WorldWideScience

Sample records for apolipoprotein a-i bound

  1. Radioimmunoassay of apolipoprotein A-I of rat serum

    International Nuclear Information System (INIS)

    Fainaru, M.; Havel, R.J.; Felker, T.E.

    1976-01-01

    A double antibody radioimmunoassay technique was developed for quantification of apolipoprotein A-I, the major apoprotein of rat high density lipoprotein. Apo A-I was labelled with 125 I by the chloramine-T method. 125 I-labeled apo A-I had the same electrophoretic mobility as unlabeled apo A-I and more than 80% of the 125 I was precipitated by rabbit anti apo A-I antibodies. The assay is sensitive at the level of 0.5-5 ng, and has intraassay and interassay coefficients of variation of 4.5 and 6.5% respectively. The specificity of the assay was established by competitive displacement of 125 I-labeled apo A-I from its antibody by apo A-I and lipoproteins containing apo A-I, but not by rat albumin and other apoproteins. Immunoreactivity of high density lipoprotein and serum was only about 35% of that of their delipidated forms when Veronal buffer was used as a diluent. Inclusion of 5 mM sodium decyl sulfate in the incubation mixture brought out reactivity equivalent to that found after delipidation. Completeness of the reaction was verified by comparison with the amount of apo A-I in chromatographic fractions of the total apoprotein of high density lipoprotein. Content (weight %, mean values +- S.D.) of immunoassayable apo A-I was: 62.3 +- 5.9 in high density lipoprotein; 1.7 +- 0.3 in low density lipoprotein; 0.09 +- 0.03 in very low density lipoprotein and 25.0 +- 5.0 in lymph chylomicrons. Concentration in whole serum was 51.4 +- 8.9 mg/dl and 33.6 +- 4.1 mg/dl for female and male rats, respectively (p 1.21 g/ml and <1% in lipoproteins of d<1.063 g/ml

  2. Analysis of apolipoprotein A-I as a substrate for matrix metalloproteinase-14

    International Nuclear Information System (INIS)

    Park, Jun Hyoung; Park, Sung-Min; Park, Ki-Hoon; Cho, Kyung-Hyun; Lee, Seung-Taek

    2011-01-01

    Highlights: → MMP-14 degrades apoA-I more efficiently than other tested MMPs. → Lipid-free apoA-I is more susceptible to MMPs than lipid-bound apoA-I. → MMP-14 cleavage sites on apoA-I have been determined. → Cleavage of apoA-I by MMP-14 impairs its ability to form HDL. -- Abstract: Substrates for matrix metalloproteinase (MMP)-14 were previously identified in human plasma using proteomic techniques. One putative MMP-14 substrate was apolipoprotein A-I (apoA-I), a major component of high-density lipoprotein (HDL). In vitro cleavage assays showed that lipid-free apoA-I is a more accessible substrate for MMP-14 compared to lipid-bound apoA-I, and that MMP-14 is more prone to digest apoA-I than MMP-3. The 28-kDa apoA-I was cleaved into smaller fragments of 27, 26, 25, 22, and 14-kDa by MMP-14. ApoA-I sites cleaved by MMP-14 were determined by isotope labeling of C-termini derived from the cleavage and analysis of the labeled peptides by mass spectrometry, along with N-terminal sequencing of the fragments. Cleavage of apoA-I by MMP-14 resulted in a loss of ability to form HDL. Our results suggest that cleavage of lipid-free apoA-I by MMP-14 may contribute to reduced HDL formation, and this may be occurring during the development of various vascular diseases as lipid metabolism is disrupted.

  3. Trimerization of apolipoprotein A-I retards plasma clearance and preserves antiatherosclerotic properties

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Laurberg, Jacob Marsvin; Andersen, Mikkel Holmen

    2008-01-01

    An increased plasma level of the major high-density lipoprotein (HDL) component, apolipoprotein A-I (apoA-I) is the aim of several therapeutic strategies for combating atherosclerotic disease. HDL therapy by direct intravenous administration of apoA-I is a plausible way; however, a fast renal...

  4. Effect of treatment with human apolipoprotein A-I on atherosclerosis in uremic apolipoprotein-E deficient mice

    DEFF Research Database (Denmark)

    Pedersen, Tanja Xenia; Bro, Susanne; Andersen, Mikkel H

    2009-01-01

    OBJECTIVE: Uremia markedly increases the risk of atherosclerosis. Thus, effective anti-atherogenic treatments are needed for uremic patients. This study examined effects of non-lipidated recombinant human apoA-I (h-apoA-I) and a recombinant trimeric apoA-I molecule (TripA-I) on lipid metabolism a...

  5. Apolipoproteins A-I, B, and C-III and Obesity in Young Adult Cherokee

    Directory of Open Access Journals (Sweden)

    Wenyu Wang

    2017-01-01

    Full Text Available Since young adult Cherokee are at increased risk for both diabetes and cardiovascular disease, we assessed association of apolipoproteins (A-I, B, and C-III in non-HDL and HDL with obesity and related risk factors. Obese participants (BMI ≥ 30 aged 20–40 years (n=476 were studied. Metabolically healthy obese (MHO individuals were defined as not having any of four components of the ATP-III metabolic syndrome after exclusion of waist circumference, and obese participants not being MHO were defined as metabolically abnormal obese (MAO. Associations were evaluated by correlation and regression modeling. Obesity measures, blood pressure, insulin resistance, lipids, and apolipoproteins were significantly different between groups except for total cholesterol, LDL-C, and HDL-apoC-III. Apolipoproteins were not correlated with obesity measures with the exception of apoA-I with waist and the waist : height ratio. In a logistic regression model apoA-I and the apoB : apoA-I ratio were significantly selected for identifying those being MHO, and the result (C-statistic = 0.902 indicated that apoA-I and the apoB : apoA-I ratio can be used to identify a subgroup of obese individuals with a significantly less atherogenic lipid and apolipoprotein profile, particularly in obese Cherokee men in whom MHO is more likely.

  6. Predictive value of serum apolipoprotein B/apolipoprotein A-I ratio in metabolic syndrome risk: a Chinese cohort study.

    Science.gov (United States)

    Chou, Yu-Ching; Kuan, Jen-Chun; Bai, Chyi-Huey; Yang, Tsan; Chou, Wan-Yun; Hsieh, Po-Chien; You, San-Lin; Hwang, Lee-Ching; Chen, Chien-Hua; Wei, Cheng-Yu; Sun, Chien-An

    2015-06-01

    The purpose of this study was to evaluate whether the apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio is a promising risk predictor of metabolic syndrome (MetS) and to determine the optimal cut-off value of this ratio in detecting subjects with MetS in a Chinese population. A prospective study was conducted using a representative sample of non-institutionized people in Taiwan. A total of 3,343 participants with mean age (±SD) of 39.86 (±15.61) years old were followed up from 2002 to 2007. The primary outcome was the incidence of MetS. The MetS was defined according to a unified criterion established by several major organizations. There were 462 cases of incident MetS during a mean follow-up period of 5.26 years. A significantly stepwise increase in the incidence of MetS across quartiles of the apoB/apoA-I ratio was noted in both sexes after adjustment for potential confounders (p for trend risk of MetS in both men [adjusted hazard ratio (HR) = 6.29, 95 % confidence interval (CI) = 2.79-9.13] and women (adjusted HR = 3.82, 95 % CI = 1.06-6.63). Comparisons of receiver operating characteristics curves indicated that the predictive ability of apoB/apoA-I ratio to detect MetS was better than conventional lipid ratio measurements. Furthermore, the optimal cut-off value of apoB/apoA-I ratio for MetS diagnosis was 0.71 in men and 0.56 in women. These results suggest that an elevated apoB/apoA-I ratio might constitute a potentially crucial measure linked to the risk of developing MetS.

  7. Both serum apolipoprotein B and the apolipoprotein B/apolipoprotein A-I ratio are associated with carotid intima-media thickness.

    Directory of Open Access Journals (Sweden)

    Fei Huang

    Full Text Available BACKGROUND: Previous studies indicated that apolipoprotein measurements predicted cardiovascular disease (CVD risk; however, associations between apolipoproteins and carotid intima-media thickness (CIMT were less explored. METHODOLOGY AND PRINCIPAL FINDINGS: The cross-sectional study included 6069 participants aged 40 years or older with NGT from Shanghai, China. Serum fasting traditional lipids (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG], apoA-I and apoB were assessed. A high-resolution B-mode ultrasonography was performed to measure CIMT. We found CIMT increased progressively across the quartiles of serum apoB (p for trend <0.0001. In logistic regression, concentrations of apoB (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.18-1.36, TC (OR 1.23, 95% CI 1.14-1.32, LDL-C (OR 1.25, 95% CI 1.16-1.34 and TG (OR 1.11, 95% CI 1.04-1.20 were significantly related to elevated CIMT after adjusted for age and sex. Meanwhile, the apoB/apoA-I ratio (OR 1.25, 95% CI 1.17-1.34 related to elevated CIMT. ApoB (OR 1.23, 95% CI 1.00-1.51 and the apoB/apoA-I ratio (OR 1.19, 95% CI 1.04-1.36 remained significantly associated with elevated CIMT, after adjusted for the traditional CVD risk factors including traditional lipids. CONCLUSIONS AND SIGNIFICANCE: There were significant associations between serum apoB, the apoB/apoA-I ratio and elevated CIMT. Serum apoB and the apoB/apoA-I ratio might be independent predictors of early atherosclerosis in NGT.

  8. Simultaneous Quantification of Apolipoprotein A-I and Apolipoprotein B by Liquid-Chromatography–Multiple-Reaction–Monitoring Mass Spectrometry

    Science.gov (United States)

    Agger, Sean A.; Marney, Luke C.; Hoofnagle, Andrew N.

    2011-01-01

    BACKGROUND If liquid-chromatography–multiple-reaction–monitoring mass spectrometry (LC-MRM/MS) could be used in the large-scale preclinical verification of putative biomarkers, it would obviate the need for the development of expensive immunoassays. In addition, the translation of novel biomarkers to clinical use would be accelerated if the assays used in preclinical studies were the same as those used in the clinical laboratory. To validate this approach, we developed a multiplexed assay for the quantification of 2 clinically well-known biomarkers in human plasma, apolipoprotein A-I and apolipoprotein B (apoA-I and apoB). METHODS We used PeptideAtlas to identify candidate peptides. Human samples were denatured with urea or trifluoroethanol, reduced and alkylated, and digested with trypsin. We compared reversed-phase chromatographic separation of peptides with normal flow and microflow, and we normalized endogenous peptide peak areas to internal standard peptides. We evaluated different methods of calibration and compared the final method with a nephelometric immunoassay. RESULTS We developed a final method using trifluoroethanol denaturation, 21-h digestion, normal flow chromatography-electrospray ionization, and calibration with a single normal human plasma sample. For samples injected in duplicate, the method had intraassay CVs <6% and interassay CVs <12% for both proteins, and compared well with immunoassay (n = 47; Deming regression, LC-MRM/MS = 1.17 × immunoassay – 36.6; Sx|y = 10.3 for apoA-I and LC-MRM/MS = 1.21 × immunoassay + 7.0; Sx|y = 7.9 for apoB). CONCLUSIONS Multiplexed quantification of proteins in human plasma/serum by LC-MRM/MS is possible and compares well with clinically useful immunoassays. The potential application of single-point calibration to large clinical studies could simplify efforts to reduce day-to-day digestion variability. PMID:20923952

  9. Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Lundegaard, Christiane; Tybjærg-Hansen, Anne; Grande, Peer

    2010-01-01

    Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD).......Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD)....

  10. Effect of TNFα on activities of different promoters of human apolipoprotein A-I gene

    International Nuclear Information System (INIS)

    Orlov, Sergey V.; Mogilenko, Denis A.; Shavva, Vladimir S.; Dizhe, Ella B.; Ignatovich, Irina A.; Perevozchikov, Andrej P.

    2010-01-01

    Research highlights: → TNFα stimulates the distal alternative promoter of human apoA-I gene. → TNFα acts by weakening of promoter competition within apoA-I gene (promoter switching). → MEK1/2 and nuclear receptors PPARα and LXRs take part in apoA-I promoter switching. -- Abstract: Human apolipoprotein A-I (ApoA-I) is a major structural and functional protein component of high-density lipoproteins. The expression of the apolipoprotein A-I gene (apoA-I) in hepatocytes is repressed by pro-inflammatory cytokines such as IL-1β and TNFα. Recently, two novel additional (alternative) promoters for human apoA-I gene have been identified. Nothing is known about the role of alternative promoters in TNFα-mediated downregulation of apoA-I gene. In this article we report for the first time about the different effects of TNFα on two alternative promoters of human apoA-I gene. Stimulation of HepG2 cells by TNFα leads to activation of the distal alternative apoA-I promoter and downregulation of the proximal alternative and the canonical apoA-I promoters. This effect is mediated by weakening of the promoter competition within human apoA-I 5'-regulatory region (apoA-I promoter switching) in the cells treated by TNFα. The MEK1/2-ERK1/2 cascade and nuclear receptors PPARα and LXRs are important for TNFα-mediated apoA-I promoter switching.

  11. Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis.

    Science.gov (United States)

    Bisoendial, Radjesh; Tabet, Fatiha; Tak, Paul P; Petrides, Francine; Cuesta Torres, Luisa F; Hou, Liming; Cook, Adam; Barter, Philip J; Weninger, Wolfgang; Rye, Kerry-Anne

    2015-11-01

    Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo) A-I, the principal apolipoprotein of high-density lipoproteins, to preserve the normal function of lymphatic endothelial cells treated with TNF. TNF decreased the ability of lymphatic endothelial cells to form tube-like structures. Preincubation of lymphatic endothelial cells with apoA-I attenuated the TNF-mediated inhibition of tube formation in a concentration-dependent manner. In addition, apoA-I reversed the TNF-mediated suppression of lymphatic endothelial cell migration and lymphatic outgrowth in thoracic duct rings. ApoA-I also abrogated the negative effect of TNF on lymphatic neovascularization in an ATP-binding cassette transporter A1-dependent manner. At the molecular level, this involved downregulation of TNF receptor-1 and the conservation of prospero-related homeobox gene-1 expression, a master regulator of lymphangiogenesis. ApoA-I also re-established the normal phenotype of the lymphatic network in the diaphragms of human TNF transgenic mice. ApoA-I restores the neovascularization capacity of the lymphatic system during TNF-mediated inflammation. This study provides a proof-of-concept that high-density lipoprotein-based therapeutic strategies may attenuate chronic inflammation via its action on lymphatic vasculature. © 2015 American Heart Association, Inc.

  12. Selective oxidation of methionine residues in apolipoprotein A-I and its potential biological consequences

    International Nuclear Information System (INIS)

    Panzenboeck, U.; Waldeck, R.; Rye, K.A.; Sloane, T.; Kritharides, L.; Stocker, R.

    1998-01-01

    The earliest stages of HDL oxidation are accompanied by the oxidation of specific Met residues in apolipoprotein AI and AII and the formation of Met sulfoxides (Met(O)) has been proposed to play a significant role in the reduction and hence detoxification of lipid hydroperoxides associated with HDL. Oxidation of HDL may generally decrease the anti-atherogenic properties of this lipoprotein, although both, the inhibition and the enhancement of cholesterol removal from cells has been reported for different types of oxidation. In light of these findings we have investigated the secondary structure, lipid affinity, LCAT activation and cholesterol-efflux promoting properties of native and selectively oxidized apo A-I(apo A-I +32 , containing Met(O) at Met l12 and Met l48 ) in purified or reconstituted forms. Data obtained by circular dichroism revealed that selective oxidation of Met residues 112 and 148 does not alter alpha helicity of the protein in solution, indicating that this oxidation is not sufficient to influence significantly this type of secondary structure of apo A-I in its 'lipid-free' form. The lipid affinity of native apo A-I and apo A-I +32 was determined as the rate of clearance of DMPC multilamellar to small unilamellar vesicles. Compared with the native protein, apo A-I +32 induced a 2-3 fold faster rate of clearance, suggesting that the increased hydrophilicity due Met(O) increased the rate for protein-lipid interactions. Met residues 112 and 148 reside in the hydrophobic faces of helices 5 and 7, and both these regions have been suggested to be important for both, LCAT activation and cholesterol efflux. Kinetic experiments have revealed that the affinity for LCAT is comparable for HDL reconstituted with either apo A-I or apo A-I +32 . Efflux of [ 3 H]-cholesterol from lipid-laden human monocytederived macrophages to isolated apolipoproteins was enhanced for apo A-I +32 compared with apo A-I, consistent with the DMPC clearance data. Together these

  13. Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain.

    Science.gov (United States)

    Zensi, Anja; Begley, David; Pontikis, Charles; Legros, Celine; Mihoreanu, Larisa; Büchel, Claudia; Kreuter, Jörg

    2010-12-01

    Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30 min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.

  14. The concentration of apolipoprotein A-I decreases during experimentally induced acute-phase processes in pigs

    DEFF Research Database (Denmark)

    Carpintero, R.; Pineiro, M.; Andres, M.

    2005-01-01

    In this work, apolipoprotein A-I (ApoA-I) was purified from pig sera. The responses of this protein after sterile inflammation and in animals infected with Actinobacillus pleuropneumoniae or Streptococcus suis were investigated. Decreases in the concentrations of ApoA-I, two to five times lower...

  15. Selective labelling of apolipoproteins A-I and C-I at methionine residues by (TH) methyl exchange

    Energy Technology Data Exchange (ETDEWEB)

    Hancock, W.S.; Harding, D.R.K.; Barling, P.M.; Sparrow, J.T.

    1985-01-01

    Apolipoproteins C-I and A-I were radioactively labelled with tritium by (TH)-methyl exchange. The methionine residues were first methylated with (TH)-methyl iodide at pH4 and the reaction products were purified by gel filtration and cation exchange chromatography. The products were then demethylated with 2-mercaptoethanol (6 M) at pH 8.6 to regenerate the apolipoproteins in an unmodified but tritiated form. The specific radioactivity for apolipoprotein C-I and A-I was 3.5 x 10W and 1.5 x 10X dpm/pmol respectively. The properties of (TH)-apolipoprotein C-I were examined by reversed phase HPLC and by incorporation into very low density lipoproteins (VLDL).

  16. Caveolin-1-mediated apolipoprotein A-I membrane binding sites are not required for cholesterol efflux.

    Directory of Open Access Journals (Sweden)

    Soazig Le Lay

    Full Text Available Caveolin-1 (Cav1, a structural protein required for the formation of invaginated membrane domains known as caveolae, has been implicated in cholesterol trafficking and homeostasis. Here we investigated the contribution of Cav1 to apolipoprotein A-I (apoA-I cell surface binding and intracellular processing using mouse embryonic fibroblasts (MEFs derived from wild type (WT or Cav1-deficient (Cav1(-/- animals. We found that cells expressing Cav1 have 2.6-fold more apoA-I binding sites than Cav1(-/- cells although these additional binding sites are not associated with detergent-free lipid rafts. Further, Cav1-mediated binding targets apoA-I for internalization and degradation and these processes are not correlated to cholesterol efflux. Despite lower apoA-I binding, cholesterol efflux from Cav1(-/- MEFs is 1.7-fold higher than from WT MEFs. Stimulation of ABCA1 expression with an LXR agonist enhances cholesterol efflux from both WT and Cav1(-/- cells without increasing apoA-I surface binding or affecting apoA-I processing. Our results indicate that there are at least two independent lipid binding sites for apoA-I; Cav1-mediated apoA-I surface binding and uptake is not linked to cholesterol efflux, indicating that membrane domains other than caveolae regulate ABCA1-mediated cholesterol efflux.

  17. Apolipoprotein A-I metabolism in cynomolgus monkey. Identification and characterization of beta-migrating pools

    International Nuclear Information System (INIS)

    Melchior, G.W.; Castle, C.K.

    1989-01-01

    Fresh plasma from control (C) and hypercholesterolemic (HC) cynomolgus monkeys was analyzed by agarose electrophoresis-immunoblotting with antibody to cynomolgus monkey apolipoprotein (apo) A-I. Two bands were evident on the autoradiogram: an alpha-migrating band (high density lipoprotein) and a beta-migrating band that comigrated exactly with cynomolgus monkey low density lipoprotein (LDL). The presence of beta-migrating apo A-I in the plasma of these monkeys was confirmed by Geon-Pevikon preparative electrophoresis, crossed immunoelectrophoresis, and isotope dilution studies in which radiolabeled apo A-I was found to equilibrate also with alpha- and beta-migrating pools of apo A-I in the plasma. Subfractionation of C and HC plasma by agarose column chromatography (Bio-Gel A-0.5M and A-15M) followed by agarose electrophoresis-immunoblotting indicated that the beta-migrating apo A-I in C was relatively homogeneous and eluted with proteins of Mr approximately 50 kD [apo A-I(50 kD)], whereas two beta-migrating fractions were identified in HC, one that eluted with the 50-kD proteins, and the other that eluted in the LDL Mr range [apo A-I(LDL)]. The apo A-I(LDL) was precipitated by antibody to cynomolgus monkey apo B. The apo A-I(50 kD) accounted for 5 +/- 1% (mean +/- SD) of the plasma apo A-I in C plasma, and 15 +/- 7% in HC plasma. No apo A-I(LDL) was detected in C plasma, but that fraction accounted for 9 +/- 7% of the apo A-I in HC plasma. These data establish the presence of multiple pools of apo A-I in the cynomolgus monkey, which must be taken into consideration in any comprehensive model of apo A-I metabolism in this species

  18. Serum concentrations of cholesterol, apolipoprotein A-I and apolipoprotein B in a total of 1694 meat-eaters, fish-eaters, vegetarians and vegans.

    Science.gov (United States)

    Bradbury, K E; Crowe, F L; Appleby, P N; Schmidt, J A; Travis, R C; Key, T J

    2014-02-01

    The objective of this study was to describe serum lipid concentrations, including apolipoproteins A-I and B, in different diet groups. A cross-sectional analysis of a sample of 424 meat-eaters, 425 fish-eaters, 423 vegetarians and 422 vegans, matched on sex and age, from the European Prospective Investigation into Cancer and Nutrition-Oxford cohort. Serum concentrations of total, and high-density lipoprotein (HDL) cholesterol, as well as apolipoproteins A-I and B were measured, and serum non-HDL cholesterol was calculated. Vegans had the lowest body mass index (BMI) and the highest and lowest intakes of polyunsaturated and saturated fat, respectively. After adjustment for age, alcohol and physical activity, compared with meat-eaters, fish-eaters and vegetarians, serum concentrations of total and non-HDL cholesterol and apolipoprotein B were significantly lower in vegans. Serum apolipoprotein A-I concentrations did not differ between the diet groups. In males, the mean serum total cholesterol concentration was 0.87 mmol/l lower in vegans than in meat-eaters; after further adjustment for BMI this difference was 0.76 mmol/l. In females, the difference in total cholesterol between these two groups was 0.6 mmol/l, and after further adjustment for BMI was 0.55 mmol/l. [corrected]. In this study, which included a large number of vegans, serum total cholesterol and apolipoprotein B concentrations were lower in vegans compared with meat-eaters, fish-eaters and vegetarians. A small proportion of the observed differences in serum lipid concentrations was explained by differences in BMI, but a large proportion is most likely due to diet.

  19. A model of lipid-free apolipoprotein A-I revealed by iterative molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Xing Zhang

    Full Text Available Apolipoprotein A-I (apo A-I, the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS. Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore, by integrating various experimental results, we proposed a new structural model for lipid-free apo A-I, which contains a bundled four-helix N-terminal domain (1-192 that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193-243. This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation.

  20. Erythrocyte-bound apolipoprotein B in relation to atherosclerosis, serum lipids and ABO blood group.

    Directory of Open Access Journals (Sweden)

    Boudewijn Klop

    Full Text Available INTRODUCTION: Erythrocytes carry apolipoprotein B on their membrane, but the determining factors of erythrocyte-bound apolipoprotein B (ery-apoB are unknown. We aimed to explore the determinants of ery-apoB to gain more insight into potential mechanisms. METHODS: Subjects with and without CVD were included (N = 398. Ery-apoB was measured on fresh whole blood samples using flow cytometry. Subjects with ery-apoB levels ≤ 0.20 a.u. were considered deficient. Carotid intima media thickness (CIMT was determined as a measure of (subclinical atherosclerosis. RESULTS: Mean ery-apoB value was 23.2% lower in subjects with increased CIMT (0.80 ± 0.09 mm, N = 140 compared to subjects with a normal CIMT (0.57 ± 0.08 mm, N = 258 (P = 0.007, adjusted P<0.001. CIMT and ery-apoB were inversely correlated (Spearman's r: -0.116, P = 0.021. A total of 55 subjects (13.6% were considered ery-apoB deficient, which was associated with a medical history of CVD (OR: 1.86, 95% CI 1.04-3.33; adjusted OR: 1.55; 95% CI 0.85-2.82. Discontinuation of statins in 54 subjects did not influence ery-apoB values despite a 58.4% increase in serum apolipoprotein B. Subjects with blood group O had significantly higher ery-apoB values (1.56 ± 0.94 a.u. when compared to subjects with blood group A (0.89 ± 1.15 a.u, blood group B (0.73 ± 0.1.12 a.u. or blood group AB (0.69 ± 0.69 a.u. (P-ANOVA = 0.002. CONCLUSION: Absence or very low values of ery-apoB are associated with clinical and subclinical atherosclerosis. While serum apolipoprotein B is not associated with ery-apoB, the ABO blood group seems to be a significant determinant.

  1. Substituted Benzamides Containing Azaspiro Rings as Upregulators of Apolipoprotein A-I Transcription

    Directory of Open Access Journals (Sweden)

    Bin Hong

    2012-06-01

    Full Text Available Apolipoprotein A-I (Apo A-I is the principal protein component of high density lipoprotein (HDL, which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future.

  2. Expression of human apolipoprotein A-I epitopes in high density lipoproteins and in serum

    International Nuclear Information System (INIS)

    Marcel, Y.L.; Jewer, D.; Vezina, C.; Milthorp, P.; Weech, P.K.

    1987-01-01

    The expression and immunoreactivity of apolipoprotein (apo) A-I epitopes in high density lipoproteins (HDL) and serum has been investigated using two series of monoclonal antibodies (Mabs) which have been described elsewhere. Series 1 Mabs, identified as 3D4, 6B8, and 5G6, were obtained by immunization and screening with apoA-I, and series 2 Mabs, identified as 2F1, 4H1, 3G10, 4F7, and 5F6, were obtained by immunization and screening with HDL. These Mabs were characterized with respect to their binding to HDL particles in solution. In series 2 Mabs, 2F1, 3G10, and 4F7, which react with apoA-I CNBr-fragments 1 and 2, could precipitate 100% of 125 I-labeled HDL, while 4H1 and 5F6, which react with CNBr fragments 1 and 3, precipitated 90 and 60% of 125 I-labeled HDL, respectively. Therefore, three distinct epitopes mapped to CNBr fragments 1 and 2 have been identified which are expressed on all HDL particles, indicating that several antigenic do mains exist on apoA-I which have the same conformation on all apoA-I-containing lipoproteins. The Mabs reacting at these sites have significantly higher affinity constants for 125 I-labeled HDL than those that failed to precipitate 100% of HDL. This suggests that the high affinity Mabs react with apoA-I epitopes that are both expressed on all lipoproteins and located in thermo-dynamically stable regions of the molecules. All Mabs from series 1 precipitated 35% or less of 125 I-labeled HDL prepared from freshly collected serum, but the proportion of HDL particles expressing the epitopes for these Mabs doubled or more upon serum storage at 4 degrees C. The time course of the alteration of apoA-I antigen in vitro was measured in three normolipemic donors

  3. Effect of an isoenergetic traditional Mediterranean diet on apolipoprotein A-I kinetic in men with metabolic syndrome

    Science.gov (United States)

    The impact of the Mediterranean diet (MedDiet) on high-density lipoprotein (HDL) kinetics has not been studied to date. The objective of this study was therefore to investigate the effect of the MedDiet in the absence of changes in body weight on apolipoprotein (apo) A-I kinetic in men with metaboli...

  4. Iowa Mutant Apolipoprotein A-I (ApoA-IIowa) Fibrils Target Lysosomes.

    Science.gov (United States)

    Kameyama, Hirokazu; Nakajima, Hiroyuki; Nishitsuji, Kazuchika; Mikawa, Shiho; Uchimura, Kenji; Kobayashi, Norihiro; Okuhira, Keiichiro; Saito, Hiroyuki; Sakashita, Naomi

    2016-07-28

    The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1-83) of apoA-I containing this mutation deposit as amyloid fibrils in patients' tissues and organs, but the mechanisms of cellular degradation and cytotoxicity have not yet been clarified. In this study, we demonstrated degradation of apoA-IIowa fibrils via the autophagy-lysosomal pathway in human embryonic kidney 293 cells. ApoA-IIowa fibrils induced an increase in lysosomal pH and the cytosolic release of the toxic lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils depended on cathepsin B and was ameliorated by increasing the degradation of apoA-IIowa fibrils. Thus, although apoA-IIowa fibril transport to lysosomes and fibril degradation in lysosomes may have occurred, the presence of an excess number of apoA-IIowa fibrils, more than the lysosomes could degrade, may be detrimental to cells. Our results thus provide evidence that the target of apoA-IIowa fibrils is lysosomes, and we thereby gained a novel insight into the mechanism of AApoA1 amyloidosis.

  5. Abnormal histopathology, fat percent and hepatic apolipoprotein A I and apolipoprotein B100 mRNA expression in fatty liver hemorrhagic syndrome and their improvement by soybean lecithin.

    Science.gov (United States)

    Song, Yalu; Ruan, Jiming; Luo, Junrong; Wang, Tiancheng; Yang, Fei; Cao, Huabin; Huang, Jianzhen; Hu, Guoliang

    2017-10-01

    To investigate the etiopathogenesis of fatty liver hemorrhagic syndrome (FLHS) and the protective effects of soybean lecithin against FLHS in laying hens, 135 healthy 300-day-old Hyline laying hens were randomly divided into groups: control (group 1), diseased (group 2), and protected (group 3). Each group contained 45 layers with 3 replicates. The birds in these 3 groups were fed a control diet, a high-energy/low-protein (HELP) diet or the HELP diet supplemented with 3% soybean lecithin instead of maize. The fat percent in the liver was calculated. Histopathological changes in the liver were determined by staining, and the mRNA expression levels of apolipoproteinA I (apoA I) and apolipoprotein B100 (apoB100) in the liver were determined by RT-PCR. The results showed that the fat percent in the liver of group 2 was much higher (P steatosis in the liver cell on d 30 and 60. The mRNA expression levels of apoA I and apoB100 in the livers were variable throughout the experiment. The expression level of apoA I in group 2 significantly decreased on d 60 (P < 0.05); the expression level of apoB100 slightly increased on d 30 in group 2, while it sharply decreased on d 60. Compared to group 1, the expression level of apoB100 showed no significant difference in group 3 (P < 0.05). This study indicated that FLHS induced pathological changes and abnormal expression of apoA I and apoB100 in the livers of laying hens and that soybean lecithin alleviated these abnormal changes. © 2017 Poultry Science Association Inc.

  6. Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis

    NARCIS (Netherlands)

    Bisoendial, Radjesh; Tabet, Fatiha; Tak, Paul P.; Petrides, Francine; Cuesta Torres, Luisa F.; Hou, Liming; Cook, Adam; Barter, Philip J.; Weninger, Wolfgang; Rye, Kerry-Anne

    2015-01-01

    Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo)

  7. High yield of recombinant human Apolipoprotein A-I expressed in Pichia pastoris by using mixed-mode chromatography.

    Science.gov (United States)

    Narasimhan Janakiraman, Vignesh; Noubhani, Abdelmajid; Venkataraman, Krishnan; Vijayalakshmi, Mookambeswaran; Santarelli, Xavier

    2016-01-01

    A vast majority of the cardioprotective properties exhibited by High-Density Lipoprotein (HDL) is mediated by its major protein component Apolipoprotein A-I (ApoA1). In order to develop a simplified bioprocess for producing recombinant human Apolipoprotein A-I (rhApoA1) in its near-native form, rhApoA1was expressed without the use of an affinity tag in view of its potential therapeutic applications. Expressed in Pichia pastoris at expression levels of 58.2 mg ApoA1 per litre of culture in a reproducible manner, the target protein was purified by mixed-mode chromatography using Capto™ MMC ligand with a purity and recovery of 84% and 68%, respectively. ApoA1 purification was scaled up to Mixed-mode Expanded Bed Adsorption chromatography to establish an 'on-line' process for the efficient capture of rhApoA1 directly from the P. pastoris expression broth. A polishing step using anion exchange chromatography enabled the recovery of ApoA1 up to 96% purity. Purified ApoA1 was identified and verified by RPLC-ESI-Q-TOF mass spectrometry. This two-step process would reduce processing times and therefore costs in comparison to the twelve-step procedure currently used for recovering rhApoA1 from P. pastoris. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Gordon

    2016-09-01

    Full Text Available Apolipoprotein A-I (apoA-I and high-density lipoproteins (HDL mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury, asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of acute lung injury, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach.

  9. Apolipoprotein A-I configuration and cell cholesterol efflux activity of discoidal lipoproteins depend on the reconstitution process.

    Science.gov (United States)

    Cuellar, Luz Ángela; Prieto, Eduardo Daniel; Cabaleiro, Laura Virginia; Garda, Horacio Alberto

    2014-01-01

    Discoidal high-density lipoproteins (D-HDL) are critical intermediates in reverse cholesterol transport. Most of the present knowledge of D-HDL is based on studies with reconstituted lipoprotein complexes of apolipoprotein A-I (apoA-I) obtained by cholate dialysis (CD). D-HDL can also be generated by the direct microsolubilization (DM) of phospholipid vesicles at the gel/fluid phase transition temperature, a process mechanistically similar to the "in vivo" apoAI lipidation via ABCA1. We compared the apoA-I configuration in D-HDL reconstituted with dimyristoylphosphatidylcholine by both procedures using fluorescence resonance energy transfer measurements with apoA-I tryptophan mutants and fluorescently labeled cysteine mutants. Results indicate that apoA-I configuration in D-HDL depends on the reconstitution process and are consistent with a "double belt" molecular arrangement with different helix registry. As reported by others, a configuration with juxtaposition of helices 5 of each apoAI monomer (5/5 registry) predominates in D-HDL obtained by CD. However, a configuration with helix 5 of one monomer juxtaposed with helix 2 of the other (5/2 registry) would predominate in D-HDL generated by DM. Moreover, we also show that the kinetics of cholesterol efflux from macrophage cultures depends on the reconstitution process, suggesting that apoAI configuration is important for this HDL function. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Metabolism of apolipoproteins A-I and A-II in human high-density lipoprotein: a mathematical approach for analysis of their specific activity decay curves

    International Nuclear Information System (INIS)

    Atmeh, R.F.

    1987-01-01

    The differential rate equations describing the compartmental model of human high-density lipoprotein (HDL) were integrated by means of Laplace transforms and an exponential equation was obtained for each of the three compartments. These equations were used to fit the observed plasma decay data and give estimates for the rate constants of the system by means of a written computer program. Furthermore, these estimates were used to calculate the exponential constants of the integrated equations. Consequently, the amount of label in any of the intravascular, extravascular, and urine compartments can be calculated as a fraction of the original dose of label at any time point. This method was tested using data for the (AI)HDL subclass because it contains only apolipoprotein A-I as the major apolipoprotein and does not contain apolipoprotein A-II. The calculated plasma and urine radioactivity data were compared with the experimentally obtained data from two normolipoproteinemic subjects and found to be in good agreement. The significance of this method is its application to the analysis of the decay data of the individual apolipoproteins of (AI + AII) HDL subclass where the urinary radioactivity data resulting from the individual apolipoprotein breakdown on the native particle cannot be measured experimentally at present. Such data are essential for the detailed calculation of the kinetic parameters of these apolipoproteins

  11. Secretion of apolipoproteins A-I and B by HepG2 cells: regulation by substrates and metabolic inhibitors.

    Science.gov (United States)

    Kempen, H J; Imbach, A P; Giller, T; Neumann, W J; Hennes, U; Nakada, N

    1995-08-01

    It was the aim of this study to i) compare the effects of glucose and other hexoses with that of oleate on secretion of apolipoproteins (apos) A-I and B by HepG2 cells, and ii) document the effect of various metabolic inhibitors on the secretion of these apos in the absence or presence of extra glucose/oleate. i) The addition of 10 mM glucose increased secretion of apoA-I and apoB, as measured by enzyme immunoassay, by about 60% when cells were incubated for 48 h in DMEM + 10% fetal calf serum. The addition of extra glucose also increased the mRNA levels for these apos. Increased radioactivity was also found in these apolipoproteins by immunoprecipitation after metabolic labeling with [35S]methionine for 48 h. However, in a pulse-chase experiment (15 min labeling, 2 h chase), glucose was found to increase apoA-I synthesis but not apoB synthesis. More labeled apoB appeared in the medium during the chase because glucose inhibited its intracellular degradation. The effect of glucose on secretion of these apos could be mimicked by fructose and mannose but not by 6-deoxyglucose, showing that the hexoses must enter the cells and be phosphorylated. In contrast, the addition of 0.5 mM oleate had a weak inhibitory effect on secretion of apoA-I whereas it increased the secretion of apoB by more than twofold. The combination of 10 mM glucose and 0.5 mM oleate had no greater effect than glucose alone on apoA-I secretion but increased apoB secretion by fourfold. ii) Inhibiting glycolysis (by glucosamine) lowered secretion of both apoA-I and apoB, while inhibiting lipogenesis (using 8-Br-cyclic AMP or 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA)) did not affect apoA-I secretion but clearly decreased that of apoB. However, the inhibitory effect of TOFA on apoB secretion was much smaller in the presence of 0.5 mM oleate instead of extra glucose. Actinomycin-D and cycloheximide strongly suppressed the stimulatory effect of glucose on secretion of both apolipoproteins

  12. The paradox of high apolipoprotein A-I levels independently predicting incident type-2 diabetes among Turks.

    Science.gov (United States)

    Onat, A; Hergenç, G; Bulur, S; Uğur, M; Küçükdurmaz, Z; Can, G

    2010-06-25

    Predictive value of apolipoprotein (apo) A-I for incident hypertension, metabolic syndrome (MetS), type 2 diabetes (DM) and coronary heart disease (CHD) needs further exploration. A representative sample of Turkish adults was studied with this purpose prospectively. Sex-specific apoA-I tertiles were examined regarding cardiometabolic risk. A total of 1044 men and 1067 women (aged 49+/-12 years at baseline) were followed up over 7.4 years. High serum apoA-I levels were significantly associated in multivariable analysis with female sex, aging, alcohol intake, (inversely) cigarette smoking and, in women, with systolic blood pressure. Risk of diabetes was predicted in logistic regression in both genders by top versus bottom apoA-I tertile (RR 1.98; [95%CI 1.31; 3.0]), additive to age, body mass index (BMI), C-reactive protein (CRP), HDL-cholesterol and lipid lowering drugs. By adding sex hormone-binding globulin to the model in a subset of the sample, the association between high apoA-I and incident diabetes was attenuated only in women. ApoA-I tertiles tended to be positively associated also with hypertension and CHD only in women but this did not reach significance. High compared with low serum apoA-I levels nearly double the risk for incident diabetes, additively to age, BMI, CRP, HDL-cholesterol among Turks. Systemic inflammation concomitant with prevailing MetS might turn apoA-I into proinflammatory particles. Copyright 2008 Elsevier Ireland Ltd. All rights reserved.

  13. The association between the apolipoprotein B/A-I ratio and coronary calcification may differ depending on kidney function in a healthy population.

    Directory of Open Access Journals (Sweden)

    Seok-Hyung Kim

    Full Text Available The apolipoprotein B/A-1 ratio has been reported to be one of the strongest risk predictors of cardiovascular events. However, its prognostic value for cardiovascular disease is still uncertain, especially in patients with chronic kidney disease. This study aimed to investigate whether the association between the apolipoprotein B/A-I ratio and coronary artery calcification differed according to kidney function in a healthy population.Of the data from 7,780 participants from the medical records database in Gangnam Severance Hospital from 2005 through 2016, a cross-sectional analysis included participants with an estimated glomerular filtration rate (eGFR ≥ 60 mL/min/1.73 m2 determined based on the Chronic Kidney Disease -Epidemiology Collaboration equation (n  =  1,800. Mild renal insufficiency was defined as an eGFR of 60-90 mL/min/1.73 m2. Coronary artery calcification measured with computed tomography was defined as an above-zero score. Logistic regression analyses were used to determine the association between coronary calcification and the apolipoprotein B/A-I ratio according to eGFR by adjusting for the influence of confounders.The mean apolipoprotein B/A-I level was significantly higher in the participants with coronary artery calcification than in the participants without coronary artery calcification. The apolipoprotein B/A-I ratio was significantly different according to coronary artery calcification in the participants with normal kidney function, but in the participants with mild renal insufficiency, it was not different. After adjusting for age, male sex, systolic blood pressure, body mass index, current smoking status, and fasting plasma glucose, the apolipoprotein B/A-I ratio was significantly associated with an increased risk of coronary artery calcification in participants with normal kidney function (odds ratio = 2.411, p = 0.011, while in the participants with mild renal insufficiency, the apolipoprotein B/A-I ratio was

  14. The thyroxine-binding site of human apolipoprotein-A-I: Location in the N-terminal domain

    International Nuclear Information System (INIS)

    Benvenga, S.; Cahnmann, H.J.; Robbins, J.

    1991-01-01

    We tested the ability of nine monoclonal antibodies (MAb) against human apolipoprotein-A-I (apoA-I), the 28.3-kDa major apoprotein of high density lipoproteins (HDL), to inhibit its photoaffinity labeling with [125I]T4. Two forms were evaluated: isolated lipid-free apoA-I (Sigma or Calbiochem) and lipid-complexed apoA-I [HDL2, (density, 1.063-1.125 g/ml) and HDL3 (density, 1.125-1.210 g/ml)]. After labeling with 0.5 nM [125I]T4 in the presence of MAb or normal mouse IgG, the products were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent densitometric quantitation of radioactivity associated with the 28.3-kDa band. Group I MAbs, namely those having epitopes in the N-terminal portion of apoA-I, include MAb 16 (epitopes at residues 1-16), 4 and 14 (residues 1-86), and 18 (residues 98-105); group II includes MAbs 7,10, 15, and 17 (epitopes at residues 87-148); group III includes MAb 9 (residues 149-243). All group I MAbs inhibited [125I]T4 binding to isolated apoA-I with this order of potency: MAb 16 greater than MAb 14 greater than MAb 4 greater than MAb 18. In the case of lipid-associated apoA-I, the pattern of hierarchy was variable, presumably related to the known markedly polydisperse nature of HDL, but a constant feature, in contrast to the case of isolated apoA-I, was that MAb 4 was more potent than MAb 14. Group II MAbs gave less than 3% inhibition in both isolated and lipid-complexed apoA-I. Group III MAb 9 either failed to inhibit or gave 18-27% inhibition (one preparation each of HDL2 and HDL3). We conclude that the T4 site of apoA-I is in the N-terminal domain of apoA-I, closer to the epitope for MAb 16 than to that for MAb 18, and that conformational changes occurring when apoA-I is associated with lipids in the HDL particle alter the spatial relationship between some epitopes and the T4 site

  15. Lipid profile, apolipoprotein A-I and oxidative stress in professional footballers, sedentary individuals, and their relatives.

    Science.gov (United States)

    Zanella, Aline Margioti; Nakazone, Marcelo Arruda; Pinhel, Marcela Augusta Souza; Souza, Dorotéia Rossi Silva

    2011-03-01

    To evaluate whether lipid profile (LP), apolipoprotein A-1 (apo A-I) and malondialdehyde (MDA) have any relationship with physical exercise by comparing the groups of footballers (FG) with sedentary individuals (CG) and their relatives (RFG and RCG). Twenty individuals from FG and CG, 60 from RFG, and 57 from RCG were studied. FG showed lower levels of total cholesterol (119.5 ± 37.9 mg/dL), LDL-cholesterol fraction (53.6 ± 30.3), apo A-I (116.7 ± 11.9), and higher level of HDL-cholesterol fraction (HDLc) (49.7 ± 8.5) compared to RFG (148.3 ± 36.9, P = 0.02; 82.4 ± 37.7, P < 0.01; 124.6 ± 10.2, P = 0.03; and 42.7 ± 7.7, P < 0.01; respectively). Moreover, FG had reduced levels of MDA (101.0 ± 77.0 ng/mL) compared to CG (290.0 ± 341.0, P = 0.03) and RFG (209.9 ± 197.5, P = 0.04). These results suggest an association between physical exercise and lower levels of MDA in FG. Physical activity seems to promote beneficial effects on the LP regardless of the genetic influence considering HDLc levels.

  16. Comparison of apolipoprotein (apoB/apoA-I and lipoprotein (total cholesterol/HDL ratio determinants. Focus on obesity, diet and alcohol intake.

    Directory of Open Access Journals (Sweden)

    Gianluca Tognon

    Full Text Available The ratio between apolipoprotein B and apolipoprotein A-I (apoB/apoA-I has been suggested to be a powerful and more accurate predictor of future cardiovascular disease risk than total cholesterol and HDL cholesterol. Since diet and lifestyle can directly influence dyslipidemia, it is of interest to identify modifiable factors that are associated with high levels of the apolipoprotein ratio and if they can have a different association with a more traditional indicator of cardiovascular risk such as total cholesterol/HDL. The relationship between obesity and dyslipidemia is established and it is of interest to determine which factors can modify this association. This study investigated the cross-sectional association of obesity, diet and lifestyle factors with apoB/apoA-I and total cholesterol/HDL respectively, in a Swedish population of 2,907 subjects (1,537 women as part of the INTERGENE study. The apolipoprotein and lipoprotein ratios were highly correlated, particularly in women, and obesity was strongly associated with both. Additionally, age, cigarette smoking and alcohol intake were important determinants of these ratios. Alcohol was the only dietary factor that appreciably attenuated the association between obesity and each of the ratios, with a stronger attenuation in women. Other dietary intake and lifestyle-related factors such as smoking status and physical activity had a lower effect on this association. Because the apolipoprotein and lipoprotein ratios share similar diet and lifestyle determinants as well as being highly correlated, we conclude that either of these ratios may be a sufficient indicator of dyslipidemia.

  17. Transfer of C-terminal residues of human apolipoprotein A-I to insect apolipophorin III creates a two-domain chimeric protein with enhanced lipid binding activity.

    Science.gov (United States)

    Horn, James V C; Ellena, Rachel A; Tran, Jesse J; Beck, Wendy H J; Narayanaswami, Vasanthy; Weers, Paul M M

    2017-08-01

    Apolipophorin III (apoLp-III) is an insect apolipoprotein (18kDa) that comprises a single five-helix bundle domain. In contrast, human apolipoprotein A-I (apoA-I) is a 28kDa two-domain protein: an α-helical N-terminal domain (residues 1-189) and a less structured C-terminal domain (residues 190-243). To better understand the apolipoprotein domain organization, a novel chimeric protein was engineered by attaching residues 179 to 243 of apoA-I to the C-terminal end of apoLp-III. The apoLp-III/apoA-I chimera was successfully expressed and purified in E. coli. Western blot analysis and mass spectrometry confirmed the presence of the C-terminal domain of apoA-I within the chimera. While parent apoLp-III did not self-associate, the chimera formed oligomers similar to apoA-I. The chimera displayed a lower α-helical content, but the stability remained similar compared to apoLp-III, consistent with the addition of a less structured domain. The chimera was able to solubilize phospholipid vesicles at a significantly higher rate compared to apoLp-III, approaching that of apoA-I. The chimera was more effective in protecting phospholipase C-treated low density lipoprotein from aggregation compared to apoLp-III. In addition, binding interaction of the chimera with phosphatidylglycerol vesicles and lipopolysaccharides was considerably improved compared to apoLp-III. Thus, addition of the C-terminal domain of apoA-I to apoLp-III created a two-domain protein, with self-association, lipid and lipopolysaccharide binding properties similar to apoA-I. The apoA-I like behavior of the chimera indicate that these properties are independent from residues residing in the N-terminal domain of apoA-I, and that they can be transferred from apoA-I to apoLp-III. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Apolipoprotein A-I and B levels, dyslipidemia and metabolic syndrome in south-west Chinese women with PCOS.

    Science.gov (United States)

    Zhang, Jinxia; Fan, Ping; Liu, Hongwei; Bai, Huai; Wang, Ying; Zhang, Feng

    2012-08-01

    What are the relationships between apolipoprotein (apo) A-I and apoB concentrations, the apoB/apoA-I ratio and the prevalences of dyslipidemia and metabolic syndrome (MS) in south-west Chinese women with polycystic ovary syndrome (PCOS). There is a relatively high incidence of dyslipidemia and MS in south-west Chinese women with PCOS, especially in patients without hyperandrogenism. Patients with dyslipidemia are more obese, and have a more adverse glucose and lipid metabolic profile and higher apoB levels and apoB/apoA-I ratio. The increased apoB levels and apoB/A1 ratio and the MS are strongly associated with PCOS, suggesting that there is an increased risk of cardiovascular diseases in these patients. Dyslipidemia and MS have been widely studied in women with PCOS, but to date no data from south-west Chinese subjects have been available. The apoB/apoA-I ratio has been reported to be strongly associated with MS and insulin resistance (IR) and to be a reliable parameter that reflects lipid disturbances and the potential to develop atherosclerosis, but its relationship with PCOS is unclear. DESIGN This case-control study included 406 patients with PCOS and 342 control women between 17 and 40 years of age from a population in south-west China during 2006-2011. The diagnosis of PCOS was based on the revised 2003 Rotterdam criteria. The control group, consisting of women with infertility due to a Fallopian obstruction or the husband's infertility, women undergoing a pre-pregnancy check and healthy volunteers, was recruited from the same hospital during the same period. All women were not taking any medication known to affect carbohydrate or lipid or hormone metabolism for at least 3 months prior to the study, and were studied during the follicular phase of their menstrual cycle. MS was assessed by the National Cholesterol Education Program-Adult treatment Panel (NCEP-ATP) III criteria modified for Asian populations. Dyslipidemia was defined by one or more of the

  19. High-dose recombinant apolipoprotein A-I(milano) mobilizes tissue cholesterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein e-deficient mice. Potential implications for acute plaque stabilization.

    Science.gov (United States)

    Shah, P K; Yano, J; Reyes, O; Chyu, K Y; Kaul, S; Bisgaier, C L; Drake, S; Cercek, B

    2001-06-26

    Repeated doses of recombinant apolipoprotein A-I(Milano) phospholipid complex (apoA-I(m)) reduce atherosclerosis and favorably change plaque composition in rabbits and mice. In this study, we tested whether a single high dose of recombinant apoA-I(m) could rapidly mobilize tissue cholesterol and reduce plaque lipid and macrophage content in apoE-deficient mice. High cholesterol-fed, 26-week-old apoE-deficient mice received a single intravenous injection of saline (n=16), 1080 mg/kg dipalmitoylphosphatidylcholine (DPPC; n=14), or 400 mg/kg of recombinant apoA-I(m) complexed with DPPC (1:2.7 weight ratio; n=18). Blood was sampled before and 1 and 48 hours after injection, and aortic root plaques were evaluated for lipid content and macrophage content after oil-red O and immunostaining, respectively. One hour after injection, the plasma cholesterol efflux-promoting capacity was nearly 2-fold higher in recombinant apoA-I(m)-treated mice compared with saline and DPPC-treated mice (P<0.01). Compared with baseline values, serum free cholesterol, an index of tissue cholesterol mobilization, increased 1.6-fold by 1 hour after recombinant apoA-I(m) injection, and it remained significantly elevated at 48 hours (P<0.01). Mice receiving recombinant apoA-I(m) had 40% to 50% lower lipid content (P<0.01) and 29% to 36% lower macrophage content (P<0.05) in their plaques compared with the saline- and DPPC-treated mice, respectively. A single high dose of recombinant apoA-I(m) rapidly mobilizes tissue cholesterol and reduces plaque lipid and macrophage content in apoE-deficient mice. These findings suggest that this strategy could rapidly change plaque composition toward a more stable phenotype.

  20. Mitochondrial function is involved in regulation of cholesterol efflux to apolipoprotein (apoA-I from murine RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Allen Anne Marie

    2012-12-01

    Full Text Available Abstract Background Mitochondrial DNA damage, increased production of reactive oxygen species and progressive respiratory chain dysfunction, together with increased deposition of cholesterol and cholesteryl esters, are hallmarks of atherosclerosis. This study investigated the role of mitochondrial function in regulation of macrophage cholesterol efflux to apolipoprotein A-I, by the addition of established pharmacological modulators of mitochondrial function. Methods Murine RAW 264.7 macrophages were treated with a range of concentrations of resveratrol, antimycin, dinitrophenol, nigericin and oligomycin, and changes in viability, cytotoxicity, membrane potential and ATP, compared with efflux of [3H]cholesterol to apolipoprotein (apo A-I. The effect of oligomycin treatment on expression of genes implicated in macrophage cholesterol homeostasis were determined by quantitative polymerase chain reaction, and immunoblotting, relative to the housekeeping enzyme, Gapdh, and combined with studies of this molecule on cholesterol esterification, de novo lipid biosynthesis, and induction of apoptosis. Significant differences were determined using analysis of variance, and Dunnett’s or Bonferroni post t-tests, as appropriate. Results The positive control, resveratrol (24 h, significantly enhanced cholesterol efflux to apoA-I at concentrations ≥30 μM. By contrast, cholesterol efflux to apoA-I was significantly inhibited by nigericin (45%; ppAbca1 mRNA. Oligomycin treatment did not affect cholesterol biosynthesis, but significantly inhibited cholesterol esterification following exposure to acetylated LDL, and induced apoptosis at ≥30 μM. Finally, oligomycin induced the expression of genes implicated in both cholesterol efflux (Abca1, Abcg4, Stard1 and cholesterol biosynthesis (Hmgr, Mvk, Scap, Srebf2, indicating profound dysregulation of cholesterol homeostasis. Conclusions Acute loss of mitochondrial function, and in particular Δψm, reduces

  1. Rosuvastatin does not affect human apolipoprotein A-I expression in genetically modified mice: a clue to the disputed effect of statins on HDL.

    Science.gov (United States)

    Marchesi, Marta; Parolini, Cinzia; Caligari, Silvia; Gilio, Donatella; Manzini, Stefano; Busnelli, Marco; Cinquanta, Paola; Camera, Marina; Brambilla, Marta; Sirtori, Cesare R; Chiesa, Giulia

    2011-11-01

    Besides a significant reduction of low-density lipoprotein (LDL) cholesterol, statins moderately increase high-density lipoprotein (HDL) levels. In vitro studies have indicated that this effect may be the result of an increased expression of apolipoprotein (apo)A-I, the main protein component of HDL. The aim of the present study was to investigate in vivo the effect of rosuvastatin on apoA-I expression and secretion in a transgenic mouse model for human apoA-I. Human apoA-I transgenic mice were treated for 28 days with 5, 10 or 20 mg·kg(-1) ·day(-1) of rosuvastatin, the most effective statin in raising HDL levels. Possible changes of apoA-I expression by treatment were investigated by quantitative real-time RT-PCR on RNA extracted from mouse livers. The human apoA-I secretion rate was determined in primary hepatocytes isolated from transgenic mice from each group after treatment. Rosuvastatin treatment with 5 and 10 mg·kg(-1) ·day(-1) did not affect apoA-I plasma levels, whereas a significant decrease was observed in mice treated with 20 mg·kg(-1) ·day(-1) of rosuvastatin (-16%, P < 0.01). Neither relative hepatic mRNA concentrations of apoA-I nor apoA-I secretion rates from primary hepatocytes were influenced by rosuvastatin treatment at each tested dose. In human apoA-I transgenic mice, rosuvastatin treatment does not increase either apoA-I transcription and hepatic secretion, or apoA-I plasma levels. These results support the hypothesis that other mechanisms may account for the observed HDL increase induced by statin therapy in humans. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  2. Fibrate-modulated expression of fibrinogen, plasminogen activator inhibitor-1 and apolipoprotein A-I in cultured cynomolgus monkey hepatocytes. Role of the peroxisome proliferator-activated receptor-α

    NARCIS (Netherlands)

    Kockx, M.; Princen, H.M.G.; Kooistra, T.

    1998-01-01

    Fibrates are used to lower plasma triglycerides and cholesterol levels in hyperlipidemic patients. In addition, fibrates have been found to alter the plasma concentrations of fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and apolipoprotein A-I (apo A-I). We have investigated the in vitro

  3. Reduced biliary sterol output with no change in total faecal excretion in mice expressing a human apolipoprotein A-I variant.

    Science.gov (United States)

    Parolini, Cinzia; Caligari, Silvia; Gilio, Donatella; Manzini, Stefano; Busnelli, Marco; Montagnani, Marco; Locatelli, Marcello; Diani, Erika; Giavarini, Flavio; Caruso, Donatella; Roda, Enrico; Roda, Aldo; Sirtori, Cesare R; Chiesa, Giulia

    2012-10-01

    Apolipoprotein (apo)A-I(M) (ilano), is a molecular variant of apoA-I(wild-type), associated with dramatically low HDL-cholesterol levels, but no increased risk for cardiovascular disease. In view of the present uncertainties on the role of apoA-I in liver cholesterol removal by way of bile acids and neutral sterols, and of the greater capacity of apoA-I(M) (ilano) to remove arterial cholesterol, biliary sterol metabolism was evaluated in transgenic mice expressing apoA-I(M) (ilano). ApoA-I(M) (ilano) mice were fed a high-cholesterol/high-fat diet, and compared with human apoA-I(wild-type) mice. Plasma lipid levels, hepatic bile flow and composition, hepatic and intestinal cholesterol and bile acid content, and faecal sterol content were measured. Moreover, the expression of hepatic ABCA1, SR-B1 and that of hepatic and intestinal genes involved in bile acid metabolism were evaluated. The dietary treatment led to a strong elevation in HDL-cholesterol levels in A-I(M) (ilano) mice, associated with an increased expression of hepatic ABCA1. ApoA-I(M) (ilano) mice showed lower cholesterol output from the liver compared with apoA-I(wild-type) mice, in the absence of liver sterol accumulation. Faecal excretion of neutral sterols and bile acids was similar in the two mouse lines. In spite of a different response to the dietary challenge, with an increased ABCA1 expression and a lower hepatic cholesterol output in apoA-I(M) (ilano) mice, the net sterol excretion is comparable in the two transgenic lines. © 2012 John Wiley & Sons A/S.

  4. Impact of Serum Apolipoprotein A-I on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer: a Propensity Score-Matched Analysis

    Directory of Open Access Journals (Sweden)

    Qi Quan

    2017-04-01

    Full Text Available PURPOSE: We aimed to investigate the role of apolipoprotein A-I (ApoA-I as a predictor of prognosis and treatment efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC treated with first-line chemotherapy with or without bevacizumab. METHODS: We conducted a retrospective study on consecutive patients who were diagnosed with mCRC at Sun Yat-sen University Cancer Center. According to their pretreatment ApoA-I level, patients were divided into low– and high–ApoA-I groups. Propensity score-matched method was performed to balance baseline characteristics between two groups. Based on whether they accepted bevacizumab as a first-line therapy, patients were further divided into the chemo + bevacizumab group and the chemo group. Overall survival (OS and progression-free survival (PFS were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: The optimal cutoff value for the ApoA-I level was determined to be 1.105 g/l. In the propensity-matched cohort of 508 patients, low ApoA-I was significantly associated with inferior OS (P < .001 and PFS (P < .001 than high ApoA-I. Multivariate analysis showed that ApoA-I level was an independent prognostic maker of OS (P < .001 and PFS (P = .001. PFS (P < .001 in either the high– or low–ApoA-I groups could be extended significantly after the administration of bevacizumab, and patients with a high ApoA-I level also had a better OS in the chemo + bevacizumab group than the chemo group (P = .049. CONCLUSIONS: Patients with a low ApoA-I level have poor prognoses, and they did not display an OS benefit from bevacizumab.

  5. Apolipoprotein B is a calcium binding protein

    International Nuclear Information System (INIS)

    Dashti, N.; Lee, D.M.; Mok, T.

    1986-01-01

    Human hepatocarcinoma Hep G2 cells were grown in culture medium containing [ 45 Ca 2+ ]. The secreted lipoproteins of d 45 Ca] from the gels showed that the peak of radioactivity corresponded to the apolipoprotein B band. The molar ratio of the incorporated [ 45 Ca 2+ ] and apolipoprotein B was close to unity. No radioactivity was found associated with any other secreted apolipoproteins. To confirm these findings, apolipoprotein B-containing lipoproteins were precipitated with anti-apolipoprotein B and high density lipoproteins were precipitated with anti-apolipoprotein A-I. Only the former precipitate was radioactive. These results suggest that apolipoprotein B is a calcium binding protein

  6. IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1

    Directory of Open Access Journals (Sweden)

    Zijian Xie

    2012-03-01

    Full Text Available It is known that the ATP-binding cassette transporter A1 (ABCA1 plays a major role in cholesterol homeostasis and high density lipoprotein (HDL metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I will mediate the assembly of nascent HDL and cellular cholesterol efflux, which suggests a possible receptor-ligand interaction between ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput screening (HTS method was developed to identify the synthetic and natural compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based-ELISA-like high-throughput screen was conducted in a 96-well format using Chinese hamster ovary (CHO cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced Green Fluorecence Protein expression vector and the known ABCA1 inhibitor glibenclamide as the antagonist control. From 2,600 compounds, a xanthone compound (IMB 2026791 was selected using this HTS assay, and it was proved as an apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot analysis. The [3H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells and PMA induced THP-1 macrophages (human acute monocytic leukemia cell further confirmed the compound as an accelerator of cholesterol efflux in a dose-dependent manner with an EC50 of 25.23 μM.

  7. OS041. Apolipoprotein A-I protects normal integration of the trophoblast into endothelial cellular networks in an in vitro model of preeclampsia.

    Science.gov (United States)

    Charlton, F; Xu, B; Makris, A; Hennessy, A; Rye, K-A

    2012-07-01

    Failure of the trophoblast to appropriately invade uterine spiral arteries is thought to be an initiating event in preeclampsia, a disorder associated with endothelial dysfunction. A dyslipidemia characterised by low plasma levels of high density lipoproteins (HDL) and elevated triglycerides has also been described in preeclampsia. The pro-inflammatory cytokine TNF-α inhibits trophoblast invasion of uterine endothelial cells. Previous work using an in vitro JEG-3 cell/Uterine endothelial cell co-culture model investigated the effect of apoliopoprotein A-I, the main apolipoprotein component of HDL, on trophoblast incorporation into endothelial tubules in the presence and absence of TNF-α. These effects are now investigated using the human invasive trophoblast cell line HTR-8/SVneo. This study asks if apoA-I, which has established anti-inflammatory properties, can protect against the deleterious effect of TNF-α on trophoblast-endothelial cell interactions. The in vitro trophoblast-uterine endothelial cell co-culture model was used to investigate the effect of apoA-I on trophoblast incorporation into endothelial tubules in the presence and absence of TNF-α. Uterine endothelial cells were pre-incubated with lipid free apoA-I (final apoA-I concentration 1 mg/mL) for 16h prior to seeding on matrigel coated plates. Tubules formed within 4h. Fluorescence-labelled HTR-8/SVneo trophoblast cells were then co-cultured with the endothelial cells±TNF-α (final concentration of 0.2ng/mL). Bright field and fluorescent images were captured after 24h. The effect of TNF-α on HTR-8/SVneo cell invasion was quantified with Image J software. Integration of HTR-8/SVneo trophoblast cells into uterine endothelial tubular networks was also imaged using live cell imaging techniques (Zeiss Axiovert). TNF-α inhibited HTR-8/SVneo (trophoblast) cell integration into endothelial tubular structures by 24.1±3.7% pintegration of trophoblast into endothelial tubular structures in the presence

  8. Bioinformatic Analysis of Plasma Apolipoproteins A-I and A-II Revealed Unique Features of A-I/A-II HDL Particles in Human Plasma

    Science.gov (United States)

    Kido, Toshimi; Kurata, Hideaki; Kondo, Kazuo; Itakura, Hiroshige; Okazaki, Mitsuyo; Urata, Takeyoshi; Yokoyama, Shinji

    2016-01-01

    Plasma concentration of apoA-I, apoA-II and apoA-II-unassociated apoA-I was analyzed in 314 Japanese subjects (177 males and 137 females), including one (male) homozygote and 37 (20 males and 17 females) heterozygotes of genetic CETP deficiency. ApoA-I unassociated with apoA-II markedly and linearly increased with HDL-cholesterol, while apoA-II increased only very slightly and the ratio of apoA-II-associated apoA-I to apoA-II stayed constant at 2 in molar ratio throughout the increase of HDL-cholesterol, among the wild type and heterozygous CETP deficiency. Thus, overall HDL concentration almost exclusively depends on HDL with apoA-I without apoA-II (LpAI) while concentration of HDL containing apoA-I and apoA-II (LpAI:AII) is constant having a fixed molar ratio of 2 : 1 regardless of total HDL and apoA-I concentration. Distribution of apoA-I between LpAI and LpAI:AII is consistent with a model of statistical partitioning regardless of sex and CETP genotype. The analysis also indicated that LpA-I accommodates on average 4 apoA-I molecules and has a clearance rate indistinguishable from LpAI:AII. Independent evidence indicated LpAI:A-II has a diameter 20% smaller than LpAI, consistent with a model having two apoA-I and one apoA-II. The functional contribution of these particles is to be investigated. PMID:27526664

  9. Metrological traceability in mass spectrometry-based targeted protein quantitation: a proof-of-principle study for serum apolipoproteins A-I and B100.

    Science.gov (United States)

    Smit, Nico P M; Romijn, Fred P H T M; van den Broek, Irene; Drijfhout, Jan W; Haex, Martin; van der Laarse, Arnoud; van der Burgt, Yuri E M; Cobbaert, Christa M

    2014-09-23

    In this study, we have followed up on previous liquid chromatography (LC) multiple reaction monitoring (MRM) mass spectrometry (MS) approaches for measurement of apolipoprotein (apo) A-I and apo B100 in serum aiming for implementation of a multiplexed assay in a clinical chemistry laboratory with full metrological traceability. Signature peptides were selected and detected by dynamic MRM, and stable isotope labeled (SIL)-peptides were used as internal standards. Five apo A-I and four apo B100 peptides were measured in serum digests with linearity (R(2)>0.992) in the physiologically relevant concentration ranges. Linearity with regard to protein concentration was ascertained at five concentration levels (R(2)>0.926 and R(2)>0.965, for the apo A-I and apo B100 peptides, respectively). Three native value-assigned sera were used as external calibrators for further method verification. Imprecision values on sample preparation and LC-MS/MS acquisition were below the established minimal specifications for apo A-I and apo B100 (5.0% and 5.3%, respectively). Correlation of LC-MS/MS results with immunoturbidimetric assay results, for normo- and hypertriglyceridemic samples, showed R(2)>0.944 for apo A-I and R(2)>0.964 for apo B100. This LC-MS/MS method has potential for clinical application in normo- and dyslipidemic patients. Measurement of apo A-I and apo B100 may offer an alternative to high and low density lipoprotein cholesterol (HDL-c and LDL-c) methods for cardiovascular disease risk assessment in dyslipidemic patients [1]. An LC-MS/MS method for apo A-I and apo B100 has the advantage of antibody independent and specific detection of protein signature peptides. The introduction of an LC-MS/MS method for apo A-I and apo B100 can serve as an example for many existing and newly developed (multiplex) biomarker methods in quantitative clinical chemistry proteomics (qCCP). Such LC-MS/MS methods should meet basic clinical chemistry principles with regard to test evaluation

  10. Apolipoprotein M

    Directory of Open Access Journals (Sweden)

    Nilsson-Ehle Peter

    2004-10-01

    Full Text Available Abstract Apolipoprotein M (apoM is a 26-kDa protein that is mainly associated with high-density lipoprotein (HDL in human plasma, with a small proportion present in triglyceride-rich lipoproteins (TGRLP and low-density lipoproteins (LDL. Human apoM gene is located in p21.31 on chromosome 6 (chromosome 17, in mouse. Human apoM cDNA (734 base pairs encodes 188-amino acid residue-long protein. It belongs to lipocalin protein superfamily. Human tissue expression array study indicates that apoM is only expressed in liver and in kidney and small amounts are found in fetal liver and kidney. In situ apoM mRNA hybridization demonstrates that apoM is exclusively expressed in the hepatocytes and in the tubule epithelial cells in kidney. Expression of apoM could be regulated by platelet activating factor (PAF, transforming growth factors (TGF, insulin-like growth factor (IGF and leptin in vivo and/or in vitro. It has been demonstrated that apoM expression is dramatically decreased in apoA-I deficient mouse. Hepatocyte nuclear factor-1α (HNF-1α is an activator of apoM gene promoter. Deficiency of HNF-1α mouse shows lack of apoM expression. Mutations in HNF-1α (MODY3 have reduced serum apoM levels. Expression of apoM is significantly decreased in leptin deficient (ob/ob mouse or leptin receptor deficient (db/db mouse. ApoM concentration in plasma is positively correlated to leptin level in obese subjects. These may suggest that apoM is related to the initiation and progression of MODY3 and/or obesity.

  11. Impact of corpulence parameters and haemoglobin A1c on metabolic control in type 2 diabetic patients: comparison of apolipoprotein B/A-I ratio with fasting and postprandial conventional lipid ratios

    Directory of Open Access Journals (Sweden)

    Mustapha Diaf

    2015-05-01

    Full Text Available Background and objective: The incidence of diabetes co-morbidities could probably be better assessed by studying its associations with major corpulence parameters and glycaemic control indicators. We assessed the utility of body mass index (BMI, waist circumference (WC, and glycosylated haemoglobin (HbA1c levels in metabolic control for type 2 diabetic patients. Methods: Fasting and postprandial blood samples were collected from 238 type 2 diabetic patients aged 57.4±11.9 years. The sera were analysed for glucose, HbA1c, total cholesterol (TC, triglycerides (TG, high-density lipoprotein cholesterol (HDL-c, low-density lipoprotein cholesterol (LDL-c, and apolipoproteins (apoA-I and apoB. Ratios of lipids and apolipoproteins were calculated and their associations with BMI, WC, and HbA1c levels were analysed. Results: Our investigation showed increases in most fasting and postprandial lipid parameters according to BMI and WC. In men, postprandial HDL-c and TG levels were significantly higher (p<0.05 in overweight and obese patients, respectively, as well as in patients with abdominal obesity. Contrariwise, postprandial TC levels were significantly higher (p<0.01 in overweight and abdominal obese women. However, elevations of apoA-I and apoB levels were according to BMI and WC in both genders. There was a strong influence of BMI, WC, and HbA1c levels on the apoB/apoA-I ratio compared to traditional fasting and postprandial lipid ratios in both men and women. The apoB/apoA-I ratio was more correlated with postprandial TC/HDL and LDL-c/HDL-c ratios in men and with postprandial TG/HDL-c in women. Conclusion: The apoB/apoA-I ratio is helpful in assessing metabolic risk caused by overall obesity, abdominal obesity and impaired glycaemia in type 2 diabetic patients.

  12. Apolipoprotein M

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Dahlbäck, B; Nielsen, L B

    2006-01-01

    ApoM is a novel apolipoprotein mainly present in high-density lipoprotein (HDL). It belongs to the lipocalin protein superfamily and may bind a small but so far unknown lipophilic ligand. It is secreted without cleavage of its hydrophobic signal peptide, which probably anchors apoM...... in the phospholipid moiety of plasma lipoproteins. Recent studies suggest that apoM may affect HDL metabolism and have anti-atherogenic functions. The subfraction of human HDL that contains apoM therefore protects LDL from oxidation and mediates cholesterol efflux more efficiently then HDL without apoM. In addition...... to hepatocytes, apoM is highly expressed in kidney proximal tubule cells. Recent data suggest that apoM is secreted into the pre-urine from the tubule cells but is normally taken up again in a megalin-dependent fashion. Further studies of mice with genetically modified apoM expression will be essential...

  13. Apolipoprotein nanodiscs with telodendrimer

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Juntao; He, Wei; Lam, Kit S.; Henderson, Paul; Coleman, Matthew; Cheng, R. Holland; Xing, Li

    2017-05-09

    The present invention provides a nanodisc with a membrane scaffold protein. The nanodisc includes a membrane scaffold protein, a telodendrimer and a lipid. The membrane scaffold protein can be apolipoprotein. The telodendrimer has the general formula PEG-L-D-(R).sub.n, wherein D is a dendritic polymer; L is a bond or a linker linked to the focal point group of the dendritic polymer; each PEG is a poly(ethylene glycol) polymer; each R is and end group of the dendritic polymer, or and end group with a covalently bound hydrophobic group, hydrophilic group, amphiphilic compound, or drug; and subscript n is an integer from 2 to 20. Cell free methods of making the nanodiscs are also provided.

  14. The effect of an apolipoprotein A-I-containing high-density lipoprotein-mimetic particle (CER-001) on carotid artery wall thickness in patients with homozygous familial hypercholesterolemia: The Modifying Orphan Disease Evaluation (MODE) study.

    Science.gov (United States)

    Hovingh, G Kees; Smits, Loek P; Stefanutti, Claudia; Soran, Handrean; Kwok, See; de Graaf, Jacqueline; Gaudet, Daniel; Keyserling, Constance H; Klepp, Heather; Frick, Jennifer; Paolini, John F; Dasseux, Jean-Louis; Kastelein, John J P; Stroes, Erik S

    2015-05-01

    Patients with homozygous familial hypercholesterolemia (HoFH) are at extremely elevated risk for early cardiovascular disease because of exposure to elevated low-density lipoprotein cholesterol (LDL-C) plasma levels from birth. Lowering LDL-C by statin therapy is the cornerstone for cardiovascular disease prevention, but the residual risk in HoFH remains high, emphasizing the need for additional therapies. In the present study, we evaluated the effect of serial infusions with CER-001, a recombinant human apolipoprotein A-I (apoA-I)-containing high-density lipoprotein-mimetic particle, on carotid artery wall dimensions in patients with HoFH. Twenty-three patients (mean age 39.4 ± 13.5 years, mean LDL-C 214.2 ± 81.5 mg/dL) with genetically confirmed homozygosity or compound heterozygosity for LDLR, APOB, PCSK9, or LDLRAP1 mutations received 12 biweekly infusions with CER-001 (8 mg/kg). Before and 1 hour after the first infusion, lipid values were measured. Magnetic resonance imaging (3-T magnetic resonance imaging) scans of the carotid arteries were acquired at baseline and after 24 weeks to assess changes in artery wall dimensions. After CER-001 infusion, apoA-I increased from 114.8 ± 20.7 mg/dL to 129.3 ± 23.0 mg/dL. After 24 weeks, mean vessel wall area (primary end point) decreased from 17.23 to 16.75 mm(2) (P = .008). A trend toward reduction of mean vessel wall thickness was observed (0.75 mm at baseline and 0.74 mm at follow-up, P = .0835). In HoFH, 12 biweekly infusions with an apoA-I-containing high-density lipoprotein-mimetic particle resulted in a significant reduction in carotid mean vessel wall area, implying that CER-001 may reverse atherogenic changes in the arterial wall on top of maximal low-density lipoprotein-lowering therapy. This finding supports further clinical evaluation of apoA-I-containing particles in patients with HoFH. Copyright © 2015 Mosby, Inc. All rights reserved.

  15. Putative apolipoprotein A-I, natural killer cell enhancement factor and lysozyme g are involved in the early immune response of brown-marbled grouper, Epinephelus fuscoguttatus, Forskal, to Vibrio alginolyticus.

    Science.gov (United States)

    Low, C-F; Shamsudin, M N; Chee, H-Y; Aliyu-Paiko, M; Idrus, E S

    2014-08-01

    The gram-negative bacterium, Vibrio alginolyticus, has frequently been identified as the pathogen responsible for the infectious disease called vibriosis. This disease is one of the major challenges facing brown-marbled grouper aquaculture, causing fish farmers globally to suffer substantial economic losses. The objective of this study was to investigate the proteins involved in the immune response of brown-marbled grouper fingerlings during their initial encounter with pathogenic organisms. To achieve this objective, a challenge experiment was performed, in which healthy brown-marbled grouper fingerlings were divided into two groups. Fish in the treated group were subjected to intraperitoneal injection with an infectious dose of V. alginolyticus suspended in phosphate-buffered saline (PBS), and those in the control group were injected with an equal volume of PBS. Blood samples were collected from a replicate number of fish from both groups at 4 h post-challenge and analysed for immune response-related serum proteins via two-dimensional gel electrophoresis. The results showed that 14 protein spots were altered between the treated and control groups; these protein spots were further analysed to determine the identity of each protein via MALDI-TOF/TOF. Among the altered proteins, three were clearly overexpressed in the treated group compared with the control; these were identified as putative apolipoprotein A-I, natural killer cell enhancement factor and lysozyme g. Based on these results, these three highly expressed proteins participate in immune response-related reactions during the initial exposure (4 h) of brown-marbled grouper fingerling to V. alginolyticus infection. © 2013 John Wiley & Sons Ltd.

  16. Opposing effects of apolipoprotein m on catabolism of apolipoprotein B-containing lipoproteins and atherosclerosis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Pedersen, Tanja Xenia; Gordts, Philip L S M

    2010-01-01

    Rationale: Plasma apolipoprotein (apo)M is mainly associated with high-density lipoprotein (HDL). HDL-bound apoM is antiatherogenic in vitro. However, plasma apoM is not associated with coronary heart disease in humans, perhaps because of a positive correlation with plasma low-density lipoprotein...

  17. Affinity of serum apolipoproteins for lipid monolayers

    International Nuclear Information System (INIS)

    Ibdah, J.A.

    1987-01-01

    The effects of lipid composition and packing as well as the structure of the protein on the affinities of apolipoproteins for lipid monolayers have been investigated. The adsorption of 14 C-reductively methylated human apolipoproteins A-I and A-II at saturating subphase concentrations to monolayers prepared with synthetic lipids or lipoprotein surface lipids spread at various initial surface pressures has been studied. The adsorption of apolipoproteins is monitored by following the surface radioactivity using a gas flow counter and Wilhelmy plate, respectively. The physical states of the lipid monolayers are evaluated by measurement of the surface pressure-molecular area isotherms using a Langmuir-Adam surface balance. The probable helical regions in various apolipoproteins have been predicted using a secondary structure analysis computer program. The mean residue hydrophobicity and mean residue hydrophobic moment for the predicted helical segments have been calculated. The surface properties of synthetic peptides which are amphipathic helix analogs have been investigated at the air-water and lipid-water interfaces

  18. Clinical chemistry of common apolipoprotein E isoforms

    NARCIS (Netherlands)

    Brouwer, DAJ; vanDoormaal, JJ; Muskiet, FAJ

    1996-01-01

    Apolipoprotein E plays a central role in clearance of lipoprotein remnants by serving as a ligand for low-density lipoprotein and apolipoprotein E receptors. Three common alleles (apolipoprotein E(2), E(3) and E(4)) give rise to six phenotypes. Apolipoprotein E(3) is the ancestral form. Common

  19. Isolation and characterization of human apolipoprotein M-containing lipoproteins

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo; Axler, Olof

    2006-01-01

    Apolipoprotein M (apoM) is a novel apolipoprotein with unknown function. In this study, we established a method for isolating apoM-containing lipoproteins and studied their composition and the effect of apoM on HDL function. ApoM-containing lipoproteins were isolated from human plasma...... with immunoaffinity chromatography and compared with lipoproteins lacking apoM. The apoM-containing lipoproteins were predominantly of HDL size; approximately 5% of the total HDL population contained apoM. Mass spectrometry showed that the apoM-containing lipoproteins also contained apoJ, apoA-I, apoA-II, apoC-I, apo...

  20. Targeting nanodisks via a single chain variable antibody - Apolipoprotein chimera

    International Nuclear Information System (INIS)

    Iovannisci, David M.; Beckstead, Jennifer A.; Ryan, Robert O.

    2009-01-01

    Nanodisks (ND) are nanometer scale complexes of phospholipid and apolipoprotein that have been shown to function as drug delivery vehicles. ND harboring significant quantities of the antifungal agent, amphotericin B, or the bioactive isoprenoid, all trans retinoic acid, have been generated and characterized. As currently formulated, ND possess limited targeting capability. In this study, we constructed a single chain variable antibody (scFv).apolipoprotein chimera and assessed the ability of this fusion protein to form ND and recognize the antigen to which the scFv is directed. Data obtained revealed that α-vimentin scFv.apolipoprotein A-I is functional in ND formation and antigen recognition, opening the door to the use of such chimeras in targeting drug-enriched ND to specific tissues.

  1. Apolipoprotein Mimetic Peptides: A New Approach for the Treatment of Asthma

    Directory of Open Access Journals (Sweden)

    Xianglan eYao

    2012-03-01

    Full Text Available New treatments are needed for severe asthmatics to improve disease control and avoid severe toxicities associated with oral corticosteroids. We have used a murine model of house dust mite (HDM-induced asthma to identify steroid-unresponsive genes that might represent targets for new therapeutic approaches for severe asthma. This strategy identified apolipoprotein E as a steroid-unresponsive gene with increased mRNA expression in the lungs of HDM-challenged mice. Furthermore, apolipoprotein E functioned as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in experimental HDM-induced asthma. The ability of apolipoprotein E, which is expressed by lung macrophages, to attenuate AHR and goblet cell hyperplasia is mediated by low density lipoprotein (LDL receptors expressed by airway epithelial cells. Consistent with this, administration of an apolipoprotein E mimetic peptide, corresponding to amino acids 130 to 149 of the LDL receptor-binding domain of the holo-apoE protein, significantly reduced AHR and goblet cell hyperplasia in HDM-challenged apoE-/- mice. These findings identified the apolipoprotein E - LDL receptor pathway as a new druggable target for asthma that can be activated by administration of apoE mimetic peptides. Similarly, apolipoprotein A-I may have therapeutic potential in asthma based upon its anti-inflammatory, anti-oxidative and anti-fibrotic properties. Furthermore, administration of apolipoprotein A-I mimetic peptides has attenuated airway inflammation, airway remodeling and airway hyperreactivity in murine models of experimental asthma. Thus, site-directed delivery of inhaled apolipoprotein E or apolipoprotein A-I mimetic peptides may represent novel treatment approaches that can be developed for asthma, including severe disease.

  2. Effects of apolipoproteins on the kinetics of cholesterol exchange

    International Nuclear Information System (INIS)

    Letizia, J.Y.; Phillips, M.C.

    1991-01-01

    The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of [ 14 C]cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of [ 14 C]cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t 1/2 for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles

  3. Apolipoprotein E and familial longevity

    DEFF Research Database (Denmark)

    Schupf, Nicole; Barral, Sandra; Perls, Thomas

    2013-01-01

    Exceptional longevity is associated with substantial heritability. The ε4 allele in apolipoprotein E and the linked G allele in rs2075650 of TOMM40 have been associated with increased mortality and the ε2 allele with decreased mortality, although inconsistently. Offspring from long-lived families...

  4. Influence of Peripheral Artery Disease and Statin Therapy on Apolipoprotein Profiles

    Directory of Open Access Journals (Sweden)

    Andrew W. Gardner

    2013-01-01

    Full Text Available Apolipoprotein B is a stronger predictor of myocardial infarction than LDL cholesterol, and it is inversely related to physical activity and modifiable with exercise training. As such, apolipoprotein measures may be of particular relevance for subjects with PAD and claudication. We compared plasma apolipoprotein profiles in 29 subjects with peripheral artery disease (PAD and intermittent claudication and in 39 control subjects. Furthermore, we compared the plasma apolipoprotein profiles of subjects with PAD either treated (n=17 or untreated (n=12 with statin medications. For the apolipoprotein subparticle analyses, subjects with PAD had higher age-adjusted Lp-B:C (P<0.05 and lower values of Lp-A-I:A-II (P<0.05 than controls. The PAD group taking statins had lower age-adjusted values for apoB (P<0.05, Lp-A-II:B:C:D:E (P<0.05, Lp-B:E + Lp-B:C:E (P<0.05, Lp-B:C (P<0.05, and Lp-A-I (P<0.05 than the untreated PAD group. Subjects with PAD have impaired apolipoprotein profiles than controls, characterized by Lp-B:C and Lp-A-I:A-II. Furthermore, subjects with PAD on statin medications have a more favorable risk profile, particularly noted in multiple apolipoprotein subparticles. The efficacy of statin therapy to improve cardiovascular risk appears more evident in the apolipoprotein sub-particle profile than in the more traditional lipid profile of subjects with PAD and claudication. This trial is registered with ClinicalTrials.gov NCT00618670.

  5. Importance of apolipoprotein A-I in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Lidia A Gardner

    2015-11-01

    Full Text Available Jean-Martin Charcot has first described multiple sclerosis (MS as a disease of the central nervous system (CNS over a century ago. MS remains incurable today, and treatment options are limited to disease modifying drugs. Over the years, significant advances in understanding disease pathology have been made in autoimmune and neurodegenerative components. Despite the fact that brain is the most lipid rich organ in human body, the importance of lipid metabolism has not been extensively studied in this disorder. In MS, the CNS is under attack by a person’s own immune system. Autoantigens and autoantibodies are known to cause devastation of myelin through up regulation of T-cells and cytokines, which penetrate through the blood brain barrier to cause inflammation and myelin destruction.The anti-inflammatory role of high-density lipoproteins (HDLs has been implicated in a plethora of biological processes: vasodilation, immunity to infection, oxidation, inflammation, and apoptosis. However it is not known what role HDL plays in neurological function and myelin repair in MS. Understanding of lipid metabolism in the CNS and in the periphery might unveil new therapeutic targets and explain the partial success of some existing MS therapies.

  6. Multiple system atrophy and apolipoprotein E.

    Science.gov (United States)

    Ogaki, Kotaro; Martens, Yuka A; Heckman, Michael G; Koga, Shunsuke; Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Wernick, Anna I; Walton, Ronald L; Soto, Alexandra I; Vargas, Emily R; Nielsen, Henrietta M; Fujioka, Shinsuke; Kanekiyo, Takahisa; Uitti, Ryan J; van Gerpen, Jay A; Cheshire, William P; Wszolek, Zbigniew K; Low, Phillip A; Singer, Wolfgang; Dickson, Dennis W; Bu, Guojun; Ross, Owen A

    2018-04-01

    Dysregulation of the specialized lipid metabolism involved in myelin synthesis and maintenance by oligodendrocytes has been associated with the unique neuropathology of MSA. We hypothesized that apolipoprotein E, which is associated with neurodegeneration, may also play a role in the pathogenesis of MSA. This study evaluated genetic associations of Apolipoprotein E alleles with risk of MSA and α-synuclein pathology, and also examined whether apolipoprotein E isoforms differentially affect α-synuclein uptake in a oligodendrocyte cell. One hundred sixty-eight pathologically confirmed MSA patients, 89 clinically diagnosed MSA patients, and 1,277 control subjects were genotyped for Apolipoprotein E. Human oligodendrocyte cell lines were incubated with α-synuclein and recombinant human apolipoprotein E, with internalized α-synuclein imaged by confocal microscopy and cells analyzed by flow cytometry. No significant association with risk of MSA or was observed for either Apolipoprotein E ɛ2 or ɛ4. α-Synuclein burden was also not associated with Apolipoprotein E alleles in the pathologically confirmed patients. Interestingly, in our cell assays, apolipoprotein E ɛ4 significantly reduced α-synuclein uptake in the oligodendrocytic cell line. Despite differential effects of apolipoprotein E isoforms on α-synuclein uptake in a human oligodendrocytic cell, we did not observe a significant association at the Apolipoprotein E locus with risk of MSA or α-synuclein pathology. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

  7. Effect of lipid composition and packing on the adsorption of apolipoproteins to lipid monolayers

    International Nuclear Information System (INIS)

    Ibdah, J.A.; Lund-Katz, S.; Phillips, M.C.

    1987-01-01

    The monolayer system has been used to study the effects of lipoprotein surface lipid composition and packing on the affinities of apolipoproteins for the surfaces of lipoprotein particles. The adsorption of apolipoproteins injected beneath lipid monolayers prepared with pure lipids or lipoprotein surface lipids is evaluated by monitoring the surface pressure of the film and the surface concentration (Gamma) of 14 C-labelled apolipoprotein. At a given initial film pressure (π/sub i/) there is a higher adsorption of human apo A-I to unsaturated phosphatidylcholine (PC) monolayers compared to saturated PC monolayers (e.g., at π/sub i/ = 10 mN/m, Gamma = 0.35 and 0.06 mg/m 2 for egg PC and distearoyl PC, respectively, with 3 x 10 -4 mg/ml apo A-I in the subphase). In addition, adsorption of apo A-I is less to an egg sphingomyelin monolayer than to an egg PC monolayer. The adsorption of apo A-I to PC monolayers is decreased by addition of cholesterol. Generally, apo A-I adsorption diminishes as the lipid molecular area decreases. Apo A-I adsorbs more to monolayers prepared with HDL 3 surface lipids than with LDL surface lipids. These studies suggest that lipoprotein surface lipid composition and packing are crucial factors influencing the transfer and exchange of apolipoproteins among various lipoprotein classes during metabolism of lipoprotein particles

  8. Apolipoprotein and lipid abnormalities in chronic liver failure

    Directory of Open Access Journals (Sweden)

    Spósito A.C.

    1997-01-01

    Full Text Available Total serum lipids, as well as apolipoproteins A-I (apo A-I and B (apo B, were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P<0.001. Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P<0.001. However, the reduction of HDL cholesterol (HDLc was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05. We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver

  9. Amphotericin B induced interdigitation of apolipoprotein stabilized nanodisk bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, T; Weers, P M; Sulchek, T; Hoeprich, P D; Ryan, R O

    2006-12-07

    Amphotericin B nanodisks (AMB-ND) are ternary complexes of AMB, phospholipid (PL) and apolipoprotein organized as discrete nanometer scale disk-shaped bilayers. In gel filtration chromatography experiments, empty ND lacking AMB elute as a single population of particles with a molecular weight in the range of 200 kDa. AMB-ND formulated at a 4:1 PL:AMB weight ratio, separated into two peaks. Peak 1 eluted at the position of control ND lacking AMB while the second peak, containing all of the AMB present in the original sample, eluted in the void volume. When ND prepared with increased AMB (1:1 phospholipid:AMB molar ratio) were subjected to gel filtration chromatography, an increased proportion of phospholipid and apolipoprotein were recovered in the void volume with the AMB. Prior to gel filtration the AMB-ND sample could be passed through a 0.22 {micro}m filter without loss of AMB while the voided material was lost. Native gel electrophoresis studies corroborated the gel permeation chromatography data. Far UV circular dichroism analyses revealed that apoA-I associated with AMB-ND denatures at a lower guanidine HCl concentration than apoA-I associated with ND lacking AMB. Atomic force microscopy revealed that AMB induces compression of the ND bilayer thickness consistent with bilayer interdigitation, a phenomenon that is likely related to the ability of AMB to induce pore formation in susceptible membranes.

  10. Cerebrospinal Fluid Apolipoprotein E Levels in Delirium

    Directory of Open Access Journals (Sweden)

    Gideon A. Caplan

    2017-07-01

    Full Text Available Background/Aims: Delirium and the apolipoprotein E ε4 allele are risk factors for late-onset Alzheimer disease (LOAD, but the connection is unclear. We looked for an association. Methods: Inpatients with delirium (n = 18 were compared with LOAD outpatients (n = 19, assaying blood and cerebrospinal fluid (CSF using multiplex ELISA. Results: The patients with delirium had a higher Confusion Assessment Method (CAM score (5.6 ± 1.2 vs. 0.0 ± 0.0; p < 0.001 and Delirium Index (13.1 ± 4.0 vs. 2.9 ± 1.2; p = 0.001 but a lower Mini-Mental State Examination (MMSE score (14.3 ± 6.8 vs. 20.8 ± 4.6; p = 0.003. There was a reduction in absolute CSF apolipoprotein E level during delirium (median [interquartile range]: 9.55 μg/mL [5.65–15.05] vs. 16.86 μg/mL [14.82–20.88]; p = 0.016 but no differences in apolipoprotein A1, B, C3, H, and J. There were no differences in blood apolipoprotein levels, and no correlations between blood and CSF apolipoprotein levels. CSF apolipoprotein E correlated negatively with the CAM score (r = –0.354; p = 0.034 and Delirium Index (r = –0.341; p = 0.042 but not with the Acute Physiology and Chronic Health Evaluation (APACHE index, or the MMSE or Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE. Conclusion: Reduced CSF apolipoprotein E levels during delirium may be a mechanistic link between two important risk factors for LOAD.

  11. Apolipoprotein E and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Adriana Moreno Valladares

    2006-01-01

    Full Text Available Apolipoprotein E is a polymorphic glycoprotein who interacts with the lipoprotein receptors (LRP-Receptor Related Protein and the receptors for low density lipoproteins of (LDL receptors. When lipoproteins bring up the receptors begins lipids captation and degradation which allows cholesterol utilization, taking place an intracellular auto regulation. The three isoforms of greater importance: Apo E2, E3 and E4 are product of three alleles e2, e3, e4 of one only gene. This factor is related with the amount of lipoproteins that contains ApoE for E/B receptors. A low concentration of lipoproteins with ApoE can increase the activity of LDL receptors and consequently downward the circulating LDL. In the other hand particles with Apo E3 or Apo E4, can cause a downward regulation of LDL and in this way produces a LDL plasma elevation. Many studies in human populations have concluded that this polymorphism of apoE and the plasma variation of lipoproteins are associated with cardiovascular risk. Cardiovascular disease is the result of different interaction between factors which are genetic factor specially ApoE polymorphism e4 allelic of ApoE can explain, in some degree, the greater frequency of cardiovascular disease in those who carries it.

  12. Polymorphisms in apolipoprotein B and risk of ischemic stroke

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan Skov

    2007-01-01

    Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown.......Apolipoprotein B levels associate with risk of ischemic stroke. APOB polymorphisms may influence levels of apolipoprotein B and low-density lipoprotein (LDL), but whether they associate with risk of ischemic stroke is unknown....

  13. Apolipoprotein E in umbilical cord blood plasma

    International Nuclear Information System (INIS)

    Forte, T.M.; Davis, P.A.; Blum, C.B.

    1983-01-01

    Adolipoprotein E (apo E), with a molecular weight of approximately 37,000 daltons, is a minor apolipoprotein constituent in adult plasma lipoproteins. This apolipoprotein, like apolipoprotein B, is a ligand recognized by specific lipoprotein receptor sites (B-E receptors) on cell surfaces. We have recently shown that a pronounced apo E band appears in umbilical cord blood low-density (LDL) lipoproteins and also in high density (HDL) lipoproteins. Densitometric scans of Coomassie blue G-250 stained polyacrylamide gels suggested that apo E was probably elevated in cord blood lipoproteins. To pursue this suggestion, apo E in cord blood was quantitated by radioimmunoassay and correlated with cord blood lipid levels. In addition, apo E levels in 20 normal adult volunteers were also examined

  14. Specificity determinants in the interaction of apolipoprotein(a) kringles with tetranectin and LDL.

    Science.gov (United States)

    Caterer, Nigel R; Graversen, Jonas H; Jacobsen, Christian; Moestrup, Søren K; Sigurskjold, Bent W; Etzerodt, Michael; Thøgersen, Hans C

    2002-11-01

    Lipoprotein(a) is composed of low density lipoprotein and apolipoprotein(a). Apolipoprotein(a) has evolved from plasminogen and contains 10 different plasminogen kringle 4 homologous domains [KIV(1-110)]. Previous studies indicated that lipoprotein(a) non-covalently binds the N-terminal region of lipoprotein B100 and the plasminogen kringle 4 binding plasma protein tetranectin. In this study recombinant KIV(2), KIV(7) and KIV(10) derived from apolipoprotein(a) were produced in E. coli and the binding to tetranectin and low density lipoprotein was examined. Only KIV(10) bound to tetranectin and binding was similar to that of plasminogen kringle 4 to tetranectin. Only KIV(7) bound to LDL. In order to identify the residues responsible for the difference in specificity between KIV(7) and KIV(10), a number of surface-exposed residues located around the lysine binding clefts were exchanged. Ligand binding analysis of these derivatives showed that Y62, and to a minor extent W32 and E56, of KIV(7) are important for LDL binding to KIV(7), whereas R32 and D56 of KIV(10) are required for tetranectin binding of KIV(10).

  15. Effects of apolipoprotein M in uremic atherosclerosis

    DEFF Research Database (Denmark)

    Bosteen, Markus Høybye; Madsen Svarrer, Eva Martha; Bisgaard, Line Stattau

    2017-01-01

    BACKGROUND AND AIMS: Chronic kidney disease is characterized by uremia and causes premature death, partly due to accelerated atherosclerosis. Apolipoprotein (apo) M is a plasma carrier protein for the lipid sphingosine-1-phosphate (S1P). The Apom-S1P complex associates with HDL, and may contribute...

  16. Plasma lipoproteins as mediators of the oxidative stress induced by UV light in human skin: a review of biochemical and biophysical studies on mechanisms of apolipoprotein alteration, lipid peroxidation, and associated skin cell responses.

    Science.gov (United States)

    Filipe, Paulo; Morlière, Patrice; Silva, João N; Mazière, Jean-Claude; Patterson, Larry K; Freitas, João P; Santus, R

    2013-01-01

    There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL) and low-density lipoprotein (LDL) as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces (•)Trp and (•)O2 (-) radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO(•)) by α -tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α -tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α -tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α -tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

  17. Plasma Lipoproteins as Mediators of the Oxidative Stress Induced by UV Light in Human Skin: A Review of Biochemical and Biophysical Studies on Mechanisms of Apolipoprotein Alteration, Lipid Peroxidation, and Associated Skin Cell Responses

    Directory of Open Access Journals (Sweden)

    Paulo Filipe

    2013-01-01

    Full Text Available There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL and low-density lipoprotein (LDL as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces •Trp and O2•- radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO• by α-tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α-tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α-tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α-tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

  18. In the absence of endogenous mouse apolipoprotein E, apolipoprotein E*2(Arg-158 → Cys) transgenic mice develop more severe hyperlipoproteinemia than apolipoprotein E*3-Leiden transgenic mice

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Dijk, K.W. van; Hof, H.B. van 't; Gorp, P.J.J. van; Zee, A. van der; Boom, H. van der; Breuer, M.L.; Hofker, M.H.; Havekesf, L.M.

    1996-01-01

    Apolipoprotein E*2(Arg-155 → Cys) (APOE*2) transgenic mice were generated and compared to the previously generated apolipoprotein E*3- Leiden (APOE*3-Leiden) transgenic mice to study the variable expression of hyperlipoproteinemia associated with these two APOE variants. In the presence of the

  19. Apical secretion of apolipoproteins from enterocytes

    DEFF Research Database (Denmark)

    Danielsen, E M; Hansen, Gert Helge; Poulsen, Mona Dam

    1993-01-01

    Synthesis and secretion of apolipoproteins in pig small intestine was studied by pulse-chase labeling of jejunal segments, kept in organ culture. Apo A-1 and apo B-48 were the two major proteins released, constituting 25 and 10%, respectively, of the total amount of labeled protein in the mucosal...... in the soluble fraction, suggesting a basolateral secretion into the intercellular space, and both this accumulation and the release to the medium was prevented by culture at 20 degrees C. The specific radioactivity of apo A-1 and apo B-48 released to the medium was significantly higher than...... that enterocytes release most of their newly made free apo A-1 and a significant portion of apo B-48 by exocytosis via the brush border membrane into the intestinal lumen. Fat absorption reduced apolipoprotein secretion to the medium and induced the formation of chylomicrons, containing apo A-1 at their surface...

  20. Apolipoprotein A5 in health and disease

    Czech Academy of Sciences Publication Activity Database

    Hubáček, J. A.; Adámková, V.; Vrablík, M.; Kadlecová, Michaela; Zicha, Josef; Kuneš, Jaroslav; Piťha, J.; Suchánek, P.; Poledne, R.

    2009-01-01

    Roč. 58, Suppl.2 (2009), S101-S109 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:IKEM(CZ) 00023001; GA MŠk(CZ) MEB060808; GA MZd(CZ) NR8895; GAMZd(CZ) NR9393 Institutional research plan: CEZ:AV0Z50110509 Keywords : apolipoprotein A5 * plasma triglycerides * myocardial infarction Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 1.430, year: 2009

  1. A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

    Science.gov (United States)

    Sakurai, Toshihiro; Sakurai-Ikuta, Akiko; Sviridov, Denis; Freeman, Lita; Ahsan, Lusana; Remaley, Alan T.

    2015-01-01

    Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E–knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 ± 6% and 85 ± 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia. PMID:25395590

  2. Apolipoprotein M mediates sphingosine-1-phosphate efflux from erythrocytes

    DEFF Research Database (Denmark)

    Christensen, Pernille M.; Bosteen, Markus H.; Hajny, Stefan

    2017-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid implicated in e.g. angiogenesis, lymphocyte trafficking, and endothelial barrier function. Erythrocytes are a main source of plasma S1P together with platelets and endothelial cells. Apolipoprotein M (apoM) in HDL carries 70% of plasma S1P, whereas...... 30% is carried by albumin. The current aim was to investigate the role of apoM in export of S1P from human erythrocytes. Erythrocytes exported S1P more efficiently to HDL than to albumin, particularly when apoM was present in HDL. In contrast, export of sphingosine to HDL was unaffected...... by the presence of apoM. The specific ability of apoM to promote export of S1P was independent of apoM being bound in HDL particles. Treatment with MK-571, an inhibitor of the ABCC1 transporter, effectively reduced export of S1P from human erythrocytes to apoM, whereas the export was unaffected by inhibitors...

  3. Influence of apolipoprotein-E gene on lipid profile, physical activity and body fat relationship

    Directory of Open Access Journals (Sweden)

    Thales Boaventura Rachid Nascimento

    2012-03-01

    Full Text Available Physical activity and body fat modify lipemia, and this effect seems to be influenced by apolipoprotein-E (APOE gene polymorphism. Thus, the purpose of this article was to review main results of studies that have analyzed the relation of APOE gene with physical activity and body fat on triglycerides, total cholesterol and low (LDL and high density lipoprotein (HDL concentrations. The Scientific Electronic Library Online – SciELO, Web of Science and PubMed database were used to locate the articles. The keywords used in combination were: apoe genotype, apolipoprotein-E polymorphism, physical exercise, physical activity, aerobic exercise, body fat and obesity. Originals scientific investigations performed with humans were included, and excluded those ones which involved samples with diseases, except obesity and/or lipemic disorders. It was observed a trend, that ε2 allele carriers are the ones with the greater improvements on lipemia from physical exercise. In addition, the body fat impact on the elevation of triglycerides and LDL are stronger in carriers of the ε2 and ε4 allele, respectively. Considering the small number of originals scientific investigations and their divergent results, reliable inferences can not be made about the APOE gene polymorphism influences on physical activity and body fat effect on lipemia. Thus, further studies with others populations and more volunteers for allele, as well as others exercise modalities and intensities, are necessary.

  4. Major lipids, apolipoproteins, and risk of vascular disease

    DEFF Research Database (Denmark)

    Collaboration, Emerging Risk Factors; Di Angelantonio, Emanuele; Sarwar, Nadeem

    2009-01-01

    CONTEXT: Associations of major lipids and apolipoproteins with the risk of vascular disease have not been reliably quantified. OBJECTIVE: To assess major lipids and apolipoproteins in vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Individual records were supplied on 302,430 people without...

  5. The apolipoprotein m-sphingosine-1-phosphate axis

    DEFF Research Database (Denmark)

    Arkensteijn, Bas W C; Berbée, Jimmy F P; Rensen, Patrick C N

    2013-01-01

    Apolipoprotein M (apoM) is a plasma apolipoprotein that mainly associates with high-density lipoproteins. Hence, most studies on apoM so far have investigated its effect on and association with lipid metabolism and atherosclerosis. The insight into apoM biology recently took a major turn. Apo...

  6. The common polymorphism of apolipoprotein E

    DEFF Research Database (Denmark)

    Gerdes, Ulrik

    2003-01-01

    from only 10-15% in southern Europe to 40-50% in the north. The gradient may be a trace of the demic expansion of agriculture that began about 10,000 years ago, but it may also reflect the possibility that APOE*4 carriers are less likely to develop vitamin D deficiency. The common APOE polymorphism......Apolipoprotein E (apoE) has important functions in systemic and local lipid transport, but also has other functions. The gene (APOE) shows a common polymorphism with three alleles--APOE*2, APOE*3, and APOE*4. Their frequencies vary substantially around the world, but APOE*3 is the most common...

  7. Apolipoprotein M - a new biomarker in sepsis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2012-01-01

    Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship...... to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence...... on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation....

  8. Apolipoprotein e4 allele and cognitive decline in elderly men

    NARCIS (Netherlands)

    Feskens, E.J.M.; Havekes, L.M.; Kalmijn, S.; Knijff, P. de; Launer, L.J.; Kromhout, D.

    1994-01-01

    Objectives - To determine whether polymorphism of apolipoprotein E - notably, the e4 allele - predicts cognitive deterioration in the general population. Design - Population based cohort investigated in 1990 and in 1993. Setting - Zutphen, the Netherlands. Subjects - Representative cohort of 538

  9. Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

    DEFF Research Database (Denmark)

    Elsøe, Sara; Christoffersen, Christina; Luchoomun, Jayraz

    2013-01-01

    The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice.......The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice....

  10. Serum apolipoproteins in relation to intakes of fish in population of Arkhangelsk County

    Directory of Open Access Journals (Sweden)

    Petrenya Natalia

    2012-06-01

    Full Text Available Abstract Background Diets rich in omega-3 fatty acids and low in saturated fat were found beneficially associated with blood lipids and cardio-vascular health. Lean reindeer meet and local cold water white-fish species high in omega-3 are among the main sources of nutrients in the rural area of the Nenets Autonomous Okrug (NAO in Russia and are not normally consumed by the urban population from the same region. The aims of the study were firstly, to compare serum lipid profiles of residents of urban (Arkhangelsk city and rural (NAO regions of Arkhangelsk County, and secondly, to investigate the effects of fish consumption on the predictor of cardiovascular events apolipoprotein (Apo B/ApoA-I ratio in these populations. Methods A cross-sectional study conducted in Arkhangelsk County, Russia. Sample size of 249 adults: 132 subjects from Arkhangelsk city, aged 21–70 and 117 subject (87% Ethnic Nenets from NAO, aged 18–69. Results We observed more favorable lipid levels in NAO compared to Arkhangelsk participants. Age-adjusted geometric means of ApoB/ApoA-I ratio were 1.02 and 0.98 in men and women from Arkhangelsk; 0.84 and 0.91 in men and women from NAO respectively. Age and consumption of animal fat were positively associated with ApoB/ApoA-I ratio in women (pooled samples from Arkhangelsk and NAO. Body mass index and low levels of physical activity were positively associated with ApoB/ApoA-I ratio in men (pooled samples from Arkhangelsk and NAO. Reported oily fish consumption was not significantly correlated with ApoB/ApoA-I ratio. Conclusion The population sample from rural NAO, consisting largely of the indigenous Arctic population Nenets with healthier dietary sources, had a relatively less atherogenic lipid profile compared to the urban Arkhangelsk group. Fish consumption had no effect on apolipoproteins profile.

  11. Perceptron Mistake Bounds

    OpenAIRE

    Mohri, Mehryar; Rostamizadeh, Afshin

    2013-01-01

    We present a brief survey of existing mistake bounds and introduce novel bounds for the Perceptron or the kernel Perceptron algorithm. Our novel bounds generalize beyond standard margin-loss type bounds, allow for any convex and Lipschitz loss function, and admit a very simple proof.

  12. Apolipoprotein B, the villain in the drama?

    Science.gov (United States)

    Yu, Qi; Zhang, Yaping; Xu, Cang-Bao

    2015-02-05

    Low-density lipoprotein (LDL) is the major atherogenic lipoprotein and the primary target of lipid-lowering therapy for treating ischemic cardiovascular disease. Apolipoprotein B (apoB), an important structural component of LDL, plays a key role in cholesterol transport and removal in vascular wall. On the other hand, under pathological process, apoB interacts with the arterial wall to initiate the cascade of events that leads to atherosclerosis. However, interactions between apoB and vascular wall remain to be determined. Here, we address a pathological role of apoB per se and whole LDL particle in dysfunction of vascular endothelium and smooth muscle cells i.e. decreased endothelium-dependent vasodilation and increased receptor-mediated vasoconstriction. We intend to discuss: i) how apoB is responsible for the deleterious effects of LDL in the development of ischemic cardiovascular disease; ii) why vaccine based on peptides derived from apoB-100 is a promising therapy for treating ischemic cardiovascular disease, and iii) direct inhibition of apoB production should be a better therapeutic option than simple LDL-cholesterol lowering therapy in the patients with severe hypercholesterolemia at high cardiovascular risk with statin intolerance. In conclusion, apoB, but not cholesterol, plays a major role in LDL-induced dysfunction of endothelium, suggesting that direct apoB-targeting agents might be a promising therapy for the treatment of ischemic cardiovascular disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Apolipoprotein J (clusterin) and Alzheimer's disease.

    Science.gov (United States)

    Calero, M; Rostagno, A; Matsubara, E; Zlokovic, B; Frangione, B; Ghiso, J

    2000-08-15

    Apolipoprotein J (clusterin) is a ubiquitous multifunctional glycoprotein capable of interacting with a broad spectrum of molecules. In pathological conditions, it is an amyloid associated protein, co-localizing with fibrillar deposits in systemic and localized amyloid disorders. In Alzheimer's disease, the most frequent form of amyloidosis in humans and the major cause of dementia in the elderly, apoJ is present in amyloid plaques and cerebrovascular deposits but is rarely seen in NFT-containing neurons. ApoJ expression is up-regulated in a wide variety of insults and may represent a defense response against local damage to neurons. Four different mechanisms of action could be postulated to explain the role of apoJ as a neuroprotectant during cellular stress: (1) function as an anti-apoptotic signal, (2) protection against oxidative stress, (3) inhibition of the membrane attack complex of complement proteins locally activated as a result of inflammation, and (4) binding to hydrophobic regions of partially unfolded, stressed proteins, and therefore avoiding aggregation in a chaperone-like manner. This review focuses on the association of apoJ in biological fluids with Alzheimer's soluble Abeta. This interaction prevents Abeta aggregation and fibrillization and modulates its blood-brain barrier transport at the cerebrovascular endothelium. Copyright 2000 Wiley-Liss, Inc.

  14. Circuit lower bounds in bounded arithmetics

    Czech Academy of Sciences Publication Activity Database

    Pich, Ján

    2015-01-01

    Roč. 166, č. 1 (2015), s. 29-45 ISSN 0168-0072 R&D Projects: GA AV ČR IAA100190902 Keywords : bounded arithmetic * circuit lower bounds Subject RIV: BA - General Mathematics Impact factor: 0.582, year: 2015 http://www.sciencedirect.com/science/article/pii/S0168007214000888

  15. DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

  16. Thyroid hormones upregulate apolipoprotein E gene expression in astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Roman, Corina; Fuior, Elena V.; Trusca, Violeta G. [Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest (Romania); Kardassis, Dimitris [University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology of Hellas, Heraklion, Crete (Greece); Simionescu, Maya [Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest (Romania); Gafencu, Anca V., E-mail: anca.gafencu@icbp.ro [Institute of Cellular Biology and Pathology “Nicolae Simionescu”, Bucharest (Romania)

    2015-12-04

    Apolipoprotein E (apoE), a protein mainly involved in lipid metabolism, is associated with several neurodegenerative disorders including Alzheimer's disease. Despite numerous attempts to elucidate apoE gene regulation in the brain, the exact mechanism is still uncovered. The mechanism of apoE gene regulation in the brain involves the proximal promoter and multienhancers ME.1 and ME.2, which evolved by gene duplication. Herein we questioned whether thyroid hormones and their nuclear receptors have a role in apoE gene regulation in astrocytes. Our data showed that thyroid hormones increase apoE gene expression in HTB14 astrocytes in a dose-dependent manner. This effect can be intermediated by the thyroid receptor β (TRβ) which is expressed in these cells. In the presence of triiodothyronine (T3) and 9-cis retinoic acid, in astrocytes transfected to overexpress TRβ and retinoid X receptor α (RXRα), apoE promoter was indirectly activated through the interaction with ME.2. To determine the location of TRβ/RXRα binding site on ME.2, we performed DNA pull down assays and found that TRβ/RXRα complex bound to the region 341–488 of ME.2. This result was confirmed by transient transfection experiments in which a series of 5′- and 3′-deletion mutants of ME.2 were used. These data support the existence of a biologically active TRβ binding site starting at 409 in ME.2. In conclusion, our data revealed that ligand-activated TRβ/RXRα heterodimers bind with high efficiency on tissue-specific distal regulatory element ME.2 and thus modulate apoE gene expression in the brain. - Highlights: • T3 induce a dose-dependent increase of apoE expression in astrocytes. • Thyroid hormones activate apoE promoter in a cell specific manner. • Ligand activated TRβ/RXRα bind on the distal regulatory element ME.2 to modulate apoE. • The binding site of TRβ/RXRα heterodimer is located at 409 bp on ME.2.

  17. Thyroid hormones upregulate apolipoprotein E gene expression in astrocytes

    International Nuclear Information System (INIS)

    Roman, Corina; Fuior, Elena V.; Trusca, Violeta G.; Kardassis, Dimitris; Simionescu, Maya; Gafencu, Anca V.

    2015-01-01

    Apolipoprotein E (apoE), a protein mainly involved in lipid metabolism, is associated with several neurodegenerative disorders including Alzheimer's disease. Despite numerous attempts to elucidate apoE gene regulation in the brain, the exact mechanism is still uncovered. The mechanism of apoE gene regulation in the brain involves the proximal promoter and multienhancers ME.1 and ME.2, which evolved by gene duplication. Herein we questioned whether thyroid hormones and their nuclear receptors have a role in apoE gene regulation in astrocytes. Our data showed that thyroid hormones increase apoE gene expression in HTB14 astrocytes in a dose-dependent manner. This effect can be intermediated by the thyroid receptor β (TRβ) which is expressed in these cells. In the presence of triiodothyronine (T3) and 9-cis retinoic acid, in astrocytes transfected to overexpress TRβ and retinoid X receptor α (RXRα), apoE promoter was indirectly activated through the interaction with ME.2. To determine the location of TRβ/RXRα binding site on ME.2, we performed DNA pull down assays and found that TRβ/RXRα complex bound to the region 341–488 of ME.2. This result was confirmed by transient transfection experiments in which a series of 5′- and 3′-deletion mutants of ME.2 were used. These data support the existence of a biologically active TRβ binding site starting at 409 in ME.2. In conclusion, our data revealed that ligand-activated TRβ/RXRα heterodimers bind with high efficiency on tissue-specific distal regulatory element ME.2 and thus modulate apoE gene expression in the brain. - Highlights: • T3 induce a dose-dependent increase of apoE expression in astrocytes. • Thyroid hormones activate apoE promoter in a cell specific manner. • Ligand activated TRβ/RXRα bind on the distal regulatory element ME.2 to modulate apoE. • The binding site of TRβ/RXRα heterodimer is located at 409 bp on ME.2.

  18. Scattering by bound nucleons

    International Nuclear Information System (INIS)

    Tezuka, Hirokazu.

    1984-10-01

    Scattering of a particle by bound nucleons is discussed. Effects of nucleons that are bound in a nucleus are taken as a structure function. The way how to calculate the structure function is given. (author)

  19. Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats.

    Science.gov (United States)

    Zhang, Linda S; Sato, Hirokazu; Yang, Qing; Ryan, Robert O; Wang, David Q-H; Howles, Philip N; Tso, Patrick

    2015-12-01

    Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid (n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bile duct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate (n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins. Copyright © 2015 the American Physiological Society.

  20. Birth Weight, Cord Blood Lipoprotein and Apolipoprotein Levels in Indian Newborns

    Directory of Open Access Journals (Sweden)

    Simmi Kharb

    2010-01-01

    Full Text Available Objectives: Primordial prevention of chronic disease is of clinical andpublic health importance. Considering the fetal onset of atherosclerosis,we aimed to determine the cord blood level of lipoproteins andapolipoproteins as well as their correlation with birth weight and gestationalage.Methods: This cross-sectional study comprised 100 healthy Indiannewborns. Ten ml. of cord blood was collected from placental end ofumbilical vein. Serum was separated by centrifugation and analyzed onthe same day for lipid profile including total cholesterol (TC, triglycerides(TG, high density lipoprotein- cholesterol (HDL-C, very lowdensity lipoprotein-cholesterol (VLDL and low density lipoproteincholesterol(LDL-C, apolipoproteins A-I and B (ApoA-I, ApoB.Atherogenic index (AI was calculated as the ratio of ApoB to ApoA-I.Results: Cord blood of female newborns had higher TC, HDL-C,LDL-C, Apo A-I, Apo B and AI as compared to male newborns,whereas TG and VLDL-C were higher in male than in female newborns.Significant positive correlation was observed between cordblood Apo A-I and HDL-C (r= 0.45, p0.05.Conclusions: These findings are another confirmatory evidence forthe association of prenatal factors with cord blood lipid profile, andcan serve as starting point for studying lipid transport system changesduring early life.

  1. Circulating Apolipoprotein A1, Haptoglobin and Α2 Macroglobulin ...

    African Journals Online (AJOL)

    α2-MG), Apolipoprotein A1 (Apo-1) and Haptoglobin (HP) as non-invasive index of the presence of cirrhosis in chronic hepatitis C patients in relation to the histopathological findings. Subjects and Methods: The study was carried out on 20 ...

  2. Apolipoprotein E and carotid artery atherosclerosis - The Rotterdam study

    NARCIS (Netherlands)

    Slooter, AJC; Bots, ML; Havekes, LM; del Sol, AI; Cruts, M; Grobbee, DE; Hofman, A; Van Broeckhoven, C; Witteman, JCM; van Duijn, CM

    Background and Purpose-Carotid artery atherosclerosis is a strong predictor for future stroke. It is yet unclear whether the apolipoprotein E polymorphism (APOE) is related to atherosclerosis in the carotid arteries. The aim of the present study was to investigate the role of APOE in carotid artery

  3. In search of new structural states of exchangeable apolipoproteins

    International Nuclear Information System (INIS)

    Xicohtencatl-Cortes, J.; Castillo, R.; Mas-Oliva, J.

    2004-01-01

    Based upon state of the art biophysical experimentation, this article focuses on the different structural arrangements exchangeable apolipoproteins achieve when placed on Langmuir monolayers and subjected to changes in lateral pressure. We have studied the monolayers of apolipoproteins CI, CIII, AI, AII, and E that show as secondary structure a high percentage of amphipathic α-helix. This has been achieved employing techniques such as Brewster angle microscopy, synchrotron X-ray diffraction, and surface pressure measurements. In addition, the lateral order of protein arrays has been also studied by atomic force microscopy. These monolayers show that a phase transition from a two-dimensional disorder fluid to an ordered state is detected at relatively high lateral pressure, where unusual one-dimensional solid phases are discovered. While several helices that conform the apolipoprotein are confined to the interface, others are uniformly tilted toward the hydrophobic air or the phospholipid fatty acid chains. Our results suggest that a similar ordering might also occur when these apolipoproteins are attached to a lipoprotein particle such as a high density lipoprotein (HDL) particle. Therefore, changes from a nascent or discoidal HDL to a mature spherical HDL might in parallel involve structural changes as those described in our Langmuir interfaces. Current experimentation is being carried out in order to elucidate if the structural states already found are related to the efficiency of lipid transfer between lipoprotein particles or lipoproteins and the plasma membrane of cells, as well as receptor ligand recognition

  4. Apolipoprotein a5 and hypertriglyceridemia in prague hypertriglyceridemic rats

    Czech Academy of Sciences Publication Activity Database

    Kadlecová, Michaela; Hojná, Silvie; Bohuslavová, R.; Hubáček, J. A.; Zicha, Josef; Kuneš, Jaroslav

    2006-01-01

    Roč. 55, č. 4 (2006), s. 373-379 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GA305/03/0769 Institutional research plan: CEZ:AV0Z50110509 Keywords : metabolic syndrome * apolipoprotein A5 * rat Subject RIV: ED - Physiology Impact factor: 2.093, year: 2006

  5. Binding of recombinant apolipoprotein(a) to extracellular matrix proteins

    NARCIS (Netherlands)

    van der Hoek, Y. Y.; Sangrar, W.; Côté, G. P.; Kastelein, J. J.; Koschinsky, M. L.

    1994-01-01

    Elevated levels of lipoprotein(a), which consists of apolipoprotein(a) [apo(a)] covalently linked to a low-density lipoprotein-like moiety, is an independent risk factor for the development of atherosclerosis. We show that a recombinant form of apo(a) [r-apo(a)] binds strongly to fibronectin and

  6. Demonstration Of An Abnormality Of Apolipoprotein Ciii And Genetic ...

    African Journals Online (AJOL)

    Gout is the principal clinical manifestation of hyperuricaemia and leading cause of inflammatory arthritis in adult men. Lipids and apolipoproteins therefore plays an important role in the pathophysiology of the changes seen in hyperuricaemia. We conducted a study on the relationship between APOC3 SstI polymorphism ...

  7. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B

    2004-01-01

    Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... of lipid transfer from the mother to the developing fetus....

  8. Apolipoprotein E*3-Leiden transgenic mice mode for hypolipidaemic drugs

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Pearce, N.J.; Bergö, M.; Staels, B.; Yates, J.W.; Gribble, A.D.; Bond, B.C.; Hofker, M.H.; Havekes, L.M.; Groot, P.H.E.

    1998-01-01

    Apolipoprotein (APO) E*3-Leiden mice with impaired chylomicron and VLDL (very low density lipoprotein) remnant metabolism display hyperlipidaemia and atherosclerosis. In the present study, these mice were used for testing the hypolipidaemic effect of two marketed agents, lovastatin (CAS 75330-75-5)

  9. Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke

    DEFF Research Database (Denmark)

    Khan, Tauseef A; Shah, Tina; Prieto, David

    2013-01-01

    At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less c...

  10. Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

    NARCIS (Netherlands)

    Dallinga-Thie, G. M.; van Tol, A.; Hattori, H.; van Vark-van der Zee, L. C.; Jansen, H.; Sijbrands, E. J. G.

    2006-01-01

    Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in patients with type

  11. Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

    NARCIS (Netherlands)

    Dallinga-Thie, GM; Van Tol, A; Hattori, H; van Vark-van de Zee, LC; Jansen, H; Sijbrands, EJG

    Aims/hypothesis: Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in

  12. Physical Uncertainty Bounds (PUB)

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, Diane Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Dean L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-03-19

    This paper introduces and motivates the need for a new methodology for determining upper bounds on the uncertainties in simulations of engineered systems due to limited fidelity in the composite continuum-level physics models needed to simulate the systems. We show that traditional uncertainty quantification methods provide, at best, a lower bound on this uncertainty. We propose to obtain bounds on the simulation uncertainties by first determining bounds on the physical quantities or processes relevant to system performance. By bounding these physics processes, as opposed to carrying out statistical analyses of the parameter sets of specific physics models or simply switching out the available physics models, one can obtain upper bounds on the uncertainties in simulated quantities of interest.

  13. A strategy for solubilizing delipidated apolipoprotein with lysophosphatidylcholine and reconstitution with phosphatidylcholine

    International Nuclear Information System (INIS)

    Kawooya, J.K.; Wells, M.A.; Law, J.H.

    1989-01-01

    The apolipoproteins of insect lipophorin were dissociated in guanidinium chloride and isolated by gel permeation chromatography. Over 98% of the total lipid in lipophorin was associated with apolipophorin I (apoLp-I), thus suggesting this apolipoprotein to be the lipid binding component of the particle. ApoLp-I was delipidated with ethanol/ether and solubilized in buffer that contained radioactive lysophosphatidylcholine ([ 3 H]LPC) above the critical micellar concentration. Sonic irradiation of radioactive phosphatidylcholine ([ 14 C]PC) with [ 3 H]LPC-solubilized apoLp-I at a molar ratio of 318 resulted in reconstituted lipophorin I (RLp-I). [ 3 H]LPC was bound to fatty acid free bovine serum albumin and was separated from RLp-I by density gradient ultracentrifugation and gel permeation chromatography. Negatively stained RLp-I particles were quasispherical with an average radius of 55 angstrom, and their overall morphology and secondary structure were similar to those of native hemolymph lipophorin. The RLp-I particle had a ρ = 1.137 g/mL, a M r ∼ 5.2 x 10 5 , and a [ 14 C]PC:apoLp-I molar ratio of 308. From the compositional analysis, molecular size, trypsinization, and lipolysis with phospholipase A 2 , the authors concluded that each RLp-I particle contained one molecule of apoLp-I and a monomolecular layer of [ 14 C]PC. When injected into the hemolymph of adult moths in vivo, RLp-I was loaded with lipid, as judged by a decrease in its density both in the presence and in the absence of adipokinetic hormone. The similarities in morphology and immunology of RLp-I and native lipophorin, together with the ability of RLp-I to load lipid, suggest that reconstituted lipophorins may serve as models to probe lipophorin structure and function

  14. Influences of apolipoprotein E on soluble and heparin-immobilized hepatic lipase

    International Nuclear Information System (INIS)

    Landis, B.A.; Rotolo, F.S.; Meyers, W.C.; Clark, A.B.; Quarfordt, S.H.

    1987-01-01

    The effect of human apolipoprotein E (apoE), either alone or in combination with apoC, on the lipolysis of a radiolabeled triglyceride emulsion was studied with hepatic lipase in solution and immobilized on heparin-Sepharose. The soluble hepatic lipase was inhibited, whereas the heparin-immobilized lipase was stimulated by apoE. This stimulation was attenuated by combining apoE with either apoC-II or C-III. The heparin-immobilized lipase demonstrated much less lipolysis of the zwitterionic phosphatidylcholine-stabilized triglyceride emulsion than did the soluble enzyme. This difference was less when the emulsion was stabilized by a nonionic detergent. apoE inhibited lipase activity when assayed under conditions (0.4 M NaCl) of bound enzyme and unbound substrate. Increasing the emulsion apoE content beyond optimum inhibited lipolysis by the immobilized enzyme. Kinetic analysis of phosphatidylcholine-stabilized triglyceride emulsions revealed a significant decrease in immobilized enzyme K/sub m/ and an increase in V/sub max/ when the emulsion was supplemented with apoE. Distributing the immobilized lipase in clustered aggregates produced more lipolysis than when the same enzyme content was uniformly bound

  15. Photon virtual bound state

    International Nuclear Information System (INIS)

    Inoue, J.; Ohtaka, K.

    2004-01-01

    We study virtual bound states in photonics, which are a vectorial extension of electron virtual bound states. The condition for these states is derived. It is found that the Mie resonant state which satisfies the condition that the size parameter is less than the angular momentum should be interpreted as a photon virtual bound state. In order to confirm the validity of the concept, we compare the photonic density of states, the width of which represents the lifetime of the photon virtual bound states, with numerical results

  16. The DMM Bound

    DEFF Research Database (Denmark)

    Emiris, Ioannis Z.; Mourrain, Bernard; Tsigaridas, Elias

    2010-01-01

    ) resultant by means of mixed volume, as well as recent advances on aggregate root bounds for univariate polynomials, and are applicable to arbitrary positive dimensional systems. We improve upon Canny's gap theorem [7] by a factor of O(dn-1), where d bounds the degree of the polynomials, and n is the number...... bound on the number of steps that subdivision-based algorithms perform in order to isolate all real roots of a polynomial system. This leads to the first complexity bound of Milne's algorithm [22] in 2D....

  17. Differential interaction of Apolipoprotein-E isoforms with insulin receptors modulates brain insulin signaling in mutant human amyloid precursor protein transgenic mice.

    Science.gov (United States)

    Chan, Elizabeth S; Chen, Christopher; Cole, Gregory M; Wong, Boon-Seng

    2015-09-08

    It is unclear how human apolipoprotein E4 (ApoE4) increases the risk for Alzheimer's disease (AD). Although Aβ levels can lead to insulin signaling impairment, these experiments were done in the absence of human ApoE. To examine ApoE role, we crossed the human ApoE-targeted replacement mice with mutant human amyloid precursor protein (APP) mice. In 26 week old mice with lower Aβ levels, the expression and phosphorylation of insulin signaling proteins remained comparable among APP, ApoE3xAPP and ApoE4xAPP mouse brains. When the mice aged to 78 weeks, these proteins were markedly reduced in APP and ApoE4xAPP mouse brains. While Aβ can bind to insulin receptor, how ApoE isoforms modulate this interaction remains unknown. Here, we showed that ApoE3 had greater association with insulin receptor as compared to ApoE4, regardless of Aβ42 concentration. In contrast, ApoE4 bound more Aβ42 with increasing peptide levels. Using primary hippocampal neurons, we showed that ApoE3 and ApoE4 neurons are equally sensitive to physiological levels of insulin. However, in the presence of Aβ42, insulin failed to elicit a downstream response only in ApoE4 hippocampal neurons. Taken together, our data show that ApoE genotypes can modulate this Aβ-mediated insulin signaling impairment.

  18. Association between a specific apolipoprotein B mutation and familial defective apolipoprotein B-100

    International Nuclear Information System (INIS)

    Soria, L.F.; Ludwig, E.H.; Clarke, H.R.G.; McCarthy, B.J.; Vega, G.L.; Grundy, S.M.

    1989-01-01

    Familial defective apolipoprotein (apo) B-100 is a genetic disease that leads to hypercholesterolemia and to an increased serum concentration of low density lipoproteins that bind defectively to the apoB,E(LDL) receptor. The disorder appears to result from a mutation in the gene for apoB-100. Extensive sequence analysis of the two alleles of one subject heterozygous for the disorder has revealed a previously unreported mutation in the codon for amino acid 3500 that results in the substitution of glutamine for arginine. This same mutant allele occurs in six other, unrelated subjects and in eight affected relatives in two of these families. A partial haplotype of this mutant apoB-100 allele was constructed by sequence analysis and restriction enzyme digestion at positions where variations in the apoB-100 are known to occur. This haplotype is the same in three probands and four affected members of one family and lacks a polymorphic Xba I site whose presence has been correlated with high cholesterol levels. Thus, it appears that the mutation in the codon for amino acid 3500 (CGG → CAG), a CG mutational hot spot, defines a minor apoB-100 allele associated with defective low density lipoproteins and hypercholesterolemia

  19. Reversal of hypercholesterolemia in apolipoprotein E2 and apolipoprotein E3-Leiden transgenic mice by adenovirus-mediated gene transfer of the VLDL receptor

    NARCIS (Netherlands)

    Dijk, K.W. van; Vlijmen, B.J.M. van; Zee, A. van der; Hof, B. van 't; Boom, H. van der; Kobayashi, K.; Chan, L.; Havekes, L.M.; Hofker, M.H.

    1998-01-01

    We have investigated the interaction of apolipoprotein E2(Arg158- Cys) (apoE2) and apolipoprotein E3Leiden (apoE3-Leiden) with the very low density lipoprotein (VLDL) receptor in vivo and in vitro to define the possible role of this receptor in lipoprotein metabolism and atherosclerosis. The in vivo

  20. Bounded Gaussian process regression

    DEFF Research Database (Denmark)

    Jensen, Bjørn Sand; Nielsen, Jens Brehm; Larsen, Jan

    2013-01-01

    We extend the Gaussian process (GP) framework for bounded regression by introducing two bounded likelihood functions that model the noise on the dependent variable explicitly. This is fundamentally different from the implicit noise assumption in the previously suggested warped GP framework. We...... with the proposed explicit noise-model extension....

  1. Bounded Intention Planning Revisited

    OpenAIRE

    Sievers Silvan; Wehrle Martin; Helmert Malte

    2014-01-01

    Bounded intention planning provides a pruning technique for optimal planning that has been proposed several years ago. In addition partial order reduction techniques based on stubborn sets have recently been investigated for this purpose. In this paper we revisit bounded intention planning in the view of stubborn sets.

  2. Bounding species distribution models

    Directory of Open Access Journals (Sweden)

    Thomas J. STOHLGREN, Catherine S. JARNEVICH, Wayne E. ESAIAS,Jeffrey T. MORISETTE

    2011-10-01

    Full Text Available Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for “clamping” model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART and maximum entropy (Maxent models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5: 642–647, 2011].

  3. Bounding Species Distribution Models

    Science.gov (United States)

    Stohlgren, Thomas J.; Jarnevich, Cahterine S.; Morisette, Jeffrey T.; Esaias, Wayne E.

    2011-01-01

    Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5): 642-647, 2011].

  4. Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

    DEFF Research Database (Denmark)

    Bartels, Emil D; Ploug, Thorkil; Størling, Joachim

    2014-01-01

    Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design. In t...... accumulation and attenuates peripheral insulin resistance in obese mice........ In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apo......Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design...

  5. Organically bound tritium

    International Nuclear Information System (INIS)

    Diabate, S.; Strack, S.

    1993-01-01

    Tritium released into the environment may be incorporated into organic matter. Organically bound tritium in that case will show retention times in organisms that are considerably longer than those of tritiated water which has significant consequences on dose estimates. This article reviews the most important processes of organically bound tritium production and transport through food networks. Metabolic reactions in plant and animal organisms with tritiated water as a reaction partner are of great importance in this respect. The most important production process, in quantitative terms, is photosynthesis in green plants. The translocation of organically bound tritium from the leaves to edible parts of crop plants should be considered in models of organically bound tritium behavior. Organically bound tritium enters the human body on several pathways, either from the primary producers (vegetable food) or at a higher tropic level (animal food). Animal experiments have shown that the dose due to ingestion of organically bound tritium can be up to twice as high as a comparable intake of tritiated water in gaseous or liquid form. In the environment, organically bound tritium in plants and animals is often found to have higher specific tritium concentrations than tissue water. This is not due to some tritium enrichment effects but to the fact that no equilibrium conditions are reached under natural conditions. 66 refs

  6. Deeply bound pionic atom

    International Nuclear Information System (INIS)

    Toki, Hiroshi; Yamazaki, Toshimitsu

    1989-01-01

    The standard method of pionic atom formation does not produce deeply bound pionic atoms. A study is made on the properties of deeply bound pionic atom states by using the standard pion-nucleus optical potential. Another study is made to estimate the cross sections of the formation of ls pionic atom states by various methods. The pion-nucleus optical potential is determined by weakly bound pionic atom states and pion nucleus scattering. Although this potential may not be valid for deeply bound pionic atoms, it should provide some hint on binding energies and level widths of deeply bound states. The width of the ls state comes out to be 0.3 MeV and is well separated from the rest. The charge dependence of the ls state is investigated. The binding energies and the widths increase linearly with Z azbove a Z of 30. The report then discusses various methods to populate deeply bound pionic atoms. In particular, 'pion exchange' reactions are proposed. (n, pπ) reaction is discussed first. The cross section is calculated by assuming the in- and out-going nucleons on-shell and the produced pion in (n1) pionic atom states. Then, (n, dπ - ) cross sections are estimated. (p, 2 Heπ - ) reaction would have cross sections similar to the cross section of (n, dπ - ) reaction. In conclusion, it seems best to do (n, p) experiment on heavy nuclei for deeply bound pionic atom. (Nogami, K.)

  7. cDNA sequences of two apolipoproteins from lamprey

    International Nuclear Information System (INIS)

    Pontes, M.; Xu, X.; Graham, D.; Riley, M.; Doolittle, R.F.

    1987-01-01

    The messages for two small but abundant apolipoproteins found in lamprey blood plasma were cloned with the aid of oligonucleotide probes based on amino-terminal sequences. In both cases, numerous clones were identified in a lamprey liver cDNA library, consistent with the great abundance of these proteins in lamprey blood. One of the cDNAs (LAL1) has a coding region of 105 amino acids that corresponds to a 21-residue signal peptide, a putative 8-residue propeptide, and the 76-residue mature protein found in blood. The other cDNA (LAL2) codes for a total of 191 residues, the first 23 of which constitute a signal peptide. The two proteins, which occur in the high-density lipoprotein fraction of ultracentrifuged plasma, have amino acid compositions similar to those of apolipoproteins found in mammalian blood; computer analysis indicates that the sequences are largely helix-permissive. When the sequences were searched against an amino acid sequence data base, rat apolipoprotein IV was the best matching candidate in both cases. Although a reasonable alignment can be made with that sequence and LAL1, definitive assignment of the two lamprey proteins to typical mammalian classes cannot be made at this point

  8. Postmenopausal hypertension, abdominal obesity, apolipoprotein and insulin resistance.

    Science.gov (United States)

    Ben Ali, Samir; Belfki-Benali, Hanen; Ahmed, Decy Ben; Haddad, Najet; Jmal, Awatef; Abdennebi, Monia; Romdhane, Habiba Ben

    This study aimed to evaluate the association of abdominal obesity, apolipoprotein and insulin resistance (IR) with the risk of hypertension in postmenopausal women. We analyzed a total of 242 women aged between 35 and 70 years. Blood pressure (BP), anthropometric indices, lipid profile, fasting glucose, insulin, C-reactive protein (CRP) and apolipoprotein concentrations were measured. Homeostasis model assessment (HOMA) was used to assess IR. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg or current treatment with antihypertensive drugs. Women with hypertension showed significantly higher mean values of age, SBP and DBP, waist circumference (WC), fasting plasma glucose (FPG), insulin, HOMAIR and the apolipoprotein B (apoB). When analyses were done according to the menopausal status, higher prevalence of hypertension was observed in postmenopausal women (72.8% vs. 26.0%, p menopause (p = 0.008) were significantly associated with higher risk for hypertension. These results suggest that changes in WC, apoB and IR accompanying menopause lead to a greater prevalence of hypertension in postmenopausal women.

  9. ApoA-I induces S1P release from endothelial cells through ABCA1 and SR-BI in a positive feedback manner.

    Science.gov (United States)

    Liu, Xing; Ren, Kun; Suo, Rong; Xiong, Sheng-Lin; Zhang, Qing-Hai; Mo, Zhong-Cheng; Tang, Zhen-Li; Jiang, Yue; Peng, Xiao-Shan; Yi, Guang-Hui

    2016-12-01

    Sphingosine-1-phosphate (S1P), which has emerged as a pivotal signaling mediator that participates in the regulation of multiple cellular processes, is derived from various cells, including vascular endothelial cells. S1P accumulates in lipoproteins, especially HDL, and the majority of free plasma S1P is bound to HDL. We hypothesized that HDL-associated S1P is released through mechanisms associated with the HDL maturation process. ApoA-I, a major HDL apolipoprotein, is a critical factor for nascent HDL formation and lipid trafficking via ABCA1. Moreover, apoA-I is capable of promoting bidirectional lipid movement through SR-BI. In the present study, we confirmed that apoA-I can facilitate the production and release of S1P by HUVECs. Furthermore, we demonstrated that ERK1/2 and SphK activation induced by apoA-I is involved in the release of S1P from HUVECs. Inhibitor and siRNA experiments showed that ABCA1 and SR-BI are required for S1P release and ERK1/2 phosphorylation induced by apoA-I. However, the effects triggered by apoA-I were not suppressed by inhibiting ABCA1/JAK2 or the SR-BI/Src pathway. S1P released due to apoA-I activation can stimulate the (ERK1/2)/SphK1 pathway through S1PR (S1P receptor) 1/3. These results indicated that apoA-I not only promotes S1P release through ABCA1 and SR-BI but also indirectly activates the (ERK1/2)/SphK1 pathway by releasing S1P to trigger their receptors. In conclusion, we suggest that release of S1P induced by apoA-I from endothelial cells through ABCA1 and SR-BI is a self-positive-feedback process: apoA-I-(ABCA1 and SR-BI)-(S1P release)-S1PR-ERK1/2-SphK1-(S1P production)-(more S1P release induced by apoA-I).

  10. Effect of fatty acids on the synthesis and secretion of apolipoprotein B by rat hepatocytes

    International Nuclear Information System (INIS)

    Suresh Kumar, N.; Abraham, Rita; Suresh Kumar, G.; Sudhakaran, P.R.; Kurup, P.A.

    1992-01-01

    The modulation of apolipoprotein B synthesis and secretion by fatty acids in rat hepatocytes was studied. Maximum apolipoprotein B production was obtained in the case of oleic acid followed by linoleic, stearic and palmitic/linolenic acid when compared to control which was not supplemented with any fatty acids. Oleic acid was found to exert a concentration dependent increase in the secretion of [ 3 H] apolipoprotein B into the medium while that associated with the cell layer was not affected. Pulse chase experiments in the presence of oleic acid showed that it caused an increase in the secretion of apolipoprotein B into the medium. 14 C-acetate incorporation into cholesterol and cholesteryl ester associated with the cell layer and secreted very low density lipoproteins also showed an increase in the presence of oleic acid indicating an increase in cholesterogenesis. The effect of oleic acid on [ 3 H] apolipoprotein B and very low density lipoprotein secretion appeared to be mediated through cholesterol as (i)ketoconazole, an inhibitor of cholesterol synthesis caused significant reduction in the stimulatory effect of oleic acid on apolipoprotein secretion and (ii) mevinolin, another inhibitor of cholesterol synthesis also reversed the stimulatory effect of oleic acid on apolipoprotein B secretion. These results indicated that oleic acid may influence apolipoprotein B synthesis and secretion in hepatocytes probably by affecting cholesterol/cholesteryl ester formation which may be a critical component in the secretion of apolipoprotein B as lipoproteins. (author). 21 refs., 4 figs., 2 tabs

  11. Influence of apolipoproteins on the association between lipids and insulin sensitivity

    DEFF Research Database (Denmark)

    Baldi, Simona; Bonnet, Fabrice; Laville, Martine

    2013-01-01

    We evaluated whether the association of insulin sensitivity with HDL cholesterol (HDL) and triglycerides is influenced by major plasma apolipoproteins, as suggested by recent experimental evidence....

  12. Bounded Rationality and Budgeting

    OpenAIRE

    Ibrahim, Mukdad

    2016-01-01

    This article discusses the theory of bounded rationality which had been introduced by Herbert Simon in the 1950s. Simon introduced the notion of bounded rationality stating that while decision-makers strive for rationality, they are limited by the effect of the environment, their information process capacity and by the constraints on their information storage and retrieval capabilities. Moreover, this article tries to specifically blend this notion into budgeting, using the foundations of inc...

  13. Virial Expansion Bounds

    Science.gov (United States)

    Tate, Stephen James

    2013-10-01

    In the 1960s, the technique of using cluster expansion bounds in order to achieve bounds on the virial expansion was developed by Lebowitz and Penrose (J. Math. Phys. 5:841, 1964) and Ruelle (Statistical Mechanics: Rigorous Results. Benjamin, Elmsford, 1969). This technique is generalised to more recent cluster expansion bounds by Poghosyan and Ueltschi (J. Math. Phys. 50:053509, 2009), which are related to the work of Procacci (J. Stat. Phys. 129:171, 2007) and the tree-graph identity, detailed by Brydges (Phénomènes Critiques, Systèmes Aléatoires, Théories de Jauge. Les Houches 1984, pp. 129-183, 1986). The bounds achieved by Lebowitz and Penrose can also be sharpened by doing the actual optimisation and achieving expressions in terms of the Lambert W-function. The different bound from the cluster expansion shows some improvements for bounds on the convergence of the virial expansion in the case of positive potentials, which are allowed to have a hard core.

  14. Bound and rebound states

    International Nuclear Information System (INIS)

    Orzalesi, C.A.

    1979-01-01

    In relativistic quantum theory, bound states generate forces in the crossed channel; such forces can affect the binding and self-consistent solutions should be sought for the bound-state problem. The author investigates how self-consistency can be achieved by successive approximations, in a simple scalar model and with successive relativistic eikonal approximations (EAs). Within the generalized ladder approximation, some exact properties of the resulting ''first generation'' bound states are discussed. The binding energies in this approximation are rather small even for rather large values of the primary coupling constant. The coupling of the constituent particles to the first-generation reggeon is determined by a suitable EA and a new generalized ladder amplitude is constructed with rungs given either by the primary gluons or by the first-generation reggeons. The resulting new (second-generation) bound states are found in a reggeized EA. The size of the corrections to the binding energies due to the rebinding effects is surprisingly large. The procedure is then iterated, so as to find - again in an EA - the third-generation bound states. The procedure is found to be self-consistent already at this stage: the third-generation bound states coincide with those of second generation, and no further rebinding takes place in the higher iterations of the approximation method. Features - good and bad - of the model are discussed, as well as the possible relevance of rebinding mechanisms in hadron dynamics. (author)

  15. The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Ahnström, Josefin; Axler, Olof

    2008-01-01

    Lipoproteins consist of lipids solubilized by apolipoproteins. The lipid-binding structural motifs of apolipoproteins include amphipathic alpha-helixes and beta-sheets. Plasma apolipoprotein (apo) M lacks an external amphipathic motif but, nevertheless, is exclusively associated with lipoproteins...... (mainly high density lipoprotein). Uniquely, however, apoM is secreted to plasma without cleavage of its hydrophobic NH(2)-terminal signal peptide. To test whether the signal peptide serves as a lipoprotein anchor for apoM in plasma, we generated mice expressing a mutated apoM(Q22A) cDNA in the liver (apoM......(Q22A)-Tg mice (transgenic mice)) and compared them with mice expressing wild-type human apoM (apoM-Tg mice). The substitution of the amino acid glutamine 22 with alanine in apoM(Q22A) results in secretion of human apoM without a signal peptide. The human apoM mRNA level in liver and the amount...

  16. Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Obinata, Hideru; Kumaraswamy, Sunil B

    2011-01-01

    Protection of the endothelium is provided by circulating sphingosine-1-phosphate (S1P), which maintains vascular integrity. We show that HDL-associated S1P is bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated human ApoM(+) HDL contained S1P, whereas ApoM(-) HDL did...... not. Moreover, HDL in Apom(-/-) mice contains no S1P, whereas HDL in transgenic mice overexpressing human apoM has an increased S1P content. The 1.7-Å structure of the S1P-human apoM complex reveals that S1P interacts specifically with an amphiphilic pocket in the lipocalin fold of apoM. Human ApoM......(+) HDL induced S1P(1) receptor internalization, downstream MAPK and Akt activation, endothelial cell migration, and formation of endothelial adherens junctions, whereas apoM(-) HDL did not. Importantly, lack of S1P in the HDL fraction of Apom(-/-) mice decreased basal endothelial barrier function in lung...

  17. Bounded Tamper Resilience

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Faust, Sebastian; Mukherjee, Pratyay

    2013-01-01

    Related key attacks (RKAs) are powerful cryptanalytic attacks where an adversary can change the secret key and observe the effect of such changes at the output. The state of the art in RKA security protects against an a-priori unbounded number of certain algebraic induced key relations, e.......g., affine functions or polynomials of bounded degree. In this work, we show that it is possible to go beyond the algebraic barrier and achieve security against arbitrary key relations, by restricting the number of tampering queries the adversary is allowed to ask for. The latter restriction is necessary......-protocols (including the Okamoto scheme, for instance) are secure even if the adversary can arbitrarily tamper with the prover’s state a bounded number of times and obtain some bounded amount of leakage. Interestingly, for the Okamoto scheme we can allow also independent tampering with the public parameters. We show...

  18. Massive Galileon positivity bounds

    Science.gov (United States)

    de Rham, Claudia; Melville, Scott; Tolley, Andrew J.; Zhou, Shuang-Yong

    2017-09-01

    The EFT coefficients in any gapped, scalar, Lorentz invariant field theory must satisfy positivity requirements if there is to exist a local, analytic Wilsonian UV completion. We apply these bounds to the tree level scattering amplitudes for a massive Galileon. The addition of a mass term, which does not spoil the non-renormalization theorem of the Galileon and preserves the Galileon symmetry at loop level, is necessary to satisfy the lowest order positivity bound. We further show that a careful choice of successively higher derivative corrections are necessary to satisfy the higher order positivity bounds. There is then no obstruction to a local UV completion from considerations of tree level 2-to-2 scattering alone. To demonstrate this we give an explicit example of such a UV completion.

  19. Serum apolipoprotein e level is not increased in Alzheimer's disease : The Rotterdam study

    NARCIS (Netherlands)

    Slooter, A.J.C.; Knijff, P. de; Hofman, A.; Cruts, M.; Breteler, M.M.B.; Broeckhoven, C. van; Havekes, L.M.; Duijn, C.M. van

    1998-01-01

    The APOE*4 allele of the apolipoprotein E gene (APOE) is an important risk factor for Alzheimer's disease. It has been suggested that levels of apolipoprotein E (apoE) in plasma are increased in Alzheimer's disease. In this population-based study, we found that serum apoE levels were lower in

  20. Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with hyperthyroidism

    DEFF Research Database (Denmark)

    Klausen, I C; Hegedüs, L; Hansen, P S

    1995-01-01

    Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apoB) is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are ...

  1. Genetic association of apolipoprotein E with age-related macular degeneration

    NARCIS (Netherlands)

    M. Kliffen (Mike); C.M. van Duijn (Cornelia); M. Cruts (Marc); D.E. Grobbee (Diederick); P.T.V.M. de Jong (Paulus); C.C.W. Klaver (Caroline); C. van Broeckhoven (Christine); A. Hofman (Albert)

    1998-01-01

    textabstractAge-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an

  2. Reduced apolipoprotein glycosylation in patients with the metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Olga V Savinova

    Full Text Available The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.Very low density (VLDL, intermediate/low density (IDL/LDL, hereafter LDL, and high density lipoproteins (HDL fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.Metabolic syndrome patients differed from healthy controls in the following ways: (1 total plasma--apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2 VLDL--apoB, apoC3, and apoE were increased; (3 LDL--apoC3 was increased, (4 HDL--associated constitutive serum amyloid A protein (SAA4 was reduced (p<0.05 vs. controls for all. In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all. Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all. Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001.Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.

  3. Human placenta secretes apolipoprotein B-100-containing lipoproteins

    DEFF Research Database (Denmark)

    Munk-Madsen, Eva; Lindegaard, Marie Louise Skakkebæk; Andersen, Claus B

    2004-01-01

    Supply of lipids from the mother is essential for fetal growth and development. In mice, disruption of yolk sac cell secretion of apolipoprotein (apo) B-containing lipoproteins results in embryonic lethality. In humans, the yolk sac is vestigial. Nutritional functions are instead established very...... lipoproteins secreted from placental tissue showed spherical particles with a diameter of 47 +/- 10 nm. These results demonstrate that human placenta expresses both apoB and MTP and consequently synthesize and secrete apoB-100-containing lipoproteins. Placental lipoprotein formation constitutes a novel pathway...

  4. Bounded variation and around

    CERN Document Server

    Appell, Jürgen; Merentes Díaz, Nelson José

    2013-01-01

    This monographis a self-contained exposition of the definition and properties of functionsof bounded variation and their various generalizations; the analytical properties of nonlinear composition operators in spaces of such functions; applications to Fourier analysis, nonlinear integral equations, and boundary value problems. The book is written for non-specialists. Every chapter closes with a list of exercises and open problems.

  5. Clinical application of human serum apolipoprotein B ria

    International Nuclear Information System (INIS)

    He Rongxia

    1988-01-01

    The serum apolipoprotein B (Apo B) was measured in 89 normal subjects with radioimmunoassay method established by the authors, among them 50 patients with coronary heart disease (CHD), 19 patients with cerebrae-vascular accident (CVA) and 46 patients with hyperlipemia. Meanwhile the serum cholesterol and triglyceride were also measured. Although cholesterol, triglyceride, and Apo B levels in disease groups were all significantly higher than control group, there are more overlap between the control and disease group for cholesterol and triglyceride. The Apo B level was 723.9 +- 195.9 mg/L in control group, 1097 +- 236.0 mg/L in CHD group and in CVA group, and this difference was highly significant (P < 0.001). Besides, less overlap of the Apo B value between disease and countrol group was observed in both disease groups. When the Apo B was used as single parameter for the diagnosis CHD, the accuracy rate reached 82%. The results of this study indicated that measurement of Apo B can offer important prediction for coronary artery disease, especially in those having normal levels of plasma cholesterol. In conclusion, the study of apolipoprotein is more significant than lipid component in discriminating between atherosclerotic patients and normal persons

  6. Hydrogen Production by a Hyperthermophilic Membrane-Bound Hydrogenase in Soluble Nanolipoprotein Particles

    Energy Technology Data Exchange (ETDEWEB)

    Baker, S E; Hopkins, R C; Blanchette, C; Walsworth, V; Sumbad, R; Fischer, N; Kuhn, E; Coleman, M; Chromy, B; Letant, S; Hoeprich, P; Adams, M W; Henderson, P T

    2008-10-22

    Hydrogenases constitute a promising class of enzymes for ex vivo hydrogen production. Implementation of such applications is currently hindered by oxygen sensitivity and, in the case of membrane-bound hydrogenases (MBH), poor water solubility. Nanolipoprotein particles (NLPs), formed from apolipoproteins and phospholipids, offer a novel means to incorporate MBH into in a well-defined water-soluble matrix that maintains the enzymatic activity and is amenable to incorporation into more complex architectures. We report the synthesis, hydrogen-evolving activity and physical characterization of the first MBH-NLP assembly. This may ultimately lead to the development of biomimetic hydrogen production devices.

  7. Maps of Bounded Rationality

    OpenAIRE

    Kahneman, Daniel

    2002-01-01

    The work cited by the Nobel committee was done jointly with the late Amos Tversky (1937-1996) during a long and unusually close collaboration. Together, we explored the psychology of intuitive beliefs and choices and examined their bounded rationality. This essay presents a current perspective on the three major topics of our joint work: heuristics of judgment, risky choice, and framing effects. In all three domains we studied intuitions - thoughts and preferences that come to mind quickly an...

  8. Bounded Satisfiability for PCTL

    OpenAIRE

    Bertrand, Nathalie; Fearnley, John; Schewe, Sven

    2012-01-01

    While model checking PCTL for Markov chains is decidable in polynomial-time, the decidability of PCTL satisfiability, as well as its finite model property, are long standing open problems. While general satisfiability is an intriguing challenge from a purely theoretical point of view, we argue that general solutions would not be of interest to practitioners: such solutions could be too big to be implementable or even infinite. Inspired by bounded synthesis techniques, we turn to the more appl...

  9. Dietary Flaxseed Oil Prevents Western-Type Diet-Induced Nonalcoholic Fatty Liver Disease in Apolipoprotein-E Knockout Mice

    Directory of Open Access Journals (Sweden)

    Hao Han

    2017-01-01

    Full Text Available The prevalence of nonalcoholic fatty liver disease (NAFLD has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs, mainly eicosapentaenoic acid (EPA, C20:5n-3 and docosahexaenoic acid (DHA, C22:6n-3, is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3, a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD, or a WTD diet containing 10% flaxseed oil (WTD + FO for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC, triacylglycerol catabolism (PPARα, CPT1A, and ACOX1, inflammation (NF-κB, IL-6, TNF-α, and MCP-1, and oxidative stress (ROS, MDA, GSH, and SOD.

  10. Relationship between depression and apolipoproteins A and B: a case-control study

    Directory of Open Access Journals (Sweden)

    Masoumeh Sadeghi

    2011-01-01

    Full Text Available OBJECTIVE: To investigate the relation between major depressive disorder and metabolic risk factors of coronary heart disease. INTRODUCTION: Little evidence is available indicating a relationship between major depressive disorder and metabolic risk factors of coronary heart disease such as lipoprotein and apolipoprotein. METHODS: This case-control study included 153 patients with major depressive disorder who fulfilled the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV, and 147 healthy individuals. All participants completed a demographic questionnaire and Hamilton rating scale for depression. Anthropometric characteristics were recorded. Blood samples were taken and total cholesterol, high-and low-density lipoproteins and apolipoproteins A and B were measured. To analyze the data, t-test, χ2 test, Pearson correlation test and linear regression were applied. RESULTS: Depression was a negative predictor of apolipoprotein A (β = -0.328, p<0.01 and positive predictor of apolipoprotein B (β = 0.290, p<0.05. Apolipoprotein A was inversely predicted by total cholesterol (β = -0.269, p<0.05 and positively predicted by high-density lipoprotein (β = 0.401, p<0.01. Also, low-density lipoprotein was a predictor of apolipoprotein B (β = 0.340, p<0.01. The severity of depression was correlated with the increment in serum apolipoprotein B levels and the decrement in serum apolipoprotein A level. CONCLUSION: In view of the relationship between apolipoproteins A and B and depression, it would seem that screening of these metabolic risk factors besides psychological interventions is necessary in depressed patients

  11. Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

    Science.gov (United States)

    Lamon-Fava, S; Fisher, E C; Nelson, M E; Evans, W J; Millar, J S; Ordovas, J M; Schaefer, E J

    1989-01-01

    Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

  12. Universal bounds on current fluctuations.

    Science.gov (United States)

    Pietzonka, Patrick; Barato, Andre C; Seifert, Udo

    2016-05-01

    For current fluctuations in nonequilibrium steady states of Markovian processes, we derive four different universal bounds valid beyond the Gaussian regime. Different variants of these bounds apply to either the entropy change or any individual current, e.g., the rate of substrate consumption in a chemical reaction or the electron current in an electronic device. The bounds vary with respect to their degree of universality and tightness. A universal parabolic bound on the generating function of an arbitrary current depends solely on the average entropy production. A second, stronger bound requires knowledge both of the thermodynamic forces that drive the system and of the topology of the network of states. These two bounds are conjectures based on extensive numerics. An exponential bound that depends only on the average entropy production and the average number of transitions per time is rigorously proved. This bound has no obvious relation to the parabolic bound but it is typically tighter further away from equilibrium. An asymptotic bound that depends on the specific transition rates and becomes tight for large fluctuations is also derived. This bound allows for the prediction of the asymptotic growth of the generating function. Even though our results are restricted to networks with a finite number of states, we show that the parabolic bound is also valid for three paradigmatic examples of driven diffusive systems for which the generating function can be calculated using the additivity principle. Our bounds provide a general class of constraints for nonequilibrium systems.

  13. High-density lipoprotein apolipoproteins in urine: I. Characterization in normal subjects and in patients with proteinuria.

    Science.gov (United States)

    Gomo, Z A; Henderson, L O; Myrick, J E

    1988-09-01

    A high-resolution two-dimensional electrophoretic method for protein, with silver staining, has been used to characterize and identify urinary high-density-lipoprotein apolipoproteins (HDL-Apos) and their isoforms in healthy subjects and in patients with kidney disease. Analytical techniques based on both molecular mass and ultracentrifugal flotation properties were used to isolate urinary lipoprotein particles with characteristics identical to those of HDL in plasma. HDL-Apos identified in urine of normal subjects and patients with glomerular proteinuria were Apos A-I, A-II, and C. Five isoforms of Apo A-I were present. Immunostaining of electroblotted proteins further confirmed the presence of HDL-Apos in urine. Creatinine clearance rate was decreased in the patients with proteinuria, and ranged from 32.5 to 40 mL/min. Concentrations of cholesterol and triglycerides in serum were greater in the patients' group, whereas mean HDL-cholesterol (0.68, SD 0.10 mmol/L) and Apo A-I (0.953, SD 0.095 g/L) were significantly (each P less than 0.01) lower. Results of this study suggest that measurement of urinary Apo A-I will reflect excretion of HDL in urine.

  14. A bound on chaos

    Energy Technology Data Exchange (ETDEWEB)

    Maldacena, Juan [School of Natural Sciences, Institute for Advanced Study,1 Einstein Drive, Princeton, NJ (United States); Shenker, Stephen H. [Stanford Institute for Theoretical Physics and Department of Physics, Stanford University,382 Via Pueblo Mall, Stanford, CA (United States); Stanford, Douglas [School of Natural Sciences, Institute for Advanced Study,1 Einstein Drive, Princeton, NJ (United States)

    2016-08-17

    We conjecture a sharp bound on the rate of growth of chaos in thermal quantum systems with a large number of degrees of freedom. Chaos can be diagnosed using an out-of-time-order correlation function closely related to the commutator of operators separated in time. We conjecture that the influence of chaos on this correlator can develop no faster than exponentially, with Lyapunov exponent λ{sub L}≤2πk{sub B}T/ℏ. We give a precise mathematical argument, based on plausible physical assumptions, establishing this conjecture.

  15. Apolipoprotein E-epsilon 4 frequency in affective disorder

    DEFF Research Database (Denmark)

    Kessing, L V; Jørgensen, O S

    1999-01-01

    -Bråne-Steen Dementia Rating Scale, and the Global Deterioration Scale. RESULTS: The frequency of APOE-epsilon 4 allele was approximately the same in unipolar patients (.189) and in bipolar patients (.167). Although patients showed more cognitive impairment than controls, no significant overall difference was found...... was found with gender, age at onset, the number of affective episodes, the presence of psychotic features, or the prevalence of familial affective disorder. CONCLUSIONS: It seems that cognitive impairment in affective disorder can be attributed to pathways other than the APOE genotype.......BACKGROUND: The epsilon 4 allele of apolipoprotein E (APOE) as well as affective disorder have been found to be associated with Alzheimer's disease, but it is unclear whether cognitive impairment in affective disorder or subtypes of affective disorder is mediated by the epsilon 4 allele of APOE...

  16. Function and Comorbidities of Apolipoprotein E in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Valérie Leduc

    2011-01-01

    Full Text Available Alzheimer's disease (AD—the most common type of dementia among the elderly—represents one of the most challenging and urgent medical mysteries affecting our aging population. Although dominant inherited mutation in genes involved in the amyloid metabolism can elicit familial AD, the overwhelming majority of AD cases, dubbed sporadic AD, do not display this Mendelian inheritance pattern. Apolipoprotein E (APOE, the main lipid carrier protein in the central nervous system, is the only gene that has been robustly and consistently associated with AD risk. The purpose of the current paper is thus to highlight the pleiotropic roles and the structure-function relationship of APOE to stimulate both the functional characterization and the identification of novel lipid homeostasis-related molecular targets involved in AD.

  17. Apolipoprotein E Regulates Amyloid Formation within Endosomes of Pigment Cells

    Directory of Open Access Journals (Sweden)

    Guillaume van Niel

    2015-10-01

    Full Text Available Accumulation of toxic amyloid oligomers is a key feature in the pathogenesis of amyloid-related diseases. Formation of mature amyloid fibrils is one defense mechanism to neutralize toxic prefibrillar oligomers. This mechanism is notably influenced by apolipoprotein E variants. Cells that produce mature amyloid fibrils to serve physiological functions must exploit specific mechanisms to avoid potential accumulation of toxic species. Pigment cells have tuned their endosomes to maximize the formation of functional amyloid from the protein PMEL. Here, we show that ApoE is associated with intraluminal vesicles (ILV within endosomes and remain associated with ILVs when they are secreted as exosomes. ApoE functions in the ESCRT-independent sorting mechanism of PMEL onto ILVs and regulates the endosomal formation of PMEL amyloid fibrils in vitro and in vivo. This process secures the physiological formation of amyloid fibrils by exploiting ILVs as amyloid nucleating platforms.

  18. Increased concentration of clusterin/apolipoprotein J (apoJ) in hyperlipemic serum is paradoxically associated with decreased apoJ content in lipoproteins.

    Science.gov (United States)

    Rull, Anna; Martínez-Bujidos, Maria; Pérez-Cuellar, Montserrat; Pérez, Antonio; Ordóñez-Llanos, Jordi; Sánchez-Quesada, José Luis

    2015-08-01

    Clusterin/apolipoprotein J (apoJ) circulates in blood in part associated to lipoproteins or in unbound form. When bound to HDL, apoJ is antiatherogenic by inhibiting endothelial cell apoptosis; thus, any factor modifying apoJ association to HDL would decrease its antiatherogenic function. However, the exact distribution of apoJ in each lipoprotein fraction, or in lipoprotein-non bound form has not been specifically investigated either in normolipemia or in dyslipemia. Basic lipid profile and apoJ concentration were determined in sera from 70 subjects, including a wide range of cholesterol and triglyceride concentrations. Lipoproteins were isolated by ultracentrifugation and their lipid and apolipoprotein composition was assessed. In the overall population, serum apoJ positively associated with cholesterol, triglyceride and VLDL-C concentrations, and HDL-C and triglyceride were independent predictors of increased apoJ concentration. Approximately, 20.5% of circulating apoJ was associated with lipoproteins (18.5% HDL, 0.9% LDL and 1.1% VLDL) and 79.5% was not bound to lipoproteins. Serum apoJ concentration was higher in hypercholesterolemic (HC), hypertriglyceridemic (HTG) and combined hyperlipidemic (CHL) sera compared to normolipemic (NL) sera (HC, 98.15 ± 33.6 mg/L; HTG, 103.3 ± 36.8 mg/L; CHL, 131.7 ± 26.8 mg/L; NL, 66.7 ± 33.8 mg/L; P lipoproteins in the NL group whereas this proportion rounded 15% in hyperlipidemic subjects. Our findings indicate that hyperlipidemia increases the concentration of apoJ in serum but, in turn, the content of lipoprotein-associated apoJ decreases. The redistribution of apoJ in hyperlipidemia could compromise the antiatherogenic properties of HDL. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Apolipoprotein M affecting lipid metabolism or just catching a ride with lipoproteins in the circulation?

    DEFF Research Database (Denmark)

    Dahlbäck, B; Nielsen, Lars Bo

    2009-01-01

    Apolipoprotein M (apoM) is a novel apolipoprotein found mainly in high-density lipoproteins (HDL). Its function is yet to be defined. ApoM (25 kDa) has a typical lipocalin ss-barrel fold and a hydrophobic pocket. Retinoids bind apoM but with low affinity and may not be the natural ligands. ApoM r......; possible mechanisms include increased formation of pre-ss HDL, enhanced cholesterol mobilization from foam cells, and increased antioxidant properties....

  20. Relativistic bound states

    International Nuclear Information System (INIS)

    Ritchie, Burke

    2006-01-01

    The Hamiltonian for Dirac's second-order equation depends nonlinearly on the potential V and the energy E. For this reason the magnetic contribution to the Hamiltonian for s-waves, which has a short range, is attractive for a repulsive Coulomb potential (V>0) and repulsive for an attractive Coulomb potential (V 2 . Usually solutions are found in the regime E=mc 2 +ε , where except for high Z, ε 2 . Here it is shown that for V>0 the attractive magnetic term and the linear repulsive term combine to support a bound state near E=0.5mc 2 corresponding to a binding energy E b =-ε =0.5mc 2

  1. Bounding approaches to system identification

    CERN Document Server

    Norton, John; Piet-Lahanier, Hélène; Walter, Éric

    1996-01-01

    In response to the growing interest in bounding error approaches, the editors of this volume offer the first collection of papers to describe advances in techniques and applications of bounding of the parameters, or state variables, of uncertain dynamical systems. Contributors explore the application of the bounding approach as an alternative to the probabilistic analysis of such systems, relating its importance to robust control-system design.

  2. Market access through bound tariffs

    DEFF Research Database (Denmark)

    Sala, Davide; Yalcin, Erdal; Schröder, Philipp

    2010-01-01

    on the risk that exporters face in destination markets. The present paper formalizes the underlying interaction of risk, fixed export costs and firms' market entry decisions based on techniques known from the real options literature; doing so we highlight the important role of bound tariffs at the extensive...... margin of trade. We find that bound tariffs are more effective with higher risk destination markets, that a large binding overhang may still command substantial market access, and that reductions in bound tariffs generate effective market access even when bound rates are above current and longterm...

  3. Market Access through Bound Tariffs

    DEFF Research Database (Denmark)

    Sala, Davide; Schröder, Philipp J.H.; Yalcin, Erdal

    on the risk that exporters face in destination markets. The present paper formalizes the underlying interaction of risk, fixed export costs and firms' market entry decisions based on techniques known from the real options literature; doing so we highlight the important role of bound tariffs at the extensive...... margin of trade. We find that bound tariffs are more effective with higher risk destination markets, that a large binding overhang may still command substantial market access, and that reductions in bound tariffs generate effective market access even when bound rates are above current and long...

  4. Quivers of Bound Path Algebras and Bound Path Coalgebras

    Directory of Open Access Journals (Sweden)

    Dr. Intan Muchtadi

    2010-09-01

    Full Text Available bras and coalgebras can be represented as quiver (directed graph, and from quiver we can construct algebras and coalgebras called path algebras and path coalgebras. In this paper we show that the quiver of a bound path coalgebra (resp. algebra is the dual quiver of its bound path algebra (resp. coalgebra.

  5. Atorvastatin decreases apolipoprotein C-III in apolipoprotein B-containing lipoprotein and HDL in type 2 diabetes: a potential mechanism to lower plasma triglycerides

    NARCIS (Netherlands)

    Dallinga-Thie, Geesje M.; Berk-Planken, Ingrid I. L.; Bootsma, Aart H.; Jansen, Hans

    2004-01-01

    Apolipoprotein (apo)C-III is a constituent of HDL (HDL apoC-III) and of apoB-containing lipoproteins (LpB:C-III). It slows the clearance of triglyceride-rich lipoproteins (TRLs) by inhibition of the activity of the enzyme lipoprotein lipase (LPL) and by interference with lipoprotein binding to

  6. Influence of apolipoprotein-E gene on lipid profile, physical activity and body fat relationship. DOI:10.5007/1980-0037.2012v14n2p221

    Directory of Open Access Journals (Sweden)

    Thales Boaventura Rachid Nascimento

    2012-02-01

    Full Text Available Physical activity and body fat modify lipemia, and this effect seems to be influenced by apolipoprotein-E (APOE gene polymorphism. Thus, the purpose of this article was to review main results of studies that have analyzed the relation of APOE gene with physical activity and body fat on triglycerides, total cholesterol and low (LDL and high density lipoprotein (HDL concentrations. The Scientific Electronic Library Online – SciELO, Web of Science and PubMed database were used to locate the articles. The keywords used in combination were: apoe genotype, apolipoprotein-E polymorphism, physical exercise, physical activity, aerobic exercise, body fat and obesity. Originals scientific investigations performed with humans were included, and excluded those ones which involved samples with diseases, except obesity and/or lipemic disorders. It was observed a trend, that ε2 allele carriers are the ones with the greater improvements on lipemia from physical exercise. In addition, the body fat impact on the elevation of triglycerides and LDL are stronger in carriers of the ε2 and ε4 allele, respectively. Considering the small number of originals scientific investigations and their divergent results, reliable inferences can not be made about the APOE gene polymorphism influences on physical activity and body fat effect on lipemia. Thus, further studies with others populations and more volunteers for allele, as well as others exercise modalities and intensities, are necessary.

  7. Hypercholesterolemia and apolipoprotein B expression: Regulation by selenium status

    Directory of Open Access Journals (Sweden)

    Bansal Mohinder P

    2005-11-01

    Full Text Available Abstract Background Apolipoprotein B (apoB contains ligand-binding domain for the binding of LDL to LDL-R site, which enables the removal of LDL from circulation. Our recent data showed that selenium (Se is involved in the lipid metabolism. The present study was aimed to understand the effect of Se deficiency (0.02 ppm and selenium supplementation (1 ppm on apoB expression in liver during hypercholesterolemia in male Sprague Dawley rats. Animals were fed with control and high cholesterol diet (2% for 1 and 2 months. ApoB levels by ELISA and protein expression by western blot was done. Hepatic LDL receptor (LDL-R activity (in vivo and mRNA expression by RT-PCR was monitored. Results In selenium deficiency and on high cholesterol diet (HCD feeding apoB levels increased and LDL-R expression decreased significantly after 2 months. On 1 ppm selenium supplementation apoB expression significantly decreased and LDL-R expression increased after 2 months. But after one month of treatment there was no significant change observed in apoB and LDL-R expression. Conclusion So the present study demonstrates that Se deficiency leads to up regulation of apoB expression during experimental hypercholesterolemia. Selenium supplementation upto 1 ppm leads to downregulation of apoB expression. Further, this study will highlight the nutritional value of Se supplementation in lipid metabolism.

  8. Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy.

    Science.gov (United States)

    Liu, Chia-Chen; Liu, Chia-Chan; Kanekiyo, Takahisa; Xu, Huaxi; Bu, Guojun

    2013-02-01

    Apolipoprotein E (Apo-E) is a major cholesterol carrier that supports lipid transport and injury repair in the brain. APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the ε4 allele are at increased risk of AD compared with those carrying the more common ε3 allele, whereas the ε2 allele decreases risk. Presence of the APOE ε4 allele is also associated with increased risk of cerebral amyloid angiopathy and age-related cognitive decline during normal ageing. Apo-E-lipoproteins bind to several cell-surface receptors to deliver lipids, and also to hydrophobic amyloid-β (Aβ) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. Apo-E isoforms differentially regulate Aβ aggregation and clearance in the brain, and have distinct functions in regulating brain lipid transport, glucose metabolism, neuronal signalling, neuroinflammation, and mitochondrial function. In this Review, we describe current knowledge on Apo-E in the CNS, with a particular emphasis on the clinical and pathological features associated with carriers of different Apo-E isoforms. We also discuss Aβ-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk, and consider how to design effective strategies for AD therapy by targeting Apo-E.

  9. Apolipoprotein E genotypes associated with Alzheimer disease and concomitant stroke.

    Science.gov (United States)

    Fekih-Mrissa, Najiba; Klai, Sarra; Mrad, Meriem; Mansour, Malek; Zaouali, Jamel; Gritli, Nasreddine; Mrissa, Ridha

    2014-04-01

    The ɛ4 allele of the apolipoprotein E (APOE) gene is a well-characterized genetic risk factor for Alzheimer disease (AD). The association between stroke and a higher risk for AD has also been reported. Our study sought to determine the relationship between the APOE gene and AD and the comorbid risk of stroke. The subjects of this study consisted of 48 patients with AD and 48 members of a control group. All subjects were genotyped for APOE. The results clearly show a significant increased risk of AD in carriers of the APOE ε3/ε4 genotype (P = .003, odds ratio [OR] = 4.1) or ε4 allele (P = .001, OR = 4.2). The risk for stroke in AD patients was also increased for carriers of the APOE ε3/ε4 genotype (P = .02, OR = 9.0) and for carriers of the APOE ε4 allele (P = .004, OR = 5.5). The present study is the first to establish a relationship between APOE ε4 and concomitant AD and stroke in the Tunisian population. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  10. Cooperative unfolding of apolipoprotein A-1 induced by chemical denaturation.

    Science.gov (United States)

    Eckhardt, D; Li-Blatter, X; Schönfeld, H-J; Heerklotz, H; Seelig, J

    2018-05-25

    Apolipoprotein A-1 (Apo A-1) plays an important role in lipid transfer and obesity. Chemical unfolding of α-helical Apo A-1 is induced with guanidineHCl and monitored with differential scanning calorimetry (DSC) and CD spectroscopy. The unfolding enthalpy and the midpoint temperature of unfolding decrease linearly with increasing guanidineHCl concentration, caused by the weak binding of denaturant. At room temperature, binding of 50-60 molecules guanidineHCl leads to a complete Apo A-1 unfolding. The entropy of unfolding decreases to a lesser extent than the unfolding enthalpy. Apo A-1 chemical unfolding is a dynamic multi-state equilibrium that is analysed with the Zimm-Bragg theory modified for chemical unfolding. The chemical Zimm-Bragg theory predicts the denaturant binding constant K D and the protein cooperativity σ. Chemical unfolding of Apo A-1 is two orders of magnitude less cooperative than thermal unfolding. The free energy of thermal unfolding is ~0.2 kcal/mol per amino acid residue and ~1.0 kcal/mol for chemical unfolding at room temperature. The Zimm-Bragg theory calculates conformational probabilities and the chemical Zimm-Bragg theory predicts stretches of α-helical segments in dynamic equilibrium, unfolding and refolding independently and fast. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Apolipoprotein M in lipid metabolism and cardiometabolic diseases

    DEFF Research Database (Denmark)

    Borup, Anna; Christensen, Pernille Meyer; Nielsen, Lars B.

    2015-01-01

    : The apoM/S1P axis and its implications in atherosclerosis and lipid metabolism have been thoroughly studied. Owing to the discovery of the apoM/S1P axis, the scope of apoM research has broadened. ApoM and S1P have been implicated in lipid metabolism, that is by modulating HDL particles. Also......PURPOSE: This review will address recent findings on apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) in lipid metabolism and inflammatory diseases. RECENT FINDINGS: ApoM's likely role(s) in health and disease has become more diverse after the discovery that apoM functions...... as a chaperone for S1P. Hence, apoM has recently been implicated in lipid metabolism, diabetes and rheumatoid arthritis through in-vivo, in-vitro and genetic association studies. It remains to be established to which degree such associations with apoM can be attributed to its ability to bind S1P. SUMMARY...

  12. Glucose Regulates the Expression of the Apolipoprotein A5 Gene

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Moitrot, Emmanuelle; Rommens, Corinne; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2008-04-07

    The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.

  13. Apolipoprotein D Internalization Is a Basigin-dependent Mechanism.

    Science.gov (United States)

    Najyb, Ouafa; Brissette, Louise; Rassart, Eric

    2015-06-26

    Apolipoprotein D (apoD), a member of the lipocalin family, is a 29-kDa secreted glycoprotein that binds and transports small lipophilic molecules. Expressed in several tissues, apoD is up-regulated under different stress stimuli and in a variety of pathologies. Numerous studies have revealed that overexpression of apoD led to neuroprotection in various mouse models of acute stress and neurodegeneration. This multifunctional protein is internalized in several cells types, but the specific internalization mechanism remains unknown. In this study, we demonstrate that the internalization of apoD involves a specific cell surface receptor in 293T cells, identified as the transmembrane glycoprotein basigin (BSG, CD147); more particularly, its low glycosylated form. Our results show that internalized apoD colocalizes with BSG into vesicular compartments. Down-regulation of BSG disrupted the internalization of apoD in cells. In contrast, overexpression of basigin in SH-5YSY cells, which poorly express BSG, restored the uptake of apoD. Cyclophilin A, a known ligand of BSG, competitively reduced apoD internalization, confirming that BSG is a key player in the apoD internalization process. In summary, our results demonstrate that basigin is very likely the apoD receptor and provide additional clues on the mechanisms involved in apoD-mediated functions, including neuroprotection. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Apolipoprotein E and presenilin-1 genotypes in Huntington's disease.

    Science.gov (United States)

    Panas, M; Avramopoulos, D; Karadima, G; Petersen, M B; Vassilopoulos, D

    1999-07-01

    Huntington's disease (HD) is an autosomal dominant degenerative disease of the central nervous system manifested by involuntary movements (chorea), psychiatric manifestations, and cognitive impairment with a variable age at onset. This variability is mainly attributed to genetic factors. The so-called aging genes [e.g., those for apolipoprotein E (APOE) and presenilin-1 (PS-1) have been implicated in determining the age at onset of Alzheimer's disease, a disease sharing common clinical features with HD. In 60 unrelated patients suffering from HD (mean age at onset 40.1 years, range 20-65) we determined number of CAG repeats and the distribution of the APOE alleles (epsilon2, epsilon3, epsilon4) and PS-1 alleles. The results showed that: (a) The age at onset was higher in the group of patients with the epsilon4 allele (51.6 vs. 38.0 P<0.002), (b) The correlation between the age at onset and the number of CAG repeats was strong in patients with the epsilon3/epsilon3 genotype while it was not detected in patients with epsilon3/epsilon4 genotype. (c) No correlation was found between age at onset and PS-1 alleles. In conclusion, APOE seems to be a significant factor influencing the age at onset of Huntington's disease.

  15. Bounds for Asian basket options

    Science.gov (United States)

    Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

    2008-09-01

    In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

  16. Product differentiation under bounded rationality

    NARCIS (Netherlands)

    Vermeulen, B.; Poutré, La J.A.; Kok, de A.G.; Pyka, A.; Handa, H.; Ishibuchi, H.; Ong, Y.-S.; Tan, K.-C.

    2015-01-01

    We study product differentiation equilibria and dynamics on the Salop circle under bounded rationality. Due to bounded rationality, firms tend to agglomerate in pairs. Upon adding a second tier of component suppliers, downstream assemblers may escape pairwise horizontal agglomeration. Moreover, we

  17. Metabolism of organically bound tritium

    International Nuclear Information System (INIS)

    Travis, C.C.

    1984-01-01

    The classic methodology for estimating dose to man from environmental tritium ignores the fact that organically bound tritium in foodstuffs may be directly assimilated in the bound compartment of tissues without previous oxidation. We propose a four-compartment model consisting of a free body water compartment, two organic compartments, and a small, rapidly metabolizing compartment. The utility of this model lies in the ability to input organically bound tritium in foodstuffs directly into the organic compartments of the model. We found that organically bound tritium in foodstuffs can increase cumulative total body dose by a factor of 1.7 to 4.5 times the free body water dose alone, depending on the bound-to-loose ratio of tritium in the diet. Model predictions are compared with empirical measurements of tritium in human urine and tissue samples, and appear to be in close agreement. 10 references, 4 figures, 3 tables

  18. [Apolipoprotein e polymorphism and cognitive function change of the elderly in a rural area, Korea].

    Science.gov (United States)

    Kim, Sang Kyu; Hwang, Tae Yoon; Lee, Kyeong Soo; Kang, Pock Soo; Cho, Hee Soon; Bae, Young Kyung

    2009-07-01

    The aim of this study is to examine the cognitive function change related to aging, the incidence of cognitive impairment, and the association between apolipoprotein E polymorphism and cognitive impairment through a follow-up of the elderly with normal cognitive ability at baseline. Two hundred and fifteen subjects aged 65 and over were surveyed in February, 1998 (baseline survey), and their cognitive function was assessed again in 2003 (1st follow-up) and the once again in 2006 (2nd follow-up). Ninety one subjects completed all surveys up through the 2nd follow-up and their cognitive function scores using MMSE-K (Korean Version of the Mini-Mental State Examination) and the distribution of apolipoprotein E allele were analyzed. The cognitive function scores decreased with aging and the difference between baseline and the 2nd follow-up scores of the study increased with the age group. The incidence rate of cognitive impairment through an 8-year follow-up was 38.5% and higher in older age groups. Age was the only significant factor for incidence of cognitive impairment, but there was no significant association between apolipoprotein E genotype and incidence of cognitive impairment. The cognition of the elderly decreased with aging and the association of apolipoprotein E genotype with incidence of cognitive impairment was not significant in this study. To confirm the association between apolipoprotein E polymorphism and incidence of cognitive impairment further studies will be needed.

  19. Increase of arginase activity in old apolipoprotein-E deficient mice under Western diet associated with changes in neurovascular unit

    Directory of Open Access Journals (Sweden)

    Badaut Jérôme

    2012-06-01

    Full Text Available Abstract Aging and atherosclerosis are well-recognized risk factors for cardiac and neurovascular diseases. The Apolipoprotein E deficient (ApoE−/− mouse on a high-fat diet is a classical model of atherosclerosis, characterized by the presence of atherosclerotic plaques in extracranial vessels but not in cerebral arteries. Increase in arginase activity was shown to participate in vascular dysfunction in the peripheral arteries of atherosclerotic mice by changing the level of nitric oxide (NO. NO plays a key role in the physiological functions of the neurovascular unit (NVU. However, the regulation of arginase expression and activity in the brain was never investigated in association with changes in the NVU, ApoE deficiency and high fat diet. Fourteen-month-old ApoE−/− mice on high-fat diet exhibited deposition of lipids in the NVU, impairment of blood–brain barrier properties, astrogliosis and an increase of aquaporin 4 staining. In association with these changes, brain arginase activity was significantly increased in the old ApoE−/− mice as compared to old wild type mice, with an increase in the level of arginase type I in the blood vessels. In conclusion, aging in this classical mouse model of atherosclerosis induces an increase in the level and activity of arginase I that may impair NO synthesis and contribute to changes in the NVU leading to blood–brain barrier leakage and inflammation.

  20. Quantitation of apolipoprotein epsilon gene expression by competitive polymerase chain reaction in a patient with familial apolipoprotein E deficiency.

    Science.gov (United States)

    Dobmeyer, J M; Rexin, M; Dobmeyer, T S; Klein, S A; Rossol, R; Feussner, G

    1998-06-22

    A simple method of obtaining semiquantitative and reliable data on apolipoprotein (apo) sigma gene expression is described. We detected apo sigma specific sequences by reverse transcription (rT)-PCR. For quantitative measurement, an apo sigma DNA standard was produced allowing the development of a competitive PCR-method. The efficiency of RNA extraction and cDNA synthesis was controlled by quantitation of a housekeeping gene (glyceraldehyde-3-phosphatedehydrogenase, G3PDH) in separate reactions. To imitate a defined induction of apo sigma gene expression, serial twofold dilutions of total RNA were reversely transcribed and the respective cDNAs used to perform a competitive apo sigma and G3PDH PCR. The change in apo sigma cDNA and G3PDH cDNA was 1.7-2.3-fold with an expected value of 2.0-fold. Standard deviations in three independently performed experiments were within a range of < 15% of the mean, indicating low intra-assay variation and high reproducibility. To illustrate this method, apo sigma gene expression was measured in a patient with complete lack of functional active apo E in comparison to healthy controls. The method presented here might be valuable in assessment of apo sigma gene expression in human disease.

  1. [Fundamental evaluation of apolipoprotein B-48 by chemiluminescence enzyme immunoassay--identification of apolipoprotein B-48 with immunoblotting].

    Science.gov (United States)

    Sato, Itsuko; Fujioka, Yoshio; Hayashi, Fujio; Mukai, Masahiko; Kawano, Seiji; Ishikawa, Yuichi; Yamashita, Shizuya; Kumagai, Shunichi

    2007-06-01

    Apolipoprotein B-48 (apo B-48) is a constituent of chylomicrons and chylomicron remnants, and its fasting concentration has been reported to be a marker of postprandial hyperlipidemia, which is thought to be a risk factor of atherosclerosis. We evaluated the serum apo B-48 concentrations by chemiluminescence enzyme immunoassay (CLEIA), which was recently introduced as Lumipulse f fully automated immunosaasy analyzer by Fujirebio Inc (Tokyo, Japan), and performed immunoblotting on agarose gel electrophoresis with anti-apo B-48 antibody. Apo B-48 assay was intra-assay reproducible (CVs: 1.9-3.1%) and inter-assay reproducible (CVs: 2.2-4.4%). The assay range for apo B-48 was from 0.2 to 40.0 microg/ml. The effects of interfering substances such as free/conjugated birirubin, hemoglobin, Intrafat, ascorbic acid and rheumatoid factor were negligible. For storage, it was preferable to freeze, and to avoid frozen-thaw process as much as possible. Anti-apo B-48 antibody was reactive over a wide range from origin to the position of very-low-density lipoproteins in immunoblotting after agarose gel electrophoresis. Apo B-48 measurement by CLEIA was feasible to clinical use for the assessment of lipoprotein metabolism.

  2. Molecular Characterization and Growth Association of Two Apolipoprotein A-Ib Genes in Common Carp (Cyprinus carpio).

    Science.gov (United States)

    Wang, Xinhua; Yu, Xiaomu; Tong, Jingou

    2016-09-16

    Apolipoprotein A-I (ApoA-I) is functionally involved in the transportation and metabolism of lipids in vertebrates. In this study, two isoforms of apoA-Ib in common carp (Cyprinus carpio L.) were characterized. Sequence comparison and phylogenetic analysis showed that C. carpio ApoA-Ib is relatively conserved within cyprinid fishes. During embryonic development, C. carpio apoA-Ib was first expressed at the stage of multi-cells, and the highest mRNA level was observed at the stage of optic vesicle. A ubiquitous expression pattern was detected in various tissues with extreme predominance in the liver. Significantly different expression levels were observed between light and heavy body weight groups and also in the compensatory growth test. Seventeen and eight single-nucleotide polymorphisms (SNPs) were identified in matured mRNA of the C. carpio apoA-Ib.1 and apoA-Ib.2, respectively. Two of these SNPs (apoA-Ib.2-g.183A>T and apoA-Ib.2-g.1753C>T) were significantly associated with body weight and body length in two populations of common carp. These results indicate that apoA-Ib may play an important role in the modulation of growth and development in common carp.

  3. Atherosclerosis, apolipoprotein E and the prevalence of dementia and Alzheimer's disease in a population-based study: the Rotterdam Study

    NARCIS (Netherlands)

    A. Ott (Alewijn); M.L. Bots (Michiel); A.J.C. Slooter (Arjen); F. van Harskamp (Frans); C.M. van Duijn (Cornelia); D.E. Grobbee (Diederick); M.M.B. Breteler (Monique); C. van Broeckhoven (Christine); A. Hofman (Albert)

    1997-01-01

    textabstractBACKGROUND: Vascular disorders have been implicated in dementia, but whether atherosclerosis is related to the most frequent type of dementia, Alzheimer's disease, is not known. The apolipoprotein-E genotype has been associated with Alzheimer's disease, and we postulate that it plays a

  4. Curvature bound from gravitational catalysis

    Science.gov (United States)

    Gies, Holger; Martini, Riccardo

    2018-04-01

    We determine bounds on the curvature of local patches of spacetime from the requirement of intact long-range chiral symmetry. The bounds arise from a scale-dependent analysis of gravitational catalysis and its influence on the effective potential for the chiral order parameter, as induced by fermionic fluctuations on a curved spacetime with local hyperbolic properties. The bound is expressed in terms of the local curvature scalar measured in units of a gauge-invariant coarse-graining scale. We argue that any effective field theory of quantum gravity obeying this curvature bound is safe from chiral symmetry breaking through gravitational catalysis and thus compatible with the simultaneous existence of chiral fermions in the low-energy spectrum. With increasing number of dimensions, the curvature bound in terms of the hyperbolic scale parameter becomes stronger. Applying the curvature bound to the asymptotic safety scenario for quantum gravity in four spacetime dimensions translates into bounds on the matter content of particle physics models.

  5. Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.

    Science.gov (United States)

    Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine

    2018-02-01

    The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. Apoe -/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r e/e ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe -/- Mc1r e/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe -/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe -/- Mc1r e/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C high monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C high monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation. © 2017 The Authors.

  6. IL-25 inhibits atherosclerosis development in apolipoprotein E deficient mice.

    Directory of Open Access Journals (Sweden)

    Polyxeni T Mantani

    Full Text Available IL-25 has been implicated in the initiation of type 2 immunity and in the protection against autoimmune inflammatory diseases. Recent studies have identified the novel innate lymphoid type 2 cells (ILC2s as an IL-25 target cell population. The purpose of this study was to evaluate if IL-25 has any influence on atherosclerosis development in mice.Administration of 1 μg IL-25 per day for one week to atherosclerosis-prone apolipoprotein (apoE deficient mice, had limited effect on the frequency of T cell populations, but resulted in a large expansion of ILC2s in the spleen. The expansion was accompanied by increased levels of anti-phosphorylcholine (PC natural IgM antibodies in plasma and elevated levels of IL-5 in plasma and spleen. Transfer of ILC2s to apoE deficient mice elevated the natural antibody-producing B1a cell population in the spleen. Treatment of apoE/Rag-1 deficient mice with IL-25 was also associated with extensive expansion of splenic ILC2s and increased plasma IL-5, suggesting ILC2s to be the source of IL-5. Administration of IL-25 in IL-5 deficient mice resulted in an expanded ILC2 population, but did not stimulate generation of anti-PC IgM, indicating that IL-5 is not required for ILC2 expansion but for the downstream production of natural antibodies. Additionally, administration of 1 μg IL-25 per day for 4 weeks in apoE deficient mice reduced atherosclerosis in the aorta both during initiation and progression of the disease.The present findings demonstrate that IL-25 has a protective role in atherosclerosis mediated by innate responses, including ILC2 expansion, increased IL-5 secretion, B1a expansion and natural anti-PC IgM generation, rather than adaptive Th2 responses.

  7. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lasrich, Dorothee; Bartelt, Alexander [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Grewal, Thomas, E-mail: thomas.grewal@sydney.edu.au [Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW 2006 (Australia); Heeren, Joerg, E-mail: heeren@uke.de [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

    2015-09-10

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation.

  8. Interaction of an atypical Plasmodium falciparum ETRAMP with human apolipoproteins

    Directory of Open Access Journals (Sweden)

    Sahasrabudhe Sudhir

    2008-10-01

    Full Text Available Abstract Background In order to establish a successful infection in the human host, the malaria parasite Plasmodium falciparum must establish interactions with a variety of human proteins on the surface of different cell types, as well as with proteins inside the host cells. To better understand this aspect of malaria pathogenesis, a study was conducted with the goal of identifying interactions between proteins of the parasite and those of its human host. Methods A modified yeast two-hybrid methodology that preferentially selects protein fragments that can be expressed in yeast was used to conduct high-throughput screens with P. falciparum protein fragments against human liver and cerebellum libraries. The resulting dataset was analyzed to exclude interactions that are not likely to occur in the human host during infection. Results An initial set of 2,200 interactions was curated to remove proteins that are unlikely to play a role in pathogenesis based on their annotation or localization, and proteins that behave promiscuously in the two-hybrid assay, resulting in a final dataset of 456 interactions. A cluster that implicates binding between P. falciparum PFE1590w/ETRAMP5, a putative parasitophorous vacuole membrane protein, and human apolipoproteins ApoA, ApoB and ApoE was selected for further analysis. Different isoforms of ApoE, which are associated with different outcomes of malaria infection, were shown to display differential interactions with PFE1590w. Conclusion A dataset of interactions between proteins of P. falciparum and those of its human host was generated. The preferential interaction of the P. falciparum PFE1590w protein with the human ApoE ε3 and ApoE ε4 isoforms, but not the ApoE ε2 isoform, supports the hypothesis that ApoE genotype affects risk of malaria infection. The dataset contains other interactions of potential relevance to disease that may identify possible vaccine candidates and drug targets.

  9. Combining Alphas via Bounded Regression

    Directory of Open Access Journals (Sweden)

    Zura Kakushadze

    2015-11-01

    Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

  10. Improved Range Searching Lower Bounds

    DEFF Research Database (Denmark)

    Larsen, Kasper Green; Nguyen, Huy L.

    2012-01-01

    by constructing a hard input set and query set, and then invoking Chazelle and Rosenberg's [CGTA'96] general theorem on the complexity of navigation in the pointer machine. For the group model, we show that input sets and query sets that are hard for range reporting in the pointer machine (i.e. by Chazelle...... and Rosenberg's theorem), are also hard for dynamic range searching in the group model. This theorem allows us to reuse decades of research on range reporting lower bounds to immediately obtain a range of new group model lower bounds. Amongst others, this includes an improved lower bound for the fundamental...

  11. Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins

    DEFF Research Database (Denmark)

    Varkey, Jobin; Isas, Jose Mario; Mizuno, Naoko

    2010-01-01

    Synucleins and apolipoproteins have been implicated in a number of membrane and lipid trafficking events. Lipid interaction for both types of proteins is mediated by 11 amino acid repeats that form amphipathic helices. This similarity suggests that synucleins and apolipoproteins might have...... of amphipathic helices alone. Moreover, we frequently observed that a-synuclein caused membrane structures that had the appearance of nascent budding vesicles. The ability to function as a minimal machinery for vesicle budding agrees well with recent findings that a-synuclein plays a role in vesicle trafficking...

  12. Bound states in string nets

    Science.gov (United States)

    Schulz, Marc Daniel; Dusuel, Sébastien; Vidal, Julien

    2016-11-01

    We discuss the emergence of bound states in the low-energy spectrum of the string-net Hamiltonian in the presence of a string tension. In the ladder geometry, we show that a single bound state arises either for a finite tension or in the zero-tension limit depending on the theory considered. In the latter case, we perturbatively compute the binding energy as a function of the total quantum dimension. We also address this issue in the honeycomb lattice where the number of bound states in the topological phase depends on the total quantum dimension. Finally, the internal structure of these bound states is analyzed in the zero-tension limit.

  13. On functions of bounded semivariation

    Czech Academy of Sciences Publication Activity Database

    Monteiro, Giselle Antunes

    2015-01-01

    Roč. 40, č. 2 (2015), s. 233-276 ISSN 0147-1937 Institutional support: RVO:67985840 Keywords : semivariation * functions of bounded variation * regulated functions Subject RIV: BA - General Mathematics http://projecteuclid.org/euclid.rae/1491271216

  14. Computational Lower Bounds Using Diagonalization

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 7. Computational Lower Bounds Using Diagonalization - Languages, Turing Machines and Complexity Classes. M V Panduranga Rao. General Article Volume 14 Issue 7 July 2009 pp 682-690 ...

  15. Intralipid decreases apolipoprotein M levels and insulin sensitivity in rats.

    Directory of Open Access Journals (Sweden)

    Lu Zheng

    Full Text Available BACKGROUND: Apolipoprotein M (ApoM is a constituent of high-density lipoproteins (HDL. It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels. AIMS: To assess the effects of increased free fatty acids (FFAs levels after short-term Intralipid infusion on insulin sensitivity and hepatic ApoM gene expression. METHODS: Adult male Sprague-Dawley (SD rats infused with 20% Intralipid solution for 6 h. Glucose infusion rates (GIR were determined by hyperinsulinemic-euglycemic clamp during Intralipid infusion and plasma FFA levels were measured by colorimetry. Rats were sacrificed after Intralipid treatment and livers were sampled. Human embryonic kidney 293T cells were transfected with a lentivirus mediated human apoM overexpression system. Goto-Kakizaki (GK rats were injected with the lentiviral vector and insulin tolerance was assessed. Gene expression was assessed by real-time RT-PCR and PCR array. RESULTS: Intralipid increased FFAs by 17.6 folds and GIR was decreased by 27.1% compared to the control group. ApoM gene expression was decreased by 40.4% after Intralipid infusion. PPARβ/δ expression was not changed by Intralipid. Whereas the mRNA levels of Acaca, Acox1, Akt1, V-raf murine sarcoma 3611 viral oncogene homolog, G6pc, Irs2, Ldlr, Map2k1, pyruvate kinase and RBC were significantly increased in rat liver after Intralipid infusion. The Mitogen-activated protein kinase 8 (MAPK8 was significantly down-regulated in 293T cells overexpressing ApoM. Overexpression of human ApoM in GK rats could enhance the glucose-lowering effect of exogenous insulin. CONCLUSION: These results suggest that Intralipid could decrease hepatic ApoM levels. ApoM overexpression may have a potential role in improving insulin resistance in vivo and modulating apoM expression might be a future therapeutic strategy against insulin resistance in type 2 diabetes.

  16. Sildenafil restores endothelial function in the apolipoprotein E knockout mouse

    Directory of Open Access Journals (Sweden)

    Balarini Camille M

    2013-01-01

    Full Text Available Abstract Background Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS and nitric oxide (NO. Sildenafil, a selective phosphodiesterase-5 (PDE5 inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE−/− mice. Methods ApoE−/− mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage were compared to the untreated apoE−/− and the wild-type (WT mice. Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor or apocynin (NADPH oxidase inhibitor. In addition, the atherosclerotic lesions were quantified and superoxide production was assessed. Results Sildenafil restored the vasodilator response to acetylcholine (ACh in the aortic rings of the apoE−/− mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE−/− mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta. Conclusion This is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous

  17. HDL-apoA-I exchange: rapid detection and association with atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Mark S Borja

    Full Text Available High density lipoprotein (HDL cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease.

  18. Improving prediction of ischemic cardiovascular disease in the general population using apolipoprotein B

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Gorm Boje

    2007-01-01

    Apolipoprotein B (apoB) levels predict fatal myocardial infarction. Whether apoB also predicts nonfatal ischemic cardiovascular events is unclear. We tested the following hypotheses: apoB predicts ischemic cardiovascular events, and apoB is a better predictor of ischemic cardiovascular events tha...

  19. Hyperlipidemia and cutaneous abnormalities in transgenic mice overexpressing human apolipoprotein C1

    NARCIS (Netherlands)

    Jong, M. C.; Gijbels, M. J.; Dahlmans, V. E.; Gorp, P. J.; Koopman, S. J.; Ponec, M.; Hofker, M. H.; Havekes, L. M.

    1998-01-01

    Transgenic mice were generated with different levels of human apolipoprotein C1 (APOC1) expression in liver and skin. At 2 mo of age, serum levels of cholesterol, triglycerides (TG), and FFA were strongly elevated in APOC1 transgenic mice compared with wild-type mice. These elevated levels of serum

  20. Apolipoprotein E in Temporal Lobe Epilepsy: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2006-01-01

    Full Text Available Purpose: To investigate the relationship of apolipoprotein E (apoE genotype, plasma levels of apoE and lipids in temporal lobe epilepsy (TLE patients in Asian Indians. Status of plasma levels of Apo E in epilepsy patients has not been reported till date.

  1. Apolipoprotein D is associated with long-term outcome in patients with schizophrenia

    DEFF Research Database (Denmark)

    Hansen, Thomas Folkmann; Hemmingsen, R P; Wang, A G

    2006-01-01

    Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second, gene...

  2. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    International Nuclear Information System (INIS)

    Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-01-01

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  3. Plasma apolipoprotein M is reduced in metabolic syndrome but does not predict intima media thickness

    DEFF Research Database (Denmark)

    Dullaart, Robin P F; Plomgaard, Peter; de Vries, Rindert

    2009-01-01

    BACKGROUND: Apolipoprotein (apo) M may exert anti-atherogenic properties in experimental studies. Its hepatic gene expression may be linked to glucose and lipid metabolism. Plasma apoM is decreased in obese mouse models. We hypothesized that plasma apoM is lower in metabolic syndrome (Met...

  4. Apolipoprotein E4 reduces evoked hippocampal acetylcholine release in adult mice

    Czech Academy of Sciences Publication Activity Database

    Dolejší, Eva; Liraz, O.; Rudajev, Vladimír; Zimčík, Pavel; Doležal, Vladimír; Michaelson, D. M.

    2016-01-01

    Roč. 136, č. 3 (2016), s. 503-509 ISSN 0022-3042 R&D Projects: GA MŠk(CZ) LH13269 Institutional support: RVO:67985823 Keywords : acetylcholine release * Alzheimer's disease (AD) * apolipoprotein E4 (apoE4) * hippocampus Subject RIV: FH - Neurology Impact factor: 4.083, year: 2016

  5. Expression of apolipoprotein B in the kidney attenuates renal lipid accumulation

    DEFF Research Database (Denmark)

    Krzystanek, Marcin; Pedersen, Tanja Xenia; Bartels, Emil Daniel

    2010-01-01

    The ability to produce apolipoprotein (apo) B-containing lipoproteins enables hepatocytes, enterocytes, and cardiomyocytes to export triglycerides. In this study, we examined secretion of apoB-containing lipoproteins from mouse kidney and its putative impact on triglyceride accumulation in the tu...

  6. Lipid, lipoprotein, and apolipoprotein profiles in active and sedentary men with tetraplegia

    NARCIS (Netherlands)

    Dallmeijer, A J; Hopman, M T; van der Woude, L H

    1997-01-01

    OBJECTIVE: To investigate whether the risk profile of coronary heart disease (CHD) is more favorable in physically active men with tetraplegia compared with sedentary men with tetraplegia. DESIGN: Using a cross-sectional design, the lipid and (apo)lipoprotein concentrations of 11 active and 13

  7. Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice

    DEFF Research Database (Denmark)

    Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin

    2012-01-01

    Apolipoprotein E (apoE) is an endogenous negative regulator of airway hyperreactivity (AHR) and mucous cell metaplasia in experimental models of house dust mite (HDM)-induced airway disease. The gene encoding human apoE is polymorphic, with three common alleles (e2, e3, and e4) reflecting single ...

  8. Apolipoprotein C3 deficiency results in diet-induced obesity and aggravated insulin resistance in mice

    NARCIS (Netherlands)

    Duivenvoorden, Ilse; Teusink, Bas; Rensen, Patrick C.; Romijn, Johannes A.; Havekes, Louis M.; Voshol, Peter J.

    2005-01-01

    Our aim was to study whether the absence of apolipoprotein (apo) C3, a strong inhibitor of lipoprotein lipase (LPL), accelerates the development of obesity and consequently insulin resistance. Apoc3(-/-) mice and wild-type littermates were fed a high-fat (46 energy %) diet for 20 weeks. After 20

  9. Protection from obesity and insulin resistance in mice overexpressing human apolipoprotein C1

    NARCIS (Netherlands)

    Jong, M. C.; Voshol, P. J.; Muurling, M.; Dahlmans, V. E.; Romijn, J. A.; Pijl, H.; Havekes, L. M.

    2001-01-01

    Apolipoprotein (APO) C1 is a 6.6-kDa protein present in plasma and associated with lipoproteins. Using hyperinsulinemic-euglycemic clamp tests, we previously found that in APOC1 transgenic mice, the whole-body insulin-mediated glucose uptake is increased concomitant with a decreased fatty acid

  10. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    Energy Technology Data Exchange (ETDEWEB)

    Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-10-01

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  11. Electroimmunoassay, radioimmunoassay, and radial immunodiffusion assay evaluated for quantification of human apolipoprotein B

    International Nuclear Information System (INIS)

    Curry, M.D.; Gustafson, A.; Alaupovic, P.; McConathy, W.J.

    1978-01-01

    We examined three immunoassay techniques for measuring apolipoprotein B in serum and major lipoprotein density fractions from normolipidemic and hyperlipoproteinemic persons, comparing values by electroimmunoassay, radioimmunoassay, and radial immunodiffusion assay with those determined gravimetrically. Electroimmunoassay is faster and simpler than radioimmunoassay, and equally precise (within- and between-assay coefficients of variation for both were 5 and 7%, respectively). All the immunoassays gave results that agreed with those by gravimetry for normolipidemic sera and the corresponding lipoprotein density fractions, but only electroimmunoassay results agreed with those by gravimetry for apolipoprotein B in lipoproteins of d < 1.019 g/ml isolated from hypertriglyceridemic patients. Concentrations of apolipoprotein B in plasma, determined by electroimmunoassay in a population of normal persons and patients with primary hyperlipoproteinemias, were: normals, 980 +- 200; type 1, 700 +- 160; type IIa, 2000 +- 260; type IIb, 2180 +- 300; type III, 1300 +- 340; type IV, 1470 +- 400; and type V, 1550 +- 390 mg/liter (mean +- SD). Lipoprotein density fractions from the hyperlipoproteinemic patients each had a characteristic distribution of free and associated forms of lipoprotein family B. The absolute concentration and distribution of apolipoprotein B between the free and associated forms of lipoprotein B may represent a useful indicator of the underlying biochemical defect

  12. Apolipoprotein C3 polymorphism is associated with cognitive function in Caribbean Hispanics

    Science.gov (United States)

    Background: Apolipoprotein C3(APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired ...

  13. Simulation bounds for system availability

    International Nuclear Information System (INIS)

    Tietjen, G.L.; Waller, R.A.

    1976-01-01

    System availability is a dominant factor in the practicality of nuclear power electrical generating plants. A proposed model for obtaining either lower bounds or interval estimates on availability uses observed data on ''n'' failure-to-repair cycles of the system to estimate the parameters in the time-to-failure and time-to-repair models. These estimates are then used in simulating failure/repair cycles of the system. The availability estimate is obtained for each of 5000 samples of ''n'' failure/repair cycles to form a distribution of estimates. Specific percentile points of those simulated distributions are selected as lower simulation bounds or simulation interval bounds for the system availability. The method is illustrated with operational data from two nuclear plants for which an exponential time-to-failure and a lognormal time-to-repair are assumed

  14. Primary Genetic Investigation of a Hyperlipidemia Model: Molecular Characteristics and Variants of the Apolipoprotein E Gene in Mongolian Gerbil

    Directory of Open Access Journals (Sweden)

    Yuehuan Liu

    2014-01-01

    Full Text Available The objective of this work was to establish a novel Mongolian gerbil (Meriones unguiculatus hyperlipidemia model and to investigate its susceptibility genetic basis. Two rodent (gerbil and rat hyperlipidemia models were induced by feeding a high fat/high-cholesterol (HF/HC diet. There were significant increases of serum total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C, and high-density lipoprotein cholesterol (HDL-C in gerbils within a 4-week modeling period. About 10–30% of >8-month-old individuals developed hyperlipidemia spontaneously. The apolipoprotein E (ApoE gene was cloned by merging a sequence of rapid amplification of cDNA ends (RACE and nested polymerase chain reaction products. The results revealed an open reading frame of 948 bp, encoding a protein of 298 amino acids. The gene without a 5′-UTR region in the first intron was highly homologous to human Apo-A-I and rat Apo-A-IV. The distribution of expression of the ApoE gene in liver, brain, heart, lung, kidney, and adrenal gland was detected by an ABC immunohistochemical procedure. Three single nucleotide polymorphisms (SNPs; C97T, G781T, and A1774T were first found using PCR-single-strand conformation polymorphism (PCR-SSCP in a closed population containing 444 animals. Correlation analysis confirmed that new SNPs , age, and gender were associated significantly (P<0.05 with hyperlipidemia.

  15. Relativistic bound state wave functions

    International Nuclear Information System (INIS)

    Micu, L.

    2005-01-01

    A particular method of writing the bound state wave functions in relativistic form is applied to the solutions of the Dirac equation with confining potentials in order to obtain a relativistic description of a quark antiquark bound system representing a given meson. Concerning the role of the effective constituent in the present approach we first observe that without this additional constituent we couldn't expand the bound state wave function in terms of products of free states. Indeed, we notice that if the wave function depends on the relative coordinates only, all the expansion coefficients would be infinite. Secondly we remark that the effective constituent enabled us to give a Lorentz covariant meaning to the potential energy of the bound system which is now seen as the 4th component of a 4-momentum. On the other side, by relating the effective constituent to the quantum fluctuations of the background field which generate the binding, we provided a justification for the existence of some spatial degrees of freedom accompanying the interaction potential. These ones, which are quite unusual in quantum mechanics, in our model are the natural consequence of the the independence of the quarks and can be seen as the effect of the imperfect cancellation of the vector momenta during the quantum fluctuations. Related with all these we remark that the adequate representation for the relativistic description of a bound system is the momentum representation, because of the transparent and easy way of writing the conservation laws and the transformation properties of the wave functions. The only condition to be fulfilled is to find a suitable way to take into account the potential energy of the bound system. A particular feature of the present approach is that the confining forces are due to a kind of glue where both quarks are embedded. This recalls other bound state models where the wave function is factorized in terms of constituent wave functions and the confinement is

  16. Four-quark bound states

    International Nuclear Information System (INIS)

    Zouzou, S.

    1986-01-01

    In the framework of simple non-relativistic potential models, we examine the system consisting of two quarks and two antiquarks with equal or unequal masses. We search for possible bound states below the threshold for the spontaneous dissociation into two mesons. We solve the four body problem by empirical or systematic variational methods and we include the virtual meson-meson components of the wave function. With standard two-body potentials, there is no proliferation of multiquarks. With unequal quark masses, we obtain however exotic (anti Qanti Qqq) bound states with a baryonic antidiquark-quark-quark structure very analogous to the heavy flavoured (Q'qq) baryons. (orig.)

  17. Bound entanglement and local realism

    International Nuclear Information System (INIS)

    Kaszlikowski, Dagomir; Zukowski, Marek; Gnacinski, Piotr

    2002-01-01

    We show using a numerical approach, which gives necessary and sufficient conditions for the existence of local realism, that the bound entangled state presented in Bennett et al. [Phys. Rev. Lett. 82, 5385 (1999)] admits a local and realistic description. We also find the lowest possible amount of some appropriate entangled state that must be ad-mixed to the bound entangled state so that the resulting density operator has no local and realistic description and as such can be useful in quantum communication and quantum computation

  18. Metabolic hormones, apolipoproteins, adipokines, and cytokines in the alveolar lining fluid of healthy adults: compartmentalization and physiological correlates.

    Directory of Open Access Journals (Sweden)

    Carlos O Mendivil

    Full Text Available Our current understanding of hormone regulation in lung parenchyma is quite limited. We aimed to quantify a diverse array of biologically relevant protein mediators in alveolar lining fluid (ALF, compared to serum concentrations, and explore factors associated with protein compartmentalization on either side of the air-blood barrier.Participants were 24 healthy adult non-smoker volunteers without respiratory symptoms or significant medical conditions, with normal lung exams and office spirometry. Cell-free bronchoalveolar lavage fluid and serum were analyzed for 24 proteins (including enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines using a highly sensitive multiplex ELISA. Measurements were normalized to ALF concentrations. The ALF:serum concentration ratios were examined in relation to measures of protein size, hydrophobicity, charge, and to participant clinical and spirometric values.ALF measurements from 24 individuals detected 19 proteins, including adiponectin, adipsin, apoA-I, apoA-II, apoB, apoC-II, apoC-III, apoE, C-reactive protein, ghrelin, glucose-dependent insulinotropic peptide (GIP, glucagon-like peptide-1 (GLP-1, glucagon, insulin, leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, resistin, and visfatin. C-peptide and serpin E1 were not detected in ALF for any individual, and IL-6, IL-10, and TNF-alpha were not detected in either ALF or serum for any individual. In general, ALF levels were similar or lower in concentration for most proteins compared to serum. However, ghrelin, resistin, insulin, visfatin and GLP-1 had ALF concentrations significantly higher compared to serum. Importantly, elevated ALF:serum ratios of ghrelin, visfatin and resistin correlated with protein net charge and isoelectric point, but not with molecular weight or hydrophobicity.Biologically relevant enteric and metabolic hormones, apolipoproteins, adipokines, and cytokines can be detected in the ALF of

  19. Semiclassical bounds in magnetic bottles

    Czech Academy of Sciences Publication Activity Database

    Barseghyan, Diana; Exner, Pavel; Kovařík, H.; Weidl, T.

    2016-01-01

    Roč. 28, č. 1 (2016), s. 1650002 ISSN 0129-055X R&D Projects: GA ČR(CZ) GA14-06818S Institutional support: RVO:61389005 Keywords : magnetic Laplacian * discrete spectrum * eigenvalue bounds Subject RIV: BE - Theoretical Physics Impact factor: 1.426, year: 2016

  20. Positivity bounds for Sivers functions

    International Nuclear Information System (INIS)

    Kang Zhongbo; Soffer, Jacques

    2011-01-01

    We generalize a positivity constraint derived initially for parity-conserving processes to the parity-violating ones, and use it to derive non-trivial bounds on several Sivers functions, entering in the theoretical description of single spin asymmetry for various processes.

  1. Bound states of 'dressed' particles

    International Nuclear Information System (INIS)

    Shirokov, M.I.

    1994-01-01

    A new approach to the problem of bound states in relativistic quantum field theories is suggested. It uses the creation - destruction operators of 'dresses' particles which have been granted by Faddeev's (1963) 'dressing' formalism. Peculiarities of the proposed approach as compared to the known ones are discussed. 8 refs. (author)

  2. Quantum lower bound for sorting

    OpenAIRE

    Shi, Yaoyun

    2000-01-01

    We prove that \\Omega(n log(n)) comparisons are necessary for any quantum algorithm that sorts n numbers with high success probability and uses only comparisons. If no error is allowed, at least 0.110nlog_2(n) - 0.067n + O(1) comparisons must be made. The previous known lower bound is \\Omega(n).

  3. Unconditional lower bounds against advice

    NARCIS (Netherlands)

    Buhrman, H.; Fortnow, L.; Santhanam, R.

    2009-01-01

    We show several unconditional lower bounds for exponential time classes against polynomial time classes with advice, including: (1) For any constant c, NEXP not in P^{NP[n^c]} (2) For any constant c, MAEXP not in MA/n^c (3) BPEXP not in BPP/n^{o(1)}. It was previously unknown even whether NEXP in

  4. Binding energies of two deltas bound states

    International Nuclear Information System (INIS)

    Sato, Hiroshi; Saito, Koichi.

    1982-06-01

    Bound states of the two-deltas system are investigated by employing the realistic one boson exchange potential. It is found that there exist many bound states in each isospin channel and also found that the tensor interaction plays important role in producing these bound states. Relationship between these bound states and dibaryon resonances is discussed. (J.P.N.)

  5. A symmetric Roos bound for linear codes

    NARCIS (Netherlands)

    Duursma, I.M.; Pellikaan, G.R.

    2006-01-01

    The van Lint–Wilson AB-method yields a short proof of the Roos bound for the minimum distance of a cyclic code. We use the AB-method to obtain a different bound for the weights of a linear code. In contrast to the Roos bound, the role of the codes A and B in our bound is symmetric. We use the bound

  6. Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles

    Science.gov (United States)

    Nakamura, Shota; Ono, Chikako; Shiokawa, Mai; Yamamoto, Satomi; Motomura, Takashi; Okamoto, Toru; Okuzaki, Daisuke; Yamamoto, Masahiro; Saito, Izumu; Wakita, Takaji; Koike, Kazuhiko; Matsuura, Yoshiharu

    2014-01-01

    Apolipoprotein B (ApoB) and ApoE have been shown to participate in the particle formation and the tissue tropism of hepatitis C virus (HCV), but their precise roles remain uncertain. Here we show that amphipathic α-helices in the apolipoproteins participate in the HCV particle formation by using zinc finger nucleases-mediated apolipoprotein B (ApoB) and/or ApoE gene knockout Huh7 cells. Although Huh7 cells deficient in either ApoB or ApoE gene exhibited slight reduction of particles formation, knockout of both ApoB and ApoE genes in Huh7 (DKO) cells severely impaired the formation of infectious HCV particles, suggesting that ApoB and ApoE have redundant roles in the formation of infectious HCV particles. cDNA microarray analyses revealed that ApoB and ApoE are dominantly expressed in Huh7 cells, in contrast to the high level expression of all of the exchangeable apolipoproteins, including ApoA1, ApoA2, ApoC1, ApoC2 and ApoC3 in human liver tissues. The exogenous expression of not only ApoE, but also other exchangeable apolipoproteins rescued the infectious particle formation of HCV in DKO cells. In addition, expression of these apolipoproteins facilitated the formation of infectious particles of genotype 1b and 3a chimeric viruses. Furthermore, expression of amphipathic α-helices in the exchangeable apolipoproteins facilitated the particle formation in DKO cells through an interaction with viral particles. These results suggest that amphipathic α-helices in the exchangeable apolipoproteins play crucial roles in the infectious particle formation of HCV and provide clues to the understanding of life cycle of HCV and the development of novel anti-HCV therapeutics targeting for viral assembly. PMID:25502789

  7. A study of serum lipid profile and serum apolipoproteins A1 and B in Indian male violent criminal offenders.

    Science.gov (United States)

    Chakrabarti, Nandini; Sinha, V K

    2006-01-01

    High cholesterol has been advanced as the most important factor in the development of coronary artery disease. Most panels have recommended population-wide dietary restrictions, yet a body of evolving data yields evidence of the hazards of low cholesterol, including links to aggression and hostility. The aim of this study was to compare the serum lipid profile and serum apolipoproteins A1 and B of men with a violent criminal record and men with no criminal history. Fasting blood samples were collected from 30 men with a known history of violent crime and 30 men with no criminal record. Serum lipid profile and serum apolipoproteins A1 and B were measured in each sample, and compared between the two groups. The group with the violent criminal record showed significantly lower total cholesterol, lower LDL cholesterol, higher apolipoprotein A1 and lower apolipoprotein B compared with the control group. Lower total cholesterol, lower LDL cholesterol, higher apolipoprotein A1 and lower apolipoprotein B could predispose to violence. Future research might explore the possibility that diets offered in prison could affect relevant pathways in lipid metabolism. Copyright (c) 2006 John Wiley & Sons, Ltd.

  8. Computer simulation of bounded plasmas

    International Nuclear Information System (INIS)

    Lawson, W.S.

    1987-01-01

    The problems of simulating a one-dimensional bounded plasma system using particles in a gridded space are systematically explored and solutions to them are given. Such problems include the injection of particles at the boundaries, the solution of Poisson's equation, and the inclusion of an external circuit between the confining boundaries. A recently discovered artificial cooling effect is explained as being a side-effect of quiet injection, and its potential for causing serious but subtle errors in bounded simulation is noted. The methods described in the first part of the thesis are then applied to the simulation of an extension of the Pierce diode problem, specifically a Pierce diode modified by an external circuit between the electrodes. The results of these simulations agree to high accuracy with theory when a theory exists, and also show some interesting chaotic behavior in certain parameter regimes. The chaotic behavior is described in detail

  9. Bounded Rationality in Transposition Processes

    DEFF Research Database (Denmark)

    Vollaard, Hans; Martinsen, Dorte Sindbjerg

    2014-01-01

    Studies explaining the timeliness and correctness of the transposition of EU directives into national legislation have provided rather inconclusive findings. They do not offer a clear-cut prediction concerning the transposition of the patients’ rights directive, which is one of the first that con......Studies explaining the timeliness and correctness of the transposition of EU directives into national legislation have provided rather inconclusive findings. They do not offer a clear-cut prediction concerning the transposition of the patients’ rights directive, which is one of the first...... that concerns the organisation and financing of national healthcare systems. This article applies the perspective of bounded rationality to explain (irregularities in) the timely and correct transposition of EU directives. The cognitive and organisational constraints long posited by the bounded rationality...

  10. 78 FR 18326 - Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math...

    Science.gov (United States)

    2013-03-26

    ...; Comment Request; Upward Bound and Upward Bound Math Science Annual Performance Report AGENCY: The Office... considered public records. Title of Collection: Upward Bound and Upward Bound Math Science Annual Performance...) and Upward Bound Math and Science (UBMS) Programs. The Department is requesting a new APR because of...

  11. Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by apolipoprotein N-acyltransferase BCG_2070c.

    Science.gov (United States)

    Brülle, Juliane K; Tschumi, Andreas; Sander, Peter

    2013-10-05

    Lipoproteins are virulence factors of Mycobacterium tuberculosis. Bacterial lipoproteins are modified by the consecutive action of preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the formation of mature triacylated lipoproteins. Lnt homologues are found in Gram-negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive bacteria, although N-acylation is observed. In fast-growing Mycobacterium smegmatis, the molecular structure of the lipid modification of lipoproteins was resolved recently as a diacylglyceryl residue carrying ester-bound palmitic acid and ester-bound tuberculostearic acid and an additional amide-bound palmitic acid. We exploit the vaccine strain Mycobacterium bovis BCG as model organism to investigate lipoprotein modifications in slow-growing mycobacteria. Using Escherichia coli Lnt as a query in BLASTp search, we identified BCG_2070c and BCG_2279c as putative lnt genes in M. bovis BCG. Lipoproteins LprF, LpqH, LpqL and LppX were expressed in M. bovis BCG and BCG_2070c lnt knock-out mutant and lipid modifications were analyzed at molecular level by matrix-assisted laser desorption ionization time-of-flight/time-of-flight analysis. Lipoprotein N-acylation was observed in wildtype but not in BCG_2070c mutants. Lipoprotein N- acylation with palmitoyl and tuberculostearyl residues was observed. Lipoproteins are triacylated in slow-growing mycobacteria. BCG_2070c encodes a functional Lnt in M. bovis BCG. We identified mycobacteria-specific tuberculostearic acid as further substrate for N-acylation in slow-growing mycobacteria.

  12. Spectrum of gluino bound states

    International Nuclear Information System (INIS)

    Chanowitz, M.; Sharpe, S.; California Univ., Berkeley

    1983-01-01

    Using the bag model to first order in αsub(s) we find that if light gluinos exist they will appear as constituents of electrically charged bound states which are stable against strong interaction decay. We review the present experimental constraints and conclude that light, long-lived charged hadrons containing gluinos might exist with lifetimes between 2x10 - 8 and 10 - 14 s. (orig.)

  13. Cyclotron transitions of bound ions

    Science.gov (United States)

    Bezchastnov, Victor G.; Pavlov, George G.

    2017-06-01

    A charged particle in a magnetic field possesses discrete energy levels associated with particle rotation around the field lines. The radiative transitions between these levels are the well-known cyclotron transitions. We show that a bound complex of particles with a nonzero net charge displays analogous transitions between the states of confined motion of the entire complex in the field. The latter bound-ion cyclotron transitions are affected by a coupling between the collective and internal motions of the complex and, as a result, differ from the transitions of a "reference" bare ion with the same mass and charge. We analyze the cyclotron transitions for complex ions by including the coupling within a rigorous quantum approach. Particular attention is paid to comparison of the transition energies and oscillator strengths to those of the bare ion. Selection rules based on integrals of collective motion are derived for the bound-ion cyclotron transitions analytically, and the perturbation and coupled-channel approaches are developed to study the transitions quantitatively. Representative examples are considered and discussed for positive and negative atomic and cluster ions.

  14. Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Natsume, Midori; Baba, Seigo

    2014-01-01

    Previous studies in humans have shown that the cacao polyphenols, (-)-epicatechin and its oligomers, prevent in vitro and ex vivo low-density lipoprotein oxidation mediated by free radical generators and metal ions and also reduce plasma LDL-cholesterol levels. The aim of this study was to examine the effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice. Mice aged 8 weeks (n = 90) were randomized into three groups, and fed either normal mouse chow (controls) or chow supplemented with 0.25 or 0.40 % cacao polyphenols for 16 weeks. The mean plaque area in cross-sections of the brachiocephalic trunk was measured and found to be lower in the 0.25 % cacao polyphenol group than in the control group (p cacao polyphenol group (p cacao polyphenols inhibit the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice by reducing oxidative stress and inflammatory responses.

  15. Apolipoprotein D is associated with long-term outcome in patients with schizophrenia

    DEFF Research Database (Denmark)

    Hansen, T; Hemmingsen, R P; Wang, A G

    2006-01-01

    Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second, gene......D alleles, genotypes or haplotypes to be associated with disease. However, we did find that long-term clinical outcome was associated with the ApoD polymorphism rs7659 (P = 0.041) following adjustment for lifetime clinical global impression, age at first admission and gender.......Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second...

  16. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, J.; Poulsen, P.; Vaag, A.

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco...... on the insulin-to-glucose ratio (p = 0.04), and E4154K (EcoRI RFLP) influenced HOMAbeta (p = 0.04). Significant interactions were observed between genotype in T71I (ApaLI RFLP), A591V (AluI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) and glucose tolerance on lipid-related parameters (0.03

  17. Comparison of lipoprotein electrophoresis and apolipoprotein e genotyping in investigating dysbetalipoproteinemia

    International Nuclear Information System (INIS)

    Ahmed, F.; Kadiki, A.E.

    2017-01-01

    Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty-two patients had both apo E genotyping and lipoprotein electrophoresis. Of these, 16 patients showed broad beta band on electrophoresis. However, only 3 of them had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E genotyping results showed poor concordance. This was primarily due to visual interpretation error of lipoprotein electrophoresis which may over diagnose dysbetalipoproteinemia. (author)

  18. Comparison of Lipoprotein Electrophoresis and Apolipoprotein E Genotyping in Investigating Dysbetalipoproteinemia.

    Science.gov (United States)

    Ahmed, Farhan; El-Kadiki, Alia; Gibbons, Stephen

    2017-06-01

    Dysbetalipoproteinemia is often associated with apolipoprotein E2E2 homozygosity; however, lipoprotein electrophoresis may also be used to assist in the diagnosis. The aim of this study was to compare apolipoprotein E (apo E) genotyping and lipoprotein electrophoresis in investigating dysbetalipoproteinemia. Data were collected over a three-year period from a lipid clinic in a tertiary referral centre and reviewed for apo E genotyping and lipoprotein electrophoresis. Sixty-two patients had both apo E genotyping and lipoprotein electrophoresis. Of these, 16 patients showed broad beta band on electrophoresis. However, only 3 of them had apo E2E2 homozygosity on genotyping. Lipoprotein electrophoresis and apo E genotyping results showed poor concordance. This was primarily due to visual interpretation error of lipoprotein electrophoresis which may over diagnose dysbetalipoproteinemia.

  19. Measurement of apolipoprotein B radioactivity in whole blood plasma by precipitation with isopropanol

    International Nuclear Information System (INIS)

    Yamada, N.; Havel, R.J.

    1986-01-01

    A method to measure apolipoprotein B radioactivity in whole blood plasma is described that is suitable for routine use in kinetic experiments in vivo. Radiolabeled apolipoprotein B is precipitated from plasma diluted 15- to 30-fold in the presence of carrier low density lipoproteins by 50% isopropanol. The amount of radioiodine in apoB is estimated from the difference between total radioiodine concentration in whole plasma and the fraction soluble in 50% isopropanol. Addition of up to 100 microliters of plasma to radioiodinated lipoproteins did not alter the percent of radioiodine precipitated in 1500 microliters of 50% isopropanol. The percent of radioiodine precipitated by isopropanol 3 min after intravenous injection of homologous radioiodinated very low density lipoproteins, intermediate density lipoproteins, and low density lipoproteins into rabbits was almost identical to that in the injected lipoproteins (y = 1.009 X +/- 0.462; r = 0.997)

  20. Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals

    OpenAIRE

    Souza, D.R.S.; Nakazone, M.A.; Pinhel, M.A.S.; Alvares, R.M.; Monaco, A.C.; Pinheiro, A.; Barros, C.F.D.C.; Cury, P.M.; Cunrath, G.S.; Netinho, J.G.

    2009-01-01

    We evaluated genetic variants of apolipoprotein E (APOE HhaI) and their association with serum lipids in colorectal cancer (CRC), together with eating habits and personal history. Eight-seven adults with CRC and 73 controls were studied. APOE*2 (rs7412) and APOE*4 (rs429358) were identified by polymerase chain reaction-restriction fragment length polymorphism. APOE gene polymorphisms were similar in both groups, but the ε4/ε4 genotype (6%) was present only in controls. The patients ...

  1. Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

    1994-09-15

    Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

  2. The effect of the addition of resistance training to a dietary education intervention on apolipoproteins and diet quality in overweight and obese older adults

    Directory of Open Access Journals (Sweden)

    Valente EA

    2011-09-01

    Full Text Available Elizabeth A Valente1, Megan E Sheehy1, Joshua J Avila2, Julie A Gutierres2, Matthew J Delmonico2, Ingrid E Lofgren11Department of Nutrition and Food Sciences, 2Department of Kinesiology, University of Rhode Island, Kingston, RI, USAObjectives: The aim of the study was to examine the additive effect of resistance training (RT to a dietary education (DE intervention on emerging coronary heart disease (CHD risk factors, concentration of apolipoproteins B (apoB and A-I (apoA-I, and Dietary Approaches to Stop Hypertension (DASH Diet Index scores in overweight and obese older adults.Patients and methods: This was an ancillary study of a randomized clinical trial held in the Fall of 2008 at the University of Rhode Island. Participants were overweight or obese subjects (mean body mass index [BMI] of 31.7 kg/m2 randomized into two groups, one participating in DE only (n = 12 and the other participating in DE plus RT (DERT (n = 15. The intervention involved all subjects participating in 30 minutes of DE per week for 10 weeks. Subjects in the DERT group participated in an additional 40 minutes of RT three times per week for 10 weeks. Measurements taken were anthropometric (height, weight, waist circumference, and body composition using the BOD POD® [Body Composition System, v 2.14; Life Measurement Instruments, Concord, CA], clinical (blood pressure, and biochemical (lipid profile and apoB and apoA-I concentrations, and the DASH Diet Index was used to measure diet quality.Results: 27 subjects (11 males, 16 females, with a mean age of 66.6 ± 4.3 years, were included in analyses. The DERT subjects had significantly better triacylglycerol and apoB concentrations and DASH Diet Index scores than the DE subjects post-intervention. Improvements were seen within the DE group in energy intake, fat-free mass, and systolic blood pressure and within the DERT group in body weight, percentage of body fat, BMI, diastolic blood pressure, and oxidized low

  3. Labeling schemes for bounded degree graphs

    DEFF Research Database (Denmark)

    Adjiashvili, David; Rotbart, Noy Galil

    2014-01-01

    We investigate adjacency labeling schemes for graphs of bounded degree Δ = O(1). In particular, we present an optimal (up to an additive constant) log n + O(1) adjacency labeling scheme for bounded degree trees. The latter scheme is derived from a labeling scheme for bounded degree outerplanar...... graphs. Our results complement a similar bound recently obtained for bounded depth trees [Fraigniaud and Korman, SODA 2010], and may provide new insights for closing the long standing gap for adjacency in trees [Alstrup and Rauhe, FOCS 2002]. We also provide improved labeling schemes for bounded degree...

  4. Is Apolipoprotein E4 an Important Risk Factor for Dementia in Persons with Down Syndrome?

    Science.gov (United States)

    Rohn, Troy T; McCarty, Katie L; Love, Julia E; Head, Elizabeth

    2014-12-08

    Down syndrome is one of the most common genetic causes of intellectual disability and is characterized by a number of behavioral as well as cognitive symptoms. Triplication of all or part of human chromosome 21 has been considered as the main cause of Down syndrome. Due to the location of the amyloid precursor protein on chromosome 21, many of the neuropathological features of early-onset Alzheimer's disease including senile plaques and neurofibrillary tangles are also present in Down syndrome patients who are either demented or nondemented. Significant advances in medical treatment have increased longevity in people with Down syndrome resulting in an increased population that may be subjected to many of the same risk factors as those with Alzheimer's disease. It is well established that harboring one or both apolipoprotein E4 alleles greatly increases the risk for Alzheimer's disease. However, whether apolipoprotein E4 contributes to an earlier onset of dementia or increased mortality in Down syndrome patients is still a matter of debate. The purpose of this mini review is to provide an updated assessment on apolipoprotein E4 status and risk potential of developing dementia and mortality associated with Down syndrome.

  5. Interactions of metals and Apolipoprotein E in Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    He eXu

    2014-06-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia, which is characterized by the neuropathological accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs. Clinically, patients will endure a gradual erosion of memory and other higher order cognitive functions. Whilst the underlying etiology of the disease remains to be definitively identified, a body of work has developed over the last two decades demonstrating that AD plasma/serum and brain are characterized by a dyshomeostasis in a number of metal ions. Furthermore, these metals (such as zinc, copper and iron play roles in the regulation of the levels AD-related proteins, including the amyloid precursor protein (APP and tau. It is becoming apparent that metals also interact with other proteins, including apolipoprotein E (ApoE. The Apolipoprotein E gene (APOE is critically associated with AD, with APOE4 representing the strongest genetic risk factor for the development of late-onset AD whereas APOE2 appears to have a protective role. In this review we will summarize the evidence supporting a role for metals in the function of Apolipoprotein E (ApoE and its consequent role in the pathogenesis of AD.

  6. Altered plasma apolipoprotein modifications in patients with pancreatic cancer: protein characterization and multi-institutional validation.

    Directory of Open Access Journals (Sweden)

    Kazufumi Honda

    Full Text Available BACKGROUND: Among the more common human malignancies, invasive ductal carcinoma of the pancreas has the worst prognosis. The poor outcome seems to be attributable to difficulty in early detection. METHODS: We compared the plasma protein profiles of 112 pancreatic cancer patients with those of 103 sex- and age-matched healthy controls (Cohort 1 using a newly developed matrix-assisted laser desorption/ionization (oMALDI QqTOF (quadrupole time-of-flight mass spectrometry (MS system. RESULTS: We found that hemi-truncated apolipoprotein AII dimer (ApoAII-2; 17252 m/z, unglycosylated apolipoprotein CIII (ApoCIII-0; 8766 m/z, and their summed value were significantly decreased in the pancreatic cancer patients [P = 1.36×10(-21, P = 4.35×10(-14, and P = 1.83×10(-24 (Mann-Whitney U-test; area-under-curve values of 0.877, 0.798, and 0.903, respectively]. The significance was further validated in a total of 1099 plasma/serum samples, consisting of 2 retrospective cohorts [Cohort 2 (n = 103 and Cohort 3 (n = 163] and a prospective cohort [Cohort 4 (n = 833] collected from 8 medical institutions in Japan and Germany. CONCLUSIONS: We have constructed a robust quantitative MS profiling system and used it to validate alterations of modified apolipoproteins in multiple cohorts of patients with pancreatic cancer.

  7. Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers.

    Science.gov (United States)

    Khadem-Ansari, Mohammad H; Rasmi, Yousef; Ramezani, Fatemeh

    2010-01-01

    It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density lipoprotein-cholesterol (HDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB) and homocysteine (Hcy) levels in healthy human volunteers. Twenty six healthy and nonsmoking males, aged between 25-60 years, who were under no medication asked to consume 150 ml of RGj twice per day for one month. Serum HDL-C, apoAI, apoB and plasma Hcy levels were measured before and after one month RGj consumption. HDL-C levels after RGj consumption were significantly higher than the corresponding levels before the RGj consumption (41.44 ± 4.50 and 44.37 ± 4.30 mg/dl; P0.05). Hcy levels were decreased after RGj consumption (7.70 ± 2.80 and 6.20 ± 2.30 µmol/l; P<0.001). The present study demonstrates that RGj consumption can significantly increase serum HDL-C levels and decrease Hcy levels. These findings may have important implications for the prevention of atherosclerosis in healthy individuals.

  8. Association of apolipoprotein b/apolipoprotein A1 ratio and coronary artery stenosis and plaques detected by multi-detector computed tomography in healthy population.

    Science.gov (United States)

    Jung, Chang Hee; Hwang, Jenie Yoonoo; Shin, Mi Seon; Yu, Ji Hee; Kim, Eun Hee; Bae, Sung Jin; Yang, Dong Hyun; Kang, Joon-Won; Park, Joong-Yeol; Kim, Hong-Kyu; Lee, Woo Je

    2013-05-01

    Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT.

  9. Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

    Directory of Open Access Journals (Sweden)

    García-Arias Carlota

    2009-06-01

    Full Text Available Abstract Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases and 31 patients with severe hypertriglyceridaemia (controls were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS. Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood.

  10. Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

    Science.gov (United States)

    2009-01-01

    Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood. PMID:19534808

  11. The algebras of bounded and essentially bounded Lebesgue measurable functions

    Directory of Open Access Journals (Sweden)

    Mortini Raymond

    2017-04-01

    Full Text Available Let X be a set in ℝn with positive Lebesgue measure. It is well known that the spectrum of the algebra L∞(X of (equivalence classes of essentially bounded, complex-valued, measurable functions on X is an extremely disconnected compact Hausdorff space.We show, by elementary methods, that the spectrum M of the algebra ℒb(X, ℂ of all bounded measurable functions on X is not extremely disconnected, though totally disconnected. Let ∆ = { δx : x ∈ X} be the set of point evaluations and let g be the Gelfand topology on M. Then (∆, g is homeomorphic to (X, Τdis,where Tdis is the discrete topology. Moreover, ∆ is a dense subset of the spectrum M of ℒb(X, ℂ. Finally, the hull h(I, (which is homeomorphic to M(L∞(X, of the ideal of all functions in ℒb(X, ℂ vanishing almost everywhere on X is a nowhere dense and extremely disconnected subset of the Corona M \\ ∆ of ℒb(X, ℂ.

  12. Voronoi Diagrams Without Bounding Boxes

    Science.gov (United States)

    Sang, E. T. K.

    2015-10-01

    We present a technique for presenting geographic data in Voronoi diagrams without having to specify a bounding box. The method restricts Voronoi cells to points within a user-defined distance of the data points. The mathematical foundation of the approach is presented as well. The cell clipping method is particularly useful for presenting geographic data that is spread in an irregular way over a map, as for example the Dutch dialect data displayed in Figure 2. The automatic generation of reasonable cell boundaries also makes redundant a frequently used solution to this problem that requires data owners to specify region boundaries, as in Goebl (2010) and Nerbonne et al (2011).

  13. Sensitivity analysis using probability bounding

    International Nuclear Information System (INIS)

    Ferson, Scott; Troy Tucker, W.

    2006-01-01

    Probability bounds analysis (PBA) provides analysts a convenient means to characterize the neighborhood of possible results that would be obtained from plausible alternative inputs in probabilistic calculations. We show the relationship between PBA and the methods of interval analysis and probabilistic uncertainty analysis from which it is jointly derived, and indicate how the method can be used to assess the quality of probabilistic models such as those developed in Monte Carlo simulations for risk analyses. We also illustrate how a sensitivity analysis can be conducted within a PBA by pinching inputs to precise distributions or real values

  14. Bounded Densities and Their Derivatives

    DEFF Research Database (Denmark)

    Kozine, Igor; Krymsky, V.

    2009-01-01

    This paper describes how one can compute interval-valued statistical measures given limited information about the underlying distribution. The particular focus is on a bounded derivative of a probability density function and its combination with other available statistical evidence for computing ...... quantities of interest. To be able to utilise the evidence about the derivative it is suggested to adapt the ‘conventional’ problem statement to variational calculus and the way to do so is demonstrated. A number of examples are given throughout the paper....

  15. Removal of bound metal fasteners

    Science.gov (United States)

    Kramer, R. F.

    1981-04-01

    This project explored the removal of bound metal fasteners through the use of ultrasonically assisted wrenches. Two wrenches were designed, fabricated and tested. Previous studies had indicated an increase in thread tension for a given torque application under the influence of ultrasonics. Based on this, the loosening of seized and corroded fasteners with the aid of ultrasonics was explored. Experimental data confirmed our prior analysis of the torque-tension relationship under the influence of ultrasonics; however, our progress did not satisfy the requirements necessary to loosen seized studs in a shipyard environment.

  16. Space mappings with bounded distortion

    CERN Document Server

    Reshetnyak, Yu G

    1989-01-01

    This book is intended for researchers and students concerned with questions in analysis and function theory. The author provides an exposition of the main results obtained in recent years by Soviet and other mathematicians in the theory of mappings with bounded distortion, an active direction in contemporary mathematics. The mathematical tools presented can be applied to a broad spectrum of problems that go beyond the context of the main topic of investigation. For a number of questions in the theory of partial differential equations and the theory of functions with generalized derivatives, this is the first time they have appeared in an internationally distributed monograph.

  17. Determining Normal-Distribution Tolerance Bounds Graphically

    Science.gov (United States)

    Mezzacappa, M. A.

    1983-01-01

    Graphical method requires calculations and table lookup. Distribution established from only three points: mean upper and lower confidence bounds and lower confidence bound of standard deviation. Method requires only few calculations with simple equations. Graphical procedure establishes best-fit line for measured data and bounds for selected confidence level and any distribution percentile.

  18. On semidefinite programming bounds for graph bandwidth

    NARCIS (Netherlands)

    de Klerk, E.; Nagy, M.; Sotirov, R.

    2013-01-01

    In this paper, we propose two new lower bounds on graph bandwidth and cyclic bandwidth based on semidefinite programming (SDP) relaxations of the quadratic assignment problem. We compare the new bounds with two other SDP bounds reported in [A. Blum, G. Konjevod, R. Ravi, and S. Vempala,

  19. Observational Bounds on Cosmic Doomsday

    Energy Technology Data Exchange (ETDEWEB)

    Shmakova, Marina

    2003-07-11

    Recently it was found, in a broad class of models, that the dark energy density may change its sign during the evolution of the universe. This may lead to a global collapse of the universe within the time t{sub c} {approx} 10{sup 10}-10{sup 11} years. Our goal is to find what bounds on the future lifetime of the universe can be placed by the next generation of cosmological observations. As an example, we investigate the simplest model of dark energy with a linear potential V({phi}) = V{sub 0}(1 + {alpha}{phi}). This model can describe the present stage of acceleration of the universe if {alpha} is small enough. However, eventually the field {phi} rolls down, V({phi}) becomes negative, and the universe collapses. The existing observational data indicate that the universe described by this model will collapse not earlier than t{sub c} {approx_equal} 10 billion years from the present moment. We show that the data from SNAP and Planck satellites may extend the bound on the ''doomsday'' time to tc 40 billion years at the 95% confidence level.

  20. Quantum bounds on Bell inequalities

    Science.gov (United States)

    Pál, Károly F.; Vértesi, Tamás

    2009-02-01

    We have determined the maximum quantum violation of 241 tight bipartite Bell inequalities with up to five two-outcome measurement settings per party by constructing the appropriate measurement operators in up to six-dimensional complex and eight-dimensional real-component Hilbert spaces using numerical optimization. Out of these inequalities 129 have been introduced here. In 43 cases higher-dimensional component spaces gave larger violation than qubits, and in three occasions the maximum was achieved with six-dimensional spaces. We have also calculated upper bounds on these Bell inequalities using a method proposed recently. For all but 20 inequalities the best solution found matched the upper bound. Surprisingly, the simplest inequality of the set examined, with only three measurement settings per party, was not among them, despite the high dimensionality of the Hilbert space considered. We also computed detection threshold efficiencies for the maximally entangled qubit pair. These could be lowered in several instances if degenerate measurements were also allowed.

  1. Megalin is a receptor for apolipoprotein M, and kidney-specific megalin-deficiency confers urinary excretion of apolipoprotein M

    DEFF Research Database (Denmark)

    Faber, Kirsten; Hvidberg, Vibeke; Moestrup, Søren K

    2006-01-01

    . In addition, apoM is expressed at high levels in the kidney tubule cells. In this study, we show that the multiligand receptor megalin, which is expressed in kidney proximal tubule cells, is a receptor for apoM and mediates its uptake in the kidney. To examine apoM binding to megalin, a recombinant apo....... To examine the importance of apoM binding by megalin in vivo, we analyzed mice with a tissue-specific deficiency of megalin in the kidney. Megalin deficiency was associated with pronounced urinary excretion of apoM, whereas apoM was not detected in normal mouse, human, or rat urine. Gel filtration analysis...... showed that the urinary apoM-containing particles were small and devoid of apoA-I. The results suggest that apoM binds to megalin and that megalin-mediated endocytosis in kidney proximal tubules prevents apoM excretion in the urine....

  2. Capacity Bounds for Parallel Optical Wireless Channels

    KAUST Repository

    Chaaban, Anas; Rezki, Zouheir; Alouini, Mohamed-Slim

    2016-01-01

    A system consisting of parallel optical wireless channels with a total average intensity constraint is studied. Capacity upper and lower bounds for this system are derived. Under perfect channel-state information at the transmitter (CSIT), the bounds have to be optimized with respect to the power allocation over the parallel channels. The optimization of the lower bound is non-convex, however, the KKT conditions can be used to find a list of possible solutions one of which is optimal. The optimal solution can then be found by an exhaustive search algorithm, which is computationally expensive. To overcome this, we propose low-complexity power allocation algorithms which are nearly optimal. The optimized capacity lower bound nearly coincides with the capacity at high SNR. Without CSIT, our capacity bounds lead to upper and lower bounds on the outage probability. The outage probability bounds meet at high SNR. The system with average and peak intensity constraints is also discussed.

  3. VORONOI DIAGRAMS WITHOUT BOUNDING BOXES

    Directory of Open Access Journals (Sweden)

    E. T. K. Sang

    2015-10-01

    Full Text Available We present a technique for presenting geographic data in Voronoi diagrams without having to specify a bounding box. The method restricts Voronoi cells to points within a user-defined distance of the data points. The mathematical foundation of the approach is presented as well. The cell clipping method is particularly useful for presenting geographic data that is spread in an irregular way over a map, as for example the Dutch dialect data displayed in Figure 2. The automatic generation of reasonable cell boundaries also makes redundant a frequently used solution to this problem that requires data owners to specify region boundaries, as in Goebl (2010 and Nerbonne et al (2011.

  4. Spectral computations for bounded operators

    CERN Document Server

    Ahues, Mario; Limaye, Balmohan

    2001-01-01

    Exact eigenvalues, eigenvectors, and principal vectors of operators with infinite dimensional ranges can rarely be found. Therefore, one must approximate such operators by finite rank operators, then solve the original eigenvalue problem approximately. Serving as both an outstanding text for graduate students and as a source of current results for research scientists, Spectral Computations for Bounded Operators addresses the issue of solving eigenvalue problems for operators on infinite dimensional spaces. From a review of classical spectral theory through concrete approximation techniques to finite dimensional situations that can be implemented on a computer, this volume illustrates the marriage of pure and applied mathematics. It contains a variety of recent developments, including a new type of approximation that encompasses a variety of approximation methods but is simple to verify in practice. It also suggests a new stopping criterion for the QR Method and outlines advances in both the iterative refineme...

  5. The age dependency of gene expression for plasma lipids, lipoproteins, and apolipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Snieder, H.; Doornen, L.J.P. van; Boomsma, D.I. [Vrije Universiteit, Amsterdam (Netherlands)

    1997-03-01

    The aim of this study was to investigate and disentangle the genetic and nongenetic causes of stability and change in lipids and (apo)lipoproteins that occur during the lifespan. Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) were measured in a group of 160 middle-aged parents and their twin offspring (first project) and in a group of 203 middle-aged twin pairs (second project). Combining the data of both projects enabled the estimation of the extent to which measured lipid parameters are influenced by different genes in adolescence and adulthood. To that end, an extended quantitative genetic model was specified, which allowed the estimation of heritabilities for each sex and generation separately. Heritabilities were similar for both sexes and both generations. Larger variances in the parental generation could be ascribed to proportional increases in both unique environmental and additive genetic variance from childhood to adulthood, which led to similar heritability estimates in adolescent and middle-aged twins. Although the magnitudes of heritabilities were similar across generations, results showed that, for total cholesterol, triglycerides, HDL, and LDL, partly different genes are expressed in adolescence compared to adulthood. For triglycerides, only 46% of the genetic variance was common to both age groups; for total cholesterol this was 80%. Intermediate values were found for HDL (66%) and LDL (76%). For ApoA1, ApoB, and Lp(a), the same genes seem to act in both generations. 56 refs., 2 figs., 5 tabs.

  6. Sex differences in apolipoprotein A1 and nevirapine-induced toxicity

    OpenAIRE

    Aline Marinho; Clara Dias; Alexandra Antunes; Umbelina Caixas; Teresa Branco; Matilde Marques; Emília Monteiro; Sofia Pereira

    2014-01-01

    Nevirapine (NVP) is associated with severe liver and skin toxicity through sulfotransferase (SULT) bioactivation of the phase I metabolite 12-hydroxy-NVP [1–3]. The female sex, a well-known risk factor for NVP-induced toxicity, is associated with higher SULT expression [4] and lower plasma levels of 12-hydroxy-NVP [3]. Interestingly, apolipoprotein A1 (ApoA1) increases SULT2B1 activity and ApoA1 synthesis is increased by NVP [5, 6]. Herein, we explore the effect of ApoA1 levels on NVP metabol...

  7. Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Michael D. Shapiro

    2017-02-01

    Full Text Available Cholesterol-rich, apolipoprotein B (apoB-containing lipoproteins are now widely accepted as the most important causal agents of atherosclerotic cardiovascular disease. Multiple unequivocal and orthogonal lines of evidence all converge on low-density lipoprotein and related particles as being the principal actors in the genesis of atherosclerosis. Here, we review the fundamental role of atherogenic apoB-containing lipoproteins in cardiovascular disease and several other humoral and parietal factors that are required to initiate and maintain arterial degeneration. The biology of foam cells and their interactions with high-density lipoproteins, including cholesterol efflux, are also briefly reviewed.

  8. Effects of dietary saturated fat on LDL subclasses and apolipoprotein CIII in men

    OpenAIRE

    Faghihnia, Nastaran; Mangravite, Lara M.; Chiu, Sally; Bergeron, Nathalie; Krauss, Ronald M.

    2012-01-01

    Background/Objectives Small dense LDL particles and apolipoprotein (apo) CIII are risk factors for cardiovascular disease (CVD) that can be modulated by diet, but there is little information regarding the effects of dietary saturated fat on their plasma levels. We tested the effects of high vs. low saturated fat intake in the context of a high beef protein diet on levels and composition of LDL subclasses and on apoCIII levels in plasma and LDL. Subjects/Methods Following consumption of a base...

  9. Molecular basis of the apolipoprotein H (beta 2-glycoprotein I) protein polymorphism

    DEFF Research Database (Denmark)

    Sanghera, Dharambir K; Kristensen, Torsten; Hamman, Richard F

    1997-01-01

    Apolipoprotein H (apoH, protein; APOH, gene) is considered to be an essential cofactor for the binding of certain antiphospholipid autoantibodies to anionic phospholipids. APOH exhibits a genetically determined structural polymorphism due to the presence of three common alleles (APOH*1, APOH*2...... was observed sporadically in blacks (0.008), it was present at a polymorphic frequency in Hispanics (0.027) and non-Hispanic whites (0.059). The identification of the molecular basis of the APOH protein polymorphism will help to elucidate the structural – functional relationship of apoH in the production...

  10. LNA-enhanced detection of single nucleotide polymorphisms in the apolipoprotein E

    DEFF Research Database (Denmark)

    Jacobsen, Nana; Bentzen, Joan; Meldgaard, Michael

    2002-01-01

    Genotyping of single nucleotide polymorphisms (SNPs) in large populations presents a great challenge, especially if the SNPs are embedded in GC-rich regions, such as the codon 112 SNP in the human apolipoprotein E (apoE). In the present study, we have used immobilized locked nucleic acid (LNA...... was applied to a panel of patient samples with simultaneous genotyping of the patients by DNA sequencing. The apoE genotyping assays for the codons 112 and 158 SNPs resulted in unambiguous results for all patient samples, concurring with those obtained by DNA sequencing....

  11. Apolipoprotein M binds oxidized phospholipids and increases the antioxidant effect of HDL

    DEFF Research Database (Denmark)

    Elsøe, Sara; Ahnström, Josefin; Christoffersen, Christina

    2012-01-01

    Oxidation of LDL plays a key role in the development of atherosclerosis. HDL may, in part, protect against atherosclerosis by inhibiting LDL oxidation. Overexpression of HDL-associated apolipoprotein M (apoM) protects mice against atherosclerosis through a not yet clarified mechanism. Being a lip...... a lipocalin, apoM contains a binding pocket for small lipophilic molecules. Here, we report that apoM likely serves as an antioxidant in HDL by binding oxidized phospholipids, thus enhancing the antioxidant potential of HDL....

  12. Increased plasma apolipoprotein (a) levels in IDDM patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Tarnow, L; Rossing, P; Nielsen, F S

    1996-01-01

    OBJECTIVE: The relative mortality from cardiovascular disease (CVD) is increased 40-fold in IDDM patients suffering from diabetic nephropathy as compared with nondiabetic subjects on average. We assessed the potential contribution of dyslipidemia in general and elevated serum apolipoprotein (a.......0001. Multiple logistic regression analysis of cardiovascular risk factors revealed that plasma apo(a) concentration > 300 U/l is an independent risk factor for coronary heart disease, odds ratio 1.86 (1.03-3.36) (P Dyslipidemia and raised plasma concentrations of apo(a), particularly > 300...

  13. The relation between dietary intake of vegetable oils and serum lipids and apolipoprotein levels in central Iran

    Directory of Open Access Journals (Sweden)

    Hossein Khosravi Boroujeni

    2012-01-01

    Full Text Available BACKGROUND: The detrimental effects of partially hydrogenated vegetable oils (PHVOs on apolipoproteins have been reported from several parts of the world. However, little data is available in this regard from the understudied region of the Middle East. The present study therefore tried to evaluate the association between type of vegetable oils and serum lipids and apolipoprotein levels among Iranians. METHODS: In this cross-sectional study, data from 1772 people (795 men and 977 women aged 19-81 years, who were selected with multistage cluster random sampling method from three cities of Isfahan, Najaf Abad and Arak in "Isfahan Healthy Heart Program" (IHHP, was used. To assess participants' usual dietary intakes, a validated food frequency questionnaire was used. Hydrogenated vegetable oil (commonly consumed for cooking in Iran and margarine were considered as the category of PHVOs. Soy, sunflower, corn, olive and canola oils were considered as non-HVOs. After an overnight fasting, serum cholesterol (total, low density lipoprotein (LDL and high density lipoprotein (HDL cholesterol and triglyceride as well as apolipoproteins A and B were measured using standard methods. RESULTS: Participants with the highest intakes of non-HVOs and PHVOs were younger and had lower weight than those with lowest intakes. High consumption of non-HVOs and PHVOs was associated with lower intakes of energy, carbohydrate, dietary fiber, and higher intakes of fruits, vegetables, meat, milk and grains. No overall significant differences were found in serum lipids and apolipoprotein levels across the quartiles of non-HVOs and PHVOs after controlling for potential confounding. CONCLUSION: We did not find any significant associations between hydrogenated or non-hydrogenated vegetable oil and serum lipid and apolipoprotein levels. Thus, further studies are needed in this region to explore this association. Keywords: Vegetable Oils, Cardiovascular Risk Factors, Lipids

  14. Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil

    Directory of Open Access Journals (Sweden)

    Sumeet S Mitter

    2012-01-01

    Full Text Available OBJECTIVE: Apolipoprotein E4 may benefit children during early periods of life when the body is challenged by infection and nutritional decline. We examined whether apolipoprotein E4 affects intestinal barrier function, improving short-term growth and long-term cognitive outcomes in Brazilian shantytown children. METHODS: A total of 213 Brazilian shantytown children with below-median height-for-age z-scores (HAZ received 200,000 IU of retinol (every four months, zinc (40 mg twice weekly, or both for one year, with half of each group receiving glutamine supplementation for 10 days. Height-for-age z-scores, weight-for-age z-scores, weight-forheight z-scores, and lactulose:mannitol ratios were assessed during the initial four months of treatment. An average of four years (range 1.4-6.6 later, the children underwent cognitive testing to evaluate non-verbal intelligence, coding, verbal fluency, verbal learning, and delayed verbal learning. Apolipoprotein E4 carriage was determined by PCR analysis for 144 children. RESULTS: Thirty-seven children were apolipoprotein E4(+, with an allele frequency of 13.9%. Significant associations were found for vitamin A and glutamine with intestinal barrier function. Apolipoprotein E4(+ children receiving glutamine presented significant positive Pearson correlations between the change in height-for-age z-scores over four months and delayed verbal learning, along with correlated changes over the same period in weight-for-age z-scores and weight-for-height z-scores associated with non-verbal intelligence quotients. There was a significant correlation between vitamin A supplementation of apolipoprotein E4(+ children and improved delta lactulose/mannitol. Apolipoprotein E4(- children, regardless of intervention, exhibited negative Pearson correlations between the change in lactulose-to-mannitol ratio over four months and verbal learning and non-verbal intelligence. CONCLUSIONS: During development, apolipoprotein E4 may

  15. Instanton bound states in ABJM theory

    Energy Technology Data Exchange (ETDEWEB)

    Hatsuda, Yasuyuki [DESY Hamburg (Germany). Theory Group; Tokyo Institute of Technology (Japan). Dept. of Physics; Moriyama, Sanefumi [Nagoya Univ. (Japan). Kobayashi Maskawa Inst. and Graduate School of Mathematics; Okuyama, Kazumi [Shinshu Univ., Matsumoto, Nagano (Japan). Dept. of Physics

    2013-06-15

    The partition function of the ABJM theory receives non-perturbative corrections due to instanton effects. We study these non-perturbative corrections, including bound states of worldsheet instantons and membrane instantons, in the Fermi-gas approach. We require that the total non-perturbative correction should be always finite for arbitrary Chern-Simons level. This finiteness is realized quite non-trivially because each bound state contribution naively diverges at some levels. The poles of each contribution should be canceled out in total. We use this pole cancellation mechanism to find unknown bound state corrections from known ones. We conjecture a general expression of the bound state contribution. Summing up all the bound state contributions, we find that the effect of bound states is simply incorporated into the worldsheet instanton correction by a redefinition of the chemical potential in the Fermi-gas system. Analytic expressions of the 3- and 4-membrane instanton corrections are also proposed.

  16. Bounded elements in Locally C*-algebras

    International Nuclear Information System (INIS)

    El Harti, Rachid

    2001-09-01

    In order to get more useful information about Locally C*-algebras, we introduce in this paper the notion of bounded elements. First, we study the connection between bounded elements and spectrally bounded elements. Some structural results of Locally C*-algebras are established in Theorems 1 , 2 and 3. As an immediate consequence of Theorem 3, we give a characterization of the connected component of the identity in the group of unitary elements for a Locally C*-algebra. (author)

  17. Fuzzy upper bounds and their applications

    Energy Technology Data Exchange (ETDEWEB)

    Soleimani-damaneh, M. [Department of Mathematics, Faculty of Mathematical Science and Computer Engineering, Teacher Training University, 599 Taleghani Avenue, Tehran 15618 (Iran, Islamic Republic of)], E-mail: soleimani_d@yahoo.com

    2008-04-15

    This paper considers the concept of fuzzy upper bounds and provides some relevant applications. Considering a fuzzy DEA model, the existence of a fuzzy upper bound for the objective function of the model is shown and an effective approach to solve that model is introduced. Some dual interpretations are provided, which are useful for practical purposes. Applications of the concept of fuzzy upper bounds in two physical problems are pointed out.

  18. Bounded cohomology of discrete groups

    CERN Document Server

    Frigerio, Roberto

    2017-01-01

    The author manages a near perfect equilibrium between necessary technicalities (always well motivated) and geometric intuition, leading the readers from the first simple definition to the most striking applications of the theory in 13 very pleasant chapters. This book can serve as an ideal textbook for a graduate topics course on the subject and become the much-needed standard reference on Gromov's beautiful theory. -Michelle Bucher The theory of bounded cohomology, introduced by Gromov in the late 1980s, has had powerful applications in geometric group theory and the geometry and topology of manifolds, and has been the topic of active research continuing to this day. This monograph provides a unified, self-contained introduction to the theory and its applications, making it accessible to a student who has completed a first course in algebraic topology and manifold theory. The book can be used as a source for research projects for master's students, as a thorough introduction to the field for graduate student...

  19. Some Improved Nonperturbative Bounds for Fermionic Expansions

    Energy Technology Data Exchange (ETDEWEB)

    Lohmann, Martin, E-mail: marlohmann@gmail.com [Universita di Roma Tre, Dipartimento di Matematica (Italy)

    2016-06-15

    We reconsider the Gram-Hadamard bound as it is used in constructive quantum field theory and many body physics to prove convergence of Fermionic perturbative expansions. Our approach uses a recursion for the amplitudes of the expansion, discovered in a model problem by Djokic (2013). It explains the standard way to bound the expansion from a new point of view, and for some of the amplitudes provides new bounds, which avoid the use of Fourier transform, and are therefore superior to the standard bounds for models like the cold interacting Fermi gas.

  20. Rapid radioimmunoassay of human apolipoproteins C-II and C-III

    Energy Technology Data Exchange (ETDEWEB)

    Gustafson, S; Oestlund-Lindqvist, A M; Vessby, B [Uppsala Univ. (Sweden)

    1984-06-01

    Apolipoprotein (apo) C-II is an activator of lipoprotein lipase, while apo C-III has the ability to inhibit apo C-II activated lipolysis. In order to study further the relationship between lipoprotein lipase mediated hydrolysis and the serum concentrations of apo C-II and apo C-III radioimmunoassays for these apolipoproteins have been developed. Formalin-treated Staphylococcus aureus Cowan I was used for immunoprecipitation and were shown to give rapid uptake of immune complexes that could easily be harvested by centrifugation. The assays were shown to be sensitive (10 ..mu..g/1), specific, precise (inter- and intra-assay coefficients of variation below 10%), rapid (completed in less than 6 h) and simple to perform. Delipidation of serum and lipoproteins had no effect on the results, indicating that the immunologically active sites of apo C-II and apo C-III are exposed to the aqueous environment under assay conditions. Serum apo C-II and apo C-III levels of normolipidaemic subjects were approximately 25 mg/1 and 110 mg/1, respectively. Highly significant positive correlations were found between VLDL apo C-II and VLDL apo C-III, respectively, and VLDL triglycerides, VLDL cholesterol and total serum TG. There was also a highly significant correlation between the HDL cholesterol concentration and the HDL apo C-III concentration.

  1. Selection on alleles affecting human longevity and late-life disease: the example of apolipoprotein E.

    Directory of Open Access Journals (Sweden)

    Fotios Drenos

    2010-04-01

    Full Text Available It is often claimed that genes affecting health in old age, such as cardiovascular and Alzheimer diseases, are beyond the reach of natural selection. We show in a simulation study based on known genetic (apolipoprotein E and non-genetic risk factors (gender, diet, smoking, alcohol, exercise that, because there is a statistical distribution of ages at which these genes exert their influence on morbidity and mortality, the effects of selection are in fact non-negligible. A gradual increase with each generation of the epsilon2 and epsilon3 alleles of the gene at the expense of the epsilon4 allele was predicted from the model. The epsilon2 allele frequency was found to increase slightly more rapidly than that for epsilon3, although there was no statistically significant difference between the two. Our result may explain the recent evolutionary history of the epsilon 2, 3 and 4 alleles of the apolipoprotein E gene and has wider relevance for genes affecting human longevity.

  2. Apolipoprotein E in Temporal Lobe Epilepsy: A Case-Control Study

    Science.gov (United States)

    Kumar, Amit; Tripathi, Manjari; Pandey, Ravindra M.; Ramakrishnan, Lakshmy; Srinivas, M.; Luthra, Kalpana

    2006-01-01

    Purpose: To investigate the relationship of apolipoprotein E (apoE) genotype, plasma levels of apoE and lipids in temporal lobe epilepsy (TLE) patients in Asian Indians. Status of plasma levels of Apo E in epilepsy patients has not been reported till date. Methods: ApoE gene polymorphism was analyzed in 58 patients with temporal lobe epilepsy (TLE) and 57 age and sex approximated controls using Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). Levels of plasma apoE and lipids were measured using ELISA and enzymatic kits respectively. Results: The distribution of ApoE genotype in epilepsy patients and controls was comparable. Higher levels of plasma ApoE were observed in TLE patients as compared to controls (p = 0.0001). Individuals with plasma levels of apoE > 190 mg/L were at 20 times higher odds (95%CI = 2.46–163.34, p = 0.005), while those with levels of apoE between 150–190 mg/L were at 4.9 times higher odds (95% CI = 1.85–13.9, p = 0.001), to develop TLE. Conclusions: We have observed for the first time, high levels of plasma apoE in epilepsy patients. The findings of this case-control study suggest that apolipoprotein E may play an important role in epilepsy. PMID:17264404

  3. Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding

    International Nuclear Information System (INIS)

    Innerarity, T.L.; Weisgraber, K.H.; Arnold, K.S.; Mahley, R.W.; Krauss, R.M.; Vega, G.L.; Grundy, S.M.

    1987-01-01

    Previous in vivo turnover studies suggested that retarded clearance of low density lipoproteins (LDL) from the plasma of some hypercholesterolemic patients is due to LDL with defective receptor binding. The present study examined this postulate directly by receptor binding experiments. The LDL from a hypercholesterolemic patient (G.R.) displayed a reduced ability to bind to the LDL receptors on normal human fibroblasts. The G.R. LDL possessed 32% of normal receptor binding activity. Likewise, the G.R. LDL were much less effective than normal LDL in competing with 125 I-labeled normal LDL for cellular uptake and degradation and in stimulating intracellular cholesteryl ester synthesis. The defect in LDL binding appears to be due to a genetic abnormality of apolipoprotein B-100: two brothers of the proband possess LDL defective in receptor binding, whereas a third brother and the proband's son have normally binding LDL. Further, the defect in receptor binding does not appear to be associated wit an abnormal lipid composition or structure of the LDL. Normal and abnormal LDL subpopulations were partially separated from plasma of two subjects by density-gradient ultracentrifugation, a finding consistent with the presence of a normal and a mutant allele. The affected family members appear to be heterozygous for this disorder, which has been designated familial defective apolipoprotein B-100. These studies indicate that the defective receptor binding results in inefficient clearance of LDL and the hypercholesterolemia observed in these patients

  4. A simple approach for human recombinant apolipoprotein E4 expression and purification.

    Science.gov (United States)

    Argyri, Letta; Skamnaki, Vassiliki; Stratikos, Efstratios; Chroni, Angeliki

    2011-10-01

    We report a simple expression and purification procedure for the production of recombinant apolipoprotein E4 (apoE4), an important protein for the lipid homeostasis in humans that plays critical roles in the pathogenesis of cardiovascular and neurodegenerative diseases. Our approach is based on the expression of a thioredoxin-apoE4 fusion construct in bacterial cells and subsequent removal of the fused thioredoxin using the highly specific 3C protease, avoiding costly and laborious lipidation-delipidation steps used before. Our approach results in rapid, high-yield production of structurally and functionally competent apoE4 as evidenced by secondary structure measurements, thermal and chemical melting profiles and the kinetic profile of solubilization of dimyristoyl-phosphatidylcholine (DMPC) vesicles. This protocol is appropriate for laboratories with little experience in apolipoprotein biochemistry and will facilitate future studies on the role of apoE4 in the pathogenesis of cardiovascular disease and neurodegenerative diseases, including Alzheimer's disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Variational lower bound on the scattering length

    International Nuclear Information System (INIS)

    Rosenberg, L.; Spruch, L.

    1975-01-01

    The scattering length A characterizes the zero-energy scattering of one system by another. It was shown some time ago that a variational upper bound on A could be obtained using methods, of the Rayleigh-Ritz type, which are commonly employed to obtain upper bounds on energy eigenvalues. Here we formulate a method for obtaining a variational lower bound on A. Once again the essential idea is to express the scattering length as a variational estimate plus an error term and then to reduce the problem of bounding the error term to one involving bounds on energy eigenvalues. In particular, the variational lower bound on A is rigorously established provided a certin modified Hamiltonian can be shown to have no discrete states lying below the level of the continuum threshold. It is unfortunately true that necessary conditions for the existence of bound states are not available for multiparticle systems in general. However, in the case of positron-atom scattering the adiabatic approximation can be introduced as an (essentially) solvable comparison problem to rigorously establish the nonexistence of bound states of the modified Hamiltonian. It has recently been shown how the validity of the variational upper bound on A can be maintained when the target ground-state wave function is imprecisely known. Similar methods can be used to maintain the variational lower bound on A. Since the bound is variational, the error in the calculated scattering length will be of second order in the error in the wave function. The use of the adiabatic approximation in the present context places no limitation in principle on the accuracy achievable

  6. Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I

    DEFF Research Database (Denmark)

    Rajakumar, Chandheeb; Ban, Matthew R; Cao, Henian

    2009-01-01

    Carnitine palmitoyltransferase IA, encoded by CPT1A, is a key regulator of fatty acid metabolism. Previously, a loss of function mutation, namely c.1436 CT (p.P479L), was reported in CPT1A in the homozygous state in Canadian aboriginal male with presumed CPT1A deficiency. In order to determine...

  7. The intravenous injection of oxidized LDL- or Apolipoprotein B100 – Coupled splenocytes promotes Th1 polarization in wildtype and Apolipoprotein E – Deficient mice

    International Nuclear Information System (INIS)

    Steinmetz, Martin; Ponnuswamy, Padmapriya; Laurans, Ludivine; Esposito, Bruno; Tedgui, Alain; Mallat, Ziad

    2015-01-01

    Background: Th1 responses in atherosclerosis are mainly associated with the aggravation of atherosclerotic plaques, whereas Th2 responses lead to a less pronounced disease in mouse models. The fixation of antigens on cells by means of ethylene carbodiimide (ECDI), and subsequent injection of these antigen-coupled splenocytes (Ag-SP) to induce tolerance against the attached antigens, has been successfully used to treat murine type 1 diabetes or encephalomyelitis in. We analyzed this approach in a mouse model for atherosclerosis. Methods and results: OTII-transgenic mice that were treated with a single dose of 5 × 10 7 OVA-coupled splenocytes (OVA-SP), had decreased splenocyte proliferation, and lower IFNγ production in vitro upon antigen recall. However, in vivo CD4 cell activation was increased. To try lipoprotein-derived, “atherosclerosis-associated” antigens, we first tested human oxidized LDL. In wild type mice, an increase of IFNγ production upon in vitro recall was detected in the oxLDL-SP group. In Apolipoprotein E − deficient (ApoE−/−) mice that received oxLDL-SP every 5 weeks for 20 weeks, we did not find any difference of atherosclerotic plaque burden, but again increased IFNγ production. To overcome xenogenous limitations, we then examined the effects of mouse Apolipoprotein B100 peptides P3 and P6. ApoB100-SP treatment again promoted a more IFNγ pronounced response upon in vitro recall. Flow cytometry analysis of cytokine secreting spleen cells revealed CD4 positive T cells to be mainly the source for IFNγ. In ApoE−/− mice that were administered ApoB100-SP during 20 weeks, the atherosclerotic plaque burden in aortic roots as well as total aorta was unchanged compared to PBS treated controls. Splenocyte proliferation upon antigen recall was not significantly altered in ApoB100-SP treated ApoE−/− mice. Conclusion: Although we did not observe a relevant anti-atherosclerotic benefit, the treatment with antigen

  8. The intravenous injection of oxidized LDL- or Apolipoprotein B100 – Coupled splenocytes promotes Th1 polarization in wildtype and Apolipoprotein E – Deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Martin, E-mail: martin.steinmetz@ukb.uni-bonn.de [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Internal Medicine II, University Hospital Bonn, 53105 Bonn (Germany); Ponnuswamy, Padmapriya; Laurans, Ludivine; Esposito, Bruno; Tedgui, Alain [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Mallat, Ziad [INSERM, Unit 970, Paris Cardiovascular Research Center, 75015 Paris (France); Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke' s Hospital, Cambridge, CB2 2QQ (United Kingdom)

    2015-08-14

    Background: Th1 responses in atherosclerosis are mainly associated with the aggravation of atherosclerotic plaques, whereas Th2 responses lead to a less pronounced disease in mouse models. The fixation of antigens on cells by means of ethylene carbodiimide (ECDI), and subsequent injection of these antigen-coupled splenocytes (Ag-SP) to induce tolerance against the attached antigens, has been successfully used to treat murine type 1 diabetes or encephalomyelitis in. We analyzed this approach in a mouse model for atherosclerosis. Methods and results: OTII-transgenic mice that were treated with a single dose of 5 × 10{sup 7} OVA-coupled splenocytes (OVA-SP), had decreased splenocyte proliferation, and lower IFNγ production in vitro upon antigen recall. However, in vivo CD4 cell activation was increased. To try lipoprotein-derived, “atherosclerosis-associated” antigens, we first tested human oxidized LDL. In wild type mice, an increase of IFNγ production upon in vitro recall was detected in the oxLDL-SP group. In Apolipoprotein E − deficient (ApoE−/−) mice that received oxLDL-SP every 5 weeks for 20 weeks, we did not find any difference of atherosclerotic plaque burden, but again increased IFNγ production. To overcome xenogenous limitations, we then examined the effects of mouse Apolipoprotein B100 peptides P3 and P6. ApoB100-SP treatment again promoted a more IFNγ pronounced response upon in vitro recall. Flow cytometry analysis of cytokine secreting spleen cells revealed CD4 positive T cells to be mainly the source for IFNγ. In ApoE−/− mice that were administered ApoB100-SP during 20 weeks, the atherosclerotic plaque burden in aortic roots as well as total aorta was unchanged compared to PBS treated controls. Splenocyte proliferation upon antigen recall was not significantly altered in ApoB100-SP treated ApoE−/− mice. Conclusion: Although we did not observe a relevant anti-atherosclerotic benefit, the treatment with antigen

  9. Stacked spheres and lower bound theorem

    Indian Academy of Sciences (India)

    BASUDEB DATTA

    2011-11-20

    Nov 20, 2011 ... Preliminaries. Lower bound theorem. On going work. Definitions. An n-simplex is a convex hull of n + 1 affinely independent points. (called vertices) in some Euclidean space R. N . Stacked spheres and lower bound theorem. Basudeb Datta. Indian Institute of Science. 2 / 27 ...

  10. A strongly quasiconvex PAC-Bayesian bound

    DEFF Research Database (Denmark)

    Thiemann, Niklas; Igel, Christian; Wintenberger, Olivier

    2017-01-01

    We propose a new PAC-Bayesian bound and a way of constructing a hypothesis space, so that the bound is convex in the posterior distribution and also convex in a trade-off parameter between empirical performance of the posterior distribution and its complexity. The complexity is measured by the Ku...

  11. On the range of completely bounded maps

    Directory of Open Access Journals (Sweden)

    Richard I. Loebl

    1978-01-01

    Full Text Available It is shown that if every bounded linear map from a C*-algebra α to a von Neumann algebra β is completely bounded, then either α is finite-dimensional or β⫅⊗Mn, where is a commutative von Neumann algebra and Mn is the algebra of n×n complex matrices.

  12. Bounds in the location-allocation problem

    DEFF Research Database (Denmark)

    Juel, Henrik

    1981-01-01

    Develops a family of stronger lower bounds on the objective function value of the location-allocation problem. Solution methods proposed to solve problems in location-allocation; Efforts to develop a more efficient bound solution procedure; Determination of the locations of the sources....

  13. Experimental evidence for bounds on quantum correlations.

    Science.gov (United States)

    Bovino, F A; Castagnoli, G; Degiovanni, I P; Castelletto, S

    2004-02-13

    We implemented the experiment proposed by Cabello in the preceding Letter to test the bounds of quantum correlation. As expected from the theory we found that, for certain choices of local observables, Tsirelson's bound of the Clauser-Horne-Shimony-Holt inequality (2 x square root of 2) is not reached by any quantum states.

  14. Exponential Lower Bounds For Policy Iteration

    OpenAIRE

    Fearnley, John

    2010-01-01

    We study policy iteration for infinite-horizon Markov decision processes. It has recently been shown policy iteration style algorithms have exponential lower bounds in a two player game setting. We extend these lower bounds to Markov decision processes with the total reward and average-reward optimality criteria.

  15. Conductivity bound from dirty black holes

    Energy Technology Data Exchange (ETDEWEB)

    Bitaghsir Fadafan, Kazem, E-mail: bitaghsir@shahroodut.ac.ir

    2016-11-10

    We propose a lower bound of the dc electrical conductivity in strongly disordered, strongly interacting quantum field theories using holography. We study linear response of black holes with broken translational symmetry in Einstein–Maxwell-dilaton theories of gravity. Using the generalized Stokes equations at the horizon, we derive the lower bound of the electrical conductivity for the dual two dimensional disordered field theory.

  16. No-arbitrage bounds for financial scenarios

    DEFF Research Database (Denmark)

    Geyer, Alois; Hanke, Michael; Weissensteiner, Alex

    2014-01-01

    We derive no-arbitrage bounds for expected excess returns to generate scenarios used in financial applications. The bounds allow to distinguish three regions: one where arbitrage opportunities will never exist, a second where arbitrage may be present, and a third, where arbitrage opportunities...

  17. SHARP ENTRYWISE PERTURBATION BOUNDS FOR MARKOV CHAINS.

    Science.gov (United States)

    Thiede, Erik; VAN Koten, Brian; Weare, Jonathan

    For many Markov chains of practical interest, the invariant distribution is extremely sensitive to perturbations of some entries of the transition matrix, but insensitive to others; we give an example of such a chain, motivated by a problem in computational statistical physics. We have derived perturbation bounds on the relative error of the invariant distribution that reveal these variations in sensitivity. Our bounds are sharp, we do not impose any structural assumptions on the transition matrix or on the perturbation, and computing the bounds has the same complexity as computing the invariant distribution or computing other bounds in the literature. Moreover, our bounds have a simple interpretation in terms of hitting times, which can be used to draw intuitive but rigorous conclusions about the sensitivity of a chain to various types of perturbations.

  18. New bounds on isotropic Lorentz violation

    International Nuclear Information System (INIS)

    Carone, Christopher D.; Sher, Marc; Vanderhaeghen, Marc

    2006-01-01

    Violations of Lorentz invariance that appear via operators of dimension four or less are completely parametrized in the Standard Model Extension (SME). In the pure photonic sector of the SME, there are 19 dimensionless, Lorentz-violating parameters. Eighteen of these have experimental upper bounds ranging between 10 -11 and 10 -32 ; the remaining parameter, k-tilde tr , is isotropic and has a much weaker bound of order 10 -4 . In this Brief Report, we point out that k-tilde tr gives a significant contribution to the anomalous magnetic moment of the electron and find a new upper bound of order 10 -8 . With reasonable assumptions, we further show that this bound may be improved to 10 -14 by considering the renormalization of other Lorentz-violating parameters that are more tightly constrained. Using similar renormalization arguments, we also estimate bounds on Lorentz-violating parameters in the pure gluonic sector of QCD

  19. Covariant entropy bound and loop quantum cosmology

    International Nuclear Information System (INIS)

    Ashtekar, Abhay; Wilson-Ewing, Edward

    2008-01-01

    We examine Bousso's covariant entropy bound conjecture in the context of radiation filled, spatially flat, Friedmann-Robertson-Walker models. The bound is violated near the big bang. However, the hope has been that quantum gravity effects would intervene and protect it. Loop quantum cosmology provides a near ideal setting for investigating this issue. For, on the one hand, quantum geometry effects resolve the singularity and, on the other hand, the wave function is sharply peaked at a quantum corrected but smooth geometry, which can supply the structure needed to test the bound. We find that the bound is respected. We suggest that the bound need not be an essential ingredient for a quantum gravity theory but may emerge from it under suitable circumstances.

  20. Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Mensink, R.P.; Hof, H.B. van 't; Offermans, R.F.G.; Hofker, M.H.; Havekes, L.M.

    1998-01-01

    Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. In the present study we therefore used hyperlipidentic apolipoprotein (APO) E*3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VDL)

  1. Effect of Mediterranean diet with and without weight loss on apolipoprotein B100 metabolism in men with metabolic syndrome

    Science.gov (United States)

    The objective of this study was to assess the effect of a Mediterranean diet (MedDiet) with and without weight loss (WL) on apolipoprotein B100 (apoB100) metabolism in men with metabolic syndrome. The diet of 19 men with metabolic syndrome (age, 24–62 years) was first standardized to a North America...

  2. Apolipoprotein A-IV inhibits AgRP/NPY neurons and activates POMC neurons in the arcuate nucleus

    Science.gov (United States)

    Apolipoprotein A-IV (apoA-IV) in the brain potently suppresses food intake. However the mechanisms underlying its anorexigenic effects remain to be identified. We first examined the effects of apoA-IV on cellular activities in hypothalamic neurons that co-express agouti-related peptide (AgRP) and ne...

  3. Lipid profiles reflecting high and low risk for coronary heart disease : Contribution of apolipoprotein E polymorphism and lifestyle

    NARCIS (Netherlands)

    Boer, J.M.A.; Feskens, E.J.M.; Schouten, E.G.; Havekes, L.M.; Seidell, J.C.; Kromhout, D.

    1998-01-01

    To elucidate the role of modifiable factors and the apolipoprotein E polymorphism in explaining lipid profiles reflecting low, average and high risk for coronary heart disease, we selected subjects from a large population-based study. Subjects with low total cholesterol (TC) (< 15th percentile) and

  4. Lipid profiles reflecting high and low risk for coronary heart disease: contribution of apolipoprotein E polymorphism and lifestyle.

    NARCIS (Netherlands)

    Boer, J.M.A.; Feskens, E.J.M.; Schouten, E.G.; Havekes, L.M.; Seidell, J.C.; Kromhout, D.

    1998-01-01

    To elucidate the role of modifiable factors and the apolipoprotein E polymorphism in explaining lipid profiles reflecting low, average and high risk for coronary heart disease, we selected subjects from a large population-based study. Subjects with low total cholesterol (TC) (<15th percentile)

  5. The transport of triglycerides through the secretory pathway of hepatocytes is impaired in apolipoprotein E deficient mice.

    NARCIS (Netherlands)

    Mensenkamp, A.R.; Luyn, M.J.A. van; Havinga, R.; Teusink, B.; Waterman, I.J.; Mann, C.J.; Elzinga, B.M.; Verkade, H.J.; Zammit, V.A.; Havekes, L.M.; Shoulders, C.C.; Kuipers, F.

    2004-01-01

    BACKGROUND/AIMS: Apolipoprotein E (apoE)-deficient mice develop hepatic steatosis and secrete reduced levels of VLDL-TG. METHODS AND RESULTS: We examined the effects of apoE-deficiency on intracellular lipid homeostasis and secretion of triglycerides (TG). We show that intracellular TG turnover and

  6. The transport of triglycerides through the secretory pathway of hepatocytes is impaired in apolipoprotein E deficient mice

    NARCIS (Netherlands)

    Mensenkamp, AR; van Luyn, MJA; Havinga, R; Teusink, B; Waterman, IJ; Mann, CJ; Elzinga, BM; Verkade, HJ; Zammit, VA; Havekes, LM; Shoulders, CC; Kuipers, F

    Background/Aims: Apolipoprotein E (apoE)-deficient mice develop hepatic steatosis and secrete reduced levels of VLDL-TG. Methods and results: We examined the effects of apoE-deficiency on intracellular lipid homeostasis and secretion of triglycerides (TG). We show that intracellular TG turnover and

  7. An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients

    NARCIS (Netherlands)

    Pullinger, Clive R.; Aouizerat, Bradley E.; Movsesyan, Irina; Durlach, Vincent; Sijbrands, Eric J.; Nakajima, Katsuyuki; Poon, Annie; Dallinga-Thie, Geesje M.; Hattori, Hiroaki; Green, Lauri L.; Kwok, Pui-Yan; Havel, Richard J.; Frost, Philip H.; Malloy, Mary J.; Kane, John P.

    2008-01-01

    Apolipoprotein A-V (apoA-V) is an important regulator of plasma levels of triglyceride (TG) in mice. In humans, APOA5 genetic variation is associated with TG in several populations. In this study, we determined the effects of the p.185Gly>Cys (c.553G>T; rs2075291) polymorphism on plasma TG levels in

  8. An apolipoprotein A-V gene SNP is associated with marked hypertriglyceridemia among Asian-American patients

    NARCIS (Netherlands)

    C.R. Pullinger (Clive); B.E. Aouizerat (Bradley); I. Movsesyan (Irina); V. Durlach (Vincent); E.J.G. Sijbrands (Eric); K. Nakajima (Katsuyuki); A. Poon (Annie); G.M. Dallinga-Thie (Geesje); H. Hattori (Hiroaki); L.L. Green (Lauri); P.-Y. Kwok (Pui-Yan); R.J. Havel (Richard); P.H. Frost (Philip); M.J. Malloy (Mary); J.P. Kane (John)

    2008-01-01

    textabstractApolipoprotein A-V (apoA-V) is an important regulator of plasma levels of triglyceride (TG) in mice. In humans, APOA5 genetic variation is associated with TG in several populations. In this study, we determined the effects of the p.185Gly>Cys (c.553G>T; rs2075291) polymorphism on plasma

  9. High-salt diet combined with elevated angiotensin II accelerates atherosclerosis in apolipoprotein E-deficient mice

    DEFF Research Database (Denmark)

    Johansson, Maria E; Bernberg, Evelina; Andersson, Irene J

    2009-01-01

    to atherosclerosis. METHODS: Apolipoprotein E-deficient (ApoE-/-) mice received standard or high-salt diet (8%) alone or in combination with fixed angiotensin II (Ang II) infusion (0.5 microg/kg per min). BP was measured using telemetry, and plaque burden was assessed in the thoracic aorta and innominate artery. We...

  10. Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake

    NARCIS (Netherlands)

    Berg, S.A.A. van den; Heemskerk, M.M.; Geerling, J.J.; Klinken, J.B. van; Schaap, F.G.; Bijland, S.; Berbée, J.F.P.; Harmelen, V.J.A. van; Pronk, A.C.M.; Schreurs, M.; Havekes, L.M.; Rensen, P.C.N.; Dijk, K.W. van

    2013-01-01

    Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the

  11. Apolipoprotein A5 deficiency aggravates high-fat diet-induced obesity due to impaired central regulation of food intake

    NARCIS (Netherlands)

    van den Berg, Sjoerd A. A.; Heemskerk, Mattijs M.; Geerling, Janine J.; van Klinken, Jan-Bert; Schaap, Frank G.; Bijland, Silvia; Berbee, Jimmy F. P.; van Harmelen, Vanessa J. A.; Pronk, Amanda C. M.; Bijker-Schreurs, Marijke; Havekes, Louis M.; Rensen, Patrick C. N.; van Dijk, Ko Willems

    Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the

  12. Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism

    NARCIS (Netherlands)

    Helgadottir, Anna; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Holm, Hilma; Patel, Riyaz S.; Gudnason, Thorarinn; Jones, Gregory T.; van Rij, Andre M.; Eapen, Danny J.; Baas, Annette F.; Tregouet, David-Alexandre; Morange, Pierre-Emmanuel; Emmerich, Joseph; Lindblad, Bengt; Gottsater, Anders; Kiemeny, Lambertus A.; Lindholt, Jes S.; Sakalihasan, Natzi; Ferrell, Robert E.; Carey, David J.; Elmore, James R.; Tsao, Philip S.; Grarup, Niels; Jorgensen, Torben; Witte, Daniel R.; Hansen, Torben; Pedersen, Oluf; Pola, Roberto; Gaetani, Eleonora; Magnadottir, Hulda B.; Wijmenga, Cisca; Tromp, Gerard; Ronkainen, Antti; Ruigrok, Ynte M.; Blankensteijn, Jan D.; Mueller, Thomas; Wells, Philip S.; Corral, Javier; Manuel Soria, Jose; Carlos Souto, Juan; Peden, John F.; Jalilzadeh, Shapour; Mayosi, Bongani M.; Keavney, Bernard; Strawbridge, Rona J.; Sabater-Lleal, Maria; Gertow, Karl; Baldassarre, Damiano; Nyyssonen, Kristiina; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Tremoli, Elena; de Faire, Ulf; Humphries, Steve E.; Hamsten, Anders; Haraldsdottir, Vilhelmina; Olafsson, Isleifur; Magnusson, Magnus K.; Samani, Nilesh J.; Levey, Allan I.; Markus, Hugh S.; Kostulas, Konstantinos; Dichgans, Martin; Berger, Klaus; Kuhlenbaeumer, Gregor; Ringelstein, E. Bernd; Stoll, Monika; Seedorf, Udo; Rothwell, Peter M.; Powell, Janet T.; Kuivaniemi, Helena; Onundarson, Pall T.; Valdimarsson, Einar; Matthiasson, Stefan E.; Gudbjartsson, Daniel F.; Thorgeirsson, Guomundur; Quyyumi, Arshed A.; Watkins, Hugh; Farrall, Martin; Thorsteinsdottir, Unnur; Stefansson, Kari

    2012-01-01

    Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with

  13. Roles of high apolipoprotein E blood levels and HDL in development of familial dysbetalipoproteinemia in ε2ε2 subjects

    NARCIS (Netherlands)

    Corsetti, James P; Sparks, Charles E; Bakker, Stephan J L; Gruppen, Eke G; Dullaart, Robin P F

    2017-01-01

    OBJECTIVE: Familial dysbetalipoproteinemia (FD) or Type III hyperlipoproteinemia is a mixed hyperlipidemia closely associated with the ε2ε2 genotype of the common APOE polymorphism although not all homozygotes progress to FD. Unlike the polymorphism, few studies explore effects of apolipoprotein E

  14. Impact of lipoprotein(a) levels and apolipoprotein(a) isoform size on risk of coronary heart disease

    NARCIS (Netherlands)

    Hopewell, J. C.; Seedorf, U.; Farrall, M.; Parish, S.; Kyriakou, T.; Goel, A.; Hamsten, A.; Collins, R.; Watkins, H.; Clarke, R.; van der Hout, Annemarie H.

    Objectives. Observational and genetic studies have shown that lipoprotein(a) [Lp(a)] levels and apolipoprotein( a) [apo(a)] isoform size are both associated with coronary heart disease (CHD) risk, but the relative independence of these risk factors remains unclear. Clarification of this uncertainty

  15. Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics

    DEFF Research Database (Denmark)

    Rune, Ida; Rolin, Bidda; Lykkesfeldt, Jens

    2018-01-01

    In the apolipoprotein E-deficient mouse, the gut microbiota has an impact on the development of atherosclerosis, but whether such correlations are also present in rats requires investigation. Therefore, we studied female SD-Apoe tm1sage (Apoe -/-) rats fed either a Western diet or a low-fat control...

  16. Preoperative apolipoprotein CI levels correlate positively with the proinflammatory response in patients experiencing endotoxemia following elective cardiac surgery

    NARCIS (Netherlands)

    Schippers, E.F.; Berbée, J.F.P.; Disseldorp, I.M. van; Versteegh, M.I.M.; Havekes, L.M.; Rensen, P.C.N.; Dissel, J.T. van

    2008-01-01

    Objective: Experimental models show that apolipoprotein CI (apoCI) binds and enhances the inflammatory response to endotoxin. We studied in patients undergoing cardiopulmonary bypass surgery (CPB) and experiencing endotoxemia during reperfusion whether plasma apoCI levels correlate with the

  17. Apolipoprotein E deficiency increases remnant lipoproteins and accelerates progressive atherosclerosis, but not xanthoma formation, in gene modified minipigs

    DEFF Research Database (Denmark)

    Shim, Jeong; Poulsen, Christian Bo; Hagensen, Mette K.

    2017-01-01

    Summary: Deficiency of apolipoprotein E (APOE) causes familial dysbetalipoproteinemia in humans resulting in a higher risk of atherosclerotic disease. In mice, APOE deficiency results in a severe atherosclerosis phenotype, but it is unknown to what extent this is unique to mice. In this study, AP...

  18. Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease

    DEFF Research Database (Denmark)

    Mattsson, Niklas; Groot, Colin; Jansen, Willemijn J

    2018-01-01

    INTRODUCTION: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. METHODS: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cog...

  19. Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis

    International Nuclear Information System (INIS)

    Huff, M.W.; Breckenridge, W.C.; Strong, W.L.; Wolfe, B.M.

    1988-01-01

    The C apolipoproteins are normally transferred to high density lipoproteins (HDL) after lipolysis of very low density lipoprotein (VLDL) triglyceride. In previous studies, a loss of plasma C apolipoproteins was documented after heparin-induced lipolysis in hypertriglyceridemic subjects. The present studies were designed to determine if this decline in plasma C apolipoproteins was due to their clearance with VLDL remnants. Five Type IV hypertriglyceridemic and two normal subjects were injected with 125I-VLDL and 131I-low density lipoproteins (LDL) to document kinetically an excess of VLDL apolipoprotein (apo) B flux relative to LDL apo B flux in the Type IV subjects. A mean of 46% VLDL apo B was cleared from the circulation, without conversion to intermediate density lipoprotein (IDL) or LDL. Heparin was then infused (9000 IU over 4 hours) to generate an excess of VLDL remnants that were not converted to IDL or LDL. VLDL triglyceride, apo B, and apo C concentrations fell at a similar rate. VLDL apo B declined by 42% (p less than 0.01). However, no increases were observed in IDL or LDL apo B in the Type IV subjects. This resulted in a 14% (p less than 0.01) decline in plasma apo B concentrations, indicating a clearance of VLDL remnants. VLDL apo C-II and C-III concentrations fell by 42% (p less than 0.025) and 52% (p less than 0.01), respectively. During the first 2.5 hours of infusion, they were almost quantitatively recovered in HDL. Thereafter, the C apolipoproteins declined in HDL during which time VLDL apo C concentrations continued to decline

  20. Apolipoprotein M

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2013-01-01

    for S1P. S1P is a bioactive lipid with effects on angiogenesis, lymphocyte trafficking, endothelial cell migration, and inflammation. A drug targeting the S1P-system (fingolimod) is now used for treatment of multiple sclerosis. It improves the blood–brain barrier and inhibits migration of lymphocytes...

  1. Apolipoprotein CII

    Science.gov (United States)

    ... lipoprotein ( VLDL ), which is made up of mostly triglycerides (a type of fat in your blood). This ... gov/pubmed/23257303 . Semenkovich CF. Disorders of lipid metabolism. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  2. Continuous bounded cohomology of locally compact groups

    CERN Document Server

    2001-01-01

    Recent research has repeatedly led to connections between important rigidity questions and bounded cohomology. However, the latter has remained by and large intractable. This monograph introduces the functorial study of the continuous bounded cohomology for topological groups, with coefficients in Banach modules. The powerful techniques of this more general theory have successfully solved a number of the original problems in bounded cohomology. As applications, one obtains, in particular, rigidity results for actions on the circle, for representations on complex hyperbolic spaces and on Teichmüller spaces. A special effort has been made to provide detailed proofs or references in quite some generality.

  3. Positivity bounds on double parton distributions

    International Nuclear Information System (INIS)

    Diehl, Markus; Kasemets, Tomas

    2013-03-01

    Double hard scattering in proton-proton collisions is described in terms of double parton distributions. We derive bounds on these distributions that follow from their interpretation as probability densities, taking into account all possible spin correlations between two partons in an unpolarized proton. These bounds constrain the size of the polarized distributions and can for instance be used to set upper limits on the effects of spin correlations in double hard scattering. We show that the bounds are stable under leading-order DGLAP evolution to higher scales.

  4. Remarks on Bousso's covariant entropy bound

    CERN Document Server

    Mayo, A E

    2002-01-01

    Bousso's covariant entropy bound is put to the test in the context of a non-singular cosmological solution of general relativity found by Bekenstein. Although the model complies with every assumption made in Bousso's original conjecture, the entropy bound is violated due to the occurrence of negative energy density associated with the interaction of some the matter components in the model. We demonstrate how this property allows for the test model to 'elude' a proof of Bousso's conjecture which was given recently by Flanagan, Marolf and Wald. This corroborates the view that the covariant entropy bound should be applied only to stable systems for which every matter component carries positive energy density.

  5. The bound state problem and quark confinement

    International Nuclear Information System (INIS)

    Chaichian, M.; Demichev, A.P.; Nelipa, N.F.

    1980-01-01

    A quantum field-theoretic model in which quark is confined is considered. System of equations for the Green functions of colour singlet and octet bound states is obtained. The method is based on the nonperturbative Schwinger-Dyson equations with the use of Slavnov-Taylor identities. It is shown that in the framework of the model if there exist singlet, then also exist octet bound states of the quark-antiquark system. Thus in general, confinement of free quarks does not mean absence of their coloured bound states. (author)

  6. Quasi-bound states in continuum

    International Nuclear Information System (INIS)

    Nakamura, Hiroaki; Hatano, Naomichi; Garmon, Sterling; Petrosky, Tomio

    2007-08-01

    We report the prediction of quasi-bound states (resonant states with very long lifetimes) that occur in the eigenvalue continuum of propagating states for a wide region of parameter space. These quasi-bound states are generated in a quantum wire with two channels and an adatom, when the energy bands of the two channels overlap. A would-be bound state that lays just below the upper energy band is slightly destabilized by the lower energy band and thereby becomes a resonant state with a very long lifetime (a second QBIC lays above the lower energy band). (author)

  7. Apolipoprotein(a) in insulin-dependent diabetic patients with and without diabetic nephropathy

    DEFF Research Database (Denmark)

    Gall, M A; Rossing, P; Hommel, E

    1992-01-01

    Insulin-dependent diabetic patients with diabetic nephropathy have a highly increased morbidity and mortality from cardiovascular diseases. To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute...... to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50...... healthy subjects (group 4). The groups were matched with regard to sex, age and body mass index. The diabetic groups were also matched with regard to diabetes duration. The level of apo(a) was approximately the same in the four groups, being: 122 (x/ divided by 4.2) U l-1, 63 (x/ divided by 4.4) U l-1...

  8. Plasma lipid oxidation predicts atherosclerotic status better than cholesterol in diabetic apolipoprotein E deficient mice

    DEFF Research Database (Denmark)

    Petersen, Karen Ekkelund; Lykkesfeldt, Jens; Raun, Kirsten

    2017-01-01

    Increased levels of oxidative stress have been suggested to play a detrimental role in the development of diabetes-related vascular complications. Here, we investigated whether the concentration of malondialdehyde, a marker of lipid oxidation correlated to the degree of aortic plaque lesions...... in a proatherogenic diabetic mouse model. Three groups of apolipoprotein E knockout mice were studied for 20 weeks, a control, a streptozotocin-induced diabetic, and a diabetic enalapril-treated group. Enalapril was hypothesized to lower oxidative stress level and thus the plaque burden. Both diabetic groups were...... significantly different from the control group as they had higher blood glucose, HbA1c, total cholesterol, low-density lipoprotein, very low-density lipoprotein, together with a lower high-density lipoprotein concentration and body weight. Animals in the diabetic group had significantly higher plaque area...

  9. Apolipoprotein E gene polymorphism and Alzheimer's disease in Chinese population: a meta-analysis

    Science.gov (United States)

    Liu, Mengying; Bian, Chen; Zhang, Jiqiang; Wen, Feng

    2014-03-01

    The relationship between Apolipoprotein E (ApoE) genotype and the risk of Alzheimer's disease (AD) is relatively well established in Caucasians, but less established in other ethnicities. To examine the association between ApoE polymorphism and the onset of AD in Chinese population, we searched the commonly used electronic databases between January 2000 and November 2013 for relevant studies. Total 20 studies, including 1576 cases and 1741 controls, were retrieved. The results showed statistically significant positive association between risk factor ɛ4 allele carriers and AD in Chinese population (OR = 3.93, 95% CI = 3.37-4.58, P risk suffering from AD than controls in Chinese population. The results also provide a support for the protection effect of ApoE ɛ3 allele in developing AD.

  10. Association of apolipoprotein e gene polymorphisms with blood lipids and their interaction with dietary factors

    DEFF Research Database (Denmark)

    Shatwan, Israa M.; Winther, Kristian Hillert; Ellahi, Basma

    2018-01-01

    of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. Methods: The population studied for this investigation included 660 individuals from...... the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ......Background: Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association...

  11. Association of Apolipoprotein E Polymorphism with Ischemic Stroke Subtypes in Taiwan

    Directory of Open Access Journals (Sweden)

    Chiou-Lian Lai

    2007-10-01

    Full Text Available The aim of this study was to clarify whether the apolipoprotein E gene (APOE is related to ischemic stroke subtypes in Taiwan's Chinese population. Using the classification of Cerebrovascular Diseases III, 143 patients with lacunar infarction, 114 patients with atherothrombotic infarction, and 112 healthy controls were enrolled. APOE genotype was determined using polymerase chain reaction. Regarding the distribution of APOE genotypes, the frequency of ϵ3/ϵ4 genotypes in lacunar patients was significantly different from that in control subjects, by logistic regression, using ϵ3/ϵ3 as a reference group. There was no significant difference between atherothrombotic patients and the control group in the distribution of APOE genotypes or alleles. The present finding suggests that there is a probable association between ϵ3/ϵ4 genotype and lacunar infarcts, but not atherothrombotic infarcts. This indicates that genetic factors may play a role, at least partially, in lacunar infarction in Taiwan's Chinese population.

  12. Comparison of Serum Apolipoprotein Levels of Diabetic Children and Healthy Children with or without Diabetic Parents

    Directory of Open Access Journals (Sweden)

    Mohammad Hashemi

    2012-01-01

    Full Text Available Introduction. The association of diabetes and atherosclerosis with disorders of lipids and lipoproteins, notably high apolipoprotein B (apoB and low apolipoprotein A1(apoA1 is well established. Because of the beginning of the atherosclerosis' process from early life, in this study, the plasma levels of apoA1 and apoB were compared in diabetic children with type I diabetes mellitus(DM, healthy children with diabetic parents (HDPs,and healthy children with nondiabetic parents (HNDPs. Methods. This case-control study was conducted among 90 children aged 9–18 years. Serum levels of apoA and apoB were compared among 30 diabetic children (DM, 30 healthy children with diabetic parents (HDPs, and 30 healthy children with nondiabetic parents (HNDP. Results. The mean serum apoA1 was higher in DM (153±69 mg/dL followed by HNDPs (138±58 mg/dL and HDPs (128±56 mg/dl, but the difference was not statistically significant. The mean apoB value in HNDPs was significantly lower than DM and HDPs (90±21 mg/dL versus 127±47 and 128±38 mg/dL, P0.05. Conclusions. Diabetic children and healthy children with diabetic parent(s are at higher risk of dyslipidemia and atherosclerosis. Thus for primordial and primary prevention of atherosclerosis, we suggest screening these children for low plasma apoA1 and high plasma apoB levels.

  13. Secretion of hepatitis C virus envelope glycoproteins depends on assembly of apolipoprotein B positive lipoproteins.

    Directory of Open Access Journals (Sweden)

    Vinca Icard

    Full Text Available The density of circulating hepatitis C virus (HCV particles in the blood of chronically infected patients is very heterogeneous. The very low density of some particles has been attributed to an association of the virus with apolipoprotein B (apoB positive and triglyceride rich lipoproteins (TRL likely resulting in hybrid lipoproteins known as lipo-viro-particles (LVP containing the viral envelope glycoproteins E1 and E2, capsid and viral RNA. The specific infectivity of these particles has been shown to be higher than the infectivity of particles of higher density. The nature of the association of HCV particles with lipoproteins remains elusive and the role of apolipoproteins in the synthesis and assembly of the viral particles is unknown. The human intestinal Caco-2 cell line differentiates in vitro into polarized and apoB secreting cells during asymmetric culture on porous filters. By using this cell culture system, cells stably expressing E1 and E2 secreted the glycoproteins into the basal culture medium after one week of differentiation concomitantly with TRL secretion. Secreted glycoproteins were only detected in apoB containing density fractions. The E1-E2 and apoB containing particles were unique complexes bearing the envelope glycoproteins at their surface since apoB could be co-immunoprecipitated with E2-specific antibodies. Envelope protein secretion was reduced by inhibiting the lipidation of apoB with an inhibitor of the microsomal triglyceride transfer protein. HCV glycoproteins were similarly secreted in association with TRL from the human liver cell line HepG2 but not by Huh-7 and Huh-7.5 hepatoma cells that proved deficient for lipoprotein assembly. These data indicate that HCV envelope glycoproteins have the intrinsic capacity to utilize apoB synthesis and lipoprotein assembly machinery even in the absence of the other HCV proteins. A model for LVP assembly is proposed.

  14. Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen

    International Nuclear Information System (INIS)

    Eaton, D.L.; Fless, G.M.; Kohr, W.J.; McLean, J.W.; Xu, Q.T.; Miller, C.G.; Lawn, R.M.; Scanu, A.M.

    1987-01-01

    Apolipoprotein(a) [apo(a)] is a glycoprotein with M/sub r/ ∼ 280,000 that is disulfide linked to apolipoprotein B in lipoprotein(a) particles. Elevated plasma levels of lipoprotein(a) are correlated with atherosclerosis. Partial amino acid sequence of apo(a) shows that it has striking homology to plasminogen. Plasminogen is a plasma serine protease zymogen that consists of five homologous and tandemly repeated domains called kringles and a trypsin-like protease domain. The amino-terminal sequence obtained for apo(a) is homologous to the beginning of kringle 4 but not the amino terminus of plasminogen. Apo(a) was subjected to limited proteolysis by trypsin or V8 protease, and fragments generated were isolated and sequenced. Sequences obtained from several of these fragments are highly (77-100%) homologous to plasminogen residues 391-421, which reside within kringle 4. Analysis of these internal apo(a) sequences revealed that apo(a) may contain at least two kringle 4-like domains. A sequence obtained from another tryptic fragment also shows homology to the end of kringle 4 and the beginning of kringle 5. Sequence data obtained from the two tryptic fragments shows homology with the protease domain of plasminogen. One of these sequences is homologous to the sequences surrounding the activation site of plasminogen. Plasminogen is activated by the cleavage of a specific arginine residue by urokinase and tissue plasminogen activator; however, the corresponding site in apo(a) is a serine that would not be cleaved by tissue plasminogen activator or urokinase. Using a plasmin-specific assay, no proteolytic activity could be demonstrated for lipoprotein(a) particles. These results suggest that apo(a) contains kringle-like domains and an inactive protease domain

  15. Serum apolipoprotein E concentration and polymorphism influence serum lipid levels in Chinese Shandong Han population.

    Science.gov (United States)

    Han, ShuYi; Xu, YiHui; Gao, MeiHua; Wang, YunShan; Wang, Jun; Liu, YanYan; Wang, Min; Zhang, XiaoQian

    2016-12-01

    Apolipoprotein E (ApoE), which has been shown to influence serum lipid parameters, can bind to multiple types of lipids and plays an important role in the metabolism and homeostasis of lipids and lipoproteins. A previous study showed that ApoE concentration significantly affects serum lipid levels independently of ApoE polymorphism. The serum lipid levels were also closely correlated with dietary habits, and Shandong cuisine is famous for its high salt and oil contents, which widely differ among the different areas in China. Therefore, studying the effect of ApoE polymorphism on ApoE concentration and serum lipid levels in Shandong province is very important.A total of 815 subjects including 285 men and 530 women were randomly selected and studied from Jinan, Shandong province. In order to evaluate the association of ApoE polymorphism and serum level on lipid profiles, the ApoE genotypes, as well as levels of fasting serum ApoE and other lipid parameters, were detected in all subjects.The frequency of the ApoE E3 allele was highest (83.1%), while those of E2 and E4 were 9.4% and 7.5%, respectively, which are similar to those in other Asian populations. ApoE2 allele carriers showed significantly increased ApoE levels but lower levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and Apolipoprotein B (ApoB).We found that ApoE level is influenced by ApoE polymorphism in a gene-dependent manner. The ApoE polymorphism showed different influences on serum lipid parameters with increasing age and body mass index (BMI) in our Shandong Han population.

  16. Apolipoprotein C3 polymorphisms, cognitive function and diabetes in Caribbean origin Hispanics.

    Directory of Open Access Journals (Sweden)

    Caren E Smith

    Full Text Available Apolipoprotein C3 (APOC3 modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3 gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.We examined whether APOC3 single nucleotide polymorphisms (SNPs m482 (rs2854117 and 3u386 (rs5128 were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45-74 living in the Boston metropolitan area.Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009, Stroop color naming score (P = 0.014 and Stroop color-word score (P = 0.022 compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032 and total cholesterol (P = 0.028 compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004, total cholesterol (P = 0.003 and glucose (P = 0.016 compared to CC subjects.In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted.

  17. Tight Bounds for Distributed Functional Monitoring

    DEFF Research Database (Denmark)

    Woodruff, David P.; Zhang, Qin

    2011-01-01

    $, our bound resolves their main open question. Our lower bounds are based on new direct sum theorems for approximate majority, and yield significant improvements to problems in the data stream model, improving the bound for estimating $F_p, p > 2,$ in $t$ passes from $\\tilde{\\Omega}(n^{1-2/p}/(\\eps^{2/p......} t))$ to $\\tilde{\\Omega}(n^{1-2/p}/(\\eps^{4/p} t))$, giving the first bound for estimating $F_0$ in $t$ passes of $\\Omega(1/(\\eps^2 t))$ bits of space that does not use the gap-hamming problem, and showing a distribution for the gap-hamming problem with high external information cost or super...

  18. Redshift-space limits of bound structures

    NARCIS (Netherlands)

    Duenner, Rolando; Reisenegger, Andreas; Meza, Andres; Araya, Pablo A.; Quintana, Hernan

    2007-01-01

    An exponentially expanding Universe, possibly governed by a cosmological constant, forces gravitationally bound structures to become more and more isolated, eventually becoming causally disconnected from each other and forming so-called 'island universes'. This new scenario reformulates the question

  19. Error Bounds: Necessary and Sufficient Conditions

    Czech Academy of Sciences Publication Activity Database

    Outrata, Jiří; Kruger, A.Y.; Fabian, Marián; Henrion, R.

    2010-01-01

    Roč. 18, č. 2 (2010), s. 121-149 ISSN 1877-0533 R&D Projects: GA AV ČR IAA100750802 Institutional research plan: CEZ:AV0Z10750506; CEZ:AV0Z10190503 Keywords : Error bounds * Calmness * Subdifferential * Slope Subject RIV: BA - General Mathematics Impact factor: 0.333, year: 2010 http://library.utia.cas.cz/separaty/2010/MTR/outrata-error bounds necessary and sufficient conditions.pdf

  20. Malabsorption of protein bound vitamin B12.

    OpenAIRE

    Dawson, D W; Sawers, A H; Sharma, R K

    1984-01-01

    Patients with subnormal serum vitamin B12 concentrations were tested for absorption of protein bound vitamin B12 and compared with controls. Absorption of the protein bound vitamin appeared to decrease with increasing age in healthy subjects. Differences between the result of this test and the result of the Schilling test in patients who had undergone gastric surgery were confirmed; such differences were also seen in some patients who had iron deficiency anaemia, an excessive alcohol intake, ...

  1. New Spectral Features from Bound Dark Matter

    DEFF Research Database (Denmark)

    Catena, Riccardo; Kouvaris, Chris

    2016-01-01

    We demonstrate that dark matter particles gravitationally bound to the Earth can induce a characteristic nuclear recoil signal at low energies in direct detection experiments. The new spectral feature we predict can provide the ultimate smoking gun for dark matter discovery for experiments...... with positive signal but unclear background. The new feature is universal, in that the ratio of bound over halo dark matter event rates at detectors is independent of the dark matter-nucleon cross section....

  2. Automatic bounding estimation in modified NLMS algorithm

    International Nuclear Information System (INIS)

    Shahtalebi, K.; Doost-Hoseini, A.M.

    2002-01-01

    Modified Normalized Least Mean Square algorithm, which is a sign form of Nlm based on set-membership (S M) theory in the class of optimal bounding ellipsoid (OBE) algorithms, requires a priori knowledge of error bounds that is unknown in most applications. In a special but popular case of measurement noise, a simple algorithm has been proposed. With some simulation examples the performance of algorithm is compared with Modified Normalized Least Mean Square

  3. Akt inhibition promotes ABCA1-mediated cholesterol efflux to ApoA-I through suppressing mTORC1.

    Directory of Open Access Journals (Sweden)

    Fumin Dong

    Full Text Available ATP-binding cassette transporter A1 (ABCA1 plays an essential role in mediating cholesterol efflux to apolipoprotein A-I (apoA-I, a major housekeeping mechanism for cellular cholesterol homeostasis. After initial engagement with ABCA1, apoA-I directly interacts with the plasma membrane to acquire cholesterol. This apoA-I lipidation process is also known to require cellular signaling processes, presumably to support cholesterol trafficking to the plasma membrane. We report here that one of major signaling pathways in mammalian cells, Akt, is also involved. In several cell models that express ABCA1 including macrophages, pancreatic beta cells and hepatocytes, inhibition of Akt increases cholesterol efflux to apoA-I. Importantly, Akt inhibition has little effect on cells expressing non-functional mutant of ABCA1, implicating a specific role of Akt in ABCA1 function. Furthermore, we provide evidence that mTORC1, a major downstream target of Akt, is also a negative regulator of cholesterol efflux. In cells where mTORC1 is constitutively activated due to tuberous sclerosis complex 2 deletion, cholesterol efflux to apoA-I is no longer sensitive to Akt activity. This suggests that Akt suppresses cholesterol efflux through mTORC1 activation. Indeed, inhibition of mTORC1 by rapamycin or Torin-1 promotes cholesterol efflux. On the other hand, autophagy, one of the major pathways of cholesterol trafficking, is increased upon Akt inhibition. Furthermore, Akt inhibition disrupts lipid rafts, which is known to promote cholesterol efflux to apoA-I. We therefore conclude that Akt, through its downstream targets, mTORC1 and hence autophagy, negatively regulates cholesterol efflux to apoA-I.

  4. Absolute Lower Bound on the Bounce Action

    Science.gov (United States)

    Sato, Ryosuke; Takimoto, Masahiro

    2018-03-01

    The decay rate of a false vacuum is determined by the minimal action solution of the tunneling field: bounce. In this Letter, we focus on models with scalar fields which have a canonical kinetic term in N (>2 ) dimensional Euclidean space, and derive an absolute lower bound on the bounce action. In the case of four-dimensional space, we show the bounce action is generically larger than 24 /λcr, where λcr≡max [-4 V (ϕ )/|ϕ |4] with the false vacuum being at ϕ =0 and V (0 )=0 . We derive this bound on the bounce action without solving the equation of motion explicitly. Our bound is derived by a quite simple discussion, and it provides useful information even if it is difficult to obtain the explicit form of the bounce solution. Our bound offers a sufficient condition for the stability of a false vacuum, and it is useful as a quick check on the vacuum stability for given models. Our bound can be applied to a broad class of scalar potential with any number of scalar fields. We also discuss a necessary condition for the bounce action taking a value close to this lower bound.

  5. Generalized surface tension bounds in vacuum decay

    Science.gov (United States)

    Masoumi, Ali; Paban, Sonia; Weinberg, Erick J.

    2018-02-01

    Coleman and De Luccia (CDL) showed that gravitational effects can prevent the decay by bubble nucleation of a Minkowski or AdS false vacuum. In their thin-wall approximation this happens whenever the surface tension in the bubble wall exceeds an upper bound proportional to the difference of the square roots of the true and false vacuum energy densities. Recently it was shown that there is another type of thin-wall regime that differs from that of CDL in that the radius of curvature grows substantially as one moves through the wall. Not only does the CDL derivation of the bound fail in this case, but also its very formulation becomes ambiguous because the surface tension is not well defined. We propose a definition of the surface tension and show that it obeys a bound similar in form to that of the CDL case. We then show that both thin-wall bounds are special cases of a more general bound that is satisfied for all bounce solutions with Minkowski or AdS false vacua. We discuss the limit where the parameters of the theory attain critical values and the bound is saturated. The bounce solution then disappears and a static planar domain wall solution appears in its stead. The scalar field potential then is of the form expected in supergravity, but this is only guaranteed along the trajectory in field space traced out by the bounce.

  6. Apolipoprotein AIF gene variant S347 is associated with increased risk of coronary heart disease and lower apolipoprotein AIV plasma concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Wai-man R.; Hawe, Emma; Li, Lai K.; Miller, George J.; Nicaud, Viviane; Pennacchio, Len A.; Humphries, Steve E.; Talmud, Philippa J.

    2003-01-30

    The impact of common variants in the apolipoprotein gene cluster (APOC3-A4-A5) on prospective CHD risk was examined in healthy UK men. Of the 2808 men followed over nine years, 187 had a clinically defined CHD event. Examination of 9 single nucleotide polymorphisms (SNPs) in this group revealed that homozygotes for APOA4 S347 had significantly increased risk of CHD [Hazard ratio (HR) of 2.07 (95%CI 1.04-4.12)] while men homozygous for APOC3 1100T were protected (HR 0.28 (95%CI 0.09-0.87)). In stepwise multiple regression analysis, after entering all the variants and adjusting for established risk factors APOA4 T347S alone remained in the model. Using nine-SNP haplotype analysis, highest risk-estimate haplotypes carried APOA4 S347 and rare alleles of the two flanking intergenic markers. The protective effect of APOC31100T could be explained by negative linkage disequilibrium with these alleles. To determine the association of APOA4 T347S with apoAIVlevels, the relationship was examined in over 1600 healthy young European men and women. S347 homozygotes had significantly lower apoAIV plasma levels (13.48 + 0.6mg/dl) compared to carriers of the T347 allele (14.85 + 0.12 mg/dl) (p=0.025). These results demonstrate that genetic variation in and around APOA4, independent of effects of TG, is associated with risk of CHD and apoAIV levels, supporting an anti-atherogenic role for apoAIV.

  7. Lifestyle and Dietary Determinants of Serum Apolipoprotein A1 and Apolipoprotein B Concentrations: Cross-Sectional Analyses within a Swedish Cohort of 24,984 Individuals

    Directory of Open Access Journals (Sweden)

    Kasper Frondelius

    2017-02-01

    Full Text Available Low serum apolipoprotein (Apo A1 concentrations and high serum ApoB concentrations may be better markers of the risk of cardiovascular disease than high-density lipoprotein (HDL and low-density lipoprotein (LDL. However, the associations between modifiable lifestyle factors and Apo concentrations have not been investigated in detail. Therefore, this study investigated the associations between Apo concentrations and education, lifestyle factors and dietary intake (macronutrients and 34 food groups. These cross-sectional associations were examined among 24,984 individuals in a Swedish population-based cohort. Baseline examinations of the cohort were conducted between 1991 and 1996. Dietary intake was assessed using a modified diet history method. The main determinants of high ApoA1 concentrations (r between 0.05 and 0.25 were high alcohol consumption, high physical activity, non-smoking, and a low body mass index (BMI, and the main determinants of high ApoB concentrations were smoking and a high BMI. The intake of sucrose and food products containing added sugar (such as pastries, sweets, chocolate, jam/sugar and sugar-sweetened beverages was negatively correlated with ApoA1 concentrations and positively correlated with ApoB concentrations and the ApoB/ApoA1 ratio, whereas the intake of fermented dairy products, such as fermented milk and cheese, was positively correlated with ApoA1 concentrations and negatively correlated with the ApoB/ApoA1 ratio. These results indicate that smoking, obesity, low physical activity, low alcohol consumption and a diet high in sugar and low in fermented dairy products are correlated with an unfavorable Apo profile.

  8. Lifestyle and Dietary Determinants of Serum Apolipoprotein A1 and Apolipoprotein B Concentrations: Cross-Sectional Analyses within a Swedish Cohort of 24,984 Individuals.

    Science.gov (United States)

    Frondelius, Kasper; Borg, Madelene; Ericson, Ulrika; Borné, Yan; Melander, Olle; Sonestedt, Emily

    2017-02-28

    Low serum apolipoprotein (Apo) A1 concentrations and high serum ApoB concentrations may be better markers of the risk of cardiovascular disease than high-density lipoprotein (HDL) and low-density lipoprotein (LDL). However, the associations between modifiable lifestyle factors and Apo concentrations have not been investigated in detail. Therefore, this study investigated the associations between Apo concentrations and education, lifestyle factors and dietary intake (macronutrients and 34 food groups). These cross-sectional associations were examined among 24,984 individuals in a Swedish population-based cohort. Baseline examinations of the cohort were conducted between 1991 and 1996. Dietary intake was assessed using a modified diet history method. The main determinants of high ApoA1 concentrations ( r between 0.05 and 0.25) were high alcohol consumption, high physical activity, non-smoking, and a low body mass index (BMI), and the main determinants of high ApoB concentrations were smoking and a high BMI. The intake of sucrose and food products containing added sugar (such as pastries, sweets, chocolate, jam/sugar and sugar-sweetened beverages) was negatively correlated with ApoA1 concentrations and positively correlated with ApoB concentrations and the ApoB/ApoA1 ratio, whereas the intake of fermented dairy products, such as fermented milk and cheese, was positively correlated with ApoA1 concentrations and negatively correlated with the ApoB/ApoA1 ratio. These results indicate that smoking, obesity, low physical activity, low alcohol consumption and a diet high in sugar and low in fermented dairy products are correlated with an unfavorable Apo profile.

  9. Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease.

    OpenAIRE

    Harrington, C. R.; Louwagie, J.; Rossau, R.; Vanmechelen, E.; Perry, R. H.; Perry, E. K.; Xuereb, J. H.; Roth, M.; Wischik, C. M.

    1994-01-01

    Alzheimer's disease (AD) is associated with an increased frequency of the apolipoprotein E type epsilon 4 allele. To address both the disease and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body type (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary complicat...

  10. Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells.

    Science.gov (United States)

    Sayılan Özgün, Gülben; Özgün, Eray; Tabakçıoğlu, Kıymet; Süer Gökmen, Selma; Eskiocak, Sevgi; Çakır, Erol

    2017-12-01

    Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. In vitro experimental study. HepG2 cells were incubated with 0 (control), 10, 50 and 200 μM of caffeine for 24 hours. Cell viability was evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels were measured by western blotting. We observed a significant increase on apolipoprotein A-1 and paraoxonase-1 protein levels in the cells incubated with 50 µM of caffeine and a significant increase on paraoxonase-1 protein level in the cells incubated with 200 µM of caffeine. Our study showed that caffeine does not change paraoxonase-3 protein level, but the higher doses used in our study do cause an increase in both apolipoprotein A-1 and paraoxonase-1 protein levels in liver cells.

  11. Upper bounds on superpartner masses from upper bounds on the Higgs boson mass.

    Science.gov (United States)

    Cabrera, M E; Casas, J A; Delgado, A

    2012-01-13

    The LHC is putting bounds on the Higgs boson mass. In this Letter we use those bounds to constrain the minimal supersymmetric standard model (MSSM) parameter space using the fact that, in supersymmetry, the Higgs mass is a function of the masses of sparticles, and therefore an upper bound on the Higgs mass translates into an upper bound for the masses for superpartners. We show that, although current bounds do not constrain the MSSM parameter space from above, once the Higgs mass bound improves big regions of this parameter space will be excluded, putting upper bounds on supersymmetry (SUSY) masses. On the other hand, for the case of split-SUSY we show that, for moderate or large tanβ, the present bounds on the Higgs mass imply that the common mass for scalars cannot be greater than 10(11)  GeV. We show how these bounds will evolve as LHC continues to improve the limits on the Higgs mass.

  12. Bounds on poloidal kinetic energy in plane layer convection

    Science.gov (United States)

    Tilgner, A.

    2017-12-01

    A numerical method is presented that conveniently computes upper bounds on heat transport and poloidal energy in plane layer convection for infinite and finite Prandtl numbers. The bounds obtained for the heat transport coincide with earlier results. These bounds imply upper bounds for the poloidal energy, which follow directly from the definitions of dissipation and energy. The same constraints used for computing upper bounds on the heat transport lead to improved bounds for the poloidal energy.

  13. NcoI dimorphic site located 8kb 3' to the human apolipoprotein AIV (APOA4) gene

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, R T; Malloy, M J; Kane, J P; Frossard, P M

    1988-02-11

    pA4C3 a 0.5kb fragment from the 3' end of the human apolipoprotein AIV cDNA was isolated from a human intestine cDNA library and cloned into the EcoRI site of the plasmid pUC18. NcoI (CCATGG) (New England Biolabs) detects a single two-allele polymorphism with a band at either 18.6kb or at 12.6kb. The human apolipoprotein AI-CIII-AIV gene complex has been assigned to the long arm of chromosome 11 by Southern blot analysis of human-Chinese hamster cell hybrids. Co-dominant segregation was demonstrated in one family of six individuals.

  14. The-1131T > C Polymorphism in the Apolipoprotein A5 Gene is Related to Hypertriglyceridemia in Taiwanese Aborigines

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Huang

    2008-04-01

    Full Text Available The prevalence of hypertriglyceridemia, considered to be an independent risk factor for the development of cardiovascular disease, is high in Taiwanese aborigines. This study was undertaken to examine the effect of the -1131T > C polymorphism in the apolipoprotein A5 gene on serum triglyceride levels in female Taiwanese aborigines. This was a cross-sectional study, and a total of 316 unrelated female Taiwanese aborigines were genotyped at the -1131T > C polymorphism in apolipoprotein A5 using the polymerase chain reaction-restriction fragment length polymorphism method. Serum triglyceride ≥150 mg/dL was defined as the hypertriglyceridemia group and triglyceride C polymorphism of the Apo A5 gene influences serum triglyceride levels in female Taiwanese aborigines, and that differences exist in the frequency of the C allele among people of various ethnicities.

  15. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Langsted, A.; Freiberg, J.J.; Nordestgaard, Børge

    2008-01-01

    BACKGROUND: Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events. METHODS AND RESULTS: We cross-sectionally studied 33 391 individuals 20 to 95...... to HDL cholesterol, and ratio of apolipoprotein B to apolipoprotein A1 did not change in response to normal food intake. The maximum changes after normal food and fluid intake from fasting levels were -0.2 mmol/L for total cholesterol, -0.2 mmol/L for low-density lipoprotein cholesterol, -0.1 mmol...... years of age from the Copenhagen General Population Study. We also studied 9319 individuals 20 to 93 years of age from the Copenhagen City Heart Study, 1166 of whom developed cardiovascular events during 14 years of follow-up. Compared with fasting levels, total cholesterol, low-density lipoprotein...

  16. Bounds for nonlinear composites via iterated homogenization

    Science.gov (United States)

    Ponte Castañeda, P.

    2012-09-01

    Improved estimates of the Hashin-Shtrikman-Willis type are generated for the class of nonlinear composites consisting of two well-ordered, isotropic phases distributed randomly with prescribed two-point correlations, as determined by the H-measure of the microstructure. For this purpose, a novel strategy for generating bounds has been developed utilizing iterated homogenization. The general idea is to make use of bounds that may be available for composite materials in the limit when the concentration of one of the phases (say phase 1) is small. It then follows from the theory of iterated homogenization that it is possible, under certain conditions, to obtain bounds for more general values of the concentration, by gradually adding small amounts of phase 1 in incremental fashion, and sequentially using the available dilute-concentration estimate, up to the final (finite) value of the concentration (of phase 1). Such an approach can also be useful when available bounds are expected to be tighter for certain ranges of the phase volume fractions. This is the case, for example, for the "linear comparison" bounds for porous viscoplastic materials, which are known to be comparatively tighter for large values of the porosity. In this case, the new bounds obtained by the above-mentioned "iterated" procedure can be shown to be much improved relative to the earlier "linear comparison" bounds, especially at low values of the porosity and high triaxialities. Consistent with the way in which they have been derived, the new estimates are, strictly, bounds only for the class of multi-scale, nonlinear composites consisting of two well-ordered, isotropic phases that are distributed with prescribed H-measure at each stage in the incremental process. However, given the facts that the H-measure of the sequential microstructures is conserved (so that the final microstructures can be shown to have the same H-measure), and that H-measures are insensitive to length scales, it is conjectured

  17. Thermalization Time Bounds for Pauli Stabilizer Hamiltonians

    Science.gov (United States)

    Temme, Kristan

    2017-03-01

    We prove a general lower bound to the spectral gap of the Davies generator for Hamiltonians that can be written as the sum of commuting Pauli operators. These Hamiltonians, defined on the Hilbert space of N-qubits, serve as one of the most frequently considered candidates for a self-correcting quantum memory. A spectral gap bound on the Davies generator establishes an upper limit on the life time of such a quantum memory and can be used to estimate the time until the system relaxes to thermal equilibrium when brought into contact with a thermal heat bath. The bound can be shown to behave as {λ ≥ O(N^{-1} exp(-2β overline{ɛ}))}, where {overline{ɛ}} is a generalization of the well known energy barrier for logical operators. Particularly in the low temperature regime we expect this bound to provide the correct asymptotic scaling of the gap with the system size up to a factor of N -1. Furthermore, we discuss conditions and provide scenarios where this factor can be removed and a constant lower bound can be proven.

  18. Universal bounds in even-spin CFTs

    Energy Technology Data Exchange (ETDEWEB)

    Qualls, Joshua D. [Department of Physics, National Taiwan University,Taipei, Taiwan (China)

    2015-12-01

    We prove using invariance under the modular S− and ST−transformations that every unitary two-dimensional conformal field theory (CFT) having only even-spin primary operators (with no extended chiral algebra and with right- and left-central charges c,c̃>1) contains a primary operator with dimension Δ{sub 1} satisfying 0<Δ{sub 1}<((c+c̃)/24)+0.09280…. After deriving both analytical and numerical bounds, we discuss how to extend our methods to bound higher conformal dimensions before deriving lower and upper bounds on the number of primary operators in a given energy range. Using the AdS{sub 3}/CFT{sub 2} dictionary, the bound on Δ{sub 1} proves the lightest massive excitation in appropriate theories of 3D matter and gravity with cosmological constant Λ<0 can be no heavier than 1/8G{sub N}+O(√(−Λ)); the bounds on the number of operators are related via AdS/CFT to the entropy of states in the dual gravitational theory. In the flat-space approximation, the limiting mass is exactly that of the lightest BTZ black hole.

  19. Apolipoprotein E Gene Polymorphism and Its Association with Cardiovascular Heart Disease Risk Factors in Type 2 Diabetes Mellitus

    OpenAIRE

    Amani Ashari; Julia Omar; Arif Hashim; Shahrul Hamid

    2016-01-01

    Apolipoprotein E (APOE) gene polymorphism has influence on serum lipids which relates to cardiovascular risk. The purpose of this study was to determine the frequency distribution of APOE alleles among Malaysian Type 2 Diabetes Mellitus (DM) patients with and without coronary artery disease (CAD) and their association with serum lipid profiles. A total of 115 patients were recruited in which 78 patients had Type 2 DM without CAD and 37 patients had Type 2 DM with CAD. The APOE polymorphism wa...

  20. Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice

    OpenAIRE

    Gu, Zhen; Li, Fengqiao; Zhang, Yi Ping; Shields, Lisa B.E.; Hu, Xiaoling; Zheng, Yiyan; Yu, Panpan; Zhang, Yongjie; Cai, Jun; Vitek, Michael P.; Shields, Christopher B.

    2014-01-01

    Objective Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG1...

  1. Plasma levels of sphingosine-1-phosphate and apolipoprotein M in patients with monogenic disorders of HDL metabolism

    NARCIS (Netherlands)

    Karuna, Ratna; Park, Rebekka; Othman, Alaa; Holleboom, Adriaan G.; Motazacker, Mohammad Mahdi; Sutter, Iryna; Kuivenhoven, Jan Albert; Rohrer, Lucia; Matile, Hugues; Hornemann, Thorsten; Stoffel, Markus; Rentsch, Katharina M.; von Eckardstein, Arnold

    2011-01-01

    Apolipoprotein M (apoM) has been identified as a specific sphingosine-1-phosphate (S1P) binding protein of HDL. To investigate the in vivo effects of disturbed apoM or HDL metabolism we quantified S1P and apoM in plasmas of wild-type, apoM-knock-out, and apoM transgenic mice as well as 50 patients

  2. Lipoprotein (a)--lipid profile and apolipoprotein B in children of young parents with coronary artery disease.

    Science.gov (United States)

    Khalil, Anita; Aggarwal, Amit; Arora, Sarika; Bhattacharya, Jayashree

    2011-01-01

    To evaluate lipoprotein(a), apolipoprotein B and lipid profile in children of young parents with coronary artery disease. Analytical observational study. Tertiary care hospital. The study included 80 children (9-18 years) out of which 40 were children of young parents (one or both) with established coronary artery disease (CAD), while the other 40 were children of parents with no evidence of CAD (controls). All were evaluated for fasting blood glucose, lipid profile, apolipoprotein B and lipoprotein (a) - Lp(a). Two sample 't' test was applied for analysis of continuous variables between study & control group. The study group children had significantly higher levels of total serum cholesterol (p = 0.004), LDL cholesterol (p = 0.002), lipoprotein a (p = 0.001) as compared to children of the control group. A significant difference in apolipoprotein B levels (p = 0.044) was observed in children in the adolescent age group (14-18 years). Both systolic and diastolic blood pressures were significantly higher without any significant difference being observed for weight and body mass index between the two groups. Higher levels of pro-atherogenic factors in children with family history of premature CAD indicate that the combined effects of "nature and nurture" are responsible for development of accelerated atherosclerosis especially in Indians. Tracking of Lp(a) levels from childhood may be a better option than detecting other elements of dyslipidemia which are not fully expressed until middle age.

  3. Influence of depleted uranium on hepatic cholesterol metabolism in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Souidi, M; Racine, R; Grandcolas, L; Grison, S; Stefani, J; Gourmelon, P; Lestaevel, P

    2012-04-01

    Depleted uranium (DU) is uranium with a lower content of the fissile isotope U-235 than natural uranium. It is a radioelement and a waste product from the enrichment process of natural uranium. Because of its very high density, it is used in the civil industry and for military purposes. DU exposure can affect many vital systems in the human body, because in addition to being weakly radioactive, uranium is a toxic metal. It should be emphasized that, to be exposed to radiation from DU, you have to eat, drink, or breathe it, or get it on your skin. This particular study is focusing on the health effects of DU for the cholesterol metabolism. Previous studies on the same issue have shown that the cholesterol metabolism was modulated at molecular level in the liver of laboratory rodents contaminated for nine months with DU. However, this modulation was not correlated with some effects at organs or body levels. It was therefore decided to use a "pathological model" such as hypercholesterolemic apolipoprotein E-deficient laboratory mice in order to try to clarify the situation. The purpose of the present study is to assess the effects of a chronic ingestion (during 3 months) of a low level DU-supplemented water (20 mg L(-1)) on the above mentioned mice in order to determine a possible contamination effect. Afterwards the cholesterol metabolism was studied in the liver especially focused on the gene expressions of cholesterol-catabolising enzymes (CYP7A1, CYP27A1 and CYP7B1), as well as those of associated nuclear receptors (LXRα, FXR, PPARα, and SREBP 2). In addition, mRNA levels of other enzymes of interest were measured (ACAT 2, as well as HMGCoA Reductase and HMGCoA Synthase). The gene expression study was completed with SRB1 and LDLr, apolipoproteins A1 and B and membrane transporters ABC A1, ABC G5. The major effect induced by a low level of DU contamination in apo-E deficient mice was a decrease in hepatic gene expression of the enzyme CYP7B1 (-23%) and nuclear

  4. Yukawa Bound States and Their LHC Phenomenology

    Directory of Open Access Journals (Sweden)

    Enkhbat Tsedenbaljir

    2013-01-01

    Full Text Available We present the current status on the possible bound states of extra generation quarks. These include phenomenology and search strategy at the LHC. If chiral fourth-generation quarks do exist their strong Yukawa couplings, implied by current experimental lower bound on their masses, may lead to formation of bound states. Due to nearly degenerate 4G masses suggested by Precision Electroweak Test one can employ “heavy isospin” symmetry to classify possible spectrum. Among these states, the color-octet isosinglet vector ω 8 is the easiest to be produced at the LHC. The discovery potential and corresponding decay channels are covered in this paper. With possible light Higgs at ~125 GeV two-Higgs doublet version is briefly discussed.

  5. Bounded Gaps between Products of Special Primes

    Directory of Open Access Journals (Sweden)

    Ping Ngai Chung

    2014-03-01

    Full Text Available In their breakthrough paper in 2006, Goldston, Graham, Pintz and Yıldırım proved several results about bounded gaps between products of two distinct primes. Frank Thorne expanded on this result, proving bounded gaps in the set of square-free numbers with r prime factors for any r ≥ 2, all of which are in a given set of primes. His results yield applications to the divisibility of class numbers and the triviality of ranks of elliptic curves. In this paper, we relax the condition on the number of prime factors and prove an analogous result using a modified approach. We then revisit Thorne’s applications and give a better bound in each case.

  6. Braneworld black holes and entropy bounds

    Directory of Open Access Journals (Sweden)

    Y. Heydarzade

    2018-01-01

    Full Text Available The Bousso's D-bound entropy for the various possible black hole solutions on a 4-dimensional brane is checked. It is found that the D-bound entropy here is apparently different from that of obtained for the 4-dimensional black hole solutions. This difference is interpreted as the extra loss of information, associated to the extra dimension, when an extra-dimensional black hole is moved outward the observer's cosmological horizon. Also, it is discussed that N-bound entropy is hold for the possible solutions here. Finally, by adopting the recent Bohr-like approach to black hole quantum physics for the excited black holes, the obtained results are written also in terms of the black hole excited states.

  7. Energy conditions bounds and supernovae data

    International Nuclear Information System (INIS)

    Lima, M.P.; Vitenti, S.D.P.; Reboucas, M.J.

    2008-01-01

    The energy conditions play an important role in the description of some important properties of the Universe, including the current accelerating expansion phase and the possible recent phase of super-acceleration. In a recent work we have provided a detailed study of the energy conditions for the recent past by deriving bounds from energy conditions and by making the confrontation of the bounds with supernovae data. Here, we extend and update these results in two different ways. First, by carrying out a new statistical analysis for q(z) estimates needed for the confrontation between the bounds and supernovae data. Second, by providing a new picture of the energy conditions fulfillment and violation in the light of the recently compiled Union set of 307 type Ia supernovae and by using two different statistical approaches

  8. Bound water in Kevlar 49 fibers

    International Nuclear Information System (INIS)

    Garza, R.G.; Pruneda, C.O.; Morgan, R.J.

    1981-01-01

    From elemental analyses, thermogravimetric-mass spectroscopy studies and re-evaluation of previous water diffusion studies in Kevlar 49 fibers it is concluded that these fibers can contain two types of sorbed moisture. The fibers can absorb up to approx. 6 wt % loosely bound water with an activation energy for outgassing by desorption of 6 kcal/mole. This loosely bound water is a direct result of the presence of Na 2 SO 4 impurities and the perturbations they induce on the packing of the rod-like poly (p-phenylene terephthalamide) macromolecules. Kevlar 49 fibers also inherently contain up to 30 wt % additional water which is tightly bound within the crystal lattice. This water exhibits an activation energy for outgassing by diffusion of approx. 40 kcal/mole and is only evolved from the fiber in significant quantities at t > 350 0 C over a period of hours

  9. Cosmological implications of Dark Matter bound states

    Energy Technology Data Exchange (ETDEWEB)

    Mitridate, Andrea [Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126, Pisa (Italy); Redi, Michele; Smirnov, Juri [INFN, Sezione di Firenze, and Dipartimento di Fisica e Astronomia, Università di Firenze, Via G. Sansone 1, 50019 Sesto Fiorentino (Italy); Strumia, Alessandro, E-mail: andrea.mitridate@gmail.com, E-mail: michele.redi@fi.infn.it, E-mail: juri.smirnov@mpi-hd.mpg.de, E-mail: alessandro.strumia@cern.ch [Dipartimento di Fisica dell' Università di Pisa and INFN, Pisa (Italy)

    2017-05-01

    We present generic formulæ for computing how Sommerfeld corrections together with bound-state formation affects the thermal abundance of Dark Matter with non-abelian gauge interactions. We consider DM as a fermion 3plet (wino) or 5plet under SU(2) {sub L} . In the latter case bound states raise to 11.5 TeV the DM mass required to reproduce the cosmological DM abundance and give indirect detection signals such as (for this mass) a dominant γ-line around 70 GeV. Furthermore, we consider DM co-annihilating with a colored particle, such as a squark or a gluino, finding that bound state effects are especially relevant in the latter case.

  10. Comparison of Lasserre's Measure-based Bounds for Polynomial Optimization to Bounds Obtained by Simulated Annealing

    NARCIS (Netherlands)

    de Klerk, Etienne; Laurent, Monique

    We consider the problem of minimizing a continuous function f over a compact set K. We compare the hierarchy of upper bounds proposed by Lasserre in [SIAM J. Optim. 21(3) (2011), pp. 864-885] to bounds that may be obtained from simulated annealing. We show that, when f is a polynomial and K a convex

  11. Career Development and Personal Functioning Differences between Work-Bound and Non-Work Bound Students

    Science.gov (United States)

    Creed, Peter A.; Patton, Wendy; Hood, Michelle

    2010-01-01

    We surveyed 506 Australian high school students on career development (exploration, planning, job-knowledge, decision-making, indecision), personal functioning (well-being, self-esteem, life satisfaction, school satisfaction) and control variables (parent education, school achievement), and tested differences among work-bound, college-bound and…

  12. Dihydrotestosterone regulating apolipoprotein M expression mediates via protein kinase C in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Yi-zhou Ye

    2012-12-01

    Full Text Available Abstract Background Administration of androgens decreases plasma concentrations of high-density lipid cholesterol (HDL-C. However, the mechanisms by which androgens mediate lipid metabolism remain unknown. This present study used HepG2 cell cultures and ovariectomized C57BL/6 J mice to determine whether apolipoprotein M (ApoM, a constituent of HDL, was affected by dihydrotestosterone (DHT. Methods HepG2 cells were cultured in the presence of either DHT, agonist of protein kinase C (PKC, phorbol-12-myristate-13-acetate (PMA, blocker of androgen receptor flutamide together with different concentrations of DHT, or DHT together with staurosporine at different concentrations for 24 hrs. Ovariectomized C57BL/6 J mice were treated with DHT or vehicle for 7d or 14d and the levels of plasma ApoM and livers ApoM mRNA were measured. The mRNA levels of ApoM, ApoAI were determined by real-time RT-PCR. ApoM and ApoAI were determined by western blotting analysis. Results Addition of DHT to cell culture medium selectively down-regulated ApoM mRNA expression and ApoM secretion in a dose-dependent manner. At 10 nM DHT, the ApoM mRNA levels were about 20% lower than in untreated cells and about 40% lower at 1000 nM DHT than in the control cells. The secretion of ApoM into the medium was reduced to a similar extent. The inhibitory effect of DHT on ApoM secretion was not blocked by the classical androgen receptor blocker flutamide but by an antagonist of PKC, Staurosporine. Agonist of PKC, PMA, also reduced ApoM. At 0.5 μM PMA, the ApoM mRNA levels and the secretion of ApoM into the medium were about 30% lower than in the control cells. The mRNA expression levels and secretion of another HDL-associated apolipoprotein AI (ApoAI were not affected by DHT. The levels of plasma ApoM and liver ApoM mRNA of DHT-treated C57BL/6 J mice were lower than those of vehicle-treated mice. Conclusions DHT directly and selectively down-regulated the level of ApoM mRNA and the

  13. A note on BPS vortex bound states

    Directory of Open Access Journals (Sweden)

    A. Alonso-Izquierdo

    2016-02-01

    Full Text Available In this note we investigate bound states, where scalar and vector bosons are trapped by BPS vortices in the Abelian Higgs model with a critical ratio of the couplings. A class of internal modes of fluctuation around cylindrically symmetric BPS vortices is characterized mathematically, analyzing the spectrum of the second-order fluctuation operator when the Higgs and vector boson masses are equal. A few of these bound states with low values of quantized magnetic flux are described fully, and their main properties are discussed.

  14. A note on BPS vortex bound states

    Energy Technology Data Exchange (ETDEWEB)

    Alonso-Izquierdo, A., E-mail: alonsoiz@usal.es [Departamento de Matematica Aplicada, Universidad de Salamanca (Spain); Garcia Fuertes, W., E-mail: wifredo@uniovi.es [Departamento de Fisica, Universidad de Oviedo (Spain); Mateos Guilarte, J., E-mail: guilarte@usal.es [Departamento de Fisica Fundamental, Universidad de Salamanca (Spain)

    2016-02-10

    In this note we investigate bound states, where scalar and vector bosons are trapped by BPS vortices in the Abelian Higgs model with a critical ratio of the couplings. A class of internal modes of fluctuation around cylindrically symmetric BPS vortices is characterized mathematically, analyzing the spectrum of the second-order fluctuation operator when the Higgs and vector boson masses are equal. A few of these bound states with low values of quantized magnetic flux are described fully, and their main properties are discussed.

  15. [Membrane-bound cytokine and feedforward regulation].

    Science.gov (United States)

    Wu, Ke-Fu; Zheng, Guo-Guang; Ma, Xiao-Tong; Song, Yu-Hua

    2013-10-01

    Feedback and feedforward widely exist in life system, both of them are the basic processes of control system. While the concept of feedback has been widely used in life science, feedforward regulation was systematically studied in neurophysiology, awaiting further evidence and mechanism in molecular biology and cell biology. The authors put forward a hypothesis about the feedforward regulation of membrane bound macrophage colony stimulation factor (mM-CSF) on the basis of their previous work. This hypothesis might provide a new direction for the study on the biological effects of mM-CSF on leukemia and solid tumors, and contribute to the study on other membrane bound cytokines.

  16. The covariant entropy bound in gravitational collapse

    International Nuclear Information System (INIS)

    Gao, Sijie; Lemos, Jose P. S.

    2004-01-01

    We study the covariant entropy bound in the context of gravitational collapse. First, we discuss critically the heuristic arguments advanced by Bousso. Then we solve the problem through an exact model: a Tolman-Bondi dust shell collapsing into a Schwarzschild black hole. After the collapse, a new black hole with a larger mass is formed. The horizon, L, of the old black hole then terminates at the singularity. We show that the entropy crossing L does not exceed a quarter of the area of the old horizon. Therefore, the covariant entropy bound is satisfied in this process. (author)

  17. Bound states in curved quantum waveguides

    International Nuclear Information System (INIS)

    Exner, P.; Seba, P.

    1987-01-01

    We study free quantum particle living on a curved planar strip Ω of a fixed width d with Dirichlet boundary conditions. It can serve as a model for electrons in thin films on a cylindrical-type substrate, or in a curved quantum wire. Assuming that the boundary of Ω is infinitely smooth and its curvature decays fast enough at infinity, we prove that a bound state with energy below the first transversal mode exists for all sufficiently small d. A lower bound on the critical width is obtained using the Birman-Schwinger technique. (orig.)

  18. Lower Bounds for External Memory Dictionaries

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Fagerberg, Rolf

    2003-01-01

    We study trade-offs between the update time and the query time for comparison based external memory dictionaries. The main contributions of this paper are two lower bound trade offs between the I/O complexity of member queries and insertions: If N < M insertions perform at most δ · N/B I/Os, then......We study trade-offs between the update time and the query time for comparison based external memory dictionaries. The main contributions of this paper are two lower bound trade offs between the I/O complexity of member queries and insertions: If N

  19. Finding Maximal Pairs with Bounded Gap

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Lyngsø, Rune B.; Pedersen, Christian N. S.

    1999-01-01

    . In this paper we present methods for finding all maximal pairs under various constraints on the gap. In a string of length n we can find all maximal pairs with gap in an upper and lower bounded interval in time O(n log n+z) where z is the number of reported pairs. If the upper bound is removed the time reduces...... to O(n+z). Since a tandem repeat is a pair where the gap is zero, our methods can be seen as a generalization of finding tandem repeats. The running time of our methods equals the running time of well known methods for finding tandem repeats....

  20. Bound constrained quadratic programming via piecewise

    DEFF Research Database (Denmark)

    Madsen, Kaj; Nielsen, Hans Bruun; Pinar, M. C.

    1999-01-01

    of a symmetric, positive definite matrix, and is solved by Newton iteration with line search. The paper describes the algorithm and its implementation including estimation of lambda/sub 1/ , how to get a good starting point for the iteration, and up- and downdating of Cholesky factorization. Results of extensive......We consider the strictly convex quadratic programming problem with bounded variables. A dual problem is derived using Lagrange duality. The dual problem is the minimization of an unconstrained, piecewise quadratic function. It involves a lower bound of lambda/sub 1/ , the smallest eigenvalue...

  1. Quantum Kolmogorov complexity and bounded quantum memory

    International Nuclear Information System (INIS)

    Miyadera, Takayuki

    2011-01-01

    The effect of bounded quantum memory in a primitive information protocol has been examined using the quantum Kolmogorov complexity as a measure of information. We employed a toy two-party protocol in which Bob, by using a bounded quantum memory and an unbounded classical memory, estimates a message that was encoded in qubits by Alice in one of the bases X or Z. Our theorem gave a nontrivial effect of the memory boundedness. In addition, a generalization of the uncertainty principle in the presence of quantum memory has been obtained.

  2. Increased intra-abdominal fat may lower HDL levels by increasing the fractional catabolic rate of Lp A-I in postmenopausal women.

    Science.gov (United States)

    Vajo, Zoltan; Terry, James G; Brinton, Eliot A

    2002-02-01

    High-density lipoprotein (HDL) particles without apolipoprotein A-II (Lp A-I) may be more anti-atherogenic than HDL with apo A-II (Lp A-I/AII) and Lp A-I is reported selectively to be reduced in cases of intra-abdominal obesity. We explored the mechanisms of this reduction by studying the turnover of Lp A-I and Lp A-I/A-II in postmenopausal women well characterized for total body, regional and sub-regional adiposity by body mass index (BMI), truncal girth ratio, and abdominal magnetic resonance imaging (MRI), respectively. We tested for possible cause-effect relationships by measuring inter-correlations among these variables. Intra-abdominal fat area correlated strongly and positively with the fractional catabolic rate (FCR) of Lp A-I (r=0.98, P=0.003). Intra-abdominal fat only showed a non-significant trend toward correlation with the FCR of Lp A-I/A-II (r=0.84, P=0.07), and had no correlation with the production or transport rate (TR) of either Lp A-I or Lp A-I/A-II (r=0.48 and 0.02, respectively, P>0.1). Subjects were studied both with and without estrogen replacement, allowing exploration of a possible interaction of adiposity with estrogen effects on HDL turnover. Response of HDL turnover to estrogen did not correlate with adiposity, except for a parameter of waist to hip ratio (WHR), which predicted the increase in LP A-I TR with estrogen (r=0.84, P=0.04). We conclude that intra-abdominal fat may lower HDL levels by increasing the FCR of Lp A-I, suggesting a mechanism by which central adiposity may be proatherogenic.

  3. Host-derived apolipoproteins play comparable roles with viral secretory proteins Erns and NS1 in the infectious particle formation of Flaviviridae.

    Directory of Open Access Journals (Sweden)

    Takasuke Fukuhara

    2017-06-01

    Full Text Available Amphipathic α-helices of exchangeable apolipoproteins have shown to play crucial roles in the formation of infectious hepatitis C virus (HCV particles through the interaction with viral particles. Among the Flaviviridae members, pestivirus and flavivirus possess a viral structural protein Erns or a non-structural protein 1 (NS1 as secretory glycoproteins, respectively, while Hepacivirus including HCV has no secretory glycoprotein. In case of pestivirus replication, the C-terminal long amphipathic α-helices of Erns are important for anchoring to viral membrane. Here we show that host-derived apolipoproteins play functional roles similar to those of virally encoded Erns and NS1 in the formation of infectious particles. We examined whether Erns and NS1 could compensate for the role of apolipoproteins in particle formation of HCV in apolipoprotein B (ApoB and ApoE double-knockout Huh7 (BE-KO, and non-hepatic 293T cells. We found that exogenous expression of either Erns or NS1 rescued infectious particle formation of HCV in the BE-KO and 293T cells. In addition, expression of apolipoproteins or NS1 partially rescued the production of infectious pestivirus particles in cells upon electroporation with an Erns-deleted non-infectious RNA. As with exchangeable apolipoproteins, the C-terminal amphipathic α-helices of Erns play the functional roles in the formation of infectious HCV or pestivirus particles. These results strongly suggest that the host- and virus-derived secretory glycoproteins have overlapping roles in the viral life cycle of Flaviviridae, especially in the maturation of infectious particles, while Erns and NS1 also participate in replication complex formation and viral entry, respectively. Considering the abundant hepatic expression and liver-specific propagation of these apolipoproteins, HCV might have evolved to utilize them in the formation of infectious particles through deletion of a secretory viral glycoprotein gene.

  4. Models of bounded rationality under certainty

    NARCIS (Netherlands)

    Rasouli, S.; Timmermans, H.J.P.; Rasouli, S.; Timmermans, H.J.P.

    2015-01-01

    Purpose This chapter reviews models of decision-making and choice under conditions of certainty. It allows readers to position the contribution of the other chapters in this book in the historical development of the topic area. Theory Bounded rationality is defined in terms of a strategy to simplify

  5. Sobolev spaces on bounded symmetric domains

    Czech Academy of Sciences Publication Activity Database

    Engliš, Miroslav

    Roč. 60, č. 12 ( 2015 ), s. 1712-1726 ISSN 1747-6933 Institutional support: RVO:67985840 Keywords : bounded symmetric domain * Sobolev space * Bergman space Subject RIV: BA - General Mathematics Impact factor: 0.466, year: 2015 http://www.tandfonline.com/doi/abs/10.1080/17476933. 2015 .1043910

  6. Properties of Excitons Bound to Ionized Donors

    DEFF Research Database (Denmark)

    Skettrup, Torben; Suffczynski, M.; Gorzkowski, W.

    1971-01-01

    Binding energies, interparticle distances, oscillator strengths, and exchange corrections are calculated for the three-particle complex corresponding to an exciton bound to an ionized donor. The results are given as functions of the mass ratio of the electron and hole. Binding of the complex is o...

  7. Bogomol'nyi bounds for cosmic strings

    International Nuclear Information System (INIS)

    Comtet, A.; Gibbons, G.W.; Cambridge Univ.

    1987-09-01

    We establish Bogomol'nyi inequalities for the deficit angle of some cylindrically symmetric asymptotically local flat (CALF) spacetimes containing cosmic strings. These results prove the stability against arbitrary cylindrical deformations of those configurations which saturate the bound. Such configurations satisfy first order equations which can, in some cases, be solved exactly

  8. Bounding the bias of contrastive divergence learning

    DEFF Research Database (Denmark)

    Fischer, Anja; Igel, Christian

    2011-01-01

    Optimization based on k-step contrastive divergence (CD) has become a common way to train restricted Boltzmann machines (RBMs). The k-step CD is a biased estimator of the log-likelihood gradient relying on Gibbs sampling. We derive a new upper bound for this bias. Its magnitude depends on k...

  9. Bound States in the Mirror TBA

    NARCIS (Netherlands)

    Arutyunov, G.E.; Frolov, S.; van Tongeren, S.J.

    2012-01-01

    The spectrum of the light-cone AdS_5 \\times S^5 superstring contains states composed of particles with complex momenta including in particular those which turn into bound states in the decompactification limit. We propose the mirror TBA description for these states. We focus on a three-particle

  10. Harmonic maps of the bounded symmetric domains

    International Nuclear Information System (INIS)

    Xin, Y.L.

    1994-06-01

    A shrinking property of harmonic maps into R IV (2) is proved which is used to classify complete spacelike surfaces of the parallel mean curvature in R 4 2 with a reasonable condition on the Gauss image. Liouville-type theorems of harmonic maps from the higher dimensional bounded symmetric domains are also established. (author). 25 refs

  11. Scattering theory methods for bound state problems

    International Nuclear Information System (INIS)

    Raphael, R.B.; Tobocman, W.

    1978-01-01

    For the analysis of the properties of a bound state system one may use in place of the Schroedinger equation the Lippmann-Schwinger (LS) equation for the wave function or the LS equation for the reactance operator. Use of the LS equation for the reactance operator constrains the solution to have correct asymptotic behaviour, so this approach would appear to be desirable when the bound state wave function is to be used to calculate particle transfer form factors. The Schroedinger equation based N-level analysis of the s-wave bound states of a square well is compared to the ones based on the LS equation. It is found that the LS equation methods work better than the Schroedinger equation method. The method that uses the LS equation for the wave function gives the best results for the wave functions while the method that uses the LS equation for the reactance operator gives the best results for the binding energies. The accuracy of the reactance operator based method is remarkably insensitive to changes in the oscillator constant used for the harmonic oscillator function basis set. It is also remarkably insensitive to the number of nodes in the bound state wave function. (Auth.)

  12. Lower bounds on scintillation detector timing performance

    International Nuclear Information System (INIS)

    Clinthorne, N.H.; Rogers, W.L.; Hero, A.O. III.; Petrick, N.A.

    1990-01-01

    Fundamental method-independent limits on the timing performance of scintillation detectors are useful for identifying regimes in which either present timing methods are nearly optimal or where a considerable performance gain might be realized using better pulse processing techniques. Several types of lower bounds on mean-squared timing error (MSE) performance have been developed and applied to scintillation detectors. The simple Cramer-Rao (CR) bound can be useful in determining the limiting MSE for scintillators having a relatively high rate of photon problction such as BaF 2 and NaI(Tl); however, it tends to overestimate the achievalbe performance for scintillators with lower rates such as BGO. For this reason, alternative bounds have been developed using rate-distortion theory or by assuming that the conversion of energy to scintillation light must pass through excited states which have exponential lifetime densities. The bounds are functions of the mean scintillation pulse shape, the scintillation intensity, and photodetector characteristics; they are simple to evaluate and can be used to conveniently assess the limiting timing performance of scintillation detectors. (orig.)

  13. Efficiency gains, bounds, and risk in finance

    NARCIS (Netherlands)

    Sarisoy, Cisil

    2015-01-01

    This thesis consists of three chapters. The first chapter analyzes efficiency gains in the estimation of expected returns based on asset pricing models and examines the economic implications of such gains in portfolio allocation exercises. The second chapter provides nonparametric efficiency bounds

  14. Book Selection, Collection Development, and Bounded Rationality.

    Science.gov (United States)

    Schwartz, Charles A.

    1989-01-01

    Reviews previously proposed schemes of classical rationality in book selection, describes new approaches to rational choice behavior, and presents a model of book selection based on bounded rationality in a garbage can decision process. The role of tacit knowledge and symbolic content in the selection process are also discussed. (102 references)…

  15. Monotonicity and bounds on Bessel functions

    Directory of Open Access Journals (Sweden)

    Larry Landau

    2000-07-01

    Full Text Available survey my recent results on monotonicity with respect to order of general Bessel functions, which follow from a new identity and lead to best possible uniform bounds. Application may be made to the "spreading of the wave packet" for a free quantum particle on a lattice and to estimates for perturbative expansions.

  16. Collisional properties of weakly bound heteronuclear dimers

    NARCIS (Netherlands)

    Marcelis, B.; Kokkelmans, S.J.J.M.F.; Shlyapnikov, G.V.; Petrov, D.S.

    2008-01-01

    We consider collisional properties of weakly bound heteronuclear molecules (dimers) formed in a two-species mixture of atoms with a large mass difference. We focus on dimers containing light fermionic atoms as they manifest collisional stability due to an effective dimer-dimer repulsion originating

  17. Bounded Rationality of Generalized Abstract Fuzzy Economies

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2014-01-01

    Full Text Available By using a nonlinear scalarization technique, the bounded rationality model M for generalized abstract fuzzy economies in finite continuous spaces is established. Furthermore, by using the model M, some new theorems for structural stability and robustness to (λ,ϵ-equilibria of generalized abstract fuzzy economies are proved.

  18. Bounded Rationality in Individual Decision Making

    OpenAIRE

    Camerer, Colin F.

    1998-01-01

    The main objectives of this paper are: (i) To give a pithy, opinionated summary of what has been learned about bounded rationality in individual decision making from experiments in economics and psychology (drawing on my 1995 Handbook of Experimental Economics chapter); and (ii) mention some promising new directions for research which would be included if that chapter were written today.

  19. [HDL-C/apoA-I]: A multivessel cardiometabolic risk marker in women with T2DM.

    Science.gov (United States)

    Hermans, Michel P; Valensi, Paul; Ahn, Sylvie A; Rousseau, Michel F

    2018-01-01

    Although women have higher high-density lipoprotein cholesterol (HDL-C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL-C to its main apolipoprotein (apoA-I) as [HDL-C/apoA-I]. This ratio estimates HDL sizes and provides indices as to their number, cholesterol load, and density. We stratified 280 Caucasian T2DM women according to [HDL-C/apoA-I] quartiles (Q) to determine how they are segregated according to cardiometabolic risk, β-cell function, glycaemic control, and vascular complications. Five parameters were derived from combined determination of HDL-C and apoA-I: HDL size, HDL number, cholesterol load per particle (pP), apoA-I pP, and HDL density. An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA-I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and β-cell function (32% vs 23%); exogenous insulin (44 vs 89 U·d -1 ); and glycaemic control (glycated haemoglobin, 56 vs 61 mmol·mol -1 ), associated with lower prevalence of microvascular/macrovascular complications: all-cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all-cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P women according to metabolic phenotype, macrovascular and coronary damage, β-cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Nanobody-Based Apolipoprotein E Immunosensor for Point-of-Care Testing.

    Science.gov (United States)

    Ren, Xiang; Yan, Junrong; Wu, Dan; Wei, Qin; Wan, Yakun

    2017-09-22

    Alzheimer's disease (AD) biomarkers can reflect the neurochemical indicators used to estimate the risk in clinical nephrology. Apolipoprotein E (ApoE) is an early biomarker for AD in clinical diagnosis. In this research, through bactrian camel immunization, lymphocyte isolation, RNA extraction, and library construction, ApoE-specific Nbs with high affinity were successfully separated from an immune phage display nanobody library. Herein, a colorimetric immunosensor was developed for the point-of-care testing of ApoE by layer-by-layer nanoassembly techniques and novel nanobodies (Nbs). Using highly oriented Nbs as the capture and detection antibodies, an on-site immunosensor was developed by detecting the mean gray value of fade color due to the glutaraldehyde@3-aminopropyltrimethoxysilane oxidation by H 2 O 2 . The detection limit of AopE is 0.42 pg/mL, and the clinical analysis achieves a good performance. The novel easily operated immunosensor may have potential application in the clinical diagnosis and real-time monitoring for AD.

  1. Evolutionary analysis of apolipoprotein E by Maximum Likelihood and complex network methods

    Directory of Open Access Journals (Sweden)

    Leandro de Jesus Benevides

    Full Text Available Abstract Apolipoprotein E (apo E is a human glycoprotein with 299 amino acids, and it is a major component of very low density lipoproteins (VLDL and a group of high-density lipoproteins (HDL. Phylogenetic studies are important to clarify how various apo E proteins are related in groups of organisms and whether they evolved from a common ancestor. Here, we aimed at performing a phylogenetic study on apo E carrying organisms. We employed a classical and robust method, such as Maximum Likelihood (ML, and compared the results using a more recent approach based on complex networks. Thirty-two apo E amino acid sequences were downloaded from NCBI. A clear separation could be observed among three major groups: mammals, fish and amphibians. The results obtained from ML method, as well as from the constructed networks showed two different groups: one with mammals only (C1 and another with fish (C2, and a single node with the single sequence available for an amphibian. The accordance in results from the different methods shows that the complex networks approach is effective in phylogenetic studies. Furthermore, our results revealed the conservation of apo E among animal groups.

  2. Plasma levels of apolipoprotein E and risk of dementia in the general population

    DEFF Research Database (Denmark)

    Rasmussen, Katrine L.; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G

    2015-01-01

    OBJECTIVE: The apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and dementia. However, it remains unclear whether plasma levels of apoE confer additional risk. We tested this hypothesis. METHODS: Using 75,708 participants from the general population, we tested...... whether low plasma levels of apoE at study enrollment were associated with increased risk of future Alzheimer disease and all dementia, and whether this association was independent of ε2/ε3/ε4 APOE genotype. RESULTS: Multifactorially adjusted hazard ratios (HRs) for Alzheimer disease and all dementia...... adjustment for ε2/ε3/ε4 APOE genotype, plasma apoE tertiles remained associated with Alzheimer disease (p for trend = 0.007) and all dementia (p for trend = 0.04). Plasma apoE tertiles did not interact with ε2/ε3/ε4 APOE genotype on risk of Alzheimer disease (p = 0.53) or all dementia (p = 0...

  3. Apolipoprotein E Genotype and Sex Influence Glucose Tolerance in Older Adults: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Angela J. Hanson

    2016-03-01

    Full Text Available Background: Glucose intolerance and apolipoprotein ε4 allele (E4+ are risk factors for Alzheimer's disease (AD. Insulin sensitizers show promise for treating AD, but are less effective in E4+ individuals. Little is known about how the APOE genotype influences glucose metabolism. Methods: Cross-sectional analysis of 319 older adults who underwent oral glucose tolerance tests; a subset had insulin, amyloid beta (Aβ42, and Mini Mental Status Examination. Glucose and insulin patterns with respect to cognitive diagnosis, E4 status, and sex were examined with analysis of covariance and Pearson correlation. Results: People with cognitive impairment had higher fasting insulin levels. E4 status did not affect fasting glucose values, whereas men had higher fasting glucose levels than women. E4+ men had the lowest and E4+ women had the highest glucose levels, compared to E4- groups; insulin did not differ by sex or E4 group. E4 status and sex moderated correlations between metabolic measures and AD risk factors including age and Aβ. Conclusions: Insulin resistance was associated with cognitive impairment, and sex, E4 status, and glucose values are interrelated in older adults at risk of AD. Understanding glucose metabolism for different APOE and sex groups may help elucidate differences in therapeutic responses.

  4. Taurine reduces the secretion of apolipoprotein B100 and lipids in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Nagao Koji

    2008-10-01

    Full Text Available Abstract Background Higher concentrations of serum lipids and apolipoprotein B100 (apoB are major individual risk factors of atherosclerosis and coronary heart disease. Therefore ameliorative effects of food components against the diseases are being paid attention in the affluent countries. The present study was undertaken to investigate the effect of taurine on apoB secretion and lipid metabolism in human liver model HepG2 cells. Results The results demonstrated that an addition of taurine to the culture media reduces triacylglycerol (TG-mass in the cells and the medium. Similarly, cellular cholesterol-mass was decreased. Taurine inhibited the incorporation of [14C] oleate into cellular and medium TG, suggesting the inhibition of TG synthesis. In addition, taurine reduced the synthesis of cellular cholesterol ester and its secretion, suggesting the inhibition of acyl-coenzyme A:cholesterol acyltransferase activity. Furthermore, taurine reduced the secretion of apoB, which is a major protein component of very low-density lipoprotein. Conclusion This is a first report to demonstrate that taurine inhibits the secretion of apoB from HepG2 cells.

  5. Evaluation of Apolipoprotein A5 Polymorphism in Coronary- Heart Disease Patients

    Directory of Open Access Journals (Sweden)

    Somayeh Haqparast

    2012-02-01

    Full Text Available Background and Objectives: Apolipoprotein A5 (APOA5 gene is important in determining plasma triglyceride levels, a major cardiovascular disease risk factor. Mutation in this gene affected plasma triglyceride level. We looked for possible associations of the APOA5 gene polymorphism S19W with coronary heart disease (CHD in a sample of Iranian population. Materials and Methods: A total of 73 CHD patients and 55 controls were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP for this single nucleotide polymorphism. Serum lipids and Fast Blood Sugar concentrations were measured in all subjects with enzymatic method. Results: Allele frequencies observed in our population were 0.041 for the W allele and 0.959 for the S allele which are similar to other populations (p>0.05. There is no evidence that APOA5 S19W, is a risk factor of CHD in our sample (p>0.05. In addition, we observed no association between the APOA5 W allele and elevated plasma TG levels (p>0.05 in the CHD group. This result was also present in the control group (p>0.05. Conclusion: The APO A5 gene polymorphism in S19W gene has no association with the high susceptibility to CHD.

  6. Regulation of the Apolipoprotein Gene Cluster by a Long Noncoding RNA

    Directory of Open Access Journals (Sweden)

    Paul Halley

    2014-01-01

    Full Text Available Apolipoprotein A1 (APOA1 is the major protein component of high-density lipoprotein (HDL in plasma. We have identified an endogenously expressed long noncoding natural antisense transcript, APOA1-AS, which acts as a negative transcriptional regulator of APOA1 both in vitro and in vivo. Inhibition of APOA1-AS in cultured cells resulted in the increased expression of APOA1 and two neighboring genes in the APO cluster. Chromatin immunoprecipitation (ChIP analyses of a ∼50 kb chromatin region flanking the APOA1 gene demonstrated that APOA1-AS can modulate distinct histone methylation patterns that mark active and/or inactive gene expression through the recruitment of histone-modifying enzymes. Targeting APOA1-AS with short antisense oligonucleotides also enhanced APOA1 expression in both human and monkey liver cells and induced an increase in hepatic RNA and protein expression in African green monkeys. Furthermore, the results presented here highlight the significant local modulatory effects of long noncoding antisense RNAs and demonstrate the therapeutic potential of manipulating the expression of these transcripts both in vitro and in vivo.

  7. Subcellular distribution of apolipoprotein E along the lipoprotein synthetic pathway of rat liver

    International Nuclear Information System (INIS)

    Cole, T.G.; Stockhausen, D.C.

    1986-01-01

    Apolipoprotein E (apoE) is synthesized by the liver and is secreted as a component of VLDL. To define the intracellular locations of apoE, liver from 10 nonfasted male rats were removed and subcellular organelles prepared by differential pelleting through sucrose gradients. Mass of apoE was measured by radioimmunoassay. Approximately 10% of total hepatic apoE was recovered in rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SER) and Golgi fractions. Concentrations of apoE (ng/mg protein) were: homogenate, 302 +/- 59; RER, 653 +/- 251; SER, 1250 +/- 471; Golgi, 11,044 +/- 4291. Total apoE content of each reaction (μg/organelle) was: homogenate (whole liver), 517 +/- 103; RER, 15 +/- 3; SER, 9 +/- 3; Golgi, 28 +/- 8. These data indicate that along the putative pathway of lipoprotein synthesis (RER->SER->Golgi), apoE concentration increases in each successive organelle and that flux of apoE is apparently most rapid through SER. Furthermore, the majority of apoE in the rat liver is apparently not directly associated with the lipoprotein synthetic pathway and may be associated with internalized lipoproteins or may be involved in non-lipoprotein related functions

  8. Mechanism of lipid lowering in mice expressing human apolipoprotein A5

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart-Najib, Jamila; Bauge, Eric; Niculescu, Loredan-Stefan; Pham, Tatiana; Thomas, Benoit; Rommens, Corinne; Majd, Zouher; Brewer, Bryan; Rubin, Edward M.; Pennacchio, Len A.; Fruchart, Jean-Charles

    2004-01-15

    Recently, we reported that apoAV plays key role in triglycerides lowering. Here, we attempted to determine the mechanism underlying this hypotriglyceridemic effect. We showed that triglyceride turnover is faster in hAPOA5 transgenic compared to wild type mice. Moreover, both apoB and apoCIII are decreased and LPL activity is increased in postheparin plasma of hAPOA5 transgenic mice. These data suggest a decrease in size and number of VLDL. To further investigate the mechanism of hAPOA5 in hyperlipidemic background, we intercrossed hAPOA5 and hAPOC3 transgenic mice. The effect resulted in a marked decreased of VLDL triglyceride, cholesterol, apolipoproteins B and CIII. In postprandial state, the triglyceride response is abolished in hAPOA5 transgenic mice. We demonstrated that in response to the fat load in hAPOA5XhAPOC3 mice, apoAV shifted from HDL to VLDL, probably to limit the elevation of triglycerides. In vitro, apoAV activates lipoprotein lipase. However, apoAV does not interact with LPL but interacts physically with apoCIII. This interaction does not seem to displace apoCIII from VLDL but may induce conformational change in apoCIII and consequently change in its function leading the activation of lipoprotein lipase.

  9. Autoimmune severe hypertriglyceridemia induced by anti-apolipoprotein C-II antibody.

    Science.gov (United States)

    Yamamoto, Hiroyasu; Tanaka, Minoru; Yoshiga, Satomi; Funahashi, Tohru; Shimomura, Iichiro; Kihara, Shinji

    2014-05-01

    Among type V hyperlipoproteinemias, only one-fourth of the patients have genetic defects in lipoprotein lipase (LPL) or in its associated molecules; the exact mechanism in other patients is usually unknown. The aim of the study was to report a case of severe hypertriglyceridemia induced by anti-apolipoprotein (apo) C-II autoantibody and to clarify its pathogenesis. A 29-year-old Japanese woman presented with severe persistent hypertriglyceridemia since the age of 20 years. The past history was negative for acute pancreatitis, eruptive xanthomas, or lipemia retinalis. LPL mass and activities were normal. Plasma apo C-II levels were extremely low, but no mutation was observed in APOC2. Apo C-II protein was detected in the serum by immunoprecipitation and Western blotting. Large amounts of IgG and IgM were incorporated with apo C-II protein coimmunoprecipitated by anti-apo C-II antibody. IgG, but not IgM, purified from the serum prevented interaction of apo C-II with lipid substrate and diminished LPL hydrolysis activity. We identified anti-apo C-II antibody in a myeloma-unrelated severe hypertriglyceridemic patient. In vitro analysis confirmed that the autoantibody disrupted the interaction between apo C-II and lipid substrate, suggesting the etiological role of anti-apo C-II antibody in severe hypertriglyceridemia in this patient.

  10. Apolipoprotein A5: A newly identified gene impacting plasmatriglyceride levels in humans and mice

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Rubin, Edward M.

    2002-09-15

    Apolipoprotein A5 (APOA5) is a newly described member of theapolipoprotein gene family whose initial discovery arose from comparativesequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functionalstudies in mice indicated that alteration in the level of APOA5significantly impacted plasma triglyceride concentrations. Miceover-expressing human APOA5 displayed significantly reducedtriglycerides, while mice lacking apoA5 had a large increase in thislipid parameter. Studies in humans have also suggested an important rolefor APOA5 in determining plasma triglyceride concentrations. In theseexperiments, polymorphisms in the human gene were found to define severalcommon haplotypes that were associated with significant changes intriglyceride concentrations in multiple populations. Several separateclinical studies have provided consistent and strong support for theeffect with 24 percent of Caucasians, 35 percent of African-Americans and53 percent of Hispanics carrying APOA5 haplotypes associated withincreased plasma triglyceride levels. In summary, APOA5 represents anewly discovered gene involved in triglyceride metabolism in both humansand mice whose mechanism of action remains to be deciphered.

  11. Subarachnoid hemorrhage: tests of association with apolipoprotein E and elastin genes

    Directory of Open Access Journals (Sweden)

    Sauerbeck Laura

    2007-07-01

    Full Text Available Abstract Background Apolipoprotein E (APOE and elastin (ELN are plausible candidate genes involved in the pathogenesis of stroke. We tested for association of variants in APOE and ELN with subarachnoid hemorrhage (SAH in a population-based study. We genotyped 12 single nucleotide polymorphisms (SNPs on APOE and 10 SNPs on ELN in a sample of 309 Caucasian individuals, of whom 107 are SAH cases and 202 are age-, race-, and gender-matched controls from the Greater Cincinnati/Northern Kentucky region. Associations were tested at genotype, allele, and haplotype levels. A genomic control analysis was performed to check for spurious associations resulting from population substructure. Results At the APOE locus, no individual SNP was associated with SAH after correction for multiple comparisons. Haplotype analysis revealed significant association of the major haplotype (Hap1 in APOE with SAH (p = 0.001. The association stemmed from both the 5' promoter and the 3' region of the APOE gene. APOE ε2 and ε 4 were not significantly associated with SAH. No association was observed for ELN at genotype, allele, or haplotype level and our study failed to confirm previous reports of ELN association with aneurysmal SAH. Conclusion This study suggests a role of the APOE gene in the etiology of aneurysmal SAH.

  12. Clinical relevance of apolipoprotein E genotyping based on a family history of Alzheimer's disease.

    Science.gov (United States)

    Luckhoff, Hilmar K; Brand, Theresa; van Velden, Dawid P; Kidd, Martin; Fisher, Leslie R; van Rensburg, Susan J; Kotze, Maritha J

    2015-01-01

    Having a family history of Alzheimer' s disease (AD) may potentiate cumulative risk associated with phenotypic expression of the ε-4 allele of the apolipoprotein E (APOE) gene. In this study, we compared the genotype distribution and allele frequencies of APOE ε-2 (rs7412) and ε -4 (rs429358) in 537 South African individuals participating in a chronic disease screening program, in order to establish whether AD family history modulates the expression of their dyslipidemic effects. Significant differences in the genotype distribution for APOE ε-2 (p=0.034) as well as APOE ε-4 (p=0.038) were found between study participants with (n=67) and without (n=470) a family history of AD. LDL cholesterol levels were inversely associated with physical activity in the study group with a positive family history of AD (pfamilial hypercholesterolemia, clinical inquiry regarding family history was identified as an important determinant of eligibility for APOE genotyping performed in the context of chronic disease risk management. To our knowledge, this is the first study to demonstrate the modulating influence of AD family history on expression of a dyslipidemic phenotype associated with the APOE ε-4 allele. Our findings provide the scientific rationale supporting a novel clinical application for APOE genotyping as a means of identifying a genetic subgroup of dyslipidemic patients set to derive the greatest benefit from early lifestyle-based interventions aimed at decreasing cumulative risk for cardiovascular disease and prevention of AD later in life.

  13. Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol.

    Science.gov (United States)

    Sharma, Vineeta; Forte, Trudy M; Ryan, Robert O

    2013-04-01

    Apolipoprotein (apo) A-V functions to modulate intracellular and extracellular triacylglycerol metabolism. The present review addresses molecular mechanisms underlying these effects. The relevance of apoA-V to human disease conditions is illustrated by the strong correlation between single nucleotide polymorphisms in APOA5, elevated plasma triacylglycerol and dyslipidemic disease. Despite undergoing processing for secretion from hepatocytes, a portion of apoA-V escapes this destiny and accumulates as a component of cytosolic lipid droplets. Expression of recombinant apoA-V in hepatocarcinoma cells results in increased lipid droplet size and number at the expense of triacylglycerol secretion.ApoA-V modulates atherosclerosis in hypercholesterolemic apoE null mice. ApoE null/human apoA-V transgenic mice had reduced levels of triacylglycerol and cholesterol in plasma along with decreased aortic lesion size. ApoA-V modulates triacylglycerol metabolic fate. Following its synthesis, apoA-V enters the endoplasmic reticulum and associates with membrane defects created by triacylglycerol accumulation. Association of apoA-V with endoplasmic reticulum membrane defects promotes nascent lipid droplets budding toward the cytosol. Despite its low concentration in plasma (∼150 ng/ml), apoA-V modulates lipoprotein metabolism by binding to glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. This interaction effectively localizes triacylglycerol-rich lipoproteins in the vicinity of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein1's other ligand, lipoprotein lipase.

  14. Functional blockage of EMMPRIN ameliorates atherosclerosis in apolipoprotein E-deficient mice.

    Science.gov (United States)

    Liu, Hong; Yang, Li-xia; Guo, Rui-wei; Zhu, Guo-Fu; Shi, Yan-Kun; Wang, Xian-mei; Qi, Feng; Guo, Chuan-ming; Ye, Jin-shan; Yang, Zhi-hua; Liang, Xing

    2013-10-09

    Extracellular matrix metalloproteinase inducer (EMMPRIN), a 58-kDa cell surface glycoprotein, has been identified as a key receptor for transmitting cellular signals mediating metalloproteinase activities, as well as inflammation and oxidative stress. Clinical evidence has revealed that EMMPRIN is expressed in human atherosclerotic plaque; however, the relationship between EMMPRIN and atherosclerosis is unclear. To evaluate the functional role of EMMPRIN in atherosclerosis, we treated apolipoprotein E-deficient (ApoE(-/-)) mice with an EMMPRIN function-blocking antibody. EMMPRIN was found to be up-regulated in ApoE(-/-) mice fed a 12-week high-fat diet in contrast to 12 weeks of normal diet. Administration of a function-blocking EMMPRIN antibody (100 μg, twice per week for 4 weeks) to ApoE(-/-) mice, starting after 12 weeks of high-fat diet feeding caused attenuated and more stable atherosclerotic lesions, less reactive oxygen stress generation on plaque, as well as down-regulation of circulating interleukin-6 and monocyte chemotactic protein-1 in ApoE(-/-) mice. The benefit of EMMPRIN functional blockage was associated with reduced metalloproteinases proteolytic activity, which delayed the circulating monocyte transmigrating into atherosclerotic lesions. EMMPRIN antibody intervention ameliorated atherosclerosis in ApoE(-/-) mice by the down-regulation of metalloproteinase activity, suggesting that EMMPRIN may be a viable therapeutic target in atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Hippocampal infusions of apolipoprotein E peptides induce long-lasting cognitive impairment.

    Science.gov (United States)

    Eddins, Donnie; Klein, Rebecca C; Yakel, Jerrel L; Levin, Edward D

    2009-04-29

    The inheritance of the varepsilon4 allele of apolipoprotein E (ApoE4) and cholinergic system dysfunction have long been associated with the pathology of Alzheimer's disease (AD). Recently, in vitro studies have established a direct link between ApoE and cholinergic function in that synthetic peptides containing segments of the ApoE protein (ApoE(133-149) and ApoE(141-148)) interact with alpha7 nicotinic acetylcholine receptors (nAChRs) in the hippocampus. This raises the possibility that ApoE peptides may contribute to cognitive impairment in AD in that the hippocampus plays a key role in cognitive functioning. To test this, we acutely infused ApoE peptides into the ventral hippocampus of female Sprague-Dawley rats and assessed the resultant effects on radial-arm maze choice accuracy over a period of weeks after the infusion. Local ventral hippocampal infusion of ApoE peptides caused significant cognitive impairment in radial-arm maze learning that persisted several weeks after the acute infusion. This persisting deficit may be an important model for understanding the relationship between ApoE protein-induced neurotoxicity and cognitive impairment as well as serve as a platform for the development of new therapies to avoid neurotoxicity and cognitive decline.

  16. Human plasma lipid modulation in schistosomiasis mansoni depends on apolipoprotein E polymorphism.

    Directory of Open Access Journals (Sweden)

    Caíque Silveira Martins da Fonseca

    Full Text Available Schistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis.Blood samples were used for APOE genotyping and to measure total cholesterol (TC, LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; Pε3>ε4 was absent in patients (ε2 or ε4>ε3, and the increase in HDL-C of ε2 or ε4 patients compared to ε3 patients was not seen in the control groups.We confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat associated morbidities.

  17. Orphan nuclear receptor Nur77 participates in human apolipoprotein A5 gene expression

    International Nuclear Information System (INIS)

    Song, Kwang-Hoon

    2010-01-01

    The orphan nuclear receptor Nur77 (NR4A1) has been reported to play a crucial role in the modulation of diverse metabolic processes in liver. Here, we reported the identification of human apolipoprotein A5 (ApoA5), which implicated in lowering plasma triglyceride levels, as a novel target gene of Nur77. Nur77 induced the human ApoA5 promoter activity. Using 5'-deletion and mutagenesis of human ApoA5 promoter analysis and chromatin immunoprecipitation assays, it was shown that Nur77 directly regulated human ApoA5 gene expression by binding to a Nur77 response element (AAAGGTCA) located in the proximal human ApoA5 promoter region. In addition, we demonstrated that blocking of Nur77 transcriptional activity via overexpression of dominant negative Nur77 suppressed human ApoA5 promoter activity and mRNA expression in human hepatoma cells, HepG2. Taken together, our results demonstrated that Nur77 is a novel regulator of human ApoA5 gene expression and provide a new insight into the role of this orphan nuclear receptor in lipoprotein metabolism and triglyceride homeostasis.

  18. Increased sensitivity of apolipoprotein E knockout mice to copper-induced oxidative injury to the liver.

    Science.gov (United States)

    Chen, Yuan; Li, Bin; Zhao, Ran-ran; Zhang, Hui-feng; Zhen, Chao; Guo, Li

    2015-04-10

    Apolipoprotein E (ApoE) genotypes are related to clinical presentations in patients with Wilson's disease, indicating that ApoE may play an important role in the disease. However, our understanding of the role of ApoE in Wilson's disease is limited. High copper concentration in Wilson's disease induces excessive generation of free oxygen radicals. Meanwhile, ApoE proteins possess antioxidant effects. We therefore determined whether copper-induced oxidative damage differ in the liver of wild-type and ApoE knockout (ApoE(-/-)) mice. Both wild-type and ApoE(-/-) mice were intragastrically administered with 0.2 mL of copper sulfate pentahydrate (200 mg/kg; a total dose of 4 mg/d) or the same volume of saline daily for 12 weeks, respectively. Copper and oxidative stress markers in the liver tissue and in the serum were assessed. Our results showed that, compared with the wild-type mice administered with copper, TBARS as a marker of lipid peroxidation, the expression of oxygenase-1 (HO-1), NAD(P)H dehydrogenase, and quinone 1 (NQO1) significantly increased in the ApoE(-/-) mice administered with copper, meanwhile superoxide dismutase (SOD) activity significantly decreased. Thus, it is concluded that ApoE may protect the liver from copper-induced oxidative damage in Wilson's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Possible Alzheimer’s Disease in an Apolipoprotein E2 Homozygote

    Science.gov (United States)

    Ignatov, Ignat; Belden, Christine; Jacobson, Sandra; Connor, Donald; Sabbagh, Marwan N.

    2010-01-01

    The objective of this study was to describe a case of Alzheimer’s disease in an ApoE ε2/ε2 homozygote. ApoE ε2/ε2 is the rarest of the apolipoprotein E genotypes, representing only 1.4% of the population. There is only one case reported in the literature of a nonagenarian with minimal cognitive changes whose brain showed AD pathology on postmortem study. Here we report an 87-year-old ApoE ε2/ε2 female who meets clinical criteria for Alzheimer’s disease, with confirmation from neuropsychological testing and PET scan. Clinical course is typical for Alzheimer’s disease with decline on the Mini-Mental Status Examination from a score of 25 to 19 over 3.5 years. The patient is currently treated with donepezil and memantine. In conclusion, a clinically confirmed case of Alzheimer’s disease is rare in Apo E2 homozygotes but can occur. PMID:19158419

  20. Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer's disease in a Southern Brazilian population

    Directory of Open Access Journals (Sweden)

    de-Andrade F.M.

    2000-01-01

    Full Text Available Apolipoprotein E (protein: apo E; gene: APOE plays an important role in the multifactorial etiology of both Alzheimer's disease (AD and lipid level concentrations. The polymerase chain reaction (PCR was used to investigate the APOE gene polymorphism in 446 unrelated Caucasians, among them 23 AD patients, and 100 Afro-Brazilians living in Porto Alegre, Brazil. The frequencies of the APOE*2, APOE*3 and APOE*4 alleles were 0.075, 0.810 and 0.115 in Caucasians and 0.075, 0.700 and 0.225 in Afro-Brazilians, respectively (c2 = 8.72, P = 0.013. A highly significant association was observed between the APOE*4 allele and AD in this population-based sample. The APOE*4 frequency in AD patients (39% was about four times higher than in the general Caucasian population (11.5%. The influence of each of the three common APOE alleles on lipid traits was evaluated by the use of the average excess statistic. The E*2 allele is associated with lower levels of triglycerides and of total and non-HDL cholesterol in both men and women. Conversely, the E*4 allele is associated with higher levels of these traits in women only. The effect of APOE alleles was of greater magnitude in women.

  1. Apolipoprotein e genotype, plasma cholesterol, and cancer: a Mendelian randomization study.

    LENUS (Irish Health Repository)

    Trompet, Stella

    2009-12-01

    Observational studies have shown an association between low plasma cholesterol levels and increased risk of cancer, whereas most randomized clinical trials involving cholesterol-lowering medications have not shown this association. Between 1997 and 2002, the authors assessed the association between plasma cholesterol levels and cancer risk, free from confounding and reverse causality, in a Mendelian randomization study using apolipoprotein E (ApoE) genotype. ApoE genotype, plasma cholesterol levels, and cancer incidence and mortality were measured during a 3-year follow-up period among 2,913 participants in the Prospective Study of Pravastatin in the Elderly at Risk. Subjects within the lowest third of plasma cholesterol level at baseline had increased risks of cancer incidence (hazard ratio (HR) = 1.90, 95% confidence interval (CI): 1.34, 2.70) and cancer mortality (HR = 2.03, 95% CI: 1.23, 3.34) relative to subjects within the highest third of plasma cholesterol. However, carriers of the ApoE2 genotype (n = 332), who had 9% lower plasma cholesterol levels than carriers of the ApoE4 genotype (n = 635), did not have increased risk of cancer incidence (HR = 0.86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk.

  2. Synergistic associations of depression and apolipoprotein E genotype with incidence of dementia.

    Science.gov (United States)

    Kim, Jae-Min; Stewart, Robert; Kim, Seon-Young; Kim, Sung-Wan; Bae, Kyung-Yeol; Yang, Su-Jin; Shin, Il-Seon; Yoon, Jin-Sang

    2011-09-01

    A cohort study of Japanese-American men suggested interactive effects of depression and apolipoprotein E (APOE) e4 allele on risk of incident dementia. In another sample of East Asian origin, we sought to replicate the findings and to explore individual depressive symptoms where this interaction was most evident. Of 625 Korean community elders without dementia at baseline, 518 (83%) were followed over a 2.4-year period and were clinically assessed for incident dementia. Depression was identified by the Geriatric Mental State Schedule (GMS), and nine individual depressive symptoms relevant to DSM-IV major depressive episode criteria were extracted. APOE genotype was ascertained. Covariates included age, gender, education, and disability. There were synergistic interactions between depression and APOE e4 on incident dementia independent of covariates. This interaction was particularly strong for four depressive symptoms: depressed mood, worthlessness, concentration difficulty, and suicidal ideation. We were able to replicate the previous study, finding that, at least in East Asian origin populations, the APOE e4 allele is a stronger predictor of incident dementia in the presence of depressive syndrome, and particular depressive symptoms. Copyright © 2010 John Wiley & Sons, Ltd.

  3. Longitudinal Trajectories of Cholesterol from Midlife through Late Life according to Apolipoprotein E Allele Status

    Directory of Open Access Journals (Sweden)

    Brian Downer

    2014-10-01

    Full Text Available Background: Previous research indicates that total cholesterol levels increase with age during young adulthood and middle age and decline with age later in life. This is attributed to changes in diet, body composition, medication use, physical activity, and hormone levels. In the current study we utilized data from the Framingham Heart Study Original Cohort to determine if variations in apolipoprotein E (APOE, a gene involved in regulating cholesterol homeostasis, influence trajectories of total cholesterol, HDL cholesterol, and total: HDL cholesterol ratio from midlife through late life. Methods: Cholesterol trajectories from midlife through late life were modeled using generalized additive mixed models and mixed-effects regression models. Results: APOE e2+ subjects had lower total cholesterol levels, higher HDL cholesterol levels, and lower total: HDL cholesterol ratios from midlife to late life compared to APOE e3 and APOE e4+ subjects. Statistically significant differences in life span cholesterol trajectories according to gender and use of cholesterol-lowering medications were also detected. Conclusion: The findings from this research provide evidence that variations in APOE modify trajectories of serum cholesterol from midlife to late life. In order to efficiently modify cholesterol through the life span, it is important to take into account APOE allele status.

  4. Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.

    Science.gov (United States)

    Freedman, B I; Julian, B A; Pastan, S O; Israni, A K; Schladt, D; Gautreaux, M D; Hauptfeld, V; Bray, R A; Gebel, H M; Kirk, A D; Gaston, R S; Rogers, J; Farney, A C; Orlando, G; Stratta, R J; Mohan, S; Ma, L; Langefeld, C D; Hicks, P J; Palmer, N D; Adams, P L; Palanisamy, A; Reeves-Daniel, A M; Divers, J

    2015-06-01

    Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. Apolipoprotein D expression does not predict breast cancer recurrence among tamoxifen-treated patients

    DEFF Research Database (Denmark)

    Klebaner, Daniella; Hamilton-Dutoit, Stephen; Ahern, Thomas P

    2017-01-01

    confounding using logistic regression. RESULTS: Cytoplasmic ApoD expression was seen in 68% of ER+ tumors, in 66% of ER- tumors, and in 66% of controls across both groups. In women with ER+ tumors, the associations of cytoplasmic ApoD expression with recurrence (OR = 1.0; 95% CI = 0.7 to 1.4) and increasing...... cytoplasmic expression with recurrence (OR = 1.0; 95% CI = 0.996 to 1.003) were null, as were those for women with ER- tumors. Associations for nuclear ApoD expression and combined nuclear and cytoplasmic expression were similarly near-null. CONCLUSION: ApoD expression is likely not a predictor of recurrence......BACKGROUND: Apolipoprotein D (ApoD) has been proposed as a predictor of breast cancer recurrence among estrogen receptor-positive (ER+), tamoxifen-treated patients. METHODS: We conducted a population-based case-control study nested in a population of 11,251 women aged 35-69 years at diagnosis...

  6. Developmental co-expression of small molecular weight apolipoprotein B synthesis and triacylglycerol secretion

    International Nuclear Information System (INIS)

    Coleman, R.A.; Haynes, E.B.; Sand, T.M.; Davis, R.A.

    1987-01-01

    The development of the liver's ability to coordinately express the synthesis and secretion of the two major components of very low density lipoproteins (VLDL): triacylglycerol (TG) and apolipoprotein B (apo B) was examined in cultured hepatocytes obtained from fetal, suckling and adult rats. Hepatocytes from fetal and suckling rats synthesized and secreted TG at rates lower than that displayed by adult cells. When TG synthesis was equalized by adding oleic acid to the culture medium, fetal cells still secreted only 39% as much TG as did adult cells. To determine the basis for the apparent defect in VLDL assembly/secretion displayed by fetal cells, the synthesis and secretion of [ 35 S]methionine-labeled apo B was quantified by immunoprecipitation. Although adult and fetal cells synthesized and secreted large molecular weight apo B at similar rates, the synthesis and secretion of small molecular weight apo B was 2-fold greater in adult cells. These data suggest that the ability to assemble/secrete VLDL triacylglycerol varies in parallel with the developmental expression of small molecular weight apo B. Furthermore, these studies show the usefulness of the cultured rat hepatocyte model for examining the ontogeny and regulation of VLDL assembly/secretion

  7. Meta-analysis of peripheral blood apolipoprotein E levels in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Chong Wang

    Full Text Available BACKGROUND: Peripheral blood Apolipoprotein E (ApoE levels have been proposed as biomarkers of Alzheimer's disease (AD, but previous studies on levels of ApoE in blood remain inconsistent. This meta-analysis was designed to re-examine the potential role of peripheral ApoE in AD diagnosis and its potential value as a candidate biomarker. METHODS: We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane library, and BIOSIS previews for case-control studies measuring ApoE levels in serum or plasma from AD subjects and healthy controls. The pooled weighted mean difference (WMD and 95% confidence interval (CI were used to estimate the association between ApoE levels and AD risk. RESULTS: Eight studies with a total of 2250 controls and 1498 AD cases were identified and analyzed. The pooled WMD from a random-effect model of AD participants compared with the healthy controls was -5.59 mg/l (95% CI: [-8.12, -3.06]. The overall pattern in WMD was not varied by characteristics of study, including age, country, assay method, publication year, and sample type. CONCLUSIONS: Our meta-analysis supports a lowered level of blood ApoE in AD patients, and indicates its potential value as an important risk factor for AD. Further investigation employing standardized assay for ApoE measurement are still warranted to uncover the precise role of ApoE in the pathophysiology of AD.

  8. Apolipoprotein E-specific innate immune response in astrocytes from targeted replacement mice

    Directory of Open Access Journals (Sweden)

    Montine Thomas J

    2006-04-01

    Full Text Available Abstract Background Inheritance of the three different alleles of the human apolipoprotein (apo E gene (APOE are associated with varying risk or clinical outcome from a variety of neurologic diseases. ApoE isoform-specific modulation of several pathogenic processes, in addition to amyloid β metabolism in Alzheimer's disease, have been proposed: one of these is innate immune response by glia. Previously we have shown that primary microglia cultures from targeted replacement (TR APOE mice have apoE isoform-dependent innate immune activation and paracrine damage to neurons that is greatest with TR by the ε4 allele (TR APOE4 and that derives from p38 mitogen-activated protein kinase (p38MAPK activity. Methods Primary cultures of TR APOE2, TR APOE3 and TR APOE4 astrocytes were stimulated with lipopolysaccharide (LPS. ApoE secretion, cytokine production, and nuclear factor-kappa B (NF-κB subunit activity were measured and compared. Results Here we showed that activation of primary astrocytes from TR APOE mice with LPS led to TR APOE-dependent differences in cytokine secretion that were greatest in TR APOE2 and that were associated with differences in NF-κB subunit activity. Conclusion Our results suggest that LPS activation of innate immune response in TR APOE glia results in opposing outcomes from microglia and astrocytes as a result of TR APOE-dependent activation of p38MAPK or NF-κB signaling in these two cell types.

  9. Association between iris constitution and apolipoprotein e gene polymorphism in hypertensives.

    Science.gov (United States)

    Um, Jae-Young; Hwang, Chung-Yeon; Hwang, Woo-Jun; Kang, Sung-Do; Do, Keum-Rok; Cho, Ju-Jang; Cho, Jae-Woon; Kim, Sung-Hoon; Shin, Tae-Yong; Kim, Yun-Kyung; Kim, Hyung-Min; Hong, Seung-Heon

    2004-12-01

    Iridology is a complementary and alternative medicine (CAM) that involves the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris. Iris constitution has a strong familial aggregation and heredity is implicated. Apolipoprotein E (apoE) gene polymorphism is one of the most well-studied genetic markers for vascular diseases, including hypertension. In this study, we investigated the relationship between iris constitution and apoE polymorphism in hypertensives. We classified 87 hypertensives and 79 controls according to iris constitution and determined the apoE genotype of each individual. A significantly higher percentage of individuals with neurogenic constitutions was found in the hypertensive group when compared with the control group (chi(2) = 40.244, p < 0.001). In addition, a neurogenic constitution increased the relative risk for hypertension for subjects with an apo epsilon2 or an epsilon4 allele (chi(2) = 4.086, p = 0.049, odds ratio = 2.633, confidence interval = 1.004-6.905). Our results imply that a neurogenic iris constitution enhances the relative risk for hypertension in subjects with the apo epsilon2 or epsilon4 allele. Furthermore, we attempted to evaluate the efficacy of iris constitutional medicine and to find an association with hypertension.

  10. Apolipoprotein A-IV interacts synergistically with melanocortins to reduce food intake.

    Science.gov (United States)

    Gotoh, Koro; Liu, Min; Benoit, Stephen C; Clegg, Deborah J; Davidson, W Sean; D'Alessio, David; Seeley, Randy J; Tso, Patrick; Woods, Stephen C

    2006-01-01

    Apolipoprotein (apo) A-IV is an anorexigenic gastrointestinal peptide that is also synthesized in the hypothalamus. The goal of these experiments was to determine whether apo A-IV interacts with the central melanocortin (MC) system in the control of feeding. The third ventricular (i3vt) administration of a subthreshold dose of apo A-IV (0.5 microg) potentiated i3vt MC-induced (metallothionein-II, 0.03 nmol) suppression of 30-min feeding in Long-Evans rats. A subthreshold dose of the MC antagonist (SHU9119, 0.1 nmol, i3vt) completely attenuated the anorectic effect of i3vt apo A-IV (1.5 microg). The i3vt apo A-IV significantly elevated the expression of c-Fos in neurons of the paraventricular nucleus of the hypothalamus, but not in the arcuate nucleus or median eminence. In addition, c-Fos expression was not colocalized with proopiomelanocortin-positive neurons. These data support a synergistic interaction between apo A-IV and melanocortins that reduces food intake by acting downstream of the arcuate.

  11. Apolipoproteins C-II and C-III as nutritional markers unaffected by inflammation.

    Science.gov (United States)

    Isshiki, Miwa; Hirayama, Satoshi; Ueno, Tsuyoshi; Ito, Masayuki; Furuta, Ayaka; Yano, Kouji; Yamatani, Kotoko; Sugihara, Masami; Idei, Mayumi; Miida, Takashi

    2018-06-01

    Rapid turnover proteins (RTPs), such as transthyretin (TTR), retinol binding protein (RBP), and transferrin (Tf), provide an accurate assessment of nutritional status but are susceptible to inflammation. Lipid-related markers, which have short half-lives in serum, may be better suited for nutritional assessment. We sought to identify sensitive nutritional markers unaffected by inflammation. Fasting serum samples were collected from 30 malnourished inpatients and 25 healthy volunteers. Malnourished inpatients were divided into 2 groups: a low-C-reactive protein (CRP) group (CRP group (CRP ≥ 20 mg/l, n = 15). Lipid-related markers, traditional nutritional markers, RTPs, micronutrients, and ketone bodies were measured and compared among the groups. Apolipoprotein (Apo)C-II and ApoC-III concentrations were lower in malnourished inpatients than in the control group. There was no significant difference in ApoC-II and ApoC-III between the low- and high-CRP groups. Carnitine transporters and ketone bodies did not show a significant difference among the three groups. Albumin, TTR, RBP, and Tf concentrations were lowest in the high-CRP group, intermediate in the low-CRP group, and highest in the control group. These results indicate that ApoC-II and ApoC-III are appropriate nutritional biomarkers unaffected by inflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Phosphorylation-dependent down-regulation of apolipoprotein A5 by insulin

    Energy Technology Data Exchange (ETDEWEB)

    Nowak, Maxine; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Rommens, Corinne; Martin, Genevieve; Duran-Sandoval, Daniel; Staels, Bart; Rubin, Edward M.; Pennacchio, Len A.; Taskinen, Marja-Riitta; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-02-15

    The apolipoprotein A5 (APOA5) gene has been shown to be important in lowering plasma triglyceride levels. Since several studies have shown that hyperinsulinemia is associated with hypertriglyceridemia, we sought to determine whether APOA5 gene is regulated by insulin. We show here that cell and mouse treatments with insulin down-regulated APOA5 expression in a dose-dependent manner. Furthermore, we determined that insulin decreases APOA5 promoter activity and subsequent deletion analyses revealed an E-box-containing fragment. We showed that Upstream Stimulatory Factors, USF1/USF2, bind to the identified E-box in the APOA5 promoter. Moreover, in cotransfection studies, USF1 stimulates APOA5 promoter activity. The treatment with insulin reduces the binding of USF1/USF2 to APOA5 promoter. The inhibition of PI3K pathway with wortmannin abolished the insulin s effect on APOA5 gene transcription. Using oligoprecipitation method of USF from nuclear extracts, we demonstrated that phosphorylated USF1 failed to bind to APOA5 promoter. This indicates that the APOA5 gene transrepression by insulin involves a phosphorylation of USF through PI3K, that modulate their binding to APOA5 promoter and results in APOA5 down-regulation. The effect of exogenous hyperinsulinemia in healthy men shows a decrease of the plasma ApoAV level. These data suggest a potential mechanism involving APOA5 gene in hypertriglyceridemia associated with hyperinsulinemia.

  13. Apolipoprotein C-II and C-III metabolism in a kindred of familial hypobetalipoproteinemia

    International Nuclear Information System (INIS)

    Malmendier, C.L.; Delcroix, C.; Lontie, J.F.; Dubois, D.Y.

    1991-01-01

    Three affected members of a kindred with asymptomatic hypobetalipoproteinemia (HBL) showed low levels of triglycerides, low-density lipoprotein (LDL)-cholesterol, and apolipoproteins (apo) B, C-II, and C-III. Turnover of iodine-labeled apo C-II and apo C-III associated in vitro to plasma lipoproteins was studied after intravenous injection. Radioactivity in plasma and lipoproteins (95% recovered in high-density lipoprotein [HDL] density range) and in 24-hour urine samples was observed for 16 days. A parallelism of the slowest slopes of plasma decay curves was observed between apo C-II and apo C-III, indicating a partial common catabolic route. Urine/plasma radioactivity ratio (U/P) varied with time, suggesting heterogeneity of metabolic pathways. A new compartmental model using the SAAM program was built, not only fitting simultaneously plasma and urine data, but also taking into account the partial common metabolism of lipoprotein particles (LP) containing apo C-II and apo C-III. The low apo C-II and C-III plasma concentrations observed in HBL compared with normal resulted from both an increased catabolism and a reduced synthesis, these changes being more marked for apo C-III. The modifications in the rate constants of the different pathways calculated from the new model are in favor of an increased direct removal of particles following the fast pathway, likely in the very-low-density lipoprotein (VLDL) density range

  14. Orphan nuclear receptor Nur77 participates in human apolipoprotein A5 gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kwang-Hoon, E-mail: ksong@kiom.re.kr [Korea Institute of Oriental Medicine, Daejeon 305-811 (Korea, Republic of)

    2010-01-29

    The orphan nuclear receptor Nur77 (NR4A1) has been reported to play a crucial role in the modulation of diverse metabolic processes in liver. Here, we reported the identification of human apolipoprotein A5 (ApoA5), which implicated in lowering plasma triglyceride levels, as a novel target gene of Nur77. Nur77 induced the human ApoA5 promoter activity. Using 5'-deletion and mutagenesis of human ApoA5 promoter analysis and chromatin immunoprecipitation assays, it was shown that Nur77 directly regulated human ApoA5 gene expression by binding to a Nur77 response element (AAAGGTCA) located in the proximal human ApoA5 promoter region. In addition, we demonstrated that blocking of Nur77 transcriptional activity via overexpression of dominant negative Nur77 suppressed human ApoA5 promoter activity and mRNA expression in human hepatoma cells, HepG2. Taken together, our results demonstrated that Nur77 is a novel regulator of human ApoA5 gene expression and provide a new insight into the role of this orphan nuclear receptor in lipoprotein metabolism and triglyceride homeostasis.

  15. Sharp Bounds for Symmetric and Asymmetric Diophantine Approximation

    Institute of Scientific and Technical Information of China (English)

    Cornelis KRAAIKAMP; Ionica SMEETS

    2011-01-01

    In 2004,Tong found bounds for the approximation quality of a regular continued fraction convergent to a rational number,expressed in bounds for both the previous and next approximation.The authors sharpen his results with a geometric method and give both sharp upper and lower bounds.The asymptotic frequencies that these bounds occur are also calculated.

  16. Diagnostic Magnetic Resonance Imaging of Atherosclerosis in Apolipoprotein E Knockout Mouse Model Using Macrophage-Targeted Gadolinium-Containing Synthetic Lipopeptide Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Zu T Shen

    Full Text Available Cardiovascular disease is the leading cause of death in Western cultures. The vast majority of cardiovascular events, including stroke and myocardial infarction, result from the rupture of vulnerable atherosclerotic plaques, which are characterized by high and active macrophage content. Current imaging modalities including magnetic resonance imaging (MRI aim to characterize anatomic and structural features of plaques rather than their content. Previously, we reported that macrophage-targeted delivery of gadolinium (Gd-based contrast agent (GBCA-HDL using high density lipoproteins (HDL-like particles significantly enhances the detection of plaques in an apolipoprotein (apo E knockout (KO mouse model, with an atherosclerotic wall/muscle normalized enhancement ratio (NER of 120% achieved. These particles are comprised of lipids and synthetic peptide fragments of the major protein of HDL, apo A-I, that contain a naturally occurring modification which targets the particles to macrophages. Targeted delivery minimizes the Gd dose and thus reduces the adverse effects of Gd. The aims of the current study were to test whether varying the GBCA-HDL particle shape and composition can further enhance atherosclerotic plaque MRI and control organ clearance of these agents. We show that the optimized GBCA-HDL particles are efficiently delivered intracellularly to and uptaken by both J774 macrophages in vitro and more importantly, by intraplaque macrophages in vivo, as evidenced by NER up to 160% and higher. This suggests high diagnostic power of our GBCA-HDL particles in the detection of vulnerable atherosclerotic plaques. Further, in contrast to discoidal, spherical GBCA-HDL exhibit hepatic clearance, which could further diminish adverse renal effects of Gd. Finally, activated macrophages are reliable indicators of any inflamed tissues and are implicated in other areas of unmet clinical need such as rheumatoid arthritis, sepsis and cancer, suggesting the

  17. Bounds on fluid permeability for viscous flow through porous media

    International Nuclear Information System (INIS)

    Berryman, J.G.

    1985-01-01

    General properties of variational bounds on Darcy's constant for slow viscous flow through porous media are studied. The bounds are also evaluated numerically for the penetrable sphere model. The bound of Doi depending on two-point correlations and the analytical bound of Weissberg and Prager give comparable results in the low density limit but the analytical bound is superior for higher densities. Prager's bound depending on three-point correlation functions is worse than the analytical bound at low densities but better (although comparable to it) at high densities. A procedure for methodically improving Prager's three point bound is presented. By introducing a Gaussian trial function, the three-point bound is improved by an order of magnitude for moderate values of porosity. The new bounds are comparable in magnitude to the Kozeny--Carman empirical relation for porous materials

  18. Upper bounds for reversible circuits based on Young subgroups

    DEFF Research Database (Denmark)

    Abdessaied, Nabila; Soeken, Mathias; Thomsen, Michael Kirkedal

    2014-01-01

    We present tighter upper bounds on the number of Toffoli gates needed in reversible circuits. Both multiple controlled Toffoli gates and mixed polarity Toffoli gates have been considered for this purpose. The calculation of the bounds is based on a synthesis approach based on Young subgroups...... that results in circuits using a more generalized gate library. Starting from an upper bound for this library we derive new bounds which improve the existing bound by around 77%....

  19. Age-dependent interaction of apolipoprotein E gene with eastern birthplace in Finland affects severity of coronary atherosclerosis and risk of fatal myocardial infarction--Helsinki Sudden Death Study.

    Science.gov (United States)

    Tyynelä, Petri; Goebeler, Sirkka; Ilveskoski, Erkki; Mikkelsson, Jussi; Perola, Markus; Lehtimäki, Terho; Karhunen, Pekka J

    2013-05-01

    Mortality from coronary heart disease (CHD) has been constantly higher in eastern late settlement regions compared to western early settlements in Finland, unrelated to classical risk factors. In line with this, eastern birthplace was an age-dependent predictor of severe coronary atherosclerosis and pre-hospital sudden coronary death among male residents of Helsinki. We investigated a possible interaction of apolipoprotein E (APOE) gene with birthplace on the risk of myocardial infarction (MI) and coronary atherosclerosis. APOE genotypes were analyzed in the Helsinki Sudden Death Study series comprising out-of-hospital deaths among males aged 33-70 years (n = 577), who were born in high (east, n = 273) or low (west, n = 304) CHD mortality area. Eastern-born men ≤ 55 years carried 30% more often (P = 0.017) and older men 40% less often (P = 0.022) the APOE ϵ4 allele compared to western-born men (P = 0.003 for birthplace-by-age interaction). In multivariate analysis, the ϵ4 allele associated with the risk of out-of-hospital MI (odds ratio 2.58; 95% CI 1.20-5.55; P = 0.016) only in eastern-born men and with advanced atherosclerosis in both regions of origin, respectively. Birthplace-bound risk of CHD was age-dependently modified by APOE ϵ4 allele, suggesting genetic differences in CHD susceptibility between early and late settlement regions in Finland and providing one explanation for the eastern high mortality.

  20. Optima and bounds for irreversible thermodynamic processes

    International Nuclear Information System (INIS)

    Hoffmann, K.H.

    1990-01-01

    In this paper bounds and optima for irreversible thermodynamic processes and their application in different fields are discussed. The tools of finite time thermodynamics are presented and especially optimal control theory is introduced. These methods are applied to heat engines, including models of the Diesel engine and a light-driven engine. Further bounds for irreversible processes are introduced, discussing work deficiency and its relation to thermodynamic length. Moreover the problem of dissipation in systems composed of several subsystems is studied. Finally, the methods of finite time thermodynamics are applied to thermodynamic processes described on a more microscopic level. The process used as an example is simulated annealing. It is shown how optimal control theory is applied to find the optimal cooling schedule for this important stochastic optimization method

  1. Bounded excursion stable gravastars and black holes

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, P [Instituto de Fisica, Universidade Federal Fluminense, Avenida Litoranea, s/n, Boa Viagem 24210-340, Niteroi, RJ (Brazil); Miguelote, A Y; Chan, R [Coordenacao de Astronomia e Astrofisica, Observatorio Nacional, Rua General Jose Cristino, 77, Sao Cristovao 20921-400, Rio de Janeiro, RJ (Brazil); Da Silva, M F; Wang, Anzhong [Departamento de Fisica Teorica, Instituto de Fisica, Universidade do Estado do Rio de Janeiro, Rua Sao Francisco Xavier 524, Maracana 20550-900, Rio de Janeiro-RJ (Brazil); Santos, N O, E-mail: pedrosennarocha@gmail.com, E-mail: yasuda@on.br, E-mail: chan@on.br, E-mail: mfasnic@gmail.com, E-mail: N.O.Santos@qmul.ac.uk, E-mail: anzhong_wang@baylor.edu [LERMA/CNRS-FRE 2460, Universite Pierre et Marie Curie, ERGA, Boite 142, 4 Place Jussieu, 75005 Paris Cedex 05 (France)

    2008-06-15

    Dynamical models of prototype gravastars were constructed in order to study their stability. The models are the Visser-Wiltshire three-layer gravastars, in which an infinitely thin spherical shell of stiff fluid divides the whole spacetime into two regions, where the internal region is de Sitter, and the external one is Schwarzschild. It is found that in some cases the models represent the 'bounded excursion' stable gravastars, where the thin shell is oscillating between two finite radii, while in other cases they collapse until the formation of black holes occurs. In the phase space, the region for the 'bounded excursion' gravastars is very small in comparison to that of black holes, but not empty. Therefore, although the possibility of the existence of gravastars cannot be excluded from such dynamical models, our results indicate that, even if gravastars do indeed exist, that does not exclude the possibility of the existence of black holes.

  2. Optimal Bounds in Parametric LTL Games

    Directory of Open Access Journals (Sweden)

    Martin Zimmermann

    2011-06-01

    Full Text Available We consider graph games of infinite duration with winning conditions in parameterized linear temporal logic, where the temporal operators are equipped with variables for time bounds. In model checking such specifications were introduced as "PLTL" by Alur et al. and (in a different version called "PROMPT-LTL" by Kupferman et al.. We present an algorithm to determine optimal variable valuations that allow a player to win a game. Furthermore, we show how to determine whether a player wins a game with respect to some, infinitely many, or all valuations. All our algorithms run in doubly-exponential time; so, adding bounded temporal operators does not increase the complexity compared to solving plain LTL games.

  3. Asymptotic Sharpness of Bounds on Hypertrees

    Directory of Open Access Journals (Sweden)

    Lin Yi

    2017-08-01

    Full Text Available The hypertree can be defined in many different ways. Katona and Szabó introduced a new, natural definition of hypertrees in uniform hypergraphs and investigated bounds on the number of edges of the hypertrees. They showed that a k-uniform hypertree on n vertices has at most (nk−1$\\left( {\\matrix{n \\cr {k - 1} } } \\right$ edges and they conjectured that the upper bound is asymptotically sharp. Recently, Szabó verified that the conjecture holds by recursively constructing an infinite sequence of k-uniform hypertrees and making complicated analyses for it. In this note we give a short proof of the conjecture by directly constructing a sequence of k-uniform k-hypertrees.

  4. A holographic bound for D3-brane

    Energy Technology Data Exchange (ETDEWEB)

    Momeni, Davood; Myrzakul, Aizhan; Myrzakulov, Ratbay [Eurasian National University, Eurasian International Center for Theoretical Physics, Astana (Kazakhstan); Eurasian National University, Department of General Theoretical Physics, Astana (Kazakhstan); Faizal, Mir [University of British Columbia-Okanagan, Irving K. Barber School of Arts and Sciences, Kelowna, BC (Canada); University of Lethbridge, Department of Physics and Astronomy, Lethbridge, AB (Canada); Bahamonde, Sebastian [University College London, Department of Mathematics, London (United Kingdom)

    2017-06-15

    In this paper, we will regularize the holographic entanglement entropy, holographic complexity and fidelity susceptibility for a configuration of D3-branes. We will also study the regularization of the holographic complexity from the action for a configuration of D3-branes. It will be demonstrated that for a spherical shell of D3-branes the regularized holographic complexity is always greater than or equal to the regularized fidelity susceptibility. Furthermore, we will also demonstrate that the regularized holographic complexity is related to the regularized holographic entanglement entropy for this system. Thus, we will obtain a holographic bound involving regularized holographic complexity, regularized holographic entanglement entropy and regularized fidelity susceptibility of a configuration of D3-brane. We will also discuss a bound for regularized holographic complexity from action, for a D3-brane configuration. (orig.)

  5. Bound states in weakly disordered spin ladders

    Energy Technology Data Exchange (ETDEWEB)

    Arlego, M. [Departamento de Fisica, Universidad Nacional de La Plata, CC 67 (1900) La Plata (Argentina)]. E-mail: arlego@venus.fisica.unlp.edu.ar; Brenig, W. [Institut fuer Theoretische Physik, Technische Universitaet Braunschweig (Germany); Cabra, D.C. [Laboratoire de Physique Theorique, Universite Louis Pasteur Strasbourg (France); Heidrich-Meisner, F. [Institut fuer Theoretische Physik, Technische Universitaet Braunschweig (Germany); Honecker, A. [Institut fuer Theoretische Physik, Technische Universitaet Braunschweig (Germany); Rossini, G. [Departamento de Fisica, Universidad Nacional de La Plata, CC 67 (1900) La Plata (Argentina)

    2005-04-30

    We study the appearance of bound states in the spin gap of spin-12 ladders induced by weak bond disorder. Starting from the strong-coupling limit, i.e., the limit of weakly coupled dimers, we perform a projection on the single-triplet subspace and derive the position of bound states for the single impurity problem of one modified coupling as well as for small impurity clusters. The case of a finite concentration of impurities is treated with the coherent-potential approximation (CPA) in the strong-coupling limit and compared with numerical results. Further, we analyze the details in the structure of the density of states and relate their origin to the influence of impurity clusters.

  6. Entanglement detection with bounded reference frames

    International Nuclear Information System (INIS)

    Costa, Fabio; Brukner, Caslav; Harrigan, Nicholas; Rudolph, Terry

    2009-01-01

    Quantum experiments usually assume the existence of perfect, classical reference frames (RFs), which allow for the specification of measurement settings (e.g. orientation of the Stern-Gerlach magnet in spin measurements) with arbitrary precision. If the RFs are 'bounded' (i.e. quantum systems themselves, having a finite number of degrees of freedom), only limited precision can be attained. Using spin coherent states as bounded RFs, we have found the minimum size needed for them to violate local realism for entangled spin systems. For composite systems of spin 1/2 particles, RFs of very small size are sufficient for the violation; however, to see this violation for macroscopic entangled spins, the size of the RF must be at least quadratically larger than that of the spins. The unavailability of such RFs gives a possible explanation for the non-observance of violation of local realism in everyday experience.

  7. A proof of the conformal collider bounds

    Energy Technology Data Exchange (ETDEWEB)

    Hofman, Diego M. [Institute for Theoretical Physics, University of Amsterdam, Science Park 904, Postbus 94485, 1090 GL, Amsterdam (Netherlands); Li, Daliang [Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States); Meltzer, David [Department of Physics, Yale University, New Haven, CT 06511 (United States); Poland, David [Department of Physics, Yale University, New Haven, CT 06511 (United States); School of Natural Sciences, Institute for Advanced Study, Princeton, NJ 08540 (United States); Rejon-Barrera, Fernando [Institute for Theoretical Physics, University of Amsterdam, Science Park 904, Postbus 94485, 1090 GL, Amsterdam (Netherlands)

    2016-06-20

    In this paper, we prove that the “conformal collider bounds” originally proposed in http://dx.doi.org/10.1088/1126-6708/2008/05/012 hold for any unitary parity-preserving conformal field theory (CFT) with a unique stress tensor in dimensions d≥3. In particular this implies that the ratio of central charges for a unitary 4d CFT lies in the interval (31/18)≥(a/c)≥(1/3). For superconformal theories this is further reduced to (3/2)≥(a/c)≥(1/2). The proof relies only on CFT first principles — in particular, bootstrap methods — and thus constitutes the first complete field theory proof of these bounds. We further elaborate on similar bounds for non-conserved currents and relate them to results obtained recently from deep inelastic scattering.

  8. Efficiency bounds for nonequilibrium heat engines

    International Nuclear Information System (INIS)

    Mehta, Pankaj; Polkovnikov, Anatoli

    2013-01-01

    We analyze the efficiency of thermal engines (either quantum or classical) working with a single heat reservoir like an atmosphere. The engine first gets an energy intake, which can be done in an arbitrary nonequilibrium way e.g. combustion of fuel. Then the engine performs the work and returns to the initial state. We distinguish two general classes of engines where the working body first equilibrates within itself and then performs the work (ergodic engine) or when it performs the work before equilibrating (non-ergodic engine). We show that in both cases the second law of thermodynamics limits their efficiency. For ergodic engines we find a rigorous upper bound for the efficiency, which is strictly smaller than the equivalent Carnot efficiency. I.e. the Carnot efficiency can be never achieved in single reservoir heat engines. For non-ergodic engines the efficiency can be higher and can exceed the equilibrium Carnot bound. By extending the fundamental thermodynamic relation to nonequilibrium processes, we find a rigorous thermodynamic bound for the efficiency of both ergodic and non-ergodic engines and show that it is given by the relative entropy of the nonequilibrium and initial equilibrium distributions. These results suggest a new general strategy for designing more efficient engines. We illustrate our ideas by using simple examples. -- Highlights: ► Derived efficiency bounds for heat engines working with a single reservoir. ► Analyzed both ergodic and non-ergodic engines. ► Showed that non-ergodic engines can be more efficient. ► Extended fundamental thermodynamic relation to arbitrary nonequilibrium processes

  9. Recent advances in bound state quantum electrodynamics

    International Nuclear Information System (INIS)

    Brodsky, S.J.; Lepage, G.P.

    1977-06-01

    Recent developments are reviewed in four areas of computational quantum electrodynamics: a new relativistic two-body formalism equal in rigor to the Bethe-Salpeter formalism but with strong calculational advantages is discussed; recent work on the computation of the decay rate of bound systems (positronium in particular) is presented; limits on possible composite structure of leptons are discussed; a new multidimensional integration program ('VEGAS') suitable for higher order calculations is presented

  10. Bounding probabilistic safety assessment probabilities by reality

    International Nuclear Information System (INIS)

    Fragola, J.R.; Shooman, M.L.

    1991-01-01

    The investigation of the failure in systems where failure is a rare event makes the continual comparisons between the developed probabilities and empirical evidence difficult. The comparison of the predictions of rare event risk assessments with historical reality is essential to prevent probabilistic safety assessment (PSA) predictions from drifting into fantasy. One approach to performing such comparisons is to search out and assign probabilities to natural events which, while extremely rare, have a basis in the history of natural phenomena or human activities. For example the Segovian aqueduct and some of the Roman fortresses in Spain have existed for several millennia and in many cases show no physical signs of earthquake damage. This evidence could be used to bound the probability of earthquakes above a certain magnitude to less than 10 -3 per year. On the other hand, there is evidence that some repetitive actions can be performed with extremely low historical probabilities when operators are properly trained and motivated, and sufficient warning indicators are provided. The point is not that low probability estimates are impossible, but continual reassessment of the analysis assumptions, and a bounding of the analysis predictions by historical reality. This paper reviews the probabilistic predictions of PSA in this light, attempts to develop, in a general way, the limits which can be historically established and the consequent bounds that these limits place upon the predictions, and illustrates the methodology used in computing such limits. Further, the paper discusses the use of empirical evidence and the requirement for disciplined systematic approaches within the bounds of reality and the associated impact on PSA probabilistic estimates

  11. Multipartite secret key distillation and bound entanglement

    International Nuclear Information System (INIS)

    Augusiak, Remigiusz; Horodecki, Pawel

    2009-01-01

    Recently it has been shown that quantum cryptography beyond pure entanglement distillation is possible and a paradigm for the associated protocols has been established. Here we systematically generalize the whole paradigm to the multipartite scenario. We provide constructions of new classes of multipartite bound entangled states, i.e., those with underlying twisted Greenberger-Horne-Zeilinger (GHZ) structure and nonzero distillable cryptographic key. We quantitatively estimate the key from below with the help of the privacy squeezing technique.

  12. Closed form bound-state perturbation theory

    Directory of Open Access Journals (Sweden)

    Ollie J. Rose

    1980-01-01

    Full Text Available The perturbed Schrödinger eigenvalue problem for bound states is cast into integral form using Green's Functions. A systematic algorithm is developed and applied to the resulting equation giving rise to approximate solutions expressed as functions of the given perturbation parameter. As a by-product, convergence radii for the traditional Rayleigh-Schrödinger and Brillouin-Wigner perturbation theories emerge in a natural way.

  13. Exact BPS bound for noncommutative baby Skyrmions

    International Nuclear Information System (INIS)

    Domrin, Andrei; Lechtenfeld, Olaf; Linares, Román; Maceda, Marco

    2013-01-01

    The noncommutative baby Skyrme model is a Moyal deformation of the two-dimensional sigma model plus a Skyrme term, with a group-valued or Grassmannian target. Exact abelian solitonic solutions have been identified analytically in this model, with a singular commutative limit. Inside any given Grassmannian, we establish a BPS bound for the energy functional, which is saturated by these baby Skyrmions. This asserts their stability for unit charge, as we also test in second-order perturbation theory

  14. The organically bound tritium: an analyst vision

    International Nuclear Information System (INIS)

    Ansoborlo, E.; Baglan, N.

    2009-01-01

    The authors report the work of a work group on tritium analysis. They recall the different physical forms of tritium: gas (HT, hydrogen-tritium), water vapour (HTO or tritiated water) or methane (CH3T), but also in organic compounds (OBT, organically bound tritium) which are either exchangeable or non-exchangeable. They evoke measurement techniques and methods, notably to determine the tritium volume activity. They discuss the possibilities to analyse and distinguish exchangeable and non-exchangeable OBTs

  15. New approach to calculate bound state eigenvalues

    International Nuclear Information System (INIS)

    Gerck, E.; Gallas, J.A.C.

    1983-01-01

    A method of solving the radial Schrodinger equation for bound states is discussed. The method is based on a new piecewise representation of the second derivative operator on a set of functions that obey the boundary conditions. This representation is trivially diagonalised and leads to closed form expressions of the type E sub(n)=E(ab+b+c/n+...) for the eigenvalues. Examples are given for the power-law and logarithmic potentials. (Author) [pt

  16. A sorting network in bounded arithmetic

    Czech Academy of Sciences Publication Activity Database

    Jeřábek, Emil

    2011-01-01

    Roč. 162, č. 4 (2011), s. 341-355 ISSN 0168-0072 R&D Projects: GA AV ČR IAA1019401; GA MŠk(CZ) 1M0545 Institutional research plan: CEZ:AV0Z10190503 Keywords : bounded arithmetic * sorting network * proof complexity * monotone sequent calculus Subject RIV: BA - General Mathematics Impact factor: 0.450, year: 2011 http://www.sciencedirect.com/science/article/pii/S0168007210001272

  17. Heterogeneity, Bounded Rationality and Market Dysfunctionality

    OpenAIRE

    Xue-Zhong He; Lei Shi

    2008-01-01

    As the main building blocks of the modern finance theory, homogeneity and rational expectation have faced difficulty in explaining many market anomalies, stylized factors, and market inefficiency in empirical studies. As a result, heterogeneity and bounded rationality have been used as an alterative paradigm of asset price dynamics and this paradigm has been widely recognized recently in both academic and financial market practitioners. Within the framework of Chiarella, Dieci and He (2006a, ...

  18. Kinetic simulation on collisional bounded plasma

    International Nuclear Information System (INIS)

    Zhu, S.P.; Sato, Tetsuya; Tomita, Yukihiro; Hatori, Tadatsugu

    1998-01-01

    A self-consistent kinetic simulation model on collisional bounded plasma is presented. The electric field is given by solving Poisson equation and collisions among particles (including charged particles and neutral particles) are included. The excitation and ionization of neutral particle, and recombination are also contained in the present model. The formation of potential structure near a boundary for a discharge system was used as an application of this model. (author)

  19. Analysis of the organically bound tritium

    International Nuclear Information System (INIS)

    Baglan, N.; Alanic, G.

    2011-01-01

    In environmental samples, tritium is very often combined with the fraction of bulk water accumulated in the sample but also in the form of organically bound tritium. When the tritium is organically bound, 2 forms can coexist: the exchangeable fraction and the non-exchangeable fraction. The analysis of the different forms of tritium present in the sample is necessary to assess the sanitary hazards due to tritium. The total tritium is obtained from the analysis of the water released when the fresh sample is burnt while the organically bound tritium is obtained from the analysis of the water released when the dry extract of the sample is burnt. The measurement of the exchangeable fraction and the non-exchangeable fraction requires an additional stage of labile exchange. The exchangeable fraction is determined from the analysis of the water released during the labile exchange and the non-exchangeable fraction is determined from the water released during the combustion of the dry extract of the labile exchange

  20. Search for quasi bound η mesons

    International Nuclear Information System (INIS)

    Machner, H

    2015-01-01

    The search for a quasi bound η meson in atomic nuclei is reviewed. This tentative state is studied theoretically as well as experimentally. The theory starts from elastic η nucleon scattering which is derived from production data within some models. From this interaction the η nucleus interaction is derived. Model calculations predict binding energies and widths of the quasi bound state. Another method is to derive the η nucleus interaction from excitation functions of η production experiments. The s wave interaction is extracted from such data via final state interaction (FSI) theorem. We give the derivation of s wave amplitudes in partial wave expansion and in helicity amplitudes and their relation to observables. Different experiments extracting the FSI are discussed as are production experiments. So far only three experiments give evidence for the existence of the quasi bound state: a pion double charge exchange experiment, an effective mass measurement, and a transfer reaction at recoil free kinematics with observation of the decay of the state. (topical review)

  1. Lower bounds for the minimum distance of algebraic geometry codes

    DEFF Research Database (Denmark)

    Beelen, Peter

    , such as the Goppa bound, the Feng-Rao bound and the Kirfel-Pellikaan bound. I will finish my talk by giving several examples. Especially for two-point codes, the generalized order bound is fairly easy to compute. As an illustration, I will indicate how a lower bound can be obtained for the minimum distance of some...... description of these codes in terms of order domains has been found. In my talk I will indicate how one can use the ideas behind the order bound to obtain a lower bound for the minimum distance of any AG-code. After this I will compare this generalized order bound with other known lower bounds...

  2. ApoA-I/A-II-HDL positively associates with apoB-lipoproteins as a potential atherogenic indicator.

    Science.gov (United States)

    Kido, Toshimi; Kondo, Kazuo; Kurata, Hideaki; Fujiwara, Yoko; Urata, Takeyoshi; Itakura, Hiroshige; Yokoyama, Shinji

    2017-11-29

    We recently reported distinct nature of high-density lipoproteins (HDL) subgroup particles with apolipoprotein (apo) A-I but not apoA-II (LpAI) and HDL having both (LpAI:AII) based on the data from 314 Japanese. While plasma HDL level almost exclusively depends on concentration of LpAI having 3 to 4 apoA-I molecules, LpAI:AII appeared with almost constant concentration regardless of plasma HDL levels having stable structure with two apoA-I and one disulfide-dimeric apoA-II molecules (Sci. Rep. 6; 31,532, 2016). The aim of this study is further characterization of LpAI:AII with respect to its role in atherogenesis. Association of LpAI, LpAI:AII and other HDL parameters with apoB-lipoprotein parameters was analyzed among the cohort data above. ApoA-I in LpAI negatively correlated with the apoB-lipoprotein parameters such as apoB, triglyceride, nonHDL-cholesterol, and nonHDL-cholesterol + triglyceride, which are apparently reflected in the relations of the total HDL parameters to apoB-lipoproteins. In contrast, apoA-I in LpAI:AII and apoA-II positively correlated to the apoB-lipoprotein parameters even within their small range of variation. These relationships are independent of sex, but may slightly be influenced by the activity-related CETP mutations. The study suggested that LpAI:AII is an atherogenic indicator rather than antiatherogenic. These sub-fractions of HDL are to be evaluated separately for estimating atherogenic risk of the patients.

  3. In vivo human apolipoprotein E isoform fractional turnover rates in the CNS.

    Directory of Open Access Journals (Sweden)

    Kristin R Wildsmith

    Full Text Available Apolipoprotein E (ApoE is the strongest genetic risk factor for Alzheimer's disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4 each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer's disease (AD. Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS, we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis.

  4. Apolipoprotein E4 causes early olfactory network abnormalities and short-term olfactory memory impairments.

    Science.gov (United States)

    Peng, Katherine Y; Mathews, Paul M; Levy, Efrat; Wilson, Donald A

    2017-02-20

    While apolipoprotein (Apo) E4 is linked to increased incidence of Alzheimer's disease (AD), there is growing evidence that it plays a role in functional brain irregularities that are independent of AD pathology. However, ApoE4-driven functional differences within olfactory processing regions have yet to be examined. Utilizing knock-in mice humanized to ApoE4 versus the more common ApoE3, we examined a simple olfactory perceptual memory that relies on the transfer of information from the olfactory bulb (OB) to the piriform cortex (PCX), the primary cortical region involved in higher order olfaction. In addition, we have recorded in vivo resting and odor-evoked local field potentials (LPF) from both brain regions and measured corresponding odor response magnitudes in anesthetized young (6-month-old) and middle-aged (12-month-old) ApoE mice. Young ApoE4 compared to ApoE3 mice exhibited a behavioral olfactory deficit coinciding with hyperactive odor-evoked response magnitudes within the OB that were not observed in older ApoE4 mice. Meanwhile, middle-aged ApoE4 compared to ApoE3 mice exhibited heightened response magnitudes in the PCX without a corresponding olfactory deficit, suggesting a shift with aging in ApoE4-driven effects from OB to PCX. Interestingly, the increased ApoE4-specific response in the PCX at middle-age was primarily due to a dampening of baseline spontaneous activity rather than an increase in evoked response power. Our findings indicate that early ApoE4-driven olfactory memory impairments and OB network abnormalities may be a precursor to later network dysfunction in the PCX, a region that not only is targeted early in AD, but may be selectively vulnerable to ApoE4 genotype. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Relevance of apolipoprotein E4 for the lipid profile of Brazilian patients with coronary artery disease

    Directory of Open Access Journals (Sweden)

    D.R.S. Souza

    2007-02-01

    Full Text Available Apolipoprotein E (apoE - e2, e3, e4 alleles plays a role in the regulation of lipid metabolism, with the e4 considered to be a risk factor for coronary artery disease (CAD. We aimed to evaluate the apoE polymorphisms in Brazilians with CAD and their influence on the lipid profile and other risk factors (hypertension, diabetes mellitus, smoking. Two hundred individuals were examined: 100 patients with atherosclerosis confirmed by coronary angiography and 100 controls. Blood samples were drawn to determine apoE polymorphisms and lipid profile. As expected, the e3 allele was prevalent in the CAD (0.87 and non-CAD groups (0.81; P = 0.099, followed by the e4 allele (0.09 and 0.14, respectively; P = 0.158. The e3/3 (76 and 78% and e3/4 (16 and 23% were the most common genotypes for patients and controls, respectively. The lipid profile was altered in patients compared to controls (P < 0.05, independently of the e4 allele. However, in the controls this allele was prevalent in individuals with elevated LDL-cholesterol levels only (odds ratio = 2.531; 95% CI = 1.028-6.232. The frequency of risk factors was higher in the CAD group (P < 0.05, but their association with the lipid profile was not demonstrable in e4 carriers. In conclusion, the e4 allele is not associated with CAD or lipid profile in patients with atherosclerosis. However, its frequency in the non-CAD group is associated with increased levels of LDL-cholesterol, suggesting an independent effect of the e4 allele on lipid profile when the low frequency of other risk factors in this group is taken into account.

  6. Endothelial dysfunction of resistance vessels in female apolipoprotein E-deficient mice

    Directory of Open Access Journals (Sweden)

    Vasquez Elisardo C

    2010-05-01

    Full Text Available Abstract Background The effects of hypercholesterolemia on vasomotricity in apolipoprotein E-deficient (ApoE mice, a murine model of spontaneous atherosclerosis, are still unclear. The studies were mostly performed in conductance vessels from male mice fed a high-fat diet. In the present study, we evaluated the endothelial function of resistance vessels from normal C57BL/6 (C57 and hypercholesterolemic (ApoE female mice in both normal and ovariectomized conditions. Methods Twenty week-old C57 and ApoE mice underwent ovariectomy or sham surgery and were studied 30 days later. The vascular reactivities to norepinephrine (NE, 10-9 to 2 × 10-3 mol/L, acetylcholine (ACh and sodium nitroprusside (SNP (10-10 to 10-3 mol/L were evaluated in the isolated mesenteric arteriolar bed through dose-response curves. Results ACh-induced relaxation was significantly reduced (P 50 (-5.67 ± 0.18 vs. -6.23 ± 0.09 mol/L. Ovariectomy caused a significant impairment in ACh-induced relaxation in the C57 group (maximal response: 61 ± 4% but did not worsen the deficient state of relaxation in ApoE animals (maximal response: 39 ± 5%. SNP-induced vasorelaxation and NE-induced vasoconstriction were similar in ApoE and C57 female mice. Conclusion These data show an impairment of endothelial function in the resistance vessels of spontaneously atherosclerotic (ApoE-deficient female mice compared with normal (C57 female mice. The endothelial dysfunction in hypercholesterolemic animals was so marked that ovariectomy, which impaired endothelial function in C57 mice, did not cause additional vascular damage in ApoE-deficient mice.

  7. Endothelial surface layer degradation by chronic hyaluronidase infusion induces proteinuria in apolipoprotein E-deficient mice.

    Directory of Open Access Journals (Sweden)

    Marijn C Meuwese

    Full Text Available OBJECTIVE: Functional studies show that disruption of endothelial surface layer (ESL is accompanied by enhanced sensitivity of the vasculature towards atherogenic stimuli. However, relevance of ESL disruption as causal mechanism for vascular dysfunction remains to be demonstrated. We examined if loss of ESL through enzymatic degradation would affect vascular barrier properties in an atherogenic model. METHODS: Eight week old male apolipoprotein E deficient mice on Western-type diet for 10 weeks received continuous active or heat-inactivated hyaluronidase (10 U/hr, i.v. through an osmotic minipump during 4 weeks. Blood chemistry and anatomic changes in both macrovasculature and kidneys were examined. RESULTS: Infusion with active hyaluronidase resulted in decreased ESL (0.32±0.22 mL and plasma volume (1.03±0.18 mL compared to inactivated hyaluronidase (0.52±0.29 mL and 1.28±0.08 mL, p<0.05 respectively.Active hyaluronidase increased proteinuria compared to inactive hyaluronidase (0.27±0.02 vs. 0.15±0.01 µg/µg protein/creatinin, p<0.05 without changes in glomerular morphology or development of tubulo-interstitial inflammation. Atherosclerotic lesions in the aortic branches showed increased matrix production (collagen, 32±5 vs. 18±3%; glycosaminoglycans, 11±5 vs. 0.1±0.01%, active vs. inactive hyaluronidase, p<0.05. CONCLUSION: ESL degradation in apoE deficient mice contributes to reduced increased urinary protein excretion without significant changes in renal morphology. Second, the induction of compositional changes in atherogenic plaques by hyaluronidase point towards increased plaque vulnerability. These findings support further efforts to evaluate whether ESL restoration is a valuable target to prevent (micro vascular disease progression.

  8. Effects of simvastatin on apolipoprotein M in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Nilsson-Ehle Peter

    2011-07-01

    Full Text Available Abstract Objective To investigate effects of lipid lowering drug, simvastatin, on apolipoprotein M expression in the hyperlipidemic mice and in hepatic cell line, HepG2 cells. Methods Swiss male mice were randomly divided into the high fat group and control group, and were intragastrically fed with 0.9% saline (control group or lipid emulsion (high fat group at the daily dosage of 15 ml/kg body weight, respectively. After 8 weeks feeding, the hyperlipidemic model was successfully induced and these hyperlipidemic mice were then randomly divided into three experimental groups: vehicle control group, high-dose simvastatin-treated group (100 mg/kg body weight, and low-dose simvastatin-treated group (10 mg/kg body weight. Mice were dosed daily for 6 weeks of simvastatin before mice were sacrificed for determining serum lipid profile and apoM protein levels that was determined by using dot blotting analysis. Effects of simvastatin on apoM mRNA expression in the HepG2 cells were determined by real-time RT-PCR. Results Comparing to high fat model mice without simvastatin treatment, 100 mg/kg simvastatin could significantly increase serum total cholesterol (P P Conclusion The present study suggested that simvastatin, in vivo, had no effect on apoM levels in the hyperlipidemic mouse model. ApoM serum levels in mice were significantly correlated to the animal's age, whereas in cell cultures simvastatin does inhibit apoM expression in the HepG2 cells. The mechanism behind it is not known yet.

  9. Synergistic effects of high fat feeding and apolipoprotein E deletion on enterocytic amyloid-beta abundance

    Directory of Open Access Journals (Sweden)

    Dhaliwal Satvinder S

    2008-04-01

    Full Text Available Abstract Background Amyloid-β (Aβ, a key protein found in amyloid plaques of subjects with Alzheimer's disease is expressed in the absorptive epithelial cells of the small intestine. Ingestion of saturated fat significantly enhances enterocytic Aβ abundance whereas fasting abolishes expression. Apolipoprotein (apo E has been shown to directly modulate Aβ biogenesis in liver and neuronal cells but it's effect in enterocytes is not known. In addition, apo E modulates villi length, which may indirectly modulate Aβ as a consequence of differences in lipid absorption. This study compared Aβ abundance and villi length in wild-type (WT and apo E knockout (KO mice maintained on either a low-fat or high-fat diet. Wild-type C57BL/6J and apo E KO mice were randomised for six-months to a diet containing either 4% (w/w unsaturated fats, or chow comprising 16% saturated fats and 1% cholesterol. Quantitative immunohistochemistry was used to assess Aβ abundance in small intestinal enterocytes. Apo E KO mice given the low-fat diet had similar enterocytic Aβ abundance compared to WT controls. Results The saturated fat diet substantially increased enterocytic Aβ in WT and in apo E KO mice, however the effect was greater in the latter. Villi height was significantly greater in apo E KO mice than for WT controls when given the low-fat diet. However, WT mice had comparable villi length to apo E KO when fed the saturated fat and cholesterol enriched diet. There was no effect of the high-fat diet on villi length in apo E KO mice. Conclusion The findings of this study are consistent with the notion that lipid substrate availability modulates enterocytic Aβ. Apo E may influence enterocytic lipid availability by modulating absorptive capacity.

  10. Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.

    Science.gov (United States)

    Qamar, Arman; Khetarpal, Sumeet A; Khera, Amit V; Qasim, Atif; Rader, Daniel J; Reilly, Muredach P

    2015-08-01

    Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; Ptriglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma triglyceride-rich lipoproteins and cardiovascular risk in T2DM. © 2015 American Heart Association, Inc.

  11. Functional network endophenotypes unravel the effects of apolipoprotein E epsilon 4 in middle-aged adults.

    Directory of Open Access Journals (Sweden)

    Joseph S Goveas

    Full Text Available Apolipoprotein E-ε4 (APOE-ε4 accentuates memory decline, structural volume loss and cerebral amyloid deposition in cognitively healthy adults. We investigated whether APOE-ε4 carriers will show disruptions in the intrinsic cognitive networks, including the default mode (DMN, executive control (ECN and salience (SN networks, relative to noncarriers in middle-aged healthy adults; and the extent to which episodic-memory performance is related to the altered functional connectivity (Fc in these networks. Resting-state functional connectivity MRI (R-fMRI was used to measure the differences in the DMN, ECN and SN Fc between 20 APOE-ε4 carriers and 26 noncarriers. Multiple linear regression analyses were performed to determine the relationship between episodic-memory performance and Fc differences in the three resting-state networks across all subjects. There were no significant differences in the demographic and neuropsychological characteristics and the gray-matter volumes in the carriers and noncarriers. While mostly diminished DMN and ECN functional connectivities were seen, enhanced connections to the DMN structures were found in the SN in ε4 carriers. Altered DMN and ECN were associated with episodic memory performance. Significant Fc differences in the brain networks implicated in cognition were seen in middle-aged individuals with a genetic risk for AD, in the absence of cognitive decline and gray-matter atrophy. Prospective studies are essential to elucidate the potential of R-fMRI technique as a biomarker for predicting conversion from normal to early AD in healthy APOE-ε4 carriers.

  12. Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

    Directory of Open Access Journals (Sweden)

    L. Parzianello

    2008-06-01

    Full Text Available Apolipoprotein CIII (apo-CIII participates in the regulation of triglyceride-rich lipoprotein metabolism. Several polymorphic sites have been detected within and around the apo-CIII gene. Here, we examined the relationship between apo-CIII SstI polymorphism (CC, CG, GG genotypes and plasma triglyceride (TG levels in a group of 159 Japanese individuals living in Southern Brazil. The sample was divided into a group of Japanese descendants (N = 51 with high TG (HTG; >200 mg/dL and a group of Japanese descendants (N = 108 with normal TG (NTG; <200 mg/dL. TG and total cholesterol levels were analyzed by an enzymatic method using the Labtest-Diagnostic kit and high- and low-density lipoproteins by a direct method using the Labtest-Diagnostic kit and DiaSys Diagnostic System International kit, respectively. A 428-bp sequence of apo-CIII gene was amplified using oligonucleotide primers 5' GGT GAC CGA TGG CTT CAG TTC CCT GA 3' and 5' CAG AAG GTG GAT AGA GCG CTG GCC T 3'. The PCR products were digested with a restriction endonuclease SstI. Rare G allele was highly prevalent in our study population (0.416 compared to Caucasians (0.00-0.11. G allele was almost two times more prevalent in the HTG group compared to the NTG group (P < 0.001. The genotype distribution was consistent with the Hardy-Weinberg equilibrium. There was a significant association between rare G allele and HTG in Japanese individuals living in Southern Brazil as indicated by one-way ANOVA, P < 0.05.

  13. Cognitive function and apolipoprotein E in very old adults: findings from the Nun Study.

    Science.gov (United States)

    Riley, K P; Snowdon, D A; Saunders, A M; Roses, A D; Mortimer, J A; Nanayakkara, N

    2000-03-01

    The epsilon4 allele of apolipoprotein E (APOE) has been associated with Alzheimer' s disease and with milder forms of cognitive impairment. We investigated the possibility that the absence of the epsilon4 allele may predict the maintenance of high cognitive function among very old individuals. Our data are from the Nun Study, a longitudinal study of aging and Alzheimer's disease in 678 Catholic sisters. All sisters participate in annual functional exams that include the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. High cognitive function was defined as intact scores on five of the CERAD tests. A total of 241 participants aged 75 to 98 met this criterion at the first exam. Findings showed that 62% of the 241 participants maintained intact scores on the five CERAD tests throughout their participation in the study. Life table analyses indicated that those without the APOE epsilon4 allele spent more time with intact cognitive function than those with the epsilon4 allele (p = .007). Cox regression analyses indicated that those without the epsilon4 allele had half the risk of losing their intact status during the study when compared with those with the epsilon4 allele (p < .01). Our findings suggest that the APOE epsilon4 allele may be included among the variables that predict high cognitive function in cognitively intact, very old adults. Although the presence or absence of the epsilon4 allele is known to be related to the risk of dementia, it also appears to be related to maintaining high levels of cognitive function in old age.

  14. Rosuvastatin reduces atherosclerotic lesions and promotes progenitor cell mobilisation and recruitment in apolipoprotein E knockout mice.

    Science.gov (United States)

    Schroeter, Marco R; Humboldt, Tim; Schäfer, Katrin; Konstantinides, Stavros

    2009-07-01

    Statins enhance incorporation of bone marrow-derived cells into experimental neointimal lesions. However, the contribution of progenitor cells to progression of spontaneous atherosclerotic plaques, and the possible modulatory role of statins in this process, remain poorly understood. We compared the effects of rosuvastatin (1 and 10mg/kg BW) and pravastatin (10mg/kg) on progenitor cell mobilisation, recruitment into atherosclerotic plaques, and lesion growth. Statins were administered over 8 weeks to apolipoprotein E knockout mice on atherogenic diet. In addition, mice were lethally irradiated, followed by transplantation of bone marrow from LacZ transgenic mice. Rosuvastatin reduced lesion area and intima-to-media ratio at the brachiocephalic artery compared to vehicle, while both parameters were not significantly altered by pravastatin. Rosuvastatin also augmented endothelialisation (P<0.05) and reduced the smooth muscle cells (SMC) content (P=0.042) of lesions. Numbers of c-kit, sca-1 and flk-1, sca-1 double-positive progenitor cells were significantly increased in rosuvastatin compared to control-treated mice, both in the bone marrow and the peripheral blood. Similarly, the number of spleen-derived acLDL, lectin double-positive progenitor cells (P=0.001) and colony-forming units (P=0.0104) was significantly increased in mice treated with rosuvastatin compared to vehicle alone. In the bone marrow, increased Akt and p42/44 MAP kinase phosphorylation and upregulated SDF1alpha mRNA expression were observed. Importantly, rosuvastatin treatment also increased the plasma levels of c-kit ligand (P=0.003), and the number of c-kit-positive cells within atherosclerotic lesions (P=0.041). Our findings suggest that rosuvastatin reduces the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilisation and recruitment into vascular lesions.

  15. Leisure activities, apolipoprotein E e4 status, and the risk of dementia.

    Science.gov (United States)

    Yang, Sheng-Ying; Weng, Pei-Hsuan; Chen, Jen-Hau; Chiou, Jeng-Min; Lew-Ting, Chih-Yin; Chen, Ta-Fu; Sun, Yu; Wen, Li-Li; Yip, Ping-Keung; Chu, Yi-Min; Chen, Yen-Ching

    2015-12-01

    Leisure activities have been associated with a decreased risk of dementia. However, to date, no study has explored how apolipoprotein E (ApoE) e4 status or vascular risk factors modified the association between leisure activities and dementia risks. This case-control study recruited patients (age ≥ 60 years) with Alzheimer's disease (AD; n = 292) and vascular dementia (VaD; n = 144) and healthy controls (n = 506) from three teaching hospitals in Taiwan between 2007 and 2010. Information on patient's leisure activities were obtained through a questionnaire. Conditional logistic regression models were used to assess the association of leisure activities and ApoE e4 status with the risk of dementia. High-frequency physical activity was associated with a decreased risk of AD [adjusted odds ratio (AOR) = 0.45], and the results become more evident among ApoE e4 carriers with AD (AOR = 0.30) and VaD (AOR = 0.26). Similar findings were observed for cognitive (AOR = 0.42) and social activities (AOR = 0.55) for AD. High-frequency physical, cognitive, and social activities were associated with a decreased risk of VaD (AOR = 0.29-0.60). Physical and social activities significantly interacted with each other on the risk of VaD (pinteraction = 0.04). Physical activity consistently protects against AD and VaD. Significant interactions were identified across different types of leisure activities in lowering dementia risk. Copyright © 2014. Published by Elsevier B.V.

  16. Apolipoprotein E (APOE) ε4 and episodic memory decline in Alzheimer's disease: A review.

    Science.gov (United States)

    El Haj, Mohamad; Antoine, Pascal; Amouyel, Philippe; Lambert, Jean-Charles; Pasquier, Florence; Kapogiannis, Dimitrios

    2016-05-01

    A growing body of research has examined the relationship between episodic memory decline, the cognitive hallmark of Alzheimer's disease (AD), and the presence of Apolipoprotein E ε4 (APOE ε4) allele, a major genetic risk factor for the disease. Our review attempts to summarize and critically evaluate this literature. We performed a systematic search for studies assessing episodic memory in AD patients who were genotyped for APOE ε4 and identified fourteen papers. Although most of these papers reported significant relationships between APOE ε4 and episodic memory decline in AD, some papers did not confirm this relationship. Our review links this controversy to the conflicting literature about the effects of APOE ε4 on general cognitive functioning in AD. We identify several shortcoming and limitations of the research on the relationship between APOE ε4 and episodic memory in AD, such as small sample sizes, non-representative populations, lack of comparison of early-onset vs. late-onset disease, and lack of comparison among different genotypes that include APOE ε4 (i.e., zero, one, or two ε4 alleles). Another major shortcoming of the reviewed literature was the lack of comprehensive evaluation of episodic memory decline, since episodic memory was solely evaluated with regard to encoding and retrieval, omitting evaluation of core episodic features that decline in AD, such as context recall (e.g., how, where, and when an episodic event has occurred) and subjective experience of remembering (e.g., reliving, emotion and feeling during episodic recollection). Future research taking these limitations into consideration could illuminate the nature of the relationship between APOE ε4 and episodic memory decline in AD. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Apolipoprotein A-II polymorphism: relationships to behavioural and hormonal mediators of obesity

    Science.gov (United States)

    Smith, CE; Ordovás, JM; Sánchez-Moreno, C; Lee, Y-C; Garaulet, M

    2011-01-01

    Background The interaction between apolipoprotein A-II (APOA2) m265 genotype and saturated fat for obesity traits has been more extensively demonstrated than for any other locus, but behavioural and hormonal mechanisms underlying this relationship are unexplored. In this study, we evaluated relationships between APOA2 and obesity risk with particular focus on patterns of eating and ghrelin, a hormonal regulator of food intake. Design Cross-sectional study. Subjects Overweight and obese subjects (n = 1225) were evaluated at baseline in five weight loss clinics in southeastern Spain. Methods Behavioural data were assessed using a checklist of weight loss obstacles. Logistic regression models were fitted to estimate the risk of a specific behaviour associated with APOA2 genotype. Relationships between APOA2 genotype and saturated fat intakes for anthropometric traits and plasma ghrelin were evaluated by analysis of variance. To construct categorical variables to evaluate interactions, saturated fat intake was dichotomized into high and low according to the population median intake or as tertiles. Results Homozygous minor (CC) subjects were more likely to exhibit behaviours that impede weight loss (‘Do you skip meals’, odds ratio (OR) = 2.09, P=0.008) and less likely to exhibit the protective behaviour of ‘Do you plan meals in advance’ (OR = 0.64, P=0.034). Plasma ghrelin for CC subjects consuming low saturated fat was lower compared with (1) CC subjects consuming high saturated fat, (2) TT + TC carriers consuming low saturated fat and (3) TT+TC carriers consuming high saturated fat (all Pghrelin. Expansion of knowledge of APOA2 and obesity to include modulation of specific behaviours and hormonal mediators not only broadens understanding of gene–diet interactions, but also facilitates the pragmatic, future goal of developing dietary guidelines based on genotype. PMID:21386805

  18. Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals.

    Science.gov (United States)

    Souza, D R S; Nakazone, M A; Pinhel, M A S; Alvares, R M; Monaco, A C; Pinheiro, A; Barros, C F D C; Cury, P M; Cunrath, G S; Netinho, J G

    2009-05-01

    We evaluated genetic variants of apolipoprotein E (APOE HhaI) and their association with serum lipids in colorectal cancer (CRC), together with eating habits and personal history. Eight-seven adults with CRC and 73 controls were studied. APOE*2 (rs7412) and APOE*4 (rs429358) were identified by polymerase chain reaction-restriction fragment length polymorphism. APOE gene polymorphisms were similar in both groups, but the epsilon4/epsilon4 genotype (6%) was present only in controls. The patients had reduced levels (mean +/- SD) of total cholesterol and low-density lipoprotein cholesterol fraction (180.4 +/- 49.5 and 116.1 +/- 43.1 mg/dL, respectively) compared to controls (204.2 +/- 55.6, P = 0.135 and 134.7 +/- 50.8 mg/dL; P = 0.330, respectively) indicating that they were not statistically significant after the Bonferroni correction. The APOE*4 allele was associated with lower levels of total cholesterol, low- and high-density lipoprotein cholesterol fraction and increased levels of very low-density lipoprotein cholesterol fraction and triglycerides only among patients (P = 0.014). There was a positive correlation between the altered lipid profile and increased body mass indexes in both groups (P hypertension and overweight was observed in controls (P < 0.002). In conclusion, the presence of the epsilon4/epsilon4 genotype only in controls may be due to a protective effect against CRC. Lower lipid profile values among patients, even those on lipid-rich diets associated with the APOE*4 allele, suggest alterations in the lipid synthesis and metabolism pathways in CRC.

  19. Association between apolipoprotein E genotype, serum lipids, and colorectal cancer in Brazilian individuals

    Directory of Open Access Journals (Sweden)

    D.R.S. Souza

    2009-05-01

    Full Text Available We evaluated genetic variants of apolipoprotein E (APOE HhaI and their association with serum lipids in colorectal cancer (CRC, together with eating habits and personal history. Eight-seven adults with CRC and 73 controls were studied. APOE*2 (rs7412 and APOE*4 (rs429358 were identified by polymerase chain reaction-restriction fragment length polymorphism. APOE gene polymorphisms were similar in both groups, but the ε4/ε4 genotype (6% was present only in controls. The patients had reduced levels (mean ± SD of total cholesterol and low-density lipoprotein cholesterol fraction (180.4 ± 49.5 and 116.1 ± 43.1 mg/dL, respectively compared to controls (204.2 ± 55.6, P = 0.135 and 134.7 ± 50.8 mg/dL; P = 0.330, respectively indicating that they were not statistically significant after the Bonferroni correction. The APOE*4 allele was associated with lower levels of total cholesterol, low- and high-density lipoprotein cholesterol fraction and increased levels of very low-density lipoprotein cholesterol fraction and triglycerides only among patients (P = 0.014. There was a positive correlation between the altered lipid profile and increased body mass indexes in both groups (P < 0.010. Moreover, a higher rate of hypertension and overweight was observed in controls (P < 0.002. In conclusion, the presence of the ε4/ε4 genotype only in controls may be due to a protective effect against CRC. Lower lipid profile values among patients, even those on lipid-rich diets associated with the APOE*4 allele, suggest alterations in the lipid synthesis and metabolism pathways in CRC.

  20. Apolipoprotein(a Kringle-IV Type 2 Copy Number Variation Is Associated with Venous Thromboembolism.

    Directory of Open Access Journals (Sweden)

    Elena Sticchi

    Full Text Available In addition to the established association between high lipoprotein(a [Lp(a] concentrations and coronary artery disease, an association between Lp(a and venous thromboembolism (VTE has also been described. Lp(a is controlled by genetic variants in LPA gene, coding for apolipoprotein(a, including the kringle-IV type 2 (KIV-2 size polymorphism. Aim of the study was to investigate the role of LPA gene KIV-2 size polymorphism and single nucleotide polymorphisms (SNPs (rs1853021, rs1800769, rs3798220, rs10455872 in modulating VTE susceptibility. Five hundred and sixteen patients with VTE without hereditary and acquired thrombophilia and 1117 healthy control subjects, comparable for age and sex, were investigated. LPA KIV-2 polymorphism, rs3798220 and rs10455872 SNPs were genotyped by TaqMan technology. Concerning rs1853021 and rs1800769 SNPs, PCR-RFLP assay was used. LPA KIV-2 repeat number was significantly lower in patients than in controls [median (interquartile range 11(6-17 vs 15(9-25, p<0.0001]. A significantly higher prevalence of KIV-2 repeat number ≤7 was observed in patients than in controls (33.5% vs 15.5%, p<0.0001. KIV-2 repeat number was independently associated with VTE (p = 4.36 x10-9, as evidenced by the general linear model analysis adjusted for transient risk factors. No significant difference in allele frequency for all SNPs investigated was observed. Haplotype analysis showed that LPA haplotypes rather than individual SNPs influenced disease susceptibility. Receiver operating characteristic curves analysis showed that a combined risk prediction model, including KIV-2 size polymorphism and clinical variables, had a higher performance in identifying subjects at VTE risk than a clinical-only model, also separately in men and women.

  1. Age-Related Effects of the Apolipoprotein E Gene on Brain Function.

    Science.gov (United States)

    Matura, Silke; Prvulovic, David; Hartmann, Daniel; Scheibe, Monika; Sepanski, Beate; Butz, Marius; Oertel-Knöchel, Viola; Knöchel, Christian; Karakaya, Tarik; Fußer, Fabian; Hattingen, Elke; Pantel, Johannes

    2016-03-16

    The apolipoprotein E (ApoE) ɛ4 allele is a well-established genetic risk factor for sporadic Alzheimer's disease. Some evidence suggests a negative role of the ApoE ɛ4 allele for cognitive performance in late life, while beneficial effects on cognition have been shown in young age. We investigated age-related effects of the ApoE gene on brain function by assessing cognitive performance, as well as functional activation patterns during retrieval of Face-Name pairs in a group of young (n = 50; age 26.4±4.6 years, 25 ɛ4 carriers) and old (n = 40; age 66.1±7.0 years, 20 ɛ4 carriers) participants. A cross-sectional factorial design was used to examine the effects of age, ApoE genotype, and their interaction on both cognitive performance and the blood oxygenation level dependent (BOLD) brain response during retrieval of Face-Name pairs. While there were no genotype-related differences in cognitive performance, we found a significant interaction of age and ApoE genotype on task-related activation bilaterally in anterior cingulate gyrus and superior frontal gyrus, as well as left and right insula. Old age was associated with increased activity in ɛ4 carriers. The increased BOLD response in old ɛ4 carriers during retrieval could indicate a neurocognitive disadvantage associated with the ɛ4 allele with increasing age. Furthermore, recruitment of neuronal resources resulted in enhanced memory performance in young ɛ4 carriers, pointing to a better neurofunctional capacity associated with the ApoE4 genotype in young age.

  2. Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

    International Nuclear Information System (INIS)

    Xiao, Hong-Bo; Lu, Xiang-Yang; Sun, Zhi-Liang; Zhang, Heng-Bo

    2011-01-01

    Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE −/− ) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE −/− mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of ApoE −/− mice. -- Graphical abstract: Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of ApoE −/− mice. Highlights: ► OPN–CD44 pathway plays a critical role in the development of atherosclerosis. ► We examine lesion area, OPN and CD44 changes after kaempferol treatment. ► Kaempferol treatment decreased atherosclerotic lesion area in ApoE −/− mice. ► Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE −/− mice. ► Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis.

  3. Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Hong-Bo, E-mail: xhbzhb@yahoo.com [College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128 (China); Lu, Xiang-Yang; Sun, Zhi-Liang [Hunan Agricultural University, Changsha 410128 (China); Zhang, Heng-Bo [Furong District Red Cross Hospital, Changsha 410126 (China)

    2011-12-15

    Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE{sup -/-}) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE{sup -/-} mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. -- Graphical abstract: Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. Highlights: Black-Right-Pointing-Pointer OPN-CD44 pathway plays a critical role in the development of atherosclerosis. Black-Right-Pointing-Pointer We examine lesion area, OPN and CD44 changes after kaempferol treatment. Black-Right-Pointing-Pointer Kaempferol treatment decreased atherosclerotic lesion area in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis.

  4. Apolipoprotein E expression and behavioral toxicity of high charge, high energy (HZE) particle radiation

    Science.gov (United States)

    Higuchi, Yoshinori; Nelson, Gregory A.; Vazquez, Marcelo; Laskowitz, Daniel T.; Slater, James M.; Pearlstein, Robert D.

    2002-01-01

    Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. METHODS: Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. ROTAROD TEST: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. OPEN FIELD TEST: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. MORRIS WATER MAZE: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. CONCLUSIONS: These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the CNS. ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process.

  5. Apolipoprotein A-IV constrains HPA and behavioral stress responsivity in a strain-dependent manner.

    Science.gov (United States)

    Packard, Amy E B; Zhang, Jintao; Myers, Brent; Ko, Chih-Wei; Wang, Fei; Tso, Patrick; Ulrich-Lai, Yvonne M

    2017-12-01

    There is a critical gap in our knowledge of the mechanisms that govern interactions between daily life experiences (e.g., stress) and metabolic diseases, despite evidence that stress can have profound effects on cardiometabolic health. Apolipoprotein A-IV (apoA-IV) is a protein found in chylomicrons (lipoprotein particles that transport lipids throughout the body) where it participates in lipid handling and the regulation of peripheral metabolism. Moreover, apoA-IV is expressed in brain regions that regulate energy balance including the arcuate nucleus. Given that both peripheral and central metabolic processes are important modulators of hypothalamic-pituitary-adrenocortical (HPA) axis activity, the present work tests the hypothesis that apoA-IV activity affects stress responses. As emerging data suggests that apoA-IV actions can vary with background strain, we also explore the strain-dependence of apoA-IV stress regulation. These studies assess HPA axis, metabolic (hyperglycemia), and anxiety-related behavioral responses to psychogenic stress in control (wildtype) and apoA-IV-deficient (KO) mice on either the C57Bl/6J (C57) or 129×1/SvJ (129) background strain. The results indicate that apoA-IV KO increases post-stress corticosterone and anxiety-related behavior specifically in the 129 strain, and increases stress-induced hyperglycemia exclusively in the C57 strain. These data support the hypothesis that apoA-IV is a novel factor that limits stress reactivity in a manner that depends on genetic background. An improved understanding of the complex relationship among lipid homeostasis, stress sensitivity, and genetics is needed to optimize the development of personalized treatments for stress- and metabolism-related diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Stronger relationship of serum apolipoprotein A-1 and B with diabetic retinopathy than traditional lipids

    Directory of Open Access Journals (Sweden)

    B S Ankit

    2017-01-01

    Full Text Available Aim: Diabetic retinopathy (DR is the most common preventable cause of blindness where early detection and treatment can be sight-saving. Search for biomarkers of the disease has been relentless. We aimed to determine whether lipoproteins apolipoproteins A1 and B1 (Apo-A1 and Apo-B1 have stronger associations with DR in contrast to conventionally measured low-density lipoprotein (LDL and high-density lipoprotein cholesterol levels. Materials and Methods: We performed a cross-sectional study and studied 117 patients. Serum lipid profile was assessed by autoanalyzer. Serum Apo-A1 and Apo-B were measured using immunoturbidimetric kit on an autoanalyzer. Apo-B/A1 ratio was calculated. Retinopathy was graded from the digital retinal photographs, taken with nonmydriatic auto fundus camera and classified according to International Clinical DR Disease Severity Scale. Results: Mean Apo-A1 for mild, moderate, severe retinopathy, and proliferative DR (PDR shows a significant negative correlation (P = 0.001 with severity of retinopathy. Mean Apo-B for mild, moderate, severe, PDR displayed a significant positive correlation with severity of retinopathy (P = 0.001. Mean Apo-B/A1 for mild, moderate, severe, PDR showed highly significant positive correlation with severity of retinopathy (P < 0.001. In contrast, mean LDL for mild, moderate, severe, PDR showed insignificant association with severity of DR (P = 0.081. Conclusion: Apo-A1 and Apo-B have a stronger association with the development of DR than traditional lipids and can thus facilitate early detection and treatment of the disease.

  7. Angiotensin converting enzyme inhibitors and Alzheimer disease in the presence of the apolipoprotein E4 allele.

    Science.gov (United States)

    Qiu, Wendy Wei Qiao; Lai, Angela; Mon, Timothy; Mwamburi, Mkaya; Taylor, Warren; Rosenzweig, James; Kowall, Neil; Stern, Robert; Zhu, Haihao; Steffens, David C

    2014-02-01

    The effect of angiotensin converting enzyme (ACE) inhibitors on Alzheimer disease (AD) remains unclear, with conflicting results reported. We studied the interaction of the Apolipoprotein E (ApoE) genotype and ACE inhibitors on AD. This was a cross-sectional study of homebound elderly with an AD diagnosis and documentation of medications taken. ApoE genotype was determined. A total of 355 subjects with status on ApoE alleles and cognitive diagnoses were studied. The average age (mean ± SD) of this population was 73.3 ± 8.3 years old, and 73% were female. Cross-sectionally, there was no difference in the number of AD cases between ApoE4 carriers and ApoE4 non-carriers or between ACE inhibitor users and non-users in the homebound elderly. ApoE4 carriers treated with ACE inhibitors, however, had more diagnoses of AD compared with those who did not have the treatment (28% versus 6%, p = 0.01) or ApoE4 non-carriers treated with an ACE inhibitor (28% versus 10%, p = 0.03). ACE inhibitor use was associated with AD diagnosis only in the presence of an E4 allele. Using multivariate logistic regression analysis, we found that in diagnosed AD cases there was a significant interaction between ApoE4 and ACE inhibitor use (odds ratio: 20.85; 95% confidence interval: 3.08-140.95; p = 0.002) after adjusting for age, sex, ethnicity, and education. The effects of ACE inhibitors on AD may be different depending on ApoE genotype. A prospective study is needed to determine whether ACE inhibitor use accelerates or poorly delays AD development in ApoE4 carriers compared with ApoE4 non-carriers. Copyright © 2014. Published by Elsevier Inc.

  8. Apolipoprotein E expression and behavioral toxicity of high charge, high energy (HZE) particle radiation

    International Nuclear Information System (INIS)

    Higuchi, Yoshinori; Nelson, G.A.; Slater, J.M.; Pearlstein, R.D.; Laskowitz, D.T.

    2002-01-01

    Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. Rotarod test: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. Open field test: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. Morris water maze: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the central nervous system (CNS). ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process. (author)

  9. A FDG-PET Study of Metabolic Networks in Apolipoprotein E ε4 Allele Carriers.

    Directory of Open Access Journals (Sweden)

    Zhijun Yao

    Full Text Available Recently, some studies have applied the graph theory in brain network analysis in Alzheimer's disease (AD and Mild Cognitive Impairment (MCI. However, relatively little research has specifically explored the properties of the metabolic network in apolipoprotein E (APOE ε4 allele carriers. In our study, all the subjects, including ADs, MCIs and NCs (normal controls were divided into 165 APOE ε4 carriers and 165 APOE ε4 noncarriers. To establish the metabolic network for all brain regions except the cerebellum, cerebral glucose metabolism data obtained from FDG-PET (18F-fluorodeoxyglucose positron emission tomography were segmented into 90 areas with automated anatomical labeling (AAL template. Then, the properties of the networks were computed to explore the between-group differences. Our results suggested that both APOE ε4 carriers and noncarriers showed the small-world properties. Besides, compared with APOE ε4 noncarriers, the carriers showed a lower clustering coefficient. In addition, significant changes in 6 hub brain regions were found in between-group nodal centrality. Namely, compared with APOE ε4 noncarriers, significant decreases of the nodal centrality were found in left insula, right insula, right anterior cingulate, right paracingulate gyri, left cuneus, as well as significant increases in left paracentral lobule and left heschl gyrus in APOE ε4 carriers. Increased local short distance interregional correlations and disrupted long distance interregional correlations were found, which may support the point that the APOE ε4 carriers were more similar with AD or MCI in FDG uptake. In summary, the organization of metabolic network in APOE ε4 carriers indicated a less optimal pattern and APOE ε4 might be a risk factor for AD.

  10. Apolipoprotein L1 confers pH-switchable ion permeability to phospholipid vesicles.

    Science.gov (United States)

    Bruno, Jonathan; Pozzi, Nicola; Oliva, Jonathan; Edwards, John C

    2017-11-03

    Apolipoprotein L1 (ApoL1) is a human serum protein conferring resistance to African trypanosomes, and certain ApoL1 variants increase susceptibility to some progressive kidney diseases. ApoL1 has been hypothesized to function like a pore-forming colicin and has been reported to have permeability effects on both intracellular and plasma membranes. Here, to gain insight into how ApoL1 may function in vivo , we used vesicle-based ion permeability, direct membrane association, and intrinsic fluorescence to study the activities of purified recombinant ApoL1. We found that ApoL1 confers chloride-selective permeability to preformed phospholipid vesicles and that this selectivity is strongly pH-sensitive, with maximal activity at pH 5 and little activity above pH 7. When ApoL1 and lipid were allowed to interact at low pH and were then brought to neutral pH, chloride permeability was suppressed, and potassium permeability was activated. Both chloride and potassium permeability linearly correlated with the mass of ApoL1 in the reaction mixture, and both exhibited lipid selectivity, requiring the presence of negatively charged lipids for activity. Potassium, but not chloride, permease activity required the presence of calcium ions in both the association and activation steps. Direct assessment of ApoL1-lipid associations confirmed that ApoL1 stably associates with phospholipid vesicles, requiring low pH and the presence of negatively charged phospholipids for maximal binding. Intrinsic fluorescence of ApoL1 supported the presence of a significant structural transition when ApoL1 is mixed with lipids at low pH. This pH-switchable ion-selective permeability may explain the different effects of ApoL1 reported in intracellular and plasma membrane environments. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Human apolipoprotein e resequencing by proteomic analysis and its application to serotyping.

    Directory of Open Access Journals (Sweden)

    Motoi Nishimura

    Full Text Available BACKGROUND: Apolipoprotein E (ApoE typing is considered important because of the association between ApoE and Alzheimer's disease and familial dyslipidemia and is currently performed by genetic testing (APOE genotyping. ApoE levels in plasma and serum are clinically determined by immunoassay. METHODS: Combining an ApoE immunoassay reagent with proteomic analysis using an Orbitrap mass spectrometer, we attempted to resequence ApoE from trace amounts of serum for typing (serotyping. Most (24 of 33 ApoE mutant proteins registered to date with Online Mendelian Inheritance in Man, such as ApoE2 and ApoE4, involve lysine and arginine mutations. Digestion of mutant ApoE with trypsin will thus result in fragments that differ substantially from wild-type ApoE3 in terms of mass, making serotyping ideally suited to mass spectrometry analysis. RESULTS: The mean coverage of the amino acid sequence of full-length ApoE was 91.6% in the protein resequence. Residues 112 and 158 (which are mutated in ApoE2 and ApoE4 were covered in all samples, and the protein sequences were used for serotyping. Serotypes including all heterozygous combinations (ApoE2/E3, E2/E4, E3/E4 corresponded exactly to the APOE genotyping results in each of the subjects. CONCLUSION: Our novel ApoE serotyping method with protein resequencing requires no synthesis of stable isotope-labeled peptides or genome analysis. The method can use residual blood from samples collected for routine clinical tests, thus enabling retrospective studies with preserved body fluids. The test could be applied to samples from subjects whose DNA is unavailable. In future studies, we hope to demonstrate the capability of our method to detect rare ApoE mutations.

  12. Apolipoprotein E expression and behavioral toxicity of high charge, high energy (HZE) particle radiation

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Yoshinori; Nelson, G.A.; Slater, J.M.; Pearlstein, R.D. [Loma Linda Univ., CA (United States). Medical Center; Vazquez, M. [Brookhaven National Lab., Upton, NY (United States); Laskowitz, D.T. [Duke Univ., Durham, NC (United States). Medical Center

    2002-12-01

    Apolipoprotein E (apoE) is a lipid binding protein that plays an important role in tissue repair following brain injury. In the present studies, we have investigated whether apoE affects the behavioral toxicity of high charge, high energy (HZE) particle radiation. Sixteen male apoE knockout (KO) mice and sixteen genetically matched wild-type (WT) C57BL mice were used in this experiment. Half of the KO and half of the WT animals were irradiated with 600 MeV/amu iron particles (2 Gy whole body). The effect of irradiation on motor coordination and stamina (Rotarod test), exploratory behavior (open field test), and spatial working and reference memory (Morris water maze) was assessed. Rotarod test: Performance was adversely affected by radiation exposure in both KO and WT groups at 30 d after irradiation. By 60 d after radiation, the radiation effect was lost in WT, but still apparent in irradiated KO mice. Open field test: Radiation reduced open field exploratory activity 14, 28, 56, 84, and 168 d after irradiation of KO mice, but had no effect on WT mice. Morris water maze: Radiation adversely affected spatial working memory in the KO mice, but had no discernible effect in the WT mice as assessed 180 d after irradiation. In contrast, irradiated WT mice showed marked impairment of spatial reference memory in comparison to non-irradiated mice, while no effect of radiation was observed in KO mice. These studies show that apoE expression influences the behavioral toxicity of HZE particle radiation and suggest that apoE plays a role in the repair/recovery from radiation injury of the central nervous system (CNS). ApoE deficiency may exacerbate the previously reported effects of HZE particle radiation in accelerating the brain aging process. (author)

  13. Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI as biomarkers of recovery.

    Directory of Open Access Journals (Sweden)

    Valentina Peta

    Full Text Available There is a clear need for better biomarkers of drug-induced-liver-injury (DILI.We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI.We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC of ActiTest components as predictors of recovery outcome defined as an ALT <2x the upper limit of normal (ULN, and BILI <2x ULN.After adjudication, 154 patients were considered to have DILI and 22 were considered to have acute liver injury without DILI. A multivariate regression analysis (ActiTest-DILI patent pending combining the ActiTest components without BILI and ALT (used as references, apolipoprotein-A1, haptoglobin, alpha-2-macroglobulin and GGT, age and gender, resulted in a significant prediction of recovery with 67.0% accuracy (77/115 and an AUROC of 0.724 (P<0.001 vs. no prediction 0.500. Repeated apolipoprotein-A1 and haptoglobin remained significantly higher in the DILI cases that recovered (n = 65 versus those that did not (n = 16, at inclusion, at 4-8 weeks and at 8-12 weeks. The same results were observed after stratification on APAP cases and non-APAP cases.We identified that apolipoprotein-A1 and haptoglobin had significant predictive values for the prediction of recovery at 12 weeks in DILI, enabling the construction of a new prognostic panel, the DILI-ActiTest, which needs to be independently validated.

  14. Apolipoprotein B levels, APOB alleles, and risk of ischemic cardiovascular disease in the general population, a review

    DEFF Research Database (Denmark)

    Benn, Marianne

    2009-01-01

    capturing the entire variation in APOB cannot be identified, and thus most polymorphisms must be evaluated separately in association studies; (3) APOB mutations and polymorphisms are associated with a range of apolipoprotein B and LDL cholesterol levels, although the magnitude of effect sizes of common...... for the E4154K polymorphism that possibly predicts a reduction in risk of ischemic cerebrovascular disease and ischemic stroke, common APOB polymorphisms with modest effect sizes on lipid levels do not predict risk of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease...

  15. Apolipoprotein CIII Reduces Proinflammatory Cytokine-Induced Apoptosis in Rat Pancreatic Islets via the Akt Prosurvival Pathway

    DEFF Research Database (Denmark)

    Størling, Joachim; Juntti-Berggren, Lisa; Olivecrona, Gunilla

    2011-01-01

    Apolipoprotein CIII (ApoCIII) is mainly synthesized in the liver and is important for triglyceride metabolism. The plasma concentration of ApoCIII is elevated in patients with type 1 diabetes (T1D), and in vitro ApoCIII causes apoptosis in pancreatic ß-cells in the absence of inflammatory stress...... of the survival serine-threonine kinase Akt. Inhibition of the Akt signaling pathway by the phosphatidylinositol 3 kinase inhibitor LY294002 counteracted the antiapoptotic effect of ApoCIII on cytokine-induced apoptosis. We conclude that ApoCIII in the presence of T1D-relevant proinflammatory cytokines reduces...

  16. Association of apolipoprotein M with high-density lipoprotein kinetics in overweight-obese men

    DEFF Research Database (Denmark)

    Ooi, Esther M M; Watts, Gerald F; Chan, Dick C

    2009-01-01

    cholesterol and HDL cholesterol (ptriglyceride, NEFA, insulin, glucose, HOMA score or adiponectin concentrations. Plasma apoM was positively associated with both apoA-I and apoA-II concentrations (r=0.406, p...%). The kinetics of HDL apoA-I and apoA-II were measured using intravenous administration of D(3)-leucine, gas chromatography-mass spectrometry and multi-compartmental modeling. RESULTS: Plasma apoM was inversely associated with body mass index and positively associated with plasma total cholesterol, LDL...... apoM and triglycerides were significant, independent predictors of HDL apoA-I FCR (adjusted R(2)=16%, p

  17. OPRA capacity bounds for selection diversity over generalized fading channels

    KAUST Repository

    Hanif, Muhammad Fainan; Yang, Hongchuan; Alouini, Mohamed-Slim

    2014-01-01

    , lower and upper bounds on OPRA capacity for selection diversity scheme are presented. These bounds hold for variety of fading channels including log-normal and generalized Gamma distributed models and have very simple analytic expressions for easy

  18. Unexpected strong attraction in the presence of continuum bound state

    International Nuclear Information System (INIS)

    Delfino, A.; Frederico, T.

    1992-06-01

    The result of few-particle ground-state calculation employing a two-particle non-local potential supporting a continuum bound state in addition to a negative-energy bound state has occasionally revealed unexpected large attraction in producing a very strongly bound ground state. In the presence of the continuum bound state the difference of phase shift between zero and infinite energies has an extra jump of φ as in the presence of an additional bound state. The wave function of the continuum bound state is identical with that of a strongly bound negative-energy state, which leads us to postulate a pseudo bound state in the two-particle system in order to explain the unexpected attraction. The role of the Pauli forbidden states is expected to be similar to these pseudo states. (author)

  19. Bounded Perturbation Regularization for Linear Least Squares Estimation

    KAUST Repository

    Ballal, Tarig; Suliman, Mohamed Abdalla Elhag; Al-Naffouri, Tareq Y.

    2017-01-01

    This paper addresses the problem of selecting the regularization parameter for linear least-squares estimation. We propose a new technique called bounded perturbation regularization (BPR). In the proposed BPR method, a perturbation with a bounded

  20. Bound values for Hall conductivity of heterogeneous medium under ...

    Indian Academy of Sciences (India)

    - ditions in inhomogeneous medium has been studied. It is shown that bound values for. Hall conductivity differ from bound values for metallic conductivity. This is due to the unusual character of current percolation under quantum Hall effect ...