTV, SUVmax and SULmax with treatment response, local recurrence, distant metastasis and disease-related death. Receiver-operating characteristic (ROC) curve analysis was done to obtain optimal predictive cut-off values for MTV and SULmax which were found to have a predictive value. Local recurrence-free (LRFS), disease-free (DFS) and overall survival (OS) were examined according to these cut-offs. Forty six patients had complete response, 15 had partial response, and 1 had stable disease 6 weeks after the completion of treatment. Median follow-up of the entire cohort was 18 months. Of 46 complete responders 10 had local recurrence, and of 16 partial or no responders 10 had local progression. Eighteen patients died. Adaptive threshold-based MTV had significant predictive value for treatment response (p=0.011), local recurrence/progression (p=0.050), and disease-related death (p=0.024). SULmax had a predictive value for local recurrence/progression (p=0.030). ROC curves analysis revealed a cut-off value of 14.00 mL for

  10. Beta-adrenergic receptors are critical for weight loss but not for other metabolic adaptations to the consumption of a ketogenic diet in male mice

    Directory of Open Access Journals (Sweden)

    Nicholas Douris

    2017-08-01

    Conclusions: The response of β-less mice distinguishes at least two distinct categories of physiologic effects in mice consuming KD. In the liver, KD regulates peroxisome proliferator-activated receptor alpha (PPARα-dependent pathways through an action of FGF21 independent of the SNS and beta-adrenergic receptors. In sharp contrast, induction of interscapular brown adipose tissue (BAT and increased energy expenditure absolutely require SNS signals involving action on one or more β-adrenergic receptors. In this way, the key metabolic actions of FGF21 in response to KD have diverse effector mechanisms.

  11. The yak genome and adaptation to life at high altitude

    DEFF Research Database (Denmark)

    Qiu, Qiang; Zhang, Guojie; Ma, Tao

    2012-01-01

    . Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment...... important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans....

  12. Profiling of Indigenous Microbial Community Dynamics and Metabolic Activity During Enrichment in Molasses-Supplemented Crude Oil-Brine Mixtures for Improved Understanding of Microbial Enhanced Oil Recovery

    DEFF Research Database (Denmark)

    Halim, Amalia Yunita; Pedersen, Dorthe Skou; Nielsen, Sidsel Marie

    2015-01-01

    Anaerobic incubations using crude oil and brine from a North Sea reservoir were conducted to gain increased understanding of indigenous microbial community development, metabolite production, and the effects on the oil–brine system after addition of a complex carbon source, molasses, with or with...... of molasses has potential as microbial enhanced oil recovery (MEOR) strategy in North Sea oil reservoirs.......Anaerobic incubations using crude oil and brine from a North Sea reservoir were conducted to gain increased understanding of indigenous microbial community development, metabolite production, and the effects on the oil–brine system after addition of a complex carbon source, molasses....... The microbial growth caused changes in the crude oil–brine system: formation of oil emulsions, and reduction of interfacial tension (IFT). Reduction in IFT was associated with microbes being present at the oil–brine interphase. These findings suggest that stimulation of indigenous microbial growth by addition...

  13. Understanding Resilience Dimensions and Adaptive Strategies to the Impact of Recurrent Droughts in Borana Zone, Oromia Region, Ethiopia: A Grounded Theory Approach

    Directory of Open Access Journals (Sweden)

    Zewdie Birhanu

    2017-01-01

    Full Text Available Recurrent shocks and stresses are increasingly deteriorating pastoralist communities’ resilience capacities in many aspects. A context specific resilience framework is essential to strengthen pastoralist community’s resilience capacity towards the impact of recurrent drought. Hence, the present study was aimed to develop a context specific and data driven resilience building framework towards impacts of recurrent droughts in the case of Borana pastoralists in Ethiopia. Qualitative grounded theory approach was employed to guide the study process. The data were collected through focus group discussions and in-depth interviews in two drought affected districts of Borana Zone during October 2013. The analysis was assisted by ATLAS. ti 7.1.4. The analysis provided a context specific resilience building conceptual tool, which consists of, closely interconnected, eight dimensions operating at multiple capacities and levels: environment (underlying vulnerability factor; livestock, infrastructures/social services, and wealth (immediate causes and effects; community network/social capital, as well as governance, peace and security (support and enabling factors oriented, psychosocial, and human capital (as eventual outcomes and impacts. The resilience capacities of these pastoralist communities have been eroded, leaving them without sufficient and effective adaptive strategies. The emergent resilience framework can serve as a useful guidance to design context-specific interventions that makes the people and the system resilient to the impacts of recurrent droughts.

  14. Genetic and metabolic engineering in diatoms.

    Science.gov (United States)

    Huang, Weichao; Daboussi, Fayza

    2017-09-05

    Diatoms have attracted considerable attention due to their success in diverse environmental conditions, which probably is a consequence of their complex origins. Studies of their metabolism will provide insight into their adaptation capacity and are a prerequisite for metabolic engineering. Several years of investigation have led to the development of the genome engineering tools required for such studies, and a profusion of appropriate tools is now available for exploring and exploiting the metabolism of these organisms. Diatoms are highly prized in industrial biotechnology, due to both their richness in natural lipids and carotenoids and their ability to produce recombinant proteins, of considerable value in diverse markets. This review provides an overview of recent advances in genetic engineering methods for diatoms, from the development of gene expression cassettes and gene delivery methods, to cutting-edge genome-editing technologies. It also highlights the contributions of these rapid developments to both basic and applied research: they have improved our understanding of key physiological processes; and they have made it possible to modify the natural metabolism to favour the production of specific compounds or to produce new compounds for green chemistry and pharmaceutical applications.This article is part of the themed issue 'The peculiar carbon metabolism in diatoms'. © 2017 The Author(s).

  15. Mycobacterium tuberculosis Metabolism

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    during lactation. There was no effect of prenatal UN on glucose tolerance during G-IGTT, however, during RG-IGTT LOW was more glucose intolerant and apparently more insulin resistant compared to NORM. In conclusion, UN during late fetal life in sheep impairs subsequent pancreatic insulin secretory...... of a feed restriction period (RG-IGTT)), and a third around peak lactation (L-IGTT). LOW had lower basal insulin concentrations during lactation, and significantly decreased absolute insulin secretion during the L-IGTT in spite of similar glucose tolerance, indicating increased insulin sensitivity in LOW...... capacity during adult life, and reduces plasticity of down-regulation of insulin secretion in response to a metabolic challenge. Furthermore, prenatal UN appears to programme mechanisms, which in young adult females can shift the insulin hypersensitivity observed during early lactation into an insulin...

  17. Left ventricular vascular and metabolic adaptations to high-intensity interval and moderate intensity continuous training: a randomized trial in healthy middle-aged men.

    Science.gov (United States)

    Eskelinen, Jari-Joonas; Heinonen, Ilkka; Löyttyniemi, Eliisa; Hakala, Juuso; Heiskanen, Marja A; Motiani, Kumail K; Virtanen, Kirsi; Pärkkä, Jussi P; Knuuti, Juhani; Hannukainen, Jarna C; Kalliokoski, Kari K

    2016-12-01

    High-intensity interval training (HIIT) has become popular, time-sparing alternative to moderate intensity continuous training (MICT), although the cardiac vascular and metabolic effects of HIIT are incompletely known. We compared the effects of 2-week interventions with HIIT and MICT on myocardial perfusion and free fatty acid and glucose uptake. Insulin-stimulated myocardial glucose uptake was decreased by training without any significantly different response between the groups, whereas free fatty acid uptake remained unchanged. Adenosine-stimulated myocardial perfusion responded differently to the training modes (change in mean HIIT: -19%; MICT: +9%; P = 0.03 for interaction) and was correlated with myocardial glucose uptake for the entire dataset and especially after HIIT training. HIIT and MICT induce similar metabolic and functional changes in the heart, although myocardial vascular hyperaemic reactivity is impaired after HIIT, and this should be considered when prescribing very intense HIIT for previously untrained subjects. High-intensity interval training (HIIT) is a time-efficient way of obtaining the health benefits of exercise, although the cardiac effects of this training mode are incompletely known. We compared the effects of short-term HIIT and moderate intensity continuous training (MICT) interventions on myocardial perfusion and metabolism and cardiac function in healthy, sedentary, middle-aged men. Twenty-eight healthy, middle-aged men were randomized to either HIIT or MICT groups (n = 14 in both) and underwent six cycle ergometer training sessions within 2 weeks (HIIT session: 4-6 × 30 s all-out cycling/4 min recovery, MICT session 40-60 min at 60% V̇O2 peak ). Cardiac magnetic resonance imaging (CMRI) was performed to measure cardiac structure and function and positron emission tomography was used to measure myocardial perfusion at baseline and during adenosine stimulation, insulin-stimulated glucose uptake (MGU) and fasting free

  18. The purpose of adaptation.

    Science.gov (United States)

    Gardner, Andy

    2017-10-06

    A central feature of Darwin's theory of natural selection is that it explains the purpose of biological adaptation. Here, I: emphasize the scientific importance of understanding what adaptations are for, in terms of facilitating the derivation of empirically testable predictions; discuss the population genetical basis for Darwin's theory of the purpose of adaptation, with reference to Fisher's 'fundamental theorem of natural selection'; and show that a deeper understanding of the purpose of adaptation is achieved in the context of social evolution, with reference to inclusive fitness and superorganisms.

  19. Farmer innovation driven by needs and understanding: building the capacities of farmer groups for improved cooking stove construction and continued adaptation

    Science.gov (United States)

    Uckert, G.; Hafner, J.; Graef, F.; Hoffmann, H.; Kimaro, A.; Sererya, O.; Sieber, S.

    2017-12-01

    Enhancing food security is one of the main goals of subsistence farmers in Sub-Saharan Africa. This study investigates the implementation of improved loam-made cooking stoves and its contribution to coping and livelihood strategies. Controlled combustion, air as well as smoke flue, and heat insulation facilitate the more efficient fuel consumption of improved cooking stoves compared to traditional stoves—namely three stone fires. Although the majority of small-scale farmers in Sub-Saharan Africa rely on the free public good of firewood, the increasing time needed for collecting firewood implies high opportunity costs for productive members of the family. The primary outcomes for users of improved stoves are reduced fuel consumption, greater safety, saved time, and reduced smoke in the kitchen. The paper illustrates part of the output, outcome, and impact of a participatory action research approach for implementing improved cooking stoves. Special emphasis was put on enabling the villagers to construct their stoves without external support, hence having locally manufactured stoves made of mud, bricks, and dried grass. The impact pathway of improved cooking stoves followed the training-of-trainers concept, where members of the initially established farmer groups were trained to construct stoves on their own. Special focus was given to knowledge exchange and knowledge transfer in order to increase firewood efficiency and overall satisfaction of users of improved cook stoves. Encouraging the members to further adapt the stoves enabled them to scale-up the construction of improved cooked stoves into a business model and increase dissemination while creating income. Although many important benefits, like time and knowledge gain, were identified by the farmers after adoption of the new technology, we found adoption rates differed significantly between regions.

  20. Understanding hydrologic budgets, dynamics in an arid basin and explore spatial scaling properties using Process-based Adaptive Watershed Simulator (PAWS)

    Science.gov (United States)

    Fang, K.; Shen, C.; Salve, R.

    2013-12-01

    The Southern California hot desert hosts a fragile ecosystem as well as a range of human economic activities, primarily mining, energy production and recreation. This inland arid landscape is characterized by occasional intensive precipitation events and year-round strong potential evapotranspiration. In this landscape, water and especially groundwater is vital for ecosystem functions and human use. However, the impact of recent development on the sustainability of groundwater resources in the area has not been thoroughly investigated. We apply an integrated, physically-based hydrologic-land surface model, the Process-based Adaptive Watershed Simulator + Community Land Model (PAWS+CLM) to evaluate the sustainability of the groundwater resources in the area. We elucidate the spatio-temporal patterns of hydrologic fluxes and budgets. The modeling results indicate that mountain front recharge is the essential recharging mechanism for the alluvial aquifer. Although pumping activities do not exceed annual-average recharge values, they are still expected to contribute significantly to groundwater drawdown in business-as-usual scenario. The impact of groundwater withdrawals is significant on the desert ecosystem. The relative importance of groundwater flow on NPP rises significantly as compared to other ecosystems. We further evaluate the fractal scaling properties of soil moisture in this very arid system and found the relationship to be much more static in time than that found in a humid continental climate system. The scaling exponents can be predicted using simple functions of the mean. Therefore, multi-scale model based on coarse-resolution surrogate model is expected to perform well in this system. The modeling result is also important for assessing the groundwater sustainability and impact of human activities in the desert environment.

  1. Proteomic analysis of endothelial cold-adaptation

    Directory of Open Access Journals (Sweden)

    Zieger Michael AJ

    2011-12-01

    Full Text Available Abstract Background Understanding how human cells in tissue culture adapt to hypothermia may aid in developing new clinical procedures for improved ischemic and hypothermic protection. Human coronary artery endothelial cells grown to confluence at 37°C and then transferred to 25°C become resistant over time to oxidative stress and injury induced by 0°C storage and rewarming. This protection correlates with an increase in intracellular glutathione at 25°C. To help understand the molecular basis of endothelial cold-adaptation, isolated proteins from cold-adapted (25°C/72 h and pre-adapted cells were analyzed by quantitative proteomic methods and differentially expressed proteins were categorized using the DAVID Bioinformatics Resource. Results Cells adapted to 25°C expressed changes in the abundance of 219 unique proteins representing a broad range of categories such as translation, glycolysis, biosynthetic (anabolic processes, NAD, cytoskeletal organization, RNA processing, oxidoreductase activity, response-to-stress and cell redox homeostasis. The number of proteins that decreased significantly with cold-adaptation exceeded the number that increased by 2:1. Almost half of the decreases were associated with protein metabolic processes and a third were related to anabolic processes including protein, DNA and fatty acid synthesis. Changes consistent with the suppression of cytoskeletal dynamics provided further evidence that cold-adapted cells are in an energy conserving state. Among the specific changes were increases in the abundance and activity of redox proteins glutathione S-transferase, thioredoxin and thioredoxin reductase, which correlated with a decrease in oxidative stress, an increase in protein glutathionylation, and a recovery of reduced protein thiols during rewarming from 0°C. Increases in S-adenosylhomocysteine hydrolase and nicotinamide phosphoribosyltransferase implicate a central role for the methionine

  2. Mathematical modelling of metabolism

    DEFF Research Database (Denmark)

    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...

  3. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

    Directory of Open Access Journals (Sweden)

    Sung Sik eChoe

    2016-04-01

    Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  4. Transcriptome Profiling Using Single-Molecule Direct RNA Sequencing Approach for In-depth Understanding of Genes in Secondary Metabolism Pathways of Camellia sinensis

    Directory of Open Access Journals (Sweden)

    Qingshan Xu

    2017-07-01

    Full Text Available Characteristic secondary metabolites, including flavonoids, theanine and caffeine, are important components of Camellia sinensis, and their biosynthesis has attracted widespread interest. Previous studies on the biosynthesis of these major secondary metabolites using next-generation sequencing technologies limited the accurately prediction of full-length (FL splice isoforms. Herein, we applied single-molecule sequencing to pooled tea plant tissues, to provide a more complete transcriptome of C. sinensis. Moreover, we identified 94 FL transcripts and four alternative splicing events for enzyme-coding genes involved in the biosynthesis of flavonoids, theanine and caffeine. According to the comparison between long-read isoforms and assemble transcripts, we improved the quality and accuracy of genes sequenced by short-read next-generation sequencing technology. The resulting FL transcripts, together with the improved assembled transcripts and identified alternative splicing events, enhance our understanding of genes involved in the biosynthesis of characteristic secondary metabolites in C. sinensis.

  5. Profiling of Indigenous Microbial Community Dynamics and Metabolic Activity During Enrichment in Molasses-Supplemented Crude Oil-Brine Mixtures for Improved Understanding of Microbial Enhanced Oil Recovery.

    Science.gov (United States)

    Halim, Amalia Yunita; Pedersen, Dorthe Skou; Nielsen, Sidsel Marie; Lantz, Anna Eliasson

    2015-06-01

    Anaerobic incubations using crude oil and brine from a North Sea reservoir were conducted to gain increased understanding of indigenous microbial community development, metabolite production, and the effects on the oil-brine system after addition of a complex carbon source, molasses, with or without nitrate to boost microbial growth. Growth of the indigenous microbes was stimulated by addition of molasses. Pyrosequencing showed that specifically Anaerobaculum, Petrotoga, and Methanothermococcus were enriched. Addition of nitrate favored the growth of Petrotoga over Anaerobaculum. The microbial growth caused changes in the crude oil-brine system: formation of oil emulsions, and reduction of interfacial tension (IFT). Reduction in IFT was associated with microbes being present at the oil-brine interphase. These findings suggest that stimulation of indigenous microbial growth by addition of molasses has potential as microbial enhanced oil recovery (MEOR) strategy in North Sea oil reservoirs.

  6. Copepods in ice-covered seas—Distribution, adaptations to seasonally limited food, metabolism, growth patterns and life cycle strategies in polar seas

    Science.gov (United States)

    Conover, R. J.; Huntley, M.

    1991-07-01

    rhythms under or near the ice have also been observed for several species. In the Northern Hemisphere larger zooplanktonic species may take two, three, or possibly more years to reach maturity, but the grand strategy, apparently used by all, is to assure that their young have reached active feeding stages by the time of maximum primary production in the water column so that maximum growth, often, but not always, with emphasis on lipid storage, can occur during the often brief, but usually intense, summer bloom. The rate of growth of arctic or antarctic zooplankton is not so important as assuring a high level of fecundity when maturity comes. Overwintering is probably not a great hardship and diapause may not be a useful strategy because the environmental temperature is constantly near the freezing point of sea water, and basal metabolism accordingly low. Nonetheless, feeding behaviour and metabolic rates have strong seasonal signals. In the absence of other stimuli, light must be involved in the transformation from winter to summer metabolism and visa versa but the mechanisms still remain obscure.

  7. Astrocytes and energy metabolism.

    Science.gov (United States)

    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.

  8. Triglyceride metabolism in exercising muscle.

    Science.gov (United States)

    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.

  9. Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

    KAUST Repository

    Abdallah, Abdallah

    2015-10-21

    Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.

  10. Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

    KAUST Repository

    Abdallah, Abdallah; Hill-Cawthorne, Grant A.; Otto, Thomas D.; Coll, Francesc; Guerra-Assunç ã o, José Afonso; Gao, Ge; Naeem, Raeece; Ansari, Hifzur Rahman; Malas, Tareq Majed Yasin; Adroub, Sabir; Verboom, Theo; Ummels, Roy; Zhang, Huoming; Panigrahi, Aswini Kumar; McNerney, Ruth; Brosch, Roland; Clark, Taane G.; Behr, Marcel A.; Bitter, Wilbert; Pain, Arnab

    2015-01-01

    Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.

  11. Adaptive ethnography

    DEFF Research Database (Denmark)

    Berth, Mette

    2005-01-01

    This paper focuses on the use of an adaptive ethnography when studying such phenomena as young people's use of mobile media in a learning perspective. Mobile media such as PDAs and mobile phones have a number of affordances which make them potential tools for learning. However, before we begin to...... formal and informal learning contexts. The paper also proposes several adaptive methodological techniques for studying young people's interaction with mobiles.......This paper focuses on the use of an adaptive ethnography when studying such phenomena as young people's use of mobile media in a learning perspective. Mobile media such as PDAs and mobile phones have a number of affordances which make them potential tools for learning. However, before we begin...... to design and develop educational materials for mobile media platforms we must first understand everyday use and behaviour with a medium such as a mobile phone. The paper outlines the research design for a PhD project on mobile learning which focuses on mobile phones as a way to bridge the gap between...

  12. The Role of the Immune System in Metabolic Health and Disease.

    Science.gov (United States)

    Zmora, Niv; Bashiardes, Stavros; Levy, Maayan; Elinav, Eran

    2017-03-07

    In addition to the immune system's traditional roles of conferring anti-infectious and anti-neoplastic protection, it has been recently implicated in the regulation of systemic metabolic homeostasis. This cross-talk between the immune and the metabolic systems is pivotal in promoting "metabolic health" throughout the life of an organism and plays fundamental roles in its adaptation to ever-changing environmental makeups and nutritional availability. Perturbations in this intricate immune-metabolic cross-talk contribute to the tendency to develop altered metabolic states that may culminate in metabolic disorders such as malnutrition, obesity, type 2 diabetes mellitus (T2DM), and other features of the metabolic syndrome. Regulators of immune-metabolic interactions include host genetics, nutritional status, and the intestinal microbiome. In this Perspective, we highlight current understanding of immune-metabolism interactions, illustrate differences among individuals and between populations in this respect, and point toward future avenues of research possibly enabling immune harnessing as means of personalized treatment for common metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Combined use of δ¹³C, δ18O and δ15N tracks nitrogen metabolism and genotypic adaptation of durum wheat to salinity and water deficit.

    Science.gov (United States)

    Yousfi, Salima; Serret, Maria Dolores; Márquez, Antonio José; Voltas, Jordi; Araus, José Luis

    2012-04-01

    • Accurate phenotyping remains a bottleneck in breeding for salinity and drought resistance. Here the combined use of stable isotope compositions of carbon (δ¹³C), oxygen (δ¹⁸O) and nitrogen (δ¹⁵N) in dry matter is aimed at assessing genotypic responses of durum wheat under different combinations of these stresses. • Two tolerant and two susceptible genotypes to salinity were grown under five combinations of salinity and irrigation regimes. Plant biomass, δ¹³C, δ¹⁸O and δ¹⁵N, gas-exchange parameters, ion and N concentrations, and nitrate reductase (NR) and glutamine synthetase (GS) activities were measured. • Stresses significantly affected all traits studied. However, only δ¹³C, δ¹⁸O, δ¹⁵N, GS and NR activities, and N concentration allowed for clear differentiation between tolerant and susceptible genotypes. Further, a conceptual model explaining differences in biomass based on such traits was developed for each growing condition. • Differences in acclimation responses among durum wheat genotypes under different stress treatments were associated with δ¹³C. However, except for the most severe stress, δ¹³C did not have a direct (negative) relationship to biomass, being mediated through factors affecting δ¹⁸O or N metabolism. Based upon these results, the key role of N metabolism in durum wheat adaptation to salinity and water stress is highlighted. No claim to original US government works. New Phytologist © 2012 New Phytologist Trust.

  14. Effects of Feeding Milk Replacer Ad Libitum or in Restricted Amounts for the First Five Weeks of Life on the Growth, Metabolic Adaptation, and Immune Status of Newborn Calves

    Science.gov (United States)

    Schäff, Christine T.; Gruse, Jeannine; Maciej, Josefine; Mielenz, Manfred; Wirthgen, Elisa; Hoeflich, Andreas; Schmicke, Marion; Pfuhl, Ralf; Jawor, Paulina; Stefaniak, Tadeusz

    2016-01-01

    The pre-weaning period is critical for calf health and growth, and intensive milk feeding programs may assist postnatal development by improving body growth and organ maturation. The aim of the present work was to study the effects of ad libitum milk replacer (MR) feeding on the growth, metabolic adaptation, health, and immune status of newborn calves. Twenty-eight newborn Holstein and Holstein x Charolais crossbred calves were fed ad libitum (ADLIB) or in restricted amounts (6 liters per day; RES) during the first five weeks of life. The MR intake in the ADLIB treatment was gradually reduced at weeks 6 and 7, and all calves then received 6 liters of MR per day until day 60. Blood samples were collected to measure the plasma concentrations of metabolites, insulin, insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP), immunoglobulins, and acute phase proteins. The expression of mRNA associated with both the somatotropic axis and gluconeogenic enzymes was measured in the liver on day 60. Intensive feeding improved MR intake and growth in ADLIB without influencing concentrate intake. Carcass weight, perirenal fat, and muscle mass were greater in ADLIB. Plasma concentrations of glucose, triglycerides, insulin, and IGF-I were greater, whereas plasma concentrations of β-hydroxybutyrate, total protein, albumin, urea, IGFBP-2 and -4, and fibrinogen were lower at distinct time points in ADLIB. The hepatic mRNA expression of cytosolic phosphoenolpyruvate carboxykinase was greater in ADLIB. Most metabolic and endocrine differences occurred during the MR feeding period, but a slightly greater concentrate intake was associated with increased plasma IGF-I and insulin at the end of the study. The immune and health status of the calves were not affected by MR feeding. However, increased plasma fibrinogen in the RES group suggested differences in the acute phase response. PMID:28036351

  15. A Mathematical Model of Metabolism and Regulation Provides a Systems-Level View of How Escherichia coli Responds to Oxygen

    Directory of Open Access Journals (Sweden)

    Michael eEderer

    2014-03-01

    Full Text Available The efficient redesign of bacteria for biotechnological purposes, such as biofuel production, waste disposal or specific biocatalytic functions, requires a quantitative systems-level understanding of energy supply, carbon and redox metabolism. The measurement of transcript levels, metabolite concentrations and metabolic fluxes per se gives an incomplete picture. An appreciation of the interdependencies between the different measurement values is essential for systems-level understanding. Mathematical modeling has the potential to provide a coherent and quantitative description of the interplay between gene expression, metabolite concentrations and metabolic fluxes. Escherichia coli undergoes major adaptations in central metabolism when the availability of oxygen changes. Thus, an integrated description of the oxygen response provides a benchmark of our understanding of carbon, energy and redox metabolism. We present the first comprehensive model of the central metabolism of E. coli that describes steady-state metabolism at different levels of oxygen availability. Variables of the model are metabolite concentrations, gene expression levels, transcription factor activities, metabolic fluxes and biomass concentration. We analyze the model with respect to the production capabilities of central metabolism of E. coli. In particular, we predict how precursor and biomass concentration are affected by product formation.

  16. Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption.

    Science.gov (United States)

    McGill, Anne-Thea

    2014-01-01

    The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal. The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated. The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A 'dual system' is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans. The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing 'common or garden' food, appears to have occurred. Insufficient consumption of food micronutrients prevents optimal human NRF2 function. Inefficient oxidation of excess energy forces central and non-adipose cells to store excess toxic lipid. Oxidative stress and

  17. Effects of recombinant bovine somatotropin during the periparturient period on innate and adaptive immune responses, systemic inflammation, and metabolism of dairy cows.

    Science.gov (United States)

    Silva, P R B; Machado, K S; Da Silva, D N Lobão; Moraes, J G N; Keisler, D H; Chebel, R C

    2015-07-01

    The aim of this experiment was to determine effects of treating peripartum dairy cows with body condition score ≥3.75 with recombinant bovine somatotropin (rbST) on immune, inflammatory, and metabolic responses. Holstein cows (253±1d of gestation) were assigned randomly to 1 of 3 treatments: untreated control (n=53), rbST87.5 (n=56; 87.5mg of rbST), and rbST125 (n=57; 125mg of rbST). Cows in the rbST87.5 and rbST125 treatments received rbST weekly from -21 to 28d relative to calving. Growth hormone, insulin-like growth factor 1, haptoglobin, tumor necrosis factor α, nonesterified fatty acids, β-hydroxybutyrate, glucose, and cortisol concentrations were determined weekly from -21 to 21d relative to calving. Blood sampled weekly from -14 to 21d relative to calving was used for hemogram and polymorphonuclear leukocyte (PMNL) expression of adhesion molecules, phagocytosis, and oxidative burst. Cows were vaccinated with ovalbumin at -21, -7, and 7d relative to calving, and blood was collected weekly from -21 to 21d relative to calving to determine IgG anti-ovalbumin concentrations. A subsample of cows had liver biopsied -21, -7, and 7d relative to calving to determine total lipids, triglycerides, and glycogen content. Growth hormone concentrations prepartum (control=11.0±1.2, rbST87.5=14.1±1.2, rbST125=15.1±1.3ng/mL) and postpartum (control=14.4±1.1, rbST87.5=17.8±1.2, rbST125=21.8±1.1ng/mL) were highest for rbST125 cows. Cows treated with rbST had higher insulin-like growth factor 1 concentrations than control cows (control=110.5±4.5, rbST87.5=126.2±4.5, rbST125=127.2±4.5ng/mL) only prepartum. Intensity of L-selectin expression was higher for rbST125 than for control and rbST87.5 cows [control=3,590±270, rbST87.5=3,279±271, rbST125=4,371±279 geometric mean fluorescence intensity (GMFI)] in the prepartum period. The PMNL intensities of phagocytosis (control=3,131±130, rbST87.5=3,391±133, rbST125=3,673±137 GMFI) and oxidative burst (control=9,588±746

  18. A PRACTICAL MODEL OF LOW-VOLUME HIGH-INTENSITY INTERVAL TRAINING INDUCES PERFORMANCE AND METABOLIC ADAPTATIONS THAT RESEMBLE 'ALL-OUT' SPRINT INTERVAL TRAINING

    Directory of Open Access Journals (Sweden)

    Mahdi Bayati

    2011-09-01

    Full Text Available Recently, a novel type of high-intensity interval training known as sprint interval training has demonstrated increases in aerobic and anaerobic performance with very low time commitment. However, this type of training program is unpractical for general populations. The present study compared the impact of a low-volume high-intensity interval training to a "all-out" sprint interval training. Twenty-four active young males were recruited and randomized into three groups: (G1: 3-5 cycling bouts × 30-s all-out with 4 min recovery; G2: 6- 10 cycling bouts × 125% Pmax with 2 min recovery and a non-trained control group. They all performed a VO2max test, a time to exhaustion at Pmax (Tmax and a Wingate test before and after the intervention. Capillary blood lactate was taken at rest, 3, and 20 min after the Wingate trial. Training was performed 3 sessions per week for 4 weeks. In G1, significant improvements (p < 0.05 following training were found in VO2max (9.6%, power at VO2max (12.8%, Tmax (48.4%, peak power output (10.3% and mean power output (17.1%. In G2, significant improvements following training were found in VO2max (9.7%, power at VO2max (16.1%, Tmax (54.2%, peak power output (7.4%; p < 0.05, but mean power output did not change significantly. Blood lactate recovery (20th min significantly decreased in G1 and G2 when compared with pre-testing and the CON group (p < 0.05. In conclusion, the results of the current study agree with earlier work demonstrating the effectiveness of 30-s all-out training program to aerobic and anaerobic adaptations. Of substantial interest is that the low volume high intensity training provides similar results but involves only half the intensity with double the repetitions

  19. Adaptive therapy.

    Science.gov (United States)

    Gatenby, Robert A; Silva, Ariosto S; Gillies, Robert J; Frieden, B Roy

    2009-06-01

    A number of successful systemic therapies are available for treatment of disseminated cancers. However, tumor response is often transient, and therapy frequently fails due to emergence of resistant populations. The latter reflects the temporal and spatial heterogeneity of the tumor microenvironment as well as the evolutionary capacity of cancer phenotypes to adapt to therapeutic perturbations. Although cancers are highly dynamic systems, cancer therapy is typically administered according to a fixed, linear protocol. Here we examine an adaptive therapeutic approach that evolves in response to the temporal and spatial variability of tumor microenvironment and cellular phenotype as well as therapy-induced perturbations. Initial mathematical models find that when resistant phenotypes arise in the untreated tumor, they are typically present in small numbers because they are less fit than the sensitive population. This reflects the "cost" of phenotypic resistance such as additional substrate and energy used to up-regulate xenobiotic metabolism, and therefore not available for proliferation, or the growth inhibitory nature of environments (i.e., ischemia or hypoxia) that confer resistance on phenotypically sensitive cells. Thus, in the Darwinian environment of a cancer, the fitter chemosensitive cells will ordinarily proliferate at the expense of the less fit chemoresistant cells. The models show that, if resistant populations are present before administration of therapy, treatments designed to kill maximum numbers of cancer cells remove this inhibitory effect and actually promote more rapid growth of the resistant populations. We present an alternative approach in which treatment is continuously modulated to achieve a fixed tumor population. The goal of adaptive therapy is to enforce a stable tumor burden by permitting a significant population of chemosensitive cells to survive so that they, in turn, suppress proliferation of the less fit but chemoresistant

  20. Metabolic imaging using PET

    International Nuclear Information System (INIS)

    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. Understanding adaptation decisions in Morocco's plains and ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2011-04-21

    Apr 21, 2011 ... In Morocco, the threat posed by climate change has been recognized for some time by decision-makers at national and provincial levels. Erratic rainfall, an overall decline in precipitation, and recurring heat waves are creating chronic water shortages in the agricultural areas that support 80% of the ...

  2. Quantifying the Adaptive Cycle.

    Directory of Open Access Journals (Sweden)

    David G Angeler

    Full Text Available The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative approach for testing premises (reorganisation, conservatism, adaptation in the adaptive cycle, using Baltic Sea phytoplankton communities as an example of such complex system dynamics. Phytoplankton organizes in recurring spring and summer blooms, a well-established paradigm in planktology and succession theory, with characteristic temporal trajectories during blooms that may be consistent with adaptive cycle phases. We used long-term (1994-2011 data and multivariate analysis of community structure to assess key components of the adaptive cycle. Specifically, we tested predictions about: reorganisation: spring and summer blooms comprise distinct community states; conservatism: community trajectories during individual adaptive cycles are conservative; and adaptation: phytoplankton species during blooms change in the long term. All predictions were supported by our analyses. Results suggest that traditional ecological paradigms such as phytoplankton successional models have potential for moving the adaptive cycle from a metaphor to a framework that can improve our understanding how complex systems organize and reorganize following collapse. Quantifying reorganization, conservatism and adaptation provides opportunities to cope with the intricacies and uncertainties associated with fast ecological change, driven by shifting system controls. Ultimately, combining traditional ecological paradigms with heuristics of complex system dynamics using quantitative approaches may help refine ecological theory and improve our understanding of the resilience of ecosystems.

  3. Adaptation in Living Systems

    Science.gov (United States)

    Tu, Yuhai; Rappel, Wouter-Jan

    2018-03-01

    Adaptation refers to the biological phenomenon where living systems change their internal states in response to changes in their environments in order to maintain certain key functions critical for their survival and fitness. Adaptation is one of the most ubiquitous and arguably one of the most fundamental properties of living systems. It occurs throughout all biological scales, from adaptation of populations of species over evolutionary time to adaptation of a single cell to different environmental stresses during its life span. In this article, we review some of the recent progress made in understanding molecular mechanisms of cellular-level adaptation. We take the minimalist (or the physicist) approach and study the simplest systems that exhibit generic adaptive behaviors, namely chemotaxis in bacterium cells (Escherichia coli) and eukaryotic cells (Dictyostelium). We focus on understanding the basic biochemical interaction networks that are responsible for adaptation dynamics. By combining theoretical modeling with quantitative experimentation, we demonstrate universal features in adaptation as well as important differences in different cellular systems. Future work in extending the modeling framework to study adaptation in more complex systems such as sensory neurons is also discussed.

  4. Adaptive management

    DEFF Research Database (Denmark)

    Rist, Lucy; Campbell, Bruce Morgan; Frost, Peter

    2013-01-01

    Adaptive management (AM) emerged in the literature in the mid-1970s in response both to a realization of the extent of uncertainty involved in management, and a frustration with attempts to use modelling to integrate knowledge and make predictions. The term has since become increasingly widely used...... in scientific articles, policy documents and management plans, but both understanding and application of the concept is mixed. This paper reviews recent literature from conservation and natural resource management journals to assess diversity in how the term is used, highlight ambiguities and consider how...... the concept might be further assessed. AM is currently being used to describe many different management contexts, scales and locations. Few authors define the term explicitly or describe how it offers a means to improve management outcomes in their specific management context. Many do not adhere to the idea...

  5. Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models.

    Science.gov (United States)

    Bakker, Barbara M; van Eunen, Karen; Jeneson, Jeroen A L; van Riel, Natal A W; Bruggeman, Frank J; Teusink, Bas

    2010-10-01

    Human metabolic diseases are typically network diseases. This holds not only for multifactorial diseases, such as metabolic syndrome or Type 2 diabetes, but even when a single gene defect is the primary cause, where the adaptive response of the entire network determines the severity of disease. The latter may differ between individuals carrying the same mutation. Understanding the adaptive responses of human metabolism naturally requires a systems biology approach. Modelling of metabolic pathways in micro-organisms and some mammalian tissues has yielded many insights, qualitative as well as quantitative, into their control and regulation. Yet, even for a well-known pathway such as glycolysis, precise predictions of metabolite dynamics from experimentally determined enzyme kinetics have been only moderately successful. In the present review, we compare kinetic models of glycolysis in three cell types (African trypanosomes, yeast and skeletal muscle), evaluate their predictive power and identify limitations in our understanding. Although each of these models has its own merits and shortcomings, they also share common features. For example, in each case independently measured enzyme kinetic parameters were used as input. Based on these 'lessons from glycolysis', we will discuss how to make best use of kinetic computer models to advance our understanding of human metabolic diseases.

  6. Technology transfer for adaptation

    Science.gov (United States)

    Biagini, Bonizella; Kuhl, Laura; Gallagher, Kelly Sims; Ortiz, Claudia

    2014-09-01

    Technology alone will not be able to solve adaptation challenges, but it is likely to play an important role. As a result of the role of technology in adaptation and the importance of international collaboration for climate change, technology transfer for adaptation is a critical but understudied issue. Through an analysis of Global Environment Facility-managed adaptation projects, we find there is significantly more technology transfer occurring in adaptation projects than might be expected given the pessimistic rhetoric surrounding technology transfer for adaptation. Most projects focused on demonstration and early deployment/niche formation for existing technologies rather than earlier stages of innovation, which is understandable considering the pilot nature of the projects. Key challenges for the transfer process, including technology selection and appropriateness under climate change, markets and access to technology, and diffusion strategies are discussed in more detail.

  7. Adaptation of intertidal biofilm communities is driven by metal ion and oxidative stresses

    KAUST Repository

    Zhang, Weipeng; Wang, Yong; Lee, On On; Tian, Renmao; Cao, Huiluo; Gao, Zhaoming; Li, Yongxin; Yu, Li; Xu, Ying; Qian, Pei-Yuan

    2013-01-01

    Marine organisms in intertidal zones are subjected to periodical fluctuations and wave activities. To understand how microbes in intertidal biofilms adapt to the stresses, the microbial metagenomes of biofilms from intertidal and subtidal zones were compared. The genes responsible for resistance to metal ion and oxidative stresses were enriched in both 6-day and 12-day intertidal biofilms, including genes associated with secondary metabolism, inorganic ion transport and metabolism, signal transduction and extracellular polymeric substance metabolism. In addition, these genes were more enriched in 12-day than 6-day intertidal biofilms. We hypothesize that a complex signaling network is used for stress tolerance and propose a model illustrating the relationships between these functions and environmental metal ion concentrations and oxidative stresses. These findings show that bacteria use diverse mechanisms to adapt to intertidal zones and indicate that the community structures of intertidal biofilms are modulated by metal ion and oxidative stresses.

  8. Adaptation of intertidal biofilm communities is driven by metal ion and oxidative stresses

    KAUST Repository

    Zhang, Weipeng

    2013-11-11

    Marine organisms in intertidal zones are subjected to periodical fluctuations and wave activities. To understand how microbes in intertidal biofilms adapt to the stresses, the microbial metagenomes of biofilms from intertidal and subtidal zones were compared. The genes responsible for resistance to metal ion and oxidative stresses were enriched in both 6-day and 12-day intertidal biofilms, including genes associated with secondary metabolism, inorganic ion transport and metabolism, signal transduction and extracellular polymeric substance metabolism. In addition, these genes were more enriched in 12-day than 6-day intertidal biofilms. We hypothesize that a complex signaling network is used for stress tolerance and propose a model illustrating the relationships between these functions and environmental metal ion concentrations and oxidative stresses. These findings show that bacteria use diverse mechanisms to adapt to intertidal zones and indicate that the community structures of intertidal biofilms are modulated by metal ion and oxidative stresses.

  9. Metabolic Syndrome

    Science.gov (United States)

    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 ...

  10. Metabolic Reprogramming in Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  11. Metabolic Reprogramming in Thyroid Carcinoma

    Science.gov (United States)

    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

  12. Adaptive Rationality, Adaptive Behavior and Institutions

    Directory of Open Access Journals (Sweden)

    Volchik Vyacheslav, V.

    2015-12-01

    Full Text Available The economic literature focused on understanding decision-making and choice processes reveals a vast collection of approaches to human rationality. Theorists’ attention has moved from absolutely rational, utility-maximizing individuals to boundedly rational and adaptive ones. A number of economists have criticized the concepts of adaptive rationality and adaptive behavior. One of the recent trends in the economic literature is to consider humans irrational. This paper offers an approach which examines adaptive behavior in the context of existing institutions and constantly changing institutional environment. It is assumed that adaptive behavior is a process of evolutionary adjustment to fundamental uncertainty. We emphasize the importance of actors’ engagement in trial and error learning, since if they are involved in this process, they obtain experience and are able to adapt to existing and new institutions. The paper aims at identifying relevant institutions, adaptive mechanisms, informal working rules and practices that influence actors’ behavior in the field of Higher Education in Russia (Rostov Region education services market has been taken as an example. The paper emphasizes the application of qualitative interpretative methods (interviews and discourse analysis in examining actors’ behavior.

  13. Pyruvate Kinase Triggers a Metabolic Feedback Loop that Controls Redox Metabolism in Respiring Cells

    NARCIS (Netherlands)

    Grüning, N.M.; Rinnerthaler, M.; Bluemlein, K.; Mulleder, M.; Wamelink, M.M.C.; Lehrach, H.; Jakobs, C.A.J.M.; Breitenbach, M.; Ralser, M.

    2011-01-01

    In proliferating cells, a transition from aerobic to anaerobic metabolism is known as the Warburg effect, whose reversal inhibits cancer cell proliferation. Studying its regulator pyruvate kinase (PYK) in yeast, we discovered that central metabolism is self-adapting to synchronize redox metabolism

  14. Metabolic changes in malnutrition.

    Science.gov (United States)

    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.

  15. [Bone Cell Biology Assessed by Microscopic Approach. A mathematical approach to understand bone remodeling].

    Science.gov (United States)

    Kameo, Yoshitaka; Adachi, Taiji

    2015-10-01

    It is well known that bone tissue can change its outer shape and internal structure by remodeling according to a changing mechanical environment. However, the mechanism of bone functional adaptation induced by the collaborative metabolic activities of bone cells in response to mechanical stimuli remains elusive. In this article, we focus on the hierarchy of bone structure and function from the microscopic cellular level to the macroscopic tissue level. We provide an overview of a mathematical approach to understand the adaptive changes in trabecular morphology under the application of mechanical stress.

  16. Adaptive Education.

    Science.gov (United States)

    Anderson, Lorin W.

    1979-01-01

    Schools have devised several ways to adapt instruction to a wide variety of student abilities and needs. Judged by criteria for what adaptive education should be, most learning for mastery programs look good. (Author/JM)

  17. Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    Science.gov (United States)

    Cook, Donald N.; Kang, Hong Soon; Jetten, Anton M.

    2015-01-01

    In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID:26878025

  18. Retinoic Acid-Related Orphan Receptors (RORs: Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    Directory of Open Access Journals (Sweden)

    Donald N. Cook

    2015-12-01

    Full Text Available In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs. We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated.

  19. Homeoviscous adaptation and the regulation of membrane lipids

    DEFF Research Database (Denmark)

    Ernst, Robert; Ejsing, Christer S; Antonny, Bruno

    2016-01-01

    Biological membranes are complex and dynamic assemblies of lipids and proteins. Poikilothermic organisms including bacteria, fungi, reptiles, and fish do not control their body temperature and must adapt their membrane lipid composition in order to maintain membrane fluidity in the cold. This ada......Biological membranes are complex and dynamic assemblies of lipids and proteins. Poikilothermic organisms including bacteria, fungi, reptiles, and fish do not control their body temperature and must adapt their membrane lipid composition in order to maintain membrane fluidity in the cold....... This adaptive response was termed homeoviscous adaptation and has been frequently studied with a specific focus on the acyl chain composition of membrane lipids. Massspectrometry-based lipidomics can nowadays provide more comprehensive insights into the complexity of lipid remodeling during adaptive responses...... such as neurons maintain unique lipid compositions with specific physicochemical properties. To date little is known about the sensory mechanisms regulating the acyl chain profile in such specialized cells or during adaptive responses. Here we summarize our current understanding of lipid metabolic networks...

  20. RESISTANT HYPERTENSION IN A PATIENT WITH METABOLIC SYNDROME

    OpenAIRE

    O. M. Drapkina; J. S. Sibgatullina

    2016-01-01

    Clinical case of resistant hypertension in a patient with metabolic syndrome is presented. Features of hypertension in metabolic syndrome and features of metabolic syndrome in women of pre- and postmenopausal age are also considered. Understanding the features of metabolic syndrome in women, as well as features of hypertension and metabolic syndrome will improve the results of treatment in patients with resistant hypertension.

  1. Ovarian tumor-initiating cells display a flexible metabolism

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Ovarian tumor-initiating cells display a flexible metabolism

    International Nuclear Information System (INIS)

    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

  3. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial lighting ceases...

  4. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    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...

  5. Characterization of recombinant B. abortus strain RB51SOD towards understanding the uncorrelated innate and adaptive immune responses induced by RB51SOD compared to its parent vaccine strain RB51

    Directory of Open Access Journals (Sweden)

    Jianguo eZhu

    2011-11-01

    Full Text Available Brucella abortus is a Gram-negative, facultative intracellular pathogen for several mammals, including humans. Live attenuated B. abortus strain RB51 is currently the official vaccine used against bovine brucellosis in the United States and several other countries. Overexpression of protective B. abortus antigen Cu/Zn superoxide dismutase (SOD in a recombinant strain of RB51 (strain RB51SOD significantly increases its vaccine efficacy against virulent B. abortus challenge in a mouse model. An attempt has been made to better understand the mechanism of the enhanced protective immunity of RB51SOD compared to its parent strain RB51. We previously reported that RB51SOD stimulated enhanced Th1 immune response. In this study, we further found that T effector cells derived from RB51SOD-immunized mice exhibited significantly higher cytotoxic T lymphocyte (CTL activity than T effector cells derived from RB51-immunized mice against virulent B. abortus-infected target cells. Meanwhile, the macrophage responses to these two strains were also studied. Compared to RB51, RB51SOD cells had a lower survival rate in macrophages and induced lower levels of macrophage apoptosis and necrosis. The decreased survival of RB51SOD cells correlates with the higher sensitivity of RB51SOD, compared to RB51, to the bactericidal action of either Polymyxin B or sodium dodecyl sulfate (SDS. Furthermore, a physical damage to the outer membrane of RB51SOD was observed by electron microscopy. Possibly due to the physical damage, overexpressed Cu/Zn SOD in RB51SOD was found to be released into the bacterial cell culture medium. Therefore, the stronger adaptive immunity induced by RB51SOD did not correlate with the low level of innate immunity induced by RB51SOD compared to RB51. This unique and apparently contradictory profile is likely associated with the differences in outer membrane integrity and Cu/Zn SOD release.

  6. Glucose metabolism regulates T cell activation, differentiation and functions

    Directory of Open Access Journals (Sweden)

    Clovis Steve Palmer

    2015-01-01

    Full Text Available The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The Warburg effect originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

  7. Dealing with hunger: Metabolic stress responses in tumors

    Directory of Open Access Journals (Sweden)

    Michael A Reid

    2013-01-01

    Full Text Available Increased nutrient uptake and usage is a hallmark of many human malignancies. During the course of tumorigenesis, cancer cells often outstrip their local nutrient supply leading to periods of nutrient deprivation. Interestingly, cancer cells often develop strategies to adapt and survive these challenging conditions. Accordingly, understanding these processes is critical for developing therapies that target cancer metabolism. Exciting new progress has been made in elucidating the mechanisms used by cancer cells under nutrient restricted conditions. In this review, we highlight recent studies that have brought insight into how cancer cells deal with low nutrient environments.

  8. What is Metabolic Syndrome?

    Science.gov (United States)

    ... 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 ...

  9. Teaching Audience Adaptation Using Connected Presentations and Teamwork

    Science.gov (United States)

    Opt, Susan K.

    2017-01-01

    Courses: Introduction to Communication, Public Speaking, Persuasion, Business Communication. Objective: This activity increases students' understanding of audience adaptation and improves their ability to adapt presentations to specific audiences.

  10. Prenatal factors contribute to the emergence of kwashiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model.

    Directory of Open Access Journals (Sweden)

    Terrence E Forrester

    Full Text Available Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor and non-oedematous (marasmus syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity.We reviewed the records of all children admitted with severe acute malnutrition to the Tropical Metabolism Research Unit Ward of the University Hospital of the West Indies, Kingston, Jamaica during 1962-1992. We used Wellcome criteria to establish the diagnoses of kwashiorkor (n = 391, marasmus (n = 383, and marasmic-kwashiorkor (n = 375. We recorded participants' birth weights, as determined from maternal recall at the time of admission. Those who developed kwashiorkor had 333 g (95% confidence interval 217 to 449, p<0.001 higher mean birthweight than those who developed marasmus.These data are consistent with a model suggesting that plastic mechanisms operative in utero induce potential marasmics to develop with a metabolic physiology more able to adapt to postnatal undernutrition than those of higher birthweight. Given the different mortality risks of these different syndromes, this observation is supportive of the predictive adaptive response hypothesis and is the first empirical demonstration of the advantageous effects of such a

  11. Adaptability Responding Effectively to Change

    CERN Document Server

    (CCL), Center for Creative Leadership; Calarco, Allan

    2011-01-01

    In today's business world, the complexity and pace of change can be daunting. Adaptability has become recognized as a necessary skill for leaders to develop to be effective in this environment. Even so, leaders rarely know what they can do to become more adaptable and foster adaptability in others. This guidebook contributes to a greater understanding of adaptability and the cognitive, emotional, and dispositional flexibility it requires. Leaders will learn how to develop their adaptability and to become more effective for themselves, the people they lead, and their organizations.

  12. ADAPT Dataset

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Diagnostics and Prognostics Testbed (ADAPT) Project Lead: Scott Poll Subject Fault diagnosis in electrical power systems Description The Advanced...

  13. The Burmese python genome reveals the molecular basis for extreme adaptation in snakes.

    Science.gov (United States)

    Castoe, Todd A; de Koning, A P Jason; Hall, Kathryn T; Card, Daren C; Schield, Drew R; Fujita, Matthew K; Ruggiero, Robert P; Degner, Jack F; Daza, Juan M; Gu, Wanjun; Reyes-Velasco, Jacobo; Shaney, Kyle J; Castoe, Jill M; Fox, Samuel E; Poole, Alex W; Polanco, Daniel; Dobry, Jason; Vandewege, Michael W; Li, Qing; Schott, Ryan K; Kapusta, Aurélie; Minx, Patrick; Feschotte, Cédric; Uetz, Peter; Ray, David A; Hoffmann, Federico G; Bogden, Robert; Smith, Eric N; Chang, Belinda S W; Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Richardson, Michael K; Mackessy, Stephen P; Bronikowski, Anne M; Bronikowsi, Anne M; Yandell, Mark; Warren, Wesley C; Secor, Stephen M; Pollock, David D

    2013-12-17

    Snakes possess many extreme morphological and physiological adaptations. Identification of the molecular basis of these traits can provide novel understanding for vertebrate biology and medicine. Here, we study snake biology using the genome sequence of the Burmese python (Python molurus bivittatus), a model of extreme physiological and metabolic adaptation. We compare the python and king cobra genomes along with genomic samples from other snakes and perform transcriptome analysis to gain insights into the extreme phenotypes of the python. We discovered rapid and massive transcriptional responses in multiple organ systems that occur on feeding and coordinate major changes in organ size and function. Intriguingly, the homologs of these genes in humans are associated with metabolism, development, and pathology. We also found that many snake metabolic genes have undergone positive selection, which together with the rapid evolution of mitochondrial proteins, provides evidence for extensive adaptive redesign of snake metabolic pathways. Additional evidence for molecular adaptation and gene family expansions and contractions is associated with major physiological and phenotypic adaptations in snakes; genes involved are related to cell cycle, development, lungs, eyes, heart, intestine, and skeletal structure, including GRB2-associated binding protein 1, SSH, WNT16, and bone morphogenetic protein 7. Finally, changes in repetitive DNA content, guanine-cytosine isochore structure, and nucleotide substitution rates indicate major shifts in the structure and evolution of snake genomes compared with other amniotes. Phenotypic and physiological novelty in snakes seems to be driven by system-wide coordination of protein adaptation, gene expression, and changes in the structure of the genome.

  14. Physiological adaptation in desert birds

    NARCIS (Netherlands)

    Williams, JB; Tieleman, BI; Williams, Joseph B.

    We call into question the idea that birds have not evolved unique physiological adaptations to desert environments. The rate at which desert larks metabolize energy is lower than in mesic species within the same family, and this lower rate of living translates into a lower overall energy requirement

  15. [Metabolic acidosis].

    Science.gov (United States)

    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.

  16. Adaptation to walking with an exoskeleton that assists ankle extension.

    Science.gov (United States)

    Galle, S; Malcolm, P; Derave, W; De Clercq, D

    2013-07-01

    The goal of this study was to investigate adaptation to walking with bilateral ankle-foot exoskeletons with kinematic control that assisted ankle extension during push-off. We hypothesized that subjects would show a neuromotor and metabolic adaptation during a 24min walking trial with a powered exoskeleton. Nine female subjects walked on a treadmill at 1.36±0.04ms(-1) during 24min with a powered exoskeleton and 4min with an unpowered exoskeleton. Subjects showed a metabolic adaptation after 18.5±5.0min, followed by an adapted period. Metabolic cost, electromyography and kinematics were compared between the unpowered condition, the beginning of the adaptation and the adapted period. In the beginning of the adaptation (4min), a reduction in metabolic cost of 9% was found compared to the unpowered condition. This reduction was accompanied by reduced muscular activity in the plantarflexor muscles, as the powered exoskeleton delivered part of the necessary ankle extension moment. During the adaptation this metabolic reduction further increased to 16%, notwithstanding a constant exoskeleton assistance. This increased reduction is the result of a neuromotor adaptation in which subjects adapt to walking with the exoskeleton, thereby reducing muscular activity in all leg muscles. Because of the fast adaptation and the significant reductions in metabolic cost we want to highlight the potential of an ankle-foot exoskeleton with kinematic control that assists ankle extension during push-off. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Higher Plants in Space: Microgravity Perception, Response, and Adaptation

    Science.gov (United States)

    Zheng, Hui Qiong; Han, Fei; Le, Jie

    2015-11-01

    Microgravity is a major abiotic stress in space. Its effects on plants may depend on the duration of exposure. We focused on two different phases of microgravity responses in space. When higher plants are exposed to short-term (seconds to hours) microgravity, such as on board parabolic flights and sounding rockets, their cells usually exhibit abiotic stress responses. For example, Ca 2+-, lipid-, and pH-signaling are rapidly enhanced, then the production of reactive oxygen species and other radicals increase dramatically along with changes in metabolism and auxin signaling. Under long-term (days to months) microgravity exposure, plants acclimatize to the stress by changing their metabolism and oxidative response and by enhancing other tropic responses. We conclude by suggesting that a systematic analysis of regulatory networks at the molecular level of higher plants is needed to understand the molecular signals in the distinct phases of the microgravity response and adaptation.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Ambiguous Adaptation

    DEFF Research Database (Denmark)

    Møller Larsen, Marcus; Lyngsie, Jacob

    2017-01-01

    We investigate the connection between contract duration, relational mechanisms, and premature relationship termination. Based on an analysis of a large sample of exchange relationships in the global service-provider industry, we argue that investments in either longer contract duration or more in...... ambiguous reference points for adaption and thus increase the likelihood of premature termination by restricting the parties' set of adaptive actions....

  20. Climate adaptation

    Science.gov (United States)

    Kinzig, Ann P.

    2015-03-01

    This paper is intended as a brief introduction to climate adaptation in a conference devoted otherwise to the physics of sustainable energy. Whereas mitigation involves measures to reduce the probability of a potential event, such as climate change, adaptation refers to actions that lessen the impact of climate change. Mitigation and adaptation differ in other ways as well. Adaptation does not necessarily have to be implemented immediately to be effective; it only needs to be in place before the threat arrives. Also, adaptation does not necessarily require global, coordinated action; many effective adaptation actions can be local. Some urban communities, because of land-use change and the urban heat-island effect, currently face changes similar to some expected under climate change, such as changes in water availability, heat-related morbidity, or changes in disease patterns. Concern over those impacts might motivate the implementation of measures that would also help in climate adaptation, despite skepticism among some policy makers about anthropogenic global warming. Studies of ancient civilizations in the southwestern US lends some insight into factors that may or may not be important to successful adaptation.

  1. Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship.

    Science.gov (United States)

    Netea-Maier, Romana T; Smit, Johannes W A; Netea, Mihai G

    2018-01-28

    In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production of lactate, nitric oxide, reactive oxygen species, prostaglandins and other byproducts of arachidonic acid metabolism that influence both the composition of the inflammatory microenvironment and the function of the tumor-associated macrophages (TAMs). In response to cues present in the TME, among which products of altered tumor cell metabolism, TAMs are also required to reprogram their metabolism, with activation of glycolysis, fatty acid synthesis and altered nitrogen cycle metabolism. These changes result in functional reprogramming of TAMs which includes changes in the production of cytokines and angiogenetic factors, and contribute to the tumor progression and metastasis. Understanding the metabolic changes governing the intricate relationship between the tumor cells and the TAMs represents an essential step towards developing novel therapeutic approaches targeting the metabolic reprogramming of the immune cells to potentiate their tumoricidal potential and to circumvent therapy resistance. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Adaptive steganography

    Science.gov (United States)

    Chandramouli, Rajarathnam; Li, Grace; Memon, Nasir D.

    2002-04-01

    Steganalysis techniques attempt to differentiate between stego-objects and cover-objects. In recent work we developed an explicit analytic upper bound for the steganographic capacity of LSB based steganographic techniques for a given false probability of detection. In this paper we look at adaptive steganographic techniques. Adaptive steganographic techniques take explicit steps to escape detection. We explore different techniques that can be used to adapt message embedding to the image content or to a known steganalysis technique. We investigate the advantages of adaptive steganography within an analytical framework. We also give experimental results with a state-of-the-art steganalysis technique demonstrating that adaptive embedding results in a significant number of bits embedded without detection.

  3. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    the investigations of lighting scenarios carried out in two test installations: White Cube and White Box. The test installations are discussed as large-scale experiential instruments. In these test installations we examine what could potentially occur when light using LED technology is integrated and distributed......Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial lighting ceases...

  4. Drug Metabolism

    Indian Academy of Sciences (India)

    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 ...

  5. Drug Metabolism

    Indian Academy of Sciences (India)

    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-.

  6. Metabolic Myopathies.

    Science.gov (United States)

    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.

  7. Animal metabolism

    International Nuclear Information System (INIS)

    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

  8. Cellular plasticity enables adaptation to unforeseen cell-cycle rewiring challenges.

    Directory of Open Access Journals (Sweden)

    Yair Katzir

    Full Text Available The fundamental dynamics of the cell cycle, underlying cell growth and reproduction, were previously found to be robust under a wide range of environmental and internal perturbations. This property was commonly attributed to its network structure, which enables the coordinated interactions among hundreds of proteins. Despite significant advances in deciphering the components and autonomous interactions of this network, understanding the interfaces of the cell cycle with other major cellular processes is still lacking. To gain insight into these interfaces, we used the process of genome-rewiring in yeast by placing an essential metabolic gene HIS3 from the histidine biosynthesis pathway, under the exclusive regulation of different cell-cycle promoters. In a medium lacking histidine and under partial inhibition of the HIS3p, the rewired cells encountered an unforeseen multitasking challenge; the cell-cycle regulatory genes were required to regulate the essential histidine-pathway gene in concert with the other metabolic demands, while simultaneously driving the cell cycle through its proper temporal phases. We show here that chemostat cell populations with rewired cell-cycle promoters adapted within a short time to accommodate the inhibition of HIS3p and stabilized a new phenotypic state. Furthermore, a significant fraction of the population was able to adapt and grow into mature colonies on plates under such inhibiting conditions. The adapted state was shown to be stably inherited across generations. These adaptation dynamics were accompanied by a non-specific and irreproducible genome-wide transcriptional response. Adaptation of the cell-cycle attests to its multitasking capabilities and flexible interface with cellular metabolic processes and requirements. Similar adaptation features were found in our previous work when rewiring HIS3 to the GAL system