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Sample records for circulating sphingolipid concentrations

  1. Genetic determinants of circulating sphingolipid concentrations in European populations.

    Directory of Open Access Journals (Sweden)

    Andrew A Hicks

    2009-10-01

    Full Text Available Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI, cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS between 318,237 single-nucleotide polymorphisms (SNPs and levels of circulating sphingomyelin (SM, dihydrosphingomyelin (Dih-SM, ceramide (Cer, and glucosylceramide (GluCer single lipid species (33 traits; and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32 in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08x10(-66. The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3 associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4 or less. Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be

  2. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

    NARCIS (Netherlands)

    A. Demirkan (Ayşe); C.M. van Duijn (Cornelia); P. Ugocsai (Peter); A.J. Isaacs (Aaron); P.P. Pramstaller (Peter Paul); G. Liebisch (Gerhard); J.F. Wilson (James); A. Johansson (Åsa); I. Rudan (Igor); Y.S. Aulchenko (Yurii); A.V. Kirichenko (Anatoly); A.C.J.W. Janssens (Cécile); R.C. Jansen (Ritsert); C. Gnewuch (Carsten); I. Domingues (Inês); C. Pattaro (Cristian); S.H. Wild (Sarah); I. Jonasson (Inger); O. Polasek (Ozren); I.V. Zorkoltseva (Irina); A. Hofman (Albert); L.C. Karssen (Lennart); M.V. Struchalin (Maksim); J. Floyd (Jamie); W. Igl (Wilmar); Z. Biloglav (Zrinka); L. Broer (Linda); A. Pfeufer (Arne); I. Pichler (Irene); S. Campbell (Susan); G. Zaboli (Ghazal); I. Kolcic (Ivana); F. Rivadeneira Ramirez (Fernando); J.E. Huffman (Jennifer); N. Hastie (Nick); A.G. Uitterlinden (André); L. Franke (Lude); C.S. Franklin (Christopher); V. Vitart (Veronique); C.P. Nelson (Christopher P.); M. Preuss (Michael); J.C. Bis (Joshua); C.J. O'Donnell (Christopher); N. Franceschini (Nora); J.C.M. Witteman (Jacqueline); T.I. Axenovich (Tatiana); B.A. Oostra (Ben); T. Meitinger (Thomas); A.A. Hicks (Andrew); C. Hayward (Caroline); A.F. Wright (Alan); U. Gyllensten (Ulf); H. Campbell (Harry); G. Schmitz (Gerd)

    2012-01-01

    textabstractPhospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological,

  3. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; van Duijn, Cornelia M; Ugocsai, Peter

    2012-01-01

    , and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57...

  4. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

    Directory of Open Access Journals (Sweden)

    Ayşe Demirkan

    Full Text Available Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034 on plasma levels of 24 sphingomyelins (SPM, 9 ceramides (CER, 57 phosphatidylcholines (PC, 20 lysophosphatidylcholines (LPC, 27 phosphatidylethanolamines (PE, and 16 PE-based plasmalogens (PLPE, as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204 and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57. After a correction for multiple comparisons (P-value<2.2×10(-9, we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1 and two with sphingolipids (PLD2 and APOE explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3 suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2 to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our

  5. Sphingolipid trafficking - Sorted out?

    OpenAIRE

    van Meer, G.; Burger, K.N.J.

    1992-01-01

    Studies of intracellular membrane traffic have traditionally focused on the protein components of membranes, but what about lipids? Recent findings have drawn attention to the transport of one type of lipid, the sphingolipids. Their unique physical properties may allow them to aggregate into microdomains in membranes that concentrate sphingolipids into specific transport pathways. Gerrit van Meer and Koert Burger consider here the routes of sphingolipid biosynthesis and transport, and the rol...

  6. Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study.

    Science.gov (United States)

    Checa, A; Idborg, H; Zandian, A; Sar, D Garcia; Surowiec, I; Trygg, J; Svenungsson, E; Jakobsson, P-J; Nilsson, P; Gunnarsson, I; Wheelock, C E

    2017-09-01

    Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C 16:0 -ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C 16:0 -ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C 16:0 - and C 24:1 -hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated

  7. Sphingolipids and Lipoproteins in Health and Metabolic Disorders.

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    Iqbal, Jahangir; Walsh, Meghan T; Hammad, Samar M; Hussain, M Mahmood

    2017-07-01

    Sphingolipids are structurally and functionally diverse molecules with significant physiologic functions and are found associated with cellular membranes and plasma lipoproteins. The cellular and plasma concentrations of sphingolipids are altered in several metabolic disorders and may serve as prognostic and diagnostic markers. Here we discuss various sphingolipid transport mechanisms and highlight how changes in cellular and plasma sphingolipid levels contribute to cardiovascular disease, obesity, diabetes, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). Understanding of the mechanisms involved in intracellular transport, secretion, and extracellular transport may provide novel information that might be amenable to therapeutic targeting for the treatment of various metabolic disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Sphingolipids in macroautophagy.

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    Lavieu, Grégory; Scarlatti, Francesca; Sala, Giusy; Carpentier, Stéphane; Levade, Thierry; Ghidoni, Riccardo; Botti, Joëlle; Codogno, Patrice

    2008-01-01

    Sphingolipids are constituents of biological membranes. Ceramide and sphingosine 1-phosphate (S1P) also act as second messengers and are part of a rheostat system, in which ceramide promotes cell death and growth arrest, and S1P induces proliferation and maintains cell survival. As macroautophagy is a lysosomal catabolic mechanism involved in determining the duration of the lifetime of cells, we raised the question of its regulation by sphingolipid messengers. Using chemical and genetic methods, we have shown by GFP-LC3 staining and analysis of the degradation of long-lived proteins that both ceramide and S1P stimulate autophagy.

  9. Sphingolipid trafficking - Sorted out?

    NARCIS (Netherlands)

    van Meer, G.; Burger, K.N.J.

    1992-01-01

    Studies of intracellular membrane traffic have traditionally focused on the protein components of membranes, but what about lipids? Recent findings have drawn attention to the transport of one type of lipid, the sphingolipids. Their unique physical properties may allow them to aggregate into

  10. Melanin-concentrating hormone in peripheral circulation in the human.

    Science.gov (United States)

    Naufahu, J; Alzaid, F; Fiuza Brito, M; Doslikova, B; Valencia, T; Cunliffe, A; Murray, J F

    2017-03-01

    Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5-1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5-55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role. © 2017 Society for Endocrinology.

  11. Sphingolipid metabolism diseases.

    Science.gov (United States)

    Kolter, Thomas; Sandhoff, Konrad

    2006-12-01

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

  12. Elevated circulating plasma endothelin-1 concentrations in cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Emmeluth, C; Henriksen, Jens Henrik

    1993-01-01

    veins on the one hand and the femoral artery on the other (P > 0.1), indicating no major net elimination or release in the liver, kidney or lower limb. A significant negative correlation was found between systolic and diastolic blood pressures on the one hand and circulating ET-1 on the other (r = -0.......70, P vein catheterization (n = 8), no significant differences were found in ET-1 plasma concentration between the liver, renal, or femoral...

  13. Orm family proteins mediate sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Breslow, David K; Collins, Sean R; Bodenmiller, Bernd

    2010-01-01

    a conserved complex with serine palmitoyltransferase, the first and rate-limiting enzyme in sphingolipid production. We also define a regulatory pathway in which phosphorylation of Orm proteins relieves their inhibitory activity when sphingolipid production is disrupted. Changes in ORM gene expression...... or mutations to their phosphorylation sites cause dysregulation of sphingolipid metabolism. Our work identifies the Orm proteins as critical mediators of sphingolipid homeostasis and raises the possibility that sphingolipid misregulation contributes to the development of childhood asthma....

  14. Increased Circulating Betatrophin Concentrations in Patients with Type 2 Diabetes

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    Daniel Espes

    2014-01-01

    Full Text Available Betatrophin has recently been described as a key hormone to stimulate beta-cell mass expansion in response to insulin resistance and obesity in mice. The finding has generated an interest in the development of antidiabetic drugs with betatrophin as the active component. However, the circulating levels of betatrophin in patients with type 2 diabetes are not well known. Betatrophin concentrations in plasma of 27 type 2 diabetes patients and 18 gender-, age-, and BMI-matched controls were measured. Study participants were characterized with regard to BMI, waist and hip circumference, blood pressure, and fasting plasma blood lipids, creatinine, glucose, HbA1c, and C-peptide. HOMA2 indices were calculated. Betatrophin was 40% higher in patients with type 2 diabetes (893±80 versus 639±66 pg/mL. Betatrophin positively correlated with age in the controls and with HbA1c in the type 2 diabetes patients. All study participants were insulin resistant with mean HOMA2B IR in both groups exceeding 2 and HOMA2%S<50%. Control individuals had impaired fasting glucose concentrations. In this report on betatrophin concentrations in type 2 diabetes and insulin resistance, elevated betatrophin levels were measured in the patients with type 2 diabetes. Future studies are clearly needed to delineate the exact role, if any, of betatrophin in regulating human beta-cell mass.

  15. Sphingolipid Organization in the Plasma Membrane and the Mechanisms That Influence It.

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    Kraft, Mary L

    2016-01-01

    Sphingolipids are structural components in the plasma membranes of eukaryotic cells. Their metabolism produces bioactive signaling molecules that modulate fundamental cellular processes. The segregation of sphingolipids into distinct membrane domains is likely essential for cellular function. This review presents the early studies of sphingolipid distribution in the plasma membranes of mammalian cells that shaped the most popular current model of plasma membrane organization. The results of traditional imaging studies of sphingolipid distribution in stimulated and resting cells are described. These data are compared with recent results obtained with advanced imaging techniques, including super-resolution fluorescence detection and high-resolution secondary ion mass spectrometry (SIMS). Emphasis is placed on the new insight into the sphingolipid organization within the plasma membrane that has resulted from the direct imaging of stable isotope-labeled lipids in actual cell membranes with high-resolution SIMS. Super-resolution fluorescence techniques have recently revealed the biophysical behaviors of sphingolipids and the unhindered diffusion of cholesterol analogs in the membranes of living cells are ultimately in contrast to the prevailing hypothetical model of plasma membrane organization. High-resolution SIMS studies also conflicted with the prevailing hypothesis, showing sphingolipids are concentrated in micrometer-scale membrane domains, but cholesterol is evenly distributed within the plasma membrane. Reductions in cellular cholesterol decreased the number of sphingolipid domains in the plasma membrane, whereas disruption of the cytoskeleton eliminated them. In addition, hemagglutinin, a transmembrane protein that is thought to be a putative raft marker, did not cluster within sphingolipid-enriched regions in the plasma membrane. Thus, sphingolipid distribution in the plasma membrane is dependent on the cytoskeleton, but not on favorable interactions with

  16. A view on sphingolipids and disease.

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    Kolter, Thomas

    2011-09-01

    Sphingolipid and glycosphingolipid levels and expression of sphingolipid metabolizing enzymes are altered in a variety of diseases or in response to drug treatment. Inherited defects of enzymes and other proteins required for the lysosomal degradation of these lipids lead to human sphingolipidoses. Also genetic defects that affect sphingolipid biosynthesis are known. Although the molecular details are often far from clear, (glyco)sphingolipids have been implicated to play a role in atherosclerosis, insulin resistance, cancer, and infections by pathogens. More general aspects of selected diseases are discussed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Relationship among Phosphorus Circulation Activity, Bacterial Biomass, pH, and Mineral Concentration in Agricultural Soil

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    Dinesh Adhikari

    2017-12-01

    Full Text Available Improvement of phosphorus circulation in the soil is necessary to enhance phosphorus availability to plants. Phosphorus circulation activity is an index of soil’s ability to supply soluble phosphorus from organic phosphorus in the soil solution. To understand the relationship among phosphorus circulation activity; bacterial biomass; pH; and Fe, Al, and Ca concentrations (described as mineral concentration in this paper in agricultural soil, 232 soil samples from various agricultural fields were collected and analyzed. A weak relationship between phosphorus circulation activity and bacterial biomass was observed in all soil samples (R2 = 0.25, and this relationship became significantly stronger at near-neutral pH (6.0–7.3; R2 = 0.67. No relationship between phosphorus circulation activity and bacterial biomass was observed at acidic (pH < 6.0 or alkaline (pH > 7.3 pH. A negative correlation between Fe and Al concentrations and phosphorus circulation activity was observed at acidic pH (R2 = 0.72 and 0.73, respectively, as well as for Ca at alkaline pH (R2 = 0.64. Therefore, bacterial biomass, pH, and mineral concentration should be considered together for activation of phosphorus circulation activity in the soil. A relationship model was proposed based on the effects of bacterial biomass and mineral concentration on phosphorus circulation activity. The suitable conditions of bacterial biomass, pH, and mineral concentration for phosphorus circulation activity could be estimated from the relationship model.

  18. Circulating hyaluronate: concentration in different vascular beds in man

    DEFF Research Database (Denmark)

    Bentsen, K D; Henriksen, Jens Henrik Sahl; Laurent, T C

    1986-01-01

    The plasma concentration of hyaluronate (hyaluronic acid; HA) was measured in different vascular beds in order to determine regional kinetics of endogenous HA in fasting, supine subjects with normal (n = 6) or moderately decreased kidney function (n = 9). In both groups hepatic venous HA was sign......The plasma concentration of hyaluronate (hyaluronic acid; HA) was measured in different vascular beds in order to determine regional kinetics of endogenous HA in fasting, supine subjects with normal (n = 6) or moderately decreased kidney function (n = 9). In both groups hepatic venous HA...

  19. Sphingolipid and Ceramide Homeostasis: Potential Therapeutic Targets

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    Simon A. Young

    2012-01-01

    Full Text Available Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed a plethora of functions from the formation of structural domains to polarized cellular trafficking and signal transduction. Recent research has identified and characterised many of the key enzymes involved in sphingolipid metabolism and this has led to a heightened interest in the possibility of targeting these processes for therapies against cancers, Alzheimer's disease, and numerous important human pathogens. In this paper we outline the major pathways in eukaryotic sphingolipid metabolism and discuss these in relation to disease and therapy for both chronic and infectious conditions.

  20. Sphingolipid and Ceramide Homeostasis: Potential Therapeutic Targets

    Science.gov (United States)

    Young, Simon A.; Mina, John G.; Denny, Paul W.; Smith, Terry K.

    2012-01-01

    Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed a plethora of functions from the formation of structural domains to polarized cellular trafficking and signal transduction. Recent research has identified and characterised many of the key enzymes involved in sphingolipid metabolism and this has led to a heightened interest in the possibility of targeting these processes for therapies against cancers, Alzheimer's disease, and numerous important human pathogens. In this paper we outline the major pathways in eukaryotic sphingolipid metabolism and discuss these in relation to disease and therapy for both chronic and infectious conditions. PMID:22400113

  1. Obese Hypertensive Men Have Lower Circulating Proatrial Natriuretic Peptide Concentrations Despite Greater Left Atrial Size

    DEFF Research Database (Denmark)

    Asferg, Camilla L; Andersen, Ulrik B; Linneberg, Allan

    2018-01-01

    BACKGROUND: Obese persons have lower circulating natriuretic peptide (NP) concentrations. It has been proposed that this natriuretic handicap plays a role in obesity-related hypertension. In contrast, hypertensive patients with left atrial enlargement have higher circulating NP concentrations....... On this background, we investigated whether obese hypertensive men could have lower circulating NP concentrations despite evidence of pressure-induced greater left atrial size. METHODS: We examined 98 obese men (body mass index [BMI] ≥ 30.0 kg/m2) and 27 lean normotensive men (BMI 20.0-24.9 kg/m2). All men were...... using echocardiography, and we measured fasting serum concentrations of midregional proatrial NP (MR-proANP). RESULTS: Of the 98 obese men, 62 had hypertension and 36 were normotensive. The obese hypertensive men had greater left atrial size (mean ± SD: 28.7 ± 6.0 ml/m2) compared with the lean...

  2. Sphingolipid biosynthesis in man and microbes.

    Science.gov (United States)

    Harrison, Peter J; Dunn, Teresa M; Campopiano, Dominic J

    2018-06-04

    A new review covering up to 2018Sphingolipids are essential molecules that, despite their long history, are still stimulating interest today. The reasons for this are that, as well as playing structural roles within cell membranes, they have also been shown to perform a myriad of cell signalling functions vital to the correct function of eukaryotic and prokaryotic organisms. Indeed, sphingolipid disregulation that alters the tightly-controlled balance of these key lipids has been closely linked to a number of diseases such as diabetes, asthma and various neuropathologies. Sphingolipid biogenesis, metabolism and regulation is mediated by a large number of enzymes, proteins and second messengers. There appears to be a core pathway common to all sphingolipid-producing organisms but recent studies have begun to dissect out important, species-specific differences. Many of these have only recently been discovered and in most cases the molecular and biochemical details are only beginning to emerge. Where there is a direct link from classic biochemistry to clinical symptoms, a number a drug companies have undertaken a medicinal chemistry campaign to try to deliver a therapeutic intervention to alleviate a number of diseases. Where appropriate, we highlight targets where natural products have been exploited as useful tools. Taking all these aspects into account this review covers the structural, mechanistic and regulatory features of sphingolipid biosynthetic and metabolic enzymes.

  3. Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution.

    Science.gov (United States)

    Rosenbaum, M; Pietrobelli, A; Vasselli, J R; Heymsfield, S B; Leibel, R L

    2001-09-01

    Circulating concentrations of leptin normalized to total adipose tissue mass are significantly greater in females than in males. Rates of leptin expression (per gram of adipose tissue) are significantly greater in subcutaneous (SAT) than visceral (VAT) adipose tissue and the relative amount of fat stored as SAT vs VAT is significantly greater in pre-menopausal females than in males. Gender-related differences in the relative amounts of SAT and VAT may account for the greater circulating leptin concentration relative to fat-mass in females than males. We examined body composition and anatomic fat distribution by dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), and post-absorptive circulating concentrations of leptin and insulin in 58 subjects (26 females, 32 males). Stepwise multiple linear regression analyses, treating gender as a dichotomous variable, were performed to determine inter-relationships among leptin concentrations and insulin concentrations, VAT and SAT. Body composition by DEXA and MRI were highly correlated (r(2)=0.97, P<0.0001). There were significant gender effects on leptin/total fat mass (males, 0.17+/-0.01 ng/ml/kg; females, 0.49+/-0.05 ng/ml/kg; P<0.0001) and relative amounts of fat in SAT and VAT depots (ratio of SAT/VAT; males, 12.3+/-1.5; females, 32.9+/-3.2; P<0.0001). Circulating leptin concentration was significantly correlated with insulin concentration (P=0.001), SAT (P<0.0001) and gender (P=0.033). Circulating concentrations of insulin were significantly correlated with VAT, but not SAT, in males and with SAT, but not VAT, in females. The sexual dimorphism in the relationship between leptin and adipose tissue mass cannot be explained by differences in the relative amounts of VAT and SAT. Thus, the sexual dimorphism in plasma leptin concentration appears to reflect, at least in part, effects of circulating concentrations of gonadal steroids (especially androgens) and/or primary genetic differences that are

  4. Iron and obesity status-associated insulin resistance influence circulating fibroblast-growth factor-23 concentrations.

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    José Manuel Fernández-Real

    Full Text Available Fibroblast growth factor 23 (FGF-23 is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD. Circulating intact FGF-23 (iFGF-23 and C-terminal (CtFGF-23 concentrations (ELISA were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1; and in association with fat mass and bone mineral density (DEXA and atherosclerosis (intima media thickness, IMT in 78 subjects (52 women with a wide range of adiposity (Cohort 2. Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance.

  5. Associations of maternal circulating 25-hydroxyvitamin D3 concentration with pregnancy and birth outcomes.

    Science.gov (United States)

    Rodriguez, A; García-Esteban, R; Basterretxea, M; Lertxundi, A; Rodríguez-Bernal, C; Iñiguez, C; Rodriguez-Dehli, C; Tardón, A; Espada, M; Sunyer, J; Morales, E

    2015-11-01

    To investigate the association of maternal circulating 25-hydroxyvitamin D3 [25(OH)D3] concentration with pregnancy and birth outcomes. Prospective cohort study. Four geographical areas of Spain, 2003-2008. Of 2382 mother-child pairs participating in the INfancia y Medio Ambiente (INMA) Project. Maternal circulating 25(OH)D3 concentration was measured in pregnancy (mean [SD] 13.5 [2.2] weeks of gestation). We tested associations of maternal 25(OH)D3 concentration with pregnancy and birth outcomes. Gestational diabetes mellitus (GDM), preterm delivery, caesarean section, fetal growth restriction (FGR) and small-for-gestational age (SGA), anthropometric birth outcomes including weight, length and head circumference (HC). Overall, 31.8% and 19.7% of women had vitamin D insufficiency [25(OH)D3 20-29.99 ng/ml] and deficiency [25(OH)D3 < 20 ng/ml], respectively. After adjustment, there was no association between maternal 25(OH)D3 concentration and risk of GDM or preterm delivery. Women with sufficient vitamin D [25(OH)D3 ≥ 30 ng/ml] had a decreased risk of caesarean section by obstructed labour compared with women with vitamin D deficiency [relative risk (RR) = 0.60, 95% CI 0.37, 0.97). Offspring of mothers with higher circulating 25(OH)D3 concentration tended to have smaller HC [coefficient (SE) per doubling concentration of 25(OH)D3, -0.10 (0.05), P = 0.038]. No significant associations were found for other birth outcomes. This study did not find any evidence of an association between vitamin D status in pregnancy and GDM, preterm delivery, FGR, SGA and anthropometric birth outcomes. Results suggest that sufficient circulating vitamin D concentration [25(OH)D3 ≥ 30 ng/ml] in pregnancy may reduce the risk of caesarean section by obstructed labour. © 2014 Royal College of Obstetricians and Gynaecologists.

  6. Oxygen concentration diffusion analysis of lead-bismuth-cooled, natural-circulation reactor

    International Nuclear Information System (INIS)

    Ito, Kei; Sakai, Takaaki

    2001-11-01

    The feasibility study on fast breeder reactors in Japan has been conducted at JNC and related organizations. The Phase-I study has finished in March, 2001. During the Phase-I activity, lead-bismuth eutectic coolant has been selected as one of the possible coolant options and a medium-scale plant, cooled by a lead-bismuth natural circulation flow was studied. On the other side, it is known that lead-bismuth eutectic has a problem of structural material corrosiveness. It was found that oxygen concentration control in the eutectic plays an important role on the corrosion protection. In this report, we have developed a concentration diffusion analysis code (COCOA: COncentration COntrol Analysis code) in order to carry out the oxygen concentration control analysis. This code solves a two-dimensional concentration diffusion equation by the finite differential method. It is possible to simulate reaction of oxygen and hydrogen by the code. We verified the basic performance of the code and carried out oxygen concentration diffusion analysis for the case of an oxygen increase by a refueling process in the natural circulation reactor. In addition, characteristics of the oxygen control system was discussed for a different type of the control system as well. It is concluded that the COCOA code can simulate diffusion of oxygen concentration in the reactor. By the analysis of a natural circulation medium-scale reactor, we make clear that the ON-OFF control and PID control can well control oxygen concentration by choosing an appropriate concentration measurement point. In addition, even when a trouble occurs in the oxygen emission or hydrogen emission system, it observes that control characteristic drops away. It is still possible, however, to control oxygen concentration in such case. (author)

  7. Association of circulating active and total ghrelin concentrations with dry matter intake, growth, and carcass characteristics of finishing beef cattle

    Science.gov (United States)

    Ghrelin is a gut peptide that when acylated is thought to stimulate appetite. Circulating ghrelin concentrations could potentially be used as a predictor of DMI in cattle. The objective of this experiment was to determine the association of circulating ghrelin concentrations with DMI and other produ...

  8. Membrane domains and polarized trafficking of sphingolipids

    NARCIS (Netherlands)

    Maier, O; Slimane, TA; Hoekstra, D

    The plasma membrane of polarized cells consists of distinct domains, the apical and basolateral membrane that are characterized by a distinct lipid and protein content. Apical protein transport is largely mediated by (glyco)sphingolipid-cholesterol enriched membrane microdomains, so called rafts. In

  9. Altered Leukocyte Sphingolipid Pathway in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Larissa P. Maia

    2017-11-01

    Full Text Available Sphingolipid metabolism pathway is essential in membrane homeostasis, and its dysfunction has been associated with favorable tumor microenvironment, disease progression, and chemotherapy resistance. Its major components have key functions on survival and proliferation, with opposing effects. We have profiled the components of the sphingolipid pathway on leukocytes of breast cancer (BC patients undergoing chemotherapy treatment and without, including the five sphingosine 1-phosphate (S1P receptors, the major functional genes, and cytokines, in order to better understand the S1P signaling in the immune cells of these patients. To the best of our knowledge, this is the first characterization of the sphingolipid pathway in whole blood of BC patients. Skewed gene profiles favoring high SPHK1 expression toward S1P production during BC development was observed, which was reversed by chemotherapy treatment, and reached similar levels to those found in healthy donors. Such levels were also correlated with high levels of TNF-α. Our data revealed an important role of the sphingolipid pathway in immune cells in BC with skewed signaling of S1P receptors, which favored cancer development even under chemotherapy, and may probably be a trigger of cancer resistance. Thus, these molecules must be considered as a target pathway for combined BC therapeutics.

  10. Circulating vitamin D concentration and age-related macular degeneration: Systematic review and meta-analysis.

    Science.gov (United States)

    Annweiler, Cedric; Drouet, Morgane; Duval, Guillaume T; Paré, Pierre-Yves; Leruez, Stephanie; Dinomais, Mickael; Milea, Dan

    2016-06-01

    Vitamin D may be involved in ocular function in older adults, but there is no current consensus on a possible association between circulating concentrations of 25-hydroxyvitamin D (25OHD) and the occurrence of age-related macular degeneration (AMD). Our objective was to systematically review and quantitatively assess the association of circulating 25OHD concentration with AMD. A Medline search was conducted in November 2015, with no date limit, using the MeSH terms "Vitamin D" OR "Vitamin D deficiency" OR "Ergocalciferols" OR 'Cholecalciferol' combined with "Age-related macular degeneration" OR "Macular degeneration" OR "Retinal degeneration" OR "Macula lutea" OR "Retina". Fixed and random-effects meta-analyses were performed to compute (i) standard mean difference in 25OHD concentration between AMD and non-AMD patients; (ii) AMD risk according to circulating 25OHD concentration. Of the 243 retrieved studies, 11 observational studies-10 cross-sectional studies and 1 cohort study-met the selection criteria. The number of participants ranged from 65 to 17,045 (52-100% women), and the number with AMD ranged from 31 to 1440. Circulating 25OHD concentration was 15% lower in AMD compared with non-AMD on average. AMD was inversely associated with the highest 25OHD quintile compared with the lowest (summary odds ratio (OR)=0.83 [95%CI:0.71-0.97]), notably late AMD (summary OR=0.47 [95%CI:0.28-0.79]). Circulating 25OHD<50nmol/L was also associated with late-stage AMD (summary OR=2.18 [95%CI:1.34-3.56]), an association that did not persist when all categories of AMD were considered (summary OR=1.26 [95%CI:0.90-1.76]). In conclusion, this meta-analysis provides evidence that high 25OHD concentrations may be protective against AMD, and that 25OHD concentrations below 50nmol/L are associated with late AMD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

    DEFF Research Database (Denmark)

    Pedersen, Henrik Duelund; Falk, Bo Torkel; Häggström, Jens

    2005-01-01

    Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations...... has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range...... of asymptomatic MR (median serum IGF-1: 76.7 µg/L; 25-75 percentile, 59.8-104.9 µg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated...

  12. The COST733 circulation type classification software: an example for surface ozone concentrations in Central Europe

    Science.gov (United States)

    Demuzere, Matthias; Kassomenos, P.; Philipp, A.

    2011-08-01

    In the framework of the COST733 Action "Harmonisation and Applications of Weather Types Classifications for European Regions" a new circulation type classification software (hereafter, referred to as cost733class software) is developed. The cost733class software contains a variety of (European) classification methods and is flexible towards choice of domain of interest, input variables, time step, number of circulation types, sequencing and (weighted) target variables. This work introduces the capabilities of the cost733class software in which the resulting circulation types (CTs) from various circulation type classifications (CTCs) are applied on observed summer surface ozone concentrations in Central Europe. Firstly, the main characteristics of the CTCs in terms of circulation pattern frequencies are addressed using the baseline COST733 catalogue (cat 2.0), at present the latest product of the new cost733class software. In a second step, the probabilistic Brier skill score is used to quantify the explanatory power of all classifications in terms of the maximum 8 hourly mean ozone concentrations exceeding the 120-μg/m3 threshold; this was based on ozone concentrations from 130 Central European measurement stations. Averaged evaluation results over all stations indicate generally higher performance of CTCs with a higher number of types. Within the subset of methodologies with a similar number of types, the results suggest that the use of CTCs based on optimisation algorithms are performing slightly better than those which are based on other algorithms (predefined thresholds, principal component analysis and leader algorithms). The results are further elaborated by exploring additional capabilities of the cost733class software. Sensitivity experiments are performed using different domain sizes, input variables, seasonally based classifications and multiple-day sequencing. As an illustration, CTCs which are also conditioned towards temperature with various weights

  13. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...... the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

  14. Inflammaging and Frailty Status Do Not Result in an Increased Extracellular Vesicle Concentration in Circulation

    Directory of Open Access Journals (Sweden)

    Ainhoa Alberro

    2016-07-01

    Full Text Available In the last decades extracellular vesicles (EVs have emerged as key players for intercellular communication. In the case of inflammation, several studies have reported that EV levels are increased in circulation during inflammatory episodes. Based on this, we investigated whether aging results in elevated EV number, as a basal proinflammatory status termed “inflammaging” has been described in aged individuals. Moreover, we also hypothesized that frailty and dependence conditions of the elderly could affect EV concentration in plasma. Results showed that inflammaging, frailty or dependence status do not result in EV increase, at least in the total number of EVs in circulation. These results open a new perspective for investigating the role of EVs in human aging and in the inflammaging process.

  15. Inflammaging and Frailty Status Do Not Result in an Increased Extracellular Vesicle Concentration in Circulation.

    Science.gov (United States)

    Alberro, Ainhoa; Sáenz-Cuesta, Matías; Muñoz-Culla, Maider; Mateo-Abad, Maider; Gonzalez, Esperanza; Carrasco-Garcia, Estefania; Araúzo-Bravo, Marcos J; Matheu, Ander; Vergara, Itziar; Otaegui, David

    2016-07-20

    In the last decades extracellular vesicles (EVs) have emerged as key players for intercellular communication. In the case of inflammation, several studies have reported that EV levels are increased in circulation during inflammatory episodes. Based on this, we investigated whether aging results in elevated EV number, as a basal proinflammatory status termed "inflammaging" has been described in aged individuals. Moreover, we also hypothesized that frailty and dependence conditions of the elderly could affect EV concentration in plasma. Results showed that inflammaging, frailty or dependence status do not result in EV increase, at least in the total number of EVs in circulation. These results open a new perspective for investigating the role of EVs in human aging and in the inflammaging process.

  16. Plant sphingolipids: decoding the enigma of the Sphinx.

    Science.gov (United States)

    Pata, Mickael O; Hannun, Yusuf A; Ng, Carl K-Y

    2010-02-01

    Sphingolipids are a ubiquitous class of lipids present in a variety of organisms including eukaryotes and bacteria. In the last two decades, research has focused on characterizing the individual species of this complex family of lipids, which has led to a new field of research called 'sphingolipidomics'. There are at least 500 (and perhaps thousands of) different molecular species of sphingolipids in cells, and in Arabidopsis alone it has been reported that there are at least 168 different sphingolipids. Plant sphingolipids can be divided into four classes: glycosyl inositol phosphoceramides (GIPCs), glycosylceramides, ceramides, and free long-chain bases (LCBs). Numerous enzymes involved in plant sphingolipid metabolism have now been cloned and characterized, and, in general, there is broad conservation in the way in which sphingolipids are metabolized in animals, yeast and plants. Here, we review the diversity of sphingolipids reported in the literature, some of the recent advances in our understanding of sphingolipid metabolism in plants, and the physiological roles that sphingolipids and sphingolipid metabolites play in plant physiology.

  17. Autophagy in the light of sphingolipid metabolism

    DEFF Research Database (Denmark)

    Harvald, Eva Bang; Olsen, Anne Sofie Braun; Færgeman, Nils J.

    2015-01-01

    Maintenance of cellular homeostasis requires tight and coordinated control of numerous metabolic pathways, which are governed by interconnected networks of signaling pathways and energy-sensing regulators. Autophagy, a lysosomal degradation pathway by which the cell self-digests its own components......, has over the past decade been recognized as an essential part of metabolism. Autophagy not only rids the cell of excessive or damaged organelles, misfolded proteins, and invading microorganisms, it also provides nutrients to maintain crucial cellular functions. Besides serving as essential structural...... moieties of biomembranes, lipids including sphingolipids are increasingly being recognized as central regulators of a number of important cellular processes, including autophagy. In the present review we describe how sphingolipids, with special emphasis on ceramides and sphingosine-1-phosphate, can act...

  18. Sphingolipids as a new factor in the pathomechanism of preeclampsia - Mass spectrometry analysis.

    Directory of Open Access Journals (Sweden)

    Karol Charkiewicz

    Full Text Available The aim of the study was to analyse a panel of 11 sphingolipids in plasma and three blood fractions (platelet-poor plasma, platelets and red blood cells of women with mild preeclampsia.We recruited 21 women between 25-40 weeks gestation with diagnosed mild preeclampsia to the study group and 36 healthy women with uncomplicated pregnancies, who corresponded with the study group according to gestational age, to the control group. To assess the concentration of 11 sphingolipids in the blood plasma and blood fractions, we used ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/MS/MS.We showed a significant increase in the concentration of eight sphingolipids in the plasma of women with preeclampsia in comparison to the control group: Sph (p = 0.0032, S1P (p = 0.0289, C20-Cer (p < 0.0001, C18-Cer (p < 0.0001, C16-Cer (p = 0.012, C18:1-Cer (p = 0.003, C22-Cer (p = 0.0071, and C24:1-Cer (p = 0.0085.We showed that selected sphingolipids, especially C20-Cer and C18-Cer, are totally new factors in the pathomechanism of PE and that these bioactive lipids may play an important role in apoptosis and autophagy.

  19. Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.

    Science.gov (United States)

    Olson, D K; Fröhlich, F; Farese, R V; Walther, T C

    2016-08-01

    Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. Copyright © 2015. Published by Elsevier B.V.

  20. The role of sphingolipids in neuronal plasticity of the brain.

    Science.gov (United States)

    Sonnino, Sandro; Prinetti, Alessandro

    2016-05-01

    This Editorial highlights a study by Müller et al. in which the authors suggest a new sphingolipid-dependent mechanism for behavioral extinction. Their study should be considered in the broad perspective of sphingolipid metabolic pathways and traffic (depicted in the graphic). Read the highlighted article 'A sphingolipid mechanism for behavioral extinction' on page 589. © 2016 International Society for Neurochemistry.

  1. Field estimates of groundwater circulation depths in two mountainous watersheds in the western U.S. and the effect of deep circulation on solute concentrations in streamflow

    Science.gov (United States)

    Frisbee, Marty D.; Tolley, Douglas G.; Wilson, John L.

    2017-04-01

    Estimates of groundwater circulation depths based on field data are lacking. These data are critical to inform and refine hydrogeologic models of mountainous watersheds, and to quantify depth and time dependencies of weathering processes in watersheds. Here we test two competing hypotheses on the role of geology and geologic setting in deep groundwater circulation and the role of deep groundwater in the geochemical evolution of streams and springs. We test these hypotheses in two mountainous watersheds that have distinctly different geologic settings (one crystalline, metamorphic bedrock and the other volcanic bedrock). Estimated circulation depths for springs in both watersheds range from 0.6 to 1.6 km and may be as great as 2.5 km. These estimated groundwater circulation depths are much deeper than commonly modeled depths suggesting that we may be forcing groundwater flow paths too shallow in models. In addition, the spatial relationships of groundwater circulation depths are different between the two watersheds. Groundwater circulation depths in the crystalline bedrock watershed increase with decreasing elevation indicative of topography-driven groundwater flow. This relationship is not present in the volcanic bedrock watershed suggesting that both the source of fracturing (tectonic versus volcanic) and increased primary porosity in the volcanic bedrock play a role in deep groundwater circulation. The results from the crystalline bedrock watershed also indicate that relatively deep groundwater circulation can occur at local scales in headwater drainages less than 9.0 km2 and at larger fractions than commonly perceived. Deep groundwater is a primary control on streamflow processes and solute concentrations in both watersheds.

  2. Circulating Irisin Concentrations Are Associated with a Favourable Lipid Profile in the General Population.

    Directory of Open Access Journals (Sweden)

    Simon Oelmann

    Full Text Available Irisin is a myokine, which is mainly inversely associated with the risk for non-communicable diseases. Irisin improves cellular energy metabolism by uncoupling the mitochondrial respiratory chain resulting in increased energy expenditure using lipids. To date potential associations between irisin concentration and lipid profile are poorly understood. Therefore, this investigation aimed to evaluate potential associations between irisin and lipid levels in the general population.Data of 430 men and 537 women from the population-based Study of Health in Pomerania (SHIP-TREND with available irisin and lipid concentrations were used. Analyses of variance, linear and logistic regression models adjusted for age, HBA1c, waist circumference, physical activity, smoking, alcohol consumption, systolic blood pressure, ALAT were calculated.We detected significantly inverse associations between irisin and circulating levels of total [beta coefficient 0.21 (standard error 0.08, p = 0.01], low-density cholesterol [-0.16 (0.07, p = 0.03] and triglycerides [-0.17 (0.08, p = 0.02] for men. Females without lipid lowering medication had an inverse association between irisin and total cholesterol [-0.12 (0.06, p = 0.05]. Further, male subjects with irisin concentrations in the third tertile had an increased odds for elevated low-density cholesterol [odds ratio 1.96 (95% confidence interval 1.07-3.48, p = 0.03 and triglyceride [1.95 (1.09-3.47, p = 0.02] levels, even after exclusion of subjects with lipid lowering medication. In addition, our data revealed an annual rhythm of serum irisin levels with peak levels arise in winter and summer months.This is the first investigation to report a significant association between circulating irisin and a favourable lipid profile in the general population. This may infer that higher irisin concentrations are associated with a reduced risk for non-communicable diseases.

  3. Surface ozone concentrations in Europe: Links with the regional-scale atmospheric circulation

    Science.gov (United States)

    Davies, T. D.; Kelly, P. M.; Low, P. S.; Pierce, C. E.

    1992-06-01

    Daily surface ozone observations from 1978 (1976 for some analyses) to 1988 for Bottesford (United Kingdom), Cabauw, Kloosterburen (The Netherlands), Hohenpeissenberg, Neuglobsow, Hamburg, and Arkona (Germany) are used to analyze links between surface ozone variations and the atmospheric circulation. A daily Europe-wide synoptic classification highlights marked differences between surface ozone/meteorology relationships in summer and winter. These relationships are characterized by correlations between daily surface ozone concentrations at each station and a local subregional surface pressure gradient (a wind speed index). Although there are geographical variations, which are explicable in terms of regional climatology, there are distinct annual cycles. In summer, the surface ozone/wind speed relationship exhibits the expected negative sign; however, in winter, the relationship is, in the main, strongly positive, especially at those stations which are more influenced by the vigorous westerlies. Spring and autumn exhibit negative, positive, or transitional (between summer and winter) behavior, depending on geographical position. It is suggested that these relationships reflect the importance of vertical exchange from the free troposphere to the surface in the nonsummer months. Composite surface pressure patterns and surface pressure anomaly (from the long-term mean) patterns associated with high surface ozone concentrations on daily and seasonal time scales are consistent with the surface ozone/wind speed relationships. Moreover, they demonstrate that high surface ozone concentrations, in a climatological time frame, can be associated with mean surface pressure patterns which have a synoptic reality and are robust. Such an approach may be useful in interpreting past variations in surface ozone and may help to isolate the effect of human activity. It is also possible that assessments can be made of the effect of projected future changes in the atmospheric circulation

  4. Polarized sphingolipid transport from the subapical compartment : Evidence for distinct sphingolipid domains

    NARCIS (Netherlands)

    van Ijzendoorn, SCD; Hoekstra, D

    1999-01-01

    In polarized HepG2 cells, the sphingolipids glucosylceramide and sphingomyelin (SM), transported along the reverse transcytotic pathway, are sorted in subapical compartments (SACs), and subsequently targeted to either apical or basolateral plasma membrane domains, respectively. In the present study,

  5. Characterization of fluidization regime in circulating fluidized bed reactor with high solid particle concentration using computational fluid dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Chalermsinsuwan, Benjapon; Thummakul, Theeranan; Piumsomboon, Pornpote [Chulalongkorn University, Bangkok (Thailand); Gidaspow, Dimitri [Armour College of Engineering, Chicago (United States)

    2014-02-15

    The hydrodynamics inside a high solid particle concentration circulating fluidized bed reactor was investigated using computational fluid dynamics simulation. Compared to a low solid particle reactor, all the conventional fluidization regimes were observed. In addition, two unconventional fluidization regimes, circulating-turbulent and dense suspension bypassing regimes, were found with only primary gas injection. The circulating-turbulent fluidization regime showed uniformly dense solid particle distribution in all the system directions, while the dense suspension bypassing fluidization regime exhibited the flow of solid particles at only one side system wall. Then, comprehensive fluidization regime clarification and mapping were evaluated using in-depth system parameters. In the circulating-turbulent fluidization regime, the total granular temperature was low compared to the adjacent fluidization regimes. In the dense suspension bypassing fluidization regime, the highest total granular temperature was obtained. The circulating-turbulent and dense suspension bypassing fluidization regimes are suitable for sorption and transportation applications, respectively.

  6. Mesoscale circulation systems and ozone concentrations during ESCOMPTE: a case study from IOP 2b

    Science.gov (United States)

    Kalthoff, N.; Kottmeier, C.; Thürauf, J.; Corsmeier, U.; Saїd, F.; Fréjafon, E.; Perros, P. E.

    2005-03-01

    The main objective of 'Expérience sur Site pour COntraindre les Modèles de Pollution atmosphérique et de Transport d'Emissions' (ESCOMPTE) is to generate a relevant data set for testing and evaluating mesoscale chemistry-transport models (CTMs). During ESCOMPTE, measurements have been performed at numerous surface stations, by radars and lidars, and several aircraft in the planetary boundary layer. The data from these different sources have been merged to obtain a consistent description of the spatial distribution of wind, temperature, humidity, and ozone for the photosmog episode on June 25, 2001 (IOP 2b). On this day, moderate synoptic winds favour the evolution of different mesoscale circulation systems. During daytime, the sea breeze penetrates towards the north in the Rhône valley. As the winds above the sea breeze layer come from the east, polluted air from the metropolitan area of Marseille leads to an increase of ozone at elevated layers above the convective boundary layer (CBL). At the mountainous station of Luberon about 55 km north of Marseille around noon, when the CBL top surpasses the height of the mountain summit, polluted air with ozone concentrations of about 120 ppbv arrived from southerly directions, thus indicating the passage of the city plume of Marseille. At Cadarache and Vinon in the Durance valley, about 60 km inland, the ozone maximum at the surface and at flight level 920 m MSL appears between 14 and 15 UTC. At this time, southwesterly valley winds prevail in the valley, while southerly winds occur above. This finding highlights the height-dependent advection of ozone due to interacting mesoscale circulation systems. These dynamical processes need to be represented adequately in CTMs to deliver a realistic description of the ozone concentration fields.

  7. Abnormal islet sphingolipid metabolism in type 1 diabetes

    DEFF Research Database (Denmark)

    Holm, Laurits J; Krogvold, Lars; Hasselby, Jane P

    2018-01-01

    AIMS/HYPOTHESIS: Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis....... Transcriptional analysis was used to evaluate expression of sphingolipid-related genes in isolated human islets. Genome-wide association studies (GWAS) and a T cell proliferation assay were used to identify type 1 diabetes related polymorphisms and test how these affect cellular islet autoimmunity. Finally, we...... diabetes, which were associated with reduced expression of enzymes involved in sphingolipid metabolism. Next, we discovered eight gene polymorphisms (ORMDL3, SPHK2, B4GALNT1, SLC1A5, GALC, PPARD, PPARG and B4GALT1) involved in sphingolipid metabolism that contribute to the genetic predisposition to type 1...

  8. Translational Aspects of Sphingolipid Metabolism in Renal Disorders

    Directory of Open Access Journals (Sweden)

    Alaa Abou Daher

    2017-11-01

    Full Text Available Sphingolipids, long thought to be passive components of biological membranes with merely a structural role, have proved throughout the past decade to be major players in the pathogenesis of many human diseases. The study and characterization of several genetic disorders like Fabry’s and Tay Sachs, where sphingolipid metabolism is disrupted, leading to a systemic array of clinical symptoms, have indeed helped elucidate and appreciate the importance of sphingolipids and their metabolites as active signaling molecules. In addition to being involved in dynamic cellular processes like apoptosis, senescence and differentiation, sphingolipids are implicated in critical physiological functions such as immune responses and pathophysiological conditions like inflammation and insulin resistance. Interestingly, the kidneys are among the most sensitive organ systems to sphingolipid alterations, rendering these molecules and the enzymes involved in their metabolism, promising therapeutic targets for numerous nephropathic complications that stand behind podocyte injury and renal failure.

  9. Placental growth factor concentration in maternal circulation decreases after fetal death: lessons from a case series study.

    Science.gov (United States)

    Beharier, Ofer; Shusterman, Eden; Szaingurten-Solodkin, Irit; Weintraub, Adi Y; Sheiner, Eyal; Swissa, Shani S; Gitler, Daniel; Hershkovitz, Reli

    2015-11-01

    Placental growth factor (PlGF) has been suggested as a possible biomarker for major placenta-related disorders such as preeclampsia and intrauterine growth restriction. However, experimental findings suggest that PlGF concentrations may be influenced by other factors besides the placenta. In the present study, we examined how acute fetal injury affects PlGF concentrations in maternal circulation. We therefore monitored PlGF concentrations in maternal circulation before and after feticide. A prospective comparative study was performed. Blood samples were drawn prospectively between January and July 2012, before and after feticide at predetermined time points in relation to the procedure (0, 30, 60, and 120 min). The levels of lactate dehydrogenase (LDH) in the maternal circulation were measured to detect acute tissue damage. PlGF concentrations were measured by standard human ELISA. Following feticide (60 and 120 min), PlGF concentrations decreased significantly compared to the concentrations before feticide. LDH concentrations did not change before and after feticide. Our finding, along with the detailed review of the literature described in our work, supports a new concept in which primary fetal distress can affect PlGF concentration in maternal circulation. A large-scale study is required to strengthen our finding.

  10. Macrophage sphingolipids are essential for the entry of mycobacteria.

    Science.gov (United States)

    Viswanathan, Gopinath; Jafurulla, Md; Kumar, G Aditya; Raghunand, Tirumalai R; Chattopadhyay, Amitabha

    2018-07-01

    Mycobacteria are intracellular pathogens that can invade and survive within host macrophages. Mycobacterial infections remain a major cause of mortality and morbidity worldwide, with serious concerns of emergence of multi and extensively drug-resistant tuberculosis. While significant advances have been made in identifying mycobacterial virulence determinants, the detailed molecular mechanism of internalization of mycobacteria into host cells remains poorly understood. Although several studies have highlighted the crucial role of sphingolipids in mycobacterial growth, persistence and establishment of infection, the role of sphingolipids in the entry of mycobacteria into host cells is not known. In this work, we explored the role of host membrane sphingolipids in the entry of Mycobacterium smegmatis into J774A.1 macrophages. Our results show that metabolic depletion of sphingolipids in host macrophages results in a significant reduction in the entry of M. smegmatis. Importantly, the entry of Escherichia coli into host macrophages under similar conditions remained invariant, implying the specificity of the requirement of sphingolipids in mycobacterial entry. To the best of our knowledge, our results constitute the first report demonstrating the role of host macrophage sphingolipids in the entry of mycobacteria. Our results could help in the development of novel therapeutic strategies targeting sphingolipid-mediated entry of mycobacteria into host cells. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Neuronal sphingolipidoses: Membrane lipids and sphingolipid activator proteins regulate lysosomal sphingolipid catabolism.

    Science.gov (United States)

    Sandhoff, Konrad

    2016-11-01

    Glycosphingolipids and sphingolipids of cellular plasma membranes (PMs) reach luminal intra-lysosomal vesicles (LVs) for degradation mainly by pathways of endocytosis. After a sorting and maturation process (e.g. degradation of sphingomyelin (SM) and secretion of cholesterol), sphingolipids of the LVs are digested by soluble enzymes with the help of activator (lipid binding and transfer) proteins. Inherited defects of lipid-cleaving enzymes and lipid binding and transfer proteins cause manifold and fatal, often neurodegenerative diseases. The review summarizes recent findings on the regulation of sphingolipid catabolism and cholesterol secretion from the endosomal compartment by lipid modifiers, an essential stimulation by anionic membrane lipids and an inhibition of crucial steps by cholesterol and SM. Reconstitution experiments in the presence of all proteins needed, hydrolase and activator proteins, reveal an up to 10-fold increase of ganglioside catabolism just by the incorporation of anionic lipids into the ganglioside carrying membranes, whereas an additional incorporation of cholesterol inhibits GM2 catabolism substantially. It is suggested that lipid and other low molecular modifiers affect the genotype-phenotype relationship observed in patients with lysosomal diseases. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  12. The GARP complex is required for cellular sphingolipid homeostasis

    DEFF Research Database (Denmark)

    Fröhlich, Florian; Petit, Constance; Kory, Nora

    2015-01-01

    (GARP) complex, which functions in endosome-to-Golgi retrograde vesicular transport, as a critical player in sphingolipid homeostasis. GARP deficiency leads to accumulation of sphingolipid synthesis intermediates, changes in sterol distribution, and lysosomal dysfunction. A GARP complex mutation...... analogous to a VPS53 allele causing progressive cerebello-cerebral atrophy type 2 (PCCA2) in humans exhibits similar, albeit weaker, phenotypes in yeast, providing mechanistic insights into disease pathogenesis. Inhibition of the first step of de novo sphingolipid synthesis is sufficient to mitigate many...

  13. Local Cytokine Concentrations and Oxygen Pressure Are Related to Maturation of the Collateral Circulation in Humans

    NARCIS (Netherlands)

    Schirmer, Stephan H.; van Royen, Niels; Moerland, Perry D.; Fledderus, Joost O.; Henriques, José P.; van der Schaaf, René J.; Vis, Marije M.; Baan, Jan; Koch, Karel T.; Horrevoets, Anton J. G.; Hoefer, Imo E.; Piek, Jan J.

    2009-01-01

    Objectives Our aim was to determine cytokine and oxygen gradients over the collateral circulation in humans. Background The molecular background of the maturation of the collateral circulation in response to coronary narrowing is poorly understood in humans, partly because of difficulties in

  14. Sphingolipid Metabolism Correlates with Cerebrospinal Fluid Beta Amyloid Levels in Alzheimer’s Disease

    Science.gov (United States)

    Fonteh, Alfred N.; Ormseth, Cora; Chiang, Jiarong; Cipolla, Matthew; Arakaki, Xianghong; Harrington, Michael G.

    2015-01-01

    Sphingolipids are important in many brain functions but their role in Alzheimer’s disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but not impaired

  15. Sphingolipid metabolism correlates with cerebrospinal fluid Beta amyloid levels in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Alfred N Fonteh

    Full Text Available Sphingolipids are important in many brain functions but their role in Alzheimer's disease (AD is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but

  16. Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

    Science.gov (United States)

    Knapp, Paweł; Bodnar, Lubomir; Błachnio-Zabielska, Agnieszka; Świderska, Magdalena; Chabowski, Adrian

    2017-10-01

    The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100μl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100μl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100μl (AUC:0.77, P=0.0136) was noticed. Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Remote ischemic preconditioning does not increase circulating or effector organ concentrations of proopiomelanocortin derivates

    DEFF Research Database (Denmark)

    Birkelund, Thomas; Obad, Damir; Matejec, Reginald

    2015-01-01

    Objectives. The aim of the present study was to compare changes in circulating levels of proopiomelanocortin (POMC) derivates and lactate after remote ischemic preconditioning (IPC) and physical exercise. Introduction. Remote IPC (rIPC) is cardioprotective following acute myocardial infarction....... Results. While rIPC was not associated with any significant increase in circulating POMC derivates or lactate, exercise induced significant elevation of both compared with baseline. Conclusions. We were not able to demonstrate a detectable increase in circulating POMC derivates by a standard rIPC stimulus...

  18. Second to fourth digit ratio (2D:4D and concentrations of circulating sex hormones in adulthood

    Directory of Open Access Journals (Sweden)

    Morris Howard A

    2011-04-01

    Full Text Available Abstract Background The second to fourth digit ratio (2D:4D is used as a marker of prenatal sex hormone exposure. The objective of this study was to examine whether circulating concentrations of sex hormones and SHBG measured in adulthood was associated with 2D:4D. Methods This analysis was based on a random sample from the Melbourne Collaborative Cohort Study. The sample consisted of of 1036 men and 620 post-menopausal women aged between 39 and 70 at the time of blood draw. Concentrations of circulating sex hormones were measured from plasma collected at baseline (1990-1994, while digit length was measured from hand photocopies taken during a recent follow-up (2003-2009. The outcome measures were circulating concentrations of testosterone, oestradiol, dehydroepiandrosterone sulphate, androstenedione, Sex Hormone Binding Globulin, androstenediol glucoronide for men only and oestrone sulphate for women only. Free testosterone and oestradiol were estimated using standard formulae derived empirically. Predicted geometric mean hormone concentrations (for tertiles of 2D:4D and conditional correlation coefficients (for continuous 2D:4D were obtained using mixed effects linear regression models. Results No strong associations were observed between 2D:4D measures and circulating concentrations of hormones for men or women. For males, right 2D:4D was weakly inversely associated with circulating testosterone (predicted geometric mean testosterone was 15.9 and 15.0 nmol/L for the lowest and highest tertiles of male right 2D:4D respectively (P-trend = 0.04. There was a similar weak association between male right 2D:4D and the ratio of testosterone to oestradiol. These associations were not evident in analyses of continuous 2D:4D. Conclusions There were no strong associations between any adult circulating concentration of sex hormone or SHGB and 2D:4D. These results contribute to the growing body of evidence indicating that 2D:4D is unrelated to adult sex

  19. Making Sense of the Yeast Sphingolipid Pathway.

    Science.gov (United States)

    Megyeri, Márton; Riezman, Howard; Schuldiner, Maya; Futerman, Anthony H

    2016-12-04

    Sphingolipids (SL) and their metabolites play key roles both as structural components of membranes and as signaling molecules. Many of the key enzymes and regulators of SL metabolism were discovered using the yeast Saccharomyces cerevisiae, and based on the high degree of conservation, a number of mammalian homologs were identified. Although yeast continues to be an important tool for SL research, the complexity of SL structure and nomenclature often hampers the ability of new researchers to grasp the subtleties of yeast SL biology and discover new modulators of this intricate pathway. Moreover, the emergence of lipidomics by mass spectrometry has enabled the rapid identification of SL species in yeast and rendered the analysis of SL composition under various physiological and pathophysiological conditions readily amenable. However, the complex nomenclature of the identified species renders much of the data inaccessible to non-specialists. In this review, we focus on parsing both the classical SL nomenclature and the nomenclature normally used during mass spectrometry analysis, which should facilitate the understanding of yeast SL data and might shed light on biological processes in which SLs are involved. Finally, we discuss a number of putative roles of various yeast SL species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...

  1. Meta-analysis of genome-wide association studies for circulating phylloquinone concentrations

    Science.gov (United States)

    Background: Poor vitamin K status is linked to greater risk of several chronic diseases. Age, sex, and diet are determinants of circulating vitamin K; however, there is still large unexplained interindividual variability in vitamin K status. Although a strong genetic component has been hypothesized,...

  2. Variable aromatase inhibitor plasma concentrations do not correlate with circulating estrogen concentrations in post-menopausal breast cancer patients.

    Science.gov (United States)

    Hertz, Daniel L; Speth, Kelly A; Kidwell, Kelley M; Gersch, Christina L; Desta, Zeruesenay; Storniolo, Anna Maria; Stearns, Vered; Skaar, Todd C; Hayes, Daniel F; Henry, N Lynn; Rae, James M

    2017-10-01

    The aromatase inhibitors (AI) exemestane (EXE), letrozole (LET), and anastrozole suppress estrogen biosynthesis, and are effective treatments for estrogen receptor (ER)-positive breast cancer. Prior work suggests that anastrozole blood concentrations are associated with the magnitude of estrogen suppression. The objective of this study was to determine whether the magnitude of estrogen suppression, as determined by plasma estradiol (E2) concentrations, in EXE or LET treated patients is associated with plasma AI concentrations. Five hundred post-menopausal women with ER-positive breast cancer were enrolled in the prospective Exemestane and Letrozole Pharmacogenetic (ELPh) Study conducted by the COnsortium on BReast cancer phArmacogomics (COBRA) and randomly assigned to either drug. Estrogen concentrations were measured at baseline and after 3 months of AI treatment and drug concentrations were measured after 1 or 3 months. EXE or LET concentrations were compared with 3-month E2 concentration or the change from baseline to 3 months using several complementary statistical procedures. Four-hundred patients with on-treatment E2 and AI concentrations were evaluable (EXE n = 200, LET n = 200). Thirty (7.6%) patients (EXE n = 13, LET n = 17) had 3-month E2 concentrations above the lower limit of quantification (LLOQ) (median: 4.75; range: 1.42-63.8 pg/mL). EXE and LET concentrations were not associated with on-treatment E2 concentrations or changes in E2 concentrations from baseline (all p > 0.05). Steady-state plasma AI concentrations do not explain variability in E2 suppression in post-menopausal women receiving EXE or LET therapy, in contrast with prior evidence in anastrozole treated patients.

  3. Abnormal islet sphingolipid metabolism in type 1 diabetes.

    Science.gov (United States)

    Holm, Laurits J; Krogvold, Lars; Hasselby, Jane P; Kaur, Simranjeet; Claessens, Laura A; Russell, Mark A; Mathews, Clayton E; Hanssen, Kristian F; Morgan, Noel G; Koeleman, Bobby P C; Roep, Bart O; Gerling, Ivan C; Pociot, Flemming; Dahl-Jørgensen, Knut; Buschard, Karsten

    2018-04-18

    Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes and whether increasing the levels of the sphingolipid sulfatide would prevent models of diabetes in NOD mice. We examined the amount and distribution of sulfatide in human pancreatic islets by immunohistochemistry, immunofluorescence and electron microscopy. Transcriptional analysis was used to evaluate expression of sphingolipid-related genes in isolated human islets. Genome-wide association studies (GWAS) and a T cell proliferation assay were used to identify type 1 diabetes related polymorphisms and test how these affect cellular islet autoimmunity. Finally, we treated NOD mice with fenofibrate, a known activator of sulfatide biosynthesis, to evaluate the effect on experimental autoimmune diabetes development. We found reduced amounts of sulfatide, 23% of the levels in control participants, in pancreatic islets of individuals with newly diagnosed type 1 diabetes, which were associated with reduced expression of enzymes involved in sphingolipid metabolism. Next, we discovered eight gene polymorphisms (ORMDL3, SPHK2, B4GALNT1, SLC1A5, GALC, PPARD, PPARG and B4GALT1) involved in sphingolipid metabolism that contribute to the genetic predisposition to type 1 diabetes. These gene polymorphisms correlated with the degree of cellular islet autoimmunity in a cohort of individuals with type 1 diabetes. Finally, using fenofibrate, which activates sulfatide biosynthesis, we completely prevented diabetes in NOD mice and even reversed the disease in half of otherwise diabetic animals. These results indicate that islet sphingolipid metabolism is abnormal in type 1 diabetes and suggest that modulation may represent a novel therapeutic approach. The RNA expression data is

  4. Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of Candida albicans.

    Directory of Open Access Journals (Sweden)

    Fikadu G Tafesse

    2015-10-01

    Full Text Available The ability of phagocytes to clear pathogens is an essential attribute of the innate immune response. The role of signaling lipid molecules such as phosphoinositides is well established, but the role of membrane sphingolipids in phagocytosis is largely unknown. Using a genetic approach and small molecule inhibitors, we show that phagocytosis of Candida albicans requires an intact sphingolipid biosynthetic pathway. Blockade of serine-palmitoyltransferase (SPT and ceramide synthase-enzymes involved in sphingolipid biosynthesis- by myriocin and fumonisin B1, respectively, impaired phagocytosis by phagocytes. We used CRISPR/Cas9-mediated genome editing to generate Sptlc2-deficient DC2.4 dendritic cells, which lack serine palmitoyl transferase activity. Sptlc2-/- DC2.4 cells exhibited a stark defect in phagocytosis, were unable to bind fungal particles and failed to form a normal phagocytic cup to engulf C. albicans. Supplementing the growth media with GM1, the major ganglioside present at the cell surface, restored phagocytic activity of Sptlc2-/- DC2.4 cells. While overall membrane trafficking and endocytic pathways remained functional, Sptlc2-/- DC2.4 cells express reduced levels of the pattern recognition receptors Dectin-1 and TLR2 at the cell surface. Consistent with the in vitro data, compromised sphingolipid biosynthesis in mice sensitizes the animal to C. albicans infection. Sphingolipid biosynthesis is therefore critical for phagocytosis and in vivo clearance of C. albicans.

  5. The influence of atmospheric circulation on the air pollution concentration and temperature inversion in Sosnowiec. Case study

    Directory of Open Access Journals (Sweden)

    Widawski Artur

    2015-06-01

    Full Text Available Sosnowiec is located in the Katowice Region, which is the most urbanized and industrialized region in Poland. Urban areas of such character favor enhancement of pollution concentration in the atmosphere and the consequent emergence of smog. Local meteorological and circulation conditions significantly influence not only on the air pollution level but also change air temperature considerably in their centers and immediate vicinities. The synoptic situation also plays the major role in dispersal and concentration of air pollutants and changes in temperature profile. One of the most important are the near-ground (100 m inversions of temperature revealed their highest values on clear winter days and sometimes stay still for the whole day and night. Air temperature inversions in Sosnowiec occur mainly during anticyclone stagnation (Ca-anticyclone centre and Ka-anticyclonic ridge and in anticyclones with air advection from the south and southwest (Sa and SWa which cause significantly increase of air pollution values. The detailed evaluation of the influence of circulation types on the appearance of a particular concentration of pollutants carried out in this work has confirmed the predominant influence of individual circulation types on the development of air pollution levels at the Katowice region. This paper presents research case study results of the thermal structure of the near-ground atmospheric layer (100 m and air pollution parameters (PM10, SO2, NO, NO2 changes in selected days of 2005 year according to regional synoptic circulation types. The changes in urban environment must be taken into account in analyses of multiyear trends of air temperature and air conditions on the regional and global scales.

  6. Tumor PDT-associated immune response: relevance of sphingolipids

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush; Separovic, Duska M.

    2010-02-01

    Sphingolipids have become recognized as essential effector molecules in signal transduction with involvement in various aspects of cell function and death, immune response and cancer treatment response. Major representatives of sphingolipids family, ceramide, sphingosine and sphingosine-1-phosphate (S1P), have attracted interest in their relevance to tumor response to photodynamic therapy (PDT) because of their roles as enhancers of apoptosis, mediators of cell growth and vasculogenesis, and regulators of immune response. Our recent in vivo studies with mouse tumor models have confirmed that PDT treatment has a pronounced impact on sphingolipid profile in the targeted tumor and that significant advances in therapeutic gain with PDT can be attained by combining this modality with adjuvant treatment with ceramide analog LCL29.

  7. Controlling thermal properties of dense gas fluidized beds for concentrated solar power by internal and external solids circulation

    Science.gov (United States)

    Ammendola, Paola; Bareschino, Piero; Chirone, Riccardo; Salatino, Piero; Solimene, Roberto

    2017-06-01

    Fluidization technology displays a long record of success stories, mostly related to applications to thermal and thermochemical processes, which are fostering extension to novel and relatively unexplored fields. Application of fluidized beds to collection and thermal storage of solar radiation in Concentrated Solar Power (CSP) is one of the most promising, a field which poses challenging issues and great opportunities to fluidization scientists and technologists. The potential of this growing field calls for reconsideration of some of the typical design and operation guidelines and criteria, with the goal of exploiting the inherently good thermal performances of gas-fluidized beds at their best. "Creative" and non-conventional design and operation of fluidized beds, like those based on internal and external solids circulation, may be beneficial to the enhancement of thermal diffusivity and surface-to-bed heat transfer, improving the potential for application in the very demanding context of CSP with thermal energy storage. This paper investigated: i) a fluidized bed configuration with an uneven distribution of the fluidizing gas to promote vortices in the scale of bed height (internal solids circulation); ii) a dual fluidized bed configuration characterized by an external solids circulation achieved by the operation of a riser and a bubbling fluidized bed. CFD simulations showed the hydrodynamics conditions under which the internal solids circulation was established. The hydrodynamic characterization of the external solids circulation was achieved by an experimental study carried out with different cold models. The dual fluidized bed system was optimized in terms of operating conditions and geometrical features of the connections between two fluidized beds.

  8. Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis.

    Science.gov (United States)

    Mina, John G M; Denny, P W

    2018-02-01

    Sphingolipids (SLs) are an integral part of all eukaryotic cellular membranes. In addition, they have indispensable functions as signalling molecules controlling a myriad of cellular events. Disruption of either the de novo synthesis or the degradation pathways has been shown to have detrimental effects. The earlier identification of selective inhibitors of fungal SL biosynthesis promised potent broad-spectrum anti-fungal agents, which later encouraged testing some of those agents against protozoan parasites. In this review we focus on the key enzymes of the SL de novo biosynthetic pathway in protozoan parasites of the Apicomplexa and Kinetoplastidae, outlining the divergence and interconnection between host and pathogen metabolism. The druggability of the SL biosynthesis is considered, alongside recent technology advances that will enable the dissection and analyses of this pathway in the parasitic protozoa. The future impact of these advances for the development of new therapeutics for both globally threatening and neglected infectious diseases is potentially profound.

  9. Radon concentration and exhalation measurements with semiconductor detector and electrostatic precipitator working in a closed circulation system

    International Nuclear Information System (INIS)

    Wojcik, M.; Morawska, L.

    1982-01-01

    An apparatus is described and a method presented for the determination of concentration of radon emanated from solid and liquid samples. In this method an object or a sample of air is closed in an hermetically sealed chamber. The air contaminated by radon and its daughters is circulated in a closed system a few times through an electrostatic precipitator mounted in one housing with a semiconductor Si Li detector. The concentration of radon is determined by the alpha activity measurement of its daughters. The sensitivity of the apparatus is very high. While calculating a radon concentration from an activity measurement of RaA (fast method) the sensitivity is about 0.07 pCi/l and when measuring the activity of RaC' (slow method) it is 0.008 pCi/l. Due to the application of an electrostatic precipitator and a silicon detector it is possible to perform alpha spectrometric measurements and thus separate activities of RaA, RaC', and ThC and to calculate 222 Rn or 220 Rn concentrations. The efficiency of RaA, RaB, RaC, ThB and ThC collection is constant, due to the method involving the circulation of the air through the electrostatic precipitator several times. (author)

  10. Fumonisin B₁ (FB₁) Induces Lamellar Separation and Alters Sphingolipid Metabolism of In Vitro Cultured Hoof Explants.

    Science.gov (United States)

    Reisinger, Nicole; Dohnal, Ilse; Nagl, Veronika; Schaumberger, Simone; Schatzmayr, Gerd; Mayer, Elisabeth

    2016-03-24

    One of the most important hoof diseases is laminitis. Yet, the pathology of laminitis is not fully understood. Different bacterial toxins, e.g. endotoxins or exotoxins, seem to play an important role. Additionally, ingestion of mycotoxins, toxic secondary metabolites of fungi, might contribute to the onset of laminitis. In this respect, fumonsins are of special interest since horses are regarded as species most susceptible to this group of mycotoxins. The aim of our study was to investigate the influence of fumonisin B₁ (FB₁) on primary isolated epidermal and dermal hoof cells, as well as on the lamellar tissue integrity and sphingolipid metabolism of hoof explants in vitro. There was no effect of FB₁ at any concentration on dermal or epidermal cells. However, FB₁ significantly reduced the separation force of explants after 24 h of incubation. The Sa/So ratio was significantly increased in supernatants of explants incubated with FB₁ (2.5-10 µg/mL) after 24 h. Observed effects on Sa/So ratio were linked to significantly increased sphinganine concentrations. Our study showed that FB₁ impairs the sphingolipid metabolism of explants and reduces lamellar integrity at non-cytotoxic concentrations. FB₁ might, therefore, affect hoof health. Further in vitro and in vivo studies are necessary to elucidate the effects of FB₁ on the equine hoof in more detail.

  11. Comparative effects of fumonisins on sphingolipid metabolism and toxicity in ducks and turkeys.

    Science.gov (United States)

    Benlasher, Emad; Geng, Xiuyu; Nguyen, Ngoc Thanh Xuan; Tardieu, Didier; Bailly, Jean-Denis; Auvergne, Alain; Guerre, Philippe

    2012-03-01

    Fumonisins (FBs) are mycotoxins that are found worldwide in maize and maize products. Their main toxic effects have been well characterized in poultry, but differences between species have been demonstrated. Ducks appeared very sensitive to toxicity, whereas turkeys are more resistant. At the same time, alterations of sphingolipid metabolism, with an increase of the concentration of the free sphinganine (Sa) in serum and liver, have been demonstrated in the two species, but the link between the toxicity of FBs and Sa accumulation remains difficult to interpret. The aim of the present work was to compare the effects of FBs (10 mg FB1 + FB2/kg body weight) on sphingolipid metabolism in ducks and turkeys. Growth, feed consumption, and serum biochemistry were also investigated to evaluate toxicity. The main results showed that FBs increased Sa concentrations in liver and serum in ducks and turkeys, but these accumulations were not directly correlated with toxicity. Sa accumulation was higher in the livers of turkeys than in ducks, whereas Sa levels were higher in the sera of ducks than in turkeys. Hepatic toxicity was more pronounced in ducks than in turkeys and accompanied a decrease of body weight and an increase of serum biochemistry in ducks but not in turkeys. So, although FBs increase Sa concentration in the livers of both species, this effect is not directly proportional to toxicity. The mechanisms of FB toxicity and/or the mechanisms of protection of ducks and turkeys to the Sa accumulation within the liver remain to be established.

  12. Preformed and regenerated phosphate in ocean general circulation models: can right total concentrations be wrong?

    Directory of Open Access Journals (Sweden)

    O. Duteil

    2012-05-01

    Full Text Available Phosphate distributions simulated by seven state-of-the-art biogeochemical ocean circulation models are evaluated against observations of global ocean nutrient distributions. The biogeochemical models exhibit different structural complexities, ranging from simple nutrient-restoring to multi-nutrient NPZD type models. We evaluate the simulations using the observed volume distribution of phosphate. The errors in these simulated volume class distributions are significantly larger when preformed phosphate (or regenerated phosphate rather than total phosphate is considered. Our analysis reveals that models can achieve similarly good fits to observed total phosphate distributions for a~very different partitioning into preformed and regenerated nutrient components. This has implications for the strength and potential climate sensitivity of the simulated biological carbon pump. We suggest complementing the use of total nutrient distributions for assessing model skill by an evaluation of the respective preformed and regenerated nutrient components.

  13. Two New Sphingolipids from the Leaves of Piper betle L.

    OpenAIRE

    Chen, Duo-Zhi; Xiong, Hua-Bin; Tian, Kai; Guo, Jun-Ming; Huang, Xiang-Zhong; Jiang, Zhi-Yong

    2013-01-01

    Two new sphingolipids, pipercerebrosides A (1) and B (2), were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay.

  14. Two new sphingolipids from the leaves of Piper betle L.

    Science.gov (United States)

    Chen, Duo-Zhi; Xiong, Hua-Bin; Tian, Kai; Guo, Jun-Ming; Huang, Xiang-Zhong; Jiang, Zhi-Yong

    2013-09-12

    Two new sphingolipids, pipercerebrosides A (1) and B (2), were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay.

  15. Two New Sphingolipids from the Leaves of Piper betle L.

    Directory of Open Access Journals (Sweden)

    Zhi-Yong Jiang

    2013-09-01

    Full Text Available Two new sphingolipids, pipercerebrosides A (1 and B (2, were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay.

  16. Sphingolipid trafficking and protein sorting in epithelial cells

    NARCIS (Netherlands)

    Slimane, TA; Hoekstra, D

    2002-01-01

    Sphingolipids represent a minor, but highly dynamic subclass of lipids in all eukaryotic cells. They are involved in functions that range from structural protection to signal transduction and protein sorting, and participate in lipid raft assembly. In polarized epithelial cells, which display an

  17. Preanalytical Biases in the Measurement of Human Blood Sphingolipids

    Directory of Open Access Journals (Sweden)

    Robert Brunkhorst

    2018-05-01

    Full Text Available Dysregulation of blood sphingolipids is an emerging topic in clinical science. The objective of this study was to determine preanalytical biases that typically occur in clinical and translational studies and that influence measured blood sphingolipid levels. Therefore, we collected blood samples from four healthy male volunteers to investigate the effect of storage conditions (time, temperature, long-term storage, freeze–thaw cycles, blood drawing (venous or arterial sampling, prolonged venous compression, and sample preparation (centrifugation, freezing on sphingolipid levels measured by LC-MS/MS. Our data show that sphingosine 1-phosphate (S1P and sphinganine 1-phosphate (SA1P were upregulated in whole blood samples in a time- and temperature-dependent manner. Increased centrifugation at higher speeds led to lower amounts of S1P and SA1P. All other preanalytical biases did not significantly alter the amounts of S1P and SA1P. Further, in almost all settings, we did not detect differences in (dihydroceramide levels. In summary, besides time-, temperature-, and centrifugation-dependent changes in S1P and SA1P levels, sphingolipids in blood remained stable under practically relevant preanalytical conditions.

  18. Complex modulation of peptidolytic activity of cathepsin D by sphingolipids

    Czech Academy of Sciences Publication Activity Database

    Žebrakovská, Iva; Máša, Martin; Srp, Jaroslav; Horn, Martin; Vávrová, K.; Mareš, Michael

    2011-01-01

    Roč. 1811, č. 12 (2011), s. 1097-1104 ISSN 1388-1981 R&D Projects: GA AV ČR IAA400550705 Institutional research plan: CEZ:AV0Z40550506 Keywords : sphingolipid * phospholipid * inhibition * activation * cathepsin D * enzyme regulation Subject RIV: CE - Biochemistry Impact factor: 5.269, year: 2011

  19. Association between Intake of Sugar-Sweetened Beverages and Circulating 25-Hydroxyvitamin D Concentration among Premenopausal Women

    Directory of Open Access Journals (Sweden)

    Caroline S. Duchaine

    2014-07-01

    Full Text Available Intake of sugar-sweetened beverages has increased in North America and seems to have several adverse health effects possibly through decreased circulating 25-hydroxyvitamin D (25(OHD concentrations. The aim of this cross-sectional study was to evaluate the association between sugar-sweetened beverages intake and 25(OHD concentrations among premenopausal women. Intake of sugar-sweetened beverages including colas, other carbonated beverages and sweet fruit drinks was assessed using a validated food frequency questionnaire among 741 premenopausal women. Plasma concentrations of 25(OHD were quantified by radioimmunoassay. The association between sugar-sweetened beverages intake and 25(OHD concentrations was evaluated using multivariate generalized linear models and Spearman correlations. A higher intake of colas was associated with lower mean 25(OHD levels (67.0, 63.7, 64.7 and 58.5 nmol/L for never, <1, 1–3 and >3 servings/week, respectively; r = −0.11 (p = 0.004. A correlation was observed between intake of other carbonated beverages and 25(OHD concentrations but was not statistically significant (r = −0.06 (p = 0.10. No association was observed between intake of sweet fruit drinks and 25(OHD concentrations. This study suggests that high intake of colas may decrease 25(OHD levels in premenopausal women. Considering the high consumption of these drinks in the general population and the possible consequences of vitamin D deficiency on health, this finding needs further investigation.

  20. Circulating ghrelin concentrations fluctuate relative to nutritional status and influence feeding behavior in cattle.

    Science.gov (United States)

    Wertz-Lutz, A E; Knight, T J; Pritchard, R H; Daniel, J A; Clapper, J A; Smart, A J; Trenkle, A; Beitz, D C

    2006-12-01

    The objective of these experiments was to establish the relationship of plasma ghrelin concentrations with feed intake and hormones indicative of nutritional state of cattle. In Exp.1, 4 steers (BW 450 +/- 14.3 kg) were used in a crossover design to compare plasma ghrelin concentrations of feed-deprived steers with those of steers allowed to consume feed and to establish the relationship of plasma ghrelin concentrations with those of GH, insulin (INS), glucose (GLU), and NEFA. After adaptation to a once-daily feed offering (0800), 2 steers continued the once-daily feeding schedule (FED), whereas feed was withheld from the other 2 steers (FAST). Serial blood samples were collected via indwelling jugular catheter from times equivalent to 22 h through 48 h of feed deprivation. Average plasma ghrelin concentrations were greater (P ruminants.

  1. Circulating carotenoid concentrations are positively correlated with later clutch initiation in Florida Scrub-Jays (Aphelocoma coerulescens).

    Science.gov (United States)

    Heiss, Rebecca S; Cohen, Alan A; Bowman, Reed; Boughton, Raoul K; Bridge, Eli; McGraw, Kevin J; Schoech, Stephan J

    2011-02-01

    Antioxidants play key roles in preventing free radical damage to various molecules, cells, and tissues, but it is not well understood how variation in antioxidant levels may relate to the reproductive success or health of wild animals. We explored the relationship between circulating antioxidant concentrations and both body condition and timing of reproduction in male and female Florida Scrub-Jays (Aphelocoma coerulescens), a cooperatively breeding passerine bird. We examined whether levels of uric acid, vitamin E, and carotenoids (all potentially important antioxidants) were linked to body condition and timing of reproduction, two measures that are directly related to reproductive success. Antioxidant concentrations were not correlated with body condition, but they were related to timing of first clutch initiation, though not always in the predicted direction. Elevated circulating levels of carotenoids were associated with delayed clutch initiation in female breeders. Relatively higher vitamin E levels in control birds were associated with earlier clutch initiation, whereas male breeders that received long-term food supplementation had elevated levels of vitamin E and delayed reproduction. Several potential explanations for the link between elevated levels of antioxidants and delayed clutch initiation are discussed. Separate explanations for each sex include, but are not limited to, oxidative stress as a result of territory defense efforts in males, different dietary regimes due to supplementation, and mobilized plasma antioxidants in females that were coping with a stressor. © 2010 Wiley-Liss, Inc.

  2. Circulating leptin concentrations do not distinguish menstrual status in exercising women.

    Science.gov (United States)

    Corr, M; De Souza, M J; Toombs, R J; Williams, N I

    2011-03-01

    Low concentrations of leptin secondary to low body fat or other modulators are thought to be a key signal whereby an energy deficit suppresses the reproductive axis in exercising women resulting in functional hypothalamic amenorrhea (FHA). The purpose of this study was to first examine leptin concentrations in exercising women with and without FHA to address whether there is a threshold concentration of leptin below which reproductive function is suppressed. Secondly, we examined the role of adiposity and other possible modulators of leptin to ascertain whether leptin regulation differs depending on reproductive status. This study assessed 50 exercising, premenopausal women (aged 18-30 years) over the course of one menstrual cycle (eumenorrheic women) or one 28-day monitoring period (amenorrheic women). Quantification of daily urinary ovarian steroids and menstrual history were used to determine menstrual status. Body composition was assessed using dual energy X-ray absorptiometry, and leptin was determined by enzyme-linked immunoassay. Key modulators of leptin such as serum insulin concentration, carbohydrate intake, glucose availability, indirect indices of sympathetic nervous activity and other factors were assessed using linear regression. Percentage body fat (%BF) (21.0 ± 1.0 versus 26.8 ± 0.7%; P exercising women with amenorrhea (ExAmen; n = 24) compared with the exercising ovulatory women (ExOvul; n = 26). However, the ranges in leptin were similar for each group (ExAmen: 0.30-16.98 ng/ml; ExOvul: 2.57-18.28 ng/ml), and after adjusting for adiposity the difference in leptin concentration was no longer significant. Significant predictors of log leptin in ExAmen included %BF (β = 0.826, P exercising women, but the modulation of leptin concentrations may differ depending on reproductive status.

  3. Reduction of indoor particles concentration using re-circulating filtration units in Danish dwellings

    DEFF Research Database (Denmark)

    Spilak, Michal; Frederiksen, Marie; Karottki, Gabriela D.

    2012-01-01

    air was recirculated through the unit during two weeks in a randomized and double blinded design. The measurements included concentration of PM2.5 and ultrafine particles (UPC), carbon dioxide, temperature and relative humidity, ventilation, air flow through the unit, allergen and fungal levels....... Additional information was collected through questionnaires. Several medical tests were made, however the results are not included in this paper. Preliminary results showed significant decrease in PM2.5 concentration during the filtered period compared to placebo period. Likewise was UPC significantly lower...

  4. Circulating adiponectin concentration and body composition are altered in response to high-intensity interval training.

    Science.gov (United States)

    Shing, Cecilia M; Webb, Jessica J; Driller, Matthew W; Williams, Andrew D; Fell, James W

    2013-08-01

    Adiponectin influences metabolic adaptations that would prove beneficial to endurance athletes, and yet to date there is little known about the response of adiponectin concentrations to exercise, and, in particular, the response of this hormone to training in an athlete population. This study aimed to determine the response of plasma adiponectin concentrations to acute exercise after 2 different training programs and to determine the influence of the training on body composition. Seven state-level representative rowers (age: 19 ± 1.2 years [mean ± SD], height: 1.77 ± 0.10 m, body mass: 74.0 ± 10.7 kg, VO2peak 62.1 ± 7.0 ml·kg·min) participated in the double-blind, randomized crossover investigation. Rowers performed an incremental graded exercise test before and after completing 4 weeks of high-intensity interval ergometer training and 4 weeks of traditional ergometer rowing training. Rowers' body composition was assessed at baseline and after each training program. Significant increases in plasma adiponectin concentration occurred in response to maximal exercise after completion of the high-intensity interval training (p = 0.016) but not after traditional ergometer rowing training (p = 0.69). The high-intensity interval training also resulted in significant increases in mean 4-minute power output (p = 0.002) and VO2peak (p = 0.05), and a decrease in body fat percentage (p = 0.022). Mean 4-minute power output, VO2peak, and body fat percentage were not significantly different after 4 weeks of traditional ergometer rowing training (p > 0.05). Four weeks of high-intensity interval training is associated with an increase in adiponectin concentration in response to maximal exercise and a reduction in body fat percentage. The potential for changes in adiponectin concentration to reflect positive training adaptations and athlete performance level should be further explored.

  5. The relationship between typhoons' peripheral circulation and ground-level ozone concentrations in central Taiwan.

    Science.gov (United States)

    Cheng, Wan-Li; Lai, Li-Wei; Den, Walter; Wu, Meng-Ting; Hsueh, Chao-An; Lin, Pay-Liam; Pai, Chueh-Ling; Yan, Yeou-Lih

    2014-02-01

    Surface data of meteorological parameters (wind speed, wind direction, and mixing height) and air pollutant concentrations (O3, NO, and NO2) were collected for a 92-day period associated with typhoon formation in 2005. The influence of typhoons on O3 concentration were defined by azimuth and distance from Taiwan, and Types A, B, and C correspond to typhoons less than 1,500 km from Taiwan and located between azimuths 45° and 135°, 135° and 225°, and 225° and 45°, respectively. Type D corresponds to typhoons more than 1,500 km from Taiwan. Titration reactions were conducted at three temporal phases: 2000-0700, 0800-1100, and 1200-1400 LST (Local Standard Time). The air pollution model (TAPM) was used to simulate wind fields and trajectories of air masses. It was determined that typhoon position affected O3 concentration, temporal and spatial patterns of O3 titration and vertical meteorological characteristics, which were not all at the statistically significant level.

  6. Circulating asprosin concentrations are increased in type 2 diabetes mellitus and independently associated with fasting glucose and triglyceride.

    Science.gov (United States)

    Zhang, Lei; Chen, Chao; Zhou, Nan; Fu, Yuming; Cheng, Xingbo

    2017-11-03

    Asprosin has been identified as a novel hormone enriched in white adipose tissue and is pathologically increased in insulin-resistant mice and humans. However, information regarding the role of asprosin in type 2 diabetes mellitus (T2DM) remains unavailable. Via conducting a hospital-based study, we purposed to ascertain the potential relationship between circulating asprosin concentrations and T2DM. The study recruited 84 adults with T2DM and 86 controls with normal glucose tolerance. They matched in age, body mass index (BMI), and sex. Serum asprosin concentrations were measured via ELISA method. Compared to the controls, serum asprosin concentrations were significantly increased in the T2DM adults (Pglucose and triglyceride were independently associated with serum asprosin in T2DM. Asprosin concentrations are increased in adults with T2DM. The results suggest that asprosin might serve as a risk factor associated with the pathogenesis of T2DM, but not an ideal biomarker for predicting T2DM. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. SPHINGOLIPID-DEPENDENT FUSION OF SEMLIKI FOREST VIRUS WITH CHOLESTEROL-CONTAINING LIPOSOMES REQUIRES BOTH THE 3-HYDROXYL GROUP AND THE DOUBLE-BOND OF THE SPHINGOLIPID BACKBONE

    NARCIS (Netherlands)

    CORVER, J; MOESBY, L; ERUKULLA, RK; REDDY, KC; BITTMAN, R; WILSCHUT, J

    Low-pH-induced membrane fusion of Semliki Forest virus (SFV) in a model system is mediated by sphingolipids in the target membrane; ceramide is the sphingolipid minimally required (J. L. Nieva, R. Bron, J. Corver, and J. Wilschut, EMBO J. 13:2797-2804, 1994). Here, using various ceramide analogs, we

  8. Circulating cytokine concentrations in dogs with different degrees of myxomatous mitral valve disease

    DEFF Research Database (Denmark)

    Zois, Nora Elisabeth; Moesgaard, Sophia Gry; Kjelgaard-Hansen, Mads

    2012-01-01

    , IL-15, IL-18, keratinocyte-derived chemokine, interferon-c-induced protein and monocyte chemoattractant protein-1 (MCP-1) were measured using a canine-specific multiplex immunoassay. CHF dogs had significantly higher MCP-1 concentrations than dogs with no or minimal MR. Among the CKCS, IL-2 and IL-7...... decreased with increasing left atrial size and IL-7 also decreased with increasing MR. IL-8 decreased with increasing left ventricular end-systolic internal dimensions. MCP-1 was increased in CHF dogs compared to healthy control dogs and IL-2, IL-7 and IL-8 decreased with increasing indices of disease...

  9. Circulating ghrelin, leptin, and soluble leptin receptor concentrations and cardiometabolic risk factors in a community-based sample.

    Science.gov (United States)

    Ingelsson, Erik; Larson, Martin G; Yin, Xiaoyan; Wang, Thomas J; Meigs, James B; Lipinska, Izabella; Benjamin, Emelia J; Keaney, John F; Vasan, Ramachandran S

    2008-08-01

    The conjoint effects and relative importance of ghrelin, leptin, and soluble leptin receptor (sOB-R), adipokines involved in appetite control and energy expenditure in mediating cardiometabolic risk, is unknown. The objective of the study was to study the cross-sectional relations of these adipokines to cardiometabolic risk factors in a community-based sample. We measured circulating ghrelin, leptin, and sOB-R in 362 participants (mean age 45 yr; 54% women) of the Framingham Third Generation Cohort. Body mass index, waist circumference (WC), blood pressure, lipid measures, fasting glucose, smoking, and metabolic syndrome (MetS) were measured. Ghrelin and leptin concentrations were significantly higher in women (P risk.

  10. Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Perez-Cornago, Aurora; Appleby, Paul N.; Tipper, Sarah; Key, Timothy J.; Allen, Naomi E.; Nieters, Alexandra; Vermeulen, Roel; Roulland, Sandrine; Casabonne, Delphine; Kaaks, Rudolf; Fortner, Renee T.; Boeing, Heiner; Trichopoulou, Antonia; La Vecchia, Carlo; Klinaki, Eleni; Hansen, Louise; Tjønneland, Anne; Bonnet, Fabrice; Fagherazzi, Guy; Boutron-Ruault, Marie Christine; Pala, Valeria; Masala, Giovanna; Sacerdote, Carlotta; Peeters, Petra H.; Bueno-de-Mesquita, H. Bas; Weiderpass, Elisabete; Dorronsoro, Miren; Quirós, J. Ramón; Barricarte, Aurelio; Gavrila, Diana; Agudo, Antonio; Borgquist, Signe; Rosendahl, Ann H.; Melin, Beatrice; Wareham, Nick; Khaw, Kay Tee; Gunter, Marc; Riboli, Elio; Vineis, Paolo; Travis, Ruth C.

    2017-01-01

    Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested

  11. Sphingolipids in human synovial fluid--a lipidomic study.

    Directory of Open Access Journals (Sweden)

    Marta Krystyna Kosinska

    Full Text Available Articular synovial fluid (SF is a complex mixture of components that regulate nutrition, communication, shock absorption, and lubrication. Alterations in its composition can be pathogenic. This lipidomic investigation aims to quantify the composition of sphingolipids (sphingomyelins, ceramides, and hexosyl- and dihexosylceramides and minor glycerophospholipid species, including (lysophosphatidic acid, (lysophosphatidylglycerol, and bis(monoacylglycerophosphate species, in the SF of knee joints from unaffected controls and from patients with early (eOA and late (lOA stages of osteoarthritis (OA, and rheumatoid arthritis (RA. SF without cells and cellular debris from 9 postmortem donors (control, 18 RA, 17 eOA, and 13 lOA patients were extracted to measure lipid species using electrospray ionization tandem mass spectrometry--directly or coupled with hydrophilic interaction liquid chromatography. We provide a novel, detailed overview of sphingolipid and minor glycerophospholipid species in human SF. A total of 41, 48, and 50 lipid species were significantly increased in eOA, lOA, and RA SF, respectively when compared with normal SF. The level of 21 lipid species differed in eOA SF versus SF from lOA, an observation that can be used to develop biomarkers. Sphingolipids can alter synovial inflammation and the repair responses of damaged joints. Thus, our lipidomic study provides the foundation for studying the biosynthesis and function of lipid species in health and most prevalent joint diseases.

  12. Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids

    International Nuclear Information System (INIS)

    Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten

    2005-01-01

    Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to low pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids

  13. The way we view cellular (glyco)sphingolipids.

    Science.gov (United States)

    Hoetzl, Sandra; Sprong, Hein; van Meer, Gerrit

    2007-11-01

    Mammalian cells synthesize ceramide in the endoplasmic reticulum (ER) and convert this to sphingomyelin and complex glycosphingolipids on the inner, non-cytosolic surface of Golgi cisternae. From there, these lipids travel towards the outer, non-cytosolic surface of the plasma membrane and all membranes of the endocytic system, where they are eventually degraded. At the basis of the selective, anterograde traffic out of the Golgi lies the propensity of the sphingolipids to self-aggregate with cholesterol into microdomains termed 'lipid rafts'. At the plasma membrane surface these rafts are thought to function as the scaffold for various types of (glyco) signaling domains of different protein and lipid composition that can co-exist on one and the same cell. In the past decade, various unexpected findings on the sites where sphingolipid-mediated events occur have thrown a new light on the localization and transport mechanisms of sphingolipids. These findings are largely based on biochemical experiments. Further progress in the field is hampered by a lack of morphological techniques to localize lipids with nanometer resolution. In the present paper, we critically evaluate the published data and discuss techniques and potential improvements.

  14. The Role of Sphingolipids on Innate Immunity to Intestinal Salmonella Infection.

    Science.gov (United States)

    Huang, Fu-Chen

    2017-08-07

    Salmonella spp. remains a major public health problem for the whole world. To reduce the use of antimicrobial agents and drug-resistant Salmonella , a better strategy is to explore alternative therapy rather than to discover another antibiotic. Sphingolipid- and cholesterol-enriched lipid microdomains attract signaling proteins and orchestrate them toward cell signaling and membrane trafficking pathways. Recent studies have highlighted the crucial role of sphingolipids in the innate immunity against infecting pathogens. It is therefore mandatory to exploit the role of the membrane sphingolipids in the innate immunity of intestinal epithelia infected by this pathogen. In the present review, we focus on the role of sphingolipids in the innate immunity of intestinal epithelia against Salmonella infection, including adhesion, autophagy, bactericidal effect, barrier function, membrane trafficking, cytokine and antimicrobial peptide expression. The intervention of sphingolipid-enhanced foods to make our life healthy or pharmacological agents regulating sphingolipids is provided at the end.

  15. Daily rhythm of circulating fat soluble vitamin concentration (A, D, E and K in the horse

    Directory of Open Access Journals (Sweden)

    Caola Giovanni

    2004-07-01

    Full Text Available Abstract Background Many physiological processes of mammalian species exhibit daily rhythmicity. An intrinsic relationship exists between fat soluble vitamins (A, D, E and K and several body functions. Few investigations on the rhythmic pattern of vitamins in domestic animals have been carried out. The present study evaluated the circadian rhythmicity of fat soluble vitamins in the horse. Methods Blood samples from 5 Thoroughbred mares were collected at four-hour intervals over a 48-hour period (starting at 8:00 hours on day 1 and finishing at 4:00 on day 2 via an intravenous cannula inserted into the jugular vein. Fat soluble vitamin concentration in the serum (A, D, E and K was measured by HPLC. One-way repeated measures analysis of variance (ANOVA was used to determine significant differences. p values Results ANOVA showed a highly significant effect of time in all the horses for the vitamins studied (p Conclusion Fat soluble vitamins exhibit daily rhythmicity with diurnal peak. Further investigations could help optimize the use of these substances according to their circadian (or other rhythms.

  16. Circulating progesterone concentrations in nonlactating Holstein cows during reuse of intravaginal progesterone implants sanitized by autoclave or chemical disinfection.

    Science.gov (United States)

    Melo, L F; Monteiro, P L J; Oliveira, L H; Guardieiro, M M; Drum, J N; Wiltbank, M C; Sartori, R

    2018-04-01

    The aim of this study was to compare plasma progesterone (P4) concentrations in nonlactating, multiparous Holstein cows (n = 24) treated with 2 types of intravaginal implants containing either 1.0 or 1.9 g of P4 either at the first use or during reuse of the implants after sanitizing the implant by autoclave or chemical disinfection. In a completely randomized design with a 2 × 3 factorial arrangement and 2 replicates, every cow underwent 2 of 6 treatments. Two sources of P4 [controlled internal drug release (1.9 g of P4) from Zoetis (São Paulo, Brazil), and Sincrogest (1.0 g of P4) from Ourofino (Cravinhos, Brazil)] and 3 types of processing, new (N), reused after autoclave (RA), and reused after chemical disinfection (RC), were used. After inducing luteolysis to avoid endogenous circulating P4, the cows were randomized in 1 of 6 treatments (1.9 g of N, 1.9 g of RA, 1.9 g of RC, 1.0 g of N, 1.0 g of RA, and 1.0 g RC). Cows were treated with the implants for 8 d and during this period blood samples were collected at 0, 2, 12, 24, 48, 72, 96, 120, 144, 168, and 192 h. Statistical analyses were performed using Proc-Mixed and the mean ± standard error of the mean P4 concentrations were calculated using the Proc-Means procedures of SAS 9.4 (SAS Institute Inc., Cary, NC). No interaction between treatments was observed. Comparing types of implant, average P4 concentrations during treatments were greater for 1.9 g than 1.0 g (1.46 vs. 1.14 ± 0.04 ng/mL). When types of processing were compared, average P4 concentrations did not differ between autoclaved and new inserts (1.46 vs. 1.37 ± 0.05 ng/mL; respectively), but both were greater than chemically disinfected implants (1.09 ± 0.04 ng/mL). Within 1.9-g P4 inserts, P4 concentrations from autoclaved implants were greater than new, which were greater than chemically disinfected (1.67 ± 0.06 vs. 1.49 ± 0.07 vs. 1.21 ± 0.05 ng/mL; respectively). For 1.0-g P4 implants, P4 concentrations from autoclaved did not differ

  17. Impacts of large-scale circulation on urban ambient concentrations of gaseous elemental mercury in New York, USA

    Directory of Open Access Journals (Sweden)

    H. Mao

    2017-09-01

    Full Text Available The impact of large-scale circulation on urban gaseous elemental mercury (GEM was investigated through analysis of 2008–2015 measurement data from an urban site in New York City (NYC, New York, USA. Distinct annual cycles were observed in 2009–2010 with mixing ratios in warm seasons (i.e., spring–summer 10–20 ppqv ( ∼  10–25 % higher than in cool seasons (i.e., fall–winter. This annual cycle was disrupted in 2011 by an anomalously strong influence of the US East Coast trough in that warm season and was reproduced in 2014 associated with a particularly strong Bermuda High. The US East Coast trough axis index (TAI and intensity index (TII were used to characterize the effect of the US East Coast trough on NYC GEM, especially in winter and summer. The intensity and position of the Bermuda High appeared to have a significant impact on GEM in warm seasons. Regional influence on NYC GEM was supported by the GEM–carbon monoxide (CO correlation with r of 0.17–0.69 (p ∼  0 in most seasons. Simulated regional and local anthropogenic contributions to wintertime NYC anthropogenically induced GEM concentrations were averaged at  ∼  75 % and 25 %, with interannual variation ranging over 67 %–83 % and 17 %–33 %, respectively. Results from this study suggest the possibility that the increasingly strong Bermuda High over the past decades could dominate over anthropogenic mercury emission control in affecting ambient concentrations of mercury via regional buildup and possibly enhancing natural and legacy emissions.

  18. 4-Hydroxynonenal Contributes to Angiogenesis through a Redox-Dependent Sphingolipid Pathway: Prevention by Hydralazine Derivatives

    Directory of Open Access Journals (Sweden)

    Caroline Camaré

    2017-01-01

    Full Text Available The neovascularization of atherosclerotic lesions is involved in plaque development and may contribute to intraplaque hemorrhage and plaque fragilization and rupture. Among the various proangiogenic agents involved in the neovascularization process, proatherogenic oxidized LDLs (oxLDLs contribute to the formation of tubes via the generation of sphingosine 1-phosphate (S1P, a major mitogenic and proangiogenic sphingolipid mediator. In this study, we investigated whether 4-hydroxynonenal (4-HNE, an aldehydic lipid oxidation product abundantly present in oxLDLs, contributes to their proangiogenic properties. Immunofluorescence analysis of human atherosclerotic lesions from carotid endarterectomy showed the colocalization of HNE-adducts with CD31, a marker of endothelial cells, suggesting a close relationship between 4-HNE and neovessel formation. In vitro, low 4-HNE concentration (0.5–1 µM elicited the formation of tubes by human microvascular endothelial cells (HMEC-1, whereas higher concentrations were not angiogenic. The formation of tubes by 4-HNE involved the generation of reactive oxygen species and the activation of the sphingolipid pathway, namely, the neutral type 2 sphingomyelinase and sphingosine kinase-1 (nSMase2/SK-1 pathway, indicating a role for S1P in the angiogenic signaling of 4-HNE. Carbonyl scavengers hydralazine and bisvanillyl-hydralazone inhibited the nSMase2/SK1 pathway activation and the formation of tubes on Matrigel® evoked by 4-HNE. Altogether, these results emphasize the role of 4-HNE in the angiogenic effect of oxLDLs and point out the potential interest of pharmacological carbonyl scavengers to prevent the neovascularization process.

  19. Synthesis of a Panel of Carbon-13-Labelled (Glyco)Sphingolipids

    NARCIS (Netherlands)

    Wisse, Patrick; Gold, Henrik; Mirzaian, Mina; Ferraz, Maria J.; Lutteke, Ginger; van den Berg, Richard J. B. H. N.; van den Elst, Hans; Lugtenburg, Johan; van der Marel, Gijsbert A.; Aerts, Johannes M. F. G.; Codee, Jeroen D. C.; Overkleeft, Herman S.

    2015-01-01

    The synthesis of a focussed library of sphingolipids differing in the number and position of C-13 labels is described. The synthesised sphingolipids differ in substitution at both the sphingosine amine (either palmitoylated or unmodified) and the sphingosine primary hydroxyl (unmodified or

  20. Circulating concentrations of folate and vitamin B12 in relation to prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition study.

    NARCIS (Netherlands)

    Johansson, M.; Appleby, P.N.; Allen, N.E.; Travis, R.C.; Roddam, A.W.; Egevad, L.; Jenab, M.; Rinaldi, S.; Kiemeney, L.A.L.M.; Bueno-De-Mesquita, H.B.; Vollset, S.E.; Ueland, P.M.; Sanchez, M.J.; Quiros, J.R.; Gonzalez, C.A.; Larrañaga, N.; Chirlaque, M.D.; Ardanaz, E.; Sieri, S.; Palli, D.; Vineis, P.; Tumino, R.; Linseisen, J.; Kaaks, R.; Boeing, H.; Pischon, T.; Psaltopoulou, T.; Trichopoulou, A.; Trichopoulos, D.; Khaw, K.T.; Bingham, S.; Hallmans, G.; Riboli, E.; Stattin, P; Key, T.J.

    2008-01-01

    BACKGROUND: Determinants of one-carbon metabolism, such as folate and vitamin B(12), have been implicated in cancer development. Previous studies have not provided conclusive evidence for the importance of circulating concentrations of folate and vitamin B(12) in prostate cancer etiology. The aim of

  1. Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer.

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bonfrer, J.M.; Korse, C.M.; Doorn, J. van; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.M.; Leeuwen, F.E. van; Veer, L.J. van 't; Rookus, M.A.; Kampman, E.

    2007-01-01

    BACKGROUND: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding

  2. Lycopene supplementation elevates circulating insulin-like growth factor-binding protein-1 and-2 concentrations in persons at greater risk of colorectal cancer

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bonfrer, J.M.; Korse, C.M.; Doorn, J.; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.M.; Leeuwen, van F.E.; van't Veer, L.J.; Rookus, M.A.; Kampman, E.

    2007-01-01

    Background: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding

  3. The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation.

    LENUS (Irish Health Repository)

    Harmon, D

    2012-02-03

    Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37 degrees C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol\\/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor-alpha were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg\\/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass. IMPLICATIONS: Enhancement of gamma-aminobutyric acid(A)-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.

  4. Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Greenfield, Jerry R; Farooqi, I Sadaf; Keogh, Julia M

    2008-01-01

    objective was to determine whether glutamine increases circulating GLP-1 and GIP concentrations in vivo and, if so, whether this is associated with an increase in plasma insulin. DESIGN: We recruited 8 healthy normal-weight volunteers (LEAN), 8 obese individuals with type 2 diabetes or impaired glucose...... plasma insulin concentrations. Glutamine stimulated glucagon secretion in all 3 study groups. CONCLUSION: Glutamine effectively increases circulating GLP-1, GIP, and insulin concentrations in vivo and may represent a novel therapeutic approach to stimulating insulin secretion in obesity and type 2......BACKGROUND: Incretin hormones, such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in meal-related insulin secretion. We previously demonstrated that glutamine is a potent stimulus of GLP-1 secretion in vitro. OBJECTIVE: Our...

  5. Sphingolipids and plant defense/disease: the "death" connection and beyond

    Directory of Open Access Journals (Sweden)

    Robert eBerkey

    2012-04-01

    Full Text Available Sphingolipids comprise a major class of structural materials and lipid signaling molecules in all eukaryotic cells. Over the past two decades, there has been a phenomenal growth in the study of sphingolipids (i.e. sphingobiology at an average rate of >1000 research articles per year. Sphingolipid studies in plants, though accounting for only a small fraction (~6% of the total number of publications, have also enjoyed proportionally rapid growth in the past decade. Concomitant with the growth of sphingobiology, there has also been tremendous progress in our understanding of the molecular mechanisms of plant innate immunity. In this review, we (i cross examine and analyze the major findings that establish and strengthen the intimate connections between sphingolipid metabolism and plant programmed cell death (PCD associated with plant defense or disease; (ii highlight and compare key bioactive sphingolipids involved in the regulation of plant PCD and possibly defense; (iii discuss the potential role of sphingolipids in polarized membrane/protein trafficking and formation of lipid rafts as subdomains of cell membranes in relation to plant defense; and (iv where possible, attempt to identify potential parallels for immunity-related mechanisms involving sphingolipids across kingdoms.

  6. Association between circulating ascorbic acid, α-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study.

    Science.gov (United States)

    García-Bailo, Bibiana; Roke, Kaitlin; Mutch, David M; El-Sohemy, Ahmed; Badawi, Alaa

    2012-11-16

    Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. Participants (n = 1,007) from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson's correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates. We observed weak micronutrient-cytokine correlations, moderate correlations between certain cytokines, and strong correlations between specific cytokines, particularly interleukin 1- receptor antagonist (IL-1RA), interferon-γ (IFN-γ), and platelet-derived growth factor BB (PDGF-bb). After full covariate adjustment, circulating α-tocopherol was inversely associated with IFN-γ and regulated upon activation normal T-cell expressed and secreted (RANTES). We observed an unexpected positive association between ascorbic acid and IFN-γ. 25(OH)D was not associated with

  7. Association between circulating ascorbic acid, α-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    García-Bailo Bibiana

    2012-11-01

    Full Text Available Abstract Background Inflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OHD may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults. Methods Participants (n = 1,007 from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson’s correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates. Results We observed weak micronutrient-cytokine correlations, moderate correlations between certain cytokines, and strong correlations between specific cytokines, particularly interleukin 1- receptor antagonist (IL-1RA, interferon-γ (IFN-γ, and platelet-derived growth factor BB (PDGF-bb. After full covariate adjustment, circulating α-tocopherol was inversely associated with IFN-γ and regulated upon activation normal T-cell expressed and secreted (RANTES. We observed an unexpected positive association between ascorbic

  8. Regulation of stem-cell mediated host immunity by the sphingolipid ...

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

    Regulation of stem-cell mediated host immunity by the sphingolipid pathway ... in the generation of mature immune cells and the functioning of the surrounding ... methods with human cells and genetically engineered mice to examine how the ...

  9. Sphingolipid topology and the dynamic organization and function of membrane proteins.

    Science.gov (United States)

    van Meer, Gerrit; Hoetzl, Sandra

    2010-05-03

    When acquiring internal membranes and vesicular transport, eukaryotic cells started to synthesize sphingolipids and sterols. The physical differences between these and the glycerophospholipids must have enabled the cells to segregate lipids in the membrane plane. Localizing this event to the Golgi then allowed them to create membranes of different lipid composition, notably a thin, flexible ER membrane, consisting of glycerolipids, and a sturdy plasma membrane containing at least 50% sphingolipids and sterols. Besides sorting membrane proteins, in the course of evolution the simple sphingolipids obtained key positions in cellular physiology by developing specific interactions with (membrane) proteins involved in the execution and control of signaling. The few signaling sphingolipids in mammals must provide basic transmission principles that evolution has built upon for organizing the specific regulatory pathways tuned to the needs of the different cell types in the body. Copyright 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  10. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

    OpenAIRE

    Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu

    2011-01-01

    Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components...

  11. Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

    OpenAIRE

    Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-Hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

    2012-01-01

    Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 ?M) for 24 hr induced...

  12. Fiber Specific Changes in Sphingolipid Metabolism in Skeletal Muscles of Hyperthyroid Rats

    OpenAIRE

    Chabowski, A.; ?endzian-Piotrowska, M.; Mik?osz, A.; ?ukaszuk, B.; Kurek, K.; G?rski, J.

    2013-01-01

    Thyroid hormones (T3, T4) are well known modulators of different cellular signals including the sphingomyelin pathway. However, studies regarding downstream effects of T3 on sphingolipid metabolism in skeletal muscle are scarce. In the present work we sought to investigate the effects of hyperthyroidism on the activity of the key enzymes of ceramide metabolism as well as the content of fundamental sphingolipids. Based on fiber/metabolic differences, we chose three different skeletal muscles, ...

  13. A Lipidomics Approach to Assess the Association Between Plasma Sphingolipids and Verbal Memory Performance in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation: A C18:0 Signature for Cognitive Response to Exercise.

    Science.gov (United States)

    Saleem, Mahwesh; Herrmann, Nathan; Dinoff, Adam; Mielke, Michelle M; Oh, Paul I; Shammi, Prathiba; Cao, Xingshan; Venkata, Swarajya Lakshmi Vattem; Haughey, Norman J; Lanctôt, Krista L

    2017-01-01

    Early subtle deficits in verbal memory, which may indicate early neural risk, are common in patients with coronary artery disease (CAD). While exercise can improve cognition, cognitive response to exercise is heterogeneous. Sphingolipids have been associated with the development and progression of CAD, and impairments in sphingolipid metabolism may play roles in neurodegeneration and in the neural adaptation response to exercise. In this study, change in plasma concentrations of sphingolipids was assessed in relation to change in verbal memory performance and in other cognitive domains among CAD subjects undertaking a 6-month cardiac rehabilitation (CR) program. Patients with CAD (n = 120, mean age = 64±6 y, 84% male, years of education = 16±3) underwent CR with neuropsychological assessments and blood collected at baseline, 3-, and 6-months. Z-scores based on age, gender, and education were combined for verbal memory, visuospatial memory, processing speed, executive function, and global cognition tasks to calculate cognitive domain Z-scores. Plasma sphingolipid concentrations were measured from fasting blood samples using high performance liquid chromatography coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Mixed models were used to identify sphingolipids significantly associated with performance in verbal memory and other cognitive domains, adjusting for potential confounders. A decrease in ceramide C18:0 concentration was significantly associated with improvement in verbal memory performance (b[SE] = -0.51 [0.25], p = 0.04), visuospatial memory (b[SE] = -0.44 [0.22], p = 0.05), processing speed (b[SE] = -0.89 [0.32], p = 0.007), and global cognition (b[SE] = -1.47 [0.59], p = 0.01) over 6 months of CR. Plasma ceramide C18:0 concentrations may be a sensitive marker of cognitive response to exercise in patients with CAD.

  14. Circulating Angiopoietin-2 and Its Soluble Receptor Tie-2 Concentrations Are Related to Renal Function in Two Population-Based Cohorts

    DEFF Research Database (Denmark)

    Hennings, Anna; Hannemann, Anke; Rettig, Rainer

    2016-01-01

    BACKGROUND: An intact angiopoietin/Tie-2 ligand receptor system is indispensable for life. High circulating angiopoietin-2 (Ang-2) concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate the associ......BACKGROUND: An intact angiopoietin/Tie-2 ligand receptor system is indispensable for life. High circulating angiopoietin-2 (Ang-2) concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate...... the associations between renal function and serum Ang-2 or serum Tie-2 concentrations in the general population. METHODS: Data of 3081 and 4088 subjects from two population-based studies, the Study of Health in Pomerania (SHIP-1) and SHIP-Trend, were used. Renal function was assessed by serum creatinine, cystatin...... C concentration, creatinine-based estimated glomerular filtration rate [eGFR(crea)], cystatin C-based eGFR [eGFR(cys)] and urinary albumin-to-creatinine ratio (uACR). Analyses of variance and linear regression models were calculated. RESULTS: In both cohorts, strong positive associations between...

  15. Circulating Angiopoietin-2 and Its Soluble Receptor Tie-2 Concentrations Are Related to Renal Function in Two Population-Based Cohorts.

    Science.gov (United States)

    Hennings, Anna; Hannemann, Anke; Rettig, Rainer; Dörr, Marcus; Nauck, Matthias; Völzke, Henry; Lerch, Markus M; Lieb, Wolfgang; Friedrich, Nele

    2016-01-01

    An intact angiopoietin/Tie-2 ligand receptor system is indispensable for life. High circulating angiopoietin-2 (Ang-2) concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate the associations between renal function and serum Ang-2 or serum Tie-2 concentrations in the general population. Data of 3081 and 4088 subjects from two population-based studies, the Study of Health in Pomerania (SHIP-1) and SHIP-Trend, were used. Renal function was assessed by serum creatinine, cystatin C concentration, creatinine-based estimated glomerular filtration rate [eGFR(crea)], cystatin C-based eGFR [eGFR(cys)] and urinary albumin-to-creatinine ratio (uACR). Analyses of variance and linear regression models were calculated. In both cohorts, strong positive associations between serum cystatin C concentrations and serum Ang-2 or Tie-2 concentrations as well as inverse associations between eGFR(cys) and serum Ang-2 or Tie-2 concentrations were found. These relations were also present in a subpopulation without hypertension or diabetes mellitus type 2. Furthermore, we detected weak U-shaped associations between serum creatinine concentrations or eGFR(crea) and serum Ang-2 concentrations. With respect to uACR a strong positive association with serum Ang-2 concentrations was revealed. Serum Ang-2 concentrations are strongly associated with sensitive parameters of renal impairment like serum cystatin C, uACR and eGFR(cys). These findings persisted even after exclusion of subjects with hypertension or diabetes mellitus type 2, conditions that predispose to chronic renal disease and are associated with increased Ang-2 concentrations. Interestingly, we did not detect the same strong relations between serum creatinine and eGFR(crea) with serum Ang-2 concentration. Additionally, significant association of serum Tie-2 concentrations with cystatin C and eGFR(cys) were detected.

  16. Circulating Angiopoietin-2 and Its Soluble Receptor Tie-2 Concentrations Are Related to Renal Function in Two Population-Based Cohorts.

    Directory of Open Access Journals (Sweden)

    Anna Hennings

    Full Text Available An intact angiopoietin/Tie-2 ligand receptor system is indispensable for life. High circulating angiopoietin-2 (Ang-2 concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate the associations between renal function and serum Ang-2 or serum Tie-2 concentrations in the general population.Data of 3081 and 4088 subjects from two population-based studies, the Study of Health in Pomerania (SHIP-1 and SHIP-Trend, were used. Renal function was assessed by serum creatinine, cystatin C concentration, creatinine-based estimated glomerular filtration rate [eGFR(crea], cystatin C-based eGFR [eGFR(cys] and urinary albumin-to-creatinine ratio (uACR. Analyses of variance and linear regression models were calculated.In both cohorts, strong positive associations between serum cystatin C concentrations and serum Ang-2 or Tie-2 concentrations as well as inverse associations between eGFR(cys and serum Ang-2 or Tie-2 concentrations were found. These relations were also present in a subpopulation without hypertension or diabetes mellitus type 2. Furthermore, we detected weak U-shaped associations between serum creatinine concentrations or eGFR(crea and serum Ang-2 concentrations. With respect to uACR a strong positive association with serum Ang-2 concentrations was revealed.Serum Ang-2 concentrations are strongly associated with sensitive parameters of renal impairment like serum cystatin C, uACR and eGFR(cys. These findings persisted even after exclusion of subjects with hypertension or diabetes mellitus type 2, conditions that predispose to chronic renal disease and are associated with increased Ang-2 concentrations. Interestingly, we did not detect the same strong relations between serum creatinine and eGFR(crea with serum Ang-2 concentration. Additionally, significant association of serum Tie-2 concentrations with cystatin C and eGFR(cys were detected.

  17. Occurrence of bioactive sphingolipids in meat and fish products

    DEFF Research Database (Denmark)

    Hellgren, Lars

    2001-01-01

    /neutral glycolipids varied from 1 to 2.9, while in poultry this ratio varied between 5.2 to 19.2 and in red meat it varied from 1.6 to 8.3. The fatty acid composition of sphingomyelin in fish was dominated by C24:1 (Delta (9)) or C22:1 (Delta (9)), while C16:0 and C18:0 were the dominating sphingomyelin species....... Therefore we investigated the contents of sphingomyelin and neutral glycosphingolipids in commonly consumed meat and fish products. Sphingomyelin and glycosphingolipids were found in all foodstuffs studied. The total amount varied between 118 +/- 17 nmol/g (cod) to 589 +/- 39 nmol/g (chicken leg). Generally......, lower amounts of sphingolipids were determined in fish meat than in red meat and poultry, while poultry was the richest source of this class of lipids. However, fish meat contained a relatively high content of neutral glycolipids compared with other types of meat. Thus, in fish the ratio sphingomyelin...

  18. Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-α treatment

    Science.gov (United States)

    Checa, Antonio; Xu, Ning; Sar, Daniel G.; Haeggström, Jesper Z.; Ståhle, Mona; Wheelock, Craig E.

    2015-07-01

    Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis.

  19. Temporal changes in sphingolipids and systemic insulin sensitivity during the transition from gestation to lactation.

    Directory of Open Access Journals (Sweden)

    J Eduardo Rico

    Full Text Available Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition. Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in

  20. Temporal changes in sphingolipids and systemic insulin sensitivity during the transition from gestation to lactation

    Science.gov (United States)

    Rico, J. Eduardo; Saed Samii, Sina; Mathews, Alice T.; Lovett, Jacqueline; Haughey, Norman J.; McFadden, Joseph W.

    2017-01-01

    Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition). Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in peripartal sphingolipids

  1. Low concentration of circulating antimüllerian hormone is not predictive of reduced fecundability in young healthy women

    DEFF Research Database (Denmark)

    Hagen, Casper; Vestergaard, Sonja; Juul, Anders

    2012-01-01

    OBJECTIVE: To evaluate whether circulating levels of antimüllerian hormone (AMH) predict fecundability in young healthy women. DESIGN: Prospective cohort study. SETTING: General community. PATIENT(S): A total of 186 couples who intended to discontinue contraception to become pregnant were followed...... compared with women with low or medium AMH levels, and they had higher levels of LH (geometric mean: 8.4 vs. 5.3 IU/L) and LH:FSH ratio (2.4 vs. 1.8). After exclusion of women with irregular cycles, women with high AMH still had reduced fecundability (FR 0.48; 95% CI 0.27-0.85) and elevated LH:FSH ratio (2...

  2. Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis.

    Directory of Open Access Journals (Sweden)

    Yuichi Hirata

    Full Text Available Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2 encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.

  3. Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis.

    Science.gov (United States)

    Hirata, Yuichi; Ikeda, Kazutaka; Sudoh, Masayuki; Tokunaga, Yuko; Suzuki, Akemi; Weng, Leiyun; Ohta, Masatoshi; Tobita, Yoshimi; Okano, Ken; Ozeki, Kazuhisa; Kawasaki, Kenichi; Tsukuda, Takuo; Katsume, Asao; Aoki, Yuko; Umehara, Takuya; Sekiguchi, Satoshi; Toyoda, Tetsuya; Shimotohno, Kunitada; Soga, Tomoyoshi; Nishijima, Masahiro; Taguchi, Ryo; Kohara, Michinori

    2012-01-01

    Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2) encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM) fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT) inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.

  4. Establishment of HeLa cell mutants deficient in sphingolipid-related genes using TALENs.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Yamaji

    Full Text Available Sphingolipids are essential components in eukaryotes and have various cellular functions. Recent developments in genome-editing technologies have facilitated gene disruption in various organisms and cell lines. We here show the disruption of various sphingolipid metabolic genes in human cervical carcinoma HeLa cells by using transcription activator-like effector nucleases (TALENs. A TALEN pair targeting the human CERT gene (alternative name COL4A3BP encoding a ceramide transport protein induced a loss-of-function phenotype in more than 60% of HeLa cells even though the cell line has a pseudo-triploid karyotype. We have isolated several loss-of-function mutant clones for CERT, UGCG (encoding glucosylceramide synthase, and B4GalT5 (encoding the major lactosylceramide synthase, and also a CERT/UGCG double-deficient clone. Characterization of these clones supported previous proposals that CERT primarily contributes to the synthesis of SM but not GlcCer, and that B4GalT5 is the major LacCer synthase. These newly established sphingolipid-deficient HeLa cell mutants together with our previously established stable transfectants provide a 'sphingolipid-modified HeLa cell panel,' which will be useful to elucidate the functions of various sphingolipid species against essentially the same genomic background.

  5. Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations in chicken embryos

    Energy Technology Data Exchange (ETDEWEB)

    Egloff, Caroline [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Crump, Doug, E-mail: doug.crump@ec.gc.ca [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Porter, Emily; Williams, Kim L.; Letcher, Robert J.; Gauthier, Lewis T. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Kennedy, Sean W. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5 (Canada)

    2014-09-15

    The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highest doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • TBOEP is not embryolethal to chicken embryos. • TEP affected embryonic viability, morphometric endpoints, and thyroid hormone levels. • TEP altered mRNA levels of xenobiotic and lipid metabolism genes. • TEP increased plasma bile acids and caused gallbladder hypotrophy

  6. Nitric oxide-sphingolipid interplays in plant signalling: a new enigma from the Sphinx?

    Directory of Open Access Journals (Sweden)

    Isabelle eGuillas

    2013-09-01

    Full Text Available Nitric oxide (NO emerged as one of the major signalling molecules operating during plant development and plant responses to its environment. Beyond the identification of the direct molecular targets of NO, a series of studies considered its interplay with other actors of signal transduction and the integration of nitric oxide into complex signalling networks. Beside the close relationships between NO and calcium or phosphatidic acid signalling pathways that are now well-established, recent reports paved the way for interplays between NO and sphingolipids. This mini-review summarises our current knowledge of the influence NO and sphingolipids might exert on each other in plant physiology. Based on comparisons with examples from the animal field, it further indicates that, although sphingolipid-NO interplays are common features in signalling networks of eukaryotic cells, the underlying mechanisms and molecular targets significantly differ.

  7. Evaluation of sphingolipids in Wistar rats treated to prolonged and single oral doses of fumonisin b₁.

    Science.gov (United States)

    Direito, Glória M; Almeida, Adriana P; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

    2009-01-01

    The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B(1) (FB(1)). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB(1). Prolonged exposure to FB(1) caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB(1). Animals receiving a single dose of FB(1) presented variations in Sa and So levels and in the Sa/So ratio.

  8. Newly identified essential amino acid residues affecting ^8-sphingolipid desaturase activity revealed by site-directed mutagenesis

    Science.gov (United States)

    In order to identify amino acid residues crucial for the enzymatic activity of ^8-sphingolipid desaturases, a sequence comparison was performed among ^8-sphingolipid desaturases and ^6-fatty acid desaturase from various plants. In addition to the known conserved cytb5 (cytochrome b5) HPGG motif and...

  9. Sphingolipids in Congenital Diaphragmatic Hernia; Results from an International Multicenter Study.

    Directory of Open Access Journals (Sweden)

    Kitty G Snoek

    Full Text Available Congenital diaphragmatic hernia is a severe congenital anomaly with significant mortality and morbidity, for instance chronic lung disease. Sphingolipids have shown to be involved in lung injury, but their role in the pathophysiology of chronic lung disease has not been explored. We hypothesized that sphingolipid profiles in tracheal aspirates could play a role in predicting the mortality/ development of chronic lung disease in congenital diaphragmatic hernia patients. Furthermore, we hypothesized that sphingolipid profiles differ between ventilation modes; conventional mechanical ventilation versus high-frequency oscillation.Sphingolipid levels in tracheal aspirates were determined at days 1, 3, 7 and 14 in 72 neonates with congenital diaphragmatic hernia, born after > 34 weeks gestation at four high-volume congenital diaphragmatic hernia centers. Data were collected within a multicenter trial of initial ventilation strategy (NTR 1310.36 patients (50.0% died or developed chronic lung disease, 34 patients (47.2% by stratification were initially ventilated by conventional mechanical ventilation and 38 patients (52.8% by high-frequency oscillation. Multivariable logistic regression analysis with correction for side of the defect, liver position and observed-to-expected lung-to-head ratio, showed that none of the changes in sphingolipid levels were significantly associated with mortality /development of chronic lung disease. At day 14, long-chain ceramides 18:1 and 24:0 were significantly elevated in patients initially ventilated by conventional mechanical ventilation compared to high-frequency oscillation.We could not detect significant differences in temporal sphingolipid levels in congenital diaphragmatic hernia infants with mortality/development of chronic lung disease versus survivors without development of CLD. Elevated levels of ceramides 18:1 and 24:0 in the conventional mechanical ventilation group when compared to high

  10. Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision?

    Science.gov (United States)

    Lavieu, Gregory; Scarlatti, Francesca; Sala, Giusy; Levade, Thierry; Ghidoni, Riccardo; Botti, Joëlle; Codogno, Patrice

    2007-01-01

    Sphingolipids are major constituents of biological membrane and some of them behave as second messengers involved in the cell fate decision. Ceramide and sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide promotes cell death and S1P increases cell survival. We have shown that both sphingolipids are able to trigger autophagy with opposing outcomes on cell survival. Here we discuss and speculate on the diverging functions of the autophagic pathways induced by ceramide and S1P, respectively.

  11. HPLC for simultaneous quantification of total ceramide, glucosylceramide, and ceramide trihexoside concentrations in plasma

    NARCIS (Netherlands)

    Groener, Johanna E. M.; Poorthuis, Ben J. H. M.; Kuiper, Sijmen; Helmond, Mariette T. J.; Hollak, Carla E. M.; Aerts, Johannes M. F. G.

    2007-01-01

    BACKGROUND: Simple, reproducible assays are needed for the quantification of sphingolipids, ceramide (Cer), and sphingoid bases. We developed an HPLC method for simultaneous quantification of total plasma concentrations of Cer, glucosylceramide (GlcCer), and ceramide trihexoside (CTH). METHODS:

  12. Circulating TNF-alpha and IL-6 concentrations and TNF-alpha -308 G>A polymorphism in children with premature adrenarche

    Directory of Open Access Journals (Sweden)

    Pauliina eUtriainen

    2010-11-01

    Full Text Available Premature adrenarche (PA, the early rise in adrenal androgen production leading to prepubertal signs of androgen action, has been connected with adverse metabolic features. The metabolic syndrome is characterized by low grade inflammation which in turn is associated with increases in circulating proinflammatory cytokines, like tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6. We tested the hypothesis that serum concentrations of TNF-α and IL-6 are increased in PA by studing 73 children with PA and 98 age- and gender-matched controls. Serum TNF-α and IL-6 concentrations were measured using a multiplex bead array. The subjects were genotyped for the TNF-α gene -308 G>A polymorphism (known to affect TNF-α gene transcription, and genotype-phenotype associations were studied. The mean serum TNF-α concentration was higher in the PA than control children (20.4 vs. 18.4 pg/ml, P=0.048, whereas there was no significant difference in the mean serum IL-6 concentrations between the study groups. The difference in TNF-α was not explained by excess body weight in the PA subjects as the difference remained significant after BMI-adjustment (P=0.038. In the PA group, TNF-α concentration was not associated with metabolic-endocrine features, but high IL-6 was associated with lower birth weight. There was no difference in the genotype distribution of the TNF-α gene -308 G>A polymorphism between the PA and control groups. In conclusion, PA was associated with increased serum TNF-α concentrations which, unexpectedly, were not connected with BMI or insulin resistance. The TNF-α gene -308 G>A polymorphism does not seem to be associated with the development of PA.

  13. Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes

    DEFF Research Database (Denmark)

    Pfleger, C.; Kaas, A.; Hansen, L.

    2008-01-01

    Th1 related chemokines CCL3 and CCL5 and Th2 related CCL4 as ligands of the receptor CCR5 contribute to disease development in animal models of type 1 diabetes. In humans, no data are available addressing the role of these chemokines regarding disease progression and remission. We investigated...... longitudinally circulating concentrations of CCR5 ligands of 256 newly diagnosed patients with type 1 diabetes. CCR5 ligands were differentially associated with beta-cell function and clinical remission. CCL5 was decreased in remitters and positively associated with HbA1c suggestive of a Th1 associated...... of CCR5 by therapeutic agents such as maraviroc may provide a new therapeutic target to ameliorate disease progression in type 1 diabetes. (C) 2008 Elsevier Inc. All rights reserved Udgivelsesdato: 2008/7...

  14. Concentration of circulating miRNA-containing particles in serum enhances miRNA detection and reflects CRC tissue-related deregulations.

    Science.gov (United States)

    ElSharawy, Abdou; Röder, Christian; Becker, Thomas; Habermann, Jens K; Schreiber, Stefan; Rosenstiel, Philip; Kalthoff, Holger

    2016-11-15

    The emerging potential of miRNAs as biomarkers for cancer detection demands parallel evaluation of strategies for reliable identification of disease-related signatures from easily accessible and pertinent body compartments. Here, we addressed whether efficient concentration of circulating miRNA-carrying particles is a rationale for miRNA biomarker discovery. We systematically compared miRNA signatures in 93 RNA preparations from three serum entities (whole serum, particle-concentrated, and particle-depleted fractions) and corresponding tissue samples from patients with colorectal cancer (CRC) as a model disease. Significant differences between whole sera and particle-concentrated serum fractions of CRC patients emerged for 45 of 742 tested miRNAs. Twenty-eight of these 45 miRNAs were differentially expressed between particle-concentrated serum fractions of metastatic CRC- and healthy individuals. Over half of these candidates (15 of 28) showed deregulations only in concentrated serum fractions, but not in whole sera, compared to the respective controls.Our results also provided evidence of a consistent downregulation of miR-486 and miR-92a, and further showed a possible "strand-specific" deregulation of extracellular miRNAs in CRC. More importantly, most of the identified miRNAs in the enriched sera reflected the patterns of the corresponding tumor tissues and showed links to cancer-related inflammation. Further investigation of seven serum pools revealed a subset of potential extracellular miRNA candidates to be implicated in both neoplastic and inflammatory bowel disease.Our findings demonstrate that enrichment and sensitive detection of miRNA carriers is a promising approach to detect CRC-related pathological changes in liquid biopsies, and has potential for clinical diagnostics.

  15. The response of circulating omentin-1 concentration to 16-week exercise training in male children with obesity.

    Science.gov (United States)

    Zehsaz, Farzad; Farhangi, Negin; Ghahramani, Mehri

    2016-11-01

    The purpose of the present study was to investigate the effects of the 16-week exercise training program on serum omentin-1 in relation to change in insulin resistance in obese male children. Thirty-two obese male children, aged 9-12 years, were randomly assigned into Exercise Group (ExG; n = 16) and Control Group (CG; n = 16). ExG participated in a 16-week exercise training program which combined various forms of aerobic activities and resistance training. Body composition, body mass index (BMI), waist circumference (WC), fasting glucose and insulin, homeostasis model assessment estimate of insulin resistance (HOMA2-IR), blood lipids and serum omentin-1 were assessed before and after 16 weeks of training. Exercise training significantly decreased body mass (7.5%), BMI (7.6%), WC (4.3%), body fat % (15%), fasting insulin (18.5%), total cholesterol (TC) (5.4%), low-density lipoprotein cholesterol (LDL-C) (17%) and triglyceride (TG) (7.4%) compared to CG. Between-groups comparison showed a considerable exercise-induced upregulation in omentin-1 (ES = 89; P Exercise training resulted in a significant increase in serum omentin-1 concentrations in children with obesity. The findings suggest that exercise-induced changes in omentin-1 may be associated with the beneficial effects of exercise on reduced insulin and weight lost.

  16. Transport and sorting of sphingolipids in polarized cells : the involvement of the sub-apical compartment

    NARCIS (Netherlands)

    IJzendoorn, Sven Christian David van

    1999-01-01

    The work described in this thesis has provided a novel insight into the process of sphingolipid transport and sorting in polarized cells. We have used HepG2 cells as a model system to study polarized traffic in hepatic cells. Under specific culture conditions, HepG2 cells acquire a polarized

  17. Sphingolipid topology and the dynamic organization and function of membrane proteins

    NARCIS (Netherlands)

    van Meer, G.|info:eu-repo/dai/nl/068570368; Hoetzl, S.

    2010-01-01

    When acquiring internal membranes and vesicular transport, eukaryotic cells started to synthesize sphingolipids and sterols. The physical differences between these and the glycerophospholipids must have enabled the cells to segregate lipids in the membrane plane. Localizing this event to the Golgi

  18. Low serum sphingolipids in children with attention deficit-hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Marcela Patricia Henríquez-Henríquez

    2015-08-01

    Full Text Available Background: Attention deficit-hyperactivity disorder (ADHD is the most prevalent neuropsychiatric condition in childhood. ADHD is a multifactorial trait with a strong genetic component. One neurodevelopmental hypothesis is that ADHD is associated with a lag in brain maturation. Sphingolipids are essential for brain development and neuronal functioning, but their role in ADHD pathogenesis is unexplored. We hypothesized that serum sphingolipid levels distinguish ADHD patients from unaffected subjects. Methods: We characterized serum sphingolipid profiles of ADHD patients and two control groups: non-affected relatives and non-affected subjects without a family history of ADHD. Sphingolipids were measured by LC-MS/MS in 77 participants (28 ADHD patients, 28 related controls and 21 unrelated controls. ADHD diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR. Diagnostic criteria were assessed by 2 independent observers. Groups were compared by parametrical statistics. Results: Serum sphingomyelins C16:0, C18:0, C18:1, C24:1, ceramide C24:0 and deoxy-ceramide C24:1 were significantly decreased in ADHD patients at 20-30% relative reductions. In our sample, decreased serum sphingomyelin levels distinguished ADHD patients with 79% sensitivity and 78% specificity. Conclusions: Our results showed lower levels of all major serum sphingomyelins in ADHD. These findings may reflect brain maturation and affect neuro-functional pathways characteristic for ADHD.

  19. High circulating folate and vitamin B-12 concentrations in women during pregnancy are associated with increased prevalence of atopic dermatitis in their offspring.

    Science.gov (United States)

    Kiefte-de Jong, Jessica C; Timmermans, Sarah; Jaddoe, Vincent W V; Hofman, Albert; Tiemeier, Henning; Steegers, Eric A; de Jongste, Johan C; Moll, Henriette A

    2012-04-01

    Recent studies suggest that in utero exposure of methyl donors influences programming of the fetal immune system in favor of development of allergic disease. The aim of this study was to assess whether the MTHFR C677T polymorphism, folic acid supplementation, and circulating folate and vitamin B-12 concentrations during pregnancy were associated with wheezing, shortness of breath, and atopic dermatitis in offspring. The study was a population-based birth cohort from fetal life until 48 mo (n = 8742). The use of folic acid supplementation during pregnancy was assessed by questionnaire. Plasma folate and serum vitamin B-12 concentrations and the MTHFR C677T polymorphism were available from blood collected in early pregnancy. Atopic dermatitis, wheezing, and shortness of breath in the offspring were assessed by parental-derived questionnaires at 12, 24, 36, and 48 mo. Maternal folate >16.2 nmol/L and vitamin B-12 >178 pmol/L were positively associated with the development of atopic dermatitis [adjusted OR: 1.18 (95% CI: 1.05-1.33) and adjusted OR: 1.30 (95% CI: 1.06-1.60) for the highest quartiles of folate and vitamin B-12 concentrations, respectively] but not with wheezing and shortness of breath. Maternal MTHFR C677T polymorphism and folic acid supplementation were not associated with wheezing, shortness of breath, and atopic dermatitis. No interactions were found by age, family history of atopy, folic acid supplementation, MTHFR C677T polymorphism, or maternal smoking (P-interaction > 0.10). High folate and vitamin B-12 levels during pregnancy are associated with increased prevalence of atopic dermatitis in the offspring. Potential risks of high folate and vitamin B-12 concentrations on allergic outcomes should be evaluated when discussing mandatory fortification programs.

  20. Effect of dipeptidyl peptidase-4 inhibitors on circulating tumor necrosis factor-α concentrations: A systematic review and meta-analysis of controlled trials.

    Science.gov (United States)

    Atkin, Stephen L; Katsiki, Niki; Banach, Maciej; Mikhailidis, Dimitri P; Pirro, Matteo; Sahebkar, Amirhossein

    2017-09-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes mellitus. There are also reports of an effect of these drugs in reducing inflammation through inhibition of tumor necrosis factor-α (TNF-α) that is an important mediator for several inflammatory processes. The present systematic review and meta-analysis were performed to evaluate the effect of DPP-4 inhibitors on circulating TNF-α levels in T2DM patients. A systematic review and a meta-analysis were undertaken on all controlled trials of DPP-4 inhibitors that included measurement of TNF-α. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis was performed using a random-effects model, with standardized mean difference (SMD) and 95% confidence interval (CI) as summary statistics. Meta-regression and leave-one-out sensitivity analysis were performed to assess the modifiers of treatment response. Eight eligible articles (6 with sitagliptin and 2 with vildagliptin) comprising 9 treatment arms were selected for this meta-analysis. Meta-analysis suggested a significant reduction of circulating TNF-α concentrations following treatment with DPP-4 inhibitors (SMD: -1.84, 95% CI: -2.88, -0.80, p=0.001). The effect size was robust in the sensitivity analysis and not mainly driven by a single study. A subgroup analysis did not suggest any significant difference between the TNF-α-lowering activity of sitagliptin (SMD: -1.49, 95% CI: -2.89, -0.10) and vildagliptin (SMD: -2.80, 95% CI: -4.98, -0.61) (p=0.326). This meta-analysis of the 8 available controlled trials showed that DPP-4 inhibition in patients with type 2 diabetes mellitus was associated with significant reductions in plasma TNF-α levels with no apparent difference between sitagliptin and vildagliptin. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Relationships among body composition, circulating concentrations of leptin and follistatin, and the onset of puberty and fertility in young female sheep.

    Science.gov (United States)

    Rosales Nieto, C A; Thompson, A N; Macleay, C A; Briegel, J R; Hedger, M P; Ferguson, M B; Martin, G B

    2014-12-30

    The onset of puberty depends on the attainment of critical body mass, so should also be affected by increases in the rate of accumulation of muscle and adipose tissue. Adipose tissue and reproduction are linked by leptin. For muscle, a link has not yet been identified, although one possibility is follistatin. We assessed the relationships among circulating concentrations of follistatin and leptin and the rates of growth and accumulation of muscle and fat during pubertal development in female sheep. We used 326 animals with known phenotypic values for live weight (LW), depths of eye muscle (EMD) and fat (FAT), and known breeding values at post-weaning age for body mass (PWT) and depths of eye muscle (PEMD) and fat (PFAT). Leptin concentration was positively correlated with values for EMD, PEMD, FAT, PFAT, LW and PWT (Preproductive rate (Preproductive rate (Preproductive performance. We conclude that leptin and follistatin are probably both involved in effects of accelerated accumulation of muscle and adipose tissues on the onset of puberty. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Circulating 25-hydroxyvitamin D concentrations are correlated with cardiometabolic risk among American black and white adolescents living in a year-round sunny climate.

    Science.gov (United States)

    Parikh, Samip; Guo, De-Huang; Pollock, Norman K; Petty, Karen; Bhagatwala, Jigar; Gutin, Bernard; Houk, Chris; Zhu, Haidong; Dong, Yanbin

    2012-05-01

    Low vitamin D status is common among healthy black and white adolescents residing at southern U.S. latitudes with a year-round sunny climate. Thus we aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D] and cardiometabolic risk factors in this population. 25(OH)D concentrations were measured with liquid chromatography tandem mass spectroscopy in 701 girls and boys (14-18 years old, 54% blacks, 49% females). Cardiometabolic risk was indexed by adipokines, inflammatory markers, fasting glucose, homeostatic model assessment-insulin resistance (HOMA-IR), lipid profile, and blood pressure (BP). Controlling for age, sex, race, sexual maturation, season, physical activity, and percent body fat, 25(OH)D concentrations were significantly correlated with adiponectin (r = 0.06, P = 0.05), leptin (r = -0.32, P risk factors, independent of adiposity. Clinical trials addressing the effects of vitamin D supplementation on cardiometabolic risk are warranted in adolescents irrespective of their geographical regions.

  3. Relationship of oestrus synchronization method, circulating hormones, luteinizing hormone and prostaglandin F-2 alpha receptors and luteal progesterone concentration to premature luteal regression in superovulated sheep.

    Science.gov (United States)

    Schiewe, M C; Fitz, T A; Brown, J L; Stuart, L D; Wildt, D E

    1991-09-01

    Ewes were treated with exogenous follicle-stimulating hormone (FSH) and oestrus was synchronized using either a dual prostaglandin F-2 alpha (PGF-2 alpha) injection regimen or pessaries impregnated with medroxy progesterone acetate (MAP). Natural cycling ewes served as controls. After oestrus or AI (Day 0), corpora lutea (CL) were enucleated surgically from the left and right ovaries on Days 3 and 6, respectively. The incidence of premature luteolysis was related (P less than 0.05) to PGF-2 alpha treatment and occurred in 7 of 8 ewes compared with 0 of 4 controls and 1 of 8 MAP-exposed females. Sheep with regressing CL had lower circulating and intraluteal progesterone concentrations and fewer total and small dissociated luteal cells on Day 3 than gonadotrophin-treated counterparts with normal CL. Progesterone concentration in the serum and luteal tissue was higher (P less than 0.05) in gonadotrophin-treated ewes with normal CL than in the controls; but luteinizing hormone (LH) receptors/cell were not different on Days 3 and 6. There were no apparent differences in the temporal patterns of circulating oestradiol-17 beta, FSH and LH. High progesterone in gonadotrophin-treated ewes with normal CL coincided with an increase in total luteal mass and numbers of cells, which were primarily reflected in more small luteal cells than in control ewes. Gonadotrophin-treated ewes with regressing CL on Day 3 tended (P less than 0.10) to have fewer small luteal cells and fewer (P less than 0.05) low-affinity PGF-2 alpha binding sites than sheep with normal CL. By Day 6, luteal integrity and cell viability was absent in ewes with prematurely regressed CL. These data demonstrate that (i) the incidence of premature luteal regression is highly correlated with the use of PGF-2 alpha; (ii) this abnormal luteal tissue is functionally competent for 2-3 days after ovulation, but deteriorates rapidly thereafter and (iii) luteal-dysfunctioning ewes experience a reduction in numbers of

  4. Comparison of 2 protocols to increase circulating progesterone concentration before timed artificial insemination in lactating dairy cows with or without elevated body temperature.

    Science.gov (United States)

    Pereira, M H C; Wiltbank, M C; Guida, T G; Lopes, F R; Vasconcelos, J L M

    2017-10-01

    Two treatments designed to increase circulating progesterone concentration (P4) during preovulatory follicle development were compared. One treatment used 2 intravaginal P4 implants (controlled internal drug-releasing inserts; CIDR) and the other used a GnRH treatment at beginning of the protocol. Lactating Holstein cows that had been diagnosed as nonpregnant were randomly assigned to receive timed artificial insemination (TAI) following 1 of 2 treatments (n = 1,638 breedings): (1) GnRH: CIDR+ 2 mg of estradiol (E2) benzoate + 100 µg of GnRH on d -11, PGF 2α on d -4, CIDR withdrawal + 1.0 mg of E2-cypionate + PGF 2α ) on d -2, and TAI on d 0; or (2) 2CIDR: 2 CIDR + 2 mg of E2-benzoate on d -11, 1 CIDR withdrawn + PGF 2α on d -4, second CIDR withdrawn + 1.0 mg of E2-cypionate + PGF 2α on d -2, and TAI on d 0. Milk yield was measured daily between d 0 and d 7. Rectal temperature was measured using a digital thermometer at d 0 and 7, and elevated body temperature was defined as an average rectal temperature ≥39.1°C. Pregnancy diagnoses were performed on d 32 and 60 after TAI. We detected no effect of treatments on pregnancy per AI or pregnancy loss regardless of elevated body temperature, body condition score, parity, milk yield, or presence or absence of a corpus luteum (CL) on d -11 or d -4. Pregnancy per AI at 60 d was reduced [elevated body temperature = 22.8% (162/709), no elevated body temperature 34.1% (279/817)] and pregnancy loss tended to increase [elevated body temperature = 20.2% (41/203), no elevated body temperature 14.4% (47/326)] in cows with elevated body temperature. Various physiological measurements associated with greater fertility were also reduced in cows with elevated body temperature, such as percentage of cows with a CL at PGF 2α (decreased 7.9%), ovulatory follicle diameter (decreased 0.51 mm), expression of estrus (decreased 5.1%), and ovulation near TAI (decreased 2.8%) compared with cows without elevated body temperature. A

  5. Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets.

    Science.gov (United States)

    Sun, Na; Keep, Richard F; Hua, Ya; Xi, Guohua

    2016-10-01

    Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

  6. The role of ORMDL proteins, guardians of cellular sphingolipids, in asthma

    Czech Academy of Sciences Publication Activity Database

    Paulenda, Tomáš; Dráber, Petr

    2016-01-01

    Roč. 71, č. 7 (2016), s. 918-930 ISSN 0105-4538 R&D Projects: GA ČR(CZ) GA14-00703S; GA ČR(CZ) GA14-09807S; GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : asthma * cellular membranes * endoplasmic * reticulum * ORMDL3 * sphingolipids Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.361, year: 2016

  7. Glycosylation of inositol phosphorylceramide sphingolipids is required for normal growth and reproduction in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Tartaglio, Virginia [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Rennie, Emilie A. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Cahoon, Rebecca [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Wang, George [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Baidoo, Edward [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Mortimer, Jennifer C. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Cahoon, Edgar B. [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Scheller, Henrik V. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology

    2016-09-19

    Sphingolipids are a major component of plant plasma membranes and endomembranes, and mediate a diverse range of biological processes. Study of the highly glycosylated glycosyl inositol phosphorylceramide (GIPC) sphingolipids has been slow as a result of challenges associated with the extractability of GIPCs, and their functions in the plant remain poorly characterized. We recently discovered an Arabidopsis GIPC glucuronosyltransferase, INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE 1 (IPUT1), which is the first enzyme in the GIPC glycosylation pathway. Plants homozygous for the iput1 loss-of-function mutation were unobtainable, and so the developmental effects of reduced GIPC glucuronosylation could not be analyzed in planta. Using a pollen-specific rescue construct, we have here isolated homozygous iput1 mutants. The iput1 mutants show severe dwarfism, compromised pollen tube guidance, and constitutive activation of salicyclic acid-mediated defense pathways. The mutants also possess reduced GIPCs, increased ceramides, and an increased incorporation of short-chain fatty acids and dihydroxylated bases into inositol phosphorylceramides and GIPCs. The assignment of a direct role for GIPC glycan head groups in the impaired processes in iput1 mutants is complicated by the vast compensatory changes in the sphingolipidome; however, our results reveal that the glycosylation steps of GIPC biosynthesis are important regulated components of sphingolipid metabolism. In conclusion, this study corroborates previously suggested roles for GIPC glycans in plant growth and defense, suggests important role s for them in reproduction and demonstrates that the entire sphingolipidome is sensitive to their status.

  8. Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B1

    International Nuclear Information System (INIS)

    Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S.; Swanevelder, Sonja

    2004-01-01

    In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B 1 (FB 1 ) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB 1 containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB 1 dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB 1 treatment in the control rats was significantly (P 1 initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB 1 treatment, the initiation effected by FB 1 was less (P 1 initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P 1 treatment. Although, the FB 1 -induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

  9. A conserved signaling network monitors delivery of sphingolipids to the plasma membrane in budding yeast.

    Science.gov (United States)

    Clarke, Jesse; Dephoure, Noah; Horecka, Ira; Gygi, Steven; Kellogg, Douglas

    2017-10-01

    In budding yeast, cell cycle progression and ribosome biogenesis are dependent on plasma membrane growth, which ensures that events of cell growth are coordinated with each other and with the cell cycle. However, the signals that link the cell cycle and ribosome biogenesis to membrane growth are poorly understood. Here we used proteome-wide mass spectrometry to systematically discover signals associated with membrane growth. The results suggest that membrane trafficking events required for membrane growth generate sphingolipid-dependent signals. A conserved signaling network appears to play an essential role in signaling by responding to delivery of sphingolipids to the plasma membrane. In addition, sphingolipid-dependent signals control phosphorylation of protein kinase C (Pkc1), which plays an essential role in the pathways that link the cell cycle and ribosome biogenesis to membrane growth. Together these discoveries provide new clues as to how growth--dependent signals control cell growth and the cell cycle. © 2017 Clarke et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  10. Cholesterol, sphingolipids, and glycolipids: What do we know about their role in raft-like membranes?

    DEFF Research Database (Denmark)

    Rog, T.; Vattulainen, I.

    2014-01-01

    Lipids rafts are considered to be functional nanoscale membrane domains enriched in cholesterol and sphingolipids, characteristic in particular of the external leaflet of cell membranes. Lipids, together with membrane-associated proteins, are therefore considered to form nanoscale units with pote......Lipids rafts are considered to be functional nanoscale membrane domains enriched in cholesterol and sphingolipids, characteristic in particular of the external leaflet of cell membranes. Lipids, together with membrane-associated proteins, are therefore considered to form nanoscale units...... with potential specific functions. Although the understanding of the structure of rafts in living cells is quite limited, the possible functions of rafts are widely discussed in the literature, highlighting their importance in cellular functions. In this review, we discuss the understanding of rafts that has...... emerged based on recent atomistic and coarse-grained molecular dynamics simulation studies on the key lipid raft components, which include cholesterol, sphingolipids, glycolipids, and the proteins interacting with these classes of lipids. The simulation results are compared to experiments when possible...

  11. TOR Complex 2-Ypk1 Signaling Maintains Sphingolipid Homeostasis by Sensing and Regulating ROS Accumulation

    Directory of Open Access Journals (Sweden)

    Brad J. Niles

    2014-02-01

    Full Text Available Reactive oxygen species (ROS are produced during normal metabolism and can function as signaling molecules. However, ROS at elevated levels can damage cells. Here, we identify the conserved target of rapamycin complex 2 (TORC2/Ypk1 signaling module as an important regulator of ROS in the model eukaryotic organism, S. cerevisiae. We show that TORC2/Ypk1 suppresses ROS produced both by mitochondria as well as by nonmitochondrial sources, including changes in acidification of the vacuole. Furthermore, we link vacuole-related ROS to sphingolipids, essential components of cellular membranes, whose synthesis is also controlled by TORC2/Ypk1 signaling. In total, our data reveal that TORC2/Ypk1 act within a homeostatic feedback loop to maintain sphingolipid levels and that ROS are a critical regulatory signal within this system. Thus, ROS sensing and signaling by TORC2/Ypk1 play a central physiological role in sphingolipid biosynthesis and in the maintenance of cell growth and viability.

  12. Fiber specific changes in sphingolipid metabolism in skeletal muscles of hyperthyroid rats.

    Science.gov (United States)

    Chabowski, A; Zendzian-Piotrowska, M; Mikłosz, A; Łukaszuk, B; Kurek, K; Górski, J

    2013-07-01

    Thyroid hormones (T3, T4) are well known modulators of different cellular signals including the sphingomyelin pathway. However, studies regarding downstream effects of T3 on sphingolipid metabolism in skeletal muscle are scarce. In the present work we sought to investigate the effects of hyperthyroidism on the activity of the key enzymes of ceramide metabolism as well as the content of fundamental sphingolipids. Based on fiber/metabolic differences, we chose three different skeletal muscles, with diverse fiber compositions: soleus (slow-twitch oxidative), red (fast-twitch oxidative-glycolytic) and white (fast-twitch glycolytic) section of gastrocnemius. We demonstrated that T3 induced accumulation of sphinganine, ceramide, sphingosine, as well as sphingomyelin, mostly in soleus and in red, but not white section of gastrocnemius. Concomitantly, the activity of serine palmitoyltransferase and acid/neutral ceramidase was increased in more oxidative muscles. In conclusion, hyperthyroidism induced fiber specific changes in the content of sphingolipids that were relatively more related to de novo synthesis of ceramide rather than to its generation via hydrolysis of sphingomyelin.

  13. Animal source food intake and association with blood cholesterol, glycerophospholipids and sphingolipids in a northern Swedish population

    Directory of Open Access Journals (Sweden)

    Wilmar Igl

    2013-08-01

    Full Text Available Background . The high intake of game meat in populations with a subsistence-based diet may affect their blood lipids and health status. Objective . To examine the association between diet and circulating levels of blood lipid levels in a northern Swedish population. Study design . We compared a group with traditional lifestyle (TLS based on reindeer herding (TLS group with those from the same area with a non-traditional lifestyle (NTLS typical of more industrialized regions of Sweden (NTLS group. The analysis was based on self-reported intake of animal source food (i.e. non-game meat, game meat, fish, dairy products and eggs and the serum blood level of a number of lipids [total cholesterol (TC, low-density lipoprotein cholesterol (LDL, high-density lipoprotein cholesterol (HDL, triglycerides (TG, glycerophospholipids and sphingolipids]. Results . The TLS group had higher cholesterol, LDL and HDL levels than the reference group. Of the TLS group, 65% had cholesterol levels above the threshold for increased risk of coronary heart disease (≥240 mg/dl, as compared to 38% of the NTLS group. Self-reported consumption of game meat was positively associated with TC and LDL. Conclusions . The high game meat consumption of the TLS group is associated with increased cholesterol levels. High intake of animal protein and fat and low fibre is known to increase the risk of cardiovascular disease, but other studies of the TLS in northern Sweden have shown comparable incidences of cardiovascular disease to the reference (NTLS group from the same geographical area. This indicates that factors other than TC influence disease risk. One such possible factor is dietary phospholipids, which are also found in high amounts specifically in game meat and have been shown to inhibit cholesterol absorption.

  14. Animal source food intake and association with blood cholesterol, glycerophospholipids and sphingolipids in a northern Swedish population.

    Science.gov (United States)

    Igl, Wilmar; Kamal-Eldin, Afaf; Johansson, Asa; Liebisch, Gerhard; Gnewuch, Carsten; Schmitz, Gerd; Gyllensten, Ulf

    2013-01-01

    The high intake of game meat in populations with a subsistence-based diet may affect their blood lipids and health status. To examine the association between diet and circulating levels of blood lipid levels in a northern Swedish population. We compared a group with traditional lifestyle (TLS) based on reindeer herding (TLS group) with those from the same area with a non-traditional lifestyle (NTLS) typical of more industrialized regions of Sweden (NTLS group). The analysis was based on self-reported intake of animal source food (i.e. non-game meat, game meat, fish, dairy products and eggs) and the serum blood level of a number of lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglycerides (TG), glycerophospholipids and sphingolipids]. The TLS group had higher cholesterol, LDL and HDL levels than the reference group. Of the TLS group, 65% had cholesterol levels above the threshold for increased risk of coronary heart disease (≥ 240 mg/dl), as compared to 38% of the NTLS group. Self-reported consumption of game meat was positively associated with TC and LDL. The high game meat consumption of the TLS group is associated with increased cholesterol levels. High intake of animal protein and fat and low fibre is known to increase the risk of cardiovascular disease, but other studies of the TLS in northern Sweden have shown comparable incidences of cardiovascular disease to the reference (NTLS) group from the same geographical area. This indicates that factors other than TC influence disease risk. One such possible factor is dietary phospholipids, which are also found in high amounts specifically in game meat and have been shown to inhibit cholesterol absorption.

  15. Cranberry juice consumption lowers markers of cardiometabolic risk, including blood pressure and circulating C-reactive protein, triglyceride, and glucose concentrations in adults.

    Science.gov (United States)

    Novotny, Janet A; Baer, David J; Khoo, Christina; Gebauer, Sarah K; Charron, Craig S

    2015-06-01

    Cardiometabolic risk is the risk of cardiovascular disease (CVD), diabetes, or stroke, which are leading causes of mortality and morbidity worldwide. The objective of this study was to determine the potential of low-calorie cranberry juice (LCCJ) to lower cardiometabolic risk. A double-blind, placebo-controlled, parallel-arm study was conducted with controlled diets. Thirty women and 26 men (mean baseline characteristics: 50 y; weight, 79 kg; body mass index, 28 kg/m(2)) completed an 8-wk intervention with LCCJ or a flavor/color/energy-matched placebo beverage. Twice daily volunteers consumed 240 mL of LCCJ or the placebo beverage, containing 173 or 62 mg of phenolic compounds and 6.5 or 7.5 g of total sugar per 240-mL serving, respectively. Fasting serum triglycerides (TGs) were lower after consuming LCCJ and demonstrated a treatment × baseline interaction such that the participants with higher baseline TG concentrations were more likely to experience a larger treatment effect (1.15 ± 0.04 mmol/L vs. 1.25 ± 0.04 mmol/L, respectively; P = 0.027). Serum C-reactive protein (CRP) was lower for individuals consuming LCCJ than for individuals consuming the placebo beverage [ln transformed values of 0.522 ± 0.115 ln(mg/L) vs. 0.997 ± 0.120 ln(mg/L), P = 0.0054, respectively, and equivalent to 1.69 mg/L vs. 2.71 mg/L back-transformed]. LCCJ lowered diastolic blood pressure (BP) compared with the placebo beverage (69.2 ± 0.8 mm Hg for LCCJ vs. 71.6 ± 0.8 mm Hg for placebo; P = 0.048). Fasting plasma glucose was lower (P = 0.03) in the LCCJ group (5.32 ± 0.03 mmol/L) than in the placebo group (5.42 ± 0.03 mmol/L), and LCCJ had a beneficial effect on homeostasis model assessment of insulin resistance for participants with high baseline values (P = 0.035). LCCJ can improve several risk factors of CVD in adults, including circulating TGs, CRP, and glucose, insulin resistance, and diastolic BP. This trial was registered at clinicaltrials.gov as NCT01295684. © 2015

  16. Quantifying the dose-response relationship between circulating folate concentrations and colorectal cancer in cohort studies: a meta-analysis based on a flexible meta-regression model.

    Science.gov (United States)

    Chuang, Shu-Chun; Rota, Matteo; Gunter, Marc J; Zeleniuch-Jacquotte, Anne; Eussen, Simone J P M; Vollset, Stein Emil; Ueland, Per Magne; Norat, Teresa; Ziegler, Regina G; Vineis, Paolo

    2013-10-01

    Most epidemiologic studies on folate intake suggest that folate may be protective against colorectal cancer, but the results on circulating (plasma or serum) folate are mostly inconclusive. We conducted a meta-analysis of case-control studies nested within prospective studies on circulating folate and colorectal cancer risk by using flexible meta-regression models to test the linear and nonlinear dose-response relationships. A total of 8 publications (10 cohorts, representing 3,477 cases and 7,039 controls) were included in the meta-analysis. The linear and nonlinear models corresponded to relative risks of 0.96 (95% confidence interval (CI): 0.91, 1.02) and 0.99 (95% CI: 0.96, 1.02), respectively, per 10 nmol/L of circulating folate in contrast to the reference value. The pooled relative risks when comparing the highest with the lowest category were 0.80 (95% CI: 0.61, 0.99) for radioimmunoassay and 1.03 (95% CI: 0.83, 1.22) for microbiological assay. Overall, our analyses suggest a null association between circulating folate and colorectal cancer risk. The stronger association for the radioimmunoassay-based studies could reflect differences in cohorts and study designs rather than assay performance. Further investigations need to integrate more accurate measurements and flexible modeling to explore the effects of folate in the presence of genetic, lifestyle, dietary, and hormone-related factors.

  17. Theoretical effect of concentration, circulation rate, stages, pressure and temperature of single amine and amine mixture solvents on gas sweetening performance

    Directory of Open Access Journals (Sweden)

    Nilay Kumar Sarker

    2016-09-01

    Full Text Available This simulation experiment performed by Aspen Hysys is about theoretical investigation of gas sweetening performance of single amine solvents MEA1, MDEA2, DEA3, DGA4, DIPA5 and mixed amine solvents DGA–MEA, DEA–MDEA and SULFOLANE6–MDEA. Sweet gas having very high percentage of methane is produced by MEA (95.36%, DGA–MEA (95.37%, DEA–MDEA (95.51% and SULFOLANE–MDEA (95.10% and DGA (93.76% shows lowest performance. DGA, SULFOLANE–MDEA, MDEA remove H2S at a lower circulation rate and DEA, DIPA need higher but satisfactory circulation rate. Increasing stage number shows positive effect on DEA, DIPA and SULFOLANE–MDEA. Pressure change has no significant effect. Temperature increase and methane percentage are negatively correlated for all solvents (except low circulating DIPA. With temperature increase H2S composition increases for DEA–MDEA, DGA–MEA; CO2 increases for DEA–MDEA, DGA–MEA and high circulating SULFOLANE–MDEA.

  18. High circulating folate and vitamin B-12 concentrations in women during pregnancy are associated with increased prevalence of atopic dermatitis in their offspring

    NARCIS (Netherlands)

    J.C. Kiefte-de Jong (Jessica); S. Timmermans (Sarah); V.W.V. Jaddoe (Vincent); A. Hofman (Albert); H.W. Tiemeier (Henning); E.A.P. Steegers (Eric); J.C. de Jongste (Johan); H.A. Moll (Henriëtte)

    2012-01-01

    textabstractRecent studies suggest that in utero exposure of methyl donors influences programming of the fetal immune system in favor of development of allergic disease. The aim of this study was to assess whether the MTHFR C677T polymorphism, folic acid supplementation, and circulating folate and

  19. Sphingolipids: Key Regulators of Apoptosis and Pivotal Players in Cancer Drug Resistance

    Directory of Open Access Journals (Sweden)

    Paola Giussani

    2014-03-01

    Full Text Available Drug resistance elicited by cancer cells still constitutes a huge problem that frequently impairs the efficacy of both conventional and novel molecular therapies. Chemotherapy usually acts to induce apoptosis in cancer cells; therefore, the investigation of apoptosis control and of the mechanisms used by cancer cells to evade apoptosis could be translated in an improvement of therapies. Among many tools acquired by cancer cells to this end, the de-regulated synthesis and metabolism of sphingolipids have been well documented. Sphingolipids are known to play many structural and signalling roles in cells, as they are involved in the control of growth, survival, adhesion, and motility. In particular, in order to increase survival, cancer cells: (a counteract the accumulation of ceramide that is endowed with pro-apoptotic potential and is induced by many drugs; (b increase the synthesis of sphingosine-1-phosphate and glucosylceramide that are pro-survivals signals; (c modify the synthesis and the metabolism of complex glycosphingolipids, particularly increasing the levels of modified species of gangliosides such as 9-O acetylated GD3 (αNeu5Ac(2-8αNeu5Ac(2-3βGal(1-4βGlc(1-1Cer or N-glycolyl GM3 (αNeu5Ac (2-3βGal(1-4βGlc(1-1Cer and de-N-acetyl GM3 (NeuNH(2βGal(1-4βGlc(1-1Cer endowed with anti-apoptotic roles and of globoside Gb3 related to a higher expression of the multidrug resistance gene MDR1. In light of this evidence, the employment of chemical or genetic approaches specifically targeting sphingolipid dysregulations appears a promising tool for the improvement of current chemotherapy efficacy.

  20. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

    Science.gov (United States)

    Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu; LaRiviere, Patrick J.; Sammani, Saad; Lussier, Yves A.; Dudek, Steven M.; Natarajan, Viswanathan; Weichselbaum, Ralph R.; Garcia, Joe G. N.

    2011-01-01

    Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components serve as modulators and novel therapeutic targets of RILI. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to sphingosine 1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage fluid, and lung tissue. Mice with a targeted deletion of SphK1 (SphK1−/−) or with reduced expression of S1P receptors (S1PR1+/−, S1PR2−/−, and S1PR3−/−) exhibited marked RILI susceptibility. Finally, studies of 3 potent vascular barrier-protective S1P analogs, FTY720, (S)-FTY720-phosphonate (fTyS), and SEW-2871, identified significant RILI attenuation and radiation-induced gene dysregulation by the phosphonate analog, fTyS (0.1 and 1 mg/kg i.p., 2×/wk) and to a lesser degree by SEW-2871 (1 mg/kg i.p., 2×/wk), compared with those in controls. These results support the targeting of S1P signaling as a novel therapeutic strategy in RILI.—Mathew, B., Jacobson, J. R., Berdyshev, E., Huang, Y., Sun, X., Zhao, Y., Gerhold, L. M., Siegler, J., Evenoski, C., Wang, T., Zhou, T., Zaidi, R., Moreno-Vinasco, L., Bittman, R., Chen, C. T., LaRiviere, P. J., Sammani, S., Lussier, Y. A., Dudek, S. M., Natarajan, V., Weichselbaum, R. R., Garcia, J. G. N. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs. PMID:21712494

  1. Ophiamides A-B, new potent urease inhibitory sphingolipids from Heliotropium ophioglossum.

    Science.gov (United States)

    Firdous, Sadiqa; Ansari, Nida Hassan; Fatima, Itrat; Malik, Abdul; Afza, Nighat; Iqbal, Lubna; Lateef, Mehreen

    2012-07-01

    Ophiamides A (1) and B (2), two new sphingolipids have been isolated from the n-hexane subfraction of the MeOH extract of the whole plant of Heliotropium ophioglossum along with glycerol monopalmitate (3) and β-sitosterol 3-O-β-D: -glucoside (4) reported for the first time from this species. Their structures were elucidated by spectroscopic techniques including MS and 2D-NMR spectroscopy. Both the compounds 1 and 2 showed potent inhibitory activity against the enzyme urease.

  2. Evaluation of Sphingolipids in Wistar Rats Treated to Prolonged and Single Oral Doses of Fumonisin B1

    Science.gov (United States)

    Direito, Glória M.; Almeida, Adriana P.; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

    2009-01-01

    The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B1 (FB1). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB1. Prolonged exposure to FB1 caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB1. Animals receiving a single dose of FB1 presented variations in Sa and So levels and in the Sa/So ratio. PMID:19333435

  3. Actin filaments and microtubules are involved in different membrane traffic pathways that transport sphingolipids to the apical surface of polarized HepG2 cells

    NARCIS (Netherlands)

    Zegers, MMP; Zaal, KJM; van Ijzendoorn, SCD; Klappe, K; Hoekstra, D

    In polarized HepG2 hepatoma cells, sphingolipids are transported to the apical, bile canalicular membrane by two different transport routes, as revealed with fluorescently tagged sphingolipid analogs. One route involves direct, transcytosis-independent transport of Golgi-derived glucosylceramide and

  4. Synthesis and processing of sphingolipid activator protein-2 (SAP-2) in cultured human fibroblasts

    International Nuclear Information System (INIS)

    Fujibayashi, S.; Wenger, D.A.

    1986-01-01

    Sphingolipid activator proteins (SAP) are relatively small molecular weight proteins that stimulate the enzymatic hydrolysis of sphingolipids in the presence of specific lysosomal hydrolases. SAP-2 has previously been demonstrated to activate the hydrolysis of glucosylceramide, galactosylceramide, and, possibly, sphingomyelin. Using monospecific rabbit antibodies against human spleen SAP-2, the synthesis and processing of SAP-2 were studied in cultured human fibroblasts. When [ 35 S]methionine was presented in the medium to control human cells for 4 h, five major areas of radiolabeling were found. These had apparent molecular weights of 73,000, 68,000, 50,000, 12,000, and 9000. Further studies indicated that the major extracellular product in normal cells given NH4Cl along with the [ 35 S]methionine and in medium from cultures from patients with I cell disease had an apparent molecular weight of 73,000. The Mr = 68,000 and 73,000 species can be converted to a species with an apparent molecular weight of 50,000 by the action of endoglycosidase F. After labeling cells for 1 h followed by a 1-h chase, the Mr = 12,000 and 9000 species appear. Treatment of the immunoprecipitated mixture with endoglycosidase F resulted in conversion of these species to one band with an apparent molecular weight of 7600. These studies indicate that this relatively low molecular weight protein is rapidly synthesized from a relatively large molecular weight highly glycosylated precursor

  5. A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell

    Science.gov (United States)

    Clay, Lori; Caudron, Fabrice; Denoth-Lippuner, Annina; Boettcher, Barbara; Buvelot Frei, Stéphanie; Snapp, Erik Lee; Barral, Yves

    2014-01-01

    In many cell types, lateral diffusion barriers compartmentalize the plasma membrane and, at least in budding yeast, the endoplasmic reticulum (ER). However, the molecular nature of these barriers, their mode of action and their cellular functions are unclear. Here, we show that misfolded proteins of the ER remain confined into the mother compartment of budding yeast cells. Confinement required the formation of a lateral diffusion barrier in the form of a distinct domain of the ER-membrane at the bud neck, in a septin-, Bud1 GTPase- and sphingolipid-dependent manner. The sphingolipids, but not Bud1, also contributed to barrier formation in the outer membrane of the dividing nucleus. Barrier-dependent confinement of ER stress into the mother cell promoted aging. Together, our data clarify the physical nature of lateral diffusion barriers in the ER and establish the role of such barriers in the asymmetric segregation of proteotoxic misfolded proteins during cell division and aging. DOI: http://dx.doi.org/10.7554/eLife.01883.001 PMID:24843009

  6. (Glyco)sphingolipids are sorted in sub-apical compartments in HepG2 cells : A role for non-Golgi-related intracellular sites in the polarized distribution of (glyco)sphingolipids

    NARCIS (Netherlands)

    van IJzendoorn, SCD; Hoekstra, D

    1998-01-01

    In polarized HepG2 cells, the fluorescent sphingolipid analogues of glucosylceramide (C-6-NBD-GlcCer) and sphingomyelin (C-6-NBD-SM) display a preferential localization at the apical and basolateral domain, respectively, which is expressed during apical to basolateral transcytosis of the lipids (van

  7. Ablation of the Galnt3 gene leads to low-circulating intact fibroblast growth factor 23 (Fgf23) concentrations and hyperphosphatemia despite increased Fgf23 expression.

    Science.gov (United States)

    Ichikawa, Shoji; Sorenson, Andrea H; Austin, Anthony M; Mackenzie, Donald S; Fritz, Timothy A; Moh, Akira; Hui, Siu L; Econs, Michael J

    2009-06-01

    Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia. The disease is caused by inactivating mutations in fibroblast growth factor 23 (FGF23), Klotho (KL), and uridine diphosphate-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). In vitro studies indicate that GALNT3 O-glycosylates a phosphaturic hormone, FGF23, and prevents its proteolytic processing, thereby allowing secretion of intact FGF23. In this study we generated mice lacking the Galnt3 gene, which developed hyperphosphatemia without apparent calcifications. In response to hyperphosphatemia, Galnt3-deficient mice had markedly increased Fgf23 expression in bone. However, compared with wild-type and heterozygous littermates, homozygous mice had only about half of circulating intact Fgf23 levels and higher levels of C-terminal Fgf23 fragments in bone. Galnt3-deficient mice also exhibited an inappropriately normal 1,25-dihydroxyvitamin D level and decreased alkaline phosphatase activity. Furthermore, renal expression of sodium-phosphate cotransporters and Kl were elevated in Galnt3-deficient mice. Interestingly, there were sex-specific phenotypes; only Galnt3-deficient males showed growth retardation, infertility, and significantly increased bone mineral density. In summary, ablation of Galnt3 impaired secretion of intact Fgf23, leading to decreased circulating Fgf23 and hyperphosphatemia, despite increased Fgf23 expression. Our findings indicate that Galnt3-deficient mice have a biochemical phenotype of tumoral calcinosis and provide in vivo evidence that Galnt3 plays an essential role in proper secretion of Fgf23 in mice.

  8. Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions

    Science.gov (United States)

    Kovacs, Erika; Harmat, Veronika; Tóth, Judit; Vértessy, Beáta G.; Módos, Károly; Kardos, József; Liliom, Károly

    2010-01-01

    Lipid-protein interactions are rarely characterized at a structural molecular level due to technical difficulties; however, the biological significance of understanding the mechanism of these interactions is outstanding. In this report, we provide mechanistic insight into the inhibitory complex formation of the lipid mediator sphingosylphosphorylcholine with calmodulin, the most central and ubiquitous regulator protein in calcium signaling. We applied crystallographic, thermodynamic, kinetic, and spectroscopic approaches using purified bovine calmodulin and bovine cerebral microsomal fraction to arrive at our conclusions. Here we present 1) a 1.6-Å resolution crystal structure of their complex, in which the sphingolipid occupies the conventional hydrophobic binding site on calmodulin; 2) a peculiar stoichiometry-dependent binding process: at low or high protein-to-lipid ratio calmodulin binds lipid micelles or a few lipid molecules in a compact globular conformation, respectively, and 3) evidence that the sphingolipid displaces calmodulin from its targets on cerebral microsomes. We have ascertained the specificity of the interaction using structurally related lipids as controls. Our observations reveal the structural basis of selective calmodulin inhibition by the sphingolipid. On the basis of the crystallographic and biophysical characterization of the calmodulin–sphingosylphosphorylcholine interaction, we propose a novel lipid-protein binding model, which might be applicable to other interactions as well.—Kovacs, E., Harmat, V., Tóth, J., Vértessy, B. G., Módos, K., Kardos, J., Liliom, K. Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions. PMID:20522785

  9. The sphingolipid long-chain base-Pkh1/2-Ypk1/2 signaling pathway regulates eisosome assembly and turnover

    DEFF Research Database (Denmark)

    Luo, Guangzuo; Gruhler, Albrecht; Liu, Ying

    2008-01-01

    Eisosomes are recently described fungal structures that play roles in the organization of the plasma membrane and endocytosis. Their major protein components are Pil1 and Lsp1, and previous studies showed that these proteins are phosphorylated by the sphingolipid long-chain base-activated Pkh1...... that phosphorylation is critical for eisosome organization. We also found that eisosomes are dynamic structures and disassemble when the Ypk protein kinases, which are activated by the sphingolipid-Pkh signaling pathway, are inactivated or when the sphingolipid signal is pharmacologically blocked with myriocin. We...

  10. Nitric oxide-sphingolipid interplays in plant signalling: a new enigma from the Sphinx?

    Science.gov (United States)

    Guillas, Isabelle; Puyaubert, Juliette; Baudouin, Emmanuel

    2013-09-12

    Nitric oxide (NO) emerged as one of the major signaling molecules operating during plant development and plant responses to its environment. Beyond the identification of the direct molecular targets of NO, a series of studies considered its interplay with other actors of signal transduction and the integration of NO into complex signaling networks. Beside the close relationships between NO and calcium or phosphatidic acid signaling pathways that are now well-established, recent reports paved the way for interplays between NO and sphingolipids (SLs). This mini-review summarizes our current knowledge of the influence NO and SLs might exert on each other in plant physiology. Based on comparisons with examples from the animal field, it further indicates that, although SL-NO interplays are common features in signaling networks of eukaryotic cells, the underlying mechanisms and molecular targets significantly differ.

  11. Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity.

    Science.gov (United States)

    Montoliu, Ivan; Scherer, Max; Beguelin, Fiona; DaSilva, Laeticia; Mari, Daniela; Salvioli, Stefano; Martin, Francois-Pierre J; Capri, Miriam; Bucci, Laura; Ostan, Rita; Garagnani, Paolo; Monti, Daniela; Biagi, Elena; Brigidi, Patrizia; Kussmann, Martin; Rezzi, Serge; Franceschi, Claudio; Collino, Sebastiano

    2014-01-01

    As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot- gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

  12. The Impact of Cholesterol, DHA, and Sphingolipids on Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Marcus O. W. Grimm

    2013-01-01

    Full Text Available Alzheimer’s disease (AD is a devastating neurodegenerative disorder currently affecting over 35 million people worldwide. Pathological hallmarks of AD are massive amyloidosis, extracellular senile plaques, and intracellular neurofibrillary tangles accompanied by an excessive loss of synapses. Major constituents of senile plaques are 40–42 amino acid long peptides termed β-amyloid (Aβ. Aβ is produced by sequential proteolytic processing of the amyloid precursor protein (APP. APP processing and Aβ production have been one of the central scopes in AD research in the past. In the last years, lipids and lipid-related issues are more frequently discussed to contribute to the AD pathogenesis. This review summarizes lipid alterations found in AD postmortem brains, AD transgenic mouse models, and the current understanding of how lipids influence the molecular mechanisms leading to AD and Aβ generation, focusing especially on cholesterol, docosahexaenoic acid (DHA, and sphingolipids/glycosphingolipids.

  13. Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network

    DEFF Research Database (Denmark)

    Klemm, Robin W; Ejsing, Christer S.; Surma, Michal A

    2009-01-01

    The trans-Golgi network (TGN) is the major sorting station in the secretory pathway of all eukaryotic cells. How the TGN sorts proteins and lipids to generate the enrichment of sphingolipids and sterols at the plasma membrane is poorly understood. To address this fundamental question in membrane...... trafficking, we devised an immunoisolation procedure for specific recovery of post-Golgi secretory vesicles transporting a transmembrane raft protein from the TGN to the cell surface in the yeast Saccharomyces cerevisiae. Using a novel quantitative shotgun lipidomics approach, we could demonstrate that TGN...... than the late Golgi membrane, as measured by C-Laurdan spectrophotometry, strongly suggests that lipid rafts play a role in the TGN-sorting machinery....

  14. Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.

    Science.gov (United States)

    McClay, Joseph L; Vunck, Sarah A; Batman, Angela M; Crowley, James J; Vann, Robert E; Beardsley, Patrick M; van den Oord, Edwin J

    2015-09-01

    Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.015) and protein biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects.

  15. Impacts of pre-existing ocean cyclonic circulation on sea surface chlorophyll-a concentrations off northeastern Taiwan following episodic typhoon passages

    Science.gov (United States)

    Xu, Fanghua; Yao, Yuan; Oey, Leo; Lin, Yanluan

    2017-08-01

    Off northeastern Taiwan, enhancement of sea surface chlorophyll-a (Chl-a) concentration is frequently found after typhoon passages. From 1998 to 2013, 46 typhoon events are analyzed to examine the variations in Chl-a concentration from satellite ocean color data. On average, Chl-a concentration increased by 38% after a typhoon passage. Noticeably, four remarkable Chl-a increases after typhoons coincide with pre-existing oceanic cyclones in the study area. The Chl-a increase is significantly anticorrelated (p typhoons, we conduct a series of numerical experiments to simulate the oceanic response to Typhoon Kaemi (2006) with or without a pre-existing oceanic cyclone, and with or without strong typhoon winds. The results show that the experiment with a pre-existing oceanic cyclone produces the largest upwelling due to cyclone intensification, mainly induced by the positive wind stress curl dipole northeast of Taiwan.

  16. Glucose intolerance and the amount of visceral adipose tissue contribute to an increase in circulating triglyceride concentrations in Caucasian obese females.

    Science.gov (United States)

    Berings, Margot; Wehlou, Charline; Verrijken, An; Deschepper, Ellen; Mertens, Ilse; Kaufman, Jean-Marc; Van Gaal, Luc F; Ouwens, D Margriet; Ruige, Johannes B

    2012-01-01

    Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2), cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG) concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2. 913 obese females unknown to have diabetes were recruited (mean age: 41.2 ± SD 12.3; median BMI: 36.2, IQR 32.9-40.2). Visceral (VAT) and subcutaneous abdominal adipose tissue volumes were quantified with computed tomography. Glucose, insulin, and triglyceride concentrations were determined in fasting state and following a 75 gram oral glucose tolerance test. Based on fasting and 2 h post-load glucose levels, 27% of the women had impaired glucose tolerance (IGT), and 8% had newly diagnosed DM2. Fasting TG concentrations were similar between the IGT- and DM2-groups, and increased as compared to women with normal glucose tolerance (NGT). Even when adjusting for age, hip circumference and VAT, fasting TG concentrations remained elevated as compared to NGT. Mixed modelling analysis of post-load responses showed that TG concentrations declined more slowly in the DM2-group as compared to IGT and NGT. However, when adjusting for VAT the difference in decline between the glucose tolerance groups disappeared. Glucose intolerance associates with elevated fasting TG concentrations in obese Caucasian women. We propose that glucose intolerance and increased VAT reduce lipid disposal mechanisms and may accelerate lipotoxicity.

  17. Glucose intolerance and the amount of visceral adipose tissue contribute to an increase in circulating triglyceride concentrations in Caucasian obese females.

    Directory of Open Access Journals (Sweden)

    Margot Berings

    Full Text Available CONTEXT: Lipotoxicity is a risk factor for developing obesity-related metabolic complications, including non-alcoholic fatty liver disease, type 2 diabetes (DM2, cardiovascular disease and stroke. Yet, the mechanisms underlying the development of lipotoxicity itself remain poorly understood. Here, we investigated whether glucose intolerance aggravates lipotoxicity by evaluating the association between triglyceride (TG concentrations and glucose tolerance status in a cross-sectional study on obese Caucasian women at risk for DM2. METHODS: 913 obese females unknown to have diabetes were recruited (mean age: 41.2 ± SD 12.3; median BMI: 36.2, IQR 32.9-40.2. Visceral (VAT and subcutaneous abdominal adipose tissue volumes were quantified with computed tomography. Glucose, insulin, and triglyceride concentrations were determined in fasting state and following a 75 gram oral glucose tolerance test. RESULTS: Based on fasting and 2 h post-load glucose levels, 27% of the women had impaired glucose tolerance (IGT, and 8% had newly diagnosed DM2. Fasting TG concentrations were similar between the IGT- and DM2-groups, and increased as compared to women with normal glucose tolerance (NGT. Even when adjusting for age, hip circumference and VAT, fasting TG concentrations remained elevated as compared to NGT. Mixed modelling analysis of post-load responses showed that TG concentrations declined more slowly in the DM2-group as compared to IGT and NGT. However, when adjusting for VAT the difference in decline between the glucose tolerance groups disappeared. CONCLUSIONS: Glucose intolerance associates with elevated fasting TG concentrations in obese Caucasian women. We propose that glucose intolerance and increased VAT reduce lipid disposal mechanisms and may accelerate lipotoxicity.

  18. Identification of Two Suppressors of CSG2 Calcium Sensitivity, SCS7 and SUR2, as Genes Encoding Hydroxylases of the Sphingolipid Biosynthetic Pathway of Saccharomyces cerevisiae

    National Research Council Canada - National Science Library

    Haak, Dale A

    1997-01-01

    .... The biochemical significance of much of this structural variability is not well understood. The sphingolipids of the yeast Saccharomyces cerevisiae undergo the a-hydroxylation of the very long chain fatty acid (VLCFA...

  19. Profiling of Plasma Metabolites Suggests Altered Mitochondrial Fuel Usage and Remodeling of Sphingolipid Metabolism in Individuals With Type 2 Diabetes and Kidney Disease

    Directory of Open Access Journals (Sweden)

    Jian-Jun Liu

    2017-05-01

    Discussion: DKD is associated with altered fuel substrate use and remodeling of sphingolipid metabolism in T2DM with DKD. Associations of albuminuria and impaired filtration function with distinct metabolomic signatures suggest different pathophysiology underlying these 2 manifestations of DKD.

  20. Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies.

    Science.gov (United States)

    Rodríguez, Alexander J; Nunes, Vania dos Santos; Mastronardi, Claudio A; Neeman, Teresa; Paz-Filho, Gilberto J

    2016-03-01

    The adipocytokines leptin and adiponectin have been variously associated with diabetic microvascular complications. No comprehensive clinical data exist examining the association between adipocytokines and the presence of these complications. This is a systematic review of cross-sectional studies comparing circulating adipocytokines in patients with type 2 diabetes mellitus (T2DM), with and without microvascular complications. Studies were retrieved from MEDLINE, EMBASE, Scopus and Cochrane databases. Study quality was evaluated using a modified Newcastle-Ottawa Scale. Meta-analysis was performed using an inverse-variance model, providing standardised mean differences (SMD) and 95% confidence intervals (CI). Heterogeneity was determined by I(2) statistic. Amongst 554 identified studies, 28 were included in the review. Study quality range was 3.5-9 (maximum 11). Higher leptin levels were associated with microalbuminuria (SMD=0.41; 95% CI=0.14-0.67; n=901; p=0.0003), macroalbuminuria (SMD=0.68; 95% CI=0.30-1.06; n=406; p=0.0004), and neuropathy (SMD=0.26; 95% CI=0.07-0.44; n=609; p=0.008). Higher adiponectin levels were associated with microalbuminuria (SMD=0.55; 95% CI=0.29-0.81, n=274; p1), macroalbuminuria (SMD=1.37; 95% CI=0.78-1.97, n=246; p1), neuropathy (SMD=0.25; 95% CI=0.14-0.36; n=1516; p1), and retinopathy (SMD=0.38; 95% CI=0.25-0.51; n=1306; p1). Meta-regression suggested no influence of body mass index and duration of diabetes on effect size, and a weak trend in terms of age on effect size. Our meta-analysis suggests leptin and adiponectin levels are higher in T2DM patients with microvascular complications. Studies were limited by cross-sectional design. Large prospective analyses are required to validate these findings. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Circulating fat-soluble vitamin concentrations and nutrient composition of aquatic prey eaten by American oystercatchers (Haematopus palliatus) in the southeastern United States

    Science.gov (United States)

    Carlson-Bremer, Daphne; Norton, Terry M.; Sanders, Felicia J.; Winn, Brad; Spinks, Mark D.; Glatt, Batsheva A.; Mazzaro, Lisa; Jodice, Patrick G.R.; Chen, Tai C.; Dierenfeld, Ellen S.

    2014-01-01

    The American oystercatcher (Haematopus palliatus palliatus) is currently listed as a species of high concern by the United States Shorebird Conservation Plan. Because nutritional status directly impacts overall health and reproduction of individuals and populations, adequate management of a wildlife population requires intimate knowledge of a species' diet and nutrient requirements. Fat-soluble vitamin concentrations in blood plasma obtained from American oystercatchers and proximate, vitamin, and mineral composition of various oystercatcher prey species were determined as baseline data to assess nutritional status and nutrient supply. Bird and prey species samples were collected from the Cape Romain region, South Carolina, USA, and the Altamaha River delta islands, Georgia, USA, where breeding populations appear relatively stable in recent years. Vitamin A levels in blood samples were higher than ranges reported as normal for domestic avian species, and vitamin D concentrations were lower than anticipated based on values observed in poultry. Vitamin E levels were within ranges previously reported for avian groups with broadly similar feeding niches such as herons, gulls, and terns (eg, aquatic/estuarine/marine). Prey species (oysters, mussels, clams, blood arks [Anadara ovalis], whelks [Busycon carica], false angel wings [Petricola pholadiformis]) were similar in water content to vertebrate prey, moderate to high in protein, and moderate to low in crude fat. Ash and macronutrient concentrations in prey species were high compared with requirements of carnivores or avian species. Prey items analyzed appear to meet nutritional requirements for oystercatchers, as estimated by extrapolation from domestic carnivores and poultry species; excesses, imbalances, and toxicities—particularly of minerals and fat-soluble vitamins—may warrant further investigation.

  2. AnSBBR with circulation applied to biohydrogen production treating sucrose based wastewater: effects of organic loading, influent concentration and cycle length

    Directory of Open Access Journals (Sweden)

    D. A. Santos

    2014-09-01

    Full Text Available An anaerobic sequencing batch biofilm reactor (AnSBBR containing immobilized biomass and operating with recirculation of the liquid phase (total liquid volume 4.5 L; treated volume per cycle 1.9 L was used to treat sucrose-based wastewater at 30 ºC and produce biohydrogen. The influence of applied volumetric organic load was studied by varying the influent concentration at 3600 and 5400 mgCOD.L-1 and using cycle lengths of 4, 3 and 2 hours, obtaining in this manner volumetric organic loads of 9, 12, 13.5, 18 and 27 gCOD.L-1.d-1. Different performance indicators were used: productivity and yield of biohydrogen per applied and removed load, reactor stability and efficiency based on the applied and removed organic loads, both in terms of organic matter (measured as COD and carbohydrate (sucrose. The results revealed system stability (32-37% of H2 in biogas during biohydrogen production, as well as substrate consumption (12-19% COD; 97-99% sucrose. Conversion efficiencies decreased when the influent concentration was increased (at constant cycle length and when cycle lengths were reduced (at constant influent concentrations. The best yield was 4.16 mol-H2.kg-SUC-1 (sucrose load at 9 gCOD.L-1.d-1 (3600 mgCOD.L-1 and 4 h with H2 content in the biogas of 36% (64% CO2 and 0% CH4. However, the best specific molar productivity of hydrogen was 8.5 molH2.kgTVS-1.d-1 (32% H2; 68% CO2; 0% CH4, at 18 gCOD.L-1.d-1 (5400 mgCOD.L-1 and 3 h, indicating that the best productivity tends to occur at higher organic loads, as this parameter involves the "biochemical generation" of biogas, whereas the best yield tends to occur at lower and/or intermediate organic loads, as this parameter involves "biochemical consumption" of the substrate. The most significant metabolites were ethanol, acetic acid and butyric acid. Microbiological analyses revealed that the biomass contained bacilli and endospore filaments and showed no significant variations in morphology between

  3. Extensive changes in innate immune gene expression in obese Göttingen minipigs do not lead to changes in concentrations of circulating cytokines and acute phase proteins

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard; Skovgaard, Kerstin; Moesgaard, S. G.

    2014-01-01

    not been studied in Göttingen minipigs. Therefore, we studied the expression of innate immune genes in liver and adipose tissues as well as serum concentrations of cytokines and acute phase proteins in obese vs. lean Göttingen minipigs. In the liver, of 35 investigated genes, the expression of nine...... was significantly different in obese pigs (three up-regulated, six down-regulated). Of 33 genes in adipose tissues, obesity was associated with changed expression of 12 genes in the visceral adipose tissue (VAT) (three up-regulated), 11 in the abdominal retroperitoneal adipose tissue (RPAT) (seven of these up......-regulated) and eight in the subcutaneous adipose tissue (SAT) from the neck (five of which were up-regulated). Obesity-associated expression changes were observed for three genes in all adipose tissues, namely chemokine (C-C motif) ligand 3-like 1 (up-regulated), CD200 molecule (down-regulated) and interleukin 1...

  4. Loss of circadian rhythm of circulating insulin concentration induced by high-fat diet intake is associated with disrupted rhythmic expression of circadian clock genes in the liver.

    Science.gov (United States)

    Honma, Kazue; Hikosaka, Maki; Mochizuki, Kazuki; Goda, Toshinao

    2016-04-01

    Peripheral clock genes show a circadian rhythm is correlated with the timing of feeding in peripheral tissues. It was reported that these clock genes are strongly regulated by insulin action and that a high-fat diet (HFD) intake in C57BL/6J mice for 21days induced insulin secretion during the dark phase and reduced the circadian rhythm of clock genes. In this study, we examined the circadian expression patterns of these clock genes in insulin-resistant animal models with excess secretion of insulin during the day. We examined whether insulin resistance induced by a HFD intake for 80days altered blood parameters (glucose and insulin concentrations) and expression of mRNA and proteins encoded by clock and functional genes in the liver using male ICR mice. Serum insulin concentrations were continuously higher during the day in mice fed a HFD than control mice. Expression of lipogenesis-related genes (Fas and Accβ) and the transcription factor Chrebp peaked at zeitgeber time (ZT)24 in the liver of control mice. A HFD intake reduced the expression of these genes at ZT24 and disrupted the circadian rhythm. Expression of Bmal1 and Clock, transcription factors that compose the core feedback loop, showed circadian variation and were synchronously associated with Fas gene expression in control mice, but not in those fed a HFD. These results indicate that the disruption of the circadian rhythm of insulin secretion by HFD intake is closely associated with the disappearance of circadian expression of lipogenic and clock genes in the liver of mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Leptin administration to overweight and obese subjects for 6 months increases free leptin concentrations but does not alter circulating hormones of the thyroid and IGF axes during weight loss induced by a mild hypocaloric diet.

    Science.gov (United States)

    Shetty, Greeshma K; Matarese, Giuseppe; Magkos, Faidon; Moon, Hyun-Seuk; Liu, Xiaowen; Brennan, Aoife M; Mylvaganam, Geetha; Sykoutri, Despina; Depaoli, Alex M; Mantzoros, Christos S

    2011-08-01

    Short-term energy deprivation reduces leptin concentrations and alters the levels of circulating hormones of the hypothalamic-pituitary-peripheral axis in lean subjects. Whether the reduction in leptin concentration during long-term weight loss in obese individuals is linked to the same neuroendocrine changes seen in lean, leptin-sensitive subjects remains to be fully clarified. In this study, 24 overweight and obese adults (16 women and eight men; body mass index (BMI): 27.5-38.0 kg/m(2)) were prescribed a hypocaloric diet (-500 kcal/day) and were randomized to receive recombinant methionyl leptin (n=18, metreleptin, 10 mg/day self-injected s.c.) or placebo (n=6, same volume and time as metreleptin) for 6 months. Metreleptin administration did not affect weight loss beyond that induced by hypocaloric diet alone (P for interaction=0.341) but increased the serum concentrations of total leptin by six- to eight-fold (Phypocaloric diet in overweight and obese subjects.

  6. Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

    Science.gov (United States)

    Mor, Visesato; Rella, Antonella; Farnoud, Amir M.; Singh, Ashutosh; Munshi, Mansa; Bryan, Arielle; Naseem, Shamoon; Konopka, James B.; Ojima, Iwao; Bullesbach, Erika; Ashbaugh, Alan; Linke, Michael J.; Cushion, Melanie; Collins, Margaret; Ananthula, Hari Krishna; Sallans, Larry; Desai, Pankaj B.; Wiederhold, Nathan P.; Fothergill, Annette W.; Kirkpatrick, William R.; Patterson, Thomas; Wong, Lai Hong; Sinha, Sunita; Giaever, Guri; Nislow, Corey; Flaherty, Patrick; Pan, Xuewen; Cesar, Gabriele Vargas; de Melo Tavares, Patricia; Frases, Susana; Miranda, Kildare; Rodrigues, Marcio L.; Luberto, Chiara; Nimrichter, Leonardo

    2015-01-01

    ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. PMID:26106079

  7. Efficient replacement of plasma membrane outer leaflet phospholipids and sphingolipids in cells with exogenous lipids.

    Science.gov (United States)

    Li, Guangtao; Kim, JiHyun; Huang, Zhen; St Clair, Johnna R; Brown, Deborah A; London, Erwin

    2016-12-06

    Our understanding of membranes and membrane lipid function has lagged far behind that of nucleic acids and proteins, largely because it is difficult to manipulate cellular membrane lipid composition. To help solve this problem, we show that methyl-α-cyclodextrin (MαCD)-catalyzed lipid exchange can be used to maximally replace the sphingolipids and phospholipids in the outer leaflet of the plasma membrane of living mammalian cells with exogenous lipids, including unnatural lipids. In addition, lipid exchange experiments revealed that 70-80% of cell sphingomyelin resided in the plasma membrane outer leaflet; the asymmetry of metabolically active cells was similar to that previously defined for erythrocytes, as judged by outer leaflet lipid composition; and plasma membrane outer leaflet phosphatidylcholine had a significantly lower level of unsaturation than phosphatidylcholine in the remainder of the cell. The data also provided a rough estimate for the total cellular lipids residing in the plasma membrane (about half). In addition to such lipidomics applications, the exchange method should have wide potential for investigations of lipid function and modification of cellular behavior by modification of lipids.

  8. Assessing the usefulness of B-mode and colour Doppler sonography, and measurements of circulating progesterone concentrations for determining ovarian responses in superovulated ewes.

    Science.gov (United States)

    Oliveira, Mef; Ribeiro, I F; Rodriguez, Mgk; Maciel, G S; Fonseca, J F; Brandão, F Z; Bartlewski, P M

    2018-06-01

    The main goal of this study was to assess the usefulness of two imaging modalities, namely the B-mode and colour Doppler sonography, and serum progesterone (P 4 ) concentrations for determining the ovarian response in superovulated ewes. Twenty-four sexually mature Santa Inês ewes underwent the superovulatory treatment consisting of eight injections of porcine FSH (total dose of 200 or 133 or 100 mg; n = 8 ewes/total dose) given at 12-hr intervals and initiated 48 hr before CIDR ® (Pfizer Inc., Auckland, New Zealand) removal. Six days after natural mating, the ovaries of all donor ewes were visualized and examined with transrectal ultrasonography and then with videolaparoscopy to identify and enumerate corpora lutea (CL) and luteinized unovulated follicles (LUFs). Jugular blood samples were collected just prior to ovarian examinations. The total number of CL (r = .78 and 0.83, p ewes. © 2018 Blackwell Verlag GmbH.

  9. Effects of orally administered fumonisin B₁ (FB₁), partially hydrolysed FB₁, hydrolysed FB₁ and N-(1-deoxy-D-fructos-1-yl) FB₁ on the sphingolipid metabolism in rats.

    Science.gov (United States)

    Hahn, Irene; Nagl, Veronika; Schwartz-Zimmermann, Heidi Elisabeth; Varga, Elisabeth; Schwarz, Christiane; Slavik, Veronika; Reisinger, Nicole; Malachová, Alexandra; Cirlini, Martina; Generotti, Silvia; Dall'Asta, Chiara; Krska, Rudolf; Moll, Wulf-Dieter; Berthiller, Franz

    2015-02-01

    Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in maize-based food and feed. Alkaline processing like nixtamalisation of maize generates partially and fully hydrolysed FB1 (pHFB1 and HFB1) and thermal treatment in the presence of reducing sugars leads to formation of N-(1-deoxy-D-fructos-1-yl) fumonisin B1 (NDF). The toxicity of these metabolites, in particular their effect on the sphingolipid metabolism, is either unknown or discussed controversially. We produced high purity FB1, pHFB1a+b, HFB1 and NDF and fed them to male Sprague Dawley rats for three weeks. Once a week, urine and faeces samples were collected over 24 h and analysed for fumonisin metabolites as well as for the sphinganine (Sa) to sphingosine (So) ratio by validated LC-MS/MS based methods. While the latter was significantly increased in the FB1 positive control group, the Sa/So ratios of the partially and fully hydrolysed fumonisins were indifferent from the negative control group. Although NDF was partly cleaved during digestion, the liberated amounts of FB1 did not raise the Sa/So ratio. These results show that the investigated alkaline and thermal processing products of FB1 were, at the tested concentrations, non-toxic for rats, and suggest that according food processing can reduce fumonisin toxicity for humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Sphingolipid base modifying enzymes in sunflower (Helianthus annuus): cloning and characterization of a C4-hydroxylase gene and a new paralogous Δ8-desaturase gene.

    Science.gov (United States)

    Moreno-Pérez, Antonio J; Martínez-Force, Enrique; Garcés, Rafael; Salas, Joaquín J

    2011-05-15

    Sphingolipids are components of plant cell membranes that participate in the regulation of important physiological processes. Unlike their animal counterparts, plant sphingolipids are characterized by high levels of base C4-hydroxylation. Moreover, desaturation at the Δ8 position predominates over the Δ4 desaturation typically found in animal sphingolipids. These modifications are due to the action of C4-hydroxylases and Δ8-long chain base desaturases, and they are important for complex sphingolipids finally becoming functional. The long chain bases of sunflower sphingolipids have high levels of hydroxylated and unsaturated moieties. Here, a C4-long chain base hydroxylase was functionally characterized in sunflower plant, an enzyme that could complement the sur2Δ mutation when heterologously expressed in this yeast mutant deficient in hydroxylation. This hydroxylase was ubiquitously expressed in sunflower, with the highest levels found in the developing cotyledons. In addition, we identified a new Δ8-long base chain desaturase gene that displays strong homology to a previously reported desaturase gene. This desaturase was also expressed in yeast and was able to change the long chain base composition of the transformed host. We studied the expression of this desaturase and compared it with that of the other isoform described in sunflower. The desaturase form studied in this paper displayed higher expression levels in developing seeds. Copyright © 2010 Elsevier GmbH. All rights reserved.

  11. Methods of staining and visualization of sphingolipid enriched and non-enriched plasma membrane regions of Arabidopsis thaliana with fluorescent dyes and lipid analogues

    Directory of Open Access Journals (Sweden)

    Blachutzik Jörg O

    2012-08-01

    Full Text Available Abstract Background Sterols and Sphingolipids form lipid clusters in the plasma membranes of cell types throughout the animal and plant kingdoms. These lipid domains provide a medium for protein signaling complexes at the plasma membrane and are also observed to be principal regions of membrane contact at the inception of infection. We visualized different specific fluorescent lipophilic stains of the both sphingolipid enriched and non-sphingolipid enriched regions in the plasma membranes of live protoplasts of Arabidopsis thaliana. Results Lipid staining protocols for several fluorescent lipid analogues in plants are presented. The most emphasis was placed on successful protocols for the single and dual staining of sphingolipid enriched regions and exclusion of sphingolipid enriched regions on the plasma membrane of Arabidopsis thaliana protoplasts. A secondary focus was placed to ensure that these staining protocols presented still maintain cell viability. Furthermore, the protocols were successfully tested with the spectrally sensitive dye Laurdan. Conclusion Almost all existing staining procedures of the plasma membrane with fluorescent lipid analogues are specified for animal cells and tissues. In order to develop lipid staining protocols for plants, procedures were established with critical steps for the plasma membrane staining of Arabidopsis leaf tissue and protoplasts. The success of the plasma membrane staining protocols was additionally verified by measurements of lipid dynamics by the fluorescence recovery after photobleaching technique and by the observation of new phenomena such as time dependent lipid polarization events in living protoplasts, for which a putative physiological relevance is suggested.

  12. Current relevance of fungal and trypanosomatid glycolipids and sphingolipids: studies defining structures conspicuously absent in mammals

    Directory of Open Access Journals (Sweden)

    Helio K. Takahashi

    2009-09-01

    Full Text Available Recently, glycosphingolipids have been attracting attention due to their role on biological systems as second messengers or modulators of signal transduction, affecting several events, which range from apoptosis to regulation of the cell cycle. In pathogenic fungi, glycolipids are expressed in two classes: neutral monohexosylceramides (glucosyl-or galactosylceramide and acidic glycosylinositol phosphorylceramides (the latter class carries longer glycan chains. It is worth to mention that monohexosylceramides exhibit significant structural differences in their lipid moieties compared to their mammalian counterparts, whereas the glycosylinositol phosphorylceramides exhibit remarkable structural differences in their carbohydrate moieties in comparison to mammal glycosphingolipids counterpart. We observed that glycosylinositol phosphorylceramides are capable of promoting immune response in infected humans. In addition, inhibiting fungal glycosphingolipid biosynthetic pathways leads to an inhibition of colony formation, spore germination, cell cycle, dimorphism and hyphal growth. Other pathogens, such as trypanosomatids, also present unique glycolipids, which may have an important role for the parasite development and/or disease establishment. Regarding host-pathogen interaction, cell membrane rafts, which are enriched in sphingolipids and sterols, participate in parasite/fungal infection. In this review, it is discussed the different biological roles of (glyco (sphingolipids of pathogenic/opportunistic fungi and trypanosomatids.Recentemente, glicoesfingolipídeos têm atraído atenção devido ao seu papel na biologia celular como segundo-mensageiro ou moduladores da transdução de sinal, afetando vários eventos, desde apoptose até a regulação do ciclo celular. Em fungos patogênicos, existem duas classes de glicolipídeos: monohexosil ceramidas neutras (glucosil-ou galactosilceramida e glicosilinositol fosforilceramidas (os quais apresentam

  13. MRP- and BCL-2-mediated drug resistance in human SCLC: effects of apoptotic sphingolipids in vitro.

    Science.gov (United States)

    Khodadadian, M; Leroux, M E; Auzenne, E; Ghosh, S C; Farquhar, D; Evans, R; Spohn, W; Zou, Y; Klostergaard, J

    2009-10-01

    Multidrug-resistance-associated protein (MRP) and BCL-2 contribute to drug resistance expressed in SCLC. To establish whether MRP-mediated drug resistance affects sphingolipid (SL)-induced apoptosis in SCLC, we first examined the human SCLC cell line, UMCC-1, and its MRP over-expressing, drug-resistant subline, UMCC-1/VP. Despite significantly decreased sensitivity to doxorubicin (Dox) and to the etoposide, VP-16, the drug-selected line was essentially equally as sensitive to treatment with exogenous ceramide (Cer), sphingosine (Sp) or dimethyl-sphingosine (DMSP) as the parental line. Next, we observed that high BCL-2-expressing human H69 SCLC cells, that were approximately 160-fold more sensitive to Dox than their combined BCL-2 and MRP-over-expressing (H69AR) counterparts, were only approximately 5-fold more resistant to DMSP. Time-lapse fluorescence microscopy of either UMCC cell line treated with DMSP-Coumarin revealed comparable extents and kinetics of SL uptake, further ruling out MRP-mediated effects on drug uptake. DMSP potentiated the cytotoxic activity of VP-16 and Taxol, but not Dox, in drug-resistant UMCC-1/VP cells. However, this sensitization did not appear to involve DMSP-mediated effects on the function of MRP in drug export; nor did DMSP strongly shift the balance of pro-apoptotic Sps and anti-apoptotic Sp-1-Ps in these cells. We conclude that SL-induced apoptosis markedly overcomes or bypasses MRP-mediated drug resistance relevant to SCLC and may suggest a novel therapeutic approach to chemotherapy for these tumors.

  14. Nucleotide sequence of cloned cDNA for human sphingolipid activator protein 1 precursor

    International Nuclear Information System (INIS)

    Dewji, N.N.; Wenger, D.A.; O'Brien, J.S.

    1987-01-01

    Two cDNA clones encoding prepro-sphingolipid activator protein 1 (SAP-1) were isolated from a λ gt11 human hepatoma expression library using polyclonal antibodies. These had inserts of ≅ 2 kilobases (λ-S-1.2 and λ-S-1.3) and both were both homologous with a previously isolated clone (λ-S-1.1) for mature SAP-1. The authors report here the nucleotide sequence of the longer two EcoRI fragments of S-1.2 and S-1.3 that were not the same and the derived amino acid sequences of mature SAP-1 and its prepro form. The open reading frame encodes 19 amino acids, which are colinear with the amino-terminal sequence of mature SAP-1, and extends far beyond the predicted carboxyl terminus of mature SAP-1, indicating extensive carboxyl-terminal processing. The nucleotide sequence of cDNA encoding prepro-SAP-1 includes 1449 bases from the assigned initiation codon ATG at base-pair 472 to the stop codon TGA at base-pair 1921. The first 23 amino acids coded after the initiation ATG are characteristic of a signal peptide. The calculated molecular mass for a polypeptide encoded by 1449 bases is ≅ 53 kDa, in keeping with the reported value for pro-SAP-1. The data indicate that after removal of the signal peptide mature SAP-1 is generated by removing an additional 7 amino acids from the amino terminus and ≅ 373 amino acids from the carboxyl terminus. One potential glycosylation site was previously found in mature SAP-1. Three additional potential glycosylation sites are present in the processed carboxyl-terminal polypeptide, which they designate as P-2

  15. Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B{sub 1}

    Energy Technology Data Exchange (ETDEWEB)

    Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S; Swanevelder, Sonja

    2004-07-15

    In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B{sub 1} (FB{sub 1}) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB{sub 1} containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB{sub 1} dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB{sub 1} treatment in the control rats was significantly (P<0.05) enhanced by the 2-AAF/PH cancer promotion treatment. The nodular and surrounding Sa levels returned to baseline following FB{sub 1} initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB{sub 1} treatment, the initiation effected by FB{sub 1} was less (P<0.01) sensitive to the accumulation of Sa in the nodular and surrounding tissues than DEN initiation and the 2-AAF/PH control treatment. In contrast, the So level of FB{sub 1} initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P<0.05) higher with the secondary FB{sub 1} treatment. Although, the FB{sub 1}-induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

  16. Snapping Turtles (Chelydra serpentina) from Canadian Areas of Concern across the southern Laurentian Great Lakes: Chlorinated and brominated hydrocarbon contaminants and metabolites in relation to circulating concentrations of thyroxine and vitamin A.

    Science.gov (United States)

    Letcher, Robert J; Lu, Zhe; de Solla, Shane R; Sandau, Courtney D; Fernie, Kimberly J

    2015-11-01

    The metabolites of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as well as other halogenated phenolic contaminants (HPCs) have been shown to have endocrine-disrupting properties, and have been reported with increasing frequency in the blood of wildlife, and mainly in mammals and birds. However, little is known about the persistence, accumulation and distribution of these contaminants in long-lived freshwater reptiles. In the present study, in addition to a large suite of chlorinated and brominated contaminants, metabolites and HPCs, we assessed and compared hydroxylated (OH) PCBs and OH-PBDEs relative to PCBs and PBDEs, respectively, in the plasma of adult male common snapping turtles (Chelydra serpentina). Blood samples were collected from 62 snapping turtles (2001-2004) at 12 wetland sites between the Detroit River and the St. Lawrence River on the Canadian side of the Laurentian Great Lakes of North America. Turtles were sampled from sites designated as Areas of Concern (AOCs) and from a relatively clean reference site in southern Georgian Bay (Tiny Marsh), Lake Huron. Plasma concentrations of Σ46PCB (10-340 ng/g wet weight (ww)) and Σ28OH-PCB (3-83 ng/g ww) were significantly greater (pturtles from the Turkey Creek and Muddy Creek-Wheatley Harbour sites in Lake Erie compared with the reference site turtles. The HPC, pentachlorophenol (PCP), had a mean concentration of 9.6±1.1 ng/g ww. Of the 28 OH-CB congeners screened for, 4-OH-CB187 (42±7 ng/g ww) was the most concentrated of all HPCs measured. Of the 14 OH-BDE congeners examined, four (4'-OH-BDE17, 3-OH-BDE47, 5-OH-BDE47 and 4'-OH-BDE49) were consistently found in all plasma samples. p,p'-DDE was the most concentrated of the 18 organochlorine pesticides (OCPs) examined. The mean concentrations of circulating total thyroxine (TT4), dehydroretinol and retinol in the plasma of the male snapping turtles regardless of sampling site were 5.4±0.3, 81±4.7 and 291±13 ng

  17. 1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane and tris(methylphenyl) phosphate cause significant effects on development, mRNA expression, and circulating bile acid concentrations in chicken embryos

    Energy Technology Data Exchange (ETDEWEB)

    Crump, Doug, E-mail: doug.crump@ec.gc.ca [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Porter, Emily; Egloff, Caroline; Williams, Kim L.; Letcher, Robert J.; Gauthier, Lewis T. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Kennedy, Sean W. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5 (Canada)

    2014-06-15

    1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane (DBE-DBCH; formerly abbreviated as TBECH) and tris(methylphenyl) phosphate (TMPP; formerly abbreviated as TCP) are additive flame retardants that are detected in the environment and biota. A recent avian in vitro screening study of 16 flame retardants identified DBE-DBCH and TMPP as important chemicals for follow-up in ovo evaluation based on their effects on cytotoxicity and mRNA expression in avian hepatocytes. In this study, technical mixtures of DBE-DBCH and TMPP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 54,900 ng/g and from 0 to 261,400 ng/g, respectively, to determine effects on pipping success, development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations. Both compounds were detectable in embryos at pipping and the β-DBE-DBCH isomer was depleted more rapidly than the α-isomer in tissue samples. DBE-DBCH had limited effects on the endpoints measured, with the exception of the up-regulation of two phase I metabolizing enzymes, CYP3A37 and CYP2H1. TMPP exposure caused embryonic deformities, altered growth, increased liver somatic index (LSI) and plasma bile acid concentrations, and altered mRNA expression levels of genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Overall, TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH albeit at concentrations several orders of magnitude greater than those detected in the environment. The increase in plasma bile acid concentrations was a useful phenotypic anchor as it was associated with a concomitant increase in LSI, discoloration of the liver tissue, and modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • DBE-DBCH and TMPP are not embryolethal to chicken embryos. • TMPP caused deformities, morphometric alterations, and increased plasma bile acids. • DBE-DBCH and TMPP altered mRNA levels

  18. Circulation of Stars

    Science.gov (United States)

    Boitani, P.

    2016-01-01

    Since the dawn of man, contemplation of the stars has been a primary impulse in human beings, who proliferated their knowledge of the stars all over the world. Aristotle sees this as the product of primeval and perennial “wonder” which gives rise to what we call science, philosophy, and poetry. Astronomy, astrology, and star art (painting, architecture, literature, and music) go hand in hand through millennia in all cultures of the planet (and all use catasterisms to explain certain phenomena). Some of these developments are independent of each other, i.e., they take place in one culture independently of others. Some, on the other hand, are the product of the “circulation of stars.” There are two ways of looking at this. One seeks out forms, the other concentrates on the passing of specific lore from one area to another through time. The former relies on archetypes (for instance, with catasterism), the latter constitutes a historical process. In this paper I present some of the surprising ways in which the circulation of stars has occurred—from East to West, from East to the Far East, and from West to East, at times simultaneously.

  19. Protein-enriched diet, with the use of lean red meat, combined with progressive resistance training enhances lean tissue mass and muscle strength and reduces circulating IL-6 concentrations in elderly women: a cluster randomized controlled trial.

    Science.gov (United States)

    Daly, Robin M; O'Connell, Stella L; Mundell, Niamh L; Grimes, Carley A; Dunstan, David W; Nowson, Caryl A

    2014-04-01

    Physical inactivity, inadequate dietary protein, and low-grade systemic inflammation contribute to age-related muscle loss, impaired function, and disability. We assessed the effects of progressive resistance training (PRT) combined with a protein-enriched diet facilitated through lean red meat on lean tissue mass (LTM), muscle size, strength and function, circulating inflammatory markers, blood pressure, and lipids in elderly women. In a 4-mo cluster randomized controlled trial, 100 women aged 60-90 y who were residing in 15 retirement villages were allocated to receive PRT with lean red meat (∼160 g cooked) to be consumed 6 d/wk [resistance training plus lean red meat (RT+Meat) group; n = 53] or control PRT [1 serving pasta or rice/d; control resistance training (CRT) group; n = 47)]. All women undertook PRT 2 times/wk and received 1000 IU vitamin D3/d. The mean (± SD) protein intake was greater in the RT+Meat group than in the CRT group throughout the study (1.3 ± 0.3 compared with 1.1 ± 0.3 g · kg⁻¹ · d⁻¹, respectively; P < 0.05). The RT+Meat group experienced greater gains in total body LTM (0.45 kg; 95% CI: 0.07, 0.84 kg), leg LTM (0.22 kg; 95% CI: 0.02, 0.42 kg), and muscle strength (18%; 95% CI: 0.03, 0.34) than did the CRT group (all P < 0.05). The RT+Meat group also experienced a 10% greater increase in serum insulin-like growth factor I (P < 0.05) and a 16% greater reduction in the proinflammatory marker interleukin-6 (IL-6) (P < 0.05) after 4 mo. There were no between-group differences for the change in blood lipids or blood pressure. A protein-enriched diet equivalent to ∼1.3 g · kg⁻¹ · d⁻¹ achieved through lean red meat is safe and effective for enhancing the effects of PRT on LTM and muscle strength and reducing circulating IL-6 concentrations in elderly women. This trial was registered at the Australian Clinical Trials Registry as ACTRN12609000223235.

  20. A combined fluorescence spectroscopy, confocal and 2-photon microscopy approach to re-evaluate the properties of sphingolipid domains.

    Science.gov (United States)

    Pinto, Sandra N; Fernandes, Fábio; Fedorov, Alexander; Futerman, Anthony H; Silva, Liana C; Prieto, Manuel

    2013-09-01

    The aim of this study is to provide further insight about the interplay between important signaling lipids and to characterize the properties of the lipid domains formed by those lipids in membranes containing distinct composition. To this end, we have used a combination of fluorescence spectroscopy, confocal and two-photon microscopy and a stepwise approach to re-evaluate the biophysical properties of sphingolipid domains, particularly lipid rafts and ceramide (Cer)-platforms. By using this strategy we were able to show that, in binary mixtures, sphingolipids (Cer and sphingomyelin, SM) form more tightly packed gel domains than those formed by phospholipids with similar acyl chain length. In more complex lipid mixtures, the interaction between the different lipids is intricate and is strongly dictated by the Cer-to-Chol ratio. The results show that in quaternary phospholipid/SM/Chol/Cer mixtures, Cer forms gel domains that become less packed as Chol is increased. Moreover, the extent of gel phase formation is strongly reduced in these mixtures, even though Cer molar fraction is increased. These results suggest that in biological membranes, lipid domains such as rafts and ceramide platforms, might display distinctive biophysical properties depending on the local lipid composition at the site of the membrane where they are formed, further highlighting the potential role of membrane biophysical properties as an underlying mechanism for mediating specific biological processes. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Extensive sphingolipid depletion does not affect lipid raft integrity or lipid raft localization and efflux function of the ABC transporter MRP1

    NARCIS (Netherlands)

    Klappe, Karin; Dijkhuis, Anne-Jan; Hummel, Ina; van Dam, Annie; Ivanova, Pavlina T.; Milne, Stephen B.; Myers, David S.; Brown, H. Alex; Permentier, Hjalmar; Kok, Jan W.

    2010-01-01

    We show that highly efficient depletion of sphingolipids in two different cell lines does not abrogate the ability to isolate Lubrol-based DRMs (detergent-resistant membranes) or detergent-free lipid rafts from these cells. Compared with control, DRM/detergent-free lipid raft fractions contain equal

  2. Microwave circulator design

    CERN Document Server

    Linkhart, Douglas K

    2014-01-01

    Circulator design has advanced significantly since the first edition of this book was published 25 years ago. The objective of this second edition is to present theory, information, and design procedures that will enable microwave engineers and technicians to design and build circulators successfully. This resource contains a discussion of the various units used in the circulator design computations, as well as covers the theory of operation. This book presents numerous applications, giving microwave engineers new ideas about how to solve problems using circulators. Design examples are provided, which demonstrate how to apply the information to real-world design tasks.

  3. Vascular Endothelial Growth Factor (VEGF) mRNA Isoforms are Altered in Bovine Granulosa Cells (GC) by Circulating Progestin Concentrations (P4) and May Indicate Follicle Status and Oocyte Competence

    Science.gov (United States)

    Previously, Melengestrol Acetate (MGA) fed for 14 d (0.5mg/cow/d; < 1 ng/ml P4) resulted in persistent follicles with increased size, decreased number of GC/follicular fluid (FF) volume, and less fertile oocytes. An experiment was conducted to determine effects of circulating P4 on amount of mRNA fo...

  4. Circulation pump mounting

    International Nuclear Information System (INIS)

    Skalicky, A.

    1976-01-01

    The suspension is described of nuclear reactor circulating pumps enabling their dilatation with a minimum reverse force consisting of spacing rods supported with one end in the anchor joints and provided with springs and screw joints engaging the circulating pump shoes. The spacing rods are equipped with side vibration dampers anchored in the shaft side wall and on the body of the circulating pump drive body. The negative reverse force F of the spacing rods is given by the relation F=Q/l.y, where Q is the weight of the circulating pump, l is the spatial distance between the shoe joints and anchor joints, and y is the deflection of the circulating pump vertical axis from the mean equilibrium position. The described suspension is advantageous in that that the reverse force for the deflection from the mean equilibrium position is minimal, dynamic behaviour is better, and construction costs are lower compared to suspension design used so far. (J.B.)

  5. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    KAUST Repository

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Lawrence J.; Bower, Amy S.; Kö hl, Armin; Gopalakrishnan, Ganesh; Rivas, David

    2014-01-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented

  6. 19q13.12 microdeletion syndrome fibroblasts display abnormal storage of cholesterol and sphingolipids in the endo-lysosomal system.

    Science.gov (United States)

    Zhao, Kexin; van der Spoel, Aarnoud; Castiglioni, Claudia; Gale, Sarah; Fujiwara, Hideji; Ory, Daniel S; Ridgway, Neale D

    2018-06-01

    Microdeletions in 19q12q13.12 cause a rare and complex haploinsufficiency syndrome characterized by intellectual deficiency, developmental delays, and neurological movement disorders. Variability in the size and interval of the deletions makes it difficult to attribute the complex clinical phenotype of this syndrome to an underlying gene(s). As an alternate approach, we examined the biochemical and metabolic features of fibroblasts from an affected individual to derive clues as to the molecular basis for the syndrome. Immunofluorescence and electron microscopy of affected fibroblasts revealed an abnormal endo-lysosomal compartment that was characterized by rapid accumulation of lysosomotropic dyes, elevated LAMP1 and LAMP2 expression and vacuoles containing membrane whorls, common features of lysosomal lipid storage disorders. The late endosomes-lysosomes (LE/LY) of affected fibroblasts accumulated low-density lipoprotein cholesterol, and displayed reduced cholesterol esterification and increased de novo cholesterol synthesis, indicative of defective cholesterol transport to the endoplasmic reticulum. Affected fibroblasts also had increased ceramide and sphingolipid mass, altered glycosphingolipid species and accumulation of a fluorescent lactosylceramide probe in LE/LY. Autophagosomes also accumulated in affected fibroblasts because of decreased fusion with autolysosomes, a defect associated with other lysosomal storage diseases. Attempts to correct the cholesterol/sphingolipid storage defect in fibroblasts with cyclodextrin, sphingolipid synthesis inhibitors or by altering ion transport were unsuccessful. Our data show that 19q13.12 deletion fibroblasts have abnormal accumulation of cholesterol and sphingolipids in the endo-lysosomal system that compromises organelle function and could be an underlying cause of the clinical features of the syndrome. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Combining chemical genomics screens in yeast to reveal spectrum of effects of chemical inhibition of sphingolipid biosynthesis

    Directory of Open Access Journals (Sweden)

    Giaever Guri

    2009-01-01

    Full Text Available Abstract Background Single genome-wide screens for the effect of altered gene dosage on drug sensitivity in the model organism Saccharomyces cerevisiae provide only a partial picture of the mechanism of action of a drug. Results Using the example of the tumor cell invasion inhibitor dihydromotuporamine C, we show that a more complete picture of drug action can be obtained by combining different chemical genomics approaches – analysis of the sensitivity of ρ0 cells lacking mitochondrial DNA, drug-induced haploinsufficiency, suppression of drug sensitivity by gene overexpression and chemical-genetic synthetic lethality screening using strains deleted of nonessential genes. Killing of yeast by this chemical requires a functional mitochondrial electron-transport chain and cytochrome c heme lyase function. However, we find that it does not require genes associated with programmed cell death in yeast. The chemical also inhibits endocytosis and intracellular vesicle trafficking and interferes with vacuolar acidification in yeast and in human cancer cells. These effects can all be ascribed to inhibition of sphingolipid biosynthesis by dihydromotuporamine C. Conclusion Despite their similar conceptual basis, namely altering drug sensitivity by modifying gene dosage, each of the screening approaches provided a distinct set of information that, when integrated, revealed a more complete picture of the mechanism of action of a drug on cells.

  8. Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.

    Science.gov (United States)

    Saroha, Ashish; Pewzner-Jung, Yael; Ferreira, Natalia S; Sharma, Piyush; Jouan, Youenn; Kelly, Samuel L; Feldmesser, Ester; Merrill, Alfred H; Trottein, François; Paget, Christophe; Lang, Karl S; Futerman, Anthony H

    2017-01-01

    The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T ( i NKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of i NKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of i NKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for i NKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in i NKT cell physiology.

  9. Membrane organization determines barrier properties of endothelial cells and short-chain sphingolipid-facilitated doxorubicin influx.

    Science.gov (United States)

    van Hell, A J; Klymchenko, A; Gueth, D M; van Blitterswijk, W J; Koning, G A; Verheij, M

    2014-09-01

    The endothelial lining and its outer lipid membrane are the first major barriers drug molecules encounter upon intravenous administration. Our previous work identified lipid analogs that counteract plasma membrane barrier function for a series of amphiphilic drugs. For example, short-chain sphingolipids (SCS), like N-octanoyl-glucosylceramide, effectively elevated doxorubicin accumulation in tumor cells, both in vitro and in vivo, and in endothelial cells, whereas other (normal) cells remained unaffected. We hypothesize here that local membrane lipid composition and the degree of lipid ordering define SCS efficacy in individual cells. To this end, we study the differential effect of SCS on bovine aortic endothelial cells (BAEC) in its confluent versus proliferative state, as a model system. While their (plasma membrane) lipidome stays remarkably unaltered when BAECs reach confluency, their lipids segregate to form apical and basolateral domains. Using probe NR12S, we reveal that lipids in the apical membrane are more condensed/liquid-ordered. SCS preferentially attenuate the barrier posed by these condensed membranes and facilitate doxorubicin influx in these particular membrane regions. We confirm these findings in MDCK cells and artificial membranes. In conclusion, SCS-facilitated drug traversal acts on condensed membrane domains, elicited by confluency in resting endothelium. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. A hybrid mathematical modeling approach of the metabolic fate of a fluorescent sphingolipid analogue to predict cancer chemosensitivity.

    Science.gov (United States)

    Molina-Mora, J A; Kop-Montero, M; Quirós-Fernández, I; Quiros, S; Crespo-Mariño, J L; Mora-Rodríguez, R A

    2018-04-13

    Sphingolipid (SL) metabolism is a complex biological system that produces and transforms ceramides and other molecules able to modulate other cellular processes, including survival or death pathways key to cell fate decisions. This signaling pathway integrates several types of stress signals, including chemotherapy, into changes in the activity of its metabolic enzymes, altering thereby the cellular composition of bioactive SLs. Therefore, the SL pathway is a promising sensor of chemosensitivity in cancer and a target hub to overcome resistance. However, there is still a gap in our understanding of how chemotherapeutic drugs can disturb the SL pathway in order to control cellular fate. We propose to bridge this gap by a systems biology approach to integrate i) a dynamic model of SL analogue (BODIPY-FL fluorescent-sphingomyelin analogue, SM-BOD) metabolism, ii) a Gaussian mixture model (GMM) of the fluorescence features to identify how the SL pathway senses the effect of chemotherapy and iii) a fuzzy logic model (FLM) to associate SL composition with cell viability by semi-quantitative rules. Altogether, this hybrid model approach was able to predict the cell viability of double experimental perturbations with chemotherapy, indicating that the SL pathway is a promising sensor to design strategies to overcome drug resistance in cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication.

    Directory of Open Access Journals (Sweden)

    Anahí Capmany

    2010-11-01

    Full Text Available Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.

  12. Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication.

    Science.gov (United States)

    Capmany, Anahí; Damiani, María Teresa

    2010-11-22

    Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.

  13. Circulating sex hormones and breast cancer risk factors in postmenopausal women : reanalysis of 13 studies

    NARCIS (Netherlands)

    Key, T. J.; Appleby, P. N.; Reeves, G. K.; Roddam, A. W.; Helzlsouer, K. J.; Alberg, A. J.; Rollison, D. E.; Dorgan, J. F.; Brinton, L. A.; Overvad, K.; Kaaks, R.; Trichopoulou, A.; Clavel-Chapelon, F.; Panico, S.; Duell, E. J.; Peeters, P. H. M.; Rinaldi, S.; Riboli, E.; Fentiman, I. S.; Dowsett, M.; Manjer, J.; Lenner, P.; Hallmans, G.; Baglietto, L.; English, D. R.; Giles, G. G.; Hopper, J. L.; Severi, G.; Morris, H. A.; Koenig, K.; Zeleniuch-Jacquotte, A.; Arslan, A. A.; Toniolo, P.; Shore, R. E.; Krogh, V.; Micheli, A.; Berrino, F.; Muti, P.; Barrett-Connor, E.; Laughlin, G. A.; Kabuto, M.; Akiba, S.; Stevens, R. G.; Neriishi, K.; Land, C. E.; Cauley, J. A.; Lui, Li Yung; Cummings, Steven R.; Gunter, M. J.; Rohan, T. E.

    2011-01-01

    BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone

  14. Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

    International Nuclear Information System (INIS)

    Kamendi, Harriet; Zhou, Ying; Crosby, Meredith; Keirstead, Natalie; Snow, Debra; Bentley, Patricia; Patel, Nilaben; Barthlow, Herbert; Luo, Wenli; Dragan, Yvonne; Bialecki, Russell

    2015-01-01

    Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalized by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.

  15. Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kamendi, Harriet, E-mail: harriet_kamendi@kandih.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Zhou, Ying, E-mail: yingzhou526@gmail.com [Oncology Innovative Medicines and Early Development, AstraZeneca, Waltham, MA 02451 (United States); Crosby, Meredith, E-mail: Meredith.crosby@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Keirstead, Natalie, E-mail: Nkeirstead@alnylam.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Snow, Debra, E-mail: Debra.snow@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Bentley, Patricia, E-mail: patricia.bentley@abbvie.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Patel, Nilaben, E-mail: patelnilaben@yahoo.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Barthlow, Herbert, E-mail: Herbert.barthlow@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Luo, Wenli, E-mail: Wenli.luo@astrazeneca.com [Discovery Sciences, Innovative Medicines, AstraZeneca, Waltham, MA 02451 (United States); Dragan, Yvonne, E-mail: Yvonne.P.Dragan@takeda.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Bialecki, Russell, E-mail: russell.bialecki@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States)

    2015-12-15

    Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalized by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.

  16. Inflammatory reactions in placental blood of Plasmodium falciparum-infected women and high concentrations of soluble E-selectin and a circulating P. falciparum protein in the cord sera

    DEFF Research Database (Denmark)

    Jakobsen, P H; Rasheed, F N; Bulmer, J N

    1998-01-01

    concentrations measured in the placenta. Markers of inflammatory reactions: IL-10, sIL-2R, sIL-4R, and soluble tumour necrosis factor receptor I (sTNF-RI) were found in high concentrations in the placenta, indicating that inflammatory reactions take place in the placenta which has been regarded...... as an immunoprivileged site. Concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intracellular adhesion molecule-1 (sICAM-1), potential adhesion receptors for malaria parasites, were associated with an active P. falciparum infection in the placenta although the associations did not reach...

  17. Arctic circulation regimes.

    Science.gov (United States)

    Proshutinsky, Andrey; Dukhovskoy, Dmitry; Timmermans, Mary-Louise; Krishfield, Richard; Bamber, Jonathan L

    2015-10-13

    Between 1948 and 1996, mean annual environmental parameters in the Arctic experienced a well-pronounced decadal variability with two basic circulation patterns: cyclonic and anticyclonic alternating at 5 to 7 year intervals. During cyclonic regimes, low sea-level atmospheric pressure (SLP) dominated over the Arctic Ocean driving sea ice and the upper ocean counterclockwise; the Arctic atmosphere was relatively warm and humid, and freshwater flux from the Arctic Ocean towards the subarctic seas was intensified. By contrast, during anticylonic circulation regimes, high SLP dominated driving sea ice and the upper ocean clockwise. Meanwhile, the atmosphere was cold and dry and the freshwater flux from the Arctic to the subarctic seas was reduced. Since 1997, however, the Arctic system has been under the influence of an anticyclonic circulation regime (17 years) with a set of environmental parameters that are atypical for this regime. We discuss a hypothesis explaining the causes and mechanisms regulating the intensity and duration of Arctic circulation regimes, and speculate how changes in freshwater fluxes from the Arctic Ocean and Greenland impact environmental conditions and interrupt their decadal variability. © 2015 The Authors.

  18. Flow and separation in gas centrifuge with Beams type circulation

    International Nuclear Information System (INIS)

    Ajsen, Eh.M.; Borisevich, V.D.; Levin, E.V.

    1992-01-01

    Structure of the secondary circulation flows in the working chamber of gas centrifuge for uranium isotope separation is studied using the numerical methods. Influence of the circulation thermal component on the centrifuge efficiency is analyzed. The contribution of useful component concentration difference of binary isotope mixture in feeding flows to the centrifuge efficiency is determined. Dependence of concentration optimal difference, whereby the maximum efficiency is achieved, on temperature distribution on the rotor side wall is found

  19. Controlled humidity gas circulators

    International Nuclear Information System (INIS)

    Gruner, S.M.

    1981-01-01

    A programmable circulator capable of regulating the humidity of a gas stream over a wide range of humidity is described. An optical dew-point hygrometer is used as a feedback element to control the addition or removal of water vapor. Typical regulation of the gas is to a dew-point temperature of +- 0.2 0 C and to an accuracy limited by the dew-point hygrometer

  20. Fluid circulation control device

    International Nuclear Information System (INIS)

    Benard, Henri; Henocque, Jean.

    1982-01-01

    Horizontal fluid circulation control device, of the type having a pivoting flap. This device is intended for being fitted in the pipes of hydraulic installation, particularly in a bleed and venting system of a nuclear power station shifting radioactive or contaminated liquids. The characteristic of this device is the cut-out at the top of the flap to allow the air contained in the pipes to flow freely [fr

  1. Arabidopsis dynamin-related protein 1E in sphingolipid-enriched plasma membrane domains is associated with the development of freezing tolerance.

    Science.gov (United States)

    Minami, Anzu; Tominaga, Yoko; Furuto, Akari; Kondo, Mariko; Kawamura, Yukio; Uemura, Matsuo

    2015-08-01

    The freezing tolerance of Arabidopsis thaliana is enhanced by cold acclimation, resulting in changes in the compositions and function of the plasma membrane. Here, we show that a dynamin-related protein 1E (DRP1E), which is thought to function in the vesicle trafficking pathway in cells, is related to an increase in freezing tolerance during cold acclimation. DRP1E accumulated in sphingolipid and sterol-enriched plasma membrane domains after cold acclimation. Analysis of drp1e mutants clearly showed that DRP1E is required for full development of freezing tolerance after cold acclimation. DRP1E fused with green fluorescent protein was visible as small foci that overlapped with fluorescent dye-labelled plasma membrane, providing evidence that DRP1E localizes non-uniformly in specific areas of the plasma membrane. These results suggest that DRP1E accumulates in sphingolipid and sterol-enriched plasma membrane domains and plays a role in freezing tolerance development during cold acclimation. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  2. Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites.

    Science.gov (United States)

    Mina, John G; Thye, Julie K; Alqaisi, Amjed Q I; Bird, Louise E; Dods, Robert H; Grøftehauge, Morten K; Mosely, Jackie A; Pratt, Steven; Shams-Eldin, Hosam; Schwarz, Ralph T; Pohl, Ehmke; Denny, Paul W

    2017-07-21

    Toxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause fetal damage and abortion in both animals and humans. Sphingolipids are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Here we report the identification, isolation, and analyses of the Toxoplasma serine palmitoyltransferase, an enzyme catalyzing the first and rate-limiting step in sphingolipid biosynthesis: the condensation of serine and palmitoyl-CoA. In all eukaryotes analyzed to date, serine palmitoyltransferase is a highly conserved heterodimeric enzyme complex. However, biochemical and structural analyses demonstrated the apicomplexan orthologue to be a functional, homodimeric serine palmitoyltransferase localized to the endoplasmic reticulum. Furthermore, phylogenetic studies indicated that it was evolutionarily related to the prokaryotic serine palmitoyltransferase, identified in the Sphingomonadaceae as a soluble homodimeric enzyme. Therefore this enzyme, conserved throughout the Apicomplexa, is likely to have been obtained via lateral gene transfer from a prokaryote. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. The effect of the bioactive sphingolipids S1P and C1P on multipotent stromal cells--new opportunities in regenerative medicine.

    Science.gov (United States)

    Marycz, Krzysztof; Śmieszek, Agnieszka; Jeleń, Marta; Chrząstek, Klaudia; Grzesiak, Jakub; Meissner, Justyna

    2015-09-01

    Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) belong to a family of bioactive sphingolipids that act as important extracellular signaling molecules and chemoattractants. This study investigated the influence of S1P and C1P on the morphology, proliferation activity and osteogenic properties of rat multipotent stromal cells derived from bone marrow (BMSCs) and subcutaneous adipose tissue (ASCs). We show that S1P and C1P can influence mesenchymal stem cells (MSCs), each in a different manner. S1P stimulation promoted the formation of cellular aggregates of BMSCs and ASCs, while C1P had an effect on the regular growth pattern and expanded intercellular connections, thereby increasing the proliferative activity. Although osteogenic differentiation of MSCs was enhanced by the addition of S1P, the effectiveness of osteoblast differentiation was more evident in BMSCs, particularly when biochemical and molecular marker levels were considered. The results of the functional osteogenic differentiation assay, which includes an evaluation of the efficiency of extracellular matrix mineralization (SEM-EDX), revealed the formation of numerous mineral aggregates in BMSC cultures stimulated with S1P. Our data demonstrated that in an appropriate combination, the bioactive sphingolipids S1P and C1P may find wide application in regenerative medicine, particularly in bone regeneration with the use of MSCs.

  4. The relationship of maternal characteristics and circulating progesterone concentrations with reproductive outcome in the bottlenose dolphin (Tursiops truncatus) after artificial insemination, with and without ovulation induction, and natural breeding.

    Science.gov (United States)

    O'Brien, J K; Robeck, T R

    2012-08-01

    Bottlenose dolphins (Tursiops truncatus) undergoing natural breeding and artificial insemination (AI) were examined to characterize serum progesterone concentrations and determine relationships among age, parity, and reproductive outcome. Progesterone profiles of five cycle types (n = 119 total cycles from 54 animals) were characterized as follows: (i) conception and production of a live term calf (conceptive-term, n = 73); (ii) conception and abortion after Day 60 (conceptive-abortion, n = 12); (iii) unknown conception status with prolonged, elevated progesterone and absence of a fetus (conceptive-unknown, n = 14); (iv) conception failure with normal luteal phase progesterone concentrations (non-conceptive, n = 14, AI cycles only); and (v) conception failure with progesterone insufficiency occuring after spontaneous ovulation or owing to premature ovulation induction using GnRH (non-conceptive-PI, n = 6, AI cycles only). By Day 21 post-insemination (PI), progesterone concentrations were similar (P > 0.05) among conceptive-term, conceptive-abortion and conceptive-unknown, and higher (P 0.05) progesterone concentrations than conceptive-abortion and unknown conception status cycles. Parity was not associated with reproductive outcome based on cycle type (P > 0.05). Age of females in conceptive-unknown (26.5 ± 10.1 yrs) and conceptive-abortion (22.1 ± 9.4 yrs) groups was higher (P < 0.05) than in conceptive-term (15.7 ± 7.2 yrs). The conceptive-unknown cycle type possibly represents undetected early embryonic loss occurring before Day 60 PI. Length of gestation using known conception dates was 376.1 ± 11.0 days and the range of this parameter (355-395 days) has implications for peri-parturient management procedures for the species. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Exercise increases circulating GDF15 in humans

    DEFF Research Database (Denmark)

    Kleinert, Maximilian; Clemmensen, Christoffer; Sjøberg, Kim Anker

    2018-01-01

    OBJECTIVE: The growth differentiation factor 15 (GDF15) is a stress-sensitive circulating factor that regulates systemic energy balance. Since exercise is a transient physiological stress that has pleiotropic effects on whole-body energy metabolism, we herein explored the effect of exercise on a......) circulating GDF15 levels and b) GDF15 release from skeletal muscle in humans. METHODS: Seven healthy males either rested or exercised at 67% of their VO2max for 1 h and blood was sampled from the femoral artery and femoral vein before, during, and after exercise. Plasma GDF15 concentrations were determined...... in these samples. RESULTS: Plasma GDF15 levels increased 34% with exercise (p exercise. There was no difference between the arterial and venous GDF15 concentration before, during, and after exercise. During...

  6. Correlates of Circulating 25-Hydroxyvitamin D

    OpenAIRE

    McCullough, Marjorie L.; Weinstein, Stephanie J.; Freedman, D. Michal; Helzlsouer, Kathy; Flanders, W. Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong

    2010-01-01

    Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geogra...

  7. Cutaneous water loss and sphingolipids in the stratum corneum of house sparrows, Passer domesticus L., from desert and mesic environments as determined by reversed phase high-performance liquid chromatography coupled with atmospheric pressure photospray ionization mass spectrometry.

    Science.gov (United States)

    Muñoz-Garcia, Agustí; Ro, Jennifer; Brown, Johnie C; Williams, Joseph B

    2008-02-01

    Because cutaneous water loss (CWL) represents half of total water loss in birds, selection to reduce CWL may be strong in desert birds. We previously found that CWL of house sparrows from a desert population was about 25% lower than that of individuals from a mesic environment. The stratum corneum (SC), the outer layer of the epidermis, serves as the primary barrier to water vapor diffusion through the skin. The avian SC is formed by layers of corneocytes embedded in a lipid matrix consisting of cholesterol, free fatty acids and two classes of sphingolipids, ceramides and cerebrosides. The SC of birds also serves a thermoregulatory function; high rates of CWL keep body temperatures under lethal limits in episodes of heat stress. In this study, we used high-performance liquid chromatography coupled with atmospheric pressure photoionization-mass spectrometry (HPLC/APPI-MS) to identify and quantify over 200 sphingolipids in the SC of house sparrows from desert and mesic populations. Principal components analysis (PCA) led to the hypotheses that sphingolipids in the SC of desert sparrows have longer carbon chains in the fatty acid moiety and are more polar than those found in mesic sparrows. We also tested the association between principal components and CWL in both populations. Our study suggested that a reduction in CWL found in desert sparrows was, in part, the result of modifications in chain length and polarity of the sphingolipids, changes that apparently determine the interactions of the lipid molecules within the SC.

  8. Radiology of liver circulation

    International Nuclear Information System (INIS)

    Hermine, C.L.

    1985-01-01

    This book proposes that careful evaluation of the arterioportogram is the cornerstone in assessing portal flow obstruction, being the most consistent of all observations including liver histology, portal venous pressure, size and number of portosystemic collaterals, and wedged hepatic venous pressure. Very brief chapters cover normal hepatic circulation and angiographic methods. Contrast volumes and flow rates for celiac, hepatic, and superior mesenteric injection are given, with the timing for venous phase radiographs. In the main body of the text, portal obstruction is divided very simply into presinusoidal (all proximal causes) and postsinusoidal (all distal causes, including Budd-Chiari). Changes are discussed regarding the splenic artery and spleen; hepatic artery and its branches; portal flow rate and direction; and arterioportal shunting and portosystemic collateral circulation in minimal, moderate, severe, and very severe portal obstruction and in recognizable entities such as prehepatic portal and hepatic venous obstructions. The major emphasis in this section is the recognition and understanding of flow changes by which level and severity of obstruction are assessed (not simply the anatomy of portosystemic collateral venous flow). Excellent final chapters discuss the question of portal hypertension without obstruction, and the contribution of arterioportography to the treatment of portal hypertension, again with an emphasis on hemodynamics before and after shunt surgery. There is a fascinating final chapter on segmental intrahepatic obstruction without portal hypertension that explains much of the unusual contrast enhancement sometimes seen in CT scanning of hepatic mass lesions

  9. Ocean bio-geophysical modeling using mixed layer-isopycnal general circulation model coupled with photosynthesis process

    Digital Repository Service at National Institute of Oceanography (India)

    Nakamoto, S.; Saito, H.; Muneyama, K.; Sato, T.; PrasannaKumar, S.; Kumar, A.; Frouin, R.

    -chemical system that supports steady carbon circulation in geological time scale in the world ocean using Mixed Layer-Isopycnal ocean General Circulation model with remotely sensed Coastal Zone Color Scanner (CZCS) chlorophyll pigment concentration....

  10. A novel NMR-based assay to measure circulating concentrations of branched-chain amino acids: Elevation in subjects with type 2 diabetes mellitus and association with carotid intima media thickness.

    Science.gov (United States)

    Wolak-Dinsmore, Justyna; Gruppen, Eke G; Shalaurova, Irina; Matyus, Steven P; Grant, Russell P; Gegen, Ray; Bakker, Stephan J L; Otvos, James D; Connelly, Margery A; Dullaart, Robin P F

    2018-04-01

    Plasma branched-chain amino acid (BCAA) levels, measured on nuclear magnetic resonance (NMR) metabolomics research platforms or by mass spectrometry, have been shown to be associated with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). We developed a new test for quantification of BCAA on a clinical NMR analyzer and used this test to determine the clinical correlates of BCAA in 2 independent cohorts. The performance of the NMR-based BCAA assay was evaluated. A method comparison study was performed with mass spectrometry (LC-MS/MS). Plasma BCAA were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1209; 376 T2DM subjects) and in a Groningen cohort (n = 123; 67 T2DM subjects). In addition, carotid intima media thickness (cIMT) was measured successfully in 119 subjects from the Groningen cohort. NMR-based BCAA assay results were linear over a range of concentrations. Coefficients of variation for inter- and intra-assay precision ranged from 1.8-6.0, 1.7-5.4, 4.4-9.1, and 8.8-21.3%, for total BCAA, valine, leucine, and isoleucine, respectively. BCAA quantified from the same samples using NMR and LC-MS/MS were highly correlated (R 2  = 0.97, 0.95 and 0.90 for valine, leucine and isoleucine). In both cohorts total and individual BCAA were elevated in T2DM (P = 0.01 to ≤0.001). Moreover, cIMT was associated with BCAA independent of age, sex, T2DM and metabolic syndrome (MetS) categorization or alternatively of individual MetS components. BCAA levels, measured by NMR in the clinical laboratory, are elevated in T2DM and may be associated with cIMT, a proxy of subclinical atherosclerosis. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Anti-cyclonic circulation driven by the estuarine circulation in a gulf type ROFI

    Science.gov (United States)

    Fujiwara, T.; Sanford, L. P.; Nakatsuji, K.; Sugiyama, Y.

    1997-08-01

    Baroclinic residual circulation processes are examined in gulf type Regions Of Freshwater Influence (ROFIs), which have large rivers discharging into a rounded head wider than the Rossby internal deformation radius. Theoretical and observational investigations concentrate on Ise Bay, Japan, with supporting data from Osaka Bay and Tokyo Bay. Simplified analytical solutions are derived to describe the primary features of the circulation. Three dimensional residual current data collected using moored current meters and shipboard acoustic doppler current profilers (ADCPs), satellite imagery and density structure data observed using STDs, are presented for comparison to the theoretical predictions. There are three key points to understanding the resulting circulation in gulf type ROFIs. First, there are likely to be three distinct water masses: the river plume, a brackish upper layer, and a higher salinity lower layer. Second, baroclinic processes in gulf type ROFIs are influenced by the Earth's rotation at first order. Residual currents are quasi-geostrophic and potential vorticity is approximately conserved. Third, the combined effects of a classical longitudinal estuarine circulation and the Earth's rotation are both necessary to produce the resulting circulation. Anti-cyclonic vorticity is generated in the upper layer by the horizontal divergence associated with upward entrainment, which is part of the estuarine circulation. The interaction between anti-cyclonic vorticity and horizontal divergence results in two regions of qualitatively different circulation, with gyre-like circulation near the bay head and uniformly seaward anti-cyclonicly sheared flow further towards the mouth. The stagnation point separating the two regions is closer to (further away from) the bay head for stronger (weaker) horizontal divergence, respectively. The vorticity and spin-up time of this circulation are-(ƒ-ω 1)/2 and h/2w 0, respectively, where ƒ is the Coriolis parameter, ω 1 is

  12. Circulation Systems Past and Present

    Directory of Open Access Journals (Sweden)

    Maurice J. Freedman

    1981-01-01

    Full Text Available A review of the development of circulation systems shows two areas of change. The librarian's perception of circulation control has shifted from a broad service orientation to a narrow record-keeping approach and recently back again. The technological development of circulation sys-tems has evolved from manual systems to the online systems of today. The trade-offs and deficiencies of earlier systems in relation to the comprehensive services made possible by the online computer are detailed.

  13. The ocean circulation inverse problem

    National Research Council Canada - National Science Library

    Wunsch, C

    1996-01-01

    .... This book addresses the problem of inferring the state of the ocean circulation, understanding it dynamically, and even forecasting it through a quantitative combination of theory and observation...

  14. Exercise increases circulating GDF15 in humans

    Directory of Open Access Journals (Sweden)

    Maximilian Kleinert

    2018-03-01

    Full Text Available Objective: The growth differentiation factor 15 (GDF15 is a stress-sensitive circulating factor that regulates systemic energy balance. Since exercise is a transient physiological stress that has pleiotropic effects on whole-body energy metabolism, we herein explored the effect of exercise on a circulating GDF15 levels and b GDF15 release from skeletal muscle in humans. Methods: Seven healthy males either rested or exercised at 67% of their VO2max for 1 h and blood was sampled from the femoral artery and femoral vein before, during, and after exercise. Plasma GDF15 concentrations were determined in these samples. Results: Plasma GDF15 levels increased 34% with exercise (p < 0.001 and further increased to 64% above resting values at 120 min (p < 0.001 after the cessation of exercise. There was no difference between the arterial and venous GDF15 concentration before, during, and after exercise. During a resting control trial, GDF15 levels measured in the same subjects were unaltered. Conclusions: Vigorous submaximal exercise increases circulating GDF15 levels in humans, but skeletal muscle tissue does not appear to be the source. Keywords: Skeletal muscle, Growth differentiation factor 15, Recovery, Physical activity

  15. Genetic Variants Associated with Circulating Parathyroid Hormone.

    Science.gov (United States)

    Robinson-Cohen, Cassianne; Lutsey, Pamela L; Kleber, Marcus E; Nielson, Carrie M; Mitchell, Braxton D; Bis, Joshua C; Eny, Karen M; Portas, Laura; Eriksson, Joel; Lorentzon, Mattias; Koller, Daniel L; Milaneschi, Yuri; Teumer, Alexander; Pilz, Stefan; Nethander, Maria; Selvin, Elizabeth; Tang, Weihong; Weng, Lu-Chen; Wong, Hoi Suen; Lai, Dongbing; Peacock, Munro; Hannemann, Anke; Völker, Uwe; Homuth, Georg; Nauk, Matthias; Murgia, Federico; Pattee, Jack W; Orwoll, Eric; Zmuda, Joseph M; Riancho, Jose Antonio; Wolf, Myles; Williams, Frances; Penninx, Brenda; Econs, Michael J; Ryan, Kathleen A; Ohlsson, Claes; Paterson, Andrew D; Psaty, Bruce M; Siscovick, David S; Rotter, Jerome I; Pirastu, Mario; Streeten, Elizabeth; März, Winfried; Fox, Caroline; Coresh, Josef; Wallaschofski, Henri; Pankow, James S; de Boer, Ian H; Kestenbaum, Bryan

    2017-05-01

    Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies ( n =22,653 and n =6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 ( P =4.2 × 10 -53 ), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 ( P =6.6 × 10 -17 ), rs219779 adjacent to CLDN14 ( P =3.5 × 10 -16 ), rs4443100 near RTDR1 ( P =8.7 × 10 -9 ), and rs73186030 near CASR ( P =4.8 × 10 -8 ). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued. Copyright © 2017 by the American Society of Nephrology.

  16. Genetic architecture of circulating lipid levels

    DEFF Research Database (Denmark)

    Demirkan, Ayşe; Amin, Najaf; Isaacs, Aaron

    2011-01-01

    Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid...... the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify...... an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models...

  17. Seawater bicarbonate removal during hydrothermal circulation

    Science.gov (United States)

    Proskurowski, G. K.; Seewald, J.; Sylva, S. P.; Reeves, E.; Lilley, M. D.

    2013-12-01

    High temperature fluids sampled at hydrothermal vents represent a complex alteration product of water-rock reactions on a multi-component mixture of source fluids. Sources to high-temperature hydrothermal samples include the 'original' seawater present in the recharge limb of circulation, magmatically influenced fluids added at depth as well as any seawater entrained during sampling. High-temperature hydrothermal fluids are typically enriched in magmatic volatiles, with CO2 the dominant species, characterized by concentrations of 10's-100's of mmol/kg (1, 2). Typically, the high concentration of CO2 relative to background seawater bicarbonate concentrations (~2.3 mmol/kg) obscures a full analysis of the fate of seawater bicarbonate during high-temperature hydrothermal circulation. Here we present data from a suite of samples collected over the past 15 years from high-temperature hydrothermal vents at 9N, Endeavour, Lau Basin, and the MAR that have endmember CO2 concentrations less than 10 mmol/kg. Using stable and radiocarbon isotope measurements these samples provide a unique opportunity to examine the balance between 'original' seawater bicarbonate and CO2 added from magmatic sources. Multiple lines of evidence from multiple hydrothermal settings consistently points to the removal of ~80% of the 'original' 2.3 mmol/kg seawater bicarbonate. Assuming that this removal occurs in the low-temperature, 'recharge' limb of hydrothermal circulation, this removal process is widely occurring and has important contributions to the global carbon cycle over geologic time. 1. Lilley MD, Butterfield DA, Lupton JE, & Olson EJ (2003) Magmatic events can produce rapid changes in hydrothermal vent chemistry. Nature 422(6934):878-881. 2. Seewald J, Cruse A, & Saccocia P (2003) Aqueous volatiles in hydrothermal fluids from the Main Endeavour Field, northern Juan de Fuca Ridge: temporal variability following earthquake activity. Earth and Planetary Science Letters 216(4):575-590.

  18. Sino-Danish Brain Circulation

    DEFF Research Database (Denmark)

    Bertelsen, Rasmus Gjedssø; Du, Xiangyun; Søndergaard, Morten Karnøe

    2014-01-01

    China is faced with urgent needs to develop an economically and environmentally sustainable economy based on innovation and knowledge. Brain circulation and research and business investments from the outside are central for this development. Sino-American brain circulation and research...... and investment by overseas researchers and entrepreneurs are well described. In that case, the US is the center of global R&D and S&T. However, the brain circulation and research and investments between a small open Scandinavian economy, such as Denmark, and the huge developing economy of China are not well...... understood. In this case, Denmark is very highly developed, but a satellite in the global R&D and S&T system. With time and the growth of China as a R&D and S&T power house, both Denmark and China will benefit from brain circulation between them. Such brain circulation is likely to play a key role in flows...

  19. Normothermal or Hypothermal Extracorporeal Circulation Regimens in Patients with Acquired Heart Disease

    Directory of Open Access Journals (Sweden)

    V. V. Lomivorotov

    2013-01-01

    Full Text Available Background. Hypothermal extracorporeal circulation has been used in cardiosurgery over 50 years. However, recent trials have not shown its predominant effect on the protection of the brain, lung, and myocardium in patients during surgery. We have presumed that when normothermal extracorporeal circulation used in patients with acquired heart disease, its pathophysiological effect on the body is comparable with that of hypothermal extracorporeal circulation. Subjects and methods. One hundred and forty patients who were to undergo acquired heart disease correction were randomized into two equal groups: that using hypothermal or normothermal extracorporeal circulation. Perioperative troponin I and NT-proBNP concentrations, postoperative clinical course, and hospital morbidity and mortality rates were estimated. Results. There were no significant differences in the concentrations of troponin I and NT-proBNP at the study stages. In the normothermal extracorporeal circulation group patients with isolated aortic stenosis, the concentration of troponin I was higher than that in the hypothermal extracorporeal circulation group. Analyzing the postoperative course indicated that the duration of mechanical ventilation was significantly lower in the hypothermal extracorporeal circulation group than in the normothermal extracorporeal circulation group. There were no differences in hospital complications and mortality rates. Conclusion. Hypothermal versus normothermal extracorporeal circulation in the correction of acquired heart diseases has no predominant effect on tro-ponin I and NT-proBNP concentrations, postoperative clinical course, and hospital complications and mortality rates. Key words: extracorporeal circulation, hypothermia, acquired heart disease, troponin I, NT-proBNP.

  20. Natural Circulation with Boiling

    Energy Technology Data Exchange (ETDEWEB)

    Mathisen, R P

    1967-09-15

    A number of parameters with dominant influence on the power level at hydrodynamic instability in natural circulation, two-phase flow, have been studied experimentally. The geometrical dependent quantities were: the system driving head, the boiling channel and riser dimensions, the single-phase as well as the two phase flow restrictions. The parameters influencing the liquid properties were the system pressure and the test section inlet subcooling. The threshold of instability was determined by plotting the noise characteristics in the mass flow records against power. The flow responses to artificially obtained power disturbances at instability conditions were also measured in order to study the nature of hydrodynamic instability. The results presented give a review over relatively wide ranges of the main parameters, mainly concerning the coolant performance in both single and parallel boiling channel flow. With regard to the power limits the experimental results verified that the single boiling channel performance was intimately related to that of the parallel channels. In the latter case the additional inter-channel factors with attenuating effects were studied. Some optimum values of the parameters were observed.

  1. Value of circulating DNA concentration and integrity as a screening ...

    African Journals Online (AJOL)

    Ebtsam R. Zaher

    2012-07-17

    Jul 17, 2012 ... c Cancer Research and Management Department, Medical Research Institute, Alexandria University, Egypt .... spectrum of DNA fragments with different strand lengths, ...... stem cells and cancer metastasis: state of the issue.

  2. Containment air circulation for optimal hydrogen recombination

    International Nuclear Information System (INIS)

    Spinks, N.; Krause, M.

    1997-01-01

    An accepted first-line defense for hydrogen mitigation is to design for the hydrogen to be rapidly mixed with the containment atmosphere and diluted to below flammability concentrations. Then, as hydrogen continues to be produced in the longer term, recombiners can be used to remove hydrogen: recombiners can be located in forced-air ducts or passive recombiners can be distributed within containment and the heat of recombination used to promote local air circulation. However, this principle does not eliminate the possibility of high hydrogen concentrations at locations removed from the recombiners. An improvement on this strategy is to arrange for a specific, buoyancy-driven, overall circulation of the containment atmosphere such that the recombiners can be located within the recirculation flow, immediately downstream of the hydrogen source. This would make the mixing process more predictable and solve the mass-transfer problem associated with distributed recombiners. Ideally, the recombiners would be located just above the hydrogen source so that the heat of recombination would assist the overall circulation. In this way, the hydrogen would be removed as close as possible to the source, thereby minimizing the amount of hydrogen immediately downstream of the source and reducing the hydrogen concentration to acceptable levels at other locations. Such a strategy requires the containment volume to be divided into an upflow path, past the hydrogen source and the recombiner, and a downflow path to complete the circuit. The flow could be generated actively using fans or passively using buoyancy forces arising from the difference in density of gases in the upfiow and downflow paths; the gases in the downflow path being cooled at an elevated heat sink. (author)

  3. Correlates of Circulating 25-Hydroxyvitamin D

    Science.gov (United States)

    McCullough, Marjorie L.; Weinstein, Stephanie J.; Freedman, D. Michal; Helzlsouer, Kathy; Flanders, W. Dana; Koenig, Karen; Kolonel, Laurence; Laden, Francine; Le Marchand, Loic; Purdue, Mark; Snyder, Kirk; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Virtamo, Jarmo; Yang, Gong; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Ashby, Jason; Bertrand, Kimberly; Cai, Hui; Chen, Yu; Gallicchio, Lisa; Giovannucci, Edward; Jacobs, Eric J.; Hankinson, Susan E.; Hartge, Patricia; Hartmuller, Virginia; Harvey, Chinonye; Hayes, Richard B.; Horst, Ronald L.; Shu, Xiao-Ou

    2010-01-01

    Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes. PMID:20562191

  4. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    Science.gov (United States)

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry J.; Bower, Amy S.; Köhl, Armin; Gopalakrishnan, Ganesh; Rivas, David

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24°N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model's winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow.

  5. Does liver-intestine significantly degrade circulating endogenous substance P in man?

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Schaffalitzky de Muckadell, O B; Bülow, J B

    1986-01-01

    Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P was determi......Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P....... The results indicate that degradation of circulating endogenous substance P in man is not confined to liver-intestine or kidney but may take place in many tissues....

  6. Vitamin E γ-Tocotrienol Inhibits Cytokine-Stimulated NF-κB Activation by Induction of Anti-Inflammatory A20 via Stress Adaptive Response Due to Modulation of Sphingolipids.

    Science.gov (United States)

    Wang, Yun; Park, Na-Young; Jang, Yumi; Ma, Averil; Jiang, Qing

    2015-07-01

    NF-κB plays a central role in pathogenesis of inflammation and cancer. Many phytochemicals, including γ-tocotrienol (γTE), a natural form of vitamin E, have been shown to inhibit NF-κB activation, but the underlying mechanism has not been identified. In this study, we show that γTE inhibited cytokine-triggered activation of NF-κB and its upstream regulator TGF-β-activated kinase-1 in murine RAW 264.7 macrophages and primary bone marrow-derived macrophages. In these cells, γTE induced upregulation of A20, an inhibitor of NF-κB. Knockout of A20 partially diminished γTE's anti-NF-κB effect, but γTE increased another NF-κB inhibitor, Cezanne, in A20(-/-) cells. In search of the reason for A20 upregulation, we found that γTE treatment increased phosphorylation of translation initiation factor 2, IκBα, and JNK, indicating induction of endoplasmic reticulum stress. Liquid chromatography-tandem mass spectrometry analyses revealed that γTE modulated sphingolipids, including enhancement of intracellular dihydroceramides, sphingoid bases in de novo synthesis of the sphingolipid pathway. Chemical inhibition of de novo sphingolipid synthesis partially reversed γTE's induction of A20 and the anti-NF-κB effect. The importance of dihydroceramide increase is further supported by the observation that C8-dihydroceramide mimicked γTE in upregulating A20, enhancing endoplasmic reticulum stress, and attenuating TNF-triggered NF-κB activation. Our study identifies a novel anti-NF-κB mechanism where A20 is induced by stress-induced adaptive response as a result of modulation of sphingolipids, and it demonstrates an immunomodulatory role of dihydrocermides. Copyright © 2015 by The American Association of Immunologists, Inc.

  7. Familial Resemblance for Serum Metabolite Concentrations

    NARCIS (Netherlands)

    Draisma, H.H.M.; Beekman, M.; Pool, R.; van Ommen, G.J.B; Vaarhorst, A.A.M.; de Craen, A.J.; Willemsen, G.; Slagboom, P.E.; Boomsma, D.I.

    2013-01-01

    Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of

  8. Seasonal overturning circulation in the Red Sea: 2. Winter circulation

    KAUST Repository

    Yao, Fengchao

    2014-04-01

    The shallow winter overturning circulation in the Red Sea is studied using a 50 year high-resolution MITgcm (MIT general circulation model) simulation with realistic atmospheric forcing. The overturning circulation for a typical year, represented by 1980, and the climatological mean are analyzed using model output to delineate the three-dimensional structure and to investigate the underlying dynamical mechanisms. The horizontal model circulation in the winter of 1980 is dominated by energetic eddies. The climatological model mean results suggest that the surface inflow intensifies in a western boundary current in the southern Red Sea that switches to an eastern boundary current north of 24N. The overturning is accomplished through a cyclonic recirculation and a cross-basin overturning circulation in the northern Red Sea, with major sinking occurring along a narrow band of width about 20 km along the eastern boundary and weaker upwelling along the western boundary. The northward pressure gradient force, strong vertical mixing, and horizontal mixing near the boundary are the essential dynamical components in the model\\'s winter overturning circulation. The simulated water exchange is not hydraulically controlled in the Strait of Bab el Mandeb; instead, the exchange is limited by bottom and lateral boundary friction and, to a lesser extent, by interfacial friction due to the vertical viscosity at the interface between the inflow and the outflow. Key Points Sinking occurs in a narrow boundary layer along the eastern boundary Surface western boundary current switches into an eastern boundary current Water exchange in the Strait of Bab el Mandeb is not hydraulically controlled © 2014. American Geophysical Union. All Rights Reserved.

  9. Accumulation of sphingolipid activator proteins (SAPs) A and D in granular osmiophilic deposits in miniature Schnauzer dogs with ceroid-lipofuscinosis.

    Science.gov (United States)

    Palmer, D N; Tyynelä, J; van Mil, H C; Westlake, V J; Jolly, R D

    1997-03-01

    The neuronal ceroid-lipofuscinoses (NCL, Batten disease) are fatal inherited neurodegenerative diseases of children characterized by retinal and brain atrophy and the accumulation of electron-dense storage bodies in cells. Mutations in different genes underlie different major forms. The infantile disease (CLN-1, McKusick 256730) is distinguished by the storage of the sphingolipid activator proteins (SAPs) A and D in distinctive granular osmiophilic deposits (GRODs). This contrasts with the other major forms, where subunit c of mitochondrial ATP synthase is stored in various multilamellar profiles. Ceroid-lipofuscinoses also occur in dogs, including a form in miniature Schnauzers with distinctive granular osmiophilic deposit-like storage bodies. Antisera to SAPs A and D reacted to these storage bodies in situ. The presence of SAP D was confirmed by Western blotting and of SAP A by protein sequencing. Neither subunit c of mitochondrial ATP synthase nor of vacuolar ATPase is stored. This suggests that there are two families of ceroid-lipofuscinoses, the subunit c-storing forms, and those in which SAPs A and D, and perhaps other proteins, accumulate. Further work is required to determine whether other forms with granular osmiophilic deposits belong to the latter class and the genetic relationships between them and the human infantile disease.

  10. Plasma membrane proteins Slm1 and Slm2 mediate activation of the AGC kinase Ypk1 by TORC2 and sphingolipids in S. cerevisiae.

    Science.gov (United States)

    Niles, Brad J; Powers, Ted

    2012-10-15

    The PH domain-containing proteins Slm1 and Slm2 were originally identified as substrates of the rapamycin-insensitive TOR complex 2 (TORC2) and as mediators of signaling by the lipid second messenger phosphatidyl-inositol-4,5-bisphosphate (PI4,5P2) in budding yeast S. cerevisiae. More recently, these proteins have been identified as critical effectors that facilitate phosphorylation and activation of the AGC kinases Ypk1 and Ypk2 by TORC2. Here, we review the molecular basis for this regulation as well as place it within the context of recent findings that have revealed Slm1/2 and TORC2-dependent phosphorylation of Ypk1 is coupled to the biosynthesis of complex sphingolipids and to their levels within the plasma membrane (PM) as well as other forms of PM stress. Together, these studies reveal the existence of an intricate homeostatic feedback mechanism, whereby the activity of these signaling components is linked to the biosynthesis of PM lipids according to cellular need.

  11. The Invertibility, Explicit Determinants, and Inverses of Circulant and Left Circulant and g-Circulant Matrices Involving Any Continuous Fibonacci and Lucas Numbers

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang

    2014-01-01

    Full Text Available Circulant matrices play an important role in solving delay differential equations. In this paper, circulant type matrices including the circulant and left circulant and g-circulant matrices with any continuous Fibonacci and Lucas numbers are considered. Firstly, the invertibility of the circulant matrix is discussed and the explicit determinant and the inverse matrices by constructing the transformation matrices are presented. Furthermore, the invertibility of the left circulant and g-circulant matrices is also studied. We obtain the explicit determinants and the inverse matrices of the left circulant and g-circulant matrices by utilizing the relationship between left circulant, g-circulant matrices and circulant matrix, respectively.

  12. Circulating serum trefoil factors increase dramatically during pregnancy

    DEFF Research Database (Denmark)

    Samson, Mie Hessellund; Vestergaard, E M; Milman, N

    2008-01-01

    Trefoil factors (TFF1-3) are 7-12 kDa peptides secreted by mucosal surfaces, with changing levels of expression reflected in serum concentrations. The genes for the peptides are located on chromosome 21, the chromosome duplicated in trisomy 21. We studied the levels of circulating TFFs in pregnant...

  13. Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer

    OpenAIRE

    Stolzenberg-Solomon, Rachael Z.; Jacobs, Eric J.; Arslan, Alan A.; Qi, Dai; Patel, Alpa V.; Helzlsouer, Kathy J.; Weinstein, Stephanie J.; McCullough, Marjorie L.; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974?2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated w...

  14. Proper Sizing of Circulation Pumps

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Nørgaard, Jørgen

    2007-01-01

    The paper describes the preliminary results from field tests of replacing various types of old pumps used for circulating water in heating systems in single- and double-family houses with new types of pumps. The tests were carried out in Denmark for the Danish Electricity Savings Trust, but the r......The paper describes the preliminary results from field tests of replacing various types of old pumps used for circulating water in heating systems in single- and double-family houses with new types of pumps. The tests were carried out in Denmark for the Danish Electricity Savings Trust...

  15. Increased circulating calcitonin in cirrhosis. Relation to severity of disease and calcitonin gene-related peptide

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Schifter, S; Møller, S

    2000-01-01

    circulating plasma concentrations of CT in patients with cirrhosis in relation to the severity of disease and the plasma level of CGRP. Moreover, the kinetics of CT was evaluated for different organ systems by determination of arteriovenous extraction. Thirty-nine patients with cirrhosis (Child...... system, lower extremities, or peripheral circulation, but there was a substantial rate of pulmonary disposal and clearance (P

  16. Refractory experience in circulating fluidized bed combustors, Task 7

    Energy Technology Data Exchange (ETDEWEB)

    Vincent, R.Q.

    1989-11-01

    This report describes the results of an investigation into the status of the design and selection of refractory materials for coal-fueled circulating fluidized-bed combustors. The survey concentrated on operating units in the United States manufactured by six different boiler vendors: Babcock and Wilcox, Combustion Engineering, Foster Wheeler, Keeler Dorr-Oliver, Pyropower, and Riley Stoker. Information was obtained from the boiler vendors, refractory suppliers and installers, and the owners/operators of over forty units. This work is in support of DOE's Clean Coal Technology program, which includes circulating fluidized-bed technology as one of the selected concepts being evaluated.

  17. VanderLaan Circulant Type Matrices

    Directory of Open Access Journals (Sweden)

    Hongyan Pan

    2015-01-01

    Full Text Available Circulant matrices have become a satisfactory tools in control methods for modern complex systems. In the paper, VanderLaan circulant type matrices are presented, which include VanderLaan circulant, left circulant, and g-circulant matrices. The nonsingularity of these special matrices is discussed by the surprising properties of VanderLaan numbers. The exact determinants of VanderLaan circulant type matrices are given by structuring transformation matrices, determinants of well-known tridiagonal matrices, and tridiagonal-like matrices. The explicit inverse matrices of these special matrices are obtained by structuring transformation matrices, inverses of known tridiagonal matrices, and quasi-tridiagonal matrices. Three kinds of norms and lower bound for the spread of VanderLaan circulant and left circulant matrix are given separately. And we gain the spectral norm of VanderLaan g-circulant matrix.

  18. Circulating Heat Shock Protein 70 in Health, Aging and Disease

    Directory of Open Access Journals (Sweden)

    Demanet Christian

    2011-03-01

    Full Text Available Abstract Background Heat shock proteins (Hsp are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters. Results Serum Hsp70, Interleukin (IL -10, IL-6 and Tumor Necrosis Factor (TNF alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years. In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L showed significantly (p = 0.007 higher Hsp70 values; and Hsp70 correlated positively (p Conclusions The present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients.

  19. A comprehensive lipidomic screen of pancreatic β-cells using mass spectroscopy defines novel features of glucose-stimulated turnover of neutral lipids, sphingolipids and plasmalogens

    Directory of Open Access Journals (Sweden)

    Gemma L. Pearson

    2016-06-01

    Full Text Available Objective: Glucose promotes lipid remodelling in pancreatic β-cells, and this is thought to contribute to the regulation of insulin secretion, but the metabolic pathways and potential signalling intermediates have not been fully elaborated. Methods: Using mass spectrometry (MS we quantified changes in approximately 300 lipid metabolites in MIN6 β-cells and isolated mouse islets following 1 h stimulation with glucose. Flux through sphingolipid pathways was also assessed in 3H-sphinganine-labelled cells using TLC. Results: Glucose specifically activates the conversion of triacylglycerol (TAG to diacylglycerol (DAG. This leads indirectly to the formation of 18:1 monoacylglycerol (MAG, via degradation of saturated/monounsaturated DAG species, such as 16:0_18:1 DAG, which are the most abundant, immediate products of glucose-stimulated TAG hydrolysis. However, 16:0-containing, di-saturated DAG species are a better direct marker of TAG hydrolysis since, unlike the 18:1-containing DAGs, they are predominately formed via this route. Using multiple reaction monitoring, we confirmed that in islets under basal conditions, 18:1 MAG is the most abundant species. We further demonstrated a novel site of glucose to enhance the conversion of ceramide to sphingomyelin (SM and galactosylceramide (GalCer. Flux and product:precursor analyses suggest regulation of the enzyme SM synthase, which would constitute a separate mechanism for localized generation of DAG in response to glucose. Phosphatidylcholine (PC plasmalogen (P species, specifically those containing 20:4, 22:5 and 22:6 side chains, were also diminished in the presence of glucose, whereas the more abundant phosphatidylethanolamine plasmalogens were unchanged. Conclusion: Our results highlight 18:1 MAG, GalCer, PC(P and DAG/SM as potential contributors to metabolic stimulus-secretion coupling. Author Video: Author Video Watch what authors say about their articles Keywords: Pancreatic β-cell, Insulin

  20. Multiple states in the late Eocene ocean circulation

    Science.gov (United States)

    Baatsen, M. L. J.; von der Heydt, A. S.; Kliphuis, M.; Viebahn, J.; Dijkstra, H. A.

    2018-04-01

    The Eocene-Oligocene Transition (EOT) marks a major step within the Cenozoic climate in going from a greenhouse into an icehouse state, with the formation of a continental-scale Antarctic ice sheet. The roles of steadily decreasing CO2 concentrations versus changes in ocean circulation at the EOT are still debated and the threshold for Antarctic glaciation is obscured by uncertainties in global geometry. Here, a detailed study of the late Eocene ocean circulation is carried out using an ocean general circulation model under two slightly different geography reconstructions of the middle-to-late Eocene (38 Ma). Using the same atmospheric forcing, both geographies give a profoundly different equilibrium ocean circulation state. The underlying reason for this sensitivity is the presence of multiple equilibria characterised by either North or South Pacific deep water formation. A possible shift from a southern towards a northern overturning circulation would result in significant changes in the global heat distribution and consequently make the Southern Hemisphere climate more susceptible for significant cooling and ice sheet formation on Antarctica.

  1. Concentrated Ownership

    DEFF Research Database (Denmark)

    Rose, Caspar

    2014-01-01

    This entry summarizes the main theoretical contributions and empirical findings in relation to concentrated ownership from a law and economics perspective. The various forms of concentrated ownership are described as well as analyzed from the perspective of the legal protection of investors......, especially minority shareholders. Concentrated ownership is associated with benefits and costs. Concentrated ownership may reduce agency costs by increased monitoring of top management. However, concentrated ownership may also provide dominating owners with private benefits of control....

  2. Journalism as Cultures of Circulation

    DEFF Research Database (Denmark)

    Bødker, Henrik

    2013-01-01

    The universe of journalism has always consisted of interspersed texts, meanings and practices. Yet, much journalism research has often isolated either texts and/or contexts and as such assumed relations between professional practices, informed (rational) readers and (conceived) core texts...... of journalism. It is, however, more important than ever to shift attention away from texts to the processes through which they are circulated. This is partly because the many cultural forms of journalism (textual, institutional, technological, material, behavioural and imagined) are undergoing significant......, likes, comments, searches, journalist roles, writing and reading positions and identities etc. Such forms will be traced within the mediation of a specific event with the overall aim of beginning a theorization of the landscape of journalism as highly interrelated cultures of circulation....

  3. Radioisotopic evaluation of portal circulation

    International Nuclear Information System (INIS)

    Maliska, C.; Rosenthal, D.

    1986-01-01

    The use of a radio-tracer of portal circulation through the intestine, should prevent cruel punctures in the portal-vein or spleen as it is usually the case with traditional methods in the study of portal-system. The absorption of I-131 and Tc-99m, previously cheked in rabbits presented similar results in dogs. The time of circulation between terminal large-intestine and the liver (t-RF) was determined by external counting at hepatic level by recording radioactivity variation-time. In healthy animals the t-RF was from 20to 60 seconds, with average time of 42 seconds. In 2 animals with partial binding of portal-vein the t-RF went up to 110 and 120 seconds. (Author) [pt

  4. Ocean circulation generated magnetic signals

    DEFF Research Database (Denmark)

    Manoj, C.; Kuvshinov, A.; Maus, S.

    2006-01-01

    Conducting ocean water, as it flows through the Earth's magnetic field, generates secondary electric and magnetic fields. An assessment of the ocean-generated magnetic fields and their detectability may be of importance for geomagnetism and oceanography. Motivated by the clear identification...... of ocean tidal signatures in the CHAMP magnetic field data we estimate the ocean magnetic signals of steady flow using a global 3-D EM numerical solution. The required velocity data are from the ECCO ocean circulation experiment and alternatively from the OCCAM model for higher resolution. We assume...... of the magnetic field, as compared to the ECCO simulation. Besides the expected signatures of the global circulation patterns, we find significant seasonal variability of ocean magnetic signals in the Indian and Western Pacific Oceans. Compared to seasonal variation, interannual variations produce weaker signals....

  5. Observations of Local Seychelles Circulation

    Science.gov (United States)

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Observations of Local Seychelles Circulation Geno...goal for the proposed work is to develop predictive capabilities for physical oceanography for the Seychelles region in support of locally relevant...observations in the Seychelles region that will lead to long-term data collection efforts. In collaboration with local partnerships, we will carry out

  6. Circulating nucleic acids and evolution.

    Science.gov (United States)

    Anker, Philippe; Stroun, Maurice

    2012-06-01

    J.B. Lamarck in 1809 was the first to present a theory of evolution. He proposed it was due to the adaptation of species to environmental changes, this adaptation being acquired by the offspring. In 1868, Darwin suggested that cells excrete gemmules, which circulate through the body and reach the gonads where they are transmitted to the next generation. His main argument came from graft hybrids. In the fifties and sixties, Russian geneticists, rejecting neo-Darwinism, said that acquired characteristics were the basis of evolution. The main experiments on which they based their theory were the transmission of hereditary characteristics by a special technique of grafting between two varieties of plants. We repeated this kind of experiment and also succeeded in obtaining hereditary modifications of the pupil plants that acquired some characteristics of the mentor variety. Rather than adopting the views of the Russian scientists, we suggested that DNA was circulating between the mentor and pupil plants. Hirata's group have shown recently, by using molecular techniques such as cloning, RFLP PCR and sequencing some genes of their graft hybrids of pepper plants, that transfer of informative molecules from the mentor to the pupil plant does exist. Nucleic acids are actively released by cells; they circulate in the body. They can transform oncogenically or trigger antibody response but the only genetic transformation showing that DNA can go from the soma to the germen comes from graft hybrids. This suggests that circulating nucleic acids, in this case DNA, like Darwin's gemmules, play a role in the mechanism of evolution.

  7. Improvement of Classification of Enterprise Circulating Funds

    OpenAIRE

    Rohanova Hanna O.

    2014-01-01

    The goal of the article lies in revelation of possibilities of increase of efficiency of managing enterprise circulating funds by means of improvement of their classification features. Having analysed approaches of many economists to classification of enterprise circulating funds, systemised and supplementing them, the article offers grouping classification features of enterprise circulating funds. In the result of the study the article offers an expanded classification of circulating funds, ...

  8. Hall Effect Gyrators and Circulators

    Science.gov (United States)

    Viola, Giovanni; DiVincenzo, David P.

    2014-04-01

    The electronic circulator and its close relative the gyrator are invaluable tools for noise management and signal routing in the current generation of low-temperature microwave systems for the implementation of new quantum technologies. The current implementation of these devices using the Faraday effect is satisfactory but requires a bulky structure whose physical dimension is close to the microwave wavelength employed. The Hall effect is an alternative nonreciprocal effect that can also be used to produce desired device functionality. We review earlier efforts to use an Ohmically contacted four-terminal Hall bar, explaining why this approach leads to unacceptably high device loss. We find that capacitive coupling to such a Hall conductor has much greater promise for achieving good circulator and gyrator functionality. We formulate a classical Ohm-Hall analysis for calculating the properties of such a device, and show how this classical theory simplifies remarkably in the limiting case of the Hall angle approaching 90°. In this limit, we find that either a four-terminal or a three-terminal capacitive device can give excellent circulator behavior, with device dimensions far smaller than the ac wavelength. An experiment is proposed to achieve GHz-band gyration in millimeter (and smaller) scale structures employing either semiconductor heterostructure or graphene Hall conductors. An inductively coupled scheme for realizing a Hall gyrator is also analyzed.

  9. Encoders for block-circulant LDPC codes

    Science.gov (United States)

    Divsalar, Dariush (Inventor); Abbasfar, Aliazam (Inventor); Jones, Christopher R. (Inventor); Dolinar, Samuel J. (Inventor); Thorpe, Jeremy C. (Inventor); Andrews, Kenneth S. (Inventor); Yao, Kung (Inventor)

    2009-01-01

    Methods and apparatus to encode message input symbols in accordance with an accumulate-repeat-accumulate code with repetition three or four are disclosed. Block circulant matrices are used. A first method and apparatus make use of the block-circulant structure of the parity check matrix. A second method and apparatus use block-circulant generator matrices.

  10. Elliptical concentrators.

    Science.gov (United States)

    Garcia-Botella, Angel; Fernandez-Balbuena, Antonio Alvarez; Bernabeu, Eusebio

    2006-10-10

    Nonimaging optics is a field devoted to the design of optical components for applications such as solar concentration or illumination. In this field, many different techniques have been used to produce optical devices, including the use of reflective and refractive components or inverse engineering techniques. However, many of these optical components are based on translational symmetries, rotational symmetries, or free-form surfaces. We study a new family of nonimaging concentrators called elliptical concentrators. This new family of concentrators provides new capabilities and can have different configurations, either homofocal or nonhomofocal. Translational and rotational concentrators can be considered as particular cases of elliptical concentrators.

  11. Evidence of the Lower Thermospheric Winter-to-Summer Circulation From SABER CO2 Observations

    Science.gov (United States)

    Qian, Liying; Burns, Alan; Yue, Jia

    2017-10-01

    Numerical studies have shown that there is a lower thermospheric winter-to-summer circulation that is driven by wave dissipation and that it plays a significant role in trace gas distributions in the mesosphere and lower thermosphere, and in the composition of the thermosphere. However, the characteristics of this circulation are poorly known. Direct observations of it are difficult, but it leaves clear signatures in tracer distributions. The Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) onboard the Thermosphere Ionosphere Mesosphere Energetics and Dynamics satellite has obtained CO2 concentration from 2002 to present. This data set, combined with simulations by the Whole Atmosphere Community Climate Model, provides an unprecedented opportunity to infer the morphology of this circulation in both the summer and winter hemispheres. Our study show that there exists a maximum vertical gradient of CO2 at summer high latitudes, driven by the convergence of the upwelling of the mesospheric circulation and the downwelling of the lower thermospheric circulation; in the winter hemisphere, the maximum vertical gradient of CO2 is located at a higher altitude, driven by the convergence of the upwelling of the lower thermospheric circulation and the downwelling of the solar-driven thermospheric circulation; the bottom of the lower thermospheric circulation is located between 95 km and 100 km, and it has a vertical extent of 10 km. Analysis of the SABER CO2 and temperature at summer high latitudes showed that the bottom of this circulation is consistently higher than the mesopause height by 10 km.

  12. Radon concentration inversions in the troposphere

    International Nuclear Information System (INIS)

    Pereira, E.B.

    1987-07-01

    Vertical concentrations of radon in the lower troposphere were obtained in Southern Brazil up to 7Km high and have shown unexpected inverted profiles. The presence of low pressure center systems southwest to the flight path suggested that inversions might have been originated by a vertical transport mechanism based on the large scale circulation of developing synoptic systems. A simple friction-driven circulation model was contructed and the transport equation was solved. (author) [pt

  13. Concentration risk

    Directory of Open Access Journals (Sweden)

    Matić Vesna

    2016-01-01

    Full Text Available Concentration risk has been gaining a special dimension in the contemporary financial and economic environment. Financial institutions are exposed to this risk mainly in the field of lending, mostly through their credit activities and concentration of credit portfolios. This refers to the concentration of different exposures within a single risk category (credit risk, market risk, operational risk, liquidity risk.

  14. Nutrient Restriction Increases Circulating and Hepatic Ceramide in Dairy Cows Displaying Impaired Insulin Tolerance.

    Science.gov (United States)

    Davis, Amanda N; Clegg, J L; Perry, C A; McFadden, J W

    2017-09-01

    The progression of insulin resistance in dairy cows represents a maternal adaptation to support milk production during heightened energy demand; however, excessive adipose tissue lipolysis can develop. In diabetic non-ruminants, the mechanisms that mediate insulin resistance involve the sphingolipid ceramide. We tested the hypothesis that ceramide accumulates in dairy cows experiencing lipolysis and insulin resistance. Nine dairy cows were utilized in a replicated 3 × 3 Latin square design. Cows were ad libitum fed, nutrient-restricted (NR), or NR with nicotinic acid (NA; 5 mg of NA/h per kg BW; delivered i.v.) for 34 h. When provided access, cows were ad libitum fed a mixed ration of grass hay and ground corn to meet requirements. Intake for NR cows was limited to vitamins and minerals. Nicotinic acid was administered to suppress lipolysis. Saline was infused in cows not provided NA. At 32 and 33 h of treatment, a liver biopsy and insulin tolerance test were performed, respectively. Samples were analyzed using colorimetry, immunoassay, and mass spectrometry. Nutrient restriction increased serum fatty acids and ceramide levels, and impaired insulin sensitivity; however, NA infusion was unable to prevent these responses. We also show that NR increases hepatic ceramide accumulation, a response that was positively associated with serum ceramide supply. Our data demonstrate that circulating and hepatic 24:0-Cer are inversely associated with systemic insulin tolerance, an effect not observed for the 16:0 moiety. In conclusion, our results suggest that ceramide accrual represents a metabolic adaptation to nutrient restriction and impaired insulin action in dairy cows.

  15. EFFECT OF ACUTE STRESS ON PLASMA CONCENTRATIONS OF SEX AND STRESS HORMONES IN JUVENILE ALLIGATORS LIVING IN CONTROL AND CONTAMINATED LAKES

    Science.gov (United States)

    Environmental contaminants can act as stressors, inducing elevated circulating concentrations of stress hormones such as corticosterone and cortisol. Development in contaminated eggs has been reported to modify circulating sex steroid hormone concentrations in alligators (Alligat...

  16. Concentrator Photovoltaics

    CERN Document Server

    Luque, Antonio L

    2007-01-01

    Photovoltaic solar-energy conversion is one of the most promising technologies for generating renewable energy, and conversion of concentrated sunlight can lead to reduced cost for solar electricity. In fact, photovoltaic conversion of concentrated sunlight insures an efficient and cost-effective sustainable power resource. This book gives an overview of all components, e.g. cells, concentrators, modules and systems, for systems of concentrator photovoltaics. The authors report on significant results related to design, technology, and applications, and also cover the fundamental physics and market considerations. Specific contributions include: theory and practice of sunlight concentrators; an overview of concentrator PV activities; a description of concentrator solar cells; design and technology of modules and systems; manufacturing aspects; and a market study.

  17. Vertical circulation and thermospheric composition: a modelling study

    OpenAIRE

    H. Rishbeth; I. C. F. Müller-Wodarg; I. C. F. Müller-Wodarg

    1999-01-01

    The coupled thermosphere-ionosphere-plasmasphere model CTIP is used to study the global three-dimensional circulation and its effect on neutral composition in the midlatitude F-layer. At equinox, the vertical air motion is basically up by day, down by night, and the atomic oxygen/molecular nitrogen [O/N2] concentration ratio is symmetrical about the equator. At solstice there is a summer-to-winter flow of air, with downwelling at subauroral latitudes in winter that produc...

  18. Diarrhea caused by circulating agents.

    Science.gov (United States)

    Fabian, Elisabeth; Kump, Patrizia; Krejs, Guenter J

    2012-09-01

    Circulating agents cause intestinal secretion or changes in motility with decreased intestinal transit time, resulting in secretory-type diarrhea. Secretory diarrhea as opposed to osmotic diarrhea is characterized by large-volume, watery stools, often more than 1 L per day; by persistence of diarrhea when patients fast; and by the fact that on analysis of stool-water, measured osmolarity is identical to that calculated from the electrolytes present. Although sodium plays the main role in water and electrolyte absorption, chloride is the major ion involved in secretion. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Vasculitis of the mesenteric circulation.

    Science.gov (United States)

    Koster, Matthew J; Warrington, Kenneth J

    2017-02-01

    Vasculitis of the mesenteric circulation is an uncommon but life-threatening manifestation of systemic vasculitis. Initial symptoms are frequently non-specific and therefore patients often present to primary care physicians and gastroenterologists with abdominal pain or gastrointestinal bleeding. Given the severity of the conditions associated with mesenteric vasculitis, it is imperative to appropriately diagnose and initiate treatment of suspected cases. This review will focus on diseases commonly associated with vasculitis of the mesenteric vessels. Imaging characteristics and clinical features assisting in diagnosis as well as initial approaches to treatment are emphasized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Autonomic Regulation of Splanchnic Circulation

    Directory of Open Access Journals (Sweden)

    Kathleen A Fraser

    1991-01-01

    Full Text Available The role of the autonomic nervous system in circulatory regulation of the splanchnic organs (stomach, small intestine, colon, liver, pancreas and spleen is reviewed. In general, the sympathetic nervous system is primarily involved in vasoconstriction, while the parasympathetic contributes to vasodilation. Vasoconstriction in the splanchnic circulation appears to be mediated by alpha-2 receptors and vasodilation by activation of primary afferent nerves with subsequent release of vasodilatory peptides, or by stimulation of beta-adrenergic receptors. As well, an important function of the autonomic nervous system is to provide a mechanism by which splanchnic vascular reserve can be mobilized during stress to maintain overall cardiovascular homeostasis.

  1. Circulating prostacyclin metabolites in the dog

    International Nuclear Information System (INIS)

    Taylor, B.M.; Shebuski, R.J.; Sun, F.F.

    1983-01-01

    The present study was designed to determine the concentration of prostacyclin (PGI2) metabolites in the blood of the dog. After a bolus i.v. dose of [11 beta- 3 H]PGI2 (5 micrograms/kg) into each of five dogs, blood samples were withdrawn at 0.33, 0.67, 1, 3, 5, 20, 30, 60 and 120 min postdrug administration. Plasma samples were extracted and the radioactive components were analyzed by two-dimensional thin-layer chromatography with autoradiofluorography and radio-high-performance liquid chromatography. The compounds were identified by comparing their mobility with synthetic standards; only parallel responses observed in both tests constituted positive identification. Seven metabolites were identified by these two techniques: 6-keto-prostaglandin (PG)F1 alpha; 6-keto-PGE1; 2,3-dinor-6-keto-PGF 1 alpha; 2,3-dinor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha; and 2,3,18,19-tetranor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha. Several additional compounds, both polar and nonpolar in nature, which did not co-chromatograph with any of our standards were also detected. Early samples consisted predominantly of 6-keto-PGF 1 alpha and other 20-carbon metabolites. By 30 min, the predominant metabolites were the 16- and 18-carbon dicarboxylic acids. By 60 min, 85% of the radioactivity was associated with two unidentified polar compounds. The evidence suggests that 6-keto-PGF 1 alpha probably reflects only the transient levels of freshly entering PGI2 in the circulation, whereas levels of the most polar metabolites (e.g., dihydro-diketo-carboxyl tetranor-PGF 2 alpha) may be a better measure of the overall PGI2 presence due to its longer half-life in circulation

  2. Intestinal circulation during inhalation anesthesia

    International Nuclear Information System (INIS)

    Tverskoy, M.; Gelman, S.; Fowler, K.C.; Bradley, E.L.

    1985-01-01

    This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of 86 Rb and 9-microns spheres labeled with 141 Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and isoflurane anesthesia were accompanied by a much lower arteriovenous oxygen content difference (AVDO 2 ) and oxygen uptake than pentobarbital or nitrous oxide. Compared with pentobarbital, enflurane anesthesia was not accompanied by marked differences in VR, F, Cl-Rb, and Cl-Sph; halothane at 2 MAC decreased VR and increased F and Cl-Rb while isoflurane increased VR and decreased F. alpha-Adrenoceptor blockade with phentolamine (1 mg . kg-1) abolished isoflurane-induced vasoconstriction, suggesting that the increase in VR was mediated via circulating catecholamines

  3. Roadmap for cardiovascular circulation model

    Science.gov (United States)

    Bradley, Christopher P.; Suresh, Vinod; Mithraratne, Kumar; Muller, Alexandre; Ho, Harvey; Ladd, David; Hellevik, Leif R.; Omholt, Stig W.; Chase, J. Geoffrey; Müller, Lucas O.; Watanabe, Sansuke M.; Blanco, Pablo J.; de Bono, Bernard; Hunter, Peter J.

    2016-01-01

    Abstract Computational models of many aspects of the mammalian cardiovascular circulation have been developed. Indeed, along with orthopaedics, this area of physiology is one that has attracted much interest from engineers, presumably because the equations governing blood flow in the vascular system are well understood and can be solved with well‐established numerical techniques. Unfortunately, there have been only a few attempts to create a comprehensive public domain resource for cardiovascular researchers. In this paper we propose a roadmap for developing an open source cardiovascular circulation model. The model should be registered to the musculo‐skeletal system. The computational infrastructure for the cardiovascular model should provide for near real‐time computation of blood flow and pressure in all parts of the body. The model should deal with vascular beds in all tissues, and the computational infrastructure for the model should provide links into CellML models of cell function and tissue function. In this work we review the literature associated with 1D blood flow modelling in the cardiovascular system, discuss model encoding standards, software and a model repository. We then describe the coordinate systems used to define the vascular geometry, derive the equations and discuss the implementation of these coupled equations in the open source computational software OpenCMISS. Finally, some preliminary results are presented and plans outlined for the next steps in the development of the model, the computational software and the graphical user interface for accessing the model. PMID:27506597

  4. The Dynamics of Hadley Circulation Variability and Change

    Science.gov (United States)

    Davis, Nicholas Alexander

    The Hadley circulation exerts a dominant control on the surface climate of earth's tropical belt. Its converging surface winds fuel the tropical rains, while subsidence in the subtropics dries and stabilizes the atmosphere, creating deserts on land and stratocumulus decks over the oceans. Because of the strong meridional gradients in temperature and precipitation in the subtropics, any shift in the Hadley circulation edge could project as major changes in surface climate. While climate model simulations predict an expansion of the Hadley cells in response to greenhouse gas forcings, the mechanisms remain elusive. An analysis of the climatology, variability, and response of the Hadley circulation to radiative forcings in climate models and reanalyses illuminates the broader landscape in which Hadley cell expansion is realized. The expansion is a fundamental response of the atmosphere to increasing greenhouse gas concentrations as it scales with other key climate system changes, including polar amplification, increasing static stability, stratospheric cooling, and increasing global-mean surface temperatures. Multiple measures of the Hadley circulation edge latitudes co-vary with the latitudes of the eddy-driven jets on all timescales, and both exhibit a robust poleward shift in response to forcings. Further, across models there is a robust coupling between the eddy-driving on the Hadley cells and their width. On the other hand, the subtropical jet and tropopause break latitudes, two common observational proxies for the tropical belt edges, lack a strong statistical relationship with the Hadley cell edges and have no coherent response to forcings. This undermines theories for the Hadley cell width predicated on angular momentum conservation and calls for a new framework for understanding Hadley cell expansion. A numerical framework is developed within an idealized general circulation model to isolate the mean flow and eddy responses of the global atmosphere to

  5. Functional evaluation of circulating hematopoietic progenitors in Noonan syndrome

    Science.gov (United States)

    TIMEUS, FABIO; CRESCENZIO, NICOLETTA; BALDASSARRE, GIUSEPPINA; DORIA, ALESSANDRA; VALLERO, STEFANO; FOGLIA, LUISELDA; PAGLIANO, SARA; ROSSI, CESARE; SILENGO, MARGHERITA CIRILLO; RAMENGHI, UGO; FAGIOLI, FRANCA; DI MONTEZEMOLO, LUCA CORDERO; FERRERO, GIOVANNI BATTISTA

    2013-01-01

    Noonan syndrome (NS) is an autosomal dominant disorder, characterized by short stature, multiple dysmorphisms and congenital heart defects. A myeloproliferative disorder (NS/MPD), resembling juvenile myelomonocytic leukemia (JMML), is occasionally diagnosed in infants with NS. In the present study, we performed a functional evaluation of the circulating hematopoietic progenitors in a series of NS, NS/MPD and JMML patients. The different functional patterns were compared with the aim to identify a possible NS subgroup worthy of stringent hematological follow-up for an increased risk of MPD development. We studied 27 NS and 5 JMML patients fulfilling EWOG-MDS criteria. The more frequent molecular defects observed in NS were mutations in the PTPN11 and SOS genes. The absolute count of monocytes, circulating CD34+ hematopoietic progenitors, their apoptotic rate and the number of circulating CFU-GMs cultured in the presence of decreasing concentrations or in the absence of granulocyte-macrophage colony-stimulating factor (GM-CSF) were evaluated. All JMML patients showed monocytosis >1,000/μl. Ten out of the 27 NS patients showed monocytosis >1,000/μl, which included the 3 NS/MPD patients. In JMML patients, circulating CD34+ cells were significantly increased (median, 109.8/μl; range, 44–232) with a low rate of apoptosis (median, 2.1%; range, 0.4–12.1%), and circulating CFU-GMs were hyper-responsive to GM-CSF. NS/MPD patients showed the same flow cytometric pattern as the JMML patients (median, CD34+ cells/μl, 205.7; range, 58–1374; median apoptotic rate, 1.4%; range, 0.2–2.4%) and their circulating CFU-GMs were hyper-responsive to GM-CSF. These functional alterations appeared 10 months before the typical clinical manifestations in 1 NS/MPD patient. In NS, the CD34+ absolute cell count and circulating CFU-GMs showed a normal pattern (median CD34+ cells/μl, 4.9; range, 1.3–17.5), whereas the CD34+ cell apoptotic rate was significantly decreased in

  6. Extracorporeal Circulation Causes Release of Neutrophil Gelatinase-Associated Lipocalin (NGAL

    Directory of Open Access Journals (Sweden)

    Per Jönsson

    1999-01-01

    Full Text Available Extracorporeal circulation (ECC used during cardiac surgery causes activation of several inflammatory systems. These events are not fully understood but are responsible for complications during the immediate postoperative period. Neutrophil gelatinase-associated lipocalin (NGAL, a member of the expanding lipocalin family, has recently been described as an inflammatory protein. In this study, the release of NGAL into the circulation in 41 patients undergoing heart surgery with ECC was evaluated. A 4- to 5-fold elevation of the concentration of NGAL in plasma was observed during the immediate postoperative course with a rapid elimination during the first postoperative day. Four patients undergoing lung surgery (without ECC were also studied. The plasma concentration of NGAL only increased with a factor of 1.1-2.2 over the operation. We conclude that NGAL is released into the circulation during heart surgery, probably as a result of the inflammatory activation of leukocytes initiated by the extracorporeal circulation.

  7. Uranus atmospheric dynamics and circulation

    Science.gov (United States)

    Allison, Michael; Beebe, Reta F.; Conrath, Barney J.; Hinson, David P.; Ingersoll, Andrew P.

    1991-01-01

    The observations, models, and theories relevant to the atmospheric dynamics and meteorology of Uranus are discussed. The available models for the large-scale heat transport and atmospheric dynamics as well as diagnostic interpretations of the Voyager data are reviewed. Some pertinent ideas and questions regarding the global circulation balance are considered, partly in comparison with other planetary atmospheres. The available data indicate atmospheric rotation at midlatitudes nearly 200 m/s faster than that of the planetary magnetic field. Analysis of the dynamical deformation of the shape and size of isobaric surfaces measured by the Voyager radio-occultation experiment suggests a subrotating equator at comparable altitudes. Infrared temperature retrievals above the cloud deck indicate a smaller equator-to-pole contrast than expected for purely radiative-convective equilibrium, but show local variations implying a latitudinally correlated decrease with altitude in the cloud-tracked wind.

  8. Improvement of Classification of Enterprise Circulating Funds

    Directory of Open Access Journals (Sweden)

    Rohanova Hanna O.

    2014-02-01

    Full Text Available The goal of the article lies in revelation of possibilities of increase of efficiency of managing enterprise circulating funds by means of improvement of their classification features. Having analysed approaches of many economists to classification of enterprise circulating funds, systemised and supplementing them, the article offers grouping classification features of enterprise circulating funds. In the result of the study the article offers an expanded classification of circulating funds, which clearly shows the role of circulating funds in managing enterprise finance and economy in general. The article supplements and groups classification features of enterprise circulating funds by: the organisation level, functioning character, sources of formation and their cost, and level of management efficiency. The article shows that the provided grouping of classification features of circulating funds allows exerting all-sided and purposeful influence upon indicators of efficiency of circulating funds functioning and facilitates their rational management in general. The prospect of further studies in this direction is identification of the level of attraction of loan resources by production enterprises for financing circulating funds.

  9. NPP Krsko natural circulation performance evaluation

    International Nuclear Information System (INIS)

    Segon, Velimir; Bajs, Tomislav; Frogheri, Monica

    1999-01-01

    The present document deals with an evaluation of the natural circulation performance of the Krsko nuclear power plant. Two calculation have been performed using the NPP Krsko nodalization (both similar to the LOBI A2-77 natural circulation experiment) - the first with the present steam generators at NPP Krsko (Westinghouse, 18% plugged), the second with the future steam generators (Siemens, 0% plugged). The results were evaluated using the natural circulation flow map derived in /1/, and were compared to evaluate the influence of the new steam generators on the natural circulation performance. (author)

  10. A blood circulation model for reference man

    Energy Technology Data Exchange (ETDEWEB)

    Leggett, R.W.; Eckerman, K.F. [Oak Ridge National Lab., TN (United States); Williams, L.R. [Indiana Univ., South Bend, IN (United States). Div. of Liberal Arts and Sciences

    1996-12-31

    A dynamic blood circulation model that predicts the movement and gradual dispersion of a bolus of material in the circulation after its intravenous injection into an adult human. The main purpose of the model is improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The model partitions the blood volume into 24 separate organs or tissues, right heart chamber, left heart chamber, pulmonary circulation, arterial outflow to the aorta and large arteries, and venous return via the large veins. Model results were compared to data obtained from injection of carbon 11 labeled carbon monoxide or rubidium 86.

  11. A blood circulation model for reference man

    International Nuclear Information System (INIS)

    Leggett, R.W.; Eckerman, K.F.; Williams, L.R.

    1996-01-01

    A dynamic blood circulation model that predicts the movement and gradual dispersion of a bolus of material in the circulation after its intravenous injection into an adult human. The main purpose of the model is improve the dosimetry of internally deposited radionuclides that decay in the circulation to a significant extent. The model partitions the blood volume into 24 separate organs or tissues, right heart chamber, left heart chamber, pulmonary circulation, arterial outflow to the aorta and large arteries, and venous return via the large veins. Model results were compared to data obtained from injection of carbon 11 labeled carbon monoxide or rubidium 86

  12. Basic natural circulation characteristics of SBWR

    International Nuclear Information System (INIS)

    Kuran, S.; Soekmen, C. N.

    2001-01-01

    Natural circulation is an important passive heat removal mechanism for both existing and next generation light water reactors. Simplified Boiling Water Reactor (SBWR) is one of the advanced light water reactors that rely on natural circulation for normal as well as emergency core cooling. In this study, basic natural circulation characteristics of this reactor are examined on a flow loop that simulates the operation of SBWR. On this model, effect of system operating parameters on the steady state natural circulation characteristics inside the loop is studied via solving the transcendental equation for loop flow rate

  13. Optimization of ultra-high pressure liquid chromatography - tandem mass spectrometry determination in plasma and red blood cells of four sphingolipids and their evaluation as biomarker candidates of Gaucher's disease.

    Science.gov (United States)

    Chipeaux, Caroline; de Person, Marine; Burguet, Nathalie; Billette de Villemeur, Thierry; Rose, Christian; Belmatoug, Nadia; Héron, Sylvie; Le Van Kim, Caroline; Franco, Mélanie; Moussa, Fathi

    2017-11-24

    While important advances have been recently achieved in the optimization of lipid classes' separation, information on the specific determination of medium polarity lipids such as sphingolipids (SLs) in highly complex matrices remains fragmentary. In human, disorders of SL metabolism known as sphingolipidoses are a heterogeneous group of inherited disorders affecting primarily the central nervous. Early diagnosis of these conditions is of importance notably when a corrective therapy is available. The diagnosis is generally based on the determination of specific SLs in plasma and red blood cells (RBCs). For instance, glucosylceramide (GL1), glucosylsphingosine (Lyso-GL1), sphingosine (Sph), and sphingosine-1-phosphate (S1P) are proposed as relevant biomarkers for Gaucher disease (GD). Our main objective was to evaluate these biomarker candidates in a cohort of GD patients. However, most of current methods of GL1, Lyso-GL1, Sph, and S1P determination in plasma of GD patients require at least two liquid chromatographic runs. On the other hand, except for GL1 nothing is known concerning the RBC sphingolipid content. Yet, several reversed phase LC-MS methods of SLs separation and/or determination in various media with different sample preparation approaches have been proposed since 2010. Here we focused on stationary phase selection and mobile phase composition as well as on the sample preparation step to optimize and validate an UHPLC-MS/MS method for the simultaneous quantification of the four sphingolipids in both plasma and RBCs. A comparison between seven stationary phases including two RP18, two polar embedded RP18, and three HILIC phases shows that under our conditions polar embedded RP18 phases are the most appropriate for the separation of the four SLs, in terms of efficiency, peak symmetry, and separation time. In the same way, a comparison between a single step extraction with methanol and a liquid-liquid extraction with a mixture of methanol/methyl tert

  14. Nutrient pumping by submesoscale circulations in the mauritanian upwelling system

    Science.gov (United States)

    Hosegood, P. J.; Nightingale, P. D.; Rees, A. P.; Widdicombe, C. E.; Woodward, E. M. S.; Clark, D. R.; Torres, R. J.

    2017-12-01

    Observations made within a cold filament in the Mauritanian upwelling system demonstrate that intense submesoscale circulations at the peripheral edges of the filament are likely responsible for anomalously high levels of observed primary productivity by resupplying nutrients to the euphotic zone. Measurements made on the shelf within the recently upwelled water reveal that primary production (PP) of 8.2 gC/m-2 day-1 was supported by nitrate concentrations (NC) of 8 mmol m-3. Towards the front that defined the edge of the filament containing the upwelled water as it was transported offshore, PP dropped to 1.6 gC m-2 day-1 whilst NC dropped to 5.5 mmol m-3. Thus, whilst the observed nutrients on the shelf accounted for 90% of new production, this value dropped to ∼60% near the filament's front after accounting for vertical turbulent fluxes and Ekman pumping. We demonstrate that the N15 was likely to have been supplied at the front by submesoscale circulations that were directly measured as intense vertical velocities ⩾100 m day-1 by a drifting acoustic Doppler current profiler that crossed a submesoscale surface temperature front. At the same time, a recently released tracer was subducted out of the mixed layer within 24 h of release, providing direct evidence that the frontal circulations were capable of accessing the reservoir of nutrients beneath the pycnocline. The susceptibility of the filament edge to submesoscale instabilities was demonstrated by O(1) Rossby numbers at horizontal scales of 1-10 km. The frontal circulations are consistent with instabilities arising from a wind-driven nonlinear Ekman buoyancy flux generated by the persistent northerly wind stress that has a down-front component at the northern edge of the inshore section of the filament. The prevalence of submesoscale instabilities and their associated vertical circulations are proposed to be a key mechanism operating at sub-grid scales and sustaining new production throughout the upwelling

  15. Concentrating Radioactivity

    Science.gov (United States)

    Herrmann, Richard A.

    1974-01-01

    By concentrating radioactivity contained on luminous dials, a teacher can make a high reading source for classroom experiments on radiation. The preparation of the source and its uses are described. (DT)

  16. Enhanced electrokinetic remediation of fluorine-contaminated soil by applying an ammonia continuous circulation system

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Shufa; Zhou, Ming; Zhang, Shuangyan [Henan University of Science and Technology, Luoyang (China)

    2016-02-15

    The objective of this research was to investigate the effects of ammonia continuous circulation enhanced electrokinetic remediation of fluorine contaminated soil and to analyze its influence on soil pH after remediation. An experimental study was carried out in self-made electrokinetic apparatus. The voltage gradient was set at 1.0V/cm and ammonia water with different concentrations was used as electrolyte which circulated in series. Comparative studies were made by using deionized water as electrolyte which circulated separately in one experiment and continuously in another. According to the experiment the continuous circulation of ammonia water increased the current value during the remediation process and maintained current through the soil cell stabler, which not only increased fluorine migration but also reduced energy consumption. Among the given ammonia concentrations (0, 0.01, 0.1 and 0.2mol/L) the removal rate increased with ammonia concentration. 0.2mol/L had the highest current (26.8mA), and the removal rate amounted up to 57.3%. By using ammonia circulation enhanced electrokinetic technology, the difference between pH values of cathode soil and anode soil became smaller. Ammonia continuous circulation enhanced electrokinetics can effectively remediate fluorine contaminated soil and the residual ammonia in the soil can also improve soil fertility.

  17. Dietary fatty acids modulate associations between genetic variants and circulating fatty acids in plasma and erythrocyte membranes: meta-analysis of nine studies in the CHARGE consortium

    Science.gov (United States)

    Scope: Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated i...

  18. Natural circulation in reactor coolant system

    International Nuclear Information System (INIS)

    Han, J.T.

    1987-01-01

    Reactor coolant system (RCS) natural circulation in a PWR is the buoyancy-driven coolant circulation between the core and the upper-plenum region (in-vessel circulation) with or without a countercurrent flow in the hot leg piping between the vessel and steam generators (ex-vessel circulation). This kind of multidimensional bouyancy-driven flow circulation serves as a means of transferring the heat from the core to the structures in the upper plenum, hot legs, and possibly steam generators. As a result, the RCS piping and other pressure boundaries may be heated to high temperatures at which the structural integrity is challenged. RCS natural circulation is likely to occur during the core uncovery period of the TMLB' accident in a PWR when the vessel upper plenum and hot leg are already drained and filled with steam and possibly other gaseous species. RCS natural circulation is being studied for the Surry plant during the TMLB' accident in which station blackout coincides with the loss of auxiliary feedwater and no operator actions. The effects of the multidimensional RCS natural circulation during the TMLB' accident are discussed

  19. Circulating follistatin in relation to energy metabolism

    DEFF Research Database (Denmark)

    Hansen, Jakob Schiøler; Plomgaard, Peter

    2016-01-01

    a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to-insulin ratio. The picture emerging is that conditions associated...

  20. Moderator circulation in CANDU reactors

    International Nuclear Information System (INIS)

    Fath, H.E.S.; Hussein, M.A.

    1989-01-01

    A two-dimensional computer code that is capable of predicting the moderator flow and temperature distribution inside CANDU calandria is presented. The code uses a new approach to simulate the calandria tube matrix by blocking the cells containing the tubes in the finite difference mesh. A jet momentum-dominant flow pattern is predicted in the nonisothermal case, and the effect of the buoyancy force, resulting from nuclear heating, is found to enhance the speed of circulation. Hot spots are located in low-velocity areas at the top of the calandria and below the inlet jet level between the fuel channels. A parametric study is carried out to investigate the effect of moderator inlet velocity,moderator inlet nozzle location, and geometric scaling. The results indicate that decreasing the moderator inlet velocity has no significant influence on the general features of the flow pattern (i.e., momentum dominant); however, too many high-temperature hot spots appear within the fuel channels

  1. Numerical Modeling of Ocean Circulation

    Science.gov (United States)

    Miller, Robert N.

    2007-01-01

    The modelling of ocean circulation is important not only for its own sake, but also in terms of the prediction of weather patterns and the effects of climate change. This book introduces the basic computational techniques necessary for all models of the ocean and atmosphere, and the conditions they must satisfy. It describes the workings of ocean models, the problems that must be solved in their construction, and how to evaluate computational results. Major emphasis is placed on examining ocean models critically, and determining what they do well and what they do poorly. Numerical analysis is introduced as needed, and exercises are included to illustrate major points. Developed from notes for a course taught in physical oceanography at the College of Oceanic and Atmospheric Sciences at Oregon State University, this book is ideal for graduate students of oceanography, geophysics, climatology and atmospheric science, and researchers in oceanography and atmospheric science. Features examples and critical examination of ocean modelling and results Demonstrates the strengths and weaknesses of different approaches Includes exercises to illustrate major points and supplement mathematical and physical details

  2. Circulating microparticles: square the circle

    Science.gov (United States)

    2013-01-01

    Background The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. PMID:23607880

  3. Vertical mixing by Langmuir circulations

    International Nuclear Information System (INIS)

    McWilliams, James C.; Sullivan, Peter P.

    2001-01-01

    Wind and surface wave frequently induce Langmuir circulations (LC) in the upper ocean, and the LC contribute to mixing materials down from the surface. In this paper we analyze large-eddy simulation (LES) cases based on surface-wave-averaged, dynamical equations and show that the effect of the LC is a great increase in the vertical mixing efficiency for both material properties and momentum. We provide new confirmation that the previously proposed K-profile parameterization (KPP) model accurately characterizes the turbulent transport in a weakly convective, wind-driven boundary layer with stable interior stratification. We also propose a modest generalization of KPP for the regime of weakly convective Langmuir turbulence. This makes the KPP turbulent flux profiles match those in the LES case with LC present fairly well, especially so for material properties being transported downwards from the ocean surface. However, some open issues remain about how well the present LES and KPP formulations represent Langmuir turbulence, in part because wave-breaking effects are not yet included. (Author)

  4. 46 CFR 56.50-45 - Circulating pumps.

    Science.gov (United States)

    2010-10-01

    ... APPURTENANCES Design Requirements Pertaining to Specific Systems § 56.50-45 Circulating pumps. (a) A main circulating pump and emergency means for circulating water through the main condenser shall be provided. The... circulating pump and the condenser. (b) Independent sea suctions shall be provided for the main circulating...

  5. Development of CO2 circulators

    International Nuclear Information System (INIS)

    Donaldson, J.

    1988-01-01

    The development of the basic machine types we have supplied has not been without problems. The Windscale AGR (the prototype AGR) was a small 1.2 MW vertically up circulator with an inlet temperature of 237 deg. C (459 deg. F). Oil leakage problems occurred and were cured in the works test facility and the machine went into service with no other problems. The Horizontal 5 MW machines for Hinkley/Hunterston were not so fortunate with vibration problems, interface corrosion problems (effecting the whole reactor) and material dimensional stability problems. Oil ingress problems did not show up in test work but were later reported from site. These reports were initially exagerated due to the measuring techniques which took the operators some time to resolve. In the vertical 5 MW machines for Hartlepool and Heysham 1 there are two interesting factors, firstly a spar failure and secondly shaft axial stability. Many of the problems were due to modifications at site or our inability to model all aspects of site installation from which lessons for the future can be learned. The latest stations Torness and Heysham II incorporate these lessons. The machines have been designed with so much margin that during the resolution of the reactor control rod gag problems the machines were run continuously at 20% overload (6.3 MW). From an initial accident case of 350 deg. C inlet temperature, this increased to 458 deg. C and now stands at 585 deg. C. No modifications to the impeller were required. The site experience to date is good with no operational problems reported. (author). 4 figs

  6. Circulating leptin and thyroid dysfunction

    DEFF Research Database (Denmark)

    Zimmermann-Belsing, Tina; Brabant, Georg; Holst, Jens Juul

    2003-01-01

    and triiodothyronine are involved in the starvation-induced decrease in thermogenesis. Both rodent and human studies of leptin have failed to show any consistent relationship between thyroid function and serum leptin concentrations. However, leptin might have an important role in thyroid pathophysiology due to thyroid...

  7. SpaceX Dragon Air Circulation System

    Science.gov (United States)

    Hernandez, Brenda; Piatrovich, Siarhei; Prina, Mauro

    2011-01-01

    The Dragon capsule is a reusable vehicle being developed by Space Exploration Technologies (SpaceX) that will provide commercial cargo transportation to the International Space Station (ISS). Dragon is designed to be a habitable module while it is berthed to ISS. As such, the Dragon Environmental Control System (ECS) consists of pressure control and pressure equalization, air sampling, fire detection, illumination, and an air circulation system. The air circulation system prevents pockets of stagnant air in Dragon that can be hazardous to the ISS crew. In addition, through the inter-module duct, the air circulation system provides fresh air from ISS into Dragon. To utilize the maximum volume of Dragon for cargo packaging, the Dragon ECS air circulation system is designed around cargo rack optimization. At the same time, the air circulation system is designed to meet the National Aeronautics Space Administration (NASA) inter-module and intra-module ventilation requirements and acoustic requirements. A flight like configuration of the Dragon capsule including the air circulation system was recently assembled for testing to assess the design for inter-module and intra-module ventilation and acoustics. The testing included the Dragon capsule, and flight configuration in the pressure section with cargo racks, lockers, all of the air circulation components, and acoustic treatment. The air circulation test was also used to verify the Computational Fluid Dynamics (CFD) model of the Dragon capsule. The CFD model included the same Dragon internal geometry that was assembled for the test. This paper will describe the Dragon air circulation system design which has been verified by testing the system and with CFD analysis.

  8. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A.

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management....

  9. Dual temperature concentration system

    International Nuclear Information System (INIS)

    Spevack, J.S.

    1975-01-01

    In a dual temperature isotope exchange system--exemplified by exchange of deuterium and protium between water and hydrogen sulfide gas in hot and cold towers, in which the feed stream (water) containing the desired isotope is passed through a pair of towers maintained at different temperatures wherein it effects isotope exchange with countercurrently circulated auxiliary fluid (H 2 S) and is impoverished in said isotope and then disposed of, e.g. discharged to waste,--the flow of isotope enriched auxiliary fluid between said towers (hot H 2 S saturated with water vapor) is divided and a part thereof is adjusted in its temperature (to cold tower conditions) and then passed to the auxiliary fluid impoverishing (cold) tower, while the remainder of the divided flow of such enriched auxiliary fluid is passed through a subsequent isotope concentration treatment to produce a product more highly enriched in the desired isotope and wherein it is also adjusted in its temperature and is impoverished in said isotope during said subsequent treatment before it is delivered to the said auxiliary fluid impoverishing (cold) tower. Certain provisions are made for returning to the hot tower liquid carried as vapor by the remainder of the divided flow to the subsequent isotope concentration treatment, for recovering sensible and latent heat, and for reducing passage of auxiliary fluid to waste

  10. Circulating docosahexaenoic acid levels are associated with fetal insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Jin-Ping Zhao

    Full Text Available Arachidonic acid (AA; C20∶4 n-6 and docosahexaenoic acid (DHA; C22∶6 n-3 are important long-chain polyunsaturated fatty acids (LC-PUFA in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally "programming" this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies.In a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration and beta-cell function (proinsulin-to-insulin ratio in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids were lower comparing newborns of gestational diabetic (n = 24 vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01. Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = -0.37, P <0.0001. The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity.Low circulating DHA levels are associated with compromised fetal insulin sensitivity, and may be involved in

  11. Oxy-fuel combustion on circulating fluidized bed. Chapter 5

    Energy Technology Data Exchange (ETDEWEB)

    Anthony, E.J. [Canmet, Natural Resources Canada (Canada); Hack, H. [Foster Wheeler North America Corporation (United States)

    2011-07-01

    This paper explores the developments and field tests carried out with oxy-fuel fluidized bed combustion. This method has the advantage over the other options of emitting a pure stream of CO2 which thus does not need to be concentrated to be liquefied, transported and stored. In addition, pilot scale tests have shown that oxy-fired circulating fluidized bed combustion (CFBC) results in low emission and fuel flexibility. This paper highlighted that oxy-fired CFBC might be a good option for CCS but tests performed so far have been on a small scale. To confirm the promising results of pilot tests, demonstration projects are underway and are presented herein.

  12. Sterilization of the artificial blood circulation apparatus with ozone

    Energy Technology Data Exchange (ETDEWEB)

    Pisarevskii, A A; Korukhov, N I.U.; Brazhnikov, E M; Konstantinova, M L; Razumovskii, S D

    1982-01-01

    Presented in this paper is the sterilization method of the assisted circulation unit. The method has been approved by stand testing and then applied for sterilizing the unit Ae, yeK-5 m when experimental implanting artificial heart. According to the method, ozone in concentration of 5 x 10(-3) moles/1 and with flow rate of 0,5 1/min is passed through an internal circuit of the unit during I h and 15 min. Control wash-out samples from lines have demonstrated complete sterility of the internal circuit. The method makes the sterilization process of such units much easier and may be recommended for clinical application.

  13. Relationship among circulating anti-Müllerian hormone, insulin like growth factor 1, cadmium and superovulatory response in dairy cows.

    Science.gov (United States)

    Abdel Aziz, R L; Khalil, A A Y; Abdel-Wahab, A; Hassan, N Y; Abdel-Hamied, E; Kasimanickam, R K

    2017-09-15

    The objectives of this study were 1. to determine the associations among circulating anti-Mullerian hormone (AMH), insulin like growth factor 1 (IGF1) and cadmium (Cd) concentrations of lactating Holstein cows at the time of superovulation and 2. to determine the effect of circulating AMH, IGF1 and Cd concentrations on the superovulatory response in Holstein dairy cows. Holstein cows (n = 30) were milked thrice daily and housed and fed in free stall barn as a separate group. All animals were synchronized for superovulation and flushed. Three blood samples for AMH, IGF1 and Cd analysis were collected prior to superovulation, at estrus and at the time of embryo collection. The concentrations of blood makers prior to superovulation were highly correlated to superovulatory response. Circulating concentrations of AMH, IGF1 prior to superovulation were negatively correlated to Cd concentrations (P cows were classified into quartiles (Q) of circulating AMH concentration, number of corpus luteum, and total embryos, total transferable embryos and total grade 1 embryos yield was significantly different for AMH quartiles. The superovulatory response parameters evaluated were increased with increased AMH concentrations; particularly we observed a >2-fold difference between first and fourth AMH quartiles in total transferable embryo yield and total grade 1 embryo yield. In conclusion, circulating AMH concentration was strongly associated with superovulatory response. Measuring AMH before enrolling cows in superovulation programs will likely allow practitioners to improve numbers of embryos produced and, thereby, reduce costs per embryo produced. Published by Elsevier Inc.

  14. Seawater circulating system in an aquaculture laboratory

    Digital Repository Service at National Institute of Oceanography (India)

    Chatterji, A.; Ingole, B.S.; Parulekar, A.H.

    The note gives an account, for the first time in India, of an Aquaculture Laboratory with open type seawater circulating system developed at the National Institute of Oceanography, Goa, India. Besides describing the details of the system...

  15. EOP MIT General Circulation Model (MITgcm)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data contains a regional implementation of the Massachusetts Institute of Technology general circulation model (MITgcm) at a 1-km spatial resolution for the...

  16. Seasonal Overturning Circulation in the Red Sea

    Science.gov (United States)

    Yao, F.; Hoteit, I.; Koehl, A.

    2010-12-01

    The Red Sea exhibits a distinct seasonal overturning circulation. In winter, a typical two-layer exchange structure, with a fresher inflow from the Gulf of Aden on top of an outflow from the Red Sea, is established. In summer months (June to September) this circulation pattern is changed to a three-layer structure: a surface outflow from the Red Sea on top of a subsurface intrusion of the Gulf of Aden Intermediate Water and a weakened deep outflow. This seasonal variability is studied using a general circulation model, MITgcm, with 6 hourly NCEP atmospheric forcing. The model is able to reproduce the observed seasonal variability very well. The forcing mechanisms of the seasonal variability related to seasonal surface wind stress and buoyancy flux, and water mass transformation processes associated with the seasonal overturning circulation are analyzed and presented.

  17. Blocking device especially for circulating pumps

    International Nuclear Information System (INIS)

    Susil, J.; Vychodil, V.; Lorenc, P.

    1976-01-01

    The claim of the invention is a blocking device which blocks reverse flow occurring after the shutdown of circulating pumps, namely in the operation of nuclear power plants or in pumps with a high delivery head. (F.M.)

  18. Estuarine turbidity, flushing, salinity, and circulation

    Science.gov (United States)

    Pritchard, D. W.

    1972-01-01

    The effects of estuarine turbidity, flushing, salinity, and circulation on the ecology of the Chesapeake Bay are discussed. The sources of fresh water, the variations in salinity, and the circulation patterns created by temperature and salinity changes are analyzed. The application of remote sensors for long term observation of water temperatures is described. The sources of sediment and the biological effects resulting from increased sediments and siltation are identified.

  19. [Circulating tumor cells: cornerstone of personalized medicine].

    Science.gov (United States)

    Rafii, A; Vidal, F; Rathat, G; Alix-Panabières, C

    2014-11-01

    Cancer treatment has evolved toward personalized medicine. It is mandatory for clinicians to ascertain tumor biological features in order to optimize patients' treatment. Identification and characterization of circulating tumor cells demonstrated a prognostic value in many solid tumors. Here, we describe the main technologies for identification and characterization of circulating tumor cells and their clinical application in gynecologic and breast cancers. Copyright © 2014. Published by Elsevier Masson SAS.

  20. Themes on circulation in the third world.

    Science.gov (United States)

    Chapman, M; Prothero, R M

    1983-01-01

    "This article focuses upon circulation, or reciprocal flows of people, with specific reference to Third World societies." Aspects considered include attempts to standardize terminology and to formulate typologies of population movement; the development of explanatory models of circulation and modernization, social networks, family welfare, and capitalism; and "the transfer of methods and concepts to societies and populations different from those from which they initially evolved and in which they were first tested." excerpt

  1. Blood leukocyte responses to extracorporeal circulation. 1. Short term extracorporeal circulation in dogs without and with extracorporeal irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Szemere, P.; Fliedner, T.M. (Ulm Univ. (Germany, F.R.). Abt. Klinische Physiologie)

    1983-01-01

    Short term (1 h) extracorporeal circulation without or with irradiation of blood was performed in two normal dogs in a series of experiments. The granulocyte count was constantly diminished, while the lymphocytes did not show any particular change in their concentration. In the majority of the experiments a decrease of the CFU-C content occurred to less than 70% of the initial level. There was no difference in the results of experiments with or without irradiation. In the 'bag to bag' procedures, no significant change in the blood leukocyte counts including CFU-C, was established.

  2. Surgical myocardial revascularization without extracorporeal circulation

    Directory of Open Access Journals (Sweden)

    Salomón Soriano Ordinola Rojas

    2003-05-01

    Full Text Available OBJECTIVE: To assess the immediate postoperative period of patients undergoing myocardial revascularization without extracorporeal circulation with different types of grafts. METHODS: One hundred and twelve patients, 89 (79.5% of whom were males, were revascularized without extracorporeal circulation. Their ages ranged from 39 to 85 years. The criteria for indicating myocardial revascularization without extracorporeal circulation were as follows: revascularized coronary artery caliber > 1.5 mm, lack of intramyocardial trajectory on coronary angiography, noncalcified coronary arteries, and tolerance of the heart to the different rotation maneuvers. RESULTS: Myocardial revascularization without extracorporeal circulation was performed in 112 patients. Three were converted to extracorporeal circulation, which required a longer hospital stay but did not impact mortality. During the procedure, the following events were observed: atrial fibrillation in 10 patients, ventricular fibrillation in 4, total transient atrioventricular block in 2, ventricular extrasystoles in 58, use of a device to retrieve red blood cells in 53, blood transfusion in 8, and arterial hypotension in 89 patients. Coronary angiography was performed in 20 patients on the seventh postoperative day when the grafts were patent. CONCLUSION: Myocardial revascularization without extracorporeal circulation is a reproducible technique that is an alternative for treating ischemic heart disease.

  3. Circulating 25-Hydroxyvitamin D and Risk of Epithelial Ovarian Cancer

    Science.gov (United States)

    Zheng, Wei; Danforth, Kim N.; Tworoger, Shelley S.; Goodman, Marc T.; Arslan, Alan A.; Patel, Alpa V.; McCullough, Marjorie L.; Weinstein, Stephanie J.; Kolonel, Laurence N.; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Steplowski, Emily; Visvanathan, Kala; Yu, Kai; Zeleniuch-Jacquotte, Anne; Gao, Yu-Tang; Hankinson, Susan E.; Harvey, Chinonye; Hayes, Richard B.; Henderson, Brian E.; Horst, Ronald L.; Helzlsouer, Kathy J.

    2010-01-01

    A role for vitamin D in ovarian cancer etiology is supported by ecologic studies of sunlight exposure, experimental mechanism studies, and some studies of dietary vitamin D intake and genetic polymorphisms in the vitamin D receptor. However, few studies have examined the association of circulating 25-hydroxyvitamin D (25(OH)D), an integrated measure of vitamin D status, with ovarian cancer risk. A nested case-control study was conducted among 7 prospective studies to evaluate the circulating 25(OH)D concentration in relation to epithelial ovarian cancer risk. Logistic regression models were used to estimate odds ratios and 95% confidence intervals among 516 cases and 770 matched controls. Compared with 25(OH)D concentrations of 50–<75 nmol/L, no statistically significant associations were observed for <37.5 (odds ratio (OR) = 1.21, 95% confidence interval (CI): 0.87, 1.70), 37.5–<50 (OR = 1.03, 95% CI: 0.75, 1.41), or ≥75 (OR = 1.11, 95% CI: 0.79, 1.55) nmol/L. Analyses stratified by tumor subtype, age, body mass index, and other variables were generally null but suggested an inverse association between 25(OH)D and ovarian cancer risk among women with a body mass index of ≥25 kg/m2 (Pinteraction < 0.01). In conclusion, this large pooled analysis did not support an overall association between circulating 25(OH)D and ovarian cancer risk, except possibly among overweight women. PMID:20562186

  4. [Circulating endothelial progenitor cell levels in treated hypertensive patients].

    Science.gov (United States)

    Maroun-Eid, C; Ortega-Hernández, A; Abad, M; García-Donaire, J A; Barbero, A; Reinares, L; Martell-Claros, N; Gómez-Garre, D

    2015-01-01

    Most optimally treated hypertensive patients still have an around 50% increased risk of any cardiovascular event, suggesting the possible existence of unidentified risk factors. In the last years there has been evidence of the essential role of circulating endothelial progenitor cells (EPCs) in the maintenance of endothelial integrity and function, increasing the interest in their involvement in cardiovascular disease. In this study, the circulating levels of EPCs and vascular endothelial growth factor (VEGF) are investigated in treated hypertensive patients with adequate control of blood pressure (BP). Blood samples were collected from treated hypertensive patients with controlled BP. Plasma levels of EPCs CD34+/KDR+ and CD34+/VE-cadherin+ were quantified by flow cytometry. Plasma concentration of VEGF was determined by ELISA. A group of healthy subjects without cardiovascular risk factors was included as controls. A total of 108 hypertensive patients were included (61±12 years, 47.2% men) of which 82.4% showed BP<140/90 mmHg, 91.7% and 81.5% controlled diabetes (HbA1c <7%) and cLDL (<130 or 100 mg/dL), respectively, and 85.2% were non-smokers. Around 45% of them were obese. Although patients had cardiovascular parameters within normal ranges, they showed significantly lower levels of CD34+/KDR+ and CD34+/VE-cadherin+ compared with healthy control group, although plasma VEGF concentration was higher in patients than in controls. Despite an optimal treatment, hypertensive patients show a decreased number of circulating EPCs that could be, at least in part, responsible for their residual cardiovascular risk, suggesting that these cells could be a therapeutic target. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  5. Hypoxia, leukocytes, and the pulmonary circulation.

    Science.gov (United States)

    Stenmark, Kurt R; Davie, Neil J; Reeves, John T; Frid, Maria G

    2005-02-01

    Data are rapidly accumulating in support of the idea that circulating monocytes and/or mononuclear fibrocytes are recruited to the pulmonary circulation of chronically hypoxic animals and that these cells play an important role in the pulmonary hypertensive process. Hypoxic induction of monocyte chemoattractant protein-1, stromal cell-derived factor-1, vascular endothelial growth factor-A, endothelin-1, and tumor growth factor-beta(1) in pulmonary vessel wall cells, either directly or indirectly via signals from hypoxic lung epithelial cells, may be a critical first step in the recruitment of circulating leukocytes to the pulmonary circulation. In addition, hypoxic stress appears to induce release of increased numbers of monocytic progenitor cells from the bone marrow, and these cells may have upregulated expression of receptors for the chemokines produced by the lung circulation, which thus facilitates their specific recruitment to the pulmonary site. Once present, macrophages/fibrocytes may exert paracrine effects on resident pulmonary vessel wall cells stimulating proliferation, phenotypic modulation, and migration of resident fibroblasts and smooth muscle cells. They may also contribute directly to the remodeling process through increased production of collagen and/or differentiation into myofibroblasts. In addition, they could play a critical role in initiating and/or supporting neovascularization of the pulmonary artery vasa vasorum. The expanded vasa network may then act as a conduit for further delivery of circulating mononuclear cells to the pulmonary arterial wall, creating a feedforward loop of pathological remodeling. Future studies will need to determine the mechanisms that selectively induce leukocyte/fibrocyte recruitment to the lung circulation under hypoxic conditions, their direct role in the remodeling process via production of extracellular matrix and/or differentiation into myofibroblasts, their impact on the phenotype of resident smooth muscle

  6. Arctic Ocean surface geostrophic circulation 2003–2014

    Directory of Open Access Journals (Sweden)

    T. W. K. Armitage

    2017-07-01

    Full Text Available Monitoring the surface circulation of the ice-covered Arctic Ocean is generally limited in space, time or both. We present a new 12-year record of geostrophic currents at monthly resolution in the ice-covered and ice-free Arctic Ocean derived from satellite radar altimetry and characterise their seasonal to decadal variability from 2003 to 2014, a period of rapid environmental change in the Arctic. Geostrophic currents around the Arctic basin increased in the late 2000s, with the largest increases observed in summer. Currents in the southeastern Beaufort Gyre accelerated in late 2007 with higher current speeds sustained until 2011, after which they decreased to speeds representative of the period 2003–2006. The strength of the northwestward current in the southwest Beaufort Gyre more than doubled between 2003 and 2014. This pattern of changing currents is linked to shifting of the gyre circulation to the northwest during the time period. The Beaufort Gyre circulation and Fram Strait current are strongest in winter, modulated by the seasonal strength of the atmospheric circulation. We find high eddy kinetic energy (EKE congruent with features of the seafloor bathymetry that are greater in winter than summer, and estimates of EKE and eddy diffusivity in the Beaufort Sea are consistent with those predicted from theoretical considerations. The variability of Arctic Ocean geostrophic circulation highlights the interplay between seasonally variable atmospheric forcing and ice conditions, on a backdrop of long-term changes to the Arctic sea ice–ocean system. Studies point to various mechanisms influencing the observed increase in Arctic Ocean surface stress, and hence geostrophic currents, in the 2000s – e.g. decreased ice concentration/thickness, changing atmospheric forcing, changing ice pack morphology; however, more work is needed to refine the representation of atmosphere–ice–ocean coupling in models before we can fully

  7. Lower peripheral circulation in eumenorrheic young women with premenstrual symptoms

    Directory of Open Access Journals (Sweden)

    Tatsumi Noriyuki

    2007-03-01

    Full Text Available Abstract Background A majority of women from all cultures and socioeconomic levels experience diverse psychosomatic and behavioral symptoms premenstrually, a phenomenon commonly termed premenstrual syndrome, although symptoms and discomfort levels vary from woman to woman. The underlying pathological mechanisms of premenstrual syndrome remain unknown; however, altered function or even slight disorder of the blood circulation system, which contributes to the orchestrations of the human internal environment, could cause bio-psychological changes leading to complaints and ultimately compromising a woman's overall health. The present study, therefore, investigates to what extent and how the menstrual cyclicity of peripheral circulation is associated with premenstrual symptomatology. Methods Twenty-one eumenorrheic young women participated in this study. All subjects were investigated during the follicular and late luteal phases. Cycle phase was determined by the onset of menstruation and oral temperature and was verified by concentrations of ovarian hormones, estrone, and pregnanediol in a urine sample taken early in the morning. Peripheral circulation was evaluated with the Astrim (Sysmex, Kobe, a portable non-invasive monitoring device using the principle of near-infrared spectroscopy, which calculates the venous oxygenation index (VOI based on the ratio of light absorption of oxyhemoglobin and deoxyhemoglobin, a proven reliable indicator of peripheral blood circulation. The Menstrual Distress Questionnaire was applied to measure physical, emotional, and behavioral symptoms accompanying the menstrual cycle of the subjects. Results The oral temperature and urinary ovarian hormones adjusted for creatinine significantly increased in the late luteal phase in all subjects. While 10 subjects experienced no symptoms during the menstrual cycle, 11 subjects had apparent physical and psychological discomfort in the late luteal phase. We found that VOI

  8. Circulating water pumps for nuclear power stations

    International Nuclear Information System (INIS)

    Satoh, Hiroshi; Ohmori, Tsuneaki

    1979-01-01

    Shortly, the nuclear power station with unit power output of 1100 MW will begin the operation, and the circulating water pumps manufactured recently are those of 2.4 to 4 m bore, 840 to 2170 m 3 /min discharge and 2100 to 5100 kW driving power. The circulating water pumps are one of important auxiliary machines, because if they fail, power generation capacity lowers immediately. Enormous quantity of cooling water is required to cool condensers, therefore in Japan, sea water is usually used. As siphon is formed in circulating water pipes, the total head of the pumps is not very high. The discharge of the pumps is determined so as to keep the temperature rise of discharged water lower than 7 deg. C. The quantity of cooling water for nuclear power generation is about 50% more as compared with thermal power generation because of the difference in steam conditions. The total head of the pumps is normally from 8 to 15 m. The circulating water pumps rarely stop after they started the operation, therefore it is economical to determine the motor power so that it can withstand 10% overload for a short period, instead of large power. At present, vertical shaft, oblique flow circulating water pumps are usually employed. Recently, movable blade pumps are adopted. The installation, construction and materials of the pumps and the problems are described. (Kako, I.)

  9. Cascade of circulations in fluid turbulence.

    Science.gov (United States)

    Eyink, Gregory L

    2006-12-01

    Kelvin's theorem on conservation of circulations is an essential ingredient of Taylor's theory of turbulent energy dissipation by the process of vortex-line stretching. In previous work, we have proposed a nonlinear mechanism for the breakdown of Kelvin's theorem in ideal turbulence at infinite Reynolds number. We develop here a detailed physical theory of this cascade of circulations. Our analysis is based upon an effective equation for large-scale coarse-grained velocity, which contains a turbulent-induced vortex force that can violate Kelvin's theorem. We show that singularities of sufficient strength, which are observed to exist in turbulent flow, can lead to nonvanishing dissipation of circulation for an arbitrarily small coarse-graining length in the effective equations. This result is an analog for circulation of Onsager's theorem on energy dissipation for singular Euler solutions. The physical mechanism of the breakdown of Kelvin's theorem is diffusion of lines of large-scale vorticity out of the advected loop. This phenomenon can be viewed as a classical analog of the Josephson-Anderson phase-slip phenomenon in superfluids due to quantized vortex lines. We show that the circulation cascade is local in scale and use this locality to develop concrete expressions for the turbulent vortex force by a multiscale gradient expansion. We discuss implications for Taylor's theory of turbulent dissipation and we point out some related cascade phenomena, in particular for magnetic flux in magnetohydrodynamic turbulence.

  10. Circulation as Assessment: Collection Development Policies Evaluated in Terms of Circulation at a Small Academic Library.

    Science.gov (United States)

    Dinkins, Debbi

    2003-01-01

    Discusses the use of academic library circulation statistics to assess whether user needs are being met and describes a study at Stetson University that investigated collection development practices by comparing circulation statistics for books selected by faculty in support of departmental curricula with those of librarian selections. (Author/LRW)

  11. A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes

    NARCIS (Netherlands)

    Sluijs, Ivonne; Holmes, Michael V.; van der Schouw, Yvonne T.; Beulens, Joline W J; Asselbergs, Folkert W.; Huerta, José María; Palmer, Tom M.; Arriola, Larraitz; Balkau, Beverley; Barricarte, Aurelio; Boeing, Heiner; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Franks, Paul W.; Gavrila, Diana; Kaaks, Rudolf; Khaw, Kay T ee; Kühn, Tilman; Molina-Montes, Esther; Mortensen, Lotte M axild; Nilsson, Peter M.; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sala, Núria; Schmidt, Julie A.; Scott, Robert A.; Sieri, Sabina; Slimani, Nadia; Spijkerman, Annemieke M W; Tjonneland, Anne; Travis, Ruth C.; Tumino, Rosario; van der A, Daphne L.; Sharp, Stephen J.; Forouhi, Nita G.; Langenberg, Claudia; Riboli, Elio; Wareham, Nicholas J.

    2015-01-01

    We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid-associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition

  12. Feedback between residual circulations and sediment distribution in highly turbid estuaries: an analytical model

    NARCIS (Netherlands)

    Talke, S.A.|info:eu-repo/dai/nl/304823554; de Swart, H.E.|info:eu-repo/dai/nl/073449725; Schuttelaars, H.|info:eu-repo/dai/nl/164035656

    2009-01-01

    Motivated by field studies of the Ems estuary which show longitudinal gradients in bottom sediment concentration as high as O(0.01 kg/m4), we develop an analytical model for estuarine residual circulation based on currents from salinity gradients, turbidity gradients, and freshwater discharge.

  13. Applications of environmental radon-222 to some cases of water circulation

    International Nuclear Information System (INIS)

    Kimura, S.; Komae, T.

    1980-01-01

    We have proposed three methods to analyze water circulation and the changes caused by human activities by studying the changing distribution patterns of 222 Rn concentrations in water. We investigated the results by applying the methods to some water circulation problems of Japan. The first method was a detailed analysis of the hydrogeological structure of an area, using the fact that the 222 Rn concentration of water takes a value characteristic of the aquifer. In the second method we analyzed the state of mixing of surface water and groundwater by taking advantage of the fact that the 222 Rn concentrations of the two are quite different. In the third method, we used the differing 222 Rn concentrations in vadose water and in retention water to analyze the pressure acting on the aquifer or the groundwater

  14. Experimental study of the natural circulation phenomena

    International Nuclear Information System (INIS)

    Sabundjian, Gaiane; Andrade, Delvonei Alves de; Umbehaun, Pedro E.; Torres, Walmir M.; Castro, Alfredo Jose Alvim de; Belchior Junior, Antonio; Rocha, Ricardo Takeshi Vieira da; Damy, Osvaldo Luiz de Almeida; Torres, Eduardo

    2006-01-01

    The objective of this paper is to study the natural circulation in experimental loops and extend the results to nuclear facilities. New generation of compact nuclear power plants use the natural circulation as cooling and residual heat removal systems in case of accidents or shutdown. Lately the interest in this phenomenon, by scientific community, has increased. The experimental loop, described in this paper, was assembled at Escola Politecnica - USP at the Chemical Engineering Department. It is the goal to generate information to help with the understanding of the one and two phase natural circulation phenomena. Some experiments were performed with different levels of heat power and different flow of the cooling water at the secondary circuit. The data generated from these experiments are going to be used to validate some computational thermal hydraulic codes. Experimental results for one and two phase regimes are presented as well as the proposed model to simulate the flow regimes with the RELAP5 code. (author)

  15. Systems engineering requirements impacting MHTGR circulator design

    International Nuclear Information System (INIS)

    Chi, H.W.; Baccaglini, G.M.; Potter, R.C.; Shenoy, A.S.

    1988-01-01

    At the initiation of the MHTGR program, an important task involved translating the plant users' requirements into design conditions. This was particularly true in the case of the heat transport and shutdown cooling systems since these embody many components. This paper addresses the two helium circulators in these systems. An integrated approach is being used in the development of design and design documentation for the MHTGR plant. It is an organized and systematic development of plant functions and requirements, determined by top-down design, performance, and cost trade-off studies and analyses, to define the overall plant systems, subsystems, components, and human actions. These studies, that led to the identification of the major design parameters for the two circulators, are discussed in this paper. This includes the performance information, steady state and transient data, and the various interface requirements. The design of the circulators used in the MHTGR is presented. (author). 1 ref., 17 figs

  16. Circulating microRNAs in breast cancer

    DEFF Research Database (Denmark)

    Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A

    2017-01-01

    Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in ...... circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management.......Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence...... in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising...

  17. Adjustable speed drives improve circulating water system

    International Nuclear Information System (INIS)

    Dent, R.A.; Dicic, Z.

    1994-01-01

    This paper illustrates the integration of electrical and mechanical engineering requirements to produce a solution to past problems and future operating demands. The application of adjustable speed drives in the modifications of the circulating water system at Indian Point No. 3 Nuclear Power Plant provided increased operating flexibility, efficiency and avoided otherwise costly renovations to the plant electrical systems. Rectification of the original inadequate design of the circulating water system, in addition to maximizing plant efficiency consistent with environmental considerations, formed the basis for this modification. This entailed replacement of all six circulating water pumps and motors and physical modifications to the intake system. This paper details the methodology used in this engineering task. The new system was installed successfully and has been operating reliably and economically for the past eight years

  18. Natural circulation in a scaled PWR integral test facility

    International Nuclear Information System (INIS)

    Kiang, R.L.; Jeuck, P.R. III

    1987-01-01

    Natural circulation is an important mechanism for cooling a nuclear power plant under abnormal operating conditions. To study natural circulation, we modeled a type of pressurized water reactor (PWR) that incorporates once-through steam generators. We conducted tests of single-phase natural circulations, two-phase natural circulations, and a boiler condenser mode. Because of complex geometry, the natural circulations observed in this facility exhibit some phenomena not commonly seen in a simple thermosyphon loop

  19. Experimental study of natural circulation circuit

    Energy Technology Data Exchange (ETDEWEB)

    Lemos, Wanderley F.; Su, Jian, E-mail: wlemos@lasme.coppe.ufrj.br, E-mail: sujian@lasme.coppe.ufrj.br [Coordenacao dos Programas de Pos-Graduacao de Engenharia (LASME/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Lab. de Simulacao e Metodos Numericos; Faccini, Jose L.H., E-mail: faccini@ien.gov.br [Instituto de Engenharia Nuclear (LTE/IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Lab. de Termo-Hidraulica Experimental

    2011-07-01

    This work presents an experimental study about fluid flows behavior in natural circulation, under conditions of single-phase flow. The experiment was performed through experimental thermal-hydraulic circuit built at IEN. This test equipment has performance similar to passive system of residual heat removal present in Advanced Pressurized Water Reactors (APWR). This experimental study aims to observing and analyzing the natural circulation phenomenon, using this experimental circuit that was dimensioned and built based on concepts of similarity and scale. This philosophy allows the analysis of natural circulation behavior in single-phase flow conditions proportionally to the functioning real conditions of a nuclear reactor. The experiment was performed through procedures to initialization of hydraulic feeding of primary and secondary circuits and electrical energizing of resistors installed inside heater. Power controller has availability to adjust values of electrical power to feeding resistors, in order to portray several conditions of energy decay of nuclear reactor in a steady state. Data acquisition system allows the measurement and monitoring of the evolution of the temperature in various points through thermocouples installed in strategic points along hydraulic circuit. The behavior of the natural circulation phenomenon was monitored by graphical interface on computer screen, showing the temperature evolutions of measuring points and results stored in digital spreadsheets. The results stored in digital spreadsheets allowed the getting of data to graphic construction and discussion about natural circulation phenomenon. Finally, the calculus of Reynolds number allowed the establishment for a correlation of friction in function of geometric scales of length, heights and cross section of tubing, considering a natural circulation flow throughout in the region of hot leg. (author)

  20. Fort St. Vrain circulator operating experience

    Energy Technology Data Exchange (ETDEWEB)

    Brey, H. L.

    1988-08-15

    Fort St. Vrain, on the system of Public Service Company of Colorado, is the only high-temperature gas-cooled power reactor in the United States. Four helium circulators are utilized in this plant to transfer heat from the reactor to the steam generators. These unique machines have a single stage axial flow helium compressor driven by a single stage steam turbine. A single stage water driven (pelton wheel) turbine is the back-up drive utilizing either feed water, condensate, or fire water as the driving fluid. Developmental testing of the circulators was accomplished prior to installation into Fort St. Vrain. A combined machine operating history of approximately 250,000 hours has shown these machines to be of conservative design and proven mechanical integrity. However, many problems have been encountered in operating the complex auxiliaries which are necessary for successful circulator and plant operation. It has been 15 years since initial installation of the circulators occurred at Fort St. Vrain. During this time, a number of significant issues had to be resolved dealing specifically with machine performance. These events include cavitation damage of the pelton wheels during the initial plant hot functional testing, cracks in the water turbine buckets and cervic coupling, static shutdown seal bellows failure, and, most recently, degradation of components within the steam drive assembly. Unreliable operation particularly with the circulator auxiliaries has been a focus of attention by Public Service Company of Colorado. Actions to replace or significantly modify the existing circulators and their auxiliaries are currently awaiting decisions concerning the long-term future of the Fort St. Vrain plant. (author). 10 refs, 7 figs, 2 tabs.

  1. Experimental study of natural circulation circuit

    International Nuclear Information System (INIS)

    Lemos, Wanderley F.; Su, Jian; Faccini, Jose L.H.

    2011-01-01

    This work presents an experimental study about fluid flows behavior in natural circulation, under conditions of single-phase flow. The experiment was performed through experimental thermal-hydraulic circuit built at IEN. This test equipment has performance similar to passive system of residual heat removal present in Advanced Pressurized Water Reactors (APWR). This experimental study aims to observing and analyzing the natural circulation phenomenon, using this experimental circuit that was dimensioned and built based on concepts of similarity and scale. This philosophy allows the analysis of natural circulation behavior in single-phase flow conditions proportionally to the functioning real conditions of a nuclear reactor. The experiment was performed through procedures to initialization of hydraulic feeding of primary and secondary circuits and electrical energizing of resistors installed inside heater. Power controller has availability to adjust values of electrical power to feeding resistors, in order to portray several conditions of energy decay of nuclear reactor in a steady state. Data acquisition system allows the measurement and monitoring of the evolution of the temperature in various points through thermocouples installed in strategic points along hydraulic circuit. The behavior of the natural circulation phenomenon was monitored by graphical interface on computer screen, showing the temperature evolutions of measuring points and results stored in digital spreadsheets. The results stored in digital spreadsheets allowed the getting of data to graphic construction and discussion about natural circulation phenomenon. Finally, the calculus of Reynolds number allowed the establishment for a correlation of friction in function of geometric scales of length, heights and cross section of tubing, considering a natural circulation flow throughout in the region of hot leg. (author)

  2. Fort St. Vrain circulator operating experience

    International Nuclear Information System (INIS)

    Brey, H.L.

    1988-01-01

    Fort St. Vrain, on the system of Public Service Company of Colorado, is the only high-temperature gas-cooled power reactor in the United States. Four helium circulators are utilized in this plant to transfer heat from the reactor to the steam generators. These unique machines have a single stage axial flow helium compressor driven by a single stage steam turbine. A single stage water driven (pelton wheel) turbine is the back-up drive utilizing either feed water, condensate, or fire water as the driving fluid. Developmental testing of the circulators was accomplished prior to installation into Fort St. Vrain. A combined machine operating history of approximately 250,000 hours has shown these machines to be of conservative design and proven mechanical integrity. However, many problems have been encountered in operating the complex auxiliaries which are necessary for successful circulator and plant operation. It has been 15 years since initial installation of the circulators occurred at Fort St. Vrain. During this time, a number of significant issues had to be resolved dealing specifically with machine performance. These events include cavitation damage of the pelton wheels during the initial plant hot functional testing, cracks in the water turbine buckets and cervic coupling, static shutdown seal bellows failure, and, most recently, degradation of components within the steam drive assembly. Unreliable operation particularly with the circulator auxiliaries has been a focus of attention by Public Service Company of Colorado. Actions to replace or significantly modify the existing circulators and their auxiliaries are currently awaiting decisions concerning the long-term future of the Fort St. Vrain plant. (author). 10 refs, 7 figs, 2 tabs

  3. Circulating interleukin-6 in relation to adiposity, insulin action, and insulin secretion

    DEFF Research Database (Denmark)

    Vozarova, B; Weyer, C; Hanson, K

    2001-01-01

    Plasma concentrations of interleukin-6 (IL-6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined w...... whether circulating plasma IL-6 concentrations were related to direct measures of insulin resistance and insulin secretory dysfunction in Pima Indians, a population with high rates of obesity and type 2 diabetes....

  4. Quenching phenomena in natural circulation loop

    International Nuclear Information System (INIS)

    Umekawa, Hisashi; Ozawa, Mamoru; Ishida, Naoki

    1995-01-01

    Quenching phenomena has been investigated experimentally using circulation loop of liquid nitrogen. During the quenching under natural circulation, the heat transfer mode changes from film boiling to nucleate boiling, and at the same time flux changes with time depending on the vapor generation rate and related two-phase flow characteristics. Moreover, density wave oscillations occur under a certain operating condition, which is closely related to the dynamic behavior of the cooling curve. The experimental results indicates that the occurrence of the density wave oscillation induces the deterioration of effective cooling of the heat surface in the film and the transition boiling regions, which results in the decrease in the quenching velocity

  5. Labour circulation and the urban labour process.

    Science.gov (United States)

    Standing, G

    1986-01-01

    The author investigates aspects of labor circulation, which he defines as "temporary movement between geographical areas for work or in search of work....[He attempts to determine] what roles have been played by labour circulation in the development of urban-industrial labour forces in the transition to industrial capitalism." Factors considered include the exploitation and oppression of labor migrants; the industrial-urban labor reserve; urban socioeconomic stratification and discrimination by age, sex, or race; the division of labor; and policy options. excerpt

  6. An elementary model of money circulation

    Science.gov (United States)

    Pokrovskii, Vladimir N.; Schinckus, Christophe

    2016-12-01

    This paper investigates money circulation for a system, consisting of a production system, the government, a central bank, commercial banks and many customers of the commercial banks. A set of equations for the system is written; the theory determines the main features of interaction between production and money circulation. Investigation of the equations in a steady-state situation reveals some relationship among output of the production system and monetary variables. The relation of quantity theory of money is confirmed, whereas a new concept of the efficiency of the system is introduced.

  7. Engineering Judgment and Natural Circulation Calculations

    International Nuclear Information System (INIS)

    Ferreri, J.C.; Ferreri, J.C.

    2011-01-01

    The analysis performed to establish the validity of computer code results in the particular field of natural circulation flow stability calculations is presented in the light of usual engineering practice. The effects of discretization and closure correlations are discussed and some hints to avoid undesired mistakes in the evaluations performed are given. Additionally, the results are presented for an experiment relevant to the way in which a (small) number of skilled, nuclear safety analysts and researchers react when facing the solution of a natural circulation problem. These results may be also framed in the concept of Engineering Judgment and are potentially useful for Knowledge Management activities.

  8. First circulating beam in the AA

    CERN Multimedia

    CERN PhotoLab

    1980-01-01

    On 3 July 1980, two years after project authorization, beam circulated for the first time in the AA. It was a 3.56 GeV/c proton test beam. We see an expecting crowd, minutes before the happy event. The persons are too numerous to name them all, but the 3 most prominent ones are at the centre (left to right): Roy Billinge (Joint AA Project Leader, with his hand on the control box), Eifionydd Jones (white shirt), Simon van der Meer (spiritus rector and Joint AA Project Leader). The first antiprotons were injected, made to circulate and cooled soon after, on 14 July 1980.

  9. Quenching phenomena in natural circulation loop

    Energy Technology Data Exchange (ETDEWEB)

    Umekawa, Hisashi; Ozawa, Mamoru [Kansai Univ., Osaka (Japan); Ishida, Naoki [Daihatsu Motor Company, Osaka (Japan)

    1995-09-01

    Quenching phenomena has been investigated experimentally using circulation loop of liquid nitrogen. During the quenching under natural circulation, the heat transfer mode changes from film boiling to nucleate boiling, and at the same time flux changes with time depending on the vapor generation rate and related two-phase flow characteristics. Moreover, density wave oscillations occur under a certain operating condition, which is closely related to the dynamic behavior of the cooling curve. The experimental results indicates that the occurrence of the density wave oscillation induces the deterioration of effective cooling of the heat surface in the film and the transition boiling regions, which results in the decrease in the quenching velocity.

  10. Estimation of the maternal vitamin D intake that maintains circulating 25-hydroxyvitamin D in late gestation at a concentration sufficient to keep umbilical cord sera ≥25-30 nmol/L: a dose-response, double-blind, randomized placebo-controlled trial in pregnant women at northern latitude.

    Science.gov (United States)

    O'Callaghan, Karen M; Hennessy, Áine; Hull, George Lj; Healy, Karina; Ritz, Christian; Kenny, Louise C; Cashman, Kevin D; Kiely, Mairead E

    2018-06-06

    In the absence of dose-response data, Dietary Reference Values for vitamin D in nonpregnant adults are extended to pregnancy. The aim was to estimate vitamin D intake needed to maintain maternal 25-hydroxyvitamin D [25(OH)D] in late gestation at a concentration sufficient to prevent newborn 25(OH)D D3/d from ≤18 wk of gestation. Vitamin D metabolites at 14, 24, and 36 wk of gestation and in cord sera, including 25(OH)D3, 3-epi-25(OH)D3, 24,25(OH)2D3, and 25(OH)D2 were quantified by liquid chromatography-tandem mass spectrometry. A curvilinear regression model predicted the total vitamin D intake (from diet and antenatal supplements plus treatment dose) that maintained maternal 25(OH)D in late gestation at a concentration sufficient to maintain cord 25(OH)D at ≥25-30 nmol/L. Mean ± SD baseline 25(OH)D was 54.9 ± 10.7 nmol/L. Total vitamin D intakes at the study endpoint (36 wk of gestation) were 12.1 ± 8.0, 21.9 ± 5.3, and 33.7 ± 5.1 µg/d in the placebo and 10-µg and 20-µg vitamin D3 groups, respectively; and 25(OH)D was 24.3 ± 5.8 and 29.2 ± 5.6 nmol/L higher in the 10- and 20-µg groups, respectively, compared with placebo (P D concentrations ≥50 nmol/L, 95% of cord sera were ≥30 nmol/L and 99% were >25 nmol/L. The estimated vitamin D intake required to maintain serum 25(OH)D at ≥50 nmol/L in 97.5% of women was 28.9 µg/d. Thirty micrograms of vitamin D per day safely maintained serum 25(OH)D concentrations at ≥50 nmol/L in almost all white-skinned women during pregnancy at a northern latitude, which kept 25(OH)D at >25 nmol/L in 99% and ≥30 nmol/L in 95% of umbilical cord sera. This trial was registered at www.clinicaltrials.gov as NCT02506439.

  11. Refractory experience in circulating fluidized bed combustors, Task 7. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Vincent, R.Q.

    1989-11-01

    This report describes the results of an investigation into the status of the design and selection of refractory materials for coal-fueled circulating fluidized-bed combustors. The survey concentrated on operating units in the United States manufactured by six different boiler vendors: Babcock and Wilcox, Combustion Engineering, Foster Wheeler, Keeler Dorr-Oliver, Pyropower, and Riley Stoker. Information was obtained from the boiler vendors, refractory suppliers and installers, and the owners/operators of over forty units. This work is in support of DOE`s Clean Coal Technology program, which includes circulating fluidized-bed technology as one of the selected concepts being evaluated.

  12. Bed system performance in helium circulation mode

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yean Jin; Jung, Kwang Jin; Ahn, Do Hee; Chung, Hong Suk [UST, Daejeon (Korea, Republic of); Kang, Hee Suk [KAERI, Daejeon (Korea, Republic of); Yun, Sei Hun [NFRI, Deajeon (Korea, Republic of)

    2016-05-15

    As a part of the International Thermonuclear Experimental Reactor (ITER) Project, We have conducted an experiment for storing hydrogen to depleted uranium and zirconium cobalt. The helium blanket effect has been observed in experiments using metal hydrides. The collapse of the hydrogen isotopes are accompanied by the decay heat and helium-3. Helium-3 dramatically reduces the hydrogen isotope storage capacity by surrounding the metal. This phenomenon is called a helium blanket effect. In addition the authors are working on the recovery and removal techniques of helium-3. In this paper, we discuss the equipment used to test the helium blanket effect and the results of a helium circulation experiment. The helium-3 produced surrounds the storage material surface and thus disturbs the reaction of the storage material and the hydrogen isotope. Even if the amount of helium-3 is small, the storage capacity of the SDS bed significantly drops. This phenomenon is the helium blanket effect. To resolve this phenomenon, a circulating loop was introduced. Using a circulating system, helium can be separated from the storage material. We made a helium loop that includes a ZrCo bed. Then using a metal bellows pump, we tested the helium circulation.

  13. Periodontitis and increase in circulating oxidative stress

    Directory of Open Access Journals (Sweden)

    Takaaki Tomofuji

    2009-05-01

    Full Text Available Reactive oxygen species (ROS are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress. Such oxidation may be detrimental to systemic health. For instance, previous animal studies suggested that experimental periodontitis induces oxidative damage of the liver and descending aorta by increasing circulating oxidative stress. In addition, it has been revealed that clinical parameters in chronic periodontitis patients showed a significant improvement 2 months after periodontal treatment, which was accompanied by a significant reduction of reactive oxygen metabolites in plasma. Improvement of periodontitis by periodontal treatment could reduce the occurrence of circulating oxidative stress. Furthermore, recent studies indicate that the increase in circulating oxidative stress following diabetes mellitus and inappropriate nutrition damages periodontal tissues. In such cases, therapeutic approaches to systemic oxidative stress might be necessary to improve periodontal health.

  14. Natural circulation under severe accident conditions

    International Nuclear Information System (INIS)

    Pafford, D.J.; Hanson, D.J.; Tung, V.X.; Chmielewski, S.V.

    1992-01-01

    Research is being conducted to better understand natural circulation phenomena in mixtures of steam and noncondensibles and its influence on the temperature of the vessel internals and the hot leg, pressurizer surge line, and steam generator tubes. The temperature of these structures is important because their failure prior to reactor vessel lower head failure could reduce the likelihood of containment failure as a result of direct containment heating. Computer code calculations (MELPROG, SCDAP/RELAP5/MOD3) predict high fluid temperatures in the upper plenum resulting from in-vessel natural circulation. Using a simple model for the guide tube phenomena, high upper plenum temperatures are shown to be consistent with the relatively low temperatures that were deduced metallurgically from leadscrews removed from the TMI-2 upper plenum. Evaluation of the capabilities of the RELAP5/MOD3 computer code to predict natural circulation behavior was also performed. The code was used to model the Westinghouse natural circulation experimental facility. Comparisons between code calculations and results from experiments show good agreement

  15. Detecting Holocene changes in thermohaline circulation

    OpenAIRE

    Keigwin, L. D.; Boyle, E. A.

    2000-01-01

    Throughout the last glacial cycle, reorganizations of deep ocean water masses were coincident with rapid millennial-scale changes in climate. Climate changes have been less severe during the present interglacial, but evidence for concurrent deep ocean circulation change is ambiguous.

  16. Opportunities in CARICOM Migration : Brain Circulation, Diasporic ...

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

    Opportunities in CARICOM Migration : Brain Circulation, Diasporic Tourism, and Investment. Between 1965 and 2000, about 12% of the Caribbean labour force moved to Canada and other developed countries, making the Caribbean the largest per capita source of emigrants in the world. Remittances from these emigrants ...

  17. Oceanic Circulation. A Programmed Unit of Instruction.

    Science.gov (United States)

    Marine Maritime Academy, Castine.

    This booklet contains a programmed lesson on oceanic circulation. It is designed to allow students to progress through the subject at their own speed. Since it is written in linear format, it is suggested that students proceed through the program from "frame" to succeeding "frame." Instructions for students on how to use the booklet are included.…

  18. 3D Visualization of Global Ocean Circulation

    Science.gov (United States)

    Nelson, V. G.; Sharma, R.; Zhang, E.; Schmittner, A.; Jenny, B.

    2015-12-01

    Advanced 3D visualization techniques are seldom used to explore the dynamic behavior of ocean circulation. Streamlines are an effective method for visualization of flow, and they can be designed to clearly show the dynamic behavior of a fluidic system. We employ vector field editing and extraction software to examine the topology of velocity vector fields generated by a 3D global circulation model coupled to a one-layer atmosphere model simulating preindustrial and last glacial maximum (LGM) conditions. This results in a streamline-based visualization along multiple density isosurfaces on which we visualize points of vertical exchange and the distribution of properties such as temperature and biogeochemical tracers. Previous work involving this model examined the change in the energetics driving overturning circulation and mixing between simulations of LGM and preindustrial conditions. This visualization elucidates the relationship between locations of vertical exchange and mixing, as well as demonstrates the effects of circulation and mixing on the distribution of tracers such as carbon isotopes.

  19. Efficient Circulation of Railway Rolling Stock

    NARCIS (Netherlands)

    Alfieri, A.; Groot, R.; Kroon, L.G.; Schrijver, A.

    2006-01-01

    Railway rolling stock (locomotives, carriages, and train units) is one of the most significant cost sources for operatorsof passenger trains, both public and private. Rolling stock costsare due to material acquisition, power supply, and material maintenance. The efficient circulation of rolling

  20. Efficient Circulation of Railway Rolling Stock

    NARCIS (Netherlands)

    A. Alfieri (Arianna); R. Groot (Rutger); L.G. Kroon (Leo); A. Schrijver (Lex)

    2002-01-01

    textabstractRailway rolling stock (locomotives, carriages, and train units) is one of the most significant cost sources for operatorsof passenger trains, both public and private. Rolling stock costsare due to material acquisition, power supply, and material maintenance. The efficient circulation of

  1. Efeitos do exercício crônico sobre a concentração circulante da leptina e grelina em ratos com obesidade induzida por dieta Effects of the chronic exercise on the circulating concentration of leptin and ghrelin in rats With diet-induced obesity

    Directory of Open Access Journals (Sweden)

    Ricardo Eguchi

    2008-06-01

    Full Text Available A obesidade vem se tornando uma das maiores epidemias mundiais, dessa forma, conhecer sua etiologia e mecanismos que regulam seu desenvolvimento é de grande relevância para o seu Tratamento. Portanto, o objetivo do presente estudo foi avaliar os efeitos da obesidade exógena induzida pela dieta de cafeteria e da atividade física crônica em ratos, sobre a adiposidade e a concentração sérica dos hormônios reguladores do balanço energético (leptina e grelina. Foram utilizados 32 ratos Wistar machos, divididos em quatro grupos: Sedentário alimentado com dieta padrão (SN, sedentário alimentado com dieta de cafeteria (SC, treinado alimentado com dieta padrão (TN e treinado alimentado com dieta de cafeteria (TC. A dieta de cafeteria aumentou significativamente a adiposidade central (RET e visceral (EPI (pObesity is becoming one of the biggest worldwide epidemics. Therefore, knowing its etiology and mechanisms that regulate its development is of great relevance for its treatment. Thus, the aim of the present study was to evaluate the effects of obesity induced by the palatable hyperlipidic diet and of the chronic physical activity in rats, on the adiposity and the serum concentration of regulating hormones of the energy balance (leptin and ghrelin. 32 male Wistar rats were divided in four groups: Sedentary fed with chow diet (SN, sedentary fed with cafeteria diet (SC, trained fed with chow diet (TN and trained fed with cafeteria diet (TC. The cafeteria diet led to a significant increase of central (RET and visceral (EPI adiposity (p<0.05. Conversely,the exercise training minimized the effect of the cafeteria diet, diminishing the central and visceral adiposity. Leptin was also increased in the groups fed with the cafeteria diet, suggesting increase of the resistance to the action of this hormone. Chronic physical activity did not hinder the development of hyperleptinemia. Reduction in the serum ghrelin concentration was observed only in

  2. Alcohol and dietary fibre intakes affect circulating sex hormones among premenopausal women.

    Science.gov (United States)

    Maskarinec, Gertraud; Morimoto, Yukiko; Takata, Yumie; Murphy, Suzanne P; Stanczyk, Frank Z

    2006-10-01

    The association of alcohol and fibre intake with breast cancer may be mediated by circulating sex hormone levels, which are predictors of breast cancer risk. To evaluate the relationship of alcohol and dietary fibre intake with circulating sex hormone levels among premenopausal women. A total of 205 premenopausal women completed a validated food-frequency questionnaire at baseline and after 2 years; blood samples taken at the same time were analysed for circulating sex hormone concentrations, including oestrone (E1), oestradiol (E2), free E2, progesterone, androstenedione and sex hormone-binding globulin, by radioimmunoassay. We used mixed models to estimate least-square means of sex hormone concentrations for alcohol intake categories and quartiles of dietary intake. After adjustment for covariates, alcohol consumption was moderately associated with higher circulating oestrogen levels; those who consumed more than one drink per day had 20% higher E2 (Ptrend=0.07) levels than non-drinkers. In contrast, higher dietary fibre intake was associated with lower serum levels of androstenedione (-8% between the lowest and highest quartiles of intake, Ptrend=0.06), but not oestrogens. Similarly, consumption of fruits (-12%, Ptrend=0.03), vegetables (-9%, Ptrend=0.15) and whole grains (-7%, Ptrend=0.07) showed inverse associations with androstenedione levels. The consistency of the observed differences in sex hormone levels associated with alcohol and fibre-rich foods indicates that these nutritional factors may affect sex hormone concentrations and play a role in breast cancer aetiology and prevention.

  3. Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer

    Science.gov (United States)

    Stolzenberg-Solomon, Rachael Z.; Jacobs, Eric J.; Arslan, Alan A.; Qi, Dai; Patel, Alpa V.; Helzlsouer, Kathy J.; Weinstein, Stephanie J.; McCullough, Marjorie L.; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L.; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N.

    2010-01-01

    Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974–2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50–<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (≥100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered. PMID:20562185

  4. Observations of the summer Red Sea circulation

    Science.gov (United States)

    Sofianos, Sarantis S.; Johns, William E.

    2007-06-01

    Aiming at exploring and understanding the summer circulation in the Red Sea, a cruise was conducted in the basin during the summer of 2001 involving hydrographic, meteorological, and direct current observations. The most prominent feature, characteristic of the summer circulation and exchange with the Indian Ocean, is a temperature, salinity, and oxygen minimum located around a depth of 75 m at the southern end of the basin, associated with Gulf of Aden Intermediate Water inflowing from the Gulf of Aden during the summer season as an intruding subsurface layer. Stirring and mixing with ambient waters lead to marked increases in temperature (from 16.5 to almost 33°C) and salinity (from 35.7 to more than 38 psu) in this layer by the time it reaches midbasin. The observed circulation presents a very vigorous pattern with strong variability and intense features that extend the width of the basin. A permanent cyclone, detected in the northern Red Sea, verifies previous observations and modeling studies, while in the central sector of the basin a series of very strong anticyclones were observed with maximum velocities exceeding 1 m/s. The three-layer flow pattern, representative of the summer exchange between the Red Sea and the Gulf of Aden, is observed in the strait of Bab el Mandeb. In the southern part of the basin the layer flow is characterized by strong banking of the inflows and outflows against the coasts. Both surface and intermediate water masses involved in the summer Red Sea circulation present prominent spatial variability in their characteristics, indicating that the eddy field and mixing processes play an important role in the summer Red Sea circulation.

  5. Decontamination of CAGR gas circulator components

    International Nuclear Information System (INIS)

    Rogers, L.N.; Hooper, A.J.

    1985-01-01

    This paper describes the development and full-scale trial of two methods for removal of radioactive contamination on the surfaces of CAGR gas circulator components. The two methods described are a particle impact cleaning (PIC) decontamination technique and an electrochemical technique, 'electro-swabbing', which is based on the principle of decontamination by electro-polishing. In developing these techniques it was necessary to take account of the physical and chemical nature of the surface deposits on the gas circulator components; these were shown to consist of magnetite-type oxide and carbonaceous material. In order to follow the progress of the decontamination it was also necessary to develop a surface sampling technique which was effective and precise under these conditions; an electrochemical technique, employing similar principles to the electro-swabbing process, was developed for this purpose. The full-scale trial of the PIC decontamination technique was carried out on an inlet guide vane (IGV) assembly, this having been identified as the component from the gas circulator which contributes most to the radiation dose accumulated during routine circulator maintenance. The technique was shown to be practically viable and some 99% of the radioactive contamination was readily removed from the treated surfaces with only negligible surface damage being caused. The full-scale trial of the electro-swabbing decontamination technique was carried out on a gas circulator impeller. High decontamination factors were again achieved with ≥ 99% of the radioactive contamination being removed from the treated surfaces. The technique has practical limitations in terms of handling and treatment of waste-arisings. However, the use of specially-designed swabbing electrodes may allow the treatment of constricted geometries inaccessible to techniques such as PIC. The technique is also highly suitable for the treatment of soft-finish materials and of components fabricated from a

  6. Ten residual biomass fuels for circulating fluidized-bed gasification

    Energy Technology Data Exchange (ETDEWEB)

    Drift, A. van der; Doorn, J. van [Netherlands Energy Research Foundation (ECN), Petten (Netherlands); Vermeulen, J.W. [NV Afvalzorg, Haarlem (Netherlands)

    2001-07-01

    In co-operation with a Dutch company (NV Afvalzorg) and the Dutch agency for energy and environment (Novem), ECN has successfully tested 10 different biomass residues in its 500 kW{sub th} circulating fluidized-bed gasification facility. Among the fuels used as demolition wood (both puree and mixed with sewage sludge and paper sludge), verge grass, railroad ties, cacao shells and different woody fuels. Railroad ties turn out to contain very little (heavy) metals. Initially, fuel feeding problems often impeded smooth operation. Contrary to feeding systems, the circulating fluidized-bed gasification process itself seems very flexible concerning the conversion of different kinds of biomass fuels. The fuel moisture content is one of the most important fuel characteristics. More moisture means that more air is needed to maintain the process temperature resulting in better carbon conversion and lower tar emission but also lower product gas heating value and lower cold gas efficiency. So, for a good comparison of the gasification behaviour of different fuels, the moisture content should be similar. However, the moisture content should be defined on an ash-free basis rather than on total mass (the usual way). Some of the ashes produced and retained in the second cyclone were analysed both for elemental composition and leaching behaviour. It turned out that the leaching rate of Mo and Br, elements only present in small concentrations, are preventing the ash to be considered as inert material according to the Dutch legislation for dumping on landfill sites. (Author)

  7. Performance Improvement of a Radioactive Forced Circulation Evaporator System

    International Nuclear Information System (INIS)

    Zaki, A.A.; Hala, A.A.; Othman, E.A.

    2016-01-01

    Evaporation is a proven method for treatment of liquid radioactive wastes providing both good decontamination and high concentration. In a radioactive waste treatment plant a forced circulation evaporator is used to reduce the volume of radioactive liquid wastes arising from different applications of nuclear industries. The safe operation, limiting the composition of the liquid radioactive waste at a prescribed value, with high performance efficiency, requires good control for the evaporator operating pressure and the level of liquid waste inside the separator part of the evaporator. The aim of this work was to improve the safety and performance of a forced-circulation evaporator used in a liquid radioactive wastes treatment plant. In this respect, a level controller system for this type of evaporator was designed, where proportional (P), proportional Integral (PI) and deadbeat response controllers for the separator level system were suggested. More over, an ideal 2×2(2 inputs and 2 outputs )de coupler controller for controlling the operating pressure and the product composition was developed. Computer results demonstrated that the deadbeat response has been success fully obtained from the developed separator control system. The maximum over shoot in the unit-step response curve was reduce d to 25 % and the settling time also was reduced to more than the half; about 26 minutes using Ziegler-Nichols tuning technique.The designed de coupling controller has been found effective in achieving a good trade-off between stability and performance

  8. Vertical circulation and thermospheric composition: a modelling study

    Directory of Open Access Journals (Sweden)

    H. Rishbeth

    Full Text Available The coupled thermosphere-ionosphere-plasmasphere model CTIP is used to study the global three-dimensional circulation and its effect on neutral composition in the midlatitude F-layer. At equinox, the vertical air motion is basically up by day, down by night, and the atomic oxygen/molecular nitrogen [O/N2] concentration ratio is symmetrical about the equator. At solstice there is a summer-to-winter flow of air, with downwelling at subauroral latitudes in winter that produces regions of large [O/N2] ratio. Because the thermospheric circulation is influenced by the high-latitude energy inputs, which are related to the geometry of the Earth's magnetic field, the latitude of the downwelling regions varies with longitude. The downwelling regions give rise to large F2-layer electron densities when they are sunlit, but not when they are in darkness, with implications for the distribution of seasonal and semiannual variations of the F2-layer. It is also found that the vertical distributions of O and N2 may depart appreciably from diffusive equilibrium at heights up to about 160 km, especially in the summer hemisphere where there is strong upwelling.

    Atmospheric composition and structure (thermosphere · composition and chemistry · Ionosphere (ionosphere · atmosphere interactions

  9. Vertical circulation and thermospheric composition: a modelling study

    Directory of Open Access Journals (Sweden)

    H. Rishbeth

    1999-06-01

    Full Text Available The coupled thermosphere-ionosphere-plasmasphere model CTIP is used to study the global three-dimensional circulation and its effect on neutral composition in the midlatitude F-layer. At equinox, the vertical air motion is basically up by day, down by night, and the atomic oxygen/molecular nitrogen [O/N2] concentration ratio is symmetrical about the equator. At solstice there is a summer-to-winter flow of air, with downwelling at subauroral latitudes in winter that produces regions of large [O/N2] ratio. Because the thermospheric circulation is influenced by the high-latitude energy inputs, which are related to the geometry of the Earth's magnetic field, the latitude of the downwelling regions varies with longitude. The downwelling regions give rise to large F2-layer electron densities when they are sunlit, but not when they are in darkness, with implications for the distribution of seasonal and semiannual variations of the F2-layer. It is also found that the vertical distributions of O and N2 may depart appreciably from diffusive equilibrium at heights up to about 160 km, especially in the summer hemisphere where there is strong upwelling. Atmospheric composition and structure (thermosphere · composition and chemistry · Ionosphere (ionosphere · atmosphere interactions

  10. Nonrandom distribution of iron in circulating human transferrin.

    Science.gov (United States)

    Zak, O; Aisen, P

    1986-07-01

    By combining the urea gel electrophoresis technique of Makey and Seal with Western immunoblotting, a method has been developed for analyzing the distribution of iron between the two sites of circulating human transferrin. The new method avoids exposure of samples to a nonphysiologic pH that may promote removal or redistribution of iron from the protein; this facilitates examination of multiple samples at one time. Analysis of 21 freshly drawn specimens from normal human subjects confirms previous reports that iron is not randomly distributed in the specific sites of transferrin. Rather, there is a considerable range in the ratio of occupancies of N-terminal and C-terminal sites (N:C ratio), from 0.31 to 6.87 in the present study, with the N-terminal site predominantly occupied in most subjects. The N:C ratio correlates modestly with serum iron concentration (r = .54). Possible flaws in studies indicating a random occupancy of the specific sites of circulating transferrin may lie in the low pH to which samples may be exposed during procedures based on isoelectric focusing or in drawing inferences from data considering only total monoferric transferrin rather than the two distinguishable monoferric species.

  11. Maintenance of Minute Circulation Volume during Orthotopic Liver Transplantation

    Directory of Open Access Journals (Sweden)

    D. A. Levit

    2011-01-01

    Full Text Available Objective: to optimize procedures to maintain minute circulation volume at different stages of orthotopic liver transplantation. Subjects and methods. In the period 2005—2010, Sverdlovsk Regional Clinical Hospital One performed 32 orthotopic liver transplantations, including one retransplantation. The patients’ ASA class was (4—5. The operations were carried out under general anesthesia. The mean duration of surgery was 8.1 (range 5.8—10.5 hours. The investigators applied anesthesia based on iso-fluorane 0.6—0.9 MAC (by monitoring the anesthesia depth index with cerebral state index (CSI-40-60, as well as extended central hemodynamic monitoring (prepulmonary hemodilution. All the operations were made via portofemoroaxillary bypass, by using a centrifugal Biopump. Eight surgical stages were identified: 1 run-in (after tracheal intubation; 2 liver mobilization; 3 partial bypass; 4 complete bypass (hepatectomy, a liver-free period; 5 reperfusion; 6 a postreperfusion period (bypass end; 7 biliary repair; 8 the end of an operation. The concentrations of blood parameters, electrolytes, acid-base balance, and the levels of lactate and glucose were examined. The data were processed statistically. Central hemodynamics was monitored by prepulmonary thermodilution, by calculating cardiac index (CI, stroke index, and total peripheral vascular resistance index (TPVRI at the stages: liver mobilization, postreperfusion period (bypass end, and the end of surgery. Results. Even during partial bypass, there was a significant drop in mean blood pressure (MBP as compared to the baseline levels (p<0.05. Reperfusion was also accompanied by a significant decrease in MBP and an increase in heart rate. At the end of reperfusion and in the postreperfusion period, TPVRI was halved (689.2±68.0 as compared to the baseline levels. In the postreperfusion period, central venous and pulmonary artery pressures were significantly increased by 32 and 21%, respectively

  12. Experimental investigation on natural circulation and air-injection enhanced circulation in a simple loop

    International Nuclear Information System (INIS)

    Walter Ambrosini; Nicola Forgione; Francesco Oriolo; Filippo Pellacani; Mariano Tarantino; Claudio Struckmann

    2005-01-01

    Full text of publication follows: Natural circulation represents an interesting phenomenon because of both the complex aspects characterising it and for the widespread application in industry. On the other hand, injection of a gas into a rising branch of a loop represents a means to establish or to enhance a circulation flow, as it occurs in the so-called 'air-lift' loops. Both natural circulation and gas-injection enhanced circulation are presently considered for cooling Accelerator Driven System (ADS) reactors. These are subcritical reactors in which the fission reaction chain is maintained by the injection of neutrons obtained by spallation reactions in a target through a high energy proton beam generated in an external accelerator. The capability of such reactors to be used as incinerators of long lived fission products makes them particularly interesting in the light of the closure of the nuclear fuel cycle. Some of the fluids proposed as coolants for these reactors are liquid metals, with main interest for lead and lead-bismuth eutectic (LBE). Experimental activities are being performed in support to the design of the reactor prototype by different organisations. The university of Pisa, in addition to provide cooperation in these large scale activities performed with LBE has set up a specific experimental program aimed at studying the fundamental mechanisms involved in natural circulation and gas-injection enhanced circulation. The adopted experimental facility consists in a simple loop, having a rectangular lay-out (roughly, 4 m tall and 1 m wide), equipped with a 5 kW, 1 m tall heater, a 2 m long pipe-in-pipe heat exchanger, an air injection device and a separator. The fluid adopted in the tests performed up to now is water, though studies for evaluating the feasibility of the adoption of different fluids have been undertaken. Experimental data reported in previous publications concerning this research were related to a relatively high range of gas

  13. Money circulation and debt circulation: A restatement of quantity theory of money

    OpenAIRE

    Xing, Xiaoyun; Xiong, Wanting; Chen, Liujun; Chen, Jiawei; Wang, Yougui; Stanley, H. Eugene

    2018-01-01

    Both money and debt are products of credit creation of banks. Money is always circulating among traders by facilitating commodity transactions. In contrast, debt is created by borrowing and annihilated by repayment as it is matured. However, when this creation- annihilation process is mediated by banks which are constrained by a credit capacity, there exists continuous transfer of debt among debtors, which can be defined as debt circulation. This paper presents a multi-agent model in which in...

  14. A stratiform cloud parameterization for General Circulation Models

    International Nuclear Information System (INIS)

    Ghan, S.J.; Leung, L.R.; Chuang, C.C.; Penner, J.E.; McCaa, J.

    1994-01-01

    The crude treatment of clouds in General Circulation Models (GCMs) is widely recognized as a major limitation in the application of these models to predictions of global climate change. The purpose of this project is to develop a paxameterization for stratiform clouds in GCMs that expresses stratiform clouds in terms of bulk microphysical properties and their subgrid variability. In this parameterization, precipitating cloud species are distinguished from non-precipitating species, and the liquid phase is distinguished from the ice phase. The size of the non-precipitating cloud particles (which influences both the cloud radiative properties and the conversion of non-precipitating cloud species to precipitating species) is determined by predicting both the mass and number concentrations of each species

  15. A stratiform cloud parameterization for general circulation models

    International Nuclear Information System (INIS)

    Ghan, S.J.; Leung, L.R.; Chuang, C.C.; Penner, J.E.; McCaa, J.

    1994-01-01

    The crude treatment of clouds in general circulation models (GCMs) is widely recognized as a major limitation in applying these models to predictions of global climate change. The purpose of this project is to develop in GCMs a stratiform cloud parameterization that expresses clouds in terms of bulk microphysical properties and their subgrid variability. Various clouds variables and their interactions are summarized. Precipitating cloud species are distinguished from non-precipitating species, and the liquid phase is distinguished from the ice phase. The size of the non-precipitating cloud particles (which influences both the cloud radiative properties and the conversion of non-precipitating cloud species to precipitating species) is determined by predicting both the mass and number concentrations of each species

  16. Pacific Circulation and the Resilience of its Equatorial Reefs

    Science.gov (United States)

    Cohen, A. L.; Drenkard, E.

    2012-12-01

    High rates of calcification by tropical reef-building corals are paramount to the maintenance of healthy reefs. Investigations of the impact of ocean acidification in both laboratory and field studies demonstrate unequivocally the dependence of coral and coral reef calcification on the carbonate ion concentration of seawater, a dependence predicted by fundamental laws of physical chemistry. Nevertheless, results from a new generation of experiments that exploit the biology of coral calcification, suggest that effects of ocean acidification can - in some instances - be mitigated with simultaneous manipulation of multiple factors. These laboratory results imply that coral reefs in regions projected to experience changes in, for example, nutrient delivery, light and flow, in addition to pH and carbonate ion concentration, may be more resilient (or vulnerable) to the effects of ocean acidification alone. If demonstrated to be true, these observations have profound implications for the conservation and management of coral reefs in the 21st century. We quantified spatial and temporal variability in rates of calcification of a dominant Indo-Pacific reef building coral across sites where changes in ocean circulation patterns drive variability in multiple physical, chemical and biological parameters. Such changes are occurring against a background of variability and trends in carbonate system chemistry. Our field data provide support for hypotheses based on laboratory observations, and show that impacts of ocean acidification on coral calcification can be partially and in some cases, fully, offset by simultaneous changes in multiple factors. Our results imply that projected changes in oceanic and atmospheric circulation patterns, driven by global warming, must be considered when predicting coral reef resilience, or vulnerability, to 21st century ocean acidification.

  17. Modelling the Seasonal Overturning Circulation in the Red Sea

    KAUST Repository

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry; Bower, Amy; Koehl, Armin; Gopalakrishnan, Ganesh

    2015-01-01

    The overturning circulation in the Red Sea exhibits a distinct seasonally reversing pattern and is studied using 50-year, high-resolution MIT general circulation model simulations. The seasonal water exchange in the Strait of Bab el Mandeb

  18. Silent Circulation of Ross River Virus in French Polynesia

    Directory of Open Access Journals (Sweden)

    Maite Aubry

    2015-08-01

    Discussion: Our results support the existence of autochthonous RRV transmission and suggest that this pathogen has silently circulated in French Polynesia. These findings raise the question of possible undetected circulation of RRV in other Pacific Island Countries and Territories.

  19. Circulating dendritic cells in pediatric patients with nephrotic syndrome

    African Journals Online (AJOL)

    EL-HAKIM

    nephrotic syndrome, circulating DCs were measured by flowcytometry. Results: Circulating DC count ... parents or caregivers of each child before enrollment in the study. ..... role in initiating the primary immune response. On the basis of the ...

  20. Distinct proteome pathology of circulating microparticles in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Østergaard, Ole; Nielsen, Christoffer Tandrup; Tanassi, Julia T

    2017-01-01

    BACKGROUND: The pathogenesis of systemic lupus erythematosus (SLE) is poorly understood but has been linked to defective clearance of subcellular particulate material from the circulation. This study investigates the origin, formation, and specificity of circulating microparticles (MPs) in patients...

  1. Circulation induced by diffused aeration in a shallow lake

    African Journals Online (AJOL)

    2017-01-01

    Jan 1, 2017 ... Lastly, a simple returning flow model was proposed to describe the circulation flow patterns ... method to describe the circulation patterns induced by the bub- ... 160 holes of 1 mm, which was designed to promote high mix-.

  2. Uptake and degradation of circulating proteins by the liver.

    NARCIS (Netherlands)

    Buys, Carolus Henricus Cornelis Maria

    1976-01-01

    Circulating proteins, like all proteins in a living animal, are subject to continual replacement or turnover. This process implies both synthesis and degradation, This thesis deals with the degradative part of turnover of circulating proteins. ... Summary

  3. Producing superfluid circulation states using phase imprinting

    Science.gov (United States)

    Kumar, Avinash; Dubessy, Romain; Badr, Thomas; De Rossi, Camilla; de Goër de Herve, Mathieu; Longchambon, Laurent; Perrin, Hélène

    2018-04-01

    We propose a method to prepare states of given quantized circulation in annular Bose-Einstein condensates (BEC) confined in a ring trap using the method of phase imprinting without relying on a two-photon angular momentum transfer. The desired phase profile is imprinted on the atomic wave function using a short light pulse with a tailored intensity pattern generated with a spatial light modulator. We demonstrate the realization of "helicoidal" intensity profiles suitable for this purpose. Due to the diffraction limit, the theoretical steplike intensity profile is not achievable in practice. We investigate the effect of imprinting an intensity profile smoothed by a finite optical resolution onto the annular BEC with a numerical simulation of the time-dependent Gross-Pitaevskii equation. This allows us to optimize the intensity pattern for a given target circulation to compensate for the limited resolution.

  4. Natural circulation in pressurized water reactors

    International Nuclear Information System (INIS)

    Bastos, J.L.F.; Loureiro, L.V.; Rocha, R.T.V. da; Umbehaun, P.E.

    1992-01-01

    Several analytical modelling have been done for steady-state and slow transients conditions, besides more sophisticated studies considering two and three dimensional effects in a very simple geometry. Under severe accident conditions for PWR a code to analyse natural circulation has been developed by Westinghouse. This paper discusses the problem of natural circulation in a complex geometry similar to that of nuclear power plants. A first experiment has been done at the integral test facility of 'Co-ordination of Special Projects-Ministry of Naval Affairs' (Coordenadoria para Projetos Especiais -Ministerio da Marinha, COPESP) for several flux conditions. The results obtained were compared with numerical simulations for the steady-state regime. 09 refs, 05 figs, 01 tab. (B.C.A.)

  5. Circulation policies in health science libraries.

    Science.gov (United States)

    Watkins, C; Coker, N C

    1970-10-01

    There is general agreement that library policies have considerable influence on the use of libraries. Medical school (health science) libraries of this country were surveyed as to their policies in respect to whether faculty and student use were regulated by a single policy, circulation regulations, hours library was accessible to users, accessibility of reserve material, interlibrary loan, policy on overdue material, and exit control. THE LIBRARIES WERE THEN DIVIDED INTO THREE GROUPS, HIGH, MIDDLE, AND LOW ACCORDING TO THE FOLLOWING CHARACTERISTICS: size of student body, size of faculty, size of holdings, size of library staff, annual budget, and annual circulation. Our findings would indicate that schools falling in a high category based upon these criteria tend to be more restrictive in their policies and to have different regulations for faculty and students than do schools in the low category.These findings warrant further study.

  6. Circulating elastin peptides, role in vascular pathology.

    Science.gov (United States)

    Robert, L; Labat-Robert, J

    2014-12-01

    The atherosclerotic process starts with the degradation of elastic fibers. Their presence was demonstrated in the circulation as well as several of their biological properties elucidated. We described years ago a procedure to obtain large elastin peptides by organo-alkaline hydrolysis, κ-elastin. This method enabled also the preparation of specific antibodies used to determine elastin peptides, as well as anti-elastin antibodies in body fluids and tissue extracts. Elastin peptides were determined in a large number of human blood samples. Studies were carried out to explore their pharmacological properties. Similar recent studies by other laboratories confirmed our findings and arose new interest in circulating elastin peptides for their biological activities. This recent trend justified the publication of a review of the biological and pathological activities of elastin peptides demonstrated during our previous studies, subject of this article. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. Natural circulation in simulated LMFBR fuel assemblies

    International Nuclear Information System (INIS)

    Levin, A.E.; Carbajo, J.J.; Lloyd, D.B.; Montgomery, B.H.; Rose, S.D.; Wantland, J.L.

    1985-01-01

    Natural circulation experiments have been performed using simulated liquid metal fast breeder reactor fuel assemblies in the Thermal-Hydraulic Out-of-Reactor Safety (THORS) facility, an engineering-scale sodium loop. Objective of these tests has been to provide experimental data under conditions that might be encountered during a partial or total loss of the shutdown heat removal system (SHRS) in a reactor. The experiments have included single- and two-phase tests under quasi-steady and transient conditions, at both nominal and non-nominal system conditions. Results from these test indicate that the potential for reactor damage during degraded SHRS operation is extremely slight, and that natural circulation can be a major contributor to safe operation of the system in both single- and two-phase flow during such operation

  8. On-Chip Microwave Quantum Hall Circulator

    Directory of Open Access Journals (Sweden)

    A. C. Mahoney

    2017-01-01

    Full Text Available Circulators are nonreciprocal circuit elements that are integral to technologies including radar systems, microwave communication transceivers, and the readout of quantum information devices. Their nonreciprocity arises from the interference of microwaves over the centimeter scale of the signal wavelength, in the presence of bulky magnetic media that breaks time-reversal symmetry. Here, we realize a completely passive on-chip microwave circulator with size 1/1000th the wavelength by exploiting the chiral, “slow-light” response of a two-dimensional electron gas in the quantum Hall regime. For an integrated GaAs device with 330  μm diameter and about 1-GHz center frequency, a nonreciprocity of 25 dB is observed over a 50-MHz bandwidth. Furthermore, the nonreciprocity can be dynamically tuned by varying the voltage at the port, an aspect that may enable reconfigurable passive routing of microwave signals on chip.

  9. Circulating fluidized bed boilers design and operations

    CERN Document Server

    Basu, Prabir

    1991-01-01

    This book provides practicing engineers and students with insight into the design and operation of circulating fluidized bed (CFB) boilers. Through a combination of theoretical concepts and practical experience, this book gives the reader a basic understanding of the many aspects of this subject.Important environmental considerations, including solid waste disposal and predicted emissions, are addressed individually in separate chapters. This book places an emphasis on combustion, hydrodynamics, heat transfer, and material issues, and illustrates these concepts with numerous examples of pres

  10. Music Circulation and Transmission in Tbilisi, Georgia

    OpenAIRE

    Sebald, Brigita

    2013-01-01

    This dissertation, based upon two years research in Tbilisi, Georgia, questions how popular music travels from the performer to the audience and how it circulates among audience members. After the disintegration of the Soviet Union in the early 1990s, the state-run music industry collapsed, taking the infrastructure for music distribution with it. In the years since, a music industry has not been rebuilt due to uncertain economic realities and a shaky political situation. Because of this, per...

  11. Periodontitis and increase in circulating oxidative stress

    OpenAIRE

    Takaaki Tomofuji; Koichiro Irie; Toshihiro Sanbe; Tetsuji Azuma; Daisuke Ekuni; Naofumi Tamaki; Tatsuo Yamamoto; Manabu Morita

    2009-01-01

    Reactive oxygen species (ROS) are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress). Such oxidation may be detrimental to systemic health. Fo...

  12. Engineering Judgment and Natural Circulation Calculations

    OpenAIRE

    Ferreri, J. C.

    2011-01-01

    The analysis performed to establish the validity of computer code results in the particular field of natural circulation flow stability calculations is presented in the light of usual engineering practice. The effects of discretization and closure correlations are discussed and some hints to avoid undesired mistakes in the evaluations performed are given. Additionally, the results are presented for an experiment relevant to the way in which a (small) number of skilled, nuclear safety analysts...

  13. Nitric oxide : An ally in extracorporeal circulation?

    OpenAIRE

    Melki, Vilyam

    2016-01-01

    Many complications associated with heart surgery are due to the negative effects of extracorporeal circulation (ECC). Some of these complications may be attributed to ECC-induced activation of inflammation and coagulation pathways. The inflammatory reaction may be caused by the interaction of blood components with air and the artificial surfaces of the ECC, from substances produced due to ischaemia-reperfusion injury of the heart and lungs, and from increased release of endotoxin from ischemi...

  14. The creation and circulation of public geographies

    OpenAIRE

    Kitchin, Rob; Linehan, Denis; O'Callaghan, Cian; Lawton, Philip

    2013-01-01

    In response to the commentaries, we discuss further how social media disrupts and remakes the creation and circulation of geographical knowledges and potentially reconfigures the moral economy of the social sciences. In particular, we examine questions of what is meant by public geography, the publics which such geographies serve, alternative and complementary approaches to social media, the politics of authorship within collective blogs, the politics and mechanisms of knowledge c...

  15. NUCLA Circulating Atmospheric Fluidized Bed Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    1992-02-01

    The objective of this DOE Cooperative Agreement is to conduct a cost-shared clean coal technology project to demonstrate the feasibility of circulating fluidized bed combustion technology and to evaluate economic, environmental, and operational benefits of CFB steam generators on a utility scale. At the conclusion of the Phase 2 program, testing related to satisfying these objectives was completed. Data analysis and reporting are scheduled for completion by October 1991. (VC)

  16. First circulating beam in the AA

    CERN Multimedia

    CERN PhotoLab

    1980-01-01

    On 3 July 1980, two years after project authorization, beam circulated for the first time in the AA. It was a 3.5 GeV/c proton test beam. We see an expecting crowd, minutes before the happy event. The persons are to numerous to name them all. Heribert Koziol, apparently asleep, is answering the call from an impatient director. See also 8007094.

  17. Circulating procoagulant microparticles in cancer patients

    OpenAIRE

    Thaler, Johannes; Ay, Cihan; Weinstabl, Harald; Dunkler, Daniela; Simanek, Ralph; Vormittag, Rainer; Freyssinet, Jean-Marie; Zielinski, Christoph; Pabinger, Ingrid

    2010-01-01

    Abstract Accumulating evidence indicates that microparticles (MPs) are important mediators of the interaction between cancer and the hemostatic system. We conducted a large prospective cohort study to determine whether the number of circulating procoagulant MPs is elevated in cancer patients and whether the elevated MP levels are predictive of occurrence of venous thrombembolism (VTE). We analyzed plasma samples of 728 cancer patients from the ongoing prospective observational Vien...

  18. General circulation model study of atmospheric carbon monoxide

    International Nuclear Information System (INIS)

    Pinto, J.P.; Yung, Y.L.; Rind, D.; Russell, G.L.; Lerner, J.A.; Hansen, J.E.; Hameed, S.

    1983-01-01

    The carbon monoxide cycle is studied by incorporating the known and hypothetical sources and sinks in a tracer model that uses the winds generated by a general circulation model. Photochemical production and loss terms, which depend on OH radical concentrations, are calculated in an interactive fashion. The computed global distribution and seasonal variations of CO are compared with observations to obtain constraints on the distribution and magnitude of the sources and sinks of CO, and on the tropospheric abundance of OH. The simplest model that accounts for available observations requires a low latitude plant source of about 1.3 x 10 15 g yr -1 , in addition to sources from incomplete combustion of fossil fuels and oxidation of methane. The globally averaged OH concentration calculated in the model is 7 x 10 5 cm -3 . Models that calculate globally averaged OH concentrations much lower than our nominal value are not consistent with the observed variability of CO. Such models are also inconsistent with measurements of CO isotopic abundances, which imply the existence of plant sources

  19. Blood leukocyte responses to extracorporeal circulation. 3. Long term extracorporeal circulation without and with irradiation in normal and splenectomized dogs

    Energy Technology Data Exchange (ETDEWEB)

    Szemere, P.; Fliedner, T.M. (Ulm Univ. (Germany, F.R.). Abt. Klinische Physiologie)

    1983-01-01

    Long term (12-48 h) extracorporeal circulation without and with irradiation of the blood was performed in normal and splenectomized dogs in order to observe the effect of these procedures on blood leukocyte counts including CFU-C. A transient granulocytopenia and a decrease of lymphocyte count were observed. The blood CFU-C level diminished to a very low level and remained low for the whole time of the experiments. There was no significant difference between the results of procedures with or without irradiation. The similar effect of a shortened tubing system on the blood leukocyte count is also reported. Heparin infusion alone did not decrease the peripheral CFU-C concentration. The possible explanations for the observed phenomena are discussed.

  20. Circulation in a Short Cylindrical Couette System

    Energy Technology Data Exchange (ETDEWEB)

    Akira Kageyama; Hantao Ji; Jeremy Goodman

    2003-07-08

    In preparation for an experimental study of magnetorotational instability (MRI) in liquid metal, we explore Couette flows having height comparable to the gap between cylinders, centrifugally stable rotation, and high Reynolds number. Experiments in water are compared with numerical simulations. The flow is very different from that of an ideal, infinitely long Couette system. Simulations show that endcaps co-rotating with the outer cylinder drive a strong poloidal circulation that redistributes angular momentum. Predicted toroidal flow profiles agree well with experimental measurements. Spin-down times scale with Reynolds number as expected for laminar Ekman circulation; extrapolation from two-dimensional simulations at Re less than or equal to 3200 agrees remarkably well with experiment at Re approximately equal to 106. This suggests that turbulence does not dominate the effective viscosity. Further detailed numerical studies reveal a strong radially inward flow near both endcaps. After turning vertically along the inner cylinder, these flows converge at the midplane and depart the boundary in a radial jet. To minimize this circulation in the MRI experiment, endcaps consisting of multiple, differentially rotating rings are proposed. Simulations predict that an adequate approximation to the ideal Couette profile can be obtained with a few rings.

  1. Circulation in a Short Cylindrical Couette System

    International Nuclear Information System (INIS)

    Akira Kageyama; Hantao Ji; Jeremy Goodman

    2003-01-01

    In preparation for an experimental study of magnetorotational instability (MRI) in liquid metal, we explore Couette flows having height comparable to the gap between cylinders, centrifugally stable rotation, and high Reynolds number. Experiments in water are compared with numerical simulations. The flow is very different from that of an ideal, infinitely long Couette system. Simulations show that endcaps co-rotating with the outer cylinder drive a strong poloidal circulation that redistributes angular momentum. Predicted toroidal flow profiles agree well with experimental measurements. Spin-down times scale with Reynolds number as expected for laminar Ekman circulation; extrapolation from two-dimensional simulations at Re less than or equal to 3200 agrees remarkably well with experiment at Re approximately equal to 106. This suggests that turbulence does not dominate the effective viscosity. Further detailed numerical studies reveal a strong radially inward flow near both endcaps. After turning vertically along the inner cylinder, these flows converge at the midplane and depart the boundary in a radial jet. To minimize this circulation in the MRI experiment, endcaps consisting of multiple, differentially rotating rings are proposed. Simulations predict that an adequate approximation to the ideal Couette profile can be obtained with a few rings

  2. When Prostate Cancer Circulates in the Bloodstream

    Directory of Open Access Journals (Sweden)

    Virginie Vlaeminck-Guillem

    2015-10-01

    Full Text Available Management of patients with prostate cancer is currently based on imperfect clinical, biological, radiological and pathological evaluation. Prostate cancer aggressiveness, including metastatic potential, remains difficult to accurately estimate. In an attempt to better adapt therapeutics to an individual (personalized medicine, reliable evaluation of the intrinsic molecular biology of the tumor is warranted, and particularly for all tumor sites (primary tumors and secondary sites at any time of the disease progression. As a consequence of their natural tendency to grow (passive invasion or as a consequence of an active blood vessel invasion by metastase-initiating cells, tumors shed various materials into the bloodstream. Major efforts have been recently made to develop powerful and accurate methods able to detect, quantify and/or analyze all these circulating tumor materials: circulating tumors cells, disseminating tumor cells, extracellular vesicles (including exosomes, nucleic acids, etc. The aim of this review is to summarize current knowledge about these circulating tumor materials and their applications in translational research.

  3. Diagnosis of boundary-layer circulations.

    Science.gov (United States)

    Beare, Robert J; Cullen, Michael J P

    2013-05-28

    Diagnoses of circulations in the vertical plane provide valuable insights into aspects of the dynamics of the climate system. Dynamical theories based on geostrophic balance have proved useful in deriving diagnostic equations for these circulations. For example, semi-geostrophic theory gives rise to the Sawyer-Eliassen equation (SEE) that predicts, among other things, circulations around mid-latitude fronts. A limitation of the SEE is the absence of a realistic boundary layer. However, the coupling provided by the boundary layer between the atmosphere and the surface is fundamental to the climate system. Here, we use a theory based on Ekman momentum balance to derive an SEE that includes a boundary layer (SEEBL). We consider a case study of a baroclinic low-level jet. The SEEBL solution shows significant benefits over Ekman pumping, including accommodating a boundary-layer depth that varies in space and structure, which accounts for buoyancy and momentum advection. The diagnosed low-level jet is stronger than that determined by Ekman balance. This is due to the inclusion of momentum advection. Momentum advection provides an additional mechanism for enhancement of the low-level jet that is distinct from inertial oscillations.

  4. The dynamics of the coronary collateral circulation.

    Science.gov (United States)

    Zimarino, Marco; D'Andreamatteo, Mariangela; Waksman, Ron; Epstein, Stephen E; De Caterina, Raffaele

    2014-04-01

    Coronary collaterals are present at birth, with wide interindividual variation in their functional capacity. These vessels protect jeopardized myocardium, and the number of collaterals and the extent of their coverage are associated with improved survival in patients with coronary heart disease. The collateral circulation is not a permanent set of structures, but undergoes dynamic changes with important consequences for cardioprotection. If a severe atherosclerotic lesion develops in an artery supplying tissue downstream of a total occlusion through collateral blood flow, pressure gradients across the collateral bed change. The result is that some of the collateral flow previously supplying the perfusion territory of the totally occluded artery is redirected to the perfusion territory of the donor artery, thus producing a 'collateral steal'. The collateral circulation can regress once antegrade flow in the main dependent artery is re-established, as occurs following the recanalization of a chronic total occlusion. The clinical benefits of coronary revascularization must be cautiously weighed against the risk of reducing the protective support derived from coronary collaterals. Consequently, pharmacological, gene-based, and cell-based therapeutic attempts have been made to enhance collateral function. Although such approaches have so far yielded no, or modest, beneficial results, the rapidly accruing data on coronary collateral circulation will hopefully lead to new effective therapeutic strategies.

  5. Circulation of a triaxial, charged ellipsoidal droplet

    International Nuclear Information System (INIS)

    Graber, J.L.; Rosensteel, G.

    2002-01-01

    The Kelvin circulation, which is the Casimir invariant of the general collective motion gcm(3) Lie algebra, is determined for a rapidly rotating triaxial nucleus in the classical domain. The potential energy is approximated by the sum of Coulomb repulsion and attractive surface energy terms, and the kinetic energy is adopted from the Riemann ellipsoidal model. An accurate approximation valid for both small and large deformations is reported for the potential energy. The Riemann ellipsoid theory allows for collective rotation in the continuum from rigid body motion to irrotational flow; the rigidity parametrizes this kinematical continuum. Analytic formulas are derived for the circulation, angular momentum, and energy as functions of the axis lengths, fissility, and rigidity. In particular, the bifurcation point to Jacobi triaxial shapes from noncollective oblate spheroids is given by a simple analytic formula. For a given fissility, the bifurcation point depends sensitive- ly on the rigidity. The Kelvin circulation remains approximately constant for triaxial ellipsoids as the angular momentum increases. This implies that gcm(3) is an approximate partial dynamical symmetry for rapidly rotating triaxial nuclei

  6. Hydroxylated polychlorinated biphenyls decrease circulating steroids in female polar bears (Ursus maritimus).

    Science.gov (United States)

    Gustavson, Lisa; Ciesielski, Tomasz M; Bytingsvik, Jenny; Styrishave, Bjarne; Hansen, Martin; Lie, Elisabeth; Aars, Jon; Jenssen, Bjørn M

    2015-04-01

    As a top predator in the Arctic food chain, polar bears (Ursus maritimus) are exposed to high levels of persistent organic pollutants (POPs). Because several of these compounds have been reported to alter endocrine pathways, such as the steroidogenesis, potential disruption of the sex steroid synthesis by POPs may cause implications for reproduction by interfering with ovulation, implantation and fertility. Blood samples were collected from 15 female polar bears in Svalbard (Norway) in April 2008. The concentrations of nine circulating steroid hormones; dehydroepiandrosterone (DHEA), androstenedione (AN), testosterone (TS), dihydrotestosterone (DHT), estrone (E1), 17α-estradiol (αE2), 17β-estradiol (βE2), pregnenolone (PRE) and progesterone (PRO) were determined. The aim of the study was to investigate associations among circulating levels of specific POP compounds and POP-metabolites (hydroxylated PCBs [OH-PCBs] and hydroxylated PBDEs [OH-PBDEs]), steroid hormones, biological and capture variables in female polar bears. Inverse correlations were found between circulating levels of PRE and AN, and circulating levels of OH-PCBs. There were no significant relationships between the steroid concentrations and other analyzed POPs or the variables capture date and capture location (latitude and longitude), lipid content, condition and body mass. Although statistical associations do not necessarily represent direct cause-effect relationships, the present study indicate that OH-PCBs may affect the circulating levels of AN and PRE in female polar bears and that OH-PCBs thus may interfere with the steroid homeostasis. Increase in PRO and a decrease in AN concentrations suggest that the enzyme CYP17 may be a potential target for OH-PCBs. In combination with natural stressors, ongoing climate change and contaminant exposure, it is possible that OH-PCBs may disturb the reproductive potential of polar bears. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Causes and impacts of changes in the stratospheric meridional circulation in a chemistry-climate model

    Energy Technology Data Exchange (ETDEWEB)

    Garny, Hella

    2011-05-13

    The stratospheric meridional circulation is projected to be subject to changes due to enhanced greenhouse-gas concentrations in the atmosphere. This study aims to diagnose and explain long-term changes in the stratospheric meridional circulation using the chemistry-climate model E39CA. The diagnosed strengthening of the circulation is found to be driven by increases in tropical sea surface temperatures which lead to a strengthening and upward shift of the subtropical jets. This enables enhanced vertical propagation of large scale waves into the lower stratosphere, and therefore stronger local wave forcing of the meridional circulation in the tropical lower stratosphere. The impact of changes in transport on the ozone layer is analysed using a newly developed method that allows the separation of the effects of transport and chemistry changes on ozone. It is found that future changes of mean stratospheric ozone concentrations are largely determined by changes in chemistry, while changes in transport of ozone play a minor role. (orig.)

  8. Formation of germline chimera Gaok chicken used circulation primordial germ cells (circulation PGCs fresh and thawed

    Directory of Open Access Journals (Sweden)

    Kostaman T

    2014-03-01

    Full Text Available Formation of germline chimeras by transfer of chicken primordial germ cells (PGCs is one of the effective techniques for preservation and regeneration of genetic resources in chickens. This study attempted to form germline chimeras of Gaok chicken buy purifying circulated PGCs of donor embryo before it is transferred to the recipient (White Leghorn chickens=WL and studied the ability of recipient embryo on survival in incubators, and hatchability. This study used 200 fertile eggs of Gaok and 90 fertile WL breed all of the eggs was incubated at 380C and 60% humidity in a portable incubator. PGCs-circulation of the blood collected Gaok embryos at stage 14-16 were taken from the dorsal aorta, and then purified by centrifugation method using nycodenz. PGCs-circulation results further purification frozen in liquid nitrogen before being transferred to the recipient embryo. The results showed that for the development of embryos transferred to the fresh circulation of PGCs-circulation as many as 25 cells can survive up to day 14, while one of the transferred of 50 and 100 cells into recipient embryos was hatched (10%. On the contrari recipient embryos that are transferred to the frozen PGCs-circulation the embryos development was shorter, and only survived until day 10th (treatment 25 cells, day 14th (treatment of 50 cells and day 17th (treatment of 100 cells. It is concluded that the amount of PGCs-circulation embryos transferred to the recipient is one factor that influence the success of the development germline chimeras.

  9. 19 CFR 207.63 - Circulation of draft questionnaires.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Circulation of draft questionnaires. 207.63... SUBSIDIZED EXPORTS TO THE UNITED STATES Five-Year Reviews § 207.63 Circulation of draft questionnaires. (a) The Director shall circulate draft questionnaires to the parties for comment in each full review. (b...

  10. Characteristics of the Current Sales and Circulation System in China

    Institute of Scientific and Technical Information of China (English)

    our reporter

    2001-01-01

    <正> 5 Former circulation enterprises finding new market position Those large-sized auto circulation enterprises, which used to lead the circulation system, have been suffering the twist and turns from the new system oriented by automakers. Their market shares shapely fell down and have emerged into chaos. Parts of them that are powerful enough have established new sales companies controlled by the jointly

  11. Exact Inverse Matrices of Fermat and Mersenne Circulant Matrix

    Directory of Open Access Journals (Sweden)

    Yanpeng Zheng

    2015-01-01

    Full Text Available The well known circulant matrices are applied to solve networked systems. In this paper, circulant and left circulant matrices with the Fermat and Mersenne numbers are considered. The nonsingularity of these special matrices is discussed. Meanwhile, the exact determinants and inverse matrices of these special matrices are presented.

  12. Appraisal of circulation routine duties in academic libraries | Hassan ...

    African Journals Online (AJOL)

    ... of brown charging system, book reservation, keeping of reserved collection, circulation of reserved books, treatment of overdue, lost of books on loan and library statistics among other as duties perform in circulation department of libraries. Keywords: Library Service, Circulation Duties, Challenges, Academic Libraries ...

  13. Mutation for nonsyndromic mental retardation in the trans-2-enoyl-CoA reductase TER gene involved in fatty acid elongation impairs the enzyme activity and stability, leading to change in sphingolipid profile.

    Science.gov (United States)

    Abe, Kensuke; Ohno, Yusuke; Sassa, Takayuki; Taguchi, Ryo; Çalışkan, Minal; Ober, Carole; Kihara, Akio

    2013-12-20

    Very long-chain fatty acids (VLCFAs, chain length >C20) exist in tissues throughout the body and are synthesized by repetition of the fatty acid (FA) elongation cycle composed of four successive enzymatic reactions. In mammals, the TER gene is the only gene encoding trans-2-enoyl-CoA reductase, which catalyzes the fourth reaction in the FA elongation cycle. The TER P182L mutation is the pathogenic mutation for nonsyndromic mental retardation. This mutation substitutes a leucine for a proline residue at amino acid 182 in the TER enzyme. Currently, the mechanism by which the TER P182L mutation causes nonsyndromic mental retardation is unknown. To understand the effect of this mutation on the TER enzyme and VLCFA synthesis, we have biochemically characterized the TER P182L mutant enzyme using yeast and mammalian cells transfected with the TER P182L mutant gene and analyzed the FA elongation cycle in the B-lymphoblastoid cell line with the homozygous TER P182L mutation (TER(P182L/P182L) B-lymphoblastoid cell line). We have found that TER P182L mutant enzyme exhibits reduced trans-2-enoyl-CoA reductase activity and protein stability, thereby impairing VLCFA synthesis and, in turn, altering the sphingolipid profile (i.e. decreased level of C24 sphingomyelin and C24 ceramide) in the TER(P182L/P182L) B-lymphoblastoid cell line. We have also found that in addition to the TER enzyme-catalyzed fourth reaction, the third reaction in the FA elongation cycle is affected by the TER P182L mutation. These findings provide new insight into the biochemical defects associated with this genetic mutation.

  14. Impact of sea ice cover changes on the Northern Hemisphere atmospheric winter circulation

    Directory of Open Access Journals (Sweden)

    D. Handorf

    2012-01-01

    Full Text Available The response of the Arctic atmosphere to low and high sea ice concentration phases based on European Center for Medium-Range Weather Forecast (ECMWF Re-Analysis Interim (ERA-Interim atmospheric data and Hadley Centre's sea ice dataset (HadISST1 from 1989 until 2010 has been studied. Time slices of winter atmospheric circulation with high (1990–2000 and low (2001–2010 sea ice concentration in the preceding August/September have been analysed with respect to tropospheric interactions between planetary and baroclinic waves. It is shown that a changed sea ice concentration over the Arctic Ocean impacts differently the development of synoptic and planetary atmospheric circulation systems. During the low ice phase, stronger heat release to the atmosphere over the Arctic Ocean reduces the atmospheric vertical static stability. This leads to an earlier onset of baroclinic instability that further modulates the non-linear interactions between baroclinic wave energy fluxes on time scales of 2.5–6 d and planetary scales of 10–90 d. Our analysis suggests that Arctic sea ice concentration changes exert a remote impact on the large-scale atmospheric circulation during winter, exhibiting a barotropic structure with similar patterns of pressure anomalies at the surface and in the mid-troposphere. These are connected to pronounced planetary wave train changes notably over the North Pacific.

  15. Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development.

    Science.gov (United States)

    Morales, Eva; Guxens, Mònica; Llop, Sabrina; Rodríguez-Bernal, Clara L; Tardón, Adonina; Riaño, Isolina; Ibarluzea, Jesús; Lertxundi, Nerea; Espada, Mercedes; Rodriguez, Agueda; Sunyer, Jordi

    2012-10-01

    To investigate whether circulating 25-hydroxyvitamin D(3) [25(OH)D(3)] concentration in pregnancy is associated with neuropsychological development in infants. The Spanish population-based cohort study INfancia y Medio Ambiente Project recruited pregnant women during the first trimester of pregnancy between November 2003 and February 2008. Completed data on 1820 mother-infant pairs were used. Maternal plasma 25(OH)D(3) concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.5 ± 2.1 weeks of gestation). Offspring mental and psychomotor scores were assessed by trained psychologists at age 14 months (range, 11-23) by using the Bayley Scales of Infant Development. β-Coefficients with 95% confidence intervals (CIs) of mental and psychomotor scores associated with continuous or categorical concentrations of maternal plasma 25(OH)D(3) were calculated by using linear regression analysis. The median plasma value of 25(OH)D(3) in pregnancy was 29.6 ng/mL (interquartile range, 21.8-37.3). A positive linear relationship was found between circulating concentrations of maternal 25(OH)D(3) concentrations in pregnancy and mental and psychomotor scores in the offspring. After adjustment for potential confounders, infants of mothers with 25(OH)D(3) concentrations in pregnancy >30 ng/mL showed higher mental score (β = 2.60; 95% CI 0.63-4.56) and higher psychomotor score (β = 2.32; 95% CI 0.36-4.28) in comparison with those of mothers with 25(OH)D(3) concentrations <20 ng/mL. Higher circulating concentration of maternal 25(OH)D(3) in pregnancy was associated with improved mental and psychomotor development in infants.

  16. The stability of the thermohaline circulation in a coupled ocean-atmosphere general circulation model

    Energy Technology Data Exchange (ETDEWEB)

    Schiller, A. [Max-Planck-Institut fuer Meteorologie, Hamburg (Germany); Mikolajewicz, U. [Max-Planck-Institut fuer Meteorologie, Hamburg (Germany); Voss, R. [Deutsches Klimarechenzentrum (DKRZ), Hamburg (Germany)

    1996-02-01

    The stability of the Atlantic thermohaline circulation against meltwater input is investigated in a coupled ocean-atmosphere general circulation model. The meltwater input to the Labrador Sea is increased linearly for 250 years to a maximum input of 0.625 Sv and then reduced again to 0 (both instantaneously and slowly decreasing over 250 years). The resulting freshening forces a shutdown of the formation of North Atlantic deepwater and a subsequent reversal of the thermohaline circulation of the Atlantic, filling the deep Atlantic with Antarctic bottom water. The change in the overturning pattern causes a drastic reduction of the Atlantic northward heat transport, resulting in a strong cooling with maximum amplitude over the northern North Atlantic and a southward shift of the sea-ice margin in the Atlantic. Due to the increased meridional temperature gradient, the Atlantic intertropical convergence zone is displaced southward and the westerlies in the northern hemisphere gain strength. We identify four main feedbacks affecting the stability of the thermohaline circulation: the change in the overturning circulation of the Atlantic leads to longer residence times of the surface waters in high northern latitudes, which allows them to accumulate more precipitation and runoff from the continents, which results in an increased stability in the North Atlantic.

  17. Seasonal overturning circulation in the Red Sea: 1. Model validation and summer circulation

    KAUST Repository

    Yao, Fengchao

    2014-04-01

    The overturning circulation in the Red Sea exhibits a distinct seasonally reversing pattern and is studied using high-resolution MIT general circulation model simulations. In the first part of this study, the vertical and horizontal structure of the summer overturning circulation and its dynamical mechanisms are presented from the model results. The seasonal water exchange in the Strait of Bab el Mandeb is successfully simulated, and the structures of the intruding subsurface Gulf of Aden intermediate water are in good agreement with summer observations in 2011. The model results suggest that the summer overturning circulation is driven by the combined effect of the shoaling of the thermocline in the Gulf of Aden resulting from remote winds in the Arabian Sea and an upward surface slope from the Red Sea to the Gulf of Aden set up by local surface winds in the Red Sea. In addition, during late summer two processes associated, respectively, with latitudinally differential heating and increased salinity in the southern Red Sea act together to cause the reversal of the contrast of the vertical density structure and the cessation of the summer overturning circulation. Dynamically, the subsurface northward pressure gradient force is mainly balanced by vertical viscosity resulting from the vertical shear and boundary friction in the Strait of Bab el Mandeb. Unlike some previous studies, the three-layer summer exchange flows in the Strait of Bab el Mandeb do not appear to be hydraulically controlled.

  18. Seasonal overturning circulation in the Red Sea: 1. Model validation and summer circulation

    KAUST Repository

    Yao, Fengchao; Hoteit, Ibrahim; Pratt, Larry J.; Bower, Amy S.; Zhai, Ping; Kö hl, Armin; Gopalakrishnan, Ganesh

    2014-01-01

    The overturning circulation in the Red Sea exhibits a distinct seasonally reversing pattern and is studied using high-resolution MIT general circulation model simulations. In the first part of this study, the vertical and horizontal structure of the summer overturning circulation and its dynamical mechanisms are presented from the model results. The seasonal water exchange in the Strait of Bab el Mandeb is successfully simulated, and the structures of the intruding subsurface Gulf of Aden intermediate water are in good agreement with summer observations in 2011. The model results suggest that the summer overturning circulation is driven by the combined effect of the shoaling of the thermocline in the Gulf of Aden resulting from remote winds in the Arabian Sea and an upward surface slope from the Red Sea to the Gulf of Aden set up by local surface winds in the Red Sea. In addition, during late summer two processes associated, respectively, with latitudinally differential heating and increased salinity in the southern Red Sea act together to cause the reversal of the contrast of the vertical density structure and the cessation of the summer overturning circulation. Dynamically, the subsurface northward pressure gradient force is mainly balanced by vertical viscosity resulting from the vertical shear and boundary friction in the Strait of Bab el Mandeb. Unlike some previous studies, the three-layer summer exchange flows in the Strait of Bab el Mandeb do not appear to be hydraulically controlled.

  19. Gas Cooled Fast Breeder Reactor cost estimate for a circulator test facility (modified HTGR circulator test facility)

    International Nuclear Information System (INIS)

    1979-10-01

    This is a conceptual design cost estimate for a Helium Circulator Test Facility to be located at the General Atomic Company, San Diego, California. The circulator, drive motors, controllers, thermal barrier, and circulator service module installation costs are part of the construction cost included

  20. Explicit Determinants of the RFPrLrR Circulant and RLPrFrL Circulant Matrices Involving Some Famous Numbers

    Directory of Open Access Journals (Sweden)

    Tingting Xu

    2014-01-01

    Full Text Available Circulant matrices may play a crucial role in solving various differential equations. In this paper, the techniques used herein are based on the inverse factorization of polynomial. We give the explicit determinants of the RFPrLrR circulant matrices and RLPrFrL circulant matrices involving Fibonacci, Lucas, Pell, and Pell-Lucas number, respectively.

  1. Optimization of Progressive Freeze Concentration on Apple Juice via Response Surface Methodology

    Science.gov (United States)

    Samsuri, S.; Amran, N. A.; Jusoh, M.

    2018-05-01

    In this work, a progressive freeze concentration (PFC) system was developed to concentrate apple juice and was optimized by response surface methodology (RSM). The effects of various operating conditions such as coolant temperature, circulation flowrate, circulation time and shaking speed to effective partition constant (K) were investigated. Five different level of central composite design (CCD) was employed to search for optimal concentration of concentrated apple juice. A full quadratic model for K was established by using method of least squares. A coefficient of determination (R2) of this model was found to be 0.7792. The optimum conditions were found to be coolant temperature = -10.59 °C, circulation flowrate = 3030.23 mL/min, circulation time = 67.35 minutes and shaking speed = 30.96 ohm. A validation experiment was performed to evaluate the accuracy of the optimization procedure and the best K value of 0.17 was achieved under the optimized conditions.

  2. Gas cooled fast breeder reactor design for a circulator test facility (modified HTGR circulator test facility)

    Energy Technology Data Exchange (ETDEWEB)

    1979-10-01

    A GCFR helium circulator test facility sized for full design conditions is proposed for meeting the above requirements. The circulator will be mounted in a large vessel containing high pressure helium which will permit testing at the same power, speed, pressure, temperature and flow conditions intended in the demonstration plant. The electric drive motor for the circulator will obtain its power from an electric supply and distribution system in which electric power will be taken from a local utility. The conceptual design decribed in this report is the result of close interaction between the General Atomic Company (GA), designer of the GCFR, and The Ralph M. Parson Company, architect/engineer for the test facility. A realistic estimate of total project cost is presented, together with a schedule for design, procurement, construction, and inspection.

  3. Modeling N2O Reduction and Decomposition in a Circulating Fluidized bed Boiler

    DEFF Research Database (Denmark)

    Johnsson, Jan Erik; Åmand, Lars-Erik; Dam-Johansen, Kim

    1996-01-01

    The N2O concentration was measured in a circulating fluidized bed boiler of commercial size. Kinetics for N2O reduction by char and catalytic reduction and decomposition over bed material from the combustor were determined in a laboratory fixed bed reactor. The destruction rate of N2O in the comb......The N2O concentration was measured in a circulating fluidized bed boiler of commercial size. Kinetics for N2O reduction by char and catalytic reduction and decomposition over bed material from the combustor were determined in a laboratory fixed bed reactor. The destruction rate of N2O...... in the combustion chamber and the cyclone was calculated taking three mechanisms into account: Reduction by char, catalytic decomposition over bed material and thermal decomposition. The calculated destruction rate was in good agreement with the measured destruction of N2O injected at different levels in the boiler...

  4. Power limit and quality limit of natural circulation reactor

    International Nuclear Information System (INIS)

    Zhao Guochang; Ma Changwen

    1997-01-01

    The circulation characteristics of natural circulation reactor in boiling regime are researched. It is found that, the circulation mass flow rate and the power have a peak value at a mass quality respectively. Therefore, the natural circulation reactor has a power limit under certain technological condition. It can not be increased steadily by continually increasing the mass quality. Corresponding to this, the mass quality of natural circulation reactor has a reasonable limit. The relations between the maximum power and the reactor parameters, such as the resistance coefficient, the working pressure and so on, are analyzed. It is pointed out that the power limit of natural circulation reactor is about 1000 MW at present technological condition. Taking the above result and low quality stability experimental result into account, the authors recommend that the reasonable mass quality of natural circulation reactor working in boiling regime is from 2% to 3% under the researched working pressure

  5. Natural circulation in single-phase and two-phase flow

    International Nuclear Information System (INIS)

    Cheung, F.B.; El-Genk, M.S.

    1989-01-01

    Natural circulation usually arises in a closed loop between a heat source and a heat sink were the fluid motion is driven by density difference. It may also occur in enclosures or cavities where the flow is induced primarily by temperature or concentration gradients within the fluid. The subject has recently received special attention by the heat transfer and nuclear reactor safety communities because of it importance to the areas of energy extraction, decay, heat removal in nuclear reactors, solar and geothermal heating, and cooling of electronic equipment. Although many new results and physical insights have been gained of the various natural circulation phenomena, a number of critical issues remain unresolved. These include, for example, transition from laminar to turbulent flow, buoyancy-induced turbulent flow modeling, change of flow regimes, flow field visualization, variable property effects, and flow instability. This symposium volume contains papers presented in the Natural Circulation in Single-Phase and Two-Phase Flow session at the 1989 Winter Annual Meeting of ASME, by authors from different countries including the United States, Japan, Canada, and Brazil. The papers deal with experimental and theoretical studies as well as state-of-the-art reviews, covering a broad spectrum of topics in natural circulation including: variable-conductance thermosyphons, microelectronic chip cooling, natural circulation in anisotropic porous media and in cavities, heat transfer in flat plat solar collectors, shutdown heat removal in fast reactors, cooling of light-water and heavy-water reactors. The breadth of papers contained in this volume clearly reflect the importance of the current interest in natural circulation as a means for passive cooling and heating

  6. Could circulating fetuin A be a biomarker of aortic valve stenosis?

    Science.gov (United States)

    Di Minno, Alessandro; Zanobini, Marco; Myasoedova, Veronika A; Valerio, Vincenza; Songia, Paola; Saccocci, Matteo; Di Minno, Matteo Nicola Dario; Tremoli, Elena; Poggio, Paolo

    2017-12-15

    Aortic valve stenosis (AVS) is a multifactorial-progressive pathological process. In the past decades, many studies have focus their attention on circulating biomarkers able to identify AVS and/or to predict its progression. One of the many biomarkers studied is the fetuin A. The aim of the present meta-analysis was to evaluate the correlation between fetuin A levels and end-stage AVS. A systematic search was performed in three electronic databases (PubMed, Web of Science and Scopus), looking for studies that compared control subjects with AVS patients and that have measured fetuin A circulating levels in both groups. The main outcome was to evaluate the difference in circulating fetuin A concentration in the two groups. Seven studies, enrolling 2283 AVS patients and 1549 controls, were included. Differences between control subjects and AVS patients were expressed as standardized mean difference (SMD) with pertinent 95% confidence intervals (95%CI) and standard deviation (SD), analysing the data using a random effect model. We found significantly lower circulating levels of fetuin A in AVS patients compared to healthy subjects (SMD: -0.96μg/mL, 95% CI: -1.62, -0.30; p=0.004). In addition, meta-regression analyses showed that several cardiovascular risk factors were significantly associated with circulating levels of fetuin A between patients affected by AVS and healthy controls. In conclusion, our meta-analysis shows that AVS patients have significant lower circulating levels of fetuin A compared to control subjects. However, dedicated studies with large and matched cohorts are needed to validate these findings, evaluating if there is a real link or just a mere association. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Liquid Biopsy for Cancer: Circulating Tumor Cells, Circulating Free DNA or Exosomes?

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2017-02-01

    Full Text Available Precision medicine and personalized medicine are based on the development of biomarkers, and liquid biopsy has been reported to be able to detect biomarkers that carry information on tumor development and progression. Compared with traditional ‘solid biopsy’, which cannot always be performed to determine tumor dynamics, liquid biopsy has notable advantages in that it is a noninvasive modality that can provide diagnostic and prognostic information prior to treatment, during treatment and during progression. In this review, we describe the source, characteristics, technology for detection and current situation of circulating tumor cells, circulating free DNA and exosomes used for diagnosis, recurrence monitoring, prognosis assessment and medication planning.

  8. Bottom water circulation in Cascadia Basin

    Science.gov (United States)

    Hautala, Susan L.; Paul Johnson, H.; Hammond, Douglas E.

    2009-10-01

    A combination of beta spiral and minimum length inverse methods, along with a compilation of historical and recent high-resolution CTD data, are used to produce a quantitative estimate of the subthermocline circulation in Cascadia Basin. Flow in the North Pacific Deep Water, from 900-1900 m, is characterized by a basin-scale anticyclonic gyre. Below 2000 m, two water masses are present within the basin interior, distinguished by different potential temperature-salinity lines. These water masses, referred to as Cascadia Basin Bottom Water (CBBW) and Cascadia Basin Deep Water (CBDW), are separated by a transition zone at about 2400 m depth. Below the depth where it freely communicates with the broader North Pacific, Cascadia Basin is renewed by northward flow through deep gaps in the Blanco Fracture Zone that feeds the lower limb of a vertical circulation cell within the CBBW. Lower CBBW gradually warms and returns to the south at lighter density. Isopycnal layer renewal times, based on combined lateral and diapycnal advective fluxes, increase upwards from the bottom. The densest layer, existing in the southeast quadrant of the basin below ˜2850 m, has an advective flushing time of 0.6 years. The total volume flushing time for the entire CBBW is 2.4 years, corresponding to an average water parcel residence time of 4.7 years. Geothermal heating at the Cascadia Basin seafloor produces a characteristic bottom-intensified temperature anomaly and plays an important role in the conversion of cold bottom water to lighter density within the CBBW. Although covering only about 0.05% of the global seafloor, the combined effects of bottom heat flux and diapycnal mixing within Cascadia Basin provide about 2-3% of the total required global input to the upward branch of the global thermohaline circulation.

  9. Early concepts and charts of ocean circulation

    Science.gov (United States)

    Peterson, R. G.; Stramma, L.; Kortum, G.

    Charts of ocean currents from the late nineteenth century show that already by then the patterns of surface circulation in regions away from polar latitudes were well understood. This fundamental knowledge accumulated gradually through centuries of sea travel and had reached a state of near correctness by the time dedicated research cruises, full-depth measurements and the practical application of the dynamical method were being instituted. Perhaps because of the foregoing, many of the pioneering works, critical to establishing what the upper-level circulation is like, the majority of the charts accompanying them, and several of the groundbreaking theoretical treatments on the physics of currents, are only poorly known to present-day oceanographers. In this paper we trace Western developments in knowledge and understanding of ocean circulation from the earliest times to the late-1800s transition into the modern era. We also discuss certain peripheral advances that proved critical to the subject. The earliest known ideas, dating from the Bronze Age and described by Homer, necessarily reflect severe limitations to geographical knowledge, as well as basic human predilections toward conjecture and exaggeration in the face of inadequate information. People considered the earth to be flat and circular, with the ocean flowing like a river around it. They also believed in horrific whirlpools, a concept that persisted into the Renaissance and which would later provide subject material for modern literature. From the Greek Classical Age, we find hydrologic theories of Earth's interior being laced with subterranean channels (Socrates) and all motion deriving from a divine force forever propelling the heavens toward the west, the primum mobile (Aristotle). These ideas, particularly the latter, dominated opinions about ocean circulation into the late Renaissance. By late Antiquity mariners had very likely acquired intimate knowledge of coastal currents in the Mediterranean, but

  10. Highly sensitive transient absorption imaging of graphene and graphene oxide in living cells and circulating blood

    OpenAIRE

    Junjie Li; Weixia Zhang; Ting-Fung Chung; Mikhail N. Slipchenko; Yong P. Chen; Ji-Xin Cheng; Chen Yang

    2015-01-01

    We report a transient absorption (TA) imaging method for fast visualization and quantitative layer analysis of graphene and GO. Forward and backward imaging of graphene on various substrates under ambient condition was imaged with a speed of 2??s per pixel. The TA intensity linearly increased with the layer number of graphene. Real-time TA imaging of GO in vitro with capability of quantitative analysis of intracellular concentration and ex vivo in circulating blood were demonstrated. These re...

  11. Sulfate accumulation in a sea breeze/land breeze circulation system

    OpenAIRE

    Cass, Glen R.; Shair, Frederick H.

    1984-01-01

    An atmospheric tracer study using SF_6 was conducted on July 22, 1977, to examine the origin of the high particulate sulfate concentrations observed in coastal Los Angeles County. It was found that the sea breeze/land breeze circulation system in the Los Angeles Basin both increases the retention time for sulfate formation in the marine environment and causes individual air parcels to make multiple passes over large coastal emissions sources. Day-old sulfur oxides emissions advected out to se...

  12. Circulating Dopamine and C-Peptide Levels in Fasting Nondiabetic Hypertensive Patients

    OpenAIRE

    Tomaschitz, Andreas; Ritz, Eberhard; Kienreich, Katharina; Pieske, Burkert; M?rz, Winfried; Boehm, Bernhard O.; Drechsler, Christiane; Meinitzer, Andreas; Pilz, Stefan

    2012-01-01

    OBJECTIVE Accumulating evidence supports a potential role for dopamine in the regulation of insulin secretion. We examined the association between circulating dopamine and C-peptide concentrations using data from the Graz Endocrine Causes of Hypertension (GECOH) study. RESEARCH DESIGN AND METHODS After 12 h of fasting, we measured plasma dopamine and serum C-peptide levels and established determining factors of insulin secretion in 201 nondiabetic hypertensive patients (mean age 48.1 ? 16.0 y...

  13. Dominance of physical and chemical gases properties on kinetics of gassing in NPP's circulation contours

    International Nuclear Information System (INIS)

    Piontkovskij, A.I.

    2001-01-01

    Is seen out a dominance analysis of physical and chemical matter properties on gases solubility in circulation contour NPP's heat-transfer. Is represented a concentration computation methods of gas dissolved in heat-transfer with use of in lying pressure in matter. Are analysed the computation results for diverse gases in wide range of operating parameters, and also dominance of physical and chemical gas properties on intensity of heat-exchange processes in heat-transfer with dissolved gase

  14. Precision of a new bedside method for estimation of the circulating blood volume

    DEFF Research Database (Denmark)

    Christensen, P; Eriksen, B; Henneberg, S W

    1993-01-01

    The present study is a theoretical and experimental evaluation of a modification of the carbon monoxide method for estimation of the circulating blood volume (CBV) with respect to the precision of the method. The CBV was determined from measurements of the CO-saturation of hemoglobin before and a......, determination of CBV can be performed with an amount of CO that gives rise to a harmless increase in the carboxyhemoglobin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)...

  15. Circulation, metabolism, and ventilation during prolonged exposure to carbon monoxide and to high altitude

    Energy Technology Data Exchange (ETDEWEB)

    Klausen, K.; Rasmussen, B; Gjellerod, H.; Madsen, H.; Petersen, E.

    1968-01-01

    Eight volunteers were exposed to CO (13% COHb) or high altitude (3454 m). There was no change in circulation, metabolism, or ventilation during CO exposure. With similar arterial O/sub 2/ concentration from high-altitude, V/sub e/ (BTPS) increased, Pa/sub CO/sub 2// decreased. Regulating mechanisms respond to a decrease in Pa/sub CO/sub 2// rather than a gereral lack in tissue O/sub 2/ per se.

  16. Portal pressure correlated to visceral circulation times

    Energy Technology Data Exchange (ETDEWEB)

    Friman, L [Serafimerlasarettet, Stockholm (Sweden)

    1979-01-01

    Visceral angiography was performed in 7 patients with normal portal pressure and in 10 with portal hypertension. Circulation times, size of vessels and portal pressure were determined. At celiac angiography, a direct correlation was found between time for maximum filling of portal vein and portal pressure, provided no vascular abnormalities existed. At superior mesenteric angiography such a correlation was not found; loss of flow by shunts in portal hypertension being one explanation. Portocaval shunts are common in the celiac system, but uncommon in the superior mesenteric system.

  17. Portal pressure correlated to visceral circulation times

    International Nuclear Information System (INIS)

    Friman, L.

    1979-01-01

    Visceral angiography was performed in 7 patients with normal portal pressure and in 10 with portal hypertension. Circulation times, size of vessels and portal pressure were determined. At celiac angiography, a direct correlation was found between time for maximum filling of portal vein and portal pressure, provided no vascular abnormalities existed. At superior mesenteric angiography such a correlation was not found; loss of flow by shunts in portal hypertension being one explanation. Portocaval shunts are common in the celiac system, but uncommon in the superior mesenteric system. (Auth.)

  18. Numerical optimization of circulation control airfoils

    Science.gov (United States)

    Tai, T. C.; Kidwell, G. H., Jr.; Vanderplaats, G. N.

    1981-01-01

    A numerical procedure for optimizing circulation control airfoils, which consists of the coupling of an optimization scheme with a viscous potential flow analysis for blowing jet, is presented. The desired airfoil is defined by a combination of three baseline shapes (cambered ellipse, and cambered ellipse with drooped and spiralled trailing edges). The coefficients of these shapes are used as design variables in the optimization process. Under the constraints of lift augmentation and lift-to-drag ratios, the optimal airfoils are found to lie between those of cambered ellipse and the drooped trailing edge, towards the latter as the angle of attack increases. Results agree qualitatively with available experimental data.

  19. Turnover of circulating hematopoietic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Dorie, M J; Maloney, M A; Patt, H M

    1979-10-01

    Short-term parabiosis of male and female CBA/CaJ mice was used to investigate the turnover of circulating hematopoietic stem cells. The change and subsequent disappearance of donor stem cells were monitored by spleen colony assay and chromosome analysis of individual colonies. The results revealed an exponential disappearance of pluripotent stem cells from blood with a characteristic half time of 1.7 h. Blood-borne stem cells were shown to be equilibrated with a subpopulation of marrow stem cells exhibiting a disappearance half time of 9.5 h. Splenectomy did not change the apparent rate of stem cell removal from the blood.

  20. Steam generator of the forced circulation type

    International Nuclear Information System (INIS)

    Forestier, Jean; Leblanc, Bernard; Monteil, Marcel; Monteil, Pierre

    1977-01-01

    The steam generator described is of the forced circulation single passage type comprising an outer casing including a vertical generally cylindrical side ring, an internal skirt coaxial with the outer casing, the bottom of this skirt having a free edge separated from a bottom end closing the outer casing, a central tube plate extending horizontally near a top end, in opposition to the bottom end, a peripheral tube plate, parallel to the central plate and located in the annular space under this central plate, a bundle of J shaped tubes [fr

  1. Plasma circulating fibrinogen stability and moderate beer consumption.

    Science.gov (United States)

    Gorinstein, Shela; Caspi, Abraham; Zemser, Marina; Libman, Imanuel; Goshev, Ivan; Trakhtenberg, Simon

    2003-12-01

    MODERATE BEER CONSUMPTION (MBC) IS CARDIOPROTECTIVE: it positively influences plasma lipid levels and plasma antioxidant activity in beer-consuming individuals. The connection between MBC and blood coagulation is not clearly defined. Forty-two volunteers were equally divided into experimental (EG) and control (CG) groups following coronary bypass surgery. For 30 consecutive days, only patients of the EG consumed 330 mL of beer per day (about 20 g of alcohol). A comprehensive clinical investigation of 42 patients was done. Blood samples were collected before and after the investigation for a wide range of laboratory tests. The plasma fibrinogen was denatured with 8 M urea and intrinsic fluorescence (IF), hydrophobicity and differential scanning calorimetry (DSC) were used to reveal possible qualitative changes. After 30 days of moderate beer consumption, positive changes in the plasma lipid levels, plasma anticoagulant and plasma antioxidant activities were registered in patients of the EG group. In 17 out of 21 patients of the same group, differences in plasma circulating fibrinogen's (PCF), secondary and tertiary structures were found. The stability of fibrinogen, expressed in thermodynamic parameters, has shown that the loosening of the structure takes place under ethanol and urea denaturation. Also fluorescence stability of PCF was decreased. No changes in the lipid levels, anticoagulant and antioxidant activity or changes in PCF were detected in patients of CG. In conclusion, for the first time after a short term of moderate beer consumption some qualitative changes in the plasma circulating fibrinogen were detected: differences in the emission peak response, fluorescence intensity and all thermodynamic data. Together, with the decrease in the PCF concentration it may lead to an elevation of the blood anticoagulant activity.

  2. Glacial greenhouse-gas fluctuations controlled by ocean circulation changes.

    Science.gov (United States)

    Schmittner, Andreas; Galbraith, Eric D

    2008-11-20

    Earth's climate and the concentrations of the atmospheric greenhouse gases carbon dioxide (CO(2)) and nitrous oxide (N(2)O) varied strongly on millennial timescales during past glacial periods. Large and rapid warming events in Greenland and the North Atlantic were followed by more gradual cooling, and are highly correlated with fluctuations of N(2)O as recorded in ice cores. Antarctic temperature variations, on the other hand, were smaller and more gradual, showed warming during the Greenland cold phase and cooling while the North Atlantic was warm, and were highly correlated with fluctuations in CO(2). Abrupt changes in the Atlantic meridional overturning circulation (AMOC) have often been invoked to explain the physical characteristics of these Dansgaard-Oeschger climate oscillations, but the mechanisms for the greenhouse-gas variations and their linkage to the AMOC have remained unclear. Here we present simulations with a coupled model of glacial climate and biogeochemical cycles, forced only with changes in the AMOC. The model simultaneously reproduces characteristic features of the Dansgaard-Oeschger temperature, as well as CO(2) and N(2)O fluctuations. Despite significant changes in the land carbon inventory, CO(2) variations on millennial timescales are dominated by slow changes in the deep ocean inventory of biologically sequestered carbon and are correlated with Antarctic temperature and Southern Ocean stratification. In contrast, N(2)O co-varies more rapidly with Greenland temperatures owing to fast adjustments of the thermocline oxygen budget. These results suggest that ocean circulation changes were the primary mechanism that drove glacial CO(2) and N(2)O fluctuations on millennial timescales.

  3. Circulating omentin-1 might be associated with metabolic health status in different phenotypes of body size.

    Science.gov (United States)

    Alizadeh, Shahab; Mirzaei, Khadijeh; Mohammadi, Chonur; Keshavarz, Seyed Ali; Maghbooli, Zhila

    2017-12-01

    Adipokines are mediators of body composition and are involved in obesity complications. This study aimed to assess the association of circulating omentin-1, vaspin, and RBP-4 with body composition indices and metabolic health status (MHS) in different phenotypes of body size. A total of 350 subjects were included in the current cross-sectional study. Body composition was measured using a body composition analyzer, and serum concentrations of omentin-1, vaspin, and RBP-4 were assessed by ELISA kits. Circulating omentin-1 was significantly (OR = 1.81, 95% CI: 1.00-1.91, P = 0.01) and marginally (OR = 1.63, 95%CI: 1.00-1.75, P = 0.06) associated with MHS in the overweight and obese subjects, respectively. But no association was seen between omentin-1 and MHS in normal-weight subjects. Serum levels of vaspin and RBP-4 were not correlated with MHS. Furthermore, a significant positive correlation was observed between circulating omentin-1 and body mass index (BMI) as well as fat percentage (P = 0.02) in the MHS group. Serum vaspin concentrations were not related to body composition components in both groups. In addition, in the MHS group, circulating RBP-4 was positively correlated with fat percentage and fat mass (FM) (p body water (TBW) (p < 0.0001). In contrast, in the metabolically unhealthy group, RBP-4 was negatively correlated with fat percentage, FM, and BMI (p < 0.0001) and was positively correlated with FFM and TBW (p < 0.0001). This study showed that circulating levels of omentin-1 are useful predictors of metabolic health status in overweight and obese people.

  4. The Role of Circulating Slit2, the One of the Newly Batokines, in Human Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Yea Eun Kang

    2017-09-01

    Full Text Available BackgroundSlit2 is a new secreted protein from adipose tissue that improves glucose hemostasis in mice; however, there is no study about the serum levels and precise role of Slit2 in human. The aim of this study is to explore the serum level of Slit2 in human, and to identify the role of Slit2 in diabetes mellitus (DM.MethodsThe participants of this study consist of 38 subjects with newly diagnosed DM, and 75 healthy subjects as a control group. Serum Slit2 levels were measured using an enzyme-linked immunosorbent assay. Relationship between circulating Slit2 and diabetic related factors was investigated in diabetic group compared with non-diabetic group. Additionally, the correlations between the serum level of Slit2 and diverse metabolic parameters were analyzed.ResultsCirculating Slit2 level was more decreased in diabetic group than in control group, but there was no significant difference statistically. Interestingly, serum levels of Slit2 were significantly negatively correlated to the serum concentrations of fasting glucose (coefficient r=–0.246, P=0.008, the serum concentrations of postprandial glucose (coefficient r=–0.233, P=0.017, and glycosylated hemoglobin (HbA1c; coefficient r=–0.357, P<0.001.ConclusionFrom our study, the first report of circulating Slit2 levels in human, circulating Slit2 level significantly negatively correlated with serum glucose and HbA1c. Our results suggest that the circulating Slit2 may play a role in maintainence of glucose homeostasis in human, even though exact contribution and mechanism are not yet known.

  5. Gastrointestinal Degradation of Fumonisin B₁ by Carboxylesterase FumD Prevents Fumonisin Induced Alteration of Sphingolipid Metabolism in Turkey and Swine.

    Science.gov (United States)

    Masching, Sabine; Naehrer, Karin; Schwartz-Zimmermann, Heidi-Elisabeth; Sărăndan, Mihai; Schaumberger, Simone; Dohnal, Ilse; Nagl, Veronika; Schatzmayr, Dian

    2016-03-21

    The mycotoxin fumonisin B₁ (FB₁) is a frequent contaminant of feed and causes various adverse health effects in domestic animals. Hence, effective strategies are needed to prevent the impact of fumonisins on livestock productivity. Here we evaluated the capability of the fumonisin carboxylesterase FumD to degrade FB₁ to its less toxic metabolite hydrolyzed FB₁ (HFB₁) in the gastrointestinal tract of turkeys and pigs. First, an ex vivo pig model was used to examine the activity of FumD under digestive conditions. Within 2 h of incubation with FumD, FB₁ was completely degraded to HFB₁ in the duodenum and jejunum, respectively. To test the efficacy of the commercial application of FumD (FUMzyme) in vivo, female turkeys (n = 5) received either basal feed (CON), fumonisin-contaminated feed (15 mg/kg FB₁+FB₂; FB) or fumonisin-contaminated feed supplemented with FUMzyme (15 U/kg; FB+FUMzyme) for 14 days ad libitum. Addition of FUMzyme resulted in significantly decreased levels of FB₁ in excreta, whereas HFB₁ concentrations were significantly increased. Compared to the FB group (0.24 ± 0.02), the mean serum sphinganine-to-sphingosine (Sa/So) ratio was significantly reduced in the FB+FUMzyme group (0.19 ± 0.02), thus resembling values of the CON group (0.16 ± 0.02). Similarly, exposure of piglets (n = 10) to 2 mg/kg FB₁+FB₂ for 42 days caused significantly elevated serum Sa/So ratios (0.39 ± 0.15) compared to the CON group (0.14 ± 0.01). Supplementation with FUMzyme (60 U/kg) resulted in gastrointestinal degradation of FB₁ and unaffected Sa/So ratios (0.16 ± 0.02). Thus, the carboxylesterase FumD represents an effective strategy to detoxify FB₁ in the digestive tract of turkeys and pigs.

  6. Reversibility of the effects on local circulation of high lipid concentrations in blood

    DEFF Research Database (Denmark)

    Bülow, J; Madsen, J; Højgaard, L

    1990-01-01

    Regional perfusion and vascular resistance were examined in different tissues with the radioactive microsphere technique in Göttingen minipigs before, during and after treatment with Intralipid and heparin. This treatment led to an increase in the free fatty acid/albumin molar ratio from 0.39 +/-...... fully reversible when the free fatty acid/albumin molar ratio had normalized. This vascular effect of lipid emulsions has to be considered when patients are treated with parenteral nutrition....

  7. Reversibility of the effects on local circulation of high lipid concentrations in blood

    DEFF Research Database (Denmark)

    Bülow, J; Madsen, J; Højgaard, L

    1990-01-01

    .23 to 3.43 +/- 1.37. Concomitantly a decrease in regional perfusion and an increase in regional vascular resistance was found in skin, adipose tissue, skeletal muscle, kidney, the gastro-intestinal tract, the thyroid and pancreas, while heart and liver showed vasodilatation. The vascular effects were...

  8. Radium concentrations in Adriatic coastal area and their dependence on circulation of the sea currents

    International Nuclear Information System (INIS)

    Marovic, G.; Sencar, J.; Kovac, J.; Hrsak, H.

    2002-01-01

    The aim of this study was to assess natural radioactivity in the area of the coal-fired power plant in the Plomin Bay with special emphasis on possible radiation contamination of the seawater caused by plant operation. The purpose was to determine vertical and horizontal distribution of radium and its dependence on the seawater currents at different sea depths. The level of 2 26R a in seawater was assessed four times a year, at three locations and at two sea depths. Measurements of physical, chemical and biological parameters were performed in order to provide a tangible basis for a long-term systematic monitoring of the environmental effects of plant operation on the surrounding area

  9. Upper ocean circulation modulation by phytoplankton concentration in the Equatorial Pacific and the Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Nakamoto, S.; PrasannaKumar, S.; Oberhuber, J.M.; Sammarco, P.; Muneyama, K.; Sato, T.; AjoyKumar, A.; Frouin, R.

    gradient in the upper ocean. This strengthens the geostrophically balanced westward currents in both side of the equatorial wave-guide (within 5 degree bands). Once these currents reach the western Pacific coast, they feed the Equatorial undercurrent (EUC...

  10. Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome.

    Science.gov (United States)

    Erol, Onur; Özel, Mustafa Kemal; Ellidağ, Hamit Yaşar; Toptaş, Tayfun; Derbent, Aysel Uysal; Yılmaz, Necat

    2017-07-01

    The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the authors included overweight/obese patients and glucose tolerance was not evaluated before recruitment. What the results of this study add: Our results showed that serum betatrophin levels were significantly higher in lean glucose-tolerant PCOS women than in age- and BMI-matched healthy controls. What are the implications of these findings for clinical practice and/or further research: Elevated betatrophin levels in PCOS women, in the absence of obesity and glucose intolerance, may reflect a compensatory mechanism in order to counteract metabolic syndrome-related risk factors.

  11. Active Smoking and Hematocrit and Fasting Circulating Erythropoietin Concentrations in the General Population

    NARCIS (Netherlands)

    Eisenga, Michele F.; Kieneker, Lyanne M.; Touw, Daan J.; Nolte, Ilja M.; van der Meer, Peter; Huls, Gerwin; Gaillard, Carlo A. J. M.; Bakker, Stephan J. L.

    Cigarette smoking continues to be one of the major risk factors for increased morbidity and mortality worldwide. Among many adverse health effects, smoking can induce erythrocytosis, which is commonly believed to result from elevated serum erythropoietin (EPO) levels. Currently, however, this notion

  12. Three-pattern decomposition of global atmospheric circulation: part II—dynamical equations of horizontal, meridional and zonal circulations

    Science.gov (United States)

    Hu, Shujuan; Cheng, Jianbo; Xu, Ming; Chou, Jifan

    2018-04-01

    The three-pattern decomposition of global atmospheric circulation (TPDGAC) partitions three-dimensional (3D) atmospheric circulation into horizontal, meridional and zonal components to study the 3D structures of global atmospheric circulation. This paper incorporates the three-pattern decomposition model (TPDM) into primitive equations of atmospheric dynamics and establishes a new set of dynamical equations of the horizontal, meridional and zonal circulations in which the operator properties are studied and energy conservation laws are preserved, as in the primitive equations. The physical significance of the newly established equations is demonstrated. Our findings reveal that the new equations are essentially the 3D vorticity equations of atmosphere and that the time evolution rules of the horizontal, meridional and zonal circulations can be described from the perspective of 3D vorticity evolution. The new set of dynamical equations includes decomposed expressions that can be used to explore the source terms of large-scale atmospheric circulation variations. A simplified model is presented to demonstrate the potential applications of the new equations for studying the dynamics of the Rossby, Hadley and Walker circulations. The model shows that the horizontal air temperature anomaly gradient (ATAG) induces changes in meridional and zonal circulations and promotes the baroclinic evolution of the horizontal circulation. The simplified model also indicates that the absolute vorticity of the horizontal circulation is not conserved, and its changes can be described by changes in the vertical vorticities of the meridional and zonal circulations. Moreover, the thermodynamic equation shows that the induced meridional and zonal circulations and advection transport by the horizontal circulation in turn cause a redistribution of the air temperature. The simplified model reveals the fundamental rules between the evolution of the air temperature and the horizontal, meridional

  13. Gastrointestinal Degradation of Fumonisin B1 by Carboxylesterase FumD Prevents Fumonisin Induced Alteration of Sphingolipid Metabolism in Turkey and Swine

    Directory of Open Access Journals (Sweden)

    Sabine Masching

    2016-03-01

    Full Text Available The mycotoxin fumonisin B1 (FB1 is a frequent contaminant of feed and causes various adverse health effects in domestic animals. Hence, effective strategies are needed to prevent the impact of fumonisins on livestock productivity. Here we evaluated the capability of the fumonisin carboxylesterase FumD to degrade FB1 to its less toxic metabolite hydrolyzed FB1 (HFB1 in the gastrointestinal tract of turkeys and pigs. First, an ex vivo pig model was used to examine the activity of FumD under digestive conditions. Within 2 h of incubation with FumD, FB1 was completely degraded to HFB1 in the duodenum and jejunum, respectively. To test the efficacy of the commercial application of FumD (FUMzyme in vivo, female turkeys (n = 5 received either basal feed (CON, fumonisin-contaminated feed (15 mg/kg FB1+FB2; FB or fumonisin-contaminated feed supplemented with FUMzyme (15 U/kg; FB+FUMzyme for 14 days ad libitum. Addition of FUMzyme resulted in significantly decreased levels of FB1 in excreta, whereas HFB1 concentrations were significantly increased. Compared to the FB group (0.24 ± 0.02, the mean serum sphinganine-to-sphingosine (Sa/So ratio was significantly reduced in the FB+FUMzyme group (0.19 ± 0.02, thus resembling values of the CON group (0.16 ± 0.02. Similarly, exposure of piglets (n = 10 to 2 mg/kg FB1+FB2 for 42 days caused significantly elevated serum Sa/So ratios (0.39 ± 0.15 compared to the CON group (0.14 ± 0.01. Supplementation with FUMzyme (60 U/kg resulted in gastrointestinal degradation of FB1 and unaffected Sa/So ratios (0.16 ± 0.02. Thus, the carboxylesterase FumD represents an effective strategy to detoxify FB1 in the digestive tract of turkeys and pigs.

  14. Gastrointestinal Degradation of Fumonisin B1 by Carboxylesterase FumD Prevents Fumonisin Induced Alteration of Sphingolipid Metabolism in Turkey and Swine

    Science.gov (United States)

    Masching, Sabine; Naehrer, Karin; Schwartz-Zimmermann, Heidi-Elisabeth; Sărăndan, Mihai; Schaumberger, Simone; Dohnal, Ilse; Nagl, Veronika; Schatzmayr, Dian

    2016-01-01

    The mycotoxin fumonisin B1 (FB1) is a frequent contaminant of feed and causes various adverse health effects in domestic animals. Hence, effective strategies are needed to prevent the impact of fumonisins on livestock productivity. Here we evaluated the capability of the fumonisin carboxylesterase FumD to degrade FB1 to its less toxic metabolite hydrolyzed FB1 (HFB1) in the gastrointestinal tract of turkeys and pigs. First, an ex vivo pig model was used to examine the activity of FumD under digestive conditions. Within 2 h of incubation with FumD, FB1 was completely degraded to HFB1 in the duodenum and jejunum, respectively. To test the efficacy of the commercial application of FumD (FUMzyme) in vivo, female turkeys (n = 5) received either basal feed (CON), fumonisin-contaminated feed (15 mg/kg FB1+FB2; FB) or fumonisin-contaminated feed supplemented with FUMzyme (15 U/kg; FB+FUMzyme) for 14 days ad libitum. Addition of FUMzyme resulted in significantly decreased levels of FB1 in excreta, whereas HFB1 concentrations were significantly increased. Compared to the FB group (0.24 ± 0.02), the mean serum sphinganine-to-sphingosine (Sa/So) ratio was significantly reduced in the FB+FUMzyme group (0.19 ± 0.02), thus resembling values of the CON group (0.16 ± 0.02). Similarly, exposure of piglets (n = 10) to 2 mg/kg FB1+FB2 for 42 days caused significantly elevated serum Sa/So ratios (0.39 ± 0.15) compared to the CON group (0.14 ± 0.01). Supplementation with FUMzyme (60 U/kg) resulted in gastrointestinal degradation of FB1 and unaffected Sa/So ratios (0.16 ± 0.02). Thus, the carboxylesterase FumD represents an effective strategy to detoxify FB1 in the digestive tract of turkeys and pigs. PMID:27007395

  15. Potential vorticity dynamics for global scale circulations

    International Nuclear Information System (INIS)

    Lu, C.; Schubert, W.

    1994-01-01

    One of the most notable advances in extratropical dynamics this decade has been the understanding of large-scale atmospheric and oceanic processes by using potential vorticity dynamics, the so called open-quotes IPV thinking.close quotes This analysis method has also been successfully extended to some tropical atmospheric circulation systems such as hurricanes and the Hadley circulation. The fundamental idea behind such a dynamic system rests with the fact that PV is a tracer-like quantity since it is conserved (in the absence of friction and diabatic heating) following a fluid particle and carries both significant dynamic and thermodynamic information regarding fluid motion. Thus, the prediction and inversion of PV form the most succinct dynamic view of atmospheric and oceanic motions. Furthermore, PV dynamics provides access to many insightful dynamic analyses such as: Propagation of Rossby waves, barotropic and baroclinic instabilities for shear flows, and wave-mean flow interactions. All these features make IPV analysis a very attractive tool for studying geophysical fluid systems

  16. Sustaining observations of the unsteady ocean circulation.

    Science.gov (United States)

    Frajka-Williams, E

    2014-09-28

    Sustained observations of ocean properties reveal a global warming trend and rising sea levels. These changes have been documented by traditional ship-based measurements of ocean properties, whereas more recent Argo profiling floats and satellite records permit estimates of ocean changes on a near real-time basis. Through these and newer methods of observing the oceans, scientists are moving from quantifying the 'state of the ocean' to monitoring its variability, and distinguishing the physical processes bringing signals of change. In this paper, I give a brief overview of the UK contributions to the physical oceanographic observations, and the role they have played in the wider global observing systems. While temperature and salinity are the primary measurements of physical oceanography, new transbasin mooring arrays also resolve changes in ocean circulation on daily timescales. Emerging technologies permit routine observations at higher-than-ever spatial resolutions. Following this, I then give a personal perspective on the future of sustained observations. New measurement techniques promise exciting discoveries concerning the role of smaller scales and boundary processes in setting the large-scale ocean circulation and the ocean's role in climate. The challenges now facing the scientific community include sustaining critical observations in the case of funding system changes or shifts in government priorities. These long records will enable a determination of the role and response of the ocean to climate change. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  17. Pipe Decontamination Involving String-Foam Circulation

    International Nuclear Information System (INIS)

    Turchet, J.P.; Estienne, G.; Fournel, B.

    2002-01-01

    Foam applications number for nuclear decontamination purposes has recently increased. The major advantage of foam decontamination is the reduction of secondary liquid wastes volumes. Among foam applications, we focus on foam circulation in contaminated equipment. Dynamic properties of the system ensures an homogeneous and rapid effect of the foam bed-drifted chemical reagents present in the liquid phase. This paper describes a new approach of foam decontamination for pipes. It is based on an alternated air and foam injections. We called it 'string-foam circulation'. A further reduction of liquid wastes is achieved compared to continuous foam. Secondly, total pressure loss along the pipe is controlled by the total foam length in the pipe. It is thus possible to clean longer pipes keeping the pressure under atmospheric pressure value. This ensures the non dispersion of contamination. This study describes experimental results obtained with a neutral foam as well with an acid foam on a 130 m long loop. Finally, the decontamination of a 44 meters pipe is presented. (authors)

  18. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Franck Chiappini

    2012-01-01

    Full Text Available Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1 there are few markers specific to the HCC (tumor cells versus nontumor cells and (2 they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.

  19. Importance of hemoglobin concentration to exercise: acute manipulations

    DEFF Research Database (Denmark)

    Calbet, José A L; Lundby, Carsten; Koskolou, Maria

    2006-01-01

    An acute reduction of blood hemoglobin concentration ([Hb]), even when the circulating blood volume is maintained, results in lower (.)V(O(2)(max) and endurance performance, due to the reduction of the oxygen carrying capacity of blood. Conversely, an increase of [Hb] is associated with enhanced...

  20. Exhaust circulation into dry gas desulfurization process to prevent carbon deposition in an Oxy-fuel IGCC power generation

    International Nuclear Information System (INIS)

    Kobayashi, Makoto; Nakao, Yoshinobu; Oki, Yuso

    2014-01-01

    Highlights: • Power plant with semi-closed gas turbine and O 2 –CO 2 coal gasifier was studied. • We adopt dry gas sulfur removal process to establish the system. • The exhaust gas circulation remarkably prevented carbon deposition. • Efficiency loss for exhaust gas circulation is quite small. • Appropriate operating condition of sulfur removal process is revealed. - Abstract: Semi-closed cycle operation of gas turbine fueled by oxygen–CO 2 blown coal gasification provides efficient power generation with CO 2 separation feature by excluding pre-combustion type CO 2 capture that usually brings large efficiency loss. The plant efficiency at transmission end is estimated as 44% at lower heating value (LHV) providing compressed CO 2 with concentration of 93 vol%. This power generation system will solve the contradiction between economical resource utilization and reduction of CO 2 emission from coal-fired power plant. The system requires appropriate sulfur reduction process to protect gas turbine from corrosion and environment from sulfur emission. We adopt dry gas sulfur removal process to establish the system where apprehension about the detrimental carbon deposition from coal gas. The effect of circulation of a portion of exhaust gas to the process on the retardation of carbon deposition was examined at various gas compositions. The circulation remarkably prevented carbon deposition in the sulfur removal sorbent. The impact of the circulation on the thermal efficiency is smaller than the other auxiliary power consumption. Thus, the circulation is appropriate operation for the power generation

  1. Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma

    International Nuclear Information System (INIS)

    McNeeley, Kathleen M; Annapragada, Ananth; Bellamkonda, Ravi V

    2007-01-01

    Liposomal and other nanocarrier based drug delivery vehicles can localize to tumours through passive and/or active targeting. Passively targeted liposomal nanocarriers accumulate in tumours via 'leaky' vasculature through the enhanced permeability and retention (EPR) effect. Passive accumulation depends upon the circulation time and the degree of tumour vessel 'leakiness'. After extravasation, actively targeted liposomal nanocarriers efficiently deliver their payload by receptor-mediated uptake. However, incorporation of targeting moieties can compromise circulation time in the blood due to recognition and clearance by the reticuloendothelial system, decreasing passive accumulation. Here, we compare the efficacy of passively targeted doxorubicin-loaded PEGylated liposomal nanocarriers to that of actively targeted liposomal nanocarriers in a rat 9L brain tumour model. Although folate receptor (FR)-targeted liposomal nanocarriers had significantly reduced blood circulation time compared to PEGylated liposomal nanocarriers; intratumoural drug concentrations both at 20 and 50 h after administration were equal for both treatments. Both treatments significantly increased tumour inoculated animal survival by 60-80% compared to non-treated controls, but no difference in survival was observed between FR-targeted and passively targeted nanocarriers. Therefore, alternate approaches allowing for active targeting without compromising circulation time may be important for fully realizing the benefits of receptor-mediated active targeting of gliomas

  2. Mobilization of Viable Tumor Cells Into the Circulation During Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Olga A. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); Anderson, Robin L. [The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Russell, Prudence A. [Department of Anatomical Pathology, St. Vincent Hospital, Fitzroy, VIC (Australia); Ashley Cox, R. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Ivashkevich, Alesia [Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Laboratory of DNA Repair and Genomics, Centre for Innate Immunity and Infectious Disease, Monash Institute for Medical Research, Monash University, Clayton, VIC (Australia); Swierczak, Agnieszka; Doherty, Judy P. [Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Jacobs, Daphne H.M. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Smith, Jai [Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Siva, Shankar; Daly, Patricia E. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Ball, David L. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); and others

    2014-02-01

    Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.

  3. Mobilization of Viable Tumor Cells Into the Circulation During Radiation Therapy

    International Nuclear Information System (INIS)

    Martin, Olga A.; Anderson, Robin L.; Russell, Prudence A.; Ashley Cox, R.; Ivashkevich, Alesia; Swierczak, Agnieszka; Doherty, Judy P.; Jacobs, Daphne H.M.; Smith, Jai; Siva, Shankar; Daly, Patricia E.; Ball, David L.

    2014-01-01

    Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies

  4. Influence of acidification of circulating water on differential distribution of dispersed phase

    Directory of Open Access Journals (Sweden)

    Oleksandr B. Gulyaenko

    2015-06-01

    Full Text Available The paper analyzes the connection between processing technologies of circulating water cooling tower and coagulation-aggregation properties of colloidal particles of the dispersed phase. In circulating water cooling tower when clarifying additional water the reduction of HCO3- and CO32- concentrations happens with corresponding pH increase. Absorption of atmospheric carbon dioxide by cooling tower circulating water offsets this increase. The estimation of the probability of adhesion to the surface of the dispersed phase, distributed in the volume of circulation water, and the heat exchange surface of the condenser for different degrees of evaporation of the coolant is made. The distribution of cooling water micro-disperse particles which are adsorbed on the heat exchange surfaces of the condenser (deposit formation and on the surface of larger particles (particle aggregation reflects the efficiency of applied water treatment technology. It is shown that acidification of additional water facilitates solution of most fine fractions and increases hardness of treated water.

  5. Prototype of an opto-capacitive probe for non-invasive sensing cerebrospinal fluid circulation

    Science.gov (United States)

    Myllylä, Teemu; Vihriälä, Erkki; Pedone, Matteo; Korhonen, Vesa; Surazynski, Lukasz; Wróbel, Maciej; Zienkiewicz, Aleksandra; Hakala, Jaakko; Sorvoja, Hannu; Lauri, Janne; Fabritius, Tapio; Jedrzejewska-Szczerska, Małgorzata; Kiviniemi, Vesa; Meglinski, Igor

    2017-03-01

    In brain studies, the function of the cerebrospinal fluid (CSF) awakes growing interest, particularly related to studies of the glymphatic system in the brain, which is connected with the complex system of lymphatic vessels responsible for cleaning the tissues. The CSF is a clear, colourless liquid including water (H2O) approximately with a concentration of 99 %. In addition, it contains electrolytes, amino acids, glucose, and other small molecules found in plasma. The CSF acts as a cushion behind the skull, providing basic mechanical as well as immunological protection to the brain. Disturbances of the CSF circulation have been linked to several brain related medical disorders, such as dementia. Our goal is to develop an in vivo method for the non-invasive measurement of cerebral blood flow and CSF circulation by exploiting optical and capacitive sensing techniques simultaneously. We introduce a prototype of a wearable probe that is aimed to be used for long-term brain monitoring purposes, especially focusing on studies of the glymphatic system. In this method, changes in cerebral blood flow, particularly oxy- and deoxyhaemoglobin, are measured simultaneously and analysed with the response gathered by the capacitive sensor in order to distinct the dynamics of the CSF circulation behind the skull. Presented prototype probe is tested by measuring liquid flows inside phantoms mimicking the CSF circulation.

  6. Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor α

    Directory of Open Access Journals (Sweden)

    Anne H van der Spek

    2017-11-01

    Full Text Available Innate immune cells have recently been identified as novel thyroid hormone (TH target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TRα, which is the predominant TR in these cells, has not been studied to date. Studies in TRα0/0 mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TRα affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TRα (RTHα and compared these results to healthy controls. In addition, we measured neutrophil and macrophage function in one of these RTHα patients (mutation D211G. Circulating interleukin-8 levels were elevated in 7 out of 8 RTHα patients compared to controls. These patients harbor different mutations, suggesting that this is a general feature of the syndrome of RTHα. Neutrophil spontaneous apoptosis, bacterial killing, NAPDH oxidase activity and chemotaxis were unaltered in cells derived from the RTHαD211G patient. RTHα macrophage phagocytosis and cytokine induction after LPS treatment were similar to results from control cells. The D211G mutation did not result in clinically relevant impairment of neutrophil or pro-inflammatory macrophage function. As elevated circulating IL-8 is also observed in hyperthyroidism, this observation could be due to the high-normal to high levels of circulating T3 found in patients with RTHα.

  7. Genome-wide association study of serum selenium concentrations

    DEFF Research Database (Denmark)

    Gong, Jian; Hsu, Li; Harrison, Tabitha

    2013-01-01

    Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated...... this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We...... tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p

  8. Reduced serum myostatin concentrations associated with genetic muscle disease progression.

    Science.gov (United States)

    Burch, Peter M; Pogoryelova, Oksana; Palandra, Joe; Goldstein, Richard; Bennett, Donald; Fitz, Lori; Guglieri, Michela; Bettolo, Chiara Marini; Straub, Volker; Evangelista, Teresinha; Neubert, Hendrik; Lochmüller, Hanns; Morris, Carl

    2017-03-01

    Myostatin is a highly conserved protein secreted primarily from skeletal muscle that can potently suppress muscle growth. This ability to regulate skeletal muscle mass has sparked intense interest in the development of anti-myostatin therapies for a wide array of muscle disorders including sarcopenia, cachexia and genetic neuromuscular diseases. While a number of studies have examined the circulating myostatin concentrations in healthy and sarcopenic populations, very little data are available from inherited muscle disease patients. Here, we have measured the myostatin concentration in serum from seven genetic neuromuscular disorder patient populations using immunoaffinity LC-MS/MS. Average serum concentrations of myostatin in all seven muscle disease patient groups were significantly less than those measured in healthy controls. Furthermore, circulating myostatin concentrations correlated with clinical measures of disease progression for five of the muscle disease patient populations. These findings greatly expand the understanding of myostatin in neuromuscular disease and suggest its potential utility as a biomarker of disease progression.

  9. Vitamin D modulates the association of circulating insulin-like growth factor-1 with carotid artery intima-media thickness

    NARCIS (Netherlands)

    Ameri, P.; Canepa, M.; Fabbi, P.; Leoncini, G.; Milaneschi, Y.; Mussap, M.; AlGhatrif, M.; Balbi, M.; Viazzi, F.; Murialdo, G.; Pontremoli, R.; Brunelli, C.; Ferrucci, L.

    2014-01-01

    Objective: Experimental evidence indicates that circulating insulin-like growth factor-1 (IGF-1) counteracts vascular aging and atherosclerosis, for which increased carotid artery intima-media thickness (IMT) is a marker. Yet, IGF-1 concentrations have been inconsistently associated with carotid IMT

  10. A Systematic Review and Meta-Analysis of Circulating Biomarkers Associated with Failure of Arteriovenous Fistulae for Haemodialysis.

    Directory of Open Access Journals (Sweden)

    Susan K Morton

    Full Text Available Arteriovenous fistula (AVF failure is a significant cause of morbidity and expense in patients on maintenance haemodialysis (HD. Circulating biomarkers could be valuable in detecting patients at risk of AVF failure and may identify targets to improve AVF outcome. Currently there is little consensus on the relationship between circulating biomarkers and AVF failure. The aim of this systematic review was to identify circulating biomarkers associated with AVF failure.Studies evaluating the association between circulating biomarkers and the presence or risk of AVF failure were systematically identified from the MEDLINE, EMBASE and Cochrane Library databases. No restrictions on the type of study were imposed. Concentrations of circulating biomarkers of routine HD patients with and without AVF failure were recorded and meta-analyses were performed on biomarkers that were assessed in three or more studies with a composite population of at least 100 participants. Biomarker concentrations were synthesized into inverse-variance random-effects models to calculate standardized mean differences (SMD and 95% confidence intervals (CI.Thirteen studies comprising a combined population of 1512 participants were included after screening 2835 unique abstracts. These studies collectively investigated 48 biomarkers, predominantly circulating molecules which were assessed as part of routine clinical care. Meta-analysis was performed on twelve eligible biomarkers. No significant association between any of the assessed biomarkers and AVF failure was observed.This paper is the first systematic review of biomarkers associated with AVF failure. Our results suggest that blood markers currently assessed do not identify an at-risk AVF. Further, rigorously designed studies assessing biological plausible biomarkers are needed to clarify whether assessment of circulating markers can be of any clinical value. PROSPERO registration number CRD42016033845.

  11. Nanoformulation for anticancer drug delivery: Enhanced pharmacokinetics and circulation

    Science.gov (United States)

    Parekh, Gaurav

    In this study, we have explored the application of the Layer-by-Layer (LbL) assembly technique for improving injectable drug delivery systems of low soluble anticancer drugs (e.g. Camptothecin (CPT), Paclitaxel (PTX) or Doxorubicin (DOX)). For this study, a polyelectrolyte shell encapsulates different types of drug nanocores (e.g. soft core, nanomicelle or solid lipid nanocores).The low soluble drugs tend to crystallize and precipitate in an aqueous medium. This is the reason they cannot be injected and may have low concentrations and low circulation time in the blood. Even though these drugs when present in the cancer microenvironment have high anti-tumor inhibition, the delivery to the tumor site after intravenous administration is a challenge. We have used FDA-approved biopolymers for the process and elaborated formation of 60-90 nm diameter initial cores, which was stabilized by multilayer LbL shells for controlled release and longer circulation. A washless LbL assembly process was applied as an essential advancement in nano-assembly technology using low density nanocore (lipids) and preventing aggregation. This advancement reduced the number of process steps, enhanced drug loading capacity, and prevented the loss of expensive polyelectrolytes. Finally, we elaborated a general nano-encapsulation process, which allowed these three important anticancer drug core-shell nanocapsules with diameters of ca. 100-130 nm (this small size is a record for LbL encapsulation technique) to be stable in the serum and the blood for at least one week, efficient for cancer cell culture studies, injectable to mice with circulation for 4 hrs, and effective in suppressing tumors. This work is divided into three studies. The first study (CHAPTER 4) explores the application of LbL assembly for encapsulating a soft core of albumin protein and CPT anticancer drug. In order to preserve the activity of drug in the core, a unique technique of pH reversal is employed where the first few

  12. Analysis and research on natural circulation capacity of HFETR

    International Nuclear Information System (INIS)

    Xu Taozhong; Duan Tianyuan

    2010-01-01

    For the operating characteristics of HFETR, the numerical model of HFETR was established by RELAP5/MOD3 to analysis the maximal natural circulation capacity. Combining with the reactor running condition, the influence of the system pressure was analyzed by ascending power in step method and the pool water temperature on natural circulation characteristics was analyzed by integral power method. The results show that the natural circulation capacity are 0.9 and 2.0 MW separately under low pressure and high pressure, the natural circulation capacity increases as the running pressure increases, however the natural circulation capacity decreases as the coolant temperature increases in the pressure vessel. Based on the computational result and the theoretical deduction, a correlation was proposed to predicate the relationship between the natural circulation mass flow and the core power under different coolant temperatures. (authors)

  13. Transient Atmospheric Circulation Changes in a Grand ensemble of Idealized CO2 Increase Experiments

    Science.gov (United States)

    Karpechko, A.; Manzini, E.; Kornblueh, L.

    2017-12-01

    The yearly evolution with increasing forcing of the large-scale atmospheric circulation is examined in a 68-member ensemble of 1pctCO2 scenario experiments performed with the MPI-ESM model. Each member of the experiment ensemble is integrated for 155 years, from initial conditions taken from a 2000-yr long pre-industrial control climate experiment. The 1pctCO2 scenario experiments are conducted following the protocol of including as external forcing only a CO2 concentration increase at 1%/year, till quadrupling of CO2 concentrations. MPI-ESM is the Max-Planck-Institute Earth System Model (including coupling between the atmosphere, ocean and seaice). By averaging over the 68 members (ensemble mean), atmospheric variability is greatly reduced. Thus, it is possible to investigate the sensitivity to the climate state of the atmospheric response to CO2 doubling. Indicators of global change show the expected monotonic evolution with increasing CO2 and a weak dependence of the thermodynamical response to CO2 doubling on the climate state. The surface climate response of the atmospheric circulation, diagnosed for instance by the pressure at sea level, and the eddy-driven jet response show instead a marked dependence to the climate state, for the Northern winter season. We find that as the CO2 concentration increases above doubling, Northern winter trends in some indicators of atmospheric circulation changes decrease or even reverse, posing the question on what are the causes of this nonlinear behavior. The investigation of the role of stationary waves, the meridional overturning circulation, the decrease in Arctic sea ice and the stratospheric vortex points to the latter as a plausible cause of such nonlinear response.

  14. Glacial ocean circulation and stratification explained by reduced atmospheric temperature

    OpenAIRE

    Jansen, Malte F.

    2016-01-01

    To understand climatic swings between glacial and interglacial climates we need to explain the observed fluctuations in atmospheric carbon dioxide (CO2), which in turn are most likely driven by changes in the deep ocean circulation. This study presents a model for differences in the deep ocean circulation between glacial and interglacial climates consistent with both our physical understanding and various proxy observations. The results suggest that observed changes in ocean circulation and s...

  15. Circulating levels of chromatin fragments are inversely correlated with anti-dsDNA antibody levels in human and murine systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Jørgensen, Mariann H; Rekvig, Ole Petter; Jacobsen, Rasmus S

    2011-01-01

    Anti-dsDNA antibodies represent a central pathogenic factor in Lupus nephritis. Together with nucleosomes they deposit as immune complexes in the mesangial matrix and along basement membranes within the glomeruli. The origin of the nucleosomes and when they appear e.g. in circulation is not known...... an inverse correlation between anti-dsDNA antibodies and the DNA concentration in the circulation in both murine and human serum samples. High titer of anti-DNA antibodies in human sera correlated with reduced levels of circulating chromatin, and in lupus prone mice with deposition within glomeruli....... The inverse correlation between DNA concentration and anti-dsDNA antibodies may reflect antibody-dependent deposition of immune complexes during the development of lupus nephritis in autoimmune lupus prone mice. The measurement of circulating DNA in SLE sera by using qPCR may indicate and detect...

  16. Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies

    Science.gov (United States)

    Key, T J; Appleby, P N; Reeves, G K; Roddam, A W; Helzlsouer, K J; Alberg, A J; Rollison, D E; Dorgan, J F; Brinton, L A; Overvad, K; Kaaks, R; Trichopoulou, A; Clavel-Chapelon, F; Panico, S; Duell, E J; Peeters, P H M; Rinaldi, S; Fentiman, I S; Dowsett, M; Manjer, J; Lenner, P; Hallmans, G; Baglietto, L; English, D R; Giles, G G; Hopper, J L; Severi, G; Morris, H A; Hankinson, S E; Tworoger, S S; Koenig, K; Zeleniuch-Jacquotte, A; Arslan, A A; Toniolo, P; Shore, R E; Krogh, V; Micheli, A; Berrino, F; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Lui, Li Yung; Cummings, Steven R; Gunter, M J; Rohan, T E; Strickler, H D

    2011-01-01

    Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. PMID:21772329

  17. Circulating Tumor Cells, Enumeration and Beyond

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Jian-Mei [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Krebs, Matthew [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Christie Hospital Foundation NHS Trust, Manchester M20 4BX (United Kingdom); Ward, Tim; Morris, Karen; Sloane, Robert [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Blackhall, Fiona [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Cancer and Enabling Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester M20 4BX (United Kingdom); Christie Hospital Foundation NHS Trust, Manchester M20 4BX (United Kingdom); Dive, Caroline, E-mail: cdive@picr.man.ac.uk [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Cancer and Enabling Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester M20 4BX (United Kingdom)

    2010-06-09

    The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.

  18. Electromagnetic circulation pump for corrosive gases

    International Nuclear Information System (INIS)

    Noe, P.; Delafosse, D.; Deletre, G.

    1965-01-01

    In order to transport very corrosive products (fluorinated compounds) we have been led to develop a totally metallic circulation pump capable of operating at above room temperatures and with a molecular vacuum. We have aimed at maximum simplicity both in its conception and in its operation. The tests showed that the compression ratios produced, although not high are interesting (1.5 at a pressure of 100 torr) (see curve I). The flow-rate range is very wide: about one hundred ccs/atm/min. to 3000 ccs/atm/min. (see curves IV, V, VI). The desorption of this pump presents no difficulty if both the aspiration and the reject sides are pumped together. A hole of 2 mm diameter drilled in the piston makes it possible to desorb the space between the two segments. The price of this pump is not high: 1300 F, with the electrical cabinet. (authors) [fr

  19. Passive decay heat removal by natural circulation

    International Nuclear Information System (INIS)

    Vijayan, P.K.; Venkat Raj, V.; Kakodkar, A.; Mehta, S.K.

    1990-01-01

    The standardised 235 MWe PHWRs being built in India are the pressure tube type, heavy water moderated, heavy water cooled and natural uranium fuelled reactors. Several passive safety features are incorporated in these reactors. These include: (1) Containment pressure reduction and fission product trapping with the help of suppression pool following LOCA. (2) Emergency coolant injection by means of accumulators. (3) Large heat sink provided by the low temperature moderator under accident conditions. (4) Low excess reactivity, through the use of natural uranium fuel and on power fuelling. (5) Residual heat removal by means of natural circulation, etc. of which the last item is the subject matter of this report. (author). 8 refs, 10 figs

  20. Circulating tumor cells in breast cancer.

    Science.gov (United States)

    Bidard, Francois-Clement; Proudhon, Charlotte; Pierga, Jean-Yves

    2016-03-01

    Over the past decade, technically reliable circulating tumor cell (CTC) detection methods allowed the collection of large datasets of CTC counts in cancer patients. These data can be used either as a dynamic prognostic biomarker or as tumor material for "liquid biopsy". Breast cancer appears to be the cancer type in which CTC have been the most extensively studied so far, with level-of-evidence-1 studies supporting the clinical validity of CTC count in both early and metastatic stage. This review summarizes and discusses the clinical results obtained in breast cancer patients, the issues faced by the molecular characterization of CTC and the biological findings about cancer biology and metastasis that were obtained from CTC. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Circulating tumor cells: clinical validity and utility.

    Science.gov (United States)

    Cabel, Luc; Proudhon, Charlotte; Gortais, Hugo; Loirat, Delphine; Coussy, Florence; Pierga, Jean-Yves; Bidard, François-Clément

    2017-06-01

    Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs. In particular, this review will focus on breast, lung, colorectal and prostate cancer. Three major topics concerning the clinical utility of CTC are discussed-(1) treatment based on CTCs used as liquid biopsy, (2) treatment based on CTC count or CTC variations, and (3) treatment based on CTC biomarker expression. A summary of published or ongoing phase II and III trials is also presented.

  2. Nanotoxicity in Systemic Circulation and Wound Healing.

    Science.gov (United States)

    Bakshi, Mandeep Singh

    2017-06-19

    Nanotoxicity of nanomaterials is an important issue in view of their potential applications in systemic circulation and wound healing dressing. This account specifically deals with several characteristic features of different nanomaterials which induce hemolysis and how to make them hemocompatible. The shape, size, and surface functionalities of naked metallic as well as nonmetallic nanoparticles surfaces are responsible for the hemolysis. An appropriate coating of biocompatible molecules dramatically reduces hemolysis and promotes their ability as safe drug delivery vehicles. The use of coated nanomaterials in wound healing dressing opens several new strategies for rapid wound healing processes. Properly designed nanomaterials should be selected to minimize the nanotoxicity in the wound healing process. Future directions need new synthetic methods for engineered nanomaterials for their best use in nanomedicine and nanobiotechnology.

  3. Circulating Tumor Cells, Enumeration and Beyond

    International Nuclear Information System (INIS)

    Hou, Jian-Mei; Krebs, Matthew; Ward, Tim; Morris, Karen; Sloane, Robert; Blackhall, Fiona; Dive, Caroline

    2010-01-01

    The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology

  4. The collateral circulation of the heart

    Science.gov (United States)

    2013-01-01

    The coronary arteries have been regarded as end arteries for decades. However, there are functionally relevant anastomotic vessels, known as collateral arteries, which interconnect epicardial coronary arteries. These vessels provide an alternative source of blood supply to the myocardium in cases of occlusive coronary artery disease. The relevance of these collateral arteries is a matter of ongoing debate, but increasing evidence indicates a relevant protective role in patients with coronary artery disease. The collateral circulation can be assessed by different methods; the gold standard involves intracoronary pressure measurements. While the first clinical trials to therapeutically induce growth of collateral arteries have been unavailing, recent pilot studies using external counterpulsation or growth factors such as granulocyte colony stimulating factor (G-CSF) have shown promising results. PMID:23735225

  5. Circulating tumor cells: utopia or reality?

    Science.gov (United States)

    Conteduca, Vincenza; Zamarchi, Rita; Rossi, Elisabetta; Condelli, Valentina; Troiani, Laura; Aieta, Michele

    2013-09-01

    Circulating tumor cells (CTCs) could be considered a sign of tumor aggressiveness, but highly sensitive and specific methods of CTC detection are necessary owing to the rarity and heterogeneity of CTCs in peripheral blood. This review summarizes recent studies on tumor biology, with particular attention to the metastatic cascade, and the molecular characterization and clinical significance of CTCs. Recent technological approaches to enrich and detect these cells and challenges of CTCs for individualized cancer treatment are also discussed. This review also provides an insight into the positive and negative features of the future potential applications of CTC detection, which sometimes remains still a 'utopia', but its actual utility remains among the fastest growing research fields in oncology.

  6. Particle pollution changes the atmospheric circulation

    International Nuclear Information System (INIS)

    Kristjansson, Jon Egill; Iversen, Trond; Kirkevaag, Alf; Seland, Oeyvind; Debernard, Jens; Roeed, Lars Petter

    2002-01-01

    Industrial emissions and combustion of fossil fuels create large amounts of sulfate- and carbon containing soot particles. These mix with natural particles to change the natural aerosols. Such anthropogenic changes in the aerosols may have a great impact on the climate of the earth. Altered properties of the aerosols may change the atmosphere's absorption and reflection of solar radiation and contribute to heating or cooling. This is the direct effect. Changes in the properties of aerosols may also affect the number and size of recently formed cloud droplets. This may change the ability of the clouds to reflect solar radiation and to produce precipitation. This is the indirect effect. Recent research at the University of Oslo shows that anthropogenic particles significantly change the atmospheric circulation, in particular in the tropics, but also at European latitudes

  7. Nucla circulating atmospheric fluidized bed demonstration project

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Raymond E.

    1991-10-01

    Colorado-Ute Electric Association began a study to evaluate options for upgrading and extending the life of its Nucla power station in 1982. Located in southwestern Colorado near the town of Nucla, this station was commissioned in 1959 with a local bituminous coal as its design fuel for three identical stoker-fired units, each rated at 12.6 MW(e). Poor station efficiency, high fuel costs, and spiraling boiler maintenance costs forced the Nucla Station into low priority in the CUEA dispatch order as early as 1981. Among the options CUEA considered was to serve as a host utility to demonstrate Atmospheric Fluidized Bed Combustion (AFBC) technology. The anticipated environmental benefits and apparent attractive economics of a circulating AFBC led to Colorado-Ute's decision to proceed with the design and construction of a demonstration project in 1984 at the Nucla facility.

  8. Circulating Tumor Cells, Enumeration and Beyond

    Directory of Open Access Journals (Sweden)

    Jian-Mei Hou

    2010-06-01

    Full Text Available The detection and enumeration of circulating tumor cells (CTCs has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.

  9. Instability of single-phase natural circulation

    International Nuclear Information System (INIS)

    Xie Heng; Zhang Jinling; Jia Dounan

    1997-01-01

    The author has investigated the instability of single-phase flows in natural circulation loops. The momentum equation and energy equation are made dimensionless according to some definitions, and some important dimensionless parameters are gotten. The authors decomposed the mean mass flowrate and temperature into a steady solution and a small disturbance equations. Through solving the disturbance equations, the authors get the neutral stability curves. The authors have studied the effect of the two parameters which represent the ratio of buoyancy force to the friction loss in the loop on the stability of loops. The authors also have studied the effect of the difference of height between the center of heat source and the heat sink on the stability

  10. Circulating Tumor Cells in Prostate Cancer

    International Nuclear Information System (INIS)

    Hu, Brian; Rochefort, Holly; Goldkorn, Amir

    2013-01-01

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management

  11. NUCLA Circulating Atmospheric Fluidized Bed Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Raymond E.; Heller, Thomas J.; Bush, Stuart A.

    1991-01-01

    This Annual Report on Colorado-Ute Electric Association's NUCLA Circulating Fluidized Bed (CFB) Demonstration Program covers the period from February 1987 through December 1988. The outline for presentation in this report includes a summary of unit operations along with individual sections covering progress in study plan areas that commenced during this reporting period. These include cold-mode shakedown and calibration, plant commercial performance statistics, unit start-up (cold), coal and limestone preparation and handling, ash handling system performance and operating experience, tubular air heater, baghouse operation and performance, materials monitoring, and reliability monitoring. During this reporting period, the coal-mode shakedown and calibration plan was completed. (VC)

  12. Ocean circulation code on machine connection

    International Nuclear Information System (INIS)

    Vitart, F.

    1993-01-01

    This work is part of a development of a global climate model based on a coupling between an ocean model and an atmosphere model. The objective was to develop this global model on a massively parallel machine (CM2). The author presents the OPA7 code (equations, boundary conditions, equation system resolution) and parallelization on the CM2 machine. CM2 data structure is briefly evoked, and two tests are reported (on a flat bottom basin, and a topography with eight islands). The author then gives an overview of studies aimed at improving the ocean circulation code: use of a new state equation, use of a formulation of surface pressure, use of a new mesh. He reports the study of the use of multi-block domains on CM2 through advection tests, and two-block tests

  13. Re-circulating linac vacuum system

    International Nuclear Information System (INIS)

    Wells, Russell P.; Corlett, John N.; Zholents, Alexander A.

    2003-01-01

    The vacuum system for a proposed 2.5 GeV, 10ΜA recirculating linac synchrotron light source [1] is readily achievable with conventional vacuum hardware and established fabrication processes. Some of the difficult technical challenges associated with synchrotron light source storage rings are sidestepped by the relatively low beam current and short beam lifetime requirements of a re-circulating linac. This minimal lifetime requirement leads directly to relatively high limits on the background gas pressure through much of the facility. The 10ΜA average beam current produces very little synchrotron radiation induced gas desorption and thus the need for an ante-chamber in the vacuum chamber is eliminated. In the arc bend magnets, and the insertion devices, the vacuum chamber dimensions can be selected to balance the coherent synchrotron radiation and resistive wall wakefield effects, while maintaining the modest limits on the gas pressure and minimal outgassing

  14. BIM-Enabled Conceptual Modelling and Representation of Building Circulation

    Directory of Open Access Journals (Sweden)

    Jin Kook Lee

    2014-08-01

    Full Text Available This paper describes how a building information modelling (BIM-based approach for building circulation enables us to change the process of building design in terms of its computational representation and processes, focusing on the conceptual modelling and representation of circulation within buildings. BIM has been designed for use by several BIM authoring tools, in particular with the widely known interoperable industry foundation classes (IFCs, which follow an object-oriented data modelling methodology. Advances in BIM authoring tools, using space objects and their relations defined in an IFC's schema, have made it possible to model, visualize and analyse circulation within buildings prior to their construction. Agent-based circulation has long been an interdisciplinary topic of research across several areas, including design computing, computer science, architectural morphology, human behaviour and environmental psychology. Such conventional approaches to building circulation are centred on navigational knowledge about built environments, and represent specific circulation paths and regulations. This paper, however, places emphasis on the use of ‘space objects’ in BIM-enabled design processes rather than on circulation agents, the latter of which are not defined in the IFCs' schemas. By introducing and reviewing some associated research and projects, this paper also surveys how such a circulation representation is applicable to the analysis of building circulation-related rules.

  15. Fragment Length of Circulating Tumor DNA.

    Science.gov (United States)

    Underhill, Hunter R; Kitzman, Jacob O; Hellwig, Sabine; Welker, Noah C; Daza, Riza; Baker, Daniel N; Gligorich, Keith M; Rostomily, Robert C; Bronner, Mary P; Shendure, Jay

    2016-07-01

    Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.

  16. Circulating tumor cells in melanoma patients.

    Directory of Open Access Journals (Sweden)

    Gary A Clawson

    Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids

  17. Hydrodynamics of circulating and bubbling fluidized beds

    International Nuclear Information System (INIS)

    Gidaspow, D.P.; Tsuo, Y.P.; Ding, J.

    1991-01-01

    This paper reports that a review of modeling of the hydrodynamics of fluidization of bubbling beds showed that inviscid two-fluid models were able to predict a great deal of the behavior of bubbling beds because the dominant mechanism of energy dissipation is the drag between the particles and the fluid. The formation, the growth and the bursting of bubbles were predicted. Predicted wall-to-bed heat transfer coefficients and velocity profiles of jets agreed with measurements. Time average porosity distributions agreed with measurements done using gamma-ray densitometers without the use of any adjustable parameters. However, inviscid models could not correctly predict rates of erosion around tubes immersed into fluidized beds. To correctly model such behavior, granular stresses involving solids viscosity were added into the computer model. This viscosity arises due to random collision of particles. Several models fro this viscosity were investigated and the results compared to measurements of solids distributions in two-dimensional beds and to particle velocities reported in the literature. While in the case of bubbling beds the solids viscosity plays the role of a correction, modeling of a circulating fluidized bed (CFB) without a viscosity is not possible. Recent experimental data obtained at IIT and at IGT show that in CFB the solids viscous dissipation is responsible for as much as half of the pressure drop. From such measurement, solids viscosities were computed. These were used in the two fluid hydrodynamic model, to predict radial solids distributions and solids velocities which matched the experimental distributions. Most important, the model predicted cluster formation and transient internal circulation which is responsible for the favorable characteristics of CFBs, such as good wall-to-bed heat transfer. Video tape movies of computations compared favorably with high speed movies of the experiments

  18. Circulating steroids negatively correlate with tinnitus.

    Science.gov (United States)

    Chrbolka, Pavel; Palúch, Zoltán; Hill, Martin; Alušík, Štefan

    2017-07-01

    While not a disease entity in itself; symptoms of tinnitus (from Latin tinnio - clink) accompany a number of diseases. Tinnitus prevalence increases with age, deteriorates one's quality of life, and may even result in suicidal behavior. Tinnitus develops in response to a variety of risk factors, otoxic substances, noise exposure, hearing disorders, and psychological alterations. Tinnitus is closely related to mood, depression, and psychological state. In the present study, we focused on alterations of the steroid metabolome and particularly neuroactive, neuroprotective, and immunomodulatory steroids in patients with tinnitus. The study group consisted of 28 patients without evidence of an organic cause of tinnitus as well as without associated diseases or the effect of ototoxic medications. All patients underwent a complete audiological assessment and laboratory tests including routine biochemical markers and quantification of circulating steroids using gas chromatography/mass spectrometry and immunoassays. To rule out a pathology in the cerebellopontine angle area, CT scan or MRI were performed. To diagnose stem lesions, evoked potentials were also measured. Pearson's correlations and multivariate regression were used to assess any links between tinnitus intensity and frequency on the one hand, and steroid levels on the other. Results indicated a significant and consistent negative correlation between tinnitus indices and intensity of adrenal steroidogenesis. The circulating steroid metabolome including hormones and neuroactive, neuroprotective, and immunomodulatory steroids negatively correlates with the degree of tinnitus due to hypothalamo-pituitary-adrenal axis malfunction. Our results may help explain the pathophysiology of tinnitus and improve its diagnosis. However, further studies are needed to verify our postulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Genome-Wide Association Study of Serum Selenium Concentrations

    Directory of Open Access Journals (Sweden)

    Ulrike Peters

    2013-05-01

    Full Text Available Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO Cancer Screening and the Women’s Health Initiative (WHI. We tested association between 2,474,333 single nucleotide polymorphisms (SNPs and serum selenium concentrations using linear regression models. In the first stage (PLCO 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003 in the second stage (WHI. Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11 and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI. Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.

  20. Discours en circulation et (dé)montage filmique dans Fahrenheit 9/11 [Circulating discourse and film editing in Fahrenheit 9/11

    OpenAIRE

    Andrea Landvogt; Kathrin Sartingen

    2010-01-01

    Le film documentaire est une pratique sociale discursive médiatique qui se fonde essentiellement sur des pratiques citationnelles allant de l'allusion vague à la citation exacte. L'étude se concentre surun effet qui résulte de la rhéthorique filmique caractéristique de Michael Moore: la mise en circulation de discours –verbaux, visuels et acoustiques– décontextualisés grâce aux techniques du montage. Dans la mesure où il s'agit, dans la plupart des cas, d'un montagediscordant, Moore parvient ...