WorldWideScience

Sample records for represent adaptive metabolism

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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...

  6. 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.

  7. 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...

  8. 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.

  9. Representing adaptive and adaptable Units of Learning. How to model personalized eLearning in IMS Learning Design

    NARCIS (Netherlands)

    Burgos, Daniel; Tattersall, Colin; Koper, Rob

    2006-01-01

    Burgos, D., Tattersall, C., & Koper, E. J. R. (2007). Representing adaptive and adaptable Units of Learning. How to model personalized eLearning in IMS Learning Design. In B. Fernández Manjon, J. M. Sanchez Perez, J. A. Gómez Pulido, M. A. Vega Rodriguez & J. Bravo (Eds.), Computers and Education:

  10. Representing adaptive and adaptable Units of Learning. How to model personalized eLearning in IMS Learning Design

    OpenAIRE

    Burgos, Daniel; Tattersall, Colin; Koper, Rob

    2006-01-01

    Burgos, D., Tattersall, C., & Koper, E. J. R. (2007). Representing adaptive and adaptable Units of Learning. How to model personalized eLearning in IMS Learning Design. In B. Fernández Manjon, J. M. Sanchez Perez, J. A. Gómez Pulido, M. A. Vega Rodriguez & J. Bravo (Eds.), Computers and Education: E-learning - from theory to practice. Germany: Kluwer.

  11. 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...

  12. 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…

  13. 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.

  14. 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.

  15. 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....

  16. Calculating a Continuous Metabolic Syndrome Score Using Nationally Representative Reference Values.

    Science.gov (United States)

    Guseman, Emily Hill; Eisenmann, Joey C; Laurson, Kelly R; Cook, Stephen R; Stratbucker, William

    2018-02-26

    The prevalence of metabolic syndrome in youth varies on the basis of the classification system used, prompting implementation of continuous scores; however, the use of these scores is limited to the sample from which they were derived. We sought to describe the derivation of the continuous metabolic syndrome score using nationally representative reference values in a sample of obese adolescents and a national sample obtained from National Health and Nutrition Examination Survey (NHANES) 2011-2012. Clinical data were collected from 50 adolescents seeking obesity treatment at a stage 3 weight management center. A second analysis relied on data from adolescents included in NHANES 2011-2012, performed for illustrative purposes. The continuous metabolic syndrome score was calculated by regressing individual values onto nationally representative age- and sex-specific standards (NHANES III). Resultant z scores were summed to create a total score. The final sample included 42 obese adolescents (15 male and 35 female subjects; mean age, 14.8 ± 1.9 years) and an additional 445 participants from NHANES 2011-2012. Among the clinical sample, the mean continuous metabolic syndrome score was 4.16 ± 4.30, while the NHANES sample mean was quite a bit lower, at -0.24 ± 2.8. We provide a method to calculate the continuous metabolic syndrome by comparing individual risk factor values to age- and sex-specific percentiles from a nationally representative sample. Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  17. 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

  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. 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.

  20. 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.

  1. 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

  2. Urease Activity Represents an Alternative Pathway for Mycobacterium tuberculosis Nitrogen Metabolism

    Science.gov (United States)

    Lin, Wenwei; Mathys, Vanessa; Ang, Emily Lei Yin; Koh, Vanessa Hui Qi; Martínez Gómez, Julia María; Ang, Michelle Lay Teng; Zainul Rahim, Siti Zarina; Tan, Mai Ping; Pethe, Kevin

    2012-01-01

    Urease represents a critical virulence factor for some bacterial species through its alkalizing effect, which helps neutralize the acidic microenvironment of the pathogen. In addition, urease serves as a nitrogen source provider for bacterial growth. Pathogenic mycobacteria express a functional urease, but its role during infection has yet to be characterized. In this study, we constructed a urease-deficient Mycobacterium tuberculosis strain and confirmed the alkalizing effect of the urease activity within the mycobacterium-containing vacuole in resting macrophages but not in the more acidic phagolysosomal compartment of activated macrophages. However, the urease-mediated alkalizing effect did not confer any growth advantage on M. tuberculosis in macrophages, as evidenced by comparable growth profiles for the mutant, wild-type (WT), and complemented strains. In contrast, the urease-deficient mutant exhibited impaired in vitro growth compared to the WT and complemented strains when urea was the sole source of nitrogen. Substantial amounts of ammonia were produced by the WT and complemented strains, but not with the urease-deficient mutant, which represents the actual nitrogen source for mycobacterial growth. However, the urease-deficient mutant displayed parental colonization profiles in the lungs, spleen, and liver in mice. Together, our data demonstrate a role for the urease activity in M. tuberculosis nitrogen metabolism that could be crucial for the pathogen's survival in nutrient-limited microenvironments where urea is the sole nitrogen source. Our work supports the notion that M. tuberculosis virulence correlates with its unique metabolic versatility and ability to utilize virtually any carbon and nitrogen sources available in its environment. PMID:22645285

  3. Constraining genome-scale models to represent the bow tie structure of metabolism for 13C metabolic flux analysis

    DEFF Research Database (Denmark)

    Backman, Tyler W.H.; Ando, David; Singh, Jahnavi

    2018-01-01

    for a minimum of fluxes into core metabolism to satisfy these experimental constraints. Together, these methods accelerate and automate the identification of a biologically reasonable set of core reactions for use with 13C MFA or 2S- 13C MFA, as well as provide for a substantially lower set of flux bounds......Determination of internal metabolic fluxes is crucial for fundamental and applied biology because they map how carbon and electrons flow through metabolism to enable cell function. 13C Metabolic Flux Analysis (13C MFA) and Two-Scale 13C Metabolic Flux Analysis (2S-13C MFA) are two techniques used...

  4. Short communication: Proteins from circulating exosomes represent metabolic state in transition dairy cows.

    Science.gov (United States)

    Crookenden, M A; Walker, C G; Peiris, H; Koh, Y; Heiser, A; Loor, J J; Moyes, K M; Murray, A; Dukkipati, V S R; Kay, J K; Meier, S; Roche, J R; Mitchell, M D

    2016-09-01

    Biomarkers that identify prepathological disease could enhance preventive management, improve animal health and productivity, and reduce costs. Circulating extracellular vesicles, particularly exosomes, are considered to be long-distance, intercellular communication systems in human medicine. Exosomes provide tissue-specific messages of functional state and can alter the cellular activity of recipient tissues through their protein and microRNA content. We hypothesized that exosomes circulating in the blood of cows during early lactation would contain proteins representative of the metabolic state of important tissues, such as liver, which play integral roles in regulating the physiology of cows postpartum. From a total of 150 cows of known metabolic phenotype, 10 cows were selected with high (n=5; high risk) and low (n=5; low risk) concentrations of nonesterified fatty acids, β-hydroxybutyrate, and liver triacylglycerol during wk 1 and 2 after calving. Exosomes were extracted from blood on the day of calving (d 0) and postcalving at wk 1 and wk 4, and their protein composition was determined by mass spectroscopy. Extracellular vesicle protein concentration and the number of exosome vesicles were not affected by risk category; however, the exosome protein cargo differed between the groups, with proteins at each time point identified as being unique to the high- and low-risk groups. The proteins α-2 macroglobulin, fibrinogen, and oncoprotein-induced transcript 3 were unique to the high-risk cows on d 0 and have been associated with metabolic syndrome and liver function in humans. Their presence may indicate a more severe inflammatory state and a greater degree of liver dysfunction in the high-risk cows than in the low-risk cows, consistent with the high-risk cows' greater plasma β-hydroxybutyrate and liver triacylglycerol concentrations. The commonly shared proteins and those unique to the low-risk category indicate a role for exosomes in immune function. The data

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

    Directory of Open Access Journals (Sweden)

    Tyler W. H. Backman

    2018-01-01

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

  6. 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...

  7. 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.

  8. Neandertals' large lower thorax may represent adaptation to high protein diet.

    Science.gov (United States)

    Ben-Dor, Miki; Gopher, Avi; Barkai, Ran

    2016-07-01

    Humans are limited in their capacity to convert protein into energy. We present a hypothesis that a "bell" shaped thorax and a wide pelvis evolved in Neandertals, at least in part, as an adaptation to a high protein diet. A high protein diet created a need to house an enlarged liver and urinary system in a wider lower trunk. To test the hypothesis, we applied a model developed to identify points of nutritional stress. A ratio of obligatory dietary fat to total animal fat and protein sourced calories is calculated based on various known and estimated parameters. Stress is identified when the obligatory dietary fat ratio is higher than fat content ratios in available prey. The model predicts that during glacial winters, when carbohydrates weren't available, 74%-85% of Neandertals' caloric intake would have had to come from animal fat. Large animals contain around 50% fat calories, and their fat content is diminished during winter, so a significant stressful dietary fat deficit was identified by the model. This deficit could potentially be ameliorated by an increased capability to convert protein into energy. Given that high protein consumption is associated with larger liver and kidneys in animal models, it appears likely that the enlarged inferior section of the Neandertals thorax and possibly, in part, also his wide pelvis, represented an adaptation to provide encasement for those enlarged organs. Behavioral and evolutionary implications of the hypothesis are also discussed. Am J Phys Anthropol 160:367-378, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. 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.

  10. 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 ...

  11. Sequence- and Structure-Based Functional Annotation and Assessment of Metabolic Transporters in Aspergillus oryzae: A Representative Case Study

    Directory of Open Access Journals (Sweden)

    Nachon Raethong

    2016-01-01

    Full Text Available Aspergillus oryzae is widely used for the industrial production of enzymes. In A. oryzae metabolism, transporters appear to play crucial roles in controlling the flux of molecules for energy generation, nutrients delivery, and waste elimination in the cell. While the A. oryzae genome sequence is available, transporter annotation remains limited and thus the connectivity of metabolic networks is incomplete. In this study, we developed a metabolic annotation strategy to understand the relationship between the sequence, structure, and function for annotation of A. oryzae metabolic transporters. Sequence-based analysis with manual curation showed that 58 genes of 12,096 total genes in the A. oryzae genome encoded metabolic transporters. Under consensus integrative databases, 55 unambiguous metabolic transporter genes were distributed into channels and pores (7 genes, electrochemical potential-driven transporters (33 genes, and primary active transporters (15 genes. To reveal the transporter functional role, a combination of homology modeling and molecular dynamics simulation was implemented to assess the relationship between sequence to structure and structure to function. As in the energy metabolism of A. oryzae, the H+-ATPase encoded by the AO090005000842 gene was selected as a representative case study of multilevel linkage annotation. Our developed strategy can be used for enhancing metabolic network reconstruction.

  12. Sequence- and Structure-Based Functional Annotation and Assessment of Metabolic Transporters in Aspergillus oryzae: A Representative Case Study.

    Science.gov (United States)

    Raethong, Nachon; Wong-Ekkabut, Jirasak; Laoteng, Kobkul; Vongsangnak, Wanwipa

    2016-01-01

    Aspergillus oryzae is widely used for the industrial production of enzymes. In A. oryzae metabolism, transporters appear to play crucial roles in controlling the flux of molecules for energy generation, nutrients delivery, and waste elimination in the cell. While the A. oryzae genome sequence is available, transporter annotation remains limited and thus the connectivity of metabolic networks is incomplete. In this study, we developed a metabolic annotation strategy to understand the relationship between the sequence, structure, and function for annotation of A. oryzae metabolic transporters. Sequence-based analysis with manual curation showed that 58 genes of 12,096 total genes in the A. oryzae genome encoded metabolic transporters. Under consensus integrative databases, 55 unambiguous metabolic transporter genes were distributed into channels and pores (7 genes), electrochemical potential-driven transporters (33 genes), and primary active transporters (15 genes). To reveal the transporter functional role, a combination of homology modeling and molecular dynamics simulation was implemented to assess the relationship between sequence to structure and structure to function. As in the energy metabolism of A. oryzae, the H(+)-ATPase encoded by the AO090005000842 gene was selected as a representative case study of multilevel linkage annotation. Our developed strategy can be used for enhancing metabolic network reconstruction.

  13. 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 ...

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Adaptation of Regional Representative Soil Project and Soil Judging for Cameroon

    Science.gov (United States)

    Che, Celestine Akuma

    2013-01-01

    Representative regional soils have agricultural, cultural, economic, environmental, and historical importance to Cameroon. Twenty seven regional representative soils have been identified in Cameroon. A set of laboratory exercises, assignments and exam questions have been developed utilizing the Regional Representative Soil Project (RRSP) that…

  19. 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

  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. Impact of social integration on metabolic functions: evidence from a nationally representative longitudinal study of US older adults.

    Science.gov (United States)

    Yang, Yang Claire; Li, Ting; Ji, Yinchun

    2013-12-20

    Metabolic functions may operate as important biophysiological mechanisms through which social relationships affect health. It is unclear how social embeddedness or the lack thereof is related to risk of metabolic dysregulation. To fill this gap we tested the effects of social integration on metabolic functions over time in a nationally representative sample of older adults in the United States and examined population heterogeneity in the effects. Using longitudinal data from 4,323 adults aged over 50 years in the Health and Retirement Study and latent growth curve models, we estimated the trajectories of social integration spanning five waves, 1998-2006, in relation to biomarkers of energy metabolism in 2006. We assessed social integration using a summary index of the number of social ties across five domains. We examined six biomarkers, including total cholesterol, high-density lipoprotein cholesterol, glycosylated hemoglobin, waist circumference, and systolic and diastolic blood pressure, and the summary index of the overall burden of metabolic dysregulation. High social integration predicted significantly lower risks of both individual and overall metabolic dysregulation. Specifically, adjusting for age, sex, race, and body mass index, having four to five social ties reduced the risks of abdominal obesity by 61% (odds ratio [OR] [95% confidence interval {CI}] = 0.39 [0.23, 0.67], p = .007), hypertension by 41% (OR [95% CI] = 0.59 [0.42, 0.84], p = .021), and the overall metabolic dysregulation by 46% (OR [95% CI] = 0.54 [0.40, 0.72], p < .001). The OR for the overall burden remained significant when adjusting for social, behavioral, and illness factors. In addition, stably high social integration had more potent metabolic impacts over time than changes therein. Such effects were consistent across subpopulations and more salient for the younger old (those under age 65), males, whites, and the socioeconomically disadvantaged. This study

  5. 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.

  6. 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.

  7. Does enhanced heat resistance of irradiated insects represent greater ability to adapt

    International Nuclear Information System (INIS)

    Ducoff, H.S.; MacDuff, R.A.

    1985-01-01

    Previous work from this lab demonstrated that irradiated flour beetles (Tribolium) develop resistance to oxygen with similar kinetics: greater sensitivity for about 1 week, increasing resistance over the next week, and resistance persisting for 3-6 months. This is in contrast to the rapid development of heat resistance in yeast exposed to UV or ionizing radiation and to rapid induction of heat-stress proteins in E. coli exposed to UV or nalidixic acid. The authors' early work did not distinguish between intrinsic heat resistance and enhanced ability to adapt. They tried to resolve this problem by comparing response of irradiated and of control beetles to challenge at 45 0 C with or without brief exposure to 41 0 C just prior to challenge. Mean lethal exposure time at 45 0 C was increased to about the same extent in both populations after 15 min at 41 0 C, suggesting that irradiation increases insectors' intrinsic resistance to stress rather than their ability to adapt

  8. Challenges of Representing Sub-Grid Physics in an Adaptive Mesh Refinement Atmospheric Model

    Science.gov (United States)

    O'Brien, T. A.; Johansen, H.; Johnson, J. N.; Rosa, D.; Benedict, J. J.; Keen, N. D.; Collins, W.; Goodfriend, E.

    2015-12-01

    Some of the greatest potential impacts from future climate change are tied to extreme atmospheric phenomena that are inherently multiscale, including tropical cyclones and atmospheric rivers. Extremes are challenging to simulate in conventional climate models due to existing models' coarse resolutions relative to the native length-scales of these phenomena. Studying the weather systems of interest requires an atmospheric model with sufficient local resolution, and sufficient performance for long-duration climate-change simulations. To this end, we have developed a new global climate code with adaptive spatial and temporal resolution. The dynamics are formulated using a block-structured conservative finite volume approach suitable for moist non-hydrostatic atmospheric dynamics. By using both space- and time-adaptive mesh refinement, the solver focuses computational resources only where greater accuracy is needed to resolve critical phenomena. We explore different methods for parameterizing sub-grid physics, such as microphysics, macrophysics, turbulence, and radiative transfer. In particular, we contrast the simplified physics representation of Reed and Jablonowski (2012) with the more complex physics representation used in the System for Atmospheric Modeling of Khairoutdinov and Randall (2003). We also explore the use of a novel macrophysics parameterization that is designed to be explicitly scale-aware.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Phosphorylation of Isoflavones by Bacillus subtilis BCRC 80517 May Represent Xenobiotic Metabolism.

    Science.gov (United States)

    Hsu, Chen; Wu, Bo-Yuan; Chang, Yu-Chuan; Chang, Chi-Fon; Chiou, Tai-Ying; Su, Nan-Wei

    2018-01-10

    The soy isoflavones daidzein (DAI) and genistein (GEN) have beneficial effects on human health. However, their oral bioavailability is hampered by their low aqueous solubility. Our previous study revealed two water-soluble phosphorylated conjugates of isoflavones, daidzein 7-O-phosphate and genistein 7-O-phosphate, generated via biotransformation by Bacillus subtilis BCRC80517 cultivated with isoflavones. In this study, two novel derivatives of isoflavones, daidzein 4'-O-phosphate and genistein 4'-O-phosphate, were identified by HPLC-ESI-MS/MS and 1 H, 13 C, and 31 P NMR, and their biotransformation roadmaps were proposed. Primarily, isoflavone glucosides were deglycosylated and then phosphorylated predominantly into 7-O-phosphate conjugates with traces of 4'-O-phosphate conjugates. Inevitably, trace quantities of glucosides were converted into 6″-O-succinyl glucosides. GEN was more efficiently phosphorylated than DAI. Nevertheless, the presence of GEN prolonged the time until the exponential phase of cell growth, whereas the other isoflavones showed little effect on cell growth. Our findings provide new insights into the novel microbial phosphorylation of isoflavones involved in xenobiotic metabolism.

  15. 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...

  16. 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

  17. 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

  18. [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.

  19. 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...

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. Depression, obesity, and metabolic syndrome: prevalence and risks of comorbidity in a population-based representative sample of Mexican Americans.

    Science.gov (United States)

    Olvera, Rene L; Williamson, Douglas E; Fisher-Hoch, Susan P; Vatcheva, Kristina P; McCormick, Joseph B

    2015-10-01

    We examined the prevalence of depression, obesity, and metabolic syndrome and associations between them in a population-based representative cohort of Mexican Americans living on the United States-Mexico border. The sample in this cross-sectional analysis consisted of 1,768 Mexican American adults (≥ 18 years of age) assessed between the years 2004 and 2010, with whom we tested our central hypothesis of a significant relationship between obesity and depression. Depression was measured using the Center for Epidemiologic Studies-Depression scale (CES-D) with a cutoff score of ≥ 16 for depression and a cutoff score of ≥ 27 for severe depression. We categorized body mass index (BMI) values as obese (≥ 30kg/m(2)) and later subdivided the obese subjects into obese (30-39 kg/m(2)[inclusive]) and morbidly obese (≥ 40 kg/m(2)). Metabolic syndrome was defined using the American Heart Association definition requiring at least 3 of the following: increased waist circumference, elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, elevated blood pressure, and elevated fasting glucose. Weighted data were analyzed to establish prevalence of depression, obesity, and metabolic syndrome. Univariate and multivariable weighted regression models were used to test potential associations between these disorders. Using weighted prevalence, we observed high rates of depression (30%), obesity (52%), and metabolic syndrome (45%). Univariate models revealed female gender (P = .0004), low education (P = .003), low HDL level (P = .009), and increased waist circumference (P = .03) were associated with depression. Female gender (P = .01), low education (P = .003), and morbid obesity (P = .002) were risk factors for severe depression and remained significant in multivariable models. In this large cohort of Mexican Americans, obesity, female gender, and low education were identified risk factors for depression. These indicators may serve as targets for early

  7. Child and family experiences with inborn errors of metabolism: a qualitative interview study with representatives of patient groups.

    Science.gov (United States)

    Khangura, Sara D; Tingley, Kylie; Chakraborty, Pranesh; Coyle, Doug; Kronick, Jonathan B; Laberge, Anne-Marie; Little, Julian; Miller, Fiona A; Mitchell, John J; Prasad, Chitra; Siddiq, Shabnaz; Siriwardena, Komudi; Sparkes, Rebecca; Speechley, Kathy N; Stockler, Sylvia; Trakadis, Yannis; Wilson, Brenda J; Wilson, Kumanan; Potter, Beth K

    2016-01-01

    Patient-centered health care for children with inborn errors of metabolism (IEM) and their families is important and requires an understanding of patient experiences, needs, and priorities. IEM-specific patient groups have emerged as important voices within these rare disease communities and are uniquely positioned to contribute to this understanding. We conducted qualitative interviews with IEM patient group representatives to increase understanding of patient and family experiences, needs, and priorities and inform patient-centered research and care. We developed a sampling frame of patient groups representing IEM disease communities from Canada, the United States, and United Kingdom. With consent, we interviewed participants to explore their views on experiences, needs, and outcomes that are most important to children with IEM and their families. We analyzed the data using a qualitative descriptive approach to identify key themes and sub-themes. We interviewed 18 organizational representatives between February 28 and September 17, 2014, representing 16 IEMs and/or disease categories. Twelve participants voluntarily self-identified as parents and/or were themselves patients. Three key themes emerged from the coded data: managing the uncertainty associated with raising and caring for a child with a rare disease; challenges associated with the affected child's life transitions, and; the collective struggle for improved outcomes and interventions that rare disease communities navigate. Health care providers can support children with IEM and their families by acknowledging and reducing uncertainty, supporting families through children's life transitions, and contributing to rare disease communities' progress toward improved interventions, experiences, and outcomes.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Vande Wouwer, A.

    2010-01-01

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

  17. 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...

  18. 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.

  19. 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.

  20. 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...

  1. Spatially Representing Vulnerability to Extreme Rain Events Using Midwestern Farmers' Objective and Perceived Attributes of Adaptive Capacity.

    Science.gov (United States)

    Gardezi, Maaz; Arbuckle, J Gordon

    2017-11-29

    Potential climate-change-related impacts to agriculture in the upper Midwest pose serious economic and ecological risks to the U.S. and the global economy. On a local level, farmers are at the forefront of responding to the impacts of climate change. Hence, it is important to understand how farmers and their farm operations may be more or less vulnerable to changes in the climate. A vulnerability index is a tool commonly used by researchers and practitioners to represent the geographical distribution of vulnerability in response to global change. Most vulnerability assessments measure objective adaptive capacity using secondary data collected by governmental agencies. However, other scholarship on human behavior has noted that sociocultural and cognitive factors, such as risk perceptions and perceived capacity, are consequential for modulating people's actual vulnerability. Thus, traditional assessments can potentially overlook people's subjective perceptions of changes in climate and extreme weather events and the extent to which people feel prepared to take necessary steps to cope with and respond to the negative effects of climate change. This article addresses this knowledge gap by: (1) incorporating perceived adaptive capacity into a vulnerability assessment; (2) using spatial smoothing to aggregate individual-level vulnerabilities to the county level; and (3) evaluating the relationships among different dimensions of adaptive capacity to examine whether perceived capacity should be integrated into vulnerability assessments. The result suggests that vulnerability assessments that rely only on objective measures might miss important sociocognitive dimensions of capacity. Vulnerability indices and maps presented in this article can inform engagement strategies for improving environmental sustainability in the region. © 2017 Society for Risk Analysis.

  2. 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.

  3. 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

  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. Biomonitoring role of some cellular markers during heat stress-induced changes in highly representative fresh water mollusc, Bellamya bengalensis: Implication in climate change and biological adaptation.

    Science.gov (United States)

    Dutta, Sangita Maiti; Mustafi, Soumyajit Banerjee; Raha, Sanghamitra; Chakraborty, Susanta Kumar

    2018-08-15

    °C - 72 h and 38 °C - 72 h), these enzyme activities also decreased as they failed to save the tissues from ROS. The results suggest that temperature variation does alter the active oxygen metabolism by modulating antioxidant enzyme activities, which can be used as biomarker to detect sub-lethal effects of climate change-associated pollution. The parity in environmental and laboratory experimental results may justify this laboratory experiment as model heat-stress experiment and indicate temperature as a universal stressor which alone or in combination with other water parameters initiates a consistent adapting behavior. The Bellamya bengalensis being the highest faunal representative in its habitat may serve as a good bioindicator species. Copyright © 2018. Published by Elsevier Inc.

  6. Representative Agricultural Pathways and Scenarios for Regional Integrated Assessment of Climate Change Impacts, Vulnerability, and Adaptation. 5; Chapter

    Science.gov (United States)

    Valdivia, Roberto O.; Antle, John M.; Rosenzweig, Cynthia; Ruane, Alexander C.; Vervoort, Joost; Ashfaq, Muhammad; Hathie, Ibrahima; Tui, Sabine Homann-Kee; Mulwa, Richard; Nhemachena, Charles; hide

    2015-01-01

    The global change research community has recognized that new pathway and scenario concepts are needed to implement impact and vulnerability assessment where precise prediction is not possible, and also that these scenarios need to be logically consistent across local, regional, and global scales. For global climate models, representative concentration pathways (RCPs) have been developed that provide a range of time-series of atmospheric greenhouse-gas concentrations into the future. For impact and vulnerability assessment, new socio-economic pathway and scenario concepts have also been developed, with leadership from the Integrated Assessment Modeling Consortium (IAMC).This chapter presents concepts and methods for development of regional representative agricultural pathways (RAOs) and scenarios that can be used for agricultural model intercomparison, improvement, and impact assessment in a manner consistent with the new global pathways and scenarios. The development of agriculture-specific pathways and scenarios is motivated by the need for a protocol-based approach to climate impact, vulnerability, and adaptation assessment. Until now, the various global and regional models used for agricultural-impact assessment have been implemented with individualized scenarios using various data and model structures, often without transparent documentation, public availability, and consistency across disciplines. These practices have reduced the credibility of assessments, and also hampered the advancement of the science through model intercomparison, improvement, and synthesis of model results across studies. The recognition of the need for better coordination among the agricultural modeling community, including the development of standard reference scenarios with adequate agriculture-specific detail led to the creation of the Agricultural Model Intercomparison and Improvement Project (AgMIP) in 2010. The development of RAPs is one of the cross-cutting themes in AgMIP's work

  7. 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.

  8. 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.

  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. 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

  11. 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

  12. 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.

  13. 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.

  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. 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...

  16. 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.

  17. Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche.

    Science.gov (United States)

    Van Doorslaer, Koenraad; DeSalle, Rob; Einstein, Mark H; Burk, Robert D

    2015-06-01

    In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential) is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution.

  18. Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche

    Science.gov (United States)

    Van Doorslaer, Koenraad; DeSalle, Rob; Einstein, Mark H.; Burk, Robert D.

    2015-01-01

    In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential) is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution. PMID:26086730

  19. Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche.

    Directory of Open Access Journals (Sweden)

    Koenraad Van Doorslaer

    2015-06-01

    Full Text Available In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution.

  20. Structure of the first representative of Pfam family PF09410 (DUF2006) reveals a structural signature of the calycin superfamily that suggests a role in lipid metabolism

    International Nuclear Information System (INIS)

    Chiu, Hsiu-Ju; Bakolitsa, Constantina; Skerra, Arne; Lomize, Andrei; Carlton, Dennis; Miller, Mitchell D.; Krishna, S. Sri; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Slawomir K.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Paulsen, Jessica; Reyes, Ron; Rife, Christopher L.; Bedem, Henry van den; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2009-01-01

    NE1406, the first structural representative of PF09410, reveals a lipocalin-like fold with features that suggest involvement in lipid metabolism. In addition, NE1406 provides potential structural templates for two other protein families (PF07143 and PF08622). The first structural representative of the domain of unknown function DUF2006 family, also known as Pfam family PF09410, comprises a lipocalin-like fold with domain duplication. The finding of the calycin signature in the N-terminal domain, combined with remote sequence similarity to two other protein families (PF07143 and PF08622) implicated in isoprenoid metabolism and the oxidative stress response, support an involvement in lipid metabolism. Clusters of conserved residues that interact with ligand mimetics suggest that the binding and regulation sites map to the N-terminal domain and to the interdomain interface, respectively

  1. Robust Approximation to Adaptive Control by Use of Representative Parameter Sets with Particular Reference to Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Anthony Shannon

    2006-04-01

    Full Text Available This paper describes an approach to adaptive optimal control in the presence of model parameter calculation difficulties. This has wide application in a variety of biological and biomedical research and clinical problems. To illustrate the techniques, the approach is applied to the development and implementation of a practical adaptive insulin infusion algorithm for use with patients with Type 1 diabetes mellitus.

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

    Directory of Open Access Journals (Sweden)

    Martino V. Franchi

    2017-07-01

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

  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. Structure of the first representative of Pfam family PF09410 (DUF2006) reveals a structural signature of the calycin superfamily that suggests a role in lipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Chiu, Hsiu-Ju; Bakolitsa, Constantina; Skerra, Arne; Lomize, Andrei; Carlton, Dennis; Miller, Mitchell D.; Krishna, S. Sri; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Slawomir K.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Kumar, Abhinav; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Paulsen, Jessica; Reyes, Ron; Rife, Christopher L.; van den Bedem, Henry; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-Andre; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A. (SLAC); (Michigan); (TU Munchen)

    2015-10-15

    The first structural representative of the domain of unknown function DUF2006 family, also known as Pfam family PF09410, comprises a lipocalin-like fold with domain duplication. The finding of the calycin signature in the N-terminal domain, combined with remote sequence similarity to two other protein families (PF07143 and PF08622) implicated in isoprenoid metabolism and the oxidative stress response, support an involvement in lipid metabolism. Clusters of conserved residues that interact with ligand mimetics suggest that the binding and regulation sites map to the N-terminal domain and to the interdomain interface, respectively.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Chu Zhong

    2017-06-01

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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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 ...

  1. 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.

  2. 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.

  3. 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.

  4. Assessment of Different Sampling Methods for Measuring and Representing Macular Cone Density Using Flood-Illuminated Adaptive Optics.

    Science.gov (United States)

    Feng, Shu; Gale, Michael J; Fay, Jonathan D; Faridi, Ambar; Titus, Hope E; Garg, Anupam K; Michaels, Keith V; Erker, Laura R; Peters, Dawn; Smith, Travis B; Pennesi, Mark E

    2015-09-01

    To describe a standardized flood-illuminated adaptive optics (AO) imaging protocol suitable for the clinical setting and to assess sampling methods for measuring cone density. Cone density was calculated following three measurement protocols: 50 × 50-μm sampling window values every 0.5° along the horizontal and vertical meridians (fixed-interval method), the mean density of expanding 0.5°-wide arcuate areas in the nasal, temporal, superior, and inferior quadrants (arcuate mean method), and the peak cone density of a 50 × 50-μm sampling window within expanding arcuate areas near the meridian (peak density method). Repeated imaging was performed in nine subjects to determine intersession repeatability of cone density. Cone density montages could be created for 67 of the 74 subjects. Image quality was determined to be adequate for automated cone counting for 35 (52%) of the 67 subjects. We found that cone density varied with different sampling methods and regions tested. In the nasal and temporal quadrants, peak density most closely resembled histological data, whereas the arcuate mean and fixed-interval methods tended to underestimate the density compared with histological data. However, in the inferior and superior quadrants, arcuate mean and fixed-interval methods most closely matched histological data, whereas the peak density method overestimated cone density compared with histological data. Intersession repeatability testing showed that repeatability was greatest when sampling by arcuate mean and lowest when sampling by fixed interval. We show that different methods of sampling can significantly affect cone density measurements. Therefore, care must be taken when interpreting cone density results, even in a normal population.

  5. 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.

  6. 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

  7. 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

  8. 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 ...

  9. 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.

  10. 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.

  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. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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...

  3. 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

  4. tRNA-dependent cysteine biosynthetic pathway represents a strategy to increase cysteine contents by preventing it from thermal degradation: thermal adaptation of methanogenic archaea ancestor.

    Science.gov (United States)

    Qu, Ge; Wang, Wei; Chen, Ling-Ling; Qian, Shao-Song; Zhang, Hong-Yu

    2009-10-01

    Although cysteine (Cys) is beneficial to stabilize protein structures, it is not prevalent in thermophiles. For instance, the Cys contents in most thermophilic archaea are only around 0.7%. However, methanogenic archaea, no matter thermophilic or not, contain relatively abundant Cys, which remains elusive for a long time. Recently, Klipcan et al. correlated this intriguing property of methanogenic archaea with their unique tRNA-dependent Cys biosynthetic pathway. But, the deep reasons underlying the correlation are ambiguous. Considering the facts that free Cys is thermally labile and the tRNA-dependent Cys biosynthesis avoids the use of free Cys, we speculate that the unique Cys biosynthetic pathway represents a strategy to increase Cys contents by preventing it from thermal degradation, which may be relevant to the thermal adaptation of methanogenic archaea ancestor.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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...

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Method of propagation, stimulation of rhizomes growth in vitro culture and adaptation in the open ground for the genus Miscanthus representatives

    Directory of Open Access Journals (Sweden)

    С. М. Гонтаренко

    2017-09-01

    Full Text Available Purpose. To develop a method of propagation, stimulation of rhizomes growth in vitro culture for the genus Miscanthus representatives and their adaptation in the open field without the use of greenhouse complexes for acclimatization and completion of growing. Methods. Biotechnological procedures, mathematical and statistical analyses. Results. Prescription of nutrient medium was developed for explants inoculation, sprouts propagation, rhizomes growth stimulation in vitro. Such sterile explants as seeds, buds to be removed from rhizomes, parts of  stems with bud were placed on modified media with mineral portion by Murashige and Skoog (MS that contained 0,5–1 dose of macroelements and one dose of microelements,  vitamins (10 mg/l of thia­minum, 1,0 mg/l of pyridoxine, 1,0 mg/l of nicotinic acid and 1,0 mg/l of ascorbic acid supplemented with amino acids (250 mg/l of glutamic acid, 3 mg/l of tyrosine, 3 mg/l of arginine, 2 mg/l of hydroxyproline, plant growth regulators [0,5–1,0 mg/l of GA (gibberelline acid, 0,2 mg/l of 6-BAP (6-Benzylaminopurine, 0,1 mg/l of NAA (α-naphtylacetic acid] in different variations. After seed germination, buds emerging and sprouts formation 1–2 cm in height, for propagation purpose they were passivated on the medium of other composition that differed from previous one by the content and ratio of growth regulators, especially by a high concentration of cytokinins [6-BAP (0,4–0,5 mg/l, kinetin (0,5 mg/l, adenine (0,5 mg/k] in different variations in presence of GA (0,2 mg/l. In order to stimulate rhizomes growth, microclones were transferred on media with other composition and ratio growth regulators (6-BAP (0,2–0,3 mg/l + GA (0,5–1,0 mg/l or 6-BAP (0,2–0,3 mg/l + GA (0,5–1,0 mg/l + NAA (0,1 mg/l,  in other words,  with a high content of gibberellins. After the formation of rhizomes 10–15 cm in length, miscanthus plants were planted out in the open ground. Stimulation of

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. Methyl donor deficient diets cause distinct alterations in lipid metabolism but are poorly representative of human NAFLD [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Marcus J. Lyall

    2017-08-01

    Full Text Available Background: Non-alcoholic fatty liver disease (NAFLD is a global health issue. Dietary methyl donor restriction is used to induce a NAFLD/non-alcoholic steatohepatitis (NASH phenotype in rodents, however the extent to which this model reflects human NAFLD remains incompletely understood. To address this, we undertook hepatic transcriptional profiling of methyl donor restricted rodents and compared these to published human NAFLD datasets.              Methods: Adult C57BL/6J mice were maintained on control, choline deficient (CDD or methionine/choline deficient (MCDD diets for four weeks; the effects on methyl donor and lipid biology were investigated by bioinformatic analysis of hepatic gene expression profiles followed by a cross-species comparison with human expression data of all stages of NAFLD. Results: Compared to controls, expression of the very low density lipoprotein (VLDL packaging carboxylesterases (Ces1d, Ces1f, Ces3b and the NAFLD risk allele Pnpla3 were suppressed in MCDD; with Pnpla3 and the liver predominant Ces isoform, Ces3b, also suppressed in CDD. With respect to 1-carbon metabolism, down-regulation of Chka, Chkb, Pcty1a, Gnmt and Ahcy with concurrent upregulation of Mat2a suggests a drive to maintain S-adenosylmethionine levels. There was minimal similarity between global gene expression patterns in either dietary intervention and any stage of human NAFLD, however some common transcriptomic changes in inflammatory, fibrotic and proliferative mediators were identified in MCDD, NASH and HCC. Conclusions: This study suggests suppression of VLDL assembly machinery may contribute to hepatic lipid accumulation in these models, but that CDD and MCDD rodent diets are minimally representative of human NAFLD at the transcriptional level.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Adaptive selection of diurnal minimum variation: a statistical strategy to obtain representative atmospheric CO2 data and its application to European elevated mountain stations

    Science.gov (United States)

    Yuan, Ye; Ries, Ludwig; Petermeier, Hannes; Steinbacher, Martin; Gómez-Peláez, Angel J.; Leuenberger, Markus C.; Schumacher, Marcus; Trickl, Thomas; Couret, Cedric; Meinhardt, Frank; Menzel, Annette

    2018-03-01

    Critical data selection is essential for determining representative baseline levels of atmospheric trace gases even at remote measurement sites. Different data selection techniques have been used around the world, which could potentially lead to reduced compatibility when comparing data from different stations. This paper presents a novel statistical data selection method named adaptive diurnal minimum variation selection (ADVS) based on CO2 diurnal patterns typically occurring at elevated mountain stations. Its capability and applicability were studied on records of atmospheric CO2 observations at six Global Atmosphere Watch stations in Europe, namely, Zugspitze-Schneefernerhaus (Germany), Sonnblick (Austria), Jungfraujoch (Switzerland), Izaña (Spain), Schauinsland (Germany), and Hohenpeissenberg (Germany). Three other frequently applied statistical data selection methods were included for comparison. Among the studied methods, our ADVS method resulted in a lower fraction of data selected as a baseline with lower maxima during winter and higher minima during summer in the selected data. The measured time series were analyzed for long-term trends and seasonality by a seasonal-trend decomposition technique. In contrast to unselected data, mean annual growth rates of all selected datasets were not significantly different among the sites, except for the data recorded at Schauinsland. However, clear differences were found in the annual amplitudes as well as the seasonal time structure. Based on a pairwise analysis of correlations between stations on the seasonal-trend decomposed components by statistical data selection, we conclude that the baseline identified by the ADVS method is a better representation of lower free tropospheric (LFT) conditions than baselines identified by the other methods.

  19. Adaptive selection of diurnal minimum variation: a statistical strategy to obtain representative atmospheric CO2 data and its application to European elevated mountain stations

    Directory of Open Access Journals (Sweden)

    Y. Yuan

    2018-03-01

    Full Text Available Critical data selection is essential for determining representative baseline levels of atmospheric trace gases even at remote measurement sites. Different data selection techniques have been used around the world, which could potentially lead to reduced compatibility when comparing data from different stations. This paper presents a novel statistical data selection method named adaptive diurnal minimum variation selection (ADVS based on CO2 diurnal patterns typically occurring at elevated mountain stations. Its capability and applicability were studied on records of atmospheric CO2 observations at six Global Atmosphere Watch stations in Europe, namely, Zugspitze-Schneefernerhaus (Germany, Sonnblick (Austria, Jungfraujoch (Switzerland, Izaña (Spain, Schauinsland (Germany, and Hohenpeissenberg (Germany. Three other frequently applied statistical data selection methods were included for comparison. Among the studied methods, our ADVS method resulted in a lower fraction of data selected as a baseline with lower maxima during winter and higher minima during summer in the selected data. The measured time series were analyzed for long-term trends and seasonality by a seasonal-trend decomposition technique. In contrast to unselected data, mean annual growth rates of all selected datasets were not significantly different among the sites, except for the data recorded at Schauinsland. However, clear differences were found in the annual amplitudes as well as the seasonal time structure. Based on a pairwise analysis of correlations between stations on the seasonal-trend decomposed components by statistical data selection, we conclude that the baseline identified by the ADVS method is a better representation of lower free tropospheric (LFT conditions than baselines identified by the other methods.

  20. 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

  1. 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

  2. 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...

  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. 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).

  5. 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)

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Background: A Saccharomyces cerevisiae strain carrying deletions in all three pyruvate decarboxylase (PDC) genes (also called Pdc negative yeast) represents a non-ethanol producing platform strain for the production of pyruvate derived biochemicals. However, it cannot grow on glucose as the sole...... DNA sequencing. Among these genetic changes, 4 genes were found to carry point mutations in at least two of the evolved strains: MTH1 encoding a negative regulator of the glucose-sensing signal transduction pathway, HXT2 encoding a hexose transporter, CIT1 encoding a mitochondrial citrate synthase...... further increased the maximum specific growth rate to 0.069 h-1. Conclusions: In this study, possible evolving mechanisms of Pdc negative strains on glucose were investigated by genome sequencing and reverse engineering. The non-synonymous mutations in MTH1 alleviated the glucose repression by repressing...

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Representing Development

    DEFF Research Database (Denmark)

    Representing Development presents the different social representations that have formed the idea of development in Western thinking over the past three centuries. Offering an acute perspective on the current state of developmental science and providing constructive insights into future pathways, ...

  12. 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

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

    Directory of Open Access Journals (Sweden)

    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

  14. 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

  15. 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.

  16. Representing dispositions

    Directory of Open Access Journals (Sweden)

    Röhl Johannes

    2011-08-01

    Full Text Available Abstract Dispositions and tendencies feature significantly in the biomedical domain and therefore in representations of knowledge of that domain. They are not only important for specific applications like an infectious disease ontology, but also as part of a general strategy for modelling knowledge about molecular interactions. But the task of representing dispositions in some formal ontological systems is fraught with several problems, which are partly due to the fact that Description Logics can only deal well with binary relations. The paper will discuss some of the results of the philosophical debate about dispositions, in order to see whether the formal relations needed to represent dispositions can be broken down to binary relations. Finally, we will discuss problems arising from the possibility of the absence of realizations, of multi-track or multi-trigger dispositions and offer suggestions on how to deal with them.

  17. Representing time

    Directory of Open Access Journals (Sweden)

    Luca Poncellini

    2010-06-01

    Full Text Available The analysis of natural phenomena applied to architectural planning and design is facing the most fascinating and elusive of the four dimensions through which man attempts to define life within the universe: time. We all know what time is, said St. Augustine, but nobody knows how to describe it. Within architectural projects and representations, time rarely appears in explicit form. This paper presents the results of a research conducted by students of NABA and of the Polytechnic of Milan with the purpose of representing time considered as a key element within architectural projects. Student investigated new approaches and methodologies to represent time using the two-dimensional support of a sheet of paper.

  18. 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

  19. 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.

  20. 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.

  1. 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...

  2. 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...

  3. 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

  4. 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, ...

  5. 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...

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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,

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. Structure of Bacteroides thetaiotaomicron BT2081 at 2.05 Å resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Andrew P. [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (United States); Abdubek, Polat [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA (United States); Astakhova, Tamara [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA (United States); Axelrod, Herbert L. [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (United States); Bakolitsa, Constantina [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA (United States); Cai, Xiaohui [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA (United States); Carlton, Dennis [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (United States); Chen, Connie [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA (United States); Chiu, Hsiu-Ju [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (United States); Chiu, Michelle [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA (United States); Clayton, Thomas [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (United States); Das, Debanu [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (United States); Deller, Marc C. [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (United States); Duan, Lian; Ellrott, Kyle [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA (United States); Farr, Carol L. [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (United States); Feuerhelm, Julie; Grant, Joanna C. [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA (United States); Grzechnik, Anna; Han, Gye Won [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (United States); Jaroszewski, Lukasz [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA (United States); Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA (United States); Jin, Kevin K. [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (United States); Klock, Heath E.; Knuth, Mark W. [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA (United States); Kozbial, Piotr [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA (United States); Krishna, S. Sri [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA (United States); Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA (United States); Kumar, Abhinav; Lam, Winnie W. [Joint Center for Structural Genomics, http://www.jcsg.org (United States); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (United States); Marciano, David [Joint Center for Structural Genomics, http://www.jcsg.org (US); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (US); McMullan, Daniel [Joint Center for Structural Genomics, http://www.jcsg.org (US); Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA (US); Miller, Mitchell D. [Joint Center for Structural Genomics, http://www.jcsg.org (US); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (US); Morse, Andrew T. [Joint Center for Structural Genomics, http://www.jcsg.org (US); Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA (US); Nigoghossian, Edward [Joint Center for Structural Genomics, http://www.jcsg.org (US); Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA (US); Nopakun, Amanda [Joint Center for Structural Genomics, http://www.jcsg.org (US); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (US); Okach, Linda; Puckett, Christina [Joint Center for Structural Genomics, http://www.jcsg.org (US); Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA (US); Reyes, Ron [Joint Center for Structural Genomics, http://www.jcsg.org (US); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (US); Tien, Henry J. [Joint Center for Structural Genomics, http://www.jcsg.org (US); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (US); Trame, Christine B.; Bedem, Henry van den [Joint Center for Structural Genomics, http://www.jcsg.org (US); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (US); Weekes, Dana [Joint Center for Structural Genomics, http://www.jcsg.org (US); Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA (US); Wooten, Tiffany [Joint Center for Structural Genomics, http://www.jcsg.org (US); Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA (US); Xu, Qingping [Joint Center for Structural Genomics, http://www.jcsg.org (US); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (US); Hodgson, Keith O. [Joint Center for Structural Genomics, http://www.jcsg.org (US); Photon Science, SLAC National Accelerator Laboratory, Menlo Park, CA (US); Wooley, John [Joint Center for Structural Genomics, http://www.jcsg.org (US); Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA (US); Elsliger, Marc-André [Joint Center for Structural Genomics, http://www.jcsg.org (US); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (US); Deacon, Ashley M. [Joint Center for Structural Genomics, http://www.jcsg.org (US); Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA (US); Godzik, Adam [Joint Center for Structural Genomics, http://www.jcsg.org (US); Center for Research in Biological Systems, University of California, San Diego, La Jolla, CA (US); Program on Bioinformatics and Systems Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA (US); Lesley, Scott A. [Joint Center for Structural Genomics, http://www.jcsg.org (US); Protein Sciences Department, Genomics Institute of the Novartis Research Foundation, San Diego, CA (US); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (US); Wilson, Ian A., E-mail: wilson@scripps.edu [Joint Center for Structural Genomics, http://www.jcsg.org (US); Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA (US)

    2010-10-01

    The crystal structure of BT2081 from B. thetaiotaomicron reveals a two-domain protein with a putative carbohydrate-binding site in the C-terminal domain. BT2081 from Bacteroides thetaiotaomicron (GenBank accession code NP-810994.1) is a member of a novel protein family consisting of over 160 members, most of which are found in the different classes of Bacteroidetes. Genome-context analysis lends support to the involvement of this family in carbohydrate metabolism, which plays a key role in B. thetaiotaomicron as a predominant bacterial symbiont in the human distal gut microbiome. The crystal structure of BT2081 at 2.05 Å resolution represents the first structure from this new protein family. BT2081 consists of an N-terminal domain, which adopts a β-sandwich immunoglobulin-like fold, and a larger C-terminal domain with a β-sandwich jelly-roll fold. Structural analyses reveal that both domains are similar to those found in various carbohydrate-active enzymes. The C-terminal β-jelly-roll domain contains a potential carbohydrate-binding site that is highly conserved among BT2081 homologs and is situated in the same location as the carbohydrate-binding sites that are found in structurally similar glycoside hydrolases (GHs). However, in BT2081 this site is partially occluded by surrounding loops, which results in a deep solvent-accessible pocket rather than a shallower solvent-exposed cleft.

  5. Structure of Bacteroides thetaiotaomicron BT2081 at 2.05 Å resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism

    International Nuclear Information System (INIS)

    Yeh, Andrew P.; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Bakolitsa, Constantina; Cai, Xiaohui; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Chiu, Michelle; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Ellrott, Kyle; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Kumar, Abhinav; Lam, Winnie W.; Marciano, David; McMullan, Daniel; Miller, Mitchell D.; Morse, Andrew T.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Puckett, Christina; Reyes, Ron; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Wooten, Tiffany; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The crystal structure of BT2081 from B. thetaiotaomicron reveals a two-domain protein with a putative carbohydrate-binding site in the C-terminal domain. BT2081 from Bacteroides thetaiotaomicron (GenBank accession code NP-810994.1) is a member of a novel protein family consisting of over 160 members, most of which are found in the different classes of Bacteroidetes. Genome-context analysis lends support to the involvement of this family in carbohydrate metabolism, which plays a key role in B. thetaiotaomicron as a predominant bacterial symbiont in the human distal gut microbiome. The crystal structure of BT2081 at 2.05 Å resolution represents the first structure from this new protein family. BT2081 consists of an N-terminal domain, which adopts a β-sandwich immunoglobulin-like fold, and a larger C-terminal domain with a β-sandwich jelly-roll fold. Structural analyses reveal that both domains are similar to those found in various carbohydrate-active enzymes. The C-terminal β-jelly-roll domain contains a potential carbohydrate-binding site that is highly conserved among BT2081 homologs and is situated in the same location as the carbohydrate-binding sites that are found in structurally similar glycoside hydrolases (GHs). However, in BT2081 this site is partially occluded by surrounding loops, which results in a deep solvent-accessible pocket rather than a shallower solvent-exposed cleft

  6. 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.

  7. 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.

  8. 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.

  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. Epilepsy and astrocyte energy metabolism.

    Science.gov (United States)

    Boison, Detlev; Steinhäuser, Christian

    2018-06-01

    Epilepsy is a complex neurological syndrome characterized by neuronal hyperexcitability and sudden, synchronized electrical discharges that can manifest as seizures. It is now increasingly recognized that impaired astrocyte function and energy homeostasis play key roles in the pathogenesis of epilepsy. Excessive neuronal discharges can only happen, if adequate energy sources are made available to neurons. Conversely, energy depletion during seizures is an endogenous mechanism of seizure termination. Astrocytes control neuronal energy homeostasis through neurometabolic coupling. In this review, we will discuss how astrocyte dysfunction in epilepsy leads to distortion of key metabolic and biochemical mechanisms. Dysfunctional glutamate metabolism in astrocytes can directly contribute to neuronal hyperexcitability. Closure of astrocyte intercellular gap junction coupling as observed early during epileptogenesis limits activity-dependent trafficking of energy metabolites, but also impairs clearance of the extracellular space from accumulation of K + and glutamate. Dysfunctional astrocytes also increase the metabolism of adenosine, a metabolic product of ATP degradation that broadly inhibits energy-consuming processes as an evolutionary adaptation to conserve energy. Due to the critical role of astroglial energy homeostasis in the control of neuronal excitability, metabolic therapeutic approaches that prevent the utilization of glucose might represent a potent antiepileptic strategy. In particular, high fat low carbohydrate "ketogenic diets" as well as inhibitors of glycolysis and lactate metabolism are of growing interest for the therapy of epilepsy. © 2017 Wiley Periodicals, Inc.

  12. 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

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. 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.

  18. 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.

  19. The limits of adaptation of functional protein synthesis to severe undernutrition

    International Nuclear Information System (INIS)

    Forrester, T.; Jahoor, F.; Reeds, P.

    1996-01-01

    This project was designed to investigate the limits of adaptation of protein metabolism in the stree of severe childhood malnutrition, representing as it does chronic dietary insufficiency of macronutrients and superimposed infection. The tasks included measurement of concentrations and rates of synthesis of nutrient transport proteins and hepatic acute phase proteins inseverely malnourished children during their acute illness and a recovery

  20. 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

  1. 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...

  2. 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...

  3. 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

  4. Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

    Directory of Open Access Journals (Sweden)

    Laura ePaixão

    2015-10-01

    Full Text Available Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonised by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonisation to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc on this response at the transcriptional, physiological and metabolic levels. Galactose (Gal, N-acetylglucosamine (GlcNAc and mannose (Man affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s was readily consumed and elicited a metabolic shift towards a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome. In central carbon metabolism (most represented category, Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

  5. Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism.

    Science.gov (United States)

    Paixão, Laura; Caldas, José; Kloosterman, Tomas G; Kuipers, Oscar P; Vinga, Susana; Neves, Ana R

    2015-01-01

    Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo (13)C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence.

  6. 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

  7. Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism

    International Nuclear Information System (INIS)

    Bakolitsa, Constantina; Kumar, Abhinav; Jin, Kevin K.; McMullan, Daniel; Krishna, S. Sri; Miller, Mitchell D.; Abdubek, Polat; Acosta, Claire; Astakhova, Tamara; Axelrod, Herbert L.; Burra, Prasad; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Elias, Ylva; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Grzechnik, Slawomir K.; Han, Gye Won; Jaroszewski, Lukasz; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Marciano, David; Morse, Andrew T.; Murphy, Kevin D.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Trout, Christina V.; Bedem, Henry van den; Weekes, Dana; White, Aprilfawn; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-Andre; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    Structures of the first representatives of PF06684 (DUF1185) reveal a Bacillus chorismate mutase-like fold with a potential role in amino-acid synthesis. The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis

  8. 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

  9. 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.

  10. Kidney function in obese adolescents with or without metabolic syndrome in a nationally-representative sample of pediatric population: First report from the Middle East and North Africa: The CASPIAN-III Study

    Directory of Open Access Journals (Sweden)

    Roya Kelishadi

    2013-01-01

    Full Text Available Background : Obesity in accordance with metabolic syndrome (MetS confronts populations at the higher risk of morbidity and mortality of chronic diseases including, chronic kidney diseases (CKD. The renal complication of obesity and MetS has been less debated in young adolescents. The objective of this study was to assess the kidney function in obese adolescents with or without MetS. Materials and Methods: The data used in this study were collected as part of a national study entitled Childhood and Adolescence Surveillance and Prevention of Adult Non-communicable disease Study. The present study was conducted on a sub-sample of 113 obese adolescents (body mass index >95 th percentile aged between 10 years and 16 years selected by convenient sampling from the whole population studied. Anthropometric indexes and blood pressure were examined. A 12-h fasting serum was obtained for each participant to measure blood glucose, lipid profile, quantitative C-reactive protein (hs-CRP, Cystatin-c, urea, and creatinine. Fasting spot urine was collected to determine microalbumin and creatinine. Based on the study findings, participants were assigned into two groups with and without MetS. Results: The mean of microalbuminuria was in similar ranges in two groups and while the mean glomerular filtration rate (GFR calculated by Bokenkamp′s, updated and combined Schwartz′s formulas were significantly lower in MetS + obese group in comparison with obese group. The similar result was not achieved by Filler′s formula. Among MetS components, waist circumference had a correlation with hs-CRP ( P = 0.04; r = 0.15. GFR was calculated based on the Schwartz formula and Cystatin-c formulas had no significant correlation with any MetS components. Conclusion: Our findings suggest that MetS can increase the risk of kidney dysfunction in obese adolescents. More studies are suggested in this regard in the pediatric population.

  11. List of Accredited Representatives

    Data.gov (United States)

    Department of Veterans Affairs — VA accreditation is for the sole purpose of providing representation services to claimants before VA and does not imply that a representative is qualified to provide...

  12. 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

  13. 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.

  14. Representing vision and blindness.

    Science.gov (United States)

    Ray, Patrick L; Cox, Alexander P; Jensen, Mark; Allen, Travis; Duncan, William; Diehl, Alexander D

    2016-01-01

    There have been relatively few attempts to represent vision or blindness ontologically. This is unsurprising as the related phenomena of sight and blindness are difficult to represent ontologically for a variety of reasons. Blindness has escaped ontological capture at least in part because: blindness or the employment of the term 'blindness' seems to vary from context to context, blindness can present in a myriad of types and degrees, and there is no precedent for representing complex phenomena such as blindness. We explore current attempts to represent vision or blindness, and show how these attempts fail at representing subtypes of blindness (viz., color blindness, flash blindness, and inattentional blindness). We examine the results found through a review of current attempts and identify where they have failed. By analyzing our test cases of different types of blindness along with the strengths and weaknesses of previous attempts, we have identified the general features of blindness and vision. We propose an ontological solution to represent vision and blindness, which capitalizes on resources afforded to one who utilizes the Basic Formal Ontology as an upper-level ontology. The solution we propose here involves specifying the trigger conditions of a disposition as well as the processes that realize that disposition. Once these are specified we can characterize vision as a function that is realized by certain (in this case) biological processes under a range of triggering conditions. When the range of conditions under which the processes can be realized are reduced beyond a certain threshold, we are able to say that blindness is present. We characterize vision as a function that is realized as a seeing process and blindness as a reduction in the conditions under which the sight function is realized. This solution is desirable because it leverages current features of a major upper-level ontology, accurately captures the phenomenon of blindness, and can be

  15. Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

    OpenAIRE

    Apostolos Chatzitomaris; Rudolf Hoermann; John E. Midgley; Steffen Hering; Aline Urban; Barbara Dietrich; Assjana Abood; Harald H. Klein; Harald H. Klein; Johannes W. Dietrich; Johannes W. Dietrich

    2017-01-01

    The hypothalamus–pituitary–thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy, metabolic syndrome, and adaptation to cold, produces a nearly opposite phenotype of predictive plasticity. The non-thyroidal illness syndrome (NTI...

  16. Uncertainty in adaptive capacity

    International Nuclear Information System (INIS)

    Neil Adger, W.; Vincent, K.

    2005-01-01

    The capacity to adapt is a critical element of the process of adaptation: it is the vector of resources that represent the asset base from which adaptation actions can be made. Adaptive capacity can in theory be identified and measured at various scales, from the individual to the nation. The assessment of uncertainty within such measures comes from the contested knowledge domain and theories surrounding the nature of the determinants of adaptive capacity and the human action of adaptation. While generic adaptive capacity at the national level, for example, is often postulated as being dependent on health, governance and political rights, and literacy, and economic well-being, the determinants of these variables at national levels are not widely understood. We outline the nature of this uncertainty for the major elements of adaptive capacity and illustrate these issues with the example of a social vulnerability index for countries in Africa. (authors)

  17. 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

  18. 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...

  19. 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

  20. Representing Color Ensembles.

    Science.gov (United States)

    Chetverikov, Andrey; Campana, Gianluca; Kristjánsson, Árni

    2017-10-01

    Colors are rarely uniform, yet little is known about how people represent color distributions. We introduce a new method for studying color ensembles based on intertrial learning in visual search. Participants looked for an oddly colored diamond among diamonds with colors taken from either uniform or Gaussian color distributions. On test trials, the targets had various distances in feature space from the mean of the preceding distractor color distribution. Targets on test trials therefore served as probes into probabilistic representations of distractor colors. Test-trial response times revealed a striking similarity between the physical distribution of colors and their internal representations. The results demonstrate that the visual system represents color ensembles in a more detailed way than previously thought, coding not only mean and variance but, most surprisingly, the actual shape (uniform or Gaussian) of the distribution of colors in the environment.

  1. 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

  2. METHOD OF ADAPTIVE MAGNETOTHERAPY

    OpenAIRE

    Rudyk, Valentine Yu.; Tereshchenko, Mykola F.; Rudyk, Tatiana A.

    2016-01-01

    Practical realization of adaptive control in magnetotherapy apparatus acquires an actual importance on the modern stage of development of magnetotherapy.The structural scheme of method of adaptive impulsive magnetotherapy and algorithm of adaptive control of feed-back signal during procedure of magnetotherapy is represented.A feed-back in magnetotherapy complex will be realized with control of magnetic induction and analysis of man's physiological indexes (temperature, pulse, blood prassure, ...

  3. The energy metabolism of megacities

    International Nuclear Information System (INIS)

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

    2017-01-01

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

  4. Adaptive Wavelet Transforms

    Energy Technology Data Exchange (ETDEWEB)

    Szu, H.; Hsu, C. [Univ. of Southwestern Louisiana, Lafayette, LA (United States)

    1996-12-31

    Human sensors systems (HSS) may be approximately described as an adaptive or self-learning version of the Wavelet Transforms (WT) that are capable to learn from several input-output associative pairs of suitable transform mother wavelets. Such an Adaptive WT (AWT) is a redundant combination of mother wavelets to either represent or classify inputs.

  5. 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.

  6. OSMOSE experiment representativity studies.

    Energy Technology Data Exchange (ETDEWEB)

    Aliberti, G.; Klann, R.; Nuclear Engineering Division

    2007-10-10

    The OSMOSE program aims at improving the neutronic predictions of advanced nuclear fuels through measurements in the MINERVE facility at the CEA-Cadarache (France) on samples containing the following separated actinides: Th-232, U-233, U-234, U-235, U-236, U-238, Np-237, Pu-238, Pu-239, Pu-240, Pu-241, Pu-242, Am-241, Am-243, Cm-244 and Cm-245. The goal of the experimental measurements is to produce a database of reactivity-worth measurements in different neutron spectra for the separated heavy nuclides. This database can then be used as a benchmark for integral reactivity-worth measurements to verify and validate reactor analysis codes and integral cross-section values for the isotopes tested. In particular, the OSMOSE experimental program will produce very accurate sample reactivity-worth measurements for a series of actinides in various spectra, from very thermalized to very fast. The objective of the analytical program is to make use of the experimental data to establish deficiencies in the basic nuclear data libraries, identify their origins, and provide guidelines for nuclear data improvements in coordination with international programs. To achieve the proposed goals, seven different neutron spectra can be created in the MINERVE facility: UO2 dissolved in water (representative of over-moderated LWR systems), UO2 matrix in water (representative of LWRs), a mixed oxide fuel matrix, two thermal spectra containing large epithermal components (representative of under-moderated reactors), a moderated fast spectrum (representative of fast reactors which have some slowing down in moderators such as lead-bismuth or sodium), and a very hard spectrum (representative of fast reactors with little moderation from reactor coolant). The different spectra are achieved by changing the experimental lattice within the MINERVE reactor. The experimental lattice is the replaceable central part of MINERVE, which establishes the spectrum at the sample location. This configuration

  7. Tracking the origins of Yakutian horses and the genetic basis for their fast adaptation to subarctic environments

    DEFF Research Database (Denmark)

    Librado, Pablo; Der Sarkissian, Clio; Ermini, Luca

    2015-01-01

    , extremely hairy winter coats, and acute seasonal differences in metabolic activities. The evolutionary origins of Yakutian horses and the genetic basis of their adaptations remain, however, contentious. Here, we present the complete genomes of nine present-day Yakutian horses and two ancient specimens......, likely due to the comparatively limited standing variation within gene bodies at the time the population was founded. Genes involved in hair development, body size, and metabolic and hormone signaling pathways represent an essential part of the Yakutian horse adaptive genetic toolkit. Finally, we find...

  8. Representing distance, consuming distance

    DEFF Research Database (Denmark)

    Larsen, Gunvor Riber

    Title: Representing Distance, Consuming Distance Abstract: Distance is a condition for corporeal and virtual mobilities, for desired and actual travel, but yet it has received relatively little attention as a theoretical entity in its own right. Understandings of and assumptions about distance...... are being consumed in the contemporary society, in the same way as places, media, cultures and status are being consumed (Urry 1995, Featherstone 2007). An exploration of distance and its representations through contemporary consumption theory could expose what role distance plays in forming...

  9. Representing AIDS in Comics.

    Science.gov (United States)

    Czerwiec, M K

    2018-02-01

    Matthew P. McAllister wrote: "Comic books can and have contributed positively to the discourse about AIDS: images that encourage true education, understanding and compassion can help cope with a biomedical condition which has more than a biomedical relevance" [1]. With this in mind, I combined a 23-narrator oral history and my personal memoir about an inpatient Chicago AIDS hospital unit in my book, Taking Turns: Stories from HIV/AIDS Care Unit 371. In doing so, I built upon the existing rich history of HIV/AIDS in comics, which this article will briefly describe. Although not a comprehensive review of the intersection of AIDS and comics, the book is a tour through influences that proved useful to me. In addition, in making my book, I faced a distinct ethical issue with regard to representing patient experiences with HIV/AIDS, and I describe here how I addressed it. © 2018 American Medical Association. All Rights Reserved.

  10. Representative of the municipality

    International Nuclear Information System (INIS)

    Castellnou Barcelo, J.

    2007-01-01

    Full text of publication follows. The decommissioning of the Vandellos-I nuclear power plant was a big challenge for the host community of Vandellos i l'Hospitalet de l'Infant and the close-by region. Closing down of the facility resulted in a rise of unemployment and a decrease of municipal income. The public was concerned with three issues: safety, transparency and information about the decommissioning, and economic future. Therefore, from the very beginning, municipal governments entered into negotiations with ENRESA on socio-economic benefits, including local employment in dismantling activities, and other types of financial and non-financial compensation. The ADE business association, i.e. a network of business organisations was created that guided the allotment of work to local firms. To satisfy public demand, local municipalities focused on the triad of safety, dialogue and local development, considered the three 'pillars of trust'. A Municipal Monitoring Commission was created, made up of representatives of affected municipalities, the regional government, the ADE business association, trade unions, the local university, the NPP management and ENRESA to monitor the dismantling process and regularly inform the local public. Items that were handled by this Commission included: - Work process monitoring. - Workers. - Materials Control. - Conventional and radioactive or contaminated waste management. - Emanation waste management (liquid and gas) - Safety (training and accidents). - Surveillance (radiological and environmental: dust, noise). - Effects. - Fulfillment of agreed conditions. A number of communication tools and channels were used, e.g., public information meetings, an information centre, the municipal magazine, the municipal radio station, and meetings with representatives of the local press. Particularly innovative was the idea to ask academics from the University of Tarragona to help with 'translating' technical information into language that could

  11. On Representing Instance Changes in Adaptive Process Management Systems.

    NARCIS (Netherlands)

    Rinderle, S.B.; Kreher, U; Lauer, M.; Dadam, P.; Reichert, M.U.

    2006-01-01

    By separating the process logic from the application code process management systems (PMS) offer promising perspectives for automation and management of business processes. However, the added value of PMS strongly depends on their ability to support business process changes which can affect the

  12. 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

  13. 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.

  14. 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.

  15. 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

  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. Context-specific metabolic networks are consistent with experiments.

    Directory of Open Access Journals (Sweden)

    Scott A Becker

    2008-05-01

    Full Text Available Reconstructions of cellular metabolism are publicly available for a variety of different microorganisms and some mammalian genomes. To date, these reconstructions are "genome-scale" and strive to include all reactions implied by the genome annotation, as well as those with direct experimental evidence. Clearly, many of the reactions in a genome-scale reconstruction will not be active under particular conditions or in a particular cell type. Methods to tailor these comprehensive genome-scale reconstructions into context-specific networks will aid predictive in silico modeling for a particular situation. We present a method called Gene Inactivity Moderated by Metabolism and Expression (GIMME to achieve this goal. The GIMME algorithm uses quantitative gene expression data and one or more presupposed metabolic objectives to produce the context-specific reconstruction that is most consistent with the available data. Furthermore, the algorithm provides a quantitative inconsistency score indicating how consistent a set of gene expression data is with a particular metabolic objective. We show that this algorithm produces results consistent with biological experiments and intuition for adaptive evolution of bacteria, rational design of metabolic engineering strains, and human skeletal muscle cells. This work represents progress towards producing constraint-based models of metabolism that are specific to the conditions where the expression profiling data is available.

  20. 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

  1. Arab Knowledge Society: Who Represents the Arab World Online ...

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

    Arab Knowledge Society: Who Represents the Arab World Online? ... Wikipedia's culture of openness, extensive reuse and near ubiquity makes it an ideal place to ... IWRA/IDRC webinar on climate change and adaptive water management.

  2. 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 ...

  3. 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.

  4. 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

  5. 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

  6. Metabolic disorders in menopause

    Directory of Open Access Journals (Sweden)

    Grzegorz Stachowiak

    2015-04-01

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

  7. Genomic islands predict functional adaptation in marine actinobacteria

    Energy Technology Data Exchange (ETDEWEB)

    Penn, Kevin; Jenkins, Caroline; Nett, Markus; Udwary, Daniel; Gontang, Erin; McGlinchey, Ryan; Foster, Brian; Lapidus, Alla; Podell, Sheila; Allen, Eric; Moore, Bradley; Jensen, Paul

    2009-04-01

    Linking functional traits to bacterial phylogeny remains a fundamental but elusive goal of microbial ecology 1. Without this information, it becomes impossible to resolve meaningful units of diversity and the mechanisms by which bacteria interact with each other and adapt to environmental change. Ecological adaptations among bacterial populations have been linked to genomic islands, strain-specific regions of DNA that house functionally adaptive traits 2. In the case of environmental bacteria, these traits are largely inferred from bioinformatic or gene expression analyses 2, thus leaving few examples in which the functions of island genes have been experimentally characterized. Here we report the complete genome sequences of Salinispora tropica and S. arenicola, the first cultured, obligate marine Actinobacteria 3. These two species inhabit benthic marine environments and dedicate 8-10percent of their genomes to the biosynthesis of secondary metabolites. Despite a close phylogenetic relationship, 25 of 37 secondary metabolic pathways are species-specific and located within 21 genomic islands, thus providing new evidence linking secondary metabolism to ecological adaptation. Species-specific differences are also observed in CRISPR sequences, suggesting that variations in phage immunity provide fitness advantages that contribute to the cosmopolitan distribution of S. arenicola 4. The two Salinispora genomes have evolved by complex processes that include the duplication and acquisition of secondary metabolite genes, the products of which provide immediate opportunities for molecular diversification and ecological adaptation. Evidence that secondary metabolic pathways are exchanged by Horizontal Gene Transfer (HGT) yet are fixed among globally distributed populations 5 supports a functional role for their products and suggests that pathway acquisition represents a previously unrecognized force driving bacterial diversification

  8. Rewiring carbohydrate catabolism differentially affects survival of pancreatic cancer cell lines with diverse metabolic profiles

    Science.gov (United States)

    Tataranni, Tiziana; Agriesti, Francesca; Ruggieri, Vitalba; Mazzoccoli, Carmela; Simeon, Vittorio; Laurenzana, Ilaria; Scrima, Rosella; Pazienza, Valerio; Capitanio, Nazzareno; Piccoli, Claudia

    2017-01-01

    An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient's prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1. Both cell lines were challenged to rewire their metabolism by substituting glucose with galactose as carbon source, a condition inhibiting the glycolytic flux and fostering full oxidation of the sugar carbons. The obtained data strikingly show that the mitochondrial respiration-impaired-BXPC-3 cell line was unable to sustain the metabolic adaptation required by glucose deprivation/substitution, thereby resulting in a G2\\M cell cycle shift, unbalance of the redox homeostasis, apoptosis induction. Conversely, the mitochondrial respiration-competent-PANC-1 cell line did not show clear evidence of cell sufferance. Our findings provide a strong rationale to candidate metabolism as a promising target for cancer therapy. Defining the metabolic features at time of pancreatic cancer diagnosis and likely of other tumors, appears to be crucial to predict the responsiveness to therapeutic approaches or coadjuvant interventions affecting metabolism. PMID:28476035

  9. 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.

  10. The anaerobic phototrophic metabolism of 3-chlorobenzoate by Rhodopseudomonas palustris

    Energy Technology Data Exchange (ETDEWEB)

    Kamal, V S

    1992-10-09

    The degradation of chlorinated aromatic compounds by anaerobic bacteria is now known to be an important mechanism of bioremediation. In an experimental study, a mixed phototrophic culture was found to metabolize 3-chlorobenzoate in the presence of benzoate following adaptation on a benzoate and 3-chlorobenzoate medium for 7 weeks. The dominant bacterial isolate was identified as Rhodopseudomonas palustris. Radioisotopic studies showed [sup 14]C-3-chlorobenzoate was converted by the isolate to [sup 14]CO[sub 2] and cell biomass in the absence of oxygen and in the presence of a cosubstrate red light. Cyclohexane carboxylate was able to replace the cosubstrate, benzoate. The isolate also metabolized 3-chlorobenzoate in the presence of pimelic acid, sodium acetate, and sodium succinate; however, the metabolic rate was reduced. Gas chromatography mass spectrometry and high pressure liquid chromatography indicated the intracellular presence of 3-chlorobenzoate and benzoyl-CoA. Cell-free extracts produced benzoate and benzoyl-CoA. A probable route of 3-chlorobenzoate metabolism via dehalogenation followed by steps similar to the benzoate reductive ring fission pathway is suggested. Comparison of kinetic coefficients showed a higher affinity of the isolate for benzoate. Isolates from representative samples of various freshwater and wastewater ecosystems indicated widespread ecological distribution of R. palustris and the common occurrence of the 3-chlorobenzoate metabolic phenotype. R. palustris was found to grow in mixed anaerobic cultures and retained its 3-chlorobenzoate degradation property. 91 refs., 25 figs., 14 tabs.

  11. 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)

  12. The metabolic syndrome among Danish seafarers

    DEFF Research Database (Denmark)

    Jepsen, Jørgen Riis; Rasmussen, Hanna Barbara

    2016-01-01

    Background: The metabolic syndrome (MS) represents a cluster of risk factors related to insulin resistance. Metabolic syndrome is a strong risk factor for chronic metabolic and cardiovascular diseases and is related to nutritional factors, sleep patterns, work-related stress, fatigue, and physical...

  13. Preferential attachment in the evolution of metabolic networks

    Directory of Open Access Journals (Sweden)

    Elofsson Arne

    2005-11-01

    Full Text Available Abstract Background Many biological networks show some characteristics of scale-free networks. Scale-free networks can evolve through preferential attachment where new nodes are preferentially attached to well connected nodes. In networks which have evolved through preferential attachment older nodes should have a higher average connectivity than younger nodes. Here we have investigated preferential attachment in the context of metabolic networks. Results The connectivities of the enzymes in the metabolic network of Escherichia coli were determined and representatives for these enzymes were located in 11 eukaryotes, 17 archaea and 46 bacteria. E. coli enzymes which have representatives in eukaryotes have a higher average connectivity while enzymes which are represented only in the prokaryotes, and especially the enzymes only present in βγ-proteobacteria, have lower connectivities than expected by chance. Interestingly, the enzymes which have been proposed as candidates for horizontal gene transfer have a higher average connectivity than the other enzymes. Furthermore, It was found that new edges are added to the highly connected enzymes at a faster rate than to enzymes with low connectivities which is consistent with preferential attachment. Conclusion Here, we have found indications of preferential attachment in the metabolic network of E. coli. A possible biological explanation for preferential attachment growth of metabolic networks is that novel enzymes created through gene duplication maintain some of the compounds involved in the original reaction, throughout its future evolution. In addition, we found that enzymes which are candidates for horizontal gene transfer have a higher average connectivity than other enzymes. This indicates that while new enzymes are attached preferentially to highly connected enzymes, these highly connected enzymes have sometimes been introduced into the E. coli genome by horizontal gene transfer. We speculate

  14. 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...

  15. 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 ...

  16. Effect of metabolic syndrome on mitsugumin 53 expression and function.

    Directory of Open Access Journals (Sweden)

    Hanley Ma

    Full Text Available Metabolic syndrome is a cluster of risk factors, such as obesity, insulin resistance, and hyperlipidemia that increases the individual's likelihood of developing cardiovascular diseases. Patients inflicted with metabolic disorders also suffer from tissue repair defect. Mitsugumin 53 (MG53 is a protein essential to cellular membrane repair. It facilitates the nucleation of intracellular vesicles to sites of membrane disruption to create repair patches, contributing to the regenerative capacity of skeletal and cardiac muscle tissues upon injury. Since individuals suffering from metabolic syndrome possess tissue regeneration deficiency and MG53 plays a crucial role in restoring membrane integrity, we studied MG53 activity in mice models exhibiting metabolic disorders induced by a 6 month high-fat diet (HFD feeding. Western blotting showed that MG53 expression is not altered within the skeletal and cardiac muscles of mice with metabolic syndrome. Rather, we found that MG53 levels in blood circulation were actually reduced. This data directly contradicts findings presented by Song et. al that indict MG53 as a causative factor for metabolic syndrome (Nature 494, 375-379. The diminished MG53 serum level observed may contribute to the inadequate tissue repair aptitude exhibited by diabetic patients. Furthermore, immunohistochemical analyses reveal that skeletal muscle fibers of mice with metabolic disorders experience localization of subcellular MG53 around mitochondria. This clustering may represent an adaptive response to oxidative stress resulting from HFD feeding and may implicate MG53 as a guardian to protect damaged mitochondria. Therapeutic approaches that elevate MG53 expression in serum circulation may be a novel method to treat the degenerative tissue repair function of diabetic patients.

  17. Metabolic and functional connectivity changes in mal de debarquement syndrome.

    Directory of Open Access Journals (Sweden)

    Yoon-Hee Cha

    Full Text Available Individuals with mal de debarquement syndrome (MdDS experience a chronic illusion of self-motion triggered by prolonged exposure to passive motion, such as from sea or air travel. The experience is one of rocking dizziness similar to when the individual was originally on the motion trigger such as a boat or airplane. MdDS represents a prolonged version of a normal phenomenon familiar to most individuals but which persists for months or years in others. It represents a natural example of the neuroplasticity of motion adaptation. However, the localization of where that motion adaptation occurs is unknown. Our goal was to localize metabolic and functional connectivity changes associated with persistent MdDS.Twenty subjects with MdDS lasting a median duration of 17.5 months were compared to 20 normal controls with (18F FDG PET and resting state fMRI. Resting state metabolism and functional connectivity were calculated using age, grey matter volume, and mood and anxiety scores as nuisance covariates.MdDS subjects showed increased metabolism in the left entorhinal cortex and amygdala (z>3.3. Areas of relative hypometabolism included the left superior medial gyrus, left middle frontal gyrus, right amygdala, right insula, and clusters in the left superior, middle, and inferior temporal gyri. MdDS subjects showed increased connectivity between the entorhinal cortex/amygdala cluster and posterior visual and vestibular processing areas including middle temporal gyrus, motion sensitive area MT/V5, superior parietal lobule, and primary visual cortex, while showing decreased connectivity to multiple prefrontal areas.These data show an association between resting state metabolic activity and functional connectivity between the entorhinal cortex and amygdala in a human disorder of abnormal motion perception. We propose a model for how these biological substrates can allow a limited period of motion exposure to lead to chronic perceptions of self-motion.

  18. 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.

  19. 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...

  20. 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

  1. [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.

  2. 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.

  3. 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....

  4. 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.

  5. 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.

  6. 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...

  7. 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 ...

  8. 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-.

  9. Metabolomic analysis reveals key metabolites related to the rapid adaptation of Saccharomyce cerevisiae to multiple inhibitors of furfural, acetic acid, and phenol.

    Science.gov (United States)

    Wang, Xin; Li, Bing-Zhi; Ding, Ming-Zhu; Zhang, Wei-Wen; Yuan, Ying-Jin

    2013-03-01

    During hydrolysis of lignocellulosic biomass, a broad range of inhibitors are generated, which interfere with yeast growth and bioethanol production. In order to improve the strain tolerance to multiple inhibitors--acetic acid, furfural, and phenol (three representative lignocellulose-derived inhibitors) and uncover the underlying tolerant mechanism, an adaptation experiment was performed in which the industrial Saccharomyces cerevisiae was cultivated repeatedly in a medium containing multiple inhibitors. The adaptation occurred quickly, accompanied with distinct increase in growth rate, glucose utilization rate, furfural metabolism rate, and ethanol yield, only after the first transfer. A similar rapid adaptation was also observed for the lab strains of BY4742 and BY4743. The metabolomic analysis was employed to investigate the responses of the industrial S. cereviaise to three inhibitors during the adaptation. The results showed that higher levels of 2-furoic acid, 2, 3-butanediol, intermediates in glycolytic pathway, and amino acids derived from glycolysis, were discovered in the adapted strains, suggesting that enhanced metabolic activity in these pathways may relate to resistance against inhibitors. Additionally, through single-gene knockouts, several genes related to alanine metabolism, GABA shunt, and glycerol metabolism were verified to be crucial for the resistance to multiple inhibitors. This study provides new insights into the tolerance mechanism against multiple inhibitors, and guides for the improvement of tolerant ethanologenic yeast strains for lignocellulose-bioethanol fermentation.

  10. Modeling antibiotic and cytotoxic effects of the dimeric isoquinoline IQ-143 on metabolism and its regulation in Staphylococcus aureus, Staphylococcus epidermidis and human cells

    Science.gov (United States)

    2011-01-01

    Background Xenobiotics represent an environmental stress and as such are a source for antibiotics, including the isoquinoline (IQ) compound IQ-143. Here, we demonstrate the utility of complementary analysis of both host and pathogen datasets in assessing bacterial adaptation to IQ-143, a synthetic analog of the novel type N,C-coupled naphthyl-isoquinoline alkaloid ancisheynine. Results Metabolite measurements, gene expression data and functional assays were combined with metabolic modeling to assess the effects of IQ-143 on Staphylococcus aureus, Staphylococcus epidermidis and human cell lines, as a potential paradigm for novel antibiotics. Genome annotation and PCR validation identified novel enzymes in the primary metabolism of staphylococci. Gene expression response analysis and metabolic modeling demonstrated the adaptation of enzymes to IQ-143, including those not affected by significant gene expression changes. At lower concentrations, IQ-143 was bacteriostatic, and at higher concentrations bactericidal, while the analysis suggested that the mode of action was a direct interference in nucleotide and energy metabolism. Experiments in human cell lines supported the conclusions from pathway modeling and found that IQ-143 had low cytotoxicity. Conclusions The data suggest that IQ-143 is a promising lead compound for antibiotic therapy against staphylococci. The combination of gene expression and metabolite analyses with in silico modeling of metabolite pathways allowed us to study metabolic adaptations in detail and can be used for the evaluation of metabolic effects of other xenobiotics. PMID:21418624

  11. Adapting biomodulatory strategies for treatment in new contexts: pancreatic and oral cancers (Conference Presentation)

    Science.gov (United States)

    Anbil, Sriram R.; Rizvi, Imran; Khan, Amjad P.; Celli, Jonathan P.; Maytin, Edward V.; Hasan, Tayyaba

    2016-03-01

    Biomodulation of cancer cell metabolism represents a promising approach to overcome tumor heterogeneity and poor selectivity, which contribute significantly to treatment resistance. To date, several studies have demonstrated that modulation of cell metabolism including the heme synthesis pathway serves as an elegant approach to improve the efficacy of aminolevulinic acid (ALA) based photodynamic therapy (PDT). However, the ability of biomodulation-enhanced PDT to improve outcomes in low resource settings and to address challenges in treating lethal tumors with exogenous photosensitizers remains underexplored. The ability of vitamin D or methotrexate to enhance PDT efficacy in a carcinogen-induced hamster cheek pouch model of oral squamous cell carcinoma and in 3D cell-based models for pancreatic ductal adenocarcinoma is evaluated. Challenges associated with adapting PDT regimens to low resource settings, understanding the effects of biomodulatory agents on the metabolism of cancer cells, and the differential effects of biomodulatory agents on tumor and stromal cells will be discussed.

  12. Identical metabolic rate and thermal conductance in Rock Sandpiper (Calidris ptilocnemis) subspecies with contrasting nonbreeding life histories

    Science.gov (United States)

    Ruthrauff, Daniel R.; Dekinga, Anne; Gill, Robert E.; Piersma, Theunis

    2013-01-01

    Closely related species or subspecies can exhibit metabolic differences that reflect site-specific environmental conditions. Whether such differences represent fixed traits or flexible adjustments to local conditions, however, is difficult to predict across taxa. The nominate race of Rock Sandpiper (Calidris ptilocnemis) exhibits the most northerly nonbreeding distribution of any shorebird in the North Pacific, being common during winter in cold, dark locations as far north as upper Cook Inlet, Alaska (61°N). By contrast, the tschuktschorum subspecies migrates to sites ranging from about 59°N to more benign locations as far south as ~37°N. These distributional extremes exert contrasting energetic demands, and we measured common metabolic parameters in the two subspecies held under identical laboratory conditions to determine whether differences in these parameters are reflected by their nonbreeding life histories. Basal metabolic rate and thermal conductance did not differ between subspecies, and the subspecies had a similar metabolic response to temperatures below their thermoneutral zone. Relatively low thermal conductance values may, however, reflect intrinsic metabolic adaptations to northerly latitudes. In the absence of differences in basic metabolic parameters, the two subspecies’ nonbreeding distributions will likely be more strongly influenced by adaptations to regional variation in ecological factors such as prey density, prey quality, and foraging habitat.

  13. Temporal Coordination of Carbohydrate Metabolism during Mosquito Reproduction.

    Directory of Open Access Journals (Sweden)

    Yuan Hou

    2015-07-01

    Full Text Available Hematophagous mosquitoes serve as vectors of multiple devastating human diseases, and many unique physiological features contribute to the incredible evolutionary success of these insects. These functions place high-energy demands on a reproducing female mosquito, and carbohydrate metabolism (CM must be synchronized with these needs. Functional analysis of metabolic gene profiling showed that major CM pathways, including glycolysis, glycogen and sugar metabolism, and citrate cycle, are dramatically repressed at post eclosion (PE stage in mosquito fat body followed by a sharply increase at post-blood meal (PBM stage, which were also verified by Real-time RT-PCR. Consistent to the change of transcript and protein level of CM genes, the level of glycogen, glucose and trehalose and other secondary metabolites are also periodically accumulated and degraded during the reproductive cycle respectively. Levels of triacylglycerols (TAG, which represent another important energy storage form in the mosquito fat body, followed a similar tendency. On the other hand, ATP, which is generated by catabolism of these secondary metabolites, showed an opposite trend. Additionally, we used RNA interference studies for the juvenile hormone and ecdysone receptors, Met and EcR, coupled with transcriptomics and metabolomics analyses to show that these hormone receptors function as major regulatory switches coordinating CM with the differing energy requirements of the female mosquito throughout its reproductive cycle. Our study demonstrates how, by metabolic reprogramming, a multicellular organism adapts to drastic and rapid functional changes.

  14. Genetic signatures of adaptation revealed from transcriptome sequencing of Arctic and red foxes.

    Science.gov (United States)

    Kumar, Vikas; Kutschera, Verena E; Nilsson, Maria A; Janke, Axel

    2015-08-07

    The genus Vulpes (true foxes) comprises numerous species that inhabit a wide range of habitats and climatic conditions, including one species, the Arctic fox (Vulpes lagopus) which is adapted to the arctic region. A close relative to the Arctic fox, the red fox (Vulpes vulpes), occurs in subarctic to subtropical habitats. To study the genetic basis of their adaptations to different environments, transcriptome sequences from two Arctic foxes and one red fox individual were generated and analyzed for signatures of positive selection. In addition, the data allowed for a phylogenetic analysis and divergence time estimate between the two fox species. The de novo assembly of reads resulted in more than 160,000 contigs/transcripts per individual. Approximately 17,000 homologous genes were identified using human and the non-redundant databases. Positive selection analyses revealed several genes involved in various metabolic and molecular processes such as energy metabolism, cardiac gene regulation, apoptosis and blood coagulation to be under positive selection in foxes. Branch site tests identified four genes to be under positive selection in the Arctic fox transcriptome, two of which are fat metabolism genes. In the red fox transcriptome eight genes are under positive selection, including molecular process genes, notably genes involved in ATP metabolism. Analysis of the three transcriptomes and five Sanger re-sequenced genes in additional individuals identified a lower genetic variability within Arctic foxes compared to red foxes, which is consistent with distribution range differences and demographic responses to past climatic fluctuations. A phylogenomic analysis estimated that the Arctic and red fox lineages diverged about three million years ago. Transcriptome data are an economic way to generate genomic resources for evolutionary studies. Despite not representing an entire genome, this transcriptome analysis identified numerous genes that are relevant to arctic

  15. 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

  16. UV light selectively coinduces supply pathways from primary metabolism and flavonoid secondary product formation in parsley

    Science.gov (United States)

    Logemann, Elke; Tavernaro, Annette; Schulz, Wolfgang; Somssich, Imre E.; Hahlbrock, Klaus

    2000-01-01

    The UV light-induced synthesis of UV-protective flavonoids diverts substantial amounts of substrates from primary metabolism into secondary product formation and thus causes major perturbations of the cellular homeostasis. Results from this study show that the mRNAs encoding representative enzymes from various supply pathways are coinduced in UV-irradiated parsley cells (Petroselinum crispum) with two mRNAs of flavonoid glycoside biosynthesis, encoding phenylalanine ammonia-lyase and chalcone synthase. Strong induction was observed for mRNAs encoding glucose 6-phosphate dehydrogenase (carbohydrate metabolism, providing substrates for the shikimate pathway), 3-deoxyarabinoheptulosonate 7-phosphate synthase (shikimate pathway, yielding phenylalanine), and acyl-CoA oxidase (fatty acid degradation, yielding acetyl-CoA), and moderate induction for an mRNA encoding S-adenosyl-homocysteine hydrolase (activated methyl cycle, yielding S-adenosyl-methionine for B-ring methylation). Ten arbitrarily selected mRNAs representing various unrelated metabolic activities remained unaffected. Comparative analysis of acyl-CoA oxidase and chalcone synthase with respect to mRNA expression modes and gene promoter structure and function revealed close similarities. These results indicate a fine-tuned regulatory network integrating those functionally related pathways of primary and secondary metabolism that are specifically required for protective adaptation to UV irradiation. Although the response of parsley cells to UV light is considerably broader than previously assumed, it contrasts greatly with the extensive metabolic reprogramming observed previously in elicitor-treated or fungus-infected cells. PMID:10677554

  17. Generally representative is generally representative: comment on Shuttleworth-Edwards.

    Science.gov (United States)

    Taylor, Nicola

    2016-10-01

    The aim of this paper is to provide comment on Shuttleworth-Edwards' criticism of the general population norms created for the South African adaptation of the WAIS-IV. In her criticism, she states that the norms are not applicable for any groups in South Africa, based on the fact that the norms were not stratified according to quality of education. A discussion of some of the key issues that impact on the creation of general population norms in the South African context is provided. Demographic characteristics such as education level, quality of education, urban and rural demarcations, and home language are all considered. While the utility of within-group norms is not denied, the adoption of these without reference to the general population is not advised. To recommend that practitioners simply dispense with the general population norm without evidence that it creates misclassification or does not function effectively for the intended population lacks scientific merit at the current time. The need for clinical studies and further predictive validity research using the South African adaptation of the WAIS-IV is crucial to demonstrate the continued utility of the test in the South African context. Additional reference groups will improve the amount of comparative information available for clinicians to be able to make better informed decisions for diagnosis, but the general population norms will be an important starting point in this process.

  18. Exercise training in metabolic myopathies

    DEFF Research Database (Denmark)

    Vissing, J

    2016-01-01

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

  19. Representative process sampling - in practice

    DEFF Research Database (Denmark)

    Esbensen, Kim; Friis-Pedersen, Hans Henrik; Julius, Lars Petersen

    2007-01-01

    Didactic data sets representing a range of real-world processes are used to illustrate "how to do" representative process sampling and process characterisation. The selected process data lead to diverse variogram expressions with different systematics (no range vs. important ranges; trends and....../or periodicity; different nugget effects and process variations ranging from less than one lag to full variogram lag). Variogram data analysis leads to a fundamental decomposition into 0-D sampling vs. 1-D process variances, based on the three principal variogram parameters: range, sill and nugget effect...

  20. Adaptation Insights

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

    Addressing Climate Change Adaptation in Africa through Participatory Action Research. A Regional Observatory ... while the average annual rainfall recorded between. 1968 and 1999 was .... the region of Thies. For sustainability reasons, the.

  1. Adaptation Stories

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

    By Reg'

    adaptation to climate change from various regions of the Sahel. Their .... This simple system, whose cost and maintenance were financially sustainable, brought ... method that enables him to learn from experience and save time, which he ...

  2. [Metabolic myopathies].

    Science.gov (United States)

    Papazian, Óscar; Rivas-Chacón, Rafael

    2013-09-06

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

  3. Marc Treib: Representing Landscape Architecture

    DEFF Research Database (Denmark)

    Braae, Ellen Marie

    2008-01-01

    The editor of Representing Landscape Architecture, Marc Treib, argues that there is good reason to evaluate the standard practices of representation that landscape architects have been using for so long. In the rush to the promised land of computer design these practices are now in danger of being...

  4. Does representative wind information exist?

    NARCIS (Netherlands)

    Wieringa, J.

    1996-01-01

    Representativity requirements are discussed for various wind data users. It is shown that most applications can be dealt with by using data from wind stations when these are made to conform with WMO specifications. Methods to achieve this WMO normalization are reviewed, giving minimum specifications

  5. OAS :: Member States : Permanent Representatives

    Science.gov (United States)

    Rights Actions against Corruption C Children Civil Registry Civil Society Contact Us Culture Cyber Barbados Belize Bolivia Brazil Canada Chile Colombia Costa Rica Cuba 1 Dominica (Commonwealth of) Dominican Gutierez Ambassador, Permanent Representative of Belize Diego Pary Rodríguez Bolivia Diego Pary Rodríguez

  6. Judgments of and by Representativeness

    Science.gov (United States)

    1981-05-15

    p. 4i). This hy- pothesis was studied in several contexts, including intuitive statisti- cal judgments and the prediction of professional choice (Kahneman... professional choice . Here, X is representative of M either because it is frequently associated with M (e.g., high fever commonly accompanies pneumonia

  7. WIPP facility representative program plan

    International Nuclear Information System (INIS)

    1994-01-01

    This plan describes the Department of Energy (DOE), Carlsbad Area Office (CAO) facility representative (FR) program at the Waste Isolation Pilot Plant (WIPP). It provides the following information: (1) FR and support organization authorities and responsibilities; (2) FR program requirements; and (3) FR training and qualification requirements

  8. Fasting-induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health.

    Science.gov (United States)

    Fuhrmeister, Jessica; Zota, Annika; Sijmonsma, Tjeerd P; Seibert, Oksana; Cıngır, Şahika; Schmidt, Kathrin; Vallon, Nicola; de Guia, Roldan M; Niopek, Katharina; Berriel Diaz, Mauricio; Maida, Adriano; Blüher, Matthias; Okun, Jürgen G; Herzig, Stephan; Rose, Adam J

    2016-06-01

    Recent studies have demonstrated that repeated short-term nutrient withdrawal (i.e. fasting) has pleiotropic actions to promote organismal health and longevity. Despite this, the molecular physiological mechanisms by which fasting is protective against metabolic disease are largely unknown. Here, we show that, metabolic control, particularly systemic and liver lipid metabolism, is aberrantly regulated in the fasted state in mouse models of metabolic dysfunction. Liver transcript assays between lean/healthy and obese/diabetic mice in fasted and fed states uncovered "growth arrest and DNA damage-inducible" GADD45β as a dysregulated gene transcript during fasting in several models of metabolic dysfunction including ageing, obesity/pre-diabetes and type 2 diabetes, in both mice and humans. Using whole-body knockout mice as well as liver/hepatocyte-specific gain- and loss-of-function strategies, we revealed a role for liver GADD45β in the coordination of liver fatty acid uptake, through cytoplasmic retention of FABP1, ultimately impacting obesity-driven hyperglycaemia. In summary, fasting stress-induced GADD45β represents a liver-specific molecular event promoting adaptive metabolic function. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  9. Human whole body cold adaptation.

    Science.gov (United States)

    Daanen, Hein A M; Van Marken Lichtenbelt, Wouter D

    2016-01-01

    Reviews on whole body human cold adaptation generally do not distinguish between population studies and dedicated acclimation studies, leading to confusing results. Population studies show that indigenous black Africans have reduced shivering thermogenesis in the cold and poor cold induced vasodilation in fingers and toes compared to Caucasians and Inuit. About 40,000 y after humans left Africa, natives in cold terrestrial areas seems to have developed not only behavioral adaptations, but also physiological adaptations to cold. Dedicated studies show that repeated whole body exposure of individual volunteers, mainly Caucasians, to severe cold results in reduced cold sensation but no major physiological changes. Repeated cold water immersion seems to slightly reduce metabolic heat production, while repeated exposure to milder cold conditions shows some increase in metabolic heat production, in particular non-shivering thermogenesis. In conclusion, human cold adaptation in the form of increased metabolism and insulation seems to have occurred during recent evolution in populations, but cannot be developed during a lifetime in cold conditions as encountered in temperate and arctic regions. Therefore, we mainly depend on our behavioral skills to live in and survive the cold.

  10. Is adaptation. Truly an adaptation? Is adaptation. Truly an adaptation?

    Directory of Open Access Journals (Sweden)

    Thais Flores Nogueira Diniz

    2008-04-01

    Full Text Available The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition, joined with the study of recycling, remaking, and every form of retelling. The film deals with the attempt by the scriptwriter Charles Kaufman, cast by Nicholas Cage, to adapt/translate a non-fictional book to the cinema, but ends up with a kind of film which is by no means what it intended to be: a film of action in the model of Hollywood productions. During the process of creation, Charles and his twin brother, Donald, undergo a series of adventures involving some real persons from the world of film, the author and the protagonist of the book, all of them turning into fictional characters in the film. In the film, adaptation then signifies something different from itstraditional meaning. The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition

  11. Nucleotide Metabolism

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  12. Burnout in Customer Service Representatives

    Directory of Open Access Journals (Sweden)

    Tariq Jalees

    2008-09-01

    Full Text Available The purpose and aim of this research was to (1 identify the factors that contributes towards job burnout in sales service representative (2 What are the relationships of these factors (3 To empirically test the relationships of the determinants relating to burnout in customer service representatives. Based on literature survey six different variables related to burnout were identified. The variables were (1 Emotional exhaustion.(2 Reduced personal accomplishment.(3 Job induced tension.(4 Job satisfaction.(5 Workload (6 Job satisfaction.Each of the variables contained 3 sub-variables. Five different hypotheses were developed and tested through techniques such as Z-test, F-test and regression analysis. The questionnaire administered for the study contained 15 questions including personal data. The subject was Moblink company customers sales service representative in Karachi.The valid sample size was 98 drawn through multi-cluster technique. Techniques such as measure of dispersion and measure of central tendencies were used for analyzing the data. Regression, Z-test, and F-test were used for testing the developed hypothesis.According to the respondents’ opinions, the reduced personal accomplishment had a high rating with a mean of 3.75 and job induced tension has the lowest mean of 3.58. The standard deviation of respondents’ opinions was highest for dimension depersonalization and least for dimension work load. This indicates that there is a high polarization of the respondents’ opinions on the dimension depersonalization moral and least on the dimension work load.The Skew nesses for all the dimensions were in negative except the determinants emotional exhaustion and workload. This indicates that the majority of respondents’ opinions on all the dimensions were below the mean except in the case of emotional exhaustion and workload.Five hypotheses were developed and tested:a The hypothesis relating to low level of burnout in customers

  13. 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.

  14. Strategic Adaptation

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    2015-01-01

    This article provides an overview of theoretical contributions that have influenced the discourse around strategic adaptation including contingency perspectives, strategic fit reasoning, decision structure, information processing, corporate entrepreneurship, and strategy process. The related...... concepts of strategic renewal, dynamic managerial capabilities, dynamic capabilities, and strategic response capabilities are discussed and contextualized against strategic responsiveness. The insights derived from this article are used to outline the contours of a dynamic process of strategic adaptation....... This model incorporates elements of central strategizing, autonomous entrepreneurial behavior, interactive information processing, and open communication systems that enhance the organization's ability to observe exogenous changes and respond effectively to them....

  15. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Kongshaug, Jesper; Søndergaard, Karin

    2015-01-01

    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...... to be static, and no longer acts as a kind of spatial constancy maintaining stability and order? Moreover, what new potentials open in lighting design? This book is one of four books that is published in connection with the research project entitled LED Lighting; Interdisciplinary LED Lighting Research...

  16. Adaptive test

    DEFF Research Database (Denmark)

    Kjeldsen, Lars Peter; Eriksen, Mette Rose

    2010-01-01

    Artikelen er en evaluering af de adaptive tests, som blev indført i folkeskolen. Artiklen sætter særligt fokus på evaluering i folkeskolen, herunder bidrager den med vejledning til evaluering, evalueringsværktøjer og fagspecifkt evalueringsmateriale.......Artikelen er en evaluering af de adaptive tests, som blev indført i folkeskolen. Artiklen sætter særligt fokus på evaluering i folkeskolen, herunder bidrager den med vejledning til evaluering, evalueringsværktøjer og fagspecifkt evalueringsmateriale....

  17. Representing culture in interstellar messages

    Science.gov (United States)

    Vakoch, Douglas A.

    2008-09-01

    As scholars involved with the Search for Extraterrestrial Intelligence (SETI) have contemplated how we might portray humankind in any messages sent to civilizations beyond Earth, one of the challenges they face is adequately representing the diversity of human cultures. For example, in a 2003 workshop in Paris sponsored by the SETI Institute, the International Academy of Astronautics (IAA) SETI Permanent Study Group, the International Society for the Arts, Sciences and Technology (ISAST), and the John Templeton Foundation, a varied group of artists, scientists, and scholars from the humanities considered how to encode notions of altruism in interstellar messages . Though the group represented 10 countries, most were from Europe and North America, leading to the group's recommendation that subsequent discussions on the topic should include more globally representative perspectives. As a result, the IAA Study Group on Interstellar Message Construction and the SETI Institute sponsored a follow-up workshop in Santa Fe, New Mexico, USA in February 2005. The Santa Fe workshop brought together scholars from a range of disciplines including anthropology, archaeology, chemistry, communication science, philosophy, and psychology. Participants included scholars familiar with interstellar message design as well as specialists in cross-cultural research who had participated in the Symposium on Altruism in Cross-cultural Perspective, held just prior to the workshop during the annual conference of the Society for Cross-cultural Research . The workshop included discussion of how cultural understandings of altruism can complement and critique the more biologically based models of altruism proposed for interstellar messages at the 2003 Paris workshop. This paper, written by the chair of both the Paris and Santa Fe workshops, will explore the challenges of communicating concepts of altruism that draw on both biological and cultural models.

  18. Semantic Representatives of the Concept

    Directory of Open Access Journals (Sweden)

    Elena N. Tsay

    2013-01-01

    Full Text Available In the article concept as one of the principle notions of cognitive linguistics is investigated. Considering concept as culture phenomenon, having language realization and ethnocultural peculiarities, the description of the concept “happiness” is presented. Lexical and semantic paradigm of the concept of happiness correlates with a great number of lexical and semantic variants. In the work semantic representatives of the concept of happiness, covering supreme spiritual values are revealed and semantic interpretation of their functioning in the Biblical discourse is given.

  19. Genomic insights into natural selection in the common loon (Gavia immer): evidence for aquatic adaptation.

    Science.gov (United States)

    Gayk, Zach G; Le Duc, Diana; Horn, Jeffrey; Lindsay, Alec R

    2018-04-27

    The common loon (Gavia immer) is one of five species that comprise the avian order Gaviiformes. Loons are specialized divers, reaching depths up to 60 m while staying submerged for intervals up to three minutes. In this study we used comparative genomics to investigate the genetic basis of the common loon adaptations to its ecological niche. We used Illumina short read DNA sequence data from a female bird to produce a draft assembly of the common loon (Gavia immer) genome. We identified 14,169 common loon genes, which based on well-resolved avian genomes, represent approximately 80.7% of common loon genes. Evolutionary analyses between common loon and Adelie penguin (Pygoscelis adeliae), red-throated loon (Gavia stellata), chicken (Gallus gallus), northern fulmar (Fulmarus glacialis), and rock pigeon (Columba livia) show 164 positively selected genes in common and red-throated loons. These genes were enriched for a number of protein classes, including those involved in muscle tissue development, immunoglobulin function, hemoglobin iron binding, G-protein coupled receptors, and ATP metabolism. Signatures of positive selection in these areas suggest the genus Gavia may have adapted for underwater diving by modulating their oxidative and metabolic pathways. While more research is required, these adaptations likely result in (1) compensations in oxygen respiration and energetic metabolism, (2) low-light visual acuity, and (3) elevated solute exchange. This work represents the first effort to understand the genomic adaptations of the common loon as well as other Gavia and may have implications for subsequent studies that target particular genes for loon population genetic, ecological or conservation studies.

  20. Is adaptation. Truly an adaptation?

    Directory of Open Access Journals (Sweden)

    Thais Flores Nogueira Diniz

    2006-04-01

    Full Text Available The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition, joined with the study of recycling, remaking, and every form of retelling. The film deals with the attempt by the scriptwriter Charles Kaufman, cast by Nicholas Cage, to adapt/translate a non-fictional book to the cinema, but ends up with a kind of film which is by no means what it intended to be: a film of action in the model of Hollywood productions. During the process of creation, Charles and his twin brother, Donald, undergo a series of adventures involving some real persons from the world of film, the author and the protagonist of the book, all of them turning into fictional characters in the film. In the film, adaptation then signifies something different from itstraditional meaning.

  1. Conspicuous Waste and Representativeness Heuristic

    Directory of Open Access Journals (Sweden)

    Tatiana M. Shishkina

    2017-12-01

    Full Text Available The article deals with the similarities between conspicuous waste and representativeness heuristic. The conspicuous waste is analyzed according to the classic Veblen’ interpretation as a strategy to increase social status through conspicuous consumption and conspicuous leisure. In “The Theory of the Leisure Class” Veblen introduced two different types of utility – conspicuous and functional. The article focuses on the possible benefits of the analysis of conspicuous utility not only in terms of institutional economic theory, but also in terms of behavioral economics. To this end, the representativeness heuristics is considered, on the one hand, as a way to optimize the decision-making process, which allows to examine it in comparison with procedural rationality by Simon. On the other hand, it is also analyzed as cognitive bias within the Kahneman and Twersky’ approach. The article provides the analysis of the patterns in the deviations from the rational behavior strategy that could be observed in case of conspicuous waste both in modern market economies in the form of conspicuous consumption and in archaic economies in the form of gift-exchange. The article also focuses on the marketing strategies for luxury consumption’ advertisement. It highlights the impact of the symbolic capital (in Bourdieu’ interpretation on the social and symbolic payments that actors get from the act of conspicuous waste. This allows to perform a analysis of conspicuous consumption both as a rational way to get the particular kind of payments, and, at the same time, as a form of institutionalized cognitive bias.

  2. Adaptation is...

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

    IDRC

    vital sector is under threat. While it is far from the only development challenge facing local farmers, extreme variations in the climate of West Africa in the past several decades have dealt the region a bad hand. Drought and flood now follow each other in succession. Adaptation is... “The floods spoiled our harvests and we.

  3. Ambiguous Adaptation

    DEFF Research Database (Denmark)

    Møller Larsen, Marcus; Lyngsie, Jacob

    and reciprocal adaptation of informal governance structure create ambiguity in situations of contingencies, which, subsequently, increases the likelihood of premature relationship termination. Using a large sample of exchange relationships in the global service provider industry, we find support for a hypothesis...

  4. Deep-Sea Hydrothermal Vent Viruses Compensate for Microbial Metabolism in Virus-Host Interactions.

    Science.gov (United States)

    He, Tianliang; Li, Hongyun; Zhang, Xiaobo

    2017-07-11

    Viruses are believed to be responsible for the mortality of host organisms. However, some recent investigations reveal that viruses may be essential for host survival. To date, it remains unclear whether viruses are beneficial or harmful to their hosts. To reveal the roles of viruses in the virus-host interactions, viromes and microbiomes of sediment samples from three deep-sea hydrothermal vents were explored in this study. To exclude the influence of exogenous DNAs on viromes, the virus particles were purified with nuclease (DNase I and RNase A) treatments and cesium chloride density gradient centrifugation. The metagenomic analysis of viromes without exogenous DNA contamination and microbiomes of vent samples indicated that viruses had compensation effects on the metabolisms of their host microorganisms. Viral genes not only participated in most of the microbial metabolic pathways but also formed branched pathways in microbial metabolisms, including pyrimidine metabolism; alanine, aspartate, and glutamate metabolism; nitrogen metabolism and assimilation pathways of the two-component system; selenocompound metabolism; aminoacyl-tRNA biosynthesis; and amino sugar and nucleotide sugar metabolism. As is well known, deep-sea hydrothermal vent ecosystems exist in relatively isolated environments which are barely influenced by other ecosystems. The metabolic compensation of hosts mediated by viruses might represent a very important aspect of virus-host interactions. IMPORTANCE Viruses are the most abundant biological entities in the oceans and have very important roles in regulating microbial community structure and biogeochemical cycles. The relationship between virus and host microbes is broadly thought to be that of predator and prey. Viruses can lyse host cells to control microbial population sizes and affect community structures of hosts by killing specific microbes. However, viruses also influence their hosts through manipulation of bacterial metabolism. We found

  5. Metabolic Surgery

    DEFF Research Database (Denmark)

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

    2018-01-01

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

  6. Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Sevil Ikinci

    2010-10-01

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

  7. Metabolic markers in sports medicine.

    Science.gov (United States)

    Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna

    2012-01-01

    Physical exercise induces adaptations in metabolism considered beneficial for health. Athletic performance is linked to adaptations, training, and correct nutrition in individuals with genetic traits that can facilitate such adaptations. Intense and continuous exercise, training, and competitions, however, can induce changes in the serum concentrations of numerous laboratory parameters. When these modifications, especially elevated laboratory levels, result outside the reference range, further examinations are ordered or participation in training and competition is discontinued or sports practice loses its appeal. In order to correctly interpret commonly used laboratory data, laboratory professionals and sport physicians need to know the behavior of laboratory parameters during and after practice and competition. We reviewed the literature on liver, kidney, muscle, heart, energy, and bone parameters in athletes with a view to increase the knowledge about clinical chemistry applied to sport and to stimulate studies in this field. In liver metabolism, the interpretation of serum aminotransferases concentration in athletes should consider the release of aspartate aminotransferase (AST) from muscle and of alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be elevated because of continuous hemolysis, which is typical of exercise. Muscle metabolism parameters such as creatine kinase (CK) are typically increased after exercise. This parameter can be used to interpret the physiological release of CK from muscle, its altered release due to rhabdomyolysis, or incomplete recovery due to overreaching or trauma. Cardiac markers are released during exercise, and especially endurance training. Increases in these markers should not simply be interpreted as a signal of cardiac damage or wall stress but rather as a sign of regulation of myocardial adaptation. Renal function can be followed in athletes by measuring serum creatinine concentration, but it should

  8. Cellular metabolism

    International Nuclear Information System (INIS)

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

    1977-01-01

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

  9. The metabolic syndrome in cancer survivors

    NARCIS (Netherlands)

    de Haas, Esther C.; Oosting, Sjoukje F.; Lefrandt, Joop D.; Wolffenbuttel, Bruce H. R.; Sleijfer, Dirk Th; Gietema, Jourik A.

    The metabolic syndrome, as a cluster of cardiovascular risk factors, may represent an important connection between cancer treatment and its common late effect of cardiovascular disease. Insight into the aetiology of the metabolic syndrome after cancer treatment might help to identify and treat

  10. Inherited lipodystrophies and the metabolic syndrome

    NARCIS (Netherlands)

    Monajemi, Houshang; Stroes, Erik; Hegele, Robert A.; Fliers, Eric

    2007-01-01

    Lipodystrophies represent a heterogeneous group of diseases characterized by an abnormal subcutaneous fat distribution, the extent of which can vary from localized, to partial, to generalized lipoatrophy. Whereas partial and generalized lipodystrophies are each associated with metabolic

  11. Topological analysis of metabolic control.

    Science.gov (United States)

    Sen, A K

    1990-12-01

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

  12. Metabolic syndrome presenting as abdominal pain

    Directory of Open Access Journals (Sweden)

    Mohammed Y Al-Dossary

    2017-01-01

    Full Text Available Metabolic syndrome represents a sum of risk factors that lead to the occurrence of cardiovascular and cerebrovascular events. The early detection of metabolic syndrome is extremely important in adults who are at risk. Although the physiopathological mechanisms of the metabolic syndrome are not yet clear, insulin resistance plays a key role that could explain the development of type 2 diabetes mellitus in untreated metabolic syndrome patients. Here, we present the case of a 26-year-old male who was diagnosed with metabolic syndrome and severe hypertriglyceridemia after presenting with abdominal pain. Although hypertriglyceridemia and hyperglycemia are the most common predictors of metabolic syndrome, clinicians need to be vigilant for unexpected presentations in patients at risk for metabolic syndrome. This case sheds light on the importance of early detection.

  13. Representative mass reduction in sampling

    DEFF Research Database (Denmark)

    Petersen, Lars; Esbensen, Harry Kim; Dahl, Casper Kierulf

    2004-01-01

    We here present a comprehensive survey of current mass reduction principles and hardware available in the current market. We conduct a rigorous comparison study of the performance of 17 field and/or laboratory instruments or methods which are quantitatively characterized (and ranked) for accuracy...... dividers, the Boerner Divider, the ??spoon method??, alternate/fractional shoveling and grab sampling. Only devices based on riffle splitting principles (static or rotational) passes the ultimate representativity test (with minor, but significant relative differences). Grab sampling, the overwhelmingly...... most often used mass reduction method, performs appallingly?its use must be discontinued (with the singular exception for completely homogenized fine powders). Only proper mass reduction (i.e. carried out in complete compliance with all appropriate design principles, maintenance and cleaning rules) can...

  14. Hedonic "adaptation"

    Directory of Open Access Journals (Sweden)

    Paul Rozin

    2008-02-01

    Full Text Available People live in a world in which they are surrounded by potential disgust elicitors such as ``used'' chairs, air, silverware, and money as well as excretory activities. People function in this world by ignoring most of these, by active avoidance, reframing, or adaptation. The issue is particularly striking for professions, such as morticians, surgeons, or sanitation workers, in which there is frequent contact with major disgust elicitors. In this study, we study the ``adaptation'' process to dead bodies as disgust elicitors, by measuring specific types of disgust sensitivity in medical students before and after they have spent a few months dissecting a cadaver. Using the Disgust Scale, we find a significant reduction in disgust responses to death and body envelope violation elicitors, but no significant change in any other specific type of disgust. There is a clear reduction in discomfort at touching a cold dead body, but not in touching a human body which is still warm after death.

  15. Adaptation Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Huq, Saleemul

    2011-11-15

    Efforts to help the world's poor will face crises in coming decades as climate change radically alters conditions. Action Research for Community Adapation in Bangladesh (ARCAB) is an action-research programme on responding to climate change impacts through community-based adaptation. Set in Bangladesh at 20 sites that are vulnerable to floods, droughts, cyclones and sea level rise, ARCAB will follow impacts and adaptation as they evolve over half a century or more. National and international 'research partners', collaborating with ten NGO 'action partners' with global reach, seek knowledge and solutions applicable worldwide. After a year setting up ARCAB, we share lessons on the programme's design and move into our first research cycle.

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

    Science.gov (United States)

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

    2014-10-01

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

  17. Adaptable positioner

    International Nuclear Information System (INIS)

    Labrador Pavon, I.

    1993-01-01

    This paper describes the circuits and programs in assembly language, developed to control the two DC motors that give mobility to a mechanical arm with two degrees of freedom. As a whole, the system is based in a adaptable regulator designed around a 8 bit microprocessor that, starting from a mode of regulation based in the successive approximation method, evolve to another mode through which, only one approximation is sufficient to get the right position of each motor. (Author) 22 fig. 6 ref

  18. Adaptive positioner

    International Nuclear Information System (INIS)

    Labrador Pavon, I.

    1993-01-01

    This paper describes the circuits and programs in assembly language, developed to control the two DC motors that give mobility to a mechanical arm with two degrees of freedom. As a whole, the system is based in a adaptable regulator designed around a 8 bit microprocessor that, starting from a mode of regulation based in the successive approximation method, evolve to another mode through which, only one approximation is sufficient to get the right position of each motor. (Author) 6 refs

  19. 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...

  20. Want change? Call your representative

    Science.gov (United States)

    Fischhoff, Ilya R.

    2011-07-01

    During my tenure as an AGU Congressional Science Fellow, which began in September 2010 and continues until November 2011, my time has been shared between working with the U.S. House of Representatives Natural Resource Committee Democratic staff and in the office of Rep. Ed Markey (D-Mass., ranking Democrat on the committee). I appreciate getting to work with staff, fellows, and interns who inspire me, make me laugh, and know their issues cold. Much of my work on the committee is related to fish, wildlife, oceans, lands, and water issues and is directly related to my background in ecology and evolutionary biology (I studied zebra ecology and behavior in Kenya). My assignments have included asking the Environmental Protection Agency (EPA) about why it has not changed the allowed usage of certain pesticides that the National Marine Fisheries Service has found to jeopardize the recovery of endangered Pacific salmon; helping to identify research needs and management options to combat the swiftly spreading and catastrophic white nose syndrome in North American bats; and inquiring as to whether a captive-ape welfare bill, if passed without amendment, could thwart development of a vaccine to stop the Ebola virus from continuing to cause mass mortality in endangered wild apes.

  1. Fatty acids from diet and microbiota regulate energy metabolism [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Joe Alcock

    2015-09-01

    Full Text Available A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system.

  2. 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

  3. Physiology and relevance of human adaptive thermogenesis response.

    Science.gov (United States)

    Celi, Francesco S; Le, Trang N; Ni, Bin

    2015-05-01

    In homoeothermic organisms, the preservation of core temperature represents a primal function, and its costs in terms of energy expenditure can be considerable. In modern humans, the endogenous thermoregulation mechanisms have been replaced by clothing and environmental control, and the maintenance of thermoneutrality has been successfully achieved by manipulation of the micro- and macroenvironment. The rediscovery of the presence and activity of brown adipose tissue in adult humans has renewed the interest on adaptive thermogenesis (AT) as a means to facilitate weight loss and improve carbohydrate metabolism. The aim of this review is to describe the recent advancements in the study of this function, and to assess the potential and limitations of exploiting AT for environmental/behavioral, and pharmacological interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Spectrum of metabolic myopathies.

    Science.gov (United States)

    Angelini, Corrado

    2015-04-01

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

  5. Dynamic optimal metabolic control theory: a cybernetic approach for modelling of the central nitrogen metabolism of S. cerevisiae

    NARCIS (Netherlands)

    Riel, van N.A.W.; Giuseppin, M.L.F.; Verrips, C.T.

    2000-01-01

    The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the

  6. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake.

    Science.gov (United States)

    Flavahan, William A; Wu, Qiulian; Hitomi, Masahiro; Rahim, Nasiha; Kim, Youngmi; Sloan, Andrew E; Weil, Robert J; Nakano, Ichiro; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Li, Meizhang; Lathia, Justin D; Rich, Jeremy N; Hjelmeland, Anita B

    2013-10-01

    Like all cancers, brain tumors require a continuous source of energy and molecular resources for new cell production. In normal brain, glucose is an essential neuronal fuel, but the blood-brain barrier limits its delivery. We now report that nutrient restriction contributes to tumor progression by enriching for brain tumor initiating cells (BTICs) owing to preferential BTIC survival and to adaptation of non-BTICs through acquisition of BTIC features. BTICs outcompete for glucose uptake by co-opting the high affinity neuronal glucose transporter, type 3 (Glut3, SLC2A3). BTICs preferentially express Glut3, and targeting Glut3 inhibits BTIC growth and tumorigenic potential. Glut3, but not Glut1, correlates with poor survival in brain tumors and other cancers; thus, tumor initiating cells may extract nutrients with high affinity. As altered metabolism represents a cancer hallmark, metabolic reprogramming may maintain the tumor hierarchy and portend poor prognosis.

  7. Tracking the origins of Yakutian horses and the genetic basis for their fast adaptation to subarctic environments.

    Science.gov (United States)

    Librado, Pablo; Der Sarkissian, Clio; Ermini, Luca; Schubert, Mikkel; Jónsson, Hákon; Albrechtsen, Anders; Fumagalli, Matteo; Yang, Melinda A; Gamba, Cristina; Seguin-Orlando, Andaine; Mortensen, Cecilie D; Petersen, Bent; Hoover, Cindi A; Lorente-Galdos, Belen; Nedoluzhko, Artem; Boulygina, Eugenia; Tsygankova, Svetlana; Neuditschko, Markus; Jagannathan, Vidhya; Thèves, Catherine; Alfarhan, Ahmed H; Alquraishi, Saleh A; Al-Rasheid, Khaled A S; Sicheritz-Ponten, Thomas; Popov, Ruslan; Grigoriev, Semyon; Alekseev, Anatoly N; Rubin, Edward M; McCue, Molly; Rieder, Stefan; Leeb, Tosso; Tikhonov, Alexei; Crubézy, Eric; Slatkin, Montgomery; Marques-Bonet, Tomas; Nielsen, Rasmus; Willerslev, Eske; Kantanen, Juha; Prokhortchouk, Egor; Orlando, Ludovic

    2015-12-15

    Yakutia, Sakha Republic, in the Siberian Far East, represents one of the coldest places on Earth, with winter record temperatures dropping below -70 °C. Nevertheless, Yakutian horses survive all year round in the open air due to striking phenotypic adaptations, including compact body conformations, extremely hairy winter coats, and acute seasonal differences in metabolic activities. The evolutionary origins of Yakutian horses and the genetic basis of their adaptations remain, however, contentious. Here, we present the complete genomes of nine present-day Yakutian horses and two ancient specimens dating from the early 19th century and ∼5,200 y ago. By comparing these genomes with the genomes of two Late Pleistocene, 27 domesticated, and three wild Przewalski's horses, we find that contemporary Yakutian horses do not descend from the native horses that populated the region until the mid-Holocene, but were most likely introduced following the migration of the Yakut people a few centuries ago. Thus, they represent one of the fastest cases of adaptation to the extreme temperatures of the Arctic. We find cis-regulatory mutations to have contributed more than nonsynonymous changes to their adaptation, likely due to the comparatively limited standing variation within gene bodies at the time the population was founded. Genes involved in hair development, body size, and metabolic and hormone signaling pathways represent an essential part of the Yakutian horse adaptive genetic toolkit. Finally, we find evidence for convergent evolution with native human populations and woolly mammoths, suggesting that only a few evolutionary strategies are compatible with survival in extremely cold environments.

  8. Insect Counter-Adaptations to Plant Cyanogenic Glucosides

    DEFF Research Database (Denmark)

    Pentzold, Stefan

    . This thesis presents evidence that larvae of the sequestering lepidopteran specialist Zygaena filipendulae have evolved diverse behavioural, morphological, physiological and metabolic adaptations to keep cyanogenic glucosides from its food plant Lotus corniculatus (Fabaceae) intact and thus non-toxic during...

  9. VISCOSITY DICTATES METABOLIC ACTIVITY of Vibrio ruber

    Directory of Open Access Journals (Sweden)

    Maja eBoric

    2012-07-01

    Full Text Available Little is known about metabolic activity of bacteria, when viscosity of their environment changes. In this work, bacterial metabolic activity in media with viscosity ranging from 0.8 to 29.4 mPas was studied. Viscosities up to 2.4 mPas did not affect metabolic activity of Vibrio ruber. On the other hand, at 29.4 mPas respiration rate and total dehydrogenase activity increased 8 and 4-fold, respectively. The activity of glucose-6-phosphate dehydrogenase increased up to 13-fold at higher viscosities. However, intensified metabolic activity did not result in faster growth rate. Increased viscosity delayed the onset as well as the duration of biosynthesis of prodigiosin. As an adaptation to viscous environment V. ruber increased metabolic flux through the pentose phosphate pathway and reduced synthesis of a secondary metabolite. In addition, V. ruber was able to modify the viscosity of its environment.

  10. the prevalence of metabolic syndrome among active sportsmen

    African Journals Online (AJOL)

    User

    ABSTRACT. This study sought to establish the prevalence of the metabolic syndrome (MetS) among active .... Table 1: General characteristic of the studied population stratified by exercise. Parameters ..... Prolonged adaptation to fat- rich diet ...

  11. Metabolism and virulence in Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Christoph eSchoen

    2014-08-01

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

  12. Transcriptome adaptation of the bovine mammary gland to diets rich in unsaturated fatty acids shows greater impact of linseed oil over safflower oil on gene expression and metabolic pathways.

    Science.gov (United States)

    Ibeagha-Awemu, Eveline M; Li, Ran; Ammah, Adolf A; Dudemaine, Pier-Luc; Bissonnette, Nathalie; Benchaar, Chaouki; Zhao, Xin

    2016-02-09

    Nutritional strategies can decrease saturated fatty acids (SFAs) and increase health beneficial fatty acids (FAs) in bovine milk. The pathways/genes involved in these processes are not properly defined. Next-generation RNA-sequencing was used to investigate the bovine mammary gland transcriptome following supplemental feeding with 5% linseed oil (LSO) or 5% safflower oil (SFO). Holstein cows in mid-lactation were fed a control diet for 28 days (control period) followed by supplementation with 5% LSO (12 cows) or 5% SFO (12 cows) for 28 days (treatment period). Milk and mammary gland biopsies were sampled on days-14 (control period), +7 and +28 (treatment period). Milk was used to measure fat(FP)/protein(PP) percentages and individual FAs while RNA was subjected to sequencing. Milk FP was decreased by 30.38% (LSO) or 32.42% (SFO) while PP was unaffected (LSO) or increased (SFO). Several beneficial FAs were increased by LSO (C18:1n11t, CLA:10t12c, CLA:9c11t, C20:3n3, C20:5n3, C22:5n3) and SFO (C18:1n11t, CLA:10t12c, C20:1c11, C20:2, C20:3n3) while several SFAs (C4:0, C6:0, C8:0, C14:0, C16:0, C17:0, C24:0) were decreased by both treatments (P < 0.05). 1006 (460 up- and 546 down-regulated) and 199 (127 up- and 72 down-regulated) genes were significantly differentially regulated (DE) by LSO and SFO, respectively. Top regulated genes (≥ 2 fold change) by both treatments (FBP2, UCP2, TIEG2, ANGPTL4, ALDH1L2) are potential candidate genes for milk fat traits. Involvement of SCP2, PDK4, NQO1, F2RL1, DBI, CPT1A, CNTFR, CALB1, ACADVL, SPTLC3, PIK3CG, PIGZ, ADORA2B, TRIB3, HPGD, IGFBP2 and TXN in FA/lipid metabolism in dairy cows is being reported for the first time. Functional analysis indicated similar and different top enriched functions for DE genes. DE genes were predicted to significantly decrease synthesis of FA/lipid by both treatments and FA metabolism by LSO. Top canonical pathways associated with DE genes of both treatments might be involved in lipid

  13. Evolution of metabolic network organization

    Directory of Open Access Journals (Sweden)

    Bonchev Danail

    2010-05-01

    Full Text Available Abstract Background Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. By selecting taxa representative of different lineages or lifestyles and using a comprehensive set of descriptors of the structure and complexity of their metabolic networks, one can highlight both qualitative and quantitative differences in the metabolic organization of species subject to distinct evolutionary paths or environmental constraints. Results We used a novel representation of metabolic networks, termed network of interacting pathways or NIP, to focus on the modular, high-level organization of the metabolic capabilities of the cell. Using machine learning techniques we identified the most relevant aspects of cellular organization that change under evolutionary pressures. We considered the transitions from prokarya to eukarya (with a focus on the transitions among the archaea, bacteria and eukarya, from unicellular to multicellular eukarya, from free living to host-associated bacteria, from anaerobic to aerobic, as well as the acquisition of cell motility or growth in an environment of various levels of salinity or temperature. Intuitively, we expect organisms with more complex lifestyles to have more complex and robust metabolic networks. Here we demonstrate for the first time that such organisms are not only characterized by larger, denser networks of metabolic pathways but also have more efficiently organized cross communications, as revealed by subtle changes in network topology. These changes are unevenly distributed among metabolic pathways, with specific categories of pathways being promoted to more central locations as an answer to environmental constraints. Conclusions Combining methods from graph theory and machine learning, we have shown here that evolutionary pressures not only affects gene and protein sequences, but also specific details of the complex wiring of functional modules

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

    Directory of Open Access Journals (Sweden)

    Ellis James K

    2012-06-01

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

  15. Cold-Adapted Enzymes

    Science.gov (United States)

    Georlette, D.; Bentahir, M.; Claverie, P.; Collins, T.; D'amico, S.; Delille, D.; Feller, G.; Gratia, E.; Hoyoux, A.; Lonhienne, T.; Meuwis, M.-a.; Zecchinon, L.; Gerday, Ch.

    In the last few years, increased attention has been focused on enzymes produced by cold-adapted micro-organisms. It has emerged that psychrophilic enzymes represent an extremely powerful tool in both protein folding investigations and for biotechnological purposes. Such enzymes are characterised by an increased thermosensitivity and, most of them, by a higher catalytic efficiency at low and moderate temperatures, when compared to their mesophilic counterparts. The high thermosensitivity probably originates from an increased flexibility of either a selected area of the molecular edifice or the overall protein structure, providing enhanced abilities to undergo conformational changes during catalysis at low temperatures. Structure modelling and recent crystallographic data have allowed to elucidate the structural parameters that could be involved in this higher resilience. It was demonstrated that each psychrophilic enzyme adopts its own adaptive strategy. It appears, moreover, that there is a continuum in the strategy of protein adaptation to temperature, as the previously mentioned structural parameters are implicated in the stability of thermophilic proteins. Additional 3D crystal structures, site-directed and random mutagenesis experiments should now be undertaken to further investigate the stability-flexibility-activity relationship.

  16. 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...

  17. Correlation between citric acid and nitrate metabolisms during CAM cycle in the atmospheric bromeliad Tillandsia pohliana.

    Science.gov (United States)

    Freschi, Luciano; Rodrigues, Maria Aurineide; Tiné, Marco Aurélio Silva; Mercier, Helenice

    2010-12-15

    Crassulacean acid metabolism (CAM) confers crucial adaptations for plants living under frequent environmental stresses. A wide metabolic plasticity can be found among CAM species regarding the type of storage carbohydrate, organic acid accumulated at night and decarboxylating system. Consequently, many aspects of the CAM pathway control are still elusive while the impact of this photosynthetic adaptation on nitrogen metabolism has remained largely unexplored. In this study, we investigated a possible link between the CAM cycle and the nitrogen assimilation in the atmospheric bromeliad Tillandsia pohliana by simultaneously characterizing the diel changes in key enzyme activities and metabolite levels of both organic acid and nitrate metabolisms. The results revealed that T. pohliana performed a typical CAM cycle in which phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase phosphorylation seemed to play a crucial role to avoid futile cycles of carboxylation and decarboxylation. Unlike all other bromeliads previously investigated, almost equimolar concentrations of malate and citrate were accumulated at night. Moreover, a marked nocturnal depletion in the starch reservoirs and an atypical pattern of nitrate reduction restricted to the nighttime were also observed. Since reduction and assimilation of nitrate requires a massive supply of reducing power and energy and considering that T. pohliana lives overexposed to the sunlight, we hypothesize that citrate decarboxylation might be an accessory mechanism to increase internal CO₂ concentration during the day while its biosynthesis could provide NADH and ATP for nocturnal assimilation of nitrate. Therefore, besides delivering photoprotection during the day, citrate might represent a key component connecting both CAM pathway and nitrogen metabolism in T. pohliana; a scenario that certainly deserves further study not only in this species but also in other CAM plants that nocturnally accumulate citrate

  18. Flux networks in metabolic graphs

    International Nuclear Information System (INIS)

    Warren, P B; Queiros, S M Duarte; Jones, J L

    2009-01-01

    A metabolic model can be represented as a bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a conserved metabolite property such as molecular weight. A similar flux network can be constructed by combining the primal and dual solutions to the linear programming problem that typically arises in constraint-based modelling. Such constructions may help with the visualization of flux distributions in complex metabolic networks. The analysis also explains the strong correlation observed between metabolite shadow prices (the dual linear programming variables) and conserved metabolite properties. The methods were applied to recent metabolic models for Escherichia coli, Saccharomyces cerevisiae and Methanosarcina barkeri. Detailed results are reported for E. coli; similar results were found for other organisms

  19. Carbohydrate Metabolism Disorders

    Science.gov (United States)

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

  20. Comprehensive metabolic panel

    Science.gov (United States)

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

  1. Integration of metabolism and digestion in the hyrax | Fairall | South ...

    African Journals Online (AJOL)

    Metabolic adaptations and digestive ability were integrated to explain the ecological efficiency of the hyrax (Procavia capensis). Metabolic rate was shown to decrease linearly with a drop in ambient temperature, but at a lower rate than an animal of equivalent size, the guinea-pig (Cavia porcel/us). This is achieved by ...

  2. Shift work and its association with metabolic disorders

    OpenAIRE

    Brum, Maria Carlota Borba; Dantas Filho, Fábio Fernandes; Schnorr, Claudia Carolina; Bottega, Gustavo Borchardt; Rodrigues, Ticiana da Costa

    2015-01-01

    Although the health burden of shift work has not been extensively studied, evidence suggests that it may affect the metabolic balance and cause obesity and other metabolic disorders. Sleep deprivation, circadian desynchronization and behavioral changes in diet and physical activity are among the most commonly mentioned factors in studies of the association between night work and metabolic disorders. Individual adaptation to night work depends greatly on personal factors such as family and soc...

  3. Integration of Genome Scale Metabolic Networks and Gene Regulation of Metabolic Enzymes With Physiologically Based Pharmacokinetics.

    Science.gov (United States)

    Maldonado, Elaina M; Leoncikas, Vytautas; Fisher, Ciarán P; Moore, J Bernadette; Plant, Nick J; Kierzek, Andrzej M

    2017-11-01

    The scope of physiologically based pharmacokinetic (PBPK) modeling can be expanded by assimilation of the mechanistic models of intracellular processes from systems biology field. The genome scale metabolic networks (GSMNs) represent a whole set of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metabolism enzymes are available. Here, we introduce GSMNs and review ongoing work on integration of PBPK, GSMNs, and metabolic gene regulation. We demonstrate example models. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  4. Metabolic rate and its relationship with ascites in chicken genotypes

    NARCIS (Netherlands)

    Malan, D.D.; Scheele, C.W.; Buyse, J.; Kwakernaak, C.; Siebrits, F.K.; Klis, van der J.D.; Decuypere, E.

    2003-01-01

    This review addresses the suggestion that the decline in dairy reproductive performance, as increasingly observed these days, may be due to a hampered process of metabolic adaptation in early lactating cows. In our opinion, adaptation to the negative energy balance is a gradual process. Because

  5. Model of aircraft noise adaptation

    Science.gov (United States)

    Dempsey, T. K.; Coates, G. D.; Cawthorn, J. M.

    1977-01-01

    Development of an aircraft noise adaptation model, which would account for much of the variability in the responses of subjects participating in human response to noise experiments, was studied. A description of the model development is presented. The principal concept of the model, was the determination of an aircraft adaptation level which represents an annoyance calibration for each individual. Results showed a direct correlation between noise level of the stimuli and annoyance reactions. Attitude-personality variables were found to account for varying annoyance judgements.

  6. Uncertainty in adaptive capacity; Incertitudes dans la capacite d'adaptation

    Energy Technology Data Exchange (ETDEWEB)

    Neil Adger, W.; Vincent, K. [East Anglia Univ., Tyndall Centre for Climate Change Research, School of Environmental Sciences, Norwich (United Kingdom)

    2005-03-01

    The capacity to adapt is a critical element of the process of adaptation: it is the vector of resources that represent the asset base from which adaptation actions can be made. Adaptive capacity can in theory be identified and measured at various scales, from the individual to the nation. The assessment of uncertainty within such measures comes from the contested knowledge domain and theories surrounding the nature of the determinants of adaptive capacity and the human action of adaptation. While generic adaptive capacity at the national level, for example, is often postulated as being dependent on health, governance and political rights, and literacy, and economic well-being, the determinants of these variables at national levels are not widely understood. We outline the nature of this uncertainty for the major elements of adaptive capacity and illustrate these issues with the example of a social vulnerability index for countries in Africa. (authors)

  7. Cancer cell metabolism and mitochondria: Nutrient plasticity for TCA cycle fueling.

    Science.gov (United States)

    Corbet, Cyril; Feron, Olivier

    2017-08-01

    Warburg's hypothesis that cancer cells take up a lot of glucose in the presence of ambient oxygen but convert pyruvate into lactate due to impaired mitochondrial function led to the misconception that cancer cells rely on glycolysis as their major source of energy. Most recent 13 C-based metabolomic studies, including in cancer patients, indicate that cancer cells may also fully oxidize glucose. In addition to glucose-derived pyruvate, lactate, fatty acids and amino acids supply substrates to the TCA cycle to sustain mitochondrial metabolism. Here, we discuss how the metabolic flexibility afforded by these multiple mitochondrial inputs allows cancer cells to adapt according to the availability of the different fuels and the microenvironmental conditions such as hypoxia and acidosis. In particular, we focused on the role of the TCA cycle in interconnecting numerous metabolic routes in order to highlight metabolic vulnerabilities that represent attractive targets for a new generation of anticancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Random sampling of elementary flux modes in large-scale metabolic networks.

    Science.gov (United States)

    Machado, Daniel; Soons, Zita; Patil, Kiran Raosaheb; Ferreira, Eugénio C; Rocha, Isabel

    2012-09-15

    The description of a metabolic network in terms of elementary (flux) modes (EMs) provides an important framework for metabolic pathway analysis. However, their application to large networks has been hampered by the combinatorial explosion in the number of modes. In this work, we develop a method for generating random samples of EMs without computing the whole set. Our algorithm is an adaptation of the canonical basis approach, where we add an additional filtering step which, at each iteration, selects a random subset of the new combinations of modes. In order to obtain an unbiased sample, all candidates are assigned the same probability of getting selected. This approach avoids the exponential growth of the number of modes during computation, thus generating a random sample of the complete set of EMs within reasonable time. We generated samples of different sizes for a metabolic network of Escherichia coli, and observed that they preserve several properties of the full EM set. It is also shown that EM sampling can be used for rational strain design. A well distributed sample, that is representative of the complete set of EMs, should be suitable to most EM-based methods for analysis and optimization of metabolic networks. Source code for a cross-platform implementation in Python is freely available at http://code.google.com/p/emsampler. dmachado@deb.uminho.pt Supplementary data are available at Bioinformatics online.

  9. Evolutionary adaptations to dietary changes.

    Science.gov (United States)

    Luca, F; Perry, G H; Di Rienzo, A

    2010-08-21

    Through cultural innovation and changes in habitat and ecology, there have been a number of major dietary shifts in human evolution, including meat eating, cooking, and those associated with plant and animal domestication. The identification of signatures of adaptations to such dietary changes in the genome of extant primates (including humans) may shed light not only on the evolutionary history of our species, but also on the mechanisms that underlie common metabolic diseases in modern human populations. In this review, we provide a brief overview of the major dietary shifts that occurred during hominin evolution, and we discuss the methods and approaches used to identify signals of natural selection in patterns of sequence variation. We then review the results of studies aimed at detecting the genetic loci that played a major role in dietary adaptations and conclude by outlining the potential of future studies in this area.

  10. Coping with traumatic brain injury: representative case studies.

    Science.gov (United States)

    Kwasnica, C M; Heinemann, A

    1994-04-01

    This case report compares the use of social supports and vulnerability to substance abuse for two rehabilitation clients after traumatic brain injury (TBI). Using a psychosocial assessment, the Motivational Structure Questionnaire, Adaptive Skills Battery, and Ways of Coping Checklist within a representative case method, we studied two individuals in depth to understand differences in postinjury drinking behaviors. We also examined differences in availability and use of social supports and how support was related to coping efforts. Finally, we illustrated goal-setting and the relationship between long-term planning and follow-through on goals. Social supports, adaptive problem-solving behaviors, and positive reappraisal of situations seem to be important elements in postinjury abstinence. Clinically, this research supports the need for fostering use of both social supports and substance use prevention and treatment services when working with both inpatient and outpatient TBI clients.

  11. Respiration and nitrogen assimilation: targeting mitochondria-associated metabolism as a means to enhance nitrogen use efficiency.

    Science.gov (United States)

    Foyer, Christine H; Noctor, Graham; Hodges, Michael

    2011-02-01

    Considerable advances in our understanding of the control of mitochondrial metabolism and its interactions with nitrogen metabolism and associated carbon/nitrogen interactions have occurred in recent years, particularly highlighting important roles in cellular redox homeostasis. The tricarboxylic acid (TCA) cycle is a central metabolic hub for the interacting pathways of respiration, nitrogen assimilation, and photorespiration, with components that show considerable flexibility in relation to adaptations to the different functions of mitochondria in photosynthetic and non-photosynthetic cells. By comparison, the operation of the oxidative pentose phosphate pathway appears to represent a significant limitation to nitrogen assimilation in non-photosynthetic tissues. Valuable new insights have been gained concerning the roles of the different enzymes involved in the production of 2-oxoglutarate (2-OG) for ammonia assimilation, yielding an improved understanding of the crucial role of cellular energy balance as a broker of co-ordinate regulation. Taken together with new information on the mechanisms that co-ordinate the expression of genes involved in organellar functions, including energy metabolism, and the potential for exploiting the existing flexibility for NAD(P)H utilization in the respiratory electron transport chain to drive nitrogen assimilation, the evidence that mitochondrial metabolism and machinery are potential novel targets for the enhancement of nitrogen use efficiency (NUE) is explored.

  12. Exploring natural variation of photosynthetic, primary metabolism and growth parameters in a large panel of Capsicum chinense accessions.

    Science.gov (United States)

    Rosado-Souza, Laise; Scossa, Federico; Chaves, Izabel S; Kleessen, Sabrina; Salvador, Luiz F D; Milagre, Jocimar C; Finger, Fernando; Bhering, Leonardo L; Sulpice, Ronan; Araújo, Wagner L; Nikoloski, Zoran; Fernie, Alisdair R; Nunes-Nesi, Adriano

    2015-09-01

    Collectively, the results presented improve upon the utility of an important genetic resource and attest to a complex genetic basis for differences in both leaf metabolism and fruit morphology between natural populations. Diversity of accessions within the same species provides an alternative method to identify physiological and metabolic traits that have large effects on growth regulation, biomass and fruit production. Here, we investigated physiological and metabolic traits as well as parameters related to plant growth and fruit production of 49 phenotypically diverse pepper accessions of Capsicum chinense grown ex situ under controlled conditions. Although single-trait analysis identified up to seven distinct groups of accessions, working with the whole data set by multivariate analyses allowed the separation of the 49 accessions in three clusters. Using all 23 measured parameters and data from the geographic origin for these accessions, positive correlations between the combined phenotypes and geographic origin were observed, supporting a robust pattern of isolation-by-distance. In addition, we found that fruit set was positively correlated with photosynthesis-related parameters, which, however, do not explain alone the differences in accession susceptibility to fruit abortion. Our results demonstrated that, although the accessions belong to the same species, they exhibit considerable natural intraspecific variation with respect to physiological and metabolic parameters, presenting diverse adaptation mechanisms and being a highly interesting source of information for plant breeders. This study also represents the first study combining photosynthetic, primary metabolism and growth parameters for Capsicum to date.

  13. Proteomic Dissection of the Mitochondrial DNA Metabolism Apparatus in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    SAlly A. Mackenzie

    2004-01-06

    This study involves the investigation of nuclear genetic components that regulate mitochondrial genome behavior in higher plants. The approach utilizes the advanced plant model system of Arabidopsis thaliana to identify and functionally characterize multiple components of the mitochondrial DNA replication, recombination and mismatch repair system and their interaction partners. The rationale for the research stems from the central importance of mitochondria to overall cellular metabolism and the essential nature of the mitochondrial genome to mitochondrial function. Relatively little is understood about mitochondrial DNA maintenance and transmission in higher eukaryotes, and the higher plant mitochondrial genome displays unique properties and behavior. This investigation has revealed at least three important properties of plant mitochondrial DNA metabolism components. (1) Many are dual targeted to mitochondrial and chloroplasts by novel mechanisms, suggesting that the mitochondria a nd chloroplast share their genome maintenance apparatus. (2)The MSH1 gene, originating as a component of mismatch repair, has evolved uniquely in plants to participate in differential replication of the mitochondrial genome. (3) This mitochondrial differential replication process, termed substoichiometric shifting and also involving a RecA-related gene, appears to represent an adaptive mechanism to expand plant reproductive capacity and is likely present throughout the plant kingdom.

  14. OAS :: Authorities : Permanent Representatives to the OAS

    Science.gov (United States)

    Rights Actions against Corruption C Children Civil Registry Civil Society Contact Us Culture Cyber Representative of Belize Diego Pary Rodríguez Bolivia Diego Pary Rodríguez Ambassador, Permanent Representative of Bolivia José Luiz Machado Brazil José Luiz Machado e Costa Ambassador, Permanent Representative

  15. Haloacetonitriles: metabolism and toxicity.

    Science.gov (United States)

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

    2009-01-01

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

  16. 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.

  17. Intermittent metabolic switching, neuroplasticity and brain health

    Science.gov (United States)

    Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu

    2018-01-01

    During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease. PMID:29321682

  18. Maternal capital and the metabolic ghetto: An evolutionary perspective on the transgenerational basis of health inequalities.

    Science.gov (United States)

    Wells, Jonathan C K

    2010-01-01

    There is particular interest in understanding socioeconomic and ethnic variability in health status. The developmental origins of disease hypothesis emphasize the importance of growth patterns across the life-course in relation to noncommunicable disease risk. The physiological components of cardiovascular risk, collectively termed the metabolic syndrome, derive in part from a disparity between the homeostatic "metabolic capacity" of vital organs and the "metabolic load" induced by large tissue masses, a rich diet and sedentary behavior. From an evolutionary perspective, the risk of such disparity is decreased by maternal physiology regulating offspring growth trajectory during gestation and lactation. Maternal capital, defined as phenotypic resources enabling investment in the offspring, allows effective buffering of the offspring from nutritional perturbations and represents the environmental niche initially occupied by the offspring. Offspring growth patterns are sensitive to the magnitude of maternal capital during early windows of plasticity. Offspring life-history strategy can then respond adaptively to further factors across the life-course, but only within the context of this initial maternal influence on growth. Maternal somatic capital is primarily gained or lost across generations, through variable rates of fetal and infant growth. I argue that the poor nutritional experience of populations subjected to colonialism resulted in a systematic loss of maternal capital, reflected in downward secular trends in stature. Accelerating the recovery of somatic capital within generations overloads metabolic capacity and exacerbates cardiovascular risk, reflected in increased disease rates in urbanizing and emigrant populations. Public health policies need to benefit metabolic capacity without exacerbating metabolic load. 2009 Wiley-Liss, Inc.

  19. 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

  20. Scaling of Metabolic Scaling within Physical Limits

    Directory of Open Access Journals (Sweden)

    Douglas S. Glazier

    2014-10-01

    Full Text Available Both the slope and elevation of scaling relationships between log metabolic rate and log body size vary taxonomically and in relation to physiological or developmental state, ecological lifestyle and environmental conditions. Here I discuss how the recently proposed metabolic-level boundaries hypothesis (MLBH provides a useful conceptual framework for explaining and predicting much, but not all of this variation. This hypothesis is based on three major assumptions: (1 various processes related to body volume and surface area exert state-dependent effects on the scaling slope for metabolic rate in relation to body mass; (2 the elevation and slope of metabolic scaling relationships are linked; and (3 both intrinsic (anatomical, biochemical and physiological and extrinsic (ecological factors can affect metabolic scaling. According to the MLBH, the diversity of metabolic scaling relationships occurs within physical boundary limits related to body volume and surface area. Within these limits, specific metabolic scaling slopes can be predicted from the metabolic level (or scaling elevation of a species or group of species. In essence, metabolic scaling itself scales with metabolic level, which is in turn contingent on various intrinsic and extrinsic conditions operating in physiological or evolutionary time. The MLBH represents a “meta-mechanism” or collection of multiple, specific mechanisms that have contingent, state-dependent effects. As such, the MLBH is Darwinian in approach (the theory of natural selection is also meta-mechanistic, in contrast to currently influential metabolic scaling theory that is Newtonian in approach (i.e., based on unitary deterministic laws. Furthermore, the MLBH can be viewed as part of a more general theory that includes other mechanisms that may also affect metabolic scaling.

  1. Supporting Adaptive and Adaptable Hypermedia Presentation Semantics

    NARCIS (Netherlands)

    D.C.A. Bulterman (Dick); L. Rutledge (Lloyd); L. Hardman (Lynda); J.R. van Ossenbruggen (Jacco)

    1999-01-01

    textabstractHaving the content of a presentation adapt to the needs, resources and prior activities of a user can be an important benefit of electronic documents. While part of this adaptation is related to the encodings of individual data streams, much of the adaptation can/should be guided by the

  2. Phylogenomic analysis of Candidatus ‘Izimaplasma’ species: free-living representatives from a Tenericutes clade found in methane seeps

    KAUST Repository

    Skennerton, Connor T.; Haroon, Mohamed; Briegel, Ariane; Shi, Jian; Jensen, Grant J.; Tyson, Gene W.; Orphan, Victoria J.

    2016-01-01

    ' (SILVA taxonomy) or 'RF3' (Greengenes taxonomy). Metabolic reconstruction revealed that, like cultured members of the Mollicutes, these 'NB1-n' representatives lack a tricarboxylic acid cycle and instead use anaerobic fermentation of simple sugars

  3. A white box perspective on behavioural adaptation

    DEFF Research Database (Denmark)

    Bruni, Roberto; Corradini, Andrea; Gadducci, Fabio

    2015-01-01

    We present a white-box conceptual framework for adaptation developed in the context of the EU Project ASCENS coordinated by Martin Wirsing. We called it CoDA, for Control Data Adaptation, since it is based on the notion of control data. CoDA promotes a neat separation between application and adap......We present a white-box conceptual framework for adaptation developed in the context of the EU Project ASCENS coordinated by Martin Wirsing. We called it CoDA, for Control Data Adaptation, since it is based on the notion of control data. CoDA promotes a neat separation between application...... and adaptation logic through a clear identification of the set of data that is relevant for the latter. The framework provides an original perspective from which we survey a representative set of approaches to adaptation, ranging from programming languages and paradigms to computational models and architectural...

  4. Storylines and Pathways for Adaptation in Europe,

    DEFF Research Database (Denmark)

    Hilden, Mikael; Jeuken, Ad; Zandersen, Marianne

    2018-01-01

    as a central concept that helps to understand the range of available actions and the sequence of actions that can be taken under different scenarios of climate change and societal development. The chapter stresses the need to broadly understand the factors that affect adaptation challenges and that determine......This chapter focuses on how one can place climate change and adaptation actions in a wider context of societal change. It examines ways of conceptualizing the societal context for adaptation actions and illustrates how it plays out in different regions and substance areas in Europe and how...... this information can be used in reflecting on possibilities for adaptation at different levels. It places adaptation to climate change in the frame of Representative Concentration Pathways and Shared Socioeconomic Pathways, taking into account regional differences within Europe. The adaptation pathways are used...

  5. microRNAs and lipid metabolism

    Science.gov (United States)

    Aryal, Binod; Singh, Abhishek K.; Rotllan, Noemi; Price, Nathan; Fernández-Hernando, Carlos

    2017-01-01

    Purpose of review Work over the last decade has identified the important role of microRNAs (miRNAS) in regulating lipoprotein metabolism and associated disorders including metabolic syndrome, obesity and atherosclerosis. This review summarizes the most recent findings in the field, highlighting the contribution of miRNAs in controlling low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolism. Recent findings A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33. Work over the last two years has identified additional functions of miR-33 including the regulation of macrophage activation and mitochondrial metabolism. Moreover, it has recently been shown that miR-33 regulates vascular homeostasis and cardiac adaptation in response to pressure overload. In addition to miR-33 and miR-122, recent GWAS have identified single nucleotide polymorphisms (SNP) in the proximity of miRNAs genes associated with abnormal levels of circulating lipids in humans. Several of these miRNA, such as miR-148a and miR-128-1, target important proteins that regulate cellular cholesterol metabolism, including the low-density lipoprotein receptor (LDLR) and the ATP-binding cassette A1 (ABCA1). Summary microRNAs have emerged as critical regulators of cholesterol metabolism and promising therapeutic targets for treating cardiometabolic disorders including atherosclerosis. Here, we discuss the recent findings in the field highlighting the novel mechanisms by which miR-33 controls lipid metabolism and atherogenesis and the identification of novel miRNAs that regulate LDL metabolism. Finally, we summarize the recent findings that identified miR-33 as an important non-coding RNA that controls cardiovascular homeostasis independent of its role in regulating lipid metabolism. PMID:28333713

  6. Determinism and Contingency Shape Metabolic Complementation in an Endosymbiotic Consortium.

    Science.gov (United States)

    Ponce-de-Leon, Miguel; Tamarit, Daniel; Calle-Espinosa, Jorge; Mori, Matteo; Latorre, Amparo; Montero, Francisco; Pereto, Juli

    2017-01-01

    Bacterial endosymbionts and their insect hosts establish an intimate metabolic relationship. Bacteria offer a variety of essential nutrients to their hosts, whereas insect cells provide the necessary sources of matter and energy to their tiny metabolic allies. These nutritional complementations sustain themselves on a diversity of metabolite exchanges between the cell host and the reduced yet highly specialized bacterial metabolism-which, for instance, overproduces a small set of essential amino acids and vitamins. A well-known case of metabolic complementation is provided by the cedar aphid Cinara cedri that harbors two co-primary endosymbionts, Buchnera aphidicola BCc and Ca . Serratia symbiotica SCc, and in which some metabolic pathways are partitioned between different partners. Here we present a genome-scale metabolic network (GEM) for the bacterial consortium from the cedar aphid i BSCc. The analysis of this GEM allows us the confirmation of cases of metabolic complementation previously described by genome analysis (i.e., tryptophan and biotin biosynthesis) and the redefinition of an event of metabolic pathway sharing between the two endosymbionts, namely the biosynthesis of tetrahydrofolate. In silico knock-out experiments with i BSCc showed that the consortium metabolism is a highly integrated yet fragile network. We also have explored the evolutionary pathways leading to the emergence of metabolic complementation between reduced metabolisms starting from individual, complete networks. Our results suggest that, during the establishment of metabolic complementation in endosymbionts, adaptive evolution is significant in the case of tryptophan biosynthesis, whereas vitamin production pathways seem to adopt suboptimal solutions.

  7. Regulation of Metabolic Activity by p53

    Directory of Open Access Journals (Sweden)

    Jessica Flöter

    2017-05-01

    Full Text Available Metabolic reprogramming in cancer cells is controlled by the activation of multiple oncogenic signalling pathways in order to promote macromolecule biosynthesis during rapid proliferation. Cancer cells also need to adapt their metabolism to survive and multiply under the metabolically compromised conditions provided by the tumour microenvironment. The tumour suppressor p53 interacts with the metabolic network at multiple nodes, mostly to reduce anabolic metabolism and promote preservation of cellular energy under conditions of nutrient restriction. Inactivation of this tumour suppressor by deletion or mutation is a frequent event in human cancer. While loss of p53 function lifts an important barrier to cancer development by deleting cell cycle and apoptosis checkpoints, it also removes a crucial regulatory mechanism and can render cancer cells highly sensitive to metabolic perturbation. In this review, we will summarise the major concepts of metabolic regulation by p53 and explore how this knowledge can be used to selectively target p53 deficient cancer cells in the context of the tumour microenvironment.

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

    Science.gov (United States)

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

    2017-08-01

    metabolism and to follow the efficiency of a treatment at a preclinical or clinical stage. Relevant descriptors of tumor metabolism are now required to better stratify patients for the development of personalized metabolic medicine. In this review, we discuss the current limitations in basic research and drug discovery in the field of cancer metabolism to foster the need for more clinically relevant target identification and validation. We discuss the design of adapted drug screening assays and compound efficacy evaluation methods for the discovery of innovative anti-cancer therapeutic approaches at the level of tumor energetics. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Representing cognitive activities and errors in HRA trees

    International Nuclear Information System (INIS)

    Gertman, D.I.

    1992-01-01

    A graphic representation method is presented herein for adapting an existing technology--human reliability analysis (HRA) event trees, used to support event sequence logic structures and calculations--to include a representation of the underlying cognitive activity and corresponding errors associated with human performance. The analyst is presented with three potential means of representing human activity: the NUREG/CR-1278 HRA event tree approach; the skill-, rule- and knowledge-based paradigm; and the slips, lapses, and mistakes paradigm. The above approaches for representing human activity are integrated in order to produce an enriched HRA event tree -- the cognitive event tree system (COGENT)-- which, in turn, can be used to increase the analyst's understanding of the basic behavioral mechanisms underlying human error and the representation of that error in probabilistic risk assessment. Issues pertaining to the implementation of COGENT are also discussed

  10. Adaptive Remodeling of Achilles Tendon: A Multi-scale Computational Model.

    Directory of Open Access Journals (Sweden)

    Stuart R Young

    2016-09-01

    Full Text Available While it is known that musculotendon units adapt to their load environments, there is only a limited understanding of tendon adaptation in vivo. Here we develop a computational model of tendon remodeling based on the premise that mechanical damage and tenocyte-mediated tendon damage and repair processes modify the distribution of its collagen fiber lengths. We explain how these processes enable the tendon to geometrically adapt to its load conditions. Based on known biological processes, mechanical and strain-dependent proteolytic fiber damage are incorporated into our tendon model. Using a stochastic model of fiber repair, it is assumed that mechanically damaged fibers are repaired longer, whereas proteolytically damaged fibers are repaired shorter, relative to their pre-damage length. To study adaptation of tendon properties to applied load, our model musculotendon unit is a simplified three-component Hill-type model of the human Achilles-soleus unit. Our model results demonstrate that the geometric equilibrium state of the Achilles tendon can coincide with minimization of the total metabolic cost of muscle activation. The proposed tendon model independently predicts rates of collagen fiber turnover that are in general agreement with in vivo experimental measurements. While the computational model here only represents a first step in a new approach to understanding the complex process of tendon remodeling in vivo, given these findings, it appears likely that the proposed framework may itself provide a useful theoretical foundation for developing valuable qualitative and quantitative insights into tendon physiology and pathology.

  11. Neuron-glia metabolic coupling and plasticity.

    Science.gov (United States)

    Magistretti, Pierre J

    2006-06-01

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

  12. Represented Speech in Qualitative Health Research

    DEFF Research Database (Denmark)

    Musaeus, Peter

    2017-01-01

    Represented speech refers to speech where we reference somebody. Represented speech is an important phenomenon in everyday conversation, health care communication, and qualitative research. This case will draw first from a case study on physicians’ workplace learning and second from a case study...... on nurses’ apprenticeship learning. The aim of the case is to guide the qualitative researcher to use own and others’ voices in the interview and to be sensitive to represented speech in everyday conversation. Moreover, reported speech matters to health professionals who aim to represent the voice...... of their patients. Qualitative researchers and students might learn to encourage interviewees to elaborate different voices or perspectives. Qualitative researchers working with natural speech might pay attention to how people talk and use represented speech. Finally, represented speech might be relevant...

  13. Linking metabolomics data to underlying metabolic regulation

    Directory of Open Access Journals (Sweden)

    Thomas eNägele

    2014-11-01

    Full Text Available The comprehensive experimental analysis of a metabolic constitution plays a central role in approaches of organismal systems biology.Quantifying the impact of a changing environment on the homeostasis of cellular metabolism has been the focus of numerous studies applying various metabolomics techniques. It has been proven that approaches which integrate different analytical techniques, e.g. LC-MS, GC-MS, CE-MS and H-NMR, can provide a comprehensive picture of a certain metabolic homeostasis. Identification of metabolic compounds and quantification of metabolite levels represent the groundwork for the analysis of regulatory strategies in cellular metabolism. This significantly promotes our current understanding of the molecular organization and regulation of cells, tissues and whole organisms.Nevertheless, it is demanding to elicit the pertinent information which is contained in metabolomics data sets.Based on the central dogma of molecular biology, metabolite levels and their fluctuations are the result of a directed flux of information from gene activation over transcription to translation and posttranslational modification.Hence, metabolomics data represent the summed output of a metabolic system comprising various levels of molecular organization.As a consequence, the inverse assignment of metabolomics data to underlying regulatory processes should yield information which-if deciphered correctly-provides comprehensive insight into a metabolic system.Yet, the deduction of regulatory principles is complex not only due to the high number of metabolic compounds, but also because of a high level of cellular compartmentalization and differentiation.Motivated by the question how metabolomics approaches can provide a representative view on regulatory biochemical processes, this article intends to present and discuss current metabolomics applications, strategies of data analysis and their limitations with respect to the interpretability in context of

  14. In vitro adaptation of Plasmodium falciparum reveal variations in cultivability

    OpenAIRE

    White, John; Mascarenhas, Anjali; Pereira, Ligia; Dash, Rashmi; Walke, Jayashri T.; Gawas, Pooja; Sharma, Ambika; Manoharan, Suresh Kumar; Guler, Jennifer L.; Maki, Jennifer N.; Kumar, Ashwani; Mahanta, Jagadish; Valecha, Neena; Dubhashi, Nagesh; Vaz, Marina

    2016-01-01

    Background Culture-adapted Plasmodium falciparum parasites can offer deeper understanding of geographic variations in drug resistance, pathogenesis and immune evasion. To help ground population-based calculations and inferences from culture-adapted parasites, the complete range of parasites from a study area must be well represented in any collection. To this end, standardized adaptation methods and determinants of successful in vitro adaption were sought. Methods Venous blood was collected f...

  15. Respiratory Adaptations in Acid-base Disturbances: Role of Cerebral Fluids,

    Science.gov (United States)

    1979-06-19

    The respiratory and metabolic components of acid-base homeostasis are defined. A quantitative empirical description of the (incomplete) mutual...literature. Respiratory adaptations in steady acid-base disturbances of metabolic origin (hyperventilation with hypocapnia in primary metabolic acidosis, and...hypoventilation with hypercapnia in metabolic alkalosis ) are analyzed as a function of the acidity of the cerebral fluids (cerebrospinal and cerebral interstitial fluid). (Author)

  16. Adaptation illustrations: Chapter 4

    Science.gov (United States)

    Maria Janowiak; Patricia Butler; Chris Swanston; Matt St. Pierre; Linda. Parker

    2012-01-01

    In this chapter, we demonstrate how the Adaptation Workbook (Chapter 3) can be used with the Adaptation Strategies and Approaches (Chapter 2) to develop adaptation tactics for two real-world management issues. The two illustrations in this chapter are intended to provide helpful tips to managers completing the Adaptation Workbook, as well as to show how the anticipated...

  17. Adaptive Modular Playware

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Þorsteinsson, Arnar Tumi

    2011-01-01

    In this paper, we describe the concept of adaptive modular playware, where the playware adapts to the interaction of the individual user. We hypothesize that there are individual differences in user interaction capabilities and styles, and that adaptive playware may adapt to the individual user...

  18. Resilience through adaptation

    NARCIS (Netherlands)

    Broeke, ten Guus; Voorn, van George A.K.; Ligtenberg, Arend; Molenaar, Jaap

    2017-01-01

    Adaptation of agents through learning or evolution is an important component of the resilience of Complex Adaptive Systems (CAS). Without adaptation, the flexibility of such systems to cope with outside pressures would be much lower. To study the capabilities of CAS to adapt, social simulations

  19. Representative Sampling for reliable data analysis

    DEFF Research Database (Denmark)

    Petersen, Lars; Esbensen, Kim Harry

    2005-01-01

    regime in order to secure the necessary reliability of: samples (which must be representative, from the primary sampling onwards), analysis (which will not mean anything outside the miniscule analytical volume without representativity ruling all mass reductions involved, also in the laboratory) and data...

  20. PET Metabolic Biomarkers for Cancer

    Directory of Open Access Journals (Sweden)

    Etienne Croteau

    2016-01-01

    Full Text Available The body's main fuel sources are fats, carbohydrates (glucose, proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET imaging using the glucose analog 18 F-fluorodeoxyglucose ( 18 F-FDG has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication–-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects.

  1. Metabolism and disease

    National Research Council Canada - National Science Library

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

    2011-01-01

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

  2. Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.

    Directory of Open Access Journals (Sweden)

    Wen Liang

    Full Text Available BACKGROUND: Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT, often accompanied by non-alcoholic fatty liver disease (NAFLD. In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters' with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks, inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks, genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by

  3. 14 CFR 1274.906 - Designation of New Technology Representative and Patent Representative.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Designation of New Technology... Conditions § 1274.906 Designation of New Technology Representative and Patent Representative. Designation of New Technology Representative and Patent Representative July 2002 (a) For purposes of administration...

  4. Metabolic Engineering X Conference

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

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

  5. Mice Do Not Habituate to Metabolism Cage Housing

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Jacobsen, Kirsten Rosenmaj; Darusman, Huda Shalahudin

    2013-01-01

    The metabolism cage is a barren, non-enriched, environment, combining a number of recognized environmental stressors. We investigated the ability of male BALB/c mice to acclimatize to this form of housing. For three weeks markers of acute and oxidative stress, as well as clinical signs of abnorma...... metabolism warrant caution when interpreting data obtained from metabolism cage housed mice, as their condition cannot be considered representative of a normal physiology....

  6. The Leukemic Stem Cell Niche: Adaptation to “Hypoxia” versus Oncogene Addiction

    Directory of Open Access Journals (Sweden)

    Giulia Cheloni

    2017-01-01

    Full Text Available Previous studies based on low oxygen concentrations in the incubation atmosphere revealed that metabolic factors govern the maintenance of normal hematopoietic or leukemic stem cells (HSC and LSC. The physiological oxygen concentration in tissues ranges between 0.1 and 5.0%. Stem cell niches (SCN are placed in tissue areas at the lower end of this range (“hypoxic” SCN, to which stem cells are metabolically adapted and where they are selectively hosted. The data reported here indicated that driver oncogenic proteins of several leukemias are suppressed following cell incubation at oxygen concentration compatible with SCN physiology. This suppression is likely to represent a key positive regulator of LSC survival and maintenance (self-renewal within the SCN. On the other hand, LSC committed to differentiation, unable to stand suppression because of addiction to oncogenic signalling, would be unfit to home in SCN. The loss of oncogene addiction in SCN-adapted LSC has a consequence of crucial practical relevance: the refractoriness to inhibitors of the biological activity of oncogenic protein due to the lack of their molecular target. Thus, LSC hosted in SCN are suited to sustain the long-term maintenance of therapy-resistant minimal residual disease.

  7. Nutrition and training adaptations in aquatic sports.

    Science.gov (United States)

    Mujika, Iñigo; Stellingwerff, Trent; Tipton, Kevin

    2014-08-01

    The adaptive response to training is determined by the combination of the intensity, volume, and frequency of the training. Various periodized approaches to training are used by aquatic sports athletes to achieve performance peaks. Nutritional support to optimize training adaptations should take periodization into consideration; that is, nutrition should also be periodized to optimally support training and facilitate adaptations. Moreover, other aspects of training (e.g., overload training, tapering and detraining) should be considered when making nutrition recommendations for aquatic athletes. There is evidence, albeit not in aquatic sports, that restricting carbohydrate availability may enhance some training adaptations. More research needs to be performed, particularly in aquatic sports, to determine the optimal strategy for periodizing carbohydrate intake to optimize adaptations. Protein nutrition is an important consideration for optimal training adaptations. Factors other than the total amount of daily protein intake should be considered. For instance, the type of protein, timing and pattern of protein intake and the amount of protein ingested at any one time influence the metabolic response to protein ingestion. Body mass and composition are important for aquatic sport athletes in relation to power-to-mass and for aesthetic reasons. Protein may be particularly important for athletes desiring to maintain muscle while losing body mass. Nutritional supplements, such as b-alanine and sodium bicarbonate, may have particular usefulness for aquatic athletes' training adaptation.

  8. Nuclear receptors and metabolism: from feast to famine.

    Science.gov (United States)

    Hong, Suk-Hyun; Ahmadian, Maryam; Yu, Ruth T; Atkins, Annette R; Downes, Michael; Evans, Ronald M

    2014-05-01

    The ability to adapt to cycles of feast and famine is critical for survival. Communication between multiple metabolic organs must be integrated to properly metabolise nutrients. By controlling networks of genes in major metabolic organs, nuclear hormone receptors (NHRs) play central roles in regulating metabolism in a tissue-specific manner. NHRs also establish daily rhythmicity by controlling the expression of core clock genes both centrally and peripherally. Recent findings show that many of the metabolic effects of NHRs are mediated through certain members of the fibroblast growth factor (FGF) family. This review focuses on the roles of NHRs in critical metabolic organs, including adipose tissue, liver and muscle, during the fed and fasted states, as well as their roles in circadian metabolism and downstream regulation of FGFs.

  9. Qualitative Analysis of Integration Adapter Modeling

    OpenAIRE

    Ritter, Daniel; Holzleitner, Manuel

    2015-01-01

    Integration Adapters are a fundamental part of an integration system, since they provide (business) applications access to its messaging channel. However, their modeling and configuration remain under-represented. In previous work, the integration control and data flow syntax and semantics have been expressed in the Business Process Model and Notation (BPMN) as a semantic model for message-based integration, while adapter and the related quality of service modeling were left for further studi...

  10. Verification of Representative Sampling in RI waste

    International Nuclear Information System (INIS)

    Ahn, Hong Joo; Song, Byung Cheul; Sohn, Se Cheul; Song, Kyu Seok; Jee, Kwang Yong; Choi, Kwang Seop

    2009-01-01

    For evaluating the radionuclide inventories for RI wastes, representative sampling is one of the most important parts in the process of radiochemical assay. Sampling to characterized RI waste conditions typically has been based on judgment or convenience sampling of individual or groups. However, it is difficult to get a sample representatively among the numerous drums. In addition, RI waste drums might be classified into heterogeneous wastes because they have a content of cotton, glass, vinyl, gloves, etc. In order to get the representative samples, the sample to be analyzed must be collected from selected every drum. Considering the expense and time of analysis, however, the number of sample has to be minimized. In this study, RI waste drums were classified by the various conditions of the half-life, surface dose, acceptance date, waste form, generator, etc. A sample for radiochemical assay was obtained through mixing samples of each drum. The sample has to be prepared for radiochemical assay and although the sample should be reasonably uniform, it is rare that a completely homogeneous material is received. Every sample is shredded by a 1 ∼ 2 cm 2 diameter and a representative aliquot taken for the required analysis. For verification of representative sampling, classified every group is tested for evaluation of 'selection of representative drum in a group' and 'representative sampling in a drum'

  11. Representative Sinusoids for Hepatic Four-Scale Pharmacokinetics Simulations.

    Directory of Open Access Journals (Sweden)

    Lars Ole Schwen

    Full Text Available The mammalian liver plays a key role for metabolism and detoxification of xenobiotics in the body. The corresponding biochemical processes are typically subject to spatial variations at different length scales. Zonal enzyme expression along sinusoids leads to zonated metabolization already in the healthy state. Pathological states of the liver may involve liver cells affected in a zonated manner or heterogeneously across the whole organ. This spatial heterogeneity, however, cannot be described by most computational models which usually consider the liver as a homogeneous, well-stirred organ. The goal of this article is to present a methodology to extend whole-body pharmacokinetics models by a detailed liver model, combining different modeling approaches from the literature. This approach results in an integrated four-scale model, from single cells via sinusoids and the organ to the whole organism, capable of mechanistically representing metabolization inhomogeneity in livers at different spatial scales. Moreover, the model shows circulatory mixing effects due to a delayed recirculation through the surrounding organism. To show that this approach is generally applicable for different physiological processes, we show three applications as proofs of concept, covering a range of species, compounds, and diseased states: clearance of midazolam in steatotic human livers, clearance of caffeine in mouse livers regenerating from necrosis, and a parameter study on the impact of different cell entities on insulin uptake in mouse livers. The examples illustrate how variations only discernible at the local scale influence substance distribution in the plasma at the whole-body level. In particular, our results show that simultaneously considering variations at all relevant spatial scales may be necessary to understand their impact on observations at the organism scale.

  12. Metabolic engineering tools in model cyanobacteria.

    Science.gov (United States)

    Carroll, Austin L; Case, Anna E; Zhang, Angela; Atsumi, Shota

    2018-03-26

    Developing sustainable routes for producing chemicals and fuels is one of the most important challenges in metabolic engineering. Photoautotrophic hosts are particularly attractive because of their potential to utilize light as an energy source and CO 2 as a carbon substrate through photosynthesis. Cyanobacteria are unicellular organisms capable of photosynthesis and CO 2 fixation. While engineering in heterotrophs, such as Escherichia coli, has result in a plethora of tools for strain development and hosts capable of producing valuable chemicals efficiently, these techniques are not always directly transferable to cyanobacteria. However, recent efforts have led to an increase in the scope and scale of chemicals that cyanobacteria can produce. Adaptations of important metabolic engineering tools have also been optimized to function in photoautotrophic hosts, which include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9, 13 C Metabolic Flux Analysis (MFA), and Genome-Scale Modeling (GSM). This review explores innovations in cyanobacterial metabolic engineering, and highlights how photoautotrophic metabolism has shaped their development. Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  13. KUDESAN EFFICACY IN ADOLESCENTS WITH METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    M.B. Kolesnikova

    2011-01-01

    Full Text Available Metabolic abnormalities in metabolic syndrome affect the functioning of practically all organs and systems, and most seriously — cardio-vascular system. Cardio-vascular abnormalities in metabolic syndrome manifest as arterial hypertension, Riley-Day syndrome and endothelial dysfunction that can lead to decrease of adaptive and reserve capabilities. Co-enzyme Q10 possesses cardioprotective,  stress-protective and anti-ischaemic activity. Clinical study performed on 40 children aged 10 to 17 years with constitutive obesity, complicated metabolic syndrome, has proven validity of co-enzyme Q10 treatment in patients with metabolic syndrome. The use of co-enzyme Q10 15 mg/day during 30 days has lead to improvement of psycho-emotional condition, decrease in anxiety complaints, sleep improvement, decrease in asthenic syndrome symptoms, improvement in electrophysiological heart indices Key words: metabolic syndrome, co-enzyme Q10. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 102–106.

  14. Representing Uncertainty by Probability and Possibility

    DEFF Research Database (Denmark)

    of uncertain parameters. Monte Carlo simulation is readily used for practical calculations. However, an alternative approach is offered by possibility theory making use of possibility distributions such as intervals and fuzzy intervals. This approach is well suited to represent lack of knowledge or imprecision......Uncertain parameters in modeling are usually represented by probability distributions reflecting either the objective uncertainty of the parameters or the subjective belief held by the model builder. This approach is particularly suited for representing the statistical nature or variance...

  15. Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis.

    NARCIS (Netherlands)

    Serlie, M.J.; Haan, J.H.A. de; Tack, C.J.J.; Verberne, H.J.; Ackermans, M.T.; Heerschap, A.; Sauerwein, H.P.

    2005-01-01

    The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus

  16. Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis

    NARCIS (Netherlands)

    Serlie, Mireille J. M.; de Haan, Jacco H.; Tack, Cees J.; Verberne, Hein J.; Ackermans, Mariette T.; Heerschap, Arend; Sauerwein, Hans P.

    2005-01-01

    The introduction of C-13 magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus

  17. 99mTc-MDP bone scintigraphy findings representing osteoporosis

    International Nuclear Information System (INIS)

    Nam, Dae Gun; Moon, Tae Geon; Kim, Ji Hong; Son, Seok Man; Kim, In Ju; Kim, Yong Ki

    2001-01-01

    Bone scintigraphy with 99m Tc-labeled phosphates is one of the most common procedures in evaluation of various skeletal disorders. Metabolic bone diseases show involvement of the whole skeleton and are associated with increased bone turnover and increased uptake of 99m Tc-labeled phosphates. In this study, we investigated apparently normal women who were examined with routine bone scintigraphy applied bone densitometry to correlate it with skeletal uptake in bone scan. This study includes 79 women who were performed both of bone mineral density(BMD) and bone scintigraphy. We investigated the relation of bone scan findings and BMD of lumbar, femur, radius. Regional BMD were negatively correlated with increased age. Among the bone scintigraphy findings representing metabolic bone disease, uptakes by the long bones, skull and mandible increased with age in women, while that in the costochondral junction decreased. Increased skull and mandible uptakes is associated with decreased BMD, and it has statistically significance. Our results show that increased radionuclide uptake in bone scintigraphy, especially skull and mandible uptake was associated with decreased lumbar, femur BMD in women. So that, increased skull and mandible uptake in women would be a scintigraphic sign of osteopenia or osteoporosis

  18. Control of fluxes in metabolic networks

    Science.gov (United States)

    Basler, Georg; Nikoloski, Zoran; Larhlimi, Abdelhalim; Barabási, Albert-László; Liu, Yang-Yu

    2016-01-01

    Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. PMID:27197218

  19. 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

    Evolution by natural selection under complex and dynamic environmental conditions occurs through intricate and often counterintuitive trajectories affecting many genes and metabolic solutions. To study short- and long-term evolution of bacteria in vivo , we used the natural model system of cystic fibrosis (CF) infection. In this work, we investigated how and through which trajectories evolution of Pseudomonas aeruginosa occurs when migrating from the environment to the airways of CF patients, and specifically, we determined reduction of growth rate and metabolic specialization as signatures of adaptive evolution. We show that central metabolic pathways of three distinct Pseudomonas aeruginosa lineages coevolving within the same environment become restructured at the cost of versatility during long-term colonization. Cell physiology changes from naive to adapted phenotypes resulted in (i) alteration of growth potential that particularly converged to a slow-growth phenotype, (ii) alteration of nutritional requirements due to auxotrophy, (iii) tailored preference for carbon source assimilation from CF sputum, (iv) reduced arginine and pyruvate fermentation processes, and (v) increased oxygen requirements. Interestingly, although convergence was evidenced at the phenotypic level of metabolic specialization, comparative genomics disclosed diverse mutational patterns underlying the different evolutionary trajectories. Therefore, distinct combinations of genetic and regulatory changes converge to common metabolic adaptive trajectories leading to within-host metabolic specialization. This study gives new insight into bacterial metabolic evolution during long-term colonization of a new environmental niche. IMPORTANCE Only a few examples of real-time evolutionary investigations in environments outside the laboratory are described in the scientific literature. Remembering that biological evolution, as it has progressed in nature, has not taken place in test tubes, it is not

  20. 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/

  1. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

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

  2. Services Subcontract Technical Representative (STR) handbook

    International Nuclear Information System (INIS)

    Houston, D.H.

    1997-06-01

    The purpose of this handbook is to provide guidance to Bechtel Hanford, Inc. Subcontract Representatives in their assignments. It is the intention of this handbook to ensure that subcontract work is performed in accordance with the subcontract documents

  3. REFractions: The Representing Equivalent Fractions Game

    Science.gov (United States)

    Tucker, Stephen I.

    2014-01-01

    Stephen Tucker presents a fractions game that addresses a range of fraction concepts including equivalence and computation. The REFractions game also improves students' fluency with representing, comparing and adding fractions.

  4. Representing Boolean Functions by Decision Trees

    KAUST Repository

    Chikalov, Igor

    2011-01-01

    A Boolean or discrete function can be represented by a decision tree. A compact form of decision tree named binary decision diagram or branching program is widely known in logic design [2, 40]. This representation is equivalent to other forms

  5. Request by the Resident Representative of Iraq

    International Nuclear Information System (INIS)

    1990-01-01

    The attached clarification by a spokesman of the Iraqi Ministry of Foreign Affairs is being circulated for the information of Member States pursuant to a request made by the Resident Representative of Iraq

  6. Muscle Involvement in Preservation of Metabolic Flexibility by Treatment using n-3 PUFA or Rosiglitazone in Dietary-Obese Mice

    NARCIS (Netherlands)

    Medrikova, Dasa; Schothorst, van Evert; Bunschoten, Annelies; Flachs, Pavel; Kopecky, Jan; Keijer, Jaap

    2012-01-01

    Impaired resistance to insulin, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. The hampered metabolic adaptability triggers a further damage of insulin signaling. Since skeletal muscle is the

  7. Expressing Adaptation Strategies Using Adaptation Patterns

    Science.gov (United States)

    Zemirline, N.; Bourda, Y.; Reynaud, C.

    2012-01-01

    Today, there is a real challenge to enable personalized access to information. Several systems have been proposed to address this challenge including Adaptive Hypermedia Systems (AHSs). However, the specification of adaptation strategies remains a difficult task for creators of such systems. In this paper, we consider the problem of the definition…

  8. Crisis Relocation Workshops for Transportation Industry Representatives

    Science.gov (United States)

    1979-12-01

    executive, two National Guard members, one Air Force transporta- _a ,tion representative, two Red Cross representatives, one school bus z coordinators...manaaers, local transitCD operator, and miiltary busingA authorityA Local Governa-ient 2 Fire chief, assistantI Air Force 3 Liaison Support D CPA :z...to attend the workshop. Majur trans- portation problems anticipated during crisis relocation include: 1. Transportation of carless residents; 2. The

  9. The representative model of teamwork adapted administrative management theory where leadership is owned exclusively by physician

    OpenAIRE

    Valentina Zaharia; I. Donciu; M.Dogaru; V.Perianu

    2015-01-01

    H.Fayol the organization as a complex organism that divides it into several parts, each part by executing specific operations, such as: technical (production), trade (supply, sale, exchange), financial records (accounting, statistics), security, insurance (Protection of property and persons) and administrative (foresight, organization, coordination, command and control).

  10. Acyl-Lipid Metabolism

    Science.gov (United States)

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

    2013-01-01

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

  11. Risk Gambling and Personality: Results from a Representative Swedish Sample.

    Science.gov (United States)

    Sundqvist, Kristina; Wennberg, Peter

    2015-12-01

    The association between personality and gambling has been explored previously. However, few studies are based on representative populations. This study aimed at examining the association between risk gambling and personality in a representative Swedish population. A random Swedish sample (N = 19,530) was screened for risk gambling using the Lie/Bet questionnaire. The study sample (N = 257) consisted of those screening positive on Lie/Bet and completing a postal questionnaire about gambling and personality (measured with the NODS-PERC and the HP5i respectively). Risk gambling was positively correlated with Negative Affectivity (a facet of Neuroticism) and Impulsivity (an inversely related facet of Conscientiousness), but all associations were weak. When taking age and gender into account, there were no differences in personality across game preference groups, though preferred game correlated with level of risk gambling. Risk gamblers scored lower than the population norm data with respect to Negative Affectivity, but risk gambling men scored higher on Impulsivity. The association between risk gambling and personality found in previous studies was corroborated in this study using a representative sample. We conclude that risk and problem gamblers should not be treated as a homogeneous group, and prevention and treatment interventions should be adapted according to differences in personality, preferred type of game and the risk potential of the games.

  12. 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.

  13. Dynamic optimal control of homeostasis: an integrative system approach for modeling of the central nitrogen metabolism in Saccharomyces cerevisiae.

    Science.gov (United States)

    van Riel, N A; Giuseppin, M L; Verrips, C T

    2000-01-01

    The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system encountered in advanced metabolic engineering. The CNM is the source of the cellular amino acids and proteins, including flavors and potentially valuable biomolecules; therefore, it is also of industrial interest. In the DOMC approach the cell is regarded as an optimally controlled system. Given the metabolic genotype, the cell faces a control problem to maintain an optimal flux distribution in a changing environment. The regulation is based on strategies and balances feedback control of homeostasis and feedforward regulation for adaptation. The DOMC approach is an integrative, holistic approach, not based on mechanistic descriptions and (therefore) not biased by the variation present in biochemical and molecular biological data. It is an effective tool to structure the rapidly increasing amount of data on the function of genes and pathways. The DOMC model is used successfully to predict the responses of pulses of ammonia and glutamine to nitrogen-limited continuous cultures of a wild-type strain and a glutamine synthetase-negative mutant. The simulation results are validated with experimental data.

  14. Adaptation of respiration and metabolism in Campylobacter jejuni

    NARCIS (Netherlands)

    van der Stel, A.

    2017-01-01

    Campylobacter jejuni is the most frequent cause of human food-borne bacterial gastroenteritis worldwide, however also one of the least understood enteropathogens.Instead of being a pathogen for humans, C. jejuni is part of the commensal microbiota in many warm-blooded animals, especially poultry.The

  15. 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...

  16. The compositional and evolutionary logic of metabolism

    International Nuclear Information System (INIS)

    Braakman, Rogier; Smith, Eric

    2013-01-01

    within biochemistry. Module boundaries provide the interfaces where change is concentrated, when we catalogue extant diversity of metabolic phenotypes. The same modules that organize the compositional diversity of metabolism are argued, with many explicit examples, to have governed long-term evolution. Early evolution of core metabolism, and especially of carbon-fixation, appears to have required very few innovations, and to have used few rules of composition of conserved modules, to produce adaptations to simple chemical or energetic differences of environment without diverse solutions and without historical contingency. We demonstrate these features of metabolism at each of several levels of hierarchy, beginning with the small-molecule metabolic substrate and network architecture, continuing with cofactors and key conserved reactions, and culminating in the aggregation of multiple diverse physical and biochemical processes in cells. (topical review)

  17. Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism.

    Directory of Open Access Journals (Sweden)

    Sebastiano Collino

    Full Text Available The aging phenotype in humans has been thoroughly studied but a detailed metabolic profiling capable of shading light on the underpinning biological processes of longevity is still missing. Here using a combined metabonomics approach compromising holistic (1H-NMR profiling and targeted MS approaches, we report for the first time the metabolic phenotype of longevity in a well characterized human aging cohort compromising mostly female centenarians, elderly, and young individuals. With increasing age, targeted MS profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype. We hypothesized that the overall lipidome changes specific to longevity putatively reflect centenarians' unique capacity to adapt/respond to the accumulating oxidative and chronic inflammatory conditions characteristic of their extreme aging phenotype. Our data in centenarians support promotion of cellular detoxification mechanisms through specific modulation of the arachidonic acid metabolic cascade as we underpinned increased concentration of 8,9-EpETrE, suggesting enhanced cytochrome P450 (CYP enzyme activity. Such effective mechanism might result in the activation of an anti-oxidative response, as displayed by decreased circulating levels of 9-HODE and 9-oxoODE, markers of lipid peroxidation and oxidative products of linoleic acid. Lastly, we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota as shown by the increased extrection of phenylacetylglutamine (PAG and p-cresol sulfate (PCS in urine of centenarians. Together, our novel approach in this representative Italian longevity cohort support the hypothesis that a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.

  18. 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.

  19. Nutritional and metabolic programming during the first thousand days of life

    Directory of Open Access Journals (Sweden)

    Massimo Agosti

    2017-06-01

    Full Text Available The latest scientific acquisitions are demonstrating what has already been hypothesized for more than twenty years about the development of the state of health/illness of individuals. Indeed, certain stimuli, if applied to a sensible phase of development, are able to modify, through epigenetic mechanisms, gene expression of DNA, resulting in adaptive modifications of phenotype to the environment, which may reflect negatively on the health of every individual. This concept, applied to nutrition, has opened up important prospects for research in this area. The nutritional history of an individual, linked to the development of a healthy state, would begin very early. In fact, since the pregnancy and for the next two years (for a total of about 1000 days, the maternal eating habits, the type of breastfeeding and then the main stages of nutrition in the evolutionary phase represent those sensitive moments, essential for the development of important endocrine, metabolic, immunological alterations, better known as metabolic syndrome. This condition would represent the physiopathogenetic basis for explaining a series of disorders, known as non communicable diseases (NCDs such as obesity, diabetes, hypertension, cardiovascolar disease and all those conditions that today affect the health of most industrialized countries and through the years are emerging especially in developing countries (South America, Asia, where new environmental conditions and increased food availability are changing food habits, with far-reaching public health impacts. This paper analyzes these new nutritional perspectives and the main implications of what has been termed the 1000-day theory.

  20. Mitochondrial Metabolism in Aging Heart

    Science.gov (United States)

    Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

    2016-01-01

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

  1. 48 CFR 1852.227-72 - Designation of new technology representative and patent representative.

    Science.gov (United States)

    2010-10-01

    ... CONTRACT CLAUSES Texts of Provisions and Clauses 1852.227-72 Designation of new technology representative... of New Technology Representative and Patent Representative (JUL 1997) (a) For purposes of administration of the clause of this contract entitled “New Technology” or “Patent Rights—Retention by the...

  2. 14 CFR 1260.58 - Designation of new technology representative and patent representative.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Designation of new technology... of new technology representative and patent representative. Designation of New Technology... of this grant entitled “New Technology,” the following named representatives are hereby designated by...

  3. 40 CFR 60.4112 - Changing Hg designated representative and alternate Hg designated representative; changes in...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Changing Hg designated representative and alternate Hg designated representative; changes in owners and operators. 60.4112 Section 60.4112... Generating Units Hg Designated Representative for Hg Budget Sources § 60.4112 Changing Hg designated...

  4. Adaptive Multimedia Retrieval: Semantics, Context, and Adaptation

    DEFF Research Database (Denmark)

    This book constitutes the thoroughly refereed post-conference proceedings of the 10th International Conference on Adaptive Multimedia Retrieval, AMR 2012, held in Copenhagen, Denmark, in October 2012. The 17 revised full papers presented were carefully reviewed and selected from numerous submissi......This book constitutes the thoroughly refereed post-conference proceedings of the 10th International Conference on Adaptive Multimedia Retrieval, AMR 2012, held in Copenhagen, Denmark, in October 2012. The 17 revised full papers presented were carefully reviewed and selected from numerous...... submissions. The papers cover topics of state of the art contributions, features and classification, location context, language and semantics, music retrieval, and adaption and HCI....

  5. Adaptation to climate change

    NARCIS (Netherlands)

    Carmin, J.; Tierney, K.; Chu, E.; Hunter, L.M.; Roberts, J.T.; Shi, L.; Dunlap, R.E.; Brulle, R.J.

    2015-01-01

    Climate change adaptation involves major global and societal challenges such as finding adequate and equitable adaptation funding and integrating adaptation and development programs. Current funding is insufficient. Debates between the Global North and South center on how best to allocate the

  6. Adaptation and Cultural Diffusion.

    Science.gov (United States)

    Ormrod, Richard K.

    1992-01-01

    Explores the role of adaptation in cultural diffusion. Explains that adaptation theory recognizes the lack of independence between innovations and their environmental settings. Discusses testing and selection, modification, motivation, and cognition. Suggests that adaptation effects are pervasive in cultural diffusion but require a broader, more…

  7. Adaptive user interfaces

    CERN Document Server

    1990-01-01

    This book describes techniques for designing and building adaptive user interfaces developed in the large AID project undertaken by the contributors.Key Features* Describes one of the few large-scale adaptive interface projects in the world* Outlines the principles of adaptivity in human-computer interaction

  8. Representing uncertainty on model analysis plots

    Directory of Open Access Journals (Sweden)

    Trevor I. Smith

    2016-09-01

    Full Text Available Model analysis provides a mechanism for representing student learning as measured by standard multiple-choice surveys. The model plot contains information regarding both how likely students in a particular class are to choose the correct answer and how likely they are to choose an answer consistent with a well-documented conceptual model. Unfortunately, Bao’s original presentation of the model plot did not include a way to represent uncertainty in these measurements. I present details of a method to add error bars to model plots by expanding the work of Sommer and Lindell. I also provide a template for generating model plots with error bars.

  9. Representative Democracy in Australian Local Government

    Directory of Open Access Journals (Sweden)

    Colin Hearfield

    2009-01-01

    Full Text Available In an assessment of representative democracy in Australian local government, this paper considers long-run changes in forms of political representation, methods of vote counting, franchise arrangements, numbers of local government bodies and elected representatives, as well as the thorny question of constitutional recognition. This discussion is set against the background of ongoing tensions between the drive for economic efficiency and the maintenance of political legitimacy, along with more deep-seated divisions emerging from the legal relationship between local and state governments and the resultant problems inherent in local government autonomy versus state intervention.

  10. Enhancing policy innovation by redesigning representative democracy

    DEFF Research Database (Denmark)

    Sørensen, Eva

    2016-01-01

    Policy innovation is a key aspect of public innovation, which has been largely overlooked. Political leadership, competition and collaboration are key drivers of policy innovation. It is a barrier in traditional models of representative democracy that they provide weak conditions for collaboration....... Two Danish case studies indicate that collaboration between politicians and relevant and affected stakeholders can promote policy innovation, but also that a redesign of representative democracy is needed in order to establish a productive combination of political leadership, competition...... and collaboration in political life....

  11. Representativeness elements of an hybrid reactor demonstrator

    International Nuclear Information System (INIS)

    Kerdraon, D.; Billebaud, A.; Brissot, R.; David, S.; Giorni, A.; Heuer, D.; Loiseaux, J.M.; Meplan, O.

    2000-11-01

    This document deals with the quantification of the minimum thermal power level for a demonstrator and the definition of the physical criteria which define the representative character of a demonstrator towards a power reactor. Solutions allowing to keep an acceptable flow in an industrial core, have also been studied. The document is divided in three parts: the representativeness elements, the considered solutions and the characterization of the neutrons flows at the interfaces and the dose rates at the outer surface of the vessel. (A.L.B.)

  12. 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.

  13. [Menopause and metabolic syndrome].

    Science.gov (United States)

    Meirelles, Ricardo M R

    2014-03-01

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

  14. Metabolic syndrome as a risk factor for neurological disorders.

    Science.gov (United States)

    Farooqui, Akhlaq A; Farooqui, Tahira; Panza, Francesco; Frisardi, Vincenza

    2012-03-01

    The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic 'bodyweight/appetite/satiety set point,' resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer's disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer's disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer's disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders. © Springer Basel AG 2011

  15. Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes

    DEFF Research Database (Denmark)

    You, Xinxin; Bian, Chao; Zan, Qijie

    2014-01-01

    Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansi...

  16. 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

  17. Performance analysis of joint diversity combining, adaptive modulation, and power control schemes

    KAUST Repository

    Qaraqe, Khalid A.; Bouida, Zied; Alouini, Mohamed-Slim

    2011-01-01

    Adaptive modulation and diversity combining represent very important adaptive solutions for future generations of wireless communication systems. Indeed, in order to improve the performance and the efficiency of these systems, these two techniques

  18. Metabolic syndrome and menopause

    OpenAIRE

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

    2013-01-01

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

  19. Attributes Heeded When Representing an Osmosis Problem.

    Science.gov (United States)

    Zuckerman, June Trop

    Eighteen high school science students were involved in a study to determine what attributes in the problem statement they need when representing a typical osmosis problem. In order to realize this goal students were asked to solve problems aloud and to explain their answers. Included as a part of the results are the attributes that the students…

  20. Representing Uncertainty on Model Analysis Plots

    Science.gov (United States)

    Smith, Trevor I.

    2016-01-01

    Model analysis provides a mechanism for representing student learning as measured by standard multiple-choice surveys. The model plot contains information regarding both how likely students in a particular class are to choose the correct answer and how likely they are to choose an answer consistent with a well-documented conceptual model.…

  1. Strong imploding shock, the representative curve

    International Nuclear Information System (INIS)

    Mishkin, E.A.; Alejaldre, C.

    1981-01-01

    The representative curve of the ideal gas behind the front of a spherically, or cylindrically, symmetric strong imploding shock is shown to pass through the point where the reduced pressure is maximum, P(xisub(m)) = Psub(m)sub(a)sub(x). (orig.)

  2. 28 CFR 104.4 - Personal Representative.

    Science.gov (United States)

    2010-07-01

    ... addition, as provided in § 104.21(b)(5) of this part, the Special Master may publish a list of individuals... Special Master may, in his discretion, determine that the Personal Representative for purposes of... administrator of the decedent's estate. In the event no will exists, the Special Master may, in his discretion...

  3. Adjustment Following Disability: Representative Case Studies.

    Science.gov (United States)

    Heinemann, Allen W.; Shontz, Franklin C.

    1984-01-01

    Examined adjustment following physical disability using the representative case method with two persons with quadriplegia. Results highlighted the importance of previously established coping styles as well as the role of the environment in adjustment. Willingness to mourn aided in later growth. (JAC)

  4. [Metabolic functions and sport].

    Science.gov (United States)

    Riviere, Daniel

    2004-01-01

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

  5. 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...

  6. 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).

  7. Resilience through adaptation.

    Directory of Open Access Journals (Sweden)

    Guus A Ten Broeke

    Full Text Available Adaptation of agents through learning or evolution is an important component of the resilience of Complex Adaptive Systems (CAS. Without adaptation, the flexibility of such systems to cope with outside pressures would be much lower. To study the capabilities of CAS to adapt, social simulations with agent-based models (ABMs provide a helpful tool. However, the value of ABMs for studying adaptation depends on the availability of methodologies for sensitivity analysis that can quantify resilience and adaptation in ABMs. In this paper we propose a sensitivity analysis methodology that is based on comparing time-dependent probability density functions of output of ABMs with and without agent adaptation. The differences between the probability density functions are quantified by the so-called earth-mover's distance. We use this sensitivity analysis methodology to quantify the probability of occurrence of critical transitions and other long-term effects of agent adaptation. To test the potential of this new approach, it is used to analyse the resilience of an ABM of adaptive agents competing for a common-pool resource. Adaptation is shown to contribute positively to the resilience of this ABM. If adaptation proceeds sufficiently fast, it may delay or avert the collapse of this system.

  8. Resilience through adaptation.

    Science.gov (United States)

    Ten Broeke, Guus A; van Voorn, George A K; Ligtenberg, Arend; Molenaar, Jaap

    2017-01-01

    Adaptation of agents through learning or evolution is an important component of the resilience of Complex Adaptive Systems (CAS). Without adaptation, the flexibility of such systems to cope with outside pressures would be much lower. To study the capabilities of CAS to adapt, social simulations with agent-based models (ABMs) provide a helpful tool. However, the value of ABMs for studying adaptation depends on the availability of methodologies for sensitivity analysis that can quantify resilience and adaptation in ABMs. In this paper we propose a sensitivity analysis methodology that is based on comparing time-dependent probability density functions of output of ABMs with and without agent adaptation. The differences between the probability density functions are quantified by the so-called earth-mover's distance. We use this sensitivity analysis methodology to quantify the probability of occurrence of critical transitions and other long-term effects of agent adaptation. To test the potential of this new approach, it is used to analyse the resilience of an ABM of adaptive agents competing for a common-pool resource. Adaptation is shown to contribute positively to the resilience of this ABM. If adaptation proceeds sufficiently fast, it may delay or avert the collapse of this system.

  9. Behavioural strategy: Adaptability context

    Directory of Open Access Journals (Sweden)

    Piórkowska Katarzyna

    2016-05-01

    Full Text Available The paper is embedded in the following fields: strategic management in terms of behavioural strategy concept, adaptability construct, and micro-foundations realm as well as organizational theory and psychology. Moreover, the paper concerns to some extent a multi-level approach in strategic management involving individual, team, and organizational level. The aim of the paper is to contribute to extend, on one hand, the ascertainment set in the field of behavioural strategy as behavioural strategy encompasses a mindboggling diversity of topics and methods and its conceptual unity has been hard to achieve (Powell, Lovallo, Fox 2011, p. 1371, and on the other hand, to order mixed approaches to adaptability especially to gain insights on micro-level adapting processes (individual adaptability and adaptive performance in terms of the multi-level approach. The method that has been used is literature studies and the interference is mostly deductive. The structure of the manuscript is four-fold. The first part involves the considerations in the field of adaptability and adaptive performance at the individual level. The issues of adaptability and adaptive performance at the team level have been presented in the second part. The third part encompasses the organizational adaptability assertions. Finally, the conclusion, limitations of the considerations highlighted as well as the future research directions have been emphasized. The overarching key finding is that the behavioural strategy concept may constitute the boundary spanner in exploring and explaining adaptability phenomenon at different levels of analysis.

  10. Fluoroacetylcarnitine: metabolism and metabolic effects in mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, J; Davis, E J

    1973-01-01

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

  11. Promises and Limits of Representative Bureaucracy in the Study of the EU’s Bureaucracy

    DEFF Research Database (Denmark)

    Gravier, Magali

    with the normative dimension of this theory. In an attempt to map the promises and limitations of the theory of representative bureaucracy for the study of the EU’s bureaucracy, the paper will tackle the following issues: How can this theory be adapted to fit the EU context? Can it be used despite its normative...

  12. Executive functions in persons with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Subotić Tatjana

    2016-01-01

    Full Text Available Modern man lyfestyle contributes to the increasing incidence of metabolic syndrome in the developed world. Prevalence of the metabolic syndrome in adults ranges from 20 to 25%, and it tends to increase. Each year, 3.2 million people around the world die from complications associated with this syndrome. Treatment involves cooperation of medical doctors of various specialties, but the decisive factor is patient motivation, given that the treatment requires significant lifestyle changes. Our hypothesis is that metabolic syndrome patients have reduced ability to plan, convert plan into action and effectively implement planned activities, showing signs of dysexecutive syndrome. The term executive functions comes from the English word 'executive', which also means the controlling, in neuropsychology reserved for high-level abilities that influence more basic abilities such as attention, perception, memory, thinking and speaking. The main objective of this study was to determine characteristics of executive functioning in patients with metabolic syndrome. The sample consisted of 61 subjects of both sexes, aged 20 to 60 years, divided into two groups - those with a diagnosis of metabolic syndrome and those without this diagnosis. The results suggest that people with metabolic syndrome showed significantly poorer performance in almost all indicators of executive functions, represented by Wisconsin Card Sorting Test (Wisconsin Card Sorting Test variables.

  13. The Genome Sequence of the psychrophilic archaeon, Methanococcoides burtonii: the Role of Genome Evolution in Cold-adaptation

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Michelle A.; Lauro, Federico M.; Williams, Timothy J.; Burg, Dominic; Siddiqui, Khawar S.; De Francisci, David; Chong, Kevin W.Y.; Pilak, Oliver; Chew, Hwee H.; De Maere, Matthew Z.; Ting, Lily; Katrib, Marilyn; Ng, Charmaine; Sowers, Kevin R.; Galperin, Michael Y.; Anderson, Iain J.; Ivanova, Natalia; Dalin, Eileen; Martinez, Michelle; Lapidus, Alla; Hauser, Loren; Land, Miriam; Thomas, Torsten; Cavicchioli, Ricardo

    2009-04-01

    Psychrophilic archaea are abundant and perform critical roles throughout the Earth's expansive cold biosphere. Here we report the first complete genome sequence for a psychrophilic methanogenic archaeon, Methanococcoides burtonii. The genome sequence was manually annotated including the use of a five tiered Evidence Rating system that ranked annotations from Evidence Rating (ER) 1 (gene product experimentally characterized from the parent organism) to ER5 (hypothetical gene product) to provide a rapid means of assessing the certainty of gene function predictions. The genome is characterized by a higher level of aberrant sequence composition (51%) than any other archaeon. In comparison to hyper/thermophilic archaea which are subject to selection of synonymous codon usage, M. burtonii has evolved cold adaptation through a genomic capacity to accommodate highly skewed amino acid content, while retaining codon usage in common with its mesophilic Methanosarcina cousins. Polysaccharide biosynthesis genes comprise at least 3.3% of protein coding genes in the genome, and Cell wall/membrane/envelope biogenesis COG genes are over-represented. Likewise, signal transduction (COG category T) genes are over-represented and M. burtonii has a high 'IQ' (a measure of adaptive potential) compared to many methanogens. Numerous genes in these two over-represented COG categories appear to have been acquired from {var_epsilon}- and {delta}-proteobacteria, as do specific genes involved in central metabolism such as a novel B form of aconitase. Transposases also distinguish M. burtonii from other archaea, and their genomic characteristics indicate they play an important role in evolving the M. burtonii genome. Our study reveals a capacity for this model psychrophile to evolve through genome plasticity (including nucleotide skew, horizontal gene transfer and transposase activity) that enables adaptation to the cold, and to the biological and physical changes that have

  14. Adaptive Resolution Simulation of MARTINI Solvents

    NARCIS (Netherlands)

    Zavadlav, Julija; Melo, Manuel N.; Cunha, Ana V.; de Vries, Alex H.; Marrink, Siewert J.; Praprotnik, Matej

    We present adaptive resolution dynamics simulations of aqueous and apolar solvents coarse-grained molecular models that are compatible with the MARTINI force field. As representatives of both classes solvents we have chosen liquid water and butane, respectively, at ambient temperature. The solvent

  15. Fatty acid metabolism: target for metabolic syndrome

    OpenAIRE

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

    2009-01-01

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

  16. Coevolution Based Adaptive Monte Carlo Localization (CEAMCL

    Directory of Open Access Journals (Sweden)

    Luo Ronghua

    2008-11-01

    Full Text Available An adaptive Monte Carlo localization algorithm based on coevolution mechanism of ecological species is proposed. Samples are clustered into species, each of which represents a hypothesis of the robot's pose. Since the coevolution between the species ensures that the multiple distinct hypotheses can be tracked stably, the problem of premature convergence when using MCL in highly symmetric environments can be solved. And the sample size can be adjusted adaptively over time according to the uncertainty of the robot's pose by using the population growth model. In addition, by using the crossover and mutation operators in evolutionary computation, intra-species evolution can drive the samples move towards the regions where the desired posterior density is large. So a small size of samples can represent the desired density well enough to make precise localization. The new algorithm is termed coevolution based adaptive Monte Carlo localization (CEAMCL. Experiments have been carried out to prove the efficiency of the new localization algorithm.