WorldWideScience

Sample records for metabolic turnover analysis

  1. Novel Strategy for Non-Targeted Isotope-Assisted Metabolomics by Means of Metabolic Turnover and Multivariate Analysis

    Directory of Open Access Journals (Sweden)

    Yasumune Nakayama

    2014-08-01

    Full Text Available Isotope-labeling is a useful technique for understanding cellular metabolism. Recent advances in metabolomics have extended the capability of isotope-assisted studies to reveal global metabolism. For instance, isotope-assisted metabolomics technology has enabled the mapping of a global metabolic network, estimation of flux at branch points of metabolic pathways, and assignment of elemental formulas to unknown metabolites. Furthermore, some data processing tools have been developed to apply these techniques to a non-targeted approach, which plays an important role in revealing unknown or unexpected metabolism. However, data collection and integration strategies for non-targeted isotope-assisted metabolomics have not been established. Therefore, a systematic approach is proposed to elucidate metabolic dynamics without targeting pathways by means of time-resolved isotope tracking, i.e., “metabolic turnover analysis”, as well as multivariate analysis. We applied this approach to study the metabolic dynamics in amino acid perturbation of Saccharomyces cerevisiae. In metabolic turnover analysis, 69 peaks including 35 unidentified peaks were investigated. Multivariate analysis of metabolic turnover successfully detected a pathway known to be inhibited by amino acid perturbation. In addition, our strategy enabled identification of unknown peaks putatively related to the perturbation.

  2. Relationships between Bone Turnover and Energy Metabolism

    Directory of Open Access Journals (Sweden)

    Tânia A. P. Fernandes

    2017-01-01

    Full Text Available It is well established that diabetes can be detrimental to bone health, and its chronic complications have been associated with an increased risk of osteoporotic fracture. However, there is growing evidence that the skeleton plays a key role in a whole-organism approach to physiology. The hypothesis that bone may be involved in the regulation of physiological functions, such as insulin sensitivity and energy metabolism, has been suggested. Given the roles of insulin, adipokines, and osteocalcin in these pathways, the need for a more integrative conceptual approach to physiology is emphasized. Recent findings suggest that bone plays an important role in regulating intermediary metabolism, being possibly both a target of diabetic complications and a potential pathophysiologic factor in the disease itself. Understanding the relationships between bone turnover and glucose metabolism is important in order to develop treatments that might reestablish energy metabolism and bone health. This review describes new insights relating bone turnover and energy metabolism that have been reported in the literature.

  3. Predicting Turnover Intentions and Turnover Behavior: A Multivariate Analysis.

    Science.gov (United States)

    Parasuraman, Saroj

    1982-01-01

    Assessed the relative influence of personal, attitudinal, and behavioral variables on behavioral intentions and voluntary turnover among nonsupervisory plant workers. Results show that personal variables have little direct effect on turnover; rather, their influence on turnover is channeled through their effects on behavioral intentions. (Author)

  4. Turnover and metabolism of phosphatidylglycerol acyl moieties in E. coli

    International Nuclear Information System (INIS)

    Cooper, C.L.; Rock, C.O.

    1987-01-01

    Fatty acids synthesized in mutants (plsB) blocked in de novo phospholipid biosynthesis were preferentially transferred to phosphatidylglycerol (PtdGro). The ratio of phospholipid species labeled with 32 P and [ 3 H]acetate in the absence of glycerol-3-P acyltransferase activity indicated that [ 3 H]acetate incorporation into PtdGro was due to fatty acid turnover. The magnitude of the turnover process was difficult to estimate due to a significant contraction of the acetyl-CoA pool following the inhibition of phospholipid synthesis. A possible connection between PtdGro turnover and protein acylation was investigated in an E. coli strain containing a lipoprotein expression vector. Cells were prelabeled with [ 3 H]acetate and lipoprotein expression was induced concomitant with the addition of exogenous [ 14 C]-palmitate. [ 14 C] Palmitate was assimilated into the l-position of phosphatidylethanolamine and transferred to the amino terminus of the lipoprotein. In contrast, the ester-linked lipoprotein fatty acids and PtdGro were not enriched in carbon-14 implying a metabolic relationship between these two pools. The data suggest that turnover of PtdGro acyl moieties is related to protein acylation, but a direct link between the two processes remains to be established

  5. A concept analysis of turnover intention: implications for nursing management.

    Science.gov (United States)

    Takase, Miyuki

    2010-01-01

    This paper provides a review and concept analysis of turnover intention. The aim was to promote Nurse Managers' understanding of the meanings and mechanisms of turnover intention, which could help them counteract nurse turnover. Sixty-six papers published between January 1998 and August 2007 were collected from CINAHL, PubMed, and PsycINFO databases, and were subjected to Rogers' concept analysis. The results showed that turnover intention is a multi-stage process involving the voluntary departure of employees from their current position, and is triggered by negative psychological responses to internal/external job context. These psychological responses evolve into withdrawal cognition and behaviours, and lead to actual turnover. To prevent nurse turnover, Nurse Managers should closely observe the internal and external causes of turnover, and the stage of nurses' turnover intention.

  6. Analysis and control of employee turnover.

    Science.gov (United States)

    McConnell, Charles R

    2007-01-01

    Turnover is a relatively simple and easily described concept. However, considerable confusion often results when addressing turnover because of differences in how it is defined; that is, what is counted, how it is counted, and how the turnover rates are expressed. Turnover is also costly, although not enough attention is paid to its cost because so much of it is indirect, and thus, not readily visible. There are a variety of causes of turnover, some which can be corrected and some which cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role.

  7. Brain metabolic DNA in memory processing and genome turnover.

    Science.gov (United States)

    Giuditta, Antonio; Grassi-Zucconi, Gigliola; Sadile, Adolfo G

    2017-01-01

    Sophisticated methods are currently used to investigate the properties of brain DNA and clarify its role under physiological conditions and in neurological and psychiatric disorders. Attention is now called on a DNA fraction present in the adult rat brain that is characterized by an elevated turnover and is not involved in cell division or DNA repair. The fraction, known as brain metabolic DNA (BMD), is modulated by strain, stress, circadian oscillations, exposure to enriched or impoverished environment, and notably by several training protocols and post-trial sleep. BMD is frequently localized in glial cells but is also present in neurons, often in the perinucleolar region. Its distribution in repetitive and non-repetitive DNA fractions shows that BMD differs from native DNA and that in learning rats its profile differs from that of control rats. More detailed knowledge of the molecular, cellular, and time-dependent BMD features will be necessary to define its role in memory acquisition and processing and in the pathogenesis of neurologic disorders.

  8. Amino acid metabolism and whole-body protein turnover in lambs ...

    African Journals Online (AJOL)

    The effect of protein supplementation of a wheat straw diet on the metabolism of lysine, leucine, methionine and urea, and on whole-body protein turnover rate was investigated in lambs. The metabolism of lysine and leucine is reported elsewhere (Cronje et aI., 1992); in this paper methionine metabolism is discussed, and ...

  9. Cholesterol turnover and metabolism in two patients with abetalipoproteinemia

    International Nuclear Information System (INIS)

    Goodman, D.S.; Deckelbaum, R.J.; Palmer, R.H.; Dell, R.B.; Ramakrishnan, R.; Delpre, G.; Beigel, Y.; Cooper, M.

    1983-01-01

    Total body turnover of cholesterol was studied in two patients with abetalipoproteinemia, a 32-year-old man and a 31-year-old woman. The patients received [14C]cholesterol intravenously, and the resulting specific activity-time curves (for 40 and 30 weeks, respectively) were fitted with a three-pool model. Parameters were compared with those from studies of cholesterol turnover in 82 normal and hyperlipidemic subjects. A three-pool model gave the best fit for the abetalipoproteinemic patients, as well as for the 82 previously studied subjects, suggesting general applicability of this model. Cholesterol production rates in the two abetalipoproteinemic subjects (0.82 and 0.89 g/day) were close to values predicted for persons of their body weight. Thus, total body turnover rate of cholesterol was quite normal in abetalipoproteinemia, confirming previous reports. Very low values (9.2 and 8.4 g) were found for M1, the size of the rapidly exchanging compartment pool 1, in the two abetalipoproteinemic subjects. These values were well below the values predicted (from the comparison study population) for normal persons of this size with low plasma cholesterol levels. For one patient, total body exchangeable cholesterol was very low, although not significantly below the predicted values for a person of his size. In the second patient, the observed estimate for total body exchangeable cholesterol was well within the range of values predicted for persons of her size with low to extremely low cholesterol levels

  10. Metabolic Turnover of Synaptic Proteins: Kinetics, Interdependencies and Implications for Synaptic Maintenance

    Science.gov (United States)

    Cohen, Laurie D.; Zuchman, Rina; Sorokina, Oksana; Müller, Anke; Dieterich, Daniela C.; Armstrong, J. Douglas; Ziv, Tamar; Ziv, Noam E.

    2013-01-01

    Chemical synapses contain multitudes of proteins, which in common with all proteins, have finite lifetimes and therefore need to be continuously replaced. Given the huge numbers of synaptic connections typical neurons form, the demand to maintain the protein contents of these connections might be expected to place considerable metabolic demands on each neuron. Moreover, synaptic proteostasis might differ according to distance from global protein synthesis sites, the availability of distributed protein synthesis facilities, trafficking rates and synaptic protein dynamics. To date, the turnover kinetics of synaptic proteins have not been studied or analyzed systematically, and thus metabolic demands or the aforementioned relationships remain largely unknown. In the current study we used dynamic Stable Isotope Labeling with Amino acids in Cell culture (SILAC), mass spectrometry (MS), Fluorescent Non–Canonical Amino acid Tagging (FUNCAT), quantitative immunohistochemistry and bioinformatics to systematically measure the metabolic half-lives of hundreds of synaptic proteins, examine how these depend on their pre/postsynaptic affiliation or their association with particular molecular complexes, and assess the metabolic load of synaptic proteostasis. We found that nearly all synaptic proteins identified here exhibited half-lifetimes in the range of 2–5 days. Unexpectedly, metabolic turnover rates were not significantly different for presynaptic and postsynaptic proteins, or for proteins for which mRNAs are consistently found in dendrites. Some functionally or structurally related proteins exhibited very similar turnover rates, indicating that their biogenesis and degradation might be coupled, a possibility further supported by bioinformatics-based analyses. The relatively low turnover rates measured here (∼0.7% of synaptic protein content per hour) are in good agreement with imaging-based studies of synaptic protein trafficking, yet indicate that the metabolic load

  11. Identifying molecular effects of diet through systems biology: influence of herring diet on sterol metabolism and protein turnover in mice.

    Directory of Open Access Journals (Sweden)

    Intawat Nookaew

    Full Text Available BACKGROUND: Changes in lifestyle have resulted in an epidemic development of obesity-related diseases that challenge the healthcare systems worldwide. To develop strategies to tackle this problem the focus is on diet to prevent the development of obesity-associated diseases such as cardiovascular disease (CVD. This will require methods for linking nutrient intake with specific metabolic processes in different tissues. METHODOLOGY/PRINCIPAL FINDING: Low-density lipoprotein receptor-deficient (Ldlr -/- mice were fed a high fat/high sugar diet to mimic a westernized diet, being a major reason for development of obesity and atherosclerosis. The diets were supplemented with either beef or herring, and matched in macronutrient contents. Body composition, plasma lipids and aortic lesion areas were measured. Transcriptomes of metabolically important tissues, e.g. liver, muscle and adipose tissue were analyzed by an integrated approach with metabolic networks to directly map the metabolic effects of diet in these different tissues. Our analysis revealed a reduction in sterol metabolism and protein turnover at the transcriptional level in herring-fed mice. CONCLUSION: This study shows that an integrated analysis of transcriptome data using metabolic networks resulted in the identification of signature pathways. This could not have been achieved using standard clustering methods. In particular, this systems biology analysis could enrich the information content of biomedical or nutritional data where subtle changes in several tissues together affects body metabolism or disease progression. This could be applied to improve diets for subjects exposed to health risks associated with obesity.

  12. Systematic analysis of protein turnover in primary cells.

    Science.gov (United States)

    Mathieson, Toby; Franken, Holger; Kosinski, Jan; Kurzawa, Nils; Zinn, Nico; Sweetman, Gavain; Poeckel, Daniel; Ratnu, Vikram S; Schramm, Maike; Becher, Isabelle; Steidel, Michael; Noh, Kyung-Min; Bergamini, Giovanna; Beck, Martin; Bantscheff, Marcus; Savitski, Mikhail M

    2018-02-15

    A better understanding of proteostasis in health and disease requires robust methods to determine protein half-lives. Here we improve the precision and accuracy of peptide ion intensity-based quantification, enabling more accurate protein turnover determination in non-dividing cells by dynamic SILAC-based proteomics. This approach allows exact determination of protein half-lives ranging from 10 to >1000 h. We identified 4000-6000 proteins in several non-dividing cell types, corresponding to 9699 unique protein identifications over the entire data set. We observed similar protein half-lives in B-cells, natural killer cells and monocytes, whereas hepatocytes and mouse embryonic neurons show substantial differences. Our data set extends and statistically validates the previous observation that subunits of protein complexes tend to have coherent turnover. Moreover, analysis of different proteasome and nuclear pore complex assemblies suggests that their turnover rate is architecture dependent. These results illustrate that our approach allows investigating protein turnover and its implications in various cell types.

  13. Water turnover rate and its metabolism in defaunated, refaunated and faunated male buffalo calves

    International Nuclear Information System (INIS)

    Chaudhary, L.C.; Srivastava, Arun

    1993-01-01

    In tropical countries like India, environment climatic conditions are variable throughout the year ranging from favourable to very hostile. The high temperature and humidity and often limited supply of water causes low productivity of livestock even when good quality of feed is supplied in required quantity. The turnover rate of water is related to environmental temperature, feed supply, protein or electrolyte content of the diet and also on physiological status of the animals.In the present experiment tritiated water dilution technique was used in an attempt to study the effect of removing ciliate protozoa from the rumen (defaunation) on water metabolism and its turnover rate in buffalo calves given wheat straw and concentrate mixture. (author). 18 refs., 2 tabs

  14. Indicators Used in the Dynamic Analysis of Turnover

    Directory of Open Access Journals (Sweden)

    Mihaela Loredana Ecobici

    2016-01-01

    Full Text Available The dynamic evolution of an indicator is an important aspect to be taken into consideration when analyzing the evolution in a company. Dynamic evolution uses a number of indicators that reveal aspects that the management of a company must introduce in the development strategy or in the rehabilitation process of a company. The purpose of this article is to analyse the dynamic evolution of the turnover at a company that operates in the field of industry. The finality of this article will result in a number of conclusions concerning the evolution of turnover analysed in the light of absolute modification, indices, growth rates and annual average rate of growth. The importance of the analysis of its evolution, stemming from the fact that it is in a relationship of perpetuous interdependence with the main economic factors that participate in the activity of production and marketing.

  15. Analysis of growth and tissue replacement rates by stable sulfur isotope turnover.

    Science.gov (United States)

    Arneson, L. S.; Macko, S. A.; Macavoy, S. E.

    2003-12-01

    Stable isotope analysis has become a powerful tool to study animal ecology. Analysis of stable isotope ratios of elements such as carbon, nitrogen, sulfur, hydrogen, oxygen and others have been used to trace migratory routes, reconstruct dietary sources and determine the physiological condition of individual animals. The isotopes most commonly used are carbon, due to differential carbon fractionation in C3 and C4 plants, and nitrogen, due to the approximately 3% enrichment in 15N per trophic level. Although all cells express sulfur-containing compounds, such as cysteine, methionine, and coenzyme A, the turnover rate of sulfur in tissues has not been examined in most studies, owing to the difficulty in determining the δ 34S signature. In this study, we have assessed the rate of sulfur isotopic turnover in mouse tissues following a diet change from terrestrial (7%) to marine (19%) source. Turnover models reflecting both growth rate and metabolic tissue replacement will be developed for blood, liver, fat and muscle tissues.

  16. Turnover rates in microorganisms by laser ablation electrospray ionization mass spectrometry and pulse-chase analysis

    Energy Technology Data Exchange (ETDEWEB)

    Stopka, Sylwia A.; Mansour, Tarek R.; Shrestha, Bindesh [Department of Chemistry, W.M. Keck Institute for Proteomics Technology and Applications, The George Washington University, Washington, DC 20052 (United States); Maréchal, Éric; Falconet, Denis [Laboratoire de Physiologie Cellulaire et Végétale, UMR 5168, CEA-CNRS-INRA-Univ. Grenoble Alpes, Grenoble (France); Vertes, Akos, E-mail: vertes@gwu.edu [Department of Chemistry, W.M. Keck Institute for Proteomics Technology and Applications, The George Washington University, Washington, DC 20052 (United States)

    2016-01-01

    Biochemical processes rely on elaborate networks containing thousands of compounds participating in thousands of reaction. Rapid turnover of diverse metabolites and lipids in an organism is an essential part of homeostasis. It affects energy production and storage, two important processes utilized in bioengineering. Conventional approaches to simultaneously quantify a large number of turnover rates in biological systems are currently not feasible. Here we show that pulse-chase analysis followed by laser ablation electrospray ionization mass spectrometry (LAESI-MS) enable the simultaneous and rapid determination of metabolic turnover rates. The incorporation of ion mobility separation (IMS) allowed an additional dimension of analysis, i.e., the detection and identification of isotopologs based on their collision cross sections. We demonstrated these capabilities by determining metabolite, lipid, and peptide turnover in the photosynthetic green algae, Chlamydomonas reinhardtii, in the presence of {sup 15}N-labeled ammonium chloride as the main nitrogen source. Following the reversal of isotope patterns in the chase phase by LAESI-IMS-MS revealed the turnover rates and half-lives for biochemical species with a wide range of natural concentrations, e.g., chlorophyll metabolites, lipids, and peptides. For example, the half-lives of lyso-DGTS(16:0) and DGTS(18:3/16:0), t{sub 1/2} = 43.6 ± 4.5 h and 47.6 ± 2.2 h, respectively, provided insight into lipid synthesis and degradation in this organism. Within the same experiment, half-lives for chlorophyll a, t{sub 1/2} = 24.1 ± 2.2 h, and a 2.8 kDa peptide, t{sub 1/2} = 10.4 ± 3.6 h, were also determined. - Highlights: • High-throughput pulse-chase analysis using direct sampling of biological cells. • Ion mobility separation for the elucidation of isotopologs. • Identification of isotopologs in difference heat plots of DT vs. m/z. • Simultaneous determination of turnover rates for lipids and

  17. Effects of chronic metabolic acidosis on splanchnic protein turnover and oxygen consumption in human beings.

    Science.gov (United States)

    Tessari, Paolo; Sofia, Antonella; Saffioti, Stefano; Vettore, Monica; Verzola, Daniela; Millioni, Renato; Puricelli, Lucia; Garibotto, Giacomo

    2010-04-01

    Although metabolic acidosis stimulates protein catabolism, its effects on splanchnic protein turnover and energy expenditure have not been measured in human beings. We investigated the effects of chronic metabolic acidosis (CMA) on splanchnic protein dynamics and oxygen consumption in human beings by using a leucine tracer and mass-balance techniques. Five subjects were studied after 6 days of HCl-, CaCl(2)-, and NH(4)Cl-induced acidosis; 8 subjects served as controls. Blood samples were collected from the radial artery and the hepatic veins. Measurements were performed on plasma and whole-blood samples. Based on plasma measurements, subjects who had undergone CMA had lower rates of splanchnic proteolysis (-35%) and protein synthesis (-50%; P controls, as well as a negative leucine kinetic balance (-6.81 +/- 2.48 micromol/kg/min/1.73 m(2) body surface [BS](-1)), compared with the neutral balance in control plasma samples (0.76 +/- 2.11 micromol/kg/min/1.73; P control samples, and the net leucine kinetic balance was neutral in both groups (CMA, -0.69 +/- 1.57; controls, -0.74 +/- 3.45 micromol/kg/min/1.73). In CMA whole-blood measurements, splanchnic oxygen consumption (44.8 +/- 4.3 mL/min/1.73 m(2) BS) was slightly lower than in controls (57.5 +/- 8.4 mL/min/1.73 m(2) BS; P = NS). Splanchnic protein synthesis correlated with oxygen consumption (r = 0.82; P < .001). CMA reduces splanchnic protein turnover and results in a negative leucine balance--an effect that apparently is offset by the contribution of blood cells to organ leucine (and protein) dynamics. Protein synthesis is a major contributor (about 67%) to energy expenditure in splanchnic organs. 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Use of ABC–XYZ–analysis in cost management of the cargo turnover in transport logistics

    OpenAIRE

    Chukurna O.; Davydova A.

    2017-01-01

    This article focuses on the relevance of the use of ABC–XYZ–analysis in the management of cargo turnover costs in the implementation of transport and logistics operations. It proposed by using the ABC analysis to rank suppliers or customers of freight turnover and the cost of each logistics operation (or profitability of the logistics services). On the basis of the received data to optimise logistics costs. It is proposed to use the XYZ–analysis to predict the volume of cargo turnover and a l...

  19. Protein turnover analysis in Salmonella Typhimurium during infection by dynamic SILAC, Topograph, and quantitative proteomics.

    Science.gov (United States)

    Wang, Zhe; Han, Qiang-Qiang; Zhou, Mao-Tian; Chen, Xi; Guo, Lin

    2016-07-01

    Protein turnover affects protein abundance and phenotypes. Comprehensive investigation of protein turnover dynamics has the potential to provide substantial information about gene expression. Here we report a large-scale protein turnover study in Salmonella Typhimurium during infection by quantitative proteomics. Murine macrophage-like RAW 264.7 cells were infected with SILAC labeled Salmonella. Bacterial cells were extracted after 0, 30, 60, 120, and 240 min. Mass spectrometry analyses yielded information about Salmonella protein turnover dynamics and a software program named Topograph was used for the calculation of protein half lives. The half lives of 311 proteins from intracellular Salmonella were obtained. For bacteria cultured in control medium (DMEM), the half lives for 870 proteins were obtained. The calculated median of protein half lives was 69.13 and 99.30 min for the infection group and the DMEM group, respectively, indicating an elevated protein turnover at the initial stage of infection. Gene ontology analyses revealed that a number of protein functional groups were significantly regulated by infection, including proteins involved in ribosome, periplasmic space, cellular amino acid metabolic process, ion binding, and catalytic activity. The half lives of proteins involved in purine metabolism pathway were found to be significantly shortened during infection. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. L-thyroxine 125I turnover studies. Methods of analysis and clinical application

    International Nuclear Information System (INIS)

    Snarski, A.; Snarska, J.; Neuman-Tomaszewska, B.; Krupa-Wojciechowska, B.

    1980-01-01

    The single compartmental (SC) and noncompartmental (NC) methods used for 1-T 4 125 I turnover studies are presented. The details of SC system are described. The 1-T 4 125 I turnover studies were performed in healthy people, hyperthyroid patients and in patients with protein disorders. The significant correlation between TBG capacity and thyroxine kinetics was found. The comparative studies of both NC and SC systems were carried out in additional group of patients. The SC analysis was found to be sufficiently precise for thyroxine turnover estimation. (author)

  1. Calcaneal quantitative ultrasound-bone mineral density value for evaluating bone metabolism and bone turnover in patients with osteoporotic fracture

    Directory of Open Access Journals (Sweden)

    Hong-Wei Yan

    2017-09-01

    Full Text Available Objective: To study the calcaneal quantitative ultrasound-bone mineral density (QUS-BMD value for evaluating bone metabolism and bone turnover in patients with osteoporotic fracture. Methods: A total of 150 patients who were diagnosed with osteoporotic fracture in Nuclear Industry 417 Hospital between January 2010 and March 2017 were selected as the fracture group of the research, and 70 subjects with normal bone mineral density confirmed by physical examination during the same period were selected as the control group of the research. QUSBMD apparatus was used to measure bone mineral density of calcaneus, and the serum was collected to determine the biochemical indexes of bone metabolism and bone turnover. Results: QUS-BMD value as well as serum BALP, OC, OPG levels of fracture group was significantly lower than those of control group while serum TRACP5b, RANKL, PINP, PICP, CTX and NTX levels were significantly higher than those of control group; serum BALP, OC, OPG levels of patients with osteoporosis and osteopenia were significantly lower than those of subjects with normal bone mass while TRACP5b, RANKL, PINP, PICP, CTX and NTX levels were significantly higher than those of subjects with normal bone mass; serum BALP, OC, OPG levels of patients with osteoporosis was significantly lower than those of patients with osteoporosis while TRACP5b, RANKL, PINP, PICP, CTX and NTX levels were significantly higher than those of patients with osteoporosis. Conclusion: Calcaneal QUS-BMD is valuable for evaluating the bone metabolism activity and bone turnover process in patients with osteoporotic fracture.

  2. Metabolic activity and collagen turnover in human tendon in response to physical activity

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, H; Miller, B F

    2005-01-01

    Connective tissue of the human tendon plays an important role in force transmission. The extracellular matrix turnover of tendon is influenced by physical activity. Blood flow, oxygen demand, and the level of collagen synthesis and matrix metalloproteinases increase with mechanical loading. Gene...... of overuse tendon injuries occurring during sport, work or leisure-related activities....

  3. Metabolic activity and collagen turnover in human tendon in response to physical activity

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, H; Miller, B F

    2005-01-01

    Connective tissue of the human tendon plays an important role in force transmission. The extracellular matrix turnover of tendon is influenced by physical activity. Blood flow, oxygen demand, and the level of collagen synthesis and matrix metalloproteinases increase with mechanical loading. Gene ...

  4. Metabolic substrate use and the turnover of endogenous energy reserves in broad-tailed hummingbirds (Selasphorus platycercus).

    Science.gov (United States)

    Carleton, Scott A; Bakken, Bradley Hartman; Del Rio, Carlos Martínez

    2006-07-01

    We fed broad-tailed hummingbirds (Selasphorus platycercus) diets of contrasting carbon isotope composition and measured changes in the delta(13)C of expired breath through time. By measuring the delta(13)C in the breath of fed and fasted birds we were able to quantify the fraction of metabolism fueled by assimilated sugars and endogenous energy reserves. These measurements also allowed us to estimate the fractional turnover of carbon in the hummingbirds' energy reserves. When hummingbirds were feeding, they fueled their metabolism largely ( approximately 90%) with assimilated sugars. The rate of carbon isotope incorporation into the energy reserves of hummingbirds was higher when birds were gaining as opposed to losing body mass. The average residence time of a carbon atom in the hummingbirds' energy reserves ranged from 1 to 2 days.

  5. Emergency room nurses' pathway to turnover intention: a moderated serial mediation analysis.

    Science.gov (United States)

    Bruyneel, Luk; Thoelen, Tom; Adriaenssens, Jef; Sermeus, Walter

    2017-04-01

    The aim of this study was to explore the association between the quality of the work environment, job characteristics, demographic characteristics and a pathway of job satisfaction, emotional exhaustion and turnover intention among nurses in emergency departments and perform subgroup analyses. Turnover intention among nurses is high. Multiple causes have been described, mostly in large studies of nurses working on general wards, often without considering complementarity of conceptual models and showing scant interest in the consistency of associations across subgroups of nurses. Cross-sectional multicentre survey. Convenience sample of 294 nurses in 11 Belgian emergency departments during 2014-2015. Indirect effects in the form of mediation and serial mediation were estimated to assess the association between work environment (Magnet model), job characteristics (Job Demand Control Support model) and turnover intention via job satisfaction and emotional exhaustion. Consistency of these indirect effects across subgroups of nurses was examined using moderated mediation analysis (conditional indirect effects). Several Magnet and Job Demand Control Support dimensions were related to turnover intention, either via job dissatisfaction (mediation) or via job satisfaction and emotional exhaustion (serial mediation). In the case of social support from supervisor, these indirect effects were only significant for female nurses, among whom turnover intention was higher. Last, nurses with more years of experience were less likely to indicate turnover intention. To maximize prevention of turnover intention at emergency departments, interventions could target early career nurses, work environment and job characteristics. Female nurses in particular may also benefit from improved social support from their supervisor. © 2016 John Wiley & Sons Ltd.

  6. Analysis of Soil Structure Turnover with Garnet Particles and X-Ray Microtomography.

    Science.gov (United States)

    Schlüter, Steffen; Vogel, Hans-Jörg

    2016-01-01

    Matter turnover in soil is tightly linked to soil structure which governs the heterogeneous distribution of habitats, reaction sites and pathways in soil. Thereby, the temporal dynamics of soil structure alteration is deemed to be important for essential ecosystem functions of soil but very little is known about it. A major reason for this knowledge gap is the lack of methods to study soil structure turnover directly at microscopic scales. Here we devise a conceptual approach and an image processing workflow to study soil structure turnover by labeling some initial state of soil structure with small garnet particles and tracking their fate with X-ray microtomography. The particles adhere to aggregate boundaries at the beginning of the experiment but gradually change their position relative to the nearest pore as structure formation progresses and pores are destructed or newly formed. A new metric based on the contact distances between particles and pores is proposed that allows for a direct quantification of soil structure turnover rates. The methodology is tested for a case study about soil compaction of a silty loam soil during stepwise increase of bulk density (ρ = {1.1, 1.3, 1.5} g/cm3). We demonstrate that the analysis of mean contact distances provides genuinely new insights about changing diffusion pathways that cannot be inferred neither from conventional pore space attributes (porosity, mean pore size, pore connectivity) nor from deformation analysis with digital image correlation. This structure labeling approach to quantify soil structure turnover provides a direct analogy to stable isotope labeling for the analysis of matter turnover and can be readily combined with each other.

  7. Effect of dietary fat saturation on lipid metabolism, arachidonic acid turnover and peritoneal macrophage oxidative stress in mice

    Directory of Open Access Journals (Sweden)

    L.B. Oliveros

    2004-03-01

    Full Text Available We investigated the effects of a saturated fat diet on lipid metabolism and arachidonic acid (AA turnover in mouse resident peritoneal macrophages. The pro-oxidative effect of this diet was also studied. Female C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet containing coconut oil (COCO diet, or the control diet containing soybean oil as fat source (10 mice per group. The fat content of each diet was 15% (w/w. Mice were fed for 6 weeks and then sacrificed. The concentration of total lipids, triglycerides, (LDL + VLDL-cholesterol, thiobarbituric acid-reactive substances (TBARS and reduced glutathione were increased in the plasma of mice fed the COCO diet, without changes in phospholipid or total cholesterol concentrations compared to control. The concentrations of total cholesterol, free and esterified cholesterol, triglycerides, and TBARS were increased in the macrophages of COCO-fed mice, while the content of total phospholipids did not change. The phospholipid composition showed an increase of phosphatidylcholine and a decrease of phosphatidylethanolamine. The [³H]-AA distribution in the phospholipid classes showed an increase in phosphatidylcholine and phosphatidylethanolamine. Incorporation of [³H]-cholesterol into the macrophages of COCO-fed mice and into the cholesterol ester fraction was increased. The COCO diet did not affect [³H]-AA uptake but induced an increase in [³H]-AA release. The COCO diet also enhanced AA mobilization induced by lipopolysaccharide. These results indicate that the COCO diet, high in saturated fatty acids, alters the lipid metabolism and AA turnover of peritoneal macrophages in female mice and also produces a significant degree of oxidative stress.

  8. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    2016-01-01

    Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transit...... time in humans, assessed using radio-opaque markers, is associated with overall gut microbial composition, diversity and metabolism. We find that a long colonic transit time associates with high microbial richness and is accompanied by a shift in colonic metabolism from carbohydrate fermentation...

  9. Colonic transit time is related to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...... transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencing and their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based...... on correlation analyses, we show that colonic transit time is associated with overall gut microbial composition, diversity and metabolism. A relatively prolonged colonic transit time associates with high microbial species richness and a shift in colonic metabolism from carbohydrate fermentation to protein...

  10. Colonic transit time relates to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...... transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencingand their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based...... on correlation analyses,we show that colonic transit time is associated with overall gutmicrobial composition, diversity and metabolism. A relatively prolonged colonic transit time associates with high microbial species richness and a shift in colonic metabolismfrom carbohydrate fermentation to protein...

  11. Amino acid metabolism and whole-body protein turnover in lambs ...

    African Journals Online (AJOL)

    based diets: 1. Lysine and leucine metabolism 1. P.B. Cronje*. Irene Animal Production Institute, Private Bag X2, Irene, 1675 Republic of South Africa. J.V. Nolan and A.A. Leng. Department of Microbiology, Biochemistry and Nutrition, University ...

  12. Amino acid metabolism and whole-body protein turnover in lambs ...

    African Journals Online (AJOL)

    but all estimates for the high-protein diet were significantly different (P < 0.06). The same trend was apparent in the case of whole-body protein synthesis, but leucine and methionine provided similar estimates for the high-protein diet. It was suggested that, although much stands to be gained from studies of the metabolism of ...

  13. The relationship between South Korean clinical nurses' attitudes toward organizations and voluntary turnover intention: A path analysis.

    Science.gov (United States)

    Kim, Jong Kyung; Chang, Sun Ju

    2015-08-01

    The purpose of this study was to examine the relationship between attitudes toward their organizations and voluntary turnover intention among South Korean clinical nurses. Data from a total of 312 clinical nurses in six hospitals in South Korea were collected for the study. Both hierarchical multiple regression analysis and path analysis were used to analyse the data. The overall fit of the hypothetical model was good. Voluntary turnover intention was found to have significant direct pathways to job embeddedness and organizational commitment. Organizational commitment and satisfaction with organizational rewards had indirect pathways to voluntary turnover intention through job embeddedness. All variances explained 62.3% of the voluntary turnover intention scores. The findings suggest that greater job embeddedness, organizational commitment and satisfaction with organizational rewards lead to lower voluntary turnover intention among clinical nurses in South Korea. © 2014 Wiley Publishing Asia Pty Ltd.

  14. Glucose and lactate turnover and gluconeogenesis in chronic metabolic acidosis and alkalosis in normal and diabetic dogs.

    Science.gov (United States)

    Hetenyi, G; Paradis, H; Kucharczyk, J

    1988-02-01

    The turnover rate of glucose, the irreversible disposal rate of lactate, and the rate of gluconeogenesis from lactate were calculated by tracer methods in four normal and four alloxan-diabetic dogs under control conditions as well as in chronic, stable metabolic acidosis and alkalosis. Acidosis was produced by feeding dogs 0.8-1 g.kg-1.day-1NH4Cl over 1 week, alkalosis was produced by feeding dogs a chloride-free diet and injections of furosemide. Mean plasma pH in the three states were 7.28 +/- 0.013, 7.40 +/- 0.024, and 7.51 +/- 0.015 in normal dogs, and 7.22 +/- 0.025, 7.42 +/- 0.009, and 7.49 +/- 0.002 in the diabetic dogs. Respective mean plasma bicarbonate levels were 14.6 +/- 0.88, 22.0 +/- 0.80, and 32.4 +/- 1.88 mequiv. in normal dogs, and 12.3 +/- 1.30, 22.6 +/- 0.66, and 35.0 +/- 1.14 mequiv. in diabetic animals. In normal dogs shifts in acid-base balance had no effect on the level of plasma glucose or the turnover rate of glucose. In diabetic dogs plasma glucose level was significantly elevated by alkalosis. Plasma lactate was positively correlated with plasma pH (r = 0.69, p less than 0.01) and was in general higher in diabetic than in normal animals. The increment in concentration was due to a decreased clearance of lactate from the plasma. The irreversible disposal rate was not changed by the acid-base status. Whereas a larger fraction of lactate removed from the plasma appeared in glucose in diabetic animals, this fraction was not changed significantly by shifts in the acid-base status.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Simultaneous determination of glucose turnover, alanine turnover, and gluconeogenesis in human using a double stable-isotope-labeled tracer infusion and gas chromatography-mass spectrometry analysis

    International Nuclear Information System (INIS)

    Martineau, A.; Lecavalier, L.; Falardeau, P.; Chiasson, J.L.

    1985-01-01

    We have developed and validated a new method to measure simultaneously glucose turnover, alanine turnover, and gluconeogenesis in human, in steady and non-steady states, using a double stable-isotope-labeled tracer infusion and GC-MS analysis. The method is based on the concomitant infusion and dilution of D-[2,3,4,6,6-2H5]glucose and L-[1,2,3-13C3]alanine. The choice of the tracers was done on the basis of a minimal overlap between the ions of interest and those arising from natural isotopic abundances. Alanine was chosen as the gluconeogenic substrate because it is the major gluconeogenic amino acid extracted by the liver and, with lactate, constitutes the bulk of the gluconeogenic precursors. The method was validated by comparing the results obtained during simultaneous infusion of trace amounts of both stable isotope labeled compounds with the radioactive tracers (D-[3-3H]glucose and L-[1,2,3-14C3]alanine) in a normal and a diabetic subject; the radiolabeled tracers were used as the accepted reference procedure. A slight overestimation of glucose turnover (7.3 versus 6.8 in normal and 10.8 versus 9.2 mumol/kg min in diabetic subject) was noticed when the stable isotope-labeled tracers were used. For the basal turnover rate of alanine, similar values were obtained with both methods (6.2 mumol/kg min). For gluconeogenesis, higher values were observed in the basal state with the stable isotopes (0.42 versus 0.21 mumol/kg min); however, these differences disappeared in the postprandial period after the ingestion of a mixed meal. Despite those minor differences, the overall correlation with the reference method was excellent for glucose turnover (r = 0.87) and gluconeogenesis (r = 0.86)

  16. Inorganic Carbon Turnover caused by Digestion of Carbonate Sands and Metabolic Activity of Holothurians

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Kenneth; Silverman, Jacob; Kravitz, Benjamin S.; Rivlin, Tanya; Schneider-Mor, Aya; Barbosa, Sergio; Byrne, Maria; Caldeira, Ken

    2013-11-20

    Recent measurements have shown that holothurians (sea cucumbers) play an important role in the cycling of CaCO3 in tropical coral reef systems through ingestion and processing of carbonate sediment. In this study inorganic additional aspects of carbon turnover were determined in laboratory incubations of Holothuria atra, H. leucospilota and Stichopus herrmanni from One Tree Reef, Great Barrier Reef. The pH values of the gut lumen ranged from 6.1 to 6.7 in animals with empty digestive tracts as opposed to 7.0 to 7.6 when digestive tracts were filled with sediment. Empty gut volume estimates for H. atra and S. herrmanni were 36 ± 4 mL and 151 ± 14 mL, respectively. Based on these measurements it is estimated that these species process 19 ± 2kg and 80 ± 7kg CaCO3 sand yr-1 per individual, respectively. The annual dissolution rates of H. atra and S. herrmanni of 6.5±1.9g and 9.6±1.4g, respectively, suggest that 0.05±0.02% and 0.1±0.02% of the CaCO3 processed through their gut annually is dissolved. During the incubations the CaCO3 dissolution was 0.07±0.01%, 0.04±0.01% and 0.21±0.05% of the fecal casts for H. atra, H. leucospilota and S. herrmanni, respectively. The CaCO3 saturation state for both aragonite and calcite minerals during laboratory incubations decreased markedly due to a greater increase in dissolved inorganic carbon (DIC) relative to total alkalinity (AT) as a result of respiration by the animals. Our results support the hypothesis that deposit feeders such as sea cucumbers play an important ecological role in the coral reef CaCO3 cycle.

  17. Primary Metabolic Pathways and Metabolic Flux Analysis

    DEFF Research Database (Denmark)

    Villadsen, John

    2015-01-01

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

  18. Principal Metabolic Flux Mode Analysis.

    Science.gov (United States)

    Bhadra, Sahely; Blomberg, Peter; Castillo, Sandra; Rousu, Juho; Wren, Jonathan

    2018-02-06

    In the analysis of metabolism, two distinct and complementary approaches are frequently used: Principal component analysis (PCA) and stoichiometric flux analysis. PCA is able to capture the main modes of variability in a set of experiments and does not make many prior assumptions about the data, but does not inherently take into account the flux mode structure of metabolism. Stoichiometric flux analysis methods, such as Flux Balance Analysis (FBA) and Elementary Mode Analysis, on the other hand, are able to capture the metabolic flux modes, however, they are primarily designed for the analysis of single samples at a time, and not best suited for exploratory analysis on a large sets of samples. We propose a new methodology for the analysis of metabolism, called Principal Metabolic Flux Mode Analysis (PMFA), which marries the PCA and stoichiometric flux analysis approaches in an elegant regularized optimization framework. In short, the method incorporates a variance maximization objective form PCA coupled with a stoichiometric regularizer, which penalizes projections that are far from any flux modes of the network. For interpretability, we also introduce a sparse variant of PMFA that favours flux modes that contain a small number of reactions. Our experiments demonstrate the versatility and capabilities of our methodology. The proposed method can be applied to genome-scale metabolic network in efficient way as PMFA does not enumerate elementary modes. In addition, the method is more robust on out-of-steady steady-state experimental data than competing flux mode analysis approaches. Matlab software for PMFA and SPMFA and data set used for experiments are available in https://github.com/aalto-ics-kepaco/PMFA. sahely@iitpkd.ac.in, juho.rousu@aalto.fi, Peter.Blomberg@vtt.fi, Sandra.Castillo@vtt.fi. Detailed results are in Supplementary files. Supplementary data are available at https://github.com/aalto-ics-kepaco/PMFA/blob/master/Results.zip.

  19. Identification of cardiomyocyte nuclei and assessment of ploidy for the analysis of cell turnover

    Energy Technology Data Exchange (ETDEWEB)

    Bergmann, Olaf; Zdunek, Sofia [Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Alkass, Kanar; Druid, Henrik [Department of Forensic Medicine, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Bernard, Samuel [CNRS UMR5208, Institut Camille Jordan, Universite Claude Bernard Lyon 1 (France); Frisen, Jonas, E-mail: jonas.frisen@ki.se [Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden)

    2011-01-15

    Assays to quantify myocardial renewal rely on the accurate identification of cardiomyocyte nuclei. We previously {sup 14}C birth dated human cardiomyocytes based on the nuclear localization of cTroponins T and I. A recent report by Kajstura et al. suggested that cTroponin I is only localized to the nucleus in a senescent subpopulation of cardiomyocytes, implying that {sup 14}C birth dating of cTroponin T and I positive cell populations underestimates cardiomyocyte renewal in humans. We show here that the isolation of cell nuclei from the heart by flow cytometry with antibodies against cardiac Troponins T and I, as well as pericentriolar material 1 (PCM-1), allows for isolation of close to all cardiomyocyte nuclei, based on ploidy and marker expression. We also present a reassessment of cardiomyocyte ploidy, which has important implications for the analysis of cell turnover, and iododeoxyuridine (IdU) incorporation data. These data provide the foundation for reliable analysis of cardiomyocyte turnover in humans.

  20. Inferring species richness and turnover by statistical multiresolution texture analysis of satellite imagery.

    Directory of Open Access Journals (Sweden)

    Matteo Convertino

    Full Text Available BACKGROUND: The quantification of species-richness and species-turnover is essential to effective monitoring of ecosystems. Wetland ecosystems are particularly in need of such monitoring due to their sensitivity to rainfall, water management and other external factors that affect hydrology, soil, and species patterns. A key challenge for environmental scientists is determining the linkage between natural and human stressors, and the effect of that linkage at the species level in space and time. We propose pixel intensity based Shannon entropy for estimating species-richness, and introduce a method based on statistical wavelet multiresolution texture analysis to quantitatively assess interseasonal and interannual species turnover. METHODOLOGY/PRINCIPAL FINDINGS: We model satellite images of regions of interest as textures. We define a texture in an image as a spatial domain where the variations in pixel intensity across the image are both stochastic and multiscale. To compare two textures quantitatively, we first obtain a multiresolution wavelet decomposition of each. Either an appropriate probability density function (pdf model for the coefficients at each subband is selected, and its parameters estimated, or, a non-parametric approach using histograms is adopted. We choose the former, where the wavelet coefficients of the multiresolution decomposition at each subband are modeled as samples from the generalized Gaussian pdf. We then obtain the joint pdf for the coefficients for all subbands, assuming independence across subbands; an approximation that simplifies the computational burden significantly without sacrificing the ability to statistically distinguish textures. We measure the difference between two textures' representative pdf's via the Kullback-Leibler divergence (KL. Species turnover, or [Formula: see text] diversity, is estimated using both this KL divergence and the difference in Shannon entropy. Additionally, we predict species

  1. Comprehensive analysis of glucose and xylose metabolism in Escherichia coli under aerobic and anaerobic conditions by13C metabolic flux analysis.

    Science.gov (United States)

    Gonzalez, Jacqueline E; Long, Christopher P; Antoniewicz, Maciek R

    2017-01-01

    Glucose and xylose are the two most abundant sugars derived from the breakdown of lignocellulosic biomass. While aerobic glucose metabolism is relatively well understood in E. coli, until now there have been only a handful of studies focused on anaerobic glucose metabolism and no 13 C-flux studies on xylose metabolism. In the absence of experimentally validated flux maps, constraint-based approaches such as MOMA and RELATCH cannot be used to guide new metabolic engineering designs. In this work, we have addressed this critical gap in current understanding by performing comprehensive characterizations of glucose and xylose metabolism under aerobic and anaerobic conditions, using recent state-of-the-art techniques in 13 C metabolic flux analysis ( 13 C-MFA). Specifically, we quantified precise metabolic fluxes for each condition by performing parallel labeling experiments and analyzing the data through integrated 13 C-MFA using the optimal tracers [1,2- 13 C]glucose, [1,6- 13 C]glucose, [1,2- 13 C]xylose and [5- 13 C]xylose. We also quantified changes in biomass composition and confirmed turnover of macromolecules by applying [U- 13 C]glucose and [U- 13 C]xylose tracers. We demonstrated that under anaerobic growth conditions there is significant turnover of lipids and that a significant portion of CO 2 originates from biomass turnover. Using knockout strains, we also demonstrated that β-oxidation is critical for anaerobic growth on xylose. Quantitative analysis of co-factor balances (NADH/FADH 2 , NADPH, and ATP) for different growth conditions provided new insights regarding the interplay of energy and redox metabolism and the impact on E. coli cell physiology. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  2. A retrospective analysis of employee turnover in the health care setting.

    Science.gov (United States)

    Bednar, B; McMullen, N

    1998-02-01

    Significant factors implicated in staff turnover include: variables in organizational structure; employee characteristics; needs and values, and the nature of tasks performed. This article will present the causative factors related to turnover and the conceptual models of the motivational theorists Maslow, Herzberg, Adams, and Mobley. No quantitative or qualitative research could be found on the potential causes of turnover in freestanding dialysis clinics. The staff turnover of a for-profit dialysis company for a 12 month period will be reported by job title, tenure, and level of job satisfaction.

  3. An Analysis on the Turnover of College Teachers in China from the Perspective of Institutional Economics

    Science.gov (United States)

    Zhang, Zhaojun

    2009-01-01

    Talents are the most important factor of all in the efforts to establish an innovative country. In universities and colleges, the bases for talent cultivation, the turnover of teachers in an explicit or recessive way calls for our urgent attention. This article aims at analyzing the complex causes of college teachers' turnover from the perspective…

  4. Growth versus metabolic tissue replacement in mouse tissues determined by stable carbon and nitrogen isotope analysis

    Science.gov (United States)

    Macavoy, S. E.; Jamil, T.; Macko, S. A.; Arneson, L. S.

    2003-12-01

    Stable isotope analysis is becoming an extensively used tool in animal ecology. The isotopes most commonly used for analysis in terrestrial systems are those of carbon and nitrogen, due to differential carbon fractionation in C3 and C4 plants, and the approximately 3‰ enrichment in 15N per trophic level. Although isotope signatures in animal tissues presumably reflect the local food web, analysis is often complicated by differential nutrient routing and fractionation by tissues, and by the possibility that large organisms are not in isotopic equilibrium with the foods available in their immediate environment. Additionally, the rate at which organisms incorporate the isotope signature of a food through both growth and metabolic tissue replacement is largely unknown. In this study we have assessed the rate of carbon and nitrogen isotopic turnover in liver, muscle and blood in mice following a diet change. By determining growth rates, we were able to determine the proportion of tissue turnover caused by growth versus that caused by metabolic tissue replacement. Growth was found to account for approximately 10% of observed tissue turnover in sexually mature mice (Mus musculus). Blood carbon was found to have the shortest half-life (16.9 days), followed by muscle (24.7 days). Liver carbon turnover was not as well described by the exponential decay equations as other tissues. However, substantial liver carbon turnover was observed by the 28th day after diet switch. Surprisingly, these tissues primarily reflect the carbon signature of the protein, rather than carbohydrate, source in their diet. The nitrogen signature in all tissues was enriched by 3 - 5‰ over their dietary protein source, depending on tissue type, and the isotopic turnover rates were comparable to those observed in carbon.

  5. An Analysis of the Effects of Deployment on Turnover in the United States Army Reserve

    National Research Council Canada - National Science Library

    McCloskey, Michele

    1999-01-01

    ...: involvement, demotivators, equity, reinforcement, reward relevance, and goals. Deficiencies were found in all six areas, with the most influential and interconnected determinant of post-deployment turnover stemming from poor leadership...

  6. Technology penetration and capital stock turnover. Lessons from IEA scenario analysis

    Energy Technology Data Exchange (ETDEWEB)

    Philibert, C. [International Energy Agency IEA, Organisation for Economic Co-operation and Development OECD, Paris (France)

    2007-05-15

    The aim of this paper is to reflect on the significant differences between the emissions reductions projections in mid-term and long-term scenarios, and to explore their policy implications. It draws mainly on two recent IEA publications: the 2006 World Energy Outlook (WEO), which contains energy and energy-related CO2 projections up to 2030, and the 2006-published Energy Technology Perspectives (ETP), which considers scenarios and strategies up to 2050. The analysis focuses on a comparison of the Alternative Policy Scenario of the 2006 WEO, and the various Accelerated Technology (ACT) Scenarios in the ETP. The next section provides the necessary background on these two publications and their energy-related CO2 emissions by 2030 and 2050, respectively. The third section investigates in some more depth the reasons for the large differences in the amount of emission reductions at these dates. Capital stock turnover and technology maturation lead times, in particular, are identified as primary reasons for the differences. The fourth section suggests several possible policy conclusions that can be drawn from this analysis. They include thought pieces with respect to the action required in the short-term; to the necessity of long-term signals; to the advantages and limitations of short-term targets; and to the opportunities and challenges the international community faces with respect to emission reductions in developing countries.

  7. Kinetic analysis of guanosine 5'-O-(3-thiotriphosphate) effects on phosphatidylinositol turnover in NRK cell homogenates

    International Nuclear Information System (INIS)

    Chahwala, S.B.; Fleischman, L.F.; Cantley, L.

    1987-01-01

    Addition of the guanine nucleotide analogue guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) to [ 3 H]inositol-labeled NRK cell homogenates resulted in rapid breakdown of cellular polyphosphoinositides. GTP gamma S stimulated phospholipase C, resulting in a more than 4-fold increase in the hydrolysis rates of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bis(phosphate) (PIP2). No significant effect of GTP gamma S on direct phosphatidylinositol (PI) hydrolysis was detected. There was an increase in water-soluble inositols, with inositol tris(phosphate) (IP3) levels increasing at least 10 times over the decrease seen in PIP2, indicating that PIP kinase activity was also accelerated following GTP gamma S addition. Inositol 1,4,5-tris(phosphate) peaked rapidly after GTP gamma S addition (less than 2 min) while inositol 1,3,4-tris-(phosphate) was produced more slowly and leveled off after approximately 10 min. The differential equations describing conversion between intermediates in the PI turnover pathway were solved and fitted to data obtained from both [ 3 H]inositol and [ 32 P]phosphate fluxes by nonlinear least-squares analysis. GTP gamma S effects on the pseudo-first-order rate constants for the lipase, kinase, and phosphatase steps were determined from the analysis. From these measurements it can be estimated that, in the presence of GTP gamma S and calcium buffered to 130 nM, hydrolysis of PIP2 accounts for at least 10 times as much diacylglycerol as direct PI breakdown despite the 100-fold excess of PI over PIP2. From the kinetic model it is predicted that small changes in the activities of PI and PIP kinases can have large but different effects on the level of IP3 and diacylglycerol following GTP gamma S addition. These results argue that regulation of PI and PIP kinases may be important for determining both cellular IP3 and diacylglycerol levels

  8. Developmental Climate: A Cross-level Analysis of Voluntary Turnover and Job Performance

    Science.gov (United States)

    Spell, Hannah B.; Eby, Lillian T.; Vandenberg, Robert J.

    2014-01-01

    This research investigates the influence of shared perceptions of developmental climate on individual-level perceptions of organizational commitment, engagement, and perceived competence, and whether these attitudes mediate the relationship between developmental climate and both individual voluntary turnover and supervisor-rated job performance. Survey data were collected from 361 intact employee-supervisory mentoring dyads and matched with employee turnover data collected one year later to test the proposed framework using multilevel modeling techniques. As expected, shared perceptions of developmental climate were significantly and positively related to all three individual work attitudes. In addition, both organizational commitment and perceived competence were significant mediators of the positive relationship between shared perceptions of developmental climate and voluntary turnover, as well as shared perceptions of developmental climate and supervisor-rated job performance. By contrast, no significant mediating effects were found for engagement. Theoretical implications, limitations, and future research are discussed. PMID:24748681

  9. Developmental Climate: A Cross-level Analysis of Voluntary Turnover and Job Performance.

    Science.gov (United States)

    Spell, Hannah B; Eby, Lillian T; Vandenberg, Robert J

    2014-06-01

    This research investigates the influence of shared perceptions of developmental climate on individual-level perceptions of organizational commitment, engagement, and perceived competence, and whether these attitudes mediate the relationship between developmental climate and both individual voluntary turnover and supervisor-rated job performance. Survey data were collected from 361 intact employee-supervisory mentoring dyads and matched with employee turnover data collected one year later to test the proposed framework using multilevel modeling techniques. As expected, shared perceptions of developmental climate were significantly and positively related to all three individual work attitudes. In addition, both organizational commitment and perceived competence were significant mediators of the positive relationship between shared perceptions of developmental climate and voluntary turnover, as well as shared perceptions of developmental climate and supervisor-rated job performance. By contrast, no significant mediating effects were found for engagement. Theoretical implications, limitations, and future research are discussed.

  10. When Friends Leave: A Structural Analysis of the Relationship between Turnover and Stayers' Attitudes.

    Science.gov (United States)

    Krackhardt, David; Porter, Lyman W.

    1985-01-01

    This paper investigates the effect that turnover in an organization has on the attitudes of those who remain. A longitudinal study of three fast-food restaurants explored this relationship against the background of the social network structures in each site. Results underscore the importance of structural context in studying microphenomena. (TE)

  11. Longitudinal Analysis of Personal and Work-Related Factors Associated With Turnover Among Nurses

    NARCIS (Netherlands)

    Estryn-Behar, Madeleine; van der Heijden, Beatrice; Fry, Clementine; Hasselhorn, Hans Martin

    2010-01-01

    AB Background: Although many scholars have acknowledged the relationship between personal and work-related factors associated with job search and actual turnover, there is a lack of longitudinal designs that test this relationship empirically. Objectives: This longitudinal study examines specific

  12. Employee Engagement and Turnover Intent: An Analysis of the Thai Public Sector

    Science.gov (United States)

    Tanthasith, Sitthichai

    2016-01-01

    Organizations these days are facing a number of challenges that affect their performance and productivity. As workplaces become more challenging to employees, employee engagement and turnover become critical concerns for management. Drawing on insights from the Job Demand-Resource model, this study explores the relationships between key…

  13. How Employee Turnover Affects Productivity

    DEFF Research Database (Denmark)

    Eriksen, Bo

    Research on employee turnover suggests that turnover results in negative organization-level outcomes. This paper provides a firm-level analysis of the impact of the in- and outflows of human resources on productivity and how the presence of organizational slack resources moderates the effects...... of employee turnover. Drawing on a unique longitudinal dataset of 2,926 Danish manufacturing firms that combine individual-level data with firm-level data, the paper shows that job turnover has a substantial negative effect on total productivity but that the firm’s size, its capital intensity, and its age...

  14. An Analysis of Turnover Intentions: A Reexamination of Air Force Civil Engineering Company Grade Officers

    Science.gov (United States)

    2012-03-01

    stay or leave their job is a construct called job embeddedness . Job embeddedness is basically how the employee fits in their overall environment (not...just their organization). Job embeddedness has six dimensions: links, fit, and sacrifice each associated with both the individual’s organization...2001) found evidence that supported each of the six dimensions of job embeddedness as having a significant relation to turnover in at least a

  15. Revisiting the impact of job satisfaction and organizational commitment on nurse turnover intention: an individual differences analysis.

    Science.gov (United States)

    De Gieter, Sara; Hofmans, Joeri; Pepermans, Roland

    2011-12-01

    Nurse turnover is an important contributing factor to the worldwide nursing shortage. Many studies have examined the antecedents of nurse turnover to gain a better understanding of the problem and help hospitals reduce their turnover rates. However, an important shortcoming of this research stream is its exclusive focus on explaining turnover behavior of the "average nurse", thereby disregarding individual differences between nurses and groups of nurses. To examine individual differences in the relationships between two crucial turnover antecedents - job satisfaction and organizational commitment - and nurse turnover intention. A sample of 287 nurses working for a variety of Belgian hospitals participated in the study. A survey method was used to collect quantitative data, which were analyzed through standard multiple linear regression, mixture regression models and t-tests. In the total sample of hospital nurses, both job satisfaction and organizational commitment significantly predicted nurse turnover intention. However, subsequent individual differences analyses revealed the existence of two subgroups of nurses. In the satisfaction focused group, only job satisfaction was found to predict nurse turnover intention, whereas in the satisfaction and commitment focused group both job satisfaction and organizational commitment were related to turnover intention. Furthermore, nurses in the latter group displayed stronger turnover intention, were significantly younger and had less job tenure and organizational tenure than nurses in the satisfaction focused group. The debate on the antecedents of nurse turnover still continues, as the existing models fail to fully grasp nurse turnover. The present study identifies individual differences in nurse turnover antecedents among groups of nurses as a possible reason for the absence of one comprehensive turnover model that holds for the general nursing population. Further studies are needed in order to capture the total impact

  16. High density lipoprotein (HDL) metabolism in noninsulin-dependent diabetes mellitus: measurement of HDL turnover using tritiated HDL

    Energy Technology Data Exchange (ETDEWEB)

    Golay, A.; Zech, L.; Shi, M.Z.; Chiou, Y.A.; Reaven, G.M.; Chen, Y.D.

    1987-09-01

    High density lipoprotein (HDL) kinetics were studied by injecting (/sup 3/H)apoprotein A-I (apoA-I)/HDL into 12 subjects with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM). The results indicate that the mean fractional catabolic rate (FCR) of apoA-I/HDL was significantly faster (0.63 +/- 0.07 (+/- SEM) vs. 0.39 +/- 0.02 1/day; P less than 0.001) and the apoA-I/HDL synthetic rate greater (29.4 +/- 2.9 vs. 22.9 +/- 1.3 mg/kg X day; P less than 0.02) in patients with NIDDM than in normal subjects. Furthermore, there were statistically significant inverse relationships between apoA-I/HDL FCR and plasma levels of both HDL cholesterol (r = -0.71; P less than 0.001) and apoA-I (r = -0.63; P less than 0.001). In addition, the increase in apoA-I/HDL FCR was directly related to fasting plasma glucose (r = 0.78; P less than 0.001) and insulin (r = 0.76; P less than 0.001) concentrations. These data support the view that the decrease in plasma HDL cholesterol and apoA-I levels commonly found in patients with noninsulin-dependent diabetes is due to an increase in the catabolic rate of apoA-I/HDL secondary to the defects in carbohydrate metabolism present in these patients.

  17. High density lipoprotein (HDL) metabolism in noninsulin-dependent diabetes mellitus: measurement of HDL turnover using tritiated HDL

    International Nuclear Information System (INIS)

    Golay, A.; Zech, L.; Shi, M.Z.; Chiou, Y.A.; Reaven, G.M.; Chen, Y.D.

    1987-01-01

    High density lipoprotein (HDL) kinetics were studied by injecting [ 3 H]apoprotein A-I (apoA-I)/HDL into 12 subjects with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM). The results indicate that the mean fractional catabolic rate (FCR) of apoA-I/HDL was significantly faster [0.63 +/- 0.07 (+/- SEM) vs. 0.39 +/- 0.02 1/day; P less than 0.001] and the apoA-I/HDL synthetic rate greater (29.4 +/- 2.9 vs. 22.9 +/- 1.3 mg/kg X day; P less than 0.02) in patients with NIDDM than in normal subjects. Furthermore, there were statistically significant inverse relationships between apoA-I/HDL FCR and plasma levels of both HDL cholesterol (r = -0.71; P less than 0.001) and apoA-I (r = -0.63; P less than 0.001). In addition, the increase in apoA-I/HDL FCR was directly related to fasting plasma glucose (r = 0.78; P less than 0.001) and insulin (r = 0.76; P less than 0.001) concentrations. These data support the view that the decrease in plasma HDL cholesterol and apoA-I levels commonly found in patients with noninsulin-dependent diabetes is due to an increase in the catabolic rate of apoA-I/HDL secondary to the defects in carbohydrate metabolism present in these patients

  18. Coupling of porcine bone blood flow and metabolism in high-turnover bone disease measured by [15O]H2O and [18F]fluoride ion positron emission tomography

    International Nuclear Information System (INIS)

    Piert, Morand; Machulla, Hans-Juergen; Stahlschmidt, Anke; Becker, Georg A.; Jahn, Michael; Zittel, Tilman T.

    2002-01-01

    Previously, we identified a parathyroid hormone-related high-turnover bone disease after gastrectomy in mini pigs. Dynamic [ 18 F]fluoride ion positron emission tomography (PET) revealed that bone metabolism was significantly increased, but that bone blood flow derived from permeability-surface area product (PS product)-corrected K 1 values was not. Since bone blood flow and metabolism are coupled in normal bone tissues, we hypothesised that the capillary permeability and/or surface area might be altered in high-turnover bone disease. The ''true'' bone blood flow (f H2O ) was measured in vertebral bodies by dynamic [ 15 O]H 2 O PET, followed by a 120-min dynamic [ 18 F]fluoride ion PET study, 6 months after total gastrectomy (n=5) and compared with results in sham-operated animals (n=5). Estimates for bone blood flow based on PS-corrected K 1 values (f) and the net uptake of fluoride in bone tissue (K i ), representing the bone metabolic activity, were calculated using standard compartmental modelling and non-linear fitting. Gastrectomy was followed by a significant elevation of K i and k 3 (P H2O , f, the single-pass extraction fraction of [ 18 F]fluoride (E) and the volume of distribution (DV) of [ 18 F]fluoride were not significantly different between groups. In both groups, a coupling of the mean f H2O and K i values was found, but the intercept with the y-axis was higher in high-turnover bone disease. It is concluded that in high-turnover bone disease following gastrectomy, the PS product for [ 18 F]fluoride remains unchanged. Therefore, even in high-turnover bone diseases, [ 18 F]fluoride ion PET can provide reliable blood flow estimates (f), as long as a proper PS product correction is applied. The increased bone metabolism in high-turnover bone disease after gastrectomy is mainly related to an up-regulation of the amount of ionic exchange of [ 18 F]fluoride with the bone matrix, while tracer delivery remains unchanged. (orig.)

  19. Coupling of porcine bone blood flow and metabolism in high-turnover bone disease measured by [{sup 15}O]H{sub 2}O and [{sup 18}F]fluoride ion positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Piert, Morand [Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich (Germany); Machulla, Hans-Juergen; Stahlschmidt, Anke; Becker, Georg A. [Radiopharmacy Section, PET Center, University of Tuebingen (Germany); Jahn, Michael; Zittel, Tilman T. [Department of Abdominal and Transplantation Surgery, University of Tuebingen (Germany)

    2002-07-01

    Previously, we identified a parathyroid hormone-related high-turnover bone disease after gastrectomy in mini pigs. Dynamic [{sup 18}F]fluoride ion positron emission tomography (PET) revealed that bone metabolism was significantly increased, but that bone blood flow derived from permeability-surface area product (PS product)-corrected K{sub 1} values was not. Since bone blood flow and metabolism are coupled in normal bone tissues, we hypothesised that the capillary permeability and/or surface area might be altered in high-turnover bone disease. The ''true'' bone blood flow (f{sub H2O}) was measured in vertebral bodies by dynamic [{sup 15}O]H{sub 2}O PET, followed by a 120-min dynamic [{sup 18}F]fluoride ion PET study, 6 months after total gastrectomy (n=5) and compared with results in sham-operated animals (n=5). Estimates for bone blood flow based on PS-corrected K{sub 1} values (f) and the net uptake of fluoride in bone tissue (K{sub i}), representing the bone metabolic activity, were calculated using standard compartmental modelling and non-linear fitting. Gastrectomy was followed by a significant elevation of K{sub i} and k{sub 3} (P<0.05), which was mainly caused by an increase of the fraction of bound tracer in tissue (P<0.01). In contrast, f{sub H2O}, f, the single-pass extraction fraction of [{sup 18}F]fluoride (E) and the volume of distribution (DV) of [{sup 18}F]fluoride were not significantly different between groups. In both groups, a coupling of the mean f{sub H2O} and K{sub i} values was found, but the intercept with the y-axis was higher in high-turnover bone disease. It is concluded that in high-turnover bone disease following gastrectomy, the PS product for [{sup 18}F]fluoride remains unchanged. Therefore, even in high-turnover bone diseases, [{sup 18}F]fluoride ion PET can provide reliable blood flow estimates (f), as long as a proper PS product correction is applied. The increased bone metabolism in high-turnover bone disease

  20. Pareto optimality in organelle energy metabolism analysis.

    Science.gov (United States)

    Angione, Claudio; Carapezza, Giovanni; Costanza, Jole; Lió, Pietro; Nicosia, Giuseppe

    2013-01-01

    In low and high eukaryotes, energy is collected or transformed in compartments, the organelles. The rich variety of size, characteristics, and density of the organelles makes it difficult to build a general picture. In this paper, we make use of the Pareto-front analysis to investigate the optimization of energy metabolism in mitochondria and chloroplasts. Using the Pareto optimality principle, we compare models of organelle metabolism on the basis of single- and multiobjective optimization, approximation techniques (the Bayesian Automatic Relevance Determination), robustness, and pathway sensitivity analysis. Finally, we report the first analysis of the metabolic model for the hydrogenosome of Trichomonas vaginalis, which is found in several protozoan parasites. Our analysis has shown the importance of the Pareto optimality for such comparison and for insights into the evolution of the metabolism from cytoplasmic to organelle bound, involving a model order reduction. We report that Pareto fronts represent an asymptotic analysis useful to describe the metabolism of an organism aimed at maximizing concurrently two or more metabolite concentrations.

  1. Computational Functional Analysis of Lipid Metabolic Enzymes.

    Science.gov (United States)

    Bagnato, Carolina; Have, Arjen Ten; Prados, María B; Beligni, María V

    2017-01-01

    The computational analysis of enzymes that participate in lipid metabolism has both common and unique challenges when compared to the whole protein universe. Some of the hurdles that interfere with the functional annotation of lipid metabolic enzymes that are common to other pathways include the definition of proper starting datasets, the construction of reliable multiple sequence alignments, the definition of appropriate evolutionary models, and the reconstruction of phylogenetic trees with high statistical support, particularly for large datasets. Most enzymes that take part in lipid metabolism belong to complex superfamilies with many members that are not involved in lipid metabolism. In addition, some enzymes that do not have sequence similarity catalyze similar or even identical reactions. Some of the challenges that, albeit not unique, are more specific to lipid metabolism refer to the high compartmentalization of the routes, the catalysis in hydrophobic environments and, related to this, the function near or in biological membranes.In this work, we provide guidelines intended to assist in the proper functional annotation of lipid metabolic enzymes, based on previous experiences related to the phospholipase D superfamily and the annotation of the triglyceride synthesis pathway in algae. We describe a pipeline that starts with the definition of an initial set of sequences to be used in similarity-based searches and ends in the reconstruction of phylogenies. We also mention the main issues that have to be taken into consideration when using tools to analyze subcellular localization, hydrophobicity patterns, or presence of transmembrane domains in lipid metabolic enzymes.

  2. [Association between Emotional Labor, Emotional Dissonance, Burnout and Turnover Intention in Clinical Nurses: A Multiple-Group Path Analysis across Job Satisfaction].

    Science.gov (United States)

    Back, Chi Yun; Hyun, Dae Sung; Chang, Sei Jin

    2017-12-01

    This study was conducted to investigate the influence of emotional labor, emotional dissonance, and burnout on nurse's turnover intention and examine the effect of job satisfaction on the relationships among emotional labor, emotional dissonance, burnout, and turnover intention. The sample consisted of 350 nurses recruited from 6 general hospitals in 2 cities in Korea. A multiple-group analysis was utilized. Data were analyzed using SPSS statistics 23 and AMOS 20. In the path analysis, turnover intention was directly related to burnout in clinical nurses who had a high job satisfaction (β=.24, p=.003), while it was indirectly related to emotional dissonance (β=.13, p=.002). In the multiple-group path analysis, turnover intention was directly related to emotional dissonance (β=.18, p=.033) and burnout (β=.26, p=.002) for nurses with low job satisfaction. These results indicate that manuals and guidelines to alleviate the negative effects of emotional labor, emotional dissonance, and burnout, and to increase job satisfaction are strongly required to reduce turnover intention in nurses at the organizational level as well as at the individual level. © 2017 Korean Society of Nursing Science

  3. Turnover among healthcare professionals.

    Science.gov (United States)

    Wood, Ben D

    2009-01-01

    Turnover among healthcare professionals is a costly consequence. The existing body of knowledge on healthcare professional turnover is correlated with job satisfaction levels. A landmark study differentiated 2 areas of job satisfaction categories: satisfiers and dissatisfiers (intrinsic and extrinsic motivators). The aim of this article is to examine existing research on precursors of turnover, such as burnout behaviors experienced by healthcare professionals, job satisfaction levels, employee organizational commitment, health complications which precede turnover, some current strategies to reduce turnover, and some effects CEO turnover has on employee turnover intentions.

  4. Pathway analysis and optimization in metabolic engineering

    National Research Council Canada - National Science Library

    Torres, Néstor V; Voit, Eberhard O

    2002-01-01

    ... Engineering introduces researchers and advanced students in biology and engineering to methods of optimizing biochemical systems of biotechnological relevance. It examines the development of strategies for manipulating metabolic pathways, demonstrates the need for effective systems models, and discusses their design and analysis, while placing special emp...

  5. Elucidating turnover pathways of bioactive small molecules by isotopomer analysis: the persistent organic pollutant DDT.

    Directory of Open Access Journals (Sweden)

    Ina Ehlers

    Full Text Available The persistent organic pollutant DDT (1,1,1-trichloro-2,2-bis(4-chlorophenylethane is still indispensable in the fight against malaria, although DDT and related compounds pose toxicological hazards. Technical DDT contains the dichloro congener DDD (1-chloro-4-[2,2-dichloro-1-(4-chlorophenylethyl]benzene as by-product, but DDD is also formed by reductive degradation of DDT in the environment. To differentiate between DDD formation pathways, we applied deuterium NMR spectroscopy to measure intramolecular deuterium distributions (2H isotopomer abundances of DDT and DDD. DDD formed in the technical DDT synthesis was strongly deuterium-enriched at one intramolecular position, which we traced back to 2H/1H fractionation of a chlorination step in the technical synthesis. In contrast, DDD formed by reductive degradation was strongly depleted at the same position, which was due to the incorporation of 2H-depleted hydride equivalents during reductive degradation. Thus, intramolecular isotope distributions give mechanistic information on reaction pathways, and explain a puzzling difference in the whole-molecule 2H/1H ratio between DDT and DDD. In general, our results highlight that intramolecular isotope distributions are essential to interpret whole-molecule isotope ratios. Intramolecular isotope information allows distinguishing pathways of DDD formation, which is important to identify polluters or to assess DDT turnover in the environment. Because intramolecular isotope data directly reflect isotope fractionation of individual chemical reactions, they are broadly applicable to elucidate transformation pathways of small bioactive molecules in chemistry, physiology and environmental science.

  6. KECENDERUNGAN KEPUASAN KERJA SEBAGAI TRIGGER TURNOVER

    Directory of Open Access Journals (Sweden)

    Raditya Adi Saputra

    2017-06-01

    Full Text Available The purpose of this study are: (1 To determine the effect of job satisfaction on turnover intention; (2 To determine the effect of work stress on turnover intention; (3 To determine the effect of compensation on turnover intention; (4 To determine the effect of organizational climate on turnover intention; and (5 To determine the stress of work, compensation, organizational climate and job satisfaction effect on turnover intention. The population in this study are employees of the Cooperative KOKAPURA AVIA totaling 180 people, while employees who have worked more than three years as many as 128 people. Samples were taken 97 people. The technique of collecting data using questionnaires. The analysis used is multiple regression analysis and path analysis using PLS 3.0 Smart program. Based on the results of the study concluded that: (1 Job satisfaction significantly influence employee turnover intention; (2 Work stress significantly influence employee turnover intention; (3 Compensation incentives significantly influence employee turnover intention; (4 organizational climate significantly influence employee turnover intention; and (5 Work stress, incentive compensation, organizational climate and job satisfaction simultaneously significantly influence employee turnover intention.

  7. Ecological network analysis of China's societal metabolism.

    Science.gov (United States)

    Zhang, Yan; Liu, Hong; Li, Yating; Yang, Zhifeng; Li, Shengsheng; Yang, Naijin

    2012-01-01

    Uncontrolled socioeconomic development has strong negative effects on the ecological environment, including pollution and the depletion and waste of natural resources. These serious consequences result from the high flows of materials and energy through a socioeconomic system produced by exchanges between the system and its surroundings, causing the disturbance of metabolic processes. In this paper, we developed an ecological network model for a societal system, and used China in 2006 as a case study to illustrate application of the model. We analyzed China's basic metabolic processes and used ecological network analysis to study the network relationships within the system. Basic components comprised the internal environment, five sectors (agriculture, exploitation, manufacturing, domestic, and recycling), and the external environment. We defined 21 pairs of ecological relationships in China's societal metabolic system (excluding self-mutualism within a component). Using utility and throughflow analysis, we found that exploitation, mutualism, and competition relationships accounted for 76.2, 14.3, and 9.5% of the total relationships, respectively. In our trophic level analysis, the components were divided into producers, consumers, and decomposers according to their positions in the system. Our analyses revealed ways to optimize the system's structure and adjust its functions, thereby promoting healthier socioeconomic development, and suggested ways to apply ecological network analysis in future socioeconomic research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Effects of probiotics, prebiotics, and synbiotics on mineral metabolism in ovariectomized rats — impact of bacterial mass, intestinal absorptive area and reduction of bone turn-over

    Directory of Open Access Journals (Sweden)

    Katharina E. Scholz-Ahrens

    2016-08-01

    Conclusion: SYN exerted a synergistic effect on bone mineralization, presumably due to changes in gut microbiota and ecology associated with large bowel digesta weight (most likely reflecting microbial mass and with large bowel weight (reflecting absorptive area, while bone turnover tended to be reduced as indicated by BAP.

  9. Document turn-over analysis to determine need of NPP construction in build-up structures of reinforced concrete

    International Nuclear Information System (INIS)

    Vojpe, D.K.; Lyubavin, V.K.

    1986-01-01

    Document turn-over to determine used of NPP construction in build-up structures of reinforced concrete is carried out. Ways of improving determination of needs of NPP construction board in the mentioned structures are pointed out

  10. An Evaluation of Collagen Metabolism in Non Human Primates Associated with the Bion 11 Space Program-Markers of Urinary Collagen Turnover and Muscle Connective Tissue

    Science.gov (United States)

    Vailas, Arthur C.; Martinez, Daniel A.

    1999-01-01

    Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, media] gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

  11. Analysis of Ukraine’s foreign trade turnover in context of free trade zone with European Union

    Directory of Open Access Journals (Sweden)

    К.Shymanska

    2016-06-01

    Full Text Available The implementation of the free trade zone between Ukraine and the European Union has many advantages and disadvantages for our country. The changes in Ukraine’s economic integration vector cause much dispute about its prospects and profitability. Nevertheless, the strengthening of economic and political crisis leads to the reduction in foreign trade of Ukraine with the EU. Although in recent years, many institutional limitations for the Ukrainian producers’ entrance to European markets have been removed. The analysis of Ukraine's foreign trade turnover with EU countries showed the indicators of exports and imports structure in the partner countries and allowed to reveal decreasing of intensity of these operations. This can be a negative indicator of activities for the implementation of the Association Agreement with the EU. The study has formulated the perspective directions of foreign trade policy of Ukraine, in particular with respect to the modernization of informational and technical support of the customs clearance of the goods movement, increasing control over the quality of Ukrainian goods and opportunities for the small and mediumsized entities entrance to the European markets.

  12. Descriptive analysis of staff satisfaction and turnover intention in a Malaysian University

    Science.gov (United States)

    Sidik, Mohamad Hazeem; Hamid, Mohd Rashid Ab; Ibrahim, Abdullah

    2017-05-01

    This paper discussed the descriptive analysis of staff satisfaction in education organisation. This study employed a cross-sectional study involving a total of 1042 of respondents from a university in east coast of Malaysia. The survey covers six dimensions of staff satisfaction which are leadership, staff involvement, workload, self-development, working environment and communication. From the analysis of the mean score, it reveals that the staff enjoyed moderate level of satisfaction and the findings of the study generally support the past findings in the literature. This study paved the way for in-depth investigation towards staff satisfaction at the university under study.

  13. In Silico Analysis of the Metabolic Potential and Niche Specialization of Candidate Phylum "Latescibacteria" (WS3.

    Directory of Open Access Journals (Sweden)

    Noha H Youssef

    Full Text Available The "Latescibacteria" (formerly WS3, member of the Fibrobacteres-Chlorobi-Bacteroidetes (FCB superphylum, represents a ubiquitous candidate phylum found in terrestrial, aquatic, and marine ecosystems. Recently, single-cell amplified genomes (SAGs representing the "Latescibacteria" were obtained from the anoxic monimolimnion layers of Sakinaw Lake (British Columbia, Canada, and anoxic sediments of a coastal lagoon (Etoliko lagoon, Western Greece. Here, we present a detailed in-silico analysis of the four SAGs to gain some insights on their metabolic potential and apparent ecological roles. Metabolic reconstruction suggests an anaerobic fermentative mode of metabolism, as well as the capability to degrade multiple polysaccharides and glycoproteins that represent integral components of green (Charophyta and Chlorophyta and brown (Phaeophycaea algae cell walls (pectin, alginate, ulvan, fucan, hydroxyproline-rich glycoproteins, storage molecules (starch and trehalose, and extracellular polymeric substances (EPSs. The analyzed SAGs also encode dedicated transporters for the uptake of produced sugars and amino acids/oligopeptides, as well as an extensive machinery for the catabolism of all transported sugars, including the production of a bacterial microcompartment (BMC to sequester propionaldehyde, a toxic intermediate produced during fucose and rhamnose metabolism. Finally, genes for the formation of gas vesicles, flagella, type IV pili, and oxidative stress response were found, features that could aid in cellular association with algal detritus. Collectively, these results indicate that the analyzed "Latescibacteria" mediate the turnover of multiple complex organic polymers of algal origin that reach deeper anoxic/microoxic habitats in lakes and lagoons. The implications of such process on our understanding of niche specialization in microbial communities mediating organic carbon turnover in stratified water bodies are discussed.

  14. Sensitivity analysis of the model for estimation of the Adriatic sea turnover time using fallout 90Sr as a radioactive tracer

    International Nuclear Information System (INIS)

    Franic, Z.

    2005-01-01

    Reliable data on the turnover time of water in the Adriatic Sea (approximately 35000 cubic kilometres) is extremely important for any risk analysis involving various economic activities, tourism, etc. Water exchange through the Strait of Otranto between the Adriatic and the Ionian seas has been the subject of a series of experimental investigations and more recently, of some numerical studies, is extensively presented by Cushman-Roisin et al. [1]. The turnover time of the Adriatic sea water can be easily calculated from the data on water fluxes through the Strait by calculating annual water mass flowing through the Strait and dividing it by the total volume of the Adriatic sea. Literature data on the Adriatic Sea water turnover time range from minimal 0.7 to maximal 5.0 years. Using a model describing the rate of change of 9 0S r activity concentrations in the Adriatic Sea water by function minimisation to long-term experimental data, the turnover time for 9 0S r in the Adriatic was calculated to be 3.3±0.4 years. The uncertainty was estimated by Monte Carlo analysis. As 9 0S r is a reliable radiotracer for seawater, this value also reflects the sea water turnover time. Sensitivity analysis of the model, applied by varying critical parameters over their nominal values, showed that ±25% uncertainty in the estimation of the Adriatic sea water activity results in approximately ±10% change in 9 0S r mean residence time. On the other hand, a larger input of 9 0S r, either by fallout or water influx from the Ionian Sea may lead to a shorter mean residence time.Direct proportionality between 9 0S r input into the Adriatic sea and its mean residence time in the sea water suggests that 3.3 years is the upper limit of the Adriatic sea water turnover time. Namely, re-suspension from sediments could affect 9 0S r activity concentrations, acting as additional input, especially in the northern, relatively shallow part of the Adriatic.(author)

  15. [New nurse turnover intention and influencing factors].

    Science.gov (United States)

    Han, Sang Sook; Sohn, In Soon; Kim, Nam Eun

    2009-12-01

    The study was done to identify turnover intention in new nurses according to characteristics of the nurses and other factors affecting turnover and to provide data to set up a strategy to reduce the turnover. Data were collected from 1,077 new nurses who had less than 12 months employment experience and worked in one of 188 hospitals. Eight research instruments were used. Data analysis was done using SPSS WIN 15.0 program. Several factors influence new nurse turnover intention. The average score for turnover intention was 2.12. The scores for subscales were self efficacy, 3.76, nursing performance, 3.90, job satisfaction, 2.09, organization commitment, 1.28, stress, 1.32, burnout, 2.82 and nursing organizational culture, 3.29. Turnover intention was related to self efficacy, nursing performance, job satisfaction, organization commitment, stress, burnout, nursing organizational culture, duration of in-class training, duration of on the job training, number of hospital beds, length of employment and duration of employment in current workplace. The predicting factors for turnover intention were burnout, stress, duration of employment in the current workplace, self efficacy and nursing performance. Those factors explained 51.6% of turnover intention. New nurse turnover intention can be reduced by mitigating the factors affecting this intention.

  16. Mutational analysis of PVX TGBp3 links subcellular accumulation and protein turnover

    International Nuclear Information System (INIS)

    Ju, H.-J.; Ye, C.-M.; Verchot-Lubicz, Jeanmarie

    2008-01-01

    Potato virus X (PVX) TGBp3 is required for virus cell-to-cell transport, has an N-terminal transmembrane domain, and a C-terminal cytosolic domain. In the absence of virus infection TGBp3:GFP is seen in the cortical and perinuclear ER. In PVX infected cells the TGBp3:GFP fusion is also seen in the nucleoplasm indicating that events during PVX infection trigger entry into the nucleus. Mutational analysis failed to identify a nuclear targeting domain. Mutations inhibiting TGBp3 association with the ER and inhibiting virus movement did not block TGBp3:GFP in the nucleoplasm. A mutation disrupting the N-terminal transmembrane domain of TGBp3 caused the fusion to accumulate in the nucleus indicating that nuclear import is regulated by ER interactions. Tunicamycin, an ER-stress inducing chemical, caused lower levels of GFP and TGBp3:GFP to accumulate in virus infected protoplasts. MG115 and MG132 were used to demonstrate that wild-type and mutant TGBp3:GFP fusions were degraded by the 26S proteasome. These observations are consistent with an ER-associated protein degradation (ERAD) pathway suggesting that PVX TGBp3, similar to aberrant ER proteins, is translocate to the cytoplasm for degradation. Nuclear accumulation of mutant and wild-type TGBp3:GFP is independent of other PVX proteins and may be another feature of an ERAD pathway

  17. Protein turnover in atrophying muscle: from nutritional intervention to microarray expression analysis

    Science.gov (United States)

    Stein, T. Peter; Wade, Charles E.

    2003-01-01

    PURPOSE OF REVIEW: In response to decreased usage, skeletal muscle undergoes adaptive reductive remodeling due to the decrease in tension on the weight bearing components of the musculo-skeletal system. This response occurs with uncomplicated disuse (e.g. bed rest, space flight), as a secondary consequence of several widely prevalent chronic diseases for which activity is reduced (e.g. chronic obstructive pulmonary disease and chronic heart failure) and is part of the aging process. The problem is therefore one of considerable clinical importance. RECENT FINDINGS: The impaired function and exercise intolerance is related more to the associated muscle wasting rather than to the specific organ system primarily impacted by the disease. Progress has continued in describing the use of anabolic drugs and dietary manipulation. The major advance in the field has been: (i) the discovery of the atrogin-1 gene and (ii) the application of microarray expression analysis and proteomics with the objectives of obtaining comprehensive understanding of the pathways changed with disuse atrophy. SUMMARY: Disuse atrophy is a common clinical problem. There is a need for therapeutic interventions that do not involve exercise. A better understanding of the changes, particularly at the molecular level, could indicate hitherto unsuspected sites for nutritional and pharmacological intervention.

  18. The Global Turnover Time Distribution of Soil Carbon Derived from a Meta-analysis of Radiocarbon Profiles

    Science.gov (United States)

    He, Y.; Randerson, J. T.; Allison, S. D.; Torn, M. S.; Harden, J. W.; Smith, L. J.; van der Voort, T.; Trumbore, S.

    2015-12-01

    Soil is the largest terrestrial carbon reservoir and may influence the sign and magnitude of carbon cycle feedbacks under climate change. Soil carbon turnover times provide information about the sensitivity of carbon pools to changes in inputs and warming. The spatial and vertical distribution of soil carbon turnover times emerges from the interplay between climate, vegetation, and soil properties. Radiocarbon levels of soil organic matter can be used to estimate soil carbon turnover using models that take into account radioactive decay over centuries to millennia and inputs of 14C from atmospheric weapons testing ("bomb carbon") during the second half of the 20th century. By synthesizing more than 200 soil radiocarbon profiles from all major biomes and soil orders, we 1) explored the major controlling factors for soil carbon turnover times of surface and deeper soil layers; 2) developed predictive models (tree-based regression, support vector regression and linear regression models) of Δ14C that depends on depth, climate, vegetation, and soil types; and 3) extrapolated the predictive model to produce the first global distribution of soil carbon turnover times to the depth of 1m. Preliminary results indicated that climate and depth were primary controls of the vertical distribution of Δ14C, contributing to about 70% of the variability in our model. Vegetation and soil order exerted similar level of controls (about 15% each). The predictive model performed reasonably well with an R2 of 0.81 and RMSE (root-mean-squared error) of about 50‰ for topsoil and 100‰ for subsoil, as estimated using cross-validation. Extrapolation of the predictive model to the globe in combination with existing soil carbon information (e.g., Harmonized World Soil Database) indicated that more than half of the global total soil carbon in the top 1m had a turnover time of less than 500 years. Subsoils (30-100cm) had millennium-scale turnover times, with the majority (70%) turning over

  19. Health and Turnover of Working Mothers after Childbirth via the Work-Family Interface: An Analysis across Time

    Science.gov (United States)

    Carlson, Dawn S.; Grzywacz, Joseph G.; Ferguson, Merideth; Hunter, Emily M.; Clinch, C. Randall; Arcury, Thomas A.

    2011-01-01

    This study examined organizational levers that impact work-family experiences, participant health, and subsequent turnover. Using a sample of 179 women returning to full-time work 4 months after childbirth, we examined the associations of 3 job resources (job security, skill discretion, and schedule control) with work-to-family enrichment and the…

  20. A Meta-Analysis of the Antecedents of Voluntary Turnover in Studies Involving Active Duty Military Member Populations

    Science.gov (United States)

    2011-06-01

    unfolding model of turnover, and job embeddedness theory. Time constraints significantly inhibited the search for data. Additionally, decisions were...age, embeddedness , job satisfaction, operations tempo, organizational commitment, continuance commitment, normative commitment, affective...education, number of dependents, income, debt, and age. The antecedents included were embeddedness , job satisfaction, operations tempo, organizational

  1. Genome-wide analysis of H3.3 dissociation reveals high nucleosome turnover at distal regulatory regions of embryonic stem cells.

    Science.gov (United States)

    Ha, Misook; Kraushaar, Daniel C; Zhao, Keji

    2014-01-01

    The histone variant H3.3 plays a critical role in maintaining the pluripotency of embryonic stem cells (ESCs) by regulating gene expression programs important for lineage specification. H3.3 is deposited by various chaperones at regulatory sites, gene bodies, and certain heterochromatic sites such as telomeres and centromeres. Using Tet-inhibited expression of epitope-tagged H3.3 combined with ChIP-Seq we undertook genome-wide measurements of H3.3 dissociation rates across the ESC genome and examined the relationship between H3.3-nucleosome turnover and ESC-specific transcription factors, chromatin modifiers, and epigenetic marks. Our comprehensive analysis of H3.3 dissociation rates revealed distinct H3.3 dissociation dynamics at various functional chromatin domains. At transcription start sites, H3.3 dissociates rapidly with the highest rate at nucleosome-depleted regions (NDRs) just upstream of Pol II binding, followed by low H3.3 dissociation rates across gene bodies. H3.3 turnover at transcription start sites, gene bodies, and transcription end sites was positively correlated with transcriptional activity. H3.3 is found decorated with various histone modifications that regulate transcription and maintain chromatin integrity. We find greatly varying H3.3 dissociation rates across various histone modification domains: high dissociation rates at active histone marks and low dissociation rates at heterochromatic marks. Well- defined zones of high H3.3-nucleosome turnover were detected at binding sites of ESC-specific pluripotency factors and chromatin remodelers, suggesting an important role for H3.3 in facilitating protein binding. Among transcription factor binding sites we detected higher H3.3 turnover at distal cis-acting sites compared to proximal genic transcription factor binding sites. Our results imply that fast H3.3 dissociation is a hallmark of interactions between DNA and transcriptional regulators. Our study demonstrates that H3.3 turnover and

  2. Automated metabolic gas analysis systems: a review.

    Science.gov (United States)

    Macfarlane, D J

    2001-01-01

    The use of automated metabolic gas analysis systems or metabolic measurement carts (MMC) in exercise studies is common throughout the industrialised world. They have become essential tools for diagnosing many hospital patients, especially those with cardiorespiratory disease. Moreover, the measurement of maximal oxygen uptake (VO2max) is routine for many athletes in fitness laboratories and has become a defacto standard in spite of its limitations. The development of metabolic carts has also facilitated the noninvasive determination of the lactate threshold and cardiac output, respiratory gas exchange kinetics, as well as studies of outdoor activities via small portable systems that often use telemetry. Although the fundamental principles behind the measurement of oxygen uptake (VO2) and carbon dioxide production (VCO2) have not changed, the techniques used have, and indeed, some have almost turned through a full circle. Early scientists often employed a manual Douglas bag method together with separate chemical analyses, but the need for faster and more efficient techniques fuelled the development of semi- and full-automated systems by private and commercial institutions. Yet, recently some scientists are returning back to the traditional Douglas bag or Tissot-spirometer methods, or are using less complex automated systems to not only save capital costs, but also to have greater control over the measurement process. Over the last 40 years, a considerable number of automated systems have been developed, with over a dozen commercial manufacturers producing in excess of 20 different automated systems. The validity and reliability of all these different systems is not well known, with relatively few independent studies having been published in this area. For comparative studies to be possible and to facilitate greater consistency of measurements in test-retest or longitudinal studies of individuals, further knowledge about the performance characteristics of these

  3. An Analysis of the Effect of Compensation Offerings on the Turnover Intentions of Restaurant Managing Partners for Outback Steakhouse

    OpenAIRE

    Murphy, Kevin Stephen

    2000-01-01

    The restaurant industry has long been characterized by a high rate of "turnover, low wages, primitive technology, controlling management and an unimpressive benefits package"(Sullivan, 1999). " The most serious issue for employers today -in all industries- is hiring and keeping qualified and capable employees" according to Donald Marshack, senior analyst at the U.S. Bureau of Labor Statistics (BLS)(2000). The primary purpose of this study was to examine the perceived notion that the compensat...

  4. Analysis of the Theoretical Relationships Between Work Exhaustion, Job Satisfaction, and Turnover Intention of Air Force Information Systems Managers

    Science.gov (United States)

    2003-03-01

    family’s social support system, and can be subject to the “ grass is greener on the other side” syndrome, only to experience later disappointment...Inflation may also influence turnover but that relationship is beyond the scope of this research. The ongoing change in the composition of the... Napier , A.H., and Wetherbe, J.C. “Occupational Stress, Attitudes, and Health Problems in the Information Systems Professional,” Communications of the

  5. Health and turnover of working mothers after childbirth via the work-family interface: an analysis across time.

    Science.gov (United States)

    Carlson, Dawn S; Grzywacz, Joseph G; Ferguson, Merideth; Hunter, Emily M; Clinch, C Randall; Arcury, Thomas A

    2011-09-01

    This study examined organizational levers that impact work-family experiences, participant health, and subsequent turnover. Using a sample of 179 women returning to full-time work 4 months after childbirth, we examined the associations of 3 job resources (job security, skill discretion, and schedule control) with work-to-family enrichment and the associations of 2 job demands (psychological requirements and nonstandard work schedules) with work-to-family conflict. Further, we considered subsequent impact of work-to-family conflict and enrichment on women's health (physical and mental health) 8 months after women returned to work and the impact of health on voluntary turnover 12 months after women returned to work. Having a nonstandard work schedule was directly and positively related to conflict, whereas schedule control buffered the effect of psychological requirements on conflict. Skill discretion and job security, both job resources, directly and positively related to enrichment. Work-to-family conflict was negatively related to both physical and mental health, but work-to-family enrichment positively predicted only physical health. Physical health and mental health both negatively influenced turnover. We discuss implications and opportunities for future research. PsycINFO Database Record (c) 2011 APA, all rights reserved

  6. Health and Turnover of Working Mothers After Childbirth Via the Work–Family Interface: An Analysis Across Time

    Science.gov (United States)

    Carlson, Dawn S.; Grzywacz, Joseph G.; Ferguson, Merideth; Hunter, Emily M.; Clinch, C. Randall; Arcury, Thomas A.

    2013-01-01

    This study examined organizational levers that impact work–family experiences, participant health, and subsequent turnover. Using a sample of 179 women returning to full-time work 4 months after childbirth, we examined the associations of 3 job resources (job security, skill discretion, and schedule control) with work-to-family enrichment and the associations of 2 job demands (psychological requirements and nonstandard work schedules) with work-to-family conflict. Further, we considered subsequent impact of work-to-family conflict and enrichment on women’s health (physical and mental health) 8 months after women returned to work and the impact of health on voluntary turnover 12 months after women returned to work. Having a nonstandard work schedule was directly and positively related to conflict, whereas schedule control buffered the effect of psychological requirements on conflict. Skill discretion and job security, both job resources, directly and positively related to enrichment. Work-to-family conflict was negatively related to both physical and mental health, but work-to-family enrichment positively predicted only physical health. Physical health and mental health both negatively influenced turnover. We discuss implications and opportunities for future research. PMID:21604833

  7. Bone turnover in postmenopausal osteoporosis

    International Nuclear Information System (INIS)

    Thomsen, K.

    1988-02-01

    Studies of the bone turnover in postmenopausal osteoporosis are essential, because the associated bone loss is inevitably due to the relative increase of bone resorption compared with bone formation. Measurement of the bone mineral content (BMC) in normal adults is assessed - partly on the uncorrected values and partly in proportion to the body muscle mass. The whole body retention (WBR) method is presented. The WBR and alternative urinary excretion (UE) methods used by the author are characterised and compared with the retention methods described in the literature. The representativity of WBR and UE for the estimation of bone turnover in normal subjects and patients with various bone metabolic diseases is discussed. The conclusion is that the modified retention methods used by the author have a satisfactory precision and accuracy in relation to the clinical studies carried out. The author's modification of the WBR method for determination of bone turnover and the alternative urinary excretion method (UE) consists in continuous scanning in the whole body count, using a gamma camera, and with the collimator a short distance from the volunteer. This procedure has the advantage of restricting the radioactive dose to 2 mCi (72 MBa). This is smaller by a factor of 5-10 than the dose used to measure WBR with equally simple counting equipment: With the author's procedure, using frontal counting, WBR is systematically underestimated by about 4 per cent point compared to the purely dorsal count, but since the frontal position is the most comfortable, requires a smaller radioactive dose, and the error is systematic, it is the preferred counting procedure. Correction of WBR and UE for bone mineral content is in principle a new parameter of bone turnover, whose improved accuracy increases the validity of the retention determinations. 136 refs. (EG)

  8. Protein turnover in children studied using 15N

    International Nuclear Information System (INIS)

    Pencharz, P.B.

    1983-01-01

    In 12 neonates the effect of the route of feeding on protein turnover rates was studied, and in 8 children suffering from cystic fibrosis the effect of nutritional rehabilitation on the protein metabolism was examined

  9. 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

    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...

  10. Computational systems analysis of dopamine metabolism.

    Directory of Open Access Journals (Sweden)

    Zhen Qi

    2008-06-01

    Full Text Available A prominent feature of Parkinson's disease (PD is the loss of dopamine in the striatum, and many therapeutic interventions for the disease are aimed at restoring dopamine signaling. Dopamine signaling includes the synthesis, storage, release, and recycling of dopamine in the presynaptic terminal and activation of pre- and post-synaptic receptors and various downstream signaling cascades. As an aid that might facilitate our understanding of dopamine dynamics in the pathogenesis and treatment in PD, we have begun to merge currently available information and expert knowledge regarding presynaptic dopamine homeostasis into a computational model, following the guidelines of biochemical systems theory. After subjecting our model to mathematical diagnosis and analysis, we made direct comparisons between model predictions and experimental observations and found that the model exhibited a high degree of predictive capacity with respect to genetic and pharmacological changes in gene expression or function. Our results suggest potential approaches to restoring the dopamine imbalance and the associated generation of oxidative stress. While the proposed model of dopamine metabolism is preliminary, future extensions and refinements may eventually serve as an in silico platform for prescreening potential therapeutics, identifying immediate side effects, screening for biomarkers, and assessing the impact of risk factors of the disease.

  11. Impaired insulin-stimulated nonoxidative glucose metabolism in pancreas-kidney transplant recipients. Dose-response effects of insulin on glucose turnover

    DEFF Research Database (Denmark)

    Christiansen, E; Vestergaard, H; Tibell, A

    1996-01-01

    Insulin resistance is a characteristic feature in recipients of a pancreas transplant, but the relative contribution of the liver and peripheral tissues to this abnormality within a spanning range of insulin concentrations is unknown. To assess the impact of insulin action on glucose metabolism....... The overall effects of insulin on whole-body glucose metabolism, determined as the glucose infusion rates versus the corresponding steady-state serum insulin concentrations, demonstrated a rightward shift in the dose-response curves of the transplanted groups compared with those of normal subjects. The dose......, this finding could only explain in part the degree of impairment in nonoxidative glucose metabolism. No differences were found in total hexokinase activity in muscle between normal subjects and the transplant groups at basal insulinemia or after insulin stimulation. During hyperinsulinemia, glucagon...

  12. Impaired insulin-stimulated nonoxidative glucose metabolism in pancreas-kidney transplant recipients. Dose-response effects of insulin on glucose turnover

    DEFF Research Database (Denmark)

    Christiansen, E; Vestergaard, H; Tibell, A

    1996-01-01

    , this finding could only explain in part the degree of impairment in nonoxidative glucose metabolism. No differences were found in total hexokinase activity in muscle between normal subjects and the transplant groups at basal insulinemia or after insulin stimulation. During hyperinsulinemia, glucagon......Insulin resistance is a characteristic feature in recipients of a pancreas transplant, but the relative contribution of the liver and peripheral tissues to this abnormality within a spanning range of insulin concentrations is unknown. To assess the impact of insulin action on glucose metabolism....... The overall effects of insulin on whole-body glucose metabolism, determined as the glucose infusion rates versus the corresponding steady-state serum insulin concentrations, demonstrated a rightward shift in the dose-response curves of the transplanted groups compared with those of normal subjects. The dose...

  13. IDENTIFICATION AND ANALYSIS OF BACTERIAL GENOMIC METABOLIC SIGNATURES.

    Science.gov (United States)

    Bowerman, Nathaniel; Tintle, Nathan; Dejongh, Matthew; Best, Aaron A

    2017-01-01

    With continued rapid growth in the number and quality of fully sequenced and accurately annotated bacterial genomes, we have unprecedented opportunities to understand metabolic diversity. We selected 101 diverse and representative completely sequenced bacteria and implemented a manual curation effort to identify 846 unique metabolic variants present in these bacteria. The presence or absence of these variants act as a metabolic signature for each of the bacteria, which can then be used to understand similarities and differences between and across bacterial groups. We propose a novel and robust method of summarizing metabolic diversity using metabolic signatures and use this method to generate a metabolic tree, clustering metabolically similar organisms. Resulting analysis of the metabolic tree confirms strong associations with well-established biological results along with direct insight into particular metabolic variants which are most predictive of metabolic diversity. The positive results of this manual curation effort and novel method development suggest that future work is needed to further expand the set of bacteria to which this approach is applied and use the resulting tree to test broad questions about metabolic diversity and complexity across the bacterial tree of life.

  14. The reconstruction and analysis of tissue specific human metabolic networks.

    Science.gov (United States)

    Hao, Tong; Ma, Hong-Wu; Zhao, Xue-Ming; Goryanin, Igor

    2012-02-01

    Human tissues have distinct biological functions. Many proteins/enzymes are known to be expressed only in specific tissues and therefore the metabolic networks in various tissues are different. Though high quality global human metabolic networks and metabolic networks for certain tissues such as liver have already been studied, a systematic study of tissue specific metabolic networks for all main tissues is still missing. In this work, we reconstruct the tissue specific metabolic networks for 15 main tissues in human based on the previously reconstructed Edinburgh Human Metabolic Network (EHMN). The tissue information is firstly obtained for enzymes from Human Protein Reference Database (HPRD) and UniprotKB databases and transfers to reactions through the enzyme-reaction relationships in EHMN. As our knowledge of tissue distribution of proteins is still very limited, we replenish the tissue information of the metabolic network based on network connectivity analysis and thorough examination of the literature. Finally, about 80% of proteins and reactions in EHMN are determined to be in at least one of the 15 tissues. To validate the quality of the tissue specific network, the brain specific metabolic network is taken as an example for functional module analysis and the results reveal that the function of the brain metabolic network is closely related with its function as the centre of the human nervous system. The tissue specific human metabolic networks are available at .

  15. Hierarchical analysis of dependency in metabolic networks.

    Science.gov (United States)

    Gagneur, Julien; Jackson, David B; Casari, Georg

    2003-05-22

    Elucidation of metabolic networks for an increasing number of organisms reveals that even small networks can contain thousands of reactions and chemical species. The intimate connectivity between components complicates their decomposition into biologically meaningful sub-networks. Moreover, traditional higher-order representations of metabolic networks as metabolic pathways, suffers from the lack of rigorous definition, yielding pathways of disparate content and size. We introduce a hierarchical representation that emphasizes the gross organization of metabolic networks in largely independent pathways and sub-systems at several levels of independence. The approach highlights the coupling of different pathways and the shared compounds responsible for those couplings. By assessing our results on Escherichia coli (E.coli metabolic reactions, Genetic Circuits Research Group, University of California, San Diego, http://gcrg.ucsd.edu/organisms/ecoli.html, 'model v 1.01. reactions') against accepted biochemical annotations, we provide the first systematic synopsis of an organism's metabolism. Comparison with operons of E.coli shows that low-level clusters are reflected in genome organization and gene regulation. Source code, data sets and supplementary information are available at http://www.mas.ecp.fr/labo/equipe/gagneur/hierarchy/hierarchy.html

  16. Two-Scale 13C Metabolic Flux Analysis for Metabolic Engineering.

    Science.gov (United States)

    Ando, David; Garcia Martin, Hector

    2018-01-01

    Accelerating the Design-Build-Test-Learn (DBTL) cycle in synthetic biology is critical to achieving rapid and facile bioengineering of organisms for the production of, e.g., biofuels and other chemicals. The Learn phase involves using data obtained from the Test phase to inform the next Design phase. As part of the Learn phase, mathematical models of metabolic fluxes give a mechanistic level of comprehension to cellular metabolism, isolating the principle drivers of metabolic behavior from the peripheral ones, and directing future experimental designs and engineering methodologies. Furthermore, the measurement of intracellular metabolic fluxes is specifically noteworthy as providing a rapid and easy-to-understand picture of how carbon and energy flow throughout the cell. Here, we present a detailed guide to performing metabolic flux analysis in the Learn phase of the DBTL cycle, where we show how one can take the isotope labeling data from a 13 C labeling experiment and immediately turn it into a determination of cellular fluxes that points in the direction of genetic engineering strategies that will advance the metabolic engineering process.For our modeling purposes we use the Joint BioEnergy Institute (JBEI) Quantitative Metabolic Modeling (jQMM) library, which provides an open-source, python-based framework for modeling internal metabolic fluxes and making actionable predictions on how to modify cellular metabolism for specific bioengineering goals. It presents a complete toolbox for performing different types of flux analysis such as Flux Balance Analysis, 13 C Metabolic Flux Analysis, and it introduces the capability to use 13 C labeling experimental data to constrain comprehensive genome-scale models through a technique called two-scale 13 C Metabolic Flux Analysis (2S- 13 C MFA) [1]. In addition to several other capabilities, the jQMM is also able to predict the effects of knockouts using the MoMA and ROOM methodologies. The use of the jQMM library is

  17. Preeclampsia - a risk factor for osteoporosis? Analysis of maternal Sclerostin levels and markers of bone turnover in patients with pre-eclampsia.

    Science.gov (United States)

    Wild, Julia; Pateisky, Petra; Küssel, Lorenz; Huf, Wolfgang; Ott, Johannes; Haslinger, Peter; Knöfler, Martin; Zeisler, Harald

    2014-08-01

    The role of preeclampsia (PE) in affecting bone metabolism could not be clarified in the past years. Recently Sclerostin, a new marker of bone metabolism which is known to have an inhibitory effect on bone formation causing osteoporosis, was discovered. To investigate serum levels of Sclerostin and markers of bone turnover in women with normotensive pregnancies and pregnancies complicated by PE. In this prospective study we enrolled 22 women with PE and 22 healthy pregnant women to observe serum levels of carboxyterminal propeptide of type I collagen (PICP), cross-linked carboxyl terminal telopeptide of the type I collagen (ICTP), calcium, phosphate, 25-hydroxyvitamin D and parathyroid hormone. In 16 preeclamptic and 16 healthy pregnant women, serum Sclerostin levels were analyzed. Serum levels of Sclerostin (mean ± standard deviation: healthy 10.5 ± 8.1 pmol/l versus PE 11.5 ± 9.4 pmol/l, p = 0.768), ICTP (healthy 0.3 ± 0.2 ng/ml versus PE 0.4 ± 0.1 ng/ml, p = 0.462), PICP (healthy 59.9 ± 49.9 ng/ml versus PE 89.0 ± 62.0 ng/ml, p = 0.094), phosphate (healthy 1.1 ± 0.2 mmol/l versus PE 1.2 ± 0.4 mmol/l, p = 0.162) and parathyroid hormone (healthy 26.9 ± 14 pg/ml versus PE 35.3 ± 17.6 pg/ml, p = 0.08) showed no significant differences between the groups. Significantly lower serum calcium (healthy 2.3 ± 0.1 mmol/l versus PE 2.2 ± 0.2 mmol/l, p < 0.005) and serum 25-Hydroxyvitamin D (healthy 39.3 ± 16.7 nmol/l versus PE 23.9 ± 16.9 nmol/l, p < 0.005) were observed in preeclamptic women. Pregnancies complicated by PE show no signs of high bone turnover and may not lead to a higher risk of osteoporosis in later life.

  18. BioMet Toolbox: genome-wide analysis of metabolism

    DEFF Research Database (Denmark)

    Cvijovic, M.; Olivares Hernandez, Roberto; Agren, R.

    2010-01-01

    standardized simulations. Model files for various model organisms (fungi and bacteria) are included. Overall, the BioMet Toolbox serves as a valuable resource for exploring the capabilities of these metabolic networks. BioMet Toolbox is freely available at www.sysbio.se/BioMet/....... models. Systematic analysis of biological processes by means of modelling and simulations has made the identification of metabolic networks and prediction of metabolic capabilities under different conditions possible. For facilitating such systemic analysis, we have developed the BioMet Toolbox, a web......-based resource for stoichiometric analysis and for integration of transcriptome and interactome data, thereby exploiting the capabilities of genome-scale metabolic models. The BioMet Toolbox provides an effective user-friendly way to perform linear programming simulations towards maximized or minimized growth...

  19. Effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise on markers of bone metabolism, microarchitecture and turnover in obese Zucker rats.

    Science.gov (United States)

    Nebot, Elena; Aparicio, Virginia A; Coll-Risco, Irene; Camiletti-Moirón, Daniel; Schneider, Johannes; Kapravelou, Garyfallia; Heimel, Patrick; Martínez, Rosario; Andrade, Ana; Slezak, Paul; Redl, Heinz; Porres, Jesús M; López-Jurado, María; Pietschmann, Peter; Aranda, Pilar

    2016-11-01

    Weight loss is a public health concern in obesity-related diseases such as metabolic syndrome, and the protein level of the diets seem to be crucial for the development and maintenance of bone. The nature of exercise and whether exercise in combination with moderately high-protein dietary interventions could protect against potential bone mass deficits remains unclear. To investigate the effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise (IASE) protocol on bone status, and to assess potential interaction effects (i.e. diet*IASE). Male Zucker fatty rats were randomized distributed into 4 groups (n=8): normoprotein+sedentary; normoprotein+exercise; moderately high-protein+sedentary, and moderately high-protein+exercise. Training groups conducted an IASE program, 5days/week for 2months. Markers of bone metabolism were measured in plasma. Parameters of bone mass and 3D outcomes for trabecular and cortical bone microarchitecture were assessed by micro-computed tomography. Femur length, plasma osteocalcin, sclerostin, osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, insulin, leptin, PTH, uric acid and urinary phosphorus levels were lower in the moderately high-protein compared to the normoprotein groups (all, palkaline phosphatase, aspartate aminotransferase, alanine transaminase, and urinary uric acid concentrations, and cortical total volume (TV) and bone volume (BV) were higher in the moderately high-protein (all, palkaline phosphatase levels were lower in the exercise compared to the sedentary (both, peffective to enhance trabecular bone microarchitecture and BMD, and has a partial impact on cortical bone in obese rats. Nevertheless, they do not induce any alteration on the bone turnover markers. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. In silico analysis of human metabolism: Reconstruction, contextualization and application of genome-scale models

    DEFF Research Database (Denmark)

    Geng, Jun; Nielsen, Jens

    2017-01-01

    The arising prevalence of metabolic diseases calls for a holistic approach for analysis of the underlying nature of abnormalities in cellular functions. Through mathematic representation and topological analysis of cellular metabolism, GEnome scale metabolic Models (GEMs) provide a promising fram...

  1. Comparison of direct 13C and indirect 1H-[13C] MR detection methods for the study of dynamic metabolic turnover in the human brain

    Science.gov (United States)

    Chen, Hao; De Feyter, Henk M.; Brown, Peter B.; Rothman, Douglas L.; Cai, Shuhui; de Graaf, Robin A.

    2017-10-01

    A wide range of direct 13C and indirect 1H-[13C] MR detection methods exist to probe dynamic metabolic pathways in the human brain. Choosing an optimal detection method is difficult as sequence-specific features regarding spatial localization, broadband decoupling, spectral resolution, power requirements and sensitivity complicate a straightforward comparison. Here we combine density matrix simulations with experimentally determined values for intrinsic 1H and 13C sensitivity, T1 and T2 relaxation and transmit efficiency to allow selection of an optimal 13C MR detection method for a given application and magnetic field. The indirect proton-observed, carbon-edited (POCE) detection method provides the highest accuracy at reasonable RF power deposition both at 4 T and 7 T. The various polarization transfer methods all have comparable performances, but may become infeasible at 7 T due to the high RF power deposition. 2D MR methods have limited value for the metabolites considered (primarily glutamate, glutamine and γ-amino butyric acid (GABA)), but may prove valuable when additional information can be extracted, such as isotopomers or lipid composition. While providing the lowest accuracy, the detection of non-protonated carbons is the simplest to implement with the lowest RF power deposition. The magnetic field homogeneity is one of the most important parameters affecting the detection accuracy for all metabolites and all acquisition methods.

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

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava

    2018-01-11

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

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

    Science.gov (United States)

    Cuperlovic-Culf, Miroslava

    2018-01-01

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

  4. Avifauna: Turnover on Islands.

    Science.gov (United States)

    Mayr, E

    1965-12-17

    The percentage of endemic species of birds on islands increases with island area at a double logarithmic rate. This relation is apparently due to extinction, which is more rapid the smaller the island. The turnover resulting from extinction and replacement appears to be far more rapid than hitherto suspected.

  5. Managing teacher turnover

    African Journals Online (AJOL)

    Erna Kinsey

    tion and training costs as well as loss of productivity while the newly hired teacher comes up to speed (cf. Carrel et al., 1998:572; Special. Reports, 1999:1). Ingersoll (2002:4) postulates that staffing problems are created when employees leave the organisation and have to be replaced, especially since teacher turnover is ...

  6. Managing teacher turnover

    African Journals Online (AJOL)

    Erna Kinsey

    retention and thus attrition is a function of teachers' personal characte- ristics, educational preparation, initial commitment to teaching, quality of first teaching experience, social and professional integration into teaching and external influences. Khatri, Budhwar and Fern's study of employee turnover (1999) employs a model ...

  7. Metabolic control analysis of xylose catabolism in Aspergillus

    NARCIS (Netherlands)

    Prathumpai, W.; Gabelgaard, J.B.; Wanchanthuek, P.; Vondervoort, van de P.J.I.; Groot, de M.J.L.; McIntyre, M.; Nielsen, J.

    2003-01-01

    A kinetic model for xylose catabolism in Aspergillus is proposed. From a thermodynamic analysis it was found that the intermediate xylitol will accumulate during xylose catabolism. Use of the kinetic model allowed metabolic control analysis (MCA) of the xylose catabolic pathway to be carried out,

  8. Integrated proteomic and metabolic analysis of breast cancer progression.

    Directory of Open Access Journals (Sweden)

    Patrick G Shaw

    Full Text Available One of the most persistent hallmarks of cancer biology is the preference of tumor cells to derive energy through glycolysis as opposed to the more efficient process of oxidative phosphorylation (OXPHOS. However, little is known about the molecular cascades by which oncogenic pathways bring about this metabolic switch. We carried out a quantitative proteomic and metabolic analysis of the MCF10A derived cell line model of breast cancer progression that includes parental cells and derivatives representing three different tumor grades of Ras-driven cancer with a common genetic background. A SILAC (Stable Isotope Labeling by Amino acids in Cell culture labeling strategy was used to quantify protein expression in conjunction with subcellular fractionation to measure dynamic subcellular localization in the nucleus, cytosol and mitochondria. Protein expression and localization across cell lines were compared to cellular metabolic rates as a measure of oxidative phosphorylation (OXPHOS, glycolysis and cellular ATP. Investigation of the metabolic capacity of the four cell lines revealed that cellular OXPHOS decreased with breast cancer progression independently of mitochondrial copy number or electron transport chain protein expression. Furthermore, glycolytic lactate secretion did not increase in accordance with cancer progression and decreasing OXPHOS capacity. However, the relative expression and subcellular enrichment of enzymes critical to lactate and pyruvate metabolism supported the observed extracellular acidification profiles. This analysis of metabolic dysfunction in cancer progression integrated with global protein expression and subcellular localization is a novel and useful technique for determining organelle-specific roles of proteins in disease.

  9. (Im) Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis

    NARCIS (Netherlands)

    He, F.; Fromion, V.; Westerhoff, H.V.

    2013-01-01

    Background: Metabolic control analysis (MCA) and supply-demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply-demand theory has not yet considered gene-expression regulation explicitly whilst a

  10. Thermodynamics-based Metabolite Sensitivity Analysis in metabolic networks.

    Science.gov (United States)

    Kiparissides, A; Hatzimanikatis, V

    2017-01-01

    The increasing availability of large metabolomics datasets enhances the need for computational methodologies that can organize the data in a way that can lead to the inference of meaningful relationships. Knowledge of the metabolic state of a cell and how it responds to various stimuli and extracellular conditions can offer significant insight in the regulatory functions and how to manipulate them. Constraint based methods, such as Flux Balance Analysis (FBA) and Thermodynamics-based flux analysis (TFA), are commonly used to estimate the flow of metabolites through genome-wide metabolic networks, making it possible to identify the ranges of flux values that are consistent with the studied physiological and thermodynamic conditions. However, unless key intracellular fluxes and metabolite concentrations are known, constraint-based models lead to underdetermined problem formulations. This lack of information propagates as uncertainty in the estimation of fluxes and basic reaction properties such as the determination of reaction directionalities. Therefore, knowledge of which metabolites, if measured, would contribute the most to reducing this uncertainty can significantly improve our ability to define the internal state of the cell. In the present work we combine constraint based modeling, Design of Experiments (DoE) and Global Sensitivity Analysis (GSA) into the Thermodynamics-based Metabolite Sensitivity Analysis (TMSA) method. TMSA ranks metabolites comprising a metabolic network based on their ability to constrain the gamut of possible solutions to a limited, thermodynamically consistent set of internal states. TMSA is modular and can be applied to a single reaction, a metabolic pathway or an entire metabolic network. This is, to our knowledge, the first attempt to use metabolic modeling in order to provide a significance ranking of metabolites to guide experimental measurements. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier

  11. PENGARUH KEPUASAN KERJA DAN KOMITMEN ORGANISASI TERHADAP TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    V. Mardi Widyadmono

    2017-04-01

    Full Text Available This study assesses the influence of job satisfaction and organizational commitment on Turnover Intention. Futhermore, the study identify the mediation role of organizational commitment in the relationship between job satifaction and Turnover Intention. The participants of the study are 98 employees working in private companies operated in Yogyakarta, (36 men and 62 women. Respondents complete questionnaire containing questions on job satisfaction variable, questions on organizational commitment and questions on Turnover Intention. The statistics tools applied are regression analysis to assess the relation between variables and Sobel test to measure the mediation role of organizational commitment. The results of the investigation revealed that job satisfication and organizational commitment influence negatively and significantly Turnover Intention. The higher the job satisfication and the organizational commitment of employees lead to the lower Turnover Intention. The organizational commitment does not play mediation role in the relationship between job satisfication and Turnover Intention

  12. 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...

  13. Seasonal groundwater turnover

    OpenAIRE

    Nordell, Bo; Engström, Maria

    2006-01-01

      Seasonal air temperature variations and corresponding changes in groundwater temperature cause convective movements in groundwater similar to the seasonal turnover in lakes. Numerical simulations were performed to investigate the natural conditions for thermally driven groundwater convection to take place. Thermally driven convection could be triggered by a horizontal groundwater flow, Convection then starts at a considerably lower Rayleigh number (Ra) than the general critical Rayleigh ...

  14. Stoichiometric Correlation Analysis: Principles of Metabolic Functionality from Metabolomics Data

    Directory of Open Access Journals (Sweden)

    Kevin Schwahn

    2017-12-01

    Full Text Available Recent advances in metabolomics technologies have resulted in high-quality (time-resolved metabolic profiles with an increasing coverage of metabolic pathways. These data profiles represent read-outs from often non-linear dynamics of metabolic networks. Yet, metabolic profiles have largely been explored with regression-based approaches that only capture linear relationships, rendering it difficult to determine the extent to which the data reflect the underlying reaction rates and their couplings. Here we propose an approach termed Stoichiometric Correlation Analysis (SCA based on correlation between positive linear combinations of log-transformed metabolic profiles. The log-transformation is due to the evidence that metabolic networks can be modeled by mass action law and kinetics derived from it. Unlike the existing approaches which establish a relation between pairs of metabolites, SCA facilitates the discovery of higher-order dependence between more than two metabolites. By using a paradigmatic model of the tricarboxylic acid cycle we show that the higher-order dependence reflects the coupling of concentration of reactant complexes, capturing the subtle difference between the employed enzyme kinetics. Using time-resolved metabolic profiles from Arabidopsis thaliana and Escherichia coli, we show that SCA can be used to quantify the difference in coupling of reactant complexes, and hence, reaction rates, underlying the stringent response in these model organisms. By using SCA with data from natural variation of wild and domesticated wheat and tomato accession, we demonstrate that the domestication is accompanied by loss of such couplings, in these species. Therefore, application of SCA to metabolomics data from natural variation in wild and domesticated populations provides a mechanistic way to understanding domestication and its relation to metabolic networks.

  15. PSAMM: A Portable System for the Analysis of Metabolic Models.

    Directory of Open Access Journals (Sweden)

    Jon Lund Steffensen

    2016-02-01

    Full Text Available The genome-scale models of metabolic networks have been broadly applied in phenotype prediction, evolutionary reconstruction, community functional analysis, and metabolic engineering. Despite the development of tools that support individual steps along the modeling procedure, it is still difficult to associate mathematical simulation results with the annotation and biological interpretation of metabolic models. In order to solve this problem, here we developed a Portable System for the Analysis of Metabolic Models (PSAMM, a new open-source software package that supports the integration of heterogeneous metadata in model annotations and provides a user-friendly interface for the analysis of metabolic models. PSAMM is independent of paid software environments like MATLAB, and all its dependencies are freely available for academic users. Compared to existing tools, PSAMM significantly reduced the running time of constraint-based analysis and enabled flexible settings of simulation parameters using simple one-line commands. The integration of heterogeneous, model-specific annotation information in PSAMM is achieved with a novel format of YAML-based model representation, which has several advantages, such as providing a modular organization of model components and simulation settings, enabling model version tracking, and permitting the integration of multiple simulation problems. PSAMM also includes a number of quality checking procedures to examine stoichiometric balance and to identify blocked reactions. Applying PSAMM to 57 models collected from current literature, we demonstrated how the software can be used for managing and simulating metabolic models. We identified a number of common inconsistencies in existing models and constructed an updated model repository to document the resolution of these inconsistencies.

  16. Metabolic flux analysis of heterotrophic growth in Chlamydomonas reinhardtii.

    Directory of Open Access Journals (Sweden)

    Nanette R Boyle

    Full Text Available Despite the wealth of knowledge available for C. reinhardtii, the central metabolic fluxes of growth on acetate have not yet been determined. In this study, 13C-metabolic flux analysis (13C-MFA was used to determine and quantify the metabolic pathways of primary metabolism in C. reinhardtii cells grown under heterotrophic conditions with acetate as the sole carbon source. Isotopic labeling patterns of compartment specific biomass derived metabolites were used to calculate the fluxes. It was found that acetate is ligated with coenzyme A in the three subcellular compartments (cytosol, mitochondria and plastid included in the model. Two citrate synthases were found to potentially be involved in acetyl-coA metabolism; one localized in the mitochondria and the other acting outside the mitochondria. Labeling patterns demonstrate that Acetyl-coA synthesized in the plastid is directly incorporated in synthesis of fatty acids. Despite having a complete TCA cycle in the mitochondria, it was also found that a majority of the malate flux is shuttled to the cytosol and plastid where it is converted to oxaloacetate providing reducing equivalents to these compartments. When compared to predictions by flux balance analysis, fluxes measured with 13C-MFA were found to be suboptimal with respect to biomass yield; C. reinhardtii sacrifices biomass yield to produce ATP and reducing equivalents.

  17. Metabolic pathway analysis using a nash equilibrium approach

    NARCIS (Netherlands)

    Lucia, Angelo; DiMaggio, Peter A.; Alonso-Martinez, Diego

    2018-01-01

    A novel approach to metabolic network analysis using a Nash Equilibrium (NE) formulation is proposed in which enzymes are considered players in a multi-player game. Each player has its own payoff function with the objective of minimizing the Gibbs free energy associated with the biochemical

  18. Explaining turnover intention in Korean public community hospitals: occupational differences.

    Science.gov (United States)

    Hwang, Jee-In; Chang, Hyejung

    2008-01-01

    Personnel in public hospitals had relatively low job satisfaction despite of tenure employment. High turnover rates degrade hospital image and incur additional costs related to recruitment and training. The purposes of this study were to describe the occupational differences and to identify factors affecting turnover intention among public hospital personnel. A questionnaire survey was conducted as part of Administrative Services Quality Evaluation Program by Seoul metropolitan municipality from 1 November to 1 December in 2003. The subjects were 1251 entire hospital personnel in four hospitals. The questionnaire was designed to measure job satisfaction, organizational commitment, turnover intention, and demographic characteristics. Logistic regression analysis was performed to determine factors influencing turnover intention. There were significant differences in job satisfaction, organizational commitment, and turnover intention according to the occupations. The turnover intention rates were highest among physicians, followed by paramedicals and nursing staffs and then administrators. The significant factors affecting turnover intention were involvement and loyalty among physicians, hospital type, satisfaction with systems and loyalty among nursing staffs, satisfaction with relationship and loyalty among administrators, and loyalty among paramedicals. There were different moderators that influence turnover intentions of hospital personnel. Loyalty had the most important effect upon turnover intention in all occupations. 2007 John Wiley & Sons, Ltd

  19. WUFlux: an open-source platform for 13C metabolic flux analysis of bacterial metabolism.

    Science.gov (United States)

    He, Lian; Wu, Stephen G; Zhang, Muhan; Chen, Yixin; Tang, Yinjie J

    2016-11-04

    Flux analyses, including flux balance analysis (FBA) and 13 C-metabolic flux analysis ( 13 C-MFA), offer direct insights into cell metabolism, and have been widely used to characterize model and non-model microbial species. Nonetheless, constructing the 13 C-MFA model and performing flux calculation are demanding for new learners, because they require knowledge of metabolic networks, carbon transitions, and computer programming. To facilitate and standardize the 13 C-MFA modeling work, we set out to publish a user-friendly and programming-free platform (WUFlux) for flux calculations in MATLAB ® . We constructed an open-source platform for steady-state 13 C-MFA. Using GUIDE (graphical user interface design environment) in MATLAB, we built a user interface that allows users to modify models based on their own experimental conditions. WUFlux is capable of directly correcting mass spectrum data of TBDMS (N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide)-derivatized proteinogenic amino acids by removing background noise. To simplify 13 C-MFA of different prokaryotic species, the software provides several metabolic network templates, including those for chemoheterotrophic bacteria and mixotrophic cyanobacteria. Users can modify the network and constraints, and then analyze the microbial carbon and energy metabolisms of various carbon substrates (e.g., glucose, pyruvate/lactate, acetate, xylose, and glycerol). WUFlux also offers several ways of visualizing the flux results with respect to the constructed network. To validate our model's applicability, we have compared and discussed the flux results obtained from WUFlux and other MFA software. We have also illustrated how model constraints of cofactor and ATP balances influence fluxome results. Open-source software for 13 C-MFA, WUFlux, with a user-friendly interface and easy-to-modify templates, is now available at http://www.13cmfa.org /or ( http://tang.eece.wustl.edu/ToolDevelopment.htm ). We will continue

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular...... differential turnover of lipid droplet-associated triacylglycerols and sterol esters during respiratory growth, that sphingolipid metabolism is regulated in a previously unrecognized growth stage-specific manner, and that endogenous synthesis of unsaturated fatty acids constitutes an in vivo upstream activator...... of peroxisomal biogenesis, via the heterodimeric Oaf1/Pip2 transcription factor. Our work demonstrates the pivotal role of lipid metabolism in adaptive processes and provides a resource to investigate its regulation at the cellular level....

  1. Tissue turnover rates and isotopic trophic discrimination factors in the endothermic teleost, pacific bluefin tuna (Thunnus orientalis.

    Directory of Open Access Journals (Sweden)

    Daniel J Madigan

    Full Text Available Stable isotope analysis (SIA of highly migratory marine pelagic animals can improve understanding of their migratory patterns and trophic ecology. However, accurate interpretation of isotopic analyses relies on knowledge of isotope turnover rates and tissue-diet isotope discrimination factors. Laboratory-derived turnover rates and discrimination factors have been difficult to obtain due to the challenges of maintaining these species in captivity. We conducted a study to determine tissue- (white muscle and liver and isotope- (nitrogen and carbon specific turnover rates and trophic discrimination factors (TDFs using archived tissues from captive Pacific bluefin tuna (PBFT, Thunnus orientalis, 1-2914 days after a diet shift in captivity. Half-life values for (15N turnover in white muscle and liver were 167 and 86 days, and for (13C were 255 and 162 days, respectively. TDFs for white muscle and liver were 1.9 and 1.1‰ for δ(15N and 1.8 and 1.2‰ for δ(13C, respectively. Our results demonstrate that turnover of (15N and (13C in bluefin tuna tissues is well described by a single compartment first-order kinetics model. We report variability in turnover rates between tissue types and their isotope dynamics, and hypothesize that metabolic processes play a large role in turnover of nitrogen and carbon in PBFT white muscle and liver tissues. (15N in white muscle tissue showed the most predictable change with diet over time, suggesting that white muscle δ(15N data may provide the most reliable inferences for diet and migration studies using stable isotopes in wild fish. These results allow more accurate interpretation of field data and dramatically improve our ability to use stable isotope data from wild tunas to better understand their migration patterns and trophic ecology.

  2. Exhaustive Analysis of a Genotype Space Comprising 10(15 Central Carbon Metabolisms Reveals an Organization Conducive to Metabolic Innovation.

    Directory of Open Access Journals (Sweden)

    Sayed-Rzgar Hosseini

    2015-08-01

    Full Text Available All biological evolution takes place in a space of possible genotypes and their phenotypes. The structure of this space defines the evolutionary potential and limitations of an evolving system. Metabolism is one of the most ancient and fundamental evolving systems, sustaining life by extracting energy from extracellular nutrients. Here we study metabolism's potential for innovation by analyzing an exhaustive genotype-phenotype map for a space of 10(15 metabolisms that encodes all possible subsets of 51 reactions in central carbon metabolism. Using flux balance analysis, we predict the viability of these metabolisms on 10 different carbon sources which give rise to 1024 potential metabolic phenotypes. Although viable metabolisms with any one phenotype comprise a tiny fraction of genotype space, their absolute numbers exceed 10(9 for some phenotypes. Metabolisms with any one phenotype typically form a single network of genotypes that extends far or all the way through metabolic genotype space, where any two genotypes can be reached from each other through a series of single reaction changes. The minimal distance of genotype networks associated with different phenotypes is small, such that one can reach metabolisms with novel phenotypes--viable on new carbon sources--through one or few genotypic changes. Exceptions to these principles exist for those metabolisms whose complexity (number of reactions is close to the minimum needed for viability. Increasing metabolic complexity enhances the potential for both evolutionary conservation and evolutionary innovation.

  3. Blood Lead, Bone Turnover, and Survival in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Fang, Fang; Peters, Tracy L; Beard, John D; Umbach, David M; Keller, Jean; Mariosa, Daniela; Allen, Kelli D; Ye, Weimin; Sandler, Dale P; Schmidt, Silke; Kamel, Freya

    2017-11-01

    Blood lead and bone turnover may be associated with the risk of amyotrophic lateral sclerosis (ALS). We aimed to assess whether these factors were also associated with time from ALS diagnosis to death through a survival analysis of 145 ALS patients enrolled during 2007 in the National Registry of Veterans with ALS. Associations of survival time with blood lead and plasma biomarkers of bone resorption (C-terminal telopeptides of type I collagen (CTX)) and bone formation (procollagen type I amino-terminal peptide (PINP)) were estimated using Cox models adjusted for age at diagnosis, diagnostic certainty, diagnostic delay, site of onset, and score on the Revised ALS Functional Rating Scale. Hazard ratios were calculated for each doubling of biomarker concentration. Blood lead, plasma CTX, and plasma PINP were mutually adjusted for one another. Increased lead (hazard ratio (HR) = 1.38; 95% confidence interval (CI): 1.03, 1.84) and CTX (HR = 2.03; 95% CI: 1.42, 2.89) were both associated with shorter survival, whereas higher PINP was associated with longer survival (HR = 0.59; 95% CI: 0.42, 0.83), after ALS diagnosis. No interactions were observed between lead or bone turnover and other prognostic indicators. Lead toxicity and bone metabolism may be involved in ALS pathophysiology. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  4. Evolution of amino acid metabolism inferred through cladistic analysis.

    Science.gov (United States)

    Cunchillos, Chomin; Lecointre, Guillaume

    2003-11-28

    Because free amino acids were most probably available in primitive abiotic environments, their metabolism is likely to have provided some of the very first metabolic pathways of life. What were the first enzymatic reactions to emerge? A cladistic analysis of metabolic pathways of the 16 aliphatic amino acids and 2 portions of the Krebs cycle was performed using four criteria of homology. The analysis is not based on sequence comparisons but, rather, on coding similarities in enzyme properties. The properties used are shared specific enzymatic activity, shared enzymatic function without substrate specificity, shared coenzymes, and shared functional family. The tree shows that the earliest pathways to emerge are not portions of the Krebs cycle but metabolisms of aspartate, asparagine, glutamate, and glutamine. The views of Horowitz (Horowitz, N. H. (1945) Proc. Natl. Acad. Sci. U. S. A. 31, 153-157) and Cordón (Cordón, F. (1990) Tratado Evolucionista de Biologia, Aguilar, Madrid, Spain), according to which the upstream reactions in the catabolic pathways and the downstream reactions in the anabolic pathways are the earliest in evolution, are globally corroborated; however, with some exceptions. These are due to later opportunistic connections of pathways (actually already suggested by these authors). Earliest enzymatic functions are mostly catabolic; they were deaminations, transaminations, and decarboxylations. From the consensus tree we extracted four time spans for amino acid metabolism development. For some amino acids catabolism and biosynthesis occurred at the same time (Asp, Glu, Lys, Leu, Ala, Val, Ile, Pro, Arg). For others ultimate reactions that use amino acids as a substrate or as a product are distinct in time, with catabolism preceding anabolism for Asn, Gln, and Cys and anabolism preceding catabolism for Ser, Met, and Thr. Cladistic analysis of the structure of biochemical pathways makes hypotheses in biochemical evolution explicit and parsimonious.

  5. Are You Interested? A Meta-Analysis of Relations between Vocational Interests and Employee Performance and Turnover

    Science.gov (United States)

    Van Iddekinge, Chad H.; Roth, Philip L.; Putka, Dan J.; Lanivich, Stephen E.

    2011-01-01

    A common belief among researchers is that vocational interests have limited value for personnel selection. However, no comprehensive quantitative summaries of interests validity research have been conducted to substantiate claims for or against the use of interests. To help address this gap, we conducted a meta-analysis of relations between…

  6. Analysis of Subclinical Hyperthyroidism Influence on Parameters of Bone Metabolism

    Directory of Open Access Journals (Sweden)

    I.V. Pankiv

    2016-03-01

    Full Text Available State of subclinical hypothyroidism can be considered as the optimal model for assessing the significance of thyroid stimulating hormone (TSH for bone tissue in clinical practice. Objective: to make a comparative analysis of the impact of subclinical hyperthyroidism of various origins on the performance of bone mineral density (BMD and bone metabolism parameters. Materials and methods. The study in an outpatient setting included 112 women with a diagnosis of subclinical hyperthyroidism and duration of menopause for at least 5 years. Among the examinees, endogenous subclinical hyperthyroidism has been detected in 78 women (group I, exogenous subclinical hyperthyroidism on the background of suppressive levothyroxine therapy (group II — in 34. The control group (group III included 20 women without thyroid dysfunction. Results. The study first conducted a comparative analysis of bone metabolism, BMD indicators, as well as parameters of phosphorus and calcium, blood lipids in women with subclinical hyperthyroidism of various origins. A positive correlation between markers of bone metabolism and free triiodothyronine (fT3 as hormones necessary for the development of the skeleton and to maintain its homeostasis indicates a physiological effect of parathyroid hormone and fT3 on bone tissue. It is shown that the bone metabolism and BMD depend not only on the content of TSH, but also on the causes of subclinical hyperthyroidism.Conclusions. In postmenopausal women with endogenous subclinical hyperthyroidism, there is a significant decline in BMD indices, more pronounced in the bones with the cortical structure. A negative correlation between markers of bone metabolism and TSH has been observed among all patients included in the study.

  7. PENGARUH KEPUASAN KERJA TERHADAP KOMITMEN ORGANISASI DAN TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    Agi Syarif Hidayat

    2018-03-01

    Full Text Available The high level of employee turnover in the marketing department at PT. Toyamilindo indicates low organizational commitment and high turnover intention. The purpose of this study is to determine the effect of job satisfaction on organizational commitment and turnover intention. Quantitative methods are used in this study. Population is the  employees of marketing department at PT. Toyamilindo with 50 people. Sampling technique used is sampling saturated with the number of samples of 50 people. Data collection technique uses questionnaires and regression analysis. Finding on the research results shows that there are positive and significant influence of job satisfaction on organizational commitment and negative and significant influence of job satisfaction on turnover intention, and also the influence of organizational commitment on work satisfaction to turnover intention. The managerial implications of corporate leaders must improve employee work satisfaction, especially in terms of salary.

  8. PFA toolbox: a MATLAB tool for Metabolic Flux Analysis.

    Science.gov (United States)

    Morales, Yeimy; Bosque, Gabriel; Vehí, Josep; Picó, Jesús; Llaneras, Francisco

    2016-07-11

    Metabolic Flux Analysis (MFA) is a methodology that has been successfully applied to estimate metabolic fluxes in living cells. However, traditional frameworks based on this approach have some limitations, particularly when measurements are scarce and imprecise. This is very common in industrial environments. The PFA Toolbox can be used to face those scenarios. Here we present the PFA (Possibilistic Flux Analysis) Toolbox for MATLAB, which simplifies the use of Interval and Possibilistic Metabolic Flux Analysis. The main features of the PFA Toolbox are the following: (a) It provides reliable MFA estimations in scenarios where only a few fluxes can be measured or those available are imprecise. (b) It provides tools to easily plot the results as interval estimates or flux distributions. (c) It is composed of simple functions that MATLAB users can apply in flexible ways. (d) It includes a Graphical User Interface (GUI), which provides a visual representation of the measurements and their uncertainty. (e) It can use stoichiometric models in COBRA format. In addition, the PFA Toolbox includes a User's Guide with a thorough description of its functions and several examples. The PFA Toolbox for MATLAB is a freely available Toolbox that is able to perform Interval and Possibilistic MFA estimations.

  9. 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.

  10. Collagen turnover after tibial fractures

    DEFF Research Database (Denmark)

    Joerring, S; Krogsgaard, M; Wilbek, H

    1994-01-01

    Collagen turnover after tibial fractures was examined in 16 patients with fracture of the tibial diaphysis and in 8 patients with fracture in the tibial condyle area by measuring sequential changes in serological markers of turnover of types I and III collagen for up to 26 weeks after fracture...... collagen. A group comparison showed characteristic sequential changes in the turnover of types I and III collagen in fractures of the tibial diaphysis and tibial condyles. The turnover of type III collagen reached a maximum after 2 weeks in both groups. The synthesis of type I collagen reached a maximum...... after 2 weeks in the diaphyseal fractures and after 6 weeks in the condylar fractures. The degradation of type I collagen increased after 4 days and reached a maximum at 2 weeks in both groups. The interindividual variation was wide. On a group basis, the turnover of types I and III collagen had...

  11. The relationship between bone turnover and insulin sensitivity and secretion

    DEFF Research Database (Denmark)

    Frost, Morten; Balkau, Beverley; Hatunic, Mensud

    2018-01-01

    Bone metabolism appears to influence insulin secretion and sensitivity, and insulin promotes bone formation in animals, but similar evidence in humans is limited. The objectives of this study are to explore if bone turnover markers were associated with insulin secretion and sensitivity and to det...

  12. High bone turnover in Irish professional jockeys.

    LENUS (Irish Health Repository)

    Waldron-Lynch, F

    2012-02-01

    SUMMARY: Professional jockeys are routinely exposed to high impact trauma and sustain fractures frequently. We found that jockeys restrict their caloric intake in order to maintain regulation weights, and that bone turnover is high. There are significant health and safety implications for the racing industry. INTRODUCTION: Professional jockeys routinely sustain fractures from high impact falls. Jockeys maintain a low percentage body fat and a low body mass index (BMI) to achieve low weight targets in order to race. We evaluated dietary habits and bone metabolism in jockeys. METHODS: Bone mineral density (BMD) was measured in 27 male jockeys of the 144 jockeys licensed in Ireland. Fourteen (52%) had BMD T score below -1.0, of whom 12 consented to clinical review, nutritional survey, endocrine studies, and bone turnover markers (BTM). BTM were compared to age- and sex-matched controls (n = 16). RESULTS: BMI was 20.6 +\\/- 1.7 kg\\/m(2); previous fracture frequency was 3.2 +\\/- 2.0 per rider. All had normal endocrine axes. The jockeys\\' diet as determined by a 7-day dietary recall was deficient in energy, calcium, and vitamin D intake. Compared with the control group, the jockey group had evidence of increased bone turnover. CONCLUSIONS: A substantial proportion of the professional jockeys in Ireland have low-normal BMD, low BMI, and high bone turnover that may result from weight and dietary restrictions. These factors seem to have a deleterious effect on their bone health and predispose the jockeys to a high fracture risk that should be remediated.

  13. Metabolism

    Science.gov (United States)

    ... functions: Anabolism (uh-NAB-uh-liz-um), or constructive metabolism, is all about building and storing. It ... in infants and young children. Hypothyroidism slows body processes and causes fatigue (tiredness), slow heart rate, excessive ...

  14. Metabolism

    Science.gov (United States)

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... acid phenylalanine, needed for normal growth and protein production). Inborn errors of metabolism can sometimes lead to ...

  15. Rationale for the evaluation of trabecular bone turnover

    International Nuclear Information System (INIS)

    Kimmel, D.B.; Jee, W.S.S.

    1976-01-01

    A procedure for the morphometric evaluation of trabecular bone is identified. Its scrupulous use allows total identification of bone formation and resorption rates, items necessary for the direct histologic analysis of bone turnover

  16. FluxFix: automatic isotopologue normalization for metabolic tracer analysis.

    Science.gov (United States)

    Trefely, Sophie; Ashwell, Peter; Snyder, Nathaniel W

    2016-11-25

    Isotopic tracer analysis by mass spectrometry is a core technique for the study of metabolism. Isotopically labeled atoms from substrates, such as [ 13 C]-labeled glucose, can be traced by their incorporation over time into specific metabolic products. Mass spectrometry is often used for the detection and differentiation of the isotopologues of each metabolite of interest. For meaningful interpretation, mass spectrometry data from metabolic tracer experiments must be corrected to account for the naturally occurring isotopologue distribution. The calculations required for this correction are time consuming and error prone and existing programs are often platform specific, non-intuitive, commercially licensed and/or limited in accuracy by using theoretical isotopologue distributions, which are prone to artifacts from noise or unresolved interfering signals. Here we present FluxFix ( http://fluxfix.science ), an application freely available on the internet that quickly and reliably transforms signal intensity values into percent mole enrichment for each isotopologue measured. 'Unlabeled' data, representing the measured natural isotopologue distribution for a chosen analyte, is entered by the user. This data is used to generate a correction matrix according to a well-established algorithm. The correction matrix is applied to labeled data, also entered by the user, thus generating the corrected output data. FluxFix is compatible with direct copy and paste from spreadsheet applications including Excel (Microsoft) and Google sheets and automatically adjusts to account for input data dimensions. The program is simple, easy to use, agnostic to the mass spectrometry platform, generalizable to known or unknown metabolites, and can take input data from either a theoretical natural isotopologue distribution or an experimentally measured one. Our freely available web-based calculator, FluxFix ( http://fluxfix.science ), quickly and reliably corrects metabolic tracer data for

  17. Thermodynamic principles governing metabolic operation : inference, analysis, and prediction

    NARCIS (Netherlands)

    Niebel, Bastian

    2015-01-01

    The principles governing metabolic flux are poorly understood. Because diverse organisms show similar metabolic flux patterns, we hypothesized that fundamental thermodynamic constraints might shape cellular metabolism. We developed a constraint-based model for Saccharomyces cerevisiae that included

  18. Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions

    Directory of Open Access Journals (Sweden)

    Edwards Jeremy S

    2000-07-01

    Full Text Available Abstract Background Genome sequencing and bioinformatics are producing detailed lists of the molecular components contained in many prokaryotic organisms. From this 'parts catalogue' of a microbial cell, in silico representations of integrated metabolic functions can be constructed and analyzed using flux balance analysis (FBA. FBA is particularly well-suited to study metabolic networks based on genomic, biochemical, and strain specific information. Results Herein, we have utilized FBA to interpret and analyze the metabolic capabilities of Escherichia coli. We have computationally mapped the metabolic capabilities of E. coli using FBA and examined the optimal utilization of the E. coli metabolic pathways as a function of environmental variables. We have used an in silico analysis to identify seven gene products of central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, electron transport system essential for aerobic growth of E. coli on glucose minimal media, and 15 gene products essential for anaerobic growth on glucose minimal media. The in silico tpi-, zwf, and pta- mutant strains were examined in more detail by mapping the capabilities of these in silico isogenic strains. Conclusions We found that computational models of E. coli metabolism based on physicochemical constraints can be used to interpret mutant behavior. These in silica results lead to a further understanding of the complex genotype-phenotype relation. Supplementary information: http://gcrg.ucsd.edu/supplementary_data/DeletionAnalysis/main.htm

  19. Dynamics of Adipocyte Turnover in Humans

    Energy Technology Data Exchange (ETDEWEB)

    Spalding, K; Arner, E; Westermark, P; Bernard, S; Buchholz, B; Bergmann, O; Blomqvist, L; Hoffstedt, J; Naslund, E; Britton, T; Concha, H; Hassan, M; Ryden, M; Frisen, J; Arner, P

    2007-07-16

    Obesity is increasing in an epidemic fashion in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells is thought to be most important. We show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese and even under extreme conditions, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analyzing the integration of {sup 14}C derived from nuclear bomb tests in genomic DNA. Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in obesity, suggesting a tight regulation of fat cell number that is independent of metabolic profile in adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.

  20. Primary metabolism in Lactobacillus sakei food isolates by proteomic analysis

    Directory of Open Access Journals (Sweden)

    Champomier-Vergès Marie-Christine

    2010-04-01

    Full Text Available Abstract Background Lactobacillus sakei is an important food-associated lactic acid bacterium commonly used as starter culture for industrial meat fermentation, and with great potential as a biopreservative in meat and fish products. Understanding the metabolic mechanisms underlying the growth performance of a strain to be used for food fermentations is important for obtaining high-quality and safe products. Proteomic analysis was used to study the primary metabolism in ten food isolates after growth on glucose and ribose, the main sugars available for L. sakei in meat and fish. Results Proteins, the expression of which varied depending on the carbon source were identified, such as a ribokinase and a D-ribose pyranase directly involved in ribose catabolism, and enzymes involved in the phosphoketolase and glycolytic pathways. Expression of enzymes involved in pyruvate and glycerol/glycerolipid metabolism were also affected by the change of carbon source. Interestingly, a commercial starter culture and a protective culture strain down-regulated the glycolytic pathway more efficiently than the rest of the strains when grown on ribose. The overall two-dimensional gel electrophoresis (2-DE protein expression pattern was similar for the different strains, though distinct differences were seen between the two subspecies (sakei and carnosus, and a variation of about 20% in the number of spots in the 2-DE gels was observed between strains. A strain isolated from fermented fish showed a higher expression of stress related proteins growing on both carbon sources. Conclusions It is obvious from the data obtained in this study that the proteomic approach efficiently identifies differentially expressed proteins caused by the change of carbon source. Despite the basic similarity in the strains metabolic routes when they ferment glucose and ribose, there were also interesting differences. From the application point of view, an understanding of regulatory

  1. Metabolic control analysis of xylose catabolism in Aspergillus

    DEFF Research Database (Denmark)

    Prathumpai, Wai; Gabelgaard, J.B.; Wanchanthuek, P.

    2003-01-01

    A kinetic model for xylose catabolism in Aspergillus is proposed. From a thermodynamic analysis it was found that the intermediate xylitol will accumulate during xylose catabolism. Use of the kinetic model allowed metabolic control analysis (MCA) of the xylose catabolic pathway to be carried out......, and flux control was shown to be dependent on the metabolite levels. Due to thermodynamic constraints, flux control may reside at the first step in the pathway, i.e., at the xylose reductase, even when the intracellular xylitol concentration is high. On the basis of the kinetic analysis, the general dogma...... specifying that flux control often resides at the step following an intermediate present at high concentrations was, therefore, shown not to hold. The intracellular xylitol concentration was measured in batch cultivations of two different strains of Aspergillus niger and two different strains of Aspergillus...

  2. Collagen turnover after tibial fractures

    DEFF Research Database (Denmark)

    Joerring, S; Krogsgaard, M; Wilbek, H

    1994-01-01

    Collagen turnover after tibial fractures was examined in 16 patients with fracture of the tibial diaphysis and in 8 patients with fracture in the tibial condyle area by measuring sequential changes in serological markers of turnover of types I and III collagen for up to 26 weeks after fracture....... The markers were the carboxy-terminal extension peptide of type I procollagen (PICP), the amino-terminal extension peptide of type III procollagen (PIIINP), and the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP). The latter is a new serum marker of degradation of type I...... collagen. A group comparison showed characteristic sequential changes in the turnover of types I and III collagen in fractures of the tibial diaphysis and tibial condyles. The turnover of type III collagen reached a maximum after 2 weeks in both groups. The synthesis of type I collagen reached a maximum...

  3. Causes and consequences of collective turnover: a meta-analytic review.

    Science.gov (United States)

    Heavey, Angela L; Holwerda, Jacob A; Hausknecht, John P

    2013-05-01

    Given growing interest in collective turnover (i.e., employee turnover at unit and organizational levels), the authors propose an organizing framework for its antecedents and consequences and test it using meta-analysis. Based on analysis of 694 effect sizes drawn from 82 studies, results generally support expected relationships across the 6 categories of collective turnover antecedents, with somewhat stronger and more consistent results for 2 categories: human resource management inducements/investments and job embeddedness signals. Turnover was negatively related to numerous performance outcomes, more strongly so for proximal rather than distal outcomes. Several theoretically grounded moderators help to explain average effect-size heterogeneity for both antecedents and consequences of turnover. Relationships generally did not vary according to turnover type (e.g., total or voluntary), although the relative absence of collective-level involuntary turnover studies is noted and remains an important avenue for future research. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  4. Bibliometric analysis of Indian Journal of Endocrinology and Metabolism

    Directory of Open Access Journals (Sweden)

    Garima Bhutani

    2013-01-01

    Full Text Available Background: Bibliometric analysis of the journal is a method to assess the research impact or research influence of that journal. This information can also be used to evaluate the influence/performance of a researcher and to provide a comparison between researchers. This work was aimed at performing bibliometric analysis of Indian Journal of Endocrinology and Metabolism (IJEM. Materials and Methods: The publications of year 2011-12 of IJEM were analyzed. Total number of articles published, type of articles, their authorship, and the coverage of various subspecialties was studied. The publications were also classified as Indian or foreign, from endocrine or nonendocrine departments and from academic or nonacademic institutions according to the institution of first author. Results and Conclusions: A total of 10 main issues and 7 supplementary issues were published in IJEM in year 2011 and 2012. These included a total of 605 publications, which depict a dramatic increase in the number of publications in last 2 years as compared to the previous years. Taking collectively, review articles were published in majority. Maximum number of articles was dealing with pancreas and metabolic disorders followed by thyroid. Other endocrine organs were given almost similar importance. Publications were largely originating from endocrine departments and from academic institutions. Although maximum number of articles were from India, but the publications from other countries are also on an increase. Thus, the widespread coverage of this journal suggests that IJEM has begun to represent global face of Indian endocrinology.

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

    Science.gov (United States)

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill; Ruckerbauer, David E; Hannibal-Bach, Hans Kristian; Zanghellini, Jürgen; Jensen, Ole N; Ejsing, Christer S

    2015-03-19

    Elucidating how and to what extent lipid metabolism is remodeled under changing conditions is essential for understanding cellular physiology. Here, we analyzed proteome and lipidome dynamics to investigate how regulation of lipid metabolism at the global scale supports remodeling of cellular architecture and processes during physiological adaptations in yeast. Our results reveal that activation of cardiolipin synthesis and remodeling supports mitochondrial biogenesis in the transition from fermentative to respiratory metabolism, that down-regulation of de novo sterol synthesis machinery prompts differential turnover of lipid droplet-associated triacylglycerols and sterol esters during respiratory growth, that sphingolipid metabolism is regulated in a previously unrecognized growth stage-specific manner, and that endogenous synthesis of unsaturated fatty acids constitutes an in vivo upstream activator of peroxisomal biogenesis, via the heterodimeric Oaf1/Pip2 transcription factor. Our work demonstrates the pivotal role of lipid metabolism in adaptive processes and provides a resource to investigate its regulation at the cellular level. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Metabolic control analysis of xylose catabolism in Aspergillus

    DEFF Research Database (Denmark)

    Prathumpai, Wai; Gabelgaard, J.B.; Wanchanthuek, P.

    2003-01-01

    A kinetic model for xylose catabolism in Aspergillus is proposed. From a thermodynamic analysis it was found that the intermediate xylitol will accumulate during xylose catabolism. Use of the kinetic model allowed metabolic control analysis (MCA) of the xylose catabolic pathway to be carried out...... specifying that flux control often resides at the step following an intermediate present at high concentrations was, therefore, shown not to hold. The intracellular xylitol concentration was measured in batch cultivations of two different strains of Aspergillus niger and two different strains of Aspergillus...... nidulans grown on media containing xylose, and a concentration up to 30 mM was found. Applying MCA showed that the first polyol dehydrogenase (XDH) in the catabolic pathway of xylose exerted the main flux control in the two strains of A. nidulans and A. niger NW324, but the flux control was exerted mainly...

  7. Metabolic regulation analysis of an ethanologenic Escherichia coli strain based on RT-PCR and enzymatic activities

    Directory of Open Access Journals (Sweden)

    Martinez Alfredo

    2008-05-01

    Full Text Available Abstract Background A metabolic regulation study was performed, based upon measurements of enzymatic activities, fermentation performance, and RT-PCR analysis of pathways related to central carbon metabolism, in an ethanologenic Escherichia coli strain (CCE14 derived from lineage C. In comparison with previous engineered strains, this E coli derivative has a higher ethanol production rate in mineral medium, as a result of the elevated heterologous expression of the chromosomally integrated genes encoding PDCZm and ADHZm (pyruvate decarboxylase and alcohol dehydrogenase from Zymomonas mobilis. It is suggested that this behavior might be due to lineage differences between E. coli W and C. Results This study demonstrated that the glycolytic flux is controlled, in this case, by reactions outside glycolysis, i.e., the fermentative pathways. Changes in ethanol production rate in this ethanologenic strain result in low organic acid production rates, and high glycolytic and ethanologenic fluxes, that correlate with enhanced transcription and enzymatic activity levels of PDCZm and ADHZm. Furthermore, a higher ethanol yield (90% of the theoretical in glucose-mineral media was obtained with CCE14 in comparison with previous engineered E. coli strains, such as KO11, that produces a 70% yield under the same conditions. Conclusion Results suggest that a higher ethanol formation rate, caused by ahigher PDCZm and ADHZm activities induces a metabolic state that cells compensate through enhanced glucose transport, ATP synthesis, and NAD-NADH+H turnover rates. These results show that glycolytic enzymatic activities, present in E. coli W and C under fermentative conditions, are sufficient to contend with increases in glucose consumption and product formation rates.

  8. Prevalence of metabolic syndrome and metabolic syndrome components in young adults: A pooled analysis

    Directory of Open Access Journals (Sweden)

    Paul B. Nolan

    2017-09-01

    Full Text Available Metabolic syndrome (MetSyn represents a clustering of different metabolic abnormalities. MetSyn prevalence is present in approximately 25% of all adults with increased prevalence in advanced ages. The presence of one component of MetSyn increases the risk of developing MetSyn later in life and likely represents a high lifetime burden of cardiovascular disease risk. Therefore we pooled data from multiple studies to establish the prevalence of MetSyn and MetSyn component prevalence across a broad range of ethnicities. PubMed, SCOPUS and Medline databases were searched to find papers presenting MetSyn and MetSyn component data for 18–30 year olds who were apparently healthy, free of disease, and MetSyn was assessed using either the harmonized, National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII, American Heart Association/National Heart, Blood and Lung Institute (AHA/NHBLI, or International Diabetes Federation (IDF definitions of MetSyn. After reviewing returned articles, 26,609 participants' data from 34 studies were included in the analysis and the data were pooled. MetSyn was present in 4.8–7% of young adults. Atherogenic dyslipidaemia defined as low high density lipoprotein (HDL cholesterol was the most prevalent MetSyn component (26.9–41.2%, followed by elevated blood pressure (16.6–26.6%, abdominal obesity (6.8–23.6%, atherogenic dyslipidaemia defined as raised triglycerides (8.6–15.6%, and raised fasting glucose (2.8–15.4%. These findings highlight that MetSyn is prevalent in young adults. Establishing the reason why low HDL is the most prevalent component may represent an important step in promoting primary prevention of MetSyn and reducing the incidence of subsequent clinical disease.

  9. Improvements to Kramers turnover theory.

    Science.gov (United States)

    Pollak, Eli; Ankerhold, Joachim

    2013-04-28

    The Kramers turnover problem, that is, obtaining a uniform expression for the rate of escape of a particle over a barrier for any value of the external friction was solved in the 1980s. Two formulations were given, one by Mel'nikov and Meshkov (MM) [V. I. Mel'nikov and S. V. Meshkov, J. Chem. Phys. 85, 1018 (1986)], which was based on a perturbation expansion for the motion of the particle in the presence of friction. The other, by Pollak, Grabert, and Hänggi (PGH) [E. Pollak, H. Grabert, and P. Hänggi, J. Chem. Phys. 91, 4073 (1989)], valid also for memory friction, was based on a perturbation expansion for the motion along the collective unstable normal mode of the particle. Both theories did not take into account the temperature dependence of the average energy loss to the bath. Increasing the bath temperature will reduce the average energy loss. In this paper, we analyse this effect, using a novel perturbation theory. We find that within the MM approach, the thermal energy gained from the bath diverges, the average energy gain becomes infinite implying an essential failure of the theory. Within the PGH approach increasing the bath temperature reduces the average energy loss but only by a finite small amount of the order of the inverse of the reduced barrier height. Then, this does not seriously affect the theory. Analysis and application for a cubic potential and Ohmic friction are presented.

  10. KECENDERUNGAN KEPUASAN KERJA SEBAGAI TRIGGER TURNOVER

    OpenAIRE

    Raditya Adi Saputra

    2017-01-01

    The purpose of this study are: (1) To determine the effect of job satisfaction on turnover intention; (2) To determine the effect of work stress on turnover intention; (3) To determine the effect of compensation on turnover intention; (4) To determine the effect of organizational climate on turnover intention; and (5) To determine the stress of work, compensation, organizational climate and job satisfaction effect on turnover intention. The population in this study are employees of the Coo...

  11. Bone turnover marker reference intervals in young females.

    Science.gov (United States)

    Callegari, Emma T; Gorelik, Alexandra; Garland, Suzanne M; Chiang, Cherie Y; Wark, John D

    2017-07-01

    Background The use of bone turnover markers in clinical practice and research in younger people is limited by the lack of normative data and understanding of common causes of variation in bone turnover marker values in this demographic. To appropriately interpret bone turnover markers, robust reference intervals specific to age, development and sex are necessary. This study aimed to determine reference intervals of bone turnover markers in females aged 16-25 years participating in the Safe-D study. Methods Participants were recruited through social networking site Facebook and were asked to complete an extensive, online questionnaire and attend a site visit. Participants were tested for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and total procollagen type 1 N-propeptide using the Roche Elecsys automated analyser. Reference intervals were determined using the 2.5th to 97.5th percentiles of normalized bone turnover marker values. Results Of 406 participants, 149 were excluded due to medical conditions or medication use (except hormonal contraception) which may affect bone metabolism. In the remaining 257 participants, the reference interval was 230-1000 ng/L for serum carboxy-terminal cross-linking telopeptide of type 1 collagen and 27-131  µg/L for procollagen type 1 N-propeptide. Both marker concentrations were inversely correlated with age and oral contraceptive pill use. Therefore, intervals specific to these variables were calculated. Conclusions We defined robust reference intervals for cross-linking telopeptide of type 1 collagen and procollagen type 1 N-propeptide in young females grouped by age and contraceptive pill use. We examined bone turnover markers' relationship with several lifestyle, clinical and demographic factors. Our normative intervals should aid interpretation of bone turnover markers in young females particularly in those aged 16 to 19 years where reference intervals are currently provisional.

  12. Flux balance analysis of genome-scale metabolic model of rice ...

    Indian Academy of Sciences (India)

    Here, we analyse a genome-scale metabolic model of rice leaf using Flux Balance Analysis to investigate whether it has potential metabolic flexibility to increase the biosynthesis of any of the biomass components. We initially simulate the metabolic responses under an objective to maximize the biomass components.

  13. Hepatic metallothionein turnover in toxic milk mutant mice

    International Nuclear Information System (INIS)

    Rauch, H.; Wells, A.J.

    1989-01-01

    Homozygous toxic milk (tx tx) mice are characterized by extraordinary hepatic copper levels, the excess copper being associated with metallothionein (MT). We have compared MT metabolism in normal and mutant animals. To evaluate MT turnover, animals were injected with 35 S-cysteine, followed in 24 hours by a cold cysteine chase. Animals were sacrificed daily and radioactivity in hepatic MT fractions was used to calculated MT half-life. Based on uptake of label, MT synthesis is very active in tx mice, this MT having a half life of 4-5 days. MT synthesis in normals is much lower, one fourth or less radioactivity. To increase MT synthesis, normals were primed by prior zinc (150 μg) or copper (90 μg) injection; MT label was doubled, the resulting MT showing a slow turnover rate, half-life about 6 days. Another group of normals were primed as above but with metal injections repeated daily so as to measure turnover under conditions of continuous high level MT synthesis, comparable to those prevailing in mutant animals. Although initial label uptake was the same as that of previously primed animals, turnover was hastened, half-life 2-3 days. Thus, copper accumulation in mutants is attributable at least in part to increased rate of synthesis coupled with decreased rate of turnover of MT

  14. Job turnover and regional attrition among physiotherapists in northern Ontario.

    Science.gov (United States)

    Noh, S; Beggs, C E

    1993-01-01

    Results of an initial study indicated that the most significant factor affecting retention for Physiotherapists in Northern Ontario was perceived opportunity for career development. A follow-up study was completed two years later to determine: 1) actual job turnover and regional attrition among physiotherapists in Northern Ontario; and 2) the predictive validity of variables identified in the first study regarding job turnover and regional attrition. Job turnover occurred in 29.5% of those sampled and the regional attrition rate was 12%. Discriminant function analysis revealed factors affecting job turnover and regional attrition including professional experience, practice location, opportunity for career development and size of community of residence. Based on previous intention, indicated by participants, follow-up revealed that the initial study correctly predicted 77.5% of those who changed their jobs and 74.1% of those who left Northern Ontario. Identified factors provide direction for the development of strategies for recruitment and retention of physiotherapists.

  15. Autoradiographic imaging of phosphoinositide turnover in the brain

    International Nuclear Information System (INIS)

    Hwang, P.M.; Bredt, D.S.; Snyder, S.H.

    1990-01-01

    With [ 3 H]cytidine as a precursor, phosphoinositide turnover can be localized in brain slices by selective autoradiography of the product [ 3 H]cytidine diphosphate diacylglycerol, which is membrane-bound. In the cerebellum, glutamatergic stimulation elicits an increase of phosphoinositide turnover only in Purkinje cells and the molecular layer. In the hippocampus, both glutamatergic and muscarinic cholinergic stimulation increase phosphoinositide turnover, but with distinct localizations. Cholinergic stimulation affects CA1, CA3, CA4, and subiculum, whereas glutamatergic effects are restricted to the subiculum and CA3. Imaging phosphoinositide turnover in brain slices, which are amenable to electrophysiologic studies, will permit a dynamic localized analysis of regulation of this second messenger in response to synaptic stimulation of specific neuronal pathways

  16. Carbon Use Efficiency and Turnover of Microbial Communities: Concepts and Emerging Techniques

    Science.gov (United States)

    Richter, Andreas; Fuchslueger, Lucia; Klaus, Karoline; Mooshammer, Maria; Spohn, Marie; Walker, Tom; Wanek, Wolfgang; Birgit, Wild

    2016-04-01

    Microbial element use efficiencies are fundamental for understanding organic matter decomposition and ecosystem carbon and nutrient storage. Terrestrial decomposer communities thrive on a wide range of organic substrates, which rarely ever meet their elemental demands. One of the most important mechanisms by which microbes are able to maintain their elemental homeostasis is the release of the elements in excess by regulation of the respective element use efficiencies. Microbial carbon use efficiency (CUE), also termed growth efficiency, is defined as the allocation of consumed organic carbon to growth and is thus an integrated representation of microbial metabolism. Microbial CUE is thought to decrease in response to climate warming, although this has recently been questioned. If CUE decreased, more carbon would actually be released to the atmosphere per unit of carbon consumed in a future climate, with strong repercussions on the storage of organic matter in soils, including possible positive feedbacks to climate warming. The fate of carbon, however, may also depend on the turnover rate of the microbial community, which is also thought to increase by warming, but has rarely ever been measured. It is thus of utmost importance to be able to precisely measure both CUE and turnover rates of microbial communities. So far the analysis of microbial CUE and turnover rates has been hampered by methodological and conceptional issues. Specifically, the widely used approach to estimate CUE by following the partitioning of 13C-labelled substrates between biomass incorporation and respiration is thought to inflate CUE estimates. We will briefly review different concepts and methods to measure CUE and show that they are neither conceptionally nor technically sufficiently well applicable for the purpose described above. To overcome these problems, we developed a novel technique to concurrently estimate both microbial CUE and turnover rates based on the incorporation of 18O from

  17. Histone turnover within nonproliferating cells

    International Nuclear Information System (INIS)

    Commerford, S.L.; Carsten, A.L.; Cronkite, E.P.

    1982-01-01

    The turnover of DNA and histones in the livers and brains of mice has been determined. These mice had been exposed to constant levels of tritiated water from conception until they were 8 months old. At this point, exposure to tritium was discontinued, and the tritium remaining in DNA and histones was measured at various intervals afterward. The half-lives calculated for these components (with 95% confidence limits given in parentheses) were 117 (85 to 188) days for liver histone, 318 (241 to 466) days for liver DNA, 159 (129 to 208) days for brain histone and 593 (376 to 1406) days for brain DNA. The difference between histone and DNA turnover is statistically significant for both tissues and indicates that histone turnover within tissues cannot be solely accounted for by cell turnover within the tissue but also must include histone turnover within living cells. The half-life of histone within cells is estimated to be 117 (88 to 178) days in liver and 223 (187 to 277) days in brain

  18. Metabolic control analysis of Aspergillus niger L-arabinose catabolism

    DEFF Research Database (Denmark)

    de Groot, M.J.L.; Prathumpai, Wai; Visser, J.

    2005-01-01

    A mathematical model of the L-arabinose/D-xylose catabolic pathway of Aspergillus niger was constructed based on the kinetic properties of the enzymes. For this purpose L-arabinose reductase, L-arabitol dehydrogenase and D-xylose reductase were purified using dye-affinity chromatography, and thei......A mathematical model of the L-arabinose/D-xylose catabolic pathway of Aspergillus niger was constructed based on the kinetic properties of the enzymes. For this purpose L-arabinose reductase, L-arabitol dehydrogenase and D-xylose reductase were purified using dye-affinity chromatography......-arabinose, a level that resulted in realistic intermediate concentrations in the model, flux control coefficients for L-arabinose reductase, L-arabitol dehydrogenase and L-xylulose reductase were 0.68, 0.17 and 0.14, respectively. The analysis can be used as a guide to identify targets for metabolic engineering...

  19. Metabolic flux analysis of the halophilic archaeon Haladaptatus paucihalophilus

    International Nuclear Information System (INIS)

    Liu, Guangxiu; Zhang, Manxiao; Mo, Tianlu; He, Lian; Zhang, Wei; Yu, Yi; Zhang, Qi; Ding, Wei

    2015-01-01

    This work reports the 13 C-assisted metabolic flux analysis of Haladaptatus paucihalophilus, a halophilic archaeon possessing an intriguing osmoadaption mechanism. We showed that the carbon flow is through the oxidative tricarboxylic acid (TCA) cycle whereas the reductive TCA cycle is not operative in H. paucihalophilus. In addition, both threonine and the citramalate pathways contribute to isoleucine biosynthesis, whereas lysine is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. Unexpected, the labeling patterns of glycine from the cells grown on [1- 13 C]pyruvate and [2- 13 C]pyruvate suggest that, unlike all the organisms investigated so far, in which glycine is produced exclusively from the serine hydroxymethyltransferase (SHMT) pathway, glycine biosynthesis in H. paucihalophilus involves different pathways including SHMT, threonine aldolase (TA) and the reverse reaction of glycine cleavage system (GCS), demonstrating for the first time that other pathways instead of SHMT can also make a significant contribution to the cellular glycine pool. Transcriptional analysis confirmed that both TA and GCS genes were transcribed in H. paucihalophilus, and the transcriptional level is independent of salt concentrations in the culture media. This study expands our understanding of amino acid biosynthesis and provides valuable insights into the metabolism of halophilic archaea. - Highlights: • Serine hydroxymethyltransferase, threonine aldolase, and glycine cleavage system all contribute to the glycine pool of H. paucihalophilus. • Threonine and the citramalate pathways contribute equally to the isoleucine biosynthesis in H. paucihalophilus. • Lysine in H. paucihalophilus is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. • Glycine biosynthesis is likely unrelated to the cell osmoadaption mechanism.

  20. Metabolic flux analysis of the halophilic archaeon Haladaptatus paucihalophilus

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Guangxiu; Zhang, Manxiao [Key Laboratory of Desert and Desertification, Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou, 730000 (China); Key Laboratory of Extreme Environmental Microbial Resources and Engineering, Gansu Province, Lanzhou, 730000 (China); Mo, Tianlu [Department of Chemistry, Fudan University, Shanghai, 200433 (China); He, Lian [Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071 (China); Zhang, Wei [Key Laboratory of Desert and Desertification, Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou, 730000 (China); Key Laboratory of Extreme Environmental Microbial Resources and Engineering, Gansu Province, Lanzhou, 730000 (China); Yu, Yi, E-mail: yu_yi@whu.edu.cn [Key Laboratory of Combinatory Biosynthesis and Drug Discovery (Ministry of Education), School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071 (China); Zhang, Qi, E-mail: qizhang@sioc.ac.cn [Department of Chemistry, Fudan University, Shanghai, 200433 (China); Ding, Wei, E-mail: dingw@lzu.edu.cn [Key Laboratory of Desert and Desertification, Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou, 730000 (China); Key Laboratory of Extreme Environmental Microbial Resources and Engineering, Gansu Province, Lanzhou, 730000 (China); Department of Chemistry, Fudan University, Shanghai, 200433 (China)

    2015-11-27

    This work reports the {sup 13}C-assisted metabolic flux analysis of Haladaptatus paucihalophilus, a halophilic archaeon possessing an intriguing osmoadaption mechanism. We showed that the carbon flow is through the oxidative tricarboxylic acid (TCA) cycle whereas the reductive TCA cycle is not operative in H. paucihalophilus. In addition, both threonine and the citramalate pathways contribute to isoleucine biosynthesis, whereas lysine is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. Unexpected, the labeling patterns of glycine from the cells grown on [1-{sup 13}C]pyruvate and [2-{sup 13}C]pyruvate suggest that, unlike all the organisms investigated so far, in which glycine is produced exclusively from the serine hydroxymethyltransferase (SHMT) pathway, glycine biosynthesis in H. paucihalophilus involves different pathways including SHMT, threonine aldolase (TA) and the reverse reaction of glycine cleavage system (GCS), demonstrating for the first time that other pathways instead of SHMT can also make a significant contribution to the cellular glycine pool. Transcriptional analysis confirmed that both TA and GCS genes were transcribed in H. paucihalophilus, and the transcriptional level is independent of salt concentrations in the culture media. This study expands our understanding of amino acid biosynthesis and provides valuable insights into the metabolism of halophilic archaea. - Highlights: • Serine hydroxymethyltransferase, threonine aldolase, and glycine cleavage system all contribute to the glycine pool of H. paucihalophilus. • Threonine and the citramalate pathways contribute equally to the isoleucine biosynthesis in H. paucihalophilus. • Lysine in H. paucihalophilus is synthesized through the diaminopimelate pathway and not through the α-aminoadipate pathway. • Glycine biosynthesis is likely unrelated to the cell osmoadaption mechanism.

  1. Bone mass and turnover in fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Gam, A; Egsmose, C

    1993-01-01

    Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found...... in lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.......01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia....

  2. Buckwheat seedling flavonoids do not undergo rapid turnover

    International Nuclear Information System (INIS)

    Margna, U.; Vainjaerv, T.

    1981-01-01

    Pulse-labelling with exogenous [1- 14 C]-L-phenylalanine showed that of all flavonoids of buckwheat seedling cotyledons only anthocyanins underwent a slow turnover (not more than 6-8 per cent a day) whilst the major flavonoids, rutin and four C-glycosylflavones, remained metabolically stable within at least 7 days. From excised hypocotyls pulse-labelled flavonoids (anthocyanins and rutin) began to disappear gradually beginning with the second day of incubation. As hypocotyls, however, during prolonged incubation soon began to autolyse a considerable part of that loss was obviously due to abnormal shifts in cell metabolic activities with a possibility that some microbial process was also involved. In hypocotyls of intact seedlings pulse-labelled rutin, similar to rutin in cotyledons, showed no signs of turnover. (author)

  3. Lactate turnover in fast-moving vertebrates: The control of plasma metabolite fluxes

    Energy Technology Data Exchange (ETDEWEB)

    Weber, J.M.

    1987-01-01

    The goals of this thesis were: (1) to investigate the major factors involved in the regulation of plasma metabolite turnover at the whole-organism level-using lactate as a model, and (2) to determine whether endurance-adapted animals can support higher lactate turnover rates than sedentary animals. Lactate turnover was measured by bolus injection of (U{sup {minus}14}C)lacetate in skipjack tuna, Katsuwonus pelamis, and in thoroughbred race horses, Equus caballus. In tuna, turnover rates ranged from 112 to 431 umol min{sup {minus}1} kg{sup {minus}1}, and they were positively correlated with (lactate). These rates were higher than expected for a mammal of equivalent size. Plots of resting lactate and glucose turnover rates vs body mass on a log-log scale were linear for a wide range mammalian body sizes, and they showed the same slope as the classic body mass vs metabolic rate relationship.

  4. Metabolic network reconstruction, growth characterization and 13C-metabolic flux analysis of the extremophile Thermus thermophilus HB8.

    Science.gov (United States)

    Swarup, Aditi; Lu, Jing; DeWoody, Kathleen C; Antoniewicz, Maciek R

    2014-07-01

    Thermus thermophilus is an extremely thermophilic bacterium with significant biotechnological potential. In this work, we have characterized aerobic growth characteristics of T. thermophilus HB8 at temperatures between 50 and 85°C, constructed a metabolic network model of its central carbon metabolism and validated the model using (13)C-metabolic flux analysis ((13)C-MFA). First, cells were grown in batch cultures in custom constructed mini-bioreactors at different temperatures to determine optimal growth conditions. The optimal temperature for T. thermophilus grown on defined medium with glucose was 81°C. The maximum growth rate was 0.25h(-1). Between 50 and 81°C the growth rate increased by 7-fold and the temperature dependence was described well by an Arrhenius model with an activation energy of 47kJ/mol. Next, we performed a (13)C-labeling experiment with [1,2-(13)C] glucose as the tracer and calculated intracellular metabolic fluxes using (13)C-MFA. The results provided support for the constructed network model and highlighted several interesting characteristics of T. thermophilus metabolism. We found that T. thermophilus largely uses glycolysis and TCA cycle to produce biosynthetic precursors, ATP and reducing equivalents needed for cells growth. Consistent with its proposed metabolic network model, we did not detect any oxidative pentose phosphate pathway flux or Entner-Doudoroff pathway activity. The biomass precursors erythrose-4-phosphate and ribose-5-phosphate were produced via the non-oxidative pentose phosphate pathway, and largely via transketolase, with little contribution from transaldolase. The high biomass yield on glucose that was measured experimentally was also confirmed independently by (13)C-MFA. The results presented here provide a solid foundation for future studies of T. thermophilus and its metabolic engineering applications. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  5. Review of metabolic pathways activated in cancer cells as determined through isotopic labeling and network analysis.

    Science.gov (United States)

    Dong, Wentao; Keibler, Mark A; Stephanopoulos, Gregory

    2017-09-01

    Cancer metabolism has emerged as an indispensable part of contemporary cancer research. During the past 10 years, the use of stable isotopic tracers and network analysis have unveiled a number of metabolic pathways activated in cancer cells. Here, we review such pathways along with the particular tracers and labeling observations that led to the discovery of their rewiring in cancer cells. The list of such pathways comprises the reductive metabolism of glutamine, altered glycolysis, serine and glycine metabolism, mutant isocitrate dehydrogenase (IDH) induced reprogramming and the onset of acetate metabolism. Additionally, we demonstrate the critical role of isotopic labeling and network analysis in identifying these pathways. The alterations described in this review do not constitute a complete list, and future research using these powerful tools is likely to discover other cancer-related pathways and new metabolic targets for cancer therapy. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  6. survey of pay satisfaction, job satisfaction and employee turnover

    African Journals Online (AJOL)

    The survey used Pay Satisfaction Scale (PSS), the Minnesota Satisfaction Questionnaire. (MSQ) and Turnover Intention Questionnaire (TIQ) as measures in the study. The data obtained were analyzed using Correlation Analysis and Regression Analysis. The results of the analysis indicated that the relationship between ...

  7. Integrated analysis of transcript-level regulation of metabolism reveals disease-relevant nodes of the human metabolic network.

    Science.gov (United States)

    Galhardo, Mafalda; Sinkkonen, Lasse; Berninger, Philipp; Lin, Jake; Sauter, Thomas; Heinäniemi, Merja

    2014-02-01

    Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types impact tissue homeostasis. Here, the link between the metabolic and gene regulatory networks was studied through experimental and computational analysis. Integrating gene regulation data with a human metabolic network prompted the establishment of an open-sourced web portal, IDARE (Integrated Data Nodes of Regulation), for visualizing various gene-related data in context of metabolic pathways. Motivated by increasing availability of deep sequencing studies, we obtained ChIP-seq data from widely studied human umbilical vein endothelial cells. Interestingly, we found that association of metabolic genes with multiple transcription factors (TFs) enriched disease-associated genes. To demonstrate further extensions enabled by examining these networks together, constraint-based modeling was applied to data from human preadipocyte differentiation. In parallel, data on gene expression, genome-wide ChIP-seq profiles for peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer binding protein (CEBP) α, liver X receptor (LXR) and H3K4me3 and microRNA target identification for miR-27a, miR-29a and miR-222 were collected. Disease-relevant key nodes, including mitochondrial glycerol-3-phosphate acyltransferase (GPAM), were exposed from metabolic pathways predicted to change activity by focusing on association with multiple regulators. In both cell types, our analysis reveals the convergence of microRNAs and TFs within the branched chain amino acid (BCAA) metabolic pathway, possibly providing an explanation for its downregulation in obese and diabetic conditions.

  8. Metabolic cancer biology: structural-based analysis of cancer as a metabolic disease, new sights and opportunities for disease treatment.

    Science.gov (United States)

    Masoudi-Nejad, Ali; Asgari, Yazdan

    2015-02-01

    The cancer cell metabolism or the Warburg effect discovery goes back to 1924 when, for the first time Otto Warburg observed, in contrast to the normal cells, cancer cells have different metabolism. With the initiation of high throughput technologies and computational systems biology, cancer cell metabolism renaissances and many attempts were performed to revise the Warburg effect. The development of experimental and analytical tools which generate high-throughput biological data including lots of information could lead to application of computational models in biological discovery and clinical medicine especially for cancer. Due to the recent availability of tissue-specific reconstructed models, new opportunities in studying metabolic alteration in various kinds of cancers open up. Structural approaches at genome-scale levels seem to be suitable for developing diagnostic and prognostic molecular signatures, as well as in identifying new drug targets. In this review, we have considered these recent advances in structural-based analysis of cancer as a metabolic disease view. Two different structural approaches have been described here: topological and constraint-based methods. The ultimate goal of this type of systems analysis is not only the discovery of novel drug targets but also the development of new systems-based therapy strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Biochemical markers of bone turnover

    International Nuclear Information System (INIS)

    Kim, Deog Yoon

    1999-01-01

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays

  10. Biochemical markers of bone turnover

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Deog Yoon [College of Medicine, Kyunghee Univ., Seoul (Korea, Republic of)

    1999-08-01

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays.

  11. Framework for network modularization and Bayesian network analysis to investigate the perturbed metabolic network.

    Science.gov (United States)

    Kim, Hyun Uk; Kim, Tae Yong; Lee, Sang Yup

    2011-01-01

    Genome-scale metabolic network models have contributed to elucidating biological phenomena, and predicting gene targets to engineer for biotechnological applications. With their increasing importance, their precise network characterization has also been crucial for better understanding of the cellular physiology. We herein introduce a framework for network modularization and Bayesian network analysis (FMB) to investigate organism's metabolism under perturbation. FMB reveals direction of influences among metabolic modules, in which reactions with similar or positively correlated flux variation patterns are clustered, in response to specific perturbation using metabolic flux data. With metabolic flux data calculated by constraints-based flux analysis under both control and perturbation conditions, FMB, in essence, reveals the effects of specific perturbations on the biological system through network modularization and Bayesian network analysis at metabolic modular level. As a demonstration, this framework was applied to the genetically perturbed Escherichia coli metabolism, which is a lpdA gene knockout mutant, using its genome-scale metabolic network model. After all, it provides alternative scenarios of metabolic flux distributions in response to the perturbation, which are complementary to the data obtained from conventionally available genome-wide high-throughput techniques or metabolic flux analysis.

  12. Fatty acid uptake and turnover rate in the ischemic before and after bypass surgery

    International Nuclear Information System (INIS)

    Freundlieb, C.; Hoeck, A.; Vyska, K.; Erbel, R.; Feinendegen, L.E.

    1982-01-01

    17-123-Iodo-heptadecanoic acid (IHA) turnover in myocardium signals myocardial metabolism of free fatty acids. Thus, it appeared promising to examine the influence of cardiovascular surgery on coronary perfusion and on the metabolic state of the ischemic myocardium by use of IHA. The data show that IHA uptake and elimination are two separate parameters which may be changed in the ischemic heart. The two parameters do not necessarily change in parallel. In ischemic heart disease at rest a normal IHA accumulation pattern may be associated with altered regional IHA turnover rates. On the other hand also accumulation defects without changes in IHA turnover rate were observed. Although the relationship between IHA uptake and turnover is not yet sufficiently understood that statements about the indication and prognosis of bypass surgery can be derived

  13. Correlation between lability and relative turnover rate of soluble protein of the rat liver

    International Nuclear Information System (INIS)

    Konno, Satoshi; Kimura, Shuichi

    1977-01-01

    A study was made on whether or not the lability of protein generally correlates with its metabolic turnover rate. Two fractions of soluble protein were prepared from rat liver. Using the double isotope method, it was revealed that the fraction precipitated with half-saturated ammonium sulfate had a larger turnover rate than the supernatant one. Both dietary protein depletion and starvation, though they significantly decreased total protein content, did not affect the ratio of the amount of protein the precipitate to that of the supernatant fraction. These results suggested that both fractions, though they had a different turnover rates, were equally influenced by dietary protein depletion or fasting. In consequence, the results imply that the lability of protein does not necessarily in parallel with the metabolic turnover rate. (auth.)

  14. Comparative Analysis of Yeast Metabolic Network Models Highlights Progress, Opportunities for Metabolic Reconstruction.

    Directory of Open Access Journals (Sweden)

    Benjamin D Heavner

    2015-11-01

    Full Text Available We have compared 12 genome-scale models of the Saccharomyces cerevisiae metabolic network published since 2003 to evaluate progress in reconstruction of the yeast metabolic network. We compared the genomic coverage, overlap of annotated metabolites, predictive ability for single gene essentiality with a selection of model parameters, and biomass production predictions in simulated nutrient-limited conditions. We have also compared pairwise gene knockout essentiality predictions for 10 of these models. We found that varying approaches to model scope and annotation reflected the involvement of multiple research groups in model development; that single-gene essentiality predictions were affected by simulated medium, objective function, and the reference list of essential genes; and that predictive ability for single-gene essentiality did not correlate well with predictive ability for our reference list of synthetic lethal gene interactions (R = 0.159. We conclude that the reconstruction of the yeast metabolic network is indeed gradually improving through the iterative process of model development, and there remains great opportunity for advancing our understanding of biology through continued efforts to reconstruct the full biochemical reaction network that constitutes yeast metabolism. Additionally, we suggest that there is opportunity for refining the process of deriving a metabolic model from a metabolic network reconstruction to facilitate mechanistic investigation and discovery. This comparative study lays the groundwork for developing improved tools and formalized methods to quantitatively assess metabolic network reconstructions independently of any particular model application, which will facilitate ongoing efforts to advance our understanding of the relationship between genotype and cellular phenotype.

  15. Analysis of requirements for teaching materials based on the course bioinformatics for plant metabolism

    Science.gov (United States)

    Balqis, Widodo, Lukiati, Betty; Amin, Mohamad

    2017-05-01

    A way to improve the quality of learning in the course of Plant Metabolism in the Department of Biology, State University of Malang, is to develop teaching materials. This research evaluates the needs of bioinformatics-based teaching material in the course Plant Metabolism by the Analyze, Design, Develop, Implement, and Evaluate (ADDIE) development model. Data were collected through questionnaires distributed to the students in the Plant Metabolism course of the Department of Biology, University of Malang, and analysis of the plan of lectures semester (RPS). Learning gains of this course show that it is not yet integrated into the field of bioinformatics. All respondents stated that plant metabolism books do not include bioinformatics and fail to explain the metabolism of a chemical compound of a local plant in Indonesia. Respondents thought that bioinformatics can explain examples and metabolism of a secondary metabolite analysis techniques and discuss potential medicinal compounds from local plants. As many as 65% of the respondents said that the existing metabolism book could not be used to understand secondary metabolism in lectures of plant metabolism. Therefore, the development of teaching materials including plant metabolism-based bioinformatics is important to improve the understanding of the lecture material in plant metabolism.

  16. Metabolic Flux Analysis of Shewanella spp. Reveals Evolutionary Robustness in Central Carbon Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yinjie J.; Martin, Hector Garcia; Dehal, Paramvir S.; Deutschbauer, Adam; Llora, Xavier; Meadows, Adam; Arkin, Adam; Keasling, Jay D.

    2009-08-19

    Shewanella spp. are a group of facultative anaerobic bacteria widely distributed in marine and fresh-water environments. In this study, we profiled the central metabolic fluxes of eight recently sequenced Shewanella species grown under the same condition in minimal med-ium with [3-13C] lactate. Although the tested Shewanella species had slightly different growth rates (0.23-0.29 h31) and produced different amounts of acetate and pyruvate during early exponential growth (pseudo-steady state), the relative intracellular metabolic flux distributions were remarkably similar. This result indicates that Shewanella species share similar regulation in regard to central carbon metabolic fluxes under steady growth conditions: the maintenance of metabolic robustness is not only evident in a single species under genetic perturbations (Fischer and Sauer, 2005; Nat Genet 37(6):636-640), but also observed through evolutionary related microbial species. This remarkable conservation of relative flux profiles through phylogenetic differences prompts us to introduce the concept of metabotype as an alternative scheme to classify microbial fluxomics. On the other hand, Shewanella spp. display flexibility in the relative flux profiles when switching their metabolism from consuming lactate to consuming pyruvate and acetate.

  17. Pengaruh Ketidakamanan Kerja dan Kompensasi terhadap Kepuasan Kerja dan Turnover Intention Karyawan Besakih Beach Hotel Denpasar

    OpenAIRE

    Widyasari, Ni Made; Dewi, I Gusti Ayu Manuati; Subudi, Made

    2017-01-01

    The purpose of this study was to analyze the effects of job insecurity on turnover intention, the effect of compensation on turnover intention, job insecurity influence of job insecurity on job satisfaction, job satisfaction influence on turnover intention, and the influence of compensation on job satisfaction. Samples are taken by 89 employees in Besakih Beach Hotel. Data were collected by distributing questionnaires and using path analysis. The results of this study showed that job insecuri...

  18. PENGARUH KEPUASAN KERJA DAN STRES KERJA TERHADAP TURNOVER INTENTION PADA KARYAWAN PT. UNITEX DI BOGOR

    OpenAIRE

    Waspodo, Agung AWS; Handayani, Nurul Chotimah; Paramita, Widya

    2017-01-01

    The purpose of this research are: 1) To analyze the influence of job satisfaction on employees turnover intention at PT. Unitex. 2) To analyze the influence of job stress on employees turnover intention at PT. Unitex. 3) To analyze the influence of job satisfaction and job stress simultaneously on employees turnover intention at PT. Unitex. The analysis method in this research using a simple linear and linear multiple regression. Sample of the research is 98 employees using simple random samp...

  19. Comparative analysis of the Industrial Concentration and Turnover of the pharmaceutical industry in Brazil for the segments of mark and generic drugs

    OpenAIRE

    Rosenberg, Gerson; Fonseca, Maria da Graça Derengowski; d' Avila, Luiz Antonio

    2010-01-01

    Este artigo analisa a evolução da estrutura do segmento de medicamentos de marca e genéricos no Brasil a partir de 1997. Após a entrada dos medicamentos genéricos, constatou-se que não houve diminuição significativa da concentração na indústria farmacêutica brasileira, porém, o mesmo não ocorreu em nível mundial, verificando-se um aumento da concentração a partir de 2001, impulsionado pelo expressivo processo de fusões e aquisições nos últimos anos da década de 1990. Em relação ao turnover, n...

  20. Chronic Teacher Turnover in Urban Elementary Schools

    OpenAIRE

    Kacey Guin

    2004-01-01

    This study examines the characteristics of elementary schools that experience chronic teacher turnover and the impacts of turnover on a school’s working climate and ability to effectively function. Based on evidence from staff climate surveys and case studies, it is clear that high turnover schools face significant organizational challenges. Schools with high teacher turnover rates have difficulty planning and implementing a coherent curriculum and sustaining positive working relationships am...

  1. Metabolic Engineering: Techniques for analysis of targets for genetic manipulations

    DEFF Research Database (Denmark)

    Nielsen, Jens Bredal

    1998-01-01

    enzymes. Despite the prospect of obtaining major improvement through metabolic engineering, this approach is, however, not expected to completely replace the classical approach to strain improvement-random mutagenesis followed by screening. Identification of the optimal genetic changes for improvement......Metabolic engineering has been defined as the purposeful modification of intermediary metabolism using recombinant DNA techniques. With this definition metabolic engineering includes: (1) inserting new pathways in microorganisms with the aim of producing novel metabolites, e.g., production...... of polyketides by Streptomyces; (2) production of heterologous peptides, e.g., production of human insulin, erythropoitin, and tPA; and (3) improvement of both new and existing processes, e.g., production of antibiotics and industrial enzymes. Metabolic engineering is a multidisciplinary approach, which involves...

  2. Quantitative Multilevel Analysis of Central Metabolism in Developing Oilseeds of Oilseed Rape during in Vitro Culture.

    Science.gov (United States)

    Schwender, Jörg; Hebbelmann, Inga; Heinzel, Nicolas; Hildebrandt, Tatjana; Rogers, Alistair; Naik, Dhiraj; Klapperstück, Matthias; Braun, Hans-Peter; Schreiber, Falk; Denolf, Peter; Borisjuk, Ljudmilla; Rolletschek, Hardy

    2015-07-01

    Seeds provide the basis for many food, feed, and fuel products. Continued increases in seed yield, composition, and quality require an improved understanding of how the developing seed converts carbon and nitrogen supplies into storage. Current knowledge of this process is often based on the premise that transcriptional regulation directly translates via enzyme concentration into flux. In an attempt to highlight metabolic control, we explore genotypic differences in carbon partitioning for in vitro cultured developing embryos of oilseed rape (Brassica napus). We determined biomass composition as well as 79 net fluxes, the levels of 77 metabolites, and 26 enzyme activities with specific focus on central metabolism in nine selected germplasm accessions. Overall, we observed a tradeoff between the biomass component fractions of lipid and starch. With increasing lipid content over the spectrum of genotypes, plastidic fatty acid synthesis and glycolytic flux increased concomitantly, while glycolytic intermediates decreased. The lipid/starch tradeoff was not reflected at the proteome level, pointing to the significance of (posttranslational) metabolic control. Enzyme activity/flux and metabolite/flux correlations suggest that plastidic pyruvate kinase exerts flux control and that the lipid/starch tradeoff is most likely mediated by allosteric feedback regulation of phosphofructokinase and ADP-glucose pyrophosphorylase. Quantitative data were also used to calculate in vivo mass action ratios, reaction equilibria, and metabolite turnover times. Compounds like cyclic 3',5'-AMP and sucrose-6-phosphate were identified to potentially be involved in so far unknown mechanisms of metabolic control. This study provides a rich source of quantitative data for those studying central metabolism. © 2015 American Society of Plant Biologists. All Rights Reserved.

  3. Quantitative Multilevel Analysis of Central Metabolism in Developing Oilseeds of Oilseed Rape During In Vitro Culture

    Energy Technology Data Exchange (ETDEWEB)

    Schwender, Jorg [Brookhaven National Lab. (BNL), Upton, NY (United States); Hebbelmann, Inga [Brookhaven National Lab. (BNL), Upton, NY (United States); Heinzel, Nicholas [Leibniz Inst. of Plant Genetics and Crop Plant Research, Gatersleben (Germany); Hildebrandt, Tatjana [Univ. of Hannover (Germany); Rogers, Alistair [Brookhaven National Lab. (BNL), Upton, NY (United States); Naik, Dhiraj [Brookhaven National Lab. (BNL), Upton, NY (United States); Indian Inst. of Advanced Research Koba, Gujarat (India); Klapperstuck, Matthias [Monash Univ., Melbourne, VIC (Australia); Braun, Hans -Peter [Univ. of Hannover (Germany); Schreiber, Falk [Monash Univ., Melbourne, VIC (Australia); Univ. Halle-Wittenberg, Melbourne (Australia); Denolf, Peter [Bayer CropScience (Belgium); Borisjuk, Ljudmilla [Leibniz Inst. of Plant Genetics and Crop Plant Research, Gatersleben (Germany); Rolletschek, Hardy [Leibniz Inst. of Plant Genetics and Crop Plant Research, Gatersleben (Germany)

    2015-07-01

    Seeds provide the basis for many food, feed, and fuel products. Continued increases in seed yield, composition, and quality require an improved understanding of how the developing seed converts carbon and nitrogen supplies into storage. Current knowledge of this process is often based on the premise that transcriptional regulation directly translates via enzyme concentration into flux. In an attempt to highlight metabolic control, we explore genotypic differences in carbon partitioning for in vitro cultured developing embryos of oilseed rape (Brassica napus). We determined biomass composition as well as 79 net fluxes, the levels of 77 metabolites, and 26 enzyme activities with specific focus on central metabolism in nine selected germplasm accessions. We observed a tradeoff between the biomass component fractions of lipid and starch. With increasing lipid content over the spectrum of genotypes, plastidic fatty acid synthesis and glycolytic flux increased concomitantly, while glycolytic intermediates decreased. The lipid/starch tradeoff was not reflected at the proteome level, pointing to the significance of (posttranslational) metabolic control. Enzyme activity/flux and metabolite/flux correlations suggest that plastidic pyruvate kinase exerts flux control and that the lipid/starch tradeoff is most likely mediated by allosteric feedback regulation of phosphofructokinase and ADP-glucose pyrophosphorylase. Also, quantitative data were used to calculate in vivo mass action ratios, reaction equilibria, and metabolite turnover times. Compounds like cyclic 3',5'-AMP and sucrose-6-phosphate were identified to potentially be involved in so far unknown mechanisms of metabolic control. This study provides a rich source of quantitative data for those studying central metabolism..

  4. Integrated omics analysis of specialized metabolism in medicinal plants.

    Science.gov (United States)

    Rai, Amit; Saito, Kazuki; Yamazaki, Mami

    2017-05-01

    Medicinal plants are a rich source of highly diverse specialized metabolites with important pharmacological properties. Until recently, plant biologists were limited in their ability to explore the biosynthetic pathways of these metabolites, mainly due to the scarcity of plant genomics resources. However, recent advances in high-throughput large-scale analytical methods have enabled plant biologists to discover biosynthetic pathways for important plant-based medicinal metabolites. The reduced cost of generating omics datasets and the development of computational tools for their analysis and integration have led to the elucidation of biosynthetic pathways of several bioactive metabolites of plant origin. These discoveries have inspired synthetic biology approaches to develop microbial systems to produce bioactive metabolites originating from plants, an alternative sustainable source of medicinally important chemicals. Since the demand for medicinal compounds are increasing with the world's population, understanding the complete biosynthesis of specialized metabolites becomes important to identify or develop reliable sources in the future. Here, we review the contributions of major omics approaches and their integration to our understanding of the biosynthetic pathways of bioactive metabolites. We briefly discuss different approaches for integrating omics datasets to extract biologically relevant knowledge and the application of omics datasets in the construction and reconstruction of metabolic models. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  5. Investigation of Biological Soil Crusts Metabolic Webs Using Exometabolomic Analysis

    Science.gov (United States)

    Northen, T.; Karaoz, U.; Jenkins, S.; Lau, R.; Bowen, B.; Cadillo-Quiroz, H.; Garcia-Pichel, F.; Brodie, E.; Richard, B.

    2014-12-01

    Desert biological soil crusts are simple cyanobacteria-dominated surface soil microbial communities found in areas with infrequent wetting, often extreme temperatures, low coverage of vascular plants and constitute the world's largest biofilm. They exist for extended periods in a desiccated dormant state, yet rapidly re-boot metabolism within minutes of wetting. These soil microbial communities are highly dependent on filamentous cyanobacteria such as Microcoleus vaginatusto stabilize the soil and to act as primary producers for the community through the release carbon sources to feed a diversity of heterotrophs. Exometabolomic analysis was performed using liquid chromatography coupled to tandem mass spectrometry on biological soil crust pore water and spent media of key soil bacterial isolates. Comparison of spent vs. fresh media was used to determine uptake or release of metabolites by specific microbes. To link pore water experiments with isolate studies, metabolite extracts of authentic soil were used as supplements for isolate exometabolomic profiling. Our soil metabolomics methods detected hundreds of metabolites from soils including may novel compounds. Only a small set of which being targeted by all isolates. Beyond these few metabolites, the individual bacteria examined showed specialization towards specific metabolites. Surprisingly, many of the most abundant oligosaccharides and other metabolites were ignored by these isolates. The observed specialization of biological soil crust bacteria may play a significant role in determining community structure.

  6. Community health orientation of Indian Journal of Endocrinology and Metabolism: A bibliometric analysis of Indian Journal of Endocrinology and Metabolism

    Directory of Open Access Journals (Sweden)

    Kanica Kaushal

    2015-01-01

    Full Text Available Background: Endocrine and metabolic diseases especially diabetes have become focus areas for public health professionals. Indian Journal of Endocrinology and Metabolism (IJEM, a publication of Endocrine Society of India, is a peer-reviewed online journal, which covers technical and clinical studies related to health, ethical and social issues in field of diabetes, endocrinology and metabolism. This bibliometric analysis assesses the journal from a community health perspective. Materials and Methods: Every article published in IJEM over a period of 4 years (2011-2014 was accessed to review coverage of community health in the field of endocrinology. Results: Seven editorials, 30 review articles, 41 original articles, 12 brief communications, 20 letter to editors, 4 articles on guidelines and 2 in the section "endocrinology and gender" directly or indirectly dealt with community health aspects of endocrinology. Together these amounted to 17% of all articles published through these 4 years. There were 14 articles on general, 60 pertaining to pancreas and diabetes, 10 on thyroid, 7 on pituitary/adrenal/gonads, 21 on obesity and metabolism and 4 on parathyroid and bone; all community medicine related. Conclusion: Community health is an integral part of the modern endocrinology diabetology and metabolism practice and it received adequate journal space during the last 4 years. The coverage is broad based involving all the major endocrine disorders.

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

    LENUS (Irish Health Repository)

    Burleigh, Susan C

    2011-10-18

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

  8. [Path analysis of lifestyle habits to the metabolic syndrome].

    Science.gov (United States)

    Zhu, Zhen-xin; Zhang, Cheng-qi; Tang, Fang; Song, Xin-hong; Xue, Fu-zhong

    2013-04-01

    To evaluate the relationship between lifestyle habits and the components of metabolic syndrome (MS). Based on the routine health check-up system in a certain Center for Health Management of Shandong Province, a longitudinal surveillance health check-up cohort from 2005 to 2010 was set up. There were 13 225 urban workers in Jinan included in the analysis. The content of the survey included demographic information, medical history, lifestyle habits, body mass index (BMI) and the level of blood pressure, fasting blood-glucose, and blood lipid, etc. The distribution of BMI, blood pressure, fasting blood-glucose, blood lipid and lifestyle habits between MS patients and non-MS population was compared, latent variables were extracted by exploratory factor analysis to determine the structure model, and then a partial least squares path model was constructed between lifestyle habits and the components of MS. Participants'age was (46.62 ± 12.16) years old. The overall prevalence of the MS was 22.43% (2967/13 225), 26.49% (2535/9570) in males and 11.82% (432/3655) in females. The prevalence of the MS was statistically different between males and females (χ(2) = 327.08, P vegetarian, mixed and animal food was 23.39% (694/2967), 42.50% (1261/2967) and 34.11% (1012/2967) respectively, while in non-MS population was 30.80% (3159/10 258), 46.37% (4757/10 258), 22.83% (2342/10 258) respectively. Their alcohol consumption has statistical difference (χ(2) = 374.22, P Unhealthy lifestyle habits are closely related to MS. Meat diet, excessive drinking and smoking are risk factors for MS.

  9. The Effect of Parasite Infection on Stable Isotope Turnover Rates of δ15N, δ13C and δ34S in Multiple Tissues of Eurasian Perch Perca fluviatilis.

    Directory of Open Access Journals (Sweden)

    Elizabeth Yohannes

    Full Text Available Stable isotope analysis of commercially and ecologically important fish can improve understanding of life-history and trophic ecology. However, accurate interpretation of stable isotope values requires knowledge of tissue-specific isotopic turnover that will help to describe differences in the isotopic composition of tissues and diet. We performed a diet-switch experiment using captive-reared parasite-free Eurasian perch (Perca fluviatilis and wild caught specimens of the same species, infected with the pike tapeworm Triaenophorus nodulosus living in host liver tissue. We hypothesize that metabolic processes related to infection status play a major role in isotopic turnover and examined the influence of parasite infection on isotopic turn-over rate of carbon (δ13C, nitrogen (δ15N and sulphur (δ34S in liver, blood and muscle. The δ15N and δ13C turnovers were fastest in liver tissues, followed by blood and muscle. In infected fish, liver and blood δ15N and δ13C turnover rates were similar. However, in infected fish, liver and blood δ13C turnover was faster than that of δ15N. Moreover, in infected subjects, liver δ15N and δ13C turnover rates were three to five times faster than in livers of uninfected subjects (isotopic half-life of ca.3-4 days compared to 16 and 10 days, respectively. Blood δ34S turnover rate were about twice faster in non-infected individuals implying that parasite infection could retard the turnover rate of δ34S and sulphur containing amino acids. Slower turnover rate of essential amino acid could probably decrease individual immune function. These indicate potential hidden costs of chronic and persistent infections that may have accumulated adverse effects and might eventually impair life-history fitness. For the first time, we were able to shift the isotope values of parasites encapsulated in the liver by changing the dietary source of the host. We also report variability in isotopic turnover rates between tissues

  10. Comprehensive Metabolomic Analysis in Blood, Urine, Fat, and Muscle in Men with Metabolic Syndrome: A Randomized, Placebo-Controlled Clinical Trial on the Effects of Resveratrol after Four Months' Treatment.

    Science.gov (United States)

    Korsholm, Anne Sofie; Kjær, Thomas Nordstrøm; Ornstrup, Marie Juul; Pedersen, Steen Bønløkke

    2017-03-04

    Resveratrol possesses several beneficial metabolic effects in rodents, while the effects of resveratrol in humans remain unclear. Therefore, we performed a non-targeted comprehensive metabolomic analysis on blood, urine, adipose tissue, and skeletal muscle tissue in middle-aged men with metabolic syndrome randomized to either resveratrol or placebo treatment for four months. Changes in steroid hormones across all four matrices were the most pronounced changes observed. Resveratrol treatment reduced sulfated androgen precursors in blood, adipose tissue, and muscle tissue, and increased these metabolites in urine. Furthermore, markers of muscle turnover were increased and lipid metabolism was affected, with increased intracellular glycerol and accumulation of long-chain saturated, monounsaturated, and polyunsaturated (n3 and n6) free fatty acids in resveratrol-treated men. Finally, urinary derivatives of aromatic amino acids, which mainly reflect the composition of the gut microbiota, were altered upon resveratrol treatment. In conclusion, the non-targeted metabolomics approach applied to four different matrices provided evidence of subtle but robust effects on several metabolic pathways following resveratrol treatment for four months in men with metabolic syndrome-effects that, for the most part, would not have been detected by routine analyses. The affected pathways should be the focus of future clinical trials on resveratrol's effects, and perhaps particularly the areas of steroid metabolism and the gut microbiome.

  11. Ecological relationship analysis of the urban metabolic system of Beijing, China

    International Nuclear Information System (INIS)

    Li Shengsheng; Zhang Yan; Yang Zhifeng; Liu Hong; Zhang Jinyun

    2012-01-01

    Cities can be modelled as giant organisms, with their own metabolic processes, and can therefore be studied using the same tools used for biological metabolic systems. The complicated distribution of compartments within these systems and the functional relationships among them define the system's network structure. Taking Beijing as an example, we divided the city's internal system into metabolic compartments, then used ecological network analysis to calculate a comprehensive utility matrix for the flows between compartments within Beijing's metabolic system from 1998 to 2007 and to identify the corresponding functional relationships among the system's compartments. Our results show how ecological network analysis, utility analysis, and relationship analysis can be used to discover the implied ecological relationships within a metabolic system, thereby providing insights into the system's internal metabolic processes. Such analyses provide scientific support for urban ecological management. - Highlights: ► Urban metabolic processes can be analyzed by treating cities as superorganisms. ► We developed an ecological network model for an urban system. ► We studied the system's network relationships using ecological network analysis. ► We developed indices for judging the system's synergism and degree of stability. - Using Beijing as an example of an urban superorganism, we used ecological network analysis to describe the ecological relationships among the urban metabolic system's compartments.

  12. [Clinical analysis of metabolic syndrome in vertiginous diseases].

    Science.gov (United States)

    Yamanaka, Toshiaki; Fukuda, Takehiko; Sawai, Yachiyo; Shirota, Shiho; Shimizu, Naoki; Murai, Takayuki; Okamoto, Hideyuki; Fujita, Nobuya; Hosoi, Hiroshi

    2011-01-01

    To explore the relationship between metabolic syndrome and vertigo, we measured waist circumference, plasma glucose, triglycerides and blood pressure in 333 subjects aged 20-79 years with vertigo. We found overall metabolic syndrome prevalence defined by Japanese diagnostic criteria to be 13.2%, similar to that in other national surveys by the Japanese Ministry of Health, Labour and Welfare. The 6-fold higher prevalence in men over women exceeded that of other reports, however. The highest frequency was in vertebrobasilar insufficiency (VBI) disorders, suggesting that conditions such as VBI in men with vertigo could involve metabolic syndrome as a risk factor for vertigo incidence.

  13. Large-scale transcriptome analysis reveals arabidopsis metabolic pathways are frequently influenced by different pathogens.

    Science.gov (United States)

    Jiang, Zhenhong; He, Fei; Zhang, Ziding

    2017-07-01

    Through large-scale transcriptional data analyses, we highlighted the importance of plant metabolism in plant immunity and identified 26 metabolic pathways that were frequently influenced by the infection of 14 different pathogens. Reprogramming of plant metabolism is a common phenomenon in plant defense responses. Currently, a large number of transcriptional profiles of infected tissues in Arabidopsis (Arabidopsis thaliana) have been deposited in public databases, which provides a great opportunity to understand the expression patterns of metabolic pathways during plant defense responses at the systems level. Here, we performed a large-scale transcriptome analysis based on 135 previously published expression samples, including 14 different pathogens, to explore the expression pattern of Arabidopsis metabolic pathways. Overall, metabolic genes are significantly changed in expression during plant defense responses. Upregulated metabolic genes are enriched on defense responses, and downregulated genes are enriched on photosynthesis, fatty acid and lipid metabolic processes. Gene set enrichment analysis (GSEA) identifies 26 frequently differentially expressed metabolic pathways (FreDE_Paths) that are differentially expressed in more than 60% of infected samples. These pathways are involved in the generation of energy, fatty acid and lipid metabolism as well as secondary metabolite biosynthesis. Clustering analysis based on the expression levels of these 26 metabolic pathways clearly distinguishes infected and control samples, further suggesting the importance of these metabolic pathways in plant defense responses. By comparing with FreDE_Paths from abiotic stresses, we find that the expression patterns of 26 FreDE_Paths from biotic stresses are more consistent across different infected samples. By investigating the expression correlation between transcriptional factors (TFs) and FreDE_Paths, we identify several notable relationships. Collectively, the current study

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

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

  15. PENGARUH JOB SATISFACTION TERHADAP OCB DAN TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    Febru Rida Ningsih

    2015-06-01

    Full Text Available This article aims to provide the impact of job satisfaction to OCB and turnover intention. This study used a quantitative method with a statistical analysis. Simple analysis regression used to test each hypotheses. The object of this research is a branch of national bank. Population in this research are entire employees of a brach of national bank that is e non frontliner employees. Non-probability sampling is used of this reseach. The measurement of job satiafaction and turnover intention variables used likert scale that developed by Rinaldi (2008 and measurement of OCB variable adopted from  Organ (1988.  The result of this research has shown that hypotheses one is rejected and hypotheses two is accepted. Eventually, through this article, an understanding that job satisfaction does not significantly influence to OCB but job satisfaction has significant influence to turnover intention.

  16. Partial genetic turnover in Neandertals

    DEFF Research Database (Denmark)

    Dalén, Love; Orlando, Ludovic Antoine Alexandre; Shapiro, Beth

    2012-01-01

    that recent western European neandertals (48 kyr) European neandertals. Using control region sequences, Bayesian demographic simulations provide higher support for a model of population fragmentation followed by separate demographic trajectories in subpopulations over a null model of a single stable...... population. The most parsimonious explanation for these results is that of a population turnover in western Europe during early Marine Isotope Stage 3, predating the arrival of anatomically modern humans in the region....

  17. (Im)Perfect robustness and adaptation of metabolic networks subject to metabolic and gene-expression regulation: marrying control engineering with metabolic control analysis.

    Science.gov (United States)

    He, Fei; Fromion, Vincent; Westerhoff, Hans V

    2013-11-21

    Metabolic control analysis (MCA) and supply-demand theory have led to appreciable understanding of the systems properties of metabolic networks that are subject exclusively to metabolic regulation. Supply-demand theory has not yet considered gene-expression regulation explicitly whilst a variant of MCA, i.e. Hierarchical Control Analysis (HCA), has done so. Existing analyses based on control engineering approaches have not been very explicit about whether metabolic or gene-expression regulation would be involved, but designed different ways in which regulation could be organized, with the potential of causing adaptation to be perfect. This study integrates control engineering and classical MCA augmented with supply-demand theory and HCA. Because gene-expression regulation involves time integration, it is identified as a natural instantiation of the 'integral control' (or near integral control) known in control engineering. This study then focuses on robustness against and adaptation to perturbations of process activities in the network, which could result from environmental perturbations, mutations or slow noise. It is shown however that this type of 'integral control' should rarely be expected to lead to the 'perfect adaptation': although the gene-expression regulation increases the robustness of important metabolite concentrations, it rarely makes them infinitely robust. For perfect adaptation to occur, the protein degradation reactions should be zero order in the concentration of the protein, which may be rare biologically for cells growing steadily. A proposed new framework integrating the methodologies of control engineering and metabolic and hierarchical control analysis, improves the understanding of biological systems that are regulated both metabolically and by gene expression. In particular, the new approach enables one to address the issue whether the intracellular biochemical networks that have been and are being identified by genomics and systems

  18. Supervisory turnover in outpatient substance abuse treatment.

    Science.gov (United States)

    Knight, Danica K; Broome, Kirk M; Edwards, Jennifer R; Flynn, Patrick M

    2011-01-01

    Staff turnover is a significant issue within substance abuse treatment, with implications for service delivery and organizational health. This study examined factors associated with turnover among supervisors in outpatient substance abuse treatment. Turnover was conceptualized as being an individual response to organizational-level influences, and predictors represent aggregate program measures. Participants included 532 staff (including 467 counselors and 65 clinical/program directors) from 90 programs in four regions of the USA. Using logistic regression, analyses of structural factors indicated that programs affiliated with a parent organization and those providing more counseling hours to clients had higher turnover rates. When measures of job attitudes were included, only parent affiliation and collective appraisal of satisfaction were related to turnover. Subsequent analyses identified a trend toward increased supervisory turnover when satisfaction was low following the departure of a previous supervisor. These findings suggest that organizational-level factors can be influential in supervisory turnover.

  19. Analysis of the regulation of surfactant phosphatidylcholine metabolism using stable isotopes.

    Science.gov (United States)

    Brandsma, Joost; Postle, Anthony D

    2017-05-01

    The pathways and mechanisms that regulate pulmonary surfactant synthesis, processing, secretion and catabolism have been extensively characterised using classical biochemical and analytical approaches. These have constructed a model, largely in experimental animals, for surfactant phospholipid metabolism in the alveolar epithelial cell whereby phospholipid synthesised on the endoplasmic reticulum is selectively transported to lamellar body storage vesicles, where it is subsequently processed before secretion into the alveolus. Surfactant phospholipid is a complex mixture of individual molecular species defined by the combination of esterified fatty acid groups and a comprehensive description of surfactant phospholipid metabolism requires consideration of the interactions between such molecular species. However, until recently, lipid analytical techniques have not kept pace with the considerable advances in understanding of the enzymology and molecular biology of surfactant metabolism. Refinements in electrospray ionisation mass spectrometry (ESI-MS) can now provide very sensitive platforms for the rapid characterisation of surfactant phospholipid composition in molecular detail. The combination of ESI-MS and administration of phospholipid substrates labelled with stable isotopes extends this analytical approach to the quantification of synthesis and turnover of individual molecular species of surfactant phospholipid. As this methodology does not involve radioactivity, it is ideally suited to application in clinical studies. This review will provide an overview of the metabolic processes that regulate the molecular specificity of surfactant phosphatidylcholine together with examples of how the application of stable isotope technologies in vivo has, for the first time, begun to explore regulation of the molecular specificity of surfactant synthesis in human subjects. Copyright © 2017 Elsevier GmbH. All rights reserved.

  20. Integration of a constraint-based metabolic model of Brassica napus developing seeds with 13C-Metabolic Flux Analysis

    Directory of Open Access Journals (Sweden)

    Jordan eHay

    2014-12-01

    Full Text Available The use of large-scale or genome-scale metabolic reconstructions for modeling and simulation of plant metabolism and integration of those models with large-scale omics and experimental flux data is becoming increasingly important in plant metabolic research. Here we report an updated version of bna572, a bottom-up reconstruction of oilseed rape (Brassica napus L.; Brassicaceae developing seeds with emphasis on representation of biomass-component biosynthesis. New features include additional seed-relevant pathways for isoprenoid, sterol, phenylpropanoid, flavonoid, and choline biosynthesis. Being now based on standardized data formats and procedures for model reconstruction, bna572+ is available as a COBRA-compliant Systems Biology Markup Language (SBML model and conforms to the Minimum Information Requested in the Annotation of Biochemical Models (MIRIAM standards for annotation of external data resources. Bna572+ contains 966 genes, 671 reactions, and 666 metabolites distributed among 11 subcellular compartments. It is referenced to the Arabidopsis thaliana genome, with gene-protein-reaction associations resolving subcellular localization. Detailed mass and charge balancing and confidence scoring were applied to all reactions. Using Brassica napus seed specific transcriptome data, expression was verified for 78% of bna572+ genes and 97% of reactions. Alongside bna572+ we also present a revised carbon centric model for 13C-Metabolic Flux Analysis (13C-MFA with all its reactions being referenced to bna572+ based on linear projections. By integration of flux ratio constraints obtained from 13C-MFA and by elimination of infinite flux bounds around thermodynamically infeasible loops based on COBRA loopless methods, we demonstrate improvements in predictive power of Flux Variability Analysis (FVA. Using this combined approach we characterize the difference in metabolic flux of developing seeds of two Brassica napus genotypes contrasting in starch and

  1. Flux balance analysis of genome-scale metabolic model of rice ...

    Indian Academy of Sciences (India)

    2015-09-28

    Sep 28, 2015 ... producing vitamin A–enriched golden rice (Beyer et al. 2002). On the other hand, metabolic engineering has been proven as a powerful technique for over or less production of specific metabolites in microbes (Peralta-Yahya et al. 2012). Modelling and analysis of the cellular metabolism is a key step in the ...

  2. Isotopically nonstationary metabolic flux analysis (INST-MFA) of photosynthesis and photorespiration in plants

    Science.gov (United States)

    Photorespiration is a central component of photosynthesis; however to better understand its role it should be viewed in the context of an integrated metabolic network rather than a series of individual reactions that operate independently. Isotopically nonstationary 13C metabolic flux analysis (INST...

  3. Developing human capital: what is the impact on nurse turnover?

    Science.gov (United States)

    Rondeau, Kent V; Williams, Eric S; Wagar, Terry H

    2009-09-01

    To investigate the impact that increasing human capital through staff training makes on the voluntary turnover of registered nurses. Healthcare organizations in Canada, the United Kingdom, the United States, and Australia are experiencing turbulent nursing labour markets characterized by extreme staff shortages and high levels of turnover. Organizations that invest in the development of their nursing human resources may be able to mitigate high turnover through the creation of conditions that more effectively develop and utilize their existing human capital. A questionnaire was sent to the chief nursing officers of 2208 hospitals and long-term care facilities in every province and territory of Canada yielding a response rate of 32.3%. The analysis featured a three-step hierarchical regression with two sets of control variables. After controlling for establishment demographics and local labour market conditions, perceptions of nursing human capital and the level of staff training provided were modestly associated with lower levels of establishment turnover. and implications for Nursing Management The results suggest that healthcare organizations that have made greater investments in their nursing human capital are more likely to demonstrate lower levels of turnover of their registered nursing personnel.

  4. Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

    Energy Technology Data Exchange (ETDEWEB)

    Bordbar, Aarash; Mo, Monica L.; Nakayasu, Ernesto S.; Rutledge, Alexandra C.; Kim, Young-Mo; Metz, Thomas O.; Jones, Marcus B.; Frank, Bryan C.; Smith, Richard D.; Peterson, Scott N.; Hyduke, Daniel R.; Adkins, Joshua N.; Palsson, Bernhard O.

    2012-06-26

    Macrophages are central players in the immune response, manifesting divergent phenotypes to control inflammation and innate immunity through the release of cytokines and other regulatory factor-dependent signaling pathways. In recent years, the focus on metabolism has been reemphasized as critical signaling and regulatory pathways of human pathophysiology, ranging from cancer to aging, often converge on metabolic responses. Here, we used genome-scale modeling and multi-omics (transcriptomics, proteomics, and metabolomics) analysis to assess metabolic features critical for macrophage functions. We constructed a genome-scale metabolic network for the RAW 264.7 cell line to determine metabolic modulators of macrophage activation. Metabolites well-known to be associated with immunoactivation (e.g., glucose and arginine) and immunosuppression (e.g., tryptophan and vitamin D3) were amongst the most critical effectors. Intracellular metabolic mechanisms linked to critical suppressive effectors were then assessed, identifying a suppressive role for de novo nucleotide synthesis. Finally, the underlying metabolic mechanisms of macrophage activation are identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. Our study demonstrates metabolism's role in regulating activation may be greater than previously anticipated and elucidates underlying metabolic connections between activation and metabolic effectors.

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

    Science.gov (United States)

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

    2007-05-29

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

  6. An Exploratory Study of the Role of Human Resource Management in Models of Employee Turnover

    Science.gov (United States)

    Ozolina-Ozola, Iveta

    2016-01-01

    The purpose of this paper is to present the study results of the human resource management role in the voluntary employee turnover models. The mixed methods design was applied. On the basis of the results of the search and evaluation of publications, the 16 models of employee turnover were selected. Applying the method of content analysis, the…

  7. The Effects of Autonomy and Empowerment on Employee Turnover: Test of a Multilevel Model in Teams

    Science.gov (United States)

    Liu, Dong; Zhang, Shu; Wang, Lei; Lee, Thomas W.

    2011-01-01

    Extending research on voluntary turnover in the team setting, this study adopts a multilevel self-determination theoretical approach to examine the unique roles of individual and social-contextual motivational precursors, autonomy orientation and autonomy support, in reducing team member voluntary turnover. Analysis of multilevel time-lagged data…

  8. Workplace experiences and turnover intention among adult survivors of childhood cancer.

    Science.gov (United States)

    Crom, Deborah B; Ness, Kirsten K; Martinez, Larry R; Hebl, Michelle R; Robison, Leslie L; Hudson, Melissa M; Brinkman, Tara M

    2018-03-17

    The purpose of this study was to investigate workplace experiences and turnover intention (consideration of leaving or changing a job) and to examine factors associated with turnover intention among survivors. Adult survivors of childhood cancer with a history of employment (n = 289) completed measures of workplace experiences (n = 50, 18-29 years; n = 183, 30-44 years; n = 56; > 45 years of age at follow-up). Turnover intention was assessed using three items from the Job Satisfaction Scale. Responses were dichotomized as reflecting high vs. low turnover intention. Path analysis was used to estimate the influence of demographic characteristics, treatment exposures (cranial radiation therapy [CRT]), and workplace experiences on turnover intention. Thirty percent of survivors reported high turnover intention (95% CL, 25 to 36%). Exposure to CRT (P = 0.003), older attained age (P workplace discrimination (P = 0.008), and having lower continuance (P discrimination, mediated through job satisfaction, also influenced survivors' reported intent to leave their jobs. One third of adult survivors of childhood cancer report turnover intention, which is related to their cancer treatment, but more temporally proximal, workplace discrimination. Additional research is needed to understand the consequences of turnover intention among survivors. Survivors and their health care providers should be aware of legislative policies related to workplace discrimination (e.g., American with Disabilities Act) and related implications for job turnover.

  9. Association of metabolically healthy obesity with depressive symptoms: pooled analysis of eight studies.

    Science.gov (United States)

    Jokela, M; Hamer, M; Singh-Manoux, A; Batty, G D; Kivimäki, M

    2014-08-01

    The hypothesis of metabolically healthy obesity posits that adverse health effects of obesity are largely avoided when obesity is accompanied by a favorable metabolic profile. We tested this hypothesis with depressive symptoms as the outcome using cross-sectional data on obesity, metabolic health and depressive symptoms. Data were extracted from eight studies and pooled for individual-participant meta-analysis with 30,337 men and women aged 15-105 years (mean age=46.1). Clinic measures included height, weight and metabolic risk factors (high blood pressure, high triglycerides, low high-density lipoprotein cholesterol, high C-reactive protein and high glycated hemoglobin). Depressive symptoms were assessed using clinical interview or standardized rating scales. The pooled sample comprised 7673 (25%) obese participants (body mass index ⩾30 kg m(-2)). Compared to all non-obese individuals, the OR for depressive symptoms was higher in metabolically unhealthy obese individuals with two or more metabolic risk factors (1.45; 95% confidence interval (CI)=1.30, 1.61) and for metabolically healthy obese with ⩽1 metabolic risk factor (1.19; 95% CI=1.03, 1.37), adjusted for sex, age and race/ethnicity. Metabolically unhealthy obesity was associated with higher depression risk (OR=1.23; 95% CI=1.05, 1.45) compared with metabolically healthy obesity. These associations were consistent across studies with no evidence for heterogeneity in estimates (all I(2)-valuesobese persons with a favorable metabolic profile have a slightly increased risk of depressive symptoms compared with non-obese, but the risk is greater when obesity is combined with an adverse metabolic profile. These findings suggest that metabolically healthy obesity is not a completely benign condition in relation to depression risk.

  10. Analysis of Aspergillus nidulans metabolism at the genome-scale

    DEFF Research Database (Denmark)

    David, Helga; Ozcelik, İlknur Ş; Hofmann, Gerald

    2008-01-01

    , in an objective and systematic manner. The functional assignments served as a basis to develop a mathematical model, linking 666 genes (both previously and newly annotated) to metabolic roles. The model was used to simulate metabolic behavior and additionally to integrate, analyze and interpret large-scale gene...... expression data concerning a study on glucose repression, thereby providing a means of upgrading the information content of experimental data and getting further insight into this phenomenon in A. nidulans. Conclusion: We demonstrate how pathway modeling of A. nidulans can be used as an approach to improve...

  11. Biosynthesis, Turnover, and Functions of Chitin in Insects.

    Science.gov (United States)

    Zhu, Kun Yan; Merzendorfer, Hans; Zhang, Wenqing; Zhang, Jianzhen; Muthukrishnan, Subbaratnam

    2016-01-01

    Chitin is a major component of the exoskeleton and the peritrophic matrix of insects. It forms complex structures in association with different assortments of cuticle and peritrophic matrix proteins to yield biocomposites with a wide range of physicochemical and mechanical properties. The growth and development of insects are intimately coupled with the biosynthesis, turnover, and modification of chitin. The genes encoding numerous enzymes of chitin metabolism and proteins that associate with and organize chitin have been uncovered by bioinformatics analyses. Many of these proteins are encoded by sets of large gene families. There is specialization among members within each family, which function in particular tissues or developmental stages. Chitin-containing matrices are dynamically modified at every developmental stage and are under developmental and/or physiological control. A thorough understanding of the diverse processes associated with the assembly and turnover of these chitinous matrices offers many strategies to achieve selective pest control.

  12. High-throughput metabolic state analysis: The missing link in integrated functional genomics of yeasts

    DEFF Research Database (Denmark)

    Villas-Bôas, Silas Granato; Moxley, Joel. F; Åkesson, Mats Fredrik

    2005-01-01

    The lack of comparable metabolic state assays severely limits understanding the metabolic changes caused by genetic or environmental perturbations. The present study reports the application of a novel derivatization method for metabolome analysis of yeast, coupled to data-mining software that ach......The lack of comparable metabolic state assays severely limits understanding the metabolic changes caused by genetic or environmental perturbations. The present study reports the application of a novel derivatization method for metabolome analysis of yeast, coupled to data-mining software...... that achieve comparable throughput, effort and cost compared with DNA arrays. Our sample workup method enables simultaneous metabolite measurements throughout central carbon metabolism and amino acid biosynthesis, using a standard GC-MS platform that was optimized for this Purpose. As an implementation proof...

  13. Peptide Level Turnover Measurements Enable the Study of Proteoform Dynamics.

    Science.gov (United States)

    Zecha, Jana; Meng, Chen; Zolg, Daniel Paul; Samaras, Patroklos; Wilhelm, Mathias; Kuster, Bernhard

    2018-05-01

    The coordination of protein synthesis and degradation regulating protein abundance is a fundamental process in cellular homeostasis. Today, mass spectrometry-based technologies allow determination of endogenous protein turnover on a proteome-wide scale. However, standard dynamic SILAC (Stable Isotope Labeling in Cell Culture) approaches can suffer from missing data across pulse time-points limiting the accuracy of such analysis. This issue is of particular relevance when studying protein stability at the level of proteoforms because often only single peptides distinguish between different protein products of the same gene. To address this shortcoming, we evaluated the merits of combining dynamic SILAC and tandem mass tag (TMT)-labeling of ten pulse time-points in a single experiment. Although the comparison to the standard dynamic SILAC method showed a high concordance of protein turnover rates, the pulsed SILAC-TMT approach yielded more comprehensive data (6000 proteins on average) without missing values. Replicate analysis further established that the same reproducibility of turnover rate determination can be obtained for peptides and proteins facilitating proteoform resolved investigation of protein stability. We provide several examples of differentially turned over splice variants and show that post-translational modifications can affect cellular protein half-lives. For example, N-terminally processed peptides exhibited both faster and slower turnover behavior compared with other peptides of the same protein. In addition, the suspected proteolytic processing of the fusion protein FAU was substantiated by measuring vastly different stabilities of the cleavage products. Furthermore, differential peptide turnover suggested a previously unknown mechanism of activity regulation by post-translational destabilization of cathepsin D as well as the DNA helicase BLM. Finally, our comprehensive data set facilitated a detailed evaluation of the impact of protein

  14. Dynamic analysis of sugar metabolism in different harvest seasons ...

    African Journals Online (AJOL)

    In pineapple fruits, sugar accumulation plays an important role in flavor characteristics, which varies according to the stage of fruit development. Metabolic changes in the contents of fructose, sucrose and glucose and reducing sugar related to the activities of soluble acid invertase (AI), neutral invertase (NI), sucrose ...

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

    Science.gov (United States)

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

  16. Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism

    Directory of Open Access Journals (Sweden)

    Verónica S. Martínez

    2015-12-01

    Full Text Available Metabolic flux analysis (MFA is widely used to estimate intracellular fluxes. Conventional MFA, however, is limited to continuous cultures and the mid-exponential growth phase of batch cultures. Dynamic MFA (DMFA has emerged to characterize time-resolved metabolic fluxes for the entire culture period. Here, the linear DMFA approach was extended using B-spline fitting (B-DMFA to estimate mass balanced fluxes. Smoother fits were achieved using reduced number of knots and parameters. Additionally, computation time was greatly reduced using a new heuristic algorithm for knot placement. B-DMFA revealed that Chinese hamster ovary cells shifted from 37 °C to 32 °C maintained a constant IgG volume-specific productivity, whereas the productivity for the controls peaked during mid-exponential growth phase and declined afterward. The observed 42% increase in product titer at 32 °C was explained by a prolonged cell growth with high cell viability, a larger cell volume and a more stable volume-specific productivity. Keywords: Dynamic, Metabolism, Flux analysis, CHO cells, Temperature shift, B-spline curve fitting

  17. Tritium turnover in succulent plants

    International Nuclear Information System (INIS)

    Krishnamoorthy, T.M.; Gogate, S.S.; Soman, S.D.

    1977-01-01

    Measurements of turnover rates for tissue free water tritium (TFWT) and tissue bound tritium (TBT) were carried out in three succulent plants, Opuntia sp., E. Trigona and E. Mili using tritiated water as tracer. The estimated half-times were 52, 57.5 and 80 days for TFWT and 212, 318 and 132 days for TBT in the stems of the above plants respectively. Opuntia sp. showed significant incorporation of TBT, 10% of TFWT on weight basis, while the other two plants showed lesser incorporation, 2-3% of TFWT. However, the leaves of E. Mili indicated the same level of fixation of TBT as the stem of Opuntia sp. (author)

  18. Manager's guide to reducing dental hygiene turnover.

    Science.gov (United States)

    Loiacono, C

    1989-09-01

    The purpose of this paper is to address the issue of dental hygiene turnover and provide managers with strategies for preventing and reducing turnover. Employee turnover is a problem which affects dental health care delivery and the health of the public. Employee turnover is costly to work settings and creates a stressful working environment which has an impact on professional-client relationships. To reduce or prevent turnover in a private practice setting, office managers must be informed about the causes and effects of this problem and be able to implement solutions. Some strategies managers can use to reduce turnover are hiring employees who have the same goals as the organization; improving the working climate; rewarding longevity; encouraging the active participation of all staff members in office management; improving office communication; and providing opportunities for self-growth, recognition, and greater responsibilities.

  19. Supervisory Turnover in Outpatient Substance Abuse Treatment

    OpenAIRE

    Knight, Danica K.; Broome, Kirk M.; Edwards, Jennifer R.; Flynn, Patrick M.

    2009-01-01

    Staff turnover is a significant issue within substance abuse treatment, with implications for service delivery and organizational health. This study examined factors associated with turnover among supervisors in outpatient substance abuse treatment. Turnover was conceptualized as being an individual response to organizational-level influences, and predictors represent aggregate program measures. Participants included 532 staff (including 467 counselors and 65 clinical/program directors) from ...

  20. Trade and Turnover: Theory and Evidence

    OpenAIRE

    Carl Davidson; Steven Matusz

    2005-01-01

    Is the pattern of trade correlated with cross-sector differences in job turnover? Theoretically, external shocks feed through to changes in domestic employment and cross-sector differences in turnover give rise to compensating wage differentials, which feed through to output prices. Using two different data sets on turnover, we find strong evidence that normalized US net exports by sector are negatively correlated with job destruction and worker separation rates. Weaker evidence suggests a po...

  1. Optimal Employee Turnover Rate: Theory and Evidence

    OpenAIRE

    Mark N. Harris; Kam-Ki Tang; Yi-Ping Tseng

    2002-01-01

    This paper investigates the quantitative effects of employee turnover on firms’ productivity. The Australian Business Longitudinal Survey 1995-98, a unique survey providing firm level data on both production and employee turnover, is used as the data source. Theoretical studies have advocated that firm specific human capital and job matching to be the two major, but competing, mechanisms through which turnover affects productivity. Our results indicate that the effect of job matching dominate...

  2. Job Demand and Job Satisfaction in Latent Groups of Turnover Intention Among Licensed Nurses in Taiwan Nursing Homes.

    Science.gov (United States)

    Chen, I-Hui; Brown, Roger; Bowers, Barbara J; Chang, Wen-Yin

    2015-10-01

    Nurses' turnover intention is not dichotomous; it may reflect intent to leave the profession, intent to leave a type of facility, or intent to leave a specific workplace. In a latent class analysis (LCA) of data from 186 licensed nurses (RNs and LPNs) recruited from 25 nursing homes (NHs) in Taiwan, we classified nurses into turnover intention subgroups based on seven questionnaire items and used a multilevel contrast analysis to characterize the subgroups according to demographic and facility factors, job demand, and job satisfaction. A multilevel probit model was used to examine how job demand and job satisfaction influenced subgroup membership. Three turnover subgroups were identified: high turnover intention (12%), middle turnover intention (57%), and low turnover intention (31%). The high turnover intention subgroup comprised the youngest nurses and had the lowest percentage of registered nurses (RNs); nurses in this subgroup had worked the longest at the current NH and had the greatest likelihood of working at a for-profit facility. Nurses in the middle turnover intention subgroup had the lowest likelihood of working at a for-profit facility. Nurses in the low turnover intention subgroup were primarily RNs and had the shortest work experience in the current facility. Nurses in the high and middle turnover intention subgroups reported lower intrinsic job satisfaction than those with low turnover intention. Extrinsic job satisfaction mediated the relationship between job demand and turnover intention subgroup assignment. The results of this LCA can help target interventions to address heterogeneity of turnover intention and ultimately lessen turnover. © 2015 Wiley Periodicals, Inc.

  3. Glucose tracer, kinetics and turnover in monkeys and chickens infused with ethanol, 1,3-butanediol, or fructose

    International Nuclear Information System (INIS)

    Armstrong, M.K.

    1985-01-01

    Mixtures of (2- 3 H) and (U- 14 C) glucose were injected as single doses into fasted cynomolgus monkeys to assess glucose tracer kinetics and obtain rates of turnover. Data were treated by stochastic and compartmental analyses and results from both analyses closely agreed. However, (2- 3 H) data analyzed by the compartmental analysis required three pools to fit the glucose disappearance curve while (6- 3 H) data fit a two or three pool model equally well. Turnover rates averaged 4.9-4.0, and 3.0 mg/min x kg -1 body weight with (2- 3 H), 6- 3 H) and (U- 14 C) glucose tracers, respectively. The data heuristically suggest that the slow turnover pool that was necessary to fit (2- 3 H) glucose data is related to isotope discrimination. The effects of four treatment solutions on (6- 3 H) glucose metabolism in monkeys were examined. The solutions and their rates of infusion (umoles/min x kg -1 ) were: (1) ethanol, 110; (2) 1,3-butanediol, 110; (3) fructose, 30; and (4) ethanol pus fructose, 110 and 30, respectively. The glucose clearance rate was lowest during the ethanol plus fructose infusions. Ethanol infusions (222 or 444 umoles/min x kg -1 body weight) in chickens (1500 g) fasted 64 hours did not cause hypoglycemia although the high dose slightly decreased the rate of glucose turnover 15% (14.0 versus 12.0 mg/min x kg -1 ). It was further found that neither the hepatic cytosolic nor the mitochondrial redox state significantly changed in chickens infused with the high dose of ethanol. The unchanged hepatic metabolite ratios in chickens are consistent with their unusual resistance to ethanol-induced hypoglycemia

  4. Human turnover dynamics during sleep: Statistical behavior and its modeling

    Science.gov (United States)

    Yoneyama, Mitsuru; Okuma, Yasuyuki; Utsumi, Hiroya; Terashi, Hiroo; Mitoma, Hiroshi

    2014-03-01

    Turnover is a typical intermittent body movement while asleep. Exploring its behavior may provide insights into the mechanisms and management of sleep. However, little is understood about the dynamic nature of turnover in healthy humans and how it can be modified in disease. Here we present a detailed analysis of turnover signals that are collected by accelerometry from healthy elderly subjects and age-matched patients with neurodegenerative disorders such as Parkinson's disease. In healthy subjects, the time intervals between consecutive turnover events exhibit a well-separated bimodal distribution with one mode at ⩽10 s and the other at ⩾100 s, whereas such bimodality tends to disappear in neurodegenerative patients. The discovery of bimodality and fine temporal structures (⩽10 s) is a contribution that is not revealed by conventional sleep recordings with less time resolution (≈30 s). Moreover, we estimate the scaling exponent of the interval fluctuations, which also shows a clear difference between healthy subjects and patients. We incorporate these experimental results into a computational model of human decision making. A decision is to be made at each simulation step between two choices: to keep on sleeping or to make a turnover, the selection of which is determined dynamically by comparing a pair of random numbers assigned to each choice. This decision is weighted by a single parameter that reflects the depth of sleep. The resulting simulated behavior accurately replicates many aspects of observed turnover patterns, including the appearance or disappearance of bimodality and leads to several predictions, suggesting that the depth parameter may be useful as a quantitative measure for differentiating between normal and pathological sleep. These findings have significant clinical implications and may pave the way for the development of practical sleep assessment technologies.

  5. The imperative of culture: a quantitative analysis of the impact of culture on workforce engagement, patient experience, physician engagement, value-based purchasing, and turnover

    Directory of Open Access Journals (Sweden)

    Owens K

    2017-04-01

    Full Text Available Katie Owens,1 Jim Eggers,2 Stephanie Keller,1 Audrey McDonald1 1HealthStream Engagement Institute, Pensacola, FL, 2Analytics, HealthStream, Laurel, MD, USA Abstract: Current uncertainty for the future of the health care landscape is placing an increasing amount of pressure on leadership teams to be prepared to steer their organization forward in a number of potential directions. It is commonly recognized among health care leaders that culture will either enable or disable organizational success. However, very few studies empirically link culture to health care-specific performance outcomes. Nearly every health care organization in the US specifies its cultural aspirations through mission and vision statements and values. Ambitions of patient-centeredness, care for the community, workplace of choice, and world-class quality are frequently cited; yet, little definitive research exists to quantify the importance of building high-performing cultures. Our study examined the impact of cultural attributes defined by a culture index (Cronbach’s alpha = 0.88 on corresponding performance with key health care measures. We mapped results of the culture index across data sets, compared results, and evaluated variations in performance among key indicators for leaders. Organizations that perform in the top quartile for our culture index statistically significantly outperformed those in the bottom quartile on all but one key performance indicator tested. The culture top quartile organizations outperformed every domain for employee engagement, physician engagement, patient experience, and overall value-based purchasing performance with statistical significance. Culture index top quartile performers also had a 3.4% lower turnover rate than the bottom quartile performers. Finally, culture index top quartile performers earned an additional 1% on value-based purchasing. Our findings demonstrate a meaningful connection between performance in the culture index and

  6. General metabolism of Laribacter hongkongensis: a genome-wide analysis

    Directory of Open Access Journals (Sweden)

    Curreem Shirly O

    2011-04-01

    Full Text Available Abstract Background Laribacter hongkongensis is associated with community-acquired gastroenteritis and traveler's diarrhea. In this study, we performed an in-depth annotation of the genes and pathways of the general metabolism of L. hongkongensis and correlated them with its phenotypic characteristics. Results The L. hongkongensis genome possesses the pentose phosphate and gluconeogenesis pathways and tricarboxylic acid and glyoxylate cycles, but incomplete Embden-Meyerhof-Parnas and Entner-Doudoroff pathways, in agreement with its asaccharolytic phenotype. It contains enzymes for biosynthesis and β-oxidation of saturated fatty acids, biosynthesis of all 20 universal amino acids and selenocysteine, the latter not observed in Neisseria gonorrhoeae, Neisseria meningitidis and Chromobacterium violaceum. The genome contains a variety of dehydrogenases, enabling it to utilize different substrates as electron donors. It encodes three terminal cytochrome oxidases for respiration using oxygen as the electron acceptor under aerobic and microaerophilic conditions and four reductases for respiration with alternative electron acceptors under anaerobic conditions. The presence of complete tetrathionate reductase operon may confer survival advantage in mammalian host in association with diarrhea. The genome contains CDSs for incorporating sulfur and nitrogen by sulfate assimilation, ammonia assimilation and nitrate reduction. The existence of both glutamate dehydrogenase and glutamine synthetase/glutamate synthase pathways suggests an importance of ammonia metabolism in the living environments that it may encounter. Conclusions The L. hongkongensis genome possesses a variety of genes and pathways for carbohydrate, amino acid and lipid metabolism, respiratory chain and sulfur and nitrogen metabolism. These allow the bacterium to utilize various substrates for energy production and survive in different environmental niches.

  7. In vivo turnover of the basement membrane and other heparan sulfate proteoglycans of rat glomerulus

    International Nuclear Information System (INIS)

    Beavan, L.A.; Davies, M.; Couchman, J.R.; Williams, M.A.; Mason, R.M.

    1989-01-01

    The metabolic turnover of rat glomerular proteoglycans in vivo was investigated. Newly synthesized proteoglycans were labeled during a 7-h period after injecting sodium [35S]sulfate intraperitoneally. At the end of the labeling period a chase dose of sodium sulfate was given. Subsequently at defined times (0-163 h) the kidneys were perfused in situ with 0.01% cetylpyridinium chloride in phosphate-buffered saline to maximize the recovery of 35S-proteoglycans. Glomeruli were isolated from the renal cortex and analyzed for 35S-proteoglycans by autoradiographic, biochemical, and immunochemical methods. Grain counting of autoradiographs revealed a complex turnover pattern of 35S-labeled macromolecules, commencing with a rapid phase followed by a slower phase. Biochemical analysis confirmed the biphasic pattern and showed that the total population of [35S]heparan sulfate proteoglycans had a metabolic half-life (t1/2) of 20 and 60 h in the early and late phases, respectively. Heparan sulfate proteoglycans accounted for 80% of total 35S-proteoglycans, the remainder being chondroitin/dermatan sulfate proteoglycans. Whole glomeruli were extracted with 4% 3-[(cholamidopropyl)dimethy-lammonio]-1-propanesulfonate-4 M guanidine hydrochloride, a procedure which solubilized greater than 95% of the 35S-labeled macromolecules. Of these 11-13% was immunoprecipitated by an antiserum against heparan sulfate proteoglycan which, in immunolocalization experiments, showed specificity for staining the basement membrane of rat glomeruli. Autoradiographic analysis showed that 18% of total radioactivity present at the end of the labeling period was associated with the glomerular basement membrane

  8. Flux analysis uncovers key role of functional redundancy in formaldehyde metabolism.

    Directory of Open Access Journals (Sweden)

    Christopher J Marx

    2005-02-01

    Full Text Available Genome-scale analysis of predicted metabolic pathways has revealed the common occurrence of apparent redundancy for specific functional units, or metabolic modules. In many cases, mutation analysis does not resolve function, and instead, direct experimental analysis of metabolic flux under changing conditions is necessary. In order to use genome sequences to build models of cellular function, it is important to define function for such apparently redundant systems. Here we describe direct flux measurements to determine the role of redundancy in three modules involved in formaldehyde assimilation and dissimilation in a bacterium growing on methanol. A combination of deuterium and (14C labeling was used to measure the flux through each of the branches of metabolism for growth on methanol during transitions into and out of methylotrophy. The cells were found to differentially partition formaldehyde among the three modules depending on the flux of methanol into the cell. A dynamic mathematical model demonstrated that the kinetic constants of the enzymes involved are sufficient to account for this phenomenon. We demonstrate the role of redundancy in formaldehyde metabolism and have uncovered a new paradigm for coping with toxic, high-flux metabolic intermediates: a dynamic, interconnected metabolic loop.

  9. 13C Metabolic Flux Analysis for systematic metabolic engineering of S. cerevisiae for overproduction of fatty acids.

    Directory of Open Access Journals (Sweden)

    Amit Ghosh

    2016-10-01

    Full Text Available Efficient redirection of microbial metabolism into the abundant production of desired bioproducts remains non-trivial. Here we used flux-based modeling approaches to improve yields of fatty acids in S. cerevisiae. We combined 13C labeling data with comprehensive genome-scale models to shed light onto microbial metabolism and improve metabolic engineering efforts. We concentrated on studying the balance of acetyl-CoA, a precursor metabolite for the biosynthesis of fatty acids. A genome-wide acetyl-CoA balance study showed ATP citrate lyase from Y. lipolytica as a robust source of cytoplasmic acetyl-CoA and malate synthase as a desirable target for down-regulation in terms of acetyl-CoA consumption. These genetic modifications were applied to S. cerevisiae WRY2, a strain that is capable of producing 460 mg L of free fatty acids. With the addition of ATP citrate lyase and down-regulation of malate synthase the engineered strain produced 26 per cent more free fatty acids. Further increases in free fatty acid production of 33 per cent were obtained by knocking out the cytoplasmic glycerol-3-phosphate dehydrogenase, which flux analysis had shown was competing for carbon flux upstream with the carbon flux through the acetyl-CoA production pathway in the cytoplasm. In total, the genetic interventions applied in this work increased fatty acid production by 70 per cent.

  10. OpenFLUX: efficient modelling software for 13C-based metabolic flux analysis

    Directory of Open Access Journals (Sweden)

    Nielsen Lars K

    2009-05-01

    Full Text Available Abstract Background The quantitative analysis of metabolic fluxes, i.e., in vivo activities of intracellular enzymes and pathways, provides key information on biological systems in systems biology and metabolic engineering. It is based on a comprehensive approach combining (i tracer cultivation on 13C substrates, (ii 13C labelling analysis by mass spectrometry and (iii mathematical modelling for experimental design, data processing, flux calculation and statistics. Whereas the cultivation and the analytical part is fairly advanced, a lack of appropriate modelling software solutions for all modelling aspects in flux studies is limiting the application of metabolic flux analysis. Results We have developed OpenFLUX as a user friendly, yet flexible software application for small and large scale 13C metabolic flux analysis. The application is based on the new Elementary Metabolite Unit (EMU framework, significantly enhancing computation speed for flux calculation. From simple notation of metabolic reaction networks defined in a spreadsheet, the OpenFLUX parser automatically generates MATLAB-readable metabolite and isotopomer balances, thus strongly facilitating model creation. The model can be used to perform experimental design, parameter estimation and sensitivity analysis either using the built-in gradient-based search or Monte Carlo algorithms or in user-defined algorithms. Exemplified for a microbial flux study with 71 reactions, 8 free flux parameters and mass isotopomer distribution of 10 metabolites, OpenFLUX allowed to automatically compile the EMU-based model from an Excel file containing metabolic reactions and carbon transfer mechanisms, showing it's user-friendliness. It reliably reproduced the published data and optimum flux distributions for the network under study were found quickly ( Conclusion We have developed a fast, accurate application to perform steady-state 13C metabolic flux analysis. OpenFLUX will strongly facilitate and

  11. Cardiorespiratory Fitness and Adiposity as Determinants of Metabolic Health-Pooled Analysis of Two Twin Cohorts

    DEFF Research Database (Denmark)

    Jukarainen, Sakari; Holst, René; Dalgård, Christine

    2017-01-01

    Context: The joint effects of cardiorespiratory fitness (CRF) and body composition on metabolic health are not well known. Objective: To examine the associations of CRF, fat-free mass index (FFMI), and fat mass index (FMI) with metabolic health in individual twins and controlling for genetic...... their associations with CRF and FFMI were at most weak (|β| 0.02 to 0.15). The results of the monozygotic intrapair differences analysis showed the same pattern. Conclusions: Although FMI is strongly associated with worsening of metabolic health traits, even after controlling for genetic and shared environmental...... factors, there was little evidence for the effects of CRF or FFMI on metabolic health. This suggests that changing FMI rather than CRF or FFMI may affect metabolic health irrespective of genetic or early environmental determinants....

  12. Menguji Konsistensi Korelasi Job Satisfaction dengan Intensi Turnover: Studi Meta-Analisis

    Directory of Open Access Journals (Sweden)

    Ferdinand - Hindiarto

    2017-12-01

    Full Text Available Abstract This study examines the correlation between job satisfaction and turnover intention from various studies in 2009-2016, with meta-analysis method. The used samples consist of 25 studies from 21 research journal which is found by searching on online database: ProQuest, EBSCO and EmeraldInsight via www.lib.ugm.ac.id. Analysis conduct on 2 artefacts, correction on error sampling and on error measuring. Result of the study shows that correlation between job satisfaction and turnover intention in 1st artefact is -0,46 and in 2nd artefact is -0,56. Keyword: meta-analysis, job satisfaction, turnover intention

  13. Kinetics of lactate turnover and oxidation in man

    International Nuclear Information System (INIS)

    Searle, G.L.; Shames, D.; Cavalieri, R.R.; DeGrazia, J.; Zarcone, V.; Porte, D. Jr.; Bagdade, J.D.

    1975-01-01

    The turnover and oxidation of lactic acid have been studied in man by means of 14 C-lactic acid, 14 C-glucose, and 14 C-alanine. The use of these labels in separate studies has enabled us to describe a complete scheme for the kinetics of lactic acid in man. We have determined that lactate arises from a minimum of two sources in overnight fasted man. 66% of lactate at this time arises from the metabolism of glucose while approximately 15% is derived from alanine. These sources and others unidentified supply lactate to the body pool at a rate of approximately 95 mg per kg per h. The disposal of this quantity of lactate is achieved through a minimum of three routes. Approximately 57% of the lactate turnover is oxidized to carbon dioxide, 15% is reduced to glucose, and approximately 25% is converted to alanine. The quantitative changes in the kinetics of this system that are brought on by fasting add an interesting dimension to the system. In agreement with the concepts of fuel economy in fasting the contribution of glucose carbon to lactic acid falls and, in turn, the contribution of lactate carbon to body glucose rises. The study of additional permutations of this system suggest that lactate, with pyruvate, is in the main stream of the intermediary metabolism of the body. The authors suggest that the study of this system offers promise of a fuller understanding of the derangements of metabolic disease. (author)

  14. Construction and analysis of a genome-scale metabolic network for Bacillus licheniformis WX-02.

    Science.gov (United States)

    Guo, Jing; Zhang, Hong; Wang, Cheng; Chang, Ji-Wei; Chen, Ling-Ling

    2016-05-01

    We constructed the genome-scale metabolic network of Bacillus licheniformis (B. licheniformis) WX-02 by combining genomic annotation, high-throughput phenotype microarray (PM) experiments and literature-based metabolic information. The accuracy of the metabolic network was assessed by an OmniLog PM experiment. The final metabolic model iWX1009 contains 1009 genes, 1141 metabolites and 1762 reactions, and the predicted metabolic phenotypes showed an agreement rate of 76.8% with experimental PM data. In addition, key metabolic features such as growth yield, utilization of different substrates and essential genes were identified by flux balance analysis. A total of 195 essential genes were predicted from LB medium, among which 149 were verified with the experimental essential gene set of B. subtilis 168. With the removal of 5 reactions from the network, pathways for poly-γ-glutamic acid (γ-PGA) synthesis were optimized and the γ-PGA yield reached 83.8 mmol/h. Furthermore, the important metabolites and pathways related to γ-PGA synthesis and bacterium growth were comprehensively analyzed. The present study provides valuable clues for exploring the metabolisms and metabolic regulation of γ-PGA synthesis in B. licheniformis WX-02. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  15. Genome-scale metabolic network of Cordyceps militaris useful for comparative analysis of entomopathogenic fungi.

    Science.gov (United States)

    Vongsangnak, Wanwipa; Raethong, Nachon; Mujchariyakul, Warasinee; Nguyen, Nam Ninh; Leong, Hon Wai; Laoteng, Kobkul

    2017-08-30

    The first genome-scale metabolic network of Cordyceps militaris (iWV1170) was constructed representing its whole metabolisms, which consisted of 894 metabolites and 1,267 metabolic reactions across five compartments, including the plasma membrane, cytoplasm, mitochondria, peroxisome and extracellular space. The iWV1170 could be exploited to explain its phenotypes of growth ability, cordycepin and other metabolites production on various substrates. A high number of genes encoding extracellular enzymes for degradation of complex carbohydrates, lipids and proteins were existed in C. militaris genome. By comparative genome-scale analysis, the adenine metabolic pathway towards putative cordycepin biosynthesis was reconstructed, indicating their evolutionary relationships across eleven species of entomopathogenic fungi. The overall metabolic routes involved in the putative cordycepin biosynthesis were also identified in C. militaris, including central carbon metabolism, amino acid metabolism (glycine, l-glutamine and l-aspartate) and nucleotide metabolism (adenosine and adenine). Interestingly, a lack of the sequence coding for ribonucleotide reductase inhibitor was observed in C. militaris that might contribute to its over-production of cordycepin. Copyright © 2017. Published by Elsevier B.V.

  16. Systems biology analysis of drivers underlying hallmarks of cancer cell metabolism

    Science.gov (United States)

    Zielinski, Daniel C.; Jamshidi, Neema; Corbett, Austin J.; Bordbar, Aarash; Thomas, Alex; Palsson, Bernhard O.

    2017-01-01

    Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth. We discovered that resistance to chemotherapeutic drugs in these lines broadly correlates with the amount of glucose uptake. These results support an interpretation of the Warburg effect and glutamine addiction as features of a growth state that provides resistance to metabolic stress through excess redox and energy production. Furthermore, overflow metabolism observed may indicate that mitochondrial catabolic capacity is a key constraint setting an upper limit on the rate of cofactor production possible. These results provide a greater context within which the metabolic alterations in cancer can be understood.

  17. Energy analysis for a sustainable future multi-scale integrated analysis of societal and ecosystem metabolism

    CERN Document Server

    Giampietro, Mario; Sorman, Alevgül H

    2013-01-01

    The vast majority of the countries of the world are now facing an imminent energy crisis, particularly the USA, China, India, Japan and EU countries, but also developing countries having to boost their economic growth precisely when more powerful economies will prevent them from using the limited supply of fossil energy. Despite this crisis, current protocols of energy accounting have been developed for dealing with fossil energy exclusively and are therefore not useful for the analysis of alternative energy sources. The first part of the book illustrates the weakness of existing analyses of energy problems: the science of energy was born and developed neglecting the issue of scale. The authors argue that it is necessary to adopt more complex protocols of accounting and analysis in order to generate robust energy scenarios and effective assessments of the quality of alternative energy sources. The second part of the book introduces the concept of energetic metabolism of modern societies and uses empirical res...

  18. Genetic analysis of metabolic defects in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Musilová, Alena; Šimáková, Miroslava; Kostka, Vlastimil; Mlejnek, Petr; Křen, Vladimír; Křenová, D.; Bílá, V.; Míková, B.; Jáchymová, M.; Horký, K.; Kazdová, L.; St.Lezin, E.; Kurtz, W. T.

    2002-01-01

    Roč. 13, č. 5 (2002), s. 253-258 ISSN 0938-8990 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015; GA ČR GA305/00/1646; GA MŠk NB5299 Grant - others:NIH(US) RO1 HL56028; NIH(US) PO1 HL35018; HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : metabolic defects * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.233, year: 2002

  19. Evaluation of 13C isotopic tracers for metabolic flux analysis in mammalian cells.

    Science.gov (United States)

    Metallo, Christian M; Walther, Jason L; Stephanopoulos, Gregory

    2009-11-01

    (13)C metabolic flux analysis (MFA) is the most comprehensive means of characterizing cellular metabolic states. Uniquely labeled isotopic tracers enable more focused analyses to probe specific reactions within the network. As a result, the choice of tracer largely determines the precision with which one can estimate metabolic fluxes, especially in complex mammalian systems that require multiple substrates. Here we have experimentally determined metabolic fluxes in a tumor cell line, successfully recapitulating the hallmarks of cancer cell metabolism. Using these data, we computationally evaluated specifically labeled (13)C glucose and glutamine tracers for their ability to precisely and accurately estimate fluxes in central carbon metabolism. These methods enabled us to identify the optimal tracer for analyzing individual fluxes, specific pathways, and central carbon metabolism as a whole. [1,2-(13)C(2)]glucose provided the most precise estimates for glycolysis, the pentose phosphate pathway, and the overall network. Tracers such as [2-(13)C]glucose and [3-(13)C]glucose also outperformed the more commonly used [1-(13)C]glucose. [U-(13)C(5)]glutamine emerged as the preferred isotopic tracer for the analysis of the tricarboxylic acid (TCA) cycle. These results provide valuable, quantitative information on the performance of (13)C-labeled substrates and can aid in the design of more informative MFA experiments in mammalian cell culture.

  20. PENGARUH KEAMANAN KERJA PADA TURNOVER INTENTION DENGAN KEPUASAN KERJA SEBAGAI VARIABEL PEMEDIASI

    Directory of Open Access Journals (Sweden)

    Utama I Wayan Mudiartha

    2015-10-01

    Full Text Available He aim of this study is to examine the effect of job security on exit intention, the effect of job security on job satisfaction, the influence of job satisfaction on turnover intention and the role of job satisfaction in mediating the relationship between job security and turnover intention. Data were collected from 56 contract administration employees at the three study programs of Faculty of Economic and Business, Udayana University and analyzed by linear regression analysis technique. The results show that job security is negatively impacts turnover intention, job security affects job satisfaction positively, job satisfaction affects turnover intention  negatively,and job satisfaction mediates the effect of job security on turnover intention.

  1. Metabolic screening and metabolomics analysis in the Intellectual Developmental Disorders Mexico Study

    Directory of Open Access Journals (Sweden)

    Isabel Ibarra-González

    2017-07-01

    Full Text Available Objective. Inborn errors of metabolism (IEM are genetic conditions that are sometimes associated with intellectual  developmental disorders (IDD. The aim of this study is to contribute to the metabolic characterization of IDD of unknown etiology in Mexico. Materials and methods. Metabolic screening using tandem mass spectrometry and fluorometry will be performed to rule out IEM. In addition,target metabolomic analysis will be done to characterize the metabolomic profile of patients with IDD. Conclusion. Identification of new metabolomic profiles associated withIDD of unknown etiology and comorbidities will contribute to the development of novel diagnostic and therapeutic schemes for the prevention and treatment of IDD in Mexico.

  2. Study of Stationary Phase Metabolism Via Isotopomer Analysis of Amino Acids from an Isolated Protein

    Energy Technology Data Exchange (ETDEWEB)

    Shaikh, AfshanS.; Tang, YinjieJ.; Mukhopadhyay, Aindrila; Martin, Hector Garcia; Gin, Jennifer; Benke, Peter; Keasling, Jay D.

    2009-09-14

    Microbial production of many commercially important secondary metabolites occurs during stationary phase, and methods to measure metabolic flux during this growth phase would be valuable. Metabolic flux analysis is often based on isotopomer information from proteinogenic amino acids. As such, flux analysis primarily reflects the metabolism pertinent to the growth phase during which most proteins are synthesized. To investigate central metabolism and amino acids synthesis activity during stationary phase, addition of fully 13C-labeled glucose followed by induction of green fluorescent protein (GFP) expression during stationary phase was used. Our results indicate that Escherichia coli was able to produce new proteins (i.e., GFP) in the stationary phase, and the amino acids in GFP were mostly from degraded proteins synthesized during the exponential growth phase. Among amino acid biosynthetic pathways, only those for serine, alanine, glutamate/glutamine, and aspartate/asparagine had significant activity during the stationary phase.

  3. Using PSAMM for the Curation and Analysis of Genome-Scale Metabolic Models.

    Science.gov (United States)

    Dufault-Thompson, Keith; Steffensen, Jon Lund; Zhang, Ying

    2018-01-01

    PSAMM is an open source software package that supports the iterative curation and analysis of genome-scale models (GEMs). It aims to integrate the annotation and consistency checking of metabolic models with the simulation of metabolic fluxes. The model representation in PSAMM is compatible with version tracking systems like Git, which allows for full documentation of model file changes and enables collaborative curations of large, complex models. This chapter provides a protocol for using PSAMM functions and a detailed description of the various aspects in setting up and using PSAMM for the simulation and analysis of metabolic models. The overall PSAMM workflow outlined in this chapter includes the import and export of model files, the documentation of model modifications using the Git version control system, the application of consistency checking functions for model curations, and the numerical simulation of metabolic models.

  4. Differential proteomic analysis reveals novel links between primary metabolism and antibiotic production in Amycolatopsis balhimycina

    DEFF Research Database (Denmark)

    Gallo, G.; Renzone, G.; Alduina, R.

    2010-01-01

    A differential proteomic analysis, based on 2-DE and MS procedures, was performed on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin-like antibiotic balhimycin. A comparison of proteomic profiles before and during balhimycin production characterized differentially...... available over the World Wide Web as interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps). Functional clustering analysis revealed that differentially expressed proteins belong to functional groups involved in central carbon metabolism, amino acid metabolism and protein biosynthesis......, energetic and redox balance, sugar/amino sugar metabolism, balhimycin biosynthesis and transcriptional regulation or with hypothetical and/or unknown function. Interestingly, proteins involved in the biosynthesis of balhimycin precursors, such as amino acids, amino sugars and central carbon metabolism...

  5. Job Satisfaction and Employee Turnover Intention: A Case Study of Private Hospital in Erbil

    Directory of Open Access Journals (Sweden)

    Govand Anwar

    2015-09-01

    Full Text Available Today it became a huge challenge for Human Resource Managers to retain the employees for longer time of period and decrease the rate of employee turnover. The main research objective is to find out the correlation between job satisfaction and employee turnover intention in private hospital in Erbil. A quantitative method was used to analyze the current study. 144 participants were involved in this study from private hospital in Erbil. The correlation between job satisfaction factor as independent factor and turnover as dependent factor, the value of R for the Job satisfaction is =.386** which indicates that turnover is a positive and weak correlation with turnover intention. The coefficients analysis for this study, the value Beta for turnover is = .386> 0.01, which supported the research hypothesis. This study showed that the there is a positive correlation between job satisfaction and employee turnover. Finally, on the turnover intentions of private hospital personnel in Erbil, most of them would quit in case if they have a better opportunities.

  6. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes.

    Science.gov (United States)

    Hua, Qingzhu; Zhou, Qianjun; Gan, Susheng; Wu, Jingyu; Chen, Canbin; Li, Jiaqiang; Ye, Yaoxiong; Zhao, Jietang; Hu, Guibing; Qin, Yonghua

    2016-09-28

    Red dragon fruit or red pitaya ( Hylocereus polyrhizus ) is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus . RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to "phenylpropanoid biosynthesis", "tyrosine metabolism", "flavonoid biosynthesis", "ascorbate and aldarate metabolism", "betalains biosynthesis" and "anthocyanin biosynthesis". In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA) dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level.

  7. Systematic analysis of stability patterns in plant primary metabolism.

    Directory of Open Access Journals (Sweden)

    Dorothee Girbig

    Full Text Available Metabolic networks are characterized by complex interactions and regulatory mechanisms between many individual components. These interactions determine whether a steady state is stable to perturbations. Structural kinetic modeling (SKM is a framework to analyze the stability of metabolic steady states that allows the study of the system Jacobian without requiring detailed knowledge about individual rate equations. Stability criteria can be derived by generating a large number of structural kinetic models (SK-models with randomly sampled parameter sets and evaluating the resulting Jacobian matrices. Until now, SKM experiments applied univariate tests to detect the network components with the largest influence on stability. In this work, we present an extended SKM approach relying on supervised machine learning to detect patterns of enzyme-metabolite interactions that act together in an orchestrated manner to ensure stability. We demonstrate its application on a detailed SK-model of the Calvin-Benson cycle and connected pathways. The identified stability patterns are highly complex reflecting that changes in dynamic properties depend on concerted interactions between several network components. In total, we find more patterns that reliably ensure stability than patterns ensuring instability. This shows that the design of this system is strongly targeted towards maintaining stability. We also investigate the effect of allosteric regulators revealing that the tendency to stability is significantly increased by including experimentally determined regulatory mechanisms that have not yet been integrated into existing kinetic models.

  8. Turnover, Biographical Data, and Fair Employment Practice

    Science.gov (United States)

    Cascio, Wayne F.

    1976-01-01

    Describes a study that tested the validity of using job applicants' biographical data to predict employee turnover among minority and nonminority female clerical personnel. Findings showed that even after satisfying legal requirements for using such information, turnover can be predicted quite accurately. For availability see EA 507 670.…

  9. Relationship between Job Satisfaction and Turnover Intention ...

    African Journals Online (AJOL)

    This study explores the association between job satisfaction and turnover intentions among lecturers in three public universities in Tanzania. It had three objectives: (1) to determine the level of perceived job satisfaction among lecturers; (2) to determine the association between job satisfaction and turnover intention; and (3) ...

  10. Employee Turnover: Evidence from a Case Study.

    Science.gov (United States)

    Borland, Jeff

    1997-01-01

    Patterns of employee turnover from a medium-sized law firm in Australia were examined in regard to theories of worker mobility (matching, sectoral shift, and incentive). Results support a role for matching effects, but personnel practices affect the timing of turnover. Matching and incentive-based theories do not explain the high rates of turnover…

  11. University Lecturers' Professional Empowerment and Turnover in ...

    African Journals Online (AJOL)

    Many universities in Uganda are grappling with the challenge of academic staff turnover. While research conducted so far has established different factors explaining the problems of turnover, many of which have been addressed, this challenge has not been resolved. Hitherto, attention has not been paid to whether ...

  12. AntDAS: Automatic Data Analysis Strategy for UPLC-QTOF-Based Nontargeted Metabolic Profiling Analysis.

    Science.gov (United States)

    Fu, Hai-Yan; Guo, Xiao-Ming; Zhang, Yue-Ming; Song, Jing-Jing; Zheng, Qing-Xia; Liu, Ping-Ping; Lu, Peng; Chen, Qian-Si; Yu, Yong-Jie; She, Yuanbin

    2017-10-17

    High-quality data analysis methodology remains a bottleneck for metabolic profiling analysis based on ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry. The present work aims to address this problem by proposing a novel data analysis strategy wherein (1) chromatographic peaks in the UPLC-QTOF data set are automatically extracted by using an advanced multiscale Gaussian smoothing-based peak extraction strategy; (2) a peak annotation stage is used to cluster fragment ions that belong to the same compound. With the aid of high-resolution mass spectrometer, (3) a time-shift correction across the samples is efficiently performed by a new peak alignment method; (4) components are registered by using a newly developed adaptive network searching algorithm; (5) statistical methods, such as analysis of variance and hierarchical cluster analysis, are then used to identify the underlying marker compounds; finally, (6) compound identification is performed by matching the extracted peak information, involving high-precision m/z and retention time, against our compound library containing more than 500 plant metabolites. A manually designed mixture of 18 compounds is used to evaluate the performance of the method, and all compounds are detected under various concentration levels. The developed method is comprehensively evaluated by an extremely complex plant data set containing more than 2000 components. Results indicate that the performance of the developed method is comparable with the XCMS. The MATLAB GUI code is available from http://software.tobaccodb.org/software/antdas .

  13. Predictors of turnover intention in nurse faculty.

    Science.gov (United States)

    Gormley, Denise K; Kennerly, Susan

    2011-04-01

    Turnover of nurse faculty is an increasingly important issue in nursing as the available number of qualified faculty continues to decrease. Understanding the factors that contribute to turnover is important to academic administrators to retain and recruit qualified nursing faculty. The purpose of this study was to examine predictors of turnover intention in nurse faculty working in departments and schools of nursing in Carnegie Doctoral/Research Universities-Extensive, public and private, not-for-profit institutions. The multidimensional model of organizational commitment was used to frame this study. The predictor variables explored were organizational climate, organizational commitment, work role balance, role ambiguity, and role conflict. The work roles examined were research, teaching, and service. Logistical regression was performed to examine the predictors of turnover intention. Organizational climate intimacy and disengagement, affective and continuance organizational commitment, and role ambiguity were shown to predict turnover intention in nurse faculty. Copyright 2011, SLACK Incorporated.

  14. Analysis of Piscirickettsia salmonis Metabolism Using Genome-Scale Reconstruction, Modeling, and Testing

    Directory of Open Access Journals (Sweden)

    María P. Cortés

    2017-12-01

    Full Text Available Piscirickettsia salmonis is an intracellular bacterial fish pathogen that causes piscirickettsiosis, a disease with highly adverse impact in the Chilean salmon farming industry. The development of effective treatment and control methods for piscireckttsiosis is still a challenge. To meet it the number of studies on P. salmonis has grown in the last couple of years but many aspects of the pathogen’s biology are still poorly understood. Studies on its metabolism are scarce and only recently a metabolic model for reference strain LF-89 was developed. We present a new genome-scale model for P. salmonis LF-89 with more than twice as many genes as in the previous model and incorporating specific elements of the fish pathogen metabolism. Comparative analysis with models of different bacterial pathogens revealed a lower flexibility in P. salmonis metabolic network. Through constraint-based analysis, we determined essential metabolites required for its growth and showed that it can benefit from different carbon sources tested experimentally in new defined media. We also built an additional model for strain A1-15972, and together with an analysis of P. salmonis pangenome, we identified metabolic features that differentiate two main species clades. Both models constitute a knowledge-base for P. salmonis metabolism and can be used to guide the efficient culture of the pathogen and the identification of specific drug targets.

  15. THE ROLE OF ORGANIZATIONAL COMMITMENT MEDIATION ON THE EFFECT OF PERSON-ORGANIZATION FIT AND JOB SATISFACTION TO TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    Risma N.

    2018-02-01

    Full Text Available This study aimed to analyze and find out the role of organizational commitment mediation on the effect of person-organization fit and job satisfaction to the turnover intention of marketing funding employees. The research method used was quantitative. The type of this research was causal associative by using purposive sampling method in the sample determination. Respondents are 96 employees of Marketing Funding at Bank Nusa Tenggara Barat, Indonesia. The data analysis technique used was Partial Least Square analysis. The research result showed that person-organization fit has no significant effect on turnover intention, job satisfaction has no significant effect on turnover intention, person-organization fit has significant effect on the organizational commitment, job satisfaction has significant effect on organizational commitment, organizational commitment has significant effect on turnover intention, organizational commitment fully mediates the relationship between person-organization fit on turnover intention, and organizational commitment fully mediates the relationship between job satisfaction on turnover intention.

  16. GC/TOFMS analysis of metabolites in serum and urine reveals metabolic perturbation of TCA cycle in db/db mice involved in diabetic nephropathy.

    Science.gov (United States)

    Li, Mengjie; Wang, Xufang; Aa, Jiye; Qin, Weisong; Zha, Weibin; Ge, Yongchun; Liu, Linsheng; Zheng, Tian; Cao, Bei; Shi, Jian; Zhao, Chunyan; Wang, Xinwen; Yu, Xiaoyi; Wang, Guangji; Liu, Zhihong

    2013-06-01

    Early diagnosis of diabetic nephropathy (DN) is difficult although it is of crucial importance to prevent its development. To probe potential markers and the underlying mechanism of DN, an animal model of DN, the db/db mice, was used and serum and urine metabolites were profiled using gas chromatography/time-of-flight mass spectrometry. Metabolic patterns were evaluated based on serum and urine data. Principal component analysis of the data revealed an obvious metabonomic difference between db/db mice and controls, and db/db mice showed distinctly different metabolic patterns during the progression from diabetes to early, medium, and later DN. The identified metabolites discriminating between db/db mice and controls suggested that db/db mice have perturbations in the tricarboxylic acid cycle (TCA, citrate, malate, succinate, and aconitate), lipid metabolism, glycolysis, and amino acid turnover. The db/db mice were characterized by acidic urine, high TCA intermediates in serum at week 6 and a sharp decline thereafter, and gradual elevation of free fatty acids in the serum. The sharp drop of serum TCA intermediates from week 6 to 8 indicated the downregulated glycolysis and insulin resistance. However, urinary TCA intermediates did not decrease in parallel with those in the serum from week 6 to 10, and an increased portion of TCA intermediates in the serum was excreted into the urine at 8, 10, and 12 wk than at 6 wk, indicating kidney dysfunction occurred. The relative abundances of TCA intermediates in urine relative to those in serum were suggested as an index of renal damage.

  17. Effect of collagen turnover and matrix metalloproteinase activity on healing of venous leg ulcers

    NARCIS (Netherlands)

    Meyer, F.J.; Burnand, K.G.; Abisi, S.; TeKoppele, J.M.; Els, B. van; Smith, A.

    2008-01-01

    Background: The presence of fibrous tissue in poorly healing venous leg ulcers suggests abnormal collagen metabolism. The aim was to determine whether there were differences in collagen turnover and matrix metalloproteinase (MMP) activity between ulcers that healed, those that did not heal and

  18. Chronic Teacher Turnover in Urban Elementary Schools

    Directory of Open Access Journals (Sweden)

    Kacey Guin

    2004-08-01

    Full Text Available This study examines the characteristics of elementary schools that experience chronic teacher turnover and the impacts of turnover on a school’s working climate and ability to effectively function. Based on evidence from staff climate surveys and case studies, it is clear that high turnover schools face significant organizational challenges. Schools with high teacher turnover rates have difficulty planning and implementing a coherent curriculum and sustaining positive working relationships among teachers. The reality of these organizational challenges is particularly alarming, given that high turnover schools are more likely to serve low-income and minority students. The negative relationship between teacher turnover and school functioning, and the fact that turbulent schools are disproportionately likely to serve lowincome and minority students have important implications for both district and school-level policies. Specifically: Teacher turnover rates are one indicator of school health, which school districts should consider when focusing on school improvements. Districts need to begin by developing the means to identify individual schools that experience high levels of teacher turnover. Current district policies in implementing professional development for teachers in low-performing schools are inefficient when teachers do not remain in the schools in which they are trained. In order for low-performing schools to improve, districts need to consider providing incentive programs so that high quality teachers apply for, and remain in, these schools. Future research is needed to address the causal link between turnover, organizational functioning and student outcomes. Additionally, there is a need for research examining district policies that may facilitate teacher turnover within a district, including how districts place and transfer teachers, as well as how teachers’ salaries are budgeted.

  19. Bone turnover markers: Emerging tool in the management of osteoporosis

    Directory of Open Access Journals (Sweden)

    Sahana Shetty

    2016-01-01

    Full Text Available Bone is a dynamic tissue which undergoes constant remodeling throughout the life span. Bone turnover is balanced with coupling of bone formation and resorption at various rates leading to continuous remodeling of bone. A study of bone turnover markers (BTMs provides an insight of the dynamics of bone turnover in many metabolic bone disorders. An increase in bone turnover seen with aging and pathological states such as osteoporosis leads to deterioration of bone microarchitecture and thus contributes to an increase in the risk of fracture independent of low bone mineral density (BMD. These microarchitectural alterations affecting the bone quality can be assessed by BTMs and thus may serve as a complementary tool to BMD in the assessment of fracture risk. A systematic search of literature regarding BTMs was carried out using the PubMed database for the purpose of this review. Various reliable, rapid, and cost-effective automated assays of BTMs with good sensitivity are available for the management of osteoporosis. However, BTMs are subjected to various preanalytical and analytical variations necessitating strict sample collection and assays methods along with utilizing ethnicity-based reference standards for different populations. Estimation of fracture risk and monitoring the adherence and response to therapy, which is a challenge in a chronic, asymptomatic disease such as osteoporosis, are the most important applications of measuring BTMs. This review describes the physiology of bone remodeling, various conventional and novel BTMs, and BTM assays and their role in the assessment of fracture risk and monitoring response to treatment with antiresorptive or anabolic agents.

  20. Global turnover of histone post-translational modifications and variants in human cells

    Directory of Open Access Journals (Sweden)

    Zee Barry M

    2010-12-01

    Full Text Available Abstract Background Post-translational modifications (PTMs on the N-terminal tails of histones and histone variants regulate distinct transcriptional states and nuclear events. Whereas the functional effects of specific PTMs are the current subject of intense investigation, most studies characterize histone PTMs/variants in a non-temporal fashion and very few studies have reported kinetic information about these histone forms. Previous studies have used radiolabeling, fluorescence microscopy and chromatin immunoprecipitation to determine rates of histone turnover, and have found interesting correlations between increased turnover and increased gene expression. Therefore, histone turnover is an understudied yet potentially important parameter that may contribute to epigenetic regulation. Understanding turnover in the context of histone modifications and sequence variants could provide valuable additional insight into the function of histone replacement. Results In this study, we measured the metabolic rate of labeled isotope incorporation into the histone proteins of HeLa cells by combining stable isotope labeling of amino acids in cell culture (SILAC pulse experiments with quantitative mass spectrometry-based proteomics. In general, we found that most core histones have similar turnover rates, with the exception of the H2A variants, which exhibit a wider range of rates, potentially consistent with their epigenetic function. In addition, acetylated histones have a significantly faster turnover compared with general histone protein and methylated histones, although these rates vary considerably, depending on the site and overall degree of methylation. Histones containing transcriptionally active marks have been consistently found to have faster turnover rates than histones containing silent marks. Interestingly, the presence of both active and silent marks on the same peptide resulted in a slower turnover rate than either mark alone on that same

  1. System turnover and acceptance procedure of Qingshan NPP

    International Nuclear Information System (INIS)

    Sun Guangdi; Wu Guanxin

    1993-01-01

    Turnover and acceptance process of nuclear power plant has direct influence on construction scheduling. The authors describe organization, conditions and implementation of system turnover and acceptance. The paper also gives some suggestions as reference of turnover and acceptance work

  2. Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

    Science.gov (United States)

    2014-01-01

    Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

  3. Construction of phylogenetic trees by kernel-based comparative analysis of metabolic networks

    Directory of Open Access Journals (Sweden)

    Chang Jeong-Ho

    2006-06-01

    Full Text Available Abstract Background To infer the tree of life requires knowledge of the common characteristics of each species descended from a common ancestor as the measuring criteria and a method to calculate the distance between the resulting values of each measure. Conventional phylogenetic analysis based on genomic sequences provides information about the genetic relationships between different organisms. In contrast, comparative analysis of metabolic pathways in different organisms can yield insights into their functional relationships under different physiological conditions. However, evaluating the similarities or differences between metabolic networks is a computationally challenging problem, and systematic methods of doing this are desirable. Here we introduce a graph-kernel method for computing the similarity between metabolic networks in polynomial time, and use it to profile metabolic pathways and to construct phylogenetic trees. Results To compare the structures of metabolic networks in organisms, we adopted the exponential graph kernel, which is a kernel-based approach with a labeled graph that includes a label matrix and an adjacency matrix. To construct the phylogenetic trees, we used an unweighted pair-group method with arithmetic mean, i.e., a hierarchical clustering algorithm. We applied the kernel-based network profiling method in a comparative analysis of nine carbohydrate metabolic networks from 81 biological species encompassing Archaea, Eukaryota, and Eubacteria. The resulting phylogenetic hierarchies generally support the tripartite scheme of three domains rather than the two domains of prokaryotes and eukaryotes. Conclusion By combining the kernel machines with metabolic information, the method infers the context of biosphere development that covers physiological events required for adaptation by genetic reconstruction. The results show that one may obtain a global view of the tree of life by comparing the metabolic pathway

  4. Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism.

    Science.gov (United States)

    Langsetmo, Lisa; Barr, Susan I; Dasgupta, Kaberi; Berger, Claudie; Kovacs, Christopher S; Josse, Robert G; Adachi, Jonathan D; Hanley, David A; Prior, Jerilynn C; Brown, Jacques P; Morin, Suzanne N; Davison, Kenneth S; Goltzman, David; Kreiger, Nancy

    2016-04-01

    We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks

    Science.gov (United States)

    Haraldsdóttir, Hulda S.; Fleming, Ronan M. T.

    2016-01-01

    Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network. Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling. All moiety conservation relations can be represented as nonnegative integer vectors in the left null space of the stoichiometric matrix corresponding to a biochemical network. Algorithms exist to compute such vectors based only on reaction stoichiometry but their computational complexity has limited their application to relatively small metabolic networks. Moreover, the vectors returned by existing algorithms do not, in general, represent conservation of a specific moiety with a defined atomic structure. Here, we show that identification of conserved moieties requires data on reaction atom mappings in addition to stoichiometry. We present a novel method to identify conserved moieties in metabolic networks by graph theoretical analysis of their underlying atom transition networks. Our method returns the exact group of atoms belonging to each conserved moiety as well as the corresponding vector in the left null space of the stoichiometric matrix. It can be implemented as a pipeline of polynomial time algorithms. Our implementation completes in under five minutes on a metabolic network with more than 4,000 mass balanced reactions. The scalability of the method enables extension of existing applications for moiety conservation relations to genome-scale metabolic networks. We also give examples of new applications made possible by elucidating the atomic structure of conserved moieties. PMID:27870845

  6. PENGARUH KEPUASAN KERJA DAN KOMITMEN ORGANISASI YANG DIKONTROL OLEH MASA KERJA TERHADAP TURNOVER INTENTION PT NET ARTIDAYA

    Directory of Open Access Journals (Sweden)

    Agung Wahyu Handaru

    2014-04-01

    Full Text Available The purposes of this research are 1 to know description of job satisfaction, organizational commitment, working period, and turnover intention 2 test empirically influence of job satisfaction toward turnover intention 3 test empirically influence of job satisfaction controlled by working period toward turnover intention 4 test empirically influence of organizational commitment toward turnover intention 5 test empirically influence of organizational commitment controlled by working period toward turnover intention 6 test empirically influence of job satisfaction and organizational commitment toward turnover intention, and 7 test empirically influence of job satisfaction and organizational commitment controlled by working period toward turnover intention. The object of analysis is employees of PT NET Artidaya using simple random sampling method. The data was collected by using questionnaire and cultivated. The result of t test for job satisfaction is an effect between job satisfaction toward turnover intention. The result of F test for job satisfaction controlled by working period there is an effect between job satisfaction controlled by working period toward turnover intention. The result of t test for organizational commitment there is an effect between organizational commitment toward turnover intention.

  7. Numbers of simultaneous turnovers calculated from anesthesia or operating room information management system data.

    Science.gov (United States)

    Dexter, Franklin; Marcon, Eric; Aker, John; Epstein, Richard H

    2009-09-01

    More personnel are needed to turn over operating rooms (ORs) promptly when there are more simultaneous turnovers. Anesthesia and/or OR information management system data can be analyzed statistically to quantify simultaneous turnovers to evaluate whether to add an additional turnover team. Data collected for each case at a six OR facility were room, date of surgery, time of patient entry into the OR, and time of patient exit from the OR. The number of simultaneous turnovers was calculated for each 1 min of 122 4-wk periods. Our end point was the reduction in the daily minutes of simultaneous turnovers exceeding the number of teams caused by the addition of a team. Increasing from two turnover teams to three teams reduced the mean daily minutes of simultaneous turnovers exceeding the numbers of teams by 19 min. The ratio of 19 min to 8 h valued the time of extra personnel as 4.0% of the time of OR staff, surgeons, and anesthesia providers. Validity was suggested by other methods of analyses also suggesting staffing for three simultaneous turnovers. Discrete-event simulation showed that the reduction in daily minutes of turnover times from the addition of a team would likely match or exceed the reduction in the daily minutes of simultaneous turnovers exceeding the numbers of teams. Confidence intervals for daily minutes of turnover times achieved by increasing from two to three teams were calculated using successive 4-wk periods. The distribution was sufficiently close to normal that accurate confidence intervals could be calculated using Student's t distribution (Lilliefors' test P = 0.58). Analysis generally should use 13 4-wk periods as increasing the number of periods from 6 to 13 significantly reduced the coefficient of variation of the averages but not increasing the number of periods from 6 to 9 or from 9 to 13. The number of simultaneous turnovers can be calculated for each 1 min over 1 yr. The reduction in the daily minutes of simultaneous turnovers

  8. Metabolic flux ratio analysis and multi-objective optimization revealed a globally conserved and coordinated metabolic response of E. coli to paraquat-induced oxidative stress.

    Science.gov (United States)

    Shen, Tie; Rui, Bin; Zhou, Hong; Zhang, Ximing; Yi, Yin; Wen, Han; Zheng, Haoran; Wu, Jihui; Shi, Yunyu

    2013-01-27

    The ability of a microorganism to adapt to changes in the environment, such as in nutrient or oxygen availability, is essential for its competitive fitness and survival. The cellular objective and the strategy of the metabolic response to an extreme environment are therefore of tremendous interest and, thus, have been increasingly explored. However, the cellular objective of the complex regulatory structure of the metabolic changes has not yet been fully elucidated and more details regarding the quantitative behaviour of the metabolic flux redistribution are required to understand the systems-wide biological significance of this response. In this study, the intracellular metabolic flux ratios involved in the central carbon metabolism were determined by fractional (13)C-labeling and metabolic flux ratio analysis (MetaFoR) of the wild-type E. coli strain JM101 at an oxidative environment in a chemostat. We observed a significant increase in the flux through phosphoenolpyruvate carboxykinase (PEPCK), phosphoenolpyruvate carboxylase (PEPC), malic enzyme (MEZ) and serine hydroxymethyltransferase (SHMT). We applied an ε-constraint based multi-objective optimization to investigate the trade-off relationships between the biomass yield and the generation of reductive power using the in silico iJR904 genome-scale model of E. coli K-12. The theoretical metabolic redistribution supports that the trans-hydrogenase pathway should not play a direct role in the defence mounted by E. coli against oxidative stress. The agreement between the measured ratio and the theoretical redistribution established the significance of NADPH synthesis as the goal of the metabolic reprogramming that occurs in response to oxidative stress. Our work presents a framework that combines metabolic flux ratio analysis and multi-objective optimization to investigate the metabolic trade-offs that occur under varied environmental conditions. Our results led to the proposal that the metabolic response of E

  9. Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis.

    Science.gov (United States)

    Chen, Rui; Han, Su; Liu, Xuefeng; Wang, Kunpeng; Zhou, Yong; Yang, Chundong; Zhang, Xi

    2018-05-15

    Osteoarthritis (OA) is a degenerative synovial joint disease affecting people worldwide. However, the exact pathogenesis of OA remains unclear. Metabolomics analysis was performed to obtain insight into possible pathogenic mechanisms and diagnostic biomarkers of OA. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS), followed by multivariate statistical analysis, was used to determine the serum amino acid profiles of 32 OA patients and 35 healthy controls. Variable importance for project values and Student's t-test were used to determine the metabolic abnormalities in OA. Another 30 OA patients were used as independent samples to validate the alterations in amino acids. MetaboAnalyst was used to identify the key amino acid pathways and construct metabolic networks describing their relationships. A total of 25 amino acids and four biogenic amines were detected by UPLC-TQ-MS. Differences in amino acid profiles were found between the healthy controls and OA patients. Alanine, γ-aminobutyric acid and 4-hydroxy-l-proline were important biomarkers distinguishing OA patients from healthy controls. The metabolic pathways with the most significant effects were involved in metabolism of alanine, aspartate, glutamate, arginine and proline. The results of this study improve understanding of the amino acid metabolic abnormalities and pathogenic mechanisms of OA at the molecular level. The metabolic perturbations may be important for the diagnosis and prevention of OA. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Molecular network analysis of phosphotyrosine and lipid metabolism in hepatic PTP1b deletion mice.

    Science.gov (United States)

    Miraldi, Emily R; Sharfi, Hadar; Friedline, Randall H; Johnson, Hannah; Zhang, Tejia; Lau, Ken S; Ko, Hwi Jin; Curran, Timothy G; Haigis, Kevin M; Yaffe, Michael B; Bonneau, Richard; Lauffenburger, Douglas A; Kahn, Barbara B; Kim, Jason K; Neel, Benjamin G; Saghatelian, Alan; White, Forest M

    2013-07-24

    Metabolic syndrome describes a set of obesity-related disorders that increase diabetes, cardiovascular, and mortality risk. Studies of liver-specific protein-tyrosine phosphatase 1b (PTP1b) deletion mice (L-PTP1b(-/-)) suggest that hepatic PTP1b inhibition would mitigate metabolic-syndrome through amelioration of hepatic insulin resistance, endoplasmic-reticulum stress, and whole-body lipid metabolism. However, the altered molecular-network states underlying these phenotypes are poorly understood. We used mass spectrometry to quantify protein-phosphotyrosine network changes in L-PTP1b(-/-) mouse livers relative to control mice on normal and high-fat diets. We applied a phosphosite-set-enrichment analysis to identify known and novel pathways exhibiting PTP1b- and diet-dependent phosphotyrosine regulation. Detection of a PTP1b-dependent, but functionally uncharacterized, set of phosphosites on lipid-metabolic proteins motivated global lipidomic analyses that revealed altered polyunsaturated-fatty-acid (PUFA) and triglyceride metabolism in L-PTP1b(-/-) mice. To connect phosphosites and lipid measurements in a unified model, we developed a multivariate-regression framework, which accounts for measurement noise and systematically missing proteomics data. This analysis resulted in quantitative models that predict roles for phosphoproteins involved in oxidation-reduction in altered PUFA and triglyceride metabolism.

  11. Association of sedentary behaviour with metabolic syndrome: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Charlotte L Edwardson

    Full Text Available In recent years there has been a growing interest in the relationship between sedentary behaviour (sitting and health outcomes. Only recently have there been studies assessing the association between time spent in sedentary behaviour and the metabolic syndrome. The aim of this study is to quantify the association between sedentary behaviour and the metabolic syndrome in adults using meta-analysis.Medline, Embase and the Cochrane Library were searched using medical subject headings and key words related to sedentary behaviours and the metabolic syndrome. Reference lists of relevant articles and personal databases were hand searched. Inclusion criteria were: (1 cross sectional or prospective design; (2 include adults ≥ 18 years of age; (3 self-reported or objectively measured sedentary time; and (4 an outcome measure of metabolic syndrome. Odds Ratio (OR and 95% confidence intervals for metabolic syndrome comparing the highest level of sedentary behaviour to the lowest were extracted for each study. Data were pooled using random effects models to take into account heterogeneity between studies. Ten cross-sectional studies (n = 21393 participants, one high, four moderate and five poor quality, were identified. Greater time spent sedentary increased the odds of metabolic syndrome by 73% (OR 1.73, 95% CI 1.55-1.94, p<0.0001. There were no differences for subgroups of sex, sedentary behaviour measure, metabolic syndrome definition, study quality or country income. There was no evidence of statistical heterogeneity (I(2 = 0.0%, p = 0.61 or publication bias (Eggers test t = 1.05, p = 0.32.People who spend higher amounts of time in sedentary behaviours have greater odds of having metabolic syndrome. Reducing sedentary behaviours is potentially important for the prevention of metabolic syndrome.

  12. Shifts in metabolic hydrogen sinks in the methanogenesis-inhibited ruminal fermentation: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Emilio M. Ungerfeld

    2015-02-01

    Full Text Available Maximizing the flow of metabolic hydrogen ([H] in the rumen away from CH4 and towards volatile fatty acids (VFA would increase the efficiency of ruminant production and decrease its environmental impact. The objectives of this meta-analysis were: i To quantify shifts in metabolic hydrogen sinks when inhibiting ruminal methanogenesis in vitro; and ii To understand the variation in shifts of metabolic hydrogen sinks among experiments and between batch and continuous cultures systems when methanogenesis is inhibited. Batch (28 experiments, N=193 and continuous (16 experiments, N=79 culture databases of experiments with at least 50% inhibition in CH4 production were compiled. Inhibiting methanogenesis generally resulted in less fermentation and digestion in most batch culture, but not in most continuous culture, experiments. Inhibiting CH4 production in batch cultures resulted in redirection of metabolic hydrogen towards propionate and H2 but not butyrate. In continuous cultures, there was no overall metabolic hydrogen redirection towards propionate or butyrate, and H2 as a proportion of metabolic hydrogen spared from CH4 production was numerically smaller compared to batch cultures. Dihydrogen accumulation was affected by type of substrate and methanogenesis inhibitor, with highly fermentable substrates resulting in greater redirection of metabolic hydrogen towards H2 when inhibiting methanogenesis, and some oils causing small or no H2 accumulation. In both batch and continuous culture, there was a decrease in metabolic hydrogen recovered as the sum of propionate, butyrate, CH4 and H2 when inhibiting methanogenesis, and it is speculated that as CH4 production decreases metabolic hydrogen could be increasingly incorporated into formate, microbial biomass, and, perhaps, reductive acetogenesis in continuous cultures. Energetic benefits of inhibiting methanogenesis depended on the inhibitor and its concentration and on the in vitro system.

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

    Directory of Open Access Journals (Sweden)

    Taiga Asakura

    2014-10-01

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

  14. The Influences of Job Satisfaction and Job Performance to Employee Turnover Intention at Hotel Yuta Manado

    OpenAIRE

    Panda, Farry Bobby

    2015-01-01

    This research purposing to know the influence of job satisfaction and job performance to employee turnover intention and was to find out whether there is significance influence between job satisfaction and job performance to employee turnover intention in Manado Yuta Hotel. The method of this research is saturated sampling and the data is obtained from questionnaire that distributed to the employee of manado yuta hotel. The analysis method are multiple regression analysis, statistical f test,...

  15. Pathway analysis of Pichia pastoris to elucidate methanol metabolism and its regulation for production of recombinant proteins.

    Science.gov (United States)

    Unrean, Pornkamol

    2014-01-01

    This research rationally analyzes metabolic pathways of Pichia pastoris to study the metabolic flux responses of this yeast under methanol metabolism. A metabolic model of P. pastoris was constructed and analyzed by elementary mode analysis (EMA). EMA was used to comprehensively identify the cell's metabolic flux profiles and its underlying regulation mechanisms for the production of recombinant proteins from methanol. Change in phenotypes and flux profiles during methanol adaptation with varying feed mixture of glycerol and methanol was examined. EMA identified increasing and decreasing fluxes during the glycerol-methanol metabolic shift, which well agreed with experimental observations supporting the validity of the metabolic network model. Analysis of all the identified pathways also led to the determination of the metabolic capacities as well as the optimum metabolic pathways for recombinant protein synthesis during methanol induction. The network sensitivity analysis revealed that the production of proteins can be improved by manipulating the flux ratios at the pyruvate branch point. In addition, EMA suggested that protein synthesis is optimum under hypoxic culture conditions. The metabolic modeling and analysis presented in this study could potentially form a valuable knowledge base for future research on rational design and optimization of P. pastoris by determining target genes, pathways, and culture conditions for enhanced recombinant protein synthesis. The metabolic pathway analysis is also of considerable value for production of therapeutic proteins by P. pastoris in biopharmaceutical applications. © 2013 American Institute of Chemical Engineers.

  16. Whole body and tissue cholesterol turnover in the baboon

    International Nuclear Information System (INIS)

    Dell, R.B.; Mott, G.E.; Jackson, E.M.; Ramakrishnan, R.; Carey, K.D.; McGill, H.C. Jr.; Goodman, D.S.

    1985-01-01

    Cholesterol turnover was studied in four baboons by injecting [ 14 C]cholesterol 186 days and [ 3 H]cholesterol 4 days before necropsy, and fitting a two- or three-pool model to the resulting specific activity-time data. At necropsy, cholesterol mass and specific activity were determined for the total body and for many tissues. The principal aim of this study was to estimate the extent of cholesterol synthesis in the side pools of the model, by computing the amount of side pool synthesis needed to equal the measured total body cholesterol. Central pool synthesis varied from 61 to 89% of the total cholesterol production rate. Moreover, the finding that the measured total body cholesterol fell within the range obtained from the kinetic analysis by using reasonable assumptions, provides evidence for the physiological validity of the model. A second aim of this study was to explore cholesterol turnover in various tissues. A pool model predicts that rapidly turning over tissues will have higher specific activities at early times and lower specific activities at later times after injection of tracer relative to slowly turning over tissues, except where significant synthesis occurs. Results in all four baboons were similar. Turnover rates for the different tissues loosely fell into three groups which were turning over at fast, intermediate, and slow rates. Finally, the magnitude of variation of cholesterol specific activity was moderate for several distributed tissues (fat, muscle, arteries, and the alimentary tract), but was small for liver. Cholesterol turnover in serial biopsies of skin, muscle, and fat could, however, be fitted with a single pool to estimate tissue turnover rates

  17. Systematic analysis of rice (Oryza sativa) metabolic responses to herbivory.

    Science.gov (United States)

    Alamgir, Kabir Md; Hojo, Yuko; Christeller, John T; Fukumoto, Kaori; Isshiki, Ryutaro; Shinya, Tomonori; Baldwin, Ian T; Galis, Ivan

    2016-02-01

    Plants defend against attack from herbivores by direct and indirect defence mechanisms mediated by the accumulation of phytoalexins and release of volatile signals, respectively. While the defensive arsenals of some plants, such as tobacco and Arabidopsis are well known, most of rice's (Oryza sativa) defence metabolites and their effectiveness against herbivores remain uncharacterized. Here, we used a non-biassed metabolomics approach to identify many novel herbivory-regulated metabolic signatures in rice. Most were up-regulated by herbivore attack while only a few were suppressed. Two of the most prominent up-regulated signatures were characterized as phenolamides (PAs), p-coumaroylputrescine and feruloylputrescine. PAs accumulated in response to attack by both chewing insects, i.e. feeding of the lawn armyworm (Spodoptera mauritia) and the rice skipper (Parnara guttata) larvae, and the attack of the sucking insect, the brown planthopper (Nilaparvata lugens, BPH). In bioassays, BPH insects feeding on 15% sugar solution containing p-coumaroylputrescine or feruloylputrescine, at concentrations similar to those elicited by heavy BPH attack in rice, had a higher mortality compared to those feeding on sugar diet alone. Our results highlight PAs as a rapidly expanding new group of plant defence metabolites that are elicited by herbivore attack, and deter herbivores in rice and other plants. © 2015 John Wiley & Sons Ltd.

  18. Serum leptin is correlated to high turnover in osteoporosis.

    Science.gov (United States)

    Hipmair, Gunter; Böhler, Nikolaus; Maschek, Wilma; Soriguer, Federico; Rojo-Martínez, Gemma; Schimetta, Wolfgang; Pichler, Robert

    2010-01-01

    Clinical data have suggested that obesity protects against osteoporosis. Leptin, mainly secreted by white adipose tissue, might be involved by mediating an effect on bone metabolism. This study was conducted to investigate a possible relationship of leptin and bone turn-over in postmenopausal women with osteoporosis. We measured bone mineral density (BMD), serum leptin levels and markers of bone metabolism, including osteocalcin and cross-laps in 44 patients with osteoporosis. The main group consisted of 32 postmenopausal women. Mean serum leptin was 13.1 microg/L and showed no statistically significant difference to the levels measured in a collective of normal persons adjusted for age and BMI. When related to serum cross-laps as markers of bone resorption, a positive correlation (pturnover serum bone markers, at least in postmenopausal women with osteoporosis.

  19. Empirical Prediction of Turnovers in NFL Football

    Directory of Open Access Journals (Sweden)

    Joel R. Bock

    2016-12-01

    Full Text Available Turnovers in the National Football League (NFL occur whenever a team loses possession of the ball due to a fumble, or an interception. Turnovers disrupt momentum of the offensive team, and represent lost opportunities to advance downfield and score. Teams with a positive differential turnover margin in a given game win 70 % of the time. Turnovers are statistically rare events, occurring apparently randomly. These characteristics make them difficult to predict. This investigation advances the hypothesis that turnovers are predictable in NFL football. Machine learning models are developed to learn the concept: At any point within a football game, what is the likelihood that a turnover will be observed on the next play from scrimmage? NFL play-by-play data for 32 teams spanning seven full seasons were used to train the models. Results presented suggest evidence to support the working hypothesis. Under certain conditions, both fumbles and interceptions can be anticipated at low false discovery rates (less than 15 % . When a turnover is predicted on the impending play from scrimmage, a high degree of confidence is associated with that prediction. The ability to anticipate catastrophic in-game events may lead to their management and control, ultimately improving the performance of individual athletes and their teams. This investigation contributes to the sports science literature by demonstrating the predictability of in-game events often considered to be essentially random in their occurrence. To the author’s knowledge, direct prediction of turnovers has not previously appeared in the literature, which has focused on retrospective statistical analyses of turnover margin in football games.

  20. Nurse turnover: a literature review - an update.

    Science.gov (United States)

    Hayes, Laureen J; O'Brien-Pallas, Linda; Duffield, Christine; Shamian, Judith; Buchan, James; Hughes, Frances; Laschinger, Heather K Spence; North, Nicola

    2012-07-01

    Concerns related to the complex issue of nursing turnover continue to challenge healthcare leaders in every sector of health care. Voluntary nurse turnover is shown to be influenced by a myriad of inter-related factors, and there is increasing evidence of its negative effects on nurses, patients and health care organizations. The objectives were to conduct a comprehensive review of the related literature to examine recent findings related to the issue of nursing turnover and its causes and consequences, and to identify on methodological challenges and the implications of new evidence for future studies. A comprehensive search of the recent literature related to nursing turnover was undertaken to summarize findings published in the past six years. Electronic databases: MEDLINE, CINAHL and PubMed, reference lists of journal publications. Keyword searches were conducted for publications published 2006 or later that examined turnover or turnover intention in employee populations of registered or practical/enrolled or assistant nurses working in the hospital, long-term or community care areas. Literature findings are presented using an integrative approach and a table format to report individual studies. From about 330 citations or abstracts that were initially scanned for content relevance, 68 studies were included in this summary review. The predominance of studies continues to focus on determinants of nurse turnover in acute care settings. Recent studies offer insight into generational factors that should be considered in strategies to promote stable staffing in healthcare organizations. Nursing turnover continues to present serious challenges at all levels of health care. Longitudinal research is needed to produce new evidence of the relationships between nurse turnover and related costs, and the impact on patients and the health care team. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. The validation of the turnover intention scale

    Directory of Open Access Journals (Sweden)

    Chris F.C. Bothma

    2013-04-01

    Full Text Available Orientation: Turnover intention as a construct has attracted increased research attention in the recent past, but there are seemingly not many valid and reliable scales around to measure turnover intention. Research purpose: This study focused on the validation of a shortened, six-item version of the turnover intention scale (TIS-6. Motivation for the study: The research question of whether the TIS-6 is a reliable and a valid scale for measuring turnover intention and for predicting actual turnover was addressed in this study. Research design, approach and method: The study was based on a census-based sample (n= 2429 of employees in an information, communication and technology (ICT sector company (N= 23 134 where the TIS-6 was used as one of the criterion variables. The leavers (those who left the company in this sample were compared with the stayers (those who remained in the employ of the company in this sample in respect of different variables used in the study. Main findings: It was established that the TIS-6 could measure turnover intentions reliably (α= 0.80. The TIS-6 could significantly distinguish between leavers and stayers (actual turnover, thereby confirming its criterion-predictive validity. The scale also established statistically significant differences between leavers and stayers in respect of a number of the remaining theoretical variables used in the study, thereby also confirming its differential validity. These comparisons were conducted for both the 4-month and the 4-year period after the survey was conducted. Practical/managerial implications: Turnover intention is related to a number of variables in the study which necessitates a reappraisal and a reconceptualisation of existing turnover intention models. Contribution/value-add: The TIS-6 can be used as a reliable and valid scale to assess turnover intentions and can therefore be used in research to validly and reliably assess turnover intentions or to

  2. AN ECONOMETRIC APPROACH ABOUT VOLUNTARY TURNOVER

    Directory of Open Access Journals (Sweden)

    ADALET EREN

    2013-06-01

    Full Text Available This study analyzes individual and organizational variables that affect voluntary turnover are determined in the special defence and security companies. A binomial logistic regression model is used to estimate voluntary turnover.  Binomial Logistic regression, reliability test (scale alfa, variance (ANOVA, Post-hoc/Tukey, correlation (Pearson and other basic statistical techniques  with SPSS 13 statistical packet program was used in the analyzes ofresearch data. The study finds that; situation of suppose working, number of child, number of death child, number of home’s moving, support of rent, total monthly income of household, last work’s region, number of prizes, affect voluntary turnover are determined.

  3. The Analysis of the Science and Technology Enterprise Core Employee Turnover Negative Effects – Based on the theory of psychological contract

    OpenAIRE

    Jin Xin; Li Lijun

    2015-01-01

    This article explores the problem of negative effect of resignation of core employees from scientific enterprise based on psychological contract theory and summary of references. It uses questionnaires to analyze the data and construct a model of negative effect of resignation caused by psychological contract violation. It also makes an analysis on resignation tendency and negative effect of resignation in two perspectives to provide a basis for reduction of the negative effect.

  4. The Analysis of the Science and Technology Enterprise Core Employee Turnover Negative Effects – Based on the theory of psychological contract

    Directory of Open Access Journals (Sweden)

    Jin Xin

    2015-01-01

    Full Text Available This article explores the problem of negative effect of resignation of core employees from scientific enterprise based on psychological contract theory and summary of references. It uses questionnaires to analyze the data and construct a model of negative effect of resignation caused by psychological contract violation. It also makes an analysis on resignation tendency and negative effect of resignation in two perspectives to provide a basis for reduction of the negative effect.

  5. The role of job satisfaction, work engagement, self-efficacy and agentic capacities on nurses' turnover intention and patient satisfaction.

    Science.gov (United States)

    De Simone, Silvia; Planta, Anna; Cicotto, Gianfranco

    2018-02-01

    Nurses' voluntary turnover is a worrying global phenomenon which affects service quality. Retaining nursing staff within a hospital is important to eliminate the negative influence of voluntary turnover on the quality of care and organisation costs. This research helps explain nurses' voluntary turnover by analysing the role of self-efficacy, agentic capacities, job satisfaction, and work engagement on hospital turnover intention, and to study the relationships between these variables and patient satisfaction. This study gathered data from 194 nurses and 181 patients from 22 inpatient wards at two hospitals in southern Italy. Correlation analysis revealed that job satisfaction, work engagement, self-efficacy and agentic capacities were positively interrelated and negatively correlated with turnover intention. Path analysis showed that self-efficacy, some agentic capacities (anticipation and self-regulation), job satisfaction, and work engagement had direct or indirect effects on nurses' turnover intention, and that job satisfaction exerted a stronger effect on turnover intention. Also, patient satisfaction was positively correlated with nurses' job satisfaction, work engagement, self-efficacy, self-regulation and anticipation and negatively correlated with nurses' turnover intention. Results highlighted the importance of implementing actions (for example through feedforward methodology and the goal setting technique) to improve self-efficacy, self-regulation skill, work engagement and job satisfaction in order to reduce nurses' turnover intention and increase patient satisfaction with nursing care. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. A global evolutionary and metabolic analysis of human obesity gene risk variants.

    Science.gov (United States)

    Castillo, Joseph J; Hazlett, Zachary S; Orlando, Robert A; Garver, William S

    2017-09-05

    It is generally accepted that the selection of gene variants during human evolution optimized energy metabolism that now interacts with our obesogenic environment to increase the prevalence of obesity. The purpose of this study was to perform a global evolutionary and metabolic analysis of human obesity gene risk variants (110 human obesity genes with 127 nearest gene risk variants) identified using genome-wide association studies (GWAS) to enhance our knowledge of early and late genotypes. As a result of determining the mean frequency of these obesity gene risk variants in 13 available populations from around the world our results provide evidence for the early selection of ancestral risk variants (defined as selection before migration from Africa) and late selection of derived risk variants (defined as selection after migration from Africa). Our results also provide novel information for association of these obesity genes or encoded proteins with diverse metabolic pathways and other human diseases. The overall results indicate a significant differential evolutionary pattern for the selection of obesity gene ancestral and derived risk variants proposed to optimize energy metabolism in varying global environments and complex association with metabolic pathways and other human diseases. These results are consistent with obesity genes that encode proteins possessing a fundamental role in maintaining energy metabolism and survival during the course of human evolution. Copyright © 2017. Published by Elsevier B.V.

  7. Cesium-134 and strontium-85 turnover rates in the centipede Scolopocryptops nigridia McNeill

    International Nuclear Information System (INIS)

    Yates, L.R.; Crossley, D.A. Jr.

    1979-07-01

    Radioactive tracers are providing significant information about the ecology of food chains, including such phenomena as accumulation of radioactive fission products, movement of materials along food chains, assimilation and ingestion rates, and nutrient accumulation and turnover. In this study the ingestion, assimilation and turnover to two radioactive tracers were investigated for Scolopocryptops nigridia, an abundant species in forests of the southeastern United States. The two tracers utilized, cesium-134 and strontium-85, are metabolic analogs of potassium and calcium, respectively. The research was performed as part of a larger investigation on the population ecology of the centipede species, emphasizing its relations to nutrient cycling and energy flow in a forest floor system

  8. Cesium-134 and strontium-85 turnover rates in the centipede Scolopocryptops nigridia McNeill

    Energy Technology Data Exchange (ETDEWEB)

    Yates, L R; Crossley, Jr, D A

    1979-07-01

    Radioactive tracers are providing significant information about the ecology of food chains, including such phenomena as accumulation of radioactive fission products, movement of materials along food chains, assimilation and ingestion rates, and nutrient accumulation and turnover. In this study the ingestion, assimilation and turnover to two radioactive tracers were investigated for Scolopocryptops nigridia, an abundant species in forests of the southeastern United States. The two tracers utilized, cesium-134 and strontium-85, are metabolic analogs of potassium and calcium, respectively. The research was performed as part of a larger investigation on the population ecology of the centipede species, emphasizing its relations to nutrient cycling and energy flow in a forest floor system.

  9. Multiobjective flux balancing using the NISE method for metabolic network analysis.

    Science.gov (United States)

    Oh, Young-Gyun; Lee, Dong-Yup; Lee, Sang Yup; Park, Sunwon

    2009-01-01

    Flux balance analysis (FBA) is well acknowledged as an analysis tool of metabolic networks in the framework of metabolic engineering. However, FBA has a limitation for solving a multiobjective optimization problem which considers multiple conflicting objectives. In this study, we propose a novel multiobjective flux balance analysis method, which adapts the noninferior set estimation (NISE) method (Solanki et al., 1993) for multiobjective linear programming (MOLP) problems. NISE method can generate an approximation of the Pareto curve for conflicting objectives without redundant iterations of single objective optimization. Furthermore, the flux distributions at each Pareto optimal solution can be obtained for understanding the internal flux changes in the metabolic network. The functionality of this approach is shown by applying it to a genome-scale in silico model of E. coli. Multiple objectives for the poly(3-hydroxybutyrate) [P(3HB)] production are considered simultaneously, and relationships among them are identified. The Pareto curve for maximizing succinic acid production vs. maximizing biomass production is used for the in silico analysis of various combinatorial knockout strains. This proposed method accelerates the strain improvement in the metabolic engineering by reducing computation time of obtaining the Pareto curve and analysis time of flux distribution at each Pareto optimal solution. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

  10. Metabolic syndrome risk factors and dry eye syndrome: a Meta-analysis.

    Science.gov (United States)

    Tang, Ye-Lei; Cheng, Ya-Lan; Ren, Yu-Ping; Yu, Xiao-Ning; Shentu, Xing-Chao

    2016-01-01

    To explore the relationship between metabolic risk factors and dry eye syndrome (DES). Retrieved studies on the association of metabolic syndrome risk factors (hypertension, hyperglycemia, obesity, and hyperlipidemia) and DES were collected from PubMed, Web of Science, and the Cochrane Library in December 2015. Odds ratio (OR) with 95% confidence interval (CI) were pooled to evaluate the final relationship. Subgroup analyses were conducted according to diagnostic criteria of DES. Nine cross-sectional studies and three case-control studies were included in this Meta-analysis. The pooled results showed that people with hypertension, hyperglycemia, and hyperlipidemia had a higher risk of suffering from DES (PDES symptoms. On the other hand, obesity did not increase the risk of DES. The present Meta-analysis suggests that all metabolic risk factors except obesity were risk factors for DES.

  11. Analysis of Chinese hamster ovary cell metabolism through a combined computational and experimental approach.

    Science.gov (United States)

    Chen, Ning; Bennett, Mark H; Kontoravdi, Cleo

    2014-12-01

    Optimization of cell culture processes can benefit from the systematic analysis of experimental data and their organization in mathematical models, which can be used to decipher the effect of individual process variables on multiple outputs of interest. Towards this goal, a kinetic model of cytosolic glucose metabolism coupled with a population-level model of Chinese hamster ovary cells was used to analyse metabolic behavior under batch and fed-batch cell culture conditions. The model was parameterized using experimental data for cell growth dynamics, extracellular and intracellular metabolite profiles. The results highlight significant differences between the two culture conditions in terms of metabolic efficiency and motivate the exploration of lactate as a secondary carbon source. Finally, the application of global sensitivity analysis to the model parameters highlights the need for additional experimental information on cell cycle distribution to complement metabolomic analyses with a view to parameterize kinetic models.

  12. Turnover intentions in a call center: The role of emotional dissonance, job resources, and job satisfaction.

    Science.gov (United States)

    Zito, Margherita; Emanuel, Federica; Molino, Monica; Cortese, Claudio Giovanni; Ghislieri, Chiara; Colombo, Lara

    2018-01-01

    Turnover intentions refer to employees' intent to leave the organization and, within call centers, it can be influenced by factors such as relational variables or the perception of the quality of working life, which can be affected by emotional dissonance. This specific job demand to express emotions not felt is peculiar in call centers, and can influence job satisfaction and turnover intentions, a crucial problem among these working contexts. This study aims to detect, within the theoretical framework of the Job Demands-Resources Model, the role of emotional dissonance (job demand), and two resources, job autonomy and supervisors' support, in the perception of job satisfaction and turnover intentions among an Italian call center. The study involved 318 call center agents of an Italian Telecommunication Company. Data analysis first performed descriptive statistics through SPSS 22. A path analysis was then performed through LISREL 8.72 and tested both direct and indirect effects. Results suggest the role of resources in fostering job satisfaction and in decreasing turnover intentions. Emotional dissonance reveals a negative relation with job satisfaction and a positive relation with turnover. Moreover, job satisfaction is negatively related with turnover and mediates the relationship between job resources and turnover. This study contributes to extend the knowledge about the variables influencing turnover intentions, a crucial problem among call centers. Moreover, the study identifies theoretical considerations and practical implications to promote well-being among call center employees. To foster job satisfaction and reduce turnover intentions, in fact, it is important to make resources available, but also to offer specific training programs to make employees and supervisors aware about the consequences of emotional dissonance.

  13. Turnover intentions in a call center: The role of emotional dissonance, job resources, and job satisfaction

    Science.gov (United States)

    Zito, Margherita; Molino, Monica; Cortese, Claudio Giovanni; Ghislieri, Chiara; Colombo, Lara

    2018-01-01

    Background Turnover intentions refer to employees’ intent to leave the organization and, within call centers, it can be influenced by factors such as relational variables or the perception of the quality of working life, which can be affected by emotional dissonance. This specific job demand to express emotions not felt is peculiar in call centers, and can influence job satisfaction and turnover intentions, a crucial problem among these working contexts. This study aims to detect, within the theoretical framework of the Job Demands-Resources Model, the role of emotional dissonance (job demand), and two resources, job autonomy and supervisors’ support, in the perception of job satisfaction and turnover intentions among an Italian call center. Method The study involved 318 call center agents of an Italian Telecommunication Company. Data analysis first performed descriptive statistics through SPSS 22. A path analysis was then performed through LISREL 8.72 and tested both direct and indirect effects. Results Results suggest the role of resources in fostering job satisfaction and in decreasing turnover intentions. Emotional dissonance reveals a negative relation with job satisfaction and a positive relation with turnover. Moreover, job satisfaction is negatively related with turnover and mediates the relationship between job resources and turnover. Conclusion This study contributes to extend the knowledge about the variables influencing turnover intentions, a crucial problem among call centers. Moreover, the study identifies theoretical considerations and practical implications to promote well-being among call center employees. To foster job satisfaction and reduce turnover intentions, in fact, it is important to make resources available, but also to offer specific training programs to make employees and supervisors aware about the consequences of emotional dissonance. PMID:29401507

  14. Turnover intentions in a call center: The role of emotional dissonance, job resources, and job satisfaction.

    Directory of Open Access Journals (Sweden)

    Margherita Zito

    Full Text Available Turnover intentions refer to employees' intent to leave the organization and, within call centers, it can be influenced by factors such as relational variables or the perception of the quality of working life, which can be affected by emotional dissonance. This specific job demand to express emotions not felt is peculiar in call centers, and can influence job satisfaction and turnover intentions, a crucial problem among these working contexts. This study aims to detect, within the theoretical framework of the Job Demands-Resources Model, the role of emotional dissonance (job demand, and two resources, job autonomy and supervisors' support, in the perception of job satisfaction and turnover intentions among an Italian call center.The study involved 318 call center agents of an Italian Telecommunication Company. Data analysis first performed descriptive statistics through SPSS 22. A path analysis was then performed through LISREL 8.72 and tested both direct and indirect effects.Results suggest the role of resources in fostering job satisfaction and in decreasing turnover intentions. Emotional dissonance reveals a negative relation with job satisfaction and a positive relation with turnover. Moreover, job satisfaction is negatively related with turnover and mediates the relationship between job resources and turnover.This study contributes to extend the knowledge about the variables influencing turnover intentions, a crucial problem among call centers. Moreover, the study identifies theoretical considerations and practical implications to promote well-being among call center employees. To foster job satisfaction and reduce turnover intentions, in fact, it is important to make resources available, but also to offer specific training programs to make employees and supervisors aware about the consequences of emotional dissonance.

  15. Endogenous Turnover of Cyanogenic Glycosides in Plants

    DEFF Research Database (Denmark)

    Picmanova, Martina

    through the formation of β- cyanoalanine, or, potentially, in an alternative endogenous turnover pathway circumventing the release of HCN. The investigation of the latter is the primary focus of this PhD project. Scattered data from the literature indicated that CNglcs co-occur in plants...... revealed the formation of glycosides of amides, carboxylic acids and "anitriles", including their di- and triglycosides, evidently derived from CNglcs. Based on results common to the three phylogenetically unrelated plant species, a recycling endogenous turnover pathway for CNglcs was suggested in which...... with an N-terminal TCP domain, showed that these enzymes do not recognize CNglcs as their substrates. However, the activity of NIT4s on a nitrile glucoside indicates that the enzymatic formation of glycosylated turnover products might be an integral part of the endogenous turnover of CNglcs. The elucidation...

  16. Organisational Commitment, Job Satisfaction and Turnover ...

    African Journals Online (AJOL)

    This study investigated organisational commitment, job satisfaction and turnover intentions among records management personnel in Ondo State Civil Service, Akure, Nigeria. Simple random sampling technique was used to draw 240 subjects from a population size of 275 records management personnel.

  17. Turnover of 14C-glucose in soils and its relationship with soil characters

    International Nuclear Information System (INIS)

    Ni Jinzhi; Xu Jianmin; Xie Zhengmiao; Ye Qingfu

    2001-01-01

    The turnover of 14 C-glucose added in 13 soils was studied. The turnover rate of 14 C-glucose can be divided into three phases: 0 - 3d, 3 - 28d and 28 - 294d. The range of the turnover rate and half -life of 14 C-glucose were 1.3 x 10 -1 - 2.5 x 10 -1 d -1 and 3 - 5d, 0.7x 10 -2 - 1.2 x 10 -2 d -1 and 58 - 97d, 0.5 x 10 -3 - 1.4 x 10 -3 d -1 and 491 - 1504d, respectively. Correlation analysis showed that from 0 to 3 days the turnover rate of 14 C-glucose had significant positive correlation with soil qCO 2 , from 3 to 28 days, the turnover rate of 14 C-glucose had no significant correlation with soil physico-chemical and biological properties. The turnover rate of 14 C-glucose had significant or highly significant negative correlation with soil total organic carbon, total nitrogen, CEC and significant positive correlation with soil sand content during the period from 28 to 294 days. Turnover of 14 C-glucose during the third period has close correlation with soil properties

  18. Effects of role stress on nurses' turnover intentions: The mediating effects of organizational commitment and burnout.

    Science.gov (United States)

    Han, Sang-Sook; Han, Jeong-Won; An, Young-Suk; Lim, So-Hee

    2015-10-01

    This paper was designed to extend the extant research regarding factors related to nurses' turnover intentions. This survey-based study was based on a path analysis designed to verify a hypothesized causal model involving nurses' role stress, organizational commitment, turnover intentions, and burnout. This study distributed 500 questionnaires to nurses in general hospitals with more than 500 beds located in Seoul, Korea, during 16-30 April 2012. Role conflict, an underlying factor in role stress, had no significant effect on role stress, but the results showed that role ambiguity reduced organizational commitment. On the other hand, role conflict and role ambiguity increased the level of burnout. Organizational commitment reduced turnover intentions, and burnout increased turnover intentions. Role conflict and role ambiguity had no direct effect on turnover intentions, but they had indirect effects on organizational commitment and burnout. To reduce nurses' turnover rate, this study recommends developing plans to improve their organizational commitment because it mediates role stress and turnover intention. © 2014 The Authors. Japan Journal of Nursing Science © 2014 Japan Academy of Nursing Science.

  19. On the controlling mechanism of the upper turnover states in the NTC regime

    KAUST Repository

    Ji, Weiqi

    2015-12-18

    Using n-butane, n-heptane and iso-octane as representative fuels exhibiting NTC (negative temperature coefficient) behavior, comprehensive computational studies with detailed mechanisms and theoretical analysis were performed to investigate the upper stationary point, denoted as turnover states, on the NTC curve near the higher temperature regime, where the ignition delay τ exhibits a local maximum. It is found that the global behavior of the turnover states exhibits distinctive thermodynamic and kinetic characteristics under different pressures, in that the ignition delay at the turnover states shows an Arrhenius dependence on the temperature T and an approximate inverse quadratic power law dependence on the pressure P. These global behaviors imply that the temperature and pressure of the turnover states are not independent and can be correlated by Arrhenius dependence, as ln P ∝ 1/T. Further theoretical analyses demonstrate that such turnover states result from the competition between the low-temperature chain branching reactions and the decomposition of the intermediate species, and therefore correspond to a critical value, α, of the ratio of OH production from low-temperature chemistry. In addition, the ignition delay at the turnover state can be well correlated by the analytical expression derived by Peters et al., with the further demonstration that the pressure dependence of the turnover ignition delay mainly result from the H2O2 decomposition reaction. Comparison of the present results with the literature experimental data of n-heptane ignition delay time shows very good agreement.

  20. Comparative functional genomic analysis of two Vibrio phages reveals complex metabolic interactions with the host cell

    Directory of Open Access Journals (Sweden)

    Dimitrios Skliros

    2016-11-01

    Full Text Available Sequencing and annotation was performed for two giant double stranded DNA bacteriophages, φGrn1 and φSt2 of the Myoviridae family, considered to be of great interest for phage therapy against Vibrios in aquaculture live feeds. In addition, phage-host metabolic interactions and exploitation was studied by transcript profiling of selected viral and host genes. Comparative genomic analysis with other giant Vibrio phages was also performed to establish the presence and location of homing endonucleases highlighting distinct features for both phages. Phylogenetic analysis revealed that they belong to the schizoT4like clade. Although many reports of newly sequenced viruses have provided a large set of information, basic research related to the shift of the bacterial metabolism during infection remains stagnant. The function of many viral protein products in the process of infection is still unknown. Genome annotation identified the presence of several viral ORFs participating in metabolism, including a Sir2/cobB (sirtuin protein and a number of genes involved in auxiliary NAD+ and nucleotide biosynthesis, necessary for phage DNA replication. Key genes were subsequently selected for detail study of their expression levels during infection. This work suggests a complex metabolic interaction and exploitation of the host metabolic pathways and biochemical processes, including a possible post-translational protein modification, by the virus during infection.

  1. Determination of key enzymes for threonine synthesis through in vitro metabolic pathway analysis.

    Science.gov (United States)

    Zhang, Yanfei; Meng, Qinglong; Ma, Hongwu; Liu, Yongfei; Cao, Guoqiang; Zhang, Xiaoran; Zheng, Ping; Sun, Jibin; Zhang, Dawei; Jiang, Wenxia; Ma, Yanhe

    2015-06-13

    The overexpression of key enzymes in a metabolic pathway is a frequently used genetic engineering strategy for strain improvement. Metabolic control analysis has been proposed to quantitatively determine key enzymes. However, the lack of quality data often makes it difficult to correctly identify key enzymes through control analysis. Here, we proposed a method combining in vitro metabolic pathway analysis and proteomics measurement to find the key enzymes in threonine synthesis pathway. All enzymes in the threonine synthesis pathway were purified for the reconstruction and perturbation of the in vitro pathway. Label-free proteomics technology combined with APEX (absolute protein expression measurements) data analysis method were employed to determine the absolute enzyme concentrations in the crude enzyme extract obtained from a threonine production strain during the fastest threonine production period. The flux control coefficient of each enzyme in the pathway was then calculated by measuring the flux changes after titration of the corresponding enzyme. The isoenzyme LysC catalyzing the first step in the pathway has the largest flux control coefficient, and thus its concentration change has the biggest impact on pathway flux. To verify that the key enzyme identified through in vitro pathway analysis is also the key enzyme in vivo, we overexpressed LysC in the original threonine production strain. Fermentation results showed that the threonine concentration was increased 30% and the yield was increased 20%. In vitro metabolic pathways simulating in vivo cells can be built based on precise measurement of enzyme concentrations through proteomics technology and used for the determination of key enzymes through metabolic control analysis. This provides a new way to find gene overexpression targets for industrial strain improvement.

  2. Finding elementary flux modes in metabolic networks based on flux balance analysis and flux coupling analysis: application to the analysis of Escherichia coli metabolism.

    Science.gov (United States)

    Tabe-Bordbar, Shayan; Marashi, Sayed-Amir

    2013-12-01

    Elementary modes (EMs) are steady-state metabolic flux vectors with minimal set of active reactions. Each EM corresponds to a metabolic pathway. Therefore, studying EMs is helpful for analyzing the production of biotechnologically important metabolites. However, memory requirements for computing EMs may hamper their applicability as, in most genome-scale metabolic models, no EM can be computed due to running out of memory. In this study, we present a method for computing randomly sampled EMs. In this approach, a network reduction algorithm is used for EM computation, which is based on flux balance-based methods. We show that this approach can be used to recover the EMs in the medium- and genome-scale metabolic network models, while the EMs are sampled in an unbiased way. The applicability of such results is shown by computing “estimated” control-effective flux values in Escherichia coli metabolic network.

  3. Pathway analysis of kidney cancer using proteomics and metabolic profiling

    Directory of Open Access Journals (Sweden)

    Fiehn Oliver

    2006-11-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC. We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. Results Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values Conclusion Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids of patient at high risk for this disease; we provide pilot data for such a urinary bioassay. Furthermore, we demonstrate how the knowledge of networks, processes, and pathways altered in kidney cancer may be used to influence the choice of optimal therapy.

  4. Improving production of ?-lactam antibiotics by Penicillium chrysogenum : Metabolic engineering based on transcriptome analysis

    NARCIS (Netherlands)

    Veiga, T.

    2012-01-01

    In Chapters 2-5 of this thesis, the applicability of transcriptome analysis to guide metabolic engineering strategies in P. chrysogenum is explored by investigating four cellular processes that are of potential relevance for industrial production of ?-lactam antibiotics: - Regulation of secondary

  5. An update on psoriasis and metabolic syndrome: A meta-analysis of observational studies.

    Directory of Open Access Journals (Sweden)

    Sanminder Singh

    Full Text Available The relationship between psoriasis and metabolic syndrome is not well understood. Though multiple epidemiologic studies have suggested a link between psoriasis and metabolic syndrome, there is a lack of a comprehensive meta-analysis synthesizing the results of all available observational studies to date. In this meta-analysis, we examined global data on the relationship between psoriasis and odds of metabolic syndrome by searching for studies published between 1946-2016. Specifically, we analyzed the results from 35 observational studies from 20 countries with 1,450,188 total participants, of which 46,714 were psoriasis patients. The pooled odds ratio based on random effects analysis was 2.14 (95% CI 1.84-2.48. Publication bias was present, as evidenced by an Egger test and graphical visualization through a funnel plot (p = 0.001. Based on this comprehensive meta-analysis, psoriasis patients have higher odds of having metabolic syndrome when compared with the general population.

  6. Flux balance analysis of genome-scale metabolic model of rice ...

    Indian Academy of Sciences (India)

    2015-09-28

    Sep 28, 2015 ... genome-scale metabolic model of rice leaf using Flux Balance Analysis to investigate whether it has potential .... is number of reactions. In steady state. S.v = 0. (2) where v is the flux vector of reactions (Kauffman et al. 2003). Objective function is. Z = w.v. (3). 820 .... All the reactions are not included.

  7. Gene Coexpression Analysis Reveals Complex Metabolism of the Monoterpene Alcohol Linalool in Arabidopsis FlowersW

    NARCIS (Netherlands)

    Ginglinger, J.F.; Boachon, B.; Hofer, R.; Paetz, C.; Kollner, T.G.; Miesch, L.; Lugan, R.; Baltenweck, R.; Mutterer, J.; Ullman, P.; Verstappen, F.W.A.; Bouwmeester, H.J.

    2013-01-01

    The cytochrome P450 family encompasses the largest family of enzymes in plant metabolism, and the functions of many of its members in Arabidopsis thaliana are still unknown. Gene coexpression analysis pointed to two P450s that were coexpressed with two monoterpene synthases in flowers and were thus

  8. Spatial turnover in the global avifauna.

    Science.gov (United States)

    Gaston, Kevin J; Davies, Richard G; Orme, C David L; Olson, Valerie A; Thomas, Gavin H; Ding, Tzung-Su; Rasmussen, Pamela C; Lennon, Jack J; Bennett, Peter M; Owens, Ian P F; Blackburn, Tim M

    2007-07-07

    Despite its wide implications for many ecological issues, the global pattern of spatial turnover in the occurrence of species has been little studied, unlike the global pattern of species richness. Here, using a database on the breeding distributions of birds, we present the first global maps of variation in spatial turnover for an entire taxonomic class, a pattern that has to date remained largely a matter of conjecture, based on theoretical expectations and extrapolation of inconsistent patterns from different biogeographic realms. We use these maps to test four predictions from niche theory as to the form that this variation should take, namely that turnover should increase with species richness, towards lower latitudes, and with the steepness of environmental gradients and that variation in turnover is determined principally by rare (restricted) species. Contrary to prediction, we show that turnover is high both in areas of extremely low and high species richness, does not increase strongly towards the tropics, and is related both to average environmental conditions and spatial variation in those conditions. These results are closely associated with a further important and novel finding, namely that global patterns of spatial turnover are driven principally by widespread species rather than the restricted ones. This complements recent demonstrations that spatial patterns of species richness are also driven principally by widespread species, and thus provides an important contribution towards a unified model of how terrestrial biodiversity varies both within and between the Earth's major land masses.

  9. Guided Bone Regeneration With or Without a Collagen Membrane in Rats with Induced Diabetes Mellitus: Histomorphometric and Immunolocalization Analysis of Angiogenesis and Bone Turnover Markers.

    Science.gov (United States)

    Jardini, Maria Aparecida; Tera, Tábata Mello; Meyer, Augusto Andrade; Moretto, Camilla Magnoni; Prado, Renata Falchete; Santamaria, Mauro Pedrine

    2016-01-01

    Diabetes mellitus (DM) affects the processes of repair, wound healing, and bone remodeling. This study was conducted to evaluate autologous bone graft integration, either with or without guided bone regeneration, through analyzing the expression of bone reabsorption markers and neovascularization in rats suffering from DM. Thirty adult Wistar rats were divided into two groups: The DM group received an injection of alloxan monohydrate (150 mg/kg), and the control group received an injection of sterile saline. Fifteen days afterward, an autologous bone grafting was performed in each of their arches, with the insertion of a membrane into the left arch. Euthanasia occurred in 7, 21, or 60 days after the surgery. Bone samples were processed for histomorphometric and immunohistochemical analyses. After a statistical analysis of the data, the presence of DM did not interfere negatively in the bone autograft repair. The collagen membrane favored the graft integration into the recipient bed and the bone neoformation around the graft. Greater vascularization was observed between 21 and 60 days after the surgery, which increased bone formation and resulted in the graft integration. Only the RANK marker showed a significant difference in the glycemic groups. Transglutaminase 2 was significant for the membrane presence and experimental time. It is hence concluded that diabetes mellitus does not interfere with bone reabsorption via the RANK/RANKL/OPG. The graft integration was similar between the groups; however, the results of hyperglycemia with the collagen membrane indicate greater bone growth after graft placement.

  10. The Effects of Employee Turnover on Those Who Stay.

    Science.gov (United States)

    Sheehan, Eugene P.; Hockett, Cherri

    Research on employee turnover which has examined why employees quit their jobs has identified a wide range of variables that are associated with turnover, but has provided little information about the consequences of turnover for those who remain in an organization. This study was conducted to examine whether the manner in which turnover is…

  11. Consistency Analysis of Genome-Scale Models of Bacterial Metabolism: A Metamodel Approach.

    Science.gov (United States)

    Ponce-de-Leon, Miguel; Calle-Espinosa, Jorge; Peretó, Juli; Montero, Francisco

    2015-01-01

    Genome-scale metabolic models usually contain inconsistencies that manifest as blocked reactions and gap metabolites. With the purpose to detect recurrent inconsistencies in metabolic models, a large-scale analysis was performed using a previously published dataset of 130 genome-scale models. The results showed that a large number of reactions (~22%) are blocked in all the models where they are present. To unravel the nature of such inconsistencies a metamodel was construed by joining the 130 models in a single network. This metamodel was manually curated using the unconnected modules approach, and then, it was used as a reference network to perform a gap-filling on each individual genome-scale model. Finally, a set of 36 models that had not been considered during the construction of the metamodel was used, as a proof of concept, to extend the metamodel with new biochemical information, and to assess its impact on gap-filling results. The analysis performed on the metamodel allowed to conclude: 1) the recurrent inconsistencies found in the models were already present in the metabolic database used during the reconstructions process; 2) the presence of inconsistencies in a metabolic database can be propagated to the reconstructed models; 3) there are reactions not manifested as blocked which are active as a consequence of some classes of artifacts, and; 4) the results of an automatic gap-filling are highly dependent on the consistency and completeness of the metamodel or metabolic database used as the reference network. In conclusion the consistency analysis should be applied to metabolic databases in order to detect and fill gaps as well as to detect and remove artifacts and redundant information.

  12. Pengaruh Psychological Well-Being dan Job Embeddedness Terhadap Turnover Intentions

    OpenAIRE

    Pane, Deasy Anggreini

    2016-01-01

    147049008 This research was aimed to examine the effect of psychological well-being and job embeddedness toward turnover intentions. This research used turnover intention scale, psychological well-being scale and job embeddedness scale. Data were gathered from 229 employees of Permata Bunda Hospital in Medan. Data were analyzed by using multiple regression method. The statistical analysis result showed there was a negative influence of psychological well-being and job emb...

  13. Gene expression analysis of starch metabolism using mRNAseq and the potato genome sequence

    DEFF Research Database (Denmark)

    Sønderkær, Mads; Kloosterman, Bjorn; Bachem, Christian

    2010-01-01

    starch yield than presently possible, detailed knowledge about starch metabolism is crucial. Accumulation of carbohydrates in the form of starch in potato tubers is the result of both anabolic and catabolic processes. These processes are highly redundant in terms of gene isoforms and multiple metabolic......, starch synthesis takes place not only in tubers but also in leaves in the form of transient starch during the day, which is consumed in the absence of photosynthesis during the night. This poster will present the results of a transcriptome analysis based on the draft potato genome sequence v3. Samples...

  14. Capture the fracture - use of bone turnover markers in clinical practice

    Directory of Open Access Journals (Sweden)

    Vuksanović Miljanka

    2016-01-01

    Full Text Available Bone is a living tissue, metabolically very active, with the level of turnover of about 10% per year. Bone remodeling is a well-balanced process of bone resorption, induced by osteoclasts and bone formation maintained osteoblasts. Loss of bone remodeling balance, with increased bone resorption, leads to osteoporosis. Bone turnover markers are classified as markers of bone formation and of bone resorption. During the growth and development of skeleton, bone turnover markers show higher levels of activity than in the adult period. The increase in biochemical markers peaks again in the postmenopausal period, indicating accelerated bone remodeling. Bone mineral density is an important predictor of an osteoporotic fracture. Timely assessment of risk factors of osteoporosis and bone markers can detect subjects with accelerated bone remodeling and osteoporosis. This may introduce adequate therapy and prevent fracture.

  15. The collagen turnover profile is altered in patients with inguinal and incisional hernia

    DEFF Research Database (Denmark)

    Henriksen, Nadia A; Mortensen, Joachim H; Sorensen, Lars T

    2015-01-01

    BACKGROUND: Disturbed metabolism in the extracellular matrix (ECM) contributes to formation of abdominal wall hernias. The aim of this study was to gain deeper insight into the ECM turnover in hernia patients by analyzing serum biomarkers specifically reflecting collagen synthesis and breakdown......). Patients without hernias scheduled to undergo elective operation for gallstones (n = 18) served as controls. Whole venous blood was collected preoperatively. Biomarkers for synthesis of interstitial matrix (PINP, Pro-C3, P5CP) and basement membrane (P4NP) as well as corresponding degradation (C1M, C3M, C5M......, and C4M) were measured in serum by validated, solid-phase competitive assays. RESULTS: In inguinal hernia patients, the turnover of the interstitial matrix collagens type III (P turnover of the basement membrane collagen type IV...

  16. Safety organizing, emotional exhaustion, and turnover in hospital nursing units.

    Science.gov (United States)

    Vogus, Timothy J; Cooil, Bruce; Sitterding, Mary; Everett, Linda Q

    2014-10-01

    Prior research has found that safety organizing behaviors of registered nurses (RNs) positively impact patient safety. However, little research exists on how engaging in safety organizing affects caregivers. While we know that organizational processes can have divergent effects on organizational and employee outcomes, little research exists on the effects of pursuing highly reliable performance through safety organizing on caregivers. Specifically, we examined whether, and the conditions under which, safety organizing affects RN emotional exhaustion and nursing unit turnover rates. Subjects included 1352 RNs in 50 intensive care, internal medicine, labor, and surgery nursing units in 3 Midwestern acute-care hospitals who completed questionnaires between August and December 2011 and 50 Nurse Managers from the units who completed questionnaires in December 2012. Cross-sectional analyses of RN emotional exhaustion linked to survey data on safety organizing and hospital incident reporting system data on adverse event rates for the year before survey administration. Cross-sectional analysis of unit-level RN turnover rates for the year following the administration of the survey linked to survey data on safety organizing. Multilevel regression analysis indicated that safety organizing was negatively associated with RN emotional exhaustion on units with higher rates of adverse events and positively associated with RN emotional exhaustion with lower rates of adverse events. Tobit regression analyses indicated that safety organizing was associated with lower unit level of turnover rates over time. Safety organizing is beneficial to caregivers in multiple ways, especially on nursing units with high levels of adverse events and over time.

  17. Addressing employee turnover and retention: keeping your valued performers.

    Science.gov (United States)

    McConnell, Charles R

    2011-01-01

    Employee turnover and employee retention are inextricably linked; to control turnover is to enhance retention. Turnover is a relatively simple concept; however, considerable confusion often results when addressing turnover because of differences in how it is defined; that is, what is counted, how it is counted, and how the turnover rates are expressed. Turnover is also costly, although not enough attention is paid to its cost because so much of it is indirect and thus not readily visible. There are a variety of causes of turnover, some that can be corrected and some that cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role; every improvement in turnover is a direct improvement in retention, with eventual positive effects on the bottom line.

  18. Reconstruction and analysis of a genome-scale metabolic model for Scheffersomyces stipitis

    Directory of Open Access Journals (Sweden)

    Balagurunathan Balaji

    2012-02-01

    Full Text Available Abstract Background Fermentation of xylose, the major component in hemicellulose, is essential for economic conversion of lignocellulosic biomass to fuels and chemicals. The yeast Scheffersomyces stipitis (formerly known as Pichia stipitis has the highest known native capacity for xylose fermentation and possesses several genes for lignocellulose bioconversion in its genome. Understanding the metabolism of this yeast at a global scale, by reconstructing the genome scale metabolic model, is essential for manipulating its metabolic capabilities and for successful transfer of its capabilities to other industrial microbes. Results We present a genome-scale metabolic model for Scheffersomyces stipitis, a native xylose utilizing yeast. The model was reconstructed based on genome sequence annotation, detailed experimental investigation and known yeast physiology. Macromolecular composition of Scheffersomyces stipitis biomass was estimated experimentally and its ability to grow on different carbon, nitrogen, sulphur and phosphorus sources was determined by phenotype microarrays. The compartmentalized model, developed based on an iterative procedure, accounted for 814 genes, 1371 reactions, and 971 metabolites. In silico computed growth rates were compared with high-throughput phenotyping data and the model could predict the qualitative outcomes in 74% of substrates investigated. Model simulations were used to identify the biosynthetic requirements for anaerobic growth of Scheffersomyces stipitis on glucose and the results were validated with published literature. The bottlenecks in Scheffersomyces stipitis metabolic network for xylose uptake and nucleotide cofactor recycling were identified by in silico flux variability analysis. The scope of the model in enhancing the mechanistic understanding of microbial metabolism is demonstrated by identifying a mechanism for mitochondrial respiration and oxidative phosphorylation. Conclusion The genome

  19. Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT inhibition on human cancer cells.

    Directory of Open Access Journals (Sweden)

    Vladimir Tolstikov

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide-consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry-based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer and HCT-116 (colorectal cancer cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA, and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level.

  20. A tissue-specific approach to the analysis of metabolic changes in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Jürgen Hench

    Full Text Available The majority of metabolic principles are evolutionarily conserved from nematodes to humans. Caenorhabditis elegans has widely accelerated the discovery of new genes important to maintain organismic metabolic homeostasis. Various methods exist to assess the metabolic state in worms, yet they often require large animal numbers and tend to be performed as bulk analyses of whole worm homogenates, thereby largely precluding a detailed studies of metabolic changes in specific worm tissues. Here, we have adapted well-established histochemical methods for the use on C. elegans fresh frozen sections and demonstrate their validity for analyses of morphological and metabolic changes on tissue level in wild type and various mutant strains. We show how the worm presents on hematoxylin and eosin (H&E stained sections and demonstrate their usefulness in monitoring and the identification of morphological abnormalities. In addition, we demonstrate how Oil-Red-O staining on frozen worm cross-sections permits quantification of lipid storage, avoiding the artifact-prone fixation and permeabilization procedures of traditional whole-mount protocols. We also adjusted standard enzymatic stains for respiratory chain subunits (NADH, SDH, and COX to monitor metabolic states of various C. elegans tissues. In summary, the protocols presented here provide technical guidance to obtain robust, reproducible and quantifiable tissue-specific data on worm morphology as well as carbohydrate, lipid and mitochondrial energy metabolism that cannot be obtained through traditional biochemical bulk analyses of worm homogenates. Furthermore, analysis of worm cross-sections overcomes the common problem with quantification in three-dimensional whole-mount specimens.

  1. Transcriptome Analysis of Sucrose Metabolism during Bulb Swelling and Development in Onion (Allium cepa L.

    Directory of Open Access Journals (Sweden)

    Yi Liang

    2016-09-01

    Full Text Available Allium cepa L. is a widely cultivated and economically significant vegetable crop worldwide, with beneficial dietary and health-related properties, but its sucrose metabolism is still poorly understood. To analyze sucrose metabolism during bulb swelling, and the development of sweet taste in onion, a global transcriptome profile of onion bulbs was undertaken at three different developmental stages, using RNA-seq. A total of 79,376 unigenes, with a mean length of 678 bp, was obtained. In total, 7% of annotated Clusters of Orthologous Groups (COG were involved in carbohydrate transport and metabolism. In the Kyoto Encyclopedia of Genes and Genomes (KEGG database, starch and sucrose metabolism (147, 2.40% constituted the primary metabolism pathway in the integrated library. The expression of sucrose transporter genes was greatest during the early-swelling stage, suggesting that sucrose transporters participated in sucrose metabolism mainly at an early stage of bulb development. A gene-expression analysis of the key enzymes of sucrose metabolism suggested that sucrose synthase, cell wall invertase and invertase were all likely to participate in the hydrolysis of sucrose, generating glucose and fructose. In addition, trehalose was hydrolyzed to two molecules of glucose by trehalase. From 15 to 40 days after swelling (DAS, both the glucose and fructose contents of bulbs increased, whereas the sucrose content decreased. The growth rate between 15 and 30 DAS was slower than that between 30 and 40 DAS, suggesting that the latter was a period of rapid expansion. The dataset generated by our transcriptome profiling will provide valuable information for further research.

  2. Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT) inhibition on human cancer cells.

    Science.gov (United States)

    Tolstikov, Vladimir; Nikolayev, Alexander; Dong, Sucai; Zhao, Genshi; Kuo, Ming-Shang

    2014-01-01

    Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in cellular bioenergetics. It is responsible for converting nicotinamide to nicotinamide adenine dinucleotide, an essential molecule in cellular metabolism. NAMPT has been extensively studied over the past decade due to its role as a key regulator of nicotinamide adenine dinucleotide-consuming enzymes. NAMPT is also known as a potential target for therapeutic intervention due to its involvement in disease. In the current study, we used a global mass spectrometry-based metabolomic approach to investigate the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on metabolic perturbations in human cancer cells. We treated A2780 (ovarian cancer) and HCT-116 (colorectal cancer) cell lines with FK866 in the presence and absence of nicotinic acid. Significant changes were observed in the amino acids metabolism and the purine and pyrimidine metabolism. We also observed metabolic alterations in glycolysis, the citric acid cycle (TCA), and the pentose phosphate pathway. To expand the range of the detected polar metabolites and improve data confidence, we applied a global metabolomics profiling platform by using both non-targeted and targeted hydrophilic (HILIC)-LC-MS and GC-MS analysis. We used Ingenuity Knowledge Base to facilitate the projection of metabolomics data onto metabolic pathways. Several metabolic pathways showed differential responses to FK866 based on several matches to the list of annotated metabolites. This study suggests that global metabolomics can be a useful tool in pharmacological studies of the mechanism of action of drugs at a cellular level.

  3. A comparative analysis of metal transportomes from metabolically versatile Pseudomonas

    Directory of Open Access Journals (Sweden)

    Rodrigue Agnes

    2008-09-01

    Full Text Available Abstract Background The availability of complete genome sequences of versatile Pseudomonas occupying remarkably diverse ecological niches enabled to gain insights into their adaptative assets. The objective of this study was to analyze the complete genetic repertoires of metal transporters (metal transportomes from four representative Pseudomonas species and to identify metal transporters with "Genomic Island" associated features. Methods A comparative metal transporter inventory was built for the following four Pseudomonas species: P.putida (Ppu KT2440, P.aeruginosa (Pae PA01, P.fluorescens (Pfl Pf-5 and P.syringae (Psypv.tomato DC3000 using TIGR-CMR and Transport DB. Genomic analysis of essential and toxic metal ion transporters was accomplished from the above inventory. Metal transporters with "Genomic Island" associated features were identified using Islandpath analysis. Results Dataset cataloguing has been executed for 262 metal transporters from the four spp. Additional metal ion transporters belonging to NiCoT, Ca P-type ATPase, Cu P-type ATPases, ZIP and MgtC families were identified. In Psy DC3000, 48% of metal transporters showed strong GI features while it was 45% in Ppu KT2440. In Pfl Pf-5 and Pae PA01 only 26% of their metal transporters exhibited GI features. Conclusion Our comparative inventory of 262 metal transporters from four versatile Pseudomonas spp is the complete suite of metal transportomes analysed till date in a prokaryotic genus. This study identified differences in the basic composition of metal transportomes from Pseudomonas occupying diverse ecological niches and also elucidated their novel features. Based on this inventory we analysed the role of horizontal gene transfer in expansion and variability of metal transporter families.

  4. Comparative analysis of Salmonella genomes identifies a metabolic network for escalating growth in the inflamed gut.

    Science.gov (United States)

    Nuccio, Sean-Paul; Bäumler, Andreas J

    2014-03-18

    The Salmonella genus comprises a group of pathogens associated with illnesses ranging from gastroenteritis to typhoid fever. We performed an in silico analysis of comparatively reannotated Salmonella genomes to identify genomic signatures indicative of disease potential. By removing numerous annotation inconsistencies and inaccuracies, the process of reannotation identified a network of 469 genes involved in central anaerobic metabolism, which was intact in genomes of gastrointestinal pathogens but degrading in genomes of extraintestinal pathogens. This large network contained pathways that enable gastrointestinal pathogens to utilize inflammation-derived nutrients as well as many of the biochemical reactions used for the enrichment and biochemical discrimination of Salmonella serovars. Thus, comparative genome analysis identifies a metabolic network that provides clues about the strategies for nutrient acquisition and utilization that are characteristic of gastrointestinal pathogens. IMPORTANCE While some Salmonella serovars cause infections that remain localized to the gut, others disseminate throughout the body. Here, we compared Salmonella genomes to identify characteristics that distinguish gastrointestinal from extraintestinal pathogens. We identified a large metabolic network that is functional in gastrointestinal pathogens but decaying in extraintestinal pathogens. While taxonomists have used traits from this network empirically for many decades for the enrichment and biochemical discrimination of Salmonella serovars, our findings suggest that it is part of a "business plan" for growth in the inflamed gastrointestinal tract. By identifying a large metabolic network characteristic of Salmonella serovars associated with gastroenteritis, our in silico analysis provides a blueprint for potential strategies to utilize inflammation-derived nutrients and edge out competing gut microbes.

  5. Cartilage turnover reflected by metabolic processing of type II collagen

    DEFF Research Database (Denmark)

    Gudmann, Karoline Natasja Stæhr; Wang, Jianxia; Hoielt, Sabine

    2014-01-01

    The aim of this study was to enable measurement of cartilage formation by a novel biomarker of type II collagen formation. The competitive enzyme-linked immunosorbent assay (ELISA) Pro-C2 was developed and characterized for assessment of the beta splice variant of type II procollagen (PIIBNP....... To our knowledge this is the first assay, which is able to specifically evaluate PIIBNP excretion. The Pro-C2 assay seems to provide a promising and novel marker of type II collagen formation....

  6. Unraveling the metabolism of HEK-293 cells using lactate isotopomer analysis.

    Science.gov (United States)

    Henry, Olivier; Jolicoeur, Mario; Kamen, Amine

    2011-03-01

    HEK-293 is the most extensively used human cell line for the production of viral vectors and is gaining increasing attention for the production of recombinant proteins by transient transfection. To further improve the metabolic characterization of this cell line, we have performed cultures using ¹³C-labeled substrates and measured the resulting mass isotopomer distributions in lactate by LC/MS. Simultaneous metabolite and isotopomer balancing allowed improvement and validation of the metabolic model and quantification of key intracellular pathways. We have determined the amounts of glucose carbon channeled through the PPP, incorporated into the TCA cycle for energy production and lipids biosynthesis, as well as the cytosolic and mitochondrial malic enzyme fluxes. Our analysis also revealed that glutamine did not significantly contribute to lactate formation. An improved and quantitative understanding of the central carbon metabolism is greatly needed to pursue the rational development of engineering approaches at both the cellular and process levels.

  7. MetaboTools: A Comprehensive Toolbox for Analysis of Genome-Scale Metabolic Models

    Science.gov (United States)

    Aurich, Maike K.; Fleming, Ronan M. T.; Thiele, Ines

    2016-01-01

    Metabolomic data sets provide a direct read-out of cellular phenotypes and are increasingly generated to study biological questions. Previous work, by us and others, revealed the potential of analyzing extracellular metabolomic data in the context of the metabolic model using constraint-based modeling. With the MetaboTools, we make our methods available to the broader scientific community. The MetaboTools consist of a protocol, a toolbox, and tutorials of two use cases. The protocol describes, in a step-wise manner, the workflow of data integration, and computational analysis. The MetaboTools comprise the Matlab code required to complete the workflow described in the protocol. Tutorials explain the computational steps for integration of two different data sets and demonstrate a comprehensive set of methods for the computational analysis of metabolic models and stratification thereof into different phenotypes. The presented workflow supports integrative analysis of multiple omics data sets. Importantly, all analysis tools can be applied to metabolic models without performing the entire workflow. Taken together, the MetaboTools constitute a comprehensive guide to the intra-model analysis of extracellular metabolomic data from microbial, plant, or human cells. This computational modeling resource offers a broad set of computational analysis tools for a wide biomedical and non-biomedical research community. PMID:27536246

  8. Gene-based mapping and pathway analysis of metabolic traits in dairy cows.

    Directory of Open Access Journals (Sweden)

    Ngoc-Thuy Ha

    Full Text Available The metabolic adaptation of dairy cows during the transition period has been studied intensively in the last decades. However, until now, only few studies have paid attention to the genetic aspects of this process. Here, we present the results of a gene-based mapping and pathway analysis with the measurements of three key metabolites, (1 non-esterified fatty acids (NEFA, (2 beta-hydroxybutyrate (BHBA and (3 glucose, characterizing the metabolic adaptability of dairy cows before and after calving. In contrast to the conventional single-marker approach, we identify 99 significant and biologically sensible genes associated with at least one of the considered phenotypes and thus giving evidence for a genetic basis of the metabolic adaptability. Moreover, our results strongly suggest three pathways involved in the metabolism of steroids and lipids are potential candidates for the adaptive regulation of dairy cows in their early lactation. From our perspective, a closer investigation of our findings will lead to a step forward in understanding the variability in the metabolic adaptability of dairy cows in their early lactation.

  9. Reconciliation of genome-scale metabolic reconstructions for comparative systems analysis.

    Directory of Open Access Journals (Sweden)

    Matthew A Oberhardt

    2011-03-01

    Full Text Available In the past decade, over 50 genome-scale metabolic reconstructions have been built for a variety of single- and multi- cellular organisms. These reconstructions have enabled a host of computational methods to be leveraged for systems-analysis of metabolism, leading to greater understanding of observed phenotypes. These methods have been sparsely applied to comparisons between multiple organisms, however, due mainly to the existence of differences between reconstructions that are inherited from the respective reconstruction processes of the organisms to be compared. To circumvent this obstacle, we developed a novel process, termed metabolic network reconciliation, whereby non-biological differences are removed from genome-scale reconstructions while keeping the reconstructions as true as possible to the underlying biological data on which they are based. This process was applied to two organisms of great importance to disease and biotechnological applications, Pseudomonas aeruginosa and Pseudomonas putida, respectively. The result is a pair of revised genome-scale reconstructions for these organisms that can be analyzed at a systems level with confidence that differences are indicative of true biological differences (to the degree that is currently known, rather than artifacts of the reconstruction process. The reconstructions were re-validated with various experimental data after reconciliation. With the reconciled and validated reconstructions, we performed a genome-wide comparison of metabolic flexibility between P. aeruginosa and P. putida that generated significant new insight into the underlying biology of these important organisms. Through this work, we provide a novel methodology for reconciling models, present new genome-scale reconstructions of P. aeruginosa and P. putida that can be directly compared at a network level, and perform a network-wide comparison of the two species. These reconstructions provide fresh insights into the

  10. Reconciliation of Genome-Scale Metabolic Reconstructions for Comparative Systems Analysis

    Science.gov (United States)

    Martins dos Santos, Vítor A. P.; Papin, Jason A.

    2011-01-01

    In the past decade, over 50 genome-scale metabolic reconstructions have been built for a variety of single- and multi- cellular organisms. These reconstructions have enabled a host of computational methods to be leveraged for systems-analysis of metabolism, leading to greater understanding of observed phenotypes. These methods have been sparsely applied to comparisons between multiple organisms, however, due mainly to the existence of differences between reconstructions that are inherited from the respective reconstruction processes of the organisms to be compared. To circumvent this obstacle, we developed a novel process, termed metabolic network reconciliation, whereby non-biological differences are removed from genome-scale reconstructions while keeping the reconstructions as true as possible to the underlying biological data on which they are based. This process was applied to two organisms of great importance to disease and biotechnological applications, Pseudomonas aeruginosa and Pseudomonas putida, respectively. The result is a pair of revised genome-scale reconstructions for these organisms that can be analyzed at a systems level with confidence that differences are indicative of true biological differences (to the degree that is currently known), rather than artifacts of the reconstruction process. The reconstructions were re-validated with various experimental data after reconciliation. With the reconciled and validated reconstructions, we performed a genome-wide comparison of metabolic flexibility between P. aeruginosa and P. putida that generated significant new insight into the underlying biology of these important organisms. Through this work, we provide a novel methodology for reconciling models, present new genome-scale reconstructions of P. aeruginosa and P. putida that can be directly compared at a network level, and perform a network-wide comparison of the two species. These reconstructions provide fresh insights into the metabolic similarities

  11. Transcriptome analysis of carbohydrate metabolism during bulblet formation and development in Lilium davidii var. unicolor.

    Science.gov (United States)

    Li, XueYan; Wang, ChunXia; Cheng, JinYun; Zhang, Jing; da Silva, Jaime A Teixeira; Liu, XiaoYu; Duan, Xin; Li, TianLai; Sun, HongMei

    2014-12-19

    The formation and development of bulblets are crucial to the Lilium genus since these processes are closely related to carbohydrate metabolism, especially to starch and sucrose metabolism. However, little is known about the transcriptional regulation of both processes. To gain insight into carbohydrate-related genes involved in bulblet formation and development, we conducted comparative transcriptome profiling of Lilium davidii var. unicolor bulblets at 0 d, 15 d (bulblets emerged) and 35 d (bulblets formed a basic shape with three or four scales) after scale propagation. Analysis of the transcriptome revealed that a total of 52,901 unigenes with an average sequence size of 630 bp were generated. Based on Clusters of Orthologous Groups (COG) analysis, 8% of the sequences were attributed to carbohydrate transport and metabolism. The results of KEGG pathway enrichment analysis showed that starch and sucrose metabolism constituted the predominant pathway among the three library pairs. The starch content in mother scales and bulblets decreased and increased, respectively, with almost the same trend as sucrose content. Gene expression analysis of the key enzymes in starch and sucrose metabolism suggested that sucrose synthase (SuSy) and invertase (INV), mainly hydrolyzing sucrose, presented higher gene expression in mother scales and bulblets at stages of bulblet appearance and enlargement, while sucrose phosphate synthase (SPS) showed higher expression in bulblets at morphogenesis. The enzymes involved in the starch synthetic direction such as ADPG pyrophosphorylase (AGPase), soluble starch synthase (SSS), starch branching enzyme (SBE) and granule-bound starch synthase (GBSS) showed a decreasing trend in mother scales and higher gene expression in bulblets at bulblet appearance and enlargement stages while the enzyme in the cleavage direction, starch de-branching enzyme (SDBE), showed higher gene expression in mother scales than in bulblets. An extensive transcriptome

  12. From elementary flux modes to elementary flux vectors: Metabolic pathway analysis with arbitrary linear flux constraints

    Science.gov (United States)

    Klamt, Steffen; Gerstl, Matthias P.; Jungreuthmayer, Christian; Mahadevan, Radhakrishnan; Müller, Stefan

    2017-01-01

    Elementary flux modes (EFMs) emerged as a formal concept to describe metabolic pathways and have become an established tool for constraint-based modeling and metabolic network analysis. EFMs are characteristic (support-minimal) vectors of the flux cone that contains all feasible steady-state flux vectors of a given metabolic network. EFMs account for (homogeneous) linear constraints arising from reaction irreversibilities and the assumption of steady state; however, other (inhomogeneous) linear constraints, such as minimal and maximal reaction rates frequently used by other constraint-based techniques (such as flux balance analysis [FBA]), cannot be directly integrated. These additional constraints further restrict the space of feasible flux vectors and turn the flux cone into a general flux polyhedron in which the concept of EFMs is not directly applicable anymore. For this reason, there has been a conceptual gap between EFM-based (pathway) analysis methods and linear optimization (FBA) techniques, as they operate on different geometric objects. One approach to overcome these limitations was proposed ten years ago and is based on the concept of elementary flux vectors (EFVs). Only recently has the community started to recognize the potential of EFVs for metabolic network analysis. In fact, EFVs exactly represent the conceptual development required to generalize the idea of EFMs from flux cones to flux polyhedra. This work aims to present a concise theoretical and practical introduction to EFVs that is accessible to a broad audience. We highlight the close relationship between EFMs and EFVs and demonstrate that almost all applications of EFMs (in flux cones) are possible for EFVs (in flux polyhedra) as well. In fact, certain properties can only be studied with EFVs. Thus, we conclude that EFVs provide a powerful and unifying framework for constraint-based modeling of metabolic networks. PMID:28406903

  13. Quantitative Multilevel Analysis of Central Metabolism in Developing Oilseeds of Oilseed Rape during in Vitro Culture1[OPEN

    Science.gov (United States)

    Schwender, Jörg; Hebbelmann, Inga; Heinzel, Nicolas; Hildebrandt, Tatjana; Rogers, Alistair; Klapperstück, Matthias; Schreiber, Falk; Borisjuk, Ljudmilla; Rolletschek, Hardy

    2015-01-01

    Seeds provide the basis for many food, feed, and fuel products. Continued increases in seed yield, composition, and quality require an improved understanding of how the developing seed converts carbon and nitrogen supplies into storage. Current knowledge of this process is often based on the premise that transcriptional regulation directly translates via enzyme concentration into flux. In an attempt to highlight metabolic control, we explore genotypic differences in carbon partitioning for in vitro cultured developing embryos of oilseed rape (Brassica napus). We determined biomass composition as well as 79 net fluxes, the levels of 77 metabolites, and 26 enzyme activities with specific focus on central metabolism in nine selected germplasm accessions. Overall, we observed a tradeoff between the biomass component fractions of lipid and starch. With increasing lipid content over the spectrum of genotypes, plastidic fatty acid synthesis and glycolytic flux increased concomitantly, while glycolytic intermediates decreased. The lipid/starch tradeoff was not reflected at the proteome level, pointing to the significance of (posttranslational) metabolic control. Enzyme activity/flux and metabolite/flux correlations suggest that plastidic pyruvate kinase exerts flux control and that the lipid/starch tradeoff is most likely mediated by allosteric feedback regulation of phosphofructokinase and ADP-glucose pyrophosphorylase. Quantitative data were also used to calculate in vivo mass action ratios, reaction equilibria, and metabolite turnover times. Compounds like cyclic 3′,5′-AMP and sucrose-6-phosphate were identified to potentially be involved in so far unknown mechanisms of metabolic control. This study provides a rich source of quantitative data for those studying central metabolism. PMID:25944824

  14. THE EFFECT OF JOB SATISFACTION ON IT EMPLOYEES TURNOVER INTENTION IN ISRAEL

    Directory of Open Access Journals (Sweden)

    Ladelsky Limor

    2014-07-01

    Full Text Available Employee voluntary turnover is very costly for companies, particularly for the Hi-Tech sector, where the costs of their IT labor force is expensive. Employees\\' voluntary turnover has substantial negative impacts on the companies especially costs, potential loss of valuable knowledge, skills and organizational knowledge.That is why it becomes a critical issue to take address. Studies have been carried out on the reasons which lead to this tendency, however the ability to explain and predict it remains restricted.The objective of this paper is to present the reasons for voluntary turnover of employees in the IT sector in Israel from the IT employees` perspective. A broad analysis of the field literature led to the following groups of causes affecting voluntary turnover: organizational causes: Human Resource Management (HRM related, organizational culture, job related, leadership and internal marketing related; extra organizational causes: individual and, respectively, labor market related causes. This could be approached as n light of this review this article will focus on one of the extra organizational causes of voluntary turnover, i.e. the effect of job satisfaction on voluntary turnover intention among IT employees in Hi-Tech companies in Israel. This correlation was researched in an extensive empirical study among two population groups: IT employees and IT managers and by using mixed method research (combination of quantitative and qualitative research.The findings that supported the literature show job satisfaction has a negative effect on voluntary turnover intention among IT employees in Hi-Tech companies in Israel. Additionally, it was found that job satisfaction indirectly affects voluntary turnover intentions and that emotional variables such as commitment, motivation and loyalty mediate voluntary turnover intention.This finding is supported partially in the literature which only pointed out commitment as a mediating factor in the

  15. Predictors of Staff Turnover and Turnover Intentions within Addiction Treatment Settings: Change over Time Matters

    Directory of Open Access Journals (Sweden)

    Bryan R. Garner

    2014-01-01

    Full Text Available This study examined the extent to which changes over time in clinicians’ responses to measures of work attitude (eg, job satisfaction and psychological climate (eg, supervisor support could predict actual turnover and turnover intentions above and beyond absolute levels of these respective measures. Longitudinal data for this study were collected from a sample of clinicians ( N = 96 being trained to implement an evidence-based treatment for adolescent substance use disorders. Supporting findings from a recent staff turnover study, we found job satisfaction change was able to predict actual turnover above and beyond average levels of job satisfaction. Representing new contributions to the staff turnover literature, we also found that change over time in several other key measures (eg, job satisfaction, role manageability, role clarity explained a significant amount of variance in turnover intentions above and beyond the absolute level of each respective measure. A key implication of the current study is that organizations seeking to improve their ability to assess risk for staff turnover may want to consider assessing staff at multiple points in time in order to identify systematic changes in key employee attitudes like turnover intentions and job satisfaction.

  16. The Effect of Organizational Justice on Accountants’ Job Satisfaction and Turnover Intention

    Directory of Open Access Journals (Sweden)

    Gökhan ÖZER

    2010-12-01

    Full Text Available The purpose of this study is to investigate how the accounting profession members’ who work dependently in accounting firms (vocational trainees, CAs and CPAs perception of organizational justice effect the formation of job satisfaction and turnover intention in order to understand and put forward the phenomenon of turnover among accountants. Organizational justice has been investigated under the sub-dimensions as distributive and procedurel justice. According to the findings attained as a result of the analysis of the data obtained from the survey that was carried out with 240 accountants working in different regions of Turkey and who were chosen randomly for this study; 1 as procedural justice perception increase accountants’ job satisfaction increase as well but their turnover intention decrease 2 as job satisfaction increase accountant’ turnover intention decrease

  17. Análise comparativa da concentração industrial e de turnover da indústria farmacêutica no Brasil para os segmentos de medicamentos de marca e genéricos Comparative analysis of the Industrial Concentration and Turnover of the pharmaceutical industry in Brazil for the segments of mark and generic drugs

    Directory of Open Access Journals (Sweden)

    Gerson Rosenberg

    2010-04-01

    Full Text Available Este artigo analisa a evolução da estrutura do segmento de medicamentos de marca e genéricos no Brasil a partir de 1997. Após a entrada dos medicamentos genéricos, constatou-se que não houve diminuição significativa da concentração na indústria farmacêutica brasileira, porém, o mesmo não ocorreu em nível mundial, verificando-se um aumento da concentração a partir de 2001, impulsionado pelo expressivo processo de fusões e aquisições nos últimos anos da década de 1990. Em relação ao turnover, notou-se que este foi muito baixo para o grupo das maiores empresas em ambos os segmentos de medicamentos. Entretanto, observa-se um elevado turnover com a entrada dos genéricos, mostrando o fortalecimento da indústria nacional. Verifica-se que o processo de fusões e aquisições entre empresas nacionais é pouco significativo, o que pode ser uma alternativa para as pequenas empresas farmacêuticas aumentarem a sua participação no mercado brasileiro.This paper analyzes the evolution of brand-name and generic drugs structure in Brazil since 1997. After the introduction of generic drugs it was not verified a significant decrease in the concentration of Brazilian pharmaceutical industry. The process of mergers and acquisitions in the 90's enhanced the process of concentration in the international market. However, a non-expressive turnover can be demonstrated in both pharmaceutical and generic markets. At the same time, the entrance of the generic industry in Brazil explains the invigoration of the national industry. The mergers and acquisitions process in the pharmaceutical industry is quite intense in Europe and in the USA, although in Brazil it is still not significant.

  18. GAM: a web-service for integrated transcriptional and metabolic network analysis.

    Science.gov (United States)

    Sergushichev, Alexey A; Loboda, Alexander A; Jha, Abhishek K; Vincent, Emma E; Driggers, Edward M; Jones, Russell G; Pearce, Edward J; Artyomov, Maxim N

    2016-07-08

    Novel techniques for high-throughput steady-state metabolomic profiling yield information about changes of nearly thousands of metabolites. Such metabolomic profiles, when analyzed together with transcriptional profiles, can reveal novel insights about underlying biological processes. While a number of conceptual approaches have been developed for data integration, easily accessible tools for integrated analysis of mammalian steady-state metabolomic and transcriptional data are lacking. Here we present GAM ('genes and metabolites'): a web-service for integrated network analysis of transcriptional and steady-state metabolomic data focused on identification of the most changing metabolic subnetworks between two conditions of interest. In the web-service, we have pre-assembled metabolic networks for humans, mice, Arabidopsis and yeast and adapted exact solvers for an optimal subgraph search to work in the context of these metabolic networks. The output is the most regulated metabolic subnetwork of size controlled by false discovery rate parameters. The subnetworks are then visualized online and also can be downloaded in Cytoscape format for subsequent processing. The web-service is available at: https://artyomovlab.wustl.edu/shiny/gam/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Quantifying the metabolic capabilities of engineered Zymomonas mobilis using linear programming analysis

    Directory of Open Access Journals (Sweden)

    Tsantili Ivi C

    2007-03-01

    Full Text Available Abstract Background The need for discovery of alternative, renewable, environmentally friendly energy sources and the development of cost-efficient, "clean" methods for their conversion into higher fuels becomes imperative. Ethanol, whose significance as fuel has dramatically increased in the last decade, can be produced from hexoses and pentoses through microbial fermentation. Importantly, plant biomass, if appropriately and effectively decomposed, is a potential inexpensive and highly renewable source of the hexose and pentose mixture. Recently, the engineered (to also catabolize pentoses anaerobic bacterium Zymomonas mobilis has been widely discussed among the most promising microorganisms for the microbial production of ethanol fuel. However, Z. mobilis genome having been fully sequenced in 2005, there is still a small number of published studies of its in vivo physiology and limited use of the metabolic engineering experimental and computational toolboxes to understand its metabolic pathway interconnectivity and regulation towards the optimization of its hexose and pentose fermentation into ethanol. Results In this paper, we reconstructed the metabolic network of the engineered Z. mobilis to a level that it could be modelled using the metabolic engineering methodologies. We then used linear programming (LP analysis and identified the Z. mobilis metabolic boundaries with respect to various biological objectives, these boundaries being determined only by Z. mobilis network's stoichiometric connectivity. This study revealed the essential for bacterial growth reactions and elucidated the association between the metabolic pathways, especially regarding main product and byproduct formation. More specifically, the study indicated that ethanol and biomass production depend directly on anaerobic respiration stoichiometry and activity. Thus, enhanced understanding and improved means for analyzing anaerobic respiration and redox potential in vivo are

  20. [ABDOMINAL BIOELECTRICAL IMPEDANCE ANALYSIS AND ANTHROPOMETRY FOR PREDICTING METABOLIC SYNDROME IN MIDDLE AGED MEN].

    Science.gov (United States)

    Fernández-Vázquez, Rosalía; Millán Romero, Ángel; Barbancho, Miguel Ángel; Alvero-Cruz, José Ramón

    2015-09-01

    central obesity has a higher risk of metabolic syndrome. The present work aimed to study the relationship of trunk fat and the visceral fat index, and other anthropometric indices in relation to the metabolic syndrome in middle aged male Methods: design: transversal descriptive and correlational study. 75 male, volunteers who have access to a medical assessment, with an age range of 21 to 59 years, from different professions. Weight, height, body mass index, waist circumference, gluteal circumference, waist-to-hip ratio, waist-to-height ratio, trunk fat and visceral fat level by bioelectrical abdominal impedance analysis with Tanita AB-140 (ViScan) and biochemical markers: fasting glucose, total cholesterol, and triglycerides. Likewise, the systolic and diastolic blood pressure was measured. there are significant correlations of anthropometric measurements with trunk fat and visceral fat level and the same with biochemical variables. Receptor-operator curves (ROC curve) analysis shows that the cutoff points from which arises the metabolic syndrome are 32.7% of trunk fat and a level of visceral fat of 13 with a high sensitivity and specificity, attaining the same cut-off points for the metabolic syndrome and obesity status. trunk fat and visceral fat levels determined by bioelectrical abdominal impedance analysis, values are variables very sensitive and specific for the detection of metabolic syndrome and obesity, though not over the variables and anthropometric indices. In the condition of the overweight, trunk fat and visceral fat level are more predictive than anthropometric measures. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  1. Weight-loss-associated changes in bone mineral density and bone turnover after partial weight regain with or without aerobic exercise in obese women.

    Science.gov (United States)

    Hinton, P S; Rector, R S; Linden, M A; Warner, S O; Dellsperger, K C; Chockalingam, A; Whaley-Connell, A T; Liu, Y; Thomas, T R

    2012-05-01

    Moderate, long-term weight loss results in the loss of bone mass in overweight or obese premenopausal women. However, whether these changes persist during weight maintenance or regain remains to be determined. Overweight or obese (body mass index: 25.8-42.5 kg/m(2)) women (n=40) with at least two risk factors for the metabolic syndrome participated in this 12-month study that examined the effects of prescribed weight loss and regain, with or without exercise, on bone turnover and on bone mineral density (BMD) in a subset of participants (n=24). During the first 6 month, participants lost ≈ 10% of their initial body weight via energy restriction and supervised aerobic exercise. Following weight loss, participants were randomly assigned to either an exercise or a no exercise treatment for the regain (+50% of weight lost) phase. A one-way (time) repeated measures one-factor analysis of variance (RMANOVA) tested the effects of weight loss on BMD and bone turnover, and a two-way RMANOVA (time, exercise) was used to examine the effects of exercise during weight regain. Hip (P=0.007) and lumbar spine (P=0.05) BMD decreased with weight loss, and remained reduced after weight regain with or without exercise. Likewise, the weight-loss-associated increases in osteocalcin (Pexercise. The results of the present study, which is the first to examine changes in bone mass and turnover during carefully controlled weight regain, suggest that weight-loss-induced perturbations in bone mass and turnover persist after partial weight regain, regardless of whether regular weight-bearing aerobic exercise was continued.

  2. Glutathione turnover in 14 rat tissues

    International Nuclear Information System (INIS)

    Potter, D.W.; Tran, T.

    1990-01-01

    GSH is a tripeptide found in all tissues and is important in maintaining cellular redox status. First-order rate constants for GSH turnover were determined for various tissues of Fischer male rats. Animals were administered [ 35 S]Cys by tail vein injection and GSH turnover was estimated by the decrease in GSH specific activity following incorporation of Cys, 1-102 hr after administration. Tissue nonprotein sulfhydryls (NPSH) were detected by Ellman's assay and compared with GSH and Cys concentrations determined by HPLC with electrochemical detection. [ 35 S]GSH was analyzed by HPLC equipped with a flow-through radioactivity detector. Although total GSH and Cys were usually slightly lower than NPSH concentrations for the tissues examined, both assay systems gave comparable results. An exception was the glandular stomach which had approximately 2-fold higher NPSH. Liver and kidney had rapid turnover rates with GSH half-lives between 2-5 hr, while heart and skeletal muscle tissue had half-lives of 80-90 hr. Turnover in the blood was slowest, with a half-life of 170 hr. Gastrointestinal tract tissues were shown to have intermediate turnover rates of the following order: glandular stomach > duodenum = small intestine = caecum = large intestine = colon > forestomach. GSH half-life in lung and skin was approximately 45 hr. These studies indicate that tissues utilize GSH at markedly different rates

  3. Culture environment regulates amino acid turnover and glucose utilisation in human ES cells.

    Science.gov (United States)

    Rathjen, Joy; Yeo, Christine; Yap, Charlotte; Tan, Boon Siang Nicholas; Rathjen, Peter D; Gardner, David K

    2014-06-01

    Human embryonic stem (ES) cells have been proposed as a renewable source of pluripotent cells that can be differentiated into various cell types for use in research, drug discovery and in the emerging area of regenerative medicine. Exploitation of this potential will require the development of ES cell culture conditions that promote pluripotency and a normal cell metabolism, and quality control parameters that measure these outcomes. There is, however, relatively little known about the metabolism of pluripotent cells or the impact of culture environment and differentiation on their metabolic pathways. The effect of two commonly used medium supplements and cell differentiation on metabolic indicators in human ES cells were examined. Medium modifications and differentiation were compared in a chemically defined and feeder-independent culture system. Adding serum increased glucose utilisation and altered amino acid turnover by the cells, as well as inducing a small proportion of the cells to differentiate. Cell differentiation could be mitigated by inhibiting p38 mitogen-activated protein kinase (p38 MAPK activity). The addition of Knockout Serum Replacer also increased glucose uptake and changed amino acid turnover by the cells. These changes were distinct from those induced by serum and occurred in the absence of detectable differentiation. Induction of differentiation by bone morphogenetic protein 4 (BMP4), in contrast, did not alter metabolite turnover. Deviations from metabolite turnover by ES cells in fully defined medium demonstrated that culture environment can alter metabolite use. The challenge remains to understand the impact of metabolic changes on long-term cell maintenance and the functionality of derived cell populations.

  4. The Link between HR Attributions and Employees’ Turnover Intentions

    Directory of Open Access Journals (Sweden)

    Juliana Caesaria Tandung

    2016-02-01

    Full Text Available Human Resources Management (HRM is part of the organizational functions that contribute to the effectiveness of a firm’s performance, and brings an organization a competitive advantage through the implementation of its Human Resources (HR practices. HR practices adopted by management are perceived or attributed subjectively by individual employees, and can in turn affect the employees’ attitudes and behavior (e.g. Job satisfaction and turnover intention. The purpose of this study is to contribute to the process-based approach by investigating the effect of HR attributions on turnover intentions, with job satisfaction playing a mediating role. The analysis is on the individual level, with 454 respondents from various organizations within the Netherlands. The results show that HR attributions can affect the turnover intention, through the presence of job satisfaction. Thus, it can be said that it is important to always consider the employees’ attitudes and behavior when examining their perception of HR practices, and in predicting their intention to leave.

  5. Genome-scale metabolic analysis of Clostridium thermocellum for bioethanol production

    Directory of Open Access Journals (Sweden)

    Brooks J Paul

    2010-03-01

    Full Text Available Abstract Background Microorganisms possess diverse metabolic capabilities that can potentially be leveraged for efficient production of biofuels. Clostridium thermocellum (ATCC 27405 is a thermophilic anaerobe that is both cellulolytic and ethanologenic, meaning that it can directly use the plant sugar, cellulose, and biochemically convert it to ethanol. A major challenge in using microorganisms for chemical production is the need to modify the organism to increase production efficiency. The process of properly engineering an organism is typically arduous. Results Here we present a genome-scale model of C. thermocellum metabolism, iSR432, for the purpose of establishing a computational tool to study the metabolic network of C. thermocellum and facilitate efforts to engineer C. thermocellum for biofuel production. The model consists of 577 reactions involving 525 intracellular metabolites, 432 genes, and a proteomic-based representation of a cellulosome. The process of constructing this metabolic model led to suggested annotation refinements for 27 genes and identification of areas of metabolism requiring further study. The accuracy of the iSR432 model was tested using experimental growth and by-product secretion data for growth on cellobiose and fructose. Analysis using this model captures the relationship between the reduction-oxidation state of the cell and ethanol secretion and allowed for prediction of gene deletions and environmental conditions that would increase ethanol production. Conclusions By incorporating genomic sequence data, network topology, and experimental measurements of enzyme activities and metabolite fluxes, we have generated a model that is reasonably accurate at predicting the cellular phenotype of C. thermocellum and establish a strong foundation for rational strain design. In addition, we are able to draw some important conclusions regarding the underlying metabolic mechanisms for observed behaviors of C. thermocellum

  6. A multi-tissue type genome-scale metabolic network for analysis of whole-body systems physiology

    OpenAIRE

    Bordbar, Aarash; Feist, Adam M; Usaite-Black, Renata; Woodcock, Joseph; Palsson, Bernhard O; Famili, Iman

    2011-01-01

    Abstract Background Genome-scale metabolic reconstructions provide a biologically meaningful mechanistic basis for the genotype-phenotype relationship. The global human metabolic network, termed Recon 1, has recently been reconstructed allowing the systems analysis of human metabolic physiology and pathology. Utilizing high-throughput data, Recon 1 has recently been tailored to different cells and tissues, including the liver, kidney, brain, and alveolar macrophage. These models have shown ut...

  7. Changes of Protein Turnover in Aging Caenorhabditis elegans.

    Science.gov (United States)

    Dhondt, Ineke; Petyuk, Vladislav A; Bauer, Sophie; Brewer, Heather M; Smith, Richard D; Depuydt, Geert; Braeckman, Bart P

    2017-09-01

    Protein turnover rates severely decline in aging organisms, including C. elegans However, limited information is available on turnover dynamics at the individual protein level during aging. We followed changes in protein turnover at one-day resolution using a multiple-pulse 15 N-labeling and accurate mass spectrometry approach. Forty percent of the proteome shows gradual slowdown in turnover with age, whereas only few proteins show increased turnover. Decrease in protein turnover was consistent for only a minority of functionally related protein subsets, including tubulins and vitellogenins, whereas randomly diverging turnover patterns with age were the norm. Our data suggests increased heterogeneity of protein turnover of the translation machinery, whereas protein turnover of ubiquitin-proteasome and antioxidant systems are well-preserved over time. Hence, we presume that maintenance of quality control mechanisms is a protective strategy in aging worms, although the ultimate proteome collapse is inescapable. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Reducing voluntary, avoidable turnover through selection.

    Science.gov (United States)

    Barrick, Murray R; Zimmerman, Ryan D

    2005-01-01

    The authors investigated the efficacy of several variables used to predict voluntary, organizationally avoidable turnover even before the employee is hired. Analyses conducted on applicant data collected in 2 separate organizations (N = 445) confirmed that biodata, clear-purpose attitudes and intentions, and disguised-purpose dispositional retention scales predicted voluntary, avoidable turnover (rs ranged from -.16 to -.22, R = .37, adjusted R = .33). Results also revealed that biodata scales and disguised-purpose retention scales added incremental validity, whereas clear-purpose retention scales did not explain significant incremental variance in turnover beyond what was explained by biodata and disguised-purpose scales. Furthermore, disparate impact (subgroup differences on race, sex, and age) was consistently small (average d = 0.12 when the majority group scored higher than the minority group).

  9. The prevalence, metabolic risk and effects of lifestyle intervention for metabolically healthy obesity: a systematic review and meta-analysis: A PRISMA-compliant article.

    Science.gov (United States)

    Lin, Hanli; Zhang, Liqun; Zheng, Ruizhi; Zheng, Yishan

    2017-11-01

    We conducted a systematic review and meta-analysis to firstly obtain a reliable estimation of the prevalence of metabolically healthy obese (MHO) individuals in obesity, then assessed the risk of developing metabolic abnormalities (MA) among MHO individuals. At last, we evaluated the effects of traditional lifestyle interventions on metabolic level for MHO subjects. A systematic review and meta-analysis (PRISMA) guideline were conducted, and original studies were searched up to December 31, 2016. The prevalence of MHO in obesity from each study was pooled using random effects models. The relative risks (RRs) were pooled to determine the risk of developing MA for MHO compared with metabolically healthy normal-weight (MHNW) subjects. For the meta-analysis of intervention studies, the mean difference and standardized mean differences were both estimated for each metabolic parameter within each study, and then pooled using a random-effects model. Overall, 40 population-based studies reported the prevalence of MHO in obesity, 12 cohort studies and 7 intervention studies were included in the meta-analysis. About 35.0% obese individuals were metabolically healthy in the obese subjects. There were dramatic differences in the prevalence among different areas. However, 0.49 (95% confidence intervals [CI]: 0.38 to 0.60) of the MHO individuals would develop one or more MA within 10 years. Compared with MHNW subjects, the MHO subjects presented higher risk of incident MA (pooled RR = 1.80, 95%CI: 1.53-2.11). Following intervention, there was certain and significant improvement of metabolic state for metabolically abnormal obesity (MAO) subjects. Only diastolic blood pressure had reduced for MHO individuals after intervention. Almost one-third of the obese individuals are in metabolic health. However, they are still at higher risk of advancing to unhealthy state. Therefore, it is still needed to advise MHO individuals to maintain or adopt a healthy lifestyle, so as to

  10. Strategic patent analysis in plant biotechnology: terpenoid indole alkaloid metabolic engineering as a case study.

    Science.gov (United States)

    Miralpeix, Bruna; Sabalza, Maite; Twyman, Richard M; Capell, Teresa; Christou, Paul

    2014-02-01

    The do-it-yourself patent search is a useful alternative to professional patent analysis particularly in the context of publicly funded projects where funds for IP activities may be limited. As a case study, we analysed patents related to the engineering of terpenoid indole alkaloid (TIA) metabolism in plants. We developed a focused search strategy to remove redundancy and reduce the workload without missing important and relevant patents. This resulted in the identification of approximately 50 key patents associated with TIA metabolic engineering in plants, which could form the basis of a more detailed freedom-to-operate analysis. The structural elements of this search strategy could easily be transferred to other contexts, making it a useful generic model for publicly funded research projects. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  11. Proteomic analysis uncovers a metabolic phenotype in C. elegans after nhr-40 reduction of function

    International Nuclear Information System (INIS)

    Pohludka, Michal; Simeckova, Katerina; Vohanka, Jaroslav; Yilma, Petr; Novak, Petr; Krause, Michael W.; Kostrouchova, Marta; Kostrouch, Zdenek

    2008-01-01

    Caenorhabditis elegans has an unexpectedly large number (284) of genes encoding nuclear hormone receptors, most of which are nematode-specific and are of unknown function. We have exploited comparative two-dimensional chromatography of synchronized cultures of wild type C. elegans larvae and a mutant in nhr-40 to determine if proteomic approaches will provide additional insight into gene function. Chromatofocusing, followed by reversed-phase chromatography and mass spectrometry, identified altered chromatographic patterns for a set of proteins, many of which function in muscle and metabolism. Prompted by the proteomic analysis, we find that the penetrance of the developmental phenotypes in the mutant is enhanced at low temperatures and by food restriction. The combination of our phenotypic and proteomic analysis strongly suggests that NHR-40 provides a link between metabolism and muscle development. Our results highlight the utility of comparative two-dimensional chromatography to provide a relatively rapid method to gain insight into gene function

  12. A minimal growth medium for the basidiomycetePleurotus sapidusfor metabolic flux analysis.

    Science.gov (United States)

    Fraatz, Marco A; Naeve, Stefanie; Hausherr, Vanessa; Zorn, Holger; Blank, Lars M

    2014-01-01

    Pleurotus sapidus secretes a huge enzymatic repertoire including hydrolytic and oxidative enzymes and is an example for higher basidiomycetes being interesting for biotechnology. The complex growth media used for submerged cultivation limit basic physiological analyses of this group of organisms. Using undefined growth media, only little insights into the operation of central carbon metabolism and biomass formation, i.e. , the interplay of catabolic and anabolic pathways, can be gained. The development of a chemically defined growth medium allowed rapid growth of P. sapidus in submerged cultures. As P. sapidus grew extremely slow in salt medium, the co-utilization of amino acids using 13 C-labelled glucose was investigated by gas chromatography-mass spectrometry (GC-MS) analysis. While some amino acids were synthesized up to 90% in vivo from glucose ( e.g., alanine), asparagine and/or aspartate were predominantly taken up from the medium. With this information in hand, a defined yeast free salt medium containing aspartate and ammonium nitrate as a nitrogen source was developed. The observed growth rates of P. sapidus were well comparable with those previously published for complex media. Importantly, fast growth could be observed for 4 days at least, up to cell wet weights (CWW) of 400 g L -1 . The chemically defined medium was used to carry out a 13 C-based metabolic flux analysis, and the in vivo reactions rates in the central carbon metabolism of P. sapidus were investigated. The results revealed a highly respiratory metabolism with high fluxes through the pentose phosphate pathway and TCA cycle. The presented chemically defined growth medium enables researchers to study the metabolism of P. sapidus , significantly enlarging the analytical capabilities. Detailed studies on the production of extracellular enzymes and of secondary metabolites of P. sapidus may be designed based on the reported data.

  13. Metabolic effect of obesity on polycystic ovary syndrome in adolescents: a meta-analysis.

    Science.gov (United States)

    Li, Li; Feng, Qiong; Ye, Ming; He, Yaojuan; Yao, Aling; Shi, Kun

    2017-11-01

    This meta-analysis provides an updated and comprehensive estimate of the effects of obesity on metabolic disorders in adolescent polycystic ovary syndrome (PCOS). Relevant articles consistent with the search terms published up to 31 January 2014 were retrieved from PubMed, EMBASE, PsycINFO and CENTRAL. Thirteen articles (16 independent studies) conformed to the inclusion criteria. The evaluated outcomes were the metabolic parameters of obese adolescents with PCOS (case group) relative to normal-weight adolescents with PCOS, or obese adolescents without PCOS. Compared with normal-weight adolescents with PCOS, the case group had significantly lower sex hormone-binding globulin and high-density lipoprotein cholesterol, and significantly higher triglycerides, leptin, fasting insulin, low-density lipoprotein cholesterol and free testosterone levels. Relative to obese adolescents without PCOS, the case group had significantly higher fasting insulin, low-density lipoprotein cholesterol, free testosterone levels and 2-h glucose during the oral glucose tolerance test. These results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant obesity. This study highlights the importance of preventing obesity during the management of adolescent PCOS. Impact statement What is already known about this subject: Obesity and PCOS share many of the same metabolic disorders, for example, hyperandrogenism and hyperinsulinemia with subsequent insulin resistance. Knowledge regarding metabolic features in obese adolescents with PCOS is limited, and there is concern whether obesity and PCOS are related. What do the results of this study add: Relative to PCOS adolescents of normal weight, obese adolescents with PCOS (the case group) had significantly lower SHBG and HDL-C, and significantly higher triglycerides, leptin, fasting insulin, LDL-C and free testosterone levels. The results indicate that metabolic disorders in adolescent PCOS are worsened by concomitant

  14. Systematic identification and analysis of frequent gene fusion events in metabolic pathways.

    Science.gov (United States)

    Henry, Christopher S; Lerma-Ortiz, Claudia; Gerdes, Svetlana Y; Mullen, Jeffrey D; Colasanti, Ric; Zhukov, Aleksey; Frelin, Océane; Thiaville, Jennifer J; Zallot, Rémi; Niehaus, Thomas D; Hasnain, Ghulam; Conrad, Neal; Hanson, Andrew D; de Crécy-Lagard, Valérie

    2016-06-24

    Gene fusions are the most powerful type of in silico-derived functional associations. However, many fusion compilations were made when fusions need updating to handle the current avalanche of sequenced genomes. The availability of a large fusion dataset would help probe functional associations and enable systematic analysis of where and why fusion events occur. Here we present a systematic analysis of fusions in prokaryotes. We manually generated two training sets: (i) 121 fusions in the model organism Escherichia coli; (ii) 131 fusions found in B vitamin metabolism. These sets were used to develop a fusion prediction algorithm that captured the training set fusions with only 7 % false negatives and 50 % false positives, a substantial improvement over existing approaches. This algorithm was then applied to identify 3.8 million potential fusions across 11,473 genomes. The results of the analysis are available in a searchable database at http://modelseed.org/projects/fusions/ . A functional analysis identified 3,000 reactions associated with frequent fusion events and revealed areas of metabolism where fusions are particularly prevalent. Customary definitions of fusions were shown to be ambiguous, and a stricter one was proposed. Exploring the genes participating in fusion events showed that they most commonly encode transporters, regulators, and metabolic enzymes. The major rationales for fusions between metabolic genes appear to be overcoming pathway bottlenecks, avoiding toxicity, controlling competing pathways, and facilitating expression and assembly of protein complexes. Finally, our fusion dataset provides powerful clues to decipher the biological activities of domains of unknown function.

  15. Formulation, construction and analysis of kinetic models of metabolism: A review of modelling frameworks

    DEFF Research Database (Denmark)

    Saa, Pedro A.; Nielsen, Lars K.

    2017-01-01

    Kinetic models are critical to predict the dynamic behaviour of metabolic networks. Mechanistic kinetic models for large networks remain uncommon due to the difficulty of fitting their parameters. Recent modelling frameworks promise new ways to overcome this obstacle while retaining predictive...... capabilities. In this review, we present an overview of the relevant mathematical frameworks for kinetic formulation, construction and analysis. Starting with kinetic formalisms, we next review statistical methods for parameter inference, as well as recent computational frameworks applied to the construction...

  16. Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

    OpenAIRE

    Pérez-Plasencia, Carlos; Vázquez-Ortiz, Guelaguetza; López-Romero, Ricardo; Piña-Sanchez, Patricia; Moreno, José; Salcedo, Mauricio

    2007-01-01

    Abstract Background Cervical carcinoma (CC) is a leading cause of death among women worldwide. Human papilloma virus (HPV) is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways. Results We found 2,067 genes significantly up or down-modulated (a...

  17. Effects of the mitogen concanavalin A on pathways of thymocyte energy metabolism.

    Science.gov (United States)

    Krauss, S; Buttgereit, F; Brand, M D

    1999-06-30

    The lectin concanavalin A (Con A) acts as a mitogen that preferentially activates T-cells. It stimulates the energy metabolism of thymocytes within seconds of exposure. We studied short-term effects (<30 min) of Con A on a conceptually simplified model system of rat thymocyte energy metabolism in the concentration range of 0-2 microg Con A per 107 cells, using metabolic control analysis. The model system consisted of three blocks of reactions, linked by the common intermediate mitochondrial membrane potential (Delta[psi]m): the substrate oxidation reactions, which produce the linking intermediate, and the proton conductance (or leak) and ATP turnover pathways which consume Delta[psi]m. Firstly, we used top-down elasticity analysis to establish which subsystems are targeted by Con A. Secondly, we quantitatively analysed the steady-state regulation of the system variables by Con A: how do the subsystem fluxes respond to Con A individually and as a whole? Our results indicate that: (1) steady-state respiration and Delta[psi]m increase as Con A concentration is raised, but at higher concentrations the increase in respiration is less and Delta[psi]m falls; (2) Con A independently changes the kinetics of the reactions that produce and consume Delta[psi]m: the Delta[psi]m-producing reactions are inhibited, and the reactions involved in ATP turnover are stimulated; and (3) the overall effects of Con A are mostly mediated by effects on ATP turnover.

  18. Prevalence of metabolic syndrome in Bangladesh: a systematic review and meta-analysis of the studies.

    Science.gov (United States)

    Chowdhury, Mohammad Ziaul Islam; Anik, Ataul Mustufa; Farhana, Zaki; Bristi, Piali Dey; Abu Al Mamun, B M; Uddin, Mohammad Jasim; Fatema, Jain; Akter, Tanjila; Tani, Tania Akhter; Rahman, Meshbahur; Turin, Tanvir C

    2018-03-02

    Metabolic syndrome (MS) is a cluster of health problems that set the stage for serious health conditions and places individuals at higher risk of cardiovascular disease, diabetes and stroke. The worldwide prevalence of MS in the adult population is on the rise and Bangladesh is no exception. According to some epidemiological study, MS is highly prevalent in Bangladesh and has increased dramatically in last few decades. To provide a clear picture of the current situation, we conducted a systematic review and meta-analysis with an objective to assess the prevalence of metabolic syndrome among the Bangladeshi population using data already published in the scientific literature. We searched MEDLINE, EMBASE and PubMed and manually checked references of all identified relevant publications that described the prevalence of MS in Bangladesh. Random effects meta-analysis was used to pool the prevalence. Heterogeneity was explored using formal tests and subgroup analyses. Study quality and publication bias was also explored. Electronic and grey literature search retrieved 491 potentially relevant papers. After removing duplicates, reviewing titles and abstracts and screening full texts, 10 studies were finally selected. Most of the studies were conducted in rural populations and study participants were mostly females. The weighted pooled prevalence of metabolic syndrome regardless of gender and criteria used to define metabolic syndrome, was 30.0% with high heterogeneity observed. Weighted pooled prevalence of metabolic syndrome is higher in females (32%) compared to males (25%) though not statistically significant (p = 0.434). Prevalence was highest (37%) when Modified NCEP ATP III criteria was used to define MS, while it was lowest (20%) when WHO criteria was used. In most cases, geographical area (urban/rural) was identified as a source of heterogeneity between the studies. Most of the studies met study quality assessment criteria's except adequate sample size

  19. Gene expression analysis of a critical enzyme in intermediary metabolism in oyster pathogen Perkinsus marinus .

    Science.gov (United States)

    Noell, K.

    2016-02-01

    A key regulatory component in the Krebs cycle pathway is the mitochondrial aconitase enzyme which has been posited to balance energy needs and oxidative growth total storage via citrate utilization. The presence of a cytosolic aconitase (cAcon) activity which serves as a competitor for citrate substrate has been recognized for years. cAcon is a dual function protein with mutually exclusive roles as a post transcriptional regulator of animal cell iron metabolism or as the cytosolic isoform of the iron sulfur enzyme aconitase. We are interested in establishing the role of this orthologue in Perkinsus marnius metabolism through demonstrating its function as aconitase, by looking at gene expression under certain environmental conditions. P. marinus is a close evolutionary relative of the dinoflagellates and is the causative agent of Dermo disease, which has significantly impacted oyster populations along the eastern seaboard. An understanding of intermediary metabolism will yield important insights into how c-aconitase may be involved in stress response systems such as oxidative tension and metabolite deficiency, which could be used to help aquaculturists alleviate the severe impact of "dermo" on the on the oyster population. This study will present data regarding our preliminary analysis of the gene aconitase and its role in intermediary metabolism.

  20. Optimization of 13C isotopic tracers for metabolic flux analysis in mammalian cells.

    Science.gov (United States)

    Walther, Jason L; Metallo, Christian M; Zhang, Jie; Stephanopoulos, Gregory

    2012-03-01

    Mammalian cells consume and metabolize various substrates from their surroundings for energy generation and biomass synthesis. Glucose and glutamine, in particular, are the primary carbon sources for proliferating cancer cells. While this combination of substrates generates static labeling patterns for use in (13)C metabolic flux analysis (MFA), the inability of single tracers to effectively label all pathways poses an obstacle for comprehensive flux determination within a given experiment. To address this issue we applied a genetic algorithm to optimize mixtures of (13)C-labeled glucose and glutamine for use in MFA. We identified tracer combinations that minimized confidence intervals in an experimentally determined flux network describing central carbon metabolism in tumor cells. Additional simulations were used to determine the robustness of the [1,2-(13)C(2)]glucose/[U-(13)C(5)]glutamine tracer combination with respect to perturbations in the network. Finally, we experimentally validated the improved performance of this tracer set relative to glucose tracers alone in a cancer cell line. This versatile method allows researchers to determine the optimal tracer combination to use for a specific metabolic network, and our findings applied to cancer cells significantly enhance the ability of MFA experiments to precisely quantify fluxes in higher organisms. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Metabolomics analysis reveals the metabolic and functional roles of flavonoids in light-sensitive tea leaves.

    Science.gov (United States)

    Zhang, Qunfeng; Liu, Meiya; Ruan, Jianyun

    2017-03-20

    As the predominant secondary metabolic pathway in tea plants, flavonoid biosynthesis increases with increasing temperature and illumination. However, the concentration of most flavonoids decreases greatly in light-sensitive tea leaves when they are exposed to light, which further improves tea quality. To reveal the metabolism and potential functions of flavonoids in tea leaves, a natural light-sensitive tea mutant (Huangjinya) cultivated under different light conditions was subjected to metabolomics analysis. The results showed that chlorotic tea leaves accumulated large amounts of flavonoids with ortho-dihydroxylated B-rings (e.g., catechin gallate, quercetin and its glycosides etc.), whereas total flavonoids (e.g., myricetrin glycoside, epigallocatechin gallate etc.) were considerably reduced, suggesting that the flavonoid components generated from different metabolic branches played different roles in tea leaves. Furthermore, the intracellular localization of flavonoids and the expression pattern of genes involved in secondary metabolic pathways indicate a potential photoprotective function of dihydroxylated flavonoids in light-sensitive tea leaves. Our results suggest that reactive oxygen species (ROS) scavenging and the antioxidation effects of flavonoids help chlorotic tea plants survive under high light stress, providing new evidence to clarify the functional roles of flavonoids, which accumulate to high levels in tea plants. Moreover, flavonoids with ortho-dihydroxylated B-rings played a greater role in photo-protection to improve the acclimatization of tea plants.

  2. Metabolic Effects of Hypoxia in Colorectal Cancer by 13C NMR Isotopomer Analysis

    Directory of Open Access Journals (Sweden)

    Ana M. Abrantes

    2014-01-01

    Full Text Available 13C NMR isotopomer analysis was used to characterize intermediary metabolism in three colorectal cancer cell lines (WiDr, LS1034, and C2BBe1 and determine the “metabolic remodeling” that occurs under hypoxia. Under normoxia, the three colorectal cancer cell lines present high rates of lactate production and can be seen as “Warburg” like cancer cells independently of substrate availability, since such profile was dominant at both high and low glucose media contents. The LS1034 was the less glycolytic of the three cell lines and was the most affected by the event of hypoxia, raising abruptly glucose consumption and lactate production. The other two colorectal cell lines, WiDr and C2BBe1, adapted better to hypoxia and were able to maintain their oxidative fluxes even at the very low levels of oxygen. These differential metabolic behaviors of the three colorectal cell lines show how important an adequate knowledge of the “metabolic remodeling” that follows a given cancer treatment is towards the correct (redesign of therapeutic strategies against cancer.

  3. [18F]FMeNER-D2: A systematic in vitro analysis of radio-metabolism

    International Nuclear Information System (INIS)

    Rami-Mark, Christina; Eberherr, Nadine; Berroterán-Infante, Neydher; Vanicek, Thomas; Nics, Lukas; Lanzenberger, Rupert; Hacker, Marcus; Wadsak, Wolfgang; Mitterhauser, Markus

    2016-01-01

    Introduction: The norepinephrine transporter (NET) presents an important target for therapy and diagnosis of ADHD and other neurodegenerative and psychiatric diseases. Thus, PET is the diagnostic method of choice, using radiolabeled NET-ligands derived from reboxetine. So far, [ 18 F]FMeNER-D2 showed best pharmacokinetic and -dynamic properties. However, the disadvantage of reboxetine derived PET tracers is their high metabolic cleavage—resulting in impeding signals in the PET scans, which hamper a proper quantification of the NET in cortical areas. Methods: Metabolic stability testing was performed in vitro using a plethora of human and murine enzymes. Results: No metabolism was observed using monoamine oxidase A and B or catechol-O-methyl transferase. Incubation of [ 18 F]FMeNER-D2 with CYP450-enzymes, predominantly located in the liver, led to a significant and fast metabolism of the tracer. Moreover, the arising three radiometabolites were found to be more polar than [ 18 F]FMeNER-D2. Surprisingly, definitely no formation of free [ 18 F]fluoride was observed. Conclusion: According to our in vitro data, the interfering uptake in cortical regions might be attributed to these emerging radiometabolites but does not reflect bonding in bone due to defluorination. Further research on these radiometabolites is necessary to elucidate the in vivo situation. This might include an analysis of human blood samples after injection of [ 18 F]FMeNER-D2, to enable a better correction of the PET-input function.

  4. Comparative evaluation of labelling patterns and turnover of lipids, tagged by 15 (p-123I-phenyl-)pentadecanoic and 1-14C-palmitic acid

    International Nuclear Information System (INIS)

    Reske, S.N.; Sauer, W.; Reichmann, K.; Winkler, C.; Machulla, H.J.; Knust, E.J.

    1984-01-01

    Uptake and turnover of chloroform/methanol extractable tissue lipids labelled in vivo simultaneously with 15(p- 123 I-phenyl-)pentadecanoic and 1- 14 C-palmitic acid were compared. Lipid turnover studies were performed in fasted pentobarbital-anaesthetized Wistar rats in tissues with highly varying free fatty acid turnover rates. In all tissues investigated, i.e. heart, lung, liver, spleen and kidney, both tracers labelled nearly identical lipid fractions. The main tracer uptake was found in free fatty acids, phospholipids, diglycerides and triglycerides. A highly significant correlation of uptake and turnover in main tissue lipid fractions indicated an essentially identical metabolic pathway of both tracers in intermediary tissue lipid metabolism. Concordant tracer uptake and turnover patterns in tissue of lipids with highly varying fatty acid metabolic rates suggested that intrinsic metabolic activity of the tissue and respective lipid fraction was the major determinant of metabolic handling of both iodophenyl fatty- and palmitic acid. Thus, the feasibility of iodophenylpentadecanoic acid as free fatty acid tracer for studying tissue lipid metabolism is demonstrated. (author)

  5. Analysis of Land-Use Emergy Indicators Based on Urban Metabolism: A Case Study for Beijing

    Directory of Open Access Journals (Sweden)

    Qing Huang

    2015-06-01

    Full Text Available The correlation of urban metabolism and changes in land use is an important issue in urban ecology, but recent research lacks consideration of the mechanisms and interactions between them. In this research, we did an emergy analysis of the flows of materials, energy, and capital within the socioeconomic system of Beijing. We calculated emergy-based evaluation indices of urban metabolism and land use change, to analyze the relationship between urban metabolism and land use by correlation analysis and regression analysis. Results indicate that the socio-economic activities on built-up land depend on local, non-renewable resource exploitation and external resource inputs. The emergy utilization efficiency of farmland has consistently decreased, but there remains significant utilization potential there. Urban development in Beijing relies on production activities on built-up land, which is subjected to great environmental pressure during extraction of material resources. To keep the economy developing effectively, we suggest that Beijing should commit to development of a circular economy, and change the land-use concept to “Smart Growth”. In this paper, we efficaciously solve the problem of conflicting measurement units, and avoid the disadvantages of subjective assignment. Consequently, this work provides not only a more scientific way to study land problems, but also provides a reliable reference for ecological construction and economic development in Beijing.

  6. Urban water metabolism efficiency assessment: integrated analysis of available and virtual water.

    Science.gov (United States)

    Huang, Chu-Long; Vause, Jonathan; Ma, Hwong-Wen; Yu, Chang-Ping

    2013-05-01

    Resolving the complex environmental problems of water pollution and shortage which occur during urbanization requires the systematic assessment of urban water metabolism efficiency (WME). While previous research has tended to focus on either available or virtual water metabolism, here we argue that the systematic problems arising during urbanization require an integrated assessment of available and virtual WME, using an indicator system based on material flow analysis (MFA) results. Future research should focus on the following areas: 1) analysis of available and virtual water flow patterns and processes through urban districts in different urbanization phases in years with varying amounts of rainfall, and their environmental effects; 2) based on the optimization of social, economic and environmental benefits, establishment of an indicator system for urban WME assessment using MFA results; 3) integrated assessment of available and virtual WME in districts with different urbanization levels, to facilitate study of the interactions between the natural and social water cycles; 4) analysis of mechanisms driving differences in WME between districts with different urbanization levels, and the selection of dominant social and economic driving indicators, especially those impacting water resource consumption. Combinations of these driving indicators could then be used to design efficient water resource metabolism solutions, and integrated management policies for reduced water consumption. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. A Swellable Microneedle Patch to Rapidly Extract Skin Interstitial Fluid for Timely Metabolic Analysis.

    Science.gov (United States)

    Chang, Hao; Zheng, Mengjia; Yu, Xiaojun; Than, Aung; Seeni, Razina Z; Kang, Rongjie; Tian, Jingqi; Khanh, Duong Phan; Liu, Linbo; Chen, Peng; Xu, Chenjie

    2017-10-01

    Skin interstitial fluid (ISF) is an emerging source of biomarkers for disease diagnosis and prognosis. Microneedle (MN) patch has been identified as an ideal platform to extract ISF from the skin due to its pain-free and easy-to-administrated properties. However, long sampling time is still a serious problem which impedes timely metabolic analysis. In this study, a swellable MN patch that can rapidly extract ISF is developed. The MN patch is made of methacrylated hyaluronic acid (MeHA) and further crosslinked through UV irradiation. Owing to the supreme water affinity of MeHA, this MN patch can extract sufficient ISF in a short time without the assistance of extra devices, which remarkably facilitates timely metabolic analysis. Due to covalent crosslinked network, the MN patch maintains the structure integrity in the swelling hydrated state without leaving residues in skin after usage. More importantly, the extracted ISF metabolites can be efficiently recovered from MN patch by centrifugation for the subsequent offline analysis of metabolites such as glucose and cholesterol. Given the recent trend of easy-to-use point-of-care devices for personal healthcare monitoring, this study opens a new avenue for the development of MN-based microdevices for sampling ISF and minimally invasive metabolic detection. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Transcriptomic Analysis of Metabolic Pathways in Milkfish That Respond to Salinity and Temperature Changes.

    Science.gov (United States)

    Hu, Yau-Chung; Kang, Chao-Kai; Tang, Cheng-Hao; Lee, Tsung-Han

    2015-01-01

    Milkfish (Chanos chanos), an important marine aquaculture species in southern Taiwan, show considerable euryhalinity but have low tolerance to sudden drops in water temperatures in winter. Here, we used high throughput next-generation sequencing (NGS) to identify molecular and biological processes involved in the responses to environmental changes. Preliminary tests revealed that seawater (SW)-acclimated milkfish tolerated lower temperatures than the fresh water (FW)-acclimated group. Although FW- and SW-acclimated milkfish have different levels of tolerance for hypothermal stress, to date, the molecular physiological basis of this difference has not been elucidated. Here, we performed a next-generation sequence analysis of mRNAs from four groups of milkfish. We obtained 29669 unigenes with an average length of approximately 1936 base pairs. Gene ontology (GO) analysis was performed after gene annotation. A large number of genes for molecular regulation were identified through a transcriptomic comparison in a KEGG analysis. Basal metabolic pathways involved in hypothermal tolerance, such as glycolysis, fatty acid metabolism, amino acid catabolism and oxidative phosphorylation, were analyzed using PathVisio and Cytoscape software. Our results indicate that in response to hypothermal stress, genes for oxidative phosphorylation, e.g., succinate dehydrogenase, were more highly up-regulated in SW than FW fish. Moreover, SW and FW milkfish used different strategies when exposed to hypothermal stress: SW milkfish up-regulated oxidative phosphorylation and catabolism genes to produce more energy budget, whereas FW milkfish down-regulated genes related to basal metabolism to reduce energy loss.

  9. COMPLETE-MFA: complementary parallel labeling experiments technique for metabolic flux analysis.

    Science.gov (United States)

    Leighty, Robert W; Antoniewicz, Maciek R

    2013-11-01

    We have developed a novel approach for measuring highly accurate and precise metabolic fluxes in living cells, termed COMPLETE-MFA, short for complementary parallel labeling experiments technique for metabolic flux analysis. The COMPLETE-MFA method is based on combined analysis of multiple isotopic labeling experiments, where the synergy of using complementary tracers greatly improves the precision of estimated fluxes. In this work, we demonstrate the COMPLETE-MFA approach using all singly labeled glucose tracers, [1-(13)C], [2-(13)C], [3-(13)C], [4-(13)C], [5-(13)C], and [6-(13)C]glucose to determine precise metabolic fluxes for wild-type Escherichia coli. Cells were grown in six parallel cultures on defined medium with glucose as the only carbon source. Mass isotopomers of biomass amino acids were measured by gas chromatography-mass spectrometry (GC-MS). The data from all six experiments were then fitted simultaneously to a single flux model to determine accurate intracellular fluxes. We obtained a statistically acceptable fit with more than 300 redundant measurements. The estimated flux map is the most precise flux result obtained thus far for E. coli cells. To our knowledge, this is the first time that six isotopic labeling experiments have been successfully integrated for high-resolution (13)C-flux analysis. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Inositol lipid turnover and compartmentation in canine trachealis smooth muscle

    International Nuclear Information System (INIS)

    Baron, C.B.; Pring, M.; Coburn, R.F.

    1989-01-01

    We established conditions for the study of metabolism and compartmentation of inositol phospholipids in canine trachealis muscle. Unstimulated muscle was incubated with myo-[3H]inositol for 30 min at 37 degrees C which resulted in labeling of the tissue free myo-inositol pool, whereas only a small amount of radioactivity was incorporated into inositol phospholipids or inositol phosphates. After addition of 5.5 microM carbachol, phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2), specific radioactivities increased exponentially, reaching apparent constant values in 180-240 min. Initial rates of increases in PI, PIP, and PIP2 specific radioactivities were 39, 32, and 66 times that measured in unstimulated muscle. Metabolic flux rates (nmol.100 nmol total lipid Pi-1.min-1) during development of force averaged 0.42 +/- 0.09 and during force maintenance averaged 0.14 +/- 0.01. Fractions of total PI, PIP, and PIP2 pools that were linked to muscarinic cholinergic activation were estimated to be 0.97, 0.85, and 0.65, respectively. Initial rates of increase in specific radioactivities and specific radioactivities during carbachol activation were similar in PI, PIP, and PIP2 fast active compartments, suggesting metabolic flux from PI to PIP to PIP2 was in near chemical equilibrium. Turnover times for PI, PIP, and PIP2 fast active compartments were estimated to be 21, 1.6, and 4.0 min, respectively

  11. Rest break organization in geriatric care and turnover: a multimethod cross-sectional study.

    Science.gov (United States)

    Wendsche, Johannes; Hacker, Winfried; Wegge, Jürgen; Schrod, Nadine; Roitzsch, Katharina; Tomaschek, Anne; Kliegel, Matthias

    2014-09-01

    Various determinants of nurses' work motivation and turnover behavior have been examined in previous studies. In this research, we extend this work by investigating the impact of care setting (nursing homes vs. home care services) and the important role of rest break organization. We aimed to identify direct and indirect linkages between geriatric care setting, rest break organization, and registered nurses' turnover assessed over a period of one year. We designed a multimethod cross-sectional study. 80 nursing units (n=45 nursing homes, n=35 home care) in 51 German geriatric care services employing 597 registered nurses. We gathered documentary, interview, and observational data about the organization of rest breaks, registered nurses' turnover, and additional organizational characteristics (type of ownership, location, nursing staff, clients, and client-to-staff-ratio). The findings show that the rest break system in geriatric nursing home units is more regularly as well as collectively organized and causes less unauthorized rest breaks than in home care units. Moreover, the feasibility of collective rest breaks was, as predicted, negatively associated with registered nurses' turnover and affected indirectly the relation between care setting and registered nurses' turnover. Care setting, however, had no direct impact on turnover. Furthermore, registered nurses' turnover was higher in for-profit care units than in public or non-profit units. This study reveals significant differences in rest break organization as a function of geriatric care setting and highlights the role of collective rest breaks for nursing staff retention. Our study underlines the integration of organizational context variables and features of rest break organization for the analysis of nursing turnover. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Dynamic structure of stock communities: a comparative study between stock returns and turnover rates

    Science.gov (United States)

    Su, Li-Ling; Jiang, Xiong-Fei; Li, Sai-Ping; Zhong, Li-Xin; Ren, Fei

    2017-07-01

    The detection of community structure in stock market is of theoretical and practical significance for the study of financial dynamics and portfolio risk estimation. We here study the community structures in Chinese stock markets from the aspects of both price returns and turnover rates, by using a combination of the PMFG and infomap methods based on a distance matrix. An empirical study using the overall data set shows that for both returns and turnover rates the largest communities are composed of specific industrial or conceptional sectors and the correlation inside a sector is generally larger than the correlation between different sectors. However, the community structure for turnover rates is more complex than that for returns, which indicates that the interactions between stocks revealed by turnover rates may contain more information. This conclusion is further confirmed by the analysis of the changes in the dynamics of community structures over five sub-periods. Sectors like banks, real estate, health care and New Shanghai take turns to comprise a few of the largest communities in different sub-periods, and more interestingly several specific sectors appear in the communities with different rank orders for returns and turnover rates even in the same sub-period. To better understand their differences, a comparison between the evolution of the returns and turnover rates of the stocks from these sectors is conducted. We find that stock prices only had large changes around important events while turnover rates surged after each of these events relevant to specific sectors, which shows strong evidence that the turnover rates are more susceptible to exogenous shocks than returns and its measurement for community detection may contain more useful information about market structure.

  13. Work engagement, burnout and related constructs as predictors of turnover intentions

    Directory of Open Access Journals (Sweden)

    Janine du Plooy

    2010-12-01

    Research purpose: The main purpose of the study was to determine whether work engagement, burnout, organisational citizenship behaviour (OCB and work alienation are predictors of turnover intentions. Motivation for the study: Organisations operating within the 21st century face significant challenges in the management of talent and human capital. One in particular is voluntary employee turnover and the lack of appropriate business models to track this process. Research design, approach and method: A secondary data analysis (SDA was performed in a quantitative research tradition on the cross-sectional survey data collected from a large South African Information and Communication Technologies (ICT sector company (n = 2429. Main findings: The results of the study confirmed the predictive model (work engagement, burnout, OCB and work alienation of turnover intention. Specifically, work engagement and OCBs were significantly negatively related to turnover intention; whilst burnout and work alienation were significantly positively related to turnover intention. Several third-variable relationships, such as biographic and demographic variables, indicated statistical significance. Practical/managerial implications: Practical implications of the study could impact on human resource (HR value-chain activities in the form of evidence-based and improved recruitment and selection procedures, employee retention strategies and training and development interventions. Issues concerning talent management could also be addressed. Contribution/value-add: The study described in this article took Industrial/Organisational (I/O psychological concepts and linked them in unique combinations to establish better predictive validity of a new turnover intentions model.

  14. Impact of work environment and work-related stress on turnover intention in physical therapists.

    Science.gov (United States)

    Lee, Byoung-Kwon; Seo, Dong-Kwon; Lee, Jang-Tae; Lee, A-Ram; Jeon, Ha-Neul; Han, Dong-Uk

    2016-08-01

    [Purpose] This study was conducted to provide basic data for solutions to reduce the turnover rate of physical therapists. It should help create efficient personnel and organization management by exploring the impact of the work environment and work-related stress on turnover intention and analyzing the correlation between them. [Subjects and Methods] A survey was conducted with 236 physical therapists working at medical institutions in the Daejeon and Chungcheong areas. For the analysis on the collected data, correlational and linear regression analyses were conducted using the SPSS 18.0 program and Cronbach's alpha coefficient. [Results] The results showed a statistically significant positive correlation between turnover intention and work-related stress but a statistically significant negative correlation respectively between turnover intention and work environment. Work-related stress (β=0.415) had a significant positive impact on turnover intention and work environment (β=-0.387) had a significant negative impact on turnover intention. [Conclusion] To increase satisfaction level with the profession as well as the workplace for physical therapists, improvement of the work environment was the most necessary primary improvement.

  15. Quantitative Metabolomics and Instationary 13C-Metabolic Flux Analysis Reveals Impact of Recombinant Protein Production on Trehalose and Energy Metabolism in Pichia pastoris

    NARCIS (Netherlands)

    Jorda, J.; Cueto Rojas, H.F.; Carnicer, M.; Wahl, S.A.; Ferrer, P.; Albiol, J.

    2014-01-01

    Pichia pastoris has been recognized as an effective host for recombinant protein production. In this work, we combine metabolomics and instationary 13C metabolic flux analysis (INST 13C-MFA) using GC-MS and LC-MS/MS to evaluate the potential impact of the production of a Rhizopus oryzae lipase (Rol)

  16. Comparison between elementary flux modes analysis and 13C-metabolic fluxes measured in bacterial and plant cells.

    Science.gov (United States)

    Beurton-Aimar, Marie; Beauvoit, Bertrand; Monier, Antoine; Vallée, François; Dieuaide-Noubhani, Martine; Colombié, Sophie

    2011-06-20

    (13)C metabolic flux analysis is one of the pertinent ways to compare two or more physiological states. From a more theoretical standpoint, the structural properties of metabolic networks can be analysed to explore feasible metabolic behaviours and to define the boundaries of steady state flux distributions. Elementary flux mode analysis is one of the most efficient methods for performing this analysis. In this context, recent approaches have tended to compare experimental flux measurements with topological network analysis. Metabolic networks describing the main pathways of central carbon metabolism were set up for a bacteria species (Corynebacterium glutamicum) and a plant species (Brassica napus) for which experimental flux maps were available. The structural properties of each network were then studied using the concept of elementary flux modes. To do this, coefficients of flux efficiency were calculated for each reaction within the networks by using selected sets of elementary flux modes. Then the relative differences - reflecting the change of substrate i.e. a sugar source for C. glutamicum and a nitrogen source for B. napus - of both flux efficiency and flux measured experimentally were compared. For both organisms, there is a clear relationship between these parameters, thus indicating that the network structure described by the elementary flux modes had captured a significant part of the metabolic activity in both biological systems. In B. napus, the extension of the elementary flux mode analysis to an enlarged metabolic network still resulted in a clear relationship between the change in the coefficients and that of the measured fluxes. Nevertheless, the limitations of the method to fit some particular fluxes are discussed. This consistency between EFM analysis and experimental flux measurements, validated on two metabolic systems allows us to conclude that elementary flux mode analysis could be a useful tool to complement (13)C metabolic flux analysis

  17. Resuscitation of ischemic donor livers with normothermic machine perfusion: a metabolic flux analysis of treatment in rats.

    Directory of Open Access Journals (Sweden)

    Maria-Louisa Izamis

    Full Text Available Normothermic machine perfusion has previously been demonstrated to restore damaged warm ischemic livers to transplantable condition in animal models. However, the mechanisms of recovery are unclear, preventing rational optimization of perfusion systems and slowing clinical translation of machine perfusion. In this study, organ recovery time and major perfusate shortcomings were evaluated using a comprehensive metabolic analysis of organ function in perfusion prior to successful transplantation. Two groups, Fresh livers and livers subjected to 1 hr of warm ischemia (WI received perfusion for a total preservation time of 6 hrs, followed by successful transplantation. 24 metabolic fluxes were directly measured and 38 stoichiometrically-related fluxes were estimated via a mass balance model of the major pathways of energy metabolism. This analysis revealed stable metabolism in Fresh livers throughout perfusion while identifying two distinct metabolic states in WI livers, separated at t = 2 hrs, coinciding with recovery of oxygen uptake rates to Fresh liver values. This finding strongly suggests successful organ resuscitation within 2 hrs of perfusion. Overall perfused livers regulated metabolism of perfusate substrates according to their metabolic needs, despite supraphysiological levels of some metabolites. This study establishes the first integrative metabolic basis for the dynamics of recovery during perfusion treatment of marginal livers. Our initial findings support enhanced oxygen delivery for both timely recovery and long-term sustenance. These results are expected to lead the optimization of the treatment protocols and perfusion media from a metabolic perspective, facilitating translation to clinical use.

  18. Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality.

    Science.gov (United States)

    Jiang, Yue; Xiong, Xuejian; Danska, Jayne; Parkinson, John

    2016-01-12

    Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. At the same time, our findings show how microbiome complexity and availability of

  19. Metabolic flux analysis of Cyanothece sp. ATCC 51142 under mixotrophic conditions.

    Science.gov (United States)

    Alagesan, Swathi; Gaudana, Sandeep B; Sinha, Avinash; Wangikar, Pramod P

    2013-11-01

    Cyanobacteria are a group of photosynthetic prokaryotes capable of utilizing solar energy to fix atmospheric carbon dioxide to biomass. Despite several "proof of principle" studies, low product yield is an impediment in commercialization of cyanobacteria-derived biofuels. Estimation of intracellular reaction rates by (13)C metabolic flux analysis ((13)C-MFA) would be a step toward enhancing biofuel yield via metabolic engineering. We report (13)C-MFA for Cyanothece sp. ATCC 51142, a unicellular nitrogen-fixing cyanobacterium, known for enhanced hydrogen yield under mixotrophic conditions. Rates of reactions in the central carbon metabolism under nitrogen-fixing and -non-fixing conditions were estimated by monitoring the competitive incorporation of (12)C and (13)C from unlabeled CO2 and uniformly labeled glycerol, respectively, into terminal metabolites such as amino acids. The observed labeling patterns suggest mixotrophic growth under both the conditions, with a larger fraction of unlabeled carbon in nitrate-sufficient cultures asserting a greater contribution of carbon fixation by photosynthesis and an anaplerotic pathway. Indeed, flux analysis complements the higher growth observed under nitrate-sufficient conditions. On the other hand, the flux through the oxidative pentose phosphate pathway and tricarboxylic acid cycle was greater in nitrate-deficient conditions, possibly to supply the precursors and reducing equivalents needed for nitrogen fixation. In addition, an enhanced flux through fructose-6-phosphate phosphoketolase possibly suggests the organism's preferred mode under nitrogen-fixing conditions. The (13)C-MFA results complement the reported predictions by flux balance analysis and provide quantitative insight into the organism's distinct metabolic features under nitrogen-fixing and -non-fixing conditions.

  20. Reconstruction and in silico analysis of metabolic network for an oleaginous yeast, Yarrowia lipolytica.

    Directory of Open Access Journals (Sweden)

    Pengcheng Pan

    Full Text Available With the emergence of energy scarcity, the use of renewable energy sources such as biodiesel is becoming increasingly necessary. Recently, many researchers have focused their minds on Yarrowia lipolytica, a model oleaginous yeast, which can be employed to accumulate large amounts of lipids that could be further converted to biodiesel. In order to understand the metabolic characteristics of Y. lipolytica at a systems level and to examine the potential for enhanced lipid production, a genome-scale compartmentalized metabolic network was reconstructed based on a combination of genome annotation and the detailed biochemical knowledge from multiple databases such as KEGG, ENZYME and BIGG. The information about protein and reaction associations of all the organisms in KEGG and Expasy-ENZYME database was arranged into an EXCEL file that can then be regarded as a new useful database to generate other reconstructions. The generated model iYL619_PCP accounts for 619 genes, 843 metabolites and 1,142 reactions including 236 transport reactions, 125 exchange reactions and 13 spontaneous reactions. The in silico model successfully predicted the minimal media and the growing abilities on different substrates. With flux balance analysis, single gene knockouts were also simulated to predict the essential genes and partially essential genes. In addition, flux variability analysis was applied to design new mutant strains that will redirect fluxes through the network and may enhance the production of lipid. This genome-scale metabolic model of Y. lipolytica can facilitate system-level metabolic analysis as well as strain development for improving the production of biodiesels and other valuable products by Y. lipolytica and other closely related oleaginous yeasts.

  1. Hibernation, stress, intestinal functions, and catecholoamine turnover rate in hamsters and gerbils

    Science.gov (United States)

    Musacchia, X. J.

    1973-01-01

    Bioenergetic studies on hamsters during depressed metabolic states are reported. External support of blood glucose extended the survival times of hibernating animals. Radioresistance increased in hibernating as well as in hypothermic hamsters. Marked changes in hamster catecholamine turnover rates were observed during acclimatization to high temperature stress. High radioresistance levels of the gerbil gastrointestinal system were attributed in part to the ability of the gut to maintain functional integrity.

  2. The influence of a steroid hormone and of physical exercise on protein metabolism in rats

    International Nuclear Information System (INIS)

    Menschikowski, M.; Jung, K.; Junghans, P.; Petzke, K.J.; Albrecht, V.; Akademie der Wissenschaften der DDR, Potsdam

    1989-01-01

    The influence of an anabolic steroid hormone preparation and of a physical exercise training program was studied on the nitrogen and protein metabolism in rats with the help of the 15 N tracer technique and the emission spectrometric 15 N isotope analysis. For the determination of the dynamic parameters of the protein metabolism graphic (stochastic) and computer-aided compartmental methods wer compared. Using the area method as a stochastic approach the animals showed significant differences in the protein turnover parameters under the influence of hormone treatment and (or) physical stress by swimming exercise in comparison to the controls. (author)

  3. redGEM: Systematic reduction and analysis of genome-scale metabolic reconstructions for development of consistent core metabolic models.

    Directory of Open Access Journals (Sweden)

    Meric Ataman

    2017-07-01

    Full Text Available Genome-scale metabolic reconstructions have proven to be valuable resources in enhancing our understanding of metabolic networks as they encapsulate all known metabolic capabilities of the organisms from genes to proteins to their functions. However the complexity of these large metabolic networks often hinders their utility in various practical applications. Although reduced models are commonly used for modeling and in integrating experimental data, they are often inconsistent across different studies and laboratories due to different criteria and detail, which can compromise transferability of the findings and also integration of experimental data from different groups. In this study, we have developed a systematic semi-automatic approach to reduce genome-scale models into core models in a consistent and logical manner focusing on the central metabolism or subsystems of interest. The method minimizes the loss of information using an approach that combines graph-based search and optimization methods. The resulting core models are shown to be able to capture key properties of the genome-scale models and preserve consistency in terms of biomass and by-product yields, flux and concentration variability and gene essentiality. The development of these "consistently-reduced" models will help to clarify and facilitate integration of different experimental data to draw new understanding that can be directly extendable to genome-scale models.

  4. Quantitative elementary mode analysis of metabolic pathways: the example of yeast glycolysis

    Directory of Open Access Journals (Sweden)

    Kanehisa Minoru

    2006-04-01

    Full Text Available Abstract Background Elementary mode analysis of metabolic pathways has proven to be a valuable tool for assessing the properties and functions of biochemical systems. However, little comprehension of how individual elementary modes are used in real cellular states has been achieved so far. A quantitative measure of fluxes carried by individual elementary modes is of great help to identify dominant metabolic processes, and to understand how these processes are redistributed in biological cells in response to changes in environmental conditions, enzyme kinetics, or chemical concentrations. Results Selecting a valid decomposition of a flux distribution onto a set of elementary modes is not straightforward, since there is usually an infinite number of possible such decompositions. We first show that two recently introduced decompositions are very closely related and assign the same fluxes to reversible elementary modes. Then, we show how such decompositions can be used in combination with kinetic modelling to assess the effects of changes in enzyme kinetics on the usage of individual metabolic routes, and to analyse the range of attainable states in a metabolic system. This approach is illustrated by the example of yeast glycolysis. Our results indicate that only a small subset of the space of stoichiometrically feasible steady states is actually reached by the glycolysis system, even when large variation intervals are allowed for all kinetic parameters of the model. Among eight possible elementary modes, the standard glycolytic route remains dominant in all cases, and only one other elementary mode is able to gain significant flux values in steady state. Conclusion These results indicate that a combination of structural and kinetic modelling significantly constrains the range of possible behaviours of a metabolic system. All elementary modes are not equal contributors to physiological cellular states, and this approach may open a direction toward a

  5. Phylogenomic analysis of secondary metabolism genes sheds light on their evolution in Aspergilli

    DEFF Research Database (Denmark)

    Theobald, Sebastian; Vesth, Tammi Camilla; Rasmussen, Jane Lind Nybo

    .Natural products are encoded by genes located in close proximity, called secondary metabolic gene clusters, which makes them interesting targets for genomic analysis. We use a modified version of the Secondary Metabolite Unique Regions Finder (SMURF) algorithm, combined with InterPro annotations to create...... thereof, find possible common ancestors and detect horizontal gene transfer events.Finally, we have performed large scale analysis of gene cluster dynamics and evolution, which provides us with better understanding of speciation in Aspergilli. With this new insights into the evolution of natural products...

  6. Antecedents of Norwegian Beginning Teachers' Turnover Intentions

    Science.gov (United States)

    Tiplic, Dijana; Brandmo, Christian; Elstad, Eyvind

    2015-01-01

    This study aims at exploring several individual, organizational, and contextual factors that may affect beginning teachers' turnover intentions during their first years of practice. The sample consists of 227 beginning teachers (69% female and 31% male) from 133 schools in Norway. The results show four important antecedents of beginning teachers'…

  7. Health care workplace discrimination and physician turnover.

    Science.gov (United States)

    Nunez-Smith, Marcella; Pilgrim, Nanlesta; Wynia, Matthew; Desai, Mayur M; Bright, Cedric; Krumholz, Harlan M; Bradley, Elizabeth H

    2009-12-01

    To examine the association between physician race/ ethnicity, workplace discrimination, and physician job turnover. Cross-sectional, national survey conducted in 2006-2007 of practicing physicians (n = 529) randomly identified via the American Medical Association Masterfile and the National Medical Association membership roster. We assessed the relationships between career racial/ethnic discrimination at work and several career-related dependent variables, including 2 measures of physician turnover, career satisfaction, and contemplation of career change. We used standard frequency analyses, odds ratios and chi2 statistics, and multivariate logistic regression modeling to evaluate these associations. Physicians who self-identified as nonmajority were significantly more likely to have left at least 1 job because of workplace discrimination (black, 29%; Asian, 24%; other race, 21%; Hispanic/Latino, 20%; white, 9%). In multivariate models, having experienced racial/ethnic discrimination at work was associated with high job turnover (adjusted odds ratio, 2.7; 95% CI, 1.4-4.9). Among physicians who experienced workplace discrimination, only 45% of physicians were satisfied with their careers (vs 88% among those who had not experienced workplace discrimination, p value workplace discrimination, p value Workplace discrimination is associated with physician job turnover, career dissatisfaction, and contemplation of career change. These findings underscore the importance of monitoring for workplace discrimination and responding when opportunities for intervention and retention still exist.

  8. A Turnover Model for the Mexican Maquiladoras.

    Science.gov (United States)

    Maertz, Carl P.; Stevens, Michael J.; Campion, Michael A.

    2003-01-01

    From interviews with 47 Mexican maquiladora workers, a model of voluntary turnover was created and compared with models from the United States, Canada, England, and Australia. Despite similarities, the cultural and economic environment affected the precise content of antecedents in the Mexican model. (Contains 63 references.) (SK)

  9. Primary care physician turnover in HMOs.

    Science.gov (United States)

    Kerstein, J; Pauly, M V; Hillman, A

    1994-01-01

    OBJECTIVE. We assess whether physician turnover stems from incorrect physician expectations about the practice environment or from actual constraints or rewards in that environment. DATA SOURCES. Our primary data source contains information about individual HMOs' primary care physicians incentive mechanisms and general HMO characteristics. Our secondary data source is the area resource file (ARF), which contains countywide information about the HMOs' market areas, including physician characteristics, population characteristics, and other market characteristics. DATA COLLECTION. Our primary data source is from a nationwide survey of all HMOs in operation in 1987-1988, as reported to Interstudy. PRINCIPAL FINDINGS. We find that turnover is higher on the part of physicians whose HMO enrollment comprises a greater percentage of their total practice. Our results further indicate that physicians whose compensation is dependent on the behavior of a group of other physicians are more likely to leave the plan than those who bear the risk (and control it) more directly. On the other hand, turnover is increased by basing bonuses on individual productivity and by not sharing surpluses among a group. Market characteristics also are significant in explaining physician turnover in HMOs. CONCLUSIONS. It appears that physicians accurately forecast how they will react to individual financial risk, although they dislike restrictions imposed by HMOs. PMID:8163378

  10. Does Judge Turnover Affect Judicial Performance?

    DEFF Research Database (Denmark)

    Guerra, Alice; Tagliapietra, Claudio

    2017-01-01

    Italy is among the countries with the highest litigation rate and those with the highest duration of trials. This article shows that judge turnover contributes negatively to delays in Italian courts and outlines possible policies for improvement. In Italy, judges can voluntarily move from one off...

  11. Robustness analysis of a constraint-based metabolic model links cell growth and proteomics of Thermoanaerobacter tengcongensis under temperature perturbation.

    Science.gov (United States)

    Tong, Wei; Chen, Zhen; Cao, Zhe; Wang, Quanhui; Zhang, Jiyuan; Bai, Xue; Wang, Rong; Liu, Siqi

    2013-04-05

    The integration of omic data with metabolic networks has been demonstrated to be an effective approach to elucidate the underlying metabolic mechanisms in life. Because the metabolic pathways of Thermoanaerobacter tengcongensis (T. tengcongensis) are incomplete, we used a 1-(13)C-glucose culture to monitor intracellular isotope-labeled metabolites by GC/MS and identified the gap gene in glucose catabolism, Re-citrate synthase. Based on genome annotation and biochemical information, we reconstructed the metabolic network of glucose metabolism and amino acid synthesis in T. tengcongensis, including 253 reactions, 227 metabolites, and 236 genes. Furthermore, we performed constraint based modeling (CBM)-derived robustness analysis on the model to study the dynamic changes of the metabolic network. By perturbing the culture temperature from 75 to 55 °C, we collected the bacterial growth rates and differential proteomes. Assuming that protein abundance changes represent metabolic flux variations, we proposed that the robustness analysis of the CBM model could decipher the effect of proteome change on the bacterial growth under perturbation. For approximately 73% of the reactions, the predicted cell growth changes due to such reaction flux variations matched the observed cell growth data. Our study, therefore, indicates that differential proteome data can be integrated with metabolic network modeling and that robustness analysis is a strong method for representing the dynamic change in cell phenotypes under perturbation.

  12. Metabolic syndrome prevalence in Iran: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Farajolah Maleki

    2014-07-01

    Full Text Available Background: Metabolic syndrome (MetS is a complex of risk factors which increase the risk of cardiovascular diseases, type 2 diabetes, morbidity and mortality in people. The aim of this study was to analyze the prevalence of MetS in Iran using a meta-analysis study. Methods: The SID, Magiran, Irandoc, Medlib, Google Scholar and PubMed databases were searched for MetS prevalence. 26 articles conducted between 2003 and 2013 in Iran were selected and the obtained data were analyzed by a meta-analysis using random-effects model. Heterogeneity was assessed using I2 statistics. Data were analyzed by R software and STATA (Ver. 11.2. Results: The total sample size was 60635 people with the age range of 3-90 years. The metabolic syndrome prevalence based on IDF definition was 36% (95% CI: 0.32-0.40 and based to ATPIII was 27% (95% CI: 0.22-0.32. Based on IDF definition, the MetS prevalence rates in women and men were0.39 (95% CI: 0.19-0.59 and 0.20 (95% CI: 0.10-0.29, respectively. Conclusion: The findings showed a high prevalence of metabolic syndrome in Iran, especially in women, which increases with age in both sexes. Health care providers and policy makers need to find solutions to reduce MetS risk in the society.

  13. Novel analysis of oceanic surface water metagenomes suggests importance of polyphosphate metabolism in oligotrophic environments.

    Directory of Open Access Journals (Sweden)

    Ben Temperton

    Full Text Available Polyphosphate is a ubiquitous linear homopolymer of phosphate residues linked by high-energy bonds similar to those found in ATP. It has been associated with many processes including pathogenicity, DNA uptake and multiple stress responses across all domains. Bacteria have also been shown to use polyphosphate as a way to store phosphate when transferred from phosphate-limited to phosphate-rich media--a process exploited in wastewater treatment and other environmental contaminant remediation. Despite this, there has, to date, been little research into the role of polyphosphate in the survival of marine bacterioplankton in oligotrophic environments. The three main proteins involved in polyphosphate metabolism, Ppk1, Ppk2 and Ppx are multi-domain and have differential inter-domain and inter-gene conservation, making unbiased analysis of relative abundance in metagenomic datasets difficult. This paper describes the development of a novel Isofunctional Homolog Annotation Tool (IHAT to detect homologs of genes with a broad range of conservation without bias of traditional expect-value cutoffs. IHAT analysis of the Global Ocean Sampling (GOS dataset revealed that genes associated with polyphosphate metabolism are more abundant in environments where available phosphate is limited, suggesting an important role for polyphosphate metabolism in marine oligotrophs.

  14. Analysis of metabolic and gene expression changes after hydrodynamic DNA injection into mouse liver.

    Science.gov (United States)

    Herrero, Maria Jose; Monleon, Daniel; Morales, Jose Manuel; Mata, Manuel; Serna, Eva; Aliño, Salvador Francisco

    2011-01-01

    The hydrodynamic injection in mice tail vein of a plasmid (40 µg DNA) bearing the human α1-antitrypsin gene mediates: a) good liver gene transfer resulting in therapeutic plasma levels of human protein (1 mg/ml, approximately) from days 1-10 after injection; b) low liver injury as demonstrated by a poor and transient increase of aspartate aminotransferase (AST) and alanine transaminase (ALT) in mouse plasma; 3) limited expression and metabolic changes in host liver genes and metabolites as evaluated on days 2 and 10 after injection. Groups of three mice were uninjected (control) or hydrodynamically injected with saline or plasmid DNA and then sacrificed on days 2 and 10 after injection. The results of principal component analysis (PCA) show, both in expression microarray and metabolomic analysis, that changes between control and hydrodynamically injected groups are not dramatic and tend to normalize after 10 d. The differences are even smaller between DNA and saline hydrodynamically injected mice. Hydrodynamic injection induces a complex but limited gene expression and metabolic change which includes variations in molecules related to energy metabolism and stress response. The results contribute to support that hydrodynamic method is a safe procedure of liver gene transfer but the long-term effect of hydrodynamic gene transfer procedure, remains to be studied.

  15. Satellite remote sensing data can be used to model marine microbial metabolite turnover

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Peter E.; Scott, Nicole; Post, Anton F.; Field, Dawn; Knight, Rob; Hamada, Yuki; Gilbert, Jack A.

    2014-07-29

    Sampling ecosystems, even at a local scale, at the temporal and spatial resolution necessary to capture natural variability in microbial communities are prohibitively expensive. We extrapolated marine surface microbial community structure and metabolic potential from 72 16S rRNA amplicon and 8 metagenomic observations using remotely sensed environmental parameters to create a system-scale model of marine microbial metabolism for 5904 grid cells (49 km2) in the Western English Chanel, across 3 years of weekly averages. Thirteen environmental variables predicted the relative abundance of 24 bacterial Orders and 1715 unique enzyme-encoding genes that encode turnover of 2893 metabolites. The genes’ predicted relative abundance was highly correlated (Pearson Correlation 0.72, P-value <10-6) with their observed relative abundance in sequenced metagenomes. Predictions of the relative turnover (synthesis or consumption) of CO2 were significantly correlated with observed surface CO2 fugacity. The spatial and temporal variation in the predicted relative abundances of genes coding for cyanase, carbon monoxide and malate dehydrogenase were investigated along with the predicted inter-annual variation in relative consumption or production of ~3000 metabolites forming six significant temporal clusters. These spatiotemporal distributions could possibly be explained by the co-occurrence of anaerobic and aerobic metabolisms associated with localized plankton blooms or sediment resuspension, which facilitate the presence of anaerobic micro-niches. This predictive model provides a general framework for focusing future sampling and experimental design to relate biogeochemical turnover to microbial ecology.

  16. Glucose turnover, gluconeogenesis from glycerol, and estimation of net glucose cycling in cancer patients

    International Nuclear Information System (INIS)

    Lundholm, K.; Edstroem, S.; Karlberg, I.; Ekman, L.; Schersten, T.

    1982-01-01

    A double isotope method was used in patients with progressive malignancy and in control patients to measure: glucose turnover, conversion rate of carbon skeleton of glycerol into glucose, and the interorgan cycling of glucose carbons (Cori-cycle plus alanine-glucose cycle). [U- 14 C]glycerol and [6- 3 H]glucose were given intravenously as a single dose injection. The time course of the specific radioactivities of [6- 3 H] and [U- 14 C]glucose was followed in blood. The pool size and the turnover rate of glucose were increased in the cancer group as compared with the control patients. The net recycling of glucose carbons was not increased in the cancer group, despite the increased turnover of glucose. The alterations in the metabolism of glucose did not correlate with the plasma levels of insulin or thyroid hormones (T4, T3, rT3) neither in the entire cancer group nor in those cancer patients who were repeatedly investigated at different intervals of time. The turnover rate of glucose in the cancer patients correlated inversely to their body weight index. The gluconeogenesis rate, given as the fractional conversion rate of the injected radioactive dose of [ 14 C]glycerol, or as mol glucose . kg body weight-1 . day-1, was increased in the cancer group, but still contributed only 3% of the glucose turnover rate in both cancer and control patients. We conclude that an increased gluconeogenesis from glycerol is not significant in terms of energy expenditure in patients with progressive malignancy, as has previously been concluded for the gluconeogenesis from alanine. It seems that increased turnover of glucose may contribute to inappropriately high energy expenditure in cancer patients

  17. 13CFLUX2--high-performance software suite for (13)C-metabolic flux analysis.

    Science.gov (United States)

    Weitzel, Michael; Nöh, Katharina; Dalman, Tolga; Niedenführ, Sebastian; Stute, Birgit; Wiechert, Wolfgang

    2013-01-01

    (13)C-based metabolic flux analysis ((13)C-MFA) is the state-of-the-art method to quantitatively determine in vivo metabolic reaction rates in microorganisms. 13CFLUX2 contains all tools for composing flexible computational (13)C-MFA workflows to design and evaluate carbon labeling experiments. A specially developed XML language, FluxML, highly efficient data structures and simulation algorithms achieve a maximum of performance and effectiveness. Support of multicore CPUs, as well as compute clusters, enables scalable investigations. 13CFLUX2 outperforms existing tools in terms of universality, flexibility and built-in features. Therewith, 13CFLUX2 paves the way for next-generation high-resolution (13)C-MFA applications on the large scale. 13CFLUX2 is implemented in C++ (ISO/IEC 14882 standard) with Java and Python add-ons to run under Linux/Unix. A demo version and binaries are available at www.13cflux.net.

  18. Genome-scale metabolic flux analysis of Streptomyces lividans growing on a complex medium.

    Science.gov (United States)

    D'Huys, Pieter-Jan; Lule, Ivan; Vercammen, Dominique; Anné, Jozef; Van Impe, Jan F; Bernaerts, Kristel

    2012-09-15

    Constraint-based metabolic modeling comprises various excellent tools to assess experimentally observed phenotypic behavior of micro-organisms in terms of intracellular metabolic fluxes. In combination with genome-scale metabolic networks, micro-organisms can be investigated in much more detail and under more complex environmental conditions. Although complex media are ubiquitously applied in industrial fermentations and are often a prerequisite for high protein secretion yields, such multi-component conditions are seldom investigated using genome-scale flux analysis. In this paper, a systematic and integrative approach is presented to determine metabolic fluxes in Streptomyces lividans TK24 grown on a nutritious and complex medium. Genome-scale flux balance analysis and randomized sampling of the solution space are combined to extract maximum information from exometabolome profiles. It is shown that biomass maximization cannot predict the observed metabolite production pattern as such. Although this cellular objective commonly applies to batch fermentation data, both input and output constraints are required to reproduce the measured biomass production rate. Rich media hence not necessarily lead to maximum biomass growth. To eventually identify a unique intracellular flux vector, a hierarchical optimization of cellular objectives is adopted. Out of various tested secondary objectives, maximization of the ATP yield per flux unit returns the closest agreement with the maximum frequency in flux histograms. This unique flux estimation is hence considered as a reasonable approximation for the biological fluxes. Flux maps for different growth phases show no active oxidative part of the pentose phosphate pathway, but NADPH generation in the TCA cycle and NADPH transdehydrogenase activity are most important in fulfilling the NADPH balance. Amino acids contribute to biomass growth by augmenting the pool of available amino acids and by boosting the TCA cycle, particularly

  19. Staff turnover: occasional friend, frequent foe, and continuing frustration.

    Science.gov (United States)

    McConnell, C R

    1999-09-01

    Turnover appears to be a relatively simple concept. However, considerable confusion results when discussing turnover because of differences in how it is defined--what is counted, how it is counted, and how the rate of turnover is expressed. Turnover is also costly, although not enough attention is paid to turnover's cost because so much of it is indirect and thus not readily visible. There are a variety of causes of turnover, some which can be corrected and some which cannot be avoided. Reducing or otherwise controlling turnover requires continuing management attention to its causes and constant recognition of what can and should be controlled and what cannot be controlled. Ongoing attention to turnover is an essential part of the department manager's role.

  20. Work-Related Variables and Turnover Intention among Registered Nurses.

    Science.gov (United States)

    Pooyan, Abdullah; And Others

    1990-01-01

    Health institutions have become more interested in the causes of job turnover among registered nurses. Proper management of job turnover can improve the financial health and long-term survival of health care institutions. (Author)

  1. Proteomic Analysis of the Relationship between Metabolism and Nonhost Resistance in Soybean Exposed to Bipolaris maydis

    Science.gov (United States)

    Dong, Yumei; Su, Yuan; Yu, Ping; Yang, Min; Zhu, Shusheng; Mei, Xinyue; He, Xiahong; Pan, Manhua; Zhu, Youyong; Li, Chengyun

    2015-01-01

    Nonhost resistance (NHR) pertains to the most common form of plant resistance against pathogenic microorganisms of other species. Bipolaris maydis is a non-adapted pathogen affecting soybeans, particularly of maize/soybean intercropping systems. However, no experimental evidence has described the immune response of soybeans against B. maydis. To elucidate the molecular mechanism underlying NHR in soybeans, proteomics analysis based on two-dimensional polyacrylamide gel electrophoresis (2-DE) was performed to identify proteins involved in the soybean response to B. maydis. The spread of B. maydis spores across soybean leaves induced NHR throughout the plant, which mobilized almost all organelles and various metabolic processes in response to B. maydis. Some enzymes, including ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), mitochondrial processing peptidase (MPP), oxygen evolving enhancer (OEE), and nucleoside diphosphate kinase (NDKs), were found to be related to NHR in soybeans. These enzymes have been identified in previous studies, and STRING analysis showed that most of the protein functions related to major metabolic processes were induced as a response to B. maydis, which suggested an array of complex interactions between soybeans and B. maydis. These findings suggest a systematic NHR against non-adapted pathogens in soybeans. This response was characterized by an overlap between metabolic processes and response to stimulus. Several metabolic processes provide the soybean with innate immunity to the non-adapted pathogen, B. maydis. This research investigation on NHR in soybeans may foster a better understanding of plant innate immunity, as well as the interactions between plant and non-adapted pathogens in intercropping systems. PMID:26513657

  2. Proteomic Analysis of the Relationship between Metabolism and Nonhost Resistance in Soybean Exposed to Bipolaris maydis.

    Directory of Open Access Journals (Sweden)

    Yumei Dong

    Full Text Available Nonhost resistance (NHR pertains to the most common form of plant resistance against pathogenic microorganisms of other species. Bipolaris maydis is a non-adapted pathogen affecting soybeans, particularly of maize/soybean intercropping systems. However, no experimental evidence has described the immune response of soybeans against B. maydis. To elucidate the molecular mechanism underlying NHR in soybeans, proteomics analysis based on two-dimensional polyacrylamide gel electrophoresis (2-DE was performed to identify proteins involved in the soybean response to B. maydis. The spread of B. maydis spores across soybean leaves induced NHR throughout the plant, which mobilized almost all organelles and various metabolic processes in response to B. maydis. Some enzymes, including ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO, mitochondrial processing peptidase (MPP, oxygen evolving enhancer (OEE, and nucleoside diphosphate kinase (NDKs, were found to be related to NHR in soybeans. These enzymes have been identified in previous studies, and STRING analysis showed that most of the protein functions related to major metabolic processes were induced as a response to B. maydis, which suggested an array of complex interactions between soybeans and B. maydis. These findings suggest a systematic NHR against non-adapted pathogens in soybeans. This response was characterized by an overlap between metabolic processes and response to stimulus. Several metabolic processes provide the soybean with innate immunity to the non-adapted pathogen, B. maydis. This research investigation on NHR in soybeans may foster a better understanding of plant innate immunity, as well as the interactions between plant and non-adapted pathogens in intercropping systems.

  3. Metabolic reconstruction of sulfur assimilation in the extremophile Acidithiobacillus ferrooxidans based on genome analysis

    Directory of Open Access Journals (Sweden)

    Jedlicki Eugenia

    2003-12-01

    Full Text Available Abstract Background Acidithiobacillus ferrooxidans is a gamma-proteobacterium that lives at pH2 and obtains energy by the oxidation of sulfur and iron. It is used in the biomining industry for the recovery of metals and is one of the causative agents of acid mine drainage. Effective tools for the study of its genetics and physiology are not in widespread use and, despite considerable effort, an understanding of its unusual physiology remains at a rudimentary level. Nearly complete genome sequences of A. ferrooxidans are available from two public sources and we have exploited this information to reconstruct aspects of its sulfur metabolism. Results Two candidate mechanisms for sulfate uptake from the environment were detected but both belong to large paralogous families of membrane transporters and their identification remains tentative. Prospective genes, pathways and regulatory mechanisms were identified that are likely to be involved in the assimilation of sulfate into cysteine and in the formation of Fe-S centers. Genes and regulatory networks were also uncovered that may link sulfur assimilation with nitrogen fixation, hydrogen utilization and sulfur reduction. Potential pathways were identified for sulfation of extracellular metabolites that may possibly be involved in cellular attachment to pyrite, sulfur and other solid substrates. Conclusions A bioinformatic analysis of the genome sequence of A. ferrooxidans has revealed candidate genes, metabolic process and control mechanisms potentially involved in aspects of sulfur metabolism. Metabolic modeling provides an important preliminary step in understanding the unusual physiology of this extremophile especially given the severe difficulties involved in its genetic manipulation and biochemical analysis.

  4. Metabolic reconstruction of sulfur assimilation in the extremophile Acidithiobacillus ferrooxidans based on genome analysis

    Science.gov (United States)

    Valdés, Jorge; Veloso, Felipe; Jedlicki, Eugenia; Holmes, David

    2003-01-01

    Background Acidithiobacillus ferrooxidans is a gamma-proteobacterium that lives at pH2 and obtains energy by the oxidation of sulfur and iron. It is used in the biomining industry for the recovery of metals and is one of the causative agents of acid mine drainage. Effective tools for the study of its genetics and physiology are not in widespread use and, despite considerable effort, an understanding of its unusual physiology remains at a rudimentary level. Nearly complete genome sequences of A. ferrooxidans are available from two public sources and we have exploited this information to reconstruct aspects of its sulfur metabolism. Results Two candidate mechanisms for sulfate uptake from the environment were detected but both belong to large paralogous families of membrane transporters and their identification remains tentative. Prospective genes, pathways and regulatory mechanisms were identified that are likely to be involved in the assimilation of sulfate into cysteine and in the formation of Fe-S centers. Genes and regulatory networks were also uncovered that may link sulfur assimilation with nitrogen fixation, hydrogen utilization and sulfur reduction. Potential pathways were identified for sulfation of extracellular metabolites that may possibly be involved in cellular attachment to pyrite, sulfur and other solid substrates. Conclusions A bioinformatic analysis of the genome sequence of A. ferrooxidans has revealed candidate genes, metabolic process and control mechanisms potentially involved in aspects of sulfur metabolism. Metabolic modeling provides an important preliminary step in understanding the unusual physiology of this extremophile especially given the severe difficulties involved in its genetic manipulation and biochemical analysis. PMID:14675496

  5. Proteomic Analysis of the Relationship between Metabolism and Nonhost Resistance in Soybean Exposed to Bipolaris maydis.

    Science.gov (United States)

    Dong, Yumei; Su, Yuan; Yu, Ping; Yang, Min; Zhu, Shusheng; Mei, Xinyue; He, Xiahong; Pan, Manhua; Zhu, Youyong; Li, Chengyun

    2015-01-01

    Nonhost resistance (NHR) pertains to the most common form of plant resistance against pathogenic microorganisms of other species. Bipolaris maydis is a non-adapted pathogen affecting soybeans, particularly of maize/soybean intercropping systems. However, no experimental evidence has described the immune response of soybeans against B. maydis. To elucidate the molecular mechanism underlying NHR in soybeans, proteomics analysis based on two-dimensional polyacrylamide gel electrophoresis (2-DE) was performed to identify proteins involved in the soybean response to B. maydis. The spread of B. maydis spores across soybean leaves induced NHR throughout the plant, which mobilized almost all organelles and various metabolic processes in response to B. maydis. Some enzymes, including ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), mitochondrial processing peptidase (MPP), oxygen evolving enhancer (OEE), and nucleoside diphosphate kinase (NDKs), were found to be related to NHR in soybeans. These enzymes have been identified in previous studies, and STRING analysis showed that most of the protein functions related to major metabolic processes were induced as a response to B. maydis, which suggested an array of complex interactions between soybeans and B. maydis. These findings suggest a systematic NHR against non-adapted pathogens in soybeans. This response was characterized by an overlap between metabolic processes and response to stimulus. Several metabolic processes provide the soybean with innate immunity to the non-adapted pathogen, B. maydis. This research investigation on NHR in soybeans may foster a better understanding of plant innate immunity, as well as the interactions between plant and non-adapted pathogens in intercropping systems.

  6. Government turnover in parliamentary democracies

    OpenAIRE

    Diermeier, Daniel; Merlo, Antonio

    1998-01-01

    In this paper we consider a dynamic model of government formation and termination in parliamentary democracies. Our analysis accounts for the following observed phenomena: (1) Cabinet reshuffles; (2) Cabinet replacements; (3) Early elections; (4) Surplus governments; (5) Minority governments; (6) The relative instability of minority governments.

  7. Mechanisms behind the metabolic flexibility of an invasive comb jelly

    DEFF Research Database (Denmark)

    Augustine, Starrlight; Jaspers, Cornelia; Kooijman, Sebastiaan A. L.M.

    2014-01-01

    -cycle using Dynamic Energy Budget (DEB) theory and literature data. An analysis of data obtained at temperatures ranging from 8 to 30 °C suggests that the optimum thermal tolerance range of M. leidyi is higher than 12 °C. Furthermore M. leidyi seems to undergo a so-called metabolic acceleration after hatching...... of reserve compounds and high resistance to shrinking. M. leidyi adopts the opposite strategy: it has a lowreserve capacity, high turnover rates of reserve compounds and fast shrinking...

  8. Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions

    Directory of Open Access Journals (Sweden)

    Orth Jeffrey D

    2012-05-01

    Full Text Available Abstract Background The iJO1366 reconstruction of the metabolic network of Escherichia coli is one of the most complete and accurate metabolic reconstructions available for any organism. Still, because our knowledge of even well-studied model organisms such as this one is incomplete, this network reconstruction contains gaps and possible errors. There are a total of 208 blocked metabolites in iJO1366, representing gaps in the network. Results A new model improvement workflow was developed to compare model based phenotypic predictions to experimental data to fill gaps and correct errors. A Keio Collection based dataset of E. coli gene essentiality was obtained from literature data and compared to model predictions. The SMILEY algorithm was then used to predict the most likely missing reactions in the reconstructed network, adding reactions from a KEGG based universal set of metabolic reactions. The feasibility of these putative reactions was determined by comparing updated versions of the model to the experimental dataset, and genes were predicted for the most feasible reactions. Conclusions Numerous improvements to the iJO1366 metabolic reconstruction were suggested by these analyses. Experiments were performed to verify several computational predictions, including a new mechanism for growth on myo-inositol. The other predictions made in this study should be experimentally verifiable by similar means. Validating all of the predictions made here represents a substantial but important undertaking.

  9. Semi-automated curation of metabolic models via flux balance analysis: a case study with Mycoplasma gallisepticum.

    Directory of Open Access Journals (Sweden)

    Eddy J Bautista

    Full Text Available Primarily used for metabolic engineering and synthetic biology, genome-scale metabolic modeling shows tremendous potential as a tool for fundamental research and curation of metabolism. Through a novel integration of flux balance analysis and genetic algorithms, a strategy to curate metabolic networks and facilitate identification of metabolic pathways that may not be directly inferable solely from genome annotation was developed. Specifically, metabolites involved in unknown reactions can be determined, and potentially erroneous pathways can be identified. The procedure developed allows for new fundamental insight into metabolism, as well as acting as a semi-automated curation methodology for genome-scale metabolic modeling. To validate the methodology, a genome-scale metabolic model for the bacterium Mycoplasma gallisepticum was created. Several reactions not predicted by the genome annotation were postulated and validated via the literature. The model predicted an average growth rate of 0.358±0.12[Formula: see text], closely matching the experimentally determined growth rate of M. gallisepticum of 0.244±0.03[Formula: see text]. This work presents a powerful algorithm for facilitating the identification and curation of previously known and new metabolic pathways, as well as presenting the first genome-scale reconstruction of M. gallisepticum.

  10. Predicting voluntary turnover in employees using demographic characteristics: A South African case study

    Directory of Open Access Journals (Sweden)

    Anton F. Schlechter

    2016-03-01

    Design: An exploratory research design was employed. Secondary quantitative data were extracted from an existing human resources database and analysed. Data obtained for 2592 employees in a general insurance company based in South Africa and Namibia formed the basis for the analysis. Logistic regression analysis was employed to predict employee turnover using various demographic characteristics available within the database. A likelihood ratio test was used to build a predictive model and the Akaike information criterion and Schwarz criterion were used to test how much value each variable added to the model and if its inclusion was warranted. The model was tested by conducting statistical tests of the significance of the coefficients. Deviance and Pearson goodness-of-fit statistics as well as the R-square test of significance were used. The overall goodness-of-fit of the model was also tested using the Hosmer and Lemeshow goodness-of-fit test. Findings: The current findings provide partial support for a predictive model explaining employee turnover. The model tested 14 demographic variables and the following five variables were found to have statistically significant predictive value: age, years of service, cost centre, performance score and the interaction between number of dependants and years of service. It is proposed that these five demographic variables be used as a model to help identify employees at risk of turnover or termed as flight risks. Practical implications: Gaining an understanding of the factors that influence employee voluntary turnover can be instrumental in sustaining workforce stability. The proposed model could help human resources professionals identify employees at risk of turnover using data that are readily available to them. This will further enable the use of targeted interventions to prevent turnover before it happens. Decreased levels of turnover will result in cost saving, enhanced talent management and greater competitive advantage.

  11. Factors affecting turnover intentions among public hospital doctors in a middle-level city in central China.

    Science.gov (United States)

    Zhang, Fengfan; Luo, Zhenni; Chen, Ting; Min, Rui; Fang, Pengqian

    2017-05-01

    Objective The aim of the present study was to explore prominent factors affecting turnover intentions among public hospital doctors in urban areas, particularly in Xiangyang City, Hubei Province, a middle-level city in central China. Methods Questionnaires were used to collect data from 284 public hospital doctors. Pearson's Chi-squared was used to assess whether sociodemographic and other factors were related to the turnover intentions of public hospital doctors. Binary logistic regression was performed to determine the significant factors that influence turnover intentions. Results The analysis revealed that 28.2% of public hospital doctors intended to leave the hospital where they were currently employed. Dissatisfaction with working conditions and hospital management processes, as well as work pressures, were significant factors contributing to the turnover intentions of public hospital doctors. Conclusion Research into turnover intentions indicates that public hospital doctors surveyed in urban China give greater weight to their professional environment and career development rather than salary in their employment decisions. What is known about the topic? Turnover of medical staff is a concern to hospital administrators because it is costly and detrimental to organisational performance and quality of care. Most studies have focused on the effects of individual and organisational factors on nurses' intentions to leave their employment. Income dissatisfaction was one of the determining factors of turnover intentions in previous studies. What does this paper add? The satisfaction of public hospital doctors with regard to income is not a determining factor of turnover intentions. In contrast with findings of previous studies, the doctors in public hospitals in urban China in the present study gave greater weight to their professional environment and career development in their employment decisions. What are the implications for practitioners? The findings suggest

  12. Metabolic pattern analysis of early detection in Alzheimer's disease from other types of dementias and correlated with cognitive function

    International Nuclear Information System (INIS)

    Ju, R. H.; Lee, C. W.; Jung, Y. A.; Sohn, H. S.; Kim, S. H.; Seo, T. S

    2004-01-01

    PET/CT studies have demonstrated temporoparietal hypometabolism in probable and definite Alzheimer's disease (AD), a pattern that may help differentiate AD from other types of dementias. Seeking to distinguish Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we examined brain glucose metabolism of DLB and AD. Identification of individual differences in patterns of regional cerebral glucose metabolism (rCMRglc) interactions may be important for early detection of AD. We elucidate the relationship between reduced cognitive function and cerebral metabolism. Ten patients with the diagnosis of AD, 3 DLB patients underwent 18F-FDG PET CT. We applied statistical mapping procedure to evaluate the diagnostic power of rCMRglc patterns for differentiation and also correlated with Korean-mini mental status exam (K-MMSE) score include orientation time, place, registration, attention, calculation, recaIl, language and visuospatial function. Glucose metabolic pattern analysis confirmed AD and DLB patients showed significant metabolic reductions involving parietotemporal association, posterior cingulate, and frontal association cortex. DLB patients showed significant metabolic reductions in the occipital cortex, particularly in the primary visual cortex. Covariate analysis revealed that occipital metabolic changes in DLB were independent from those in the adjacent parietotemporal cortices. AnaIysis of clinically diagnosed probable AD patients showed a significantly higher frequency of primary visual metabolic reduction among patients who fulfilled clinical criteria for DLB. occipital hypometabolism is a potential discriminate marker to distinguish DLB versus AD

  13. Salary and Ranking and Teacher Turnover: A Statewide Study

    Science.gov (United States)

    Garcia, Cynthia Martinez; Slate, John R.; Delgado, Carmen Tejeda

    2009-01-01

    This study examined three years of data obtained from the Academic Excellence Indicator System of the State of Texas regarding teacher turnover rate and teacher salary. Across all public school districts, teacher salary was consistently negatively related to teacher turnover; that is, where salary was lower, turnover rate was higher When data were…

  14. Systematic review and meta-analysis of the association between psoriasis and metabolic syndrome.

    Science.gov (United States)

    Rodríguez-Zúñiga, Milton José Max; García-Perdomo, Herney Andrés

    2017-10-01

    Several studies have shown a relationship between psoriasis and metabolic syndrome (MS), but no meta-analysis has been restricted to studies that adjusted for confounders. To determine the association between psoriasis and MS. A systematic review and meta-analysis of observational studies on psoriasis and MS in adults was performed from MEDLINE, Scopus, SciELO, Google Scholar, Science Direct, and LILACS from inception to January 2016. We performed a random effects model meta-analysis for those studies reporting adjusted odds ratios (ORs) with 95% confidence intervals (CIs). The subgroup analysis was related to geographic location, diagnosis criteria and risk of bias. In all, 14 papers including a total of 25,042 patients with psoriasis were analyzed. We found that MS was present in 31.4% of patients with psoriasis (OR, 1.42; 95% CI, 1.28-1.65). Middle Eastern studies (in Israel, Turkey, and Lebanon) (OR, 1.76, 95% CI, 0.86-2.67) reported a greater risk for MS than European studies (in Germany, Italy, the United Kingdom, Norway, and Denmark) (OR, 1.40; 95% CI, 1.25-1.55). Few adjusted studies existed, and there was inconsistency between publications. Because of the increased risk for MS, clinicians should consider screening patients with psoriasis for metabolic risk factors. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. Comparative analysis of taxonomic, functional, and metabolic patterns of microbiomes from 14 full-scale biogas reactors by metagenomic sequencing and radioisotopic analysis

    DEFF Research Database (Denmark)

    Luo, Gang; Fotidis, Ioannis; Angelidaki, Irini

    2016-01-01

    , and their relationships with the metabolic patterns. The present study used metagenomic sequencing and radioisotopic analysis to assess the taxonomic, functional, and metabolic patterns of microbiomes from 14 full-scale biogas reactors operated under various conditions treating either sludge or manure. Results...

  16. [Development and testing of a nurse turnover intention scale (NTIS)].

    Science.gov (United States)

    Yeun, Eun Ja; Kim, Heejeong

    2013-04-01

    The purpose of this study was to develop a measurement tool of nurse's turnover intention. Data were collected from questionnaires completed by 678 nurses who worked in 3 university hospitals in South Korea and analyzed using the SPSS 18.0 and AMOS 18 programs. Thirty-seven preliminary items were selected from 161 basic items extracted via a literature review and in depth interviews with 6 hospital nurses. Three steps with factor analysis were undertaken to verify the reliability and validity of the preliminary instruments. Finally, confirmative factor analysis was carried out. As a result of the analysis, 3 factors including 10 items were selected. Cronbach's Alpha for the 10 items was .83, for job satisfaction (4 items), .78, for interpersonal relationships (3 items), .80, and for work performance (3 items), .74, which was stable. This study is meaningful because through it a scale reflecting Korean culture was developed to measure turnover intention in nurses. Further studies that test the psychometrics of this scale in more diverse samples are warranted.

  17. Analysis of the mechanism and regulation of lactose transport and metabolism in Clostridium acetobutylicum ATCC 824.

    Science.gov (United States)

    Yu, Yang; Tangney, Martin; Aass, Hans C; Mitchell, Wilfrid J

    2007-03-01

    Although the acetone-butanol-ethanol fermentation of Clostridium acetobutylicum is currently uneconomic, the ability of the bacterium to metabolize a wide range of carbohydrates offers the potential for revival based on the use of cheap, low-grade substrates. We have investigated the uptake and metabolism of lactose, the major sugar in industrial whey waste, by C. acetobutylicum ATCC 824. Lactose is taken up via a phosphoenolpyruvate-dependent phosphotransferase system (PTS) comprising both soluble and membrane-associated components, and the resulting phosphorylated derivative is hydrolyzed by a phospho-beta-galactosidase. These activities are induced during growth on lactose but are absent in glucose-grown cells. Analysis of the C. acetobutylicum genome sequence identified a gene system, lacRFEG, encoding a transcriptional regulator of the DeoR family, IIA and IICB components of a lactose PTS, and phospho-beta-galactosidase. During growth in medium containing both glucose and lactose, C. acetobutylicum exhibited a classical diauxic growth, and the lac operon was not expressed until glucose was exhausted from the medium. The presence upstream of lacR of a potential catabolite responsive element (cre) encompassing the transcriptional start site is indicative of the mechanism of carbon catabolite repression characteristic of low-GC gram-positive bacteria. A pathway for the uptake and metabolism of lactose by this industrially important organism is proposed.

  18. 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.

  19. SUMOFLUX: A Generalized Method for Targeted 13C Metabolic Flux Ratio Analysis.

    Directory of Open Access Journals (Sweden)

    Maria Kogadeeva

    2016-09-01

    Full Text Available Metabolic fluxes are a cornerstone of cellular physiology that emerge from a complex interplay of enzymes, carriers, and nutrients. The experimental assessment of in vivo intracellular fluxes using stable isotopic tracers is essential if we are to understand metabolic function and regulation. Flux estimation based on 13C or 2H labeling relies on complex simulation and iterative fitting; processes that necessitate a level of expertise that ordinarily preclude the non-expert user. To overcome this, we have developed SUMOFLUX, a methodology that is broadly applicable to the targeted analysis of 13C-metabolic fluxes. By combining surrogate modeling and machine learning, we trained a predictor to specialize in estimating flux ratios from measurable 13C-data. SUMOFLUX targets specific flux features individually, which makes it fast, user-friendly, applicable to experimental design and robust in terms of experimental noise and exchange flux magnitude. Collectively, we predict that SUMOFLUX's properties realistically pave the way to high-throughput flux analyses.

  20. Metabolic flux analysis during the exponential growth phase of Saccharomyces cerevisiae in wine fermentations.

    Science.gov (United States)

    Quirós, Manuel; Martínez-Moreno, Rubén; Albiol, Joan; Morales, Pilar; Vázquez-Lima, Felícitas; Barreiro-Vázquez, Antonio; Ferrer, Pau; Gonzalez, Ramon

    2013-01-01

    As a consequence of the increase in global average temperature, grapes with the adequate phenolic and aromatic maturity tend to be overripe by the time of harvest, resulting in increased sugar concentrations and imbalanced C/N ratios in fermenting musts. This fact sets obvious additional hurdles in the challenge of obtaining wines with reduced alcohols levels, a new trend in consumer demands. It would therefore be interesting to understand Saccharomyces cerevisiae physiology during the fermentation of must with these altered characteristics. The present study aims to determine the distribution of metabolic fluxes during the yeast exponential growth phase, when both carbon and nitrogen sources are in excess, using continuous cultures. Two different sugar concentrations were studied under two different winemaking temperature conditions. Although consumption and production rates for key metabolites were severely affected by the different experimental conditions studied, the general distribution of fluxes in central carbon metabolism was basically conserved in all cases. It was also observed that temperature and sugar concentration exerted a higher effect on the pentose phosphate pathway and glycerol formation than on glycolysis and ethanol production. Additionally, nitrogen uptake, both quantitatively and qualitatively, was strongly influenced by environmental conditions. This work provides the most complete stoichiometric model used for Metabolic Flux Analysis of S. cerevisiae in wine fermentations employed so far, including the synthesis and release of relevant aroma compounds and could be used in the design of optimal nitrogen supplementation of wine fermentations.

  1. Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics.

    Science.gov (United States)

    Gatto, Francesco; Schulze, Almut; Nielsen, Jens

    2016-07-19

    Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Modeling and Robustness Analysis of Biochemical Networks of Glycerol Metabolism by Klebsiella Pneumoniae

    Science.gov (United States)

    Ye, Jianxiong; Feng, Enmin; Wang, Lei; Xiu, Zhilong; Sun, Yaqin

    Glycerol bioconversion to 1,3-propanediol (1,3-PD) by Klebsiella pneumoniae (K. pneumoniae) can be characterized by an intricate network of interactions among biochemical fluxes, metabolic compounds, key enzymes and genetic regulatory. To date, there still exist some uncertain factors in this complex network because of the limitation in bio-techniques, especially in measuring techniques for intracellular substances. In this paper, among these uncertain factors, we aim to infer the transport mechanisms of glycerol and 1,3-PD across the cell membrane, which have received intensive interest in recent years. On the basis of different inferences of the transport mechanisms, we reconstruct various metabolic networks correspondingly and subsequently develop their dynamical systems (S-systems). To determine the most reasonable metabolic network from all possible ones, we establish a quantitative definition of biological robustness and undertake parameter identification and robustness analysis for each system. Numerical results show that it is most possible that both glycerol and 1,3-PD pass the cell membrane by active transport and passive diffusion.

  3. To be certain about the uncertainty: Bayesian statistics for 13 C metabolic flux analysis.

    Science.gov (United States)

    Theorell, Axel; Leweke, Samuel; Wiechert, Wolfgang; Nöh, Katharina

    2017-11-01

    13 C Metabolic Fluxes Analysis ( 13 C MFA) remains to be the most powerful approach to determine intracellular metabolic reaction rates. Decisions on strain engineering and experimentation heavily rely upon the certainty with which these fluxes are estimated. For uncertainty quantification, the vast majority of 13 C MFA studies relies on confidence intervals from the paradigm of Frequentist statistics. However, it is well known that the confidence intervals for a given experimental outcome are not uniquely defined. As a result, confidence intervals produced by different methods can be different, but nevertheless equally valid. This is of high relevance to 13 C MFA, since practitioners regularly use three different approximate approaches for calculating confidence intervals. By means of a computational study with a realistic model of the central carbon metabolism of E. coli, we provide strong evidence that confidence intervals used in the field depend strongly on the technique with which they were calculated and, thus, their use leads to misinterpretation of the flux uncertainty. In order to provide a better alternative to confidence intervals in 13 C MFA, we demonstrate that credible intervals from the paradigm of Bayesian statistics give more reliable flux uncertainty quantifications which can be readily computed with high accuracy using Markov chain Monte Carlo. In addition, the widely applied chi-square test, as a means of testing whether the model reproduces the data, is examined closer. © 2017 Wiley Periodicals, Inc.

  4. Malonylome Analysis Reveals the Involvement of Lysine Malonylation in Metabolism and Photosynthesis in Cyanobacteria.

    Science.gov (United States)

    Ma, Yanyan; Yang, Mingkun; Lin, Xiaohuang; Liu, Xin; Huang, Hui; Ge, Feng

    2017-05-05

    As a recently validated reversible post translational modification, lysine malonylation regulates diverse cellular processes from bacteria to mammals, but its existence and function in photosynthetic organisms remain unknown. Cyanobacteria are the most ancient group of photosynthetic prokaryotes and contribute about 50% of the total primary production on Earth. Previously, we reported the lysine acetylome in the model cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis). Here we performed the first proteomic survey of lysine malonylation in Synechocystis using highly accurate tandem mass spectrometry in combination with affinity purification. We identified 598 lysine malonylation sites on 339 proteins with high confidence in total. A bioinformatic analysis suggested that these malonylated proteins may play various functions and were distributed in diverse subcellular compartments. Among them, many malonylated proteins were involved in cellular metabolism. The functional significance of lysine malonylation in the metabolic enzyme activity of phosphoglycerate kinase (PGK) was determined by site-specific mutagenesis and biochemical studies. Interestingly, 27 proteins involved in photosynthesis were found to be malonylated for the first time, suggesting that lysine malonylation may be involved in photosynthesis. Thus our results provide the first lysine malonylome in a photosynthetic organism and suggest a previously unexplored role of lysine malonylation in the regulation of metabolic processes and photosynthesis in Synechocystis as well as in other photosynthetic organisms.

  5. Metabolic flux analysis during the exponential growth phase of Saccharomyces cerevisiae in wine fermentations.

    Directory of Open Access Journals (Sweden)

    Manuel Quirós

    Full Text Available As a consequence of the increase in global average temperature, grapes with the adequate phenolic and aromatic maturity tend to be overripe by the time of harvest, resulting in increased sugar concentrations and imbalanced C/N ratios in fermenting musts. This fact sets obvious additional hurdles in the challenge of obtaining wines with reduced alcohols levels, a new trend in consumer demands. It would therefore be interesting to understand Saccharomyces cerevisiae physiology during the fermentation of must with these altered characteristics. The present study aims to determine the distribution of metabolic fluxes during the yeast exponential growth phase, when both carbon and nitrogen sources are in excess, using continuous cultures. Two different sugar concentrations were studied under two different winemaking temperature conditions. Although consumption and production rates for key metabolites were severely affected by the different experimental conditions studied, the general distribution of fluxes in central carbon metabolism was basically conserved in all cases. It was also observed that temperature and sugar concentration exerted a higher effect on the pentose phosphate pathway and glycerol formation than on glycolysis and ethanol production. Additionally, nitrogen uptake, both quantitatively and qualitatively, was strongly influenced by environmental conditions. This work provides the most complete stoichiometric model used for Metabolic Flux Analysis of S. cerevisiae in wine fermentations employed so far, including the synthesis and release of relevant aroma compounds and could be used in the design of optimal nitrogen supplementation of wine fermentations.

  6. Metabolic Flux Analysis of the Synechocystis sp. PCC 6803 ΔnrtABCD Mutant Reveals a Mechanism for Metabolic Adaptation to Nitrogen-Limited Conditions.

    Science.gov (United States)

    Nakajima, Tsubasa; Yoshikawa, Katsunori; Toya, Yoshihiro; Matsuda, Fumio; Shimizu, Hiroshi

    2017-03-01

    Metabolic flux redirection during nitrogen-limited growth was investigated in the Synechocystis sp. PCC 6803 glucose-tolerant (GT) strain under photoautotrophic conditions by isotopically non-stationary metabolic flux analysis (INST-MFA). A ΔnrtABCD mutant of Synechocystis sp. PCC 6803 was constructed to reproduce phenotypes arising during nitrogen starvation. The ΔnrtABCD mutant and the wild-type GT strain were cultured under photoautotrophic conditions by a photobioreactor. Intracellular metabolites were labeled over a time course using NaH13CO3 as a carbon source. Based on these data, the metabolic flux distributions in the wild-type and ΔnrtABCD cells were estimated by INST-MFA. The wild-type GT and ΔnrtABCD strains displayed similar distribution patterns, although the absolute levels of metabolic flux were lower in ΔnrtABCD. Furthermore, the relative flux levels for glycogen metabolism, anaplerotic reactions and the oxidative pentose phosphate pathway were increased in ΔnrtABCD. This was probably due to the increased expression of enzyme genes that respond to nitrogen depletion. Additionally, we found that the ratio of ATP/NADPH demand increased slightly in the ΔnrtABCD mutant. These results indicated that futile ATP consumption increases under nitrogen-limited conditions because the Calvin-Benson cycle and the oxidative pentose phosphate pathway form a metabolic futile cycle that consumes ATP without CO2 fixation and NADPH regeneration. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Dietary Interventions and Changes in Cardio-Metabolic Parameters in Metabolically Healthy Obese Subjects: A Systematic Review with Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Marta Stelmach-Mardas

    2016-07-01

    Full Text Available The aim of this systematic review was to assess the effect of diet on changes in parameters describing the body size phenotype of metabolically healthy obese subjects. The databases Medline, Scopus, Web of Knowledge and Embase were searched for clinical studies carried out between 1958 and June 2016 that reported the effect of dietary intervention on BMI, blood pressure, concentration of fasting triglyceride (TG, high density lipoprotein cholesterol (HDL-C, fasting glucose level, the homoeostatic model assessment of insulin resistance (HOMA-IR and high sensitivity C-Reactive Protein (hsCRP in metabolically healthy, obese subjects. Twelve clinical studies met inclusion criteria. The combined analyzed population consists of 1827 subjects aged 34.4 to 61.1 with a BMI > 30 kg/m2. Time of intervention ranged from eight to 104 weeks. The baseline characteristics related to lipid profile were more favorable for metabolically healthy obese than for metabolically unhealthy obese. The meta-analyses revealed a significant associations between restricted energy diet and BMI (95% confidence interval (CI: −0.88, −0.19, blood pressure (systolic blood pressure (SBP: −4.73 mmHg; 95% CI: −7.12, −2.33; and diastolic blood pressure (DBP: −2.75 mmHg; 95% CI: −4.30, −1.21 and TG (−0.11 mmol/l; 95% CI: −0.16, −0.06. Changes in fasting glucose, HOMA-IR and hsCRP did not show significant changes. Sufficient evidence was not found to support the use of specific diets in metabolically healthy obese subjects. This analysis suggests that the effect of caloric restriction exerts its effects through a reduction in BMI, blood pressure and triglycerides in metabolically healthy obese (MHO patients.

  8. Proteomic analysis reveals metabolic and regulatory systems involved the syntrophic and axenic lifestyle of Syntrophomonas wolfei.

    Directory of Open Access Journals (Sweden)

    Jessica Rhea Sieber

    2015-02-01

    Full Text Available Microbial syntrophy is a vital metabolic interaction necessary for the complete oxidation of organic biomass to methane in all-anaerobic ecosystems. However, this process is thermodynamically constrained and represents an ecosystem-level metabolic bottleneck. To gain insight into the physiology of this process, a shotgun proteomic approach was used to quantify the protein landscape of the model syntrophic metabolizer, Syntrophomonas wolfei, grown axenically and syntrophically with Methanospirillum hungatei. Remarkably, the abundance of most proteins as represented by normalized spectral abundance factor (NSAF value changed very little between the pure and coculture growth conditions. Among the most abundant proteins detected were GroEL and GroES chaperonins, a small heat shock protein, and proteins involved in electron transfer, beta-oxidation, and ATP synthesis. Several putative energy conservation enzyme systems that utilize NADH and ferredoxin were present. The abundance of an EtfAB2 and the membrane-bound iron-sulfur oxidoreductase (Swol_0698 gene product delineated a potential conduit for electron transfer between acyl-CoA dehydrogenases and membrane redox carriers. Proteins detected only when S. wolfei was grown with M. hungatei included a zinc-dependent dehydrogenase with a GroES domain, whose gene is present in genomes in many organisms capable of syntrophy, and transcriptional regulators responsive to environmental stimuli or the physiological status of the cell. The proteomic analysis revealed an emphasis macromolecular stability and energy metabolism to S. wolfei and presence of regulatory mechanisms responsive to external stimuli and cellular physiological status.

  9. Cost-effectiveness analysis of ultrasonography screening for nonalcoholic fatty liver disease in metabolic syndrome patients.

    Science.gov (United States)

    Phisalprapa, Pochamana; Supakankunti, Siripen; Charatcharoenwitthaya, Phunchai; Apisarnthanarak, Piyaporn; Charoensak, Aphinya; Washirasaksiri, Chaiwat; Srivanichakorn, Weerachai; Chaiyakunapruk, Nathorn

    2017-04-01

    Nonalcoholic fatty liver disease (NAFLD) can be diagnosed early by noninvasive ultrasonography; however, the cost-effectiveness of ultrasonography screening with intensive weight reduction program in metabolic syndrome patients is not clear. This study aims to estimate economic and clinical outcomes of ultrasonography in Thailand. Cost-effectiveness analysis used decision tree and Markov models to estimate lifetime costs and health benefits from societal perspective, based on a cohort of 509 metabolic syndrome patients in Thailand. Data were obtained from published literatures and Thai database. Results were reported as incremental cost-effectiveness ratios (ICERs) in 2014 US dollars (USD) per quality-adjusted life year (QALY) gained with discount rate of 3%. Sensitivity analyses were performed to assess the influence of parameter uncertainty on the results. The ICER of ultrasonography screening of 50-year-old metabolic syndrome patients with intensive weight reduction program was 958 USD/QALY gained when compared with no screening. The probability of being cost-effective was 67% using willingness-to-pay threshold in Thailand (4848 USD/QALY gained). Screening before 45 years was cost saving while screening at 45 to 64 years was cost-effective. For patients with metabolic syndromes, ultrasonography screening for NAFLD with intensive weight reduction program is a cost-effective program in Thailand. Study can be used as part of evidence-informed decision making. Findings could contribute to changes of NAFLD diagnosis practice in settings where economic evidence is used as part of decision-making process. Furthermore, study design, model structure, and input parameters could also be used for future research addressing similar questions.

  10. Analysis of agreement among definitions of metabolic syndrome in nondiabetic Turkish adults: a methodological study

    Directory of Open Access Journals (Sweden)

    Bersot Thomas P

    2007-12-01

    Full Text Available Abstract Background We aimed to explore the agreement among World Health Organization (WHO, European Group for the Study of Insulin Resistance (EGIR, National Cholesterol Education Program (NCEP, American College of Endocrinology (ACE, and International Diabetes Federation (IDF definitions of the metabolic syndrome. Methods 1568 subjects (532 men, 1036 women, mean age 45 and standard deviation (SD 13 years were evaluated in this cross-sectional, methodological study. Cardiometabolic risk factors were determined. Insulin sensitivity was calculated by HOMA-IR. Agreement among definitions was determined by the kappa statistic. ANOVA and post hoc Tukey's test were used to compare multiple groups. Results The agreement between WHO and EGIR definitions was very good (kappa: 0.83. The agreement between NCEP, ACE, and IDF definitions was substantial to very good (kappa: 0.77–0.84. The agreement between NCEP or ACE or IDF and WHO or EGIR definitions was fair (kappa: 0.32–0.37. The age and sex adjusted prevalence of metabolic syndrome was 38% by NCEP, 42% by ACE and IDF, 20% by EGIR and 19% by WHO definition. The evaluated definitions were dichotomized after analysis of design, agreement and prevalence: insulin measurement requiring definitions (WHO and EGIR and definitions not requiring insulin measurement (NCEP, ACE, IDF. One definition was selected from each set for comparison. WHO-defined subjects were more insulin resistant than subjects without the metabolic syndrome (mean and SD for log HOMA-IR, 0.53 ± 0.14 vs. 0.07 ± 0.23, respectively, p 0.05, but lower log HOMA-IR values (p Conclusion The metabolic syndrome definitions that do not require measurement of insulin levels (NCEP, ACE and IDF identify twice more patients with insulin resistance and increased Framingham risk scores and are more useful than the definitions that require measurement of insulin levels (WHO and EGIR.

  11. Transcriptomic Analysis of Metabolic Pathways in Milkfish That Respond to Salinity and Temperature Changes.

    Directory of Open Access Journals (Sweden)

    Yau-Chung Hu

    Full Text Available Milkfish (Chanos chanos, an important marine aquaculture species in southern Taiwan, show considerable euryhalinity but have low tolerance to sudden drops in water temperatures in winter. Here, we used high throughput next-generation sequencing (NGS to identify molecular and biological processes involved in the responses to environmental changes. Preliminary tests revealed that seawater (SW-acclimated milkfish tolerated lower temperatures than the fresh water (FW-acclimated group. Although FW- and SW-acclimated milkfish have different levels of tolerance for hypothermal stress, to date, the molecular physiological basis of this difference has not been elucidated. Here, we performed a next-generation sequence analysis of mRNAs from four groups of milkfish. We obtained 29669 unigenes with an average length of approximately 1936 base pairs. Gene ontology (GO analysis was performed after gene annotation. A large number of genes for molecular regulation were identified through a transcriptomic comparison in a KEGG analysis. Basal metabolic pathways involved in hypothermal tolerance, such as glycolysis, fatty acid metabolism, amino acid catabolism and oxidative phosphorylation, were analyzed using PathVisio and Cytoscape software. Our results indicate that in response to hypothermal stress, genes for oxidative phosphorylation, e.g., succinate dehydrogenase, were more highly up-regulated in SW than FW fish. Moreover, SW and FW milkfish used different strategies when exposed to hypothermal stress: SW milkfish up-regulated oxidative phosphorylation and catabolism genes to produce more energy budget, whereas FW milkfish down-regulated genes related to basal metabolism to reduce energy loss.

  12. 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

  13. 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

  14. Differential Subplastidial Localization and Turnover of Enzymes Involved in Isoprenoid Biosynthesis in Chloroplasts.

    Directory of Open Access Journals (Sweden)

    Catalina Perello

    Full Text Available Plastidial isoprenoids are a diverse group of metabolites with roles in photosynthesis, growth regulation, and interaction with the environment. The methylerythritol 4-phosphate (MEP pathway produces the metabolic precursors of all types of plastidial isoprenoids. Proteomics studies in Arabidopsis thaliana have shown that all the enzymes of the MEP pathway are localized in the plastid stroma. However, immunoblot analysis of chloroplast subfractions showed that the first two enzymes of the pathway, deoxyxylulose 5-phosphate synthase (DXS and reductoisomerase (DXR, can also be found in non-stromal fractions. Both transient and stable expression of GFP-tagged DXS and DXR proteins confirmed the presence of the fusion proteins in distinct subplastidial compartments. In particular, DXR-GFP was found to accumulate in relatively large vesicles that could eventually be released from chloroplasts, presumably to be degraded by an autophagy-independent process. Together, we propose that protein-specific mechanisms control the localization and turnover of the first two enzymes of the MEP pathway in Arabidopsis chloroplasts.

  15. The influence of vegan diet on bone mineral density and biochemical bone turnover markers.

    Science.gov (United States)

    Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Gajewska, Joanna; Chełchowska, Magdalena; Franek, Edward; Laskowska-Klita, Teresa

    2010-01-01

    Vegetarian diets can be healthy when they are well balanced and if a variety of foods is consumed. However, elimination of animal products from the diet (vegan diets) decreases the intake of some essential nutrients and may influence the bone metabolism. This is especially important in childhood and adolescence, when growth and bone turnover are most intensive. The aim of the study was to assess the effect of vegan diet on bone density (BMD) density and serum concentrations of bone metabolism markers. We examined a family on vegan diet which consisted of parents and two children. Dietary constituents were analysed using a nutritional program. Total and regional BMD were measured by dual-energy X-ray absorptiometry. Concentrations of calcium and phosphate in serum obtained from fasting patients were determined by colorimetric methods, 25-hydroxyvitamin D by the chemiluminescence method and bone turnover markers by specific enzyme immunoassays. In studied vegans, the dietary intake of phosphate was adequate while calcium and vitamin D were below the recommended range. Concentrations of calcium, phosphate and bone turnover markers in the serum of all subjects were within the physiological range, but 25-hydroxyvitamin D level was low. Age-matched Z-score total BMD was between -0.6 and 0.3 in adults, however in children it was lower (-0.9 and -1.0). Z-score BMD lumbar spine (L2-L4) was between -0.9 to -1.9 in parents and -1.5 to -1.7 in children. Our results suggest that an inadequate dietary intake of calcium and vitamin D may impair the bone turnover rate and cause a decrease in bone mineral density in vegans. The parameters of bone density and bone metabolism should be monitored in vegans, especially children, in order to prevent bone abnormalities.

  16. Increased hypothalamic serotonin turnover in inflammation-induced anorexia.

    Science.gov (United States)

    Dwarkasing, J T; Witkamp, R F; Boekschoten, M V; Ter Laak, M C; Heins, M S; van Norren, K

    2016-05-20

    Anorexia can occur as a serious complication of disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. First, we investigated the response of two hypothalamic neuronal cell lines to TNFα, IL-6 and LPS. Next, we studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. In vitro, we showed that hypothalamic neurons responded to inflammatory mediators by releasing cytokines. This inflammatory response was associated with an increased serotonin release. Mice injected with TNFα and IL-6 showed decreased food intake, associated with altered expression of inflammation-related genes in the hypothalamus. In addition, hypothalamic serotonin turnover showed to be elevated in treated mice. Overall, our results underline that peripheral inflammation reaches the hypothalamus where it affects hypothalamic serotoninergic metabolism. These hypothalamic changes in serotonin pathways are associated with decreased food intake, providing evidence for a role of serotonin in inflammation-induced anorexia.

  17. PENGARUH KEPUASAN KERJA DAN STRES KERJA TERHADAP TURNOVER INTENTION PADA KARYAWAN PT. UNITEX DI BOGOR

    Directory of Open Access Journals (Sweden)

    Agung AWS Waspodo

    2013-04-01

    Full Text Available The purpose of this research are: 1 To analyze the influence of job satisfaction on employees turnover intention at PT. Unitex. 2 To analyze the influence of job stress on employees turnover intention at PT. Unitex. 3 To analyze the influence of job satisfaction and job stress simultaneously on employees turnover intention at PT. Unitex. The analysis method in this research using a simple linear and linear multiple regression. Sample of the research is 98 employees using simple random sampling. The techniques of data collection was done by distributing questionnaires and cultivated by using SPSS 16.00. t test result on job satisfaction variable is -5.412, with a significance value of 0.000. It means job satisfaction has a significant influence on turnover intention. t test result on job stress variable is 7.353 with a significance value of 0.000. It means job stress have significant influence on turnover intention. F test result is 39.037, it means job satisfaction and job stress has a significant influence on turnover intention. Determination coefficient score (R2 for X1 and X2 is 0.451, it means turnover intention can be influenced by job satisfaction and job stress around 45,1%, then other factors around 54,9%. Linear regression formula for hypotheses 1 is Y = 55.937 – 0.191 X1. Linear regression formula for hypotheses 2 is Y = 23.370 + 0.408 X2. Multiple regression formula for hypotheses 3 is Y = 36.323 – 0.126 X1 + 0.336 X2.

  18. How Wage Compression Affects Job Turnover

    OpenAIRE

    Heyman, Fredrik

    2008-01-01

    I use Swedish establishment-level panel data to test Bertola and Rogerson’s (1997) hypothesis of a positive relation between the degree of wage compression and job reallocation. Results indicate that the effect of wage compression on job turnover is positive and significant in the manufacturing sector. The wage compression effect is stronger on job destruction than on job creation, consistent with downward wage rigidity. Further results include a strong positive relationship between the fract...

  19. Employee turnover, HRM and institutional contexts.

    OpenAIRE

    Croucher, Richard; Wood, Geoffrey; Brewster, Chris; Brookes, Michael

    2012-01-01

    Literature on comparative capitalism remains divided between approaches founded on stylized case study evidence and descriptions of broad trends, and those that focus on macro data. In contrast, this study explores the relevance of Amable’s approach to understanding differences in employment relations practice, based on firm-level micro data. The article examines employee–employer interdependence (including turnover rates) in different categories of economy as classified by Amable. The findin...

  20. Bone mass and turnover in fibromyalgia

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Gam, A; Egsmose, C

    1993-01-01

    in lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.......01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia....

  1. Cereal aphid colony turnover and persistence in winter wheat.

    Directory of Open Access Journals (Sweden)

    Linton Winder

    Full Text Available An understanding of spatial and temporal processes in agricultural ecosystems provides a basis for rational decision-making with regards to the management and husbandry of crops, supporting the implementation of integrated farming strategies. In this study we investigated the spatial and temporal distribution of aphid pests (Sitobion avenae and Metopolophium dirhodum within winter wheat fields. Using an intensive sampling programme we investigated distributions at both the small (single shoot and large (field scales. Within two fields, a grid with 82 locations was established (area 120 m by 168 m. At each location, 25 shoots were individually marked and aphid counts by observation conducted on 21 and 22 occasions as the crop matured, resulting in 43,050 and 45,100 counts being conducted in the two fields respectively. We quantified field scale spatial distributions, demonstrating that spatial pattern generally emerged, with temporal stability being both species- and field- dependent. We then measured turnover of colonies at the small (individual shoot and large (field scales by comparing consecutive pairs of sampling occasions. Four turnover categories were defined: Empty (no aphids recorded on either occasion; Colonised (aphids recorded on the second occasion but not the first; Extinction (aphids recorded on the first occasion but not the second; Stable (aphids recorded on both occasions. At the field scale, population stability soon established, but, at the small scale there was a consistently high proportion of unoccupied shoots with considerable colonisation and extinction and low stability. The redistribution of aphids within the crop at the local scale is a vulnerability which could be used to disrupt population development--by mediating exposure to ground-active natural enemies and by incurring a metabolic cost caused by the physiological demands to re-establish on a nearby host plant.

  2. PERAN STRES KERJA DAN KEPUASAN KERJA UNTUK MENGURANGI TURNOVER INTENTION

    Directory of Open Access Journals (Sweden)

    Syarifah Nazenin

    2014-09-01

    Full Text Available Tujuan penelitian ini untuk menguji pengaruh variabel stres kerja dan kepuasan kerja pada turnover intention karyawan tetap bagian produksi. Sampel penelitian ini adalah 86 responden, menggunakan metode Slovin dengan teknik probability sampling dengan jenis proportionate random sampling. Berdasarkan hasil penelitian, menunjukkan bahwa stres kerja berpengaruh positif signifikan pada turnover intention. Kemudian, kepuasan kerja berpengaruh negatif signifikan. Penelitian ini menyimpulkan, bahwa stres kerja berpengaruh positif dan signifikan pada turnover intention karyawan dan kepuasan kerja berpengaruh negatif dan signifikan terhadap turnover intention karyawan. Implikasi manajerial yang bisa dilakukan adalah dengan pengurangan tingkat stres karyawan dan membuat program untuk tujuan menekan turnover intention, seperti kesempatan promosi dan meningkatkan reward karyawan. The purpose of this study conducted to examine the effect of work stress and job satisfaction on turnover intention of employee in production department. The sample was 86 respondent, using Slovin method with proportionate random sampling technique. The result showed that job stress has a positive effect on turnover intention while job satisfaction has a negative effect on turnover intention. This study conclude that job stress has positive and significant impact on employee turnover intention and job satisfaction significantly and negatively related to turnover intention of employees. Therefore, it is recommended to managerial level people to reduce stress levels in employees and to create a program for pressing turnover intention, such as promotional opportunities and improve employee rewards.

  3. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    International Nuclear Information System (INIS)

    Feng Jianghua; Liu Huili; Zhang Limin; Bhakoo, Kishore; Lu Lehui

    2010-01-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  4. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianghua [Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, 361005 (China); Liu Huili; Zhang Limin [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Bhakoo, Kishore [Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A-STAR) 138667 (Singapore); Lu Lehui, E-mail: jianghua.feng@hotmail.com, E-mail: jianghua.feng@wipm.ac.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China)

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary {alpha}-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary {alpha}-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies ({beta}-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of

  5. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids.

    Science.gov (United States)

    Feng, Jianghua; Liu, Huili; Zhang, Limin; Bhakoo, Kishore; Lu, Lehui

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary alpha-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary alpha-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (beta-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  6. Multi-objective experimental design for (13)C-based metabolic flux analysis.

    Science.gov (United States)

    Bouvin, Jeroen; Cajot, Simon; D'Huys, Pieter-Jan; Ampofo-Asiama, Jerry; Anné, Jozef; Van Impe, Jan; Geeraerd, Annemie; Bernaerts, Kristel

    2015-10-01

    (13)C-based metabolic flux analysis is an excellent technique to resolve fluxes in the central carbon metabolism but costs can be significant when using specialized tracers. This work presents a framework for cost-effective design of (13)C-tracer experiments, illustrated on two different networks. Linear and non-linear optimal input mixtures are computed for networks for Streptomyces lividans and a carcinoma cell line. If only glucose tracers are considered as labeled substrate for a carcinoma cell line or S. lividans, the best parameter estimation accuracy is obtained by mixtures containing high amounts of 1,2-(13)C2 glucose combined with uniformly labeled glucose. Experimental designs are evaluated based on a linear (D-criterion) and non-linear approach (S-criterion). Both approaches generate almost the same input mixture, however, the linear approach is favored due to its low computational effort. The high amount of 1,2-(13)C2 glucose in the optimal designs coincides with a high experimental cost, which is further enhanced when labeling is introduced in glutamine and aspartate tracers. Multi-objective optimization gives the possibility to assess experimental quality and cost at the same time and can reveal excellent compromise experiments. For example, the combination of 100% 1,2-(13)C2 glucose with 100% position one labeled glutamine and the combination of 100% 1,2-(13)C2 glucose with 100% uniformly labeled glutamine perform equally well for the carcinoma cell line, but the first mixture offers a decrease in cost of $ 120 per ml-scale cell culture experiment. We demonstrated the validity of a multi-objective linear approach to perform optimal experimental designs for the non-linear problem of (13)C-metabolic flux analysis. Tools and a workflow are provided to perform multi-objective design. The effortless calculation of the D-criterion can be exploited to perform high-throughput screening of possible (13)C-tracers, while the illustrated benefit of multi

  7. [Prevalence of metabolic syndrome in Chinese children and adolescents: a Meta-analysis].

    Science.gov (United States)

    Ye, Peiyu; Yan, Yinkun; Ding, Wenqing; Dong, Hongbo; Liu, Qin; Huang, Guimin; Mi, Jie

    2015-08-01

    To evaluate the prevalence of metabolic syndrome (MS) in Chinese children and adolescents to provide scientific basis for early prevention of MS in the related populations. Studies on CNKI, Wanfangdata, VIP and PubMed databases on related prevalence of metabolic syndrome in Chinese children and adolescents between 2004-2014 were searched. Quality of literatures was evaluated according to the cross-sectional study standard in Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Stata 12.0 software was used to estimate the prevalence of MS, as well as on gender, weight and other factors to make subgroup analysis. According to funnel plot and Egger assess publication bias, sensitivity analysis performed by excluding the impact of any article was generated by the combined effect of the value of literature. This study included 19 papers from the literature (5 in English, 14 in Chinese). According to International Diabetes Federation (IDF), National Cholesterol Education Program III (NCEP III) and The definition and prevention recommends of metabolic syndrome in Chinese children and adolescents (CHN2012), the prevalence rates of MS in Chinese children were seen as 1.8%, 2.6% and 2.0%. According to IDF, the prevalence rates of MS appeared 2.9% in boys and 1.8% in girls, 0.2% in children with normal weight, 4.7% in overweight and 17.3% in obesity. Both the results from NCEPIII and CHN2012 showed that the prevalence rates of MS as boys > girls, obesity > overweight > normal weight. Prevalence of MS in Chinese children and adolescents showed a general trend. Data under different standards showed different prevalence rates. Obesity appeared an important risk factor of MS, suggesting that in order to control obesity in children, attention should be paid to identifying and carrying out effective interventions on children under overweight or obesity.

  8. Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

    International Nuclear Information System (INIS)

    Prieto, Elena; Dominguez-Prado, Ines; Jesus Ribelles, Maria; Arbizu, Javier; Riverol, Mario; Ortega-Cubero, Sara; Rosario Luquin, Maria; Castro, Purificacion de

    2015-01-01

    Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease. (orig.)

  9. Metabolic patterns in prion diseases: an FDG PET voxel-based analysis

    Energy Technology Data Exchange (ETDEWEB)

    Prieto, Elena; Dominguez-Prado, Ines; Jesus Ribelles, Maria; Arbizu, Javier [Clinica Universidad de Navarra, Nuclear Medicine Department, Pamplona (Spain); Riverol, Mario; Ortega-Cubero, Sara; Rosario Luquin, Maria; Castro, Purificacion de [Clinica Universidad de Navarra, Neurology Department, Pamplona (Spain)

    2015-09-15

    Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease. (orig.)

  10. Phylogenetic analysis of the allometry of metabolic rate and mitochondrial basal proton leak.

    Science.gov (United States)

    Polymeropoulos, Elias T; Oelkrug, R; White, C R; Jastroch, M

    2017-08-01

    The mitochondrial basal proton leak (MBPL) significantly contributes to high body temperatures (T b ) and basal metabolic rates (BMR) in endotherms. In endotherms at a given body mass (M), liver MBPL is higher than in ectotherms, supporting the notion that MBPL may partly explain the evolutionary increase in metabolic rate (MR), fostering endothermy. Here, we re-addressed this assumption by performing a phylogenetic analysis comparing all available liver MBPL data for ecto- and endotherms. While MBPL within endotherms negatively scales with M and BMR as shown previously, MBPL of ectotherms does not scale allometrically with M. Phylogenetic analysis reveals that this result is confounded by a positive scaling coefficient for MBPL with M for reptiles. Strikingly, the reptilian MBPL reaches endothermic levels above a body mass of 6.6kg. Thus, phylogenetic scaling of MBPL supports previous claims of endotherm-like physiological characteristics in large reptiles. It appears that diversification of ancestral ectothermic tetrapods to a body mass of at least 6kg may have been required to reach a MBPL that is beneficial for sustained high body temperatures. Novel MBPL data for the lesser hedgehog tenrec, a protoendothermic eutherian that displays reptile-like thermoregulatory patterns, fall within the endo- and ectothermic allometric regressions. Finally, we add additional evidence that within endotherms, phylogenetic differences in MR do not correlate with MBPL. Collectively, these data suggest that MBPL does not universally scale with metabolic rate in ecto- or endotherms and that an increasing MBPL with M may have played an important physiological role in the evolutionary history of reptilian thermoregulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Identifying model error in metabolic flux analysis - a generalized least squares approach.

    Science.gov (United States)

    Sokolenko, Stanislav; Quattrociocchi, Marco; Aucoin, Marc G

    2016-09-13

    The estimation of intracellular flux through traditional metabolic flux analysis (MFA) using an overdetermined system of equations is a well established practice in metabolic engineering. Despite the continued evolution of the methodology since its introduction, there has been little focus on validation and identification of poor model fit outside of identifying "gross measurement error". The growing complexity of metabolic models, which are increasingly generated from genome-level data, has necessitated robust validation that can directly assess model fit. In this work, MFA calculation is framed as a generalized least squares (GLS) problem, highlighting the applicability of the common t-test for model validation. To differentiate between measurement and model error, we simulate ideal flux profiles directly from the model, perturb them with estimated measurement error, and compare their validation to real data. Application of this strategy to an established Chinese Hamster Ovary (CHO) cell model shows how fluxes validated by traditional means may be largely non-significant due to a lack of model fit. With further simulation, we explore how t-test significance relates to calculation error and show that fluxes found to be non-significant have 2-4 fold larger error (if measurement uncertainty is in the 5-10 % range). The proposed validation method goes beyond traditional detection of "gross measurement error" to identify lack of fit between model and data. Although the focus of this work is on t-test validation and traditional MFA, the presented framework is readily applicable to other regression analysis methods and MFA formulations.

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

    DEFF Research Database (Denmark)

    Fentz, Joachim

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

  13. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis.

    Science.gov (United States)

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  14. Proteomic analysis reveals that iron availability alters the metabolic status of the pathogenic fungus Paracoccidioides brasiliensis.

    Directory of Open Access Journals (Sweden)

    Ana F A Parente

    Full Text Available Paracoccidioides brasiliensis is a thermodimorphic fungus and the causative agent of paracoccidioidomycosis (PCM. The ability of P. brasiliensis to uptake nutrients is fundamental for growth, but a reduction in the availability of iron and other nutrients is a host defense mechanism many pathogenic fungi must overcome. Thus, fungal mechanisms that scavenge iron from host may contribute to P. brasiliensis virulence. In order to better understand how P. brasiliensis adapts to iron starvation in the host we compared the two-dimensional (2D gel protein profile of yeast cells during iron starvation to that of iron rich condition. Protein spots were selected for comparative analysis based on the protein staining intensity as determined by image analysis. A total of 1752 protein spots were selected for comparison, and a total of 274 out of the 1752 protein spots were determined to have changed significantly in abundance due to iron depletion. Ninety six of the 274 proteins were grouped into the following functional categories; energy, metabolism, cell rescue, virulence, cell cycle, protein synthesis, protein fate, transcription, cellular communication, and cell fate. A correlation between protein and transcript levels was also discovered using quantitative RT-PCR analysis from RNA obtained from P. brasiliensis under iron restricting conditions and from yeast cells isolated from infected mouse spleens. In addition, western blot analysis and enzyme activity assays validated the differential regulation of proteins identified by 2-D gel analysis. We observed an increase in glycolytic pathway protein regulation while tricarboxylic acid cycle, glyoxylate and methylcitrate cycles, and electron transport chain proteins decreased in abundance under iron limiting conditions. These data suggest a remodeling of P. brasiliensis metabolism by prioritizing iron independent pathways.

  15. A High Phosphorus Diet Affects Lipid Metabolism in Rat Liver: A DNA Microarray Analysis

    Science.gov (United States)

    Chun, Sunwoo; Bamba, Takeshi; Suyama, Tatsuya; Ishijima, Tomoko; Fukusaki, Eiichiro; Abe, Keiko; Nakai, Yuji

    2016-01-01

    A high phosphorus (HP) diet causes disorders of renal function, bone metabolism, and vascular function. We previously demonstrated that DNA microarray analysis is an appropriate method to comprehensively evaluate the effects of a HP diet on kidney dysfunction such as calcification, fibrillization, and inflammation. We reported that type IIb sodium-dependent phosphate transporter is significantly up-regulated in this context. In the present study, we performed DNA microarray analysis to investigate the effects of a HP diet on the liver, which plays a pivotal role in energy metabolism. DNA microarray analysis was performed with total RNA isolated from the livers of rats fed a control diet (containing 0.3% phosphorus) or a HP diet (containing 1.2% phosphorus). Gene Ontology analysis of differentially expressed genes (DEGs) revealed that the HP diet induced down-regulation of genes involved in hepatic amino acid catabolism and lipogenesis, while genes related to fatty acid β-oxidation process were up-regulated. Although genes related to fatty acid biosynthesis were down-regulated in HP diet-fed rats, genes important for the elongation and desaturation reactions of omega-3 and -6 fatty acids were up-regulated. Concentrations of hepatic arachidonic acid and eicosapentaenoic acid were increased in HP diet-fed rats. These essential fatty acids activate peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor for fatty acid β-oxidation. Evaluation of the upstream regulators of DEGs using Ingenuity Pathway Analysis indicated that PPARα was activated in the livers of HP diet-fed rats. Furthermore, the serum concentration of fibroblast growth factor 21, a hormone secreted from the liver that promotes fatty acid utilization in adipose tissue as a PPARα target gene, was higher (p = 0.054) in HP diet-fed rats than in control diet-fed rats. These data suggest that a HP diet enhances energy expenditure through the utilization of free fatty acids

  16. Metabolic Consequences of Obstructive Sleep Apnea in Adolescents with Obesity: A Systematic Literature Review and Meta-Analysis.

    Science.gov (United States)

    Patinkin, Zachary W; Feinn, Richard; Santos, Melissa

    2017-04-01

    Adolescents who are obese are at high risk of developing obstructive sleep apnea (OSA). Although there is clear evidence associating OSA with metabolic dysfunction in adults, the evidence is less clear cut with adolescents. The purpose of this review was determine the association of sleep apnea with dyslipidemia, insulin resistance, cardiovascular disease risk, nonalcoholic fatty liver disease, and difficulty with weight loss in adolescents. A systematic literature review using PubMed, Scopus, CINAHL, Google Scholar, and PsycINFO was performed and articles were screened and reviewed with an a priori protocol. Sixteen articles were included in qualitative synthesis and 10 were included in meta-analysis. Results from the meta-analysis indicate that OSA in adolescents is associated with greater risk of dyslipidemia, insulin resistance, and hypertension. Although obesity leads to increased metabolic risk, OSA appears to independently increase metabolic impairment. Adolescents with obesity should be frequently screened for OSA to determine need for treatment and reduce this metabolic burden.

  17. Serum metabonomics coupled with Ingenuity Pathway Analysis characterizes metabolic perturbations in response to hypothyroidism induced by propylthiouracil in rats.

    Science.gov (United States)

    Wu, Si; Gao, Yue; Dong, Xin; Tan, Guangguo; Li, Wuhong; Lou, Ziyang; Chai, Yifeng

    2013-01-01

    A serum metabonomic profiling method based on ultra-performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS) was applied to investigate the metabolic changes in hypothyroid rats induced by propylthiouracil (PTU). With Significance Analysis of Microarray (SAM) for classification and selection of biomarkers, 13 potential biomarkers in rat serum were screened out. Furthermore, Ingenuity Pathway Analysis (IPA) was introduced to deeply analyze unique pathways of hypothyroidism that were primarily involved in sphingolipid metabolism, fatty acid transportation, phospholipid metabolism and phenylalanine metabolism. Our results demonstrated that the metabonomic approach integrating with IPA was a promising tool for providing a novel methodological clue to systemically dissect the underlying molecular mechanism of hypothyroidism. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Putative drug and vaccine target protein identification using comparative genomic analysis of KEGG annotated metabolic pathways of Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Damte, Dereje; Suh, Joo-Won; Lee, Seung-Jin; Yohannes, Sileshi Belew; Hossain, Md Akil; Park, Seung-Chun

    2013-07-01

    In the present study, a computational comparative and subtractive genomic/proteomic analysis aimed at the identification of putative therapeutic target and vaccine candidate proteins from Kyoto Encyclopedia of Genes and Genomes (KEGG) annotated metabolic pathways of Mycoplasma hyopneumoniae was performed for drug design and vaccine production pipelines against M.hyopneumoniae. The employed comparative genomic and metabolic pathway analysis with a predefined computational systemic workflow extracted a total of 41 annotated metabolic pathways from KEGG among which five were unique to M. hyopneumoniae. A total of 234 proteins were identified to be involved in these metabolic pathways. Although 125 non homologous and predicted essential proteins were found from the total that could serve as potential drug targets and vaccine candidates, additional prioritizing parameters characterize 21 proteins as vaccine candidate while druggability of each of the identified proteins evaluated by the DrugBank database prioritized 42 proteins suitable for drug targets. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation

    Directory of Open Access Journals (Sweden)

    Marangoni Sérgio

    2009-04-01

    Full Text Available Abstract Background Schizophrenia is likely to be a consequence of DNA alterations that, together with environmental factors, will lead to protein expression differences and the ultimate establishment of the illness. The superior temporal gyrus is implicated in schizophrenia and executes functions such as the processing of speech, language skills and sound processing. Methods We performed an individual comparative proteome analysis using two-dimensional gel electrophoresis of 9 schizophrenia and 6 healthy control patients' left posterior superior temporal gyrus (Wernicke's area – BA22p identifying by mass spectrometry several protein expression alterations that could be related to the disease. Results Our analysis revealed 11 downregulated and 14 upregulated proteins, most of them related to energy metabolism. Whereas many of the identified proteins have been previously implicated in schizophrenia, such as fructose-bisphosphate aldolase C, creatine kinase and neuron-specific enolase, new putative disease markers were also identified such as dihydrolipoyl dehydrogenase, tropomyosin 3, breast cancer metastasis-suppressor 1, heterogeneous nuclear ribonucleoproteins C1/C2 and phosphate carrier protein, mitochondrial precursor. Besides, the differential expression of peroxiredoxin 6 (PRDX6 and glial fibrillary acidic protein (GFAP were confirmed by western blot in schizophrenia prefrontal cortex. Conclusion Our data supports a dysregulation of energy metabolism in schizophrenia as well as suggests new markers that may contribute to a better understanding of this complex disease.

  20. Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

    Science.gov (United States)

    Pérez-Plasencia, Carlos; Vázquez-Ortiz, Guelaguetza; López-Romero, Ricardo; Piña-Sanchez, Patricia; Moreno, José; Salcedo, Mauricio

    2007-01-01

    Background Cervical carcinoma (CC) is a leading cause of death among women worldwide. Human papilloma virus (HPV) is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways. Results We found 2,067 genes significantly up or down-modulated (at least 2-fold) in tumor clinical samples compared to normal tissues, representing ~3.7% of analyzed genes. Cervical carcinoma was associated with an important up-regulation of Wnt signaling pathway, which was validated by in situ hybridization in clinical samples. Other up-regulated pathways were those of calcium signaling and MAPK signaling, as well as cell cycle-related genes. There was down-regulation of focal adhesion, TGF-β signaling, among other metabolic pathways. Conclusion This analysis of HPV 16 tumors transcriptome could be useful for the identification of genes and molecular pathways involved in the pathogenesis of cervical carcinoma. Understanding the possible role of these proteins in the pathogenesis of CC deserves further studies. PMID:17822553

  1. Genome wide expression analysis in HPV16 Cervical Cancer: identification of altered metabolic pathways

    Directory of Open Access Journals (Sweden)

    Salcedo Mauricio

    2007-09-01

    Full Text Available Abstract Background Cervical carcinoma (CC is a leading cause of death among women worldwide. Human papilloma virus (HPV is a major etiological factor in CC and HPV 16 is the more frequent viral type present. Our aim was to characterize metabolic pathways altered in HPV 16 tumor samples by means of transcriptome wide analysis and bioinformatics tools for visualizing expression data in the context of KEGG biological pathways. Results We found 2,067 genes significantly up or down-modulated (at least 2-fold in tumor clinical samples compared to normal tissues, representing ~3.7% of analyzed genes. Cervical carcinoma was associated with an important up-regulation of Wnt signaling pathway, which was validated by in situ hybridization in clinical samples. Other up-regulated pathways were those of calcium signaling and MAPK signaling, as well as cell cycle-related genes. There was down-regulation of focal adhesion, TGF-β signaling, among other metabolic pathways. Conclusion This analysis of HPV 16 tumors transcriptome could be useful for the identification of genes and molecular pathways involved in the pathogenesis of cervical carcinoma. Understanding the possible role of these proteins in the pathogenesis of CC deserves further studies.

  2. Proteomic analysis of an engineered isolate of Lactobacillus plantarum with enhanced raffinose metabolic capacity.

    Science.gov (United States)

    Wang, Jicheng; Hui, Wenyan; Cao, Chenxia; Jin, Rulin; Ren, Caixia; Zhang, Heping; Zhang, Wenyi

    2016-08-11

    Lactic acid bacteria that can produce alpha-galactosidase are a promising solution for improving the nutritional value of soy-derived products. For their commercial use in the manufacturing process, it is essential to understand the catabolic mechanisms that facilitate their growth and performance. In this study, we used comparative proteomic analysis to compare catabolism in an engineered isolate of Lactobacillus plantarum P-8 with enhanced raffinose metabolic capacity, with the parent (or wild-type) isolate from which it was derived. When growing on semi-defined medium with raffinose, a total of one hundred and twenty-five proteins were significantly up-regulated (>1.5 fold, P isolate, whilst and one hundred and six proteins were significantly down-regulated (isolate was able to utilise alternative carbohydrates such as sorbitol instead of raffinose to sustain cell division. To avoid acid damage the cell layer of the engineered isolate altered through a combination of de novo fatty acid biosynthesis and modification of existing lipid membrane phospholipid acyl chains. Interestingly, aspartate and glutamate metabolism was associated with this acid response. Higher intracellular aspartate and glutamate levels in the engineered isolate compared with the parent isolate were confirmed by further chemical analysis. Our study will underpin the future use of this engineered isolate in the manufacture of soymilk products.

  3. Metabolic flux analysis of Escherichia coli in glucose-limited continuous culture. I. Growth-rate-dependent metabolic efficiency at steady state.

    Science.gov (United States)

    Kayser, Anke; Weber, Jan; Hecht, Volker; Rinas, Ursula

    2005-03-01

    The Escherichia coli K-12 strain TG1 was grown at 28 degrees C in aerobic glucose-limited continuous cultures at dilution rates ranging from 0.044 to 0.415 h(-1). The rates of biomass formation, the specific rates of glucose, ammonium and oxygen uptake and the specific carbon dioxide evolution rate increased linearly with the dilution rate up to 0.3 h(-1). At dilution rates between 0.3 h(-1) and 0.4 h(-1), a strong deviation from the linear increase to lower specific oxygen uptake and carbon dioxide evolution rates occurred. The biomass formation rate and the specific glucose and ammonium uptake rates did not deviate that strongly from the linear increase up to dilution rates of 0.4 h(-1). An increasing percentage of glucose carbon flow towards biomass determined by a reactor mass balance and a decreasing specific ATP production rate concomitant with a decreasing adenylate energy charge indicated higher energetic efficiency of carbon substrate utilization at higher dilution rates. Estimation of metabolic fluxes by a stoichiometric model revealed an increasing activity of the pentose phosphate pathway and a decreasing tricarboxylic acid cycle activity with increasing dilution rates, indicative of the increased NADPH and precursor demand for anabolic purposes at the expense of ATP formation through catabolic activities. Thus, increasing growth rates first result in a more energy-efficient use of the carbon substrate for biomass production, i.e. a lower portion of the carbon substrate is channelled into the respiratory, energy-generating pathway. At dilution rates above 0.4 h(-1), close to the wash-out point, respiration rates dropped sharply and accumulation of glucose and acetic acid was observed. Energy generation through acetate formation yields less ATP compared with complete oxidation of the sugar carbon substrate, but is the result of maximized energy generation under conditions of restrictions in the tricarboxylic acid cycle or in respiratory NADH turnover

  4. In vivo versus in vitro protein abundance analysis of Shigella dysenteriae type 1 reveals changes in the expression of proteins involved in virulence, stress and energy metabolism

    Directory of Open Access Journals (Sweden)

    Donohue-Rolfe Arthur

    2011-06-01

    Full Text Available Abstract Background Shigella dysenteriae serotype 1 (SD1 causes the most severe form of epidemic bacillary dysentery. Quantitative proteome profiling of Shigella dysenteriae serotype 1 (SD1 in vitro (derived from LB cell cultures and in vivo (derived from gnotobiotic piglets was performed by 2D-LC-MS/MS and APEX, a label-free computationally modified spectral counting methodology. Results Overall, 1761 proteins were quantitated at a 5% FDR (false discovery rate, including 1480 and 1505 from in vitro and in vivo samples, respectively. Identification of 350 cytoplasmic membrane and outer membrane (OM proteins (38% of in silico predicted SD1 membrane proteome contributed to the most extensive survey of the Shigella membrane proteome reported so far. Differential protein abundance analysis using statistical tests revealed that SD1 cells switched to an anaerobic energy metabolism under in vivo conditions, resulting in an increase in fermentative, propanoate, butanoate and nitrate metabolism. Abundance increases of transcription activators FNR and Nar supported the notion of a switch from aerobic to anaerobic respiration in the host gut environment. High in vivo abundances of proteins involved in acid resistance (GadB, AdiA and mixed acid fermentation (PflA/PflB indicated bacterial survival responses to acid stress, while increased abundance of oxidative stress proteins (YfiD/YfiF/SodB implied that defense mechanisms against oxygen radicals were mobilized. Proteins involved in peptidoglycan turnover (MurB were increased, while β-barrel OM proteins (OmpA, OM lipoproteins (NlpD, chaperones involved in OM protein folding pathways (YraP, NlpB and lipopolysaccharide biosynthesis (Imp were decreased, suggesting unexpected modulations of the outer membrane/peptidoglycan layers in vivo. Several virulence proteins of the Mxi-Spa type III secretion system and invasion plasmid antigens (Ipa proteins required for invasion of colonic epithelial cells, and release

  5. [Nurses and doctors turnover: an impasse in the implementation of the Family Health Strategy].

    Science.gov (United States)

    Medeiros, Cássia Regina Gotler; Junqueira, Alvaro Gustavo Wagner; Schwingel, Glademir; Carreno, Ioná; Jungles, Lúcia Adriana Pereira; Saldanha, Olinda Maria de Fátima Lechmann

    2010-06-01

    The research analyzed the causes for turnover rate of doctors and nurses in family health strategy teams with at least two years of implementation on March 2006 in Vale do Taquari, Rio Grande do Sul State. It is a quantitative and qualitative study identifying 31 teams in 25 towns, and the turnover rate was established by year from 1999 to 2005 by professional category. There was no turnover for doctors and nurses in 1999 and 2000. Doctor turnover was 5.9% in 2002; 32.1% in 2003; 25.8% in 2004; and 64.5% in 2005. Regarding nurses, it was 27.7% in 2001; 47% in 2002; 17.8% in 2003; 41.9% in 2004; and 22.6% in 2005. The analysis of semi-structured interviews with 7 doctors and 7 nurses appointed as main causes for turnover: poor work links, fragmented education, authoritarian way of managing, no links with the community, and poor work conditions. Thus, it is necessary to make changes regarding labor links, work conditions, and education for health workers and managers, seeking for the integrality in health practices.

  6. Intention to leave the profession: antecedents and role in nurse turnover.

    Science.gov (United States)

    Parry, Julianne

    2008-10-01

    This paper is a report of a study to examine the relationship between intention to change profession and intention to change employer among newly graduated nurses. Few studies of the worldwide nursing workforce shortage consider the contribution of changing professions to the shortage. Organizational behaviour research has identified that professional commitment and organizational commitment have an important role in organizational turnover and that professional commitment and intention to change professions may have a greater role in organizational turnover than is presently understood. A model of the relationships between affective professional commitment job satisfaction, organizational commitment, intention to change professions and organizational turnover intention was developed through review of the organizational behaviour literature and tested using path analysis. The sample was drawn from all nurses in Queensland, Australia, entering the workforce for the first time in 2005. The model was tested with a final sample size of 131 nurses in the initial period of exposure to the workplace. Affective professional commitment and organizational commitment were statistically significantly related to intention to change professions. Job satisfaction, organizational commitment and intention to change professions were statistically significantly related to intention to change employer. Turnover research in nursing should include intention to change professions as well as intention to change employer. Policies and practices that enhance the development of affective professional commitment prior to exposure to the workplace and support affective professional commitment, job satisfaction and organizational commitment in the workplace are needed to help reduce nurse turnover.

  7. Factors influencing turnover intention among primary care doctors: a cross-sectional study in Chongqing, China.

    Science.gov (United States)

    Wen, Tong; Zhang, Yan; Wang, Xue; Tang, Guo

    2018-02-13

    The intention to leave a job, known as turnover intention, among primary care doctors has a significant impact on primary health care service delivery. We investigated primary care doctors' turnover intention and analysed associated factors involved in primary health facilities in Chongqing, China. A total of 440 doctors were interviewed, they were selected using a multi-stage stratified random sampling method. The survey instrument was a self-administered questionnaire which assessed socio-demographic and work-related characteristics, job satisfaction and turnover intention. The data were analysed using χ 2 test, one-way analysis of variance, exploratory factor analysis and linear regression analysis. Our study found that 42.3% of the primary care doctors we sampled in Chongqing, China, intended to resign. Location, age, job title, doctor's position level, work pressure and job satisfaction were associated with turnover intention. Job satisfaction included both employment-related job satisfaction (including "your chance of promotion", "your rate of pay" and two other items) and satisfaction with the job itself (including "the freedom to choose your own method of working", "your job safety" and two other items). Improving job satisfaction, in terms of salary, promotion and job safety, is crucial for reducing turnover intention among primary care doctors. Therefore, we suggest that the government increase its financial investment in primary care facilities, especially in less-developed areas, and reform incentive mechanisms to improve the job satisfaction of primary care doctors. The government should consider policies such as establishing a social pension programme for village-level doctors and providing more opportunities for job promotion among primary care doctors, especially township-level doctors. Attention should also be paid to the impact of rapid urbanization, which could lead to increased workload or increased opportunities for career development, thus

  8. Treatment staff turnover in organizations implementing evidence-based practices: turnover rates and their association with client outcomes.

    Science.gov (United States)

    Garner, Bryan R; Hunter, Brooke D; Modisette, Kathryn C; Ihnes, Pamela C; Godley, Susan H

    2012-03-01

    High staff turnover has been described as a problem for the substance use disorder treatment field. This assertion is based primarily on the assumption that staff turnover adversely impacts treatment delivery and effectiveness. This assumption, however, has not been empirically tested. In this study, we computed annualized rates of turnover for treatment staff (N = 249) participating in an evidence-based practice implementation initiative and examined the association between organizational-level rates of staff turnover and client-level outcomes. Annualized rates of staff turnover were 31% for clinicians and 19% for clinical supervisors. In addition, multilevel analyses did not reveal the expected relationship between staff turnover and poorer client-level outcomes. Rather, organizational-level rates of staff turnover were found to have a significant positive association with two measures of treatment effectiveness: less involvement in illegal activity and lower social risk. Possible explanations for these findings are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Inositol pyrophosphates and their unique metabolic complexity: analysis by gel electrophoresis.

    Directory of Open Access Journals (Sweden)

    Oriana Losito

    Full Text Available Inositol pyrophosphates are a recently characterized cell signalling molecules responsible for the pyrophosphorylation of protein substrates. Though likely involved in a wide range of cellular functions, the study of inositol pyrophosphates has suffered from a lack of readily available methods for their analysis.We describe a novel, sensitive and rapid polyacrylamide gel electrophoresis (PAGE-based method for the analysis of inositol pyrophosphates. Using 4',6-diamidino-2-phenylindole (DAPI and Toluidine Blue we demonstrate the unequivocal detection of various inositol pyrophosphate species.The use of the PAGE-based method reveals the likely underestimation of inositol pyrophosphates and their signalling contribution in cells when measured via traditional HPLC-based techniques. PAGE-based analyses also reveals the existence of a number of additional, previously uncharacterised pyrophosphorylated inositol reaction products, defining a more complex metabolism associated with the catalytically flexible kinase class responsible for the production of these highly energetic cell signalling molecules.

  10. Reconstruction and flux analysis of coupling between metabolic pathways of astrocytes and neurons: application to cerebral hypoxia

    Directory of Open Access Journals (Sweden)

    Akιn Ata

    2007-12-01

    Full Text Available Abstract Background It is a daunting task to identify all the metabolic pathways of brain energy metabolism and develop a dynamic simulation environment that will cover a time scale ranging from seconds to hours. To simplify this task and make it more practicable, we undertook stoichiometric modeling of brain energy metabolism with the major aim of including the main interacting pathways in and between astrocytes and neurons. Model The constructed model includes central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, lipid metabolism, reactive oxygen species (ROS detoxification, amino acid metabolism (synthesis and catabolism, the well-known glutamate-glutamine cycle, other coupling reactions between astrocytes and neurons, and neurotransmitter metabolism. This is, to our knowledge, the most comprehensive attempt at stoichiometric modeling of brain metabolism to date in terms of its coverage of a wide range of metabolic pathways. We then attempted to model the basal physiological behaviour and hypoxic behaviour of the brain cells where astrocytes and neurons are tightly coupled. Results The reconstructed stoichiometric reaction model included 217 reactions (184 internal, 33 exchange and 216 metabolites (183 internal, 33 external distribute