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Sample records for activates multiple metabolic

  1. Biochemical markers of bone metabolism reflect osteoclastic and osteoblastic activity in multiple myeloma

    DEFF Research Database (Denmark)

    Abildgaard, N; Glerup, H; Rungby, Jørgen

    2000-01-01

    In order to evaluate the use of recently developed assays of bone metabolism in multiple myeloma we performed a histomorphometric study of bone biopsies in 16 myeloma patients. Furthermore, we measured the levels of interleukin-6 (IL-6), soluble IL-6 receptor (IL-6sR), IL-1beta, tumour necrosis f...

  2. Metabolic activity of tree saps of different origin towards cultured human cells in the light of grade correspondence analysis and multiple regression modeling

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    Artur Wnorowski

    2017-06-01

    Full Text Available Tree saps are nourishing biological media commonly used for beverage and syrup production. Although the nutritional aspect of tree saps is widely acknowledged, the exact relationship between the sap composition, origin, and effect on the metabolic rate of human cells is still elusive. Thus, we collected saps from seven different tree species and conducted composition-activity analysis. Saps from trees of Betulaceae, but not from Salicaceae, Sapindaceae, nor Juglandaceae families, were increasing the metabolic rate of HepG2 cells, as measured using tetrazolium-based assay. Content of glucose, fructose, sucrose, chlorides, nitrates, sulphates, fumarates, malates, and succinates in sap samples varied across different tree species. Grade correspondence analysis clustered trees based on the saps’ chemical footprint indicating its usability in chemotaxonomy. Multiple regression modeling showed that glucose and fumarate present in saps from silver birch (Betula pendula Roth., black alder (Alnus glutinosa Gaertn., and European hornbeam (Carpinus betulus L. are positively affecting the metabolic activity of HepG2 cells.

  3. Prokaryote metabolism activity

    OpenAIRE

    Biederman, Lori

    2017-01-01

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

  4. Regulation of Metabolic Activity by p53

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    Jessica Flöter

    2017-05-01

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

  5. Defining active progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Börnsen, Lars; Ammitzbøll, Cecilie

    2017-01-01

    BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). OBJECTIVE: To compare CSF biomarkers in active and inactive...

  6. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Lidia De Riccardis

    2016-12-01

    Full Text Available Glatiramer acetate (GA; Copaxone is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS. Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+ T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+ T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+ T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  7. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients.

    Science.gov (United States)

    De Riccardis, Lidia; Ferramosca, Alessandra; Danieli, Antonio; Trianni, Giorgio; Zara, Vincenzo; De Robertis, Francesca; Maffia, Michele

    2016-12-01

    Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4 + , the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4 + T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4 + T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4 + T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

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

    International Nuclear Information System (INIS)

    Cohen, G.M.

    1990-01-01

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

  9. Noncanonical SQSTM1/p62-Nrf2 pathway activation mediates proteasome inhibitor resistance in multiple myeloma cells via redox, metabolic and translational reprogramming

    OpenAIRE

    Riz, Irene; Hawley, Teresa S.; Marsal, Jeffrey W.; Hawley, Robert G.

    2016-01-01

    Multiple Myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow, with drug resistance being a major cause of therapeutic failure. We established a carfilzomib-resistant derivative of the LP-1 MM cell line (LP-1/Cfz) and found that the transcription factor NF-E2 p45-related factor 2 (Nrf2; gene symbol NFE2L2) contributes to carfilzomib resistance. The mechanism of Nrf2 activation involved enhanced translation of Nrf2 as well as its posit...

  10. Sedentary activity associated with metabolic syndrome independent of physical activity

    DEFF Research Database (Denmark)

    Bankoski, Andrea; Harris, Tamara B; McClain, James J

    2011-01-01

    This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults.......This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults....

  11. VISCOSITY DICTATES METABOLIC ACTIVITY of Vibrio ruber

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    Maja eBoric

    2012-07-01

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

  12. Industry as a metabolic activity.

    Science.gov (United States)

    Smart, B

    1992-02-01

    The concept of "industrial economic metabolism" can provide a bridge to better understanding between environmentalists and industry. In nature each individual or species reacts to natural stimuli, competing with others for resources, extending its domain until it loses comparative advantage and comes to equilibrium with an adjacent competitor. Those species that succeed over time flourish; those that do not, diminish or disappear. Nature's rule book has no moral or ethical ingredient beyond self-interest. Corporate metabolisms are remarkably similar to those of nature. They too react to stimuli, collect and use resources, and grow or perish based on how effectively they compete. Corporate management recognizes and responds naturally and efficiently to cost and price signals. Through them it selects resources and converts them into useful products. The efficiency with which this is done is measured by profit, the lifeblood of the corporation and its means of growth. Profit thus provides a discipline on corporate behavior, encouraging efficient performers, and, by its absence, weeding out others. Unfettered by influences other than economics, the path to corporate success is unlikely to be a compassionate one. The dilemma of the manager is that to do what is socially "right" often conflicts with what must be done to survive and prosper. Fortunately, corporations' behavior can be altered by society when their purely economic role comes into conflict with other human values. The environment and the economy are not separate systems but intertwined to form a complex natural and social setting. The human-designed economic system depends on natural resource inputs, and in turn its metabolic wastes can overload the ecological system, threatening the long-term survivability of both. Increasing concern for the environment now gives the farsighted manager new latitude. There are competitive benefits in some pollution prevention. But there are not sufficiently strong forces to

  13. Multiple correlation analyses of metabolic and endocrine profiles with fertility in primiparous and multiparous cows.

    Science.gov (United States)

    Wathes, D C; Bourne, N; Cheng, Z; Mann, G E; Taylor, V J; Coffey, M P

    2007-03-01

    Results from 4 studies were combined (representing a total of 500 lactations) to investigate the relationships between metabolic parameters and fertility in dairy cows. Information was collected on blood metabolic traits and body condition score at 1 to 2 wk prepartum and at 2, 4, and 7 wk postpartum. Fertility traits were days to commencement of luteal activity, days to first service, days to conception, and failure to conceive. Primiparous and multiparous cows were considered separately. Initial linear regression analyses were used to determine relationships among fertility, metabolic, and endocrine traits at each time point. All metabolic and endocrine traits significantly related to fertility were included in stepwise multiple regression analyses alone (model 1), including peak milk yield and interval to commencement of luteal activity (model 2), and with the further addition of dietary group (model 3). In multiparous cows, extended calving to conception intervals were associated prepartum with greater concentrations of leptin and lesser concentrations of nonesterified fatty acids and urea, and postpartum with reduced insulin-like growth factor-I at 2 wk, greater urea at 7 wk, and greater peak milk yield. In primiparous cows, extended calving to conception intervals were associated with more body condition and more urea prepartum, elevated urea postpartum, and more body condition loss by 7 wk. In conclusion, some metabolic measurements were associated with poorer fertility outcomes. Relationships between fertility and metabolic and endocrine traits varied both according to the lactation number of the cow and with the time relative to calving.

  14. AMPK Activation Affects Glutamate Metabolism in Astrocytes

    DEFF Research Database (Denmark)

    Voss, Caroline Marie; Pajęcka, Kamilla; Stridh, Malin H

    2015-01-01

    acid (TCA) cycle was studied using high-performance liquid chromatography analysis supplemented with gas chromatography-mass spectrometry technology. It was found that AMPK activation had profound effects on the pathways involved in glutamate metabolism since the entrance of the glutamate carbon...... on glutamate metabolism in astrocytes was studied using primary cultures of these cells from mouse cerebral cortex during incubation in media containing 2.5 mM glucose and 100 µM [U-(13)C]glutamate. The metabolism of glutamate including a detailed analysis of its metabolic pathways involving the tricarboxylic...... skeleton into the TCA cycle was reduced. On the other hand, glutamate uptake into the astrocytes as well as its conversion to glutamine catalyzed by glutamine synthetase was not affected by AMPK activation. Interestingly, synthesis and release of citrate, which are hallmarks of astrocytic function, were...

  15. High salt diet induces metabolic alterations in multiple biological processes of Dahl salt-sensitive rats.

    Science.gov (United States)

    Wang, Yanjun; Liu, Xiangyang; Zhang, Chen; Wang, Zhengjun

    2018-06-01

    High salt induced renal disease is a condition resulting from the interactions of genetic and dietary factors causing multiple complications. To understand the metabolic alterations associated with renal disease, we comprehensively analyzed the metabonomic changes induced by high salt intake in Dahl salt-sensitive (SS) rats using GC-MS technology and biochemical analyses. Physiological features, serum chemistry, and histopathological data were obtained as complementary information. Our results showed that high salt (HS) intake for 16 weeks caused significant metabolic alterations in both the renal medulla and cortex involving a variety pathways involved in the metabolism of organic acids, amino acids, fatty acids, and purines. In addition, HS enhanced glycolysis (hexokinase, phosphofructokinase and pyruvate kinase) and amino acid metabolism and suppressed the TCA (citrate synthase and aconitase) cycle. Finally, HS intake caused up-regulation of the pentose phosphate pathway (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), the ratio of NADPH/NADP + , NADPH oxidase activity and ROS production, suggesting that increased oxidative stress was associated with an altered PPP pathway. The metabolic pathways identified may serve as potential targets for the treatment of renal damage. Our findings provide comprehensive biochemical details about the metabolic responses to a high salt diet, which may contribute to the understanding of renal disease and salt-induced hypertension in SS rats. Copyright © 2018. Published by Elsevier Inc.

  16. Metabolic benefits of physical activity

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    Špela Volčanšek

    2014-10-01

    Full Text Available Physical activity is the most beneficial intervention in prevention and treatment of chronic diseases. Life style, which has become mostly sedentary, leads to growing incidence in obesity, what could cause the first so far reduction in life expectancy in developed countries.Physical activity reduces the chronic low-grade inflammation, which plays an important role in the pathogenesis of type 2 diabetes, cardiovascular disease and certain types of cancer. Regular physical activity exerts two anti-inflammatory effects: reduction of visceral fat, which produces the majority of pro-inflammatory cytokines, and production of myokines. It has been proposed that cytokines and other peptides that are produced by muscle fibers should be classified as myokines that exert autocrine, paracrine and endocrine effects. Myokines induce muscle hypertrophy and myogenesis, stimulate fat oxidation, improve insulin sensitivity and have an anti-inflammatory effect.  Therefore, skeletal muscle has been identified as a secretory organ and this provides the basis for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, gut, bones and brain. Physical inactivity leads to an altered myokine profile, associating sedentary life style with some chronic diseases.Physical activity is recommended as a tool for weight management and prevention of weight gain, for weight loss and for prevention of weight regain. High quality studies have confirmed the important impact of exercise on improving blood glucose control in diabetic patients, and on preventing or delaying the onset of type 2 diabetes in predisposed populations. Prescribing specific exercise tailored to individual's needs is an intervention strategy for health improvement. Physical fitness counteracts the detrimental effects of obesity reducing morbidity and mortality.

  17. Dietary leucine--an environmental modifier of insulin resistance acting on multiple levels of metabolism.

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    Yazmin Macotela

    Full Text Available Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor--leucine--can modify insulin resistance by acting on multiple tissues and at multiple levels of metabolism. Mice were placed on a normal or high fat diet (HFD. Dietary leucine was doubled by addition to the drinking water. mRNA, protein and complete metabolomic profiles were assessed in the major insulin sensitive tissues and serum, and correlated with changes in glucose homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum. Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated with a decrease in hepatic steatosis and a decrease in inflammation in adipose tissue. These changes occurred despite an increase in insulin-stimulated phosphorylation of p70S6 kinase indicating enhanced activation of mTOR, a phenomenon normally associated with insulin resistance. These data indicate that modest changes in a single environmental/nutrient factor can modify multiple metabolic and signaling pathways and modify HFD induced metabolic syndrome by acting at a systemic level on multiple tissues. These data also suggest that increasing dietary leucine may provide an adjunct in the management of obesity-related insulin resistance.

  18. Modulation of multiple memory systems: from neurotransmitters to metabolic substrates.

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    Gold, Paul E; Newman, Lori A; Scavuzzo, Claire J; Korol, Donna L

    2013-11-01

    This article reviews evidence showing that neurochemical modulators can regulate the relative participation of the hippocampus and striatum in learning and memory tasks. For example, relative release of acetylcholine increases in the hippocampus and striatum reflects the relative engagement of these brain systems during learning of place and response tasks. Acetylcholine release is regulated in part by available brain glucose levels, which themselves are dynamically modified during learning. Recent findings suggest that glucose acts through astrocytes to deliver lactate to neurons. Brain glycogen is contained in astrocytes and provides a capacity to deliver energy substrates to neurons when needed, a need that can be generated by training on tasks that target hippocampal and striatal processing mechanisms. These results integrate an increase in blood glucose after epinephrine release from the adrenal medulla with provision of brain energy substrates, including lactate released from astrocytes. Together, the availability of peripheral and central energy substrates regulate the processing of learning and memory within and across multiple neural systems. Dysfunctions of the physiological steps that modulate memory--from hormones to neurotransmitters to metabolic substrates--may contribute importantly to some of the cognitive impairments seen during normal aging and during neurodegenerative diseases. Copyright © 2013 Wiley Periodicals, Inc.

  19. Multiple Electrolyte and Metabolic Emergencies in a Single Patient

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    Caprice Cadacio

    2017-01-01

    Full Text Available While some electrolyte disturbances are immediately life-threatening and must be emergently treated, others may be delayed without immediate adverse consequences. We discuss a patient with alcoholism and diabetes mellitus type 2 who presented with volume depletion and multiple life-threatening electrolyte and metabolic derangements including severe hyponatremia (serum sodium concentration [SNa] 107 mEq/L, hypophosphatemia (“undetectable,” <1.0 mg/dL, and hypokalemia (2.2 mEq/L, moderate diabetic ketoacidosis ([DKA], pH 7.21, serum anion gap [SAG] 37 and hypocalcemia (ionized calcium 4.0 mg/dL, mild hypomagnesemia (1.6 mg/dL, and electrocardiogram with prolonged QTc. Following two liters of normal saline and associated increase in SNa by 4 mEq/L and serum osmolality by 2.4 mosm/Kg, renal service was consulted. We were challenged with minimizing the correction of SNa (or effective serum osmolality to avoid the osmotic demyelinating syndrome while replacing volume, potassium, phosphorus, calcium, and magnesium and concurrently treating DKA. Our management plan was further complicated by an episode of significant aquaresis. A stepwise approach was strategized to prioritize and correct all disturbances with considerations that the treatment of one condition could affect or directly worsen another. The current case demonstrates that a thorough understanding of electrolyte physiology is required in managing complex electrolyte disturbances to avoid disastrous outcomes.

  20. Metabolism

    Science.gov (United States)

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

  1. A Urinary Metabolic Signature for Multiple Sclerosis and Neuromyelitis Optica

    DEFF Research Database (Denmark)

    Gebregiworgis, Teklab; Nielsen, Helle H; Massilamany, Chandirasegaran

    2016-01-01

    a statistically distinct metabolic signature from healthy and NMO-SD controls. A total of 27 metabolites were differentially altered in the urine from MS and NMO-SD patients and were associated with synthesis and degradation of ketone bodies, amino acids, propionate and pyruvate metabolism, tricarboxylic acid...

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

    Science.gov (United States)

    2015-10-01

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

  3. 5' adenosine monophosphate-activated protein kinase, metabolism and exercise.

    Science.gov (United States)

    Aschenbach, William G; Sakamoto, Kei; Goodyear, Laurie J

    2004-01-01

    The 5' adenosine monophosphate-activated protein kinase (AMPK) is a member of a metabolite-sensing protein kinase family that functions as a metabolic 'fuel gauge' in skeletal muscle. AMPK is a ubiquitous heterotrimeric protein, consisting of an alpha catalytic, and beta and gamma regulatory subunits that exist in multiple isoforms and are all required for full enzymatic activity. During exercise, AMPK becomes activated in skeletal muscle in response to changes in cellular energy status (e.g. increased adenosine monophosphate [AMP]/adenosine triphosphate [ATP] and creatine/phosphocreatine ratios) in an intensity-dependent manner, and serves to inhibit ATP-consuming pathways, and activate pathways involved in carbohydrate and fatty-acid metabolism to restore ATP levels. Recent evidence shows that although AMPK plays this key metabolic role during acute bouts of exercise, it is also an important component of the adaptive response of skeletal muscles to endurance exercise training because of its ability to alter muscle fuel reserves and expression of several exercise-responsive genes. This review discusses the putative roles of AMPK in acute and chronic exercise responses, and suggests avenues for future AMPK research in exercise physiology and biochemistry.

  4. Metabolic assessments during extra-vehicular activity

    Science.gov (United States)

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

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

  5. Nucleons II: cryopreservation and metabolic activity.

    Science.gov (United States)

    Reyes, R; Flores-Alonso, J C; Rodríguez-Hernández, H M; Merchant-Larios, H M; Delgado, N M

    2001-01-01

    The establishment of intracytoplasmatic sperm injection (ICSI) as a routine procedure in assisted fertilization has been used in the treatment of male infertility. The major technical problem that has arisen with the use of immotile sperm for ICSI has been differentiating between live and dead cells. Nucleons from human, pig, hamster, mouse, rat, and bull have been able to induce their chromatin decondensation by the action of heparin/GSH. Cryopreservation is deleterious to sperm function, killing more than 50% of the spermatozoa during the process. Nucleon cryostorage was performed at 5 and -5 degrees C and analyzed for total area (mu2), perimeter (mu), width (mu), and length (mu), using Metamorph Imaging System software. On the other hand, fluorescein diacetate (FDA) is hydrolyzed by intracellular estereases to produce fluorescein, which exhibits green fluorescence when excited by blue light. This fact is a striking result since the presence of this metabolic activity opens the possibility to select the nucleons for ICSI. In the present study, the authors decided to search for a suitable metabolic test, which might reflect the metabolism and viability of these chromatin structures. This is a simple cryostorage technique that after months of cryopreservation, allow the use of nucleons for ICSI with suitable fertilization and pregnancies rates.

  6. Physical activity as a metabolic stressor.

    Science.gov (United States)

    Coyle, E F

    2000-08-01

    Both physical activity and diet stimulate processes that, over time, alter the morphologic composition and biochemical function of the body. Physical activity provides stimuli that promote very specific and varied adaptations according to the type, intensity, and duration of exercise performed. There is further interest in the extent to which diet or supplementation can enhance the positive stimuli. Prolonged walking at low intensity presents little metabolic, hormonal, or cardiovascular stress, and the greatest perturbation from rest appears to be from increased fat oxidation and plasma free fatty acid mobilization resulting from a combination of increased lipolysis and decreased reesterification. More intense jogging or running largely stimulates increased oxidation of glycogen and triacylglycerol, both of which are stored directly within the muscle fibers. Furthermore, these intramuscular stores of carbohydrate and fat appear to be the primary substrates for the enhanced oxidative and performance ability derived from endurance training-induced increases in muscle mitochondrial density. Weightlifting that produces fatigue in brief periods (ie, in 15-90 s and after 15 repetitive contractions) elicits a high degree of motor unit recruitment and muscle fiber stimulation. This is a remarkably potent stimulus for altering protein synthesis in muscle and increasing neuromuscular function. The metabolic stress of physical activity can be measured by substrate turnover and depletion, cardiovascular response, hormonal perturbation, accumulation of metabolites, or even the extent to which the synthesis and degradation of specific proteins are altered, either acutely or by chronic exercise training.

  7. Sortilin and Its Multiple Roles in Cardiovascular and Metabolic Diseases

    DEFF Research Database (Denmark)

    Goettsch, Claudia; Kjølby, Mads Fuglsang; Aikawa, Elena

    2018-01-01

    Cardiovascular disease is a leading cause of morbidity and mortality in the Western world. Studies of sortilin's influence on cardiovascular and metabolic diseases goes far beyond the genome-wide association studies that have revealed an association between cardiovascular diseases and the 1p13...... locus that encodes sortilin. Emerging evidence suggests a significant role of sortilin in the pathogenesis of vascular and metabolic diseases; this includes type II diabetes mellitus via regulation of insulin resistance, atherosclerosis through arterial wall inflammation and calcification...... of sortilin's contributions to cardiovascular and metabolic diseases but focuses particularly on atherosclerosis. We summarize recent clinical findings that suggest that sortilin may be a cardiovascular risk biomarker and also discuss sortilin as a potential drug target....

  8. Natural AMPK Activators: An Alternative Approach for the Treatment and Management of Metabolic Syndrome.

    Science.gov (United States)

    Sharma, Hitender; Kumar, Sunil

    2017-01-01

    This review covers recent discoveries of phytoconstituents, herbal extracts and some semi-synthetic compounds for treating metabolic syndrome with AMPK activation as one of their mechanisms of action. Recent researches have demonstrated AMPK activation to ameliorate multiple components of metabolic syndrome by regulating a balance between anabolic and catabolic cellular reactions. The review attempts to delineate the AMPK activation by natural agents from the perspective of its functional consequences on enzymes, transcription factors and signaling molecules and also on other potential factors contributing in the amelioration of metabolic syndrome. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Assembly and multiple gene expression of thermophilic enzymes in Escherichia coli for in vitro metabolic engineering.

    Science.gov (United States)

    Ninh, Pham Huynh; Honda, Kohsuke; Sakai, Takaaki; Okano, Kenji; Ohtake, Hisao

    2015-01-01

    In vitro reconstitution of an artificial metabolic pathway is an emerging approach for the biocatalytic production of industrial chemicals. However, several enzymes have to be separately prepared (and purified) for the construction of an in vitro metabolic pathway, thereby limiting the practical applicability of this approach. In this study, genes encoding the nine thermophilic enzymes involved in a non-ATP-forming chimeric glycolytic pathway were assembled in an artificial operon and co-expressed in a single recombinant Escherichia coli strain. Gene expression levels of the thermophilic enzymes were controlled by their sequential order in the artificial operon. The specific activities of the recombinant enzymes in the cell-free extract of the multiple-gene-expression E. coli were 5.0-1,370 times higher than those in an enzyme cocktail prepared from a mixture of single-gene-expression strains, in each of which a single one of the nine thermophilic enzymes was overproduced. Heat treatment of a crude extract of the multiple-gene-expression cells led to the denaturation of indigenous proteins and one-step preparation of an in vitro synthetic pathway comprising only a limited number of thermotolerant enzymes. Coupling this in vitro pathway with other thermophilic enzymes including the H2 O-forming NADH oxidase or the malate/lactate dehydrogenase facilitated one-pot conversion of glucose to pyruvate or lactate, respectively. © 2014 Wiley Periodicals, Inc.

  10. Mutagenicity of vinyl chloride after metabolic activation

    Energy Technology Data Exchange (ETDEWEB)

    Rannug, U; Johansson, A; Ramel, C; Wachtmeister, C A

    1974-01-01

    Vinyl chloride has recently been shown to cause a malignant liver tumor disease in man after occupational exposure in PVC plants. This actualizes the problem of whether such hazards could be avoided or at least diminished in the future by a screening for mutagenicity of chemicals used in industries. The basis for such a screening procedure is the close correlation between carcinogenic and mutagenic effects of chemicals. Experiments with Salmonella bacteria showed that the carcinogenic hazard of vinyl chloride could have been traced by means of mutagenicity tests. The data indicate that vinyl chloride is not mutagenic per se but becomes mutagenic after a metabolic activation in the liver. 24 references, 1 figure, 4 tables.

  11. Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

    Directory of Open Access Journals (Sweden)

    Trevor P. Fidler

    2017-07-01

    Full Text Available Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT 1 and GLUT3 (double knockout [DKO] specifically in platelets completely abolished glucose uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic substrates, such as glutamate, increased. Thrombosis and platelet activation were decreased through impairment at multiple activation nodes, including Ca2+ signaling, degranulation, and integrin activation. DKO mice developed thrombocytopenia, secondary to impaired pro-platelet formation from megakaryocytes, and increased platelet clearance resulting from cytosolic calcium overload and calpain activation. Systemic treatment with oligomycin, inhibiting mitochondrial metabolism, induced rapid clearance of platelets, with circulating counts dropping to zero in DKO mice, but not wild-type mice, demonstrating an essential role for energy metabolism in platelet viability. Thus, substrate metabolism is essential for platelet production, activation, and survival.

  12. Metabolism

    Science.gov (United States)

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

  13. Clinical significance of reduced cerebral metabolism in multiple sclerosis. A combined PET and MRI study

    International Nuclear Information System (INIS)

    Sun, Xiayan; Tanaka, Makoto; Kondo, Susumu; Okamoto, Koichi; Hirai, Shunsaku

    1998-01-01

    Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease's natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO 2 ). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman's rank correlation coefficients. A general reduction in rCBF and rCMRO 2 in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO 2 . A correlation between the decrease in rCMRO 2 and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information. (author)

  14. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women

    Directory of Open Access Journals (Sweden)

    Katarina Melzer

    2016-07-01

    Full Text Available “Metabolic Equivalent” (MET represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O2/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry were measured in adolescent males (n = 50 and females (n = 50, women during pregnancy (gestation week 35–41, n = 46, women 24–53 weeks postpartum (n = 27, and active men (n = 30, and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h was significantly higher than that of adolescent females (1.11 kcal/kg × h, with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h and overweight (0.89 kcal/kg × h adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard.

  15. DAG tales: the multiple faces of diacylglycerol--stereochemistry, metabolism, and signaling.

    Science.gov (United States)

    Eichmann, Thomas Oliver; Lass, Achim

    2015-10-01

    The neutral lipids diacylglycerols (DAGs) are involved in a plethora of metabolic pathways. They function as components of cellular membranes, as building blocks for glycero(phospho)lipids, and as lipid second messengers. Considering their central role in multiple metabolic processes and signaling pathways, cellular DAG levels require a tight regulation to ensure a constant and controlled availability. Interestingly, DAG species are versatile in their chemical structure. Besides the different fatty acid species esterified to the glycerol backbone, DAGs can occur in three different stereo/regioisoforms, each with unique biological properties. Recent scientific advances have revealed that DAG metabolizing enzymes generate and distinguish different DAG isoforms, and that only one DAG isoform holds signaling properties. Herein, we review the current knowledge of DAG stereochemistry and their impact on cellular metabolism and signaling. Further, we describe intracellular DAG turnover and its stereochemistry in a 3-pool model to illustrate the spatial and stereochemical separation and hereby the diversity of cellular DAG metabolism.

  16. Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and rodent hepatocytes

    International Nuclear Information System (INIS)

    Bjork, J.A.; Butenhoff, J.L.; Wallace, K.B.

    2011-01-01

    Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are surface active fluorochemicals that, due to their exceptional stability to degradation, are persistent in the environment. Both PFOA and PFOS are eliminated slowly in humans, with geometric mean serum elimination half-lives estimated at 3.5 and 4.8 years, respectively. The biological activity of PFOA and PFOS in rodents is attributed primarily to transactivation of the nuclear receptor peroxisome proliferator activated receptor alpha (PPARA), which is an important regulator of lipid and carbohydrate metabolism. However, there are significant species-specific differences in the response to PFOA and PFOS exposure; non-rodent species, including humans, are refractory to several but not all of these effects. Many of the metabolic effects have been attributed to the activation of PPARA; however, recent studies using PPARα knockout mice demonstrate residual PPARA-independent effects, some of which may involve the activation of alternate nuclear receptors, including NR1I2 (PXR), NR1I3 (CAR), NR1H3 (LXRA), and NR1H4 (FXR). The objective of this investigation was to characterize the activation of multiple nuclear receptors and modulation of metabolic pathways associated with exposure to PFOA and PFOS, and to compare and contrast the effects between rat and human primary liver cells using quantitative reverse transcription PCR (RT-qPCR). Our results demonstrate that multiple nuclear receptors participate in the metabolic response to PFOA and PFOS exposure resulting in a substantial shift from carbohydrate metabolism to fatty acid oxidation and hepatic triglyceride accumulation in rat liver cells. This shift in intermediary metabolism was more pronounced for PFOA than PFOS. Furthermore, while there is some similarity in the activation of metabolic pathways between rat and humans, particularly in PPARA regulated responses; the changes in primary human cells were more subtle and possibly reflect an adaptive

  17. Active control of multiple resistive wall modes

    International Nuclear Information System (INIS)

    Brunsell, P. R.; Yadikin, D.; Gregoratto, D.; Paccagnella, R.; Liu, Y. Q.; Bolzonella, T.; Cecconello, M.; Drake, J. R.; Kuldkepp, M.; Manduchi, G.; Marchiori, G.; Marrelli, L.; Partin, P.; Menmuir, S.; Ortolani, S.; Rachlew, E.; Spizzo, S.; Zanca, P.

    2005-01-01

    Active magnetic feedback suppression of resistive wall modes is of common interest for several fusion concepts relying on close conducting walls for stabilization of ideal magnetohydrodynamic (MHD) modes. In the advanced tokamak without plasma rotation the kink mode is not completely stabilized, but rather converted into an unstable resistive wall mode (RWM) with a growth time comparable to the wall magnetic flux penetration time. The reversed field pinch (RFP) is similar to the advanced tokamak in the sense that it uses a conducting wall for kink mode stabilization. Also both configurations are susceptible to resonant field error amplification of marginally stable modes. However, the RFP has a different RWM spectrum and, in general, a range of modes is unstable. Hence, the requirement for simultaneous feedback stabilization of multiple independent RWMs arises for the RFP configuration. Recent experiments on RWM feedback stabilization, performed in the RFP device EXTRAP T2R [1], are presented. The experimental results obtained are the first demonstration of simultaneous feedback control of multiple independent RWMs [2]. Using an array of active magnetic coils, a reproducible suppression of several RWMs is achieved for the duration of the discharge, 3-5 wall times, through feedback action. An array with 64 active saddle coils at 4 poloidal times 16 toroidal positions is used. The important issues of side band generation by the active coil array and the accompanying coupling of different unstable modes through the feedback action are addressed in this study. Open loop control experiments have been carried out to quantitatively study resonant field error amplification. (Author)

  18. Linking neuronal brain activity to the glucose metabolism

    OpenAIRE

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

    2013-01-01

    Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regul...

  19. Metabolism features in the active rheumatoid disease

    Energy Technology Data Exchange (ETDEWEB)

    Cossermelli, W; Carvalho, N; Papaleo Netto, M [Sao Paulo Univ. (Brazil). Centro de Medicina Nuclear

    1974-02-01

    The /sup 131/I-labelled albumin metabolism was studied in fourteen female patients with rheumatoid arthritis. The half-life of distribution was increased while the turnover half-life and turnover rate was within normal limits. These results led to assume that synthesis and catabolism may not change this disease, not being the responsible mechanism of hypoalbuminemia. Hypoalbuminemia would appear as compensatory mechanism in view of other protein alterations, as hypergammaglobulinemia, without changes of stabilizing and metabolic properties of albumin, perhaps due to albumin molecular alterations.

  20. Metabolism features in the active rheumatoid disease

    International Nuclear Information System (INIS)

    Cossermelli, W.; Carvalho, N.; Papaleo Netto, M.

    1974-01-01

    It was studied the 131 I-labelled albumin metabolism in fourteen female patients with rheumatoid arthritis. The half-life of distribution was increased while the turnover half-life and turnover rate was within normal limits. These results led to assume that synthesis and catabolism may not change this disease, not being the responsible mechanism of hypoalbuminemia. Hypoalbuminemia would appear as compensatory mechanism in view of other protein alterations, as hypergammaglobulinemia, without changes of stabilizing and metabolic properties of albumin, perhaps due to albumin molecular alterations [pt

  1. Phase I metabolic genes and risk of lung cancer: multiple polymorphisms and mRNA expression.

    Directory of Open Access Journals (Sweden)

    Melissa Rotunno

    2009-05-01

    Full Text Available Polymorphisms in genes coding for enzymes that activate tobacco lung carcinogens may generate inter-individual differences in lung cancer risk. Previous studies had limited sample sizes, poor exposure characterization, and a few single nucleotide polymorphisms (SNPs tested in candidate genes. We analyzed 25 SNPs (some previously untested in 2101 primary lung cancer cases and 2120 population controls from the Environment And Genetics in Lung cancer Etiology (EAGLE study from six phase I metabolic genes, including cytochrome P450s, microsomal epoxide hydrolase, and myeloperoxidase. We evaluated the main genotype effects and genotype-smoking interactions in lung cancer risk overall and in the major histology subtypes. We tested the combined effect of multiple SNPs on lung cancer risk and on gene expression. Findings were prioritized based on significance thresholds and consistency across different analyses, and accounted for multiple testing and prior knowledge. Two haplotypes in EPHX1 were significantly associated with lung cancer risk in the overall population. In addition, CYP1B1 and CYP2A6 polymorphisms were inversely associated with adenocarcinoma and squamous cell carcinoma risk, respectively. Moreover, the association between CYP1A1 rs2606345 genotype and lung cancer was significantly modified by intensity of cigarette smoking, suggesting an underlying dose-response mechanism. Finally, increasing number of variants at CYP1A1/A2 genes revealed significant protection in never smokers and risk in ever smokers. Results were supported by differential gene expression in non-tumor lung tissue samples with down-regulation of CYP1A1 in never smokers and up-regulation in smokers from CYP1A1/A2 SNPs. The significant haplotype associations emphasize that the effect of multiple SNPs may be important despite null single SNP-associations, and warrants consideration in genome-wide association studies (GWAS. Our findings emphasize the necessity of post

  2. Activation of Necroptosis in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Dimitry Ofengeim

    2015-03-01

    Full Text Available Multiple sclerosis (MS, a common neurodegenerative disease of the CNS, is characterized by the loss of oligodendrocytes and demyelination. Tumor necrosis factor α (TNF-α, a proinflammatory cytokine implicated in MS, can activate necroptosis, a necrotic cell death pathway regulated by RIPK1 and RIPK3 under caspase-8-deficient conditions. Here, we demonstrate defective caspase-8 activation, as well as activation of RIPK1, RIPK3, and MLKL, the hallmark mediators of necroptosis, in the cortical lesions of human MS pathological samples. Furthermore, we show that MS pathological samples are characterized by an increased insoluble proteome in common with other neurodegenerative diseases such as Alzheimer’s disease (AD, Parkinson’s disease (PD, and Huntington’s disease (HD. Finally, we show that necroptosis mediates oligodendrocyte degeneration induced by TNF-α and that inhibition of RIPK1 protects against oligodendrocyte cell death in two animal models of MS and in culture. Our findings demonstrate that necroptosis is involved in MS and suggest that targeting RIPK1 may represent a therapeutic strategy for MS.

  3. Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism

    NARCIS (Netherlands)

    Kersten, A.H.

    2008-01-01

    Plasma lipoproteins are responsible for carrying triglycerides and cholesterol in the blood and ensuring their delivery to target organs. Regulation of lipoprotein metabolism takes place at numerous levels including via changes in gene transcription. An important group of transcription factors that

  4. Multiple spectroscopic analyses reveal the fate and metabolism of sulfamide herbicide triafamone in agricultural environments

    International Nuclear Information System (INIS)

    Wang, Mengcen; Qian, Yuan; Liu, Xiaoyu; Wei, Peng; Deng, Man; Wang, Lei; Wu, Huiming; Zhu, Guonian

    2017-01-01

    Triafamone, a sulfamide herbicide, has been extensively utilized for weed control in rice paddies in Asia. However, its fate and transformation in the environment have not been established. Through a rice paddy microcosm-based simulation trial combined with multiple spectroscopic analyses, we isolated and identified three novel metabolites of triafamone, including hydroxyl triafamone (HTA), hydroxyl triafamone glycoside (HTAG), and oxazolidinedione triafamone (OTA). When triafamone was applied to rice paddies at a concentration of 34.2 g active ingredient/ha, this was predominantly distributed in the paddy soil and water, and then rapidly dissipated in accordance with the first-order rate model, with half-lives of 4.3–11.0 days. As the main transformation pathway, triafamone was assimilated by the rice plants and was detoxified into HTAG, whereas the rest was reduced into HTA with subsequent formation of OTA. At the senescence stage, brown rice had incurred triafamone at a concentration of 0.0016 mg/kg, but the hazard quotient was <1, suggesting that long-term consumption of the triafamone-containing brown rice is relatively safe. The findings of the present study indicate that triafamone is actively metabolized in the agricultural environment, and elucidation of the link between environmental exposure to these triazine or oxazolidinedione moieties that contain metabolites and their potential impacts is warranted. - Highlights: • Multiple spectroscopic analyses were applied to investigate agrochemicals transformation in environment. • Three novel compounds were isolated and identified as triafamone metabolites. • The fate and transformation pathway of triafamone in rice paddy were revealed. • Long-term consumption of the triafamone-containing brown rice is relatively safe. • Elucidation of environmental impacts by exposure to these triazine or oxazolidinedione metabolites is warranted. - Triafamone rapidly dissipates in agricultural environments

  5. Adhesive ability and biofilm metabolic activity of Listeria ...

    African Journals Online (AJOL)

    SWEET

    2012-07-31

    Jul 31, 2012 ... monocytogenes strains were able to adhere to abiotic materials with different degrees. In fact, cold stressed strains ... packaging. Biofilms allow .... reduction of a tetrazolium salt by metabolically active cells to a colored water ...

  6. the prevalence of metabolic syndrome among active sportsmen

    African Journals Online (AJOL)

    User

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

  7. [Coactivators in energy metabolism: peroxisome proliferator-activated receptor-gamma coactivator 1 family].

    Science.gov (United States)

    Wang, Rui; Chang, Yong-sheng; Fang, Fu-de

    2009-12-01

    Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) family is highly expressed in tissues with high energy metabolism. They coactivate transcription factors in regulating genes engaged in processes such as gluconeogenesis, adipose beta-oxydation, lipoprotein synthesis and secretion, mitochondrial biogenesis, and oxidative metabolism. Protein conformation studies demonstrated that they lack DNA binding domains and act as coactivators through physical interaction with transcription factors. PGC1 activity is regulated at transcription level or by multiple covalent chemical modifications such as phosphorylation, methylation and acetylation/deacetylation. Abnormal expression of PGC1 coactivators usually is closely correlated with diseases such as diabetes, obesity, hyperglycemia, hyperlipemia, and arterial and brain neuron necrosis diseases.

  8. Metabolic alkalosis with multiple salt unbalance: an atypical onset of cystic fibrosis in a child

    Directory of Open Access Journals (Sweden)

    Dimitri Poddighe

    2017-12-01

    Full Text Available Dehydration with multiple salt abnormalities is frequently encountered in the paediatric emergency department, during acute illnesses complicated by loss of body fluids. Metabolic alkalosis is not a common finding in dehydrated children. The presence of unusual electrolyte unbalance, such as metabolic alkalosis, hyponatremia, hypochloremia and hypokalemia, without evidence of renal tubular defects, is named as pseudo-Bartter syndrome. It can occur in several clinical settings and, in infancy, it is described as a potential complication of cystic fibrosis. We report a case of pseudo-Bartter syndrome representing the onset of cystic fibrosis in childhood.

  9. Activating transcription factor 3 regulates immune and metabolic homeostasis.

    Science.gov (United States)

    Rynes, Jan; Donohoe, Colin D; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek; Uhlirova, Mirka

    2012-10-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.

  10. Multiple-Active Multiple-Passive Antenna Systems and Applications

    DEFF Research Database (Denmark)

    Tsakalaki, Elpiniki

    2013-01-01

    -passive (MAMP) antenna topologies, as explained in Sect. 8.1. Then, Sect. 8.2 proposes MAMP antenna structures with application to reconfigurable MIMO transmission in the presence of antenna mutual coupling under poor scattering channel conditions. For this purpose, the section presents an adaptive MAMP antenna...... system capable of changing its transmission parameters via passive radiators attached to tunable loads, according to the structure of the RF propagation channel. The hybrid MAMP array structure can be tractably analyzed using the active element response vector (instead of the classical steering vector...... adaptive MAMP system can be limited to practical dimensions whereas the passive antennas require no extra RF hardware, thus meeting the cost, space, and power constrains of the users’ mobile terminals. The simulation results show that the adaptive MAMP system, thanks to its “adaptivity”, is able to achieve...

  11. Peroxisome Proliferators-Activated Receptor (PPAR Modulators and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Min-Chul Cho

    2008-01-01

    Full Text Available Overweight and obesity lead to an increased risk for metabolic disorders such as impaired glucose regulation/insulin resistance, dyslipidemia, and hypertension. Several molecular drug targets with potential to prevent or treat metabolic disorders have been revealed. Interestingly, the activation of peroxisome proliferator-activated receptor (PPAR, which belongs to the nuclear receptor superfamily, has many beneficial clinical effects. PPAR directly modulates gene expression by binding to a specific ligand. All PPAR subtypes (α,γ, and σ are involved in glucose metabolism, lipid metabolism, and energy balance. PPAR agonists play an important role in therapeutic aspects of metabolic disorders. However, undesired effects of the existing PPAR agonists have been reported. A great deal of recent research has focused on the discovery of new PPAR modulators with more beneficial effects and more safety without producing undesired side effects. Herein, we briefly review the roles of PPAR in metabolic disorders, the effects of PPAR modulators in metabolic disorders, and the technologies with which to discover new PPAR modulators.

  12. Linking neuronal brain activity to the glucose metabolism.

    Science.gov (United States)

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

    2013-08-29

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

  13. STAT3 Activities and Energy Metabolism: Dangerous Liaisons

    Energy Technology Data Exchange (ETDEWEB)

    Camporeale, Annalisa, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Demaria, Marco [Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945 (United States); Monteleone, Emanuele [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Giorgi, Carlotta [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Wieckowski, Mariusz R. [Nencki Institute of Experimental Biology, Department of Biochemistry, Pasteur Str. 3, Warsaw 02-093 (Poland); Pinton, Paolo [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Poli, Valeria, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy)

    2014-07-31

    STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3{sup C/C}) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3{sup C/C} MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3{sup C/C} MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms.

  14. STAT3 Activities and Energy Metabolism: Dangerous Liaisons

    International Nuclear Information System (INIS)

    Camporeale, Annalisa; Demaria, Marco; Monteleone, Emanuele; Giorgi, Carlotta; Wieckowski, Mariusz R.; Pinton, Paolo; Poli, Valeria

    2014-01-01

    STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3 C/C ) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3 C/C MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3 C/C MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms

  15. Physical activity effects on bone metabolism.

    Science.gov (United States)

    Smith, E L; Gilligan, C

    1991-01-01

    The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows.

  16. Natural Killer Cell Activity and Interleukin-12 in Metabolically Healthy versus Metabolically Unhealthy Overweight Individuals

    Science.gov (United States)

    Kim, Minjoo; Kim, Minkyung; Yoo, Hye Jin; Lee, Jong Ho

    2017-01-01

    The purpose of this study was to determine whether the immune system is involved in the different metabolic circumstances in healthy and unhealthy overweight individuals. We examined the metabolic and immune characteristics of 117 overweight individuals. Subjects were classified as metabolically healthy overweight (MHO, n = 72) or metabolically unhealthy overweight (MUO, n = 45). The immune response was measured by circulating levels of natural killer (NK) cell activity and cytokines. Both groups were comparable with regards to age, sex distribution, smoking and drinking status, and body mass index. When compared to the MHO group, the MUO group showed higher systolic and diastolic blood pressure, serum levels of triglyceride, glucose, glucose-related markers, and lower levels of HDL cholesterol. Compared to the MHO group, the MUO group showed 39% lower interferon-γ levels (not significant) and 41% lower interleukin (IL)-12 levels (significant). The MUO group also showed lower NK cell activity at E:T ratios of 10:1, 5:1, 2.5:1, and 1.25:1 (all Ps < 0.05) than the MHO group. This study indicates that individuals displaying the MUO phenotype present an unfavorable immune system with lower NK cell activities under all assay conditions and lower serum levels of IL-12 than the activities and levels in similarly overweight MHO individuals. This result suggests that the immune system may be altered in overweight individuals who are at risk for overweight/obesity-related comorbidities. PMID:29238351

  17. Natural Killer Cell Activity and Interleukin-12 in Metabolically Healthy versus Metabolically Unhealthy Overweight Individuals

    Directory of Open Access Journals (Sweden)

    Minjoo Kim

    2017-11-01

    Full Text Available The purpose of this study was to determine whether the immune system is involved in the different metabolic circumstances in healthy and unhealthy overweight individuals. We examined the metabolic and immune characteristics of 117 overweight individuals. Subjects were classified as metabolically healthy overweight (MHO, n = 72 or metabolically unhealthy overweight (MUO, n = 45. The immune response was measured by circulating levels of natural killer (NK cell activity and cytokines. Both groups were comparable with regards to age, sex distribution, smoking and drinking status, and body mass index. When compared to the MHO group, the MUO group showed higher systolic and diastolic blood pressure, serum levels of triglyceride, glucose, glucose-related markers, and lower levels of HDL cholesterol. Compared to the MHO group, the MUO group showed 39% lower interferon-γ levels (not significant and 41% lower interleukin (IL-12 levels (significant. The MUO group also showed lower NK cell activity at E:T ratios of 10:1, 5:1, 2.5:1, and 1.25:1 (all Ps < 0.05 than the MHO group. This study indicates that individuals displaying the MUO phenotype present an unfavorable immune system with lower NK cell activities under all assay conditions and lower serum levels of IL-12 than the activities and levels in similarly overweight MHO individuals. This result suggests that the immune system may be altered in overweight individuals who are at risk for overweight/obesity-related comorbidities.

  18. Metabolic imidacloprid resistance in the brown planthopper, Nilaparvata lugens, relies on multiple P450 enzymes.

    Science.gov (United States)

    Zhang, Yixi; Yang, Yuanxue; Sun, Huahua; Liu, Zewen

    2016-12-01

    Target insensitivity contributing to imidacloprid resistance in Nilaparvata lugens has been reported to occur either through point mutations or quantitative change in nicotinic acetylcholine receptors (nAChRs). However, the metabolic resistance, especially the enhanced detoxification by P450 enzymes, is the major mechanism in fields. From one field-originated N. lugens population, an imidacloprid resistant strain G25 and a susceptible counterpart S25 were obtained to analyze putative roles of P450s in imidacloprid resistance. Compared to S25, over-expression of twelve P450 genes was observed in G25, with ratios above 5.0-fold for CYP6AY1, CYP6ER1, CYP6CS1, CYP6CW1, CYP4CE1 and CYP425B1. RNAi against these genes in vivo and recombinant tests on the corresponding proteins in vitro revealed that four P450s, CYP6AY1, CYP6ER1, CYP4CE1 and CYP6CW1, played important roles in imidacloprid resistance. The importance of the four P450s was not equal at different stages of resistance development based on their over-expression levels, among which CYP6ER1 was important at all stages, and that the others might only contribute at certain stages. The results indicated that, to completely reflect roles of P450s in insecticide resistances, their over-expression in resistant individuals, expression changes at the stages of resistance development, and catalytic activities against insecticides should be considered. In this study, multiple P450s, CYP6AY1, CYP6ER1, CYP4CE1 and CYP6CW1, have proven to be important in imidacloprid resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Metabolic-epigenetic crosstalk in macrophage activation

    NARCIS (Netherlands)

    Baardman, Jeroen; Licht, Iris; de Winther, Menno P. J.; van den Bossche, Jan

    2015-01-01

    Epigenetic enzymes are emerging as crucial controllers of macrophages, innate immune cells that determine the outcome of many inflammatory diseases. Recent studies demonstrate that the activity of particular chromatin-modifying enzymes is regulated by the availability of specific metabolites like

  20. Disturbed Glucose Metabolism in Rat Neurons Exposed to Cerebrospinal Fluid Obtained from Multiple Sclerosis Subjects

    Directory of Open Access Journals (Sweden)

    Deepali Mathur

    2017-12-01

    Full Text Available Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS. In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate the pathophysiological mechanisms underpinning axonal injury through hitherto unknown factors present in cerebrospinal fluid (CSF that may regulate axonal damage, remyelinate the axon and make functional recovery possible. We employed primary cultures of rat unmyelinated cerebellar granule neurons and treated them with CSF obtained from MS and Neuromyelitis optica (NMO patients. We performed microarray gene expression profiling to study changes in gene expression in treated neurons as compared to controls. Additionally, we determined the influence of gene-gene interaction upon the whole metabolic network in our experimental conditions using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING program. Our findings revealed the downregulated expression of genes involved in glucose metabolism in MS-derived CSF-treated neurons and upregulated expression of genes in NMO-derived CSF-treated neurons. We conclude that factors in the CSF of these patients caused a perturbation in metabolic gene(s expression and suggest that MS appears to be linked with metabolic deformity.

  1. Effects of activation of endocannabinoid system on myocardial metabolism

    Directory of Open Access Journals (Sweden)

    Agnieszka Polak

    2016-05-01

    Full Text Available Endocannabinoids exert their effect on the regulation of energy homeostasis via activation of specific receptors. They control food intake, secretion of insulin, lipids and glucose metabolism, lipid storage. Long chain fatty acids are the main myocardial energy substrate. However, the heart exerts enormous metabolic flexibility emphasized by its ability to utilzation not only fatty acids, but also glucose, lactate and ketone bodies. Endocannabinoids can directly act on the cardiomyocytes through the CB1 and CB2 receptors present in cardiomyocytes. It appears that direct activation of CB1 receptors promotes increased lipogenesis, pericardial steatosis and bioelectrical dysfunction of the heart. In contrast, stimulation of CB2 receptors exhibits cardioprotective properties, helping to maintain appropriate amount of ATP in cardiomyocytes. Furthermore, the effects of endocannabinoids at both the central nervous system and peripheral tissues, such as liver, pancreas, or adipose tissue, resulting indirectly in plasma availability of energy substrates and affects myocardial metabolism. To date, there is little evidence that describes effects of activation of the endocannabinoid system in the cardiovascular system under physiological conditions. In the present paper the impact of metabolic diseases, i. e. obesity and diabetes, as well as the cardiovascular diseases - hypertension, myocardial ischemia and myocardial infarction on the deregulation of the endocannabinoid system and its effect on the metabolism are described.

  2. Glucose metabolism regulates T cell activation, differentiation and functions

    Directory of Open Access Journals (Sweden)

    Clovis Steve Palmer

    2015-01-01

    Full Text Available The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The Warburg effect originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

  3. Correlation of Diffusion and Metabolic Alterations in Different Clinical Forms of Multiple Sclerosis

    Science.gov (United States)

    Hannoun, Salem; Bagory, Matthieu; Durand-Dubief, Francoise; Ibarrola, Danielle; Comte, Jean-Christophe; Confavreux, Christian; Cotton, Francois; Sappey-Marinier, Dominique

    2012-01-01

    Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients. PMID:22479330

  4. Glycoside hydrolases having multiple hydrolase activities

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhiwei; Friedland, Gregory D.; Chhabra, Swapnil R.; Chivian, Dylan C.; Simmons, Blake A

    2017-08-08

    Glycoside hydrolases having at least two different hydrolytic activities are provided. In one embodiment, an isolated recombinant hydrolase having at least two activities selected from a group including asparagine derivatives, glutamine derivatives, and histidine derivatives is provided. Further, a method of generating free sugars from a mixture comprising asparagine derivatives, glutamine derivatives, and histidine derivatives is provided.

  5. Metabolic activation of the bladder carcinogen 4-nitrobiphenyl (NBP)

    International Nuclear Information System (INIS)

    Swaminathan, S.

    1986-01-01

    The metabolism of NBP, a dog bladder carcinogen, was examined in vitro using rat liver tissues. NBP was metabolized by enzymes localized both in the microsomes and cytosol. The microsomal enzyme activity was inducible by Aroclor 1254 and phenobarbital. High pressure liquid chromatography analysis of the ethyl acetate extract of the reaction mixture, following incubation of [ 3 H]NBP with NADPH and microsomes, revealed four radioactive and UV absorbing peaks with retention times of 5, 8, 14 and 28 min. The peaks at 8, 14 and 28 min corresponded with 4-aminobiphenyl (ABP), NBP and azoxy biphenyl, respectively. The early eluting component with a retention time of 5 min has been tentatively identified as a ring hydroxylated derivative. In contrast to microsomal metabolism, cytosol-mediated metabolism yielded only one major metabolite identified as ABP. Cytosol-mediate reduction was inhibited by the xanthine oxidase inhibitor allopurinol. In vitro incubation of NBP with NADH and commercial preparations of xanthine oxidase also yielded ABP and the formation of the latter was blocked by allopurinol. Xanthine oxidase catalyzed also the binding of [ 3 H]NBP to DNA and proteins; the binding was inhibited by allopurinol. These data support the hypothesis that the nitro reduction step is involved in the activation of the bladder carcinogen NBP, and that the nitroreductases occur in both the microsomes and cytosol. The cytosolic activity is primarily due to xanthine oxidase

  6. Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

    Science.gov (United States)

    Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

    2012-01-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

  7. Metabolic activation of 2-methylfuran by rat microsomal systems

    International Nuclear Information System (INIS)

    Ravindranath, V.; Boyd, M.R.

    1985-01-01

    2-Methylfuran (2-MF), a constituent of cigarette smoke and coffee, causes necrosis of liver, lungs, and kidneys in rodents. 2-MF is metabolically activated by mixed-function oxidases to acetylacrolein, a reactive metabolite that binds covalently to microsomal protein. The hepatic microsomal metabolism of 2-MF to reactive metabolite required the presence of NADPH and oxygen and was dependent on incubation time and substrate concentration. The microsomal metabolism of 2-MF was inducible by pretreatment of rats with phenobarbital and was inhibited by piperonyl butoxide and N-octyl imidazole, which indicates that the metabolism of 2-MF may be mediated by cytochrome P-450. Acetylacrolein was a potent inhibitor of mixed-function oxidase and completely inhibited the microsomal metabolism of 2-MF, indicating that 2-MF is a suicide substrate for the enzyme. The sulfhydryl nucleophile cysteine was a better trapping agent of the reactive metabolite of 2-MF than N-acetylcysteine or glutathione. Lysine decreased the covalent binding of 2-MF metabolites, presumably by reacting with the aldehyde group of acetylacrolein. In addition, in the presence of NADPH, 2-MF was bioactivated by both pulmonary and renal cortical microsomes to reactive metabolites that were covalently bound to microsomal proteins

  8. Octulosonic acid derivatives from Roman chamomile (Chamaemelum nobile) with activities against inflammation and metabolic disorder.

    Science.gov (United States)

    Zhao, Jianping; Khan, Shabana I; Wang, Mei; Vasquez, Yelkaira; Yang, Min Hye; Avula, Bharathi; Wang, Yan-Hong; Avonto, Cristina; Smillie, Troy J; Khan, Ikhlas A

    2014-03-28

    Six new octulosonic acid derivatives (1-6) were isolated from the flower heads of Roman chamomile (Chamaemelum nobile). Their structures were elucidated by means of spectroscopic interpretation. The biological activity of the isolated compounds was evaluated toward multiple targets related to inflammation and metabolic disorder such as NAG-1, NF-κB, iNOS, ROS, PPARα, PPARγ, and LXR. Similar to the action of NSAIDs, all the six compounds (1-6) increased NAG-1 activity 2-3-fold. They also decreased cellular oxidative stress by inhibiting ROS generation. Compounds 3, 5, and 6 activated PPARγ 1.6-2.1-fold, while PPARα was activated 1.4-fold by compounds 5 and 6 only. None of the compounds showed significant activity against iNOS or NF-κB. This is the first report of biological activity of octulosonic acid derivatives toward multiple pathways related to inflammation and metabolic disorder. The reported anti-inflammatory, hypoglycemic, antiedemic, and antioxidant activities of Roman chamomile could be partly explained as due to the presence of these constituents.

  9. Study of the brain glucose metabolism in different stage of mixed-type multiple system atrophy

    International Nuclear Information System (INIS)

    Wang Ying; Zhang Benshu; Cai Li; Zhang Meiyun; Gao Shuo

    2014-01-01

    Objective: To investigate the brain glucose metabolism in different stage of mixed-type multiple system atrophy (MSA). Methods: Forty-six MSA patients with cerebellar or Parkinsonian symptoms and 18 healthy controls with similar age as patients were included. According to the disease duration,the patients were divided into three groups: group 1 (≤ 12 months, n=14), group 2 (13-24 months, n=13), group 3 (≥ 25 months, n=19). All patients and controls underwent 18 F-FDG PET/CT brain imaging. To compare metabolic distributions between different groups, SPM 8 software and two-sample t test were used for image data analysis. When P<0.005, the result was considered statistically significant. Results: At the level of P<0.005, the hypometabolism in group 1 (all t>3.49) was identified in the frontal lobe, lateral temporal lobe, insula lobe, anterior cingulate cortex, caudate nucleus and anterior cerebellar hemisphere. The regions of hypometabolism extended to posterolateral putamen and part of posterior cerebellar hemisphere in group 2 (all t>3.21). In group 3, the whole parts of putamen and cerebellar hemisphere were involved as hypometabolism (all t>4.08). In addition to the hypometabolism regions, there were also stabled hypermetabolism regions mainly in the parietal lobe, medial temporal lobe and the thalamus in all patient groups (all t>3.27 in group 1, all t>3.02 in group 2,all t>3.30 in group 3). Conclusions: Disease duration is closely related to the FDG metabolism in the MSA patients. Frontal lobe, lateral temporal lobe, anterior cingulate cortex and caudate nucleus can be involved at early stage of the disease. Putaminal hypometabolism begins in its posterolateral part. Cerebellar hypometabolism occurs early at its anterior part. Besides, thalamus shows hypermetabolism in the whole duration. 18 F-FDG metabolic changes of brain can reflect the development of mixed-type MSA. (authors)

  10. The Application of the Weighted k-Partite Graph Problem to the Multiple Alignment for Metabolic Pathways.

    Science.gov (United States)

    Chen, Wenbin; Hendrix, William; Samatova, Nagiza F

    2017-12-01

    The problem of aligning multiple metabolic pathways is one of very challenging problems in computational biology. A metabolic pathway consists of three types of entities: reactions, compounds, and enzymes. Based on similarities between enzymes, Tohsato et al. gave an algorithm for aligning multiple metabolic pathways. However, the algorithm given by Tohsato et al. neglects the similarities among reactions, compounds, enzymes, and pathway topology. How to design algorithms for the alignment problem of multiple metabolic pathways based on the similarity of reactions, compounds, and enzymes? It is a difficult computational problem. In this article, we propose an algorithm for the problem of aligning multiple metabolic pathways based on the similarities among reactions, compounds, enzymes, and pathway topology. First, we compute a weight between each pair of like entities in different input pathways based on the entities' similarity score and topological structure using Ay et al.'s methods. We then construct a weighted k-partite graph for the reactions, compounds, and enzymes. We extract a mapping between these entities by solving the maximum-weighted k-partite matching problem by applying a novel heuristic algorithm. By analyzing the alignment results of multiple pathways in different organisms, we show that the alignments found by our algorithm correctly identify common subnetworks among multiple pathways.

  11. Alteration In Bones Metabolism In Active Rheumatoid Arthritis

    International Nuclear Information System (INIS)

    Salem, E.S.

    2013-01-01

    The strength and integrity of the human skeleton depends on a delicate equilibrium between bone resorption and bone formation. Osteocalcin (OC) is synthesized by osteoblasts and is considered to be a marker of bone formation and helps in corporating calcium into bone tissue. Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease characterized by bone complication including bone pain, erosion and osteoporosis. The aim of the present study is to evaluate some factors responsible in bone metabolism termed OC, vitamin D (vit. D), oncostatin M (OSM), ionized calcium and alkaline phosphatase. Fifty pre-menopausal female patients with active RA and twenty healthy controls of the same age were included in the present study. Radioimmunoassay (RIA) was used to estimate serum OC and active vitamin D. The quantitative determination of ionized calcium and alkaline phosphatase were carried out colorimetrically. OSM was measured by ELISA and serum levels of OC and active vitamin D were significantly decreased in RA patients as compared to those of the control group. On the other hand, the levels of serum OSM, ionized calcium and alkaline phosphatase were significantly increased in the RA patients as compared to their healthy control subjects. The results of this study indicated that early investigation and therapy of disturbances of bone metabolism in active RA are necessary for better prognosis and exhibited the importance of OC as a diagnostic tool of alterations of bone metabolism in RA patients.

  12. Physical activity, BMI and metabolic risk in Portuguese adolescents

    Directory of Open Access Journals (Sweden)

    Fernanda Karina dos Santos

    2016-03-01

    Full Text Available DOI: http://dx.doi.org/10.5007/1980-0037.2016v18n1p103   It has been reported, in the last decades, a significant decrease in physical activity (PA levels, with a consequent increase in obesity and metabolic risk factors among youth. The aims of this study were to describe PA levels, the prevalence of overweight/obesity and metabolic risk factors, and to examine the association between PA and body mass index (BMI with metabolic risk among Portuguese youth. The sample comprises 212 Portuguese adolescents (12-16 years old. Height and weight were measured. PA was estimated with the Bouchard questionnaire (3 days recall, as well as with the use of a pedometer (used for 5 consecutive days. Metabolic risk factors comprised fasting glucose, triglycerides, HDL-cholesterol, systolic blood pressure and waist circumference. Subjects were classified as normal weight, overweight or obese according to BMI; the maturational status was indirectly estimated with the maturity offset procedure. A continuous metabolic risk score was computed (zMR and PA values were divided into tertiles. Qui-square test, t-test and ANOVA were used in statistical analyses. SPSS 18.0 and WinPepi softwares were used and p<0.05. A moderate to high prevalence of overweight/obesity and HDL-cholesterol was found, as well as a high prevalence of high blood pressure and low to moderate PA levels among Portuguese youth. The relationship between BMI and zMR showed that obese adolescents have higher zMR when compared to normal weight or overweight adolescents. This finding suggests that increased levels of PA and reduction in the prevalence of overweight/obesity may have a positive role against the development of metabolic risk factors.

  13. Relationship between metabolic syndrome and moderate-to-vigorous physical activity in youth.

    Science.gov (United States)

    Machado-Rodrigues, Aristides M; Leite, Neiva; Coelho e Silva, Manuel J; Valente-dos-Santos, João; Martins, Raul A; Mascarenhas, Luis P G; Boguszewski, Margaret C S; Padez, Cristina; Malina, Robert M

    2015-01-01

    Associations of metabolic syndrome (MetS) with lifestyle behaviors in youth is potentially important for identifying subgroups at risk and encourage interventions. This study evaluates the associations among the clustering of metabolic risk factors and moderate-to-vigorous physical activity (MVPA) in youth. The sample comprised 522 girls and 402 boys (N = 924) aged 11 to 17 years. Height, weight, waist circumference (WC), fasting glucose, high-density lipoprotein cholesterol, triglycerides, and blood pressures were measured. Cardiorespiratory fitness (CRF) was assessed using the 20-m shuttle run test. MVPA was estimated with a 3-day diary. Outcome variables were statistically normalized and expressed as z scores. A clustered metabolic risk score was computed as the mean of z scores. Multiple linear regression was used to test associations between metabolic risk and MVPA by sex, adjusted for age, WC, and CRF. After adjustment for potential confounders, MVPA was inversely associated with the clustering of metabolic risk factors in girls, but not in boys; in addition, after adjusting for WC, the statistical model of that relationship was substantially improved in girls. MVPA was independently associated with increased risk of MetS in girls. Additional efforts are needed to encourage research with different analytical approach and standardization of criteria for MetS in youth.

  14. Metabolic syndrome and cognitive decline: the role of physical activity

    Directory of Open Access Journals (Sweden)

    M. Rinaldi

    2013-01-01

    Full Text Available Metabolic Syndrome (MetS is a cluster of conditions, each of which represents a risk factor for cardiovascular disease: central obesity, hyperglycemia, dyslipidemia and hypertension. Any of these conditions and MetS itself have been associated to Alzheimer's Disease and Vascular Dementia. In recent years there is a growing evidence for the role of physical activity in preventing metabolic diseases and cognitive decline. In our research we assessed the prevalence of MetS in a sample of 154 elderly people. Furthermore, we evaluated cognition (with Mini Mental State Examination, MMSE  and the physical activity level in every patient. We found a significant association between MetS, borderline cognitive impairment and sedentary lifestyle.

  15. Active neutron multiplicity analysis and Monte Carlo calculations

    International Nuclear Information System (INIS)

    Krick, M.S.; Ensslin, N.; Langner, D.G.; Miller, M.C.; Siebelist, R.; Stewart, J.E.; Ceo, R.N.; May, P.K.; Collins, L.L. Jr

    1994-01-01

    Active neutron multiplicity measurements of high-enrichment uranium metal and oxide samples have been made at Los Alamos and Y-12. The data from the measurements of standards at Los Alamos were analyzed to obtain values for neutron multiplication and source-sample coupling. These results are compared to equivalent results obtained from Monte Carlo calculations. An approximate relationship between coupling and multiplication is derived and used to correct doubles rates for multiplication and coupling. The utility of singles counting for uranium samples is also examined

  16. Multiple Substrate Usage of Coxiella burnetii to Feed a Bipartite Metabolic Network

    Directory of Open Access Journals (Sweden)

    Ina Häuslein

    2017-06-01

    Full Text Available The human pathogen Coxiella burnetii causes Q-fever and is classified as a category B bio-weapon. Exploiting the development of the axenic growth medium ACCM-2, we have now used 13C-labeling experiments and isotopolog profiling to investigate the highly diverse metabolic network of C. burnetii. To this aim, C. burnetii RSA 439 NMII was cultured in ACCM-2 containing 5 mM of either [U-13C3]serine, [U-13C6]glucose, or [U-13C3]glycerol until the late-logarithmic phase. GC/MS-based isotopolog profiling of protein-derived amino acids, methanol-soluble polar metabolites, fatty acids, and cell wall components (e.g., diaminopimelate and sugars from the labeled bacteria revealed differential incorporation rates and isotopolog profiles. These data served to decipher the diverse usages of the labeled substrates and the relative carbon fluxes into the core metabolism of the pathogen. Whereas, de novo biosynthesis from any of these substrates could not be found for histidine, isoleucine, leucine, lysine, phenylalanine, proline and valine, the other amino acids and metabolites under study acquired 13C-label at specific rates depending on the nature of the tracer compound. Glucose was directly used for cell wall biosynthesis, but was also converted into pyruvate (and its downstream metabolites through the glycolytic pathway or into erythrose 4-phosphate (e.g., for the biosynthesis of tyrosine via the non-oxidative pentose phosphate pathway. Glycerol efficiently served as a gluconeogenetic substrate and could also be used via phosphoenolpyruvate and diaminopimelate as a major carbon source for cell wall biosynthesis. In contrast, exogenous serine was mainly utilized in downstream metabolic processes, e.g., via acetyl-CoA in a complete citrate cycle with fluxes in the oxidative direction and as a carbon feed for fatty acid biosynthesis. In summary, the data reflect multiple and differential substrate usages by C. burnetii in a bipartite-type metabolic network

  17. Prediction of residual metabolic activity after treatment in NSCLC patients

    International Nuclear Information System (INIS)

    Rios Velazquez, Emmanuel; Aerts, Hugo J.W.L.; Oberije, Cary; Ruysscher, Dirk De; Lambin, Philippe

    2010-01-01

    Purpose. Metabolic response assessment is often used as a surrogate of local failure and survival. Early identification of patients with residual metabolic activity is essential as this enables selection of patients who could potentially benefit from additional therapy. We report on the development of a pre-treatment prediction model for metabolic response using patient, tumor and treatment factors. Methods. One hundred and one patients with inoperable NSCLC (stage I-IV), treated with 3D conformal radical (chemo)-radiotherapy were retrospectively included in this study. All patients received a pre and post-radiotherapy fluorodeoxyglucose positron emission tomography-computed tomography FDG-PET-CT scan. The electronic medical record system and the medical patient charts were reviewed to obtain demographic, clinical, tumor and treatment data. Primary outcome measure was examined using a metabolic response assessment on a post-radiotherapy FDG-PET-CT scan. Radiotherapy was delivered in fractions of 1.8 Gy, twice a day, with a median prescribed dose of 60 Gy. Results. Overall survival was worse in patients with residual metabolic active areas compared with the patients with a complete metabolic response (p=0.0001). In univariate analysis, three variables were significantly associated with residual disease: larger primary gross tumor volume (GTVprimary, p=0.002), higher pre-treatment maximum standardized uptake value (SUV max , p=0.0005) in the primary tumor and shorter overall treatment time (OTT, p=0.046). A multivariate model including GTVprimary, SUV max , equivalent radiation dose at 2 Gy corrected for time (EQD2, T) and OTT yielded an area under the curve assessed by the leave-one-out cross validation of 0.71 (95% CI, 0.65-0.76). Conclusion. Our results confirmed the validity of metabolic response assessment as a surrogate of survival. We developed a multivariate model that is able to identify patients at risk of residual disease. These patients may benefit from

  18. Effects of vasoactive and metabolic active substances (measurement of RCBF)

    Energy Technology Data Exchange (ETDEWEB)

    Herrschaft, H.

    1986-09-29

    Methods, principles, normal values, reproducibility and clinical indications of rCBF-measurements, using the intraartrial 133-Xenon-clearance-technique, are presented. The effect of vaso- and metabolically active drugs on cerebral blood flow was examined in 215 patients, suffering from cerebral ischemia. Significant increase of rCBF was ascertained after intravenous injection of centrophenoxine, pyrithioxine, extractum sanguis deproteinatus, piracetam and solutions of low molecular dextran. All the other drugs tested proved to be either without any effect or caused decrease of rCBF. In 130 patients with obstructive disease of internal carotid artery after surgery at an interval of 6 - 8 weeks and 1 year a significant increase of CBF could be stated. The rank of psychological tests and quantitative EEF-investigations relating to evidence of efficacy of metabolically active drugs is discussed critically. Therapeutic efficacy and clinical relevance of vaso- and metabolically active drugs in cerebral ischemia of man are to be substantiated only by double-blind controlled studies.

  19. Effects of vasoactive and metabolic active substances (measurement of RCBF)

    International Nuclear Information System (INIS)

    Herrschaft, H.

    1986-01-01

    Methods, principles, normal values, reproducibility and clinical indications of rCBF-measurements, using the intraartrial 133-Xenon-clearance-technique, are presented. The effect of vaso- and metabolically active drugs on cerebral blood flow was examined in 215 patients, suffering from cerebral ischemia. Significant increase of rCBF was ascertained after intravenous injection of centrophenoxine, pyrithioxine, extractum sanguis deproteinatus, piracetam and solutions of low molecular dextran. All the other drugs tested proved to be either without any effect or caused decrease of rCBF. In 130 patients with obstructive disease of internal carotid artery after surgery at an interval of 6 - 8 weeks and 1 year a significant increase of CBF could be stated. The rank of psychological tests and quantitative EEF-investigations relating to evidence of efficacy of metabolically active drugs is discussed critically. Therapeutic efficacy and clinical relevance of vaso- and metabolically active drugs in cerebral ischemia of man are to be substantiated only by double-blind controlled studies. (orig.) [de

  20. Physical activity, body composition and metabolic syndrome in young adults.

    Directory of Open Access Journals (Sweden)

    Minna K Salonen

    Full Text Available Low physical activity (PA is a major risk factor for cardiovascular and metabolic disorders in all age groups. We measured intensity and volume of PA and examined the associations between PA and the metabolic syndrome (MS, its components and body composition among young Finnish adults.The study comprises 991 men and women born 1985-86, who participated in a clinical study during the years 2009-11 which included assessments of metabolism, body composition and PA. Objectively measured (SenseWear Armband five-day PA data was available from 737 participants and was expressed in metabolic equivalents of task (MET.The prevalence of MS ranged between 8-10%. Higher total mean volume (MET-hours or intensity (MET were negatively associated with the risk of MS and separate components of MS, while the time spent at sedentary level of PA was positively associated with MS.MS was prevalent in approximately every tenth of the young adults at the age of 24 years. Higher total mean intensity and volume rates as well as longer duration spent at moderate and vigorous PA level had a beneficial impact on the risk of MS. Longer time spent at the sedentary level of PA increased the risk of MS.

  1. Physical activity motivation and benefits in people with multiple sclerosis.

    Science.gov (United States)

    Fasczewski, Kimberly S; Gill, Diane L; Rothberger, Sara M

    2018-06-01

    Multiple sclerosis is a degenerative neurological disease that affects 2.1 million people worldwide. There is no cure, but an expanding body of research supports the positive impact of physical activity and suggests physical activity has benefits for the individual's psychological and physical well-being. Using Self-Determination Theory as a framework, mixed methods with a focus on qualitative interviews were used to explore physical activity motivation and benefits with a sample of highly active people with multiple sclerosis (n = 15). Disability level ranged from not disabled to wheelchair bound with the majority of participants reporting minimal impact from multiple sclerosis. Survey data were collected using a number of open-ended questions along with measures of self-efficacy, self-determined motivation, physical activity, and quality of life. Additionally, eight individuals participated in semistructured telephone interviews focused on (a) motivation and strategies used to maintain physical activity and (b) the benefits and impact of physical activity in their lives. The main findings were consistent with Self-Determination Theory; participants described feelings of accomplishment and competence in both their physical activity and daily life, as well as a sense of independence and autonomy. Similarly, all participants cited benefits, and the main themes were enhanced satisfaction with life and an overall positive outlook on life. Results provide insight into the role of physical activity in a highly active sample and have implications for professionals working in physical activity settings with the multiple sclerosis population. Interventions aimed at increasing long-term physical activity adherence should focus on increasing autonomy and competence for physical activity in the individual and promoting potential increased quality of life outcomes from physical activity participation. Implications for Rehabilitation Multiple sclerosis is a chronic

  2. Activity syndromes and metabolism in giant deep-sea isopods

    Science.gov (United States)

    Wilson, Alexander D. M.; Szekeres, Petra; Violich, Mackellar; Gutowsky, Lee F. G.; Eliason, Erika J.; Cooke, Steven J.

    2017-03-01

    Despite growing interest, the behavioural ecology of deep-sea organisms is largely unknown. Much of this scarcity in knowledge can be attributed to deepwater animals being secretive or comparatively 'rare', as well as technical difficulties associated with accessing such remote habitats. Here we tested whether two species of giant marine isopod (Bathynomus giganteus, Booralana tricarinata) captured from 653 to 875 m in the Caribbean Sea near Eleuthera, The Bahamas, exhibited an activity behavioural syndrome across two environmental contexts (presence/absence of food stimulus) and further whether this syndrome carried over consistently between sexes. We also measured routine metabolic rate and oxygen consumption in response to a food stimulus in B. giganteus to assess whether these variables are related to individual differences in personality. We found that both species show an activity syndrome across environmental contexts, but the underlying mechanistic basis of this syndrome, particularly in B. giganteus, is unclear. Contrary to our initial predictions, neither B. giganteus nor B. tricarinata showed any differences between mean expression of behavioural traits between sexes. Both sexes of B. tricarinata showed strong evidence of an activity syndrome underlying movement and foraging ecology, whereas only male B. giganteus showed evidence of an activity syndrome. Generally, individuals that were more active and bolder, in a standard open arena test were also more active when a food stimulus was present. Interestingly, individual differences in metabolism were not related to individual differences in behaviour based on present data. Our study provides the first measurements of behavioural syndromes and metabolism in giant deep-sea isopods.

  3. Comparison of Cerebral Glucose Metabolism between Possible and Probable Multiple System Atrophy

    Directory of Open Access Journals (Sweden)

    Kyum-Yil Kwon

    2009-05-01

    Full Text Available Background: To investigate the relationship between presenting clinical manifestations and imaging features of multisystem neuronal dysfunction in MSA patients, using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET. Methods: We studied 50 consecutive MSA patients with characteristic brain MRI findings of MSA, including 34 patients with early MSA-parkinsonian (MSA-P and 16 with early MSA-cerebellar (MSA-C. The cerebral glucose metabolism of all MSA patients was evaluated in comparison with 25 age-matched controls. 18F-FDG PET results were assessed by the Statistic Parametric Mapping (SPM analysis and the regions of interest (ROI method. Results: The mean time from disease onset to 18F-FDG PET was 25.9±13.0 months in 34 MSA-P patients and 20.1±11.1 months in 16 MSA-C patients. Glucose metabolism of the putamen showed a greater decrease in possible MSA-P than in probable MSA-P (p=0.031. Although the Unified Multiple System Atrophy Rating Scale (UMSARS score did not differ between possible MSA-P and probable MSA-P, the subscores of rigidity (p=0.04 and bradykinesia (p= 0.008 were significantly higher in possible MSA-P than in probable MSA-P. Possible MSA-C showed a greater decrease in glucose metabolism of the cerebellum than probable MSA-C (p=0.016. Conclusions: Our results may suggest that the early neuropathological pattern of possible MSA with a predilection for the striatonigral or olivopontocerebellar system differs from that of probable MSA, which has prominent involvement of the autonomic nervous system in addition to the striatonigral or olivopontocerebellar system.

  4. Multiple stable isotope tracer technique for studying the metabolic kinetics of amino acids in hepatic failure

    Energy Technology Data Exchange (ETDEWEB)

    Zongqin, Xia; Tengchang, Dai; Jianhua, Zhang; Yaer, Hu; Bingyao, Yu; Xingrong, Xu; Guanlu, Huang; Gengrong, Shen; Yaqiu, Zhou; Hong, Yu

    1987-08-01

    In order to study the mechanism of the imbalance of amino acid metabolism during hepatic failure, a stable isotope tracer method for observing simultaneously the metabolic kinetics of several amino acids has been established. /sup 15/N-L-Ala, (2,3-D/sub 3/)-Leu and (2,3-D/sub 3/)-Phe were chosen as nonessential, branched chain and aromatic amino acids. A single iv injection of 40 mg N-Ala, 20 mg deuterated Leu and 20 mg deuterated Phe was given to each human subject. Blood samples were taken just before and at different times (up to 60 min) after the injection. Total free amino acids were isolated from the plasma with a small dowex 50 x 8 column and converted to trifluoroacetyl derivatives. Their abundances were then analyzed with a GC-MS system and typical double exponential time course curves were found for all the three labelled amino acids. A two-pool model was designed and applied for compartmental analysis. Significant changes were found in the kinetic parameters of Phe and Leu in patients with fulminant hepatitis or heptic cirrhosis. The half-lives of both Phe pools were longer and the pool sizes were larger than normal subjects, while the half-lives and pool sizes of Leu changes in the opposite direction. No marked change was found in Ala. The significance of intracellular imbalance of Phe and Leu metabolism was discussed. It is evident that the combination of GCMS technique and multiple-tracers labelled with stable isotopes is of great potential for similar purposes.

  5. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses.

    Science.gov (United States)

    Ou, Yang; Wang, Shang-Jui; Li, Dawei; Chu, Bo; Gu, Wei

    2016-11-01

    Although p53-mediated cell-cycle arrest, senescence, and apoptosis remain critical barriers to cancer development, the emerging role of p53 in cell metabolism, oxidative responses, and ferroptotic cell death has been a topic of great interest. Nevertheless, it is unclear how p53 orchestrates its activities in multiple metabolic pathways into tumor suppressive effects. Here, we identified the SAT1 (spermidine/spermine N 1 -acetyltransferase 1) gene as a transcription target of p53. SAT1 is a rate-limiting enzyme in polyamine catabolism critically involved in the conversion of spermidine and spermine back to putrescine. Surprisingly, we found that activation of SAT1 expression induces lipid peroxidation and sensitizes cells to undergo ferroptosis upon reactive oxygen species (ROS)-induced stress, which also leads to suppression of tumor growth in xenograft tumor models. Notably, SAT1 expression is down-regulated in human tumors, and CRISPR-cas9-mediated knockout of SAT1 expression partially abrogates p53-mediated ferroptosis. Moreover, SAT1 induction is correlated with the expression levels of arachidonate 15-lipoxygenase (ALOX15), and SAT1-induced ferroptosis is significantly abrogated in the presence of PD146176, a specific inhibitor of ALOX15. Thus, our findings uncover a metabolic target of p53 involved in ferroptotic cell death and provide insight into the regulation of polyamine metabolism and ferroptosis-mediated tumor suppression.

  6. Dietary leucine--an environmental modifier of insulin resistance acting on multiple levels of metabolism

    DEFF Research Database (Denmark)

    Macotela, Yazmin; Emanuelli, Brice; Bång, Anneli M

    2011-01-01

    homeostasis and insulin signaling. After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose...... and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum. Doubling dietary leucine reversed many of the metabolite abnormalities and caused a marked improvement in glucose tolerance and insulin signaling without altering food intake or weight gain. Increased dietary leucine was also associated......Environmental factors, such as the macronutrient composition of the diet, can have a profound impact on risk of diabetes and metabolic syndrome. In the present study we demonstrate how a single, simple dietary factor--leucine--can modify insulin resistance by acting on multiple tissues...

  7. Cerebral metabolism, magnetic resonance spectroscopy and cognitive dysfunction in early multiple sclerosis: an exploratory study

    DEFF Research Database (Denmark)

    Blinkenberg, Morten; Mathiesen, Henrik K; Tscherning, Thomas

    2012-01-01

    and neurological disability. METHODS: We studied 20 recently diagnosed, clinically definite, relapsing-remitting MS patients. Global and cortical CMRglc was estimated using PET with 18-F-deoxyglucose and NAA/Cr ratio was measured using multislice echo-planar spectroscopic imaging. All subjects were neuro-psychologically......OBJECTIVES: Positron emission tomography (PET) studies have shown that cortical cerebral metabolic rate of glucose (CMRglc) is reduced in multiple sclerosis (MS). Quantitative magnetic resonance spectroscopy (MRS) measures of N-acetyl-aspartate (NAA) normalized to creatine (NAA/Cr) assess neuronal...... deterioration, and several studies have shown reductions in MS. Furthermore, both PET and MRS reductions correlate with cognitive dysfunction in MS. Our aim was to determine if changes in cortical CMRglc in early MS correlate with NAA/Cr measurements of neuronal deterioration, as well as cognitive dysfunction...

  8. Naringin ameliorates metabolic syndrome by activating AMP-activated protein kinase in mice fed a high-fat diet.

    Science.gov (United States)

    Pu, Peng; Gao, Dong-Mei; Mohamed, Salim; Chen, Jing; Zhang, Jing; Zhou, Xiao-Ya; Zhou, Nai-Jing; Xie, Jing; Jiang, Hong

    2012-02-01

    Metabolic syndrome is a low-grade inflammatory state in which oxidative stress is involved. Naringin, isolated from the Citrussinensis, is a phenolic compound with anti-oxidative and anti-inflammatory activities. The aim of this study was to explore the effects of naringin on metabolic syndrome in mice. The animal models, induced by high-fat diet in C57BL/6 mice, developed obesity, dyslipidemia, fatty liver, liver dysfunction and insulin resistance. These changes were attenuated by naringin. Further investigations revealed that the inhibitory effect on inflammation and insulin resistance was mediated by blocking activation of the MAPKs pathways and by activating IRS1; the lipid-lowering effect was attributed to inhibiting the synthesis way and increasing fatty acid oxidation; the hypoglycemic effect was due to the regulation of PEPCK and G6pase. The anti-oxidative stress of naringin also participated in the improvement of insulin resistance and lipogenesis. All of these depended on the AMPK activation. To confirm the results of the animal experiment, we tested primary hepatocytes exposed to high glucose system. Naringin was protective by phosphorylating AMPKα and IRS1. Taken together, these results suggested that naringin protected mice exposed to a high-fat diet from metabolic syndrome through an AMPK-dependent mechanism involving multiple types of intracellular signaling and reduction of oxidative damage. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Influence of metabolism on endocrine activities of bisphenol S.

    Science.gov (United States)

    Skledar, Darja Gramec; Schmidt, Jan; Fic, Anja; Klopčič, Ivana; Trontelj, Jurij; Dolenc, Marija Sollner; Finel, Moshe; Mašič, Lucija Peterlin

    2016-08-01

    Bisphenol S (BPS; bis[4-hydroxyphenyl]sulfone) is commonly used as a replacement for bisphenol A in numerous consumer products. The main goal of this study was to examine the influence of different metabolic reactions that BPS undergoes on the endocrine activity. We demonstrate that hydroxylation of the aromatic ring of BPS, catalyzed mainly by the cytochrome P450 enzymes CYP3A4 and CYP2C9, is its major in-vitro phase I biotransformation. Nevertheless, coupled oxidative-conjugative reactions analyses revealed that glucuronidation and formation of BPS glucuronide is the predominant BPS metabolic pathway. BPS reactive metabolites that can be tracked as glutathione conjugates were not detected in the present study. Two in-vitro systems were used to evaluate the endocrine activity of BPS and its two main metabolites, BPS glucuronide and hydroxylated BPS 4-(4-hydroxy-benzenesulfonyl)-benzene-1,2-diol (BPSM1). In addition, we have tested two structural analogs of BPS, bis[4-(2-hydroxyetoxy)phenyl]sulfone (BHEPS) and 4,4-sulfonylbis(2-methylphenol) (dBPS). The test systems were yeast cells, for evaluating estrogenic and androgenic activities, and the GH3.TRE-Luc reporter cell line for measuring thyroid hormone activity. BPS and BPSM1 were weak agonists of the estrogen receptor, EC50 values of 8.4 × 10(-5) M and 6.7 × 10(-4) M, respectively. Additionally, BPSM1 exhibited weak antagonistic activity toward the thyroid hormone receptor, with an IC50 of 4.3 × 10(-5) M. In contrast to BPSM1, BPS glucuronide was inactive in these assays, inhibiting neither the estrogen nor the thyroid hormone receptors. Hence, glucuronidation appears to be the most important pathway for both BPS metabolism and detoxification. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Fibroblast activation protein (FAP) as a novel metabolic target

    DEFF Research Database (Denmark)

    Sánchez-Garrido, Miguel Angel; Habegger, Kirk M; Clemmensen, Christoffer

    2016-01-01

    to block FAP enzymatic activity. RESULTS: TB administration to diet-induced obese (DIO) animals led to profound decreases in body weight, reduced food consumption and adiposity, increased energy expenditure, improved glucose tolerance and insulin sensitivity, and lowered cholesterol levels. Total...... (TB), we explored the impact of FAP inhibition on metabolic regulation in mice. METHODS: To address this question we evaluated the pharmacology of TB in various mouse models including those deficient in FGF21, GLP1 and GIP signaling. We also studied the ability of FAP to process FGF21 in vitro and TB...... and intact plasma FGF21 were observed to be elevated in TB-treated DIO mice but not lean animals where the metabolic impact of TB was significantly attenuated. Furthermore, and in stark contrast to naïve DIO mice, the administration of TB to obese FGF21 knockout animals demonstrated no appreciable effect...

  11. Simple glycolipids of microbes: Chemistry, biological activity and metabolic engineering

    Directory of Open Access Journals (Sweden)

    Ahmad Mohammad Abdel-Mawgoud

    2018-03-01

    Full Text Available Glycosylated lipids (GLs are added-value lipid derivatives of great potential. Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents, they have diverse biological activities with promising biomedical and cosmeceutical applications. Glycolipids, especially those of microbial origin, have interesting antimicrobial, anticancer, antiparasitic as well as immunomodulatory activities. Nonetheless, GLs are hardly accessing the market because of their high cost of production. We believe that experience of metabolic engineering (ME of microbial lipids for biofuel production can now be harnessed towards a successful synthesis of microbial GLs for biomedical and other applications. This review presents chemical groups of bacterial and fungal GLs, their biological activities, their general biosynthetic pathways and an insight on ME strategies for their production.

  12. Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids

    Directory of Open Access Journals (Sweden)

    Júlia T. Novaes

    2017-10-01

    Full Text Available Tetrahydrocurcumin (THC, curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa. Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC activity, histone acetyltransferase (HAT activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism.

  13. Adjuvant activity of peptidoglycan monomer and its metabolic products.

    Science.gov (United States)

    Halassy, Beata; Krstanović, Marina; Frkanec, Ruza; Tomasić, Jelka

    2003-02-14

    Peptidoglycan monomer (PGM) is a natural compound of bacterial origin. It is a non-toxic, non-pyrogenic, water-soluble immunostimulator potentiating humoral immune response to ovalbumin (OVA) in mice. It is fast degraded and its metabolic products-the pentapeptide (PP) and the disaccharide (DS)-are excreted from the mammalian organism upon parenteral administration. The present study investigates: (a). whether PGM could influence the long-living memory generation; (b). whether metabolic products retain adjuvant properties of the parent compound and contribute to its adjuvanticity. We report now that mice immunised twice with OVA+PGM had significantly higher anti-OVA IgG levels upon challenge with antigen alone 6 months later in comparison to control group immunised with OVA only. PP and DS were prepared enzymatically in vitro as apyrogenic and chemically pure compounds. When mice were immunised with OVA plus PP and DS, respectively, the level of anti-OVA IgGs in sera was not higher than in mice immunised with OVA alone, while PGM raised the level of specific antibodies. Results implicate that the adjuvant active molecule, capable of enhancing long-living memory generation, is PGM itself, and none of its metabolic products.

  14. Multiple active forms of thrombin. IV. Relative activities of meizothrombins

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, M.F.; Mann, K.G. (Univ. of Vermont College of Medicine, Burlington (USA))

    1990-06-25

    The prothrombin activation intermediates meizothrombin and meizothrombin(desF1) (meizothrombin that has been autoproteolyzed to remove fragment 1) have been obtained in a relatively pure, active form with minimal autolysis, making them suitable for enzymatic characterization. When compared at equimolar concentrations, alpha-thrombin, fragment 1.2+ alpha-thrombin, meizothrombin(desF1), and meizothrombin have approximately 100, 100, 10, and 1% activity, respectively, toward the macromolecular substrates factor V, fibrinogen, and platelets. The difference in activity of these four enzymes cannot be attributed to alterations in the catalytic triad, as all four enzymes have nearly identical catalytic efficiency toward the chromogenic substrate S2238. Further, the ability of meizothrombin and meizothrombin(desF1) to activate protein C was 75% of the activity exhibited by alpha-thrombin or fragment 1.2+ alpha-thrombin. All four enzymes bind to thrombomodulin, as judged by the enhanced rate of protein C activation upon preincubation of the enzymes with thrombomodulin. The extent of rate enhancement varied, with meizothrombin/thrombomodulin exhibiting only 50% of the alpha-thrombin/thrombomodulin rate. This difference in rate is not due to a decreased affinity of the meizothrombin for thrombomodulin since the apparent dissociation constants for the alpha-thrombin-thrombomodulin complex and the meizothrombin-thrombomodulin complex are virtually identical. The difference in the observed rate is due in part to the higher Km for protein C exhibited by the meizothrombin-thrombomodulin complex. Incubation of the thrombomodulin-enzyme complex with phospholipid vesicles caused an increase in the protein C activation rates. The kinetic constants for protein C activation in the presence of phospholipid are virtually identical for these enzyme-thrombomodulin complexes.

  15. Multiple active forms of thrombin. IV. Relative activities of meizothrombins

    International Nuclear Information System (INIS)

    Doyle, M.F.; Mann, K.G.

    1990-01-01

    The prothrombin activation intermediates meizothrombin and meizothrombin(desF1) (meizothrombin that has been autoproteolyzed to remove fragment 1) have been obtained in a relatively pure, active form with minimal autolysis, making them suitable for enzymatic characterization. When compared at equimolar concentrations, alpha-thrombin, fragment 1.2+ alpha-thrombin, meizothrombin(desF1), and meizothrombin have approximately 100, 100, 10, and 1% activity, respectively, toward the macromolecular substrates factor V, fibrinogen, and platelets. The difference in activity of these four enzymes cannot be attributed to alterations in the catalytic triad, as all four enzymes have nearly identical catalytic efficiency toward the chromogenic substrate S2238. Further, the ability of meizothrombin and meizothrombin(desF1) to activate protein C was 75% of the activity exhibited by alpha-thrombin or fragment 1.2+ alpha-thrombin. All four enzymes bind to thrombomodulin, as judged by the enhanced rate of protein C activation upon preincubation of the enzymes with thrombomodulin. The extent of rate enhancement varied, with meizothrombin/thrombomodulin exhibiting only 50% of the alpha-thrombin/thrombomodulin rate. This difference in rate is not due to a decreased affinity of the meizothrombin for thrombomodulin since the apparent dissociation constants for the alpha-thrombin-thrombomodulin complex and the meizothrombin-thrombomodulin complex are virtually identical. The difference in the observed rate is due in part to the higher Km for protein C exhibited by the meizothrombin-thrombomodulin complex. Incubation of the thrombomodulin-enzyme complex with phospholipid vesicles caused an increase in the protein C activation rates. The kinetic constants for protein C activation in the presence of phospholipid are virtually identical for these enzyme-thrombomodulin complexes

  16. In vivo enzyme activity in inborn errors of metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. (Clinical Research Centre, Harrow (England))

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  17. In vivo enzyme activity in inborn errors of metabolism

    International Nuclear Information System (INIS)

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D.

    1990-01-01

    Low-dose continuous infusions of [2H5]phenylalanine, [1-13C]propionate, and [1-13C]leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD

  18. Metabolic Syndrome and Physical Activity in Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    derya atik

    2014-06-01

    Full Text Available Purpose: This descriptive study was carried out to reveal the level of physical activity in patients who receive hemodialysis due to chronic kidney failure and to identify its relationship with the prevalence of metabolic syndrome (MetS. Material and method: The study was conducted with 55 patients at the hemodialysis units of Alanya State Hospital and Private Alanya Anadolu Hospital between 10 and 30 June 2013. The study data were collected using the National Cholesterol Education Program, the Adult Treatment Panel III (NCEP-ATP III, a data collection form containing Metabolic Syndrome Diagnosis Criteria, and the International Physical Activity Questionnaire (IPAQ. The data were analyzed using arithmetic mean +/- standard deviation (SD, number and percentage distributions, independent sample t test, crosstabs, One Way Anova, and Pearson and #8217;s Correlation Analysis. Conclusion and suggestions: It was found that 41.8% of the patients were between 50 and 65 years of age, the majority of them were male (58.2%, hemodialysis had been administered to 69.1% of them for at least 36 months, and 50.9% of them met three and more of the MetS criteria. There was no statistically significant relationship between MetS and physical activity levels, but the length of physical activity was longer in those who did not meet the MetS diagnosis criteria (p>0.05. An increase in sedentary time raised the MetS criteria (p<0.05. Conclusion: Nearly 1/2 of the patients were at risk of MetS. Physical activity level being statistically ineffective on MetS can be associated with low physical activity level and longer sedentary time. It can be said that being completely sedentary increases BMI and therefore MetS. The study can be repeated on different samples and the results can be compared. [J Contemp Med 2014; 4(2.000: 69-75

  19. PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth.

    Science.gov (United States)

    Abu Aboud, Omran; Donohoe, Dallas; Bultman, Scott; Fitch, Mark; Riiff, Tim; Hellerstein, Marc; Weiss, Robert H

    2015-06-01

    Kidney cancer [renal cell carcinoma (RCC)] is the sixth-most-common cancer in the United States, and its incidence is increasing. The current progression-free survival for patients with advanced RCC rarely extends beyond 1-2 yr due to the development of therapeutic resistance. We previously identified peroxisome proliferator-activating receptor-α (PPARα) as a potential therapeutic target for this disease and showed that a specific PPARα antagonist, GW6471, induced apoptosis and cell cycle arrest at G0/G1 in RCC cell lines associated with attenuation of cell cycle regulatory proteins. We now extend that work and show that PPARα inhibition attenuates components of RCC metabolic reprogramming, capitalizing on the Warburg effect. The specific PPARα inhibitor GW6471, as well as a siRNA specific to PPARα, attenuates the enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition, and PPARα antagonism also blocks the enhanced glycolysis that has been observed in RCC cells; this effect did not occur in normal human kidney epithelial cells. Such cell type-specific inhibition of glycolysis corresponds with changes in protein levels of the oncogene c-Myc and has promising clinical implications. Furthermore, we show that treatment with GW6471 results in RCC tumor growth attenuation in a xenograft mouse model, with minimal obvious toxicity, a finding associated with the expected on-target effects on c-Myc. These studies demonstrate that several pivotal cancer-relevant metabolic pathways are inhibited by PPARα antagonism. Our data support the concept that targeting PPARα, with or without concurrent inhibition of glycolysis, is a potential novel and effective therapeutic approach for RCC that targets metabolic reprogramming in this tumor.

  20. Effects of bagging on sugar metabolism and the activity of sugar ...

    African Journals Online (AJOL)

    To investigate the effects of bagging on sugar metabolism and the activity of sugar metabolism related enzymes in Qingzhong loquat fruit development, the contents of sucrose, glucose and soluble solids as well as the activities of sugar metabolism related enzymes were evaluated. The content of sucrose, glucose and ...

  1. Cytosolic Calcium Coordinates Mitochondrial Energy Metabolism with Presynaptic Activity

    Science.gov (United States)

    Chouhan, Amit K.; Ivannikov, Maxim V.; Lu, Zhongmin; Sugimori, Mutsuyuki; Llinas, Rodolfo R.; Macleod, Gregory T.

    2012-01-01

    Most neurons fire in bursts, imposing episodic energy demands, but how these demands are coordinated with oxidative phosphorylation is still unknown. Here, using fluorescence imaging techniques on presynaptic termini of Drosophila motor neurons (MNs), we show that mitochondrial matrix pH (pHm), inner membrane potential (Δψm), and NAD(P)H levels ([NAD(P)H]m) increase within seconds of nerve stimulation. The elevations of pHm, Δψm, and [NAD(P)H]m indicate an increased capacity for ATP production. Elevations in pHm were blocked by manipulations which blocked mitochondrial Ca2+ uptake, including replacement of extracellular Ca2+ with Sr2+, and application of either tetraphenylphosphonium chloride or KB-R7943, indicating that it is Ca2+ that stimulates presynaptic mitochondrial energy metabolism. To place this phenomenon within the context of endogenous neuronal activity, the firing rates of a number of individually identified MNs were determined during fictive locomotion. Surprisingly, although endogenous firing rates are significantly different, there was little difference in presynaptic cytosolic Ca2+ levels ([Ca2+]c) between MNs when each fires at its endogenous rate. The average [Ca2+]c level (329±11nM) was slightly above the average Ca2+ affinity of the mitochondria (281±13nM). In summary, we show that when MNs fire at endogenous rates [Ca2+]c is driven into a range where mitochondria rapidly acquire Ca2+. As we also show that Ca2+ stimulates presynaptic mitochondrial energy metabolism, we conclude that [Ca2+]c levels play an integral role in coordinating mitochondrial energy metabolism with presynaptic activity in Drosophila MNs. PMID:22279208

  2. Adaptive Active Noise Suppression Using Multiple Model Switching Strategy

    Directory of Open Access Journals (Sweden)

    Quanzhen Huang

    2017-01-01

    Full Text Available Active noise suppression for applications where the system response varies with time is a difficult problem. The computation burden for the existing control algorithms with online identification is heavy and easy to cause control system instability. A new active noise control algorithm is proposed in this paper by employing multiple model switching strategy for secondary path varying. The computation is significantly reduced. Firstly, a noise control system modeling method is proposed for duct-like applications. Then a multiple model adaptive control algorithm is proposed with a new multiple model switching strategy based on filter-u least mean square (FULMS algorithm. Finally, the proposed algorithm was implemented on Texas Instruments digital signal processor (DSP TMS320F28335 and real time experiments were done to test the proposed algorithm and FULMS algorithm with online identification. Experimental verification tests show that the proposed algorithm is effective with good noise suppression performance.

  3. Physical activity does not attenuate the relationship between daily cortisol and metabolic syndrome in obese youth.

    Science.gov (United States)

    Guseman, Emily Hill; Pfeiffer, Karin A; Carlson, Joseph J; Stansbury, Kathy; Eisenmann, Joey C

    2016-01-01

    We examined the associations among daily cortisol, physical activity (MVPA) and continuous metabolic syndrome score (cMetS) in obese youth. Fifty adolescents (mean age 14.8 ± 1.9 years) were recruited from medical clinics. Daily MVPA (min/day) was assessed by accelerometry. Saliva was sampled at prescribed times: immediately upon waking; 30 min after waking; and 3, 6 and 9 h after waking. Fasting lipids, glucose, waist circumference and blood pressure were used to calculate a continuous metabolic syndrome score (cMetS). Multiple linear regression analysis was used to examine associations among variables. The mean cMetS score was 4.16 ± 4.30 and did not differ by clinic or sex. No significant relationship was found between cortisol area under the curve (cAUC) and cMetS, nor did the interaction of MVPA with cAUC significantly predict cMetS. Physical activity, cortisol, and metabolic risk were not associated in this sample of obese adolescents. Future research should examine the role of insulin sensitivity in these relationships.

  4. Physical Activity Dimensions Associated with Impaired Glucose Metabolism

    DEFF Research Database (Denmark)

    Amadid, Hanan; Johansen, Nanna B.; Bjerregaard, Anne-Louise

    2017-01-01

    Purpose Physical activity (PA) is important in the prevention of Type 2 diabetes, yet little is known about the role of specific dimensions of PA, including sedentary time in subgroups at risk for impaired glucose metabolism (IGM). We applied a data-driven decision tool to identify dimensions of PA...... identified subgroups in which different activity dimensions were associated with IGM. Methodology and results from this study may suggest a preliminary step toward the goal of tailoring and targeting PA interventions aimed at Type 2 diabetes prevention....... associated with IGM across age, sex, and body mass index (BMI) groups. Methods This cross-sectional study included 1501 individuals (mean (SD) age, 65.6 (6.8) yr) at high risk for Type 2 diabetes from the ADDITION-PRO study. PA was measured by an individually calibrated combined accelerometer and heart rate...

  5. Metabolic Activity Interferometer: A Powerful Tool for Testing Antibiotics

    Directory of Open Access Journals (Sweden)

    Rachel R. P. Machado

    2012-01-01

    Full Text Available It is demonstrated that the efficiency of antibiotics can be tested using an interferometric method. Two antibiotics were used as models to show that an interferometric method to monitor the metabolic activity of slowly growing bacteria can be a safer method to judge antimicrobial properties of substances than conventional methods. The susceptibility of Mycobacterium bovis to hexane extract of Pterodon emarginatus and to the well-known antibiotic rifampicin was tested with the interferometric method and with the conventional microplate method. The microplate method revealed a potential activity of hexane extract against M. bovis. However, the interferometric method showed that the action of this substance is rather limited. Also in the case of rifampicin, the interferometric method was able to detect resistant bacteria.

  6. Does physical activity during pregnancy adversely influence markers of the metabolic syndrome in adult offspring?

    DEFF Research Database (Denmark)

    Danielsen, Inge; Granström, Charlotta; Rytter, Dorte

    2013-01-01

    It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring.......It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring....

  7. Epstein-Barr virus and disease activity in multiple sclerosis

    NARCIS (Netherlands)

    D. Buljevac (Dragan); H.Z. Flach (Zwenneke); J. Groen (Jan); P.A. van Doorn (Pieter); F.G.A. van der Meché (Frans); R.Q. Hintzen (Rogier); W.C.J. Hop (Wim); A.D.M.E. Osterhaus (Albert); G.J.J. van Doornum (Gerard)

    2005-01-01

    textabstractOBJECTIVES: To study in relapsing-remitting (RR) multiple sclerosis (MS) whether exacerbations and brain activity as measured by magnetic resonance imaging (MRI) are associated with plasma levels of anti-Epstein Barr (EBV) antibodies and EBV DNA. METHODS: This was a prospective study

  8. Developmental Trampoline Activities for Individuals with Multiple Handicapping Conditions.

    Science.gov (United States)

    Thomas, Bill

    1979-01-01

    The use of trampoline activities with multiple handicapped students is discussed. Management considerations in safety are noted, and developmental trampoline skills are listed beginning with bouncing for stimulation. Progression to limited independence and finally independent jumping is described. The position statement of the American Alliance…

  9. Low leucocyte myeloperoxidase activity in patients with multiple sclerosis

    NARCIS (Netherlands)

    Ramsaransing, G; Teelken, A; Prokopenko, VM; Arutjunyan, AV; De Keyser, J

    The gene for myeloperoxidase (MPO) has been implicated in multiple sclerosis (MS). By measuring H2O2 dependent oxidation of 3,3'5,5'-tetramethylbenzidine with spectrophotometry the authors investigated MPO activity in peripheral blood leucocytes from 42 patients with MS (12 with secondary

  10. Transcriptional activity of the giant barrel sponge, Xestospongia muta Holobiont: Molecular Evidence for Metabolic Interchange

    Directory of Open Access Journals (Sweden)

    Cara L Fiore

    2015-04-01

    Full Text Available Compared to our understanding of the taxonomic composition of the symbiotic microbes in marine sponges, the functional diversity of these symbionts is largely unknown. Furthermore, the application of genomic, transcriptomic, and proteomic techniques to functional questions on sponge host-symbiont interactions is in its infancy. In this study, we generated a transcriptome for the host and a metatranscriptome of its microbial symbionts for the giant barrel sponge, Xestospongia muta, from the Caribbean. In combination with a gene-specific approach, our goals were to 1 characterize genetic evidence for nitrogen cycling in X. muta, an important limiting nutrient on coral reefs 2 identify which prokaryotic symbiont lineages are metabolically active and, 3 characterize the metabolic potential of the prokaryotic community. Xestospongia muta expresses genes from multiple nitrogen transformation pathways that when combined with the abundance of this sponge, and previous data on dissolved inorganic nitrogen fluxes, shows that this sponge is an important contributor to nitrogen cycling on coral reefs. Additionally, we observed significant differences in gene expression of the archaeal amoA gene, which is involved in ammonia oxidation, between coral reef locations consistent with differences in the fluxes of dissolved inorganic nitrogen previously reported. In regards to symbiont metabolic potential, the genes in the biosynthetic pathways of several amino acids were present in the prokaryotic metatranscriptome dataset but in the host-derived transcripts only the catabolic reactions for these amino acids were present. A similar pattern was observed for the B vitamins (riboflavin, biotin, thiamin, cobalamin. These results expand our understanding of biogeochemical cycling in sponges, and the metabolic interchange highlighted here advances the field of symbiont physiology by elucidating specific metabolic pathways where there is high potential for host

  11. The CanOE strategy: integrating genomic and metabolic contexts across multiple prokaryote genomes to find candidate genes for orphan enzymes.

    Directory of Open Access Journals (Sweden)

    Adam Alexander Thil Smith

    2012-05-01

    Full Text Available Of all biochemically characterized metabolic reactions formalized by the IUBMB, over one out of four have yet to be associated with a nucleic or protein sequence, i.e. are sequence-orphan enzymatic activities. Few bioinformatics annotation tools are able to propose candidate genes for such activities by exploiting context-dependent rather than sequence-dependent data, and none are readily accessible and propose result integration across multiple genomes. Here, we present CanOE (Candidate genes for Orphan Enzymes, a four-step bioinformatics strategy that proposes ranked candidate genes for sequence-orphan enzymatic activities (or orphan enzymes for short. The first step locates "genomic metabolons", i.e. groups of co-localized genes coding proteins catalyzing reactions linked by shared metabolites, in one genome at a time. These metabolons can be particularly helpful for aiding bioanalysts to visualize relevant metabolic data. In the second step, they are used to generate candidate associations between un-annotated genes and gene-less reactions. The third step integrates these gene-reaction associations over several genomes using gene families, and summarizes the strength of family-reaction associations by several scores. In the final step, these scores are used to rank members of gene families which are proposed for metabolic reactions. These associations are of particular interest when the metabolic reaction is a sequence-orphan enzymatic activity. Our strategy found over 60,000 genomic metabolons in more than 1,000 prokaryote organisms from the MicroScope platform, generating candidate genes for many metabolic reactions, of which more than 70 distinct orphan reactions. A computational validation of the approach is discussed. Finally, we present a case study on the anaerobic allantoin degradation pathway in Escherichia coli K-12.

  12. Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

    DEFF Research Database (Denmark)

    Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio

    2015-01-01

    of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further...... and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels...

  13. Dissection of Biological Property of Chinese Acupuncture Point Zusanli Based on Long-Term Treatment via Modulating Multiple Metabolic Pathways

    Directory of Open Access Journals (Sweden)

    Guangli Yan

    2013-01-01

    Full Text Available Acupuncture has a history of over 3000 years and is a traditional Chinese medical therapy that uses hair-thin metal needles to puncture the skin at specific points on the body to promote wellbeing, while its molecular mechanism and ideal biological pathways are still not clear. High-throughput metabolomics is the global assessment of endogenous metabolites within a biologic system and can potentially provide a more accurate snap shot of the actual physiological state. We hypothesize that acupuncture-treated human would produce unique characterization of metabolic phenotypes. In this study, UPLC/ESI-HDMS coupled with pattern recognition methods and system analysis were carried out to investigate the mechanism and metabolite biomarkers for acupuncture treatment at “Zusanli” acupoint (ST-36 as a case study. The top 5 canonical pathways including alpha-linolenic acid metabolism, d-glutamine and d-glutamate metabolism, citrate cycle, alanine, aspartate, and glutamate metabolism, and vitamin B6 metabolism pathways were acutely perturbed, and 53 differential metabolites were identified by chemical profiling and may be useful to clarify the physiological basis and mechanism of ST-36. More importantly, network construction has led to the integration of metabolites associated with the multiple perturbation pathways. Urine metabolic profiling might be a promising method to investigate the molecular mechanism of acupuncture.

  14. Dissection of Biological Property of Chinese Acupuncture Point Zusanli Based on Long-Term Treatment via Modulating Multiple Metabolic Pathways.

    Science.gov (United States)

    Yan, Guangli; Zhang, Aihua; Sun, Hui; Cheng, Weiping; Meng, Xiangcai; Liu, Li; Zhang, Yingzhi; Xie, Ning; Wang, Xijun

    2013-01-01

    Acupuncture has a history of over 3000 years and is a traditional Chinese medical therapy that uses hair-thin metal needles to puncture the skin at specific points on the body to promote wellbeing, while its molecular mechanism and ideal biological pathways are still not clear. High-throughput metabolomics is the global assessment of endogenous metabolites within a biologic system and can potentially provide a more accurate snap shot of the actual physiological state. We hypothesize that acupuncture-treated human would produce unique characterization of metabolic phenotypes. In this study, UPLC/ESI-HDMS coupled with pattern recognition methods and system analysis were carried out to investigate the mechanism and metabolite biomarkers for acupuncture treatment at "Zusanli" acupoint (ST-36) as a case study. The top 5 canonical pathways including alpha-linolenic acid metabolism, d-glutamine and d-glutamate metabolism, citrate cycle, alanine, aspartate, and glutamate metabolism, and vitamin B6 metabolism pathways were acutely perturbed, and 53 differential metabolites were identified by chemical profiling and may be useful to clarify the physiological basis and mechanism of ST-36. More importantly, network construction has led to the integration of metabolites associated with the multiple perturbation pathways. Urine metabolic profiling might be a promising method to investigate the molecular mechanism of acupuncture.

  15. Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite. : Fisetin disposition and metabolism in mice

    OpenAIRE

    Touil, Yasmine,; Auzeil, Nicolas; Boulinguez, François; Saighi, Hanane; Regazzetti, Anne; Scherman, Daniel; Chabot, Guy,

    2011-01-01

    International audience; Although the natural flavonoid fisetin (3,3',4',7-tetrahydroxyflavone) has been recently identified as an anticancer agent with antiangiogenic properties in mice, its in vivo pharmacokinetics and metabolism are presently not characterized. Our purpose was to determine the pharmacokinetics and metabolism of fisetin in mice and determine the biological activity of a detected fisetin metabolite. After fisetin administration of an efficacious dose of 223 mg/kg i.p. in mice...

  16. Comorbidity and metabolic syndrome in patients with multiple sclerosis from Asturias and Catalonia, Spain.

    Science.gov (United States)

    Sicras-Mainar, Antoni; Ruíz-Beato, Elena; Navarro-Artieda, Ruth; Maurino, Jorge

    2017-07-17

    The impact of comorbidity on multiple sclerosis (MS) is a new area of interest. Limited data on the risk factors of metabolic syndrome (MetS) is currently available. The aim of this study was to estimate the presence of comorbid conditions and MetS in a sample of adult patients with MS. A retrospective, cohort study was conducted using electronic medical records from 19 primary care centres in Catalonia and Asturias, Spain. The number of chronic diseases (diagnoses), the Charlson Comorbidity Index and the individual Case-mix Index were used to assess general comorbidity variables. MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III. Patients were distributed into two groups according to the Expanded Disability Status Scale (EDSS) score: 0-3.5 and 4-10. A total of 222 patients were studied (mean age = 45.5 (SD 12.5) years, 64.4% were female and 62.2% presented a diagnosis of relapsing-remitting MS). Mean EDSS score was 3.2 (SD 2.0). Depression (32.4%), dyslipidaemia (31.1%), hypertension (23.0%) and obesity (22.5%) were the most common comorbidities. Overall MetS prevalence was 31.1% (95% CI: 25.0-37.2%). Patients with an EDSS ≥ 4.0 showed a significantly higher number of comorbidities (OR=2.2; 95% CI: 1.7-3.0; p<0.001). MS patients had a high prevalence of MetS. Screening for comorbidity should be part of standard MS care. Further studies are necessary to confirm this association and the underlying mechanisms of MS and its comorbidities.

  17. Kaempferol ameliorates symptoms of metabolic syndrome by regulating activities of liver X receptor-β.

    Science.gov (United States)

    Hoang, Minh-Hien; Jia, Yaoyao; Mok, Boram; Jun, Hee-jin; Hwang, Kwang-Yeon; Lee, Sung-Joon

    2015-08-01

    Kaempferol is a dietary flavonol previously shown to regulate cellular lipid and glucose metabolism. However, its molecular mechanisms of action and target proteins have remained elusive, probably due to the involvement of multiple proteins. This study investigated the molecular targets of kaempferol. Ligand binding of kaempferol to liver X receptors (LXRs) was quantified by time-resolved fluorescence resonance energy transfer and surface plasmon resonance analyses. Kaempferol directly binds to and induces the transactivation of LXRs, with stronger specificity for the β-subtype (EC50 = 0.33 μM). The oral administration of kaempferol in apolipoprotein-E-deficient mice (150 mg/day/kg body weight) significantly reduced plasma glucose and increased high-density lipoprotein cholesterol levels and insulin sensitivity compared with the vehicle-fed control. Kaempferol also reduced plasma triglyceride concentrations and did not cause liver steatosis, a common side effect of potent LXR activation. In immunoblotting analysis, kaempferol reduced the nuclear accumulation of sterol regulatory element-binding protein-1 (SREBP-1). Our results show that the suppression of SREBP-1 activity and the selectivity for LXR-β over LXR-α by kaempferol contribute to the reductions of plasma and hepatic triglyceride concentrations in mice fed kaempferol. They also suggest that kaempferol activates LXR-β and suppresses SREBP-1 to enhance symptoms in metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The metabolic activator FOXO1 binds hepatitis B virus DNA and activates its transcription

    International Nuclear Information System (INIS)

    Shlomai, Amir; Shaul, Yosef

    2009-01-01

    Hepatitis B virus (HBV) is a small DNA virus that targets the liver and infects humans worldwide. Recently we have shown that the metabolic regulator PGC-1α coactivates HBV transcription thereby rendering the virus susceptible to fluctuations in the nutritional status of the liver. PGC-1α coactivation of HBV is mediated through the liver-enriched nuclear receptor HNF4α and through another yet unknown transcription factor(s). Here we show that the forkhead transcription factor FOXO1, a known target for PGC-1α coactivation and a central mediator of glucose metabolism in the liver, binds HBV core promoter and activates its transcription. This activation is further enhanced in the presence of PGC-1α, implying that FOXO1 is a target for PGC-1α coactivation of HBV transcription. Thus, our results identify another key metabolic regulator as an activator of HBV transcription, thereby supporting the principle that HBV gene expression is regulated in a similar way to key hepatic metabolic genes.

  19. Metabolic signals and innate immune activation in obesity and exercise.

    Science.gov (United States)

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

  20. Pyrrolizidine Alkaloids: Metabolic Activation Pathways Leading to Liver Tumor Initiation.

    Science.gov (United States)

    Fu, Peter P

    2017-01-17

    Pyrrolizidine alkaloids (PAs) and PA N-oxides are a class of phytochemical carcinogens contained in over 6000 plant species spread around the world. It has been estimated that approximately half of the 660 PAs and PA N-oxides that have been characterized are cytotoxic, genotoxic, and tumorigenic. It was recently determined that a genotoxic mechanism of liver tumor initiation mediated by PA-derived DNA adducts is a common metabolic activation pathway of a number of PAs. We proposed this set of PA-derived DNA adducts could be a common biological biomarker of PA exposure and a potential biomarker of PA-induced liver tumor formation. We have also found that several reactive secondary pyrrolic metabolites can dissociate and interconvert to other secondary pyrrolic metabolites, resulting in the formation of the same exogenous DNA adducts. This present perspective reports the current progress on these new findings and proposes future research needed for obtaining a greater understanding of the role of this activation pathway and validating the use of this set of PA-derived DNA adducts as a biological biomarker of PA-induced liver tumor initiation.

  1. Brain energy metabolism is activated after acute and chronic administration of fenproporex in young rats.

    Science.gov (United States)

    Rezin, Gislaine T; Jeremias, Isabela C; Ferreira, Gabriela K; Cardoso, Mariane R; Morais, Meline O S; Gomes, Lara M; Martinello, Otaviana B; Valvassori, Samira S; Quevedo, João; Streck, Emilio L

    2011-12-01

    Obesity is a chronic disease of multiple etiologies, including genetic, metabolic, environmental, social, and other factors. Pharmaceutical strategies in the treatment of obesity include drugs that regulate food intake, thermo genesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine. Studies suggest that amphetamine induces neurotoxicity through generation of free radicals and mitochondrial apoptotic pathway by cytochrome c release, accompanied by a decrease of mitochondrial membrane potential. Mitochondria are intracellular organelles that play a crucial role in ATP production. Thus, in the present study we evaluated the activities of some enzymes of Krebs cycle, mitochondrial respiratory chain complexes and creatine kinase in the brain of young rats submitted to acute and chronic administration of fenproporex. In the acute administration, the animals received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or tween. In the chronic administration, the animals received a single injection daily for 14 days of fenproporex (6.25, 12.5 or 25 mg/Kg i.p.). Two hours after the last injection, the rats were sacrificed by decapitation and the brain was removed for evaluation of biochemical parameters. Our results showed that the activities of citrate synthase, malate dehydrogenase and succinate dehydrogenase were increased by acute and chronic administration of fenproporex. Complexes I, II, II-III and IV and creatine kinase activities were also increased after acute and chronic administration of the drug. Our results are consistent with others reports that showed that some psychostimulant drugs increased brain energy metabolism in young rats. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  2. Localizing Brain Activity from Multiple Distinct Sources via EEG

    Directory of Open Access Journals (Sweden)

    George Dassios

    2014-01-01

    Full Text Available An important question arousing in the framework of electroencephalography (EEG is the possibility to recognize, by means of a recorded surface potential, the number of activated areas in the brain. In the present paper, employing a homogeneous spherical conductor serving as an approximation of the brain, we provide a criterion which determines whether the measured surface potential is evoked by a single or multiple localized neuronal excitations. We show that the uniqueness of the inverse problem for a single dipole is closely connected with attaining certain relations connecting the measured data. Further, we present the necessary and sufficient conditions which decide whether the collected data originates from a single dipole or from numerous dipoles. In the case where the EEG data arouses from multiple parallel dipoles, an isolation of the source is, in general, not possible.

  3. Sodium intake and multiple sclerosis activity and progression in BENEFIT

    DEFF Research Database (Denmark)

    Fitzgerald, Kathryn C; Munger, Kassandra L; Hartung, Hans-Peter

    2017-01-01

    OBJECTIVE: To assess whether a high-salt diet, as measured by urinary sodium concentration, is associated with faster conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and MS activity and disability. METHODS: BENEFIT was a randomized clinical trial comparing early versus...... delayed interferon beta-1b treatment in 465 patients with a CIS. Each patient provided a median of 14 (interquartile range = 13-16) spot urine samples throughout the 5-year follow-up. We estimated 24-hour urine sodium excretion level at each time point using the Tanaka equations, and assessed whether...... in T2 lesion volume: -0.11, 95% CI = -0.25 to 0.04; change in EDSS: -0.01, 95% CI = -0.09 to 0.08; relapse rate: HR = 0.78, 95% CI = 0.56-1.07). Results were similar in categorical analyses using quintiles. INTERPRETATION: Our results, based on multiple assessments of urine sodium excretion over 5...

  4. Immune activation in multiple sclerosis and interferon-beta therapy

    DEFF Research Database (Denmark)

    Krakauer, Martin

    2007-01-01

    The PhD dissertation emanated from the Danish MS Research Centre, Rigshosptalet, Copenhagen. Multiple sclerosis (MS) is an inflammatory disease of the CNS. Inflammatory responses by T helper (Th)-lymphocytes are characterised by distinct cytokine expression profiles. In MS, activated Th1...... of inflammation or secondary lymphatic organs. Chemokine receptors are differentially expressed in T cells in blood and cerebrospinal fluid, indicating their role for in T-cell-recruitment to the CNS. Interferon (IFN)-beta is a first-line treatment for MS. The mechanism of action is unclear, but probably includes...... changes in lymphocyte activation, cytokine secretion, and trafficking. The aim of the studies was to shed more light on T-cell immunology in MS and IFN-beta treatment, as well as identifying putative biomarkers of treatment response and/or disease activity. In one study we identified a Th-cell subset...

  5. Basal metabolic regulatory responses and rhythmic activity of ...

    African Journals Online (AJOL)

    ... Rattus sp. Low concentrations of kola nut extract stimulated the heart by increasing rate and force of contraction as well as metabolic rate. Higher concentrations reduced rate and amplitude of beat resulting, at still higher concentrations in heart failure. Keywords: Kolanut, extract, basal metabolic rate, mammalian heart ...

  6. Does air-breathing meet metabolic demands of the juvenile snakehead, Channa argus, in multiple conditions

    Directory of Open Access Journals (Sweden)

    Yongli Li

    2017-05-01

    Full Text Available The objective of this study was to examine how the respiratory metabolism of the snakehead Channa argus changed when it shifted from breathing water to breathing air, and how increased metabolic demands caused by temperature, feeding, and exhaustive exercise affect its survival in air. The results demonstrated that the oxygen consumption rate (MO2 of the snakehead was lower for aerial respiration than aquatic respiration by 12.1, 24.5 and 20.4% at 20, 25, and 30°C, respectively. Survival time was significantly shortened with increasing temperature and was negatively correlated with the resting MO2 in air (MO2Air. No obvious feeding metabolic response was observed in the snakeheads fed at 1% and 3% body mass levels while breathing air. The maximum MO2Air of the snakehead after exhaustive exercise was significantly higher than the resting MO2Air of the control group. The results suggest that the snakehead could survive out of water by breathing air for varying lengths of time, depending on ambient temperature and metabolic demand. Additionally, some degree of metabolic depression occurs in the snakehead when breathing air. The metabolic demand associated with exercise in the snakehead, but not that associated with feeding, can be supported by its capacity for breathing air to some extent.

  7. Abnormal metabolic network activity in REM sleep behavior disorder.

    Science.gov (United States)

    Holtbernd, Florian; Gagnon, Jean-François; Postuma, Ron B; Ma, Yilong; Tang, Chris C; Feigin, Andrew; Dhawan, Vijay; Vendette, Mélanie; Soucy, Jean-Paul; Eidelberg, David; Montplaisir, Jacques

    2014-02-18

    To determine whether the Parkinson disease-related covariance pattern (PDRP) expression is abnormally increased in idiopathic REM sleep behavior disorder (RBD) and whether increased baseline activity is associated with greater individual risk of subsequent phenoconversion. For this cohort study, we recruited 2 groups of RBD and control subjects. Cohort 1 comprised 10 subjects with RBD (63.5 ± 9.4 years old) and 10 healthy volunteers (62.7 ± 8.6 years old) who underwent resting-state metabolic brain imaging with (18)F-fluorodeoxyglucose PET. Cohort 2 comprised 17 subjects with RBD (68.9 ± 4.8 years old) and 17 healthy volunteers (66.6 ± 6.0 years old) who underwent resting brain perfusion imaging with ethylcysteinate dimer SPECT. The latter group was followed clinically for 4.6 ± 2.5 years by investigators blinded to the imaging results. PDRP expression was measured in both RBD groups and compared with corresponding control values. PDRP expression was elevated in both groups of subjects with RBD (cohort 1: p abnormalities in subjects with idiopathic RBD are associated with a greater likelihood of subsequent phenoconversion to a progressive neurodegenerative syndrome.

  8. Physical activity and pediatric multiple sclerosis: Developing a research agenda.

    Science.gov (United States)

    Yeh, E Ann; Kinnett-Hopkins, Dominique; Grover, Stephanie A; Motl, Robert W

    2015-11-01

    Three-quarters of children with multiple sclerosis (MS) experience fatigue or depression, and progressive neurocognitive decline may be seen as early as two years after MS diagnosis. Furthermore, a higher magnetic resonance imaging disease burden is seen in pediatric-onset MS compared with adult-onset MS. To date, limited knowledge exists regarding behavioral methods for managing symptoms and disease progression in pediatric MS. To that end, this paper builds an evidence-based argument for the possible symptomatic and disease-modifying effects of exercise and physical activity in pediatric MS. This will be accomplished through: (a) a review of pediatric MS and its consequences; (b) a brief overview of physical activity and its consequences in children and adults with MS; and (c) a selective review of research on the neurological benefits of physical activity in pediatric populations. This topical review concludes with a list of 10 questions to guide future research on physical activity and pediatric MS. The objective of this paper is the provision of a research interest, focus and agenda involving pediatric MS and its lifelong management though exercise and physical activity behavior. Such an agenda is critical as the effects and maintenance of physical activity and exercise track across the lifespan, particularly when developed in the early stages of life. © The Author(s), 2015.

  9. Metabolic activity of Glomus intraradices in Arum- and Paris-type arbuscular mycorrhizal colonization

    NARCIS (Netherlands)

    van Aarle, IM; Cavagnaro, TR; Smith, SE; Dickson, S

    Colonization of two plant species by Glomus intraradices was studied to investigate the two morphological types (Arum and Paris), their symbiotic interfaces and metabolic activities. Root pieces and sections were stained to observe the colonization and metabolic activity of all mycorrhizal

  10. Nitric oxide synthase expression and enzymatic activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Broholm, H; Andersen, B; Wanscher, B

    2004-01-01

    We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal......NOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age...

  11. AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue

    Science.gov (United States)

    Wu, Lingyan; Zhang, Lina; Li, Bohan; Jiang, Haowen; Duan, Yanan; Xie, Zhifu; Shuai, Lin; Li, Jia; Li, Jingya

    2018-01-01

    Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic “brown-like” cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK α1/α2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a β3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPKα induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively

  12. Postprandial Monocyte Activation in Individuals With Metabolic Syndrome

    Science.gov (United States)

    Khan, Ilvira M.; Pokharel, Yashashwi; Dadu, Razvan T.; Lewis, Dorothy E.; Hoogeveen, Ron C.; Wu, Huaizhu

    2016-01-01

    Context: Postprandial hyperlipidemia has been suggested to contribute to atherogenesis by inducing proinflammatory changes in monocytes. Individuals with metabolic syndrome (MS), shown to have higher blood triglyceride concentration and delayed triglyceride clearance, may thus have increased risk for development of atherosclerosis. Objective: Our objective was to examine fasting levels and effects of a high-fat meal on phenotypes of monocyte subsets in individuals with obesity and MS and in healthy controls. Design, Setting, Participants, Intervention: Individuals with obesity and MS and gender- and age-matched healthy controls were recruited. Blood was collected from participants after an overnight fast (baseline) and at 3 and 5 hours after ingestion of a high-fat meal. At each time point, monocyte phenotypes were examined by multiparameter flow cytometry. Main Outcome Measures: Baseline levels of activation markers and postprandial inflammatory response in each of the three monocyte subsets were measured. Results: At baseline, individuals with obesity and MS had higher proportions of circulating lipid-laden foamy monocytes than controls, which were positively correlated with fasting triglyceride levels. Additionally, the MS group had increased counts of nonclassical monocytes, higher CD11c, CX3CR1, and human leukocyte antigen-DR levels on intermediate monocytes, and higher CCR5 and tumor necrosis factor-α levels on classical monocytes in the circulation. Postprandial triglyceride increases in both groups were paralleled by upregulation of lipid-laden foamy monocytes. MS, but not control, subjects had significant postprandial increases of CD11c and percentages of IL-1β+ and tumor necrosis factor-α+ cells in nonclassical monocytes. Conclusions: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation. PMID:27575945

  13. Ruptured human Achilles tendon has elevated metabolic activity up to 1 year after repair

    DEFF Research Database (Denmark)

    Eliasson, Pernilla; Couppé, Christian; Lonsdale, Markus

    2016-01-01

    PURPOSE: Following Achilles tendon rupture, running is often allowed after 6 months. However, tendon healing is slow and the metabolic status of the tendon at this point is unknown. The purpose of this study was to investigate tendon metabolism (glucose uptake) and vascularization at 3, 6 and 12...... demonstrate that the healing process as determined by metabolic activity and vascularization continues for 6 months after injury when large loads are typically allowed on the tendon. Indeed, metabolic activity remained elevated for more than 1 year after injury despite normalized vascularization. The robust...... negative correlation between tendon metabolism and patient-reported outcome suggests that a high metabolic activity 6 months after the injury may be related to a poor clinical healing outcome....

  14. Resource Constrained Planning of Multiple Projects with Separable Activities

    Science.gov (United States)

    Fujii, Susumu; Morita, Hiroshi; Kanawa, Takuya

    In this study we consider a resource constrained planning problem of multiple projects with separable activities. This problem provides a plan to process the activities considering a resource availability with time window. We propose a solution algorithm based on the branch and bound method to obtain the optimal solution minimizing the completion time of all projects. We develop three methods for improvement of computational efficiency, that is, to obtain initial solution with minimum slack time rule, to estimate lower bound considering both time and resource constraints and to introduce an equivalence relation for bounding operation. The effectiveness of the proposed methods is demonstrated by numerical examples. Especially as the number of planning projects increases, the average computational time and the number of searched nodes are reduced.

  15. Investigating tumor perfusion and metabolism using multiple hyperpolarized 13C compounds: HP001, pyruvate and urea

    DEFF Research Database (Denmark)

    von Morze, Cornelius; Larson, Peder E.Z.; Hu, Simon

    2012-01-01

    The metabolically inactive hyperpolarized agents HP001 (bis-1,1-(hydroxymethyl)-[1-13C]cyclopropane-d8) and urea enable a new type of perfusion magnetic resonance imaging based on a direct signal source that is background-free. The addition of perfusion information to metabolic information obtained...... (T1=95 s ex vivo, 32 s in vivo at 3 T) using a pulse sequence with balanced steady-state free precession and ramped flip angle over time for efficient utilization of the hyperpolarized magnetization and three-dimensional echo-planar spectroscopic imaging of urea copolarized with [1-13C...... of separate dynamic HP001 imaging and copolarized pyruvate/urea imaging were compared. A strong and significant correlation (R=0.73, P=.02) detected between the urea and HP001 data confirmed the value of copolarizing urea with pyruvate for simultaneous assessment of perfusion and metabolism....

  16. Multiple Activities of Punica granatum Linne against Acne Vulgaris.

    Science.gov (United States)

    Lee, Chia-Jung; Chen, Lih-Geeng; Liang, Wen-Li; Wang, Ching-Chiung

    2017-01-12

    Acne is a common skin condition with sebum overproduction, hyperkeratosis, Propionibacterium acnes ( P . acnes ) and Staphylococcus aureus , and inflammation. Punica granatum (pomegranate) is well-known for its anti-inflammatory effects; however, few studies have discussed the anti-acne effects of pomegranate. In this study, we found that pomegranate extract (PG-E) significantly reduced P . acnes -induced edema in Wistar rat ears. Therefore, an evaluation platform using multiple pathogenic mechanisms of acne was established to explore the anti-acne effects of pomegranate. Results showed that PG-E inhibited bacterial growth and lipase activity. Through a bioguided-fractionation-isolation system, four hydrolysable tannins, punicalagin ( 1 ), punicalin ( 2 ), strictinin A ( 3 ), and granatin B ( 4 ), were isolated. Compounds 1 and 2 had greater anti-bacterial activities and anti-testosterone-induced HaCaT proliferative effects than the others. Compounds 1 , 3 , and 4 displayed lipase inhibitory effects. Compound 4 decreased cyclooxygenase-2 expression and downregulated prostaglandin E₂ production in heat-killed P . acnes -treated RAW 246.7 cells. In conclusion, PG-E is abundant in hydrolysable tannins that display multiple anti-acne capacities, including anti-bacterial, anti-lipase, anti-keratinocyte proliferation, and anti-inflammatory actions. Hence, PG-E has great potential in the application of anti-acne and skin-care products, and punicalagin ( 1 ), the most effective component in PG-E, can be employed as a quality control marker.

  17. Physical Activity and Sedentary Behavior Associated with Components of Metabolic Syndrome among People in Rural China.

    Directory of Open Access Journals (Sweden)

    Jing Xiao

    Full Text Available Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China.The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed.Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15-40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15-30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids.Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also, recommendations are

  18. Physical Activity and Sedentary Behavior Associated with Components of Metabolic Syndrome among People in Rural China.

    Science.gov (United States)

    Xiao, Jing; Shen, Chong; Chu, Min J; Gao, Yue X; Xu, Guang F; Huang, Jian P; Xu, Qiong Q; Cai, Hui

    2016-01-01

    Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China. The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed. Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15-40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15-30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids. Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also, recommendations are developed to reduce

  19. [The study on metabolic difference of human body affected by active stress and passive stress under special events].

    Science.gov (United States)

    Guo, Guang-hong; Gu, Feng; Dong, Zhen-nan; Yuan, Xin-hong; Wang, Ling; Tian, Ya-ping

    2010-05-01

    To study the metabolic difference of body influenced by active stress and passive stress under special events. To detect serum multiple biochemistry index of 57 earthquake rescue medical team and 13 victims of a natural calamity in Wenchuan earthquake by using Hitachi 7600 automatic analyzer. Stress affected biochemistry index deeply. To compared with rescue medical team, the serum ADA, ALP and TG of victims increased obviously and TP, ALB, MAO, Cr, UA, K, Na, Cl, Ca, ApoA1 and HDL decreased obviously. Many biochemistry index have been changed under stress and it relate with stress extent. The human body function status was better in active stress than in passive stress.

  20. Predicting and preventing the future: actively managing multiple sclerosis.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2012-02-01

    Relapsing-remitting multiple sclerosis (MS) has a highly variable clinical course but a number of demographic, clinical and MRI features can guide the clinician in the assessment of disease activity and likely disability outcome. It is also clear that the inflammatory activity in the first five years of relapsing-remitting MS results in the neurodegenerative changes seen in secondary progressive MS 10-15 years later. While conventional first-line disease modifying therapy has an effect on relapses, about one third of patients have a suboptimal response to treatment. With the advent of highly active second-line therapies with their evident marked suppression of inflammation, the clinician now has the tools to manage the course of relapsing-remitting MS more effectively. The development of treatment optimisation recommendations based on the clinical response to first-line therapies can guide the neurologist in more active management of the early course of relapsing-remitting MS, with the aim of preventing both acute inflammatory axonal injury and the neurodegenerative process which leads to secondary progressive MS.

  1. Reconstructing phylogeny by aligning multiple metabolic pathways using functional module mapping

    NARCIS (Netherlands)

    Huang, Yiran; Zhong, Cheng; Lin, H.X.; Wang, Jianyi; Peng, Yuzhong

    2018-01-01

    Comparison of metabolic pathways provides a systematic way for understanding the evolutionary and phylogenetic relationships in systems biology. Although a number of phylogenetic methods have been developed, few efforts have been made to provide a unified phylogenetic framework that sufficiently

  2. Leisure-time exercise, physical activity during work and commuting, and risk of metabolic syndrome.

    Science.gov (United States)

    Kuwahara, Keisuke; Honda, Toru; Nakagawa, Tohru; Yamamoto, Shuichiro; Akter, Shamima; Hayashi, Takeshi; Mizoue, Tetsuya

    2016-09-01

    Data are limited regarding effect of intensity of leisure-time physical activity on metabolic syndrome. Furthermore, no prospective data are available regarding effect of occupational and commuting physical activity on metabolic syndrome. We compared metabolic syndrome risk by intensity level of leisure-time exercise and by occupational and commuting physical activity in Japanese workers. We followed 22,383 participants, aged 30-64 years, without metabolic syndrome until 2014 March (maximum, 5 years of follow-up). Physical activity was self-reported. Metabolic syndrome was defined by the Joint Statement criteria. We used Cox regression models to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of metabolic syndrome. During a mean follow-up of 4.1 years, 5361 workers developed metabolic syndrome. After adjustment for covariates, compared with engaging in no exercise, the HRs (95 % CIs) for metabolic equivalent hours of exercise per week were 0.99 (0.90, 1.08), 0.99 (0.90, 1.10), and 0.95 (0.83, 1.08), respectively, among individuals engaging in moderate-intensity exercise alone; 0.93 (0.75, 1.14), 0.81 (0.64, 1.02), and 0.84 (0.66, 1.06), among individuals engaging in vigorous-intensity exercise alone; and 0.90 (0.70, 1.17), 0.74 (0.62, 0.89), and 0.81 (0.69, 0.96) among individuals engaging in the two intensities. Higher occupational physical activity was weakly but significantly associated with lower risk of metabolic syndrome. Walking to and from work was not associated with metabolic syndrome. Vigorous-intensity exercise alone or vigorous-intensity combined with moderate-intensity exercise and worksite intervention for physical activity may help prevent metabolic syndrome for Japanese workers.

  3. Episodic aphasia associated with tumor active multiple sclerosis: a correlative SPECT study utilising image fusion

    International Nuclear Information System (INIS)

    Roff, G.; Campbell, A.; Lawn, N.; Henderson, A.; McCarthy, M.; Lenzo, N.

    2003-01-01

    Full text: Cerebral perfusion imaging is a common technique to assess cerebral perfusion and metabolism. It can complement anatomical imaging in assessing a number of neurological conditions. At times it can better define the clinical manifestations of a disease process than anatomical imaging alone. We present a clinical case whereby cerebral SPECT imaging helped define the physiological reason for intermittent aphasia in a patient with tumor active multiple sclerotic white matter plaques. Cerebral SPECT studies were performed during a period of aphasia and when the patient had recovered. We utilised subtraction analyses and image fusion techniques to better define the changes seen on SPECT. We discuss the neuroanatomical relationship of aphasia and the automatic fusion technique that allows accurate co-registration of the MRI and SPECT data. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc

  4. An in vitro model for screening estrogen activity of environmental samples after metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Chahbane, N.; Schramm, K.W. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Oekologische Chemie; Kettrup, A. [Technische Univ. Muenchen, Freising (Germany). Lehrstuhl fuer Oekologische Chemie

    2004-09-15

    For a few years, yeast estrogen assay (YES) was accepted as a reliable and economic model for screening of environmental estrogens. Though the chemicals directly act with estrogen receptor (ER) can be filtered out by this model, there are still chemicals act with ER only after metabolism and some chemicals eliminate their estrogen activities after metabolism. That is to say, their metabolites exert or have stronger estrogen activities than themselves, which can be called bio-activation. In this case, for the lack of the metabolism enzyme system as human and other animals, only the assay with recombinant yeast cells is insufficient. So, it is necessary to combine the YES with metabolism procedure to evaluate the estrogen activities of these chemicals. The most common method used currently for in vitro metabolic activation in mutagenicity testing and also be applied to the estrogen screening field is S-9 mixture. Also, there is an attempt to develop a chemical model for cytochrome P450 as a bio-mimetic metabolic activation system. All these methods can be used as in vitro models for metabolism. Compare with these models, using whole H4II E cells for metabolism is an alternative and with superiorities. It has the excellence of short experiment period as all other in vitro models, but is much more close to the real surroundings as in vivo. Furthermore, the activity of 7-ethoxyresorufin-O-deethylase (EROD) can be easily measured during the whole incubation period for us to discuss the metabolic activities in a quantitative foundation, not only in qualitative. Methoxychlor is one of the chemicals with bio-activation ability. When directly used in the YES, it shows weak estrogen activity. But a main metabolite of methoxychlor, 2,2-bis (p-hydroxyphenyl) - 1,1,1-trichloroethane (HPTE) is a known estrogen mimic. For the long time using methoxychlor as a pesticide and its clear background, it is an ideal chemical to establish this in vitro system.

  5. Multiple-trait estimates of genetic parameters for metabolic disease traits, fertility disorders, and their predictors in Canadian Holsteins.

    Science.gov (United States)

    Jamrozik, J; Koeck, A; Kistemaker, G J; Miglior, F

    2016-03-01

    Producer-recorded health data for metabolic disease traits and fertility disorders on 35,575 Canadian Holstein cows were jointly analyzed with selected indicator traits. Metabolic diseases included clinical ketosis (KET) and displaced abomasum (DA); fertility disorders were metritis (MET) and retained placenta (RP); and disease indicators were fat-to-protein ratio, milk β-hydroxybutyrate, and body condition score (BCS) in the first lactation. Traits in first and later (up to fifth) lactations were treated as correlated in the multiple-trait (13 traits in total) animal linear model. Bayesian methods with Gibbs sampling were implemented for the analysis. Estimates of heritability for disease incidence were low, up to 0.06 for DA in first lactation. Among disease traits, the environmental herd-year variance constituted 4% of the total variance for KET and less for other traits. First- and later-lactation disease traits were genetically correlated (from 0.66 to 0.72) across all traits, indicating different genetic backgrounds for first and later lactations. Genetic correlations between KET and DA were relatively strong and positive (up to 0.79) in both first- and later-lactation cows. Genetic correlations between fertility disorders were slightly lower. Metritis was strongly genetically correlated with both metabolic disease traits in the first lactation only. All other genetic correlations between metabolic and fertility diseases were statistically nonsignificant. First-lactation KET and MET were strongly positively correlated with later-lactation performance for these traits due to the environmental herd-year effect. Indicator traits were moderately genetically correlated (from 0.30 to 0.63 in absolute values) with both metabolic disease traits in the first lactation. Smaller and mostly nonsignificant genetic correlations were among indicators and metabolic diseases in later lactations. The only significant genetic correlations between indicators and fertility

  6. Metabolomic Analyses of Leishmania Reveal Multiple Species Differences and Large Differences in Amino Acid Metabolism.

    Directory of Open Access Journals (Sweden)

    Gareth D Westrop

    Full Text Available Comparative genomic analyses of Leishmania species have revealed relatively minor heterogeneity amongst recognised housekeeping genes and yet the species cause distinct infections and pathogenesis in their mammalian hosts. To gain greater information on the biochemical variation between species, and insights into possible metabolic mechanisms underpinning visceral and cutaneous leishmaniasis, we have undertaken in this study a comparative analysis of the metabolomes of promastigotes of L. donovani, L. major and L. mexicana. The analysis revealed 64 metabolites with confirmed identity differing 3-fold or more between the cell extracts of species, with 161 putatively identified metabolites differing similarly. Analysis of the media from cultures revealed an at least 3-fold difference in use or excretion of 43 metabolites of confirmed identity and 87 putatively identified metabolites that differed to a similar extent. Strikingly large differences were detected in their extent of amino acid use and metabolism, especially for tryptophan, aspartate, arginine and proline. Major pathways of tryptophan and arginine catabolism were shown to be to indole-3-lactate and arginic acid, respectively, which were excreted. The data presented provide clear evidence on the value of global metabolomic analyses in detecting species-specific metabolic features, thus application of this technology should be a major contributor to gaining greater understanding of how pathogens are adapted to infecting their hosts.

  7. Dietary patterns as compared with physical activity in relation to metabolic syndrome among Chinese adults

    NARCIS (Netherlands)

    He, Y.; Li, Y.; Lai, J.; Wang, D.; Zhang, J.; Fu, P.; Yang, X.; Qi, L.

    2013-01-01

    Aims: To examine the nationally-representative dietary patterns and their joint effects with physical activity on the likelihood of metabolic syndrome (MS) among 20,827 Chinese adults. Methods and results: CNNHS was a nationally representative cross-sectional observational study. Metabolic syndrome

  8. Effects of Cola-Flavored Beverages and Caffeine on Streptococcus mutans Biofilm Formation and Metabolic Activity.

    Science.gov (United States)

    Dotsey, Roger P; Moser, Elizabeth A S; Eckert, George J; Gregory, Richard L

    To examine the effects of cola-flavored beverages and caffeine on growth and metabolism of Streptococcus mutans biofilm. This study was designed to determine if carbonated beverages or caffeine can increase S. mutans growth and biofilm formation and metabolic activity in vitro, potentially leading to increased S. mutans-associated cariogenicity in children that consume them. Six different cola-flavored products, plus pure caffeine, and pure high fructose corn syrup (HFCS), at different concentrations similar to those in the beverages were tested. A 16-hour culture of S. mutans was treated with different dilutions in bacteriological media. To test for the effect on biofilm formation, the biofilm was stained with crystal violet. The absorbance was determined to evaluate biofilm growth. Biofilm metabolic activity was measured based on biofilm having the ability to reduce XTT to a water-soluble orange compound. The inclusion of HFCS in the beverages, as well as pure HFCS, significantly enhanced bacterial biofilm formation and metabolic activity. Pure caffeine and the presence of caffeine in beverages did not significantly increase biofilm formation, but pure caffeine significantly increased metabolism, and Diet Coke had significantly greater metabolic activity than Caffeine-Free Diet Coke. HFCS increases both the biofilm formation and metabolism of S. mutans, and caffeine in some cases increases metabolism of S. mutans.

  9. Physical activity and sedentary behavior in metabolically healthy obese young women

    Science.gov (United States)

    Studies of physical activity (PA) and sedentary behavior (SB) in metabolically healthy obese (MHO) have been limited to postmenopausal white women. We sought to determine whether PA and SB differ between MHO and metabolically abnormal obese (MAO), in young black and white women....

  10. Association between physical activity and metabolic syndrome among Malay adults in a developing country, Malaysia.

    Science.gov (United States)

    Chu, Anne H Y; Moy, F M

    2014-03-01

    Metabolic syndrome is a highly prevalent health problem within the adult population in developing countries. We aimed to study the association of physical activity levels and metabolic risk factors among Malay adults in Malaysia. Cross-sectional. Body mass index, waist circumference, and systolic/diastolic blood pressure, fasting blood glucose, fasting triglyceride and high-density lipoprotein cholesterol levels were measured in 686 Malay participants (aged 35-74 years). Self-reported physical activity was obtained with the validated International Physical Activity Questionnaire (Malay version) and categorized into low, moderate or high activity levels. Individuals who were classified as overweight and obese predominated (65.6%). On the basis of the modified NCEP ATP III criteria, metabolic syndrome was diagnosed in 31.9% of all participants, of whom 46.1% were men and 53.9% were women. The prevalence of metabolic syndrome among participants with low, moderate or high activity levels was 13.3%, 11.7% and 7.0%, respectively (p<0.001). Statistically significant negative associations were found between a number of metabolic risk factors and activity categories (p<0.05). The odds ratios for metabolic syndrome in the moderate and high activity categories were 0.42 (95% CI: 0.27-0.65) and 0.52 (95% CI: 0.35-0.76), respectively, adjusted for gender. Moderate and high activity levels were each associated with reduced odds for metabolic syndrome independent of gender. Although a slightly lower prevalence of metabolic syndrome was associated with high activity than with moderate activity, potential health benefits were observed when moderate activity was performed. Copyright © 2013 Sports Medicine Australia. All rights reserved.

  11. 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

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

    Directory of Open Access Journals (Sweden)

    Xiaodong Zai

    2017-11-01

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

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

    International Nuclear Information System (INIS)

    Vion-Dury, J.; Confort-Gouny, S.; Maillet, S.; Cozzone, P.J.; Nicoli, F.; Gastaut, J.L.

    1996-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Vion-Dury, J.; Confort-Gouny, S.; Maillet, S.; Cozzone, P.J. [Centre Hospitalier Universitaire de la Timone, 13 - Marseille (France); Nicoli, F. [Centre Hospitalier Universitaire de la Timone, 13 - Marseille (France)]|[Hopital Sainte-Marguerite, 13 - Marseille (France); Gastaut, J.L. [Hopital Sainte-Marguerite, 13 - Marseille (France)

    1996-07-01

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

  15. Fibroblast activation protein (FAP as a novel metabolic target

    Directory of Open Access Journals (Sweden)

    Miguel Angel Sánchez-Garrido

    2016-10-01

    Conclusions: We conclude that pharmacological inhibition of FAP enhances levels of FGF21 in obese mice to provide robust metabolic benefits not observed in lean animals, thus validating this enzyme as a novel drug target for the treatment of obesity and diabetes.

  16. Activating transcription factor 3 regulates immune and metabolic homeostasis

    Czech Academy of Sciences Publication Activity Database

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

    2012-01-01

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

  17. Quantifying interictal metabolic activity in human temporal lobe epilepsy

    International Nuclear Information System (INIS)

    Henry, T.R.; Mazziotta, J.C.; Engel, J. Jr.; Christenson, P.D.; Zhang, J.X.; Phelps, M.E.; Kuhl, D.E.

    1990-01-01

    The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on [18F]fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a single investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism

  18. Diminished neuronal metabolic activity in Alzheimer's disease. Review article

    NARCIS (Netherlands)

    Salehi, A.; Swaab, D. F.

    1999-01-01

    An increasing number of studies have appeared in the literature suggesting that Alzheimer's disease (AD) is a hypometabolic brain disorder. Decreased metabolism in AD has been revealed by a variety of in vivo and postmortem methods and techniques including positron emission tomography and glucose

  19. Chronic innate immune activation of TBK1 suppresses mTORC1 activity and dysregulates cellular metabolism.

    Science.gov (United States)

    Hasan, Maroof; Gonugunta, Vijay K; Dobbs, Nicole; Ali, Aktar; Palchik, Guillermo; Calvaruso, Maria A; DeBerardinis, Ralph J; Yan, Nan

    2017-01-24

    Three-prime repair exonuclease 1 knockout (Trex1 -/- ) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1 -/- mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism. We also genetically separated the inflammatory and metabolic phenotypes by showing that Sting deficiency rescued both inflammatory and metabolic phenotypes, whereas Irf3 deficiency only rescued inflammation on the Trex1 -/- background, and many metabolic defects persist in Trex1 -/- Irf3 -/- cells and mice. We also showed that Leptin deficiency (ob/ob) increased lipogenesis and prolonged survival of Trex1 -/- mice without dampening inflammation. Mechanistically, we identified TBK1 as a key regulator of mTORC1 activity in Trex1 -/- cells. Together, our data demonstrate that chronic innate immune activation of TBK1 suppresses mTORC1 activity, leading to dysregulated cellular metabolism.

  20. Mouse visual neocortex supports multiple stereotyped patterns of microcircuit activity.

    Science.gov (United States)

    Sadovsky, Alexander J; MacLean, Jason N

    2014-06-04

    Spiking correlations between neocortical neurons provide insight into the underlying synaptic connectivity that defines cortical microcircuitry. Here, using two-photon calcium fluorescence imaging, we observed the simultaneous dynamics of hundreds of neurons in slices of mouse primary visual cortex (V1). Consistent with a balance of excitation and inhibition, V1 dynamics were characterized by a linear scaling between firing rate and circuit size. Using lagged firing correlations between neurons, we generated functional wiring diagrams to evaluate the topological features of V1 microcircuitry. We found that circuit connectivity exhibited both cyclic graph motifs, indicating recurrent wiring, and acyclic graph motifs, indicating feedforward wiring. After overlaying the functional wiring diagrams onto the imaged field of view, we found properties consistent with Rentian scaling: wiring diagrams were topologically efficient because they minimized wiring with a modular architecture. Within single imaged fields of view, V1 contained multiple discrete circuits that were overlapping and highly interdigitated but were still distinct from one another. The majority of neurons that were shared between circuits displayed peri-event spiking activity whose timing was specific to the active circuit, whereas spike times for a smaller percentage of neurons were invariant to circuit identity. These data provide evidence that V1 microcircuitry exhibits balanced dynamics, is efficiently arranged in anatomical space, and is capable of supporting a diversity of multineuron spike firing patterns from overlapping sets of neurons. Copyright © 2014 the authors 0270-6474/14/347769-09$15.00/0.

  1. Quantification of metabolically active transient storage (MATS) in two reaches with contrasting transient storage and ecosystem respiration

    Science.gov (United States)

    Alba Argerich; Roy Haggerty; Eugènia Martí; Francesc Sabater; Jay. Zarnetske

    2011-01-01

    Water transient storage zones are hotspots for metabolic activity in streams although the contribution of different types of transient storage zones to the whole�]reach metabolic activity is difficult to quantify. In this study we present a method to measure the fraction of the transient storage that is metabolically active (MATS) in two consecutive reaches...

  2. Association of Objectively Measured Physical Activity and Metabolic Syndrome Among US Adults With Osteoarthritis.

    Science.gov (United States)

    Liu, Shao-Hsien; Waring, Molly E; Eaton, Charles B; Lapane, Kate L

    2015-10-01

    To investigate the association between objectively measured physical activity and metabolic syndrome among adults with osteoarthritis (OA). Using cross-sectional data from the 2003-2006 National Health and Nutrition Examination Survey, we identified 566 adults with OA with available accelerometer data assessed using Actigraph AM-7164 and measurements necessary to determine metabolic syndrome by the Adult Treatment Panel III. Analysis of variance was conducted to examine the association between continuous variables in each activity level and metabolic syndrome components. Logistic models estimated the relationship of quartile of daily minutes of different physical activity levels to odds of metabolic syndrome adjusted for socioeconomic and health factors. Among persons with OA, most were women average age of 62.1 years and average disease duration of 12.9 years. Half of adults with OA had metabolic syndrome (51.0%; 95% confidence interval [95% CI] 44.2%-57.8%), and only 9.6% engaged in the recommended 150 minutes per week of moderate/vigorous physical activity. Total sedentary time was associated with higher rates of metabolic syndrome and its components, while light and objectively measured moderate/vigorous physical activity was inversely associated with metabolic syndrome and its components. Higher levels of light activity were associated with lower prevalence of metabolic syndrome (quartile 4 versus quartile 1: adjusted odds ratio 0.45, 95% CI 0.24-0.84, P for linear trend physical activity, especially in light intensity, is more likely to be associated with decreasing prevalence of metabolic syndrome among persons with OA. © 2015, American College of Rheumatology.

  3. Diet composition and activity level of at risk and metabolically healthy obese American adults.

    Science.gov (United States)

    Hankinson, Arlene L; Daviglus, Martha L; Van Horn, Linda; Chan, Queenie; Brown, Ian; Holmes, Elaine; Elliott, Paul; Stamler, Jeremiah

    2013-03-01

    Obesity often clusters with other major cardiovascular disease risk factors, yet a subset of the obese appears to be protected from these risks. Two obesity phenotypes are described, (i) "metabolically healthy" obese, broadly defined as body mass index (BMI) ≥ 30 kg/m(2) and favorable levels of blood pressure, lipids, and glucose; and (ii) "at risk" obese, BMI ≥ 30 with unfavorable levels of these risk factors. More than 30% of obese American adults are metabolically healthy. Diet and activity determinants of obesity phenotypes are unclear. We hypothesized that metabolically healthy obese have more favorable behavioral factors, including less adverse diet composition and higher activity levels than at risk obese in the multi-ethnic group of 775 obese American adults ages 40-59 years from the International Population Study on Macro/Micronutrients and Blood Pressure (INTERMAP) cohort. In gender-stratified analyses, mean values for diet composition and activity behavior variables, adjusted for age, race, and education, were compared between metabolically healthy and at risk obese. Nearly one in five (149/775 or 19%) of obese American INTERMAP participants were classified as metabolically healthy obese. Diet composition and most activity behaviors were similar between obesity phenotypes, although metabolically healthy obese women reported higher sleep duration than at risk obese women. These results do not support hypotheses that diet composition and/or physical activity account for the absence of cardiometabolic abnormalities in metabolically healthy obese. Copyright © 2012 The Obesity Society.

  4. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    Science.gov (United States)

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Serum Compounds of Energy Metabolism Impairment Are Related to Disability, Disease Course and Neuroimaging in Multiple Sclerosis.

    Science.gov (United States)

    Lazzarino, Giacomo; Amorini, Angela M; Petzold, Axel; Gasperini, Claudio; Ruggieri, Serena; Quartuccio, Maria Esmeralda; Lazzarino, Giuseppe; Di Stasio, Enrico; Tavazzi, Barbara

    2017-11-01

    Multiple sclerosis (MS) is characterized by primary inflammation, demyelination, and progressive neurodegeneration. A biochemical MS feature is neuronal mitochondrial dysfunction, compensated by anaerobic metabolism increase, likely aggravating progression of neurodegeneration. Here, we characterized a pragmatic serum profile of compounds related to mitochondrial energy metabolism of potential clinical use. Blood samples of 518 well characterized (disability, disease course) MS patients and 167 healthy controls were analyzed for serum purines, pyrimidines, creatinine, and lactate. Nine of the 15 compounds assayed, hypoxanthine, xanthine, uric acid, inosine, uracil, β-pseudouridine, uridine, creatinine, and lactate, differed significantly between MS patients and controls (p < 0.0001). Using these nine compounds, a unifying Biomarker Score was calculated. Controls and MS patients had mean Biomarker Scores of 0.4 ± 0.7 and 4.4 ± 1.9, respectively (p < 0.00001). The Biomarker Score was higher in patients with progressive (6.0 ± 1.8 than with relapsing remitting disease course (3.6 ± 1.5, p < 0.00001). High association between the Biomarker Score and increase in disability (EDSS) was also observed. Additionally, in 50 patients who underwent magnetic resonance imaging (MRI), increase in the Biomarker Score correlated to neuroanatomical alterations. These results, obtained in a large cohort of MS patients evaluated for serum metabolic compounds connected to energy metabolism, demonstrated that the Biomarker Score might represent a pragmatic, resource saving, easy to obtain, laboratory tool useful to monitor MS patients and predict at an early stage who will switch from an RR to a progressive disease course. For the first time, it was also clearly shown a link between mitochondrial dysfunction and MRI lesions characteristic of MS.

  6. Regulation of sucrose metabolism in higher plants: localization and regulation of activity of key enzymes

    Science.gov (United States)

    Winter, H.; Huber, S. C.; Brown, C. S. (Principal Investigator)

    2000-01-01

    Sucrose (Suc) plays a central role in plant growth and development. It is a major end product of photosynthesis and functions as a primary transport sugar and in some cases as a direct or indirect regulator of gene expression. Research during the last 2 decades has identified the pathways involved and which enzymes contribute to the control of flux. Availability of metabolites for Suc synthesis and 'demand' for products of sucrose degradation are important factors, but this review specifically focuses on the biosynthetic enzyme sucrose-phosphate synthase (SPS), and the degradative enzymes, sucrose synthase (SuSy), and the invertases. Recent progress has included the cloning of genes encoding these enzymes and the elucidation of posttranslational regulatory mechanisms. Protein phosphorylation is emerging as an important mechanism controlling SPS activity in response to various environmental and endogenous signals. In terms of Suc degradation, invertase-catalyzed hydrolysis generally has been associated with cell expansion, whereas SuSy-catalyzed metabolism has been linked with biosynthetic processes (e.g., cell wall or storage products). Recent results indicate that SuSy may be localized in multiple cellular compartments: (1) as a soluble enzyme in the cytosol (as traditionally assumed); (2) associated with the plasma membrane; and (3) associated with the actin cytoskeleton. Phosphorylation of SuSy has been shown to occur and may be one of the factors controlling localization of the enzyme. The purpose of this review is to summarize some of the recent developments relating to regulation of activity and localization of key enzymes involved in sucrose metabolism in plants.

  7. Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria.

    Science.gov (United States)

    Hoffman, Stephen L; Billingsley, Peter F; James, Eric; Richman, Adam; Loyevsky, Mark; Li, Tao; Chakravarty, Sumana; Gunasekera, Anusha; Chattopadhyay, Rana; Li, Minglin; Stafford, Richard; Ahumada, Adriana; Epstein, Judith E; Sedegah, Martha; Reyes, Sharina; Richie, Thomas L; Lyke, Kirsten E; Edelman, Robert; Laurens, Matthew B; Plowe, Christopher V; Sim, B Kim Lee

    2010-01-01

    Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming these challenges. This progress has enabled the manufacture and release of multiple clinical lots of a 1(st) generation metabolically active, non-replicating PfSPZ vaccine, the Sanaria PfSPZ Vaccine, submission of a successful Investigational New Drug application to the US Food and Drug Administration, and initiation of safety, immunogenicity and protective efficacy studies in volunteers in MD, US. Efforts are now focused on how best to achieve submission of a successful Biologics License Application and introduce the vaccine to the primary target population of African children in the shortest possible period of time. This will require implementation of a systematic, efficient clinical development plan. Short term challenges include optimizing the (1) efficiency and scale up of the manufacturing process and quality control assays, (2) dosage regimen and method of administration, (3) potency of the vaccine, and (4) logistics of delivering the vaccine to those who need it most, and finalizing the methods for vaccine stabilization and attenuation. A medium term goal is to design and build a facility for manufacturing highly potent and stable vaccine for pivotal Phase 3 studies and commercial launch.

  8. Multiplicative point process as a model of trading activity

    Science.gov (United States)

    Gontis, V.; Kaulakys, B.

    2004-11-01

    Signals consisting of a sequence of pulses show that inherent origin of the 1/ f noise is a Brownian fluctuation of the average interevent time between subsequent pulses of the pulse sequence. In this paper, we generalize the model of interevent time to reproduce a variety of self-affine time series exhibiting power spectral density S( f) scaling as a power of the frequency f. Furthermore, we analyze the relation between the power-law correlations and the origin of the power-law probability distribution of the signal intensity. We introduce a stochastic multiplicative model for the time intervals between point events and analyze the statistical properties of the signal analytically and numerically. Such model system exhibits power-law spectral density S( f)∼1/ fβ for various values of β, including β= {1}/{2}, 1 and {3}/{2}. Explicit expressions for the power spectra in the low-frequency limit and for the distribution density of the interevent time are obtained. The counting statistics of the events is analyzed analytically and numerically, as well. The specific interest of our analysis is related with the financial markets, where long-range correlations of price fluctuations largely depend on the number of transactions. We analyze the spectral density and counting statistics of the number of transactions. The model reproduces spectral properties of the real markets and explains the mechanism of power-law distribution of trading activity. The study provides evidence that the statistical properties of the financial markets are enclosed in the statistics of the time interval between trades. A multiplicative point process serves as a consistent model generating this statistics.

  9. Mechanisms for multiple activity modes of VTA dopamine neurons

    Directory of Open Access Journals (Sweden)

    Andrew eOster

    2015-07-01

    Full Text Available Midbrain ventral segmental area (VTA dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition.

  10. Increased microglial catalase activity in multiple sclerosis grey matter.

    Science.gov (United States)

    Gray, Elizabeth; Kemp, Kevin; Hares, Kelly; Redondo, Julianna; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2014-04-22

    Chronic demyelination, on-going inflammation, axonal loss and grey matter neuronal injury are likely pathological processes that contribute to disease progression in multiple sclerosis (MS). Although the precise contribution of each process and their aetiological substrates is not fully known, recent evidence has implicated oxidative damage as a major cause of tissue injury in MS. The degree of tissue injury caused by oxidative molecules, such as reactive oxygen species (ROS), is balanced by endogenous anti-oxidant enzymes which detoxify ROS. Understanding endogenous mechanisms which protect the brain against oxidative injury in MS is important, since enhancing anti-oxidant responses is a major therapeutic strategy for preventing irreversible tissue injury in the disease. Our aims were to determine expression and activity levels of the hydrogen peroxide-reducing enzyme catalase in MS grey matter (GM). In MS GM, a catalase enzyme activity was elevated compared to control GM. We measured catalase protein expression by immune dot-blotting and catalase mRNA by a real-time polymerase chain reaction (RT-PCR). Protein analysis studies showed a strong positive correlation between catalase and microglial marker IBA-1 in MS GM. In addition, calibration of catalase mRNA level with reference to the microglial-specific transcript AIF-1 revealed an increase in this transcript in MS. This was reflected by the extent of HLA-DR immunolabeling in MS GM which was significantly elevated compared to control GM. Collectively, these observations provide evidence that microglial catalase activity is elevated in MS grey matter and may be an important endogenous anti-oxidant defence mechanism in MS. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Metabolic Profiling of Total Physical Activity and Sedentary Behavior in Community-Dwelling Men.

    Directory of Open Access Journals (Sweden)

    Kota Fukai

    Full Text Available Physical activity is known to be preventive against various non-communicable diseases. We investigated the relationship between daily physical activity level and plasma metabolites using a targeted metabolomics approach in a population-based study.A total of 1,193 participants (male, aged 35 to 74 years with fasting blood samples were selected from the baseline survey of a cohort study. Information on daily total physical activity, classified into four levels by quartile of metabolic equivalent scores, and sedentary behavior, defined as hours of sitting per day, was collected through a self-administered questionnaire. Plasma metabolite concentrations were quantified by capillary electrophoresis mass spectrometry method. We performed linear regression analysis models with multivariable adjustment and corrected p-values for multiple testing in the original population (n = 808. The robustness of the results was confirmed by replication analysis in a separate population (n = 385 created by random allocation.Higher levels of total physical activity were associated with various metabolite concentrations, including lower concentrations of amino acids and their derivatives, and higher concentrations of pipecolate (FDR p <0.05 in original population. The findings persisted after adjustment for age, body mass index, smoking, alcohol intake, and energy intake. Isoleucine, leucine, valine, 4-methyl-2-oxoisopentanoate, 2-oxoisopentanoate, alanine, and proline concentrations were lower with a shorter sitting time.Physical activity is related to various plasma metabolites, including known biomarkers for future insulin resistance or type 2 diabetes. These metabolites might potentially play a key role in the protective effects of higher physical activity and/or less sedentary behavior on non-communicable diseases.

  12. Effects of total solar eclipse on the behavioural and metabolic activities of tropical intertidal animals

    Digital Repository Service at National Institute of Oceanography (India)

    Parulekar, A.H.; Ansari, Z.A.; Verlecar, X.N.; Harkantra, S.N.

    To study the effects of total solar eclipse of 16th Feb. 1980, on the behaviour and metabolic activities of intertidal invertebrates - nematodes, gastropods and bivalves - having different habitat preference a set of relevant observations, covering...

  13. A specific metabolic pattern related to the hallucinatory activity in schizophrenia

    International Nuclear Information System (INIS)

    Huret, J.D.; Martinot, J.L.; Lesur, A.; Mazoyer, B.; Pappata, S.; Syrota, A.; Baron, J.C.; Lemperiere, T.

    1988-01-01

    A clinical and PEI study using 18 F - fluorodesoxyglucose for measuring local cerebral glucose metabolism with the aim of showing a specific pattern related to the hallucinatory activity, is presented in schizophrenic patients all experiencing hallucinations or pseudo-halluccinations

  14. Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children : The ABCD Study

    NARCIS (Netherlands)

    Vrijkotte, Tanja G M; van den Born, Bert-Jan H; Hoekstra, Christine M C A; Gademan, Maaike G J; van Eijsden, Manon; de Rooij, Susanne R; Twickler, Marcel T B

    2015-01-01

    BACKGROUND: In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system

  15. Mutagenicity of silver nanoparticles in CHO cells dependent on particle surface functionalization and metabolic activation

    Science.gov (United States)

    Guigas, Claudia; Walz, Elke; Gräf, Volker; Heller, Knut J.; Greiner, Ralf

    2017-06-01

    The potential of engineered nanomaterials to induce genotoxic effects is an important aspect of hazard identification. In this study, cytotoxicity and mutagenicity as a function of metabolic activation of three silver nanoparticle (AgNP) preparations differing in surface coating were determined in Chinese hamster ovary (CHO) subclone K1 cells. Three silver nanoparticle preparations ( x 90,0 culture medium containing 10% fetal calf serum (FCS) than in medium without FCS. The HPRT test without metabolic activation system S9 revealed that compared to the other AgNP formulations, citrate-coated Ag showed a lower genotoxic effect. However, addition of S9 increased the mutation frequency of all AgNPs and especially influenced the genotoxicity of Citrate-Ag. The results showed that exogenous metabolic activation of nanosilver is crucial even if interactions of the metabolic activation system, nanosilver, and cells are not really understood up to now.

  16. Effectiveness of physical activity intervention among government employees with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Chee Huei Phing

    2017-12-01

    Conclusion: The findings of this study suggest that physical activity intervention via aerobics classes is an effective strategy for improving step counts and reducing the prevalence of metabolic syndrome.

  17. Metabolic activity of boar semen stored in different extenders supplemented with ostrich egg yolk lipoproteins

    OpenAIRE

    Dziekońska Anna; Kinder Marek; Fraser Leyland; Strzeżek Jerzy; Kordan Władysław

    2017-01-01

    Introduction: The aim of this study was to evaluate the effect of lipoprotein fraction isolated from ostrich egg yolk (LPFo) on the metabolic activity of boar spermatozoa following liquid semen storage in different extenders and temperatures.

  18. Metabolic activity of boar semen stored in different extenders supplemented with ostrich egg yolk lipoproteins

    Directory of Open Access Journals (Sweden)

    Dziekońska Anna

    2017-03-01

    Full Text Available Introduction: The aim of this study was to evaluate the effect of lipoprotein fraction isolated from ostrich egg yolk (LPFo on the metabolic activity of boar spermatozoa following liquid semen storage in different extenders and temperatures.

  19. Relationships among ventilation-perfusion distribution, multiple inert gas methodology and metabolic blood-gas tensions.

    Science.gov (United States)

    Lee, A S; Patterson, R W; Kaufman, R D

    1987-12-01

    The retention equations upon which the Multiple Inert Gas Method is based are derived from basic principles using elementary algebra. It is shown that widely disparate distributions produce indistinguishable sets of retentions. The limits of resolution of perfused compartments in the VA/Q distribution obtainable by the use of the multiple inert gas method are explored mathematically, and determined to be at most shunt and two alveolar compartments ("tripartite" distribution). Every continuous distribution studied produced retentions indistinguishable from those of its unique "matching" tripartite distribution. When a distribution is minimally specified, it is unique. Any additional specification (increased resolution--more compartments) of the distribution results in the existence of an infinitude of possible distributions characterized by indistinguishable sets of retention values. No further increase in resolution results from the use of more tracers. When sets of retention values were extracted from published multiple inert gas method continuous distributions, and compared with the published "measured" retention sets, substantial differences were found. This illustrates the potential errors incurred in the practical, in vivo application of the multiple inert gas method. In preliminary studies, the tripartite distribution could be determined with at least comparable accuracy by blood-gas (oxygen, carbon dioxide) measurements.

  20. In vivo metabolic activity of hamster suprachiasmatic nuclei: use of anesthesia

    International Nuclear Information System (INIS)

    Schwartz, W.J.

    1987-01-01

    In vivo glucose utilization was measured in the suprachiasmatic nuclei (SCN) of Golden hamsters using the 14 C-labeled deoxyglucose technique. A circadian rhythm of SCN metabolic activity could be measured in this species, but only during pentobarbital sodium anesthesia when the surrounding background activity of adjacent hypothalamus was suppressed. Both the SCN's metabolic oscillation and its time-keeping ability are resistant to general anesthesia

  1. Effectiveness of physical activity intervention among government employees with metabolic syndrome

    OpenAIRE

    Chee Huei Phing; Hazizi Abu Saad; M.Y. Barakatun Nisak; M.T. Mohd Nasir

    2017-01-01

    Background/Objective: Our study aimed to assess the effects of physical activity interventions via standing banners (point-of-decision prompt) and aerobics classes to promote physical activity among individuals with metabolic syndrome. Methods: We conducted a cluster randomized controlled intervention trial (16-week intervention and 8-week follow-up). Malaysian government employees in Putrajaya, Malaysia, with metabolic syndrome were randomly assigned by cluster to a point-of-decision prom...

  2. Activity of carbohydrate metabolism enzymes of bone marrow cells of rats affected by radiation

    International Nuclear Information System (INIS)

    Sukhomlinov, B.F.; Grinyuk, Yu.S.; Sibirnaya, N.A.; Starikovich, L.S.; Khmil', M.V.

    1990-01-01

    The influence of ionizing radiation (154.8 mC/kg on activity of some carbohydrate metabolism dehydrogenases in cells of the whole and fractionated rat bone marrow has been investigated. Different glucose metabolism units differently responded to radiation, the highest radiation response being exhibited by pentosophosphate cycle processes. The pattern of changes in the enzyme activity of different myelocaryocyte populations was shown to depend directly on the functional specilization of cells and the energy exchange types predominated in them

  3. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Nieves Baenas

    2016-02-01

    Full Text Available We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo, a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus.

  4. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster

    Science.gov (United States)

    Baenas, Nieves; Piegholdt, Stefanie; Schloesser, Anke; Moreno, Diego A.; García-Viguera, Cristina; Rimbach, Gerald; Wagner, Anika E.

    2016-01-01

    We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus. PMID:26901196

  5. Prevalence of metabolic syndrome and its relationship with physical activity in suburban Beijing, China.

    Science.gov (United States)

    Zhang, Wei-Hong; Xue, Peng; Yao, Meng-Ying; Chang, Hai-Min; Wu, Yan; Zhang, Lei

    2013-01-01

    The present study aimed to estimate the up-to-date prevalence of metabolic syndrome and its relationship with physical activity among suburban adults in Beijing, China. A cross-sectional survey in a representative sample of 19,003 suburban adults aged 18-76 years was carried out in 2007-2008. Data was collected via questionnaires and blood pressure, anthropometric, and laboratory measurements. Of the residents aged 18-76 years in suburban Beijing, 25.9% (27.3% in men and 25.1% in women), 21.3% (19.4% in men and 22.9% in women), and 25.3% (24.2% in men and 26.1% in women) had 1 component, 2 components, and 3 or more components of metabolic syndrome, respectively. The age-standardized prevalence of metabolic syndrome and its components, including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting plasma glucose, decreased across categories with increasing physical activity. After adjusting for age, sex, education level, smoking, and alcohol consumption, residents were more likely to have metabolic syndrome across categories with decreasing physical activity; a similar relationship also applied to components of metabolic syndrome. A high prevalence of metabolic syndrome and its components is commonly present in suburban Beijing. Increasing physical activity can reduce the relative risk of metabolic syndrome and it components.

  6. In Vitro Effects of Sports and Energy Drinks on Streptococcus mutans Biofilm Formation and Metabolic Activity.

    Science.gov (United States)

    Vinson, LaQuia A; Goodlett, Amy K; Huang, Ruijie; Eckert, George J; Gregory, Richard L

    2017-09-15

    Sports and energy drinks are being increasingly consumed and contain large amounts of sugars, which are known to increase Streptococcus mutans biofilm formation and metabolic activity. The purpose of this in vitro study was to investigate the effects of sports and energy drinks on S. mutans biofilm formation and metabolic activity. S. mutans UA159 was cultured with and without a dilution (1:3 ratio) of a variety of sports and energy drinks in bacterial media for 24 hours. The biofilm was washed, fixed, and stained. Biofilm growth was evaluated by reading absorbance of the crystal violet. Biofilm metabolic activity was measured by the biofilm-reducing XTT to a water-soluble orange compound. Gatorade Protein Recovery Shake and Starbucks Doubleshot Espresso Energy were found to significantly increase biofilm (30-fold and 22-fold, respectively) and metabolic activity (2-fold and 3-fold, respectively). However, most of the remaining drinks significantly inhibited biofilm growth and metabolic activity. Several sports and energy drinks, with sugars or sugar substitutes as their main ingredients inhibited S. mutans biofilm formation. Among the drinks evaluated, Gatorade Protein Recovery Chocolate Shake and Starbucks Doubleshot Energy appear to have cariogenic potential since they increased the biofilm formation and metabolic activity of S. mutans.

  7. 3D Filament Network Segmentation with Multiple Active Contours

    Science.gov (United States)

    Xu, Ting; Vavylonis, Dimitrios; Huang, Xiaolei

    2014-03-01

    Fluorescence microscopy is frequently used to study two and three dimensional network structures formed by cytoskeletal polymer fibers such as actin filaments and microtubules. While these cytoskeletal structures are often dilute enough to allow imaging of individual filaments or bundles of them, quantitative analysis of these images is challenging. To facilitate quantitative, reproducible and objective analysis of the image data, we developed a semi-automated method to extract actin networks and retrieve their topology in 3D. Our method uses multiple Stretching Open Active Contours (SOACs) that are automatically initialized at image intensity ridges and then evolve along the centerlines of filaments in the network. SOACs can merge, stop at junctions, and reconfigure with others to allow smooth crossing at junctions of filaments. The proposed approach is generally applicable to images of curvilinear networks with low SNR. We demonstrate its potential by extracting the centerlines of synthetic meshwork images, actin networks in 2D TIRF Microscopy images, and 3D actin cable meshworks of live fission yeast cells imaged by spinning disk confocal microscopy.

  8. L-Arginine improves multiple physiological parameters in mice exposed to diet-induced metabolic disturbances

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Madsen, Andreas Nygaard; Smajilovic, Sanela

    2012-01-01

    L: -Arginine (L: -Arg) is a conditionally essential amino acid and a natural constituent of dietary proteins. Studies in obese rats and type 2 diabetic humans have indicated that dietary supplementation with L: -Arg can diminish gain in white adipose tissue (WAT) and improve insulin sensitivity....... However, the effects of L: -Arg on glucose homeostasis, body composition and energy metabolism remain unclear. In addition, no studies have, to our knowledge, examined whether L: -Arg has beneficial effects as a dietary supplement in the mouse model. In the present study, we investigated the effects of L...... groups. Glucose homeostasis experiments revealed a major effect of L: -Arg supplementation on glucose tolerance and insulin sensitivity, interestingly, independent of a parallel regulation in whole-body adiposity. Increased L: -Arg ingestion also raised energy expenditure; however, no concurrent effect...

  9. Designed multiple ligands in metabolic disease research: from concept to platform.

    Science.gov (United States)

    Gattrell, W; Johnstone, C; Patel, S; Smith, C Sambrook; Scheel, A; Schindler, M

    2013-08-01

    Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and drug monotherapy typically results in unsatisfactory treatment outcomes for patients. Even when used in combination, existing therapies lack efficacy in the long term. Designed multiple ligands (DMLs) are compounds developed to modulate multiple targets relevant to a disease. DMLs offer the potential to yield greater efficacy over monotherapies, either by modulating different biological pathways, or by boosting a single one. However, examples of DMLs progressing into clinical trials, or onto the market are rare; DML drug discovery is challenging, and perceived by some to be almost impossible. Nevertheless, with the judicious selection of biological targets, both from a biological and chemical perspective, it is possible to develop drug-like DMLs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Metabolic stress responses in Drosophila are modulated by brain neurosecretory cells that produce multiple neuropeptides.

    Directory of Open Access Journals (Sweden)

    Lily Kahsai

    Full Text Available In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a: Drosophila tachykinin (DTK, short neuropeptide F (sNPF and ion transport peptide (ITP. These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells.

  11. Metabolic activity is necessary for activation of T suppressor cells by B cells

    International Nuclear Information System (INIS)

    Elkins, K.L.; Stashak, P.W.; Baker, P.J.

    1990-01-01

    Ag-primed B cells must express cell-surface IgM, but not IgD or Ia Ag, and must remain metabolically active, in order to activate suppressor T cells (Ts) specific for type III pneumococcal polysaccharide. Ag-primed B cells that were gamma-irradiated with 1000r, or less, retained the ability to activate Ts; however, Ag-primed B cells exposed to UV light were not able to do so. gamma-Irradiated and UV-treated Ag-primed B cells both expressed comparable levels of cell-surface IgM, and both localized to the spleen after in vivo transfer; neither could proliferate in vitro in response to mitogens. By contrast, gamma-irradiated primed B cells were still able to synthesize proteins, whereas UV-treated primed B cells could not. These findings suggest that in order for Ag-primed B cells to activate Ts, they must (a) express cell-associated IgM (sIgM) antibody bearing the idiotypic determinants of antibody specific for type III pneumococcal polysaccharide, and (b) be able to synthesize protein for either the continued expression of sIgM after cell transfer, or for the elaboration of another protein molecule that is also required for the activation of Ts; this molecule does not appear to be Ia Ag

  12. CD4 T cell activation and disease activity at onset of multiple sclerosis

    DEFF Research Database (Denmark)

    Jensen, J; Langkilde, Annika Reynberg; Fenst, C

    2004-01-01

    We studied CD4 T cell activation in patients with clinically isolated syndromes (CIS) suggesting an initial attack of multiple sclerosis. The percentage of blood CD26+ CD4 T cells was increased in these patients, and correlated with magnetic resonance imaging disease activity and clinical disease...... severity. In contrast, the percentage of CD25+ CD4 T cells in cerebrospinal fluid correlated negatively with the cerebrospinal fluid concentration of myelin basic protein and the presence of IgG oligoclonal bands. These results suggest that distinct systemic and intrathecal T cell activation states...

  13. Association of physical activity with metabolic syndrome in a predominantly rural Nigerian population

    DEFF Research Database (Denmark)

    Oguoma, Victor M.; Nwose, Ezekiel U.; Nwose, Ezekiel U.

    2016-01-01

    Aims Physical activity is an essential determinant of health. However, there is dearth of evidence regarding prevalence of physical activity in developing countries, especially its association with metabolic syndrome risk factors. This study assessed the association of physical activity with meta...

  14. Multiple Active Volcanoes in the Northeast Lau Basin

    Science.gov (United States)

    Baker, E. T.; Resing, J. A.; Lupton, J. E.; Walker, S. L.; Embley, R. W.; Rubin, K. H.; Buck, N.; de Ronde, C. E.; Arculus, R. J.

    2010-12-01

    The northeast Lau Basin occupies a complex geological area between the Tafua arc front, the E-W trending Tonga Trench, and the Northeast Lau Spreading Center. These boundaries create multiple zones of extension and thus provide abundant opportunities for magma to invade the crust. The 25-km-long chain of “Mata” volcanoes lies near the center of this area, separated from both the arc front and the spreading ridge. In 2008 we discovered hydrothermal venting on the largest and most southerly of these volcanoes, W and E Mata. In 2010 we visited the 7 smaller volcanoes that form a 15-km-long arcuate sweep to the north from W and E Mata (the “North Matas”). We also revisited W and E Mata. Over each volcano we conducted CTD tows to map plumes and collect water samples. Based on the CTD results, camera tows searched for seafloor sources on three volcanoes. The N Mata volcanoes, extending from Mata Taha (1) in the south to Mata Fitu (7) in the north, lie within a prominent gap in the shallow bathymetry along the southern border of the Tonga trench. Northward from E Mata the Mata volcanoes degrade from large symmetrical cones to smaller and blocky volcanic edifices. Summit depths range from 1165 m (W Mata) to 2670 m (Mata Nima (5)). The most active volcano in the chain is the erupting W Mata, with an intense plume that extended 250 m above the summit. Hydrothermal temperature anomalies (Δθ, corrected for hydrographic masking effects) reached ˜1.7°C, with light-scattering values as high as 2-5 ΔNTU. The 2010 surveys now show that 6 of the 7 N Mata volcanoes are also hydrothermally active. Along the N Matas, Δθ and ΔNTU signals ranged from robust to weak, but distinct oxidation-reduction potential (aka Eh) anomalies confirmed active venting in each case. The most concentrated plumes were found near Mata Ua (2) and Mata Fitu (7), with Δθ and ΔNTU maxima of 0.1-0.17°C and 0.3, respectively. Despite the variability in plume strength, however, ΔNTU/Δθ ratios

  15. Metabolic and environmental aspects of fusion reactor activation products: niobium

    International Nuclear Information System (INIS)

    Easterly, C.E.; Shank, K.E.

    1977-11-01

    A summary of the metabolic and environmental aspects of niobium is presented. The toxicological symptoms from exposure to niobium are given, along with lethal concentration values for acute and chronic exposures. Existing human data are presented; animal uptake and retention data are analyzed for various routes of administration. Recommended metabolic values are also presented along with comments concerning their use and appropriateness. The natural distribution of niobium is given for freshwater, seawater, and the biosphere. Concentration factors and retention of 95 Nb in the environment are discussed with reference to: plant retention via leaf absorption; plant retention via root uptake; uptake in terrestrial animals from plants; uptake in freshwater organisms; uptake in marine organisms; and movement in soil. Conclusions are drawn regarding needs for future work in these areas. This review was undertaken because niobium is expected to be a key metal in the development of commercial fusion reactors. It is recognized that niobium will likely not be used in the first generation reactors as a structural material but will appear as an alloy in such materials as superconducting wire

  16. Metabolic and environmental aspects of fusion reactor activation products: niobium

    Energy Technology Data Exchange (ETDEWEB)

    Easterly, C.E.; Shank, K.E.

    1977-11-01

    A summary of the metabolic and environmental aspects of niobium is presented. The toxicological symptoms from exposure to niobium are given, along with lethal concentration values for acute and chronic exposures. Existing human data are presented; animal uptake and retention data are analyzed for various routes of administration. Recommended metabolic values are also presented along with comments concerning their use and appropriateness. The natural distribution of niobium is given for freshwater, seawater, and the biosphere. Concentration factors and retention of /sup 95/Nb in the environment are discussed with reference to: plant retention via leaf absorption; plant retention via root uptake; uptake in terrestrial animals from plants; uptake in freshwater organisms; uptake in marine organisms; and movement in soil. Conclusions are drawn regarding needs for future work in these areas. This review was undertaken because niobium is expected to be a key metal in the development of commercial fusion reactors. It is recognized that niobium will likely not be used in the first generation reactors as a structural material but will appear as an alloy in such materials as superconducting wire.

  17. Influences of transplantation on metabolic bone diseases in dialysis patients. Measurement of bone density with multiple X-ray photodensitometry

    International Nuclear Information System (INIS)

    Hida, Miho

    1994-01-01

    Renal osteodystrophy is a grave complication in dialysis patients. In this study, we evaluated the effect of renal transplantation (Txp) on metabolic bone diseases in renal transplant recipients (RTR), by multiple scanning X-ray photodensitometry (MD/MS). In only about 10% of RTR, bone metabolism recovered following improvement of renal function 1-2 years after Txp. Most cases showed decreased ΣGS and μ' scores on the MD/MS 1-2 years after Txp. Then ΣGS and μ' gradually increased over a long period. In seven of ten RTR with long-term graft survival (10 years<), ΣGS and μ' scores were within normal limits and densitometry bone patterns were normal. In four of five cases that received ciclosporin and had undergone Txp more than five years before, densitometry bone patterns were normal. Treatment with high doses of steroids due to acute rejection caused a sharp decline of ΣGS and μ' scores. In FK506-medicated RTR, ΣGS and μ' scores 1-2 years after Txp were decreased. In a 21-year-old female patient who had undergone Txp as the age of 13-year-old, there was little bone growth and ΣGS and μ' scores were significantly decreased. (author)

  18. HIV protease inhibitors disrupt lipid metabolism by activating endoplasmic reticulum stress and inhibiting autophagy activity in adipocytes.

    Directory of Open Access Journals (Sweden)

    Beth S Zha

    Full Text Available HIV protease inhibitors (PI are core components of Highly Active Antiretroviral Therapy (HAART, the most effective treatment for HIV infection currently available. However, HIV PIs have now been linked to lipodystrophy and dyslipidemia, which are major risk factors for cardiovascular disease and metabolic syndrome. Our previous studies have shown that HIV PIs activate endoplasmic reticulum (ER stress and disrupt lipid metabolism in hepatocytes and macrophages. Yet, little is known on how HIV PIs disrupt lipid metabolism in adipocytes, a major cell type involved in the pathogenesis of metabolic syndrome.Cultured and primary mouse adipocytes and human adipocytes were used to examine the effect of frequently used HIV PIs in the clinic, lopinavir/ritonavir, on adipocyte differentiation and further identify the underlying molecular mechanism of HIV PI-induced dysregulation of lipid metabolism in adipocytes. The results indicated that lopinavir alone or in combination with ritonavir, significantly activated the ER stress response, inhibited cell differentiation, and induced cell apoptosis in adipocytes. In addition, HIV PI-induced ER stress was closely linked to inhibition of autophagy activity. We also identified through the use of primary adipocytes of CHOP(-/- mice that CHOP, the major transcriptional factor of the ER stress signaling pathway, is involved in lopinavir/ritonavir-induced inhibition of cell differentiation in adipocytes. In addition, lopinavir/ritonavir-induced ER stress appears to be associated with inhibition of autophagy activity in adipocytes.Activation of ER stress and impairment of autophagy activity are involved in HIV PI-induced dysregulation of lipid metabolism in adipocytes. The key components of ER stress and autophagy signaling pathways are potential therapeutic targets for HIV PI-induced metabolic side effects in HIV patients.

  19. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations

    Directory of Open Access Journals (Sweden)

    Yusuke Nakatsu

    2016-09-01

    Full Text Available Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14. Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer’s disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.

  20. Physical activity and exercise priorities in community dwelling people with multiple sclerosis: a Delphi study.

    Science.gov (United States)

    Stennett, Andrea; De Souza, Lorraine; Norris, Meriel

    2018-07-01

    Exercise and physical activity have been found to be beneficial in managing disabilities caused by multiple sclerosis. Despite the known benefits, many people with multiple sclerosis are inactive. This study aimed to identify the prioritised exercise and physical activity practices of people with multiple sclerosis living in the community and the reasons why they are engaged in these activities. A four Round Delphi questionnaire scoped and determined consensus of priorities for the top 10 exercise and physical activities and the reasons why people with multiple sclerosis (n = 101) are engaged in these activities. Data were analysed using content analysis, descriptive statistics, and non-parametric tests. The top 10 exercise and physical activity practices and the top 10 reasons why people with multiple sclerosis (n = 70) engaged in these activities were identified and prioritised. Consensus was achieved for the exercise and physical activities (W = 0.744, p multiple sclerosis engaged in exercise and physical activity were diverse. These self-selected activities and reasons highlighted that people with multiple sclerosis might conceptualise exercise and physical activity in ways that may not be fully appreciated or understood by health professionals. Considerations of the views of people with multiple sclerosis may be essential if the goal of increasing physical activity in this population is to be achieved. Implications for Rehabilitation Health professionals should work collaboratively with people with multiple sclerosis to understand how they prioritise activities, the underlying reasons for their prioritisations and embed these into rehabilitation programmes. Health professionals should utilise activities prioritised by people with multiple sclerosis in the community as a way to support, promote, and sustain exercise and physical activity in this population. Rehabilitation interventions should include both the activities people with multiple

  1. Nonlinear Dielectric Spectroscopy as an Indirect Probe of Metabolic Activity in Thylakoid Membrane

    Directory of Open Access Journals (Sweden)

    John H. Miller

    2011-01-01

    Full Text Available Nonlinear dielectric spectroscopy (NDS is a non-invasive probe of cellular metabolic activity with potential application in the development of whole-cell biosensors. However, the mechanism of NDS interaction with metabolic membrane proteins is poorly understood, partly due to the inherent complexity of single cell organisms. Here we use the light-activated electron transport chain of spinach thylakoid membrane as a model system to study how NDS interacts with metabolic activity. We find protein modification, as opposed to membrane pump activity, to be the dominant source of NDS signal change in this system. Potential mechanisms for such protein modifications include reactive oxygen species generation and light-activated phosphorylation.

  2. Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate

    DEFF Research Database (Denmark)

    Green, C J; Bunprajun, T; Pedersen, B K

    2013-01-01

    in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance......  The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture...... and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism...

  3. Effect of CAR activation on selected metabolic pathways in normal and hyperlipidemic mouse livers.

    Science.gov (United States)

    Rezen, Tadeja; Tamasi, Viola; Lövgren-Sandblom, Anita; Björkhem, Ingemar; Meyer, Urs A; Rozman, Damjana

    2009-08-19

    Detoxification in the liver involves activation of nuclear receptors, such as the constitutive androstane receptor (CAR), which regulate downstream genes of xenobiotic metabolism. Frequently, the metabolism of endobiotics is also modulated, resulting in potentially harmful effects. We therefore used 1,4-Bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) to study the effect of CAR activation on mouse hepatic transcriptome and lipid metabolome under conditions of diet-induced hyperlipidemia. Using gene expression profiling with a dedicated microarray, we show that xenobiotic metabolism, PPARalpha and adipocytokine signaling, and steroid synthesis are the pathways most affected by TCPOBOP in normal and hyperlipidemic mice. TCPOBOP-induced CAR activation prevented the increased hepatic and serum cholesterol caused by feeding mice a diet containing 1% cholesterol. We show that this is due to increased bile acid metabolism and up-regulated removal of LDL, even though TCPOBOP increased cholesterol synthesis under conditions of hyperlipidemia. Up-regulation of cholesterol synthesis was not accompanied by an increase in mature SREBP2 protein. As determined by studies in CAR -/- mice, up-regulation of cholesterol synthesis is however CAR-dependent; and no obvious CAR binding sites were detected in promoters of cholesterogenic genes. TCPOBOP also affected serum glucose and triglyceride levels and other metabolic processes in the liver, irrespective of the diet. Our data show that CAR activation modulates hepatic metabolism by lowering cholesterol and glucose levels, through effects on PPARalpha and adiponectin signaling pathways, and by compromising liver adaptations to hyperlipidemia.

  4. The influence of physical activity on components of metabolic ...

    African Journals Online (AJOL)

    African Journal for Physical Activity and Health Sciences ... Inactivity causes obesity which is related to insulin resistance, hypertension, diabetes mellitus, ... of physical activity (PA) on the MS components and vascular function in children and ...

  5. Blocking hexose entry into glycolysis activates alternative metabolic conversion of these sugars and upregulates pentose metabolism in Aspergillus nidulans

    Energy Technology Data Exchange (ETDEWEB)

    Khosravi, Claire; Battaglia, Evy; Kun, Roland S.; Dalhuijsen, Sacha; Visser, Jaap; Aguilar-Pontes, Maria V.; Zhou, Miamiao; Heyman, Heino M.; Kim, Young-Mo; Baker, Scott E.; de Vries, Ronald P.

    2018-03-22

    Background: Plant biomass is the most abundant carbon source for many fungal species. In the biobased industry fungi are used to produce lignocellulolytic enzymes to degrade agricultural waste biomass. Here we evaluated if it would be possible to create an Aspergillus nidulans strain that releases but does not metabolize hexoses from plant biomass. For this purpose, metabolic mutants were generated that were impaired in glycolysis, by using hexokinase (hxkA) and glucokinase (glkA) negative strains. To prevent repression of enzyme production due to the hexose accumulation, strains were generated that combined these mutations with a deletion in creA, the repressor involved in regulating preferential use of different carbon catabolic pathways. Results: Phenotypic analysis revealed reduced growth for the hxkA1 glkA4 mutant on wheat bran. However, hexoses did not accumulate during growth of the mutants on wheat bran, suggesting that glucose metabolism is re-routed towards alternative carbon catabolic pathways. The creAΔ4 mutation in combination with preventing initial phosphorylation in glycolysis resulted in better growth than the hxkA/glkA mutant and an increased expression of pentose catabolic and pentose phosphate pathway genes. This indicates that the reduced ability to use hexoses as carbon sources created a shift towards the pentose fraction of wheat bran as a major carbon source to support growth. Conclusion: Blocking the direct entry of hexoses to glycolysis activates alternative metabolic conversion of these sugars in A. nidulans during growth on plant biomass, but also upregulates conversion of other sugars, such as pentoses.

  6. Metabolic Syndrome Remodels Electrical Activity of the Sinoatrial Node and Produces Arrhythmias in Rats

    Science.gov (United States)

    Albarado-Ibañez, Alondra; Avelino-Cruz, José Everardo; Velasco, Myrian; Torres-Jácome, Julián; Hiriart, Marcia

    2013-01-01

    In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of “metabolic syndrome rats”, compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats. We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats. PMID:24250786

  7. Total physical activity volume, physical activity intensity, and metabolic syndrome: 1999-2004 National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Churilla, James R; Fitzhugh, Eugene C

    2012-02-01

    This study examined the association of total physical activity volume (TPAV) and physical activity (PA) from three domains [leisure-time physical activity (LTPA), domestic, transportation] with metabolic syndrome. We also investigated the relationship between LTPA intensity and metabolic syndrome risk. Sample included adults who participated in the 1999-2004 National Health and Nutrition Examination Survey. Physical activity measures were created for TPAV, LTPA, domestic PA, and transportational PA. For each, a six-level measure based upon no PA (level 1) and quintiles (levels 2-6) of metabolic equivalents (MET)·min·wk(-1) was created. A three-level variable associated with the current Department of Health and Human Services (DHHS) PA recommendation was also created. SAS and SUDAAN were used for the statistical analysis. Adults reporting the greatest volume of TPAV and LTPA were found to be 36% [odds ratio (OR) 0.64; 95% confidence interval (CI) 0.49-0.83] and 42% (OR 0.58; 95% CI 0.43-0.77), respectively, less likely to have metabolic syndrome. Domestic and transportational PA provided no specific level of protection from metabolic syndrome. Those reporting a TPAV that met the DHHS PA recommendation were found to be 33% (OR 0.67; 95%; CI 0.55-0.83) less likely to have metabolic syndrome compared to their sedentary counterparts. Adults reporting engaging in only vigorous-intensity LTPA were found to be 37% (OR 0.63; 95 CI 0.42-0.96) to 56% (OR 0.44; 95% CI 0.29-0.67) less likely to have metabolic syndrome. Volume, intensity, and domain of PA may all play important roles in reducing the prevalence and risk of metabolic syndrome.

  8. A Metabolic Biofuel Cell: Conversion of Human Leukocyte Metabolic Activity to Electrical Currents

    Directory of Open Access Journals (Sweden)

    Cui X Tracy

    2011-05-01

    Full Text Available Abstract An investigation of the electrochemical activity of human white blood cells (WBC for biofuel cell (BFC applications is described. WBCs isolated from whole human blood were suspended in PBS and introduced into the anode compartment of a proton exchange membrane (PEM fuel cell. The cathode compartment contained a 50 mM potassium ferricyanide solution. Average current densities between 0.9 and 1.6 μA cm-2 and open circuit potentials (Voc between 83 and 102 mV were obtained, which were both higher than control values. Cyclic voltammetry was used to investigate the electrochemical activity of the activated WBCs in an attempt to elucidate the mechanism of electron transfer between the cells and electrode. Voltammograms were obtained for the WBCs, including peripheral blood mononuclear cells (PBMCs - a lymphocyte-monocyte mixture isolated on a Ficoll gradient, a B lymphoblastoid cell line (BLCL, and two leukemia cell lines, namely K562 and Jurkat. An oxidation peak at about 363 mV vs. SCE for the PMA (phorbol ester activated primary cells, with a notable absence of a reduction peak was observed. Oxidation peaks were not observed for the BLCL, K562 or Jurkat cell lines. HPLC confirmed the release of serotonin (5-HT from the PMA activated primary cells. It is believed that serotonin, among other biochemical species released by the activated cells, contributes to the observed BFC currents.

  9. Metaproteomics: extracting and mining proteome information to characterize metabolic activities in microbial communities.

    Science.gov (United States)

    Abraham, Paul E; Giannone, Richard J; Xiong, Weili; Hettich, Robert L

    2014-06-17

    Contemporary microbial ecology studies usually employ one or more "omics" approaches to investigate the structure and function of microbial communities. Among these, metaproteomics aims to characterize the metabolic activities of the microbial membership, providing a direct link between the genetic potential and functional metabolism. The successful deployment of metaproteomics research depends on the integration of high-quality experimental and bioinformatic techniques for uncovering the metabolic activities of a microbial community in a way that is complementary to other "meta-omic" approaches. The essential, quality-defining informatics steps in metaproteomics investigations are: (1) construction of the metagenome, (2) functional annotation of predicted protein-coding genes, (3) protein database searching, (4) protein inference, and (5) extraction of metabolic information. In this article, we provide an overview of current bioinformatic approaches and software implementations in metaproteome studies in order to highlight the key considerations needed for successful implementation of this powerful community-biology tool. Copyright © 2014 John Wiley & Sons, Inc.

  10. Metabolic activity in dormant conidia of Aspergillus niger and developmental changes during conidial outgrowth

    OpenAIRE

    Novodvorska, Michaela; Stratford, Malcolm; Blythe, Martin J.; Wilson, Raymond; Beniston, Richard G.; Archer, David B.

    2016-01-01

    The early stages of development of Aspergillus niger conidia during outgrowth were explored by combining genome-wide gene expression analysis (RNAseq), proteomics, Warburg manometry and uptake studies. Resting conidia suspended in water were demonstrated for the first time to be metabolically active as low levels of oxygen uptake and the generation of carbon dioxide were detected, suggesting that low-level respiratory metabolism occurs in conidia for maintenance. Upon triggering of spore germ...

  11. Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children: The ABCD Study.

    Directory of Open Access Journals (Sweden)

    Tanja G M Vrijkotte

    Full Text Available In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5-6 years.Cross-sectional data from an apparently healthy population (within the ABCD study were collected at age 5-6 years in 1540 children. Heart rate (HR, respiratory sinus arrhythmia (RSA; parasympathetic activity and pre-ejection period (PEP; sympathetic activity were assessed during rest. Metabolic components were waist-height ratio (WHtR, systolic blood pressure (SBP, fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed.In analysis adjusted for child's physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01, higher SBP (p<0.001 and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01. Lower PEP was only associated with higher SBP (p <0.05. Of all children, 5.6% had 3 or more (out of 5 adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001.This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5-6 years.

  12. Effects of disease duration on the clinical features and brain glucose metabolism in patients with mixed type multiple system atrophy.

    Science.gov (United States)

    Lyoo, C H; Jeong, Y; Ryu, Y H; Lee, S Y; Song, T J; Lee, J H; Rinne, J O; Lee, M S

    2008-02-01

    To study the effect of disease duration on the clinical, neuropsychological and [(18)F]-deoxyglucose (FDG) PET findings in patients with mixed type multiple system atrophy (MSA), this study included 16 controls and 37 mixed-type MSA patients with a shorter than a 3-year history of cerebellar or parkinsonian symptoms. We classified the patients into three groups according to the duration of parkinsonian or cerebellar symptoms (Group I = battery. We compared the FDG PET findings of each group of patients with controls. Group I patients frequently had memory and frontal executive dysfunction. They showed hypometabolism in the frontal cortex, anterior cerebellar hemisphere and vermis. They had parkinsonian motor deficits, but no basal ganglia hypometabolism. Group II and III patients frequently had multiple domain cognitive impairments, and showed hypometabolism in the frontal and parieto-temporal cortices. Hypometabolism of the bilateral caudate and the left posterolateral putamen was observed in Group II, and whole striatum in Group III. In summary, the cortical hypometabolism begins in the frontal cortex and spreads to the parieto-temporal cortex in MSA. This spreading pattern coincides with the progressive cognitive decline. Early caudate hypometabolism may also contribute to the cognitive impairment. Parkinsonian motor deficits precede putaminal hypometabolism that begins in its posterolateral part. Cerebellar hypometabolism occurs early in the clinical courses and seems to be a relevant metabolic descriptor of cerebellar deficits.

  13. METABOLIC SYNDROME AND PHYSICAL ACTIVITY IN CHILEAN IMMIGRANTS LIVING IN RIO GALLEGOS, SANTA CRUZ, ARGENTINA.

    Directory of Open Access Journals (Sweden)

    Inger Sally Padilla

    2012-12-01

    Full Text Available To study the frequency of metabolic syndrome, its components and its relationship with physical activity in Chilean immigrants living in Río Gallegos, Santa Cruz, Argentina.314 Chilean immigrants (165 women and 149 men were interviewed in Rio Gallegos in 2010, with healthy status in medical records (2000. Anthropometry, blood pressure control, blood test to measure glucose, triglycerides and HDL cholesterol were determined. Metabolic syndrome was established by criteria of the NCEPATPIII.The metabolic syndrome had an overall prevalence of 28.9% (95%CI: 23.9 to 34. Metabolic syndrome prevalence was larger in women (32.1% than in men (25.5%. The prevalence of its components were: abdominal obesity 56%, low levels of HDL cholesterol 48.3%, high levels of triglycerides 68.1%, hypertension 46.1% and high levels of glucose 72.5%. Inadequate physical activity was 66.2% (95%CI: 60.1 to 71.5. Immigrants had more likelihood of metabolic syndrome living in Río Gallegos for 15 years or more(β: 5.74,95%CI:2,81-11,73, p=0.000 and with inadequate physical activity (β: 3.36, 95%CI: 1.57to7.21,p=0.002. The prevalence of metabolic syndrome in Chilean immigrants living in Río Gallegos is higher than that reported in Argentina and Chile

  14. Effect of Carbon Monoxide on Active Oxygen Metabolism of Postharvest Jujube

    OpenAIRE

    Shaoying Zhang; Qin Li; Yulan Mao

    2014-01-01

    To prolong the shelf life postharvest jujube, the effect of carbon monoxide (CO) on senescence of postharvest jujube in relation to active oxygen metabolism was investigated. Jujubes were fumigated with CO gas at 5, 10, 20 or 40μmol/L for 1 h, and then stored for 30 days at room temperature. Changes in membrane permeability, malonaldehyde (MDA), H2O2, O2•− content, and activities of active oxygen metabolism associated enzymes including superoxide dismutase (SOD), catalase (CAT) and peroxidase...

  15. Differential CT Attenuation of Metabolically Active and Inactive Adipose Tissues — Preliminary Findings

    Science.gov (United States)

    Hu, Houchun H.; Chung, Sandra A.; Nayak, Krishna S.; Jackson, Hollie A.; Gilsanz, Vicente

    2010-01-01

    This study investigates differences in CT Hounsfield units (HUs) between metabolically active (brown fat) and inactive adipose tissues (white fat) due to variations in their densities. PET/CT data from 101 pediatric and adolescent patients were analyzed. Regions of metabolically active and inactive adipose tissues were identified and standard uptake values (SUVs) and HUs were measured. HUs of active brown fat were more positive (p<0.001) than inactive fat (−62.4±5.3 versus −86.7±7.0) and the difference was observed in both males and females. PMID:21245691

  16. Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR

    Directory of Open Access Journals (Sweden)

    Kavita Jadhav

    2018-03-01

    Full Text Available Objectives: Activation of the bile acid (BA receptors farnesoid X receptor (FXR or G protein-coupled bile acid receptor (GPBAR1; TGR5 improves metabolic homeostasis. In this study, we aim to determine the impact of pharmacological activation of bile acid receptors by INT-767 on reversal of diet-induced metabolic disorders, and the relative contribution of FXR vs. TGR5 to INT-767's effects on metabolic parameters. Methods: Wild-type (WT, Tgr5−/−, Fxr−/−, Apoe−/− and Shp−/− mice were used to investigate whether and how BA receptor activation by INT-767, a semisynthetic agonist for both FXR and TGR5, could reverse diet-induced metabolic disorders. Results: INT-767 reversed HFD-induced obesity dependent on activation of both TGR5 and FXR and also reversed the development of atherosclerosis and non-alcoholic fatty liver disease (NAFLD. Mechanistically, INT-767 improved hypercholesterolemia by activation of FXR and induced thermogenic genes via activation of TGR5 and/or FXR. Furthermore, INT-767 inhibited several lipogenic genes and de novo lipogenesis in the liver via activation of FXR. We identified peroxisome proliferation-activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (CEBPα as novel FXR-regulated genes. FXR inhibited PPARγ expression by inducing small heterodimer partner (SHP whereas the inhibition of CEBPα by FXR was SHP-independent. Conclusions: BA receptor activation can reverse obesity, NAFLD, and atherosclerosis by specific activation of FXR or TGR5. Our data suggest that, compared to activation of FXR or TGR5 only, dual activation of both FXR and TGR5 is a more attractive strategy for treatment of common metabolic disorders. Keywords: Farnesoid X receptor, TGR5, Atherosclerosis, Obesity, NAFLD

  17. Multiple-source multiple-harmonic active vibration control of variable section cylindrical structures: A numerical study

    Science.gov (United States)

    Liu, Jinxin; Chen, Xuefeng; Gao, Jiawei; Zhang, Xingwu

    2016-12-01

    Air vehicles, space vehicles and underwater vehicles, the cabins of which can be viewed as variable section cylindrical structures, have multiple rotational vibration sources (e.g., engines, propellers, compressors and motors), making the spectrum of noise multiple-harmonic. The suppression of such noise has been a focus of interests in the field of active vibration control (AVC). In this paper, a multiple-source multiple-harmonic (MSMH) active vibration suppression algorithm with feed-forward structure is proposed based on reference amplitude rectification and conjugate gradient method (CGM). An AVC simulation scheme called finite element model in-loop simulation (FEMILS) is also proposed for rapid algorithm verification. Numerical studies of AVC are conducted on a variable section cylindrical structure based on the proposed MSMH algorithm and FEMILS scheme. It can be seen from the numerical studies that: (1) the proposed MSMH algorithm can individually suppress each component of the multiple-harmonic noise with an unified and improved convergence rate; (2) the FEMILS scheme is convenient and straightforward for multiple-source simulations with an acceptable loop time. Moreover, the simulations have similar procedure to real-life control and can be easily extended to physical model platform.

  18. Metabolic in Vivo Labeling Highlights Differences of Metabolically Active Microbes from the Mucosal Gastrointestinal Microbiome between High-Fat and Normal Chow Diet

    NARCIS (Netherlands)

    Oberbach, Andreas; Haange, Sven Bastiaan; Schlichting, Nadine; Heinrich, Marco; Lehmann, Stefanie; Till, Holger; Hugenholtz, Floor; Kullnick, Yvonne; Smidt, Hauke; Frank, Karin; Seifert, Jana; Jehmlich, Nico; Bergen, Von Martin

    2017-01-01

    The gastrointestinal microbiota in the gut interacts metabolically and immunologically with the host tissue in the contact zone of the mucus layer. For understanding the details of these interactions and especially their dynamics it is crucial to identify the metabolically active subset of the

  19. Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism

    International Nuclear Information System (INIS)

    Umezu, K.; Sugawara, N.; Chen, C.; Haber, J.E.; Kolodner, R.D.

    1998-01-01

    Replication protein A (RPA) is a single-stranded DNA-binding protein identified as an essential factor for SV40 DNA replication in vitro. To understand the in vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS-sensitive mutants showed up to 10 4 to 10 5 times increased sensitivity to these agents. Some of the UV- and MMSsensitive mutants were killed by an HO-induced double-strand break atMAT. Physical analysis of recombination in one UV- and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type switching and single-strand annealing recombination. Two temperature-sensitive mutants were characterized in detail, and at the restrictive temperature were found to have an arrest phenotype and DNA content indicative of incomplete DNA replication. DNA sequence analysis indicated that most of the mutations altered amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken together, we conclude that RPA1 has multiple roles in vivo and functions in DNA replication, repair, and recombination, like the single-stranded DNA-binding proteins of bacteria and phages. (author)

  20. Relationship between metabolism and ovarian activity in dairy cows with different dry period lengths

    NARCIS (Netherlands)

    Chen, J.C.; Soede, N.M.; Dorland, van H.A.; Remmelink, G.J.; Bruckmaier, R.M.; Kemp, B.; Knegsel, van A.T.M.

    2015-01-01

    The objectives of the present study were to evaluate the effects of dry period length on ovarian activity in cows fed a lipogenic or a glucogenic diet within 100 days in milk (DIM) and to determine relationships between ovarian activity and energy balance and metabolic status in early lactation.

  1. Effectiveness of physical activity intervention among government employees with metabolic syndrome.

    Science.gov (United States)

    Huei Phing, Chee; Abu Saad, Hazizi; Barakatun Nisak, M Y; Mohd Nasir, M T

    2017-12-01

    Our study aimed to assess the effects of physical activity interventions via standing banners (point-of-decision prompt) and aerobics classes to promote physical activity among individuals with metabolic syndrome. We conducted a cluster randomized controlled intervention trial (16-week intervention and 8-week follow-up). Malaysian government employees in Putrajaya, Malaysia, with metabolic syndrome were randomly assigned by cluster to a point-of-decision prompt group (n = 44), an aerobics group (n = 42) or a control group (n = 103) based on sample size calculation formula. Step counts were evaluated by Lifecorder e-STEP accelerometers for all participants. Metabolic syndrome was defined according to the 'harmonizing' definition, in which individuals who have at least three of the five metabolic risk factors (waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose levels, systolic and diastolic blood pressure) will be classified as having metabolic syndrome. A total of 80% of the enrolled government employees with metabolic syndrome completed the programme. Data were analyzed using SPSS for Windows (version 20, SPSS, Chicago, IL). There were significantly higher step counts on average in the aerobics group compared to the control group over assessments. Assessments at baseline, post-intervention and follow-up showed a significant difference in step counts between the intervention and control groups. The greatest reductions in the proportions of individuals with metabolic syndrome were observed in the aerobics group with a reduction of 79.4% in the post-intervention assessment compared to the assessment at baseline. The findings of this study suggest that physical activity intervention via aerobics classes is an effective strategy for improving step counts and reducing the prevalence of metabolic syndrome.

  2. Association of physical activity with metabolic syndrome in a predominantly rural Nigerian population.

    Science.gov (United States)

    Oguoma, Victor M; Nwose, Ezekiel U; Skinner, Timothy C; Richards, Ross S; Digban, Kester A; Onyia, Innocent C

    2016-01-01

    Physical activity is an essential determinant of health. However, there is dearth of evidence regarding prevalence of physical activity in developing countries, especially its association with metabolic syndrome risk factors. This study assessed the association of physical activity with metabolic syndrome in a Nigerian population. A cross-sectional study was carried out on apparently healthy persons who are ≥ 18 years old. The World Health Organisation (WHO) Global Physical Activity Questionnaire (GPAQ) was used to collect five domains of physical activity. Participants were classified as physically active or inactive based on meeting the cut-off value of 600 MET-min/week. Metabolic syndrome was diagnosed using the Joint Scientific Statement on Harmonizing the Metabolic Syndrome criteria. Overall prevalence of physically active individuals was 50.1% (CI: 45.6-54.7%). Physical inactivity is significantly more in females (p40 years old (pmetabolic syndrome appeared more likely to be physically active (OR=1.48, CI: 0.71-3.09); physical inactivity showed to exist more among participants who were living in urban area (OR=6.61, CI: 3.40-12.85, pmetabolic syndrome risk factors. The high prevalence of physical inactivity in this study population is a clear indication that concerted efforts to improve physical activity may be required. However, it seems that metabolic syndrome is not improved by being physically active. This suggests that interventions directed at physical activity alone may not produce optimal efficacy in this study population. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  3. Pedometer assessed physical activity of people with metabolic syndrome in Poland.

    Directory of Open Access Journals (Sweden)

    Anna Owlasiuk

    2014-06-01

    Full Text Available introduction. Metabolic syndrome is a contemporary disease of civilization, an effect of lack of healthy behaviour, a consequence of lifestyle devoid of physical activity, eating poor quality food rich in calories and excessive stress. Apart from a proper diet, physical activity remains an important part of metabolic syndrome management. objective. The main objective of the work was to evaluate the physical activity of an adult population of patients with metabolic syndrome. materials and method. Adults aged 35–70 fulfilling the criteria of metabolic syndrome according to International Diabetes Federation (IDF were included. New Lifestyles NL-2000 pedometers were used to assess locomotive physical activity during an entire week. results. In the group of 100 subjects, as many as 61 people (61% represented low or sedentary activity, while nearly one fourth of the respondents – 23 (32% represented the negligible activity type. Average weekly physical activity of those in the study was 6,743 steps/day (in 100 individuals and ranged from 1,781–15,169. A great diversity was found in the study group, since the highest number of steps per day was 23,347 and the lowest – 409. No significant differences in the number of steps on weekdays and at weekends were observed (mean: 6,676/day and 6,913/day, espectively. A statistically significant negative correlation (r = -0.29 was observed between age and physical activity, between the average daily number of steps in the week and Waist Hip Ratio (WHR (r = 0.201, as well as between the average daily number of steps in the week and Body Mass Index (BMI (r = 0.226. conclusions. The majority of people with metabolic syndrome represent a low or sedentary activity type and decrease of physical activity corresponds to increasing age, BMI and WHR. No significant differences in physical activity are observed between working days and free days (weekends.

  4. Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage.

    Science.gov (United States)

    Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong; Park, Jin Gyoon; Hussein, Samer Mi; Doh, Kyung-Oh; Hui, Chi-Chung; Sung, Hoon-Ki

    2017-11-01

    Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders.

  5. Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage

    Science.gov (United States)

    Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong; Park, Jin Gyoon; Hussein, Samer MI; Doh, Kyung-Oh; Hui, Chi-chung; Sung, Hoon-Ki

    2017-01-01

    Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vascular endothelial growth factor (VEGF) expression in white adipose tissue (WAT). Furthermore, periodic adipose-VEGF overexpression could recapitulate the metabolic improvement of IF in non-fasted animals. Importantly, fasting and adipose-VEGF induce alternative activation of adipose macrophage, which is critical for thermogenesis. Human adipose gene analysis further revealed a positive correlation of adipose VEGF-M2 macrophage-WAT browning axis. The present study uncovers the molecular mechanism of IF-mediated metabolic benefit and suggests that isocaloric IF can be a preventive and therapeutic approach against obesity and metabolic disorders. PMID:29039412

  6. Physical Activity Enhances Metabolic Fitness Independently of Cardiorespiratory Fitness in Marathon Runners

    Directory of Open Access Journals (Sweden)

    M. J. Laye

    2015-01-01

    Full Text Available High levels of cardiovascular fitness (CRF and physical activity (PA are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI. Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg (similar-VO2max. The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max. Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior in runners versus sedentary controls despite similar VO2max. Furthermore, performance (velocity at VO2max, running economy, improved exercise metabolism (lactate threshold, and skeletal muscle levels of mitochondrial proteins were superior in runners versus sedentary controls with similar VO2max. In conclusion subjects with a high amount of PA have more positive metabolic health parameters independent of CRF. PA is thus a good marker against metabolic diseases.

  7. Characterization of Carbohydrate Active Enzymes Involved in Arabinogalactan Protein Metabolism

    DEFF Research Database (Denmark)

    Knoch, Eva

    and tissues, their functions and synthesis are still poorly understood. The aim of the research presented in the thesis was to characterize carbohydrate active enzymes involved in AGP biosynthesis and modification to gain insights into the biosynthesis of the glycoproteins in plants. Candidate...... glycosyltransferases and glycoside hydrolases were selected based on co-expression profiles from a transcriptomics analysis. Reverse genetics approach on a novel glucuronosyltransferase involved in AGP biosynthesis has revealed that the enzyme activity is required for normal cell elongation in etiolated seedlings....... The enzymatic activity of a hydrolase from GH family 17 was investigated, without successful determination of the activity. Members of hydrolase family 43 appeared to be localized in the Golgi-apparatus, which is also the compartment for glycan biosynthesis. The localization of these glycoside hydrolases...

  8. Metabolic activity and mRNA levels of human cardiac CYP450s involved in drug metabolism.

    Directory of Open Access Journals (Sweden)

    Veronique Michaud

    2010-12-01

    Full Text Available Tissue-specific expression of CYP450s can regulate the intracellular concentration of drugs and explain inter-subject variability in drug action. The overall objective of our study was to determine in a large cohort of samples, mRNA levels and CYP450 activity expressed in the human heart.CYP450 mRNA levels were determined by RTPCR in left ventricular samples (n = 68 of explanted hearts from patients with end-stage heart failure. Samples were obtained from ischemic and non-ischemic hearts. In some instances (n = 7, samples were available from both the left and right ventricles. A technique for the preparation of microsomes from human heart tissue was developed and CYP450-dependent activity was determined using verapamil enantiomers as probe-drug substrates.Our results show that CYP2J2 mRNA was the most abundant isoform in all human heart left ventricular samples tested. Other CYP450 mRNAs of importance were CYP4A11, CYP2E1, CYP1A1 and CYP2C8 mRNAs while CYP2B6 and CYP2C9 mRNAs were present at low levels in only some of the hearts analyzed. CYP450 mRNAs did not differ between ischemic and non-ischemic hearts and appeared to be present at similar levels in the left and right ventricles. Incubation of verapamil with heart microsomes led to the formation of nine CYP450-dependent metabolites: a major finding was the observation that stereoselectivity was reversed compared to human liver microsomes, in which the R-enantiomer is metabolized to a greater extent.This study determined cardiac mRNA levels of various CYP450 isozymes involved in drug metabolism and demonstrated the prevalent expression of CYP2J2 mRNA. It revealed that cardiomyocytes can efficiently metabolize drugs and that cardiac CYP450s are highly relevant with regard to clearance of drugs in the heart. Our results support the claim that drug metabolism in the vicinity of a drug effector site can modulate drug effects.

  9. Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

    Science.gov (United States)

    LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

    2016-02-01

    The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

  10. Physical activity enhances metabolic fitness independently of cardiorespiratory fitness in marathon runners

    DEFF Research Database (Denmark)

    Laye, M J; Nielsen, M B; Hansen, L S

    2015-01-01

    High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consisten......High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run...... consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI). Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg) (similar-VO2max......). The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max). Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior...

  11. Adhesion molecules levels in blood correlate with MRI activity and clinical activity in multiple sclerosis

    International Nuclear Information System (INIS)

    Millers, A.; Enina, G.; Platkajis, A.; Metra, M.; Kukaine, R.

    2002-01-01

    Research into pathogenesis of multiple sclerosis (MS) has prompted efforts to identify immunological markers associated with disease activity. Adhesion molecules ICAM-1 and VCAM-1 are associated with inflammatory mediated blood-brain barrier (BBB) dysfunction. In this study investigates the correlation between blood level of circulating ICAM-1 and VCAM-1 and magnetic resonance imaging (MRI) activity in different clinical phases of patients with MS. We show that RRMS and SPMS patients in clinically active phase with Gd-enhancing lesions in CNS had higher blood levels of cICAM-1 and cVCAM-1 compared these parameters levers of RRMS patients in remission stage. These results suggest that cICAM-1 and cVCAM-1 is a sensitive indicator of disease activity associated with BBB inflammatory dysfunction. Elevated blood level of cICAM-1 more strongly correlated with clinical activity and BBB damage, than cVCAM-1 and that could be used as biological marker of disease activity. Circulating VCAM-1 as an early indicator of BBB disturbance, may also serve as marker of beneficial activity in relapses phase of MS course. (authors)

  12. Activation of endogenous neural stem cells for multiple sclerosis therapy

    NARCIS (Netherlands)

    Michailidou, I.; de Vries, H.E.; Hol, E.M.; van Strien, M.E.

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic

  13. Physical Activity and Sedentary Time Associations with Metabolic Health Across Weight Statuses in Children and Adolescents

    DEFF Research Database (Denmark)

    Kuzik, Nicholas; Carson, Valerie; Andersen, Lars Bo

    2017-01-01

    classification compared with metabolically healthy (MH) classification for the NW group. More MVPA was associated with lower odds of MU classification than MH classification for NW and overweight groups. For multinomial logistic regressions, more MVPA was associated with lower odds of MH-obesity classification......, as well as MU-NW, -overweight, and -obesity classifications, compared with the MH-NW group. Furthermore, more sedentary time was associated with higher odds of MU-NW classification compared with the MH-NW group. CONCLUSIONS: More MVPA was beneficial for metabolic health and weight status, whereas lower......OBJECTIVE: The aim of this study was to examine the prevalence of metabolic health across weight statuses and the associations of physical activity and sedentary time within and across metabolic health-weight status groups. METHODS: Six studies (n = 4,581) from the International Children...

  14. Multiple effects of circadian dysfunction induced by photoperiod shifts: alterations in context memory and food metabolism in the same subjects.

    Science.gov (United States)

    McDonald, Robert J; Zelinski, Erin L; Keeley, Robin J; Sutherland, Dylan; Fehr, Leah; Hong, Nancy S

    2013-06-13

    Humans exposed to shiftwork conditions have been reported to have increased susceptibility to various health problems including various forms of dementia, cancer, heart disease, and metabolic disorders related to obesity. The present experiments assessed the effects of circadian disruption on learning and memory function and various food related processes including diet consumption rates, food metabolism, and changes in body weight. These experiments utilized a novel variant of the conditioned place preference task (CPP) that is normally used to assess Pavlovian associative learning and memory processes produced via repeated context-reward pairings. For the present experiments, the standard CPP paradigm was modified in that both contexts were paired with food, but the dietary constituents of the food were different. In particular, we were interested in whether rats could differentiate between two types of carbohydrates, simple (dextrose) and complex (starch). Consumption rates for each type of carbohydrate were measured throughout training. A test of context preference without the food present was also conducted. At the end of behavioral testing, a fasting glucose test and a glucose challenge test were administered. Chronic photoperiod shifting resulted in impaired context learning and memory processes thought to be mediated by a neural circuit centered on the hippocampus. The results also showed that preferences for the different carbohydrate diets were altered in rats experiencing photoperiod shifting in that they maintained an initial preference for the simple carbohydrate throughout training. Lastly, photoperiod shifting resulted in changes in fasting blood glucose levels and elicited weight gain. These results show that chronic photoperiod shifting, which likely resulted in circadian dysfunction, impairs multiple functions of the brain and/or body in the same individual. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  15. Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure.

    Science.gov (United States)

    Bollmann, Marc-Daniel; Revelly, Jean-Pierre; Tappy, Luc; Berger, Mette M; Schaller, Marie-Denise; Cayeux, Marie-Christine; Martinez, Alexandre; Chioléro, René-Louis

    2004-06-01

    To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. Each patient received the two buffers in a randomized sequence over two consecutive days. The following variables were determined: acid-base parameters, lactate production and utilization ((13)C lactate infusion), glucose turnover (6,6(2)H(2)-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5 mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing (13)C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8+/-0.8 vs 7.5+/-0.8 ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0+/-2.6 vs 13.6+/-2.6 mmol/kg per min) were similar. (13)C lactate was used as a metabolic substrate, as shown by (13)CO(2) excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonate.

  16. 18F-FDG PET/CT in solitary plasmacytoma: metabolic behavior and progression to multiple myeloma

    Energy Technology Data Exchange (ETDEWEB)

    Albano, Domenico; Bosio, Giovanni [Spedali Civili di Brescia, Nuclear Medicine, Brescia (Italy); Treglia, Giorgio [Oncology Institute of Southern Switzerland, Department of Nuclear Medicine and PET/CT Center, Bellinzona (Switzerland); Giubbini, Raffaele; Bertagna, Francesco [University of Brescia and Spedali Civili Brescia, Nuclear Medicine, Brescia (Italy)

    2018-01-15

    Solitary plasmacytoma (SP) is a rare plasma-cell neoplasm, which can develop both in skeletal and/or soft tissue and frequently progresses to multiple myeloma (MM). Our aim was to study the metabolic behavior of SP and the role of 18F-FDG-PET/CT in predicting progression to MM. Sixty-two patients with SP who underwent 18F-FDG-PET/CT before any treatment were included. PET images were qualitatively and semiquantitatively analyzed by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and compared with age, sex, site of primary disease, and tumor size. Fifty-one patients had positive 18F-FDG-PET/CT (average SUVbw was 8.3 ± 4.7; SUVlbm 5.8 ± 2.6; SUVbsa 2 ± 1; MTV 45.4 ± 37; TLG 227 ± 114); the remaining 11 were not 18F-FDG-avid. Tumor size was significantly higher in patients avid lesions compared to FDG not avid; no other features are associated with FDG-avidity. Progression to MM occurred in 29 patients with an average of 18.3 months; MM was more likely to develop in patients with bone plasmacytoma and in patients with 18F-FDG avid lesion. Time to transformation in MM (TTMM) was significantly shorter in patients with osseous SP, in 18F-FDG avid lesion, for SUVlbm > 5.2 and SUVbsa > 1.7. 18F-FDG pathological uptake in SP occurred in most cases, being independently associated with tumor size. PET/CT seemed to be correlated to a higher risk of transformation in MM, in particular for 18F-FDG avid plasmacytoma and SBP. Among semiquantitative features, SUVlbm > 5.2 and SUVbsa > 1.7 were significantly correlated with TTMM. (orig.)

  17. Geraniol Pharmacokinetics, Bioavailability and Its Multiple Effects on the Liver Antioxidant and Xenobiotic-Metabolizing Enzymes

    Directory of Open Access Journals (Sweden)

    Barbara Pavan

    2018-01-01

    Full Text Available Geraniol is a natural monoterpene showing anti-inflammatory, antioxidant, neuroprotective and anticancer effects. No pharmacokinetic and bioavailability data on geraniol are currently available. We therefore performed a systematic study to identify the permeation properties of geraniol across intestinal cells, and its pharmacokinetics and bioavailability after intravenous and oral administration to rats. In addition, we systematically investigated the potential hepatotoxic effects of high doses of geraniol on hepatic phase I, phase II and antioxidant enzymatic activities and undertook a hematochemical analysis on mice. Permeation studies performed via HPLC evidenced geraniol permeability coefficients across an in vitro model of the human intestinal wall for apical to basolateral and basolateral to apical transport of 13.10 ± 2.3 × 10-3 and 2.1 ± 0.1⋅× 10-3 cm/min, respectively. After intravenous administration of geraniol to rats (50 mg/kg, its concentration in whole blood (detected via HPLC decreased following an apparent pseudo-first order kinetics with a half-life of 12.5 ± 1.5 min. The absolute bioavailability values of oral formulations (50 mg/kg of emulsified geraniol or fiber-adsorbed geraniol were 92 and 16%, respectively. Following emulsified oral administration, geraniol amounts in the cerebrospinal fluid of rats ranged between 0.72 ± 0.08 μg/mL and 2.6 ± 0.2 μg/mL within 60 min. Mice treated with 120 mg/kg of geraniol for 4 weeks showed increased anti-oxidative defenses with no signs of liver toxicity. CYP450 enzyme activities appeared only slightly affected by the high dosage of geraniol.

  18. Metabolic activation of amygdala, lateral septum and accumbens circuits during food anticipatory behavior.

    Science.gov (United States)

    Olivo, Diana; Caba, Mario; Gonzalez-Lima, Francisco; Rodríguez-Landa, Juan F; Corona-Morales, Aleph A

    2017-01-01

    When food is restricted to a brief fixed period every day, animals show an increase in temperature, corticosterone concentration and locomotor activity for 2-3h before feeding time, termed food anticipatory activity. Mechanisms and neuroanatomical circuits responsible for food anticipatory activity remain unclear, and may involve both oscillators and networks related to temporal conditioning. Rabbit pups are nursed once-a-day so they represent a natural model of circadian food anticipatory activity. Food anticipatory behavior in pups may be associated with neural circuits that temporally anticipate feeding, while the nursing event may produce consummatory effects. Therefore, we used New Zealand white rabbit pups entrained to circadian feeding to investigate the hypothesis that structures related to reward expectation and conditioned emotional responses would show a metabolic rhythm anticipatory of the nursing event, different from that shown by structures related to reward delivery. Quantitative cytochrome oxidase histochemistry was used to measure regional brain metabolic activity at eight different times during the day. We found that neural metabolism peaked before nursing, during food anticipatory behavior, in nuclei of the extended amygdala (basolateral, medial and central nuclei, bed nucleus of the stria terminalis), lateral septum and accumbens core. After pups were fed, however, maximal metabolic activity was expressed in the accumbens shell, caudate, putamen and cortical amygdala. Neural and behavioral activation persisted when animals were fasted by two cycles, at the time of expected nursing. These findings suggest that metabolic activation of amygdala-septal-accumbens circuits involved in temporal conditioning may contribute to food anticipatory activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Microbial catabolic activities are naturally selected by metabolic energy harvest rate.

    Science.gov (United States)

    González-Cabaleiro, Rebeca; Ofiţeru, Irina D; Lema, Juan M; Rodríguez, Jorge

    2015-12-01

    The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate.

  20. Physical activity, stress, and metabolic risk score in 8- to 18-year-old boys.

    Science.gov (United States)

    Holmes, Megan E; Eisenmann, Joey C; Ekkekakis, Panteleimon; Gentile, Douglas

    2008-03-01

    We examined whether physical activity modifies the relationship between stress and the metabolic risk score in 8- to 18-year-old males (n = 37). Physical activity (PA) and television (TV)/videogame (VG) use were assessed via accelerometer and questionnaire, respectively. Stress was determined from self-report measures. A metabolic risk score (MRS) was created by summing age-standardized residuals for waist circumference, mean arterial pressure, glycosylated hemoglobin, and high-density lipoprotein cholesterol. Correlations between PA and MRS were low (r adolescents.

  1. Compensation in resting metabolism for experimentally increased activity

    NARCIS (Netherlands)

    Deerenberg, C; Overkamp, GJF; Visser, GH; Daan, S; Heldmaier, G.

    1998-01-01

    To study zebra finch allocation of energy to day and night at two different workloads, we assessed the daily energy turnover from: (1) metabolizable energy of the food, and (2) doubly-labeled water. In both experiments we imposed two levels of activity on captive zebra finches (Taeniopygia guttata),

  2. Understanding Fatty Acid Metabolism through an Active Learning Approach

    Science.gov (United States)

    Fardilha, M.; Schrader, M.; da Cruz e Silva, O. A. B.; da Cruz e Silva, E. F.

    2010-01-01

    A multi-method active learning approach (MALA) was implemented in the Medical Biochemistry teaching unit of the Biomedical Sciences degree at the University of Aveiro, using problem-based learning as the main learning approach. In this type of learning strategy, students are involved beyond the mere exercise of being taught by listening. Less…

  3. Multiple layers of posttranslational regulation refine circadian clock activity in Arabidopsis.

    Science.gov (United States)

    Seo, Pil Joon; Mas, Paloma

    2014-01-01

    The circadian clock is a cellular time-keeper mechanism that regulates biological rhythms with a period of ~24 h. The circadian rhythms in metabolism, physiology, and development are synchronized by environmental cues such as light and temperature. In plants, proper matching of the internal circadian time with the external environment confers fitness advantages on plant survival and propagation. Accordingly, plants have evolved elaborated regulatory mechanisms that precisely control the circadian oscillations. Transcriptional feedback regulation of several clock components has been well characterized over the past years. However, the importance of additional regulatory mechanisms such as chromatin remodeling, protein complexes, protein phosphorylation, and stability is only starting to emerge. The multiple layers of circadian regulation enable plants to properly synchronize with the environmental cycles and to fine-tune the circadian oscillations. This review focuses on the diverse posttranslational events that regulate circadian clock function. We discuss the mechanistic insights explaining how plants articulate a high degree of complexity in their regulatory networks to maintain circadian homeostasis and to generate highly precise waveforms of circadian expression and activity.

  4. Metabolic Control of Dendritic Cell Activation and Function: Recent Advances and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Bart eEverts

    2014-05-01

    Full Text Available Dendritic cells (DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cell and regulatory T cell responses. Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. Over the past decade there is a growing appreciation that these metabolic changes also underlie the capacity of immune cells to perform particular functions. This has led to the concept that the manipulation of cellular metabolism can be used to shape innate and adaptive immune responses. While most of our understanding in this area has been gained from studies with T cells and macrophages, evidence is emerging that the activation and function of DCs are also dictated by the type of metabolism these cells commit to. We here discuss these new insights and explore whether targeting of metabolic pathways in DCs could hold promise as a novel approach to manipulate the functional properties of DCs for clinical purposes.

  5. Metabolic Features of Protochlamydia amoebophila Elementary Bodies – A Link between Activity and Infectivity in Chlamydiae

    Science.gov (United States)

    Watzka, Margarete; Wultsch, Anna; Tziotis, Dimitrios; Montanaro, Jacqueline; Richter, Andreas; Schmitt-Kopplin, Philippe; Horn, Matthias

    2013-01-01

    The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB), has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS), ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from 13C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA) cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila EBs and provide

  6. Metabolic features of Protochlamydia amoebophila elementary bodies--a link between activity and infectivity in Chlamydiae.

    Directory of Open Access Journals (Sweden)

    Barbara S Sixt

    Full Text Available The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB, has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS, ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS, and ultra-performance liquid chromatography mass spectrometry (UPLC-MS was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from (13C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila

  7. Multiple nucleophilic elbows leading to multiple active sites in a single module esterase from Sorangium cellulosum

    DEFF Research Database (Denmark)

    Udatha, D.B.R.K. Gupta; Madsen, Karina Marie; Panagiotou, Gianni

    2015-01-01

    The catalytic residues in carbohydrate esterase enzyme families constitute a highly conserved triad: serine, histidine and aspartic acid. This catalytic triad is generally located in a very sharp turn of the protein backbone structure, called the nucleophilic elbow and identified by the consensus...... sequence GXSXG. An esterase from Sorangium cellulosum Soce56 that contains five nucleophilic elbows was cloned and expressed in Escherichia coli and the function of each nucleophilic elbowed site was characterized. In order to elucidate the function of each nucleophilic elbow, site directed mutagenesis....... To our knowledge, this is the first report presenting the role of multiple nucleophilic elbows in the catalytic promiscuity of an esterase. Further structural analysis at protein unit level indicates the new evolutionary trajectories in emerging promiscuous esterases....

  8. Metabolic activity in striate and extrastriate cortex in the hooded rat: contralateral and ipsilateral eye input

    International Nuclear Information System (INIS)

    Thurlow, G.A.; Cooper, R.M.

    1988-01-01

    The extent of changes in glucose metabolism resulting from ipsilateral and contralateral eye activity in the posterior cortex of the hooded rat was demonstrated by means of the C-14 2-deoxyglucose autoradiographic technique. By stimulating one eye with square wave gratings and eliminating efferent activation from the other by means of enucleation or intraocular TTX injection, differences between ipsilaterally and contralaterally based visual activity in the two hemispheres were maximized. Carbon-14 levels in layer IV of autoradiographs of coronal sections were measured and combined across sections to form right and left matrices of posterior cortex metabolic activity. A difference matrix, formed by subtracting the metabolic activity matrix of cortex contralateral to the stimulated eye from the ipsilateral depressed matrix, emphasized those parts of the visual cortex that received monocular visual input. The demarcation of striate cortex by means of cholinesterase stain and the examination of autoradiographs from sections cut tangential to the cortical surface aided in the interpretation of the difference matrices. In striate cortex, differences were maximal in the medial monocular portion, and the lateral or binocular portion was shown to be divided metabolically into a far lateral contralaterally dominant strip along the cortical representation of the vertical meridian, and a more medial region of patches of more or less contralaterally dominant binocular input. Lateral peristriate differences were less than those of striate cortex, and regions of greater and lesser monocular input could be distinguished. We did not detect differences between the two hemispheres in either anterior or medial peristriate areas

  9. Genome Sequencing of Streptomyces atratus SCSIOZH16 and Activation Production of Nocardamine via Metabolic Engineering

    Directory of Open Access Journals (Sweden)

    Yan Li

    2018-06-01

    Full Text Available The Actinomycetes are metabolically flexible microorganisms capable of producing a wide range of interesting compounds, including but by no means limited to, siderophores which have high affinity for ferric iron. In this study, we report the complete genome sequence of marine-derived Streptomyces atratus ZH16 and the activation of an embedded siderophore gene cluster via the application of metabolic engineering methods. The S. atratus ZH16 genome reveals that this strain has the potential to produce 26 categories of natural products (NPs barring the ilamycins. Our activation studies revealed S. atratus SCSIO ZH16 to be a promising source of the production of nocardamine-type (desferrioxamine compounds which are important in treating acute iron intoxication and performing ecological remediation. We conclude that metabolic engineering provides a highly effective strategy by which to discover drug-like compounds and new NPs in the genomic era.

  10. Metabolic and Co-Metabolic Transformation of Diclofenac by Enterobacter hormaechei D15 Isolated from Activated Sludge.

    Science.gov (United States)

    Aissaoui, Salima; Ouled-Haddar, Houria; Sifour, Mohamed; Harrouche, Kamel; Sghaier, Haitham

    2017-03-01

    The presence of non-steroidal anti-inflammatory drugs, such as diclofenac (DCF), in the environment, is an emerging problem due to their harmful effects on non-target organisms, even at low concentrations. We studied the biodegradation of DCF by the strain D15 of Enterobacter hormaechei. The strain was isolated from an activated sludge, and identified as E. hormaechei based on its physiological characteristics and its 16 S RNA sequence. Using HPTLC and GC-MS methods, we demonstrated that this strain metabolized DCF at an elimination rate of 52.8%. In the presence of an external carbon source (glucose), the elimination rate increased to approximately 82%. GC-MS analysis detected and identified one metabolite as 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one; it was produced as a consequence of dehydration and lactam formation reactions.

  11. Alterations in calcium metabolism during human monocyte activation

    International Nuclear Information System (INIS)

    Scully, S.P.

    1984-01-01

    Human peripheral blood monocytes have been prepared from plateletpheresis residues by counterflow centrifugal elutriation in sufficient quantities to enable quantitative studies of cell calcium. Kinetic analysis of 45 Ca exchange data in resting monocytes was compatible with a model of cellular calcium containing three exchangeable calcium pools. These pools are thought to represent a putative ectocellular pool, a putative cytoplasmic chelated pool, and a putative organelle sequestered pool. Exposure of monocytes to the plant lectin Con A at a concentration that maximally simulated superoxide production caused an increase in the size and a doubling in the exchange rate of the putative cytoplasmic pool without a change in the other cellular pools. The cytoplasmic ionized calcium, [Ca]/sub i/, measured with the fluorescent probe, Quin 2 rose from a resting level of 83 nM to 165 mN within 30 sec of exposure to Con A. This increase in cytoplasmic calcium preceded the release of superoxide radicals. Calcium transport and calcium ATPase activities were identified and characterized in plasma membrane vesicles prepared from monocytes. Both activities were strictly dependent on ATP and Mg, had a Km/sub Ca/ in the submicromolar range and were stimulated by calmodulin. Thus, it seems that monocyte calcium is in a dynamic steady state that is a balance between efflux and influx rates, and that the activation of these cells results in the transition to a new steady state. The alteration in [Ca]/sub i/ that accompany the new steady state are essential for superoxide production by human monocytes

  12. Serial MRI studies using gadolinium DTPA in active multiple sclerosis

    International Nuclear Information System (INIS)

    Miller, D.H.; Johnson, G.; Barnes, D.; Rudge, P.; McDonald, W.I.

    1988-01-01

    It has been suggested that blood brain barrier (BBB) impairment is a necessary early event in the pathogenesis of the multiple sclerosis (MS) lesions. To evaluate such an hypothesis in vivo would require: (1) serial imaging studies using a modality with high sensitivity for detecting plaques; (2) a contrast enhancing agent which demonstrates BBB impairment. A serial magnetic resonance imaging (MRI) study was undertaken of a group of MS patients using the contrast agent gadolinium-DTPA. As it has been suggested that T 1 and T 2 relaxation times are longer in acute than chronic MS lesions, these were also measured. 3 refs.; 1 figure

  13. Bone metabolic activity in hyperostosis cranialis interna measured with {sup 18}F-fluoride PET

    Energy Technology Data Exchange (ETDEWEB)

    Waterval, Jerome J.; Dongen, Thijs M.A. van; Stokroos, Robert J.; Manni, Johannes J. [Maastricht University Medical Center, Department of Otorhinolaryngology and Head and Neck Surgery, Maastricht (Netherlands); Teule, Jaap G.J.; Kemerink, Gerrit J.; Brans, Boudewijn [Maastricht University Medical Center, Department of Nuclear Medicine, Maastricht (Netherlands); Nieman, Fred H.M. [Maastricht University Medical Center, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht (Netherlands)

    2011-05-15

    {sup 18}F-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment and dysfunction of several cranial nerves. The aim of this study is to compare standardised uptake values (SUVs) at different sites in order to quantify bone metabolism in the affected anatomical regions in HCI patients. Nine affected family members, seven non-affected family members and nine non-HCI non-family members underwent {sup 18}F-fluoride PET/CT scans. SUVs were systematically measured in the different regions of interest: frontal bone, sphenoid bone, petrous bone and clivus. Moreover, the average {sup 18}F-fluoride uptake in the entire skull was measured by assessing the uptake in axial slides. Visual assessment of the PET scans of affected individuals was performed to discover the process of disturbed bone metabolism in HCI. {sup 18}F-Fluoride uptake is statistically significantly higher in the sphenoid bone and clivus regions of affected family members. Visual assessment of the scans of HCI patients is relevant in detecting disease severity and the pattern of disturbed bone metabolism throughout life. {sup 18}F-Fluoride PET/CT is useful in quantifying the metabolic activity in HCI and provides information about the process of disturbed bone metabolism in this specific disorder. Limitations are a narrow window between normal and pathological activity and the influence of age. This study emphasises that {sup 18}F-fluoride PET/CT may also be a promising diagnostic tool for other metabolic bone disorders, even those with an indolent course. (orig.)

  14. Bone metabolic activity in hyperostosis cranialis interna measured with 18F-fluoride PET

    International Nuclear Information System (INIS)

    Waterval, Jerome J.; Dongen, Thijs M.A. van; Stokroos, Robert J.; Manni, Johannes J.; Teule, Jaap G.J.; Kemerink, Gerrit J.; Brans, Boudewijn; Nieman, Fred H.M.

    2011-01-01

    18 F-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment and dysfunction of several cranial nerves. The aim of this study is to compare standardised uptake values (SUVs) at different sites in order to quantify bone metabolism in the affected anatomical regions in HCI patients. Nine affected family members, seven non-affected family members and nine non-HCI non-family members underwent 18 F-fluoride PET/CT scans. SUVs were systematically measured in the different regions of interest: frontal bone, sphenoid bone, petrous bone and clivus. Moreover, the average 18 F-fluoride uptake in the entire skull was measured by assessing the uptake in axial slides. Visual assessment of the PET scans of affected individuals was performed to discover the process of disturbed bone metabolism in HCI. 18 F-Fluoride uptake is statistically significantly higher in the sphenoid bone and clivus regions of affected family members. Visual assessment of the scans of HCI patients is relevant in detecting disease severity and the pattern of disturbed bone metabolism throughout life. 18 F-Fluoride PET/CT is useful in quantifying the metabolic activity in HCI and provides information about the process of disturbed bone metabolism in this specific disorder. Limitations are a narrow window between normal and pathological activity and the influence of age. This study emphasises that 18 F-fluoride PET/CT may also be a promising diagnostic tool for other metabolic bone disorders, even those with an indolent course. (orig.)

  15. DOHaD at the intersection of maternal immune activation and maternal metabolic stress: a scoping review.

    Science.gov (United States)

    Goldstein, J A; Norris, S A; Aronoff, D M

    2017-06-01

    The prenatal environment is now recognized as a key driver of non-communicable disease risk later in life. Within the developmental origins of health and disease (DOHaD) paradigm, studies are increasingly identifying links between maternal morbidity during pregnancy and disease later in life for offspring. Nutrient restriction, metabolic disorders during gestation, such as diabetes or obesity, and maternal immune activation provoked by infection have been linked to adverse health outcomes for offspring later in life. These factors frequently co-occur, but the potential for compounding effects of multiple morbidities on DOHaD-related outcomes has not received adequate attention. This is of particular importance in low- or middle-income countries (LMICs), which have ongoing high rates of infectious diseases and are now experiencing transitions from undernutrition to excess adiposity. The purpose of this scoping review is to summarize studies examining the effect and interaction of co-occurring metabolic or nutritional stressors and infectious diseases during gestation on DOHaD-related health outcomes. We identified nine studies in humans - four performed in the United States and five in LMICs. The most common outcome, also in seven of nine studies, was premature birth or low birth weight. We identified nine animal studies, six in mice, two in rats and one in sheep. The interaction between metabolic/nutritional exposures and infectious exposures had varying effects including synergism, inhibition and independent actions. No human studies were specifically designed to assess the interaction of metabolic/nutritional exposures and infectious diseases. Future studies of neonatal outcomes should measure these exposures and explicitly examine their concerted effect.

  16. The role of active brown adipose tissue in human metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Ozguven, Salih; Turoglu, H.T. [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Ones, Tunc [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Kozyatagi/Kadikoy, Istanbul (Turkey); Yilmaz, Yusuf; Imeryuz, Nese [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Internal Medicine, Division of Gastroenterology, Istanbul (Turkey)

    2016-02-15

    The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing {sup 18}F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). We retrospectively and prospectively analysed the {sup 18}F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD. (orig.)

  17. Polyphenols from Bee Pollen: Structure, Absorption, Metabolism and Biological Activity

    Directory of Open Access Journals (Sweden)

    Anna Rzepecka-Stojko

    2015-12-01

    Full Text Available Bee pollen constitutes a natural source of antioxidants such as phenolic acids and flavonoids, which are responsible for its biological activity. Research has indicated the correlation between dietary polyphenols and cardioprotective, hepatoprotective, anti-inflammatory, antibacterial, anticancerogenic, immunostimulating, antianaemic effects, as well as their beneficial influence on osseous tissue. The beneficial effects of bee pollen on health result from the presence of phenolic acids and flavonoids which possess anti-inflammatory properties, phytosterol and linolenic acid which play an anticancerogenic role, and polysaccharides which stimulate immunological activity. Polyphenols are absorbed in the alimentary tract, metabolised by CYP450 enzymes, and excreted with urine and faeces. Flavonoids and phenolic acids are characterised by high antioxidative potential, which is closely related to their chemical structure. The high antioxidant potential of phenolic acids is due to the presence and location of hydroxyl groups, a carboxyl group in the immediate vicinity of ortho-diphenolic substituents, and the ethylene group between the phenyl ring and the carboxyl group. As regards flavonoids, essential structural elements are hydroxyl groups at the C5 and C7 positions in the A ring, and at the C3′ and C4′ positions in the B ring, and a hydroxyl group at the C3 position in the C ring. Furthermore, both, the double bond between C2 and C3, and a ketone group at the C4 position in the C ring enhance the antioxidative potential of these compounds. Polyphenols have an ideal chemical structure for scavenging free radicals and for creating chelates with metal ions, which makes them effective antioxidants in vivo.

  18. Plateau hypoxia attenuates the metabolic activity of intestinal flora to enhance the bioavailability of nifedipine.

    Science.gov (United States)

    Zhang, Juanhong; Chen, Yuyan; Sun, Yuemei; Wang, Rong; Zhang, Junmin; Jia, Zhengping

    2018-11-01

    Nifedipine is completely absorbed by the gastrointestinal tract and its pharmacokinetics and metabolism may be influenced by microorganisms. If gut microbes are involved in the metabolism of nifedipine, plateau hypoxia may regulate the bioavailability and the therapeutic effect of nifedipine by altering the metabolic activity of the gut microbiota. We herein demonstrated for the first time that gut flora is involved in the metabolism of nifedipine by in vitro experiments. In addition, based on the results of 16S rRNA analysis of feces in rats after acute plateau, we first confirmed that the plateau environment could cause changes in the number and composition of intestinal microbes. More importantly, these changes in flora could lead to a slower metabolic activity of nifedipine in the body after an acute plateau, resulting in increased bioavailability and therapeutic efficacy of nifedipine. Our research will provide basis and new ideas for changes in the fecal flora of human acutely entering the plateau, and contribute to rational drug use of nifedipine.

  19. Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes.

    Directory of Open Access Journals (Sweden)

    Xinwei Li

    Full Text Available The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic acid and BML-275 (an AMPKα inhibitor. Acetic acid consumed a large amount of ATP, resulting in an increase in AMPKα phosphorylation. The increase in AMPKα phosphorylation increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α, which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated AMPKα phosphorylation reduced the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and the carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated AMPKα inhibited the activity of acetyl-CoA carboxylase. Consequently, the triglyceride content in the acetate-treated hepatocytes was significantly decreased. These results indicate that acetic acid activates the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows.

  20. Metabolic disruptions induced by reduced ambulatory activity in free-living humans

    DEFF Research Database (Denmark)

    Thyfault, John P; Krogh-Madsen, Rikke

    2011-01-01

    Physical inactivity likely plays a role in the development of insulin resistance and obesity; however, direct evidence is minimal and mechanisms of action remain unknown. Studying metabolic outcomes that occur after transitioning from higher to lower levels of physical activity is the best tool t...

  1. Effect of tributyltin (TBT) in the metabolic activity of TBT-resistant and sensitive estuarine bacteria.

    Science.gov (United States)

    Cruz, Andreia; Oliveira, Vanessa; Baptista, Inês; Almeida, Adelaide; Cunha, Angela; Suzuki, Satoru; Mendo, Sónia

    2012-01-01

    The effect of tributyltin (TBT) on growth and metabolic activity of three estuarine bacteria with different TBT resistance profiles was investigated in an organic-rich culture medium (TSB) and in phosphate buffered saline (PBS) buffer. Exposure to TBT was assessed by determining its effect on growth (OD(600 nm) measurement), bacterial productivity (leucine incorporation), viability (CFU counts), aggregation and cell size (from Live/Dead analysis), ATP and NADH concentrations. TBT exposure resulted in decrease of bacterial density, cell size, and metabolic activity. In addition, cell aggregates were observed in the TBT-treated cultures. TBT strongly affected bacterial cell metabolism and seemed to exert an effect on its equilibrium, interfering with cell activity. Also, TBT toxicity was lower when cells were grown in TSB than in PBS, suggesting that a nutrient-rich growth medium can protect cells from TBT toxicity. This study contributes to our understanding of the TBT-resistant cell behavior reflected in its physiology and metabolic activity. This information is of utmost importance for further studies of TBT bioremediation. Copyright © 2010 Wiley Periodicals, Inc.

  2. Physical activity, metabolic syndrome, and coronary risk: the EPIC-Norfolk prospective population study

    NARCIS (Netherlands)

    Broekhuizen, Lysette N.; Boekholdt, S. Matthijs; Arsenault, Benoit J.; Despres, Jean-Pierre; Stroes, Erik S. G.; Kastelein, John J. P.; Khaw, Kay-Tee; Wareham, Nicholas J.

    2011-01-01

    Objective: We investigated the association between physical activity, metabolic syndrome (MS), and the risk of future coronary heart disease (CHD) and mortality due to CHD in middle-aged men and women. Design: Prospective cohort study. Subjects: A total of 10,134 men and women aged 45-79 years at

  3. Complete Sucrose Metabolism Requires Fructose Phosphotransferase Activity in Corynebacterium glutamicum To Ensure Phosphorylation of Liberated Fructose

    OpenAIRE

    Dominguez, H.; Lindley, N. D.

    1996-01-01

    Sucrose uptake by Corynebacterium glutamicum involves a phosphoenolpyruvate-dependent sucrose phosphotransferase (PTS), but in the absence of fructokinase, further metabolism of the liberated fructose requires efflux of the fructose and reassimilation via the fructose PTS. Mutant strains lacking detectable fructose-transporting PTS activity accumulated fructose extracellularly but consumed sucrose at rates comparable to those of the wild-type strain.

  4. Jasmonates: Biosynthesis, metabolism, and signaling by proteins activating and repressing transcription

    Czech Academy of Sciences Publication Activity Database

    Wasternack, Claus; Song, S.

    2017-01-01

    Roč. 68, č. 6 (2017), s. 1303-1321 ISSN 0022-0957 Institutional support: RVO:61389030 Keywords : Activators * Amino acid conjugates * Biosynthesis * Jasmonic acid * Metabolism * Perception * Repressors * SCFJAZ co-receptor complex COI1 * Signaling Subject RIV: EI - Biotechnology ; Bionics OBOR OECD: Plant sciences, botany Impact factor: 5.830, year: 2016

  5. Activities of xenobiotic metabolizing enzymes in rat placenta and liver in vitro

    NARCIS (Netherlands)

    Fabian, Eric; Wang, Xinyi; Engel, Franziska; Li, Hequn; Landsiedel, Robert; Ravenzwaay, van Bennard

    2016-01-01

    In order to assess whether the placental metabolism of xenobiotic compounds should be taken into consideration for physiologically-based toxicokinetic (PBTK) modelling, the activities of seven phase I and phase II enzymes have been quantified in the 18-day placenta of untreated Wistar rats. To

  6. Angiogenic activity of sesamin through the activation of multiple signal pathways

    International Nuclear Information System (INIS)

    Chung, Byung-Hee; Lee, Jung Joon; Kim, Jong-Dai; Jeoung, Dooil; Lee, Hansoo; Choe, Jongseon; Ha, Kwon-Soo; Kwon, Young-Geun; Kim, Young-Myeong

    2010-01-01

    The natural product sesamin has been known to act as a potent antioxidant and prevent endothelial dysfunction. We here found that sesamin increased in vitro angiogenic processes, such as endothelial cell proliferation, migration, and tube formation, as well as neovascularization in an animal model. This compound elicited the activation of multiple angiogenic signal modulators, such as ERK, Akt, endothelial nitric oxide synthase (eNOS), NO production, FAK, and p38 MAPK, but not Src. The MEK inhibitor PD98059 and the PI3K inhibitor Wortmannin specifically inhibited sesamin-induced activation of the ERK and Akt/eNOS pathways. These inhibitors reduced angiogenic events, with high specificity for MEK/ERK-dependent cell proliferation and migration and PI3K/Akt-mediated tube formation. Moreover, inhibition of p38 MAPK effectively inhibited sesamin-induced cell migration. The angiogenic activity of sesamin was not associated with VEGF expression. Furthermore, this compound did not induce vascular permeability and upregulated ICAM-1 and VCAM-1 expression, which are hallmarks of vascular inflammation. These results suggest that sesamin stimulates angiogenesis in vitro and in vivo through the activation of MEK/ERK-, PI3K/Akt/eNOS-, p125 FAK -, and p38 MAPK-dependent pathways, without increasing vascular inflammation, and may be used for treating ischemic diseases and tissue regeneration.

  7. Large roads reduce bat activity across multiple species.

    Science.gov (United States)

    Kitzes, Justin; Merenlender, Adina

    2014-01-01

    Although the negative impacts of roads on many terrestrial vertebrate and bird populations are well documented, there have been few studies of the road ecology of bats. To examine the effects of large roads on bat populations, we used acoustic recorders to survey bat activity along ten 300 m transects bordering three large highways in northern California, applying a newly developed statistical classifier to identify recorded calls to the species level. Nightly counts of bat passes were analyzed with generalized linear mixed models to determine the relationship between bat activity and distance from a road. Total bat activity recorded at points adjacent to roads was found to be approximately one-half the level observed at 300 m. Statistically significant road effects were also found for the Brazilian free-tailed bat (Tadarida brasiliensis), big brown bat (Eptesicus fuscus), hoary bat (Lasiurus cinereus), and silver-haired bat (Lasionycteris noctivagans). The road effect was found to be temperature dependent, with hot days both increasing total activity at night and reducing the difference between activity levels near and far from roads. These results suggest that the environmental impacts of road construction may include degradation of bat habitat and that mitigation activities for this habitat loss may be necessary to protect bat populations.

  8. Metabolic factors affecting enhanced phosphorus uptake by activated sludge.

    Science.gov (United States)

    Boughton, W H; Gottfried, R J; Sinclair, N A; Yall, I

    1971-10-01

    Activated sludges obtained from the Rilling Road plant located at San Antonio, Tex., and from the Hyperion treatment plant located at Los Angeles, Calif., have the ability to remove all of the orthophosphate normally present in Tucson sewage within 3 hr after being added to the waste water. Phosphorus removal was independent of externally supplied sources of energy and ions, since orthophosphate and (32)P radioactivity were readily removed from tap water, glass-distilled water, and deionized water. Phosphorus uptake by Rilling sludge in the laboratory appears to be wholly biological, as it has an optimum pH range (7.7 to 9.7) and an optimum temperature range (24 to 37 C). It was inhibited by HgCl(2), iodoacetic acid, p-chloromercuribenzoic acid, NaN(3), and 2, 4-dinitrophenol (compounds that affect bacterial membrane permeability, sulfhydryl enzymes, and adenosine triphosphate synthesis). Uptake was inhibited by 1% NaCl but was not affected by 10(-3)m ethylenediaminetetraacetic acid disodium salt (a chelating agent for many metallic ions).

  9. AMPK activation through mitochondrial regulation results in increased substrate oxidation and improved metabolic parameters in models of diabetes.

    Directory of Open Access Journals (Sweden)

    Yonchu Jenkins

    Full Text Available Modulation of mitochondrial function through inhibiting respiratory complex I activates a key sensor of cellular energy status, the 5'-AMP-activated protein kinase (AMPK. Activation of AMPK results in the mobilization of nutrient uptake and catabolism for mitochondrial ATP generation to restore energy homeostasis. How these nutrient pathways are affected in the presence of a potent modulator of mitochondrial function and the role of AMPK activation in these effects remain unclear. We have identified a molecule, named R419, that activates AMPK in vitro via complex I inhibition at much lower concentrations than metformin (IC50 100 nM vs 27 mM, respectively. R419 potently increased myocyte glucose uptake that was dependent on AMPK activation, while its ability to suppress hepatic glucose production in vitro was not. In addition, R419 treatment of mouse primary hepatocytes increased fatty acid oxidation and inhibited lipogenesis in an AMPK-dependent fashion. We have performed an extensive metabolic characterization of its effects in the db/db mouse diabetes model. In vivo metabolite profiling of R419-treated db/db mice showed a clear upregulation of fatty acid oxidation and catabolism of branched chain amino acids. Additionally, analyses performed using both (13C-palmitate and (13C-glucose tracers revealed that R419 induces complete oxidation of both glucose and palmitate to CO2 in skeletal muscle, liver, and adipose tissue, confirming that the compound increases mitochondrial function in vivo. Taken together, our results show that R419 is a potent inhibitor of complex I and modulates mitochondrial function in vitro and in diabetic animals in vivo. R419 may serve as a valuable molecular tool for investigating the impact of modulating mitochondrial function on nutrient metabolism in multiple tissues and on glucose and lipid homeostasis in diabetic animal models.

  10. Metabolic activation and carcinogenicity of polycyclic hydrocarbons: A new quantum mechanical theory

    International Nuclear Information System (INIS)

    Mohammad, S.N.

    1986-01-01

    This investigation aims to describe a quantum mechanical theory of cancer, which, on the basis of certain electronic indices calculated for the parent compound, would give prediction of its P-450 mediated metabolic activation and would provide better representation of its relative carcinogenic potency when activated to its PUM. The author's theory is based on the assumption that electronic charge distribution of activated species resembles at least qualitatively the charge distribution of the parent compound, and a careful analysis of electronic characteristics of the parent compound would suffice to give reasonable estimation of the carcinogenic activities of the metabolic products. The details of the theoretical method is given and the results for some alternant and non-alternant PAHs are presented

  11. Development and evaluation of a multiple-plate fraction collector for sample processing: application to radioprofiling in drug metabolism studies.

    Science.gov (United States)

    Barros, Anthony; Ly, Van T; Chando, Theodore J; Ruan, Qian; Donenfeld, Scott L; Holub, David P; Christopher, Lisa J

    2011-04-05

    Microplate scintillation counters are utilized routinely in drug metabolism laboratories for the off-line radioanalysis of fractions collected during HPLC radioprofiling. In this process, the current fraction collection technology is limited by the number of plates that can be used per injection as well as the potential for sample loss due to dripping or spraying as the fraction collector head moves from well to well or between plates. More importantly, sample throughput is limited in the conventional process, since the collection plates must be manually exchanged after each injection. The Collect PAL, an innovative multiple-plate fraction collector, was developed to address these deficiencies and improve overall sample throughput. It employs a zero-loss design and has sub-ambient temperature control. Operation of the system is completely controlled with software and up to 24 (96- or 384-well) fraction collection plates can be loaded in a completely automated run. The system may also be configured for collection into various-sized tubes or vials. At flow rates of 0.5 or 1.0 mL/min and at collection times of 10 or 15s, the system precisely delivered 83-μL fractions (within 4.1% CV) and 250-μL fractions (within 1.4% CV), respectively, of three different mobile phases into 12 mm × 32 mm vials. Similarly, at a flow rate of 1 mL/min and 10s collection times, the system precisely dispensed mobile phase containing a [(14)C]-radiolabeled compound across an entire 96-well plate (% CV was within 5.3%). Triplicate analyses of metabolism test samples containing [(14)C]buspirone and its metabolites, derived from three different matrices (plasma, urine and bile), indicated that the Collect PAL produced radioprofiles that were reproducible and comparable to the current technology; the % CV for 9 selected peaks in the radioprofiles generated with the Collect PAL were within 9.3%. Radioprofiles generated by collecting into 96- and 384-well plates were qualitatively comparable

  12. Alternate radiolabeled markers for detecting metabolic activity of Mycobacterium leprae residing in murine macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, H.K.; Hastings, R.C.

    1985-05-01

    This study demonstrated the utility of using 4% NaOH as a murine macrophage cell-solubilizing agent to discriminate between host macrophage metabolism and that of intracellular Mycobacterium leprae. A 4% concentration of NaOH had no deleterious effect on labeled mycobacteria. Thereby, alternate radiolabeled indicators of the metabolic activity of intracellular M. leprae could be experimented with. Significant incorporation of /sup 14/C-amino acid mixture, (/sup 14/C)leucine, (/sup 14/C)uridine, and carrier-free /sup 32/P was observed in cultures containing freshly extracted (''live'') strains of M. leprae as compared with control cultures containing autoclaved bacilli.

  13. Alternate radiolabeled markers for detecting metabolic activity of Mycobacterium leprae residing in murine macrophages

    International Nuclear Information System (INIS)

    Prasad, H.K.; Hastings, R.C.

    1985-01-01

    This study demonstrated the utility of using 4% NaOH as a murine macrophage cell-solubilizing agent to discriminate between host macrophage metabolism and that of intracellular Mycobacterium leprae. A 4% concentration of NaOH had no deleterious effect on labeled mycobacteria. Thereby, alternate radiolabeled indicators of the metabolic activity of intracellular M. leprae could be experimented with. Significant incorporation of 14 C-amino acid mixture, [ 14 C]leucine, [ 14 C]uridine, and carrier-free 32 P was observed in cultures containing freshly extracted (''live'') strains of M. leprae as compared with control cultures containing autoclaved bacilli

  14. A high-throughput method for quantifying metabolically active yeast cells

    DEFF Research Database (Denmark)

    Nandy, Subir Kumar; Knudsen, Peter Boldsen; Rosenkjær, Alexander

    2015-01-01

    By redesigning the established methylene blue reduction test for bacteria and yeast, we present a cheap and efficient methodology for quantitative physiology of eukaryotic cells applicable for high-throughput systems. Validation of themethod in fermenters and highthroughput systems proved....... The drop in metabolic activity associated with the diauxic shift in yeast proved more pronounced for the MBRT-derived curve compared with OD curves, consistent with a dramatic shift in the ratio between live and dead cells at this metabolic event. This method provides a tool with numerous applications, e.......g. characterizing the death phase of stationary phase cultures, or in drug screens with pathogenic yeasts....

  15. Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPARγ activation in high fructose diet-induced metabolic syndrome.

    Science.gov (United States)

    Cannizzaro, Luca; Rossoni, Giuseppe; Savi, Federica; Altomare, Alessandra; Marinello, Cristina; Saethang, Thammakorn; Carini, Marina; Payne, D Michael; Pisitkun, Trairak; Aldini, Giancarlo; Leelahavanichkul, Asada

    2017-01-01

    The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ). Rats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half. Rats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented. Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by

  16. Electronic Nose Technology to Measure Soil Microbial Activity and Classify Soil Metabolic Status

    OpenAIRE

    Fabrizio De Cesare; Elena Di Mattia; Simone Pantalei; Emiliano Zampetti; Vittorio Vinciguerra; Antonella Macagnano

    2011-01-01

    The electronic nose (E-nose) is a sensing technology that has been widely used to monitor environments in the last decade. In the present study, the capability of an E-nose, in combination with biochemical and microbiological techniques, of both detecting the microbial activity and estimating the metabolic status of soil ecosystems, was tested by measuring on one side respiration, enzyme activities and growth of bacteria in natural but simplified soil ecosystems over 23 days of incubation thr...

  17. Determination of the activity signature of key carbohydrate metabolism enzymes in phenolic-rich grapevine tissues

    DEFF Research Database (Denmark)

    Covington, Elizabeth Dunn; Roitsch, Thomas Georg; Dermastia, Marina

    2016-01-01

    Physiological studies in plants often require enzyme extraction from tissues containing high concentrations of phenols and polyphenols. Unless removed or neutralized, such compounds may hinder extraction, inactivate enzymes, and interfere with enzyme detection. The following protocol for activity...... assays for enzymes of primary carbohydrate metabolism, while based on our recently published one for quantitative measurement of activities using coupled spectrophotometric assays in a 96-well format, is tailored to the complexities of phenolic- and anthocyanin-rich extracts from grapevine leaf...

  18. De novo Transcriptome Assembly of Chinese Kale and Global Expression Analysis of Genes Involved in Glucosinolate Metabolism in Multiple Tissues

    Science.gov (United States)

    Wu, Shuanghua; Lei, Jianjun; Chen, Guoju; Chen, Hancai; Cao, Bihao; Chen, Changming

    2017-01-01

    Chinese kale, a vegetable of the cruciferous family, is a popular crop in southern China and Southeast Asia due to its high glucosinolate content and nutritional qualities. However, there is little research on the molecular genetics and genes involved in glucosinolate metabolism and its regulation in Chinese kale. In this study, we sequenced and characterized the transcriptomes and expression profiles of genes expressed in 11 tissues of Chinese kale. A total of 216 million 150-bp clean reads were generated using RNA-sequencing technology. From the sequences, 98,180 unigenes were assembled for the whole plant, and 49,582~98,423 unigenes were assembled for each tissue. Blast analysis indicated that a total of 80,688 (82.18%) unigenes exhibited similarity to known proteins. The functional annotation and classification tools used in this study suggested that genes principally expressed in Chinese kale, were mostly involved in fundamental processes, such as cellular and molecular functions, the signal transduction, and biosynthesis of secondary metabolites. The expression levels of all unigenes were analyzed in various tissues of Chinese kale. A large number of candidate genes involved in glucosinolate metabolism and its regulation were identified, and the expression patterns of these genes were analyzed. We found that most of the genes involved in glucosinolate biosynthesis were highly expressed in the root, petiole, and in senescent leaves. The expression patterns of ten glucosinolate biosynthetic genes from RNA-seq were validated by quantitative RT-PCR in different tissues. These results provided an initial and global overview of Chinese kale gene functions and expression activities in different tissues. PMID:28228764

  19. Multiple insecticide resistance mechanisms involving metabolic changes and insensitive target sites selected in anopheline vectors of malaria in Sri Lanka

    Directory of Open Access Journals (Sweden)

    Karunaratne SHP Parakrama

    2008-08-01

    Full Text Available Abstract Background The current status of insecticide resistance and the underlying resistance mechanisms were studied in the major vector of malaria, Anopheles culicifacies, and the secondary vector, Anopheles subpictus in five districts (Anuradhapura, Kurunegala, Moneragala, Puttalam and Trincomalee of Sri Lanka. Eight other anophelines, Anopheles annularis, Anopheles barbirostris, Anopheles jamesii, Anopheles nigerrimus, Anopheles peditaeniatus, Anopheles tessellatus, Anopheles vagus and Anopheles varuna from Anuradhapura district were also tested. Methods Adult females were exposed to the WHO discriminating dosages of DDT, malathion, fenitrothion, propoxur, λ-cyhalothrin, cyfluthrin, cypermethrin, deltamethrin, permethrin and etofenprox. The presence of metabolic resistance by esterase, glutathione S-transferase (GST and monooxygenase-based mechanisms, and the sensitivity of the acetylcholinesterase target site were assessed using synergists, and biochemical, and metabolic techniques. Results All the anopheline species had high DDT resistance. All An. culicifacies and An. subpictus populations were resistant to malathion, except An. culicifacies from Kurunegala, where there was no malathion carboxylesterase activity. Kurunegala and Puttalam populations of An. culicifacies were susceptible to fenitrothion. All the An. culicifacies populations were susceptible to carbamates. Both species were susceptible to the discriminating dosages of cypermethrin and cyfluthrin, but had different levels of resistance to other pyrethroids. Of the 8 other anophelines, only An. nigerrimus and An. peditaeniatus were resistant to all the insecticides tested, probably due to their high exposure to the insecticides used in agriculture. An. vagus showed some resistance to permethrin. Esterases, GSTs and monooxygenases were elevated in both An. culicifacies and An. subpictus. AChE was most sensitive to insecticides in Kurunegala and Trincomalee An. culicifacies

  20. Graphical analysis of processes with multiple activation energies

    International Nuclear Information System (INIS)

    Lachter, J.; Bragg, R.H.; Close, E.

    1986-01-01

    The activation energies characterizing a kinetic process are derived from the slopes of the Arrhenius diagrams obtained by plotting rate constants versus reciprocal temperature. Those rate constants correspond to the shifts along the time axis needed to superpose the successive isotherms. A general method based on Chebyshev interpolation is proposed for the optimization of the superposition of the experimental data points. This method is applied to determine the activation energies of the graphitization kinetics of the interlayer spacings of pitch coke and pyrocarbon samples

  1. Do obese but metabolically normal women differ in intra-abdominal fat and physical activity levels from those with the expected metabolic abnormalities? A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Walker Mark

    2010-11-01

    Full Text Available Abstract Background Obesity remains a major public health problem, associated with a cluster of metabolic abnormalities. However, individuals exist who are very obese but have normal metabolic parameters. The aim of this study was to determine to what extent differences in metabolic health in very obese women are explained by differences in body fat distribution, insulin resistance and level of physical activity. Methods This was a cross-sectional pilot study of 39 obese women (age: 28-64 yrs, BMI: 31-67 kg/m2 recruited from community settings. Women were defined as 'metabolically normal' on the basis of blood glucose, lipids and blood pressure. Magnetic Resonance Imaging was used to determine body fat distribution. Detailed lifestyle and metabolic profiles of participants were obtained. Results Women with a healthy metabolic profile had lower intra-abdominal fat volume (geometric mean 4.78 l [95% CIs 3.99-5.73] vs 6.96 l [5.82-8.32] and less insulin resistance (HOMA 3.41 [2.62-4.44] vs 6.67 [5.02-8.86] than those with an abnormality. The groups did not differ in abdominal subcutaneous fat volume (19.6 l [16.9-22.7] vs 20.6 [17.6-23.9]. A higher proportion of those with a healthy compared to a less healthy metabolic profile met current physical activity guidelines (70% [95% CIs 55.8-84.2] vs 25% [11.6-38.4]. Intra-abdominal fat, insulin resistance and physical activity make independent contributions to metabolic status in very obese women, but explain only around a third of the variance. Conclusion A sub-group of women exists who are metabolically normal despite being very obese. Differences in fat distribution, insulin resistance, and physical activity level are associated with metabolic differences in these women, but account only partially for these differences. Future work should focus on strategies to identify those obese individuals most at risk of the negative metabolic consequences of obesity and on identifying other factors that

  2. Adiponectin activates the AMPK signaling pathway to regulate lipid metabolism in bovine hepatocytes.

    Science.gov (United States)

    Chen, Hui; Zhang, Liang; Li, Xinwei; Li, Xiaobing; Sun, Guoquan; Yuan, Xue; Lei, Liancheng; Liu, Juxiong; Yin, Liheng; Deng, Qinghua; Wang, Jianguo; Liu, Zhaoxi; Yang, Wentao; Wang, Zhe; Zhang, Hui; Liu, Guowen

    2013-11-01

    Adiponectin (Ad) plays a crucial role in hepatic lipid metabolism. However, the regulating mechanism of hepatic lipid metabolism by Ad in dairy cows is unclear. Hepatocytes from a newborn female calf were cultured in vitro and treated with different concentrations of Ad and BML-275 (an AMPKα inhibitor). The results showed that Ad significantly increased the expression of two Ad receptors. Furthermore, the phosphorylation and activity of AMPKα, as well as the expression levels and transcriptional activity of peroxisome proliferator activated receptor-α (PPARα) and its target genes involved in lipid oxidation, showed a corresponding trend of upregulation. However, the expression levels and transcriptional activity of sterol regulatory element binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) decreased in a similar manner. When BML-275 was added, the p-AMPKα level as well as the expression and activity of PPARα and its target genes were significantly decreased. However, the expression levels of SREBP-1c, ChREBP and their target genes showed a trend of upregulation. Furthermore, the triglyceride (TG) content was significantly decreased in the Ad-treated groups. These results indicate that Ad activates the AMPK signaling pathway and mediates lipid metabolism in bovine hepatocytes cultured in vitro by promoting lipid oxidation, suppressing lipid synthesis and reducing hepatic lipid accumulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Spatial localization of the first and last enzymes effectively connects active metabolic pathways in bacteria.

    Science.gov (United States)

    Meyer, Pablo; Cecchi, Guillermo; Stolovitzky, Gustavo

    2014-12-14

    Although much is understood about the enzymatic cascades that underlie cellular biosynthesis, comparatively little is known about the rules that determine their cellular organization. We performed a detailed analysis of the localization of E.coli GFP-tagged enzymes for cells growing exponentially. We found that out of 857 globular enzymes, at least 219 have a discrete punctuate localization in the cytoplasm and catalyze the first or the last reaction in 60% of biosynthetic pathways. A graph-theoretic analysis of E.coli's metabolic network shows that localized enzymes, in contrast to non-localized ones, form a tree-like hierarchical structure, have a higher within-group connectivity, and are traversed by a higher number of feed-forward and feedback loops than their non-localized counterparts. A Gene Ontology analysis of these enzymes reveals an enrichment of terms related to essential metabolic functions in growing cells. Given that these findings suggest a distinct metabolic role for localization, we studied the dynamics of cellular localization of the cell wall synthesizing enzymes in B. subtilis and found that enzymes localize during exponential growth but not during stationary growth. We conclude that active biochemical pathways inside the cytoplasm are organized spatially following a rule where their first or their last enzymes localize to effectively connect the different active pathways and thus could reflect the activity state of the cell's metabolic network.

  4. Physical activity staging distribution: establishing a heuristic using multiple studies.

    Science.gov (United States)

    Nigg, C; Hellsten, L; Norman, G; Braun, L; Breger, R; Burbank, P; Coday, M; Elliot, D; Garber, C; Greaney, M; Keteyian, S; Lees, F; Matthews, C; Moe, E; Resnick, B; Riebe, D; Rossi, J; Toobert, D; Wang, T; Welk, G; Williams, G

    2005-04-01

    The purpose of this study was to identify the population prevalence across the stages of change (SoC) for regular physical activity and to establish the prevalence of people at risk. With support from the National Institutes of Health, the American Heart Association, and the Robert Wood Johnson Foundation, nine Behavior Change Consortium studies with a common physical activity SoC measure agreed to collaborate and share data. The distribution pattern identified in these predominantly reactively recruited studies was Precontemplation (PC) = 5% (+/- 10), Contemplation (C) = 10% (+/- 10), Preparation (P) = 40% (+/- 10), Action = 10% (+/- 10), and Maintenance = 35% (+/- 10). With reactively recruited studies, it can be anticipated that there will be a higher percentage of the sample that is ready to change and a greater percentage of currently active people compared to random representative samples. The at-risk stage distribution (i.e., those not at criteria or PC, C, and P) was approximately 10% PC, 20% C, and 70% P in specific samples and approximately 20% PC, 10% C, and 70% P in the clinical samples. Knowing SoC heuristics can inform public health practitioners and policymakers about the population's motivation for physical activity, help track changes over time, and assist in the allocation of resources.

  5. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia

    Science.gov (United States)

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-01-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that—against general belief—neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress. PMID:24569689

  6. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia.

    Science.gov (United States)

    Saez, Isabel; Duran, Jordi; Sinadinos, Christopher; Beltran, Antoni; Yanes, Oscar; Tevy, María F; Martínez-Pons, Carlos; Milán, Marco; Guinovart, Joan J

    2014-06-01

    Glycogen is present in the brain, where it has been found mainly in glial cells but not in neurons. Therefore, all physiologic roles of brain glycogen have been attributed exclusively to astrocytic glycogen. Working with primary cultured neurons, as well as with genetically modified mice and flies, here we report that-against general belief-neurons contain a low but measurable amount of glycogen. Moreover, we also show that these cells express the brain isoform of glycogen phosphorylase, allowing glycogen to be fully metabolized. Most importantly, we show an active neuronal glycogen metabolism that protects cultured neurons from hypoxia-induced death and flies from hypoxia-induced stupor. Our findings change the current view of the role of glycogen in the brain and reveal that endogenous neuronal glycogen metabolism participates in the neuronal tolerance to hypoxic stress.

  7. Multiplicative multifractal modeling and discrimination of human neuronal activity

    International Nuclear Information System (INIS)

    Zheng Yi; Gao Jianbo; Sanchez, Justin C.; Principe, Jose C.; Okun, Michael S.

    2005-01-01

    Understanding neuronal firing patterns is one of the most important problems in theoretical neuroscience. It is also very important for clinical neurosurgery. In this Letter, we introduce a computational procedure to examine whether neuronal firing recordings could be characterized by cascade multiplicative multifractals. By analyzing raw recording data as well as generated spike train data from 3 patients collected in two brain areas, the globus pallidus externa (GPe) and the globus pallidus interna (GPi), we show that the neural firings are consistent with a multifractal process over certain time scale range (t 1 ,t 2 ), where t 1 is argued to be not smaller than the mean inter-spike-interval of neuronal firings, while t 2 may be related to the time that neuronal signals propagate in the major neural branching structures pertinent to GPi and GPe. The generalized dimension spectrum D q effectively differentiates the two brain areas, both intra- and inter-patients. For distinguishing between GPe and GPi, it is further shown that the cascade model is more effective than the methods recently examined by Schiff et al. as well as the Fano factor analysis. Therefore, the methodology may be useful in developing computer aided tools to help clinicians perform precision neurosurgery in the operating room

  8. Multiple forms of endopeptidase activity from jojoba seeds.

    Science.gov (United States)

    Wolf, M J; Storey, R D

    1990-01-01

    The cotyledons of 27 day post-germination jojoba seedlings (Simmondsia chinensis) contained five distinct endopeptidase activities separable by DEAE Bio-Gel and CM-cellulose ion exchange chromatography. The endopeptidases were purified 108- to 266-fold and their individuality was confirmed by activity-specific assays in native acrylamide gels along with differences in their Mr and catalytic properties. The five endopeptidases, which showed activity on model substrates and protein, were named EP Ia, EP Ib, EP II, EP III and EP IV. EP Ia was a serine proteinase with a pH optimum of ca 8 and Mr of 58,000. EP Ib, II and III were discrete cysteine proteinases showing pH optima of ca 6.8, 6.0 and 5.4 and Mr of 41,000, 47,000 and 35,000 respectively. EP IV was an aspartic acid proteinase with a ca pH optimum of 3.5 and Mr of 33,000.

  9. Metabolic equivalents of task are confounded by adiposity, which disturbs objective measurement of physical activity

    Directory of Open Access Journals (Sweden)

    Tuomo T Tompuri

    2015-08-01

    Full Text Available Physical activity refers any bodily movements produced by skeletal muscles that expends energy. Hence the amount and the intensity of physical activity can be assessed by energy expenditure. Metabolic equivalents of task (MET are multiplies of the resting metabolism reflecting metabolic rate during exercise. The standard MET is defined as 3.5 ml/min/kg. However, the expression of energy expenditure by body weight to normalize the size differences between subjects causes analytical hazards: scaling by body weight does not have a physiological, mathematical, or physical rationale. This review demonstrates by examples that false methodology may cause paradoxical observations if physical activity would be assessed by body weight scaled values such as standard METs. While standard METs are confounded by adiposity, lean mass proportional measures of energy expenditure would enable a more truthful choice to assess physical activity. While physical activity as a behavior and cardiorespiratory fitness or adiposity as a state represents major determinants of public health, specific measurements of health determinants must be understood to enable a truthful evaluation of the interactions and their independent role as a health predictor.

  10. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

    Science.gov (United States)

    Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M.; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N.

    2014-01-01

    The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α)–dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level. PMID:25082895

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Guolin Li

    2018-01-01

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

  13. Physiological community ecology: variation in metabolic activity of ecologically important rocky intertidal invertebrates along environmental gradients.

    Science.gov (United States)

    Dahlhoff, Elizabeth P; Stillman, Jonathon H; Menge, Bruce A

    2002-08-01

    Rocky intertidal invertebrates live in heterogeneous habitats characterized by steep gradients in wave activity, tidal flux, temperature, food quality and food availability. These environmental factors impact metabolic activity via changes in energy input and stress-induced alteration of energetic demands. For keystone species, small environmentally induced shifts in metabolic activity may lead to disproportionately large impacts on community structure via changes in growth or survival of these key species. Here we use biochemical indicators to assess how natural differences in wave exposure, temperature and food availability may affect metabolic activity of mussels, barnacles, whelks and sea stars living at rocky intertidal sites with different physical and oceanographic characteristics. We show that oxygen consumption rate is correlated with the activity of key metabolic enzymes (e.g., citrate synthase and malate dehydrogenase) for some intertidal species, and concentrations of these enzymes in certain tissues are lower for starved individuals than for those that are well fed. We also show that the ratio of RNA to DNA (an index of protein synthetic capacity) is highly variable in nature and correlates with short-term changes in food availability. We also observed striking patterns in enzyme activity and RNA/DNA in nature, which are related to differences in rocky intertidal community structure. Differences among species and habitats are most pronounced in summer and are linked to high nearshore productivity at sites favored by suspension feeders and to exposure to stressful low-tide air temperatures in areas of low wave splash. These studies illustrate the great promise of using biochemical indicators to test ecological models, which predict changes in community structure along environmental gradients. Our results also suggest that biochemical indices must be carefully validated with laboratory studies, so that the indicator selected is likely to respond to the

  14. Metabolic activation of pyrrolizidine alkaloids: insights into the structural and enzymatic basis.

    Science.gov (United States)

    Ruan, Jianqing; Yang, Mengbi; Fu, Peter; Ye, Yang; Lin, Ge

    2014-06-16

    Pyrrolizidine alkaloids (PAs) are natural toxins widely distributed in plants. The toxic potencies of different PAs vary significantly. PAs are mono- or diesters of necine acids with a necine base. On the basis of the necine bases, PAs are classified into three types: retronecine-type, otonecine-type, and platynecine-type. Hepatotoxic PAs contain an unsaturated necine base. PAs exert hepatotoxicity through metabolic activation by hepatic cytochromes P450s (CYPs) to generate reactive intermediates which form pyrrole-protein adducts. These adducts provide a mechanism-based biomarker to assess PA toxicity. In the present study, metabolic activation of 12 PAs from three structural types was investigated first in mice to demonstrate significant variations in hepatic metabolic activation of different PAs. Subsequently, the structural and enzymatic factors affecting metabolic activation of these PAs were further investigated by using human liver microsomes and recombinant human CYPs. Pyrrole-protein adducts were detected in the liver and blood of mice and the in vitro systems treated with toxic retronecine-type and otonecine-type PAs having unsaturated necine bases but not with a platynecine-type PA containing a saturated necine base. Retronecine-type PAs produced more pyrrole-protein adducts than otonecine-type PAs with similar necine acids, demonstrating that the structure of necine base affected PA toxic potency. Among retronecine-type PAs, open-ring diesters generated the highest amount of pyrrole-protein adducts, followed by macrocyclic diesters, while monoesters produced the least. Only CYP3A4 and CYP3A5 activated otonecine-type PAs, while all 10 CYPs studied showed the ability to activate retronecine-type PAs. Moreover, the contribution of major CYPs involved also varied significantly among retronecine-type PAs. In conclusion, our findings provide a scientific basis for predicting the toxicities of individual PAs in biological systems based on PA structural

  15. ACT-Vision: active collaborative tracking for multiple PTZ cameras

    Science.gov (United States)

    Broaddus, Christopher; Germano, Thomas; Vandervalk, Nicholas; Divakaran, Ajay; Wu, Shunguang; Sawhney, Harpreet

    2009-04-01

    We describe a novel scalable approach for the management of a large number of Pan-Tilt-Zoom (PTZ) cameras deployed outdoors for persistent tracking of humans and vehicles, without resorting to the large fields of view of associated static cameras. Our system, Active Collaborative Tracking - Vision (ACT-Vision), is essentially a real-time operating system that can control hundreds of PTZ cameras to ensure uninterrupted tracking of target objects while maintaining image quality and coverage of all targets using a minimal number of sensors. The system ensures the visibility of targets between PTZ cameras by using criteria such as distance from sensor and occlusion.

  16. Low resting metabolic rate in exercise-associated amenorrhea is not due to a reduced proportion of highly active metabolic tissue compartments.

    Science.gov (United States)

    Koehler, Karsten; Williams, Nancy I; Mallinson, Rebecca J; Southmayd, Emily A; Allaway, Heather C M; De Souza, Mary Jane

    2016-08-01

    Exercising women with menstrual disturbances frequently display a low resting metabolic rate (RMR) when RMR is expressed relative to body size or lean mass. However, normalizing RMR for body size or lean mass does not account for potential differences in the size of tissue compartments with varying metabolic activities. To explore whether the apparent RMR suppression in women with exercise-associated amenorrhea is a consequence of a lower proportion of highly active metabolic tissue compartments or the result of metabolic adaptations related to energy conservation at the tissue level, RMR and metabolic tissue compartments were compared among exercising women with amenorrhea (AMEN; n = 42) and exercising women with eumenorrheic, ovulatory menstrual cycles (OV; n = 37). RMR was measured using indirect calorimetry and predicted from the size of metabolic tissue compartments as measured by dual-energy X-ray absorptiometry (DEXA). Measured RMR was lower than DEXA-predicted RMR in AMEN (1,215 ± 31 vs. 1,327 ± 18 kcal/day, P < 0.001) but not in OV (1,284 ± 24 vs. 1,252 ± 17, P = 0.16), resulting in a lower ratio of measured to DEXA-predicted RMR in AMEN (91 ± 2%) vs. OV (103 ± 2%, P < 0.001). AMEN displayed proportionally more residual mass (P < 0.001) and less adipose tissue (P = 0.003) compared with OV. A lower ratio of measured to DXA-predicted RMR was associated with lower serum total triiodothyronine (ρ = 0.38, P < 0.001) and leptin (ρ = 0.32, P = 0.004). Our findings suggest that RMR suppression in this population is not the result of a reduced size of highly active metabolic tissue compartments but is due to metabolic and endocrine adaptations at the tissue level that are indicative of energy conservation.

  17. Long-term follow-up of metabolic activity in human alveolar echinococcosis using FDG-PET

    International Nuclear Information System (INIS)

    Reuter, S.; Gruener, B.; Kern, P.; Buck, A.K.; Blumstein, N.; Reske, S.N.

    2008-01-01

    Aim: [ 18 F]fluoro-deoxyglucose positron-emission-tomography (FDG-PET) detects metabolic activity in alveolar echinococcosis (AE). The slow changes in metabolic and morphological characteristics require long-term follow-up of patients. This is the first study to evaluate metabolic activity over may years, hereby assessing the utility of FDG-PET for the evaluation of disease progression and response to treatment. Patients, methods: 15 patients received a follow-up FDG-PET combined with computed tomography (integrated PET/CT) with a median of 6.5 years after the first PET in 1999. Number and location of enhanced metabolic activity in the area of AE lesions was determined. Quantification of intensity of metabolic activity was assessed by calculation of mean standardized uptake values. Results: AE lesions in 11/15 patients had been metabolically inactive initially, but only two showed permanent inactivity over the course of 81 months. Interestingly, in two patients metabolic activity was newly detected after 80 and 82 months. Benzimidazole treatment was intermittently discontinued in seven cases. Persisting activity at FDG-PET demanded continued benzimidazole treatment in four patients. Neither treatment duration, lesional size, calcifications nor regressive changes correlated with metabolic activity. Conclusion: treatment responses are heterogeneous and vary from progressive disease despite treatment to long-term inactive disease with discontinued treatment. Lack of metabolic activity indicates suppressed parasite activity and is not equivalent to parasite death. However, metabolic activity may remain suppressed for years, allowing for temporary treatment discontinuation. Relapses are reliably detected with PET and restarting benzimidazole treatment prevents parasite expansion. (orig.)

  18. Inferring Human Activity in Mobile Devices by Computing Multiple Contexts.

    Science.gov (United States)

    Chen, Ruizhi; Chu, Tianxing; Liu, Keqiang; Liu, Jingbin; Chen, Yuwei

    2015-08-28

    This paper introduces a framework for inferring human activities in mobile devices by computing spatial contexts, temporal contexts, spatiotemporal contexts, and user contexts. A spatial context is a significant location that is defined as a geofence, which can be a node associated with a circle, or a polygon; a temporal context contains time-related information that can be e.g., a local time tag, a time difference between geographical locations, or a timespan; a spatiotemporal context is defined as a dwelling length at a particular spatial context; and a user context includes user-related information that can be the user's mobility contexts, environmental contexts, psychological contexts or social contexts. Using the measurements of the built-in sensors and radio signals in mobile devices, we can snapshot a contextual tuple for every second including aforementioned contexts. Giving a contextual tuple, the framework evaluates the posteriori probability of each candidate activity in real-time using a Naïve Bayes classifier. A large dataset containing 710,436 contextual tuples has been recorded for one week from an experiment carried out at Texas A&M University Corpus Christi with three participants. The test results demonstrate that the multi-context solution significantly outperforms the spatial-context-only solution. A classification accuracy of 61.7% is achieved for the spatial-context-only solution, while 88.8% is achieved for the multi-context solution.

  19. N-3 fatty acids, neuronal activity and energy metabolism in the brain

    Directory of Open Access Journals (Sweden)

    Harbeby Emilie

    2012-07-01

    Full Text Available The content of docosahexaenoic acid (DHA in brain membranes is of crucial importance for the optimum development of brain functions. A lack of DHA accretion in the brain is accompanied by deficits in learning behavior linked to impairments in neurotransmission processes, which might result from alteration of brain fuel supply and hence energy metabolism. Experimental data we published support the hypothesis that n-3 fatty acids may modulate brain glucose utilization and metabolism. Indeed rats made deficient in DHA by severe depletion of total n-3 fatty acid intake have 1 a lower brain glucose utilization, 2 a decrease of the glucose transporter protein content GLUT1 both in endothelial cells and in astrocytes, 3 a repression of GLUT1 gene expression in basal state as well as upon neuronal activation. This could be due to the specific action of DHA on the regulation of GLUT1 expression since rat brain endothelial cells cultured with physiological doses of DHA had an increased GLUT1 protein content and glucose transport when compared to non-supplemented cells. These experimental data highlight the impact of n-3 fatty acids on the use of brain glucose, thereby constituting a key factor in the control of synaptic activity. This emerging role suggests that dietary intake of n-3 fatty acids can help to reduce the cognitive deficits in the elderly and possibly symptomatic cerebral metabolic alterations in Alzheimer disease by promoting brain glucose metabolism.

  20. Regulation of the yeast metabolic cycle by transcription factors with periodic activities

    Directory of Open Access Journals (Sweden)

    Pellegrini Matteo

    2011-10-01

    Full Text Available Abstract Background When growing budding yeast under continuous, nutrient-limited conditions, over half of yeast genes exhibit periodic expression patterns. Periodicity can also be observed in respiration, in the timing of cell division, as well as in various metabolite levels. Knowing the transcription factors involved in the yeast metabolic cycle is helpful for determining the cascade of regulatory events that cause these patterns. Results Transcription factor activities were estimated by linear regression using time series and genome-wide transcription factor binding data. Time-translation matrices were estimated using least squares and were used to model the interactions between the most significant transcription factors. The top transcription factors have functions involving respiration, cell cycle events, amino acid metabolism and glycolysis. Key regulators of transitions between phases of the yeast metabolic cycle appear to be Hap1, Hap4, Gcn4, Msn4, Swi6 and Adr1. Conclusions Analysis of the phases at which transcription factor activities peak supports previous findings suggesting that the various cellular functions occur during specific phases of the yeast metabolic cycle.

  1. Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation.

    Science.gov (United States)

    Rayssiguier, Yves; Libako, Patrycja; Nowacki, Wojciech; Rock, Edmond

    2010-06-01

    Magnesium (Mg) intake is inadequate in the western diet and metabolic syndrome is highly prevalent in populations around the world. Epidemiological studies suggest that high Mg intake may reduce the risk but the possibility of confounding factors exists, given the strong association between Mg and other beneficial nutriments (vegetables, fibers, cereals). The concept that metabolic syndrome is an inflammatory condition may explain the role of Mg.Mg deficiency results in a stress effect and increased susceptibility to physiological damage produced by stress. Stress activates the hypothalamic-pituitary-adrenal axis (HPA) axis and the sympathetic nervous system. The activation of the renin-angiotensin-aldosterone system is a factor in the development of insulin resistance by increasing oxidative stress. In both humans and rats, aldosteronism results in an immunostimulatory state and leads to an inflammatory phenotype. Stress response induces the release of large quantities of excitatory amino acids and activates the nuclear factor NFkappaB, promoting translation of molecules involved in cell regulation, metabolism and apoptosis. The rise in neuropeptides is also well documented. Stress-induced HPA activation has been identified to play an important role in the preferential body fat accumulation but evidence that Mg is involved in body weight regulation is lacking. One of the earliest events in the acute response to stress is endothelial dysfunction. Endothelial cells actively contribute to inflammation by elaborating cytokines, synthesizing chemical mediators and expressing adhesion molecules. Experimental Mg deficiency in rats induces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, synthesis of inflammatory cytokines and acute phase proteins, extensive production of free radicals. An increase in extracellular Mg concentration decreases inflammatory effects, while reduction in extracellular Mg results in cell activation. The

  2. Independent associations of physical activity and cardiorespiratory fitness with metabolic risk factors in children: the European youth heart study

    DEFF Research Database (Denmark)

    Ekelund, U; Anderssen, S A; Froberg, K

    2007-01-01

    AIMS/HYPOTHESIS: High levels of cardiorespiratory fitness (CRF) and physical activity (PA) are associated with a favourable metabolic risk profile. However, there has been no thorough exploration of the independent contributions of cardiorespiratory fitness and subcomponents of activity (total PA...... the association between activity and clustered risk is independent of adiposity. Our results suggest that fitness and activity affect metabolic risk through different pathways....

  3. BAD-dependent regulation of fuel metabolism and K(ATP) channel activity confers resistance to epileptic seizures.

    Science.gov (United States)

    Giménez-Cassina, Alfredo; Martínez-François, Juan Ramón; Fisher, Jill K; Szlyk, Benjamin; Polak, Klaudia; Wiwczar, Jessica; Tanner, Geoffrey R; Lutas, Andrew; Yellen, Gary; Danial, Nika N

    2012-05-24

    Neuronal excitation can be substantially modulated by alterations in metabolism, as evident from the anticonvulsant effect of diets that reduce glucose utilization and promote ketone body metabolism. We provide genetic evidence that BAD, a protein with dual functions in apoptosis and glucose metabolism, imparts reciprocal effects on metabolism of glucose and ketone bodies in brain cells. These effects involve phosphoregulation of BAD and are independent of its apoptotic function. BAD modifications that reduce glucose metabolism produce a marked increase in the activity of metabolically sensitive K(ATP) channels in neurons, as well as resistance to behavioral and electrographic seizures in vivo. Seizure resistance is reversed by genetic ablation of the K(ATP) channel, implicating the BAD-K(ATP) axis in metabolic control of neuronal excitation and seizure responses. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Effects of prolonged exercise versus multiple short exercise sessions on risk for metabolic syndrome and the atherogenic index in middle-aged obese women: a randomised controlled trial.

    Science.gov (United States)

    Chung, JinWook; Kim, KwangJun; Hong, Jeeyoung; Kong, Hyoun-Joong

    2017-08-22

    Many people, although they may recognise the positive effects of exercise, do not exercise regularly owing to lack of time. This study aimed to investigate the effects of prolonged single-session exercise and multiple short sessions of exercise on the risk of metabolic syndrome and the atherogenic index in middle-aged obese women. Thirty-six participants were divided into the single-session group, multiple-session group, and control group. The single-session group engaged in one session of treadmill exercise for 30 min a day; the multiple-session group had three sessions of 10 min a day. Both groups exercised 3 days/week for 12 weeks. The control group did not perform any exercise. The single-session group showed decreases in weight (0.97 kg [95% C.I. = 0.09-1.83], p exercise is superior to multiple short sessions for improving the risk of metabolic syndrome and the atherogenic index in middle-aged obese women. However, multiple short sessions can be recommended as an alternative to prolonged exercise when the goal is to decrease blood glucose or waist circumference.

  5. Preliminary Evidence that Self-Efficacy Predicts Physical Activity in Multiple Sclerosis

    Science.gov (United States)

    Motl, Robert W.; McAuley, Edward; Doerksen, Shawna; Hu, Liang; Morris, Katherine S.

    2009-01-01

    Individuals with multiple sclerosis (MS) are less physically active than nondiseased people. One method for increasing physical activity levels involves the identification of factors that correlate with physical activity and that are modifiable by a well designed intervention. This study examined two types of self-efficacy as cross-sectional and…

  6. HEART RATE AND PHYSICAL ACTIVITY PATTERNS IN PERSONS WITH PROFOUND INTELLECTUAL AND MULTIPLE DISABILITIES

    NARCIS (Netherlands)

    Waninge, Aly; van der Putten, Annette A. J.; Stewart, Roy E.; Steenbergen, Bert; van Wijck, Ruud; van der Schans, Cees P.

    2013-01-01

    Because physical fitness and health are related to physical activity, it is important to gain an insight into the physical activity levels of persons with profound intellectual and multiple disabilities (PIMD). The purpose of this study was to examine heart rate patterns to measure the activity

  7. Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Katalin Susztak

    2005-02-01

    Full Text Available Diabetic nephropathy (DNP is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced by glycated albumins (AGE-BSA and CML-BSA and free fatty acid palmitate through sequential activation of src kinase, and proapoptotic p38 MAPK and caspase 3. In contrast, paucity of expression of CD36 in PTECs in diabetic mice with diabetic glomerulopathy was associated with normal tubular epithelium and the absence of tubular apoptosis. Mouse PTECs lacked CD36 and were resistant to AGE-BSA-induced apoptosis. Recombinant expression of CD36 in mouse PTECs conferred susceptibility to AGE-BSA-induced apoptosis.Our findings suggest a novel role for CD36 as an essential mediator of proximal tubular apoptosis in human DNP. Because CD36 expression was induced by glucose in PTECs, and because increased CD36 mediated AGE-BSA-, CML-BSA-, and palmitate-induced PTEC apoptosis, we propose a two-step metabolic hit model for TED, a hallmark of progression in DNP.

  8. Motility, ATP levels and metabolic enzyme activity of sperm from bluegill (Lepomis macrochirus).

    Science.gov (United States)

    Burness, Gary; Moyes, Christopher D; Montgomerie, Robert

    2005-01-01

    Male bluegill displays one of two life history tactics. Some males (termed "parentals") delay reproduction until ca. 7 years of age, at which time they build nests and actively courts females. Others mature precociously (sneakers) and obtain fertilizations by cuckolding parental males. In the current study, we studied the relations among sperm motility, ATP levels, and metabolic enzyme activity in parental and sneaker bluegill. In both reproductive tactics, sperm swimming speed and ATP levels declined in parallel over the first 60 s of motility. Although sneaker sperm initially had higher ATP levels than parental sperm, by approximately 30 s postactivation, no differences existed between tactics. No differences were noted between tactics in swimming speed, percent motility, or the activities of key metabolic enzymes, although sperm from parentals had a higher ratio of creatine phosphokinase (CPK) to citrate synthase (CS). In both tactics, with increasing CPK and CS activity, sperm ATP levels increased at 20 s postactivation, suggesting that capacities for phosphocreatine hydrolysis and aerobic metabolism may influence interindividual variation in rates of ATP depletion. Nonetheless, there was no relation between sperm ATP levels and either swimming speed or percent of sperm that were motile. This suggests that interindividual variation in ATP levels may not be the primary determinant of variation in sperm swimming performance in bluegill.

  9. Reactive oxygen species in the paraventricular nucleus of the hypothalamus alter sympathetic activity during metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    JOSIANE CAMPOS CRUZ

    2015-12-01

    Full Text Available The paraventricular nucleus of the hypothalamus (PVN contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II, which activates AT1 receptors in the circumventricular organs (OCVs, mainly in the subfornical organ (SFO. Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS, leading to increases in sympathetic nerve activity (SNA. Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS: dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS.

  10. Fluvoxamine alters the activity of energy metabolism enzymes in the brain

    Directory of Open Access Journals (Sweden)

    Gabriela K. Ferreira

    2014-09-01

    Full Text Available Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent.

  11. Whole-Body MRI versus PET in assessment of multiple myeloma disease activity.

    LENUS (Irish Health Repository)

    Shortt, Conor P

    2009-04-01

    The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bone marrow aspiration and biopsy, to determine the best imaging technique for assessment of disease activity in multiple myeloma.

  12. Memory impairment in multiple sclerosis: Relevance of hippocampal activation and hippocampal connectivity

    NARCIS (Netherlands)

    Hulst, H.E.; Schoonheim, M.M.; van Geest, Q.; Uitdehaag, B.M.J.; Barkhof, F.; Geurts, J.J.G.

    2015-01-01

    Background: Memory impairment is frequent in multiple sclerosis (MS), but it is unclear what functional brain changes underlie this cognitive deterioration. Objective: To investigate functional hippocampal activation and connectivity, in relation to memory performance in MS. Methods: Structural and

  13. Photoperiodism and enzyme activity: towards a model for the control of circadian metabolic rhythms in the crassulacean Acid metabolism.

    Science.gov (United States)

    Queiroz, O; Morel, C

    1974-04-01

    Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system.

  14. Ruptured human Achilles tendon has elevated metabolic activity up to 1 year after repair

    International Nuclear Information System (INIS)

    Eliasson, Pernilla; Couppe, Christian; Magnusson, S.P.; Lonsdale, Markus; Friberg, Lars; Svensson, Rene B.; Kjaer, Michael; Neergaard, Christian

    2016-01-01

    Following Achilles tendon rupture, running is often allowed after 6 months. However, tendon healing is slow and the metabolic status of the tendon at this point is unknown. The purpose of this study was to investigate tendon metabolism (glucose uptake) and vascularization at 3, 6 and 12 months after Achilles tendon rupture as measured using PET and power Doppler ultrasonography (PDUS). The study group comprised 23 patients with surgically repaired Achilles tendon rupture who were investigated at 3 months (n = 7), 6 months (n = 7) and 12 months (n = 9) after surgery. The triceps surae complex was loaded over 20 min of slow treadmill walking while a radioactive tracer ( 18 F-FDG) was administered prior to PET. Vascularization was measured in terms of PDUS flow activity, and patient-reported outcomes were scored using the Achilles tendon rupture score (ATRS) and sports assessment (VISA-A) questionnaire. Relative glucose uptake ( 18 F-FDG) was higher in repaired tendons than in intact tendons at all time-points (6, 3 and 1.6 times higher at 3, 6 and 12 months, respectively; P ≤ 0.001), and was also higher in the tendon core than in the periphery at 3 and 6 months (P ≤ 0.02), but lower at 12 months (P = 0.06). Relative glucose uptake was negatively related to ATRS at 6 months after repair (r = -0.89, P ≤ 0.01). PDUS flow activity was higher in repaired tendons than in intact tendons at 3 and 6 months (P < 0.05 for both), but had normalized by 12 months. These data demonstrate that the healing process as determined by metabolic activity and vascularization continues for 6 months after injury when large loads are typically allowed on the tendon. Indeed, metabolic activity remained elevated for more than 1 year after injury despite normalized vascularization. The robust negative correlation between tendon metabolism and patient-reported outcome suggests that a high metabolic activity 6 months after the injury may be related to a poor clinical healing outcome. (orig.)

  15. Can body mass index, waist circumference, waist-hip ratio and waist-height ratio predict the presence of multiple metabolic risk factors in Chinese subjects?

    Directory of Open Access Journals (Sweden)

    Lu Liping

    2011-01-01

    Full Text Available Abstract Background Obesity is associated with metabolic risk factors. Body mass index (BMI, waist circumference, waist-hip ratio (WHR and waist-height ratio (WHtR are used to predict the risk of obesity related diseases. However, it has not been examined whether these four indicators can detect the clustering of metabolic risk factors in Chinese subjects. Methods There are 772 Chinese subjects in the present study. Metabolic risk factors including high blood pressure, dyslipidemia, and glucose intolerance were identified according to the criteria from WHO. All statistical analyses were performed separately according to sex by using the SPSS 12.0. Results BMI, waist circumference and WHtR values were all significantly associated with blood pressure, glucose, triglyceride and also with the number of metabolic risk factors in both male and female subjects (all of P Conclusion The BMI, waist circumference and WHtR values can similarly predict the presence of multiple metabolic risk factors in Chinese subjects.

  16. [L-arginine metabolism enzyme activities in rat liver subcellular fractions under condition of protein deprivation].

    Science.gov (United States)

    Kopyl'chuk, G P; Buchkovskaia, I M

    2014-01-01

    The features of arginase and NO-synthase pathways of arginine's metabolism have been studied in rat liver subcellular fractions under condition of protein deprivation. During the experimental period (28 days) albino male rats were kept on semi synthetic casein diet AIN-93. The protein deprivation conditions were designed as total absence of protein in the diet and consumption of the diet partially deprived with 1/2 of the casein amount compared to in the regular diet. Daily diet consumption was regulated according to the pair feeding approach. It has been shown that the changes of enzyme activities, involved in L-arginine metabolism, were characterized by 1.4-1.7 fold decrease in arginase activity, accompanied with unchanged NO-synthase activity in cytosol. In mitochondrial fraction the unchanged arginase activity was accompanied by 3-5 fold increase of NO-synthase activity. At the terminal stages of the experiment the monodirectional dynamics in the studied activities have been observed in the mitochondrial and cytosolfractions in both experimental groups. In the studied subcellular fractions arginase activity decreased (2.4-2.7 fold with no protein in the diet and 1.5 fold with partly supplied protein) and was accompanied by NO-synthase activity increase by 3.8 fold in cytosole fraction, by 7.2 fold in mitochondrial fraction in the group with no protein in the diet and by 2.2 and 3.5 fold in the group partialy supplied with protein respectively. The observed tendency is presumably caused by the switch of L-arginine metabolism from arginase into oxidizing NO-synthase parthway.

  17. Metabolism-Activated Multitargeting (MAMUT): An Innovative Multitargeting Approach to Drug Design and Development.

    Science.gov (United States)

    Mátyus, Péter; Chai, Christina L L

    2016-06-20

    Multitargeting is a valuable concept in drug design for the development of effective drugs for the treatment of multifactorial diseases. This concept has most frequently been realized by incorporating two or more pharmacophores into a single hybrid molecule. Many such hybrids, due to the increased molecular size, exhibit unfavorable physicochemical properties leading to adverse effects and/or an inappropriate ADME (absorption, distribution, metabolism, and excretion) profile. To avoid this limitation and achieve additional therapeutic benefits, here we describe a novel multitargeting strategy based on the synergistic effects of a parent drug and its active metabolite(s). The concept of metabolism-activated multitargeting (MAMUT) is illustrated using a number of examples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two......-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover......, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus...

  19. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism.

    Science.gov (United States)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John D R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-04-23

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus of glucose uptake as visualized by functional brain imaging.

  20. BAT Exosomes: Metabolic Crosstalk with Other Organs and Biomarkers for BAT Activity.

    Science.gov (United States)

    Goody, Deborah; Pfeifer, Alexander

    2018-04-10

    In the last decade, exosomes have gained interest as a new type of intercellular communication between cells and tissues. Exosomes are circulating, cell-derived lipid vesicles smaller than 200 nm that contain proteins and nucleic acids, including microRNAs (miRNAs), and are able to modify cellular targets. Exosomal miRNAs function as signalling molecules that regulate the transcription of their target genes and can cause phenotypic transformation of recipient cells. Recent studies have shown that brown fat secretes exosomes as a form of communication with other metabolic organs such as the liver. Moreover, it has been shown that levels of miRNAs in BAT-derived exosomes change after BAT activation in vitro and in vivo. Thus, BAT-derived exosomes can be used as potential biomarkers of BAT activity. Here, we review the present knowledge about BAT-derived exosomes and their role in metabolism.

  1. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism

    Science.gov (United States)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John Douglas R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using 2-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyze the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identifies the neuron as the principal locus of glucose uptake as visualized by functional brain imaging. PMID:25904018

  2. Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Aisha, M.D. [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); Nor-Ashikin, M.N.K. [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor (Malaysia); Sharaniza, A.B.R. [DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor (Malaysia); Nawawi, H. [Center for Pathology Diagnostic and Research Laboratories, Clinical Training Center, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); I-PPerForM, Universiti Teknologi MARA, Selayang 47000 Selangor (Malaysia); Froemming, G.R.A., E-mail: gabriele@salam.uitm.edu.my [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); I-PPerForM, Universiti Teknologi MARA, Selayang 47000 Selangor (Malaysia)

    2015-09-10

    Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases. - Highlights: • OFS stress transmits anabolic signals to osteoblasts. • Actin and tubulin fibers are rearranged under OFS stress. • OFS stress increases mitochondrial metabolism and proliferation. • Reduced RANKL/OPG ratio in response to OFS inhibits osteoclastogenesis. • OFS stress prevents apoptosis and stimulates ALP and OCN.

  3. Poly(adenosine 5'-diphosphate) ribose polymerase activation as a cause of metabolic dysfunction in critical illness.

    Science.gov (United States)

    Liaudet, Lucas

    2002-03-01

    Poly(adenosine 5'-diphosphate) ribose polymerase is a nuclear enzyme activated in response to genotoxic stress induced by a variety of DNA damaging agents. Several oxygen and nitrogen-centered free radicals, notably peroxynitrite, are strong inducers of DNA damage and poly(adenosine 5'-diphosphate) ribose polymerase activation in vitro and in vivo. Activation of this nuclear enzyme depletes the intracellular stores of its substrate nicotinamide adenine dinucleotide, slowing the rate of glycolysis, mitochondrial electron transport and adenosine triphosphate formation. This process triggers a severe energetic crisis within the cell, leading to acute cell dysfunction and cell necrosis. Poly(adenosine 5'-diphosphate) ribose polymerase also plays an important role in the regulation of inflammatory cascades, through a functional association with various transcription factors and transcription co-activators. Recent works identified this enzyme as a critical mediator of cellular metabolic dysfunction, inflammatory injury, and organ damage in conditions associated with overwhelming oxidative stress, including systemic inflammation, circulatory shock, and ischemia-reperfusion. Accordingly, pharmacological inhibitors of poly(adenosine 5'-diphosphate) ribose polymerase protect against cell death and tissue injury in such conditions, and may therefore represent novel therapeutic tools to limit multiple organ damage and dysfunction in critically ill patients.

  4. Metabolic mapping of functional activity in human subjects with the [18F]fluorodeoxyglucose technique

    International Nuclear Information System (INIS)

    Greenberg, J.H.; Reivich, M.; Alavi, A.

    1981-01-01

    The 2-[ 18 F]fluoro-2-deoxy-D-glucose technique was used to measure regional cerebral glucose utilization by human subjects during functional activation. Normal male volunteers subjected to one or more sensory stimuli exhibited focal increases in glucose metabolism in response to the stimulus. These results demonstrate that the technique is capable of providing functional maps in vivo related to both body region and submodality of sensory information in the human brain

  5. Radiometric detection of metabolic activity of Paracoccidiodes brasiliensis and its susceptibility to amphotericin B and Diethylstilbestrol

    International Nuclear Information System (INIS)

    Camargo, E.E.; Sato, M.K.; Del Negro, G.M.B.; Lacaz, C.S.

    1987-01-01

    A radiometric assay system has been applied to study the metabolic activity and the effect of drugs (amphotericin B and diethylstilbestrol) on the fungus Paracoccidiodes brasiliensis ''in vitro''. The Y form of the yeast, grown in liquid Sabouraud medium was inoculated into sterile reaction vials containing the 6B aerobic medium along with 2.0μCi of 14 C-substrates. (M.A.C.) [pt

  6. Bace1 activity impairs neuronal glucose metabolism: rescue by beta-hydroxybutyrate and lipoic acid

    Directory of Open Access Journals (Sweden)

    John A Findlay

    2015-10-01

    Full Text Available Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1, responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

  7. Self-Care Activities among People with Multiple Sclerosis in Denmark

    DEFF Research Database (Denmark)

    Lynning, Marie; Hanehøj, Kirsten; Karnøe Knudsen, Astrid

    2017-01-01

    Background: People with multiple sclerosis (PwMS) are known to use a wide range of medical and non-medical treatments. This study aims at investigating the use of self-care activities within this patient group. Material and Methods: The study follows a descriptive cross-sectional design based...... on an online survey among members of the Danish Multiple Sclerosis Society's permanent respondent panel. Results: The results of the study indicate that the respondents carry out a wide variety of self-care activities. These activities comprise conventional activities as well as complementary and alternative...

  8. [Interaction between CYP450 enzymes and metabolism of traditional Chinese medicine as well as enzyme activity assay].

    Science.gov (United States)

    Lu, Tu-lin; Su, Lian-lin; Ji, De; Gu, Wei; Mao, Chun-qin

    2015-09-01

    Drugs are exogenous compounds for human bodies, and will be metabolized by many enzymes after administration. CYP450 enzyme, as a major metabolic enzyme, is an important phase I drug metabolizing enzyme. In human bodies, about 75% of drug metabolism is conducted by CYP450 enzymes, and CYP450 enzymes is the key factor for drug interactions between traditional Chinese medicine( TCM) -TCM, TCM-medicine and other drug combination. In order to make clear the interaction between metabolic enzymes and TCM metabolism, we generally chose the enzymatic activity as an evaluation index. That is to say, the enhancement or reduction of CYP450 enzyme activity was used to infer the inducing or inhibitory effect of active ingredients and extracts of traditional Chinese medicine on enzymes. At present, the common method for measuring metabolic enzyme activity is Cocktail probe drugs, and it is the key to select the suitable probe substrates. This is of great significance for study drug's absorption, distribution, metabolism and excretion (ADME) process in organisms. The study focuses on the interaction between TCMs, active ingredients, herbal extracts, cocktail probe substrates as well as CYP450 enzymes, in order to guide future studies.

  9. The interpretation of physical activity, exercise, and sedentary behaviours by persons with multiple sclerosis.

    Science.gov (United States)

    Kinnett-Hopkins, Dominique; Learmonth, Yvonne; Hubbard, Elizabeth; Pilutti, Lara; Roberts, Sarah; Fanning, Jason; Wójcicki, Thomas; McAuley, Edward; Motl, Robert

    2017-11-07

    This study adopted a qualitative research design with directed content analysis and examined the interpretations of physical activity, exercise, and sedentary behaviour by persons with multiple sclerosis. Fifty three persons with multiple sclerosis who were enrolled in an exercise trial took part in semi-structured interviews regarding personal interpretations of physical activity, exercise, and sedentary behaviours. Forty three percent of participants indicated a consistent understanding of physical activity, 42% of participants indicated a consistent understanding of exercise, and 83% of participants indicated a consistent understanding of sedentary behaviour with the standard definitions. There was evidence of definitional ambiguity (i.e., 57, 58, and 11% of the sample for physical activity, exercise, and sedentary behaviour, respectively); 6% of the sample inconsistently defined sedentary behaviour with standard definitions. Some participants described physical activity in a manner that more closely aligned with exercise and confused sedentary behaviour with exercise or sleeping/napping. Results highlight the need to provide and utilise consistent definitions for accurate understanding, proper evaluation and communication of physical activity, exercise, and sedentary behaviours among persons with multiple sclerosis. The application of consistent definitions may minimise ambiguity, alleviate the equivocality of findings in the literature, and translate into improved communication about these behaviours in multiple sclerosis. Implications for Rehabilitation The symptoms of multiple sclerosis can be managed through participation in physical activity and exercise. Persons with multiple sclerosis are not engaging in sufficient levels of physical activity and exercise for health benefits. Rehabilitation professionals should use established definitions of physical activity, exercise, and sedentary behaviours when communicating about these behaviours among persons with

  10. Manipulation of dopamine metabolism contributes to attenuating innate high locomotor activity in ICR mice.

    Science.gov (United States)

    Yamaguchi, Takeshi; Nagasawa, Mao; Ikeda, Hiromi; Kodaira, Momoko; Minaminaka, Kimie; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

    2017-06-15

    Attention-deficit hyperactivity disorder (ADHD) is defined as attention deficiency, restlessness and distraction. The main characteristics of ADHD are hyperactivity, impulsiveness and carelessness. There is a possibility that these abnormal behaviors, in particular hyperactivity, are derived from abnormal dopamine (DA) neurotransmission. To elucidate the mechanism of high locomotor activity, the relationship between innate activity levels and brain monoamines and amino acids was investigated in this study. Differences in locomotor activity between ICR, C57BL/6J and CBA/N mice were determined using the open field test. Among the three strains, ICR mice showed the greatest amount of locomotor activity. The level of striatal and cerebellar DA was lower in ICR mice than in C57BL/6J mice, while the level of L-tyrosine (L-Tyr), a DA precursor, was higher in ICR mice. These results suggest that the metabolic conversion of L-Tyr to DA is lower in ICR mice than it is in C57BL/6J mice. Next, the effects of intraperitoneal injection of (6R)-5, 6, 7, 8-tetrahydro-l-biopterin dihydrochloride (BH 4 ) (a co-enzyme for tyrosine hydroxylase) and L-3,4-dihydroxyphenylalanine (L-DOPA) on DA metabolism and behavior in ICR mice were investigated. The DA level in the brain was increased by BH 4 administration, but the increased DA did not influence behavior. However, L-DOPA administration drastically lowered locomotor activity and increased DA concentration in several parts of the brain. The reduced locomotor activity may have been a consequence of the overproduction of DA. In conclusion, the high level of locomotor activity in ICR mice may be explained by a strain-specific DA metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: A review

    International Nuclear Information System (INIS)

    Xue Weiling; Warshawsky, David

    2005-01-01

    Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic compounds (HACs) constitute a major class of chemical carcinogens present in the environment. These compounds require activation to electrophilic metabolites to exert their mutagenic or carcinogenic effects. There are three principal pathways currently proposed for metabolic activation of PAH and HAC: the pathway via bay region dihydrodiol epoxide by cytochrome P450 enzymes (CYPs), the pathway via radical cation by one-electron oxidation, and the ortho-quinone pathway by dihydrodiol dehydrogenase (DD). In addition to these major pathways, a brief description of a minor metabolic activation pathway, sulfonation, for PAHs that contain a primary benzylic alcoholic group or secondary hydroxyl group(s) is included in this review. The DNA damages caused through the reactive metabolites of PAH/HAC are described involving the DNA covalent binding to form stable or depurinating adducts, the formation of apurinic sites, and the oxidative damage. The review emphasizes the chemical/biochemical reactions involved in the metabolic processes and the chemical structures of metabolites and DNA adducts

  12. Metabolic activity in dormant conidia of Aspergillus niger and developmental changes during conidial outgrowth.

    Science.gov (United States)

    Novodvorska, Michaela; Stratford, Malcolm; Blythe, Martin J; Wilson, Raymond; Beniston, Richard G; Archer, David B

    2016-09-01

    The early stages of development of Aspergillus niger conidia during outgrowth were explored by combining genome-wide gene expression analysis (RNAseq), proteomics, Warburg manometry and uptake studies. Resting conidia suspended in water were demonstrated for the first time to be metabolically active as low levels of oxygen uptake and the generation of carbon dioxide were detected, suggesting that low-level respiratory metabolism occurs in conidia for maintenance. Upon triggering of spore germination, generation of CO2 increased dramatically. For a short period, which coincided with mobilisation of the intracellular polyol, trehalose, there was no increase in uptake of O2 indicating that trehalose was metabolised by fermentation. Data from genome-wide mRNA profiling showed the presence of transcripts associated with fermentative and respiratory metabolism in resting conidia. Following triggering of conidial outgrowth, there was a clear switch to respiration after 25min, confirmed by cyanide inhibition. No effect of SHAM, salicylhydroxamic acid, on respiration suggests electron flow via cytochrome c oxidase. Glucose entry into spores was not detectable before 1h after triggering germination. The impact of sorbic acid on germination was examined and we showed that it inhibits glucose uptake. O2 uptake was also inhibited, delaying the onset of respiration and extending the period of fermentation. In conclusion, we show that conidia suspended in water are not completely dormant and that conidial outgrowth involves fermentative metabolism that precedes respiration. Copyright © 2016. Published by Elsevier Inc.

  13. Changes in element accumulation, phenolic metabolism, and antioxidative enzyme activities in the red-skin roots of Panax ginseng.

    Science.gov (United States)

    Zhou, Ying; Yang, Zhenming; Gao, Lingling; Liu, Wen; Liu, Rongkun; Zhao, Junting; You, Jiangfeng

    2017-07-01

    Red-skin root disease has seriously decreased the quality and production of Panax ginseng (ginseng). To explore the disease's origin, comparative analysis was performed in different parts of the plant, particularly the epidermis, cortex, and/or fibrous roots of 5-yr-old healthy and diseased red-skin ginseng. The inorganic element composition, phenolic compound concentration, reactive oxidation system, antioxidant concentrations such as ascorbate and glutathione, activities of enzymes related to phenolic metabolism and oxidation, and antioxidative system particularly the ascorbate-glutathione cycle were examined using conventional methods. Aluminum (Al), iron (Fe), magnesium, and phosphorus were increased, whereas manganese was unchanged and calcium was decreased in the epidermis and fibrous root of red-skin ginseng, which also contained higher levels of phenolic compounds, higher activities of the phenolic compound-synthesizing enzyme phenylalanine ammonia-lyase and the phenolic compound oxidation-related enzymes guaiacol peroxidase and polyphenoloxidase. As the substrate of guaiacol peroxidase, higher levels of H 2 O 2 and correspondingly higher activities of superoxide dismutase and catalase were found in red-skin ginseng. Increased levels of ascorbate and glutathione; increased activities of l-galactose 1-dehydrogenase, ascorbate peroxidase, ascorbic acid oxidase, and glutathione reductase; and lower activities of dehydroascorbate reductase, monodehydroascorbate reductase, and glutathione peroxidase were found in red-skin ginseng. Glutathione- S -transferase activity remained constant. Hence, higher element accumulation, particularly Al and Fe, activated multiple enzymes related to accumulation of phenolic compounds and their oxidation. This might contribute to red-skin symptoms in ginseng. It is proposed that antioxidant and antioxidative enzymes, especially those involved in ascorbate-glutathione cycles, are activated to protect against phenolic compound

  14. Intrinsic Xenobiotic Metabolizing Enzyme Activities in Early Life Stages of Zebrafish (Danio rerio).

    Science.gov (United States)

    Otte, Jens C; Schultz, Bernadette; Fruth, Daniela; Fabian, Eric; van Ravenzwaay, Bennard; Hidding, Björn; Salinas, Edward R

    2017-09-01

    Early life stages of zebrafish (Danio rerio, zf) are gaining attention as an alternative invivo test system for drug discovery, early developmental toxicity screenings and chemical testing in ecotoxicological and toxicological testing strategies. Previous studies have demonstrated transcriptional evidence for xenobiotic metabolizing enzymes (XME) during early zf development. However, elaborate experiments on XME activities during development are incomplete. In this work, the intrinsic activities of representative phase I and II XME were monitored by transformation of putative zf model substrates analyzed using photometry and high pressure liquid chromatography techniques. Six different defined stages of zf development (between 2.5 h postfertilization (hpf) to 120 hpf) were investigated by preparing a subcellular fraction from whole organism homogenates. We demonstrated that zf embryos as early as 2.5 hpf possess intrinsic metabolic activities for esterase, Aldh, Gst, and Cyp1a above the methodological detection limit. The activities of the enzymes Cyp3a and Nat were measurable during later stages in development. Activities represent dynamic patterns during development. The role of XME activities revealed in this work is relevant for the assessing toxicity in this test system and therefore contributes to a valuable characterization of zf embryos as an alternative testing organism in toxicology. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. The relationship between microbial metabolic activity and biocorrosion of carbon steel.

    Science.gov (United States)

    Dzierzewicz, Z; Cwalina, B; Chodurek, E; Wilczok, T

    1997-12-01

    The effect of metabolic activity (expressed by generation time, rate of H2S production and the activity of hydrogenase and adenosine phosphosulphate (APS)-reductase enzymes) of the 8 wild strains of Desulfovibrio desulfuricans and of their resistance to metal ions (Hg2+, Cu2+, Mn2+, Zn2+, Ni2+, Cr3+) on the rate of corrosion of carbon steel was studied. The medium containing lactate as the carbon source and sulphate as the electron acceptor was used for bacterial metabolic activity examination and in corrosive assays. Bacterial growth inhibition by metal ions was investigated in the sulphate-free medium. The rate of H2S production was approximately directly proportional to the specific activities of the investigated enzymes. These activities were inversely proportional to the generation time. The rate of microbiologically induced corrosion (MIC) of carbon steel was directly proportional to bacterial resistance to metal ions (correlation coefficient r = 0.95). The correlation between the MIC rate and the activity of enzymes tested, although weaker, was also observed (r = 0.41 for APS-reductase; r = 0.69 for hydrogenase; critical value rc = 0.30, p = 0.05, n = 40).

  16. Kynurenine pathway metabolic balance influences microglia activity: Targeting kynurenine monooxygenase to dampen neuroinflammation.

    Science.gov (United States)

    Garrison, Allison M; Parrott, Jennifer M; Tuñon, Arnulfo; Delgado, Jennifer; Redus, Laney; O'Connor, Jason C

    2018-08-01

    Chronic stress or inflammation increases tryptophan metabolism along the kynurenine pathway (KP), and the generation of neuroactive kynurenine metabolites contributes to subsequent depressive-like behaviors. Microglia regulate KP balance by preferentially producing oxidative metabolites, including quinolinic acid. Research has focused on the interplay between cytokines and HPA axis-derived corticosteroids in regulating microglial activity and effects of KP metabolites directly on neurons; however, the potential role that KP metabolites have directly on microglial activity is unknown. Here, murine microglia were stimulated with lipopolysaccharide(LPS). After 6 h, mRNA expression of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α and inducible nitric oxide synthase(iNOS) was dose-dependently increased along with the rate-limiting enzymes for oxidative KP metabolism, indoleamine-2,3-dioxygenase(IDO)-1 and kynurenine 3-monooxygenase(KMO). By 24 h post-LPS, kynurenine and quinolinic acid in the media was elevated. Inhibiting KMO with Ro 61-8048 during LPS challenge attenuated extracellular nitrite accumulation and expression of KMO and TNF-α in response to LPS. Similarly, primary microglia isolated from KMO -/- mice exhibited a significantly reduced pro-inflammatory response to LPS compared to WT controls. To determine whether the substrate (kynurenine) or end product (quinolinic acid) of KMO-dependent metabolism modulates the LPS response, microglia were treated with increasing concentrations of L-kynurenine or quinolinic acid in combination with LPS or saline. Interestingly, quinolinic acid did not impact the microglial LPS response. However, L-kynurenine had dose-dependent inhibitory effect on the LPS response. These data are the first to show an anti-inflammatory effect of KMO inhibition on microglia during immune challenge and suggest that KP metabolic balance may play a direct role in regulating microglia activity. Published by Elsevier Ltd.

  17. Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation

    NARCIS (Netherlands)

    Feige, Jérôme N.; Lagouge, Marie; Canto, Carles; Strehle, Axelle; Houten, Sander M.; Milne, Jill C.; Lambert, Philip D.; Mataki, Chikage; Elliott, Peter J.; Auwerx, Johan

    2008-01-01

    The NAD(+)-dependent deacetylase SIRT1 controls metabolic processes in response to low nutrient availability. We report the metabolic phenotype of mice treated with SRT1720, a specific and potent synthetic activator of SIRT1 that is devoid of direct action on AMPK. SRT1720 administration robustly

  18. [Important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of active ingredients of Chinese materia medica].

    Science.gov (United States)

    Bi, Xiaolin; Du, Qiu; Di, Liuqing

    2010-02-01

    Oral drug bioavailability depends on gastrointestinal absorption, intestinal transporters and metabolism enzymes are the important factors in drug gastrointestinal absorption and they can also be induced or inhibited by the active ingredients of Chinese materia medica. This article presents important application of intestinal transporters and metabolism enzymes on gastrointestinal disposal of the active ingredients of Chinese materia medica, and points out the importance of research on transport and metabolism of the active ingredients of Chinese materia medica in Chinese extract and Chinese medicinal formulae.

  19. Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite.

    Directory of Open Access Journals (Sweden)

    Varsha Agarwal

    2008-06-01

    Full Text Available Cytochrome P450 (P450 is a super-family of drug metabolizing enzymes. P450 enzymes have dual function; they can metabolize drugs to pharmacologically inactive metabolites facilitating their excretion or biotransform them to pharmacologically active metabolites which may have longer half-life than the parent drug. The variable pharmacological response to psychoactive drugs typically seen in population groups is often not accountable by considering dissimilarities in hepatic metabolism. Metabolism in brain specific nuclei may play a role in pharmacological modulation of drugs acting on the CNS and help explain some of the diverse response to these drugs seen in patient population. P450 enzymes are also present in brain where drug metabolism can take place and modify therapeutic action of drugs at the site of action. We have earlier demonstrated an intrinsic difference in the biotransformation of alprazolam (ALP in brain and liver, relatively more alpha-hydroxy alprazolam (alpha-OHALP is formed in brain as compared to liver. In the present study we show that recombinant CYP3A43 metabolizes ALP to both alpha-OHALP and 4-hydroxy alprazolam (4-OHALP while CYP3A4 metabolizes ALP predominantly to its inactive metabolite, 4-OHALP. The expression of CYP3A43 mRNA in human brain samples correlates with formation of relatively higher levels of alpha-OH ALP indicating that individuals who express higher levels of CYP3A43 in the brain would generate larger amounts of alpha-OHALP. Further, the expression of CYP3A43 was relatively higher in brain as compared to liver across different ethnic populations. Since CYP3A enzymes play a prominent role in the metabolism of drugs, the higher expression of CYP3A43 would generate metabolite profile of drugs differentially in human brain and thus impact the pharmacodynamics of psychoactive drugs at the site of action.

  20. Are barriers to physical activity similar for adults with and without abnormal glucose metabolism?

    Science.gov (United States)

    Hume, Clare; Dunstan, David; Salmon, Jo; Healy, Genevieve; Andrianopoulos, Nick; Owen, Neville

    2010-01-01

    The purpose of this study was to examine perceived barriers to physical activity among adults with and without abnormal glucose metabolism (AGM), and whether barriers varied according to physical activity status. The 1999 to 2000 Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based cross-sectional study among adults aged > or =25 years. AGM was identified through an oral glucose tolerance test. The previous week's physical activity and individual, social, and environmental barriers to physical activity were self-reported. Logistic regression analyses examined differences in barriers to physical activity between those with and without AGM, and for those with and without AGM who did and did not meet the minimum recommendation of 150 minutes/week of moderate-to-vigorous intensity physical activity. Of the 7088 participants (47.5 +/- 12.7 years; 46% male), 18.5% had AGM. Approximately 47.5% of those with AGM met the physical activity recommendation, compared to 54.7% of those without AGM (P barriers to physical activity included lack of time, other priorities, and being tired. Following adjustment for sociodemographic and behavioral factors, there were few differences in barriers to physical activity between those with and without AGM, even after stratifying according to physical activity. Adults with AGM report similar barriers to physical activity, as do those without AGM. Programs for those with AGM can therefore focus on the known generic adult-reported barriers to physical activity.

  1. Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets

    Science.gov (United States)

    Corona de la Peña, Norma; Gutiérrez-Aguilar, Manuel; Hernández-Reséndiz, Ileana; Marín-Hernández, Álvaro

    2017-01-01

    Thrombin-induced platelet activation requires substantial amounts of ATP. However, the specific contribution of each ATP-generating pathway i.e., oxidative phosphorylation (OxPhos) versus glycolysis and the biochemical mechanisms involved in the thrombin-induced activation of energy metabolism remain unclear. Here we report an integral analysis on the role of both energy pathways in human platelets activated by several agonists, and the signal transducing mechanisms associated with such activation. We found that thrombin, Trap-6, arachidonic acid, collagen, A23187, epinephrine and ADP significantly increased glycolytic flux (3–38 times vs. non-activated platelets) whereas ristocetin was ineffective. OxPhos (33 times) and mitochondrial transmembrane potential (88%) were increased only by thrombin. OxPhos was the main source of ATP in thrombin-activated platelets, whereas in platelets activated by any of the other agonists, glycolysis was the principal ATP supplier. In order to establish the biochemical mechanisms involved in the thrombin-induced OxPhos activation in platelets, several signaling pathways associated with mitochondrial activation were analyzed. Wortmannin and LY294002 (PI3K/Akt pathway inhibitors), ristocetin and heparin (GPIb inhibitors) as well as resveratrol, ATP (calcium-release inhibitors) and PP1 (Tyr-phosphorylation inhibitor) prevented the thrombin-induced platelet activation. These results suggest that thrombin activates OxPhos and glycolysis through GPIb-dependent signaling involving PI3K and Akt activation, calcium mobilization and protein phosphorylation. PMID:28817667

  2. Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism in the left ventricle

    DEFF Research Database (Denmark)

    Langfort, Jozef; Jagsz, Slawomir; Dobrzyn, Pawel

    2010-01-01

    tissue suggests that testosterone regulates HSL activity. To test whether this is also true in the heart, we measured HSL activity in the left ventricle of sedentary male rats that had been treated with testosterone supplementation or orchidectomy with or without testosterone substitution. Left ventricle...... HSL activity against TG was significantly elevated in intact rats supplemented with testosterone. HSL activity against both TG and diacylglyceride was reduced by orchidectomy, whereas testosterone replacement fully reversed this effect. Moreover, testosterone increased left ventricle free fatty acid...... levels, caused an inhibitory effect on carbohydrate metabolism in the heart, and elevated left ventricular phosphocreatine and ATP levels as compared to control rats. These data indicate that testosterone is involved in cardiac HSL activity regulation which, in turn, may affect cardiac lipid...

  3. Influence of carbofuran on certain metabolic and symbiotic activities of a cowpea Rhizobium

    International Nuclear Information System (INIS)

    Palaniappan, S.; Balasubramanian, A.

    1983-01-01

    Using carbon 14 radioisotope an in-vitro study of the effect of insecticides, carbofuran, on the metabolic and symbiotic activities of Rhizobium sp. cowpea group, was carried out. The study indicated that at 10 ppm carbofuran inhibited the in-vitro growth of the bacterium, suppressed the oxidation of all the Trichloroacetic acid (TCA) cycle intermediates, significantly reduced glucose oxidation and translocation and affected the growth and symbiotic activities of the cowpea as reflected by a reduction in the dry matter production and total nitrogen content. The insecticide was itself degraded by the Rhizobium sp. within 30 days of incubation

  4. The relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity.

    Science.gov (United States)

    Keleş, Erol; Kapusuz, Zeliha; Gürsu, Mehmet Ferit; Karlıdag, Turgut; Kaygusuz, Irfan; Bulmuş, Funda Gülcü; Yalcın, Sinasi

    2014-01-01

    To determine the presence of a relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity. A total of 30 patients who had been admitted to the Ear, Nose, and Throat (ENT) Clinic of Fırat University Medical Faculty and diagnosed as metabolic presbycusis were included in the study. The control group was composed of 30 healthy volunteers. Pure tone audiometry and impedencemeter were performed on all subjects included in the study at the audiometry laboratory of the ENT clinic. The presence of a regular hearing curve, a symmetrical sensorineural hearing loss more than 25 dB with preserved speech discrimination were accepted as criteria for metabolic presbycusis. Blood samples were drawn from the patients prior to the hearing tests. The sera were separated for measurements of total cholesterol, triglyceride, high-density lipoprotein, very low-density lipoprotein, low-density lipoprotein, human serum paraoxonase and arylesterase levels, respectively. No statistically significant difference was found between the patient and the control groups in terms of age and gender. Paraoxonase, arylesterase and paraoxonase/arylesterase, high-density lipoprotein levels were found to decrease in the study group and the difference was found to be statistically significant compared to the control group (P presbycusis. Furthermore, the results of this study make us think that there could be a relationship between metabolic presbycusis and cardiovascular diseases. In this case, metabolic presbycusis may be a determining parameter in the early diagnosis of cardiovascular diseases. We consider that this study may be the pioneer for further studies conducted with larger patient numbers.

  5. Cortical activity during olfactory stimulation in multiple chemical sensitivity: a 18F-FDG PET/CT study

    International Nuclear Information System (INIS)

    Chiaravalloti, Agostino; Di Pietro, Barbara; Pagani, Marco; Micarelli, Alessandro; Alessandrini, Marco; Genovesi, Giuseppe; Schillaci, Orazio

    2015-01-01

    To investigate the differences in brain glucose consumption during olfactory stimulation between subjects affected by multiple chemical sensitivity (MCS) and a group of healthy individuals. Two 18 F-FDG PET/CT scans were performed in 26 subjects (6 men and 20 women; mean age 46.7 ± 11 years) with a clinical diagnosis of MCS and in 11 healthy controls (6 women and 5 men; mean age 45.7 ± 11 years), the first scan after a neutral olfactory stimulation (NS) and the second after a pure olfactory stimulation (OS). Differences in 18 F-FDG uptake were analysed by statistical parametric mapping (SPM2). In controls OS led to an increase in glucose consumption in BA 18 and 19 and a reduction in glucose metabolism in BA 10, 11, 32 and 47. In MCS subjects, OS led to an increase in glucose consumption in BA 20, 23, 18 and 37 and a reduction in glucose metabolism in BA 8, 9 and 10. The results of our study suggest that cortical activity in subjects with MCS differs from that in healthy individuals during olfactory stimulation. (orig.)

  6. Cortical activity during olfactory stimulation in multiple chemical sensitivity: a {sup 18}F-FDG PET/CT study

    Energy Technology Data Exchange (ETDEWEB)

    Chiaravalloti, Agostino; Di Pietro, Barbara [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy); Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Department of Nuclear Medicine Karolinska Hospital Stockholm, Stockholm (Sweden); Micarelli, Alessandro; Alessandrini, Marco [University Tor Vergata, Department of Medical Science and Translational Medicine, Rome (Italy); Genovesi, Giuseppe [University La Sapienza, Department of Experimental Medicine, Rome (Italy); University La Sapienza, Regional Center for Diagnosis, Treatment and Prevention of MCS, Rome (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy); IRCCS Neuromed, Pozzilli (Italy)

    2015-04-01

    To investigate the differences in brain glucose consumption during olfactory stimulation between subjects affected by multiple chemical sensitivity (MCS) and a group of healthy individuals. Two {sup 18}F-FDG PET/CT scans were performed in 26 subjects (6 men and 20 women; mean age 46.7 ± 11 years) with a clinical diagnosis of MCS and in 11 healthy controls (6 women and 5 men; mean age 45.7 ± 11 years), the first scan after a neutral olfactory stimulation (NS) and the second after a pure olfactory stimulation (OS). Differences in {sup 18}F-FDG uptake were analysed by statistical parametric mapping (SPM2). In controls OS led to an increase in glucose consumption in BA 18 and 19 and a reduction in glucose metabolism in BA 10, 11, 32 and 47. In MCS subjects, OS led to an increase in glucose consumption in BA 20, 23, 18 and 37 and a reduction in glucose metabolism in BA 8, 9 and 10. The results of our study suggest that cortical activity in subjects with MCS differs from that in healthy individuals during olfactory stimulation. (orig.)

  7. Cortical activity during olfactory stimulation in multiple chemical sensitivity: a (18)F-FDG PET/CT study.

    Science.gov (United States)

    Chiaravalloti, Agostino; Pagani, Marco; Micarelli, Alessandro; Di Pietro, Barbara; Genovesi, Giuseppe; Alessandrini, Marco; Schillaci, Orazio

    2015-04-01

    To investigate the differences in brain glucose consumption during olfactory stimulation between subjects affected by multiple chemical sensitivity (MCS) and a group of healthy individuals. Two (18)F-FDG PET/CT scans were performed in 26 subjects (6 men and 20 women; mean age 46.7 ± 11 years) with a clinical diagnosis of MCS and in 11 healthy controls (6 women and 5 men; mean age 45.7 ± 11 years), the first scan after a neutral olfactory stimulation (NS) and the second after a pure olfactory stimulation (OS). Differences in (18)F-FDG uptake were analysed by statistical parametric mapping (SPM2). In controls OS led to an increase in glucose consumption in BA 18 and 19 and a reduction in glucose metabolism in BA 10, 11, 32 and 47. In MCS subjects, OS led to an increase in glucose consumption in BA 20, 23, 18 and 37 and a reduction in glucose metabolism in BA 8, 9 and 10. The results of our study suggest that cortical activity in subjects with MCS differs from that in healthy individuals during olfactory stimulation.

  8. Physical activity and not sedentary time per se influences on clustered metabolic risk in elderly community-dwelling women.

    Directory of Open Access Journals (Sweden)

    Andreas Nilsson

    Full Text Available Whether amount of time spent in sedentary activities influences on clustered metabolic risk in elderly, and to what extent such an influence is independent of physical activity behavior, remain unclear. Therefore, the aim of the study was to examine cross-sectional associations of objectively assessed physical activity and sedentary behavior on metabolic risk outcomes in a sample of elderly community-dwelling women.Metabolic risk outcomes including waist circumference, systolic and diastolic blood pressures, fasting levels of plasma glucose, HDL-cholesterol and triglycerides were assessed in 120 community-dwelling older women (65-70 yrs. Accelerometers were used to retrieve daily sedentary time, breaks in sedentary time, daily time in light (LPA and moderate-to-vigorous physical activity (MVPA, and total amount of accelerometer counts. Multivariate regression models were used to examine influence of physical activity and sedentary behavior on metabolic risk outcomes including a clustered metabolic risk score.When based on isotemporal substitution modeling, replacement of a 10-min time block of MVPA with a corresponding time block of either LPA or sedentary activities was associated with an increase in clustered metabolic risk score (β = 0.06 to 0.08, p < 0.05, and an increase in waist circumference (β = 1.78 to 2.19 p < 0.01. All associations indicated between sedentary time and metabolic risk outcomes were lost once variation in total accelerometer counts was adjusted for.Detrimental influence of a sedentary lifestyle on metabolic health is likely explained by variations in amounts of physical activity rather than amount of sedentary time per se. Given our findings, increased amounts of physical activity with an emphasis on increased time in MVPA should be recommended in order to promote a favorable metabolic health profile in older women.

  9. Joint association of physical activity in leisure and total sitting time with metabolic syndrome amongst 15,235 Danish adults

    DEFF Research Database (Denmark)

    Petersen, Christina Bjørk; Nielsen, Asser Jon; Bauman, Adrian

    2014-01-01

    and total daily sitting time were assessed by self-report in 15,235 men and women in the Danish Health Examination Survey 2007-2008. Associations between leisure time physical activity, total sitting time and metabolic syndrome were investigated in logistic regression analysis. RESULTS: Adjusted odds ratios......BACKGROUND: Recent studies suggest that physical inactivity as well as sitting time are associated with metabolic syndrome. Our aim was to examine joint associations of leisure time physical activity and total daily sitting time with metabolic syndrome. METHODS: Leisure time physical activity...... (OR) for metabolic syndrome were 2.14 (95% CI: 1.88-2.43) amongst participants who were inactive in leisure time compared to the most active, and 1.42 (95% CI: 1.26-1.61) amongst those who sat for ≥10h/day compared to physical activity, sitting time...

  10. DMPD: Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regula...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of

  11. Tributyltin toxicity in abalone (Haliotis diversicolor supertexta) assessed by antioxidant enzyme activity, metabolic response, and histopathology.

    Science.gov (United States)

    Zhou, Jin; Zhu, Xiao-shan; Cai, Zhong-hua

    2010-11-15

    A toxicity test was performed to investigate the possible harmful effects of tributyltin (TBT) on abalone (Haliotis diversicolor supertexta). Animals were exposed to TBT in a range of environmentally relevant concentrations (2, 10 and 50 ng/L) for 30 days under laboratory conditions. TBT-free conditions were used as control treatments. The activity of antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD), and malondialdehyde (MDA), along with levels of haemolymph metabolites, and hepatopancreas histopathology were analyzed. The results showed that TBT decreased SOD activity, and increased POD level and MDA production in a dose-dependent way, indicating that oxidative injury was induced by TBT. Haemolymph metabolite measurements showed that TBT increased alanine and glutamate levels, and decreased glucose content, which suggested perturbation of energy metabolism. Elevated levels of acetate and pyruvate in the haemolymph indicated partial alteration of lipid metabolism. A decrease in lactate and an increase in succinate, an intermediate of the tricarboxylic acid (TCA) cycle, indicated disturbance of amino acid metabolism. Hepatopancreas tissues also exhibited inflammatory responses characterized by histopathological changes such as cell swelling, granular degeneration, and inflammation. Taken together, these results demonstrated that TBT was a potential toxin with a variety of deleterious effects on abalone. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Blood flow to long bones indicates activity metabolism in mammals, reptiles and dinosaurs.

    Science.gov (United States)

    Seymour, Roger S; Smith, Sarah L; White, Craig R; Henderson, Donald M; Schwarz-Wings, Daniela

    2012-02-07

    The cross-sectional area of a nutrient foramen of a long bone is related to blood flow requirements of the internal bone cells that are essential for dynamic bone remodelling. Foramen area increases with body size in parallel among living mammals and non-varanid reptiles, but is significantly larger in mammals. An index of blood flow rate through the foramina is about 10 times higher in mammals than in reptiles, and even higher if differences in blood pressure are considered. The scaling of foramen size correlates well with maximum whole-body metabolic rate during exercise in mammals and reptiles, but less well with resting metabolic rate. This relates to the role of blood flow associated with bone remodelling during and following activity. Mammals and varanid lizards have much higher aerobic metabolic rates and exercise-induced bone remodelling than non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic groups are generally larger than from mammals, indicating a routinely highly active and aerobic lifestyle. The simple measurement holds possibilities offers the possibility of assessing other groups of extinct and living vertebrates in relation to body size, behaviour and habitat.

  13. Moderate daily exercise activates metabolic flexibility to prevent prenatally induced obesity.

    Science.gov (United States)

    Miles, Jennifer L; Huber, Korinna; Thompson, Nichola M; Davison, Michael; Breier, Bernhard H

    2009-01-01

    Obesity and its associated comorbidities are of major worldwide concern. It is now recognized that there are a number of metabolically distinct pathways of obesity development. The present paper investigates the effect of moderate daily exercise on the underlying mechanisms of one such pathway to obesity, through interrogation of metabolic flexibility. Pregnant Wistar rats were either fed chow ad libitum or undernourished throughout pregnancy, generating control or intrauterine growth restricted (IUGR) offspring, respectively. At 250 d of age, dual-emission x-ray absorptiometry scans and plasma analyses showed that moderate daily exercise, in the form of a measured amount of wheel running (56 m/d), prevented the development of obesity consistently observed in nonexercised IUGR offspring. Increased plasma C-peptide and hepatic atypical protein kinase Czeta levels explained increased glucose uptake and increased hepatic glycogen storage in IUGR offspring. Importantly, whereas circulating levels of retinol binding protein 4 were elevated in obese, nonexercised IUGR offspring, indicative of glucose sparing without exercise, retinol binding protein 4 levels were normalized in the exercised IUGR group. These data suggest that IUGR offspring have increased flexibility of energy storage and use and that moderate daily exercise prevents obesity development through activation of distinct pathways of energy use. Thus, despite a predisposition to develop obesity under sedentary conditions, obesity development was prevented in IUGR offspring when exercise was available. These results emphasize the importance of tailored lifestyle changes that activate distinct pathways of metabolic flexibility for obesity prevention.

  14. Icariin Is A PPARα Activator Inducing Lipid Metabolic Gene Expression in Mice

    Directory of Open Access Journals (Sweden)

    Yuan-Fu Lu

    2014-11-01

    Full Text Available Icariin is effective in the treatment of hyperlipidemia. To understand the effect of icariin on lipid metabolism, effects of icariin on PPARα and its target genes were investigated. Mice were treated orally with icariin at doses of 0, 100, 200, and 400 mg/kg, or clofibrate (500 mg/kg for five days. Liver total RNA was isolated and the expressions of PPARα and lipid metabolism genes were examined. PPARα and its marker genes Cyp4a10 and Cyp4a14 were induced 2-4 fold by icariin, and 4-8 fold by clofibrate. The fatty acid (FA binding and co-activator proteins Fabp1, Fabp4 and Acsl1 were increased 2-fold. The mRNAs of mitochondrial FA β-oxidation enzymes (Cpt1a, Acat1, Acad1 and Hmgcs2 were increased 2-3 fold. The mRNAs of proximal β-oxidation enzymes (Acox1, Ech1, and Ehhadh were also increased by icariin and clofibrate. The expression of mRNAs for sterol regulatory element-binding factor-1 (Srebf1 and FA synthetase (Fasn were unaltered by icariin. The lipid lysis genes Lipe and Pnpla2 were increased by icariin and clofibrate. These results indicate that icariin is a novel PPARα agonist, activates lipid metabolism gene expressions in liver, which could be a basis for its lipid-lowering effects and its beneficial effects against diabetes.

  15. Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

    International Nuclear Information System (INIS)

    Pols, Thijs W.H.; Ottenhoff, Roelof; Vos, Mariska; Levels, Johannes H.M.; Quax, Paul H.A.; Meijers, Joost C.M.; Pannekoek, Hans; Groen, Albert K.; Vries, Carlie J.M. de

    2008-01-01

    NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

  16. Metabolic regulation of inflammation.

    Science.gov (United States)

    Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

    2017-05-01

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

  17. Telephone-Based Physical Activity Counseling for Major Depression in People with Multiple Sclerosis

    Science.gov (United States)

    Bombardier, Charles H.; Ehde, Dawn M.; Gibbons, Laura E.; Wadhwani, Roini; Sullivan, Mark D.; Rosenberg, Dori E.; Kraft, George H.

    2013-01-01

    Objective: Physical activity represents a promising treatment for major depressive disorder (MDD) in people with multiple sclerosis (MS). We conducted a single-blind, two-arm randomized controlled trial comparing a 12-week physical activity counseling intervention delivered primarily by telephone (n = 44) to a wait-list control group (N = 48).…

  18. Coronary Heart Disease Risk between Active and Inactive Women with Multiple Sclerosis.

    Science.gov (United States)

    Slawta, Jennifer N.; McCubbin, Jeffrey A.; Wilcox, Anthony R.; Fox, Susan D.; Nalle, Darek J.; Anderson, Gail

    2002-01-01

    Investigated whether abdominal fat accumulation and levels of triglyceride, high-density lipoprotein cholesterol, and glucose differed between 123 active and inactive women with multiple sclerosis (MS). Results indicated that low-to-moderate leisure time physical activity significantly related to less abdominal fat accumulation, lower triglyceride…

  19. Social Cognitive Correlates of Physical Activity in Inactive Adults with Multiple Sclerosis

    Science.gov (United States)

    Dlugonski, Deirdre; Wojcicki, Thomas R.; McAuley, Edward; Motl, Robert W.

    2011-01-01

    Persons with multiple sclerosis (MS) are often physically inactive. This observation has prompted the search for modifiable constructs derived from established theories that act as correlates of physical activity. This study investigated self efficacy, outcome expectations, impediments, and goal setting as correlates of physical activity in…

  20. AMP-activated protein kinase: Role in metabolism and therapeutic implications.

    Science.gov (United States)

    Schimmack, Greg; Defronzo, Ralph A; Musi, Nicolas

    2006-11-01

    AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge which becomes activated in situations of energy consumption. AMPK functions to restore cellular ATP levels by modifying diverse metabolic and cellular pathways. In the skeletal muscle, AMPK is activated during exercise and is involved in contraction-stimulated glucose transport and fatty acid oxidation. In the heart, AMPK activity increases during ischaemia and functions to sustain ATP, cardiac function and myocardial viability. In the liver, AMPK inhibits the production of glucose, cholesterol and triglycerides and stimulates fatty acid oxidation. Recent studies have shown that AMPK is involved in the mechanism of action of metformin and thiazolidinediones, and the adipocytokines leptin and adiponectin. These data, along with evidence that pharmacological activation of AMPK in vivo improves blood glucose homeostasis, cholesterol concentrations and blood pressure in insulin-resistant rodents, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes, ischaemic heart disease and other metabolic diseases.

  1. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

    DEFF Research Database (Denmark)

    Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

    2012-01-01

    The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice......)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose...

  2. Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

    DEFF Research Database (Denmark)

    Lidegaard, Lærke P; Hansen, Anne-Louise Smidt; Johansen, Nanna B

    2015-01-01

    Aim/hypothesis: Little is known about the relative roles of physical activity energy expenditure (PAEE) and cardiorespiratory fitness (CRF) as determinants of glucose regulation. The aim of this study was to examine the associations of PAEE and CRF with markers of glucose metabolism, and to test...... the hypothesis that CRF modifies the association between PAEE and glucose metabolism. Methods: We analysed cross-sectional data from 755 adults from the Danish ADDITION-PRO study. On the basis of OGTT results, participants without known diabetes were classified as having normal glucose tolerance, isolated...... impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG + IGT or screen-detected diabetes mellitus. Markers of insulin sensitivity and beta cell function were determined. PAEE was measured using a combined heart rate and movement sensor. CRF (maximal oxygen uptake...

  3. Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Retrorsine, Leading to DNA Adduct Formation In Vivo

    Directory of Open Access Journals (Sweden)

    Ming W. Chou

    2005-04-01

    Full Text Available Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. The high toxicity of many pyrrolizidine alkaloids has caused considerable loss of free-ranging livestock due to liver and pulmonary lesions. Chronic exposure of toxic pyrrolizidine alkaloids to laboratory animals induces cancer. This investigation studies the metabolic activation of retrorsine, a representative naturally occurring tumorigenic pyrrolizidine alkaloid, and shows that a genotoxic mechanism is correlated to the tumorigenicity of retrorsine. Metabolism of retrorsine by liver microsomes of F344 female rats produced two metabolites, 6, 7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, at a rate of 4.8 ± 0.1 nmol/mg/min, and retrorsine-N-oxide, at a rate of 17.6±0.5 nmol/mg/min. Metabolism was enhanced 1.7-fold by using liver microsomes prepared from dexamethasone-treated rats. DHP formation was inhibited 77% and retrorsine N-oxide formation was inhibited 29% by troleandomycin, a P450 3A enzyme inhibitor. Metabolism of retrorsine with lung, kidney, and spleen microsomes from dexamethasone-treated rats also generated DHP and the N-oxide derivative. When rat liver microsomal metabolism of retrorsine occurred in the presence of calf thymus DNA, a set of DHP-derived DNA adducts was formed; these adducts were detected and quantified by using a previously developed 32P-postlabeling/HPLC method. These same DNA adducts were also found in liver DNA of rats gavaged with retrorsine. Since DHP-derived DNA adducts are suggested to be potential biomarkers of riddelliine-induced tumorigenicity, our results indicate that (i similar to the metabolic activation of riddelliine, the mechanism of retrorsine-induced carcinogenicity in rats is also through a genotoxic mechanism involving DHP; and (ii the set of DHP-derived DNA adducts found in liver DNA of rats gavaged with retrorsine or riddelliine can serve as biomarkers for the

  4. Metabolic Activation of the Tumorigenic Pyrrolizidine Alkaloid, Retrorsine, Leading to DNA Adduct Formation In Vivo

    Science.gov (United States)

    Wang, Yu-Ping; Fu, Peter P.; Chou, Ming W.

    2005-01-01

    Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. The high toxicity of many pyrrolizidine alkaloids has caused considerable loss of free-ranging livestock due to liver and pulmonary lesions. Chronic exposure of toxic pyrrolizidine alkaloids to laboratory animals induces cancer. This investigation studies the metabolic activation of retrorsine, a representative naturally occurring tumorigenic pyrrolizidine alkaloid, and shows that a genotoxic mechanism is correlated to the tumorigenicity of retrorsine. Metabolism of retrorsine by liver microsomes of F344 female rats produced two metabolites, 6, 7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), at a rate of 4.8 ± 0.1 nmol/mg/min, and retrorsine-N-oxide, at a rate of 17.6±0.5 nmol/mg/min. Metabolism was enhanced 1.7-fold by using liver microsomes prepared from dexamethasone-treated rats. DHP formation was inhibited 77% and retrorsine N-oxide formation was inhibited 29% by troleandomycin, a P450 3A enzyme inhibitor. Metabolism of retrorsine with lung, kidney, and spleen microsomes from dexamethasone-treated rats also generated DHP and the N-oxide derivative. When rat liver microsomal metabolism of retrorsine occurred in the presence of calf thymus DNA, a set of DHP-derived DNA adducts was formed; these adducts were detected and quantified by using a previously developed 32P-postlabeling/HPLC method. These same DNA adducts were also found in liver DNA of rats gavaged with retrorsine. Since DHP-derived DNA adducts are suggested to be potential biomarkers of riddelliine-induced tumorigenicity, our results indicate that (i) similar to the metabolic activation of riddelliine, the mechanism of retrorsine-induced carcinogenicity in rats is also through a genotoxic mechanism involving DHP; and (ii) the set of DHP-derived DNA adducts found in liver DNA of rats gavaged with retrorsine or riddelliine can serve as biomarkers for the tumorigenicity induced by

  5. [Lipid and metabolic profiles in adolescents are affected more by physical fitness than physical activity (AVENA study)].

    Science.gov (United States)

    García-Artero, Enrique; Ortega, Francisco B; Ruiz, Jonatan R; Mesa, José L; Delgado, Manuel; González-Gross, Marcela; García-Fuentes, Miguel; Vicente-Rodríguez, Germán; Gutiérrez, Angel; Castillo, Manuel J

    2007-06-01

    To determine whether the level of physical activity or physical fitness (i.e., aerobic capacity and muscle strength) in Spanish adolescents influences lipid and metabolic profiles. From a total of 2859 Spanish adolescents (age 13.0-18.5 years) taking part in the AVENA (Alimentación y Valoración del Estado Nutricional en Adolescentes) study, 460 (248 male, 212 female) were randomly selected for blood analysis. Their level of physical activity was determined by questionnaire. Aerobic capacity was assessed using the Course-Navette test. Muscle strength was evaluated using manual dynamometry, the long jump test, and the flexed arm hang test. A lipid-metabolic cardiovascular risk index was derived from the levels of triglycerides, low-density lipoprotein cholesterol (LDLC), high-density lipoprotein cholesterol (HDLC), and glucose. No relationship was found between the level of physical activity and lipid-metabolic index in either sex. In contrast, there was an inverse relationship between the lipid-metabolic index and aerobic capacity in males (P=.003) after adjustment for physical activity level and muscle strength. In females, a favorable lipid-metabolic index was associated with greater muscle strength (P=.048) after adjustment for aerobic capacity. These results indicate that, in adolescents, physical fitness, and not physical activity, is related to lipid and metabolic cardiovascular risk. Higher aerobic capacity in males and greater muscle strength in females were associated with lower lipid and metabolic risk factors for cardiovascular disease.

  6. Physical activity and metabolic disease among people with affective disorders: Prevention, management and implementation.

    Science.gov (United States)

    Vancampfort, Davy; Stubbs, Brendon

    2017-12-15

    One in ten and one in three of people with affective disorders experience diabetes and metabolic syndrome respectively. Physical activity (PA) and sedentary behaviour (SB) are key risk factors that can ameliorate the risk of metabolic disease among this population. However, PA is often seen as luxury and/or a secondary component within the management of people with affective disorders. The current article provides a non-systematic best-evidence synthesis of the available literature, detailing a number of suggestions for the implementation of PA into clinical practice. Whilst the evidence is unequivocal for the efficacy of PA to prevent and manage metabolic disease in the general population, it is in its infancy in this patient group. Nonetheless, action must be taken now to ensure that PA and reducing SB are given a priority to prevent and manage metabolic diseases and improve wider health outcomes. PA should be treated as a vital sign and all people with affective disorders asked about their activity levels and if appropriate advised to increase this. There is a need for investment in qualified exercise specialists in clinical practice such as physiotherapists to undertake and oversee PA in practice. Behavioural strategies such as the self-determined theory should be employed to encourage adherence. Funding is required to develop the evidence base and elucidate the optimal intervention characteristics. PA interventions should form an integral part of the multidisciplinary management of people with affective disorders and our article outlines the evidence and strategies to implement this in practice. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. A prospective, multiple-center study.

    Science.gov (United States)

    Jung, Boris; Rimmele, Thomas; Le Goff, Charlotte; Chanques, Gérald; Corne, Philippe; Jonquet, Olivier; Muller, Laurent; Lefrant, Jean-Yves; Guervilly, Christophe; Papazian, Laurent; Allaouchiche, Bernard; Jaber, Samir

    2011-01-01

    In this study, we sought describe the incidence and outcomes of severe metabolic or mixed acidemia in critically ill patients as well as the use of sodium bicarbonate therapy to treat these illnesses. We conducted a prospective, observational, multiple-center study. Consecutive patients who presented with severe acidemia, defined herein as plasma pH below 7.20, were screened. The incidence, sodium bicarbonate prescription and outcomes of either metabolic or mixed severe acidemia were analyzed. Among 2, 550 critically ill patients, 200 (8%) presented with severe acidemia, and 155 (6% of the total admissions) met the inclusion criteria. Almost all patients needed mechanical ventilation and vasopressors during their ICU stay, and 20% of them required renal replacement therapy within the first 24 hours of their ICU stay. Severe metabolic or mixed acidemia was associated with a mortality rate of 57% in the ICU. Delay of acidemia recovery as opposed to initial pH value was associated with increased mortality in the ICU. The type of acidemia did not influence the decision to administer sodium bicarbonate. The incidence of severe metabolic or mixed acidemia in critically ill patients was 6% in the present study, and it was associated with a 57% mortality rate in the ICU. In contradistinction with the initial acid-base parameters, the rapidity of acidemia recovery was an independent risk factor for mortality. Sodium bicarbonate prescription was very heterogeneous between ICUs. Further studies assessing specific treatments may be of interest in this population.

  8. Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. a prospective, multiple-center study

    Science.gov (United States)

    2011-01-01

    Introduction In this study, we sought describe the incidence and outcomes of severe metabolic or mixed acidemia in critically ill patients as well as the use of sodium bicarbonate therapy to treat these illnesses. Methods We conducted a prospective, observational, multiple-center study. Consecutive patients who presented with severe acidemia, defined herein as plasma pH below 7.20, were screened. The incidence, sodium bicarbonate prescription and outcomes of either metabolic or mixed severe acidemia were analyzed. Results Among 2, 550 critically ill patients, 200 (8%) presented with severe acidemia, and 155 (6% of the total admissions) met the inclusion criteria. Almost all patients needed mechanical ventilation and vasopressors during their ICU stay, and 20% of them required renal replacement therapy within the first 24 hours of their ICU stay. Severe metabolic or mixed acidemia was associated with a mortality rate of 57% in the ICU. Delay of acidemia recovery as opposed to initial pH value was associated with increased mortality in the ICU. The type of acidemia did not influence the decision to administer sodium bicarbonate. Conclusions The incidence of severe metabolic or mixed acidemia in critically ill patients was 6% in the present study, and it was associated with a 57% mortality rate in the ICU. In contradistinction with the initial acid-base parameters, the rapidity of acidemia recovery was an independent risk factor for mortality. Sodium bicarbonate prescription was very heterogeneous between ICUs. Further studies assessing specific treatments may be of interest in this population. PMID:21995879

  9. Mechanisms underlying metabolic and neural defects in zebrafish and human multiple acyl-CoA dehydrogenase deficiency (MADD.

    Directory of Open Access Journals (Sweden)

    Yuanquan Song

    2009-12-01

    Full Text Available In humans, mutations in electron transfer flavoprotein (ETF or electron transfer flavoprotein dehydrogenase (ETFDH lead to MADD/glutaric aciduria type II, an autosomal recessively inherited disorder characterized by a broad spectrum of devastating neurological, systemic and metabolic symptoms. We show that a zebrafish mutant in ETFDH, xavier, and fibroblast cells from MADD patients demonstrate similar mitochondrial and metabolic abnormalities, including reduced oxidative phosphorylation, increased aerobic glycolysis, and upregulation of the PPARG-ERK pathway. This metabolic dysfunction is associated with aberrant neural proliferation in xav, in addition to other neural phenotypes and paralysis. Strikingly, a PPARG antagonist attenuates aberrant neural proliferation and alleviates paralysis in xav, while PPARG agonists increase neural proliferation in wild type embryos. These results show that mitochondrial dysfunction, leading to an increase in aerobic glycolysis, affects neurogenesis through the PPARG-ERK pathway, a potential target for therapeutic intervention.

  10. Metabolic and behavioral responses to high-fat feeding in mice selectively bred for high wheel-running activity

    NARCIS (Netherlands)

    Vaanholt, L. M.; Jonas, I.; Doornbos, M.; Schubert, K. A.; Nyakas, C.; Garland, T.; Visser, G. H.; van Dijk, G.; Garland Jr., T.

    2008-01-01

    Objective: Increased dietary fat intake is a precipitating factor for the development of obesity and associated metabolic disturbances. Physically active individuals generally have a reduced risk of developing these unhealthy states, but the underlying mechanisms are poorly understood. In the

  11. Metabolic stabilization of acetylcholine receptors in vertebrate neuromuscular junction by muscle activity

    International Nuclear Information System (INIS)

    Rotzler, S.; Brenner, H.R.

    1990-01-01

    The effects of muscle activity on the growth of synaptic acetylcholine receptor (AChR) accumulations and on the metabolic AChR stability were investigated in rat skeletal muscle. Ectopic end plates induced surgically in adult soleus muscle were denervated early during development when junctional AChR number and stability were still low and, subsequently, muscles were either left inactive or they were kept active by chronic exogenous stimulation. AChR numbers per ectopic AChR cluster and AChR stabilities were estimated from the radioactivity and its decay with time, respectively, of end plate sites whose AChRs had been labeled with 125 I-alpha-bungarotoxin (alpha-butx). The results show that the metabolic stability of the AChRs in ectopic clusters is reversibly increased by muscle activity even when innervation is eliminated very early in development. 1 d of stimulation is sufficient to stabilize the AChRs in ectopic AChR clusters. Muscle stimulation also produced an increase in the number of AChRs at early denervated end plates. Activity-induced cluster growth occurs mainly by an increase in area rather than in AChR density, and for at least 10 d after denervation is comparable to that in normally developing ectopic end plates. The possible involvement of AChR stabilization in end plate growth is discussed

  12. A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress.

    Science.gov (United States)

    Kant, Shashi; Standen, Claire L; Morel, Caroline; Jung, Dae Young; Kim, Jason K; Swat, Wojciech; Flavell, Richard A; Davis, Roger J

    2017-09-19

    Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH 2 -terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress

    Directory of Open Access Journals (Sweden)

    Shashi Kant

    2017-09-01

    Full Text Available Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA activation of a non-receptor tyrosine kinase (SRC-dependent cJun NH2-terminal kinase (JNK signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway.

  14. Multiple co morbid conditions in patient with Mast Cell Activation Syndrome

    Science.gov (United States)

    2017-10-26

    conditions in patient \\\\·ith Mast Cell Activation Syndron1e Sb. GRANT NUMBER Sc. PROGRAM.ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER Maj Sofia...13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple co-n1orhid conditions in patient \\Vith Mast Cell Activation Syndrotne Sofia M. Szari.MD. and James...Defense. !NTR()D{JCT!ON: Mast cell activation disorders {MCAD) have been associated \\Vilh Connective Tissue Disorders (CTD) and orthostatic

  15. The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma

    OpenAIRE

    Hernández-García, Susana; San-Segundo, Laura; González-Méndez, Lorena; Corchete, Luis A; Misiewicz-Krzeminska, Irena; Martín-Sánchez, Montserrat; López-Iglesias, Ana-Alicia; Algarín, Esperanza Macarena; Mogollón, Pedro; Díaz-Tejedor, Andrea; Paíno, Teresa; Tunquist, Brian; Mateos, María-Victoria; Gutiérrez, Norma C; Díaz-Rodriguez, Elena

    2017-01-01

    [EN]Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor of this protein, has demonstrated activity in heavily pre-treated multiple myeloma patients. The aim of the work herein was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect. The ability of filanesib to enhance the activity of pomali...

  16. The Importance of Providing Multiple-Channel Sections in Dredging Activities to Improve Fish Habitat Environments

    Directory of Open Access Journals (Sweden)

    Hung-Pin Chiu

    2016-01-01

    Full Text Available After Typhoon Morakot, dredging engineering was conducted while taking the safety of humans and structures into consideration, but partial stream reaches were formed in the multiple-channel sections in Cishan Stream because of anthropogenic and natural influences. This study mainly explores the distribution of each fish species in both the multiple- and single-channel sections in the Cishan Stream. Parts of the environments did not exhibit significant differences according to a one-way ANOVA comparing the multiple- and single-channel sections, but certain areas of the multiple-channel sections had more diverse habitats. Each fish species was widely distributed by non-metric multidimensional scaling in the multiple-channel sections as compared to those in the single-channel sections. In addition, according to the principal component analysis, each fish species has a preferred environment, and all of them have a wide choice of habitat environments in the multiple-channel sections. Finally, the existence of multiple-channel sections could significantly affect the existence of the fish species under consideration in this study. However, no environmental factors were found to have an influence on fish species in the single-channel sections, with the exception of Rhinogobius nantaiensis. The results show that providing multiple-channel sections in dredging activities could improve fish habitat environments.

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

    DEFF Research Database (Denmark)

    Andersen, Thor Munch; Olsen, David B; Søndergaard, Hans

    2012-01-01

    To evaluate the effect of regular physical activity on metabolic risk factors and blood pressure in Inuit with high BMI consuming a western diet (high amount of saturated fatty acids and carbohydrates with a high glycemic index).......To evaluate the effect of regular physical activity on metabolic risk factors and blood pressure in Inuit with high BMI consuming a western diet (high amount of saturated fatty acids and carbohydrates with a high glycemic index)....

  18. Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism.

    Science.gov (United States)

    Dienel, Gerald A; Cruz, Nancy F

    2016-07-01

    Aerobic glycolysis occurs during brain activation and is characterized by preferential up-regulation of glucose utilization compared with oxygen consumption even though oxygen level and delivery are adequate. Aerobic glycolysis is a widespread phenomenon that underlies energetics of diverse brain activities, such as alerting, sensory processing, cognition, memory, and pathophysiological conditions, but specific cellular functions fulfilled by aerobic glycolysis are poorly understood. Evaluation of evidence derived from different disciplines reveals that aerobic glycolysis is a complex, regulated phenomenon that is prevented by propranolol, a non-specific β-adrenoceptor antagonist. The metabolic pathways that contribute to excess utilization of glucose compared with oxygen include glycolysis, the pentose phosphate shunt pathway, the malate-aspartate shuttle, and astrocytic glycogen turnover. Increased lactate production by unidentified cells, and lactate dispersal from activated cells and lactate release from the brain, both facilitated by astrocytes, are major factors underlying aerobic glycolysis in subjects with low blood lactate levels. Astrocyte-neuron lactate shuttling with local oxidation is minor. Blockade of aerobic glycolysis by propranolol implicates adrenergic regulatory processes including adrenal release of epinephrine, signaling to brain via the vagus nerve, and increased norepinephrine release from the locus coeruleus. Norepinephrine has a powerful influence on astrocytic metabolism and glycogen turnover that can stimulate carbohydrate utilization more than oxygen consumption, whereas β-receptor blockade 're-balances' the stoichiometry of oxygen-glucose or -carbohydrate metabolism by suppressing glucose and glycogen utilization more than oxygen consumption. This conceptual framework may be helpful for design of future studies to elucidate functional roles of preferential non-oxidative glucose utilization and glycogen turnover during brain

  19. Acyl-CoA synthetase activity links wild-type but not mutant a-Synuclein to brain arachidonate metabolism

    DEFF Research Database (Denmark)

    Golovko, Mikhail; Rosenberger, Thad; Færgeman, Nils J.

    2006-01-01

    Because alpha-synuclein (Snca) has a role in brain lipid metabolism, we determined the impact that the loss of alpha-synuclein had on brain arachidonic acid (20:4n-6) metabolism in vivo using Snca-/- mice. We measured [1-(14)C]20:4n-6 incorporation and turnover kinetics in brain phospholipids using......, our data demonstrate that alpha-synuclein has a major role in brain 20:4n-6 metabolism through its modulation of endoplasmic reticulum-localized acyl-CoA synthetase activity, although mutant forms of alpha-synuclein fail to restore this activity....

  20. Chromium regulation of multiple gene expression in rats with high-fructose diet-induced metabolic syndrome

    Science.gov (United States)

    Chromium (Cr) supplementation alleviates the metabolic syndrome, glucose intolerance, depression, excess body fat, and type 2 diabetes. However, not all studies have reported beneficial effects of Cr. Molecular evidence is lacking on the effects of Cr. The objective of this study was to investigate ...

  1. Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells in vitro models

    Directory of Open Access Journals (Sweden)

    Hammami Ines

    2012-07-01

    Full Text Available Abstract Background The tumor microenvironment contains a vast array of pro- and anti-inflammatory cytokines that alter myelopoiesis and lead to the maturation of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs. Incubating bone marrow (BM precursors with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF and interleukin-6 (IL-6 generated a tumor-infiltrating MDSC-like population that impaired anti-tumor specific T-cell functions. This in vitro experimental approach was used to simulate MDSC maturation, and the cellular metabolic response was then monitored. A complementary experimental model that inhibited L-arginine (L-Arg metabolizing enzymes in MSC-1 cells, an immortalized cell line derived from primary MDSCs, was used to study the metabolic events related to immunosuppression. Results Exposure of BM cells to GM-CSF and IL-6 activated, within 24 h, L-Arg metabolizing enzymes which are responsible for the MDSCs immunosuppressive potential. This was accompanied by an increased uptake of L-glutamine (L-Gln and glucose, the latter being metabolized by anaerobic glycolysis. The up-regulation of nutrient uptake lead to the accumulation of TCA cycle intermediates and lactate as well as the endogenous synthesis of L-Arg and the production of energy-rich nucleotides. Moreover, inhibition of L-Arg metabolism in MSC-1 cells down-regulated central carbon metabolism activity, including glycolysis, glutaminolysis and TCA cycle activity, and led to a deterioration of cell bioenergetic status. The simultaneous increase of cell specific concentrations of ATP and a decrease in ATP-to-ADP ratio in BM-derived MDSCs suggested cells were metabolically active during maturation. Moreover, AMP-activated protein kinase (AMPK was activated during MDSC maturation in GM-CSF and IL-6–treated cultures, as revealed by the continuous increase of AMP-to-ATP ratios and the phosphorylation of AMPK. Likewise, AMPK activity was

  2. Metabolic potential and in situ activity of marine Marinimicrobia bacteria in an anoxic water column.

    Science.gov (United States)

    Bertagnolli, Anthony D; Padilla, Cory C; Glass, Jennifer B; Thamdrup, Bo; Stewart, Frank J

    2017-11-01

    Marinimicrobia bacteria are widespread in subeuphotic areas of the oceans and particularly abundant in oxygen minimum zones (OMZs). Information on Marinimicrobia metabolism is sparse, making the biogeochemical influence of this group challenging to predict. Here, metagenome-assembled genomes representing Marinimicrobia subgroups PN262000N21 and ARCTIC96B-7 were retrieved to near completion (97% and 94%) from OMZ metagenomes, with contamination (14.1%) observed only in ARCTIC96B-7. Genes for aerobic carbon monoxide (CO) oxidation, polysulfide metabolism and hydrogen utilization were identified only in PN262000N21, while genes for partial denitrification occurred in both genomes. Transcripts mapping to these genomes increased from utilizing proteins, including sulfur transferases, were enriched at sulfidic depths. PN262000N21 transcripts encoding a protein with fibronectin domains similar to those in cellulosome-producing bacteria were also abundant, suggesting a potential for high molecular weight carbon cycling. These data provide omic-level descriptions of metabolic potential and activity in OMZ-associated Marinimicrobia, suggesting differentiation between subgroups with roles in carbon and dissimilatory inorganic nitrogen and sulfur cycling. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. Metabolic profiles and free radical scavenging activity of Cordyceps bassiana fruiting bodies according to developmental stage.

    Directory of Open Access Journals (Sweden)

    Sun-Hee Hyun

    Full Text Available The metabolic profiles of Cordyceps bassiana according to fruiting body developmental stage were investigated using gas chromatography-mass spectrometry. We were able to detect 62 metabolites, including 48 metabolites from 70% methanol extracts and 14 metabolites from 100% n-hexane extracts. These metabolites were classified as alcohols, amino acids, organic acids, phosphoric acids, purine nucleosides and bases, sugars, saturated fatty acids, unsaturated fatty acids, or fatty amides. Significant changes in metabolite levels were found according to developmental stage. Relative levels of amino acids, purine nucleosides, and sugars were higher in development stage 3 than in the other stages. Among the amino acids, valine, isoleucine, lysine, histidine, glutamine, and aspartic acid, which are associated with ABC transporters and aminoacyl-tRNA biosynthesis, also showed higher levels in stage 3 samples. The free radical scavenging activities, which were significantly higher in stage 3 than in the other stages, showed a positive correlation with purine nucleoside metabolites such as adenosine, guanosine, and inosine. These results not only show metabolic profiles, but also suggest the metabolic pathways associated with fruiting body development stages in cultivated C. bassiana.

  4. Phytochemical Composition and Metabolic Performance Enhancing Activity of Dietary Berries Traditionally Used by Native North Americans

    Science.gov (United States)

    Burns Kraft, Tristan F.; Dey, Moul; Rogers, Randy B.; Ribnicky, David M.; Gipp, David M.; Cefalu, William T.; Raskin, Ilya; Lila, Mary Ann

    2009-01-01

    Four wild berry species, Amelanchier alnifolia, Viburnum trilobum, Prunus virginiana, and Shepherdia argentea, all integral to the traditional subsistence diet of Native American tribal communities, were evaluated to elucidate phytochemical composition and bioactive properties related to performance and human health. Biological activity was screened using a range of bioassays that assessed the potential for these little-known dietary berries to affect diabetic microvascular complications, hyperglycemia, pro-inflammatory gene expression, and metabolic syndrome symptoms. Non-polar constituents from berries, including carotenoids, were potent inhibitors of aldose reductase (an enzyme involved in the etiology of diabetic microvascular complications) whereas the polar constituents, mainly phenolic acids, anthocyanins, and proanthocyanidins, were hypoglycemic agents and strong inhibitors of IL-1β and COX-2 gene expression. Berry samples also showed the ability to modulate lipid metabolism and energy expenditure in a manner consistent with improving metabolic syndrome. The results demonstrate that these berries traditionally consumed by tribal cultures contain a rich array of phytochemicals that have the capacity to promote health and protect against chronic diseases, such as diabetes. PMID:18211018

  5. Metabolic activity of sodium, measured by neutron activation, in the hands of patients suffering from bone diseases: concise communication

    International Nuclear Information System (INIS)

    Spinks, T.J.; Bewley, D.K.; Paolillo, M.; Vlotides, J.; Joplin, G.F.; Ranicar, A.S.O.

    1980-01-01

    Turnover of sodium in the human hand was studied by neutron activation. Patients suffering from various metabolic abnormalities affecting the skeleton, who were undergoing routine neutron activation for the measurement of calcium, were investigated along with a group of healthy volunteers. Neutron activation labels the sodium atoms simultaneously and with equal probability regardless of the turnover time of individual body compartments. The loss of sodium can be described either by a sum of two exponentials or by a single power function. Distinctions between patients and normal subjects were not apparent from the exponential model but were brought out by the power function. The exponent of time in the latter is a measure of clearance rate. The mean values of this parameter in (a) a group of patients suffering from acromegaly; (b) a group including Paget's disease, osteoporosis, Cushing's disease, and hyperparathyroidism; and (c) a group of healthy subjects, were found to be significantly different from each other

  6. CCR5 delta32, matrix metalloproteinase-9 and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Madsen, Hans O; Jensen, Claus V

    2000-01-01

    Chemokines and matrix metalloproteinases (MMPs) appear to be crucial in leukocyte recruitment to the central nervous system in multiple sclerosis (MS). CCR5 delta32, a truncated allele of the CC chemokine receptor CCR5 gene encoding a non-functional receptor, did not confer protection from MS. CCR5...... delta32 was, however, associated with a lower risk of recurrent clinical disease activity. High CSF levels of MMP-9 activity were also associated with recurrent disease activity. These results directly link intrathecal inflammation to disease activity in patients with MS, suggesting that treatments...... targeting CCR5 or treatment with MMP inhibitors may attenuate disease activity in MS...

  7. Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

    International Nuclear Information System (INIS)

    Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

    1986-01-01

    Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated [ 3 H]thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause

  8. Multiple metabolic alterations exist in mutant PI3K cancers, but only glucose is essential as a nutrient source.

    Directory of Open Access Journals (Sweden)

    Rebecca Foster

    Full Text Available Targeting tumour metabolism is becoming a major new area of pharmaceutical endeavour. Consequently, a systematic search to define whether there are specific energy source dependencies in tumours, and how these might be dictated by upstream driving genetic mutations, is required. The PI3K-AKT-mTOR signalling pathway has a seminal role in regulating diverse cellular processes including cell proliferation and survival, but has also been associated with metabolic dysregulation. In this study, we sought to define how mutations within PI3KCA may affect the metabolic dependency of a cancer cell, using precisely engineered isogenic cell lines. Studies revealed gene expression signatures in PIK3CA mutant cells indicative of a consistent up-regulation of glycolysis. Interestingly, the genes up- and down-regulated varied between isogenic models suggesting that the primary node of regulation is not the same between models. Additional gene expression changes were also observed, suggesting that metabolic pathways other than glycolysis, such as glutaminolysis, were also affected. Nutrient dependency studies revealed that growth of PIK3CA mutant cells is highly dependent on glucose, whereas glutamine dependency is independent of PIK3CA status. In addition, the glucose dependency exhibited by PIK3CA mutant cells could not be overridden by supplementation with other nutrients. This specific dependence on glucose for growth was further illustrated by studies evaluating the effects of targeted disruption of the glycolytic pathway using siRNA and was also found to be present across a wider panel of cancer cell lines harbouring endogenous PIK3CA mutations. In conclusion, we have found that PIK3CA mutations lead to a shift towards a highly glycolytic phenotype, and that despite suggestions that cancer cells are adept at utilising alternative nutrient sources, PIK3CA mutant cells are not able to compensate for glucose withdrawal. Understanding the metabolic

  9. Metabolic Potential and Activity in Fluids of the Coast Range Ophiolite Microbial Observatory, California, USA

    Science.gov (United States)

    Hoehler, T.; Som, S.; Schrenk, M.; McCollom, T.; Cardace, D.

    2016-01-01

    Metabolic potential and activity associated with hydrogen and carbon monoxide were characterized in fluids sampled from the the Coast Range Ophiolite Microbial Observatory (CROMO). CROMO consists of two clusters of science-dedicated wells drilled to varying depths up to 35m in the actively serpentinizing, Jurassic-age Coast Range Ophiolite of Northern California, along with a suite of pre-existing monitoring wells at the same site. Consistent with the fluid chemistry observed in other serpentinizing systems, CROMO fluids are highly alkaline, with pH up to 12.5, high in methane, with concentrations up 1600 micromolar, and low in dissolved inorganic carbon (DIC), with concentrations of 10's to 100's of micromolar. CROMO is conspicuous for fluid H2 concentrations that are consistently sub-micromolar, orders of magnitude lower than is typical of other systems. However, higher H2 concentrations (10's -100's of micromolar) at an earlier stage of fluid chemical evolution are predicted by, or consistent with: thermodynamic models for fluid chemistry based on parent rock composition equivalent to local peridotite and with water:rock ratio constrained by observed pH; the presence of magnetite at several wt% in CROMO drill cores; and concentrations of formate and carbon monoxide that would require elevated H2 if formed in equilibrium with H2 and DIC. Calculated Gibbs energy changes for reaction of H2 and CO in each of several metabolisms, across the range of fluid composition encompassed by the CROMO wells, range from bioenergetically feasible (capable of driving ATP synthesis) to thermodynamically unfavorable. Active consumption relative to killed controls was observed for both CO and H2 during incubation of fluids from the pre-existing monitoring wells; in incubations of freshly cored solids, consumption was only observed in one sample set (corresponding to the lowest pH) out of three. The specific metabolisms by which H2 and CO are consumed remain to be determined.

  10. Application of speckle image correlation for real-time assessment of metabolic activity in herpes virus-infected cells

    Science.gov (United States)

    Vladimirov, A. P.; Malygin, A. S.; Mikhailova, J. A.; Borodin, E. M.; Bakharev, A. A.; Poryvayeva, A. P.

    2014-09-01

    Earlier we reported developing a speckle interferometry technique and a device designed to assess the metabolic activity of a cell monolayer cultivated on a glass substrate. This paper aimed at upgrading the technique and studying its potential for real-time assessment of herpes virus development process. Speckle dynamics was recorded in the image plane of intact and virus-infected cell monolayer. HLE-3, L-41 and Vero cells were chosen as research targets. Herpes simplex virus-1-(HSV-1)- infected cell cultures were studied. For 24 h we recorded the digital value of optical signal I in one pixel and parameter η characterizing change in the distribution of the optical signal on 10 × 10-pixel areas. The coefficient of multiple determination calculated by η time dependences for three intact cell cultures equals 0.94. It was demonstrated that the activity parameters are significantly different for intact and virus-infected cells. The difference of η value for intact and HSV-1-infected cells is detectable 10 minutes from the experiment start.

  11. Application of speckle image correlation for real-time assessment of metabolic activity in herpes virus-infected cells

    International Nuclear Information System (INIS)

    Vladimirov, A P; Malygin, A S; Mikhailova, J A; Borodin, E M; Bakharev, A A; Poryvayeva, A P

    2014-01-01

    Earlier we reported developing a speckle interferometry technique and a device designed to assess the metabolic activity of a cell monolayer cultivated on a glass substrate. This paper aimed at upgrading the technique and studying its potential for real-time assessment of herpes virus development process. Speckle dynamics was recorded in the image plane of intact and virus-infected cell monolayer. HLE-3, L-41 and Vero cells were chosen as research targets. Herpes simplex virus-1-(HSV-1)- infected cell cultures were studied. For 24 h we recorded the digital value of optical signal I in one pixel and parameter η characterizing change in the distribution of the optical signal on 10 × 10-pixel areas. The coefficient of multiple determination calculated by η time dependences for three intact cell cultures equals 0.94. It was demonstrated that the activity parameters are significantly different for intact and virus-infected cells. The difference of η value for intact and HSV-1-infected cells is detectable 10 minutes from the experiment start.

  12. Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity.

    Directory of Open Access Journals (Sweden)

    Marc Breit

    2015-08-01

    Full Text Available The objectives of this work were the classification of dynamic metabolic biomarker candidates and the modeling and characterization of kinetic regulatory mechanisms in human metabolism with response to external perturbations by physical activity. Longitudinal metabolic concentration data of 47 individuals from 4 different groups were examined, obtained from a cycle ergometry cohort study. In total, 110 metabolites (within the classes of acylcarnitines, amino acids, and sugars were measured through a targeted metabolomics approach, combining tandem mass spectrometry (MS/MS with the concept of stable isotope dilution (SID for metabolite quantitation. Biomarker candidates were selected by combined analysis of maximum fold changes (MFCs in concentrations and P-values resulting from statistical hypothesis testing. Characteristic kinetic signatures were identified through a mathematical modeling approach utilizing polynomial fitting. Modeled kinetic signatures were analyzed for groups with similar behavior by applying hierarchical cluster analysis. Kinetic shape templates were characterized, defining different forms of basic kinetic response patterns, such as sustained, early, late, and other forms, that can be used for metabolite classification. Acetylcarnitine (C2, showing a late response pattern and having the highest values in MFC and statistical significance, was classified as late marker and ranked as strong predictor (MFC = 1.97, P < 0.001. In the class of amino acids, highest values were shown for alanine (MFC = 1.42, P < 0.001, classified as late marker and strong predictor. Glucose yields a delayed response pattern, similar to a hockey stick function, being classified as delayed marker and ranked as moderate predictor (MFC = 1.32, P < 0.001. These findings coincide with existing knowledge on central metabolic pathways affected in exercise physiology, such as β-oxidation of fatty acids, glycolysis, and glycogenolysis. The presented modeling

  13. Hepatobiliary fascioliasis with multiple aneurysms and active bleeding: A case report

    International Nuclear Information System (INIS)

    Choi, Soo Young; Kim Jae Woon; Jang, Jae Cheon

    2015-01-01

    A 52-year-old woman visited our institution with upper abdominal pain which had lasted for the past two days. Laboratory tests revealed mild leukocytosis, decreased serum hemoglobin, and peripheral blood eosinophilia. CT scans showed multiple ill-defined, hypodense lesions in the peripheral areas of both hepatic lobes and active bleeding with a subcapsular hematoma in the right hepatic lobe. Angiography also showed active bleeding in the right hepatic lobe with multiple aneurysms, so a transarterial coil embolization was performed to stop the bleeding. The endoscopic retrograde cholangiopancreatography revealed several moving flat flukes in the common bile duct, which were pathologically confirmed as Fasciola hepatica.

  14. Hepatobiliary fascioliasis with multiple aneurysms and active bleeding: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Soo Young; Kim Jae Woon; Jang, Jae Cheon [Dept. of Radiology, College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

    2015-04-15

    A 52-year-old woman visited our institution with upper abdominal pain which had lasted for the past two days. Laboratory tests revealed mild leukocytosis, decreased serum hemoglobin, and peripheral blood eosinophilia. CT scans showed multiple ill-defined, hypodense lesions in the peripheral areas of both hepatic lobes and active bleeding with a subcapsular hematoma in the right hepatic lobe. Angiography also showed active bleeding in the right hepatic lobe with multiple aneurysms, so a transarterial coil embolization was performed to stop the bleeding. The endoscopic retrograde cholangiopancreatography revealed several moving flat flukes in the common bile duct, which were pathologically confirmed as Fasciola hepatica.

  15. Metabolism and biological activity of 24,25-dihydroxyvitamin D3 in the chick

    International Nuclear Information System (INIS)

    Holick, M.F.; Baxter, L.A.; Schraufrogel, P.K.; Tavela, T.E.; DeLuca, H.F.

    1976-01-01

    The vitamin, 24R,24,25-dihydroxyvitamin D 3 , is capable of inducing a minimal intestinal calcium transport response in chicks when compared to an equal amount of 25-hydroxyvitamin D 3 . 1,24,25-Trihydroxyvitamin D 3 is also less active than 1,25-dihydroxyvitamin D 3 , and its activity is much shorter lived than that of 1,25-dihydroxyvitamin D 3 . A comparison of the metabolism of 25-hydroxy[26,27- 3 H]vitamin D 3 and 24,25-dihydroxy[26,27- 3 H]vitamin D 3 in the rat and chick shows that 24,25-dihydroxyvitamin D 3 and 1,24,25-trihydroxyvitamin D 3 disappear at least 10 times more rapidly from the blood and intestine of chicks. Furthermore, examination of the excretory products from both of these species demonstrates that chicks receiving a single dose of 24,25-dihydroxy[26,27- 3 H]vitamin D 3 excrete 66% of the total radioactivity by 48 hours, whereas rats receiving the same dose excrete less than one-half that amount. These results demonstrate that 24,25-dihydroxyvitamin D 3 is considerably less biologically active in the chick than in the rat, probably due to more rapid metabolism and excretion

  16. Stoichiometry and kinetics of poly-{beta}-hydroxybutyrate metabolism in aerobic, slow growing, activated sludge cultures

    Energy Technology Data Exchange (ETDEWEB)

    Beun, J.J.; Paletta, F.; Loosdrecht, M.C.M. Van; Heijnen, J.J.

    2000-02-20

    This paper discusses the poly-{beta}-hydroxybutyrate (PHB) metabolism in aerobic, slow growing, activated sludge cultures, based on experimental data and on a metabolic model. The dynamic conditions which occur in activated sludge processes were simulated in a 2-L sequencing batch reactor (SBR) by subjecting a mixed microbial population to successive periods of external substrate availability (feast period) and no external substrate availability (famine period). Under these conditions intracellular storage and consumption of PHB was observed. It appeared that in the feast period, 66% to almost 100% of the substrate consumed is used for storage of PHB, the remainder is used for growth and maintenance processes. Furthermore, it appeared that at high sludge retention time (SRT) the growth rate in the feast and famine periods was the same. With decreasing SRT the growth rate in the feast period increased relative to the growth rate in the famine period. Acetate consumption and PHB production in the feast period both proceeded with a zero-order rate in acetate and PHB concentration respectively. PHB consumption in the famine period could best be described kinetically with a nth order degradation equation in PHB concentration. The obtained results are discussed in the context of the general activated sludge models.

  17. Metabolic rate and thyroid activity of hens in relation to the state of feathering.

    Science.gov (United States)

    Pietras, M

    1981-01-01

    Heat production, rectal temperature and thyroid activity were determined in NH X Lg hens that were 40 and 80% defeathered. Within individual groups there was a significant increase in heat production only in hens that were 80% defeathered. In comparison with the control group, defeathered chickens had higher metabolic rates during each examined period. During the third week of the experiment there was a temporary drop in the rectal temperature of the experimental birds. After nine weeks chicken with the greatest degree of defeathering had the highest thyroid weight and the highest levels of thyroxin in the blood plasma.

  18. Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism in the left ventricle

    DEFF Research Database (Denmark)

    Langfort, Jozef; Jagsz, Slawomir; Dobrzyn, Pawel

    2010-01-01

    Fatty acids, which are the major cardiac fuel, are derived from lipid droplets stored in cardiomyocytes, among other sources. The heart expresses hormone-sensitive lipase (HSL), which regulates triglycerides (TG) breakdown, and the enzyme is under hormonal control. Evidence obtained from adipose...... levels, caused an inhibitory effect on carbohydrate metabolism in the heart, and elevated left ventricular phosphocreatine and ATP levels as compared to control rats. These data indicate that testosterone is involved in cardiac HSL activity regulation which, in turn, may affect cardiac lipid...

  19. Reduction in hepatic drug metabolizing CYP3A4 activities caused by P450 oxidoreductase mutations identified in patients with disordered steroid metabolism

    International Nuclear Information System (INIS)

    Flueck, Christa E.; Mullis, Primus E.; Pandey, Amit V.

    2010-01-01

    Research highlights: → Cytochrome P450 3A4 (CYP3A4), metabolizes 50% of drugs in clinical use and requires NADPH-P450 reductase (POR). → Mutations in human POR cause congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. → We are reporting that mutations in POR may reduce CYP3A4 activity. → POR mutants Y181D, A457H, Y459H, V492E and R616X lost 99%, while A287P, C569Y and V608F lost 60-85% CYP3A4 activity. → Reduction of CYP3A4 activity may cause increased risk of drug toxicities/adverse drug reactions in patients with POR mutations. -- Abstract: Cytochrome P450 3A4 (CYP3A4), the major P450 present in human liver metabolizes approximately half the drugs in clinical use and requires electrons supplied from NADPH through NADPH-P450 reductase (POR, CPR). Mutations in human POR cause a rare form of congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. In this study we examined the effect of mutations in POR on CYP3A4 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified CYP3A4 to perform kinetic studies. We are reporting that mutations in POR identified in patients with disordered steroidogenesis/Antley-Bixler syndrome (ABS) may reduce CYP3A4 activity, potentially affecting drug metabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had more than 99% loss of CYP3A4 activity, while POR mutations A287P, C569Y and V608F lost 60-85% activity. Loss of CYP3A4 activity may result in increased risk of drug toxicities and adverse drug reactions in patients with POR mutations.

  20. Dietary patterns as compared with physical activity in relation to metabolic syndrome among Chinese adults.

    Science.gov (United States)

    He, Y; Li, Y; Lai, J; Wang, D; Zhang, J; Fu, P; Yang, X; Qi, L

    2013-10-01

    To examine the nationally-representative dietary patterns and their joint effects with physical activity on the likelihood of metabolic syndrome (MS) among 20,827 Chinese adults. CNNHS was a nationally representative cross-sectional observational study. Metabolic syndrome was defined according to the Joint Interim Statement definition. The "Green Water" dietary pattern, characterized by high intakes of rice and vegetables and moderate intakes in animal foods was related to the lowest prevalence of MS (15.9%). Compared to the "Green Water" dietary pattern, the "Yellow Earth" dietary pattern, characterized by high intakes of refined cereal products, tubers, cooking salt and salted vegetable was associated with a significantly elevated odds of MS (odds ratio 1.66, 95%CI: 1.40-1.96), after adjustment of age, sex, socioeconomic status and lifestyle factors. The "Western/new affluence" dietary pattern characterized by higher consumption of beef/lamb, fruit, eggs, poultry and seafood also significantly associated with MS (odds ratio: 1.37, 95%CI: 1.13-1.67). Physical activity showed significant interactions with the dietary patterns in relation to MS risk (P for interaction = 0.008). In the joint analysis, participants with the combination of sedentary activity with the "Yellow Earth" dietary pattern or the "Western/new affluence" dietary pattern both had more than three times (95%CI: 2.8-6.1) higher odds of MS than those with active activity and the "Green Water" dietary pattern. Our findings from the large Chinese national representative data indicate that dietary patterns affect the likelihood of MS. Combining healthy dietary pattern with active lifestyle may benefit more in prevention of MS. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. 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....

  2. CD147: a small molecule transporter ancillary protein at the crossroad of multiple hallmarks of cancer and metabolic reprogramming.

    Science.gov (United States)

    Kendrick, Agnieszka A; Schafer, Johnathon; Dzieciatkowska, Monika; Nemkov, Travis; D'Alessandro, Angelo; Neelakantan, Deepika; Ford, Heide L; Pearson, Chad G; Weekes, Colin D; Hansen, Kirk C; Eisenmesser, Elan Z

    2017-01-24

    Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). Here, we show for the first time that CD147 interacts with membrane transporters beyond MCTs and exhibits a protective role for several of its interacting partners. CD147 prevents its interacting partner's proteasome-dependent degradation and incorrect plasma membrane localization through the CD147 transmembrane (TM) region. The interactions with transmembrane small molecule and ion transporters identified here indicate a central role of CD147 in pancreatic cancer metabolic reprogramming, particularly with respect to amino acid anabolism and calcium signaling. Importantly, CD147 genetic ablation prevents pancreatic cancer cell proliferation and tumor growth in vitro and in vivo in conjunction with metabolic rewiring towards amino acid anabolism, thus paving the way for future combined pharmacological treatments.

  3. Identification of circular RNAs from the parental genes involved in multiple aspects of cellular metabolism in barley

    DEFF Research Database (Denmark)

    Shirvanehdeh, Behrooz Darbani; Noeparvar, Shahin; Borg, Søren

    2016-01-01

    circular RNAs as novel interactors in the regulation of gene expression in plants and imply the comprehensiveness of this regulatory pathway by identifying circular RNAs for a diverse set of genes. These genes are involved in several aspects of cellular metabolism as hormonal signaling, intracellular...... protein sorting, carbohydrate metabolism and cell-wall biogenesis, respiration, amino acid biosynthesis, transcription and translation, and protein ubiquitination. Additionally, these parental loci of circular RNAs, from both nuclear and mitochondrial genomes, encode for different transcript classes...... and elucidate their cellular-level alterations across tissues and in response to micronutrients iron and zinc. In further support of circular RNAs’ functional roles in plants, we report several cases where fluctuations of circRNAs do not correlate with the levels of their parental-loci encoded linear...

  4. Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling

    KAUST Repository

    Zeis, T.; Allaman, I.; Gentner, M.; Schroder, K.; Tschopp, J.; Magistretti, Pierre J.; Schaeren-Wiemers, N.

    2015-01-01

    Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction

  5. Mining Emerging Patterns for Recognizing Activities of Multiple Users in Pervasive Computing

    DEFF Research Database (Denmark)

    Gu, Tao; Wu, Zhanqing; Wang, Liang

    2009-01-01

    Understanding and recognizing human activities from sensor readings is an important task in pervasive computing. Existing work on activity recognition mainly focuses on recognizing activities for a single user in a smart home environment. However, in real life, there are often multiple inhabitants...... activity models, and propose an Emerging Pattern based Multi-user Activity Recognizer (epMAR) to recognize both single-user and multiuser activities. We conduct our empirical studies by collecting real-world activity traces done by two volunteers over a period of two weeks in a smart home environment...... sensor readings in a home environment, and propose a novel pattern mining approach to recognize both single-user and multi-user activities in a unified solution. We exploit Emerging Pattern – a type of knowledge pattern that describes significant changes between classes of data – for constructing our...

  6. Physical activity in subjects with multiple sclerosis with focus on gender differences: a survey.

    Science.gov (United States)

    Anens, Elisabeth; Emtner, Margareta; Zetterberg, Lena; Hellström, Karin

    2014-03-10

    There is increasing research that examines gender-issues in multiple sclerosis (MS), but little focus has been placed on gender-issues regarding physical activity. The aim of the present study was to describe levels of physical activity, self-efficacy for physical activity, fall-related self-efficacy, social support for physical activity, fatigue levels and the impact of MS on daily life, in addition to investigating gender differences. The sample for this cross-sectional cohort study consisted of 287 (84 men; 29.3%) adults with MS recruited from the Swedish Multiple Sclerosis Registry. A questionnaire was sent to the subjects consisting of the self-administrated measurements: Physical Activity Disability Survey - Revised, Exercise Self-Efficacy Scale, Falls-Efficacy Scale (Swedish version), Social Influences on Physical Activity, Fatigue Severity Scale and Multiple Sclerosis Impact Scale. Response rate was 58.2%. Men were less physically active, had lower self-efficacy for physical activity and lower fall-related self-efficacy than women. This was explained by men being more physically affected by the disease. Men also received less social support for physical activity from family members. The level of fatigue and psychological consequences of the disease were similar between the genders in the total sample, but subgroups of women with moderate MS and relapsing remitting MS experienced more fatigue than men. Men were less physically active, probably a result of being more physically affected by the disease. Men being more physically affected explained most of the gender differences found in this study. However, the number of men in the subgroup analyses was small and more research is needed. A gender perspective should be considered in strategies for promoting physical activity in subjects with MS, e.g. men may need more support to be physically active.

  7. Metabolic and hemodynamic activation of postischemic rat brain by cortical spreading depression.

    Science.gov (United States)

    Kocher, M

    1990-07-01

    Following transient ischemia of the brain, the coupling between somatosensory activation and the hemodynamic-metabolic response is abolished for a certain period despite the partial recovery of somatosensory evoked responses. To determine whether this disturbance is due to alterations of the stimulus-induced neuronal excitation or to a breakdown of the coupling mechanisms, cortical spreading depression was used as a metabolic stimulus in rats before and after ischemia. Adult rats were subjected to 30 min of global forebrain ischemia and 3-6 h of recirculation. EEG, cortical direct current (DC) potential, and laser-Doppler flow were continuously recorded. Local CBF (LCBF), local CMRglc (LCMRglc), regional tissue contents of ATP, glucose, and lactate, and regional pH were determined by quantitative autoradiography, substrate-induced bioluminescence, and fluorometry. Amplitude and frequency of the DC shifts did not differ between groups. In control animals, spreading depression induced a 77% rise in cortical glucose consumption, a 66% rise in lactate content, and a drop in tissue pH of 0.3 unit. ATP and glucose contents were not depleted. During the passage of DC shifts, transient increases (less than 2 min) in laser-Doppler flow were observed, followed by a post-spreading depression hypoperfusion. A comparable although less expressed pattern of hemodynamic and metabolic changes was observed in the postischemic rats. Although baseline LCMRglc was depressed after ischemia, it was activated 47% during spreading depression. Lactate increased by 26%, pH decreased by 0.3 unit, and ATP and glucose remained unchanged. The extent of the transient increase in laser-Doppler flow did not differ from that of the control group, and a post-spreading depression hypoperfusion was also found.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Silymarin ameliorates metabolic dysfunction associated with Diet-induced Obesity via activation of farnesyl X receptor

    Directory of Open Access Journals (Sweden)

    Ming Gu

    2016-09-01

    Full Text Available AbstractBACKGROUND AND PURPOSESilymarin, a standardized extract of the milk thistle seeds, has been widely used to treat chronic hepatitis, cirrhosis and other types of toxic liver damage. . Despite increasing studies on the action of silymarin and its major active constituent, silybin in their therapeutic properties against insulin resistance, diabetes and hyperlipidaemia in vitro and in vivo, the mechanism underlying silymarin action remains unclear. EXPERIMENTAL APPROACHC57BL/6 mice were fed high-fat diet (HFD for 3 months to induce obesity, insulin resistance, hyperlipidaemia and fatty liver. These mice were then continuously treated with HFD alone or mixed with silymarin at 40 mg/100 g for additional 6 weeks. Biochemical analysis was used to test the serum lipid and bile acid profiles. FXR and NF-κB transactivities were analysed in liver using a gene reporter assay based onquantitative RT-PCR.KEY RESULTSSilymarin treatment ameliorated insulin resistance, dyslipidaemia and inflammation, and reconstituted the bile acid pool in liver of diet-induced obesity. Associated with this, silybin and silymarin enhanced FXR transactivity. Consistently, in HepG2 cells, silybin inhibited NF-κB signalling, which was enhanced by FXR activation. CONCLUSIONS AND IMPLICATIONSOur results suggest that silybin is an effective component of silymarin for treating metabolic syndrome by stimulating FXR signalling. Key words: silymarin; silybin; metabolic syndrome; non-alcoholic fatty liver disease; farnesyl X receptorAbbreviationsALT, alanine aminotransferase; AST, aspartate transaminase; BA, bile acid; DIO, diet-induced obesity; CA, cholic acid; DMSO, dimethylsulfoxide; FXR, farnesyl X receptor; HDL-c, high density lipoprotein cholesterol; HF, high-fat; IPITT, intraperitoneal insulin tolerance test; LDL-c, low density lipoprotein cholesterol; NAFLD, non-alcoholic fatty liver disease; NF-κB, nuclear factor kappa B; NR, nuclear receptor; MS, metabolic syndrome

  9. A review of Ramadan fasting and regular physical activity on metabolic syndrome indices

    Directory of Open Access Journals (Sweden)

    Seyyed Reza Attarzadeh Hosseini

    2016-03-01

    Full Text Available Introduction: Metabolic syndrome constitutes a cluster of risk factors such as obesity, hyperglycemia,  hypertension, and dyslipidemia, which increase the risk of cardiovascular diseases and type II diabetes mellitus. In this review article, we aimed to discuss the possible effects of fasting and regular physical activity on risk factors for cardiovascular diseases.  Methods: Online databases including Google Scholar, SID, PubMed, and MagIran were searched, using the following keywords:  “training”, “exercise”, “physical activity”, “fasting”, “Ramadan”, “metabolic syndrome”, “fat percentage”, “blood pressure”, “blood sugar”, “cholesterol”, “triglyceride”, and “lowdensity lipoprotein-cholesterol”. All articles including research studies, review articles, descriptive and analytical studies, and ross-sectional research, published during 2006-2015, were reviewed. In case of any errors in the methodologyof articles, they were removed from our analysis. Results:Based on our literature review, inconsistent findings have been reported on risk factors formetabolic syndrome. However, the majority of conducted studies have suggested the positive effects offasting on reducing the risk factors for metabolic syndrome. Conclusion: Although fasting in different seasons of the year has no significant impacts on mental health or physical fitness, it can reduce the risk of various diseases such as cardiovascular diseases. Also, based on the conducted studies, if individuals adhere to a proper diet, avoid excessive eating, drink sufficient amounts of fluids, and keep a healthy level of physical activity, fasting can improve their physical health.

  10. NAC-NOR mutations in tomato Penjar accessions attenuate multiple metabolic processes and prolong the fruit shelf life.

    Science.gov (United States)

    Kumar, Rakesh; Tamboli, Vajir; Sharma, Rameshwar; Sreelakshmi, Yellamaraju

    2018-09-01

    Several Penjar accessions of tomato grown in the Mediterranean exhibit prolonged shelf life and harbor alcobaca mutation. To uncover the metabolic basis underlying shelf life, we compared four Penjar accessions to Ailsa Craig. Three accessions bore alcobaca mutation, whereas the fourth was a novel NAC-NOR allele. Cuticle composition of Penjars varied widely during fruit ripening. All Penjars exhibited delayed ripening, prolonged on-vine and off-vine shelf life, low ethylene emission, and carotenoid levels. Metabolic profiling revealed shifts in Krebs cycle intermediates, amino acids, and γ-aminobutyric acid levels indicating the attenuation of respiration in Penjars during post-harvest storage. Penjar fruits also showed concerted downregulation of several cell-wall modifying genes and related metabolites. The high ABA and sucrose levels at the onset of senescence in Penjar fruits likely contribute to reduced water loss. Our analyses reveal that the attenuation of various metabolic processes by NAC-NOR mutation likely prolongs the shelf life of Penjar fruits. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Suitability of public use secondary data sets to study multiple activities.

    Science.gov (United States)

    Putnam, Michelle; Morrow-Howell, Nancy; Inoue, Megumi; Greenfield, Jennifer C; Chen, Huajuan; Lee, YungSoo

    2014-10-01

    The aims of this study were to inventory activity items within and across U.S. public use data sets, to identify gaps in represented activity domains and challenges in interpreting domains, and to assess the potential for studying multiple activity engagement among older adults using existing data. We engaged in content analysis of activity measures of 5U.S. public use data sets with nationally representative samples of older adults. Data sets included the Health & Retirement Survey (HRS), Americans' Changing Lives Survey (ACL), Midlife in the United States Survey (MIDUS), the National Health Interview Survey (NHIS), and the Panel Study of Income Dynamics survey (PSID). Two waves of each data set were analyzed. We identified 13 distinct activity domains across the 5 data sets, with substantial differences in representation of those domains among the data sets, and variance in the number and type of activity measures included in each. Our findings indicate that although it is possible to study multiple activity engagement within existing data sets, fuller sets of activity measures need to be developed in order to evaluate the portfolio of activities older adults engage in and the relationship of these portfolios to health and wellness outcomes. Importantly, clearer conceptual models of activity broadly conceived are required to guide this work. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. METs in adults while playing active video games: a metabolic chamber study.

    Science.gov (United States)

    Miyachi, Motohiko; Yamamoto, Kenta; Ohkawara, Kazunori; Tanaka, Shigeho

    2010-06-01

    Active video game systems controlled through arm gestures and motions (Nintendo Wii Sports) and video games controlled through force plate (Wii Fit Plus) are becoming increasingly popular. This study was performed to determine the energy expenditure (EE) during Wii Fit Plus and Wii Sports game activities. Twelve adult men and women performed all the activities of Wii Sports (five activities: golf, bowling, tennis, baseball, and boxing) and Wii Fit Plus (63 activities classified as yoga, resistance, balance, and aerobic exercises). Each activity was continued for at least 8 min to obtain a steady-state EE. Because EE was assessed in an open-circuit indirect metabolic chamber consisting of an airtight room (20,000 or 15,000 L), subjects were freed of apparatus to collect expired gas while playing the games. MET value was calculated from resting EE and steady-state EE during activity. The mean MET values of all 68 activities were distributed over a wide range from 1.3 METs (Lotus Focus) to 5.6 METs (single-arm stand). The mean MET values in yoga, balance, resistance, and aerobic exercise of Wii Fit Plus and Wii Sports were 2.1, 2.0, 3.2, 3.4, and 3.0 METs, respectively. Forty-six activities (67%) were classified as light intensity (6.0 METs). Time spent playing one-third of the activities supplied by motion- and gesture-controlled video games can count toward the daily amount of exercise required according to the guidelines provided by the American College of Sports Medicine and the American Heart Association, which focus on 30 min of moderate-intensity daily physical activity 5 d x wk(-1).

  13. Oncogenic MYC Activates a Feedforward Regulatory Loop Promoting Essential Amino Acid Metabolism and Tumorigenesis.

    Science.gov (United States)

    Yue, Ming; Jiang, Jue; Gao, Peng; Liu, Hudan; Qing, Guoliang

    2017-12-26

    Most tumor cells exhibit obligatory demands for essential amino acids (EAAs), but the regulatory mechanisms whereby tumor cells take up EAAs and EAAs promote malignant transformation remain to be determined. Here, we show that oncogenic MYC, solute carrier family (SLC) 7 member 5 (SLC7A5), and SLC43A1 constitute a feedforward activation loop to promote EAA transport and tumorigenesis. MYC selectively activates Slc7a5 and Slc43a1 transcription through direct binding to specific E box elements within both genes, enabling effective EAA import. Elevated EAAs, in turn, stimulate Myc mRNA translation, in part through attenuation of the GCN2-eIF2α-ATF4 amino acid stress response pathway, leading to MYC-dependent transcriptional amplification. SLC7A5/SLC43A1 depletion inhibits MYC expression, metabolic reprogramming, and tumor cell growth in vitro and in vivo. These findings thus reveal a MYC-SLC7A5/SLC43A1 signaling circuit that underlies EAA metabolism, MYC deregulation, and tumorigenesis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Litter environment affects behavior and brain metabolic activity of adult knockout mice

    Directory of Open Access Journals (Sweden)

    David Crews

    2009-08-01

    Full Text Available In mammals, the formative environment for social and anxiety-related behaviors is the family unit; in the case of rodents, this is the litter and the mother-young bond. A deciding factor in this environment is the sex ratio of the litter and, in the case of mice lacking functional copies of gene(s, the ratio of the various genotypes in the litter. Both Sex and Genotype ratios of the litter affect the nature and quality of the individual’s behavior later in adulthood, as well as metabolic activity in brain nuclei that underlie these behaviors. Mice were raised in litters reconstituted shortly after to birth to control for Sex ratio and Genotype ratio (wild type pups vs. pups lacking a functional estrogen receptor α. In both males and females the Sex and Genotype of siblings in the litter affected aggressive behaviors as well as patterns of metabolic activity in limbic nuclei in the social behavior network later in adulthood. Further, this pattern in males varied depending upon the Genotype of their brothers and sisters. Principal Components Analysis revealed two components comprised of several amygdalar and hypothalamic nuclei; the VMH showed strong correlations in both clusters, suggesting its pivotal nature in the organization of two neural networks.

  15. The metabolically active bacterial microbiome of tonsils and mandibular lymph nodes of slaughter pigs

    Directory of Open Access Journals (Sweden)

    Evelyne eMann

    2015-12-01

    Full Text Available The exploration of microbiomes in lymphatic organs is relevant for basic and applied research into explaining microbial translocation processes and understanding cross-contamination during slaughter. This study aimed to investigate whether metabolically active bacteria (MAB could be detected within tonsils and mandibular lymph nodes (MLNs of pigs. The hypervariable V1-V2 region of the bacterial 16S rRNA genes was amplified from cDNA from tonsils and MLNs of eight clinically healthy slaughter pigs. Pyrosequencing yielded 82,857 quality-controlled sequences, clustering into 576 operational taxonomic units (OTUs, which were assigned to 230 genera and 16 phyla. The actual number of detected OTUs per sample varied highly (23-171 OTUs. Prevotella zoogleoformans and Serratia proteamaculans (best type strain hits were most abundant (10.6% and 41.8% respectively in tonsils and MLNs, respectively. To explore bacterial correlation patterns between samples of each tissue, pairwise Spearman correlations (rs were calculated. In total, 194 strong positive and negative correlations |rs| ≥ 0.6 were found. We conclude that (i lymphatic organs harbor a high diversity of metabolically active bacteria, (ii the occurrence of viable bacteria in lymph nodes is not restricted to pathological processes and (iii lymphatic tissues may serve as a contamination source in pig slaughterhouses. This study confirms the necessity of the EFSA regulation with regard to a meat inspection based on visual examinations to foster a minimization of microbial contamination.

  16. Alimentary habits, physical activity, and Framingham global risk score in metabolic syndrome.

    Science.gov (United States)

    Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo

    2014-04-01

    Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases.

  17. Metabolism and prebiotics activity of anthocyanins from black rice (Oryza sativa L.) in vitro.

    Science.gov (United States)

    Zhu, Yongsheng; Sun, Hanju; He, Shudong; Lou, Qiuyan; Yu, Min; Tang, Mingming; Tu, Lijun

    2018-01-01

    Anthocyanins are naturally active substances. In this study, anthocyanins from black rice were obtained by membrane filtration and column chromatography separation. Five anthocyanin monomers in black rice extract were identified by HPLC-MS/MS, and the major anthocyanin monomer (cyanidin-3-glucoside, C3G) was purified by preparative HPLC (Pre-HPLC). The proliferative effects of the anthocyanins on Bifidobacteria and Lactobacillus were investigated by determining the media pH, bacterial populations and metabolic products. After anaerobic incubation at 37 °C for 48 h, not only the pH of the media containing C3G was lower than that of the extract of black rice anthocyanin (BRAE), but the numbers of both Bifidobacteria and Lactobacillus were also significantly increased. Furthermore, hydroxyphenylpropionic, hydroxyphenylacetic, and hydroxybenzoic acids and other metabolites were detected by GC-MS in vitro. Our results revealed that the anthocyanins and anthocyanin monomers from black rice had prebiotic activity and they were metabolized into several small molecules by Bifidobacteria and Lactobacillus.

  18. Alimentary Habits, Physical Activity, and Framingham Global Risk Score in Metabolic Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo, E-mail: anamariafeoli@hotmail.com [Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS (Brazil)

    2014-04-15

    Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p < 0.001). We obtained a reduction for intermediate risk in 25.7% of subjects. After intervention, there was a significant reduction (p < 0.01) on cardiovascular age, this being more significant in groups DIP (5.2%) and DIPE (5.3%). Proposed interventions produced beneficial effects for reducing cardiovascular risk score. This study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases.

  19. Alimentary Habits, Physical Activity, and Framingham Global Risk Score in Metabolic Syndrome

    International Nuclear Information System (INIS)

    Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo

    2014-01-01

    Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p < 0.001). We obtained a reduction for intermediate risk in 25.7% of subjects. After intervention, there was a significant reduction (p < 0.01) on cardiovascular age, this being more significant in groups DIP (5.2%) and DIPE (5.3%). Proposed interventions produced beneficial effects for reducing cardiovascular risk score. This study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases

  20. Effects of three types of physical activity on reduction of metabolic parameters involved in cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Petrović-Oggiano Gordana

    2009-01-01

    Full Text Available The aim of present study was to investigate the effects of three different types of physical activity on reduction of the metabolic parameters mainly responsible for cardiovascular diseases. This prospective-intervention study was performed at the 'ČIGOTA' Thyroid Institute on Mt. Zlatibor (Serbia between August 2004 and June 2006. Sixty-eight overweight/obese patients aged 40-70 years with hyperlipidemia were divided into three groups according to their weight and overall health. The program of physical workout included: group I - fast walking; group II - gymnastic exercises and specially chosen exercises in the swimming pool; and group III - combined physical training of higher intensity and greater length. All patients were also on a special reduced diet of 1000 kcal per day, the AHA step-2 diet. We monitored the body mass index, body composition, glucose, cholesterol (total, LDL-, and HDL-, and triglycerides before, during, and after the intervention. After 2 and particularly 12 weeks of intervention, a significant improvement of all metabolic parameters was achieved in all three groups of patients. Although most patients completed the study with normal values of all parameters, the most desirable results were achieved in group III (combined exercises with an average energy expenditure of 900 kcal per day. Our research indicates that a specially conceived program of physical activity and diet intervention resulted in significant reduction of cardiovascular risk factors.

  1. Comparative analysis of fecal microbiota and intestinal microbial metabolic activity in captive polar bears.

    Science.gov (United States)

    Schwab, Clarissa; Gänzle, Michael

    2011-03-01

    The composition of the intestinal microbiota depends on gut physiology and diet. Ursidae possess a simple gastrointestinal system composed of a stomach, small intestine, and indistinct hindgut. This study determined the composition and stability of fecal microbiota of 3 captive polar bears by group-specific quantitative PCR and PCR-DGGE (denaturing gradient gel electrophoresis) using the 16S rRNA gene as target. Intestinal metabolic activity was determined by analysis of short-chain fatty acids in feces. For comparison, other Carnivora and mammals were included in this study. Total bacterial abundance was approximately log 8.5 DNA gene copies·(g feces)-1 in all 3 polar bears. Fecal polar bear microbiota was dominated by the facultative anaerobes Enterobacteriaceae and enterococci, and the Clostridium cluster I. The detection of the Clostridium perfringens α-toxin gene verified the presence of C. perfringens. Composition of the fecal bacterial population was stable on a genus level; according to results obtained by PCR-DGGE, dominant bacterial species fluctuated. The total short-chain fatty acid content of Carnivora and other mammals analysed was comparable; lactate was detected in feces of all carnivora but present only in trace amounts in other mammals. In comparison, the fecal microbiota and metabolic activity of captive polar bears mostly resembled the closely related grizzly and black bears.

  2. Effects of Multiple Intelligences Activities on Writing Skill Development in an EFL Context

    Science.gov (United States)

    Gündüz, Zennure Elgün; Ünal, Ismail Dogan

    2016-01-01

    This study aims at exploring the effects of multiple intelligences activities versus traditional method on English writing development of the sixth grade students in Turkey. A quasi-experimental research method with a pre-test post-test design was applied. The participants were 50 sixth grade students at a state school in Ardahan in Turkey. The…

  3. Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing lesions

    NARCIS (Netherlands)

    Muris, A.H.; Rolf, L.; Damoiseaux, J.; Koeman, E.; Hupperts, R.

    2014-01-01

    Background: Fingolimod is a disease modifying therapy (DMT) in highly active relapsing remitting multiple sclerosis (RRMS), as is natalizumab. Fingolimod decreases annual relapse rates and gadolinium enhancing lesions on MRI as compared to either interferon beta (IFNβ) or placebo. The effect of

  4. Variation in the peroxisome proliferator-activated receptor δ gene in relation to common metabolic traits in 7,495 middle-aged white people

    DEFF Research Database (Denmark)

    Grarup, Niels; Albrechtsen, A.; Ek, J.

    2007-01-01

    Studies in animals reveal that peroxisome proliferator-activated receptor delta (PPARdelta) regulates glucose metabolism and insulin sensitivity in both the liver and skeletal muscles. Moreover, PPARdelta augments physical endurance and increases oxidative metabolism, thereby averting obesity. Th...

  5. Assessment of chitosan-affected metabolic response by peroxisome proliferator-activated receptor bioluminescent imaging-guided transcriptomic analysis.

    Directory of Open Access Journals (Sweden)

    Chia-Hung Kao

    Full Text Available Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholesteremic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice, which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR, a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo.

  6. Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling

    KAUST Repository

    Zeis, T.

    2015-04-01

    Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte–neuron lactate shuttle (ANLS) and the glutamate–glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1β signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1β and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others

  7. The relationship between objectively measured physical activity, salivary cortisol, and the metabolic syndrome score in girls.

    Science.gov (United States)

    DuBose, Katrina D; McKune, Andrew J

    2014-08-01

    The relationship between physical activity levels, salivary cortisol, and the metabolic syndrome (MetSyn) score was examined. Twenty-three girls (8.4 ± 0.9 years) had a fasting blood draw, waist circumference and blood pressure measured, and wore an ActiGraph accelerometer for 5 days. Saliva samples were collected to measure cortisol levels. Previously established cut points estimated the minutes spent in moderate, vigorous, and moderate-to-vigorous physical activity. A continuous MetSyn score was created from blood pressure, waist circumference, high-density-lipoprotein (HDL), triglyceride, and glucose values. Correlation analyses examined associations between physical activity, cortisol, the MetSyn score, and its related components. Regression analysis examined the relationship between cortisol, the MetSyn score, and its related components adjusting for physical activity, percent body fat, and sexual maturity. Vigorous physical activity was positively related with 30 min post waking cortisol values. The MetSyn score was not related with cortisol values after controlling for confounders. In contrast, HDL was negatively related with 30 min post waking cortisol. Triglyceride was positively related with 30 min post waking cortisol and area under the curve. The MetSyn score and many of its components were not related to cortisol salivary levels even after adjusting for physical activity, body fat percentage, and sexual maturity.

  8. Relation between presence-absence of a visible nucleoid and metabolic activity in bacterioplankton cells

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Joon, W.; Sherr, E.B.; Sherr, B.F. [Oregon State Univ., Corvallis, OR (United States)

    1996-09-01

    We investigated the report of Zweifel and Hagstroem that only a portion of marine bacteria contain nucleoids--the DNA-containing regions of procaryotic cells-- and that such bacteria correspond to the active or viable fraction of bacterioplankton. In Oregon coastal waters, 21-64% of bacteria had visible nucleoids; number of nucleoid-visible (NV) bacteria were greater than numbers of metabolically active bacteria, based on cells with active electron transport systems (ETS) and intact cell membranes. During log growth of a marine isolate, proportions of NV and ETS-active cells approached 100%. In stationary growth phase, the fraction of ETS-active cells decreased rapidly, while that of NV cells remained high for 7 d. When starved cells of the isolate were resupplied with nutrient (50 mg liter{sup -1} peptone), total cell number did not increase during the initial 6 h, but the proportion of NV cells increased from 27 to 100%, and that of ETS-active cells from 6 to 75%. In an analogous experiment with a bacterioplankton assemblage, a similar trend was observed: the number of NV cells double during the initial 6 h prior to an increase in total cell counts. These results show that some bacteria without visible nucleoids are capable of becoming NV cells, and thus have DNa in a nucleoid region not detectable with the method used here. 18 refs., 4 figs., 1 tab.

  9. Saccharomyces cerevisiae single-copy plasmids for auxotrophy compensation, multiple marker selection, and for designing metabolically cooperating communities [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Michael Mülleder

    2016-09-01

    Full Text Available Auxotrophic markers are useful tools in cloning and genome editing, enable a large spectrum of genetic techniques, as well as facilitate the study of metabolite exchange interactions in microbial communities. If unused background auxotrophies are left uncomplemented however, yeast cells need to be grown in nutrient supplemented or rich growth media compositions, which precludes the analysis of biosynthetic metabolism, and which leads to a profound impact on physiology and gene expression. Here we present a series of 23 centromeric plasmids designed to restore prototrophy in typical Saccharomyces cerevisiae laboratory strains. The 23 single-copy plasmids complement for deficiencies in HIS3, LEU2, URA3, MET17 or LYS2 genes and in their combinations, to match the auxotrophic background of the popular functional-genomic yeast libraries that are based on the S288c strain. The plasmids are further suitable for designing self-establishing metabolically cooperating (SeMeCo communities, and possess a uniform multiple cloning site to exploit multiple parallel selection markers in protein expression experiments.

  10. Physical activity, Cardio-Respiratory Fitness, and Metabolic Traits in Rural Mexican Tarahumara

    DEFF Research Database (Denmark)

    Christensen, Dirk Lund; Alcala-Sanchez, Imelda; Leal-Berumen, Irene

    2012-01-01

    Objectives: To study the association between physical activity energy expenditure (PAEE) and cardio-respiratory fitness (CRF) with key metabolic traits and anthropometric measures in the Tarahumara of Mexico. Methods: A cross-sectional study was carried out in five rural communities in Chihuahua...... suggests high levels of overweight and hypertension in the Tarahumara, and points to fitness and physical activity as potential intervention targets although findings should be confirmed in larger samples.......) to estimate CRF. Random blood glucose level and resting blood pressure (BP) were measured with standard anthropometrics. Results: Mean (SD) PAEE was 71.2 (30.3) kJ kg21 day21 and CRF was 36.6 (6.5) mlO2 min21 kg21. Mean (SD) glucose was 127.9 (32.4) mg/dl, with 3.3% having diabetes. Mean (SD) systolic...

  11. Hormonal and metabolic regulation of tomato fruit sink activity and yield under salinity

    DEFF Research Database (Denmark)

    Albacete, Alfonso; Cantero-Navarro, Elena; Balibrea, María E.

    2014-01-01

    Salinization of water and soil has a negative impact on tomato (Solanum lycopersicum L.) productivity by reducing growth of sink organs and by inducing senescence in source leaves. It has been hypothesized that yield stability implies the maintenance or increase of sink activity in the reproductive...... structures, thus contributing to the transport of assimilates from the source leaves through changes in sucrolytic enzymes and their regulation by phytohormones. In this study, classical and functional physiological approaches have been integrated to study the influence of metabolic and hormonal factors...... sucrolytic activities (mainly cwInv and sucrose synthase), sink strength, and fruit weight, whereas the ethylene-releasing compound ethephon had a negative effect in equivalent non-stressed fruits. Fruit yield was increased by both the constitutive expression of CIN1 in the fruits (up to 4-fold) or IPT...

  12. Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Ines eLassowskat

    2014-10-01

    Full Text Available Mitogen-activated protein kinases (MAPKs target a variety of protein substrates to regulate cellular signaling processes in eukaryotes. In plants, the number of identified MAPK substrates that control plant defense responses is still limited. Here, we generated transgenic Arabidopsis thaliana plants with an inducible system to simulate in vivo activation of two stress-activated MAPKs, MPK3 and MPK6. Metabolome analysis revealed that this artificial MPK3/6 activation (without any exposure to pathogens or other stresses is sufficient to drive the production of major defense-related metabolites, including various camalexin, indole glucosinolate and agmatine derivatives. An accompanying (phosphoproteome analysis led to detection of hundreds of potential phosphoproteins downstream of MPK3/6 activation. Besides known MAPK substrates, many candidates on this list possess typical MAPK-targeted phosphosites and in many cases, the corresponding phosphopeptides were detected by mass spectrometry. Notably, several of these putative phosphoproteins have been reported to be associated with the biosynthesis of antimicrobial defense substances (e.g. WRKY transcription factors and proteins encoded by the genes from the PEN pathway required for penetration resistance to filamentous pathogens. Thus, this work provides an inventory of candidate phosphoproteins, including putative direct MAPK substrates, for future analysis of MAPK-mediated defense control. (Proteomics data are available with the identifier PXD001252 via ProteomeXchange, http://proteomecentral.proteomexchange.org.

  13. GABAA receptor activity modulating piperine analogs: In vitro metabolic stability, metabolite identification, CYP450 reaction phenotyping, and protein binding.

    Science.gov (United States)

    Zabela, Volha; Hettich, Timm; Schlotterbeck, Götz; Wimmer, Laurin; Mihovilovic, Marko D; Guillet, Fabrice; Bouaita, Belkacem; Shevchenko, Bénédicte; Hamburger, Matthias; Oufir, Mouhssin

    2018-01-01

    In a screening of natural products for allosteric modulators of GABA A receptors (γ-aminobutyric acid type A receptor), piperine was identified as a compound targeting a benzodiazepine-independent binding site. Given that piperine is also an activator of TRPV1 (transient receptor potential vanilloid type 1) receptors involved in pain signaling and thermoregulation, a series of piperine analogs were prepared in several cycles of structural optimization, with the aim of separating GABA A and TRPV1 activating properties. We here investigated the metabolism of piperine and selected analogs in view of further cycles of lead optimization. Metabolic stability of the compounds was evaluated by incubation with pooled human liver microsomes, and metabolites were analyzed by UHPLC-Q-TOF-MS. CYP450 isoenzymes involved in metabolism of compounds were identified by reaction phenotyping with Silensomes™. Unbound fraction in whole blood was determined by rapid equilibrium dialysis. Piperine was the metabolically most stable compound. Aliphatic hydroxylation, and N- and O-dealkylation were the major routes of oxidative metabolism. Piperine was exclusively metabolized by CYP1A2, whereas CYP2C9 contributed significantly in the oxidative metabolism of all analogs. Extensive binding to blood constituents was observed for all compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Exploring the facilitators and barriers to engagement in physical activity for people with multiple sclerosis.

    Science.gov (United States)

    Kayes, Nicola M; McPherson, Kathryn M; Schluter, Philip; Taylor, Denise; Leete, Marta; Kolt, Gregory S

    2011-01-01

    To explore the relationship that cognitive behavioural and other previously identified variables have with physical activity engagement in people with multiple sclerosis (MS). This study adopted a cross-sectional questionnaire design. Participants were 282 individuals with MS. Outcome measures included the Physical Activity Disability Survey--Revised, Cognitive and Behavioural Responses to Symptoms Questionnaire, Barriers to Health Promoting Activities for Disabled Persons Scale, Multiple Sclerosis Self-efficacy Scale, Self-Efficacy for Chronic Diseases Scales and Chalder Fatigue Questionnaire. Multivariable stepwise regression analyses found that greater self-efficacy, greater reported mental fatigue and lower number of perceived barriers to physical activity accounted for a significant proportion of variance in physical activity behaviour, over that accounted for by illness-related variables. Although fear-avoidance beliefs accounted for a significant proportion of variance in the initial analyses, its effect was explained by other factors in the final multivariable analyses. Self-efficacy, mental fatigue and perceived barriers to physical activity are potentially modifiable variables which could be incorporated into interventions designed to improve physical activity engagement. Future research should explore whether a measurement tool tailored to capture beliefs about physical activity identified by people with MS would better predict participation in physical activity.

  15. When things don't add up: quantifying impacts of multiple stressors from individual metabolism to ecosystem processing.

    Science.gov (United States)

    Galic, Nika; Sullivan, Lauren L; Grimm, Volker; Forbes, Valery E

    2018-04-01

    Ecosystems are exposed to multiple stressors which can compromise functioning and service delivery. These stressors often co-occur and interact in different ways which are not yet fully understood. Here, we applied a population model representing a freshwater amphipod feeding on leaf litter in forested streams. We simulated impacts of hypothetical stressors, individually and in pairwise combinations that target the individuals' feeding, maintenance, growth and reproduction. Impacts were quantified by examining responses at three levels of biological organisation: individual-level body sizes and cumulative reproduction, population-level abundance and biomass and ecosystem-level leaf litter decomposition. Interactive effects of multiple stressors at the individual level were mostly antagonistic, that is, less negative than expected. Most population- and ecosystem-level responses to multiple stressors were stronger than expected from an additive model, that is, synergistic. Our results suggest that across levels of biological organisation responses to multiple stressors are rarely only additive. We suggest methods for efficiently quantifying impacts of multiple stressors at different levels of biological organisation. © 2018 John Wiley & Sons Ltd/CNRS.

  16. [Effects of waterlogging on the growth and energy-metabolic enzyme activities of different tree species].

    Science.gov (United States)

    Wang, Gui-Bin; Cao, Fu-Liang; Zhang, Xiao-Yan; Zhang, Wang-Xiang

    2010-03-01

    Aimed to understand the waterlogging tolerance and adaptation mechanisms of different tree species, a simulated field experiment was conducted to study the growth and energy-metabolic enzyme activities of one-year-old seedlings of Taxodium distichum, Carya illinoensis, and Sapium sebiferum. Three treatments were installed, i. e., CK, waterlogging, and flooding, with the treatment duration being 60 days. Under waterlogging and flooding, the relative growth of test tree species was in the order of T. distichum > C. illinoensis > S. sebiferum, indicating that T. distichum had the strongest tolerance against waterlogging and flooding, while S. sebiferum had the weakest one. Also under waterlogging and flooding, the root/crown ratio of the three tree species increased significantly, suggesting that more photosynthates were allocated in roots, and the lactate dehydrogenase (LDH) and alcohol dehydrogenase (ADH) activities of the tree species also had a significant increase. Among the test tree species, T. distichum had the lowest increment of LDH and ADH activities under waterlogging and flooding, but the increment could maintain at a higher level in the treatment duration, while for C. illinoensis and S. sebiferum, the increment was larger during the initial and medium period, but declined rapidly during the later period of treatment. The malate dehydrogenase (MDH), phosphohexose (HPI), and glucose-6-phosphate dehydrogenase (G6PDH) -6-phosphogluconate dehydrogenase (6PGDH) activities of the tree species under waterlogging and flooding had a significant decrease, and the decrement was the largest for T. distichum, being 35.6% for MDH, 21.0% for HPI, and 22.7% for G6PDH - 6PGDH under flooding. It was suggested that under waterlogging and flooding, the tree species with strong waterlogging tolerance had a higher ability to maintain energy-metabolic balance, and thus, its growth could be maintained at a certain level.

  17. Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

    Science.gov (United States)

    Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

    2017-11-01

    Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  18. Body mass index, metabolic factors, and striatal activation during stressful and neutral-relaxing states: an FMRI study.

    Science.gov (United States)

    Jastreboff, Ania M; Potenza, Marc N; Lacadie, Cheryl; Hong, Kwangik A; Sherwin, Robert S; Sinha, Rajita

    2011-02-01

    Stress is associated with alterations in neural motivational-reward pathways in the ventral striatum (VS), hormonal/metabolic changes, and weight increases. The relationship between these different factors is not well understood. We hypothesized that body mass index (BMI) status and hormonal/metabolic factors would be associated with VS activation. We used functional magnetic resonance imaging (fMRI) to compare brain responses of overweight and obese (OW/OB: BMI ≥ 25 kg/m(2): N=27) individuals with normal weight (NW: BMI<18.5-24.9 kg/m(2): N=21) individuals during exposure to personalized stress, alcohol cue, and neutral-relaxing situations using a validated, autobiographical, script-driven, guided-imagery paradigm. Metabolic factors, including fasting plasma glucose (FPG), insulin, and leptin, were examined for their association with VS activation. Consistent with previous studies, stress and alcohol cue exposure each increased activity in cortico-limbic regions. Compared with NW individuals, OW/OB individuals showed greater VS activation in the neutral-relaxing and stress conditions. FPG was correlated with VS activation. Significant associations between VS activation and metabolic factors during stress and relaxation suggest the involvement of metabolic factors in striatal dysfunction in OW/OB individuals. This relationship may contribute to non-homeostatic feeding in obesity.

  19. Life-history evolution and the microevolution of intermediary metabolism: activities of lipid-metabolizing enzymes in life-history morphs of a wing-dimorphic cricket.

    Science.gov (United States)

    Zera, Anthony J; Zhao, Zhangwu

    2003-03-01

    Although a considerable amount of information is available on the ecology, genetics, and physiology of life-history traits, much more limited data are available on the biochemical and genetic correlates of life-history variation within species. Specific activities of five enzymes of lipid biosynthesis and two enzymes of amino acid catabolism were compared among lines selected for flight-capable (LW[f]) versus flightless (SW) morphs of the cricket Gryllus firmus. These morphs, which exist in natural populations, differ genetically in ovarian growth (100-400% higher in SW) and aspects of flight capability including the size of wings and flight muscles, and the concentration of triglyceride flight fuel (40% greater in LW[f]). Consistently higher activity of each enzyme in LW(f) versus SW-selected lines, and strong co-segregation between morph and enzyme activity, demonstrated genetically based co-variance between wing morph and enzyme activity. Developmental profiles of enzyme activities strongly paralleled profiles of triglyceride accumulation during adulthood and previous measures of in vivo lipid biosynthesis. These data strongly imply that genetically based elevation in activities of lipogenic enzymes, and enzymes controlling the conversion of amino acids into lipids, is an important cause underlying the elevated accumulation of triglyceride in the LW(f) morph, a key biochemical component of the trade-off between elevated early fecundity and flight capability. Global changes in lipid and amino-acid metabolism appear to have resulted from microevolutionary alteration of regulators of metabolism. Finally, strong genotype x environment (diet) interactions were observed for most enzyme activities. Future progress in understanding the functional causes of life-history evolution requires a more detailed synthesis of the fields of life-history evolution and metabolic biochemistry. Wing polymorphism is a powerful experimental model in such integrative studies.

  20. The metabolic regulator CodY links L. monocytogenes metabolism to virulence by directly activating the virulence regulatory gene, prfA

    Science.gov (United States)

    Lobel, Lior; Sigal, Nadejda; Borovok, Ilya; Belitsky, Boris R.; Sonenshein, Abraham L.; Herskovits, Anat A.

    2015-01-01

    Summary Metabolic adaptations are critical to the ability of bacterial pathogens to grow within host cells and are normally preceded by sensing of host-specific metabolic signals, which in turn can influence the pathogen's virulence state. Previously, we reported that the intracellular bacterial pathogen Listeria monocytogenes responds to low availability of branched-chain amino acids (BCAA) within mammalian cells by up-regulating both BCAA biosynthesis and virulence genes. The induction of virulence genes required the BCAA-responsive transcription regulator, CodY, but the molecular mechanism governing this mode of regulation was unclear. In this report, we demonstrate that CodY directly binds the coding sequence of the L. monocytogenes master virulence activator gene, prfA, 15 nt downstream of its start codon, and that this binding results in up-regulation of prfA transcription specifically under low concentrations of BCAA. Mutating this site abolished CodY binding and reduced prfA transcription in macrophages, and attenuated bacterial virulence in mice. Notably, the mutated binding site did not alter prfA transcription or PrfA activity under other conditions that are known to activate PrfA, such as during growth in the presence of glucose-1-phosphate. This study highlights the tight crosstalk between L. monocytogenes metabolism and virulence' while revealing novel features of CodY-mediated regulation. PMID:25430920

  1. Dynamic activity of NF-κB in multiple trauma patients and protective effects of ulinastain

    Directory of Open Access Journals (Sweden)

    LI Jun

    2012-02-01

    Full Text Available 【Abstract】Objective: To investigate the dynamic activity of NF-κB at the early stage of injury in multiple trauma patients and the protective effects of ulinastain. Methods: From January 2008 to May 2010, patients with multiple traumas admitted to our emergency department were enrolled in this study. Their age varied from 20-55 years. All enrolled patients were assigned randomly into control group (26 cases of multiple injury without ulinastain treatment, ulinastain group (25 cases of multiple injury with ulinastain treatment, and mild injury group (20 cases for basic control. The inclusion criteria for mild injury group were AIS-2005≤3, single wound, previously healthy inhospital patients without the history of surgical intervention. In addition to routine treatment, patients in ulinastain group were intravenously injected 200 000 IU of ulinastain dissolved in 100 ml of normal saline within 12 hours after injury and subsequently injected at the interval of every 8 hours for 7 days. NF-κB activity in monocytes and the level of TNF? IL-1, IL? in serum on admission (day 0, day 1, 2, 3, 4, and 7 were measured. Data were compared and analyzed between different groups. Results: NF-κB activity in monocytes and TNF? IL-1 and IL? of these patients reached peak levels at 24 hour after trauma, with gradual decrease to normal at 72 hour after trauma. NF-κB activity and levels of TNF? IL-1 and IL? were lower in ulinastain group than control one, without any significant difference between the two groups. The mean duration for systemic inflammatory response syndrome and multiple organ dysfunction syndrome was 7 d?.1 d and 10 d?.5 d in ulinastain group and control group respectively, and showed a significant difference. Conclusions: NF-κB activity in monocytes and the levels of inflammatory cytokines in multiply injured patients increased transiently at the early stage of trauma. Ulinastain may shorten the duration of systemic inflammatory

  2. Effects of a glucokinase activator on hepatic intermediary metabolism: study with 13C-isotopomer-based metabolomics

    OpenAIRE

    Nissim, Itzhak; Horyn, Oksana; Nissim, Ilana; Daikhin, Yevgeny; Wehrli, Suzanne L.; Yudkoff, Marc; Matschinsky, Franz M.

    2012-01-01

    GKAs (glucokinase activators) are promising agents for the therapy of Type 2 diabetes, but little is known about their effects on hepatic intermediary metabolism. We monitored the fate of 13C-labelled glucose in both a liver perfusion system and isolated hepatocytes. MS and NMR spectroscopy were deployed to measure isotopic enrichment. The results demonstrate that the stimulation of glycolysis by GKA led to numerous changes in hepatic metabolism: (i) augmented flux through the TCA (tricarboxy...

  3. T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

    Science.gov (United States)

    van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

    2018-05-01

    Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4

  4. The influence of hydrologic connectivity on ecosystem metabolism and nitrate uptake in an active beaver meadow

    Science.gov (United States)

    Wegener, P.; Covino, T. P.; Wohl, E.; Kampf, S. K.; Lacy, S.

    2015-12-01

    Wetlands have been widely demonstrated to provide important watershed services, such as the sequestration of carbon (C) and removal of nitrate (NO3-) from through-flowing water. Hydrologic connectivity (degree of water and associated material exchange) between floodplain water bodies (e.g., side channels, ponds) and the main channel influence rates of C accumulation and NO3- uptake, and the degree to which wetlands contribute to enhanced water quality at the catchment scale. However, environmental engineers have largely ignored the role of hydrologic connectivity in providing essential ecosystem services, and constructed wetlands are commonly built using compacted clay and berms that result in less groundwater and surface water exchange than observed in natural wetlands. In a study of an active beaver meadow (multithreaded, riparian wetland) in Rocky Mountain National Park, CO, we show how shifts in hydrology (connectivity, residence times, flow paths) from late spring snowmelt (high connectivity) to autumn/winter baseflow (low connectivity) influence ecosystem metabolism metrics (e.g., gross primary production, ecosystem respiration, and net ecosystem productivity) and NO3- uptake rates. We use a combination of mixing analyses, tracer tests, and hydrometric methods to evaluate shifts in surface and subsurface hydrologic connections between floodplain water bodies from snowmelt to baseflow. In the main channel and three floodplain water bodies, we quantify metabolism metrics and NO3- uptake kinetics across shifting flow regimes. Results from our research indicate that NO3- uptake and metabolism dynamics respond to changing levels of hydrologic connectivity to the main channel, emphasizing the importance of incorporating connectivity in wetland mitigation practices that seek to enhance water quality at the catchment scale.

  5. Metabolic activity in the insular cortex and hypothalamus predicts hot flashes: an FDG-PET study.

    Science.gov (United States)

    Joffe, Hadine; Deckersbach, Thilo; Lin, Nancy U; Makris, Nikos; Skaar, Todd C; Rauch, Scott L; Dougherty, Darin D; Hall, Janet E

    2012-09-01

    Hot flashes are a common side effect of adjuvant endocrine therapies (AET; leuprolide, tamoxifen, aromatase inhibitors) that reduce quality of life and treatment adherence in breast cancer patients. Because hot flashes affect only some women, preexisting neurobiological traits might predispose to their development. Previous studies have implicated the insula during the perception of hot flashes and the hypothalamus in thermoregulatory dysfunction. The aim of the study was to understand whether neurobiological factors predict hot flashes. [18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET) brain scans coregistered with structural magnetic resonance imaging were used to determine whether metabolic activity in the insula and hypothalamic thermoregulatory and estrogen-feedback regions measured before and in response to AET predict hot flashes. Findings were correlated with CYP2D6 genotype because of CYP2D6 polymorphism associations with tamoxifen-induced hot flashes. We measured regional cerebral metabolic rate of glucose uptake (rCMRglu) in the insula and hypothalamus on FDG-PET. Of 18 women without hot flashes who began AET, new-onset hot flashes were reported by 10 (55.6%) and were detected objectively in nine (50%) participants. Prior to the use of all AET, rCMRglu in the insula (P ≤ 0.01) and hypothalamic thermoregulatory (P = 0.045) and estrogen-feedback (P = 0.007) regions was lower in women who reported developing hot flashes. In response to AET, rCMRglu was further reduced in the insula in women developing hot flashes (P ≤ 0.02). Insular and hypothalamic rCMRglu levels were lower in intermediate than extensive CYP2D6 metabolizers. Trait neurobiological characteristics predict hot flashes. Genetic variability in CYP2D6 may underlie the neurobiological predisposition to hot flashes induced by AET.

  6. Metabolic activation of carbon tetrachloride by the cervico-vaginal epithelium in rodents

    International Nuclear Information System (INIS)

    Brittebo, E.B.; Brandt, I.

    1989-01-01

    The metabolism and binding of 14 C-labelled carbon tetrachloride (CCl 4 ) in the genital tract of female adult or juvenile NMRI-mice and Sprague-Dawly rats (mainly in the pro-oestrous/oestrous stage) and an adult New Zealand rabbit were studied. A marked irreversible binding of radioactivity in the squamous cervico-vaginal epithelium of mice given intravenous injections of 14 C-CCl 4 was revealed by autoradiography of solvent-extracted tissue. The localization of binding in the mouse genital tract incubated with 14 C-CCl 4 under air was similar to that observed in vivo. Bound radioactivity was also present in the cylindrical epithelium of the rabbit vagina incubated with 14 C-CCl 4 in vitro. For a comparison, no preferential binding of radiolabelled diethylstilbestrol or ethinylestradiol was observed in the mouse cervico-vaginal epithelium. The level of irreversible binding to PMSG-primed (pregnant mare's serum gonadotrophin) vaginal epithelial 100 x g supernatants of mice and rats incubated with 14 C-CCl 4 under air was low. Addition of the reducing agent dithionite to the incubations increased the binding in the vaginal epithelium 20-fold. In juvenile mice and rats injected with 14 C-CCl 4 , the levels of metabolites in the epithelium were low, whereas PMSG-primed juvenile rats contained a higher level of metabolites. The results show that the cervico-vaginal epithelium can metabolically activate CCl 4 to reactive metabolites and suggest that the metabolism is under endocrine control. (author)

  7. Semi-active control of a cable-stayed bridge under multiple-support excitations.

    Science.gov (United States)

    Dai, Ze-Bing; Huang, Jin-Zhi; Wang, Hong-Xia

    2004-03-01

    This paper presents a semi-active strategy for seismic protection of a benchmark cable-stayed bridge with consideration of multiple-support excitations. In this control strategy, Magnetorheological (MR) dampers are proposed as control devices, a LQG-clipped-optimal control algorithm is employed. An active control strategy, shown in previous researches to perform well at controlling the benchmark bridge when uniform earthquake motion was assumed, is also used in this study to control this benchmark bridge with consideration of multiple-support excitations. The performance of active control system is compared to that of the presented semi-active control strategy. Because the MR fluid damper is a controllable energy- dissipation device that cannot add mechanical energy to the structural system, the proposed control strategy is fail-safe in that bounded-input, bounded-output stability of the controlled structure is guaranteed. The numerical results demonstrated that the performance of the presented control design is nearly the same as that of the active control system; and that the MR dampers can effectively be used to control seismically excited cable-stayed bridges with multiple-support excitations.

  8. Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria.

    Science.gov (United States)

    Lehouritis, Panos; Stanton, Michael; McCarthy, Florence O; Jeavons, Matthieu; Tangney, Mark

    2016-01-28

    Some chemotherapeutic drugs (prodrugs) require activation by an enzyme for efficacy. We and others have demonstrated the ability of probiotic bacteria to grow specifically within solid tumours following systemic administration, and we hypothesised that the natural enzymatic activity of these tumour-localised bacteria may be suitable for activation of certain such chemotherapeutic drugs. Several wild-type probiotic bacteria; Escherichia coli Nissle, Bifidobacterium breve, Lactococcus lactis and Lactobacillus species, were screened against a panel of popular prodrugs. All strains were capable of activating at least one prodrug. E. coli Nissle 1917 was selected for further studies because of its ability to activate numerous prodrugs and its resistance to prodrug toxicity. HPLC data confirmed biochemical transformation of prodrugs to their toxic counterparts. Further analysis demonstrated that different enzymes can complement prodrug activation, while simultaneous activation of multiple prodrugs (CB1954, 5-FC, AQ4N and Fludarabine phosphate) by E. coli was confirmed, resulting in significant efficacy improvement. Experiments in mice harbouring murine tumours validated in vitro findings, with significant reduction in tumour growth and increase in survival of mice treated with probiotic bacteria and a combination of prodrugs. These findings demonstrate the ability of probiotic bacteria, without the requirement for genetic modification, to enable high-level activation of multiple prodrugs specifically at the site of action. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. [Sedentary lifestyle is associated with metabolic and cardiovascular risk factors independent of physical activity].

    Science.gov (United States)

    Leiva, Ana María; Martínez, María Adela; Cristi-Montero, Carlos; Salas, Carlos; Ramírez-Campillo, Rodrigo; Díaz Martínez, Ximena; Aguilar-Farías, Nicolás; Celis-Morales, Carlos

    2017-04-01

    Sedentary behavior is a main risk factor for cardiovascular disease and mortality. To investigate the association between sedentary behavior and metabolic and cardiovascular risk factors. We assessed 322 participants aged between 18 to 65 years. Physical activity and sedentary behavior were measured with accelerometers (Actigraph®). Body mass index (BMI), waist circumference, percentage of body fat, diet and blood markers (glucose, lipid profile, insulin and HOMA-IR) were measured with standardized protocols. Thirty four percent of participants were physically inactive and spent on average 8.7 h/day on sedentary activities. Per one hour increase in sedentary behavior there were significant adverse changes in glucose (4.79 mg/dl), insulin (2.73 pmol/l), HOMA-IR (0.75), BMI (0.69 kg/m²), waist circumference (1.95 cm), fat mass (1.03%), total cholesterol (9.73 mg/dl), HDL-cholesterol (-3.50 mg/dl), LDL-cholesterol (10.7 mg/dl) and triglycerides (12.4 mg/dl). These findings were independent of main confounding factors including total physical activity, dietary factors, BMI and socio-demographics. The detrimental effect of sedentary behaviors on cardiometabolic and obesity-related traits is independent of physical activity levels. Therefore, reducing sedentary time should be targeted in the population apart from increasing their physical activity levels.

  10. Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase activities and incident metabolic syndrome.

    Science.gov (United States)

    Yary, T; Voutilainen, S; Tuomainen, T-P; Ruusunen, A; Nurmi, T; Virtanen, J K

    2017-08-01

    The associations of n-6 polyunsaturated fatty acids (PUFA) with metabolic syndrome have been poorly explored. We investigated the associations of the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism, delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident metabolic syndrome. We also investigated whether zinc, a cofactor for these enzymes, modifies these associations. A prospective follow-up study was conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and who were re-examined in 1998-2001. Men in the highest versus the lowest serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.18-0.51, P trend metabolic syndrome components at the re-examinations. Most associations were attenuated after adjustment for body mass index. Finally, the associations of D6D and LA were stronger among those with a higher serum zinc concentration. Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations and D5D activity were associated with a lower risk of developing metabolic syndrome and higher D6D activity was associated with a higher risk. The role of zinc also needs to be investigated in other populations. © 2016 The British Dietetic Association Ltd.

  11. Identification of Circular RNAs From the Parental Genes Involved in Multiple Aspects of Cellular Metabolism in Barley

    Directory of Open Access Journals (Sweden)

    Behrooz eDarbani

    2016-06-01

    Full Text Available RNA circularization made by head-to-tail back-splicing events is involved in the regulation of gene expression from transcriptional to post-translational levels. By exploiting RNA-Seq data and down-stream analysis, we shed light on the importance of circular RNAs in plants. The results introduce circular RNAs as novel interactors in the regulation of gene expression in plants and imply the comprehensiveness of this regulatory pathway by identifying circular RNAs for a diverse set of genes. These genes are involved in several aspects of cellular metabolism as hormonal signaling, intracellular protein sorting, carbohydrate metabolism and cell-wall biogenesis, respiration, amino acid biosynthesis, transcription and translation, and protein ubiquitination. Additionally, these parental loci of circular RNAs, from both nuclear and mitochondrial genomes, encode for different transcript classes including protein coding transcripts, microRNA, rRNA, and long non-coding/microprotein coding RNAs. The results shed light on the mitochondrial exonic circular RNAs and imply the importance of circular RNAs for regulation of mitochondrial genes. Importantly, we introduce circular RNAs in barley and elucidate their cellular-level alterations across tissues and in response to micronutrients iron and zinc. In further support of circular RNAs' functional roles in plants, we report several cases where fluctuations of circRNAs do not correlate with the levels of their parental-loci encoded linear transcripts.Keywords: circular RNAs, coding and non-coding transcripts, leaves, seeds, transfer cells, micronutrients, mitochondria

  12. Hamster activity and estrous cycles: control by a single versus multiple circadian oscillator(s).

    OpenAIRE

    Carmichael, M S; Nelson, R J; Zucker, I

    1981-01-01

    Running activity onset and estrous onset were recorded for hamsters exposed to progressively shorter daily light/dark (T) cycles. The period of the estrous cycle was a quadruple multiple of the period of the activity rhythm during entrainment to T cycles of 23.5-21.5 hr. There was no evidence of desynchronization of the activity and estrus rhythms. The very short estrous periods shown during exposure to short T cycles indicate that an intrinsic 96-hr interval for ovarian follicular maturation...

  13. Pots and Pans Activities for Parent and Child: Activities for Preschool Multiple Handicapped Children.

    Science.gov (United States)

    Van Tassel, Jean

    Intended for parents and teachers of multiply handicapped preschool children, the booklet provides lesson plans in three major areas--basic concepts, motor activities, and language activities. Each lesson plan is broken down into four parts: purpose (a descriptive statement of what the lesson hopes to accomplish), materials (list of materials…

  14. Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats.

    Directory of Open Access Journals (Sweden)

    Nady Braidy

    2011-04-01

    Full Text Available The cofactor nicotinamide adenine dinucleotide (NAD+ has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose polymerase (PARP, an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD:NADH ratio in all organs by middle age (i.e.12 months compared to young (i.e. 3 month old rats. These changes in [NAD(H] occurred in parallel with an increase in lipid peroxidation and protein carbonyls (o- and m- tyrosine formation and decline in total antioxidant capacity in these organs. An age dependent increase in DNA damage (phosphorylated H2AX was also observed in these same organs. Decreased Sirt1 activity and increased acetylated p53 were observed in organ tissues in parallel with the drop in NAD+ and moderate over-expression of Sirt1 protein. Reduced mitochondrial activity of complex I-IV was also observed in aging animals, impacting both redox status and ATP production. The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor.

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

    Science.gov (United States)

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

    2012-01-01

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

  16. A Copolymer Scaffold Functionalized with Nanodiamond Particles Enhances Osteogenic Metabolic Activity and Bone Regeneration.

    Science.gov (United States)

    Yassin, Mohammed A; Mustafa, Kamal; Xing, Zhe; Sun, Yang; Fasmer, Kristine Eldevik; Waag, Thilo; Krueger, Anke; Steinmüller-Nethl, Doris; Finne-Wistrand, Anna; Leknes, Knut N

    2017-06-01

    Functionalizing polymer scaffolds with nanodiamond particles (nDPs) has pronounced effect on the surface properties, such as improved wettability, an increased active area and binding sites for cellular attachment and adhesion, and increased ability to immobilize biomolecules by physical adsorption. This study aims to evaluate the effect of poly(l-lactide-co-ε-caprolactone) (poly(LLA-co-CL)) scaffolds, functionalized with nDPs, on bone regeneration in a rat calvarial critical size defect. Poly(LLA-co-CL) scaffolds functionalized with nDPs are also compared with pristine scaffolds with reference to albumin adsorption and seeding efficiency of bone marrow stromal cells (BMSCs). Compared with pristine scaffolds, the experimental scaffolds exhibit a reduction in albumin adsorption and a significant increase in the seeding efficiency of BMSCs (p = 0.027). In the calvarial defects implanted with BMSC-seeded poly(LLA-co-CL)/nDPs scaffolds, live imaging at 12 weeks discloses a significant increase in osteogenic metabolic activity (p = 0.016). Microcomputed tomography, confirmed by histological data, reveals a substantial increase in bone volume (p = 0.021). The results show that compared with conventional poly(LLA-co-CL) scaffolds those functionalized with nDPs promote osteogenic metabolic activity and mineralization capacity. It is concluded that poly(LLA-co-CL) composite matrices functionalized with nDPs enhance osteoconductivity and therefore warrant further study as potential scaffolding material for bone tissue engineering. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Diversity of Metabolically Active Bacteria in Water-Flooded High-Temperature Heavy Oil Reservoir

    Directory of Open Access Journals (Sweden)

    Tamara N. Nazina

    2017-04-01

    Full Text Available The goal of this work was to study the overall genomic diversity of microorganisms of the Dagang high-temperature oilfield (PRC and to characterize the metabolically active fraction of these populations. At this water-flooded oilfield, the microbial community of formation water from the near-bottom zone of an injection well where the most active microbial processes of oil degradation occur was investigated using molecular, cultural, radiotracer, and physicochemical techniques. The samples of microbial DNA and RNA from back-flushed water were used to obtain the clone libraries for the 16S rRNA gene and cDNA of 16S rRNA, respectively. The DNA-derived clone libraries were found to contain bacterial and archaeal 16S rRNA genes and the alkB genes encoding alkane monooxygenases similar to those encoded by alkB-geo1 and alkB-geo6 of geobacilli. The 16S rRNA genes of methanogens (Methanomethylovorans, Methanoculleus, Methanolinea, Methanothrix, and Methanocalculus were predominant in the DNA-derived library of Archaea cloned sequences; among the bacterial sequences, the 16S rRNA genes of members of the genus Geobacillus were the most numerous. The RNA-derived library contained only bacterial cDNA of the 16S rRNA sequences belonging to metabolically active aerobic organotrophic bacteria (Tepidimonas, Pseudomonas, Acinetobacter, as well as of denitrifying (Azoarcus, Tepidiphilus, Calditerrivibrio, fermenting (Bellilinea, iron-reducing (Geobacter, and sulfate- and sulfur-reducing bacteria (Desulfomicrobium, Desulfuromonas. The presence of the microorganisms of the main functional groups revealed by molecular techniques was confirmed by the results of cultural, radioisotope, and geochemical research. Functioning of the mesophilic and thermophilic branches was shown for the microbial food chain of the near-bottom zone of the injection well, which included the microorganisms of the carbon, sulfur, iron, and nitrogen cycles.

  18. Contrasting effects of strabismic amblyopia on metabolic activity in superficial and deep layers of striate cortex.

    Science.gov (United States)

    Adams, Daniel L; Economides, John R; Horton, Jonathan C

    2015-05-01

    To probe the mechanism of visual suppression, we have raised macaques with strabismus by disinserting the medial rectus muscle in each eye at 1 mo of age. Typically, this operation produces a comitant, alternating exotropia with normal acuity in each eye. Here we describe an unusual occurrence: the development of severe amblyopia in one eye of a monkey after induction of exotropia. Shortly after surgery, the animal demonstrated a strong fixation preference for the left eye, with apparent suppression of the right eye. Later, behavioral testing showed inability to track or to saccade to targets with the right eye. With the left eye occluded, the animal demonstrated no visually guided behavior. Optokinetic nystagmus was absent in the right eye. Metabolic activity in striate cortex was assessed by processing the tissue for cytochrome oxidase (CO). Amblyopia caused loss of CO in one eye's rows of patches, presumably those serving the blind eye. Layers 4A and 4B showed columns of reduced CO, in register with pale rows of patches in layer 2/3. Layers 4C, 5, and 6 also showed columns of CO activity, but remarkably, comparison with more superficial layers showed a reversal in contrast. In other words, pale CO staining in layers 2/3, 4A, and 4B was aligned with dark CO staining in layers 4C, 5, and 6. No experimental intervention or deprivation paradigm has been reported previously to produce opposite effects on metabolic activity in layers 2/3, 4A, and 4B vs. layers 4C, 5, and 6 within a given eye's columns. Copyright © 2015 the American Physiological Society.

  19. Increased metabolic activity in the septum and habenula during stress is linked to subsequent expression of learned helplessness behavior.

    Science.gov (United States)

    Mirrione, Martine M; Schulz, Daniela; Lapidus, Kyle A B; Zhang, Samuel; Goodman, Wayne; Henn, Fritz A

    2014-01-01

    Uncontrollable stress can have a profound effect on an organism's ability to respond effectively to future stressful situations. Behavior subsequent to uncontrollable stress can vary greatly between individuals, falling on a spectrum between healthy resilience and maladaptive learned helplessness. It is unclear whether dysfunctional brain activity during uncontrollable stress is associated with vulnerability to learned helplessness; therefore, we measured metabolic activity during uncontrollable stress that correlated with ensuing inability to escape future stressors. We took advantage of small animal positron emission tomography (PET) and 2-deoxy-2[(18)F]fluoro-D-glucose ((18)FDG) to probe in vivo metabolic activity in wild type Sprague Dawley rats during uncontrollable, inescapable, unpredictable foot-shock stress, and subsequently tested the animals response to controllable, escapable, predictable foot-shock stress. When we correlated metabolic activity during the uncontrollable stress with consequent behavioral outcomes, we found that the degree to which animals failed to escape the foot-shock correlated with increased metabolic activity in the lateral septum and habenula. When used a seed region, metabolic activity in the habenula correlated with activity in the lateral septum, hypothalamus, medial thalamus, mammillary nuclei, ventral tegmental area, central gray, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and rostromedial tegmental nucleus, caudal linear raphe, and subiculum transition area. Furthermore, the lateral septum correlated with metabolic activity in the preoptic area, medial thalamus, habenula, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and caudal linear raphe. Together, our data suggest a group of brain regions involved in sensitivity to uncontrollable stress involving the lateral septum and habenula.

  20. Increased metabolic activity in the septum and habenula during stress is linked to subsequent expression of learned helplessness behavior

    Directory of Open Access Journals (Sweden)

    Martine M Mirrione

    2014-02-01

    Full Text Available Uncontrollable stress can have a profound effect on an organism’s ability to respond effectively to future stressful situations. Behavior subsequent to uncontrollable stress can vary greatly between individuals, falling on a spectrum between healthy resilience and maladaptive learned helplessness. It is unclear whether dysfunctional brain activity during uncontrollable stress is associated with vulnerability to learned helplessness; therefore, we measured metabolic activity during uncontrollable stress that correlated with ensuing inability to escape future stressors. We took advantage of small animal positron emission tomography (PET and 2-deoxy-2[18F]fluoro-D-glucose (18FDG to probe in vivo metabolic activity in wild type Sprague Dawley rats during uncontrollable, inescapable, unpredictable foot-shock stress, and subsequently tested the animals response to controllable, escapable, predictable foot-shock stress. When we correlated metabolic activity during the uncontrollable stress with consequent behavioral outcomes, we found that the degree to which animals failed to escape the foot-shock correlated with increased metabolic activity in the lateral septum and habenula. When used a seed region, metabolic activity in the habenula correlated with activity in the lateral septum, hypothalamus, medial thalamus, mammillary nuclei, ventral tegmental area, central gray, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and rostromedial tegmental nucleus, caudal linear raphe, and subiculum transition area. Furthermore, the lateral septum correlated with metabolic activity in the preoptic area, medial thalamus, habenula, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and caudal linear raphe. Together, our data suggest a group of brain regions involved in sensitivity to uncontrollable stress involving the lateral septum and habenula.

  1. Effects of photoperiod on food intake, activity and metabolic rate in adult neutered male cats.

    Science.gov (United States)

    Kappen, K L; Garner, L M; Kerr, K R; Swanson, K S

    2014-10-01

    With the continued rise in feline obesity, novel weight management strategies are needed. To date, strategies aimed at altering physical activity, an important factor in weight maintenance, have been lacking. Photoperiod is known to cause physiological changes in seasonal mammals, including changes in body weight (BW) and reproductive status. Thus, our objective was to determine the effect of increased photoperiod (longer days) on voluntary physical activity levels, resting metabolic rate (RMR), food intake required to maintain BW, and fasting serum leptin and ghrelin concentrations in adult cats. Eleven healthy, adult, neutered, male domestic shorthair cats were used in a randomized crossover design study. During two 12-week periods, cats were exposed to either a short-day (SD) photoperiod of 8 h light: 16 h dark or a long-day (LD) photoperiod of 16 h light: 8 h dark. Cats were fed a commercial diet to maintain baseline BW. In addition to daily food intake and twice-weekly BW, RMR (via indirect calorimetry), body composition [via dual-energy X-ray absorptiometry (DEXA)] and physical activity (via Actical activity monitors) were measured at week 0 and 12 of each period. Fasting serum leptin and ghrelin concentrations were measured at week 0, 6 and 12 of each period. Average hourly physical activity was greater (p = 0.008) in LD vs. SD cats (3770 vs. 3129 activity counts/h), which was primarily due to increased (p dark period activity (1188 vs. 710 activity counts/h). This corresponded to higher (p energy intake (mean over 12-week period: 196 vs. 187 kcal/day), and increased (p = 0.048) RMR in LD cats (9.02 vs. 8.37 kcal/h). Body composition, serum leptin and serum ghrelin were not altered by photoperiod. More research is needed to determine potential mechanisms by which these physiological changes occurred and how they may apply to weight management strategies.

  2. Changes in energy metabolism in relation to physical activity due to fermentable carbohydrates in group housed, growing pigs

    NARCIS (Netherlands)

    Schrama, J.W.; Bakker, G.C.M.

    1999-01-01

    Fermentable nonstarch polysaccharides (dietary fiber) affect energy retention in group-housed growing pigs by reducing physical activity. This study assessed the effects of fermentation and bulkiness of dietary carbohydrates on physical activity in relation to energy metabolism. Eight clusters of 14

  3. Changes in energy metabolism in relation to physical activity due to fermentable carbohydrates in group-housed growing pigs

    NARCIS (Netherlands)

    Schrama, J.W.; Bakker, G.C.M.

    1999-01-01

    Fermentable nonstarch polysaccharides (dietary fiber) affect energy retention in group-housed growing pigs by reducing physical activity. This study assessed the effects of fermentation and bulkiness of dietary carbohydrates on physical activity in relation to energy metabolism. Eight clusters of 14

  4. Effects of pesticide chemicals on the activity of metabolic enzymes: focus on thiocarbamates.

    Science.gov (United States)

    Mathieu, Cécile; Duval, Romain; Xu, Ximing; Rodrigues-Lima, Fernando; Dupret, Jean-Marie

    2015-01-01

    Thiocarbamates are chemicals widely used as pesticides. Occupational exposure is associated with acute intoxication. Populations can be exposed through food and water. Moreover, certain thiocarbamates are used clinically. The widespread use of thiocarbamates raises many issues regarding their toxicological and pharmacological impact. Thiocarbamates and their metabolites can modify biological macromolecules functions, in particular enzymes, through modification of cysteine residues, chelation of metal ions or modulation of the oxidative stress. Loss of enzyme activity can lead to the disruption of metabolic pathways, and explain, at least in part, the effects of these pesticides. Additionally, their reactivity and ability to easily cross biological barrier confer them a great interest for development of clinical applications. Many advances in the study of thiocarbamates metabolism and reactivity have led to a better knowledge of biological effects of these compounds. However, more data are needed on the determination of targets and specificity. Only few data concerning the exposure to a cocktail of pesticides/chemicals are available, raising the need to evaluate the toxic side effects of representative pesticides mixtures. Moreover, the dithiocarbamate Disulfiram has shown great potential in therapeutic applications and leads to the development of pharmacological thiocarbamates derivatives, highly specific to their target and easily distributed.

  5. Adrenal activity and metabolic risk during randomized escitalopram or placebo treatment in PCOS.

    Science.gov (United States)

    Glintborg, Dorte; Altinok, Magda Lambaa; Ravn, Pernille; Stage, Kurt Bjerregaard; Højlund, Kurt; Andersen, Marianne

    2018-03-01

    Polycystic ovary syndrome (PCOS) is associated with insulin resistance, adrenal hyperactivity and decreased mental health. We aimed to investigate the changes in adrenal activity, metabolic status and mental health in PCOS during treatment with escitalopram or placebo. Forty-two overweight premenopausal women with PCOS and no clinical depression were randomized to 12-week SSRI (20 mg escitalopram/day, n  = 21) or placebo ( n  = 21). Patients underwent clinical examination, fasting blood samples, adrenocorticotroph hormone (ACTH) test, 3-h oral glucose tolerance test (OGTT) and filled in questionnaires regarding mental health and health-related quality of life (HRQoL): WHO Well-Being Index (WHO-5), Major Depression Inventory (MDI), Short Form 36 (SF-36) and PCOS questionnaire. Included women were aged 31 (6) years (mean (s.d.)) and had body mass index (BMI) 35.8 (6.5) kg/m 2 and waist 102 (12) cm. Escitalopram was associated with increased waist (median (quartiles) change 1 (0; 3) cm), P  = 0.005 vs change during placebo and increased cortisol levels (cortisol 0, cortisol 60, peak cortisol and area under the curve for cortisol during ACTH test), all P   PCOS and no clinical depression, whereas metabolic risk markers, mental health and HRQol were unchanged. © 2018 The authors.

  6. Microbial metaproteomics for characterizing the range of metabolic functions and activities of human gut microbiota.

    Science.gov (United States)

    Xiong, Weili; Abraham, Paul E; Li, Zhou; Pan, Chongle; Hettich, Robert L

    2015-10-01

    The human gastrointestinal tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome is not merely a collection of opportunistic parasites, but rather provides important functions to the host that are absolutely critical to many aspects of health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial metaproteomics provides the ability to characterize the human gut microbiota functions and metabolic activities at a remarkably deep level, revealing information about microbiome development and stability as well as their interactions with their human host. Generally, microbial and human proteins can be extracted and then measured by high performance MS-based proteomics technology. Here, we review the field of human gut microbiome metaproteomics, with a focus on the experimental and informatics considerations involved in characterizing systems ranging from low-complexity model gut microbiota in gnotobiotic mice, to the emerging gut microbiome in the GI tract of newborn human infants, and finally to an established gut microbiota in human adults. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity.

    Science.gov (United States)

    López-Lluch, Guillermo

    2017-03-01

    Mitochondria play an essential role in ageing and longevity. During ageing, a general deregulation of metabolism occurs, affecting molecular, cellular and physiological activities in the organism. Dysfunction of mitochondria has been associated with ageing and age-related diseases indicating their importance in the maintenance of cell homeostasis. Three major nutritional sensors, mTOR, AMPK and Sirtuins are involved in the control of mitochondrial physiology. These nutritional sensors control mitochondrial biogenesis, dynamics by regulating fusion and fission processes, and turnover through mito- and autophagy. Apart of the known factors involved in fusion, OPA1 and mitofusins, and fission, DRP1 and FIS1, emerging factors such as prohibitins and sestrins can play important functions in mitochondrial dynamics regulation. Mitochondria is also affected by sexual hormones that suffer drastic changes during ageing. The recent literature demonstrates the complex interaction between nutritional sensors and mitochondrial homeostasis in the physiology of adipose tissue and in the accumulation of fat in other organs such as muscle and liver. In this article, the role of mitochondrial homeostasis in ageing and age-dependent fat accumulation is revised. This review highlights the importance of mitochondria in the accumulation of fat during ageing and related diseases such as obesity, metabolic syndrome or type 2 diabetes mellitus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Reserve-building activities in multiple sclerosis patients and healthy controls: a descriptive study.

    Science.gov (United States)

    Schwartz, Carolyn E; Ayandeh, Armon; Ramanathan, Murali; Benedict, Ralph; Dwyer, Michael G; Weinstock-Guttman, Bianca; Zivadinov, Robert

    2015-08-12

    Cognitive reserve has been implicated as a possible protective factor in multiple sclerosis (MS) but to date no study has compared reserve-building activities across disease course or to healthy controls. This study aims to describe differences in reserve-building activities across the MS disease course and healthy controls. Secondary analysis of a cross-sectional cohort study that included 276 healthy controls, and subjects with clinically isolated syndrome (CIS; n = 67), relapsing-remitting MS (RRMS; n = 358) and secondary progressive MS (PMS; n = 109). Past reserve-building activities were operationalized as occupational attainment and education. Current activities comprised 6 strenuous and 6 non-strenuous activities, including 5 reserve-building activities and television-watching. Multivariate Analysis of Variance models examined group differences in past and current activities, after adjusting for covariates. There were group differences in past and current reserve-building activities. SPMS patients had lower past reserve-building activities than healthy controls. All forms of MS engaged in fewer strenuous current reserve-building pursuits than healthy controls. RRMS read less than healthy controls. SPMS engaged in fewer job-related non-strenuous activities. All MS groups watched more television than healthy controls. MS patients show significantly fewer past and present reserve-building activities. Although it is difficult to establish causality without future prospective studies, lifestyle-modifying interventions should prioritize expanding MS patients' repertoire of strenuous and non-strenuous activities.

  9. The relationship between walking, manual dexterity, cognition and activity/participation in persons with multiple sclerosis.

    Science.gov (United States)

    Kierkegaard, Marie; Einarsson, Ulrika; Gottberg, Kristina; von Koch, Lena; Holmqvist, Lotta Widén

    2012-05-01

    Multiple sclerosis has a vast impact on health, but the relationship between walking, manual dexterity, cognition and activity/participation is unclear. The specific aims were to explore the discriminative ability of measures of walking, manual dexterity and cognition, and to identify cut-off values in these measures, for prediction of independence in personal and instrumental activities of daily living (ADL) and activity/participation in social and lifestyle activities. Data from 164 persons with multiple sclerosis were collected during home visits with the following measures: the 2 × 5 m walk test, the Nine-hole Peg Test, the Symbol Digit Modalities Test, the Katz Personal and Instrumental ADL Indexes, and the Frenchay Activities Index (measuring frequency in social and lifestyle activities). The 2 × 5 m walk test and the Nine-hole Peg Test had high and better discriminative and predictive ability than the Symbol Digit Modalities Test. Cut-off values were identified. The accuracy of predictions was increased above all by combining the 2 × 5 m walk test and the Nine-hole Peg Test. The proposed cut-off values in the 2 × 5 m walk test and the Nine-hole Peg Test may be used as indicators of functioning and to identify persons risking activity limitations and participation restrictions. However, further studies are needed to confirm the usefulness in clinical practice.

  10. CALCULATING SEPARATE MAGNETIC FREE ENERGY ESTIMATES FOR ACTIVE REGIONS PRODUCING MULTIPLE FLARES: NOAA AR11158

    Energy Technology Data Exchange (ETDEWEB)

    Tarr, Lucas; Longcope, Dana; Millhouse, Margaret [Department of Physics, Montana State University, Bozeman, MT 59717 (United States)

    2013-06-10

    It is well known that photospheric flux emergence is an important process for stressing coronal fields and storing magnetic free energy, which may then be released during a flare. The Helioseismic and Magnetic Imager (HMI) on board the Solar Dynamics Observatory (SDO) captured the entire emergence of NOAA AR 11158. This region emerged as two distinct bipoles, possibly connected underneath the photosphere, yet characterized by different photospheric field evolutions and fluxes. The combined active region complex produced 15 GOES C-class, two M-class, and the X2.2 Valentine's Day Flare during the four days after initial emergence on 2011 February 12. The M and X class flares are of particular interest because they are nonhomologous, involving different subregions of the active region. We use a Magnetic Charge Topology together with the Minimum Current Corona model of the coronal field to model field evolution of the complex. Combining this with observations of flare ribbons in the 1600 A channel of the Atmospheric Imaging Assembly on board SDO, we propose a minimization algorithm for estimating the amount of reconnected flux and resulting drop in magnetic free energy during a flare. For the M6.6, M2.2, and X2.2 flares, we find a flux exchange of 4.2 Multiplication-Sign 10{sup 20} Mx, 2.0 Multiplication-Sign 10{sup 20} Mx, and 21.0 Multiplication-Sign 10{sup 20} Mx, respectively, resulting in free energy drops of 3.89 Multiplication-Sign 10{sup 30} erg, 2.62 Multiplication-Sign 10{sup 30} erg, and 1.68 Multiplication-Sign 10{sup 32} erg.

  11. Multiple-clone activation of hypnozoites is the leading cause of relapse in Plasmodium vivax infection.

    Directory of Open Access Journals (Sweden)

    Flávia Carolina F de Araujo

    Full Text Available BACKGROUND: Plasmodium vivax infection is characterized by a dormant hepatic stage, the hypnozoite that is activated at varying periods of time after clearance of the primary acute blood-stage, resulting in relapse. Differentiation between treatment failure and new infections requires characterization of initial infections, relapses, and clone multiplicity in vivax malaria infections. METHODOLOGY/PRINCIPAL FINDINGS: Parasite DNA obtained from primary/relapse paired blood samples of 30 patients with P. vivax infection in Brazil was analyzed using 10 molecular markers (8 microsatellites and MSP-1 blocks 2 and 10. Cloning of PCR products and genotyping was used to identify low-frequency clones of parasites. We demonstrated a high frequency of multiple-clone infections in both primary and relapse infections. Few alleles were identified per locus, but the combination of these alleles produced many haplotypes. Consequently, the majority of parasites involved in relapse showed haplotypes that were distinct from those of primary infections. Plasmodium vivax relapse was characterized by temporal variations in the predominant parasite clones. CONCLUSIONS/SIGNIFICANCE: The high rate of low frequency alleles observed in both primary and relapse infections, along with temporal variation in the predominant alleles, might be the source of reported heterologous hypnozoite activation. Our findings complicate the concept of heterologous activation, suggesting the involvement of undetermined mechanisms based on host or environmental factors in the simultaneous activation of multiple clones of hypnozoites.

  12. BAD-Dependent Regulation of Fuel Metabolism and KATP Channel Activity Confers Resistance to Epileptic Seizures

    OpenAIRE

    Giménez-Cassina, Alfredo; Martínez-François, Juan Ramón; Fisher, Jill K.; Szlyk, Benjamin; Polak, Klaudia; Wiwczar, Jessica; Tanner, Geoffrey R.; Lutas, Andrew; Yellen, Gary; Danial, Nika N.

    2012-01-01

    Neuronal excitation can be substantially modulated by alterations in metabolism, as evident from the anticonvulsant effect of diets that reduce glucose utilization and promote ketone body metabolism. We provide genetic evidence that BAD, a protein with dual functions in apoptosis and glucose metabolism, imparts reciprocal effects on metabolism of glucose and ketone bodies in brain cells. These effects involve phospho-regulation of BAD and are independent of its apoptotic function. BAD modific...

  13. Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage

    OpenAIRE

    Kim, Kyoung-Han; Kim, Yun Hye; Son, Joe Eun; Lee, Ju Hee; Kim, Sarah; Choe, Min Seon; Moon, Joon Ho; Zhong, Jian; Fu, Kiya; Lenglin, Florine; Yoo, Jeong-Ah; Bilan, Philip J; Klip, Amira; Nagy, Andras; Kim, Jae-Ryong

    2017-01-01

    Intermittent fasting (IF), a periodic energy restriction, has been shown to provide health benefits equivalent to prolonged fasting or caloric restriction. However, our understanding of the underlying mechanisms of IF-mediated metabolic benefits is limited. Here we show that isocaloric IF improves metabolic homeostasis against diet-induced obesity and metabolic dysfunction primarily through adipose thermogenesis in mice. IF-induced metabolic benefits require fasting-mediated increases of vasc...

  14. Palmitoleic Acid Improves Metabolic Functions in Fatty Liver by PPARα-Dependent AMPK Activation.

    Science.gov (United States)

    de Souza, Camila O; Teixeira, Alexandre A S; Biondo, Luana A; Lima Junior, Edson A; Batatinha, Helena A P; Rosa Neto, Jose C

    2017-08-01

    Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5'AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor-α (PPARα), in adipose tissue. However, in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPARα remain unknown. To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice. C57BL6 and PPARα knockout (KO) mice were fed for 12 weeks with a standard diet (SD) or high-fat diet (HF), and in the last 2 weeks were treated with oleic or palmitoleic acid. Palmitoleic acid promoted a faster uptake of glucose in the body, associated with higher insulin concentration; however, even when stimulated with insulin, palmitoleic acid did not modulate the insulin pathway (AKT, IRS). Palmitoleic acid increased the phosphorylation of AMPK, upregulated glucokinase and downregulated SREBP-1. Regarding AMPK downstream, palmitoleic acid increased the production of FGF-21 and stimulated the expression of PPARα. Palmitoleic acid treatment did not increase AMPK phosphorylation, modulate glucokinase or increase FGF-21 in liver of PPARα KO mice. In mice fed with a high-fat diet, palmitoleic acid supplementation stimulated the uptake of glucose in liver through activation of AMPK and FGF-21, dependent on PPARα. J. Cell. Physiol. 232: 2168-2177, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Tissue-specific metabolic activation and mutagenicity of 3-nitrobenzanthrone in MutaMouse.

    Science.gov (United States)

    Chen, Guosheng; Gingerich, John; Soper, Lynda; Douglas, George R; White, Paul A

    2008-10-01

    3-Nitrobenzanthrone (3-NBA) is a mutagen and suspected human carcinogen detected in diesel exhaust, airborne particulate matter, and urban soil. We investigated the tissue specific mutagenicity of 3-NBA at the lacZ locus of transgenic MutaMouse following acute single dose or 28-day repeated-dose oral administration. In the acute high dose (50 mg/kg) exposure, increased lacZ mutant frequency was observed in bone marrow and colonic epithelium, but not in liver and bladder. In the repeated-dose study, a dose-dependent increase in lacZ mutant frequency was observed in bone marrow and liver (2- and 4-fold increase above control), but not in lung or intestinal epithelium. In addition, a concentration-dependent increase in mutant frequency (8.5-fold above control) was observed for MutaMouse FE1 lung epithelial cells exposed in vitro. 1-Nitropyrene reductase, 3-NBA reductase, and acetyltransferase activities were measured in a variety of MutaMouse specimens in an effort to link metabolic activation and mutagenicity. High 3-NBA nitroreductase activities were observed in lung, liver, colon and bladder, and detectable N-acetyltransferase activities were found in all tissues except bone marrow. The relatively high 3-NBA nitroreductase activity in MutaMouse tissues, as compared with those in Salmonella TA98 and TA100, suggests that 3-NBA is readily reduced and activated in vivo. High 3-NBA nitroreductase levels in liver and colon are consistent with the elevated lacZ mutant frequency values, and previously noted inductions of hepatic DNA adducts. Despite an absence of induced lacZ mutations, the highest 3-NBA reductase activity was detected in lung. Further studies are warranted, especially following inhalation or intratracheal exposures. Published 2008 Wiley-Liss, Inc.